WITTIG REARRANGEMENTS OF SILYL ALLYLIC CYCLIC ETHERS AND [1,2] CARBON TO CARBON SILYL MIGRATION OF α-HYDROXY ALLYL SILANES By Emmanuel Wesonga Maloba A DISSERTATION Submitted to Michigan State University in partial fulfillment of the requirements for the degree of Chemistry – Doctor of Philosophy 2023 ABSTRACT The [1,2]- and [1,4]-Wittig rearrangements of cyclic α/γ-silyl allyl ethers have been studied. These rearrangements are based on the ability of the silicon atom to stabilize an α-anion. Treatment of diastereomeric 2-silyl-6-aryl-5,6-dihydro-2H-pyrans with n-butyllithium (sec-butyllithium for cis diastereomer) result in stereoconvergent ring contraction to corresponding α-silylcyclopentenols and/or (β-cyclopropyl)acylsilanes via [1,2]- and [1,4]-Wittig rearrangements respectively. Studies on expanded ring size, 2-silyl-7-aryl-2,5,6,7-tetrahydrooxepins, led to the formation of α- silylcyclohexenols and (β-cyclobutyl)acylsilanes. On the other hand, moving the silyl group to the 4-position of the dihydropyran moiety led predominantly to [1,4]-Wittig rearrangement. Concurrently, 2-silyl-3-hydroxy-5-arylcyclopentan-1-one and 2-silyl-3-hydrox-6- arylcycloyhexan-1-one can be accessed by subjecting 1-silyl-5-arylcyclopent-2-en-1-ol and 1-silyl- 6-arylcyclohex-2-en-1-ol, respectively, to m-CPBA and NaHCO3. In this transformation epoxidation triggers a [1,2]-carbon-to-carbon silyl migration. The stereochemical orientation of the resulting product is such that the α-silyl and β-hydroxy groups are trans to one another. Furthermore, the hydroxy group in the starting silane directs the epoxide formation, which in turn dictates the stereochemical outcome of the resulting β-hydroxy making this reaction stereospecific in nature. Lastly, the synthesis of 2-alkyl-2-silylalkanals can be achieved by conditions that effect spontaneous [1,2]-carbon-to-carbon silyl migration in 1-silyl-2-alkyl-2-alken-1-ols. These conditions are independent of the substituents on silicon but require an alkyl substituent at the olefin position next to the sp3 carbon bearing the silyl group. To my family: My dad Syverio; my mom Evalyne (Monica); my wife Harriet; my daughter Trixie; and my siblings; Andrew, Hildah, and Simon Thank you for your patience and all the support iii ACKNOWLEDGEMENTS I would like to express my sincere gratitude to my PhD advisor, Professor Robert E. Maleczka, Jr., for his guidance and support throughout my PhD program. I came to graduate school with zero knowledge on setting up and running organic synthesis reactions. His patience and diplomatic approach to my questions and concerns helped me grow both as a scientist and a person. Even though he was the department chair at the time I joined his research group, he always found time out of his busy schedule to follow my research progress and give me valuable suggestions. Since the purpose of PhD program is to be an independent researcher, he gave me freedom and resources to explore my own ideas. I am grateful to have had him as my mentor. I would also like to thank my PhD committee members; Professor Babak Borhan, Professor William D. Wulff and Professor Melanie Cooper for their advice and helpful suggestions during my second-year oral examination and my final defense. I appreciate the lectures given by Professor Borhan as the course instructor for CEM 845 which provided the necessary knowledge I needed to conduct my research. I thank Professor Wulff for leading the discussion in CEM 850 where I learnt the basics of proposing plausible organic synthesis reaction mechanisms. I would also like to thank him for the lectures during CEM 852 where I gained valuable knowledge of organic synthesis and contributed to his database. I would also like to thank Professor Xuefei Huang for CEM 851 which also gave me the opportunity to learn advanced physical organic chemistry, and which was applicable to my research. I would also like to thank Professor Jetze Tepe and Professor Milton R. Smith, III for CEM 956 (heterocyclic chemistry) and CEM 820 (organometallics) respectively. I would like to thank the staff at the Department of Chemistry, Michigan State University for all their support. I would like to thank Dr. Daniel Holmes and Dr. Li Xie for making sure the NMR instruments work well, Dr. Richard Staples for solving my crystal structures, Dr. Anthony iv Schilmiller for the high-resolution mass spectroscopy assistance. I would also like to thank Anna Osborn for the guidance on PhD program in chemistry always making sure we don’t miss the deadlines. I would like to thank Heidi Wardin for her work in the graduate office and the chair’s office. I would like to thank Dawn Kuhn, Bill Flick and Eric Smariege for all their help with chemical and instrument ordering. I would like to thank Bob Racico for maintaining the Chemistry building enabling us to conduct research. I would like to thank Tiphani Scott, Bethanny Potter, Mary Mroz and Brenda Franklin for all their support. I would like to thank Dr. Chrisoula Vasilieou, Dr. Fangyi Shen and Dr. Ardeshir Azadnia for the opportunity they gave me as a Teaching Assistant in their respective undergraduate courses. Most importantly, I would like to thank my family. I thank my mom (Evalyn Shikuku) and dad (Syverio Maloba) for believing in my academic ability and providing the necessary support that catapulted me to the highest level of academic achievement that I could have dreamed of. I thank my siblings; Andrew Maloba, Hildah Maloba and Simon Maloba for all their encouragement and support. Special thanks to my wife, Harriet, and my daughter, Trixie, for their unconditional love and support that helped me navigate the tough journey associated with graduate school. I would like to thank my research collaborators for their helpful discussion and suggestions. I thank Dr. Luis Martin Mori-Quiroz who laid the foundation on Wittig rearrangement of cyclic ethers. His contribution shaped some of the work reported in this dissertation to a great extent. I thank Dr. Maria del Rosario Amado Sierra for her contributions in the silyl migration by epoxidation work. I thank Nagham Al Masraf for her contributions in the synthesis of starting materials for the silyl migration by epoxidation work. I also thank her for allowing me to be her mentor both as an ACS Project Seed high school student (East Lansing High School) and an undergraduate research fellow at Michigan State University. v I would like to thank the Maleczka group members; both former and current. This group was like my second family, and I carry with me fond memories. My special gratitude goes to Professor Jonathan Dannat for the help he accorded me when I joined the group. I thank Dr. Jose Raul Montero Bastidas (Pepe), Dr. Badru Deen Barry, Dr. Fangyi Chen, Dr. Ruwandhi Jayasundara (Ruwi) and Dr. Aditya Patil (Chemical Engineer). I thank the current Maleczka group members; Thomas, Arzoo, Sean, Chris, Pauline, Anshu, Cliff, Nehali, Junhui and Jenna. Special thanks to Darshika for taking over the Wittig rearrangement project. I would like to thank all the friends I met while at graduate school. These include but not limited to, Dr. Kunli Liu, Dr. Jurick Lahiri, Zhen Li, Dr. Grace Hubbell, Dr. Shivangi Chugh, Aimen Al Hilfi, Dr. Timothe Melin, Katayoon Maghami, Dr. Dan Wanyama, Dr. Donald Akanga, Titus Omanga, Dare George, Dr. Katie Kwiatkowski, Bismarck Amaniampong, Nicholas Wills, Jesse Cantrell, Jiaojiao Wang, Rosemary Augustine and Morgan Mayieka. Special thanks to Ankush Chakraborty and Dr. Taylor Fiolek for helpful discussions during lunch on Fridays. I thank Dr. Amaya Mathes Hewage, Dr. Samantha Houchlei and Dr. Zhilin Hou for the fun moments and support during my time in graduate school. I thank Dr. Herbert Kavunja and Dr. Pauline Wambua for their guidance. Thanks to the Kenyan community in greater Lansing for the events that made me feel at home. Special thanks to my uncle, Ashitiva Mandale, for all the support he gave me. I would also like to thank my mentors throughout my academic journey. I thank Mrs. Benardine Omondi, former headmistress of Endebess Centre Primary School for identifying my unique academic talent. I thank Mr. Samuel Abraham, principal of Manor House High School, and all teachers for the support they gave me in high school. I thank the academic staff of the Department of Chemistry at the University of Nairobi for guiding and teaching me throughout my undergraduate studies. Special thanks to Professor John Mmari Onyari for encouraging me to pursue a PhD. vi TABLE OF CONTENTS LIST OF SYMBOLS AND ABBREVIATIONS ............................................................... ix CHAPTER 1. INTRODUCTION .................................................................................... 1 1.1. Background of Wittig rearrangements ............................................................ 1 1.2. First examples of Wittig rearrangements......................................................... 2 1.3. The [2,3]-Wittig rearrangement ...................................................................... 2 1.4. The [1,2]-Wittig rearrangement ...................................................................... 7 1.5. The [1,4]-Wittig rearrangement .................................................................... 14 1.6. Control of regioselectivity during Wittig rearrangements .............................. 17 REFERENCES ............................................................................................ 24 CHAPTER 2. THE [1,2]- AND [1,4]-WITTIG REARRANGEMENTS OF 2-SILYL-7-ARYL-2,5,6,7-TETRAHYDROOXEPINS ................................................. 30 2.1. Introduction ................................................................................................. 30 2.2. Expected products of [1,2]- and [1,4]-Wittig rearrangements of 2-silyl-7-aryl-2,5,6,7- tetrahydrooxepins ...................................................... 31 2.3. Synthesis of 2-silyl-7-aryl-2,5,6,7-tetrahydrooxepins .................................... 31 2.4. Wittig rearrangements of 2-trimethylsilyl-2,5,6,7-tetrahydro-7-aryl-oxepins ......................................... 32 2.5. Conclusion ................................................................................................... 34 2.6. Experimental section .................................................................................... 34 REFERENCES ............................................................................................ 66 APPENDIX ................................................................................................. 68 CHAPTER 3. SILYLCYCLOPROPANES BY SELECTIVE [1,4]-WITTIG REARRANGEMENT OF 4-SILYL-5,6-DIHYDROPYRANS ................................... 155 3.1. Introduction ............................................................................................... 155 3.2. Synthesis of 4-silyl-5,6-dihydro-2H-pyrans ................................................ 157 3.3. Optimization of reaction conditions for Wittig rearrangement .................... 158 3.4. Wittig rearrangements of 4-silyl-5,6-dihydro-2H-pyrans with alkyl substituents at the migrating carbon ............................................................ 158 3.5. Wittig rearrangements of 4-silyl-5,6-dihydro-2H-pyrans with alkyl substituents at the migrating carbon ............................................................ 160 3.6. Rearrangement of substrates bearing electron-deficient aryl groups and 2-naphthyl derivative ................................................................................. 161 3.7. Comparative studies on Wittig rearrangements of dihydropyrans ............... 163 3.8. Proposed mechanism of the [1,4]-Wittig rearrangement of 4-silyl-6-aryl(alkyl)-5,6-dihydroprans ........................................................ 163 3.9. Conclusion ................................................................................................. 164 3.10. Experimental section .................................................................................. 165 REFERENCES .......................................................................................... 240 APPENDIX ............................................................................................... 245 vii CHAPTER 4. A [1,2]-WITTIG / m-CPBA TRIGGERED [1,2]-CARBON-TO-CARBON SILYL MIGRATION APPROACH TO α-SILYL-β-HYDROXY CYCLOPENTANONES AND CYCLOHEXANONES ..... 342 4.1. Introduction ............................................................................................... 342 4.2. Synthesis of 2-silyl-6-aryl-5,6-dihydro-2H-pyrans ..................................... 343 4.3. Wittig rearrangements of 2-silyl-6-aryl-5,6-dihydro-2H-pyrans.................. 344 4.4. The [1,2]-carbon-to-carbon silyl migration in cyclic system triggered by epoxidation ................................................................................................ 346 4.5. Proposed reaction mechanism for the silyl migration.................................. 348 4.6. Conclusion ................................................................................................. 350 4.7. Experimental section .................................................................................. 350 REFERENCES .......................................................................................... 413 APPENDIX ............................................................................................... 418 CHAPTER 5. SERENDIPITOUS [1,2]-CARBON-TO-CARBON SILYL MIGRATION IN α-HYRDOXY ALLYL SILANES: ACCESS TO α-SILYL ALKANALS ................................................................................................. 601 5.1. Introduction ............................................................................................... 601 5.2. Serendipitous [1,2]-carbon-to-carbon silyl migration .................................. 602 5.3. Substrate scope for [1,2]-carbon-to-carbon silyl migration .......................... 607 5.4. Proposed reaction mechanism of the [1,2]-carbon-to-carbon silyl migration ................................................................................................... 609 5.5. Attempted mechanistic investigation of the [1,2]-carbon-to-carbon silyl migration ................................................................................................... 609 5.6. Unexpected SN2-like reaction between the O-silylated 2-phenylprop-2-en-1-ol and butyl lithiums .................................................. 611 5.7. Conclusion ................................................................................................. 612 5.8. Experimental section .................................................................................. 613 REFERENCES .......................................................................................... 635 APPENDIX ............................................................................................... 640 CHAPTER 6. FUTURE WORK.................................................................................. 696 6.1. Future work on Wittig rearrangements ....................................................... 696 6.2. Future work on silyl migration ................................................................... 697 viii LIST OF SYMBOLS AND ABBREVIATIONS APCI atmospheric-pressure chemical ionization Ar aromatic BF3•OEt2 boron trifluoride diethyl ether Bn benzyl Bz benzoyl CI chemical ionization d doublet DBU 1,8-diazabicycloundec-7-ene DCM dichloromethane DMAP 4-diaminopyridine DMF N,N-dimethylformamide DMP Dess-Martin periodinane DMSO Dimethyl sulfoxide dr Diastereomeric ratio ee enantiomeric excess EI electron ionization ESI electrospray ionization Et3N triethylamine Et2O diethyl ether EtOAc ethyl acetate equiv equivalents g gram(s) GC/MS gas chromatography / mass spectrometry ix h hour(s) HPLC high pressure liquid chromatography HRMS high resolution mass spectrometry Hz hertz i-Pr isopropyl IR infrared J NMR coupling constant m multiplet m-CPBA 3-chloroperbenzoic acid min minute mg milligram mL milliliter mp melting point MHz megahertz M molar Me methyl MeO methoxy m/z mass to charge ratio n-BuLi n-butyllithium n-Pr n-propyl NaOH sodium hydroxide NMR Nuclear Magnetic Resonance NOE nuclear Overhauser effect x Ph phenyl q quartet RCM ring-closing metathesis s singlet sat saturated sec-BuLi sec-butyllithium SiEt3 triethylsilyl SiMe2Ph phenyldimethylsilyl SiPh2Me diphenylmethylsilyl SN2 bimolecular nucleophilic substitution rt room temperature t triplet t-BuLi tert-butyllithium t-BuONa sodium tert-butoxide TBAF tetrabutylammonium fluoride TBDPS tert-butyldiphenylsilyl TBS t-butyldimethylsilyl THF tetrahydrofuran TLC thin layer chromatography TMS trimethylsilyl TMSCl trimethylsilylchloride TMSOTf trimethylsilyl trifluoromethane sulfonate xi CHAPTER 1. INTRODUCTION 1.1. Background of Wittig rearrangements Wittig rearrangements entail restructuring of bonds of carbanionic ethers (usually allylic or benzylic) leading to structural isomers. The products resulting from Wittig rearrangements are of interest since they possess functional groups which can further be exploited during organic synthesis. Multiple rearrangements are possible depending on the substrate’s nature (Scheme 1.1). Scheme 1.1: Wittig rearrangements with proposed reaction mechanisms 1 1.2. First examples of Wittig rearrangements The very first example of a [1,2]-alkyl shift was reported by Schorigin in 1924.1 Schorigin conducted further experiments on this unusual rearrangement and reported the findings a year later.2 Treatment of 1-(benzyloxy)-4-methylbenzene (1.6) with sodium at 100 °C led to the formation of phenyl(p-tolyl)methanol (1.7) (Scheme 1.2a). Later on in 1942, Wittig and Löhmann reported [1,2]- alkyl shifts of benzyl ethers to the corresponding alcohols triggered by deprotonation at the benzylic position.2 An example from their work was the rearrangement of (oxybis(methylene))dibenzene (1.8) to 1,2-diphenylethan-1-ol (1.9) on treatment with phenyllithium (Scheme 1.2b). This discovery led to what is currently known as Wittig rearrangements. Scheme 1.2: First examples of [1,2]-Wittig rearrangements 1.3. The [2,3]-Wittig rearrangement Of all the Wittig rearrangements, the [2,3]-Wittig has received the most attention from both synthetic and mechanistic standpoint. As the products of this rearrangement are homoallylic alcohols, the [2,3]-Wittig ranks highly among the known techniques for the synthesis of these alcohols in a stereoselective fashion.4-7 The first [2,3]-Wittig rearrangement was reported by Wittig in 19498 where the rearrangement of allyl fluorenyl ether (1.10) led to the formation of 9-allyl-9H- 2 fluoren-9-ol (1.11) (Scheme 1.3). Scheme 1.3: The [2,3]-Wittig rearrangement of 9-(allyloxy)-9H-fluorene At first, the reaction mechanism of the formation of alcohol 1.11 was not clear since the above reaction could proceed by either [1,2]- or [2,3]-Wittig rearrangement. In 1960, Cast and Stevens subjected allyl fluorenyl ether 1.12 with a methyl group at carbon 1′ to Wittig rearrangement conditions leading to alcohol 1.13 (Scheme 1.4).9 This was the first unambiguous scenario of [2,3]-shift that could be distinguished from the [1,2]-Wittig rearrangement. Scheme 1.4: Wittig rearrangement of 9-(but-3-en-2-yloxy)-9H-fluorene 1.3.1. Mechanism and stereochemistry of the [2,3]-Wittig rearrangement In most cases, [2,3]-Wittig rearrangements are carried out on allylic ether substrates that bear groups such as alkenes, aryl and alkynes that serve the purpose of stabilizing carbanions. Also used to stabilize the carbanion involved in this rearrangement are electron-deficient amides and esters. For example, a model substrate 1.13, proceeds by initial metalation of the substrate leading to intermediate stabilized carbanion 1.14 (Scheme 1.5). This carbanion then undergoes [2,3]-Wittig rearrangement in a concerted fashion through an envelope-like five-membered transition state 1.15 3 resulting in the formation of the homoallylic alkoxide 1.16. The homoallylic alcohol product 1.17 is formed after the resulting alkoxide 1.16 is protonated during aqueous workup.10 Scheme 1.5: Proposed mechanism of the [2,3]-Wittig rearrangement Most [2,3]-Wittig rearrangements are stereoselective, that is, they result in the formation of one alkene stereoisomer.4 This is attributed to the concerted mechanism shown in Scheme 5. For example, Wittig rearrangement of model substrate 1.18 leads to the formation of E-alkene 1.20 through transition state 1.19 where 1,3-diaxial interactions are minimized (Scheme 1.6a). Occasionally selectivity towards the Z-alkenes is observed when interactions between R and R′ become significant in transition state 1.19. In these cases, the low energy route yields Z-alkene products 1.22 via the transition state 1.21 (Scheme 1.6b). The G-group in transition states 1.19 and 1.21 prefers an equatorial orientation, hence, chirality transfer is usually quite effective. As a result, optically active substrates such as 1.18 are converted to corresponding homoallylic alcohols 1.20 and 1.22 without losing optical purity. 4 Scheme 1.6: Chirality transfer and alkene stereochemistry in [2,3]-Wittig rearrangement For internal alkenes, model allyl ethers 1.23 and 1.26 undergo diastereoselective [2,3]- Wittig rearrangement to the corresponding homoallylic alcohols 1.25 and 1.28 respectively when G = aryl, alkenyl or alkynyl (Scheme 1.7a, b).10,11 However, switching the carbanion stabilizing group to a carbonyl-containing electron withdrawing groups such as an amide or an ester (G = CONR2 (1.29) or G = COOR (1.32)) reverses the stereoselectivity (Scheme 1.7c, d). The [2,3]- Wittig rearrangements of 1.29 and 1.32 proceed via transition states 1.30 and 1.33 leading to homoallylic alcohols 1.31 and 1.34 respectively. The pseudoaxial orientation of the carbonyls in transition states 1.30 and 1.33 lead to the stabilization of the developing negative charge at C3.10 5 Scheme 1.7: [2,3]-Wittig transition state models for reactions of internal alkene substrates 1.3.2. Selected application of the [2,3]-Wittig rearrangements As mentioned earlier, the [2,3]-Wittig rearrangement is the most utilized Wittig rearrangement from a synthetic perspective. Recent examples of this rearrangement include, but are not limited to, diastereoselective rearrangement of N-allyl ammonium ylides (Scheme 1.8a).12 This is an example of the aza-Wittig rearrangement since the ethereal oxygen has been replaced by nitrogen. Use of organocatalysts to control stereochemical outcomes of [2,3]-Wittig rearrangement has also been reported recently. For instance, Kanger et al. developed a formal asymmetric [2,3]- Wittig rearrangement using Cinchona-derived amine organocatalyst α-branched ketones (Scheme 1.8b).13 6 Scheme 1.8: Recent report on [2,3]-Wittig rearrangement TBD = 1,5,7-triazabicyclo[4.4.0]dec-5-ene. p-NBA = para-Nitrobenzoic acid 1.4. The [1,2]-Wittig rearrangement The [1,2]-Wittig rearrangement is a sigmatropic shift resulting from benzyl or allyl carbanions, leading to the formation of allyl alcohol or homoallylic alcohol depending on the site of deprotonation (Scheme 1). It was the first type of Wittig rearrangement to be reported in the literature (Scheme 1.2).1-3 The [1,2]-Wittig rearrangement's synthetic utility is usually constrained by the need for harsh reaction conditions employing strong bases that are at times not compatible with some functional groups present. Additionally, intramolecular elimination processes tend to compete with [1,2]-Wittig resulting in low yields. Despite this, construction of complex molecules in a stereoselective fashion has been achieved recently via [1,2]-Wittig rearrangements of specific classes of ethers. 1.4.1. Mechanism of the [1,2]-Wittig rearrangement To carry out reactions that are expected to trigger [1,2]-Wittig rearrangements, it is important to understand the mechanism that leads to this rearrangement. This is helpful in designing 7 substrates that would eliminate or suppress other Wittig rearrangements in favor of the [1,2] shift. After its discovery, three different mechanistic pathways were proposed for the [1,2]-Wittig rearrangement (Scheme 1.9). Scheme 1.9: Proposed pathways for the [1,2]-Wittig rearrangement reaction mechanisms 1.4.1.1. The concerted mechanism (Scheme 1.9, route a) The rearrangement of carbanion 1.40 (resulting from deprotonation of 1.39) to form benzylic alkoxide 1.43 was proposed to undergo a concerted mechanism by Hauser and Kantor. 14 They argued for an intramolecular isomerization involving the 1,2-shift of an alkyl group presumably without its bonding pair of electrons to directly produce alkoxide 1.43 (Scheme 1.9, route a). The concerted mechanism was thought to be the pathway until Woodward and Hoffman developed orbital symmetry rules,15 which implied that such [1,2]-antarafacial migration was not possible geometrically. Furthermore, Fukui’s frontier orbital theory16,17 ruled out the first mechanism since if it were to occur this way then there would be inversion of stereochemistry at the migrating carbon center (Scheme 1.10a), which would not be in agreement with the results from the experiments carried out by Schöllkopf on optically active ethers. The [1,2]-Wittig rearrangements resulting from these ethers showed stereochemical retention of high degree at the migrating carbon center (Scheme 1.10b).18-20 Recent studies by Mori and Maleczka on optically 8 active dihydropyrans also showed excellent retention of stereochemistry during the [1,2]-Wittig rearrangement (Scheme 1.10c, d).21,22 Scheme 1.10: Geometrically impossible [1,2]-antarafacial migration and retention of stereochemistry 1.4.1.2. Stepwise mechanism via carbanion and carbonyl intermediates (Scheme 9, b) Following the above observation, a stepwise mechanism (Scheme 1.9, route b) involving elimination leading to a carbanion and carbonyl intermediate 1.41 was proposed. This carbanion then attacks the newly formed carbonyl 1.41 leading to the alkoxide 1.43.18,19,23 This agreed with the observed stereochemichal retention during the rearrangement. The isolation of p-nitrotoluene by Holmes when p-nitrobenzyl ethers underwent rearrangement was also considered as evidence to support this mechanism (Scheme 1.11a).24 Recently, Sanz and Faza et al. have shown evidence 9 supporting the ionic character of [1,2]-Wittig rearrangement.25 Scheme 1.11: Evidence for stepwise mechanism via carbanion and carbonyl intermediates However, there was a drawback to this mechanism (Scheme 1.9, route b). It was observed that tertiary alkyl groups migrated easily followed by secondary then primary ones, hence, ruling out stepwise mechanism involving heterolytic cleavage.26 Furthermore, significant β-hydride elimination was observed during [1,2]-Wittig rearrangements of benzyl alkyl ethers with primary alkyl groups containing protons α to the migrating carbon (Scheme 1.12).3, 26-28 Scheme 1.12: β-hydride elimination during [1,2]-Wittig rearrangements of benzyl butyl ethers 10 1.4.1.3. Stepwise mechanism via radical / radical anion intermediates (Scheme 9, route c) The above trend suggested presence of radicals as intermediates during the migration. Therefore, Lansbury, Pattison, Sidler and Bieber proposed a stepwise mechanism where following deprotonation, homolytic cleavage of the C–O bond occurs. The carbon radical and the carbon- centered radical anion recombine. The driving force here is the transfer of the formal negative charge from carbon to the electronegative oxygen atom (Scheme 1.9, route c).26 In favor of the homolytic cleavage stepwise mechanism (Scheme 1.9, route c) and against the heterolytic cleavage stepwise mechanism (Scheme 1.9, route b) was the following observation: 1-(Benzyloxy)adamantane (1.65) was found to undergo [1,2]-Wittig rearrangement to form adamantan-1-yl(phenyl)methanol (1.64) but 1-(benzyloxy)norbonane (1.66) did not (Scheme 1.13).26, 29 This follows from the reasoning that the 1-norbornyl radical bears more strain and is thus less stable than the 1-adamantyl radical,30 and the opposite is true for the corresponding anions.31 This was in agreement with the stepwise mechanism involving radical / radical anion intermediates. Scheme 1.13: Radical versus anion stability with respect to [1,2]-Wittig rearrangement 1.4.2. Rationale behind Retention of Stereochemistry after [1,2]-Wittig Rearrangement The stereochemistry retention during [1,2]-Wittig rearrangement18-20 (Scheme 1.10) suggests that the radical /radical anion pair recombines at a rate that is faster than rate of 11 racemization of that center. This has been explained as being due to the Wittig rearrangement occurring within a “solvent cage”. Radical clock experiments have been used to gather evidence for a fleeting life of the migrating radical species: The cyclopropylmethyl group in ((cyclopropylmethoxy)methyl)benzene (1.68) experienced negligible isomerization after [1,2]- Wittig rearrangement (Scheme 1.14a).23 From this observation it can be inferred that the recombination between the radical and radical anion is faster than 9.4  107 s-1, which is the time it takes for the cyclopropyl ring to open.32 Further rationalization involves inverse approach experiments: The expected [1,2]-Wittig rearrangement product 1.72 was exclusively formed from the rearrangement of ((hex-5-en-1-yloxy)methylene)dibenzene (1.71). Isomerization of the 5- hexenyl radical to form product 1.73 was not observed (Scheme 1.14b).33,34 This is in agreement with the faster rate of rearrangement and, hence, the reason behind observed retention of stereochemistry. Scheme 1.14: Radical clock experiment during [1,2]-Wittig rearrangements 1.4.3. Representative applications of [1,2]-Wittig rearrangements in total synthesis Unlike the [2,3]-Wittig rearrangement, the requirements to tune substrates in order to stabilize the radical of the migrating fragments has made the application of the [1,2]-Wittig 12 rearrangement limited.35 Furthermore, generating an -carbanionic ether by use of strong bases that do not always tolerate the functional groups that may be present has also limited the use of the [1,2]- Wittig rearrangement in total synthesis. However, Nakai took advantage of the chirality present in carbohydrates to develop a stereocontrolled acetal systems [1,2]-Wittig rearrangement.36-38 He further utilized this technology37 in one of the steps towards the total synthesis of zaragozic acid A (1.76) (Scheme 1.15).38 Scheme 1.15: Application of [1,2]-Wittig rearrangement to total synthesis of zaragozic acid A Garson et al. reported the isolation and total synthesis of (−)-(5R,6Z)-dendrolasin-5-acetate in five steps.39-42 The key step employed involved a [1,2]-Wittig rearrangement of geranyl 3- furylmethyl ether (1.77) to produce alcohol 1.78, followed by acetylation and resolution to obtain target molecule 1.79 (Scheme 1.16). 13 Scheme 1.16: Application of [1,2]-Wittig rearrangement to total synthesis of dendrolasin-5-acetate Recently, Ho and Li developed a practical method to functionalize γ‐benzyloxy vinylogous urethanes into γ‐benzyl butenolides through tandem [1,2]‐Wittig rearrangement/lactonization. As a proof of concept, they applied this development in the total synthesis of maculalactone A, planchol C and γ‐lycorane (Scheme 1.17).43 Scheme 1.17: Application of [1,2]-Wittig rearrangement to total synthesis of Maculalactone A, Planchol C and γ‐Lycorane 1.5. The [1,4]-Wittig rearrangement Transformations via [1,4]-Wittig rearrangement are rare due to the competing [1,2]-Wittig (Scheme 1.1). First reported by Falkin and Tambute in 1969, 44 the [1,4]-Wittig rearrangement results in the formation of enolate which is transformed into carbonyl after protonation. The enolate 14 can also be trapped by various electrophiles. 1.5.1. Mechanism of the [1,4]-Wittig rearrangement There are two different proposed mechanistic pathways for the [1,4]-Wittig rearrangement: An orbital symmetry allowed concerted pathway (Scheme 1.18, route a) or a stepwise mechanism like the [1,2]- case involving radical / radical anion intermediates (Scheme 1.18, route b). Scheme 1.18: Proposed mechanistic pathways for [1,4]-Wittig rearrangement Experimental evidence in support of both approaches have been reported in the literature.21,22,45 In addition, a DFT study carried out recently by Joshi et al. on dihydrofuran systems indicated that the reaction followed a stepwise mechanism during the [1,4]-Wittig rearrangement.22 1.5.2. Application of [1,4]-Wittig rearrangement The [1,4]-Wittig rearrangement has been observed during [1,2]-Wittig rearrangements.37,46- 48 Although the bases used to initiate Wittig rearrangements play a role in the selectivity between [1,2]- and [1,4]-Wittig rearrangements, the cause of the reaction is highly substrate-dependent. Generally, low temperatures tend to favor [1,4]-Wittig. There have been recent reports on high- yielding reactions that proceed via the [1,4]-Wittig rearrangement. Extensive studies on the [1,4]- Wittig rearrangement have been conducted by the Maleczka group. A highly selective [1,4]-Wittig rearrangement of α-benzyloxyallylsilane (1.89) has been reported by Onyeozili and 15 Maleczka (Scheme 1.19a).48 The enolate product 1.90 from this rearrangement could be trapped with various electrophiles leading to acylsilanes 1.91 substituted at the α-position. In 2015, Maleczka and Mori were able to tune the dihydropyrans in favor of either [1,2]- or [1,4]-Wittig rearrangement. For instance, the [1,2]-Wittig rearrangement was achieved when they employed electron-deficient aromatic groups and/or small groups on silicon. The compliment was also true (Scheme 19b).21 Surprisingly, when the silyl group was moved to form 4-silyl-6- aryl/alkyldihydropyrans, [1,4]-Wittig rearrangement was to the corresponding silylcyclopropane acetaldehydes predominated (Scheme 1.19c),49 (Chapter 3). Scheme 1.19: Selective [1,4]-Wittig rearrangement examples from Maleczka group In 2015, Xu reported that chalcone-derived allylic ethers 1.97 undergo [1,4]-Wittig rearrangement resulting in the formation of benzyl ketones 1.98, which are disubstituted at the β- position (Scheme 1.20a).50 Not surprisingly, the [1,4]-Wittig rearrangement of optically active (R,E)-(3-(benzyloxy)prop-1-ene-1,3-diyl)dibenzene (1.99) led to racemic 1,3,4-triphenylbutan-1- 16 one (1.100). This could be attributed to the change of hybridization to sp2 at the stereogenic carbon during the reaction (Scheme 1.20b). Scheme 1.20: [1,4]-Wittig rearrangement of (E)-(3-(benzyloxy)prop-1-ene-1,3-diyl)dibenzenes 1.6. Control of regioselectivity during Wittig rearrangements As illustrated in scheme 1.1 and throughout the previous discussion, the [1,2]-Wittig rearrangements tend to compete with [2,3]-Wittig, whereas the [1,4]-Wittig competes with the [1,2]-Wittig. For instance, Rautenstrauch observed [2,3]-, [1,2]-, [1,4]- and [3,4]-Wittig rearrangements when 3-methyl-1-((3-methylbut-2-en-1-yl)oxy)but-2-ene (1.101) was treated with a base, leading to formation of products 1.102, 1.103, 1.104 and 1.105 respectively (Scheme 1.21).51 17 Scheme 1.21: All possible Wittig rearrangements 1.6.1. Control of regioselectivity via metal/lithium exchange For ethers that are substituted unsymmetrically, regioselective Wittig rearrangement becomes a challenge. The ability to generate the anion can be controlled by installing a displaceable group M at either the  or ’ positions. This group can then be displaced to generate an anion, which will determine the type of Wittig rearrangement the substrate will undergo, overcoming the regioselectivity challenge (Scheme 1.22). Scheme 1.22: Control of regioselectivity via group M-directed carbanion generation The above idea led to the discovery of what is currently known as the Wittig-Still 18 rearrangement (Scheme 1.23a).52 The M-group in this case is tributyl tin. The tin-lithium exchange generates unstable carbanions, which can then isomerize via Wittig rearrangements.53 The Wittig- Still rearrangement is a powerful synthetic tool54 that has been applied widely in the total synthesis of natural product,55-59 however, toxicity of organotin60-62 led to a search for approaches involving non-toxic materials. Mulzer and List’s pioneer work on use of silicon in place of tin (Scheme 1.23b)63 motivated Maleczka and Geng to carry out regioselective Wittig rearrangement of - alkoxy silanes via silicon/lithium exchange (Scheme 1.23c).64 Scheme 1.23: Examples involving silicon-lithium exchange / Wittig rearrangements The absence of groups that could stabilize the resulting anion in Mulzer’s examples enabled efficient Si/Li exchange and subsequent Wittig rearrangement. In prior work by the Maleczka group, however, the trimethylsilyl group’s carbanion-stabilizing effect together with phenyl and olefin groups present in these molecules caused competition between deprotonation / rearrangement 19 and Si/Li exchange. Replacement of tin with silicon solved the toxicity problem. However, use of strong bases limits the substrate scope due to incompatibility of these bases with many functional groups. To solve this problem, the generation of carbanions by use of fluoride anions has been studied by Nakai,35 Reetz65 and Maleczka.66 The resulting carbanions then undergo Wittig rearrangements. In this case silyl groups are thought to be carbanion masks. Displacement of these groups generates carbanions, which then undergo Wittig rearrangements (Scheme 1.24). Scheme 1.24: Fluoride-promoted Wittig rearrangements 1.6.2. Control of regioselectivity via EWG-directed deprotonation Another way of controlling the regioselectivity of unsymmetrically substituted ethers is by modifying the pKa of the protons at the  and ’ position. This in turn determines the deprotonation 20 site and therefore the possible Wittig rearrangements. For instance, placing an EWG group at the  (or ′) position can act as an anion stabilizing group and therefore make deprotonation and Wittig rearrangement regioselective (Scheme 25). Groups such as phenyl, alkynes, carbonyls (esters, amides, ketones, aldehydes), sulfonyl, silyl, and cyano can act to stabilize the anion and are therefore good substituents (EWG) at promoting Wittig rearrangements.67,68 Scheme 1.25: Control of regioselectivity via group EWG-directed deprotonation Of particular interest are the silyl groups since they have the ability to delocalize the negative charge of adjacent carbanions through silicon’s d orbitals and, thereby stabilizing the charge.69,70 Even though this ability has been attributed to hyperconjugation,71,72 the silyl group makes the -proton more acidic by reducing the conjugated acid’s pKa. Therefore, the presence of silicon in a molecule can change the regioselective outcome of the Wittig rearrangement. For example, silicon-free bisallylic ethers were found to undergo selective deprotonation at the less substituted ′ position (Scheme 1.26a),31 however, selective deprotonation at the  position occurred after introduction of the silyl group at the  position. This was followed by Wittig 21 rearrangement (most substituted position) (Scheme 1.26b).52 In this case, vinyl trialkylsilyl group was used as the G-group. The Wittig rearrangements of 6-aryl-4-silyl-5,6-dihydro-(2H)-pyrans has also been studied. The vinyl silyl group led to exclusive deprotonation at the allylic position. The resulting carbanions underwent [1,2]- and [1,4]-Wittig rearrangements. Surprisingly, the major products isolated were mostly the result of [1,4]-Wittig rearrangement (Scheme 1.26c).49 Scheme 1.26: Silicon-directed deprotonation at the allylic position With regard to the earlier observation on competitive deprotonation vs Li/Si exchange (Scheme 1.19a),62 placing the silane group at the ’ position resulted in exclusive deprotonation and avoided the Si/Li exchange as reported by Maleczka and Onyeozili. 48 The α- benzyloxyallylsilanes were able to undergo [1,4]-Wittig rearrangement in a very efficient manner. The resulting enolate intermediates were trapped with various electrophiles. This provided a new 22 synthetic approach to substituted acylsilanes (Scheme 19a).48 Cyclic versions of the above have also been studied by the Maleczka group.21,49 Wittig rearrangements of diastereomeric 2-silyl-5,6- dihydro-6-aryl-(2H)-pyrans resulted in regiodivergent ring contractions to the corresponding α- silylcyclopentenols and/or (α-cyclopropyl)acylsilanes. The [1,4]-Wittig was found to predominate when the aryl substituent on starting pyrans contained electron donating and/or by sterics emanating from the substituents on silicon. The [1,2]-Wittig was achieved with electron withdrawing groups and smaller silyl groups. Substituting the olefin part of the dihydropyran proximal to the silyl group led to exclusive [1,2]-Wittig rearrangements. Furthermore, the cis and trans diastereomers rearranged in a convergent manner leading to the corresponding α-silylcyclopentenols and cyclopropyl acyl silanes as a single diastereomer (Scheme 19b). Regarding the relative stereochemistry of 2-silyl-6-aryl dihydropyrans, trans diastereomers are more reactive than the cis isomers. Mori hypothesized that these reactivity differences were “presumably because an optimal conformation suitable for allylic deprotonation is easily attainable” in the trans isomer and prevented by sterics in the cis. Mori’s hypothesis is consistent with conformational analysis and the fact that increased sterics about the silyl groups or aryl rings did not change the reactivity of the trans isomers, while the cis cyclic ethers become less reactive. Computational studies recently done by Joshi et al. confirmed this.22 23 REFERENCES (1) Schorigin, P. Über die Carbinol-Umlagerung von Benzyläthern. Ber. Dtsch. Chem. Ges. 1924, 57, 1634. (2) Schorigin, P. Über die Umlagerungen von Benzyläthern. Ber. Dtsch. Chem. Ges. 1925, 58, 2028. (3) Wittig, G.; Löhmann, L. Über die kationotrope Isomerisation gewisser Benzyläther bei Einwirkung von Phenyl-lithium. Liebigs Ann. Chem. 1942, 550, 260. (4) Marshall, J. A. The Wittig Rearrangement. Comprehensive Organic Synthesis 1991, 975. (5) Mikami, K.; Nakai, T. Acyclic stereocontrol via [2,3]-Wittig sigmatropic rearrangement. Synthesis 1991, 594. (6) Nakai, T.; Mikami, K. The [2,3]-Wittig rearrangement. Org. React. 1994, 46, 105. (7) Ahmad, N.M. 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[2,3]-Wittig rearrangements of (trimethylsilyl) methyl allyl ethers. Tetrahedron Lett. 1996, 37, 2403. (64) Maleczka, R. E.; Geng, F. Methyllithium-promoted Wittig rearrangements of α- alkoxysilanes. Org. Lett. 1999, 1, 1115. (65) Reetz, M. T.; Greif, N. Dyotrope Umlagerungen, XIII. Fluoridionen-katalysierte umlagerungen von allyl- und benzyl-(silylmethyl)-ethern. Chem. Ber. 1977, 110, 2958. (66) Maleczka, R. E.; Geng. F. Synthesis and Fluoride-Promoted Wittig Rearrangements of α- Alkoxysilanes. Org. Lett. 1999, 1, 1111. (67) Damrauer, R.; Crowell, A. J.; Craig, C. F. Electron, hydride, and fluoride affinities of silicon-containing species: Computational studies. J. Am. Chem. Soc. 2003, 125, 10759. (68) Chan, T. H.; Wang, D. Silylallyl anions in organic synthesis: A study in regio-and stereoselectivity. Chem. Rev. 1995, 95, 1279. (69) Mikami, K.; Kishi, N.; Nakai, T. Silicon-directed regiocontrol in wittig rearrangements of bis-allyl ethers and allyl propargyl ethers. Chem. Lett. 1989, 18, 1683. (70) Kishi, N.; Maeda, T.; Mikami, K.; Nakai, T. [2,3] Wittig rearrangement-Peterson olefination sequence: a stereocontrolled entry to terminal conjugated trienes. Tetrahedron, 1992, 48, 4087. 28 (71) Schleyer, P. V. R.; Clark, T.; Kos, A. J.; Spitznagel, G. W.; Rohde, C.; Arad, D.; Houk, K. N. Rondan, N. G. Structures and stabilities of α-hetero-substituted organolithium and organosodium compounds. Energetic unimportance of d-orbital effects. J. Am. Chem. Soc. 1984, 106, 6467. (72) Wetzel, D. M.; Brauman, J. I. Quantitative measure of. alpha.-silyl carbanion stabilization. The electron affinity of (trimethylsilyl) methyl radical. J. Am. Chem. Soc. 1988, 110, 8333. 29 CHAPTER 2. THE [1,2]- AND [1,4]-WITTIG REARRANGEMENTS OF 2-SILYL-7-ARYL-2,5,6,7-TETRAHYDROOXEPINS 2.1. Introduction The first reported Wittig rearrangement reaction was the [1,2]-Wittig.1 Despite this fact, the [1,2]-Wittig rearrangement has fewer synthetic applications compared to its [2,3]- counterpart. This is partly attributed to competition observed between the [1,2]- and the [2,3]-Wittig rearrangement. Furthermore, the [1,2]-Wittig rearrangement experiences narrower substrate scope and relatively lower yields restricting its synthetic applicability.2-11 In addition, the [1,4]-Wittig rearrangement, which was first observed by Felkin and Tambute in 1969 also competes with the [1,2]-Wittig rearrangement.7, 12-14 In 2015, Mori and Maleczka reported that diastereomeric 2-silyl-5,6-dihydro-6-aryl-(2H)- pyrans undergo stereoconvergent [1,2]- and/or [1,4]-Wittig rearrangements to afford α- silylcyclopentenols and/or (α-cyclopropyl)acylsilanes respectively (Scheme 1.1).15 Although there is usually a competition between the [1,2]- and [1,4]-Wittig pathways, they have shown that the isomerization can be selective towards the [1,2]- or [1,4]-Wittig rearrangements. For instance, the [1,2]-Wittig pathway predominated with electron-deficient aryl groups and smaller alkyl/aryl substituents on silicon. The opposite was true for the [1,4]-Wittig rearrangement. Furthermore, cis and trans dihydropyrans exhibited different reactivities, but converged to single diastereomeric Wittig products (Scheme 2.1). The [1,2]- and [1,4]-Wittig rearrangements are proposed to follow stepwise mechanism. This proposal has been supported by recent computational studies. 16 30 Scheme 2.1: [1,2]- and [1,4]-Wittig rearrangements of 2‑silyl-6-aryl-5,6-dihydropyrans15 2.2. Expected products of [1,2]- and [1,4]-Wittig rearrangements of 2-silyl-7-aryl-2,5,6,7-tetrahydrooxepins From the above results, we hypothesized that increasing the ring size of the starting material from 2‑silyl-6-aryl-5,6-dihydropyrans to 2-silyl-7-aryl-2,5,6,7-tetrahydrooxepins would enable access to 1-silyl-6-arylcyclohex-2-en-1-ols and/or (α-cyclobutyl)acylsilanes via [1,2]- and/or [1,4]- Wittig rearrangement (Scheme 2.2). To the best of our knowledge, the ring contraction of tetrahydrooxepins by Wittig rearrangements has not been previously reported. Scheme 2.2: Proposed [1,2]- and [1,4]-Wittig rearrangements of 2-silyl-7-aryl-2,5,6,7-tetrahydrooxepins 2.3. Synthesis of 2-silyl-7-aryl-2,5,6,7-tetrahydrooxepins To test the above hypothesis, we first synthesized the starting material by homoallylation of benzaldehydes followed by conversion of the resulting alcohols 2.1 to trichloroacetimidates 2.2. The trichloroacetimidates were then coupled with 1-(trimethylsilyl)prop-2-en-1-ol in the presence of catalytic amount of a Lewis acid (BF3•OEt2 or TMSOTf) to form diastereomeric dienes 2.3. The assignment of relative stereochemistry of these dienes was done after the ring closing metathesis by Grubbs 2nd generation catalyst. In some instances, the diastereomeric dienes were separable by column chromatography. In these cases, the dienes were subjected to ring closing metathesis as 31 single diastereomers. In cases where the diastereomeric dienes 2.3 were subjected to ring closing metathesis as a mixture of diastereomers (syn:anti), the resulting diastereomers of 2-silyl-2,5,6,7- tetrahydro-7-aryl-oxepins (2.4) were separable by column chromatography and their relative stereochemistry assigned by 1H NMR NOESY experiments (Scheme 2.3). Typically, the anti dienes underwent ring closing metathesis to the corresponding cis oxepins whereas the syn dienes led to trans oxepins. Scheme 2.3: Synthesis of cis/trans -silyl-2,5,6,7-tetrahydro-7-aryl-oxepins 2.4. Wittig rearrangements of 2-trimethylsilyl-2,5,6,7-tetrahydro-7-aryl-oxepins With the starting materials at hand, we subjected them to Wittig rearrangement conditions. Exposure of (trans)-2-trimethylsilyl-2,5,6,7-tetrahydro-7-aryl-oxepins (2.4) to n-butyllithium led to formation of compounds 2.5, 2.6, and 2.7 in varying yields (Table 1). 32 Table 2.1a: Wittig rearrangement of 2-trimethylsilyl-2,5,6,7-tetrahydro-7-aryl-oxepins Entry Substrate Ar % dr % dr % (2.5) (2.5) (2.6) (2.6) (2.7) 1 2.4a C6H5 25 5:1 n.d - 51 2 2.4b 4-Cl-C6H4 72 5:1 n.d - 22 3 trans-2.4c 4-OMe-C6H4 13 1.5:1 3 2:1 58 4 cis-2.4cb 4-OMe-C6H4 24 12:1 16 1:1 n.dc 5 2.4d 2-Naph 48 4:1 26 1:1 n.dd a Diastereomeric ratio determined by 1H NMR spectroscopy of the crude reaction mixture. The relative stereochemistry was determined by 1D and 2D NMR NOESY analysis. bReaction performed with sec-butyllithium (3.0 equiv.) at –10 °C for 5 hours then quenched with deuterium oxide. n.d = not detected. c48% of ortho deuterated starting material recovered. dApproximately 10% of desilylated cyclohexanone 2.8c was formed instead (see experimental section) Unlike the dihydropyrans, the cis diastereomers were resistant to rearrangement even after employing the conditions successfully used earlier on their cis dihydropyrans counterpart, that is, sec-butyllithium at –78 °C for 3 hours.1 Increasing the temperature to –10 °C led to Wittig rearrangement in case of cis-2.4c (see experimental section). Compound 2.7 was formed as a resultant of deprotonated trans-tetrahydrooxepins reluctance to rearrange. Subjecting compound 33 2.7 to butyllithium results in the formation of 2-arylcyclohexanone 2.8 with a concomitant loss of the silyl group (See experimental section). 2.5. Conclusion In summary, we report the first ring contraction of 2-trimethylsilyl-2,5,6,7-tetrahydro-7- aryl-oxepins by Wittig rearrangements, which proceeds with modest diastereoselectivities via [1,2]- and [1,4]-Wittig pathways to produce silyl cyclohexenols and cyclobutyl acyl silanes, respectively. An unexpected product resulting from alkene migration was also observed. Treatment of this unexpected product with butyllithium did not yield Wittig rearrangement products but resulted in the formation of 2-arylcyclohexan-1-one with a loss of the silyl group. Finally, unlike the cis dihydropyrans, the cis oxepins could only undergo rearrangement after increasing the reaction temperature. 2.6. Experimental section 2.6.1. General Information Unless otherwise noted, all reactions were run under a positive atmosphere of nitrogen in oven-dried or flame-dried round-bottomed flasks or conical vials or disposable drum vials capped with rubber septa. Solvents were removed by rotary evaporation under reduced pressure at temperatures lower than 45 ºC. Column chromatography was run on 230–400 mesh silica gel. Tetrahydrofuran and diethyl ether were distilled from sodium-benzophenone ketyl; dichloromethane, benzene, trimethylsilyl chloride were distilled from calcium hydride. Trimethylsilyltrifluoromethane sulfonate (TMSOTf) was redistilled and stored under nitrogen at – 10 °C before the reaction. tert-butyllithium (1.7 M in pentane) and BF3.OEt2 were used as received. n-Butyllithum (2.5 M in hexanes) and sec-butyllithium (1.4 M in cyclohexane) were purchased from Aldrich and their concentration calculated by titration with diphenylacetic acid (average of 34 three runs). 1H NMR spectra was collected in 500 MHz Varian instruments using CDCl3 as solvent, which was referenced at 7.26 ppm (residual chloroform proton) and 13C NMR spectra was collected in CDCl3 at 126 MHz and referenced at 77.0 ppm. High-resolution mass spectrometric analysis was run in TOF instruments. 2.6.2. Preparation of 1-arylpent-4-en-1-ols (2.1a – 2.1c) – general procedure A To a 250 mL 3-neck round-bottomed flask fitted with a magnetic stir bar was weighed 2.2 g of magnesium powder (90 mmol, 3.0 equiv.) and 2 crystals of iodine. The side necks of the flask were sealed by two rubber septa and a reflux condenser attached to the middle neck then purged with nitrogen. An oil bath was placed underneath the flask. This was followed by addition of 60 mL dry THF and the resulting brown suspension was vigorously stirred. Homoallylic bromide (7.6 mL, 10.13 g, 75 mmol, 2.5 equiv.) was then added slowly. After complete addition of the bromide, the temperature of the oil bath had risen to 40 °C. The mixture was then further heated on an oil bath to 80 °C (reflux) for 1 hour. The oil bath was removed, and the mixture was allowed to cool down to room temperature. The mixture was cooled down further to 0 °C by placing an ice bath underneath the flask. This was followed by dropwise addition of appropriate aryl aldehyde (30 mmol, 1.0 equiv.) as a solution in 20 mL dry THF. The resulting mixture was stirred at 0 °C to room temperature over a period of 2 hours. The mixture was then cooled to 0 °C and quenched by slow addition of 20 mL saturated aqueous ammonium chloride solution. The mixture was diluted with 40 mL of diethyl ether and 20 mL of saturated aqueous ammonium chloride solution. The 35 resulting mixture was transferred into a 1000 mL separating funnel and the layers were separated. The aqueous layer was extracted with diethyl ether (50 mL x 3). The combined organic layers were washed with saturated aqueous ammonium chloride solution (50 mL), water (50 mL x 2) and brine (50 mL) respectively and then dried over anhydrous magnesium sulfate. This was followed by filtration and the filtrate was concentrated on the rotorvap under reduced pressure affording 1- arylpent-4-en-1-ol 2.1 which was used in the next step without need for further purification. 2.6.3. Preparation of trichloroacetimidates 2.2 – general procedure B Following our reported procedure with a slight modification, 1 to a dry 250 mL round- bottomed flask fitted with a magnetic stir bar and sealed with a rubber septum was added 60 mL of dry dichloromethane under nitrogen. The desired 1-arylpent-4-en-1-ol 2.1 (20 mmol, 1.00 equiv) in dichloromethane (20 mL) was then transferred into the flask. This was followed by addition of 0.54 mL of 1,8-Diazabicyclo(5.4.0)undec-7-ene (DBU) (0.55 g, 3.6 mmol, 0.18 equiv.). After stirring for 5 minutes, the solution was cooled to 0 °C on an ice bath. This was followed by dropwise addition of 2.8 mL of tricchloroacetonitrile (4.04 g, 28 mmol, 1.40 equiv.). After 12 hours, the resulting dark brown mixture was filtered through a plug of silica (5 cm thick) to remove the dark residue. The filtrate was concentrated, and the crude mixture subjected to column chromatography (EtOAc/hexanes) to afford the desired trichloroacetimidate 2.2. 36 2.6.4. Alternative preparation of trichloroacetimidates 2.2 – general procedure C15 Following our reported procedure,15 240 mg of sodium hydride 60% w/w dispersion in mineral oil (6 mmol, 0.18 equiv) was weighed into a dry 100 mL round-bottomed flask fitted with a magnetic stir bar and 20 mL of freshly distilled diethyl ether was added into the flask. The flask was sealed with a rubber septum and purged with nitrogen. The resulting grey suspension was cooled on an ice bath and the desired 1-arylpent-4-en-1-ol 2.1 (30 mmol, 1.00 equiv) in dry diethyl ether (20 mL) was then transferred into the flask slowly resulting in a fizzy reaction. The mixture was stirred at 0 °C for 10 minutes. This was followed by dropwise addition of 4.2 mL of trichloroacetonitrile (6.06 g, 42 mmol, 1.40 equiv.). The mixture turned dark brown after complete addition of the trichloroacetonitrile. The mixture was stirred at 0 °C for 20 minutes and then the ice bath was removed, and the mixture stirred at room temperature for 1 hour. The diethyl ether was then removed by rotorvap and methanol (0.25 mL, 6.0 mmol, 0.18 equiv.) in 15 mL pentane was added to the crude mixture. The mixture was further diluted with 40 mL pentane and filtered through a plug of celite (5 cm thick). The filtrate was concentrated, and the crude mixture subjected to column chromatography (EtOAc/hexanes) to afford the desired trichloroacetimidate 2.2. 37 2.6.5. Preparation of diastereomeric dienes 2.3 – general procedure D15 A dry 250 mL round-bottomed flask with a magnetic stir bar was sealed with a rubber septum and purged with nitrogen. A solution of 1-(trimethylsilyl)prop-2-en-1-ol (10 mmol, 1 equiv) in 20 mL hexanes was transferred into the flask followed by a solution of the corresponding trichloroacetimidate 2.2 (15 mmol, 1.5 equiv.) in 20 mL hexanes. Additional 40 mL of hexanes was then added into the flask and the resulting mixture was cooled on ice bath to 0 °C while stirring. To the cold solution was added appropriate Lewis acid: BF3•OEt2 (0.12 mL, 1 mmol, 0.1 equiv.) or TMSOTf (0.18 mL, 1 mmol, 0.1 equiv.). After complete addition, a thick precipitate was formed. The mixture was stirred at 0 °C to room temperature for 6 hours and filtered through a plug of celite (5 cm thick) and the filtrate was transferred into a separating funnel. The filtrate was then washed with saturated solution of aqueous sodium bicarbonate (50 mL x 3), water (50 mL x 2) and brine (50 mL) respectively. The organic layer was dried over anhydrous sodium sulfate and then filtered. The filtrate was concentrated under reduced pressure to afford diene 2.3 as a mixture of diastereomers. The resulting crude reaction mixture was purified by column chromatography (dichloromethane/hexanes). It is important to note that some diastereomers were separable by column chromatography and hence only one of them (syn) was taken to the next step (RCM). The diastereomers that could not be separated by column chromatography were taken to the next step as a mixture. The stereochemistry of these diastereomers were determined after the RCM reaction: syn diastereomers underwent RCM to form cis dihydropyrans or tetrahyrooxepins and vice versa. 38 It is also worth noting that for most of the compounds reported herein, the syn diastereomer exhibited lower Rf value than its anti counterpart (dichloromethane/hexanes). 2.6.6. Preparation of tetrahydrooxepins 2.4 via ring closing metathesis (RCM) – general procedure E15 To a dry 250 mL round-bottomed flask with a magnetic stir bar was weighed 170 mg of Grubbs catalyst 2nd generation (0.2 mmol, 0.04 equiv.) and the flask was sealed with a rubber septum and purged with nitrogen. This was followed by addition of 80 mL of dry dichloromethane and corresponding diene 2.3 (5 mmol, 1.0 equiv) as a solution in 20 mL dry dichloromethane as a single diastereomer (syn) or as a mixture of diastereomers (syn:anti = 1:1). The resulting mixture was stirred at room temperature for 12 hours. The mixture was concentrated under reduced pressure to afford tetrahydrooxepins 2.4. The resulting crude reaction mixture was purified by column chromatography (dichloromethane/hexanes). The cis and trans diastereomers were separable by column chromatography. The stereochemistry of these diastereomers were determined by 1D NOESY experiment and confirmed with X-ray crystallography (trans-2.4d). It is also worth noting that for most of the compounds reported here the trans diastereomer has lower Rf value than its cis counterpart (dichloromethane/hexanes). 39 Synthesis of 1-phenylpent-4-en-1-ol (2.1a) Applying general procedure A to magnesium powder (2.9 g, 120 mmol, 1.2 equiv), homoallylic bromide (12.2 mL, 120 mmol, 1.2 equiv), benzaldehyde (9.65 mL, 100 mmol, 1.0 equiv), and THF (200 mL) afforded 15.8 g, 97.4 mmol (97% isolated yield) of compound 2.1a as a yellow oil after column chromatography, Rf = 0.5 (20% ethyl acetate in hexanes): 1H NMR (500 MHz, CDCl3) δ 7.39 – 7.32 (m, 4H), 7.29 (dtd, J = 7.0, 5.7, 2.5 Hz, 1H), 5.85 (ddt, J = 16.9, 10.2, 6.6 Hz, 1H), 5.05 (dq, J = 17.1, 1.7 Hz, 1H), 5.00 (ddt, J = 10.2, 2.2, 1.3 Hz, 1H), 4.68 (dd, J = 7.7, 5.5 Hz, 1H), 2.24 – 2.01 (m, 3H), 1.90 (dddd, J = 13.7, 8.8, 7.7, 6.0 Hz, 1H), 1.80 (dddd, J = 13.6, 9.2, 6.4, 5.5 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 144.6, 138.1, 128.4, 127.5, 125.9, 114.9, 73.9, 38.0, 30.0. IR (FTIR, film, cm-1) 3389, 2935, 1640, 1451, 909, 800. 2.1a is a known compound and spectroscopic data are in agreement with those reported in literature.17 Synthesis of 1-(4-chlorophenyl)pent-4-en-1-ol (2.1b) Following general procedure A, magnesium powder (2.9 g, 120 mmol, 1.2 equiv), 4- bromobut-1-ene (12.2 mL, 120 mmol, 1.2 equiv), 4-chlorobenzaldehyde (14.6 g, 100 mmol, 1.0 40 equiv.) and THF (220 mL) afforded 18.81 g, 95.6 mmol (96% isolated yield) of 1-(4- chlorophenyl)pent-4-en-1-ol 2.1b as a yellow oil after column chromatography, Rf = 0.4 (20% ethyl acetate in hexanes). 1H-NMR (500 MHz, CDCl3)  = 7.31 (d, J = 8.5 Hz, 2H), 7.26 (d, J = 8.5 Hz, 2H), 5.82 (ddt, J = 16.9, 10.2, 6.6 Hz, 1H), 5.03 (dq, J = 17.1, 1.7 Hz, 1H), 4.99 (dq, J = 10.2, 1.4 Hz, 1H), 4.66 (dd, J = 7.7, 5.5 Hz, 1H), 2.19 – 2.01 (m, 3H), 1.90 – 1.81 (m, 1H), 1.75 (dddd, J = 13.9, 9.0, 6.5, 5.5 Hz, 1H). 13 C NMR (126 MHz, CDCl3)  = 143.0, 137.9, 133.1, 128.5, 127.2, 115.2, 73.3, 38.0, 29.9. IR (FTIR, film, cm-1) ṽ = 3326, 2935, 1640, 1491, 1090, 1012, 911, 828. 2.1b is a known compound and spectroscopic data are in agreement with those reported in literature.17 Synthesis of 1-(4-methoxyphenyl)pent-4-en-1-ol (2.1c) Following general procedure A, magnesium powder (2.2 g, 90 mmol, 3.0 equiv), 4- bromobut-1-ene (7.6 mL, 75 mmol, 2.5 equiv), 3.65 mL of p-anisaldehyde (4.08 g, 30 mmol, 1.0 equiv.) and THF (120 mL) afforded 7.35 g, 38 mmol (quantitative crude yield) of 1-(4- methoxyphenyl)pent-4-en-1-ol 2.1c as a yellow oil in THF. The product was taken to the next step without further purification. 1H-NMR (500 MHz, CDCl3, ppm)  = 7.26 (d, J = 8.5 Hz, 2H), 6.88 (d, J = 8.7 Hz, 2H), 5.84 (ddt, J = 16.9, 10.2, 6.6 Hz, 1H), 5.03 (dq, J = 17.1, 1.7 Hz, 1H), 4.98 (ddt, J = 10.2, 2.2, 1.3 Hz, 1H), 4.63 (dd, J = 7.5, 5.8 Hz, 1H), 3.80 (s, 3H), 2.19 – 2.01 (m, 3H), 1.89 13 (dddd, J = 13.7, 8.9, 7.5, 6.1 Hz, 1H), 1.77 (ddt, J = 13.6, 9.3, 6.1 Hz, 1H). C{1H}-NMR (126 41 MHz, CDCl3, ppm)  = 159.0, 138.2, 136.7, 127.1, 114.8, 113.8, 73.5, 55.2, 37.9, 30.1. 2.1c is a known compound and spectroscopic data are in agreement with those reported in literature.18 Synthesis of 1-(naphthalen-2-yl)pent-4-en-1-ol (2.1d) Following general procedure A, magnesium powder (2.33 g, 96 mmol, 1.2 equiv), 4- bromobut-1-ene (9.8 mL, 96 mmol, 1.2 equiv), 2-naphthaldehyde (12.96 g, 80 mmol, 1.0 equiv.) and THF (150 mL) afforded 16.8 g, 79 mmol (99% crude yield) of 1-(naphthalen-2-yl)pent-4-en- 1-ol 2.2d as a yellow oil in THF. The product was taken to the next step without further purification. 1 H-NMR (500 MHz, CDCl3)  = 7.88 – 7.81 (m, 3H), 7.78 (s, 1H), 7.48 (qd, J = 5.2, 4.2, 2.6 Hz, 3H), 5.87 (ddt, J = 16.9, 10.1, 6.6 Hz, 1H), 5.06 (dq, J = 17.1, 1.7 Hz, 1H), 5.01 (dq, J = 10.2, 1.5 Hz, 1H), 4.91 – 4.82 (m, 1H), 2.26 – 2.04 (m, 3H), 2.04 – 1.95 (m, 1H), 1.90 (ddt, J = 13.5, 9.1, 6.0 Hz, 1H). 13C NMR (126 MHz, CDCl3)  = 141.9, 138.1, 133.2, 132.9, 128.3, 127.9, 127.7, 126.1, 125.8, 124.6, 124.0, 115.0, 74.1, 37.9, 30.0. IR (FTIR, film, cm -1) ṽ = 3324, 3055, 2919, 1638, 1507, 1270, 1017, 817, 745. 2.2d is a known compound and spectroscopic data are in agreement with those reported in literature.18 42 Synthesis of 1-phenylpent-4-en-1-yl 2,2,2-trichloroacetimidate (2.2a) Applying general procedure B to 1-phenylpent-4-en-1-ol 2.1a (15.74 g, 97 mmol, 1 equiv), DBU (2.6 mL, 17.5 mmol, 0.18 equiv), and trichloroacetonitrile (13.6 mL, 135.8 mmol, 1.4 equiv), in CH2Cl2 (180 mL) afforded 27.5 g, 89.7 mmol (92% crude yield) of compound 2.2a as a yellow liquid. 1H NMR (500 MHz, CDCl3) δ 8.26 (s, 1H), 7.43 – 7.39 (m, 2H), 7.39 – 7.33 (m, 2H), 7.33 – 7.28 (m, 1H), 5.90 – 5.78 (m, 2H), 5.06 (dq, J = 17.2, 1.6 Hz, 1H), 5.02 (dt, J = 10.1, 1.6 Hz, 1H), 2.30 – 2.12 (m, 3H), 2.00 – 1.89 (m, 1H). 13C NMR (126 MHz, CDCl3) δ 161.5, 140.2, 137.4, 128.4, 127.9, 126.1, 115.5, 91.7, 80.1, 36.1, 29.6. IR (FTIR, film, cm-1) 3341, 3065, 2943, 1661, 1284, 1071, 792. Synthesis of 1-(4-chlorophenyl)pent-4-en-1-yl 2,2,2-trichloroacetimidate (2.2b) Following general procedure B, 1-(4-chlorophenyl)pent-4-en-1-ol 2.1b (15.74 g, 80 mmol, 1.0 equiv), DBU (2.2 mL, 14.4 mmol, 0.18 equiv), trichloroacetonitrile (11.2 mL, 112 mmol, 1.4 equiv.) and dichloromethane (200 mL), 27.6 g, 80.9 mmol (>99% isolated yield) of 1-(4- chlorophenyl)pent-4-en-1-yl 2,2,2-trichloroacetimidate 2.2b was obtained as a yellow oil after column chromatography, Rf = 0.4 (10% EtOAc in hexanes). 1H NMR (500 MHz, CDCl3)  = 8.27 43 (s, 1H), 7.33 (s, 4H), 5.88 – 5.76 (m, 2H), 5.09 – 4.98 (m, 2H), 2.28 – 2.08 (m, 3H), 1.96 – 1.85 (m, 1H). 13 C NMR (126 MHz, CDCl3)  = 161.4, 138.7, 137.1, 133.7, 128.6, 127.6, 115.7, 91.5, 79.3, 36.0, 29.5. IR (FTIR, film, cm-1) ṽ = 3340, 2943, 1662, 1282, 1069, 791. HRMS (ESI), m/z [M– Cl3CONH]+ calcd for C11H12Cl: 179.0628; found: 179.0603. Synthesis of 1-(4-methoxyphenyl)pent-4-en-1-yl 2,2,2-trichloroacetimidate (2.2c) Following general procedure C, 1-(4-methoxyphenyl)pent-4-en-1-ol 2.1c (5.77 g, 30 mmol, 1.0 equiv), NaH 60% w/w dispersion in mineral oil (240 mg, 6 mmol, 0.20 equiv), trichloroacetonitrile (4.2 mL, 42 mmol, 1.4 equiv.) and diethyl ether (15 mL), 10.67 g, 31.7 mmol (quantitative crude yield) of 1-(4-methoxyphenyl)pent-4-en-1-yl 2,2,2-trichloroacetimidate 2.2c which was used in the next step without further purification. 1H NMR (500 MHz, CDCl3)  = 8.25 (s, 1H), 7.34 (d, J = 8.6 Hz, 2H), 6.90 (d, J = 8.8 Hz, 2H), 5.91 – 5.76 (m, 2H), 5.09 – 4.99 (m, 2H), 3.81 (s, 3H), 2.28 – 2.12 (m, 3H), 1.97 – 1.86 (m, 1H). 13C NMR (126 MHz, CDCl3)  = 161.5, 159.3, 137.5, 127.6, 115.4, 113.8, 91.8, 80.0, 55.2, 36.0, 29.7. IR (FTIR, cm -1) ṽ = 3362, 3239, 3177, 1690, 1609, 1381, 1108, 829 MS (GC/MS): m/z (%) = 175 (100) [M – Cl3CCONH]+, 121 (80). HRMS (ESI), m/z [M + H]+ calcd for C14H17Cl3NO2: 336.0325; found: 336.0333. 44 Synthesis of 1-(naphthalen-2-yl)pent-4-en-1-yl 2,2,2-trichloroacetimidate (2.2d) Following general procedure B, 1-(naphthalen-2-yl)pent-4-en-1-ol 2.1d (14.86 g, 70 mmol, 1.0 equiv), DBU (1.89 mL, 12.6 mmol, 0.18 equiv), trichloroacetonitrile (9.83 mL, 98 mmol, 1.4 equiv.) and dichloromethane (200 mL), 25.89 g, 72.58 mmol (quantitative crude yield) of 1- (naphthalen-2-yl)pent-4-en-1-yl 2,2,2-trichloroacetimidate 2.2d was obtained as a dark brown oil in dichloromethane. The product was used in the next step without further purification. 1H NMR (500 MHz, CDCl3, ppm)  = 8.30 (s, 1H), 7.96 – 7.80 (m, 4H), 7.56 (dd, J = 8.5, 1.8 Hz, 1H), 7.50 (qt, J = 7.2, 3.9 Hz, 2H), 6.03 (dd, J = 7.9, 5.0 Hz, 1H), 5.89 (ddt, J = 16.4, 10.0, 6.2 Hz, 1H), 5.14 – 5.00 (m, 2H), 2.36 – 2.19 (m, 3H), 2.05 (tdd, J = 10.9, 7.4, 3.9 Hz, 1H). 13 C NMR (126 MHz, CDCl3, ppm)  = 161.5, 137.5, 137.3, 133.1, 128.3, 128.0, 127.7, 126.2, 126.0, 125.4, 123.9, 115.5, 91.7, 80.2, 36.0, 29.7. IR (FTIR, cm-1) ṽ = 3337, 3057, 2941, 1661, 1284, 1071, 986, 791 MS (GC/MS): m/z (%) = 355 (0.1) [M+], 301 (15), 184 (70), 156 (45), 141 (100), 115 (48). HRMS (ESI), m/z [M + H]+ calcd for C17H17Cl3NO: 356.0376; found: 356.0370. 45 Synthesis of syn/anti-(1-((1-phenylpent-4-en-1-yl)oxy)allyl)trimethylsilane (syn/anti-2.3a) Applying general procedure D to 1-(trimethylsilyl)prop-2-en-1-ol (5.2 g, 40 mmol, 1.0 equiv), trichloroacetimidate 2.2a (17.7 g, 60 mmol, 1.5 equiv), and boron trifluoro diethyl etherate (0.5 mL, 4.0 mmol, 0.1 equiv) in hexane (200 mL) afforded after column chromatography (5% CH2Cl2 in hexanes) a total of 8.04 g, 29.3 mmol (73% isolated yield) of syn/anti-2.3a (1:1) as a colorless oil. Compounds syn-2.3a and anti-2.3a were partially separable by column chromatography. Spectroscopic data for syn-2.3a: 1H NMR (500 MHz, CDCl3) δ 7.36 – 7.30 (m, 4H), 7.25 (ddd, J = 8.7, 5.0, 3.8 Hz, 1H), 5.82 (ddt, J = 16.9, 10.2, 6.6 Hz, 1H), 5.67 (ddd, J = 17.4, 10.6, 7.1 Hz, 1H), 5.00 (dq, J = 17.2, 1.7 Hz, 1H), 4.98 – 4.89 (m, 2H), 4.83 (dt, J = 10.6, 1.8 Hz, 1H), 4.36 (t, J = 6.0 Hz, 1H), 3.78 (dt, J = 7.2, 1.5 Hz, 1H), 2.09 – 1.97 (m, 2H), 1.88 (ddt, J = 12.8, 9.3, 6.2 Hz, 1H), 1.80 – 1.71 (m, 1H), 0.09 (s, 9H). 13 C NMR (126 MHz, CDCl3, ppm) δ 143.9, 138.7, 138.0, 127.9, 126.8, 126.6, 114.4, 111.7, 80.9, 75.7, 36.2, 29.3, -3.7. Spectroscopic data for anti-2.3a: 1H NMR (500 MHz, CDCl3) δ 7.37 – 7.32 (m, 3H), 7.30 – 7.26 (m, 2H), 5.85 (ddt, J = 16.9, 10.3, 6.6 Hz, 1H), 5.77 (ddd, J = 17.4, 10.6, 7.7 Hz, 1H), 5.11 – 5.03 (m, 2H), 5.01 – 4.94 (m, 2H), 4.43 (dd, J = 8.2, 5.3 Hz, 1H), 3.43 (dt, J = 7.7, 1.3 Hz, 1H), 2.21 (dddt, J = 10.2, 5.1, 2.2, 1.2 Hz, 1H), 2.08 (dddd, J = 16.4, 8.3, 4.9, 2.0 Hz, 1H), 1.93 – 1.85 46 (m, 1H), 1.68 (dddd, J = 13.6, 9.6, 6.1, 5.3 Hz, 1H), 0.00 (s, 9H). 13C NMR (126 MHz, CDCl3, ppm) δ 143.0, 138.8, 137.8, 128.4, 128.1, 127.3, 114.3, 113.0, 78.8, 72.9, 37.7, 30.3, -4.0. Synthesis of syn/anti-(1-((1-(4-chlorophenyl)pent-4-en-1-yl)oxy)allyl)trimethylsilane (syn/anti-2.3b) Compound 2.3b was prepared following general procedure D, a solution of 2- (trimethylsilyl)prop-2-en-1-ol (3.91 g, 30 mmol, 1 equiv.) and 1-(4-chlorophenyl)pent-4-en-1-yl 2,2,2-trichloroacetimidate 2.2b (15.35 g, 45 mmol, 1.5 equiv.), BF3•OEt2 (0.37 mL, 3.0 mmol, 0.1 equiv.) and hexanes (165 mL) for 12 hours followed by workup, concentration and column chromatography, Rf for anti-2.3b = 0.6 and Rf for syn-2.3b = 0.4 (2% DCM in hexanes) afforded a total of 5.40 g, 17.5 mmol (58% isolated yield) partially separable mixture of diastereomers of compound 2.3 as colorless liquid. Spectroscopic data for syn-2.3b: 1H NMR (500 MHz, CDCl3)  = 7.27 (d, J = 8.5 Hz, 2H), 7.22 (d, J = 8.5 Hz, 2H), 5.78 (ddt, J = 16.9, 10.2, 6.6 Hz, 1H), 5.62 (ddd, J = 17.6, 10.5, 7.2 Hz, 1H), 5.01 – 4.92 (m, 2H), 4.88 (dt, J = 17.2, 1.8 Hz, 1H), 4.82 (dt, J = 10.5, 1.6 Hz, 1H), 4.31 (t, J = 6.1 Hz, 1H), 3.74 (dt, J = 7.3, 1.5 Hz, 1H), 2.06 – 1.94 (m, 2H), 1.83 (ddt, J = 13.6, 9.6, 6.0 Hz, 1H), 1.70 (ddt, J = 13.7, 9.6, 6.1 Hz, 1H), 0.06 (s, 9H). 13C NMR (126 MHz, CDCl3)  = 142.5, 138.4, 137.8, 132.4, 128.1, 127.9, 114.6, 111.9, 80.3, 76.1, 36.1, 29.2, -3.8. IR (FTIR, cm-1) ṽ = 47 3078, 2954, 2926, 1640, 1627, 1490, 1246, 839. MS (GC/MS): m/z (%) = 179 (17.5) [M – C6H13OSi]+, 125 (100). Spectroscopic data for anti-2.3b: 1H NMR (500 MHz, CDCl3, ppm)  = 7.30 (d, J = 8.4 Hz, 2H), 7.18 (d, J = 8.3 Hz, 2H), 5.85 – 5.78 (m, 1H), 5.78 – 5.70 (m, 1H), 5.06 – 4.98 (m, 2H), 4.98 – 4.92 (m, 2H), 4.39 (dd, J = 8.1, 5.4 Hz, 1H), 3.37 (dt, J = 7.8, 1.3 Hz, 1H), 2.22 – 2.12 (m, 1H), 2.09 – 2.00 (m, 1H), 1.90 – 1.79 (m, 2H), 1.63 (ddt, J = 13.5, 9.5, 5.8 Hz, 1H), -0.01 (s, 9H). 13C NMR (126 MHz, CDCl3, ppm)  = 141.5, 138.5, 137.5, 128.6, 128.3, 127.2, 114.5, 113.2, 78.1, 73.1, 37.6, 30.1, -4.0. IR (FTIR, cm-1) ṽ = 3105, 2949, 1641, 1592, 1490, 1089, 1013, 822. HRMS (APCI), m/z [M + H]+ calcd for C17H26ClOSi: 309.1441; found: 309.1428. Synthesis of syn/anti-(1-((1-(4-methoxyphenyl)pent-4-en-1-yl)oxy)allyl)trimethylsilane (syn/anti-2.3c) Compound 2.3c was prepared following general procedure D with slight modification to minimize formation of the side product as a result of elimination. A solution of 1- (trimethylsilyl)prop-2-en-1-ol (1.95 g, 15 mmol, 1 equiv.) and 1-(4-methoxyphenyl)pent-4-en-1-yl 2,2,2-trichloroacetimidate 2.2c (5.05 g, 15 mmol, 1 equiv.) in dichloromethane (120 mL) was cooled to −78 °C. TMSOTf (0.27 mL, 1.5 mmol, 0.1 equiv.) was added dropwise and the mixture stirred at –78 °C for 6 hours. The rubber septum was removed, and 7 g of sodium bicarbonate was 48 poured into the flask. The dry ice-acetone bath was removed, and the mixture was allowed to warm up to room temperature. The mixture was filtered and concentrated under reduced pressure to remove dichloromethane. Hexanes was then added to the resulting mixture resulting in the formation of white precipitate. Subsequent filtration and concentration furnished a residue which was purified by column chromatography, Rf for anti-2.3c = 0.5 and Rf for syn-2.3c = 0.3 (10% DCM in hexanes) to afford a total of 3.02 g, 9.9 mmol (66% isolated yield) partially separable mixture of diastereomers of compound 2.3c (syn:anti = 1:1) as colorless liquid. Spectroscopic data for syn-2.3c: 1H NMR (500 MHz, CDCl3, ppm)  = 7.21 (d, J = 8.5 Hz, 2H), 6.84 (d, J = 8.6 Hz, 2H), 5.80 (ddt, J = 16.8, 10.2, 6.5 Hz, 1H), 5.65 (ddd, J = 17.4, 10.5, 7.0 Hz, 1H), 4.98 (dq, J = 17.2, 1.7 Hz, 1H), 4.96 – 4.87 (m, 2H), 4.81 (ddd, J = 10.6, 2.1, 1.5 Hz, 1H), 4.28 (t, J = 6.2 Hz, 1H), 3.80 (s, 3H), 3.74 (dt, J = 7.1, 1.6 Hz, 1H), 2.05 – 1.96 (m, 2H), 1.91 – 1.81 (m, 1H), 1.76 – 1.66 (m, 1H), 0.06 (s, 9H). 13C NMR (126 MHz, CDCl3)  = 158.5, 138.7, 138.1, 136.0, 127.7, 114.3, 113.2, 111.4, 80.6, 75.5, 55.2, 36.2, 29.4, -3.7. HRMS (ESI), m/z [M – H]- calcd for C18H27O2Si: 303.1780; found: 303.1789. Spectroscopic data for anti-2.3c: 1H NMR (500 MHz, CDCl3)  = 7.17 (d, J = 8.7 Hz, 2H), 6.87 (d, J = 8.6 Hz, 2H), 5.84 (ddt, J = 16.9, 10.2, 6.5 Hz, 1H), 5.75 (ddd, J = 17.2, 10.5, 7.6 Hz, 1H), 5.06 – 4.91 (m, 4H), 4.36 (dd, J = 8.0, 5.5 Hz, 1H), 3.82 (s, 3H), 3.41 (dt, J = 7.6, 1.4 Hz, 1H), 2.23 – 2.13 (m, 1H), 2.10 – 2.00 (m, 1H), 1.88 (dddd, J = 13.5, 9.3, 8.0, 5.6 Hz, 1H), 1.65 (ddt, J = 13.5, 9.6, 5.8 Hz, 1H), -0.02 (s, 9H). 13C NMR (126 MHz, CDCl3)  = 158.8, 138.8, 137.9, 135.0, 128.4, 114.3, 113.5, 112.8, 78.3, 72.5, 55.2, 37.7, 30.3, -4.0. HRMS (APCI), m/z [M + H]+ calcd for C18H29O2Si: 305.1937; found: 305.1928. 49 Synthesis of syn/anti-trimethyl(1-((1-(naphthalen-2-yl)pent-4-en-1-yl)oxy)allyl)silane (syn/anti-2.3d) Compound 2.3d was prepared following general procedure D, a solution of 1- (trimethylsilyl)prop-2-en-1-ol (1.30 g, 10 mmol, 1 equiv.) and 1-(naphthalen-2-yl)pent-4-en-1-yl 2,2,2-trichloroacetimidate 2.2d (5.36 g, 15 mmol, 1.5 equiv.), BF3•OEt2 (0.13 mL, 1.0 mmol, 0.1 equiv.) and hexanes (80 mL) for 12 hour followed by workup, concentration and column chromatography, Rf for anti/syn-2.3d = 0.5 (10% DCM in hexanes) afforded a total of 2.19 g, 6.8 mmol (68% isolated yield) partially separable mixture of diastereomers of compound 2.3d as colorless liquid. Spectroscopic data for syn/anti-2.3d: 1H NMR (500 MHz, CDCl3)  = 7.89 – 7.80 (m, 6H), 7.75 (s, 1H), 7.70 (s, 1H), 7.54 – 7.45 (m, 6H), 5.93 – 5.78 (m, 3H), 5.69 (ddd, J = 17.5, 10.5, 7.1 Hz, 1H), 5.10 (ddd, J = 10.6, 2.0, 1.2 Hz, 1H), 5.08 – 4.93 (m, 6H), 4.82 (ddd, J = 10.6, 2.1, 1.5 Hz, 1H), 4.62 (dd, J = 8.0, 5.5 Hz, 1H), 4.54 (t, J = 6.1 Hz, 1H), 3.86 (dt, J = 7.1, 1.5 Hz, 1H), 3.49 (dt, J = 7.6, 1.4 Hz, 1H), 2.30 – 2.20 (m, 1H), 2.17 – 2.06 (m, 3H), 2.06 – 1.95 (m, 2H), 1.90 – 1.82 (m, 1H), 1.79 (ddt, J = 11.6, 9.6, 3.8 Hz, 1H), 0.13 (s, 9H), 0.04 (s, 9H). 13C NMR (126 MHz, CDCl3)  = 141.4, 140.4, 138.7, 138.0, 137.8, 133.1, 133.0, 132.8, 128.1, 127.9, 127.8, 127.7, 127.6, 126.4, 125.9, 125.8, 125.6, 125.4, 125.3, 125.1, 124.9, 114.5, 114.4, 113.0, 111.7, 81.2, 79.0, 76.0, 72.9, 50 37.5, 36.2, 30.3, 29.4, -3.7, -4.0. Spectroscopic data for syn-2.3d only: 1H NMR (500 MHz, CDCl3)  = 7.86 – 7.78 (m, 3H), 7.73 (s, 1H), 7.51 – 7.43 (m, 3H), 5.83 (ddt, J = 16.8, 10.1, 6.5 Hz, 1H), 5.67 (ddd, J = 17.4, 10.5, 7.1 Hz, 1H), 5.00 (dq, J = 17.1, 1.7 Hz, 1H), 4.98 – 4.90 (m, 2H), 4.80 (dt, J = 10.6, 1.8 Hz, 1H), 4.52 (t, J = 6.1 Hz, 1H), 3.83 (dt, J = 7.1, 1.5 Hz, 1H), 2.11 – 2.02 (m, 2H), 1.96 (ddt, J = 12.7, 9.1, 6.2 Hz, 1H), 1.83 (ddt, J = 13.4, 9.2, 6.3 Hz, 1H), 0.11 (s, 9H). 13C NMR (126 MHz, CDCl3, ppm)  = 141.4, 138.6, 138.0, 133.1, 132.8, 127.9, 127.63, 127.62, 125.8, 125.4, 125.3, 124.9, 114.5, 111.7, 81.2, 76.0, 36.2, 29.4, -3.7. HRMS (ESI), m/z [M + H]+ calcd for C21H29OSi: 325.1988; found: 325.2025. Synthesis of trans-(7-phenyl-2,5,6,7-tetrahydrooxepin-2-yl)trimethylsilane (trans-2.4a) Applying general procedure E to syn-2.3a (4.1 g, 15 mmol, 1 equiv) and second-generation Grubbs catalyst (127 mg, 0.15 mmol, 0.01 equiv) in CH2Cl2 (200 mL) afforded after column chromatography (40% CH2Cl2 in hexanes) 3.41 g, 13.8 mmol (92% isolated yield) of trans-2.4a as a colorless oil. 1H NMR (500 MHz, CDCl3) δ 7.46 – 7.40 (m, 2H), 7.37 – 7.32 (m, 2H), 7.30 – 7.25 (m, 1H), 5.78 – 5.72 (m, 1H), 5.60 (dt, J = 11.3, 2.8 Hz, 1H), 4.87 (dd, J = 10.9, 4.3 Hz, 1H), 4.04 (dtd, J = 4.5, 3.1, 1.8 Hz, 1H), 2.58 – 2.48 (m, 1H), 2.41 – 2.28 (m, 2H), 2.18 – 2.10 (m, 1H), -0.00 (s, 9H). 13C NMR (126 MHz, CDCl3) δ 142.6, 130.8, 128.6, 128.0, 127.2, 127.0, 80.3, 68.6, 33.6, 26.5, -3.1. 51 Synthesis of cis/trans- (7-(4-chlorophenyl)-2,5,6,7-tetrahydrooxepin-2-yl)trimethylsilane (cis/trans-2.4b) Compound 2.4b was prepared following general procedure E: Grubbs catalyst 2nd generation (191 mg, 0.225 mmol, 0.015 equiv.) and syn/anti-(1-((1-(4-chlorophenyl)pent-4-en-1- yl)oxy)allyl)trimethylsilane, syn:anti = 1:1, 2.4b (4.64 g, 15 mmol, 1 equiv.) and dichloromethane (120 mL) at 40 °C for 12 hours followed by concentration and column chromatography, Rf for cis- 2.4b = 0.7 and Rf for trans-2.4b = 0.4 (20% DCM in hexanes) afforded a total of 3.09 g, 11 mmol (73% isolated yield) fully separable mixture of diastereomers of compound 2.4b as colorless liquid. Spectroscopic data for cis-2.4b: 1H NMR (500 MHz, CDCl3, ppm)  = 7.28 (s, 4H), 5.69 (dddd, J = 11.9, 7.3, 4.7, 2.5 Hz, 1H), 5.54 (dt, J = 11.2, 2.6 Hz, 1H), 4.73 (dd, J = 8.4, 5.4 Hz, 1H), 4.05 (dt, J = 4.4, 3.3 Hz, 1H), 2.62 (dddd, J = 16.2, 8.1, 3.7, 1.4 Hz, 1H), 2.32 (ddt, J = 13.7, 10.5, 5.2 Hz, 1H), 2.02 – 1.93 (m, 1H), 1.83 (ddt, J = 13.6, 8.4, 5.1 Hz, 1H), 0.11 (s, 9H). 13C NMR (126 MHz, CDCl3)  = 143.7, 132.0, 130.6, 128.1, 126.6, 126.1, 80.8, 77.3, 37.4, 23.5, -3.7. IR (FTIR, film, cm-1) ṽ = 3014, 2932, 2780, 1719, 1490, 1246, 1089, 937. MS (GC/MS): m/z (%) = 280 (0.2) [M]+, 245 (0.5), 142 (95), 127 (30), 73 (100). HRMS (ESI), m/z [M – H–]+ calcd for C15H20ClOSi: 279.0972; found: 279.0959. Spectroscopic data for trans-2.4b: 1H NMR (500 MHz, CDCl3)  = 7.35 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.6 Hz, 2H), 5.73 (ddt, J = 10.1, 7.3, 2.4 Hz, 1H), 5.58 (dt, J = 11.2, 2.8 Hz, 1H), 4.82 (dd, J = 11.0, 4.4 Hz, 1H), 3.98 (dtd, J = 4.4, 2.8, 1.6 Hz, 1H), 2.50 (dddt, J = 16.2, 9.3, 4.0, 2.5 Hz, 52 1H), 2.35 – 2.24 (m, 2H), 2.10 (ddt, J = 13.2, 6.5, 2.9 Hz, 1H), -0.01 (s, 9H). 13C NMR (126 MHz, CDCl3)  = 141.2, 132.9, 130.7, 128.5, 128.4, 128.2, 79.6, 68.7, 33.7, 26.4, -3.1. HRMS (ESI), m/z [M + H]+ calcd for C15H22ClOSi: 281.1129; found: 281.1107. Synthesis of cis-(7-(4-methoxyphenyl)-2,5,6,7-tetrahydrooxepin-2-yl)trimethylsilane (cis-2.4c) Compound cis-2.4c was prepared following general procedure E: Grubbs catalyst 2nd generation (119 mg, 0.14 mmol, 0.02 equiv.) and anti-(1-((1-(4-methoxyphenyl)pent-4-en-1- yl)oxy)allyl)trimethylsilane anti-2.3c (2132 mg, 7.0 mmol, 1 equiv.) and benzene (100 mL) at 80 °C for 4 hours followed by concentration and column chromatography, Rf for cis-2.4c = 0.6 (40% DCM in hexanes) afforded a total of 1786 mg, 6.5 mmol (92% isolated yield) of compound cis- 2.4c as a colorless liquid. Spectroscopic data for cis-2.4c: 1H NMR (500 MHz, CDCl3)  = 7.29 (d, J = 8.8 Hz, 2H), 6.88 (d, J = 8.8 Hz, 2H), 5.71 (dddd, J = 11.3, 7.2, 4.7, 2.5 Hz, 1H), 5.56 (ddd, J = 11.2, 3.2, 2.1 Hz, 1H), 4.74 (dd, J = 8.4, 5.3 Hz, 1H), 4.07 (qd, J = 3.3, 1.2 Hz, 1H), 3.81 (s, 3H), 2.72 – 2.60 (m, 1H), 2.33 (ddt, J = 13.7, 10.4, 5.1 Hz, 1H), 2.00 (ddtd, J = 15.3, 7.4, 4.9, 1.2 Hz, 1H), 1.89 (ddt, J = 13.6, 8.4, 5.1 Hz, 1H), 0.13 (s, 9H). 13C NMR (126 MHz, CDCl3)  = 158.2, 137.5, 130.7, 126.3, 126.2, 113.4, 81.2, 77.1, 55.2, 37.4, 23.6, -3.7. HRMS (ESI), m/z [M – OH]+ calcd for C16H23OSi: 259.1518; found: 259.1513. 53 Synthesis of trans-(7-(4-methoxyphenyl)-2,5,6,7-tetrahydrooxepin-2-yl)trimethylsilane (trans-2.4c) Compound trans-2.4c was prepared following general procedure E: Grubbs catalyst 2nd generation (81 mg, 0.095 mmol, 0.02 equiv.) and syn-(1-((1-(4-methoxyphenyl)pent-4-en-1- yl)oxy)allyl)trimethylsilane syn-2.4c (1.45 g, 4.75 mmol, 1 equiv.) and benzene (80 mL) at 80 °C for 2 hours followed by concentration and column chromatography, Rf for trans-2.4c = 0.4 (40% DCM in hexanes) afforded 943 mg, 3.4 mmol (72% isolated yield) of compound trans-2.4c as a colorless liquid. 1H NMR (500 MHz, CDCl3)  = 7.35 (d, J = 8.3 Hz, 2H), 6.88 (d, J = 8.8 Hz, 2H), 5.74 (ddt, J = 13.6, 6.0, 3.8 Hz, 1H), 5.57 (dt, J = 11.1, 2.8 Hz, 1H), 4.84 (dd, J = 11.1, 4.5 Hz, 1H), 3.97 (dtd, J = 4.1, 2.8, 1.4 Hz, 1H), 3.81 (s, 3H), 2.52 (dddq, J = 16.7, 9.3, 5.2, 2.5 Hz, 1H), 2.40 – 2.24 (m, 2H), 2.13 – 2.05 (m, 1H), -0.02 (s, 9H). 13C NMR (126 MHz, CDCl3, ppm)  = 158.8, 134.7, 130.9, 128.7, 128.4, 113.3, 79.8, 67.9, 55.2, 33.4, 26.4, -3.2. IR (FTIR, cm-1) ṽ = 3010, 2952, 1511, 1242, 1032, 825. HRMS (ESI), m/z [M + H]+ calcd for C16H25O2Si: 277.1624; found: 277.1624. 54 Synthesis of trans-trimethyl(7-(naphthalen-2-yl)-2,5,6,7-tetrahydrooxepin-2-yl)silane (trans-2.4d) Compound trans-2.4d was prepared following general procedure E: Grubbs catalyst 2nd generation (76 mg, 0.1 mmol, 0.015 equiv.) and syn-(1-((1-(4-chlorophenyl)pent-4-en-1- yl)oxy)allyl)trimethylsilane, 2.3d (2.12 g, 6 mmol, 1 equiv.) and benzene (80 mL) at 80 °C for 2 hours followed by concentration and column chromatography, Rf for trans-2.4d = 0.5 (30% DCM in hexanes) afforded a total of 1.493 g, 5 mmol (84% isolated yield) of trans-2.4d as a light yellow crystalline solid (mp 30–32 °C). The crystal structure of compound trans-2.4d was solved by X- ray crystallography and the results deposited to the Cambridge Crystallographic Data Centre and assigned CCDC 1902771. 1H NMR (500 MHz, CDCl3)  = 7.91 – 7.78 (m, 4H), 7.57 (dd, J = 8.5, 1.7 Hz, 1H), 7.52 – 7.44 (m, 2H), 5.78 (ddt, J = 10.3, 6.7, 2.7 Hz, 1H), 5.61 (dt, J = 11.2, 2.8 Hz, 1H), 5.04 (dd, J = 10.9, 4.4 Hz, 1H), 4.05 (td, J = 4.3, 2.7 Hz, 1H), 2.59 (dddq, J = 16.4, 11.7, 4.6, 2.5 Hz, 1H), 2.48 (dtd, J = 13.6, 11.3, 1.8 Hz, 1H), 2.41 – 2.32 (m, 1H), 2.26 (dt, J = 13.8, 4.4 Hz, 1H), 0.00 (s, 9H). 13C NMR (126 MHz, CDCl3, ppm)  = 140.0, 133.0, 132.8, 130.9, 128.6, 128.0, 127.7, 127.6, 126.3, 125.9, 125.7, 124.9, 80.2, 68.6, 33.6, 26.4, -3.1. IR (FTIR, film, cm-1) ṽ = 3052, 2948, 2773, 1600, 1245, 1097, 829. HRMS (ESI), m/z [M + H]+ calcd for C19H25OSi: 297.1675; found: 297.1663. 55 2.6.7. General procedure F: Wittig rearrangement of trans-2-trimethylsilyl-2,5,6,7-tetrahydro-7-aryl-oxepins Following a reported procedure,15 freshly prepared and purified trans-2-trimethylsilyl- 2,5,6,7-tetrahydro-7-aryl-oxepin was dissolved in THF under nitrogen (concentration 0.08 M, unless otherwise noted) and the solution cooled at −78 °C (dry ice/acetone bath), n-butyllithium (1.2 equiv, 1.6 M or 2.5 M in hexanes) was added dropwise (1 drop/s) to give a colored solution. The reaction was quenched after the indicated time (10−30 min) by adding saturated NH4Cl(aq) and diluted with H2O and diethyl ether. The aqueous phase was extracted with diethyl ether three times. Combined organic extracts were washed with saturated NH4Cl(aq), H2O, and brine. The solution was dried over magnesium sulfate, filtered, quickly concentrated in a rotovap at temperatures lower than 45 °C. Column chromatography with EtOAc in hexanes afforded cyclohexenols. Other products including the ones resulting from [1,4]-Wittig rearrangement were also observed (see individual substrate). Synthesis of 2-(trimethylsilyl)-1,2,5,6-tetrahydro-[1,1'-biphenyl]-2-ol (2.5a) and 7-phenyl-4,5,6,7-tetrahydrooxepin-2-yl)trimethylsilane (2.7a) 56 Applying general procedure F to trans-trimethyl(-7- phenyl-2,5,6,7-tetrahydrooxepin-2- yl)silane 2.4a (1.6g, 6.5 mmol, 1.0 equiv), n-butyllithium (2.3 M in hexanes, 3.4 mL, 7.8 mmol, 1.2 equiv), and THF (70mL) afforded after column chromatography (5-10% EtOAc in hexanes) 404 mg, 1.64 mmol (25%) of compound 2.5a and 819 mg, 3.3 mmol (51% isolated yield) of 2.7a as colorless oils. Spectroscopic data for 2.5a: 1H NMR (500 MHz, CDCl3) δ 7.40 – 7.35 (m, 2H), 7.32 – 7.27 (m, 2H), 7.25 – 7.21 (m, 1H), 5.96 (ddd, J = 10.0, 4.8, 2.6 Hz, 1H), 5.88 (dt, J = 10.0, 1.9 Hz, 1H), 2.91 (dd, J = 10.9, 3.0 Hz, 1H), 2.20 (dtdd, J = 18.2, 5.1, 3.5, 1.6 Hz, 1H), 2.16 – 2.06 (m, 1H), 2.00 (dddd, J = 13.0, 10.9, 9.6, 5.4 Hz, 1H), 1.68 (ddt, J = 12.8, 6.3, 3.4 Hz, 1H), 1.30 (s, 1H), -0.11 (s, 9H). 13C NMR (126 MHz, CDCl3) δ 143.8, 130.8, 130.4, 129.3, 128.2, 126.5, 66.2, 47.3, 25.7, 25.3, -3.4. Synthesis of 4'-chloro-2-(trimethylsilyl)-1,2,5,6-tetrahydro-[1,1'-biphenyl]-2-ol (2.5b) and (7-(4-chlorophenyl)-4,5,6,7-tetrahydrooxepin-2-yl)trimethylsilane (2.7b) Applying general procedure F to trans-(7-(4-chlorophenyl)-2,5,6,7-tetrahydrooxepin-2- yl)trimethylsilane trans-2.4b (2.4 g, 8.5 mmol, 1.0 equiv), n-butyllithium (2.5 M in hexanes, 5.6 mL, 6.0 mmol, 1.2 equiv), and THF (100mL) afforded after column chromatography, Rf for 2.7b = 0.7 and Rf for 2.5b = 0.3 (2% EtOAc in hexanes) 667 mg, 2.4 mmol (28% isolated yield) of compound 2.5b and 515.8 mg, 1.84 mmol (21% isolated yield) of 2.7b as colorless oils. Spectroscopic data for 2.5b. 1H NMR (500 MHz, CDCl3, ppm): δ = 7.34 (d, J = 8.5 Hz, 2H), 7.27 57 (d, J = 8.4 Hz, 2H), 5.97 (ddd, J = 10.0, 4.9, 2.6 Hz, 1H), 5.89 (dt, J = 10.0, 2.0 Hz, 1H), 2.87 (dd, J = 11.2, 2.9 Hz, 1H), 2.25 – 2.07 (m, 2H), 1.96 (dddd, J = 13.0, 11.1, 9.8, 5.6 Hz, 1H), 1.64 (ddt, J = 12.6, 6.6, 3.1 Hz, 1H), 1.24 (s, 1H), -0.10 (s, 9H). 13C NMR (126 MHz, CDCl3, ppm): δ = 142.6, 132.2, 130.8, 130.7, 130.5, 128.2, 66.0, 46.7, 25.7, 25.3, -3.4. HRMS (ESI): m/z [M]+ calcd for C15H21ClOSi: 280.1050; found: 280.1015. Spectroscopic data for 2.7b. 1H NMR (500 MHz, CDCl3, ppm): δ = 7.20 (d, J = 8.6 Hz, 2H), 7.10 (d, J = 8.4 Hz, 2H), 5.03 (td, J = 4.0, 1.1 Hz, 1H), 3.28 (tq, J = 6.0, 1.7 Hz, 1H), 2.16 – 2.01 (m, 2H), 1.95 (dddd, J = 12.9, 9.5, 6.1, 3.3 Hz, 1H), 1.62 (dddd, J = 13.3, 10.9, 5.9, 3.0 Hz, 1H), 1.54 – 1.40 (m, 2H), 0.01 (s, 9H). 13C NMR (126 MHz, CDCl3, ppm): δ = 150.2, 142.9, 131.5, 129.7, 128.1, 106.1, 45.4, 32.7, 24.0, 19.2, 0.2. HRMS (ESI): m/z [M + H]+ calcd for C15H22ClOSi: 281.1129; found: 281.1147. Synthesis of 4'-methoxy-2-(trimethylsilyl)-1,2,5,6-tetrahydro-[1,1'-biphenyl]-2-ol (2.5c), 2-(2-(4-methoxyphenyl)cyclobutyl)-1-(trimethylsilyl)ethan-1-one (2.6c) and (7-(4-methoxyphenyl)-4,5,6,7-tetrahydrooxepin-2-yl)trimethylsilane (2.7c) 58 Applying general procedure F to trans-(7-(4-methoxyphenyl)-2,5,6,7-tetrahydrooxepin-2- yl)trimethylsilane trans-2.4c (885 mg, 3.2 mmol, 1.0 equiv), n-butyllithium (2.5 M in hexanes, 5.6 mL, 6.0 mmol, 1.2 equiv), and THF (100mL) afforded after column chromatography, Rf for 2.6c = 0.7, Rf for 2.7c = 0.5 and Rf for 2.5c = 0.3 (5% EtOAc in hexanes) 117 mg, 0.42 mmol (13% isolated yield) of compound 2.5c, 28 mg, 0.1 mmol (3% isolated yield) of 2.6c and 562 mg, 2 mmol, (64% isolated yield) of 2.7c as colorless oils. Spectroscopic data for 2.5c: 1H NMR (500 MHz, CDCl3, ppm): δ = 7.30 (d, J = 8.7 Hz, 2H), 7.27 (d, J = 7.8 Hz, 2H), 6.88 (d, J = 8.7 Hz, 1H), 6.85 (d, J = 8.7 Hz, 2H), 5.95 (dddd, J = 10.0, 4.8, 2.6, 0.7 Hz, 1H), 5.87 (ddd, J = 10.0, 2.3, 1.6 Hz, 1H), 5.84 – 5.79 (m, 1H), 5.69 (ddd, J = 9.9, 2.5, 1.7 Hz, 1H), 3.82 (s, 2H), 3.81 (s, 3H), 2.92 – 2.85 (m, 2H), 2.31 – 2.05 (m, 5H), 2.01 – 1.91 (m, 2H), 1.69 – 1.62 (m, 2H), 1.52 (s, 1H), 1.28 (s, 1H), -0.10 (s, 9H), -0.21 (s, 9H). 13C NMR (126 MHz, CDCl3, ppm): δ = 158.4, 158.2, 135.9, 135.1, 132.8, 130.9, 130.3, 130.2, 129.4, 127.1, 113.54, 113.47, 72.0, 66.3, 55.3, 55.2, 50.3, 46.4, 25.7, 25.52, 250.5, 25.45, -2.4, -3.4. HRMS (ESI): m/z [M + H]+ calcd for C16H25O2Si: 277.1624; found: 277.1623. Spectroscopic data for 2.6c (cis:trans = 1:1): 1H NMR (500 MHz, CDCl3, ppm): δ = 7.14 (d, J = 8.4 Hz, 1H), 7.04 (d, J = 8.4 Hz, 2H), 6.86 – 6.80 (m, 4H), 3.82 – 3.77 (m, 7H), 3.70 (q, J = 8.1 Hz, 1H), 3.20 (dtd, J = 14.6, 7.9, 7.3, 1.4 Hz, 1H), 3.01 (q, J = 8.8 Hz, 1H), 2.87 – 2.71 (m, 2H), 2.51 (dd, J = 17.6, 7.6 Hz, 1H), 2.32 – 2.23 (m, 3H), 2.23 – 2.16 (m, 2H), 2.16 – 2.05 (m, 1H), 1.98 (qd, J = 10.3, 8.6 Hz, 1H), 1.66 – 1.59 (m, 2H), 1.53 (tt, J = 10.3, 8.6 Hz, 1H), 0.13 (s, 9H), 0.00 (s, 9H). 13C NMR (126 MHz, CDCl3, ppm): δ = 248.1, 248.0, 158.0, 157.8, 136.4, 134.0, 128.8, 127.7, 113.7, 113.5, 55.3, 54.8, 50.1, 46.5, 41.6, 38.4, 33.5, 27.4, 25.6, 24.5, 23.5, -3.3, -3.4. IR (FTIR, cm–1): ṽ = 2951, 2938, 2865, 2835, 1639, 1610, 1511, 1244, 1175, 1034, 827. HRMS (ESI): m/z [M + H]+ calcd for C16H25O2Si: 277.1624; found: 277.1625. 59 Spectroscopic data for 2.7c: 1H NMR (500 MHz, CDCl3, ppm): δ = 7.31 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 8.8 Hz, 2H), 5.40 (dd, J = 6.2, 5.1 Hz, 1H), 4.50 (dd, J = 10.9, 2.4 Hz, 1H), 3.81 (s, 3H), 2.36 – 2.19 (m, 2H), 2.17 – 2.08 (m, 1H), 1.96 (dddt, J = 15.5, 11.4, 7.1, 4.2 Hz, 2H), 1.52 (dtt, J = 11.6, 6.8, 2.2 Hz, 1H), 0.06 (s, 9H). 13C NMR (126 MHz, CDCl3, ppm): δ = 166.2, 158.4, 136.4, 126.8, 122.9, 113.4, 83.2, 55.2, 39.4, 27.3, 25.5, -2.3. IR (FTIR, cm–1): ṽ = 2952, 2927, 2835, 1613, 1512, 1244, 1100, 837. HRMS (ESI): m/z [M + H]+ calcd for C16H25O2Si: 277.1624; found: 277.1624. Synthesis of 4'-methoxy-2-(trimethylsilyl)-1,2,5,6-tetrahydro-[1,1'-biphenyl]-3'-d-2-ol (2.5c-d1), 2-(2-(4-methoxyphenyl-3-d)cyclobutyl)-1-(trimethylsilyl)ethan-1-one-2-d (2.6c-d2) and (7-(4-methoxyphenyl-3-d)-2,5,6,7-tetrahydrooxepin-2-yl)trimethylsilane (cis-2.4c-d1) Compounds 2.5c-d1, 2.6c-d2, and cis-2.4c-d1 were prepared as follows: 1104 mg (4.0 mmol, 1.0 equiv) of freshly prepared and purified cis-(7-(4-methoxyphenyl)-2,5,6,7-tetrahydrooxepin-2- yl)trimethylsilane (cis-2.4c) was dissolved in 50 mL dry THF under nitrogen, and the resulting solution was cooled at −78 °C (dry ice/acetone bath), sec-butyllithium, 1.4 M in cyclohexane (8.6 60 mL, 12.0 mmol, 3.0 equiv) was added dropwise (1 drop/s) to give a dark brown solution. The reaction mixture was allowed to warm up slowly without removing the cooling bath to –10 °C. The mixture was stirred at this temperature for 5 hours then cooled back to –78 °C. The reaction was quenched at –78 °C with D2O (5 mL), and the cooling bath was removed. After warming up to room temperature, the reaction mixture was diluted with 20 mL ether and loaded into a separating funnel. The layers were separated, and the aqueous phase was extracted with diethyl ether (20 mL x 3). Combined organic extracts were washed with brine (15 mL), and dried over anhydrous magnesium sulfate, filtered, quickly concentrated in a rotovap at temperatures lower than 45 °C. The crude material was purified by column chromatography, Rf for cis-2.4c-d1 = 0.6, Rf for 2.6c-d2 = 0.4 and Rf for 2.5c-d1 = 0.3 (10% EtOAc in hexanes) 259 mg, 0.93 mmol (23% isolated yield) of compound 2.5c-d1, 172 mg, 0.62 mmol (16% isolated yield) of 2.6c-d2 and 503 mg, 1.8 mmol (45%) of recovered starting material cis-2.4c-d1 with deuterium incorporation in the aromatic ring as colorless oils. Spectroscopic data for 2.5c-d1: 1H NMR (500 MHz, CDCl3, ppm): δ = 7.29 (dq, J = 4.6, 2.3 Hz, 2H), 6.84 (d, J = 9.0 Hz, 1H), 5.94 (dddd, J = 10.0, 4.9, 2.6, 0.7 Hz, 1H), 5.86 (ddd, J = 10.0, 2.4, 1.7 Hz, 1H), 3.79 (s, 3H), 2.87 (dd, J = 10.9, 3.0 Hz, 1H), 2.18 (dtdd, J = 18.3, 5.3, 3.6, 1.6 Hz, 1H), 2.14 – 2.04 (m, 1H), 1.95 (dddd, J = 13.0, 10.9, 9.6, 5.5 Hz, 1H), 1.64 (ddt, J = 12.7, 6.3, 3.2 Hz, 1H), 1.28 (s, 1H), -0.11 (s, 9H). 13C NMR (126 MHz, CDCl3, ppm): δ = 158.2, 135.9, 130.9, 130.22, 130.20, 130.1, 113.6, 66.3, 55.1, 46.4, 25.7, 25.5, -3.4. 29Si NMR (99 MHz, CDCl3) δ = 5.03. HRMS (ESI): m/z [M – H–]+ calcd for C16H22DO2Si: 276.1536; found: 276.1523. Spectroscopic data for 2.6c-d2 (cis:trans = 1:1): 1H NMR (500 MHz, CDCl3, ppm): δ = 7.14 (dq, J = 4.1, 2.2 Hz, 2H), 7.04 (dq, J = 3.8, 2.2 Hz, 2H), 6.84 (d, J = 5.1 Hz, 1H), 6.82 (d, J = 5.1 Hz, 1H), 3.78 (s, 3H), 3.78 (s, 3H), 3.70 (q, J = 8.1 Hz, 1H), 3.19 (p, J = 7.9 Hz, 1H), 3.01 (q, J = 61 9.1 Hz, 1H), 2.85 – 2.67 (m, 2H), 2.47 (dt, J = 7.5, 2.5 Hz, 1H), 2.30 – 2.23 (m, 2H), 2.22 – 2.14 (m, 2H), 2.13 – 2.05 (m, 1H), 1.98 (qd, J = 10.3, 8.5 Hz, 1H), 1.66 – 1.58 (m, 1H), 1.58 – 1.48 (m, 1H), 0.13 (s, 9H), 0.00 (s, 9H). 13C NMR (126 MHz, CDCl3, ppm): δ = 248.2, 248.1, 157.9, 157.7, 136.3, 133.9, 128.8, 128.7, 127.7, 127.6, 113.7, 113.5, 55.2, 55.2, 54.4, 49.7, 46.4, 41.6, 38.3, 33.4, 27.4, 25.5, 24.4, 23.5, -3.3, -3.4. 29Si NMR (99 MHz, CDCl3) δ = -10.71, -10.89. HRMS (ESI): m/z [M + H]+ calcd for C16H22D2O2Si: 279.1744; found: 279.1738. Spectroscopic data for cis-2.4c-d1: 1H NMR (500 MHz, CDCl3, ppm): δ = 7.34 – 7.27 (m, 2H), 6.89 (d, J = 9.1 Hz, 1H), 5.72 (dddd, J = 11.1, 7.2, 4.7, 2.5 Hz, 1H), 5.57 (ddd, J = 11.2, 3.1, 2.1 Hz, 1H), 4.74 (dd, J = 8.4, 5.3 Hz, 1H), 4.08 (qd, J = 3.3, 1.2 Hz, 1H), 3.81 (s, 3H), 2.71 – 2.61 (m, 1H), 2.33 (ddt, J = 13.6, 10.4, 5.0 Hz, 1H), 2.05 – 1.96 (m, 1H), 1.89 (ddt, J = 13.6, 8.4, 5.2 Hz, 1H), 0.13 (s, 9H). 13 C NMR (126 MHz, CDCl3, ppm): δ = 158.1, 137.4, 130.7, 126.3, 126.23, 126.18, 113.4, 81.2, 77.1, 55.2, 37.4, 23.6, -3.7. 29Si NMR (99 MHz, CDCl3) δ = -1.06. HRMS (ESI): m/z [M – OH]+ calcd for C16H22DOSi: 260.1575; found: 260.1572. 62 Synthesis of 6-(naphthalen-2-yl)-1-(trimethylsilyl)cyclohex-2-en-1-ol (2.5d), 2-(2-(naphthalen-2-yl)cyclobutyl)-1-(trimethylsilyl)ethan-1-one (2.6d) and 2-(naphthalen-2-yl)cyclohexan-1-one (2.8d) Applying general procedure F to trans-trimethyl(7-(naphthalen-2-yl)-2,5,6,7- tetrahydrooxepin-2-yl)silane trans-2.4d (593 mg, 2.0 mmol, 1.0 equiv), n-butyllithium (2.5 M in hexanes, 5.6 mL, 6.0 mmol, 1.2 equiv), and THF (100mL) afforded after column chromatography, Rf for 2.6d = 0.7, Rf for 2.5d = 0.5, Rf for 2.5d′ = 0.4 and Rf for 2.8d = 0.3 (10% EtOAc in hexanes) 283 mg, 0.95 mmol (48% isolated yield) of compound 2.5d and 2.5d′, 156 mg, 0.53 mmol (26% isolated yield) of 2.6d and 59 mg, 0.26 mmol (13% isolated yield) of 2.8d as colorless oils. Spectroscopic data for 2.5d (silyl and naphthalenyl groups cis to one another): 1H NMR (500 MHz, CDCl3, ppm): δ = 7.85 – 7.77 (m, 4H), 7.57 (dd, J = 8.4, 1.7 Hz, 1H), 7.49 – 7.41 (m, 2H), 6.01 (ddd, J = 10.1, 5.0, 2.3 Hz, 1H), 5.93 (dt, J = 10.0, 1.9 Hz, 1H), 3.10 (dd, J = 10.6, 3.1 Hz, 1H), 2.28 – 2.05 (m, 3H), 1.78 – 1.69 (m, 1H), 1.38 (s, 1H), -0.10 (s, 9H). 13C NMR (126 MHz, CDCl3, ppm): δ = 141.5, 133.4, 132.3, 131.0, 130.4, 128.1, 127.73, 127.68, 127.6, 127.5, 125.8, 63 125.3, 66.4, 47.5, 25.7, 25.5, -3.3. HRMS (ESI): m/z [M]+ calcd for C19H24OSi: 296.1596; found: 296.1592. Spectroscopic data for 2.5d′ (silyl and naphthalenyl groups trans to one another): 1H NMR (500 MHz, CDCl3, ppm): δ = 7.85 – 7.78 (m, 3H), 7.75 (s, 1H), 7.55 (dd, J = 8.4, 1.8 Hz, 1H), 7.50 – 7.41 (m, 2H), 5.87 (dd, J = 10.0, 3.4 Hz, 1H), 5.74 (d, J = 10.3 Hz, 1H), 3.10 (dt, J = 12.8, 3.5 Hz, 1H), 2.32 – 2.26 (m, 2H), 2.10 (dp, J = 6.7, 5.1 Hz, 1H), 1.59 (s, 1H), -0.26 (s, 9H). 13C NMR (126 MHz, CDCl3, ppm): δ = 140.7, 133.3, 132.9, 132.3, 127.78, 127.76, 127.6, 127.5, 127.3, 126.7, 125.9, 125.4, 72.0, 51.3, 25.48, 25.46, -2.3. MS (GC/MS): m/z (%) = 296 (5) [M]+, 279 (38), 165 (14), 73 (100). HRMS (ESI): m/z [M – H–]+ calcd for C19H23OSi: 295.1518; found: 295.1505. Spectroscopic data for 2.6d: 1H NMR (500 MHz, CDCl3, ppm) for trans diastereomer: δ =7.82 – 7.78 (m, 2H), 7.75 (d, J = 8.5 Hz, 1H), 7.58 (s, 1H), 7.48 – 7.41 (m, 2H), 7.27 – 7.22 (m, 1H), 3.93 (q, J = 8.2 Hz, 1H), 3.40 – 3.29 (m, 1H), 2.54 (dd, J = 17.7, 7.5 Hz, 1H), 2.51 – 2.44 (m, 1H), 2.42 – 2.36 (m, 1H), 2.36 – 2.25 (m, 2H), 1.72 (ddtd, J = 11.5, 9.4, 5.8, 0.9 Hz, 1H), -0.10 (s, 9H). 13C NMR (126 MHz, CDCl3, ppm) trans diastereomer: δ = 248.0, 139.4, 133.4, 132.0, 127.54, 127.48, 127.46, 127.0, 125.8, 125.7, 125.2, 50.0, 42.4, 33.6, 24.5, 23.1, -3.6. 13C NMR (126 MHz, CDCl3, ppm) cis/trans isomers: δ = 249.2, 248.0, 139.5, 135.7, 134.4, 133.2, 133.4, 132.0, 129.8, 127.54, 127.48, 127.47, 127.3, 127.04, 127.00, 126.4, 126.1, 125.8, 125.7, 125.5, 125.2, 125.0, 50.0, 45.7, 42.4, 41.4, 33.6, 27.1, 26.2, 24.6, 23.1, 21.7, -3.3, -3.5. HRMS (ESI): m/z [M + H]+ calcd for C19H25OSi: 297.1675; found: 297.1661. Spectroscopic data for 2.8d: 1H NMR (500 MHz, CDCl3, ppm): δ = 7.63 (s, 1H), 7.53 – 7.41 (m, 2H), 7.31 (dd, J = 8.5, 1.8 Hz, 1H), 3.80 (dd, J = 12.2, 5.5 Hz, 1H), 2.59 (dtd, J = 13.7, 4.0, 1.3 Hz, 1H), 2.51 (dddd, J = 13.7, 12.4, 5.9, 1.2 Hz, 1H), 2.35 (dddd, J = 15.2, 7.3, 3.4, 2.3 Hz, 1H), 2.24 – 2.12 (m, 2H), 2.05 (dddq, J = 10.5, 6.8, 4.5, 2.4, 2.0 Hz, 1H), 1.95 – 1.82 (m, 2H). 13C 64 NMR (126 MHz, CDCl3, ppm): δ = 210.4, 136.3, 133.4, 132.5, 127.72, 127.65, 127.6, 126.92, 126.90, 125.8, 125.5, 57.4, 42.2, 35.0, 27.7, 25.2. 2.8d is a known compound, and the spectroscopic data are in agreement with those reported in the literature.19 65 REFERENCES (1) Wittig, G.; Lohmann, L. Übe die kationtrope isomerisation gewisser benzyläther bei einwirkung von phenyl-lithium. Liebigs Ann. Chem. 1942, 550, 260. (2) Schöllkopf, U. Recent results in carbanion chemistry. Angew. Chem., Int. Ed. Engl. 1970, 9, 763. (3) Schäfer, H.; Schöllkopf, U.; Walter, D. Migration tendency of alkyl groups in the Wittig rearrangement. Tetrahedron Lett. 1968, 9, 2809. (4) Sheldon, J. C.; Taylor, M. S.; Bowie, J. H.; Dua, Brian-Chia S. C.; Eichinger, P. C. H. The gas phase 1,2-Wittig rearrangement is an anion reaction. A joint experimental and theoretical study. J. Chem. Soc., Perkin Trans. 2 1999, 333. (5) Strunk, S.; Schlosser, M. Wittig rearrangement of lithiated allyl aryl ethers: A mechanistic study. Eur. J. Org. Chem. 2006, 4393. (6) Antoniotti, P.; Tonachini, G. J. Mechanism of the anionic Wittig rearrangement. An ab initio theoretical study. J. Org. Chem. 1998, 63 ,9756. (7) Schreiber, S. L.; Goulet, M. T. Stereochemistry of the 1,2-Wittig rearrangement: A synthesis of syn-1,3-diol monoethers. Tetrahedron Lett. 1987, 28, 1043. (8) Tomooka, K.; Nakai, T. [1,2]-Wittig rearrangement stereochemical features and synthetic utilities. J. Synth. Org. Chem., Jpn. 1997, 54, 1000. (9) Tomooka, K.; Yamamoto, H.; Nakai, T. Recent developments in the [1,2]-Wittig rearrangement. Liebigs Ann./Recl. 1997, 1275. (10) Yadav, J. S.; Ravishankar, R. A novel approach towards the synthesis of functionalized taxane skeleton employing Wittig rearrangement. Tetrahedron Lett. 1991, 32, 2629. (11) Maleczka, R. E., Jr.; Geng, F. Synthesis and fluoride-promoted Wittig rearrangements of α-alkoxysilanes. Org. Lett. 1999, 1, 1111. (12) Felkin, H. Tambute, A. 1,4-Alkyl shifts in the Wittig rearrangement of alkyl allyl ethers. Tetrahedron Lett. 1969, 821. (13) Courtois, G.; Miginiac, L. Transposition of allyl ethers under the action of allyl- lithium. Tetrahedron Lett. 1972, 24, 2411. (14) Rautenstrauch, V.; Büchi, G.; Wüst, H. Vinyl migration in Wittig rearrangements. J. Am. Chem. Soc. 1974, 96, 2576. (15) Mori-Quiroz, L. M.; Maleczka, R, E., Jr. Stereoconvergent [1,2]- and [1,4]-Wittig rearrangements of 2-silyl-6-aryl-5,6-dihydropyrans: A tale of steric vs electronic regiocontrol of divergent pathways. J. Org. Chem. 2015, 80, 1163. 66 (16) Nath, S. R.; Joshi, K. A. Mechanistic investigation in the [1,4] and [1,2] Wittig rearrangement reactions: a DFT study. Phys. Chem. Chem. Phys. 2018, 20, 21457. (17) Tomizuka, A.; Moriyama, K. Bromoetherification of alkenyl alcohols by aerobic oxidation of bromide: Asymmetric synthesis of 2-bromomethyl 5-substituted tetrahydrofurans. Adv. Synth. Catal. 2019, 361, 1447. (18) Chan, C-K; Huang, Y-H; Chang, M-Y. Sodium amalgam mediated desulfonylative reduction of α-functionalized β-ketosulfones. Tetrahedron, 2016, 72, 5521. (19) Cheon, C. H.; Kanno, O.; Toste, F. D. Chiral Brønsted acid from a cationic gold(I) complex: Catalytic enantioselective protonation of silyl enol ethers of ketones. J. Am. Chem. Soc. 2011, 133, 13248. 67 APPENDIX X-ray data for compound 2.4d Crystal structure confirms relative stereo chemistry, both enantiomers are present. Crystal data and experimental Figure 2.1: Crystal structure of compound 2.4d Experimental. Single yellow needle-shaped crystals of 2.4d were used as received. A suitable crystal 0.43×0.12×0.05 mm3 was selected and mounted on a nylon loop with paratone oil on a Bruker APEX-II CCD diffractometer. The crystal was kept at a steady T = 173(2) K during data collection. The structure was solved with the ShelXT (Sheldrick, G.M. (2015). Acta Cryst. A71, 3-8) structure solution program using the Intrinsic Phasing solution method and by using Olex2 (Dolomanov et al., 2009) as the graphical interface. The model was refined with version 2018/3 of ShelXL (Sheldrick, Acta Cryst. A64 2008, 112-122) using Least Squares minimization. Crystal data. C19H24OSi, Mr = 296.47, monoclinic, C2/c (No. 15), a = 32.3150(4) Å, b = 6.20960(10) Å, c = 22.7493(3) Å, β = 132.1830(10)°, α = γ = 90°, V = 3382.64(9) Å3, T = 173(2) K, Z = 8, Z' = 1, µ(CuKα) = 1.182, 25668 reflections measured, 3340 unique (Rint = 0.0417) which were used in all calculations. The final wR2 was 0.1021 (all data) and R1 was 0.0367 (I > 2(I)). 68 Table 2.2: Crystal data Compound 2.4d CCDC 1902771 Formula C19H24OSi Dcalc./ g cm-3 1.164 µ/mm-1 1.182 Formula Weight 296.47 Color yellow Shape needle Size/mm3 0.43×0.12×0.05 T/K 173(2) Crystal System monoclinic Space Group C2/c a/Å 32.3150(4) b/Å 6.20960(10) c/Å 22.7493(3) α/° 90 β/° 132.1830(10) γ/° 90 V/Å3 3382.64(9) Z 8 Z' 1 Wavelength/Å 1.541838 Radiation type CuKα Θmin/° 3.692 Θmax/° 72.149 Measured Refl. 25668 Independent Refl. 3340 Reflections with I 2924 > 2(I) Rint 0.0417 Parameters 193 Restraints 0 Largest Peak 0.293 Deepest Hole -0.226 GooF 1.044 wR2 (all data) 0.1021 wR2 0.0975 R1 (all data) 0.0425 R1 0.0367 69 Reflections: Refinement: Figure 2.2: Structure quality indicators A yellow needle-shaped crystal with dimensions 0.43×0.12×0.05 mm3 was mounted on a nylon loop with paratone oil. Data were collected using a Bruker APEX-II CCD diffractometer equipped with an Oxford Cryosystems low-temperature device, operating at T = 173(2) K. Data were measured using ω and ϕ of 1.00° per frame for 100.00 s using CuKα radiation (sealed tube, 40 kV, 30 mA). The total number of runs and images was based on the strategy calculation from the program COSMO (BRUKER, V1.61, 2009). The actually achieved resolution was Θ = 72.149. Cell parameters were retrieved using the SAINT (Bruker, V8.38A, after 2013) software and refined using SAINT (Bruker, V8.38A, after 2013) on 9911 reflections, 39 % of the observed reflections. Data reduction was performed using the SAINT (Bruker, V8.38A, after 2013) software which corrects for Lorentz polarization. The final completeness is 100.00 out to 72.149 in Θ SADABS-2016/2 (Bruker,2016/2) was used for absorption correction. wR2(int) was 0.0735 before and 0.0532 after correction. The Ratio of minimum to maximum transmission is 0.8774. The λ/2 correction factor is Not present. The structure was solved in the space group C2/c (# 15) by Intrinsic Phasing using the ShelXT (Sheldrick, G.M. (2015). Acta Cryst. A71, 3-8) structure solution program. The structure was refined by Least Squares using version 2014/6 of XL (Sheldrick, 2008) incorporated in Olex2 (Dolomanov et al., 2009). All non-hydrogen atoms were refined anisotropically. Hydrogen atom positions were calculated geometrically and refined using the riding model, except for the hydrogen atom on the non-carbon atom(s) which was found by difference Fourier methods and refined isotropically. CCDC 1902771 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures. There is a single molecule in the asymmetric unit, which is represented by the reported sum formula. In other words: Z is 8 and Z' is 1. 70 Figure 2.3: Model has Chirality at C1 (Centro SPGR) R Verify: Model has Chirality at C6 (Centro SPGR) S Verify. Being in a centrosymmetric space group means both enantiomers are present in the crystal 71 Figure 2.4: Packing diagram of 2.4d Data Plots: Diffraction data Figure 2.5: Data plots: Diffraction data 72 Figure 2.5 (cont’d) Data Plots: Refinement and data Figure 2.6: Data plots: Refinement and data Table 2.3: Reflection statistics Total reflections (after 26650 Unique reflections 3340 filtering) Completeness 0.998 Mean I/σ 25.28 hklmax collected (39, 7, 25) hklmin collected (-39, -7, -28) hklmax used (29, 7, 28) hklmin used (-39, 0, 0) Lim dmax collected 100.0 Lim dmin collected 0.77 dmax used 16.86 dmin used 0.81 Friedel pairs 3742 Friedel pairs merged 1 Inconsistent equivalents 0 Rint 0.0417 73 Table 2.3 (cont’d) Rsigma 0.0246 Intensity transformed 0 Omitted reflections 0 Omitted by user 0 (OMIT hkl) Multiplicity (3206, 3053, 1800, Maximum multiplicity 24 754, 476, 289, 284, 234, 92, 12) Removed systematic 982 Filtered off 0 absences (Shel/OMIT) Images of the crystal on the diffractometer Figure 2.7: Images of the crystal on the diffractometer 74 Table 2.4: Fractional atomic coordinates (×104) and equivalent isotropic displacement parameters (Å2×103) for 2.4d. Ueq is defined as 1/3 of the trace of the orthogonalised Uij Atom x Y z Ueq Si1 6251.6(2) 3547.1(6) 3967.8(2) 31.32(12) O1 5536.0(4) 4241.9(14) 4154.0(5) 31.5(2) C1 5847.6(6) 2421(2) 4236.2(8) 30.7(3) C2 5474.3(7) 562(2) 3721.4(9) 41.6(3) C3 4970.0(7) 142(3) 3455.3(9) 47.8(4) C4 4691.5(7) 1294(3) 3685.7(9) 47.5(4) C5 5109.8(6) 2106(2) 4539.5(8) 37.6(3) C6 5385.3(6) 4203(2) 4622.3(8) 33.2(3) C7 5877.6(6) 4880(2) 5471.9(8) 32.3(3) C8 6123.5(7) 6915(2) 5592.9(10) 39.8(3) C9 6551.7(7) 7674(2) 6334.7(10) 43.3(4) C10 6773.1(6) 6447(2) 7018.7(9) 39.0(3) C11 7224.5(7) 7161(3) 7804.0(11) 52.2(4) C12 7420.5(7) 5904(3) 8436.9(11) 58.4(5) C13 7180.1(8) 3889(3) 8325.1(10) 56.1(5) C14 6746.8(7) 3149(3) 7578.3(9) 45.7(4) C15 6533.2(6) 4401(2) 6907.3(9) 36.0(3) C16 6084.0(6) 3673(2) 6122.1(8) 34.0(3) C17 6598.9(9) 1286(3) 3899.5(14) 57.4(5) C18 5762.6(6) 5013(2) 3011.0(9) 39.0(3) C19 6787.4(6) 5447(3) 4770.3(9) 45.3(4) 75 Table 2.5: Anisotropic displacement parameters (×104) 2.4d. The anisotropic displacement factor exponent takes the form: -2π2[h2a*2 × U11+ ... +2hka* × b* × U12] Atom U11 U22 U33 U23 U13 U12 Si1 32.8(2) 28.5(2) 37.4(2) 3.82(14) 25.53(18) 1.96(14) O1 38.8(5) 27.6(4) 36.8(5) 5.9(4) 28.9(4) 4.1(4) C1 35.8(7) 26.1(6) 34.8(7) 1.9(5) 25.6(6) 0.8(5) C2 59.4(9) 31.0(7) 47.4(8) -6.3(6) 41.2(8) -8.4(7) C3 58.3(10) 47.3(9) 39.0(8) -11.6(7) 33.2(8) -22.8(8) C4 38.5(8) 61.0(10) 41.9(8) -2.4(7) 26.5(7) -16.8(7) C5 38.6(7) 43.9(8) 38.8(7) -0.2(6) 29.4(7) -5.3(6) C6 36.5(7) 33.8(7) 38.6(7) 5.0(6) 29.0(6) 4.4(6) C7 37.1(7) 30.3(6) 41.0(7) 0.2(5) 30.9(6) 1.8(6) C8 48.8(8) 32.7(7) 52.1(9) 2.7(6) 39.7(8) 0.7(6) C9 47.9(9) 33.2(7) 63.4(10) -8.0(7) 43.3(8) -7.3(6) C10 34.9(7) 39.8(8) 49.9(8) -10.1(6) 31.7(7) -0.3(6) C11 37.3(8) 55.2(10) 62.7(11) -22.6(9) 33.0(8) -4.6(7) C12 37.0(8) 76.2(12) 44.8(9) -18.6(9) 20.4(8) 7.7(9) C13 48.8(9) 71.1(12) 41.1(9) 2.1(8) 27.1(8) 17.5(9) C14 45.1(9) 51.1(9) 41.5(8) 3.9(7) 29.2(7) 8.1(7) C15 34.5(7) 39.2(7) 41.7(8) -1.6(6) 28.6(7) 3.9(6) C16 36.8(7) 30.6(7) 40.6(7) -0.9(5) 28.5(6) -2.1(6) C17 67.0(11) 42.6(9) 94.9(14) 10.9(9) 67.5(12) 12.4(8) C18 43.2(8) 40.1(7) 36.1(7) 2.3(6) 27.6(7) -1.4(6) C19 35.8(8) 48.4(9) 40.8(8) 2.5(7) 21.2(7) -7.7(7) 76 Table 2.6: Bond Lengths in Å for 2.4d Atom Atom Length/Å Si1 C1 1.9072(13) Si1 C17 1.8680(16) Si1 C18 1.8559(15) Si1 C19 1.8649(16) O1 C1 1.4402(15) O1 C6 1.4382(15) C1 C2 1.5044(19) C2 C3 1.328(2) C3 C4 1.493(2) C4 C5 1.526(2) C5 C6 1.5164(19) C6 C7 1.521(2) C7 C8 1.4180(19) C7 C16 1.3674(19) C8 C9 1.360(2) C9 C10 1.421(2) C10 C11 1.420(2) C10 C15 1.420(2) C11 C12 1.363(3) C12 C13 1.403(3) C13 C14 1.365(2) C14 C15 1.413(2) C15 C16 1.421(2) 77 Table 2.7: Bond Angles in ° for 2.4d Atom Atom Atom Angle/° C17 Si1 C1 109.25(7) C18 Si1 C1 109.17(6) C18 Si1 C17 110.94(8) C18 Si1 C19 109.72(7) C19 Si1 C1 107.68(7) C19 Si1 C17 110.02(9) C6 O1 C1 116.45(9) O1 C1 Si1 103.89(8) O1 C1 C2 112.10(11) C2 C1 Si1 113.30(9) C3 C2 C1 127.04(14) C2 C3 C4 126.15(14) C3 C4 C5 112.19(13) C6 C5 C4 112.71(12) O1 C6 C5 112.66(11) O1 C6 C7 110.56(11) C5 C6 C7 114.90(11) C8 C7 C6 117.69(12) C16 C7 C6 123.87(12) C16 C7 C8 118.41(13) C9 C8 C7 121.37(14) C8 C9 C10 121.18(14) C11 C10 C9 123.17(15) C11 C10 C15 118.70(16) C15 C10 C9 118.13(14) C12 C11 C10 120.44(17) C11 C12 C13 120.73(16) C14 C13 C12 120.41(18) C13 C14 C15 120.54(17) C10 C15 C16 118.91(13) C14 C15 C10 119.18(14) C14 C15 C16 121.91(14) C7 C16 C15 122.00(13) 78 Table 2.8: Torsion angles in ° for 2.4d Atom Atom Atom Atom Angle/° Si1 C1 C2 C3 -142.51(15) O1 C1 C2 C3 -25.3(2) O1 C6 C7 C8 56.42(16) O1 C6 C7 C16 -125.63(13) C1 O1 C6 C5 -50.23(15) C1 O1 C6 C7 79.84(14) C1 C2 C3 C4 -7.4(3) C2 C3 C4 C5 -31.9(2) C3 C4 C5 C6 81.04(17) C4 C5 C6 O1 -41.76(17) C4 C5 C6 C7 -169.59(12) C5 C6 C7 C8 -174.70(12) C5 C6 C7 C16 3.25(19) C6 O1 C1 Si1 -154.03(9) C6 O1 C1 C2 83.27(14) C6 C7 C8 C9 177.60(13) C6 C7 C16 C15 -177.84(12) C7 C8 C9 C10 0.5(2) C8 C7 C16 C15 0.1(2) C8 C9 C10 C11 179.14(14) C8 C9 C10 C15 -0.2(2) C9 C10 C11 C12 -179.65(15) C9 C10 C15 C14 179.89(13) C9 C10 C15 C16 -0.16(19) C10 C11 C12 C13 -0.1(2) C10 C15 C16 C7 0.2(2) C11 C10 C15 C14 0.5(2) C11 C10 C15 C16 -179.54(12) C11 C12 C13 C14 0.4(3) C12 C13 C14 C15 -0.1(2) C13 C14 C15 C10 -0.3(2) C13 C14 C15 C16 179.75(14) C14 C15 C16 C7 -179.84(13) C15 C10 C11 C12 -0.3(2) C16 C7 C8 C9 -0.5(2) 79 Table 2.9: Hydrogen fractional atomic coordinates (×104) and equivalent isotropic displacement parameters (Å2×103) for 2.4d. Ueq is defined as 1/3 of the trace of the orthogonalised Uij Atom x Y z Ueq H1 6117.96 1947.53 4803.17 37 H2 5614.28 -418.73 3570.24 50 H3 4767.49 -999.26 3083.29 57 H4A 4423.78 306.51 3623.63 57 H4B 4478.04 2530.58 3324.32 57 H5A 4915.08 2317.72 4733.37 45 H5B 5401.68 997.83 4877.39 45 H6 5095.22 5345.81 4396.99 40 H8 5986.08 7766.51 5146.42 48 H9 6705.7 9049.64 6396.69 52 H11 7391.04 8522.55 7889 63 H12 7723.27 6398 8959.48 70 H13 7319.7 3034.48 8771.89 67 H14 6587.52 1781.35 7509.17 55 H16 5922.26 2306.59 6046.79 41 H17A 6836.27 479.74 4399.32 86 H17B 6828.38 1867.19 3799.03 86 H17C 6314.09 323.48 3464.26 86 H18A 5471.27 4025.42 2595.97 58 H18B 5967.82 5584.8 2868.34 58 H18C 5590.34 6204.57 3063.59 58 H19A 6602.6 6597.83 4815.47 68 H19B 6997.22 6073.94 4642.44 68 H19C 7044.08 4668.02 5274.65 68 Citations COSMO-V1.61 - Software for the CCD Detector Systems for Determining Data Collection Parameters, Bruker axs, Madison, WI (2000). O.V. Dolomanov and L.J. Bourhis and R.J. Gildea and J.A.K. Howard and H. Puschmann, Olex2: A complete structure solution, refinement and analysis program, J. Appl. Cryst., (2009), 42, 339-341. Sheldrick, G.M., A short history of ShelX, Acta Cryst., (2008), A64, 339-341. Software for the Integration of CCD Detector System Bruker Analytical X-ray Systems, Bruker axs, Madison, WI (after 2013). 80 Copies of NMR Spectra 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 CHAPTER 3. SILYLCYCLOPROPANES BY SELECTIVE [1,4]-WITTIG REARRANGEMENT OF 4-SILYL-5,6-DIHYDROPYRANS This work has been adapted with permission from: Mori-Quiroz, L. M.; Maloba, E. W.; Maleczka, R. E., Jr. Silylcyclopropanes by selective [1,4]-Wittig rearrangement of 4-silyl-5,6- dihydropyrans. Org. Lett. 2021, 23, 5724 – 5728. Copyright 2021 American Chemical Scoiety. This work was done in collaboration with Dr. Luis Martin Mori-Quiroz. Dr. Mori worked on reaction design and optimization. I worked on additional substrate scope, comparative studies, and derivatization of compound 3.2c. 3.1. Introduction [1,4]-Wittig rearrangements of allyl ethers generate enolates, whereas the more common [2,3]- and [1,2]-pathways produce alkoxides.1-6 In addition, the [1,4]-Wittig pathway is inherently interwoven with the [1,2]-manifold, which typically predominates. Despite its synthetic potential, the [1,4]-migration path is largely underdeveloped with selective and efficient [1,4]-Wittig pathways being relatively rare and of limited scope.7-9 In 2006, our research group found that (1-trimethylsilyl)allylbenzyl ether rearranged selectively through the [1,4]-pathway, forming the acylsilane product.10 The apparent ability of the silyl group to allow (1) selective allylic deprotonation and (2) selective [1,4]-migration of the benzyl group led us to explore more complex acyclic analogues. These studies were hampered by lower reactivity of such higher analogues, which we speculated was due to sterics hindering access to conformations necessary for deprotonation.11 In contrast, we found that related cyclic ethers rearrange efficiently to give α-cyclopropyl acylsilanes or α-silylcyclopentenols by [1,4]- and [1,2]- Wittig migrations, respectively.12 We also learned that cis/trans diastereomers of these cyclic ethers exhibited very different rates of deprotonation, again presumably reflecting their different ability to 155 achieve the optimal conformation for deprotonation. Once deprotonated, [1,4]-migration and the competing [1,2]-pathway proceed in a stereoconvergent fashion, with [1,4]-/[1,2]- selectivity being highly sensitive to steric and electronic factors (Scheme 3.1).12 Scheme 3.1: Wittig rearrangements of 2-silyl-6-aryl-5,6-dihydropyrans A question that arose from these studies was whether relocation of the silyl group to the 4- position of the dihydropyran scaffold would favor the [1,4]- or [1,2]-pathway. Herein, we report that 4-silyl-5,6-dihydropyrans undergo highly selective [1,4]-Wittig rearrangement to afford silylcyclopropyl acetaldehydes. Silylcyclopropanes are versatile building blocks in organic synthesis. 13 For instance, they engage in reactions with both nucleophilic and electrophilic partners. Traditional synthetic approaches (Scheme 3.2) involve the cyclopropanation of vinylsilanes14-24 and the addition of silyl carbenoids to olefins.25-32 Other metal-catalyzed processes have been developed, such as the addition of silyl reagents to cyclopropenes,33-37 intramolecular C–H silylation of cyclopropanes,38 and annulation reactions.39-43 To the best of our knowledge, the synthesis of silylcyclopropanes by means of ring contraction had not been reported. 156 Scheme 3.2: General approaches to silylcyclopropanes 3.2. Synthesis of 4-silyl-5,6-dihydro-2H-pyrans For our purpose, the 4-silyl-5,6-dihydropyrans were prepared from readily available homopropargylic alcohols in three steps involving regioselective alkyne hydrosilylation using Trost catalyst44,45 or Tomooka’s Pt-catalyzed method,46 followed by O-allylation, and ring-closing metathesis (RCM) of the diene precursor using Grubbs’ second-generation catalyst (Scheme 3.3).47,48 A variety of substrates bearing different silyl groups were thus accessed. Scheme 3.3: Synthetic route to dihydropyrans 3.1 157 3.3. Optimization of reaction conditions for Wittig rearrangement We started this study by evaluating dihydropyran 3.1a under Wittig conditions used in our previous reports (Scheme 3.4). Treatment of 3.1a with n-butyllithium in THF at −78 °C for 3.5 h (conditions A) afforded exclusively [1,4]-Wittig product 3.2a in 80% yield with modest diastereoselectivity (3.3:1), together with a small amount of unreacted 3.1a (7%). The use of the stronger sec-butyllithium (conditions B) resulted in complete deprotonation followed by rearrangement to afford 3.2a in 91% yield after only 20 min. Slightly higher diastereoselectivity (4.7:1) was also realized. Under both reaction conditions, we were unable to detect any [1,2]-Wittig product by 1H NMR analysis of the crude reaction mixtures. Scheme 3.4: [1,4]-Wittig rearrangement of model substrate 3.1a 3.4. Wittig rearrangements of 4-silyl-5,6-dihydro-2H-pyrans with aryl substituents at the migrating carbon We next evaluated a variety of substrates bearing different silyl groups at the 4-position and aryl substituents at the migrating carbon (Scheme 3.5). The smaller EtMe2Si group afforded silylcyclopropylacetaldehyde 3.2b in 85% yield and 3.3:1 diastereoselectivity, whereas the more sterically demanding Et3Si group led to silylcyclopropane 3.2c in a slightly lower yield (70%) but higher diastereoselectivity (11:1). 158 Scheme 3.5: Substrate scope of aryl-substituted dihydropyrans bearing different silyl groupsa a Diastereoselectivity determined by 1H NMR of the crude reaction mixture b Reaction run on a 2 mmol scale c A small amount (<5%) of the presumed [1,2]-Wittig product within a complex mixture was observed but not fully characterized d 15% of unreacted dihydropyran 3.1h was recovered e 2.2 equiv of sec-BuLi was used Consistent with prior observations, electron-donating groups such as a 4-methyl on the phenyl group afforded exclusively silylcyclopropanes 3.2d and 3.2e bearing PhMe2Si and BnMe2Si groups in good yields and low diastereoselectivities. o-Methyl substitution at the aryl group was tolerated, leading to silylcyclopropane 3.2f in 91% yield and 8.3:1 diastereoselectivity. m-Methoxy substitution of the aryl ring, which confers an electron-deficient character to the migrating (benzylic) carbon, afforded predominantly the [1,4]-Wittig product 3.2g in 61% yield. This was in contrast with the observation in our previous work on 2- 159 silyl-6-aryl-5,6-dihydropyrans, where a near equal mixture of [1,2], and [1,4] products was observed.12 Other (hetero)aromatic substituents at the migrating center such as ferrocenyl and 2- thiophene-yl were tolerated, providing access to silylcyclopropyl acetaldehydes 3.2h and 3.2i in 69% and 71% yield, respectively. However, in contrast to all previous examples, the major diastereomer in 3.2i was trans. This outcome is best explained by the fact that 2.2 equiv of sec-BuLi was used to ensure complete allylic deprotonation of 3.2i. Such conditions were used because the 2-thiophenyl group undergoes competitive deprotonation at the 5 position, as previously observed.12 Therefore, the actual species that undergoes rearrangement is likely the dianion Li2–3.1i (Scheme 3.5, inset), whose unique electronic characteristics might be responsible for the observed stereochemistry of 3.2i. We determined the relative stereochemistry of the major diastereomer in 3.2a by NOESY studies and assigned the relative stereochemistry of compounds 3.2b–3.2i by comparison. Specifically, protons corresponding to the alkyl groups attached to silicon (Me, Et) appeared upfield in the NMR spectrum relative to those in the minor diastereomer, presumably due to shielding effects by the cis-oriented aromatic group. In addition, protons corresponding to methyl groups in dimethylsilyl products (i.e., 3.2b, 3.2d–3.2h) became inequivalent due to the expected slow rotation induced by the bulky aryl groups. We further confirmed the structure of compound 3.2c by X-ray crystallographic analysis of its 2,4-dinitrophenylhydrazine derivative (see the experimental section). 3.5. Wittig rearrangements of 4-silyl-5,6-dihydro-2H-pyrans with alkyl substituents at the migrating carbon We next evaluated dihydropyrans bearing alkyl substituents at the migrating carbon (Scheme 3.6). These substrates underwent slow deprotonation under conditions A and B (see Scheme 3.4). However, addition of sec-butyllithium at −78 °C and warming to −10 °C 160 (conditions C) allowed deprotonation and rearrangement with excellent [1,4]-selectivity. Dihydropyrans bearing PhMe2Si groups on the 4-position and n-propyl and cyclohexyl substituents at the migrating carbon led to the corresponding silylcyclopropanes 3.2j and 3.2k in 83% and 76% yields, respectively. The n-propyl-substituted dihydropyran (3.2j) rearranged with higher diastereoselectivity compared to the dihydropyrans bearing cycloalkyl groups (Scheme 3.6). Interestingly, cyclopropyl-substituted dihydropyrans 3.1l and 3.1m underwent rearrangement without observable formation of the ring-opened products. Scheme 3.6: Selective [1,4]-Wittig rearrangement of dihydropyrans 3.1 bearing alkyl groups at the migrating centera a Diastereoselectivity determined by 1HNMR of the crude reaction mixture 3.6. Rearrangement of substrates bearing electron-deficient aryl groups and 2-naphthyl derivative Dihydropyrans with electron-deficient aryl groups such as 3.1n underwent Wittig rearrangements with flipped [1,4]-/[1,2]-selectivity. Here, the predominant product was the [1,2]- Wittig alcohol 3.3n (54%), followed by the [1,4]-silylcyclopropane 3.2n (17%) and a small amount of an isomeric [1,2]-Wittig product 3.4n (6%). Formation of 4n indicates that benzylic deprotonation becomes competitive when electron-deficient aryl groups are present. Similarly, 2- pyridyl-substituted dihydropyran (3.1o) predominantly afforded diastereomeric [1,2]-Wittig 161 products 3.3o and 3.3o′ (2:1 ratio), resulting from allylic deprotonation. Unreacted 3.1o could not be isolated and instead underwent oxidation during workup and purification to give lactone 3.5o.49 Attempts to access the 4-pyridyl analogue using our established route (Scheme 3.3) were unsuccessful due to reluctance of the diene precursor to undergo ring-closing metathesis (see the experimental section). 2-Naphthyl-substituted dihydropyran (3.1p) failed to undergo Wittig rearrangement, and instead, ring-opened products 3.6p and 3.7p were observed (Scheme 3.7). Scheme 3.7: Rearrangement of substrates bearing electron-deficient aryl groups and 2-naphthyl derivative 162 3.7. Comparative studies on Wittig rearrangements of dihydropyrans On a last note, it is worth comparing the ability of silyldihydropyrans 3.1 and isomeric 3.9a/b12 to undergo clean rearrangements relative to the unsubstituted analogue 3.8 (Figure 3.1). While 3.1 and 3.9a/b undergo Wittig rearrangements in good yields, dihydropyran 3.8 reacts sluggishly to give a low yield of [1,4]-Wittig product together with a complex mixture of undetermined byproducts. On the other hand, the exclusive [1,4]-selectivity of 3.1 is independent of the nature of the silyl groups, while those of 3.9a or 3.9b are very sensitive to the sterics of the silyl group. Figure 3.1: Comparison of yields and [1,4]-/[1,2]-selectivities of 3.1 vs 2-silyl analogues 3.9a/3.9b and desilylated analogue 3.8 3.8. Proposed mechanism of the [1,4]-Wittig rearrangement of 4-silyl-6-aryl(alkyl)-5,6-dihydroprans In line with our previously proposed mechanistic hypothesis, we maintain that the [1,4]- Wittig rearrangement of silyl dihydropyrans proceeds primarily by a stepwise process involving a homolytic C–O bond cleavage and intramolecular radical/radical anion recombination (Scheme 3.8),12 a process that must be faster than ∼7 × 107 s–1 given that cyclopropyl-bearing substrates did not lead to ring opened products.50 As previously reported,12 the product distributions from 3.9a or 3.9b suggest that increasing the steric demand of the silyl group prevents [1,2]- recombination due to steric clash with the phenyl group. These observations, together with the exclusive [1,4]-selectivity displayed by 3.1 suggest that the [1,4]-/[1,2]-selectivity is determined 163 by the ability of the silyl group to transiently and locally stabilize the allylic radical,51 guiding recombination toward the Si-bearing carbon. Scheme 3.8: Proposed mechanism of the [1,4]-Wittig rearrangement of 4-silyl-6-aryl(alkyl)-5,6-dihydroprans However, there remains the question as to why varying diastereoselectivities are observed with different silyl or aryl groups (Scheme 3.5). For instance, the diastereoselectivity increases nearly 3-fold from the relatively small SiMe2Et group (3.2b, dr = 3.3:1) to the more sterically demanding SiEt3 group (3.2c, dr = 11:1). Similarly, the bulkier aryl group 2-methyl phenyl in 3.2f affords a higher diastereoselectivity (8.3:1) relative to the phenyl analogue 3.2b (Scheme 3.5). At this point, we conjecture that a concerted mechanism is operative to a certain extent and leads to the minor diastereomer (trans). In this scenario, bulkier silyl or aryl groups preclude such a competitive mechanism, indirectly leading to higher diastereoselectivity by the dominant, stepwise mechanism. 3.9. Conclusion In conclusion, silylcyclopropane acetaldehydes with a variety of silyl groups can be accessed efficiently by selective [1,4]-Wittig rearrangement of 4-silyl-5,6-dihyropyrans. High selectivity is achievable with substrates whose migrating group has an electron-neutral or electron- rich character. In general, the diastereoselectivity of the [1,4]-migration is such that the bulkier groups (silyl and aryl/alkyl) end up in a cis relationship. The rearrangement proceeds even when the substituent at the 6-position of the dihydropyran is alkyl. The [1,4]-Wittig selectivity is independent of the substituents on silicon, 164 but it is influenced by the electronic character of the migrating center. 3.10. Experimental section 3.10.1. General Information Unless otherwise noticed all reactions were run under a positive atmosphere of nitrogen in oven- dried (at least 4 hours) or flame-dried round bottom flasks or disposable drum vials capped with rubber septa. Solvents were removed by rotary evaporation at temperatures lower than 45 ºC. Column chromatography was run on 230–400 mesh silica gel. Tetrahydrofuran and diethyl ether were distilled from sodium-benzophenone ketyl; dichloromethane, benzene, trimethylsilyl chloride were distilled from calcium hydride. Acetone was distilled from drierite and used immediately. Triethylsilane, dimethylbenzylsilane, dimethylphenysilane, dimethylethylsilane, and vinyldimethylchlorosilane were used as received. n-Butyllithum (1.6 M in hexanes) and sec- butyllithium (1.4 M in cyclohexane) were purchased from Aldrich and their concentration calculated by titration with diphenylacetic acid (average of three runs). 1H NMR spectra was collected in 500 MHz and 600 MHz Varian instruments using CDCl3 as solvent, which was referenced at 7.24 ppm (residual chloroform proton) and 13C NMR spectra was collected in CDCl3 at 126 MHz or 151 MHz and referenced at 77.0 ppm. Other deuterated solvents used for NMR analysis were dimethyl sulfoxide (referenced at 2.50 for 1HNMR and 39.51 for 13 CNMR) and benzene (referenced at 7.16 for 1HNMR and 128.39 for 13 CNMR). High resolution mass spectrometric (HRMS) analysis was run in TOF instruments. 165 3.10.2. Synthesis of 4-silyl-5,6-dihydropyrans and precursors 3.10.2.1. Preparation of aryl homopropargylic alcohols 3.10 – general procedure A Following a reported procedure,52 to a vigorously stirred suspension of Zinz dust (5.3 g, 81 mmol, 3 equiv) in THF (200 mL) at 0 ºC was added propargyl bromide (80% w/w in toluene, 12 g, 81 mmol, 3 equiv) followed by TiCl4 (1M in CH2Cl2, 1.35 mL, 1.35 mmol, 0.05 equiv). After 10 minutes, the desired aryl aldehyde (27 mmol, 1 equiv) in THF (60 mL) was adde via syringe slowly. The reaction was followed by TLC and was typically complete in 3-4 hours. The reaction was quenched by adding NH4Cl (sat) (~150 mL) and slightly acidified with 1M HCl to remove the emulsion. The mixture was extracted with Et2O (3  150 mL). Combined organic extracts were dried over MgSO4 and concentrated. The product was purified by column chromatography. 3.10.2.2. Preparation of alkyl homopropargylic alcohols 3.10 – general procedure B Following a reported procedure slightly modified, 53 to a solution of 1,2-dibromoethane (0.15 mL, 1.783 mmol, 0.2 equiv) in THF (20 mL) was added Zn dust (1.17 g, 17.83 mmol, 2 equiv) with vigorous stirring. The mixture was heated at 65 ºC for 10 minutes and then cooled 166 down at room temperature. After 20 minutes trimethylsilyl chloride (23 L, 0.178 mmol, 0.02 equiv) was added dropwise and 20 minutes later the reaction was cooled down at 0 ºC. Propargyl bromide (80% w/w in toluene, 2.65 g, 17.83 mmol, 2 equiv) was added slowly with vigorous stirring. After 1 hour the mixture was cooled down at –78 ºC and the desired alkyl aldehyde (8.915 mmol, 1 equiv) was slowly added as a solution in THF (10 mL). The temperature was slowly raised to 0 ºC. The reaction was monitored by TLC until completion. The reaction was quenched by adding NH4Cl (sat) (10 mL) and extracted with Et2O (3  15 mL). Combined organic extracts were dried over MgSO4 and concentrated. The product was purified by column chromatography. 3.10.2.3. Preparation of 3-silyl homoallylic alcohols 3.11 – general procedure C Following a reported procedure,46 to a solution of the desired homopropargylic alcohol (1.286 mmol, 1 equiv) and dimethylvinylsilyl chloride (1.929 mmol, 1.5 equiv) in THF (5.6 mL) at room temperature was added imidazole (1.929 mmol, 1.5 equiv) in one portion and the mixture was stirred for 2-12 hours under nitrogen. The reaction was monitored by TLC until completion. The mixture was then filtered through a plug of celite, rinsing with hexanes, and the filtrate was concentrated and suspended in hexanes. Filtration through a plug of celite and concentration afforded the crude dimethylvinylsiloxy that was used in the next step without further purification. In some cases, it was necessary to repeat the treatment with hexanes to remove all insoluble material. 167 Alternatively, to an 8 mL conical vial fitted with a vane magnetic stir bar and sealed with a rubber septum, the desired homopropargylic alcohol (5.0 mmol, 1 equiv) and dimethylvinylsilyl chloride (6.0 mmol, 1.2 equiv) were dissolved in 5 mL of dry DMF (dried over molecular sieves) under nitrogen. Triethyl amine (1.7 mL, 12 mmol, 2.4 equiv) was added dropwise and the mixture stirred at room temperature for 5 minutes then on a pre-heated oil bath at 80 °C for 4 hours. The mixture was allowed to cool to room temperature filtered, and the filtrate was transferred to a separating funnel and a cold solution of saturated aqueous sodium hydrogen carbonate (5 mL) was added resulting in an exothermic reaction. The mixture was extracted with pentane (30 mL x 3) and the organic portion was washed with brine and dried over anhydrous magnesium sulfate. Filtration and concentration yielded the desired product which was used in the next step without further purification. To a mixture of the above O-dimethylvinylsilyl homopropargylic alcohol (1.813 mmol, 1 equiv) and the corresponding silane (1.813 mmol, 1 equiv) was added Karstedt catalyst as a solution in xylenes (2% w/w in xylenes, 80.7 L, 0.002 equiv) and the mixture was heated under nitrogen at 80 ºC for 1-1.5 hours. The reaction mixture was cooled down at room temperature and diluted with THF (18 mL) and TBAF (1M in THF, 2.18 mmol, 2.18 mL, 1.2 equiv) was added slowly. After 20 minutes the solution was concentrated and the residue subjected to column chromatography (EtOAc/hexanes) to afford the desired 3-silyl homoallylic alcohol 3.11. 3.10.2.4. Preparation of 3-silyl homoallylic alcohols 3.11 – general procedure D 168 Following a literature procedure,45 a solution of the desired homopropargylic alcohol (3.625 mmol, 1 equiv) and silane (4.35 mmol, 1.2 equiv) in dry dichloromethane was cooled down at 0 ºC and [Cp*Ru(MeCN)3]PF6 (36.6 mg, 0.072 mmol, 0.02 equiv) was added quickly, the reaction was kept under nitrogen and the cold bath was removed. After about 1 hour the reaction mixture was concentrated and the product purified by column chromatography (EtOAc/hexanes). 3.10.2.5. Etherification of 3-silyl homoallylic alcohols 3.11 to RCM precursors 3.12 – general procedure E To a solution of 3-silyl homoallylic alcohol 3.11 (0.918 mmol, 1 equiv) and allyl bromide (194 L, 2.296 mmol, 2.5 equiv) in THF (2 mL) at 0 ºC was added t-BuONa (265 mg, 2.75 mmol, 3 equiv) and the mixture was vigorously stirred at room temperature. After 4 hours the reaction was quenched with water (3 mL) and diluted with EtOAc (5 mL). The aqueous phase was extracted with EtOAc (3  5 mL). Combined organic extracts were washed with water (3 mL), brine, dried over MgSO4 and concentrated. The diene product 3.12 was purified by short column chromatography. Alternatively, sodium hydride, 60% w/w dispersion in mineral oil (345 mg, 9.0 mmol, 3.0 equiv) was weighed into a 100 mL dry round bottomed flask fitted with a magnetic stir bar. The flask was sealed and purged with nitrogen, then 20 mL THF was added followed by 0.52 mL of allyl bromide (726 mg, 6.0 mmol, 2.0 equiv) and the resulting suspension was cooled on an ice- bath at 0 °C. To the cold suspension, 3-silyl homoallylic alcohol 3.11 (3.0 mmol, 1 equiv) in THF 169 (10 mL) was added in a dropwise manner and the resulting mixture stirred at 0 °C to room temperature. After 4 hours, the reaction was quenched with saturated aqueous ammonium chloride (10 mL) and diluted with ether (20 mL) and water (10 mL). The layers were separated and the aqueous layer was extracted with ether (20 mL x 3). The combined organic layer was washed with brine and dried over anhydrous magnesium sulfate. This was followed by filtration and the filtrate was concentrated under reduced pressure on a rotorvap. The diene product 3.12 was purified by short column chromatography. 3.10.2.6. Preparation of 4-silyl dihydropyrans 3.1 via ring-closing metathesis of dienes 3.12 – general procedure F A round-bottom flask was charged with a magnetic stirred, diene 3.12 (100 mg, 0.31 mmol, 1 equiv) and benzene (6.2 mL), and then second-generation Grubbs catalyst (10.5 mg, 0.0124 mmol, 0.04 equiv) was added in one portion. A condenser was attached, and the system flushed with nitrogen. The reaction was heated in an oil bath at 80 ºC for 1-1.5 hours. The reaction was then cooled down at room temperature and concentrated. The residue was subjected to column chromatography (CH2Cl2 in hexanes) to afford the desired product 3.1 as a colorless oil. 170 Preparation of 1-phenyl-3-butyn-1-ol (3.10a) Following general procedure A, 1-Phenyl-3-butyn-1-ol (3.10a) was prepared in ~100% yield. 1H NMR (500 MHz, CDCl3) δ 7.41 – 7.34 (m, 4H), 7.34 – 7.28 (m, 1H), 4.86 (t, J = 6.4 Hz, 1H), 2.64 (dd, J = 6.4, 2.7 Hz, 2H), 2.56 (s, 1H), 2.08 (t, J = 2.7 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 142.4, 128.4, 127.9, 125.7, 80.6, 72.2, 70.9, 29.3. Spectral data are in accord with reported literature values.54 Preparation of 1-(4-methylphenyl)-3-butyn-1-ol (3.10d) Following general procedure A, 1-(4-methylphenyl)-3-butyn-1-ol (3.10d) was prepared in 94% yield. 1H NMR (500 MHz, CDCl3) δ 7.28 (d, J = 8.4 Hz, 2H), 7.18 (d, J = 7.8 Hz, 2H), 2.64 (dd, J = 6.4, 2.6 Hz, 2H), 2.35 (s, 3H), 2.31 (s, 1H), 2.07 (t, J = 2.6 Hz, 1H). Spectral data are in accord with reported literature values.55 171 Preparation of 1-(2-methylphenyl)-3-butyn-1-ol (3.10f) Following General Procedure A, 1-(2-methylphenyl)-3-butyn-1-ol (3.10f) was prepared in 90% yield. Spectral data are in accord with reported literature values. 56 Preparation of 1-(3-methoxyphenyl)-3-butyn-1-ol (3.10g) Following General Procedure A, 1-(3-methoxyphenyl)-3-butyn-1-ol (3.10g) was prepared in ~100% yield. Spectral data are in accord with reported literature values. 56 Preparation of 1-(ferrocenyl)-3-butyn-1-ol (3.10h) 172 Following General Procedure A, 1-(ferrocenyl)-3-butyn-1-ol (3.10h) was prepared in 87% yield. 1H NMR (500 MHz, CDCl3) δ 4.53 (td, J = 6.2, 4.0 Hz, 1H), 4.33 – 4.27 (m, 1H), 4.27 – 4.23 (m, 1H), 4.22 – 4.18 (m, 5H), 4.17 (dt, J = 2.4, 0.8 Hz, 2H), 2.69 – 2.49 (m, 2H), 2.24 (dd, J = 4.1, 0.5 Hz, 1H), 2.06 (td, J = 2.7, 0.5 Hz, 1H). 13 C NMR (126 MHz, CDCl3) δ 91.82, 81.1, 70.61, 68.5, 68.2, 68.1, 68.0, 67.0, 65.8, 28.2. (This compound was used in the next step without further purification. See preparation of compound 3.11h) Preparation of 1-(2-thiophenyl)-3-butyn-1-ol (3.10i) Following General Procedure A, 1-(2-thiophenyl)-3-butyn-1-ol (3.10i) was prepared in 91% yield. Spectral data are in accord with reported literature values. 57 Preparation of 1-heptyn-4-ol (3.10j) Following General Procedure B, 1-heptyn-4-ol (3.10j) was prepared in 84% yield. Spectral data are in accord with reported literature values.58 173 Preparation of 1-cyclohexylbut-3-yn-1-ol (3.10k) Following general procedure B, 1-cyclohexylbut-3-yn-1-ol (3.10k) was prepared in 84% yield. 1H NMR (500 MHz, CDCl3) δ 3.49 (dp, J = 7.2, 3.8 Hz, 1H), 2.45 (ddd, J = 16.7, 4.1, 2.7 Hz, 1H), 2.35 (ddd, J = 16.7, 7.5, 2.6 Hz, 1H), 2.05 (td, J = 2.7, 0.6 Hz, 1H), 1.97 – 1.86 (m, 2H), 1.75 (ddddd, J = 13.2, 6.4, 5.0, 3.3, 1.8 Hz, 2H), 1.66 (dddd, J = 13.6, 6.9, 3.3, 1.7 Hz, 2H), 1.46 (tdt, J = 11.7, 6.7, 3.4 Hz, 1H), 1.24 (dddd, J = 16.2, 9.0, 3.4, 1.9 Hz, 2H), 1.20 – 1.11 (m, 1H), 1.07 – 0.96 (m, 2H). 13C NMR (126 MHz, CDCl3) δ 81.3, 74.0, 70.7, 42.5, 29.0, 28.1, 26.3, 26.1, 25.9, 24.6. Spectral data are in accord with reported literature values. 57 Preparation of 1-cyclopropylbut-3-yn-1-ol (3.10l) Following General Procedure B, 1-cyclopropylbut-3-yn-1-ol (3.10l) was prepared in 73% yield. 1H NMR (500 MHz, CDCl3) δ 3.06 (ddd, J = 8.6, 6.8, 4.5 Hz, 1H), 2.56 (dddd, J = 16.7, 4.6, 2.6, 1.1 Hz, 1H), 2.47 (dddd, J = 16.9, 6.8, 2.7, 1.1 Hz, 1H), 2.06 (td, J = 2.6, 1.1 Hz, 1H), 2.02 (s, 1H), 1.09 – 0.99 (m, 1H), 0.59 – 0.51 (m, 2H), 0.37 (dddt, J = 8.8, 5.0, 2.5, 1.0 Hz, 1H), 0.26 (dddt, J = 10.5, 4.5, 2.3, 1.1 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 81.0, 74.6, 70.5, 27.1, 16.8, 2.9, 174 2.5. Preparation of 1-(3-chlorophenyl)-3-butyn-1-ol (3.10n) Following General Procedure A, 1-(3-chlorophenyl)-3-butyn-1-ol was prepared in ~100% yield. Spectral data are in accord with reported literature values. 59 Preparation of 1-(pyridin-2-yl)but-3-yn-1-ol (3.10o) Following General Procedure A, 1-(pyridin-2-yl)but-3-yn-1-ol (3.10o) was prepared in ~100% yield. 1H NMR (500 MHz, CDCl3) δ 8.54 (d, J = 4.9 Hz, 1H), 7.70 (td, J = 7.7, 1.8 Hz, 1H), 7.41 (d, J = 7.9 Hz, 1H), 7.23 (ddd, J = 7.6, 4.9, 1.2 Hz, 1H), 4.89 (t, J = 6.1 Hz, 1H), 4.49 (s, 1H), 2.70 (ddd, J = 6.1, 2.7, 1.0 Hz, 2H), 2.01 (t, J = 2.7 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 159.9, 148.3, 136.7, 122.8, 120.7, 80.4, 71.0, 70.8, 28.3. Spectral data are in accord with reported literature values.57 175 Preparation of 1-(naphthalen-2-yl)but-3-yn-1-ol (3.10p) Following General Procedure A, 1-(naphthalen-2-yl)but-3-yn-1-ol (3.10p) was prepared in ~100% yield. 1H NMR (500 MHz, CDCl3) δ 7.87 – 7.82 (m, 4H), 7.52 – 7.48 (m, 3H), 5.03 (t, J = 6.4 Hz, 1H), 2.74 (dd, J = 6.4, 2.6 Hz, 2H), 2.70 (s, 1H), 2.10 (t, J = 2.6 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 139.7, 133.1, 133.0, 128.2, 128.0, 127.6, 126.2, 126.0, 124.6, 123.6, 80.6, 72.4, 71.0, 29.3. Spectral data are in accord with reported literature values. 57 Preparation of 1-(pyridin-4-yl)but-3-yn-1-ol (3.10q) Following General Procedure A, 1-(pyridin-4-yl)but-3-yn-1-ol (3.10q) was prepared in ~100% yield as white solid that was soluble in DMF and DMSO. The solid was insoluble in THF, diethyl ether, pentane, hexanes, cyclohexane, benzene, toluene, dichloromethane, and chloroform. Spectroscopic and melting point data for this compound: mp 136 to 137 °C; 1H NMR (500 MHz, DMSO-d6) δ 8.52 (d, J = 6.2 Hz, 2H), 7.50 (d, J = 6.2 Hz, 2H), 5.84 (d, J = 4.5 Hz, 1H (OH)), 4.75 (q, J = 6.0 Hz, 1H), 2.75 (t, J = 2.6 Hz, 1H), 2.61 – 2.51 (m, 2H). 13C NMR (126 MHz, DMSO- 176 d6) δ 155.1, 149.1, 122.5, 81.4, 73.5, 69.9, 28.6. IR (neat) 3492, 3270, 3097, 1618, 1559, 1424, 1392, 1334, 1065, 1028, 845, 817 cm-1. Preparation of 3-(dimethyl(phenyl)silyl)-1-phenylbut-3-en-1-ol (3.11a) Following general procedure C, 1-phenylbut-3-yn-1-ol (3.10a) (1.68 g, 11.5 mmol, 1 equiv), dimethylvinylsilyl chloride (1.19 g, 17.5 mmol, 1.5 equiv), imidazole (2.08, 17.5 mmol, 1.5 equiv), in THF (50 mL) afforded the O-dimethylvinylsilyl derivative in nearly quantitative yield, which was used in the next step without further purification. The O-dimethylvinylsilyl intermediate (1.22 g, 5.3 mmol, 1 equiv) was then treated with dimethylphenylsilane (0.72 g, 5.3 mmol, 1 equiv), and Karstedt catalyst solution (236 L, 0.002 equiv) at 80 ºC for 1.5 h and cooled down to room temperature. Treatment with TBAF solution (6.3 mL, 6.3 mmol, 1.2 equiv), workup and purification by silica gel chromatography (12% EtOAc in hexanes) afforded 3.11a as a colorless oil (507 mg, 1.8 mmol) and a mixture its regioisomer (278 mg, 1.0 mmol) in 53% overall yield. 3.11a is a known compound and its spectral data are in accord with reported literature values.60 1H NMR (500 MHz, CDCl3)  7.53 (m, 2 H), 7.36 (m, 3 H), 7.28 (m, 2 H), 7.21 (m, 3 H), 5.84 (m, 1 H), 5.62 (m, 1 H), 4.53 (dt, J = 3.0, 9.5 Hz, 1 H), 2.58 (A of ABX system, m, 1 H), 2.43 (B of ABX system, dd, J = 10.0, 14.0 Hz, 1 H), 1.94 (d, J = 2.5 Hz, 1 H), 0.43 (s, 6 H). 13C NMR (126 MHz, CDCl3)  147.4, 144.1, 137.6, 133.9 (2 C), 130.0, 129.3, 128.3 (2 C), 128.0 (2 177 C), 127.3, 125.7 (2 C), 72.2, 47.0, -2.90, -2.99. IR (neat) 3420, 3067, 2957, 1427, 1250, 1111, 833 cm-1. Preparation of 3-(ethyldimethylsilyl)-1-phenylbut-3-en-1-ol (3.11b) Compound 3.11b was prepared by a slight modification of General Procedure C. 1- phenylbut-3-yn-1-ol (0.77 g, 5.27 mmol, 1 equiv), dimethylvinylsilyl chloride (0.95 g, 7.9 mmol, 1.5 equiv), imidazole (538 mg, 7.9 mmol, 1.5 equiv), in THF (20 mL) afforded the O- dimethylvinylsilyl derivative in nearly quantitative yield. The O-dimethylvinylsilyl intermediate (0.5 g, 2.17 mmol, 1 equiv) was then treated with ethyldimethylsilane (0.21 g, 2.39 mmol, 1.1 equiv), and Karstedt catalyst solution (97 L, 0.002 equiv) at 45 ºC for 1.5 h and cooled down to room temperature. Treatment with TBAF solution (2.4 mL, 2.4 mmol, 1.1 equiv), workup and purification by silica gel chromatography (10% EtOAc in hexanes) afforded 3.11b as a colorless oil (193 mg, 0.82 mmol) and a mixture of 3.11b and its regioisomer (200 mg, 0.85 mmol) in 77% overall yield. 1H NMR (500 MHz, CDCl3)  7.35 (m, 4 H), 7.26 (m, 1 H), 5.76 (m, 1 H), 5.53 (dt, J = 0.5, 8.0, Hz, 1 H), 4.73 (ddd, J = 2.0, 3.5, 10.0 Hz, 1 H), 2.62 (dddd, J = 0.5, 1.5, 3.5, 14.0 Hz, 1 H), 2.43 (dd, J = 9.5, 14.5 Hz, 1 H), 2.10 (m, 1 H), 0.93 (t, J = 8.0 Hz, 3 H), 0.61 (q, J = 8.0 Hz, 2 H), 0.11 (s, 6 H). 13C NMR (126 MHz, CDCl3)  148.2, 128.7, 128.4 (2 C), 127.4, 125.8 (2 C), 72.2, 47.1, 7.3, 6.9, -3.6, -3.7. IR (film) 3389, 3031, 2955, 1248, 1049, 833 cm -1. HRMS (EI) m/z 178 217.1401 [(M-HO)+; calcd for C14H21Si, 217.1413]. Preparation of 1-phenyl-3-(triethylsilyl)but-3-en-1-ol (3.11c) Following general procedure C, 1-phenylbut-3-yn-1-ol (3.10a) (1.5 g, 10.26 mmol, 1 equiv), dimethylvinylsilyl chloride (1.86 g, 15.39 mmol, 1.5 equiv), imidazole (1.05, 15.39 mmol, 1.5 equiv), in THF (45 mL) afforded the O-dimethylvinylsilyl derivative in nearly quantitative yield, which was used in the next step without further purification. The O-dimethylvinylsilyl intermediate (1.4 g, 6.07 mmol, 1 equiv) was then treated with triethylsilane (0.7 g, 6.07 mmol, 1 equiv), and Karstedt catalyst solution (230 L, 0.002 equiv) at 80 ºC for 1.5 h and cooled down to room temperature. Treatment with TBAF solution (6.1 mL, 6.1 mmol, 1 equiv), workup and purification by silica gel chromatography (9% EtOAc in hexanes) afforded 3.11c as a colorless oil (1.08 g, 4.11 mmol) and a mixture of 3.11c and its regioisomer (144 mg, 0.55 mmol) in 77% overall yield. 1H NMR (600 MHz, CDCl3)  7.37–7.32 (m, 4 H), 7.26 (m, 1 H), 5.82 (m, 1 H), 5.52 (d, J = 2.5 Hz, 1 H), 4.73 (dd, J = 2.5, 8.0 Hz, 1 H), 2.60 (m, 1 H), 2.40 (dd, J = 8.0, 11.5 Hz, 1 H), 2.13 (s, 1 H), 0.95 (t, J = 6.5 Hz, 9 H), 0.65 (dq, J = 1.5, 6.0 Hz, 6 H). 13C NMR (126 MHz, CDCl3)  146.2, 144.1, 129.5, 128.4 (2 C), 127.4, 125.8 (2 C), 72.0, 47.2, 7.3, 2.9. IR (film) 3406, 3032, 2953, 2876, 1456, 1008, 721 cm-1. HRMS (EI) m/z 245.1712 [(M-OH)+; calcd for C16H25Si, 245.1726]. 179 Preparation of 3-(dimethyl(phenyl)silyl)-1-(p-tolyl)but-3-en-1-ol (3.11d) Following general procedure C, 1-(p-tolyl)but-3-yn-1-ol (3.10d) (1.1 g, 6.9 mmol, 1 equiv), dimethylvinylsilyl chloride (1.25 g, 10.35 mmol, 1.5 equiv), imidazole (0.7, 10.35 mmol, 1.5 equiv), in THF (30 mL) afforded the O-dimethylvinylsilyl derivative in nearly quantitative yield, which was used in the next step without further purification. The O-dimethylvinylsilyl intermediate (957 mg, 3.92 mmol, 1 equiv) was then treated with phenyldimethylsilane (534 mg, 3.92 mmol, 1 equiv), and Karstedt catalyst solution (175 L, 0.002 equiv) at 80 ºC for 1.1 h and cooled down to room temperature. Treatment with TBAF solution (4.7 mL, 4.7 mmol, 1.2 equiv), workup and purification by silica gel chromatography (12% EtOAc in hexanes) afforded 3.11d as a colorless oil (233 mg, 0.79 mmol), and a mixture of 3.11d and its regioisomer (506 mg, 1.71 mmol) in 77% overall yield. 1H NMR (500 MHz, CDCl3)  7.54 (m, 2 H), 7.37 (m, 3 H), 7.11 (s, 4 H), 5.85 (m, 1 H), 5.62 (d, J = 2.5 Hz, 1 H), 4.53 (ddd, J = 2.5, 3.5, 9.5 Hz, 1 H), 2.57 (A of ABX system, m, 1 H), 2.44 (B of ABX system, dd, J = 10.0, 14.0 Hz, 1 H), 2.32 (s, 3 H), 1.92 (d, J = 2.0 Hz, 1 H), 0.438 (s, 3 H), 0.429 (s, 3 H). 13C NMR (126 MHz, CDCl3)  147.5, 141.1, 137.7, 136.9, 133.9 (2 C), 129.8, 129.2, 128.9 (2 C), 127.9 (2 C), 125.6 (2 C), 72.0, 46.9, 21.1, -2.896, - 2.977. IR (neat) 3422, 3047, 2955, 1427, 1248, 1111, 1047, 815 cm-1. HRMS (EI) m/z 279.1568 [(M-OH)+; calcd for C19H23Si, 279.1569]. 180 Preparation of 3-(ethyldimethylsilyl)-1-(o-tolyl)but-3-en-1-ol (3.11f) Following General Procedure D, 1-(o-tolyl)but-3-yn-1-ol (3.10f) (400 mg, 2.5 mmol, 1 equiv), ethyldimethylsilane (265 mg, 3 mmol, 1.2 equiv), dichloromethane (5 mL) and [Cp*Ru(MeCN)3]PF6 (25.2 mg, 0.05 mmol, 0.02 equiv) at room temperature for 1 h, followed by silica gel chromatography (10% EtOAc in hexanes) afforded 3.11f as colorless oil (435 mg, 1.75 mmol) and a mixture of 3.11f and its regioisomer (110 mg, 0.44 mmol) in 88% overall yield. 1H NMR (600 MHz, CDCl3)  7.52 (dd, J = 1.2, 7.2 Hz, 1 H), 7.23 (m, 1 H), 7.16 (dt, J = 1.8, 7.2 Hz, 1 H), 7.12 (dd, J = 0.6, 7.8 Hz, 1 H), 5.82 (m, 1 H), 5.58 (d, J = 3.0 Hz, 1 H), 4.96 (dd, J = 3.0, 9.6 Hz, 1 H), 2.59 (m, 1 H), 2.36 (dd, J = 10.2, 13.8 Hz, 1 H), 2.35 (s, 3 H), 2.05 (s, 1 H), 0.94 (t, J = 8.4 Hz, 3 H), 0.62 (q, J = 7.8 Hz, 2 H), 0.12 (s, 6 H). 13C NMR (126 MHz, CDCl3)  148.4, 142.3, 134.2, 130.3, 128.8, 127.1, 126.3, 125.3, 68.4, 45.4, 19.2, 7.3, 6.9, -3.6, -3.7. IR (film) 3408, 3052, 2953, 1458, 1248, 1049, 819 cm-1. HRMS (EI) m/z 231.1555 [(M-OH)+; calcd for C15H23Si, 231.1569]. Preparation of 3-(ethyldimethylsilyl)-1-(3-methoxyphenyl)but-3-en-1-ol (3.11g) Following General Procedure D, 1-(3-methoxyphenyl)but-3-yn-1-ol (3.10g) (400 mg, 2.27 181 mmol, 1 equiv), ethyldimethylsilane (240 mg, 2.72 mmol, 1.2 equiv), dichloromethane (4.5 mL) and [Cp*Ru(MeCN)3]PF6 (22.9 mg, 0.045 mmol, 0.02 equiv) at room temperature for 1.5 h, followed by silica gel chromatography (12–15% EtOAc in hexanes) afforded 3.11g as colorless oil (305.8 mg, 1.16 mmol) and a mixture of 3.11g and its regioisomer (28.5 mg, 0.12 mmol) in 53% overall yield. 1H NMR (500 MHz, CDCl3)  7.24 (t, J = 7.0 Hz, 1 H), 6.93 (m, 2 H), 6.80 (m, 1 H), 5.76 (m, 1 H), 5.53 (d, J = 2.5 Hz, 1 H), 4.70 (dt, J = 3.0, 4.5 Hz, 1 H), 3.81 (s, 3 H), 2.62 (m, 1 H), 2.41 (dd, J = 10.0, 14.0 Hz, 1 H), 2.08 (d, J = 2.0 Hz, 1 H), 0.93 (t, J = 8.0 Hz, 3 H), 0.60 (q, J = 8.0 Hz, 2 H), 0.10 (s, 6 H). 13 C NMR (126 MHz, CDCl3)  159.7, 148.2, 145.9, 129.4, 128.7, 118.1, 112.8, 111.3, 72.1, 55.2, 47.0, 7.3, 6.9, -3.6, -3.7. IR (film) 3049, 2955, 1603, 1255, 1045, 777 cm-1. HRMS (EI) m/z 246.1441 [(M-H2O)+; calcd for C15H22OSi, 246.1440]. Preparation of 3-(dimethyl(phenyl)silyl)-1-(ferrocenyl)but-3-en-1-ol (3.11h) Following general procedure C, 1-(ferrocenyl)but-3-yn-1-ol (3.10h) (1.6 g, 6.3 mmol, 1 equiv), dimethylvinylsilyl chloride (1.14 g, 9.4 mmol, 1.5 equiv), imidazole (642 mg, 9.4 mmol, 1.5 equiv), in THF (27 mL) afforded the O-dimethylvinylsilyl derivative in nearly quantitative yield, which was used in the next step without further purification. The O-dimethylvinylsilyl intermediate (6.3 mmol, 1 equiv) was then treated with phenyldimethylsilane (858 mg, 6.3 mmol, 1 equiv), and Karstedt catalyst solution (281 L, 0.013 mmol, 0.002 equiv) at 75 ºC for 2 h and cooled down to room temperature. Treatment with TBAF solution (7.6 mL, 7.6 mmol, 1.2 equiv), 182 workup and purification by silica gel chromatography (10% EtOAc in hexanes) afforded a mixture of 3.11h and its regioisomer (1.0:0.2 ratio) as an orange oil (1.72 g, 4.47 mmol, 71% isolated yield). 1H NMR (500 MHz, CDCl3)  7.53 (m, 2 H), 7.35 (m, 3 H), 5.79 (m, 1 H), 5.57 (d, J = 3.0 Hz, 1 H), 4.28 (dq, J = 4.0, 9.5 Hz, 1 H), 4.15 (q, J = 1.5 Hz, 1 H), 4.08 (t, J = 3.0 Hz, 2 H), 4.07 (s, 5 H), 4.01 (q, J = 3.0 Hz, 1 H), 2.51 (m, 1 H), 2.42 (dd, J = 9.0, 14.0 Hz, 1 H), 1.86 (d, J = 3.5 Hz, 1 H), 0.40 (s, 3 H), 0.39 (s, 3 H). 13C NMR (126 MHz, CDCl3)  147.3, 138.0, 134.0 (2 C), 129.2, 129.1, 127.9 (2 C), 93.3, 68.3 (5 C), 68.1, 67.7, 67.6, 66.8, 65.7, 45.1, -2.8, -2.9. IR (film) 3412, 3097, 2955, 1427, 1248, 1107, 817 cm-1. HRMS (ESI) m/z 373.1069 [(M-OH)+; calcd for C22H25FeSi, 373.1075]. Preparation of 3-(ethyldimethylsilyl)-1-(thiophen-2-yl)but-3-en-1-ol (3.11i) Following General Procedure D, 1-(thiophen-2-yl)but-3-yn-1-ol (3.10i) (400 mg, 2.63 mmol, 1 equiv), ethyldimethylsilane (278 mg, 3.15 mmol, 1.2 equiv), dichloromethane (5.3 mL) and [Cp*Ru(MeCN)3]PF6 (26.5 mg, 0.053 mmol, 0.02 equiv) at room temperature for 1.5 h, followed by silica gel chromatography (15% EtOAc in hexanes) afforded 3.11i as colorless oil (178 mg, 0.61 mmol, 23% isolated yield). 1H NMR (500 MHz, CDCl3)  7.22 (dd, J = 1.5, 5.0 Hz, 1 H), 6.96 (m, 2 H), 5.75 (m, 1 H), 5.53 (d, J = 2.5 Hz, 1 H), 4.99 (dt, J = 3.0, 9.5 Hz, 1 H), 2.73 (m, 1 H), 2.58 (dd, J = 9.5, 14.5 Hz, 1 H), 2.17 (d, J = 3.0 Hz, 1 H), 0.93 (t, J = 8.0 Hz, 3 H), 0.59 (q, J = 8.0 Hz, 2 H), 0.09 (s, 6 H). 13C NMR (126 MHz, CDCl3)  147.9, 147.6, 128.9 126.5, 124.4, 123.5, 68.5, 46.8, 7.3, 6.8, -3.7, -3.8. IR (film) 3402, 2955, 1248, 1116, 833 cm-1. HRMS (EI) m/z 183 223.0975 [(M-OH)+; calcd for C12H19SSi, 223.0977]. Preparation of 2-(dimethyl(phenyl)silyl)hept-1-en-4-ol (3.11j) Following general procedure C, hept-1-yn-4-ol (3.10j) (1.1 g, 9.8 mmol, 1 equiv), dimethylvinylsilyl chloride (1.77 g, 14.7 mmol, 1.5 equiv), imidazole (1 g, 14.7 mmol, 1.5 equiv), in THF (43 mL) afforded the O-dimethylvinylsilyl derivative in nearly quantitative yield, which was used in the next step without further purification. The O-dimethylvinylsilyl intermediate (1.9 g, 9.8 mmol, 1 equiv) was then treated with phenyldimethylsilane (1.3 g, 9.8 mmol, 1 equiv), and Karstedt catalyst solution (440 L, 0.02 mmol, 0.002 equiv) at 80 ºC for 1.5 h and cooled down to room temperature. Treatment with TBAF solution (10.5 mL, 10.5 mmol, 1.2 equiv), in THF (100 mL), workup and purification by silica gel chromatography (15% EtOAc in hexanes) afforded 3.11j as a colorless oil (845 mg, 3.40 mmol) and a mixture of 3.11j and its regioisomer (929 mg, 3.74 mmol) in 73% overall yield. 1H NMR (500 MHz, CDCl3)  7.49 (m, 2 H), 7.34 (m, 3 H), 5.78 (m, 1 H), 5.57 (d, J = 3.0 Hz, 1 H), 3.48 (m, 1 H), 2.37 (m, 1 H), 2.13 (dd, J = 9.0, 13.5 Hz, 1 H), 1.50 (s, 1 H), 1.35 (m, 3 H), 1.23 (m, 1 H), 0.84 (t, J = 6.5 Hz, 3 H), 0.39 (s, 3 H), 0.38 (s, 3 H). 13 C NMR (126 MHz, CDCl3)  147.8, 137.8, 133.8 (2 C), 129.4, 129.2, 127.9 (2 C), 69.3, 45.0, 39.1, 18.8, 14.0, -2.87, -2.93. IR (film) 3379, 3049, 2957, 2872, 1427, 1250, 1111, 817 cm -1. HRMS (EI) m/z 230.1503 [(M-H2O)+; calcd for C15H22Si, 230.1491]. 184 Preparation of 1-cyclohexyl-3-(dimethyl(phenyl)silyl)but-3-en-1-ol (3.11k) Following general procedure C, 1-cyclohexylbut-3-yn-1-ol (3.10k) (1.05 g, 6.9 mmol, 1 equiv), dimethylvinylsilyl chloride (1.25 g, 10.39 mmol, 1.5 equiv), imidazole (0.7 g, 10.39 mmol, 1.5 equiv), in THF (30 mL) afforded the O-dimethylvinylsilyl derivative in nearly quantitative yield, which was used in the next step without further purification. The O-dimethylvinylsilyl intermediate (1.06 g, 4.46 mmol, 1 equiv) was then treated with phenyldimethylsilane (608 mg, 4.46 mmol, 1 equiv), and Karstedt catalyst solution (199 L, 0.009 mmol, 0.002 equiv) at 75 ºC for 1.5 h and cooled down to room temperature. Treatment with TBAF solution (5.35 mL, 5.35 mmol, 1.2 equiv), in THF (50 mL), workup and purification by silica gel chromatography (10% EtOAc in hexanes) afforded a mixture of 3.11k and its regioisomer (1.0:0.14 ratio) as a colorless oil (856 mg, 2.99 mmol, 67% isolated yield). 1H NMR (500 MHz, CDCl3)  7.50 (m, 2 H), 7.34 (m, 3 H), 5.79 (quintet, 1 H), 5.57 (d, J = 3.0 Hz, 1 H), 3.24 (m, 1 H), 2.45 (A of ABX system, m, 1 H), 2.07 (B of ABX system, dd, J = 10.0, 13.5 Hz, 1 H), 1.75–1.67 (m, 3 H), 1.61 (m, 1 H), 1.55 (m, 1 H), 1.30–1.23 (m, 2 H), 1.22–1.08 (m, 3 H), 0.94 (m, 2 H), 0.39 (s, 3 H), 0.38 (s, 3 H). 13C NMR (126 MHz, CDCl3)  148.3, 137.8, 133.8 (2 C), 129.5, 129.1, 127.9 (2 C), 73.4, 43.3, 41.7, 28.9, 28.1, 26.5, 26.3, 26.1, -2.77, -2.86. IR (neat) 3472, 3049, 2926, 2853, 1427, 1250, 1113, 817 cm-1. HRMS (EI) m/z 288.1894 [(M)+; calcd for C18H28OSi, 288.1909]. 185 Preparation of 1-cyclopropyl-3-(dimethyl(phenyl)silyl)but-3-en-1-ol (3.11l) Following general procedure C, 1-cyclopropylbut-3-yn-1-ol (3.10l) (928 mg, 8.42 mmol, 1 equiv), dimethylvinylsilyl chloride (1.53 g, 12.64 mmol, 1.5 equiv), imidazole (861 mg, 12.64 mmol, 1.5 equiv), in THF (34 mL) afforded the O-dimethylvinylsilyl derivative in nearly quantitative yield, which was used in the next step without further purification. The O- dimethylvinylsilyl intermediate (833 mg, 4.2 mmol, 1 equiv) was then treated with phenyldimethylsilane (572 mg, 4.2 mmol, 1 equiv), and Karstedt catalyst solution (187 L, 0.008 mmol, 0.002 equiv) at 80 ºC for 1.5 h and cooled down to room temperature. Treatment with TBAF solution (4.2 mL, 4.2 mmol, 1.2 equiv), in THF (70 mL), workup and purification by silica gel chromatography (15% EtOAc in hexanes) afforded 3.11l as a colorless oil (527 mg, 2.14 mmol, 51% isolated yield). 1H NMR (500 MHz, CDCl3)  7.49 (m, 2 H), 7.34 (m, 3 H), 5.81 (m, 1 H), 5.56 (dd, J = 1.0, 3.0 Hz, 1 H), 2.76 (dt, J = 3.0, 9.0 Hz, 1 H), 2.52 (m, 1 H), 2.29 (dd, J = 4.5, 13.5 Hz, 1 H), 1.58 (s, 1 H), 0.80 (m, 1 H), 0.50–0.36 (m, 2 H), 0.38 (s, 6 H), 0.21 (m, 1 H), 0.00 (m, 1 H). 13C NMR (126 MHz, CDCl3)  147.5, 137.8, 133.8 (2 C), 129.3, 129.1, 127.9 (2 C), 74.5, 44.3, 17.3, 2.9, 2.2, -2.8, -2.9. IR (film) 3408, 3069, 2957, 2909, 1427, 1250, 1111, 817 cm-1. HRMS (EI) m/z 228.1331 [(M-H2O)+; calcd for C15H20Si, 228.1334]. 186 Preparation of 1-cyclopropyl-3-(triethylsilyl)but-3-en-1-ol (3.11m) Following general procedure C, 1-cyclopropylbut-3-yn-1-ol (3.10l) (928 mg, 8.42 mmol, 1 equiv), dimethylvinylsilyl chloride (1.53 g, 12.64 mmol, 1.5 equiv), imidazole (861 mg, 12.64 mmol, 1.5 equiv), in THF (34 mL) afforded the O-dimethylvinylsilyl derivative in nearly quantitative yield, which was used in the next step without further purification. The O- dimethylvinylsilyl intermediate (833 mg, 4.2 mmol, 1 equiv) was then treated with triethylsilane (488 mg, 4.2 mmol, 1 equiv), and Karstedt catalyst solution (187 L, 0.008 mmol, 0.002 equiv) at 80 ºC for 1.5 h and cooled down to room temperature. Treatment with TBAF solution (4.2 mL, 4.2 mmol, 1.0 equiv), in THF (70 mL), workup and purification by silica gel chromatography (10% EtOAc in hexanes) afforded 3.11m as a colorless oil (570 mg, 2.52 mmol, 60% isolated yield). 1H NMR (500 MHz, CDCl3) δ 5.76 (ddd, J = 2.9, 1.6, 1.1 Hz, 1H), 5.46 (dt, J = 3.0, 0.7 Hz, 1H), 2.93 (ddd, J = 9.7, 8.1, 3.1 Hz, 1H), 2.53 (dddd, J = 14.1, 3.1, 1.6, 0.7 Hz, 1H), 2.26 (ddt, J = 13.9, 9.6, 0.8 Hz, 1H), 0.95 – 0.84 (m, 10H), 0.59 (qd, J = 7.9, 3.1 Hz, 6H), 0.55 – 0.45 (m, 2H), 0.38 – 0.30 (m, 1H), 0.22 – 0.14 (m, 1H). 13C NMR (126 MHz, CDCl3) δ 146.2, 128.8, 74.2, 44.6, 17.4, 7.3, 3.0, 2.2. HRMS (EI) m/z 206.1484 [(M-H2O)+; calcd for C13H24Si, 206.1491]. 187 Preparation of 1-(3-chlorophenyl)-3-(ethyldimethylsilyl)but-3-en-1-ol (3.11n) Following general procedure D, 1-(3-chlorophenyl)but-3-yn-1-ol (3.10n) (400 mg, 2.21 mmol, 1 equiv), ethyldimethylsilane (234 mg, 2.66 mmol, 1.2 equiv), dichloromethane (4.4 mL) and [Cp*Ru(MeCN)3]PF6 (22.3 mg, 0.044 mmol, 0.02 equiv) at room temperature for 1.5 h, followed by silica gel chromatography (10% EtOAc in hexanes) afforded 3.11n as colorless oil (438 mg, 1.63 mmol) and a mixture of its regioisomer (47 mg, 0.17 mmol) in 81% overall yield. 1 H NMR (500 MHz, CDCl3)  7.36 (m, 2 H), 7.25–7.21 (m, 3 H), 5.76 (m, 1 H), 5.55 (dt, J = 1.0, 3.0 Hz, 1 H), 4.69 (dd, J = 3.5, 10.5 Hz, 1 H), 2.59 (m, 1 H), 2.36 (ddd, J = 0.5, 10.0, 14.0 Hz, 1 H), 2.14 (s, 1 H), 0.93 (t, J = 7.5 Hz, 3 H), 0.60 (q, J = 8.0 Hz, 2 H), 0.10 (s, 6 H). 13C NMR (126 MHz, CDCl3)  147.9, 146.2, 134.3, 129.6, 129.1, 127.5, 126.0, 123.9, 71.5, 47.1, 7.3, 6.9, -3.6, - 3.7. IR (film) 3402, 3051, 2955, 1431, 1248, 1055, 817 cm-1. HRMS (EI) m/z 251.1014 [(M-OH)+; calcd for C14H20SiCl, 251.1023]. Preparation of 1-(pyridin-2-yl)-3-(triethylsilyl)but-3-en-1-ol (3.11o) 188 Following general procedure C, 1-(pyridin-2-yl)but-3-yn-1-ol (3.10o) (2.21 g, 15.0 mmol, 1.0 equiv), dimethylvinylsilyl chloride (2.5 mL, 18.0 mmol, 1.2 equiv), triethyl amine (5.1 mL, 36.0 mmol, 2.4 equiv), in DMF (15 mL) afforded 3.08 g, 89% of O-dimethylvinylsilyl derivative, which was used in the next step without further purification. The O-dimethylvinylsilyl intermediate (1.39 g, 6.0 mmol, 1.0 equiv) was then treated with triethylsilane (0.96 mL, 6.0 mmol, 1.0 equiv), and Karstedt catalyst solution (270 L, 0.012 mmol, 0.002 equiv) at 80 ºC for 1.5 h and cooled down to room temperature. Treatment with TBAF solution 1.0 M in THF (7.2 mL, 7.2 mmol, 1.2 equiv), in THF (40 mL), workup and purification by silica gel chromatography (50% EtOAc in hexanes) afforded 350 mg, 1.32 mmol (22% isolated yield) of homoallylic alcohol 3.11o as a colorless oil and about 75% of unreacted homopropargyl alcohol. Spectroscopic data for compound 3.11o: 1H NMR (500 MHz, CDCl3) δ 8.54 (ddd, J = 4.9, 1.7, 1.0 Hz, 1H), 7.66 (td, J = 7.7, 1.8 Hz, 1H), 7.34 – 7.28 (m, 1H), 7.18 (ddd, J = 7.5, 4.8, 1.2 Hz, 1H), 5.80 (dt, J = 2.9, 1.4 Hz, 1H), 5.50 (dt, J = 2.8, 0.8 Hz, 1H), 4.83 (dd, J = 9.1, 4.1 Hz, 1H), 3.69 (s, 1H), 2.67 (dddd, J = 14.4, 4.2, 1.6, 0.8 Hz, 1H), 2.41 (ddt, J = 14.4, 9.0, 1.1 Hz, 1H), 0.94 (t, J = 7.9 Hz, 9H), 0.65 (q, J = 7.9 Hz, 6H). 13C NMR (126 MHz, CDCl3) δ 162.2, 148.4, 145.5, 136.5, 128.9, 122.2, 120.5, 71.9, 45.6, 7.3, 2.9. HRMS (ESI) m/z 264.1783 [(M + H)+; calcd for C15H26NOSi, 264.1784]. Preparation of 3-(dimethyl(phenyl)silyl)-1-(naphthalen-2-yl)but-3-en-1-ol (3.11p) Following general procedure C, 1-(naphthalen-2-yl)but-3-yn-1-ol (3.10p) (2.65 g, 13.5 189 mmol, 1 equiv), dimethylvinylsilyl chloride (2.8 mL, 20.25 mmol, 1.5 equiv), imidazole (1.38 g, 20.25 mmol, 1.5 equiv), in THF (60 mL) afforded the O-dimethylvinylsilyl derivative in nearly quantitative yield, which was used in the next step without further purification. The O- dimethylvinylsilyl intermediate (1.4 g, 5.0 mmol, 1 equiv) was then treated with dimethylphenylsilane (0.77 mL, 5.0 mmol, 1 equiv), and Karstedt catalyst solution (220 L, 0.01 mmol, 0.002 equiv) at 80 ºC for 1.5 h and cooled down to room temperature. Treatment with TBAF solution (6.0 mL, 5.0 mmol, 1.2 equiv), in THF (70 mL), workup and purification by silica gel chromatography (15% EtOAc in hexanes) afforded 3.11p as a colorless oil (1.26 g, 3.8 mmol, 76% isolated yield). 1H NMR (500 MHz, Chloroform-d) δ 7.85 – 7.80 (m, 3H), 7.66 (s, 1H), 7.63 – 7.58 (m, 2H), 7.52 – 7.45 (m, 2H), 7.45 – 7.40 (m, 3H), 7.37 (dd, J = 8.5, 1.7 Hz, 1H), 5.91 (dt, J = 2.8, 1.3 Hz, 1H), 5.68 (d, J = 2.8 Hz, 1H), 4.74 (dd, J = 9.9, 3.7 Hz, 1H), 2.72 (dddd, J = 14.1, 3.8, 1.5, 0.6 Hz, 1H), 2.56 (ddt, J = 14.1, 9.6, 1.0 Hz, 1H), 2.15 (s, 1H), 0.51 (s, 3H), 0.49 (s, 3H). 13 C NMR (126 MHz, Chloroform-d) δ 147.3, 141.4, 137.6, 133.9, 133.2, 132.8, 130.0, 129.3, 127.99, 128.97, 127.87, 127.6, 126.0, 125.6, 124.3, 123.9, 72.3, 46.9, -2.90, -2.94. IR (neat) 3424, 3051, 2955, 1427, 1248, 1111, 815 cm-1. HRMS (EI) m/z 315.1553 [(M-OH)+; calcd for C22H23Si, 315.1569]. Preparation of 1-(pyridin-4-yl)-3-(triethylsilyl)but-3-en-1-ol (3.11q) Following general procedure C, 1-(pyridin-4-yl)but-3-yn-1-ol (3.10q) (2.21 g, 15.0 mmol, 1.0 equiv), dimethylvinylsilyl chloride (2.5 mL, 18.0 mmol, 1.2 equiv), triethyl amine (5.1 mL, 190 36.0 mmol, 2.4 equiv), in DMF (15 mL) afforded 2.85 g, 82% of O-dimethylvinylsilyl derivative, which was used in the next step without further purification. The O-dimethylvinylsilyl intermediate (926 mg, 4.0 mmol, 1.0 equiv) was then treated with triethylsilane (0.64 mL, 4.0 mmol, 1.0 equiv), and Karstedt catalyst solution (180 L, 0.008 mmol, 0.002 equiv) at 80 ºC for 1.5 h and cooled down to room temperature. Treatment with TBAF solution 1.0 M in THF (4.8 mL, 4.8 mmol, 1.2 equiv), in THF (40 mL), workup and purification by silica gel chromatography (60% EtOAc in hexanes) afforded 706 mg, 2.68 mmol (67% isolated yield) of homoallylic alcohol 3.11q as a colorless oil. 1H NMR (500 MHz, CDCl3) δ 8.48 (d, J = 6.2 Hz, 2H), 7.28 (d, J = 6.1 Hz, 2H), 5.79 (dt, J = 2.7, 1.3 Hz, 1H), 5.53 (d, J = 2.7 Hz, 1H), 4.71 (dd, J = 9.8, 3.6 Hz, 1H), 3.21 (s, 1H), 2.56 (dd, J = 14.2, 3.6 Hz, 1H), 2.34 (dd, J = 14.2, 9.8 Hz, 1H), 0.93 (t, J = 7.9 Hz, 9H), 0.64 (qd, J = 7.8, 2.1 Hz, 6H). 13 C NMR (126 MHz, CDCl3) δ 153.4, 149.5, 145.3, 129.9, 120.8, 70.6, 46.7, 7.3, 2.9. HRMS (ESI) m/z 264.1788 [(M + H)+; calcd for C15H26NOSi, 264.1784]. Preparation of 3-(dimethyl(phenyl)silyl)-1-(pyridin-4-yl)but-3-en-1-ol (3.11r) The O-dimethylvinylsilyl of 1-(pyridin-4-yl)but-3-yn-1-ol (3.10q) intermediate (1273 mg, 5.5 mmol, 1.0 equiv) was treated with dimethylphenyl silane (0.84 mL, 5.5 mmol, 1.0 equiv), and Karstedt catalyst solution (250 L, 0.008 mmol, 0.002 equiv) at 80 ºC for 1.5 h and cooled down to room temperature. Treatment with TBAF solution 1.0 M in THF (6.6 mL, 6.6 mmol, 1.2 equiv), in THF (40 mL), workup and purification by silica gel chromatography (20% EtOAc in hexanes) 191 afforded 1175 mg, 4.13 mmol (75% isolated yield) of homoallylic alcohol 3.11r as a colorless oil. 1 H NMR (500 MHz, CDCl3) δ 8.41 (d, J = 6.1 Hz, 2H), 7.57 – 7.50 (m, 2H), 7.41 – 7.34 (m, 3H), 7.08 (d, J = 6.1 Hz, 2H), 5.83 (dt, J = 2.6, 1.3 Hz, 1H), 5.65 (d, J = 2.7 Hz, 1H), 4.48 (dd, J = 9.7, 3.7 Hz, 1H), 3.01 (s, 1H), 2.55 (ddd, J = 13.9, 3.7, 1.4 Hz, 1H), 2.37 (dd, J = 14.1, 9.7 Hz, 1H), 0.44 (s, 3H), 0.43 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 153.2, 149.4, 146.7, 137.4, 133.8, 130.4, 129.4, 128.0, 120.7, 70.7, 46.6, -3.0, -3.1. HRMS (ESI) m/z 284.1475 [(M + H)+; calcd for C17H22NOSi, 284.1471]. Preparation of (4-(allyloxy)-4-phenylbut-1-en-2-yl)dimethyl(phenyl)silane (3.12a) Following General Procedure E, alcohol 3.11a (486 mg, 1.72 mmol, 1 equiv), allyl bromide (0.36 mL, 4.3 mmol, 2.5 equiv), THF (3.6 mL), and t-BuONa (496 mg, 5.16 mmol, 3 equiv) afforded, after silica gel chromatography (25% CH2Cl2 in hexanes), compound 3.12a as a colorless oil (499 mg, 1.55 mmol, 90% isolated yield). 1H NMR (500 MHz, CDCl3)  7.51 (m, 2 H), 7.33 (m, 3 H), 7.27 (t, J = 6.5 Hz, 2 H), 7.22 (m, 1 H), 7.13 (m, 2H), 5.77(m, 1 H), 5.69 (m, 1 H), 5.47 (d, J = 2.5 Hz, 1 H), 5.14 (m, 1 H), 5.07 (m, 1 H), 4.19 (dd, J = 5.5, 8.0 Hz, 1 H), 3.74 (A of ABX system, ddt, J = 1.5, 5.5, 13.0 Hz, 1 H), 3.52 (B of ABX system, ddt, J = 1.5, 6.0, 13.0 Hz, 1 H), 2.64 (A of ABX system, dd, J = 8.0, 14.5 Hz, 1 H), 2.39 (B of ABX system, dd, J = 5.5, 14.5 Hz, 1 H), 0.36 (s, 6 H). 13C NMR (126 MHz, CDCl3)  146.3, 142.4, 138.3, 135.0, 134.0 (2 C), 129.2, 128.9, 128.2 (2 C), 127.7 (2 C), 127.4, 126.8 (2 C), 116.5, 80.7, 69.4, 44.7, -2.924, -2.917. IR (neat) 3067, 2955, 1427, 1248, 1111, 815 cm-1. HRMS (EI) m/z 307.1504 [(M-CH3)+; calcd for C20H23OSi, 307.1518]. 192 Preparation of (4-(allyloxy)-4-phenylbut-1-en-2-yl)(ethyl)dimethylsilane (3.12b) Following general procedure E, alcohol 3.11b (181 mg, 0.77 mmol, 1 equiv), allyl bromide (0.16 mL, 1.93 mmol, 2.5 equiv), THF (1.6 mL), and t-BuONa (223 mg, 2.32 mmol, 3 equiv) afforded, after silica gel chromatography (30% CH2Cl2 in hexanes), compound 3.12b as a colorless oil (165.2 mg, 0.60 mmol, 78% isolated yield). 1H NMR (500 MHz, CDCl3)  7.32 (m, 2 H), 7.26 (m, 2 H), 7.24 (m, 1 H), 5.86 (m, 1 H), 5.58 (m, 1 H), 5.37 (dt, J = 0.5, 3.0 Hz, 1 H), 5.19 (dq, J = 1.5, 17.0 Hz, 1 H), 5.11 (m, 1 H), 4.36 (dd, J = 5.5, 8.0 Hz, 1 H), 3.85 (ddt, A of ABX system, J = 1.5, 5.0, 12.5, Hz, 1 H), 3.72 (ddt, B of ABX system, J = 1.5, 6.0, 12.5 Hz, 1 H), 2.64 (m, 1 H), 2.39 (m, 1 H), 0.89 (t, J = 8.0 Hz, 3 H), 0.54 (q, J = 8.0 Hz, 2 H), 0.04 (s, 3 H), 0.02 (s, 3 H). 13C NMR (126 MHz, CDCl3)  147.2, 142.5, 135.0, 128.3 (2 C), 127.6, 127.4, 126.9 (2 C), 116.6, 81.1, 69.5, 44.5, 7.4, 6.8, -3.7, -3.8. IR (film) 3030, 2955, 2874, 1248, 1087, 819 cm-1. HRMS (EI) m/z 274.1748 [(M)+; calcd for C17H26OSi, 274.1753]. Preparation of (4-(allyloxy)-4-phenylbut-1-en-2-yl)triethylsilane (3.12c) Following general procedure E, alcohol 3.11c (402 mg, 1.53 mmol, 1 equiv), allyl bromide 193 (0.32 mL, 3.83 mmol, 2.5 equiv), THF (3.1 mL), and t-BuONa (442 mg, 4.59 mmol, 3 equiv) afforded, after silica gel chromatography (20% CH2Cl2 in hexanes), compound 3.12c as a colorless oil (407 mg, 1.35 mmol, 88% isolated yield). 1H NMR (500 MHz, CDCl3)  7.33–7.23 (m, 5 H), 5.86 (m, 1 H), 5.64 (m, 1 H), 5.36 (d, J = 3.5 Hz, 1 H), 5.19 (dq, J = 2.0, 17.5 Hz, 1 H), 5.10 (m, 1 H), 4.37 (dd, J = 5.5, 8.0 Hz, 1 H), 3.85 (m, 1 H), 3.71 (m, 1 H), 2.62 (dd, A of ABX system, J = 8.0, 14.5 Hz, 1 H), 2.37 (dd, B of ABX system, J = 5.5, 14.5 Hz, 1 H), 0.90 (t, J = 8.0 Hz, 9 H), 0.58 (dq, J = 2.0, 8.0 Hz, 6 H). 13C NMR (126 MHz, CDCl3) δ 144.9, 142.6, 135.0, 128.38, 128., 127.4, 126.9, 116.6, 81.0, 69.5, 44.5, 7.3, 2.8. IR (film) 3030, 2953, 1454, 1086, 924, 700 cm -1. HRMS (EI) m/z 302.2051 [(M)+; calcd for C19H30OSi, 302.2066]. Preparation of (4-(allyloxy)-4-(p-tolyl)but-1-en-2-yl)dimethyl(phenyl)silane (3.12d) Following general procedure E, alcohol 3.11d (714 mg, 2.41 mmol, 1 equiv), allyl bromide (0.51 mL, 6.02 mmol, 2.5 equiv), THF (4.9 mL), and t-BuONa (694 mg, 7.2 mmol, 3 equiv) afforded, after silica gel chromatography (25% CH2Cl2 in hexanes), compound 3.12d as a colorless oil (698 mg, 2.07 mmol, 86% isolated yield). 1H NMR (500 MHz, CDCl3)  7.51 (m, 2 H), 7.34 (m, 3 H), 7.09 (d, J = 8.0 Hz, 2 H), 7.03 (d, J = 8.0 Hz, 2 H), 5.78 (m, 1 H), 5.70 (m, 1 H), 5.47 (m, 1 H), 5.14 (m, 1 H), 5.07 (m, 1 H), 4.17 (dd, J = 5.0, 8.0 Hz, 1 H), 3.74 (A of ABX system, m, 1 H), 3.52 (B of ABX system, m, 1 H), 2.64(A of ABX system, ddd, J = 0.5, 8.0, 14.5 Hz, 1 H), 2.38 (B, of ABX system, ddd, J = 0.5, 5.0, 14.0 Hz, 1 H), 2.32 (s, 3 H), 0.364 (s, 3 H), 0.361 (s, 3 H). 13C NMR (126 MHz, CDCl3)  146.4, 139.3, 138.3, 137.0, 135.1, 134.0 (2 C), 129.1, 128.9, 194 128.8 (2 C), 127.7 (2 C), 126.8 (2 C), 116.4, 80.4, 69.3, 44.7, 21.1, -2.89, -2.91. IR (neat) 3049, 2955, 2858, 1427, 1248, 1111, 815 cm-1. HRMS (EI) m/z 321.1667 [(M-CH3)+; calcd for C21H25OSi, 321.1675]. Preparation of (4-(allyloxy)-4-(p-tolyl)but-1-en-2-yl)(benzyl)dimethylsilane (3.12e) Compound 3.12e was prepared by a modification of General Procedure D. A 25 mL round bottom flask was charged with a magnetic stirrer, 1-(1-(allyloxy)but-3-yn-1-yl)-4-methylbenzene (500 mg, 2.5 mmol, 1 equiv), dichloromethane (5 mL), and benzydimethylsilane (451 mg, 3 mmol, 1.2 equiv). The flask was flushed with nitrogen and [Cp*Ru(MeCN) 3]PF6 (25.2 mg, 0.05 mmol, 0.02 equiv) was added quickly, the reaction was kept under nitrogen. The reaction was run overnight at room temperature. The reaction mixture was concentrated and the crude product purified by silica gel chromatography (30% CH2Cl2 in hexanes) to afford 3.12e as a colorless oil (297 mg, 1.48 mmol, 59% isolated yield). 1H NMR (500 MHz, CDCl3)  7.16 (m, 5 H), 7.05 (t, J = 7.0 Hz, 1 H), 6.96 (d, J = 7.5 Hz, 2 H), 5.86 (m, 1 H), 5.64 (s, 1 H), 5.38 (s, 1 H), 5.21 (d, J = 17.5 Hz, 1 H), 5.11 (d, J = 10.0 Hz, 1 H), 4.35 (m, 1 H), 3.86 (dd, A of ABX system, J = 4.5, 12.5 Hz, 1 H), 3.71 (dd, B of ABX system, J = 5.5, 12.5 Hz, 1 H), 2.65 (dd, C of CDX system, J = 8.0, 14.5 Hz, 1 H), 2.38 (dd, J = 5.0, 14.5 Hz, 1 H), 2.34 (s, 3 H), 2.13 (s, 2 H), 0.03 (s, 3 H), 0.01 (s, 3 H). 13C NMR (126 MHz, CDCl3)  146.8, 140.0, 139.3, 137.1, 135.0, 129.0 (2 C), 128.3 (2 C), 128.2, 128.0 (2 C), 126.9 (2 C), 123.9, 116.6, 81.0, 69.4, 44.4, 25.4, 21.1, -3.5. IR (film) 3025, 2922, 1493, 1248, 1084, 815 cm-1. HRMS (EI) m/z 350.2060 [(M+); calcd for C23H30OSi, 195 350.2066]. Preparation of (4-(allyloxy)-4-(o-tolyl)but-1-en-2-yl)(ethyl)dimethylsilane (3.12f) Following general procedure E, alcohol 3.11f (412 mg, 1.66 mmol, 1 equiv), allyl bromide (0.35 mL, 4.15 mmol, 2.5 equiv), THF (3.3 mL), and t-BuONa (478 mg, 4.98 mmol, 3 equiv) afforded, after silica gel chromatography (30% CH2Cl2 in hexanes), compound 3.12f as a colorless oil (439 mg, 1.53 mmol, 92% isolated yield). 1H NMR (500 MHz, CDCl3)  7.40 (dd, J = 1.0, 7.5 Hz, 1 H), 7.20 (t, J = 7.5 Hz, 1 H), 7.15 (dt, J = 1.5, 7.5 Hz, 1 H), 7.10 (m, 1 H), 5.87 (m, 1 H), 5.67 (quintet, J = 1.5 Hz, 1 H), 5.41 (dt, J = 1.0, 3.0 Hz, 1 H), 5.19 (dq, J = 1.0, 17.5 Hz, 1 H), 5.11 (dq, J = 1.5, 10.5 Hz, 1 H), 4.64 (dd, J = 4.0, 9.0 Hz, 1 H), 3.85 (ddt, A of ABX system, J = 1.5, 5.0, 12.5 Hz, 1 H), 3.69 (ddt, B of ABX system, J =1.5, 6.0, 13.0 Hz, 1 H), 2.54 (m, 1 H), 2.34 (m, 1 H), 2.30 (s, 3 H), 0.90 (t, J = 8.0 Hz, 3 H), 0.56 (q, J = 8.0 Hz, 2 H), 0.05 (s, 3 H), 0.04 (s 3 H). 13 C NMR (126 MHz, CDCl3)  147.8, 140.8, 135.20, 135.18, 130.3, 127.1, 127.0, 126.22, 126.18, 116.5, 77.6, 69.4, 43.2, 19.3, 7.4, 6.8, -3.75, -3.78. IR (film) 3049, 2957, 1426, 1248, 1109, 815 cm-1. HRMS (EI) m/z 230.1484 [(M-OCH2CHCH2)+; calcd for C15H22Si, 230.1491]. 196 Preparation of (4-(allyloxy)-4-(3-methoxyphenyl)but-1-en-2-yl)(ethyl)dimethylsilane (3.12g) Following general procedure E, alcohol 3.11g (289 mg, 1.09 mmol, 1 equiv), allyl bromide (0.23 mL, 2.73 mmol, 2.5 equiv), THF (2.2 mL), and t-BuONa (315 mg, 3.28 mmol, 3 equiv) afforded, after silica gel chromatography (30% CH2Cl2 in hexanes), compound 3.12g as a colorless oil (283 mg, 0.93 mmol, 85% isolated yield). 1H NMR (500 MHz, CDCl3)  7.22 (t, J = 8.0 Hz, 1 H), 6.85 (m, 2 H), 6.79 (m, 1 H), 5.86 (m, 1 H), 5.60 (m, 1 H), 5.38 (d, J = 3.0 Hz, 1 H), 5.20 (dq, J = 1.5, 17.5 Hz, 1 H), 5.11 (dq, J = 1.5, 10.5 Hz, 1 H), 4.34 (dd, J = 5.0, 8.0 Hz, 1 H), 3.88 (ddt, A of ABX system, J = 1.5, 5.0, 12.5 Hz, 1 H), 3.80 (s, 3 H), 3.71 (ddt, B of ABX system, J = 1.5, 6.0, 12.5 Hz, 1 H), 2.62 (dd, C of CDX system, J = 8.0, 14.5 Hz, 1 H), 2.38 (dd, D of CDX system, J = 5.0, 14.5 Hz, 1 H), 0.89 (t, J = 8.0 Hz, 3 H), 0.54 (q, J = 8.0 Hz, 2 H), 0.04 (s, 3 H), 0.03 (s, 3 H). 13C NMR (126 MHz, CDCl3)  159.7, 147.2, 144.3, 135.0, 129.2, 127.5, 119.4, 116.7, 112.9, 112.2, 81.0, 69.6, 55.2, 44.5, 7.4, 6.8, -3.71, -3.73. IR (film) 3049, 2953, 1601, 1257, 1045, 819, 779 cm-1. HRMS (EI) m/z 246.1441 [(M-C3H6O)+; calcd for C15H22OSi, 246.1440]. Preparation of (4-(allyloxy)-4-(ferrocenyl)but-1-en-2-yl)dimethyl(phenyl)silane (3.12h) 197 Following general procedure E, alcohol 3.11h (1.72 g, 4.4 mmol, 1 equiv), allyl bromide (0.93 mL, 11 mmol, 2.5 equiv), THF (8.8 mL), and t-BuONa (1.27 g, 13.2 mmol, 3 equiv) afforded, after silica gel chromatography (25–35% CH2Cl2 in hexanes), compound 3.12h as an orange oil (1.49 g, 3.43 mmol, 78% isolated yield). 1H NMR (500 MHz, CDCl3)  7.57 (m, 2 H), 7.36 (m, 3 H), 5.85 (m, 1 H), 5.78 (ddt, J = 5.5, 10.5, 17.5 Hz, 1 H), 5.56 (d, J = 2.5 Hz, 1 H), 5.18 (dq, J = 1.2, 17.0 Hz, 1 H), 5.06 (dq, J = 1.5, 10.5 Hz, 1 H), 4.12 (dd, J = 3.5, 9.0 Hz, 1 H), 4.08 (m, 4 H), 3.99 (s, 5 H), 3.89 (ddt, J = 1.5, 5.0, 12.5 Hz, 1 H), 3.69 (ddt, J = 1.5, 5.5, 12.5 Hz, 1 H), 2.72 (A of ABX system, m, 1 H), 2.65 (B of ABX system, dd, J = 4.5, 15.0 Hz, 1 H), 0.429 (s, 3 H), 0.421 (s, 3H). 13C NMR (126 MHz, CDCl3)  147.1, 138.3, 135.4, 134.0 (2 C), 129.1, 128.4, 127.8 (2 C), 89.3, 76.1, 69.2, 68.6 (5 C), 68.4, 67.8, 67.1, 66.1, 42.1, -2.69, -2.75. IR (neat) 3070, 2955, 1427, 1248, 1107, 815 cm-1. HRMS (EI) m/z 430.1402 [(M)+; calcd for C25H30SiOFe, 430.1415]. Preparation of (4-(allyloxy)-4-(thiophen-2-yl)but-1-en-2-yl)(ethyl)dimethylsilane (3.12i) Following general procedure E, alcohol 3.11i (169 mg, 0.7 mmol, 1 equiv), allyl bromide (0.15 mL, 1.76 mmol, 2.5 equiv), THF (1.5 mL), and t-BuONa (203 mg, 2.11 mmol, 3 equiv) afforded, after silica gel chromatography (20% CH2Cl2 in hexanes), compound 3.12i as a colorless oil (166 mg, 0.59 mmol, 84% isolated yield). 1H NMR (500 MHz, CDCl3)  7.23 (dd, J = 0.5, 5.0 Hz, 1 H), 6.92 (dd, J = 3.5, 5.0 Hz, 1 H), 6.89 (dd, J = 1.0, 3.0 Hz, 1 H), 5.86 (m, 1 H), 5.59 (dt, J = 1.5, 2.5 Hz, 1 H), 5.37 (d, J = 3.0 Hz, 1 H), 5.21 (dq, J = 1.5, 17.0 Hz, 1 H), 5.13 (dq, J = 1.5, 10.0 Hz, 1 H), 6.64 (t, J = 7.0 Hz, 1 H), 3.95 (ddt, A of ABX system, J = 1.5, 5.5, 12.5 Hz, 1 H), 198 3.79 (ddt, B of ABX system, J = 1.5, 6.5, 12.5 Hz, 1 H), 2.76 (m, 1 H), 2.51 (m, 1 H), 0.89 (t, J = 8.0 Hz, 3 H), 0.54 (q, J = 8.0 Hz, 2 H), 0.04 (s, 3 H), 0.03 (s, 3 H). 13C NMR (126 MHz, CDCl3)  146.7, 146.4, 134.8, 127.7, 126.2, 125.3, 124.7, 117.0, 76.3, 69.4, 44.8, 7.3, 6.8, -3.7, -3.8. HRMS (EI) m/z 280.1310 [(M)+; calcd for C15H24SiOS, 280.1317]. Preparation of (4-(allyloxy)hept-1-en-2-yl)dimethyl(phenyl)silane (3.12j) Following general procedure E, alcohol 3.11j (828 mg, 3.33 mmol, 1 equiv), allyl bromide (0.7 mL, 8.33 mmol, 2.5 equiv), THF (6.7 mL), and t-BuONa (961 mg, 10 mmol, 3 equiv) afforded, after silica gel chromatography (20% CH2Cl2 in hexanes), compound 3.12j as a colorless oil (864 mg, 3.0 mmol, 90% isolated yield). 1H NMR (500 MHz, CDCl3)  7.49 (m, 2 H), 7.33 (m, 3 H), 5.81 (m, 1 H), 5.74 (m, 1 H), 5.49 (d, J = 3.0 Hz, 1 H), 5.16 (dq, J = 1.5, 17.0 Hz, 1 H), 5.08 (m, 1 H), 3.82 (ddt, A of ABX system, J = 1.5, 6.0, 13.0 Hz, 1 H), 3.76 (ddt, B of ABX system, J = 1.5, 6.0, 12.5 Hz, 1 H), 3.22 (m, 1 H), 2.44 (ddt, C of CDX system, J = 1.0, 5.5, 14.0 Hz, 1 H), 2.15 (dd, D of CDX system, J = 7.5, 14.0 Hz, 1 H), 1.35–1.25 (m, 3 H), 1.13 (m, 1 H), 0.79 (t, J = 7.0 Hz, 3 H), 0.38 (s, 3 H), 0.37 (s, 3 H). 13C NMR (126 MHz, CDCl3)  147.2, 138.1, 135.5, 133.9 (2 C), 129.0, 128.9, 127.7 (2 C), 116.3, 77.9, 69.9, 41.4, 36.0, 18.5, 14.1, -2.7, -2.9. IR (neat) 3062, 2924, 2851, 1248, 1111, 816 cm-1. HRMS (EI) m/z 273.1660 [(M-CH3)+; calcd for C17H25OSi, 273.1675]. 199 Preparation of (4-(allyloxy)-4-cyclohexylbut-1-en-2-yl)dimethyl(phenyl)silane (3.12k) Following general procedure E, alcohol 3.11k (827 mg, 2.87 mmol, 1 equiv), allyl bromide (0.61 mL, 7.18 mmol, 2.5 equiv), THF (6 mL), and t-BuONa (827 mg, 8.6 mmol, 3 equiv) afforded, after silica gel chromatography (20–25% CH2Cl2 in hexanes), compound 3.12k as a colorless oil (647 mg, 1.98 mmol, 69% isolated yield). 1H NMR (500 MHz, CDCl3)  7.50 (m, 2 H), 7.33 (m, 3 H), 5.81 (m, 1 H), 5.77 (m, 1 H), 5.49 (d, J = 3.0 Hz, 1 H), 5.15 (dq, J = 2.0, 17.5 Hz, 1 H), 5.05 (dq, J = 1.5, 10.5 Hz, 1 H), 3.79 (A of ABX system, ddt, J = 1.5, 5.5, 12.5 Hz, 1 H), 3.74 (B of ABX system, ddt, J = 1.5, 6.0, 13.0 Hz, 1 H), 3.02 (m, 1 H), 2.28 (d, J = 6.5 Hz, 1 H), 1.67 (m, 2 H), 1.59 (m, 2 H), 1.39–1.29 (m, 2 H), 1.15–1.01 (m, 4 H), 0.97 (m, 1 H), 0.39 (s, 3 H), 0.37 (s, 3 H). 13C NMR (126 MHz, CDCl3)  147.5, 138.3, 135.7, 133.9 (2 C), 128.9, 128.8, 127.7 (2 C), 116.0, 82.3, 71.1, 40.8, 38.0, 29.2, 27.4, 26.6, 26.5, 26.4, -2.71, -2.86. IR (neat) 3069, 2926, 2853, 1450, 1248, 1111, 817 cm-1. HRMS (EI) m/z 328.2233 [(M)+; calcd for C21H32OSi, 328.2222]. Preparation of (4-(allyloxy)-4-cyclopropylbut-1-en-2-yl)dimethyl(phenyl)silane (3.12l) Following general procedure E, alcohol 3.11l (312 mg, 1.27 mmol, 1 equiv), allyl bromide (0.27 mL, 3.17 mmol, 2.5 equiv), THF (2.5 mL), and t-BuONa (365 mg, 3.8 mmol, 3 equiv) 200 afforded, after silica gel chromatography (20–25% CH2Cl2 in hexanes), compound 3.12l as a colorless oil (290 mg, 1.02 mmol, 80% isolated yield). 1H NMR (500 MHz, CDCl3)  7.50 (m, 2 H), 7.32 (m, 3 H), 5.81 (m, 2 H), 5.48 (d, J = 2.5 Hz, 1 H), 5.18 (dq, J = 1.5, 14.5 Hz, 1 H), 5.07 (dq, J = 1.5, 9.0 Hz, 1 H), 4.04 (ddt, A of ABX system, J = 1.0, 4.5, 10.5 Hz, 1 H), 3.75 (ddt, B of ABX system, J = 1.5, 4.5, 10.5 Hz, 1 H), 2.60 (dt, J = 3.5, 6.5 Hz, 1 H), 2.45 (dd, C of CDX system, J = 6.5, 12.0 Hz, 1 H), 2.39 (dd, D of CDX system, J = 3.5, 12.0 Hz, 1 H), 0.73 (m, 1 H), 0.49 (m, 1 H), 0.36 (s, 6 H), 0.34 (m, 1 H), 0.25 (m, 1 H), -0.10 (m, 1 H). 13C NMR (126 MHz, CDCl3)  147.0, 138.4, 135.7, 134.0 (2 C), 128.9, 128.8, 127.7 (2 C), 116.0, 82.2, 69.7, 42.0, 15.1, 4.4, 1.3, -2.7, -2.8. IR (film) 3069, 3005, 2957, 2858, 1427, 1111, 815 cm-1. HRMS (EI) m/z 286.1741 [(M)+; calcd for C18H26OSi, 286.1753]. Preparation of (4-(allyloxy)-4-cyclopropylbut-1-en-2-yl)triethylsilane (3.12m) Following general procedure E, alcohol 3.11m (265 mg, 1.17 mmol, 1 equiv), allyl bromide (0.25 mL, 2.93 mmol, 2.5 equiv), THF (2.4 mL), and t-BuONa (337 mg, 3.5 mmol, 3 equiv) afforded, after silica gel chromatography (20–25% CH2Cl2 in hexanes), compound 3.12m as a colorless oil (261 mg, 0.98 mmol, 84% isolated yield). 1H NMR (600 MHz, CDCl3)  5.88 (m, 1 H), 5.48 (dt, J = 1.8, 3.0 Hz, 1 H), 5.37 (d, J = 3.0 Hz, 1 H), 5.22 (dq, J = 1.8, 17.4 Hz, 1 H), 5.09 (dq, J = 1.8, 12.0 Hz, 1 H), 4.16 (ddt, A of ABX system, J = 1.8, 6.0, 13.2 Hz, 1 H), 3.93 (ddt, B of ABX system, J = 1.2, 5.4, 12.6 Hz, 1 H), 2.79 (dt, J = 4.8, 7.8 Hz, 1 H), 2.42 (dd, C of CDX system, J = 7.2, 14.4 Hz, 1 H), 2.35 (dd, D of CDX system, J = 4.8, 14.4 Hz, 1 H), 0.91 (t, J = 7.8 201 Hz, 9 H), 0.83 (m, 1 H), 0.59 (q, J = 7.8 Hz, 6 H), 0.55 (m, 1 H), 0.43 (m, 1 H), 0.36 (m, 1 H), 0.08 (m, 1 H). 13C NMR (151 MHz, CDCl3)  145.6, 135.7, 128.0, 116.1, 82.3, 69.8, 41.9, 15.2, 7.4, 4.4, 3.0, 1.4. IR (film) 3070, 2957, 1427, 1113, 815 cm -1. HRMS (EI) m/z 266.2062 [(M)+; calcd for C16H30OSi, 266.2066]. Preparation of (4-(allyloxy)-4-(3-chlorophenyl)but-1-en-2-yl)(ethyl)dimethylsilane (3.12n) Following general procedure E, alcohol 3.11n (423 mg, 1.57 mmol, 1 equiv), allyl bromide (0.33 mL, 3.93 mmol, 2.5 equiv), THF (3.2 mL), and t-BuONa (454 mg, 4.72 mmol, 3 equiv) afforded, after silica gel chromatography (30% CH2Cl2 in hexanes), compound 3.12n as a colorless oil (442 mg, 1.43 mmol, 91% isolated yield). 1H NMR (500 MHz, CDCl3)  7.26 (s, 1 H), 7.25– 7.21 (m, 2 H), 7.15 (dt, J = 1.5, 6.5 Hz, 1 H), 5.85 (m, 1 H), 5.56 (m, 1 H), 5.38 (d, J = 2.5 Hz, 1 H), 5.20 (dq, J = 1.5, 17.0 Hz, 1 H), 5.13 (dq, J = 1.5. 10.5 Hz, 1 H), 4.33 (dd, J = 5.5, 8.0 Hz, 1 H), 3.86 (ddt, A of ABX system, J = 1.5, 5.5, 13.0 Hz, 1 H), 3.72 (ddt, B of ABX system, J = 1.5, 6.0, 13.0 Hz, 1 H), 2.61 (dd, C of CDX system, J = 8.0, 14.5 Hz, 1 H), 2.35 (dd, D of CDX system, J = 5.5, 15.0 Hz, 1 H), 0.89 (t, J = 7.5 Hz, 3 H), 0.53 (q, J = 7.5 Hz, 2 H), 0.04 (s, 3 H), 0.02 (s, 3 H). 13C NMR (126 MHz, CDCl3)  146.8, 144.8, 134.7, 134.2, 129.6, 127.9, 127.6, 127.0, 125.1, 116.9, 80.5, 69.7, 44.4, 7.3, 6.8, -3.7, -3.8. IR (film) 3060, 2955, 1427, 1248, 1092, 815 cm-1. HRMS (EI) m/z 308.1372 [(M+); calcd for C17H25OSiCl, 308.1363]. 202 Preparation of 2-(1-(allyloxy)-3-(triethylsilyl)but-3-en-1-yl)pyridine (3.12o) Following alternative general procedure E, alcohol 3.11o (356 mg, 1.35 mmol, 1 equiv), allyl bromide (0.24 mL, 2.70 mmol, 2.0 equiv), THF (30 mL), and sodium hydride, 60% w/w dispersion in mineral oil (155 mg, 4.05 mmol, 3 equiv) afforded, after silica gel chromatography (30% EtOAc in hexanes), compound 3.12o as a colorless oil (391 mg, 1.28 mmol, 95% isolated yield). 1H NMR (500 MHz, CDCl3) δ 8.55 (ddd, J = 4.9, 1.8, 0.9 Hz, 1H), 7.66 (td, J = 7.7, 1.8 Hz, 1H), 7.39 (dt, J = 7.8, 1.1 Hz, 1H), 7.16 (ddd, J = 7.5, 4.9, 1.2 Hz, 1H), 5.87 (ddt, J = 17.2, 10.5, 5.6 Hz, 1H), 5.72 (dt, J = 2.8, 1.5 Hz, 1H), 5.37 (dd, J = 2.8, 1.0 Hz, 1H), 5.22 (dq, J = 17.2, 1.7 Hz, 1H), 5.11 (dq, J = 10.4, 1.4 Hz, 1H), 4.56 (dd, J = 7.4, 5.7 Hz, 1H), 3.90 (ddt, J = 12.7, 5.3, 1.5 Hz, 1H), 3.83 (ddt, J = 12.7, 5.8, 1.4 Hz, 1H), 2.55 (dq, J = 6.9, 1.2 Hz, 2H), 0.90 (t, J = 7.9 Hz, 9H), 0.60 (qd, J = 7.9, 2.1 Hz, 6H). 13C NMR (126 MHz, CDCl3) δ 162.4, 149.0, 144.7, 136.4, 134.7, 128.2, 122.3, 120.9, 116.7, 82.2, 70.1, 42.8, 7.3, 2.8. HRMS (ESI) m/z 304.2100 [(M + H)+; calcd for C18H30NOSi, 304.2097]. Preparation of (4-(allyloxy)-4-(naphthalen-2-yl)but-1-en-2-yl)dimethyl(phenyl)silane (3.12p) Following alternative general procedure E, alcohol 3.11p (998 mg, 3.0 mmol, 1 equiv), 203 allyl bromide (0.52 mL, 6.0 mmol, 2.0 equiv), THF (30 mL), and sodium hydride, 60% w/w dispersion in mineral oil (345 mg, 9.0 mmol, 3 equiv) afforded, after silica gel chromatography (30% CH2Cl2 in hexanes), compound 3.12p as a colorless oil (1.07 g, 2.88 mmol, 96% isolated yield). 1H NMR (500 MHz, CDCl3) δ 7.85 – 7.77 (m, 3H), 7.59 – 7.54 (m, 2H), 7.52 – 7.47 (m, 3H), 7.44 – 7.36 (m, 4H), 5.84 (dddd, J = 17.2, 10.4, 6.0, 5.2 Hz, 1H), 5.74 (dt, J = 2.7, 1.3 Hz, 1H), 5.55 – 5.49 (m, 1H), 5.20 (dq, J = 17.2, 1.7 Hz, 1H), 5.14 (dq, J = 10.3, 1.4 Hz, 1H), 4.40 (dd, J = 7.8, 5.5 Hz, 1H), 3.82 (ddt, J = 12.7, 5.2, 1.5 Hz, 1H), 3.62 (ddt, J = 12.7, 6.1, 1.4 Hz, 1H), 2.80 (ddt, J = 14.3, 7.8, 1.1 Hz, 1H), 2.55 (ddt, J = 14.4, 5.5, 1.0 Hz, 1H), 0.43 (s, 3H), 0.42 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 146.2, 139.7, 138.3, 134.9, 134.0, 133.1, 133.0, 129.3, 129.0, 128.1, 127.81, 127.76, 127.7, 126.0, 125.9, 125.7, 124.6, 116.7, 80.8, 69.4, 44.6, -2.9, -3.0. IR (neat) 3051, 2957, 2856, 1427, 1248, 1111, 1082, 817 cm -1. HRMS (EI) m/z 372.1906 [(M)+; calcd for C25H28OSi, 372.1909]. Preparation of 4-(1-(allyloxy)-3-(triethylsilyl)but-3-en-1-yl)pyridine (3.12q) Following alternative general procedure E, alcohol 3.11q (606 mg, 2.30 mmol, 1 equiv), allyl bromide (0.4 mL, 4.60 mmol, 2.0 equiv), THF (30 mL), and sodium hydride, 60% w/w dispersion in mineral oil (264.5 mg, 6.90 mmol, 3 equiv) afforded, after silica gel chromatography (25% EtOAc in hexanes), compound 3.12q as a colorless oil (542 mg, 1.8 mmol, 78% isolated yield). 1H NMR (500 MHz, CDCl3) δ 8.55 (d, J = 6.0 Hz, 2H), 7.20 (d, J = 6.1 Hz, 2H), 5.85 (dddd, J = 17.2, 10.3, 6.0, 5.2 Hz, 1H), 5.63 (dt, J = 2.7, 1.4 Hz, 1H), 5.38 (d, J = 2.7 Hz, 1H), 204 5.21 (dq, J = 17.2, 1.7 Hz, 1H), 5.14 (dq, J = 10.4, 1.4 Hz, 1H), 4.36 (dd, J = 7.8, 5.4 Hz, 1H), 3.87 (ddt, J = 12.6, 5.2, 1.5 Hz, 1H), 3.75 (ddt, J = 12.6, 6.0, 1.4 Hz, 1H), 2.58 (ddt, J = 14.4, 7.9, 1.1 Hz, 1H), 2.33 (ddt, J = 14.5, 5.4, 1.2 Hz, 1H), 0.90 (t, J = 7.9 Hz, 9H), 0.58 (qd, J = 7.9, 1.7 Hz, 6H). 13C NMR (126 MHz, Chloroform-d) δ 151.5, 149.8, 144.1, 134.3, 129.0, 121.9, 117.1, 79.8, 70.0, 44.1, 7.3, 2.8. HRMS (ESI) m/z 304.2102 [(M + H)+; calcd for C18H30NOSi, 304.2097]. Preparation of 4-(1-(allyloxy)-3-(dimethyl(phenyl)silyl)but-3-en-1-yl)pyridine (3.12r) Following alternative general procedure E, alcohol 3.11r (1077 mg, 3.8 mmol, 1 equiv), allyl bromide (0.66 mL, 7.60 mmol, 2.0 equiv), THF (30 mL), and sodium hydride, 60% w/w dispersion in mineral oil (437 mg, 11.40 mmol, 3 equiv) afforded, after silica gel chromatography (30% EtOAc in hexanes), compound 3.12r as a colorless oil (1010 mg, 3.12 mmol, 82% isolated yield). 1H NMR (500 MHz, CDCl3) δ 8.50 (d, J = 6.0 Hz, 2H), 7.56 – 7.49 (m, 2H), 7.40 – 7.31 (m, 3H), 7.02 (d, J = 6.2 Hz, 2H), 5.82 – 5.72 (m, 1H), 5.67 (dt, J = 2.7, 1.3 Hz, 1H), 5.52 (d, J = 2.7 Hz, 1H), 5.16 (dq, J = 17.2, 1.6 Hz, 1H), 5.11 (dq, J = 10.4, 1.3 Hz, 1H), 4.14 (dd, J = 7.9, 5.3 Hz, 1H), 3.75 (ddt, J = 12.7, 5.2, 1.5 Hz, 1H), 3.55 (ddt, J = 12.7, 6.0, 1.4 Hz, 1H), 2.61 (dd, J = 14.2, 7.8 Hz, 1H), 2.35 (dd, J = 14.3, 5.3 Hz, 1H), 0.39 (s, 3H), 0.38 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 151.3, 149.7, 145.5, 137.9, 134.3, 133.9, 129.7, 129.1, 127.8, 121.7, 116.9, 79.4, 69.8, 44.3, -3.05, -3.08. HRMS (ESI) m/z 324.1803 [(M + H)+; calcd for C20H26NOSi, 324.1784]. 205 Preparation of dimethyl(phenyl)(2-phenyl-3,6-dihydro-2H-pyran-4-yl)silane (3.1a) Following General Procedure F, diene 3.12a (100 mg, 0.31 mmol, 1 equiv) in benzene (6.2 mL), and second-generation Grubbs catalyst (10.5 mg, 0.0124 mmol, 0.04 equiv) at 80 ºC for 70 minutes, followed by silica gel chromatography (1:1 CH2Cl2/hexanes) afforded dihydropyran 3.1a as a colorless oil (89.9 mg, 0.30 mmol, 99% isolated yield). 1H NMR (500 MHz, CDCl3)  7.50 (m, 2 H), 7.36–7.29 (m, 7 H), 7.25 (m, 1 H), 6.10 (m, 1 H), 4.47 (dd, J = 3.5, 10.0 Hz, 1 H), 4.40 (m, 2 H), 2.35–2.28 (m, 1 H), 2.26–2.21 (m, 1 H), 0.36 (s, 6 H). 13C NMR (126 MHz, CDCl3)  142.7, 137.4, 136.1, 135.1, 134.0 (2 C), 129.1, 128.3 (2 C), 127.8 (2 C), 127.4, 125.8 (2 C), 75.6, 67.7, 34.5, -3.86, -3.98. IR (neat) 3067, 2955, 2901, 2818, 1427, 1248, 1115, 833, 819 cm-1. HRMS (EI) m/z 294.1434 [(M)+; calcd for C19H22OSi, 294.1440]. Preparation of ethyldimethyl(2-phenyl-3,6-dihydro-2H-pyran-4-yl)silane (3.1b) Following General Procedure F, diene 3.12b (69.6 mg, 0.254 mmol, 1 equiv) in benzene (5.1 mL), and second-generation Grubbs catalyst (8.6 mg, 0.01 mmol, 0.04 equiv) at 80 ºC for 1 h, followed by silica gel chromatography (1:1 CH2Cl2/hexanes) afforded dihydropyran 3.1b as a 206 colorless oil (56.4 mg, 0.231 mmol, 91% isolated yield). 1H NMR (500 MHz, CDCl3)  7.35 (m, 4 H), 7.26 (m, 1 H), 6.04 (m, 1 H), 4.48 (dd, J = 3.5, 10.0 Hz, 1 H), 4.39 (m, 2 H), 2.31 (m, 1 H), 13 2.24 (m, 1 H), 0.93 (t, J = 8.0 Hz, 3 H), 0.56 (q, J = 8.0 Hz, 2 H), 0.05 (s, 6 H). C NMR (126 MHz, CDCl3)  142.9, 135.9, 134.6, 128.4 (2 C), 127.4, 125.8 (2 C), 75.7, 67.7, 34.8, 7.4, 6.1, - 4.8. IR (film) 3032, 2953, 2816, 1246, 1124, 1026, 819 cm-1. HRMS (EI) m/z 246.1426 [(M)+; calcd for C15H22OSi, 246.1440]. Preparation of triethyl(2-phenyl-3,6-dihydro-2H-pyran-4-yl)silane (3.1c) Following General Procedure F, diene 3.12c (110 mg, 0.364 mmol, 1 equiv) in benzene (7.3 mL), and second-generation Grubbs catalyst (12.3 mg, 0.015 mmol, 0.04 equiv) at 80 ºC for 1 h, followed by silica gel chromatography (30% CH2Cl2 in hexanes) afforded dihydropyran 3.1c as a colorless oil (101 mg, 0.360 mmol, 99% isolated yield).1H NMR (500 MHz, CDCl3)  7.35 (m, 4 H), 7.26 (m, 1 H), 6.03 (m, 1 H), 4.47 (dd, J = 3.0, 10.0 Hz, 1 H), 4.40 (m, 2 H), 2.31 (m, 1 H), 2.22 (m, 1 H), 0.94 (t, J = 8.0 Hz, 9 H), 0.59 (q, J = 8.0 Hz, 6 H). 13C NMR (126 MHz, CDCl3)  142.9, 135.5, 133.9, 128.4 (2 C), 127.4, 125.9 (2 C), 75.7, 67.8, 35.3, 7.4, 2.3. IR (film) 3030, 2953, 2814, 1454, 1126, 1026, 698 cm-1. HRMS (EI) m/z 274.1751 [(M)+; calcd for C17H26OSi, 274.1753]. 207 Preparation of dimethyl(phenyl)(2-(p-tolyl)-3,6-dihydro-2H-pyran-4-yl)silane (3.1d) Following General Procedure F, diene 3.12d (95 mg, 0.282 mmol, 1 equiv) in benzene (5.6 mL), and second-generation Grubbs catalyst (9.6 mg, 0.011 mmol, 0.04 equiv) at 80 ºC for 1 h, followed by silica gel chromatography (1:1 CH2Cl2/hexanes) afforded dihydropyran 3.1d as a colorless oil (89 mg, 0.279 mmol, 99% isolated yield).1H NMR (500 MHz, CDCl3)  7.50 (m, 2 H), 7.34 (m, 3 H), 7.21 (d, J = 8.0 Hz, 2 H), 7.12 (d, J = 8.0 Hz, 2 H), 6.09 (m, 1 H), 4.44 (dd, J = 3.5, 10.0 Hz, 1 H), 4.39 (m, 2 H), 2.35–2.27 (m, 1 H), 2.31 (s, 3 H), 2.22 (m, 1 H), 0.35 (s, 6 H). 13 C NMR (126 MHz, CDCl3)  139.8, 137.5, 137.0, 136.1, 135.2, 134.0 (2 C), 129.1, 129.0 (2 C), 127.8 (2 C), 125.8 (2 C), 75.5, 67.7, 34.5, 21.1, -3.85, -3.98. IR (neat) 3013, 2920, 2814, 1427, 1248, 1115, 817 cm-1. HRMS (EI) m/z 308.1596 [(M+); calcd for C20H24OSi, 308.1596]. Preparation of benzyldimethyl(2-(p-tolyl)-3,6-dihydro-2H-pyran-4-yl)silane (3.1e) Following General Procedure F, diene 3.12e (113 mg, 0.322 mmol, 1 equiv) in benzene (4 mL), and second-generation Grubbs catalyst (10.9 mg, 0.013 mmol, 0.04 equiv) at 80 ºC for 70 minutes, followed by silica gel chromatography (30% CH2Cl2 in hexanes) afforded dihydropyran 208 3.1e as a colorless oil (82 mg, 0.258 mmol, 80% isolated yield). 1H NMR (500 MHz, CDCl3)  7.23–7.18 (m, 4 H), 7.15 (d, J = 8.0 Hz, 2 H), 7.06 (t, J = 7.5 Hz, 1 H), 6.98 (d, J = 7.5 Hz, 2 H), 6.01 (m, 1 H), 4.29 (dd, J = 3.5, 10.5 Hz, 1 H), 4.36 (m, 2 H), 2.33 (s, 3 H), 2.29–2.21 (m, 1 H), 2.14 (s, 2 H), 2.09 (m, 1 H), 0.05 (s, 3 H), 0.04 (s, 3 H). 13 C NMR (126 MHz, CDCl3)  139.8, 137.0, 135.5, 135.2, 129.0 (4 C), 128.2 (4 C), 125.7, 124.1, 75.5, 67.7, 34.9, 25.0, 21.1, -4.5, -4.6. IR (film) 3030, 2957, 1492, 1112, 833 cm-1. HRMS (EI) m/z 322.1731 [(M+); calcd for C18H22OSi, 322.1753]. Preparation of ethyldimethyl(2-(o-tolyl)-3,6-dihydro-2H-pyran-4-yl)silane (3.1f) Following General Procedure F, diene 3.12f (111 mg, 0.385 mmol, 1 equiv) in benzene (8.5 mL), and second-generation Grubbs catalyst (14.5 mg, 0.017 mmol, 0.04 equiv) at 80 ºC for 1 h, followed by silica gel chromatography (45% CH2Cl2 in hexanes) afforded dihydropyran 3.1f as a colorless oil (98.8 mg, 0.381 mmol, 99% isolated yield).1H NMR (500 MHz, CDCl3)  7.40 (d, J = 7.5 Hz, 1 H), 7.17 (t, J = 7.5 Hz, 1 H), 7.10 (m, 2 H), 5.99 (m, 1 H), 4.60 (dd, J = 3.5, 10.0 Hz, 1 H), 4.34 (m, 2 H), 2.29 (s, 3 H), 2.24 (m, 1 H), 2.17 (m, 1 H), 0.88 (t, J = 8.0 Hz, 3 H), 0.51 (q, J = 8.0 Hz, 2 H), 0.00 (s, 6 H). 13C NMR (126 MHz, CDCl3)  140.9, 136.2, 134.55, 134.51, 130.2, 127.2, 126.3, 125.4, 72.7, 67.9, 33.2, 19.1, 7.4, 6.1, -4.7, -4.8. IR (film) 3370, 3009, 2953, 2814, 1460, 1246, 1124, 1032, 835 cm-1. HRMS (EI) m/z 260.1582 [(M+); calcd for C16H24OSi, 260.1596]. 209 Preparation of ethyl(2-(3-methoxyphenyl)-3,6-dihydro-2H-pyran-4-yl)dimethylsilane (3.1g) Following General Procedure F, diene 3.12g (100 mg, 0.328 mmol, 1 equiv) in benzene (5 mL), and second-generation Grubbs catalyst (11.1 mg, 0.013 mmol, 0.04 equiv) at 80 ºC for 1 h, followed by silica gel chromatography (1:1 CH2Cl2/hexanes) afforded dihydropyran 3.1g as a colorless oil (78 mg, 0.282 mmol, 86% isolated yield). 1H NMR (500 MHz, CDCl3)  7.24 (t, J = 8.0 Hz, 1 H), 6.93 (m, 2 H), 6.80 (m, 1 H), 6.02 (m, 1 H), 4.45 (dd, J = 3.5, 10.0 Hz, 1 H), 4.38 (m, 2 H), 2.30 (m, 1 H), 2.23 (m, 1 H), 0.92 (t, J = 8.0 Hz, 3 H), 0.55 (q, J = 8.0 Hz, 2 H), 0.03 (s, 6 H). 13C NMR (126 MHz, CDCl3)  159.8, 144.6, 135.9, 134.5, 129.4, 118.2, 113.1, 111.2, 75.6, 67.7, 55.2, 34.8, 7.4, 6.1, -4.8. IR (film) 3005, 2953, 1257, 1033, 775 cm-1. HRMS (EI) m/z 276.1540 [(M)+; calcd for C16H24O2Si, 276.1546]. Preparation of dimethyl(phenyl)(2-(ferrocenyl)-3,6-dihydro-2H-pyran-4-yl)silane (3.1h) Following General Procedure F, diene 3.12h (180.3 mg, 0.419 mmol, 1 equiv) in benzene (8.4 mL), and second-generation Grubbs catalyst (14.2 mg, 0.0167 mmol, 0.04 equiv) at 80 ºC for 1 h, followed by silica gel chromatography (7:3 CH2Cl2/hexanes) afforded dihydropyran 3.1h as 210 an orange oil (175.3 mg, 0.335 mmol, 70% isolated yield). 1H NMR (600 MHz, CDCl3)  7.54 (m, 2 H), 7.37 (m, 3 H), 6.07 (m, 1 H), 4.32 (dd, J = 4.0, 7.0 Hz, 1 H), 4.29 (m, 1 H), 4.25 (m, 1 H), 4.21 (m, 1 H), 4.11 (m, 2 H), 4.08 (m, 1 H), 4.06 (s, 5 H), 2.34 (m, 2 H), 0.40 (s, 3 H), 0.39 (s, 3 H). 13C NMR (151 MHz, CDCl3)  137.5, 136.1, 134.9, 133.9 (2 C), 129.1, 127.8 (2 C), 88.8, 71.7, 68.6 (5 C), 68.0, 67.6, 67.5, 66.8, 66.4, 32.4, -3.9, -4.0. IR (film) 3069, 2956, 1424, 1248, 1110, 815 cm-1. HRMS (EI) m/z 402.1108 [(M)+; calcd for C23H26OSiFe, 402.1102]. Preparation of ethyldimethyl(2-(thiophen-2-yl)-3,6-dihydro-2H-pyran-4-yl)silane (3.1i) Following General Procedure F, diene 3.12i (80 mg, 0.285 mmol, 1 equiv) in benzene (3.6 mL), and second-generation Grubbs catalyst (9.7 mg, 0.0114 mmol, 0.04 equiv) at 80 ºC for 1 h, followed by silica gel chromatography (20–25% CH2Cl2 in hexanes) afforded dihydropyran 3.1i as a colorless oil (43 mg, 0.171 mmol, 60% isolated yield).1H NMR (500 MHz, CDCl3)  7.24 (m, 1 H), 6.99 (m, 1 H), 6.96 (dd, J = 3.5, 5.0 Hz, 1 H), 6.00 (m, 1 H), 4.77 (dd, J = 3.5, 9.5 Hz, 1 H), 4.39 (m, 1 H), 4.33 (m, 1 H), 2.47 (m, 1 H), 2.37 (m, 1 H), 0.92 (t, J = 8.0 Hz, 3 H), 0.56 (q, J = 8.0 Hz, 2 H), 0.05 (s, 6 H). 13 C NMR (126 MHz, CDCl3)  145.9, 135.3, 134.4, 126.5, 124.6, 123.7, 71.4, 67.3, 34.4, 7.4, 6.0, -4.8. IR (film) 2953, 1246, 1120, 833 cm-1. HRMS (EI) m/z 252.0992 [(M)+; calcd for C13H20OSiS, 252.1004]. 211 Preparation of dimethyl(phenyl)(2-propyl-3,6-dihydro-2H-pyran-4-yl)silane (3.1j) Following General Procedure F, diene 3.12j (136 mg, 0.471 mmol, 1 equiv) in benzene (9 mL), and second-generation Grubbs catalyst (16 mg, 0.019 mmol, 0.04 equiv) at 80 ºC for 1 h, followed by silica gel chromatography (35% CH2Cl2 in hexanes) afforded dihydropyran 3.1j as a colorless oil (92 mg, 0.353 mmol, 0.75% isolated yield). 1H NMR (600 MHz, CDCl3)  7.49 (m, 2 H), 7.34 (m, 3 H), 6.02 (m, 1 H), 4.21 (m, 2 H), 3.41 (m, 1 H), 1.96 (m, 2 H), 1.50 (m, 1 H), 1.46 –1.32 (m, 3 H), 0.89 (t, J = 7.2 Hz, 3 H), 0.33 (s, 6 H). 13 C NMR (151 MHz, CDCl3)  137.7, 136.2, 134.7, 134.0 (2 C), 129.0, 127.8 (2 C), 73.3, 67.1, 38.1, 32.4, 18.7, 14.1, -3.9, -4.0. IR (film) 3069, 2957, 2812, 1427, 1248, 1130, 833 cm-1. HRMS (EI) m/z 260.1596 [(M)+; calcd for C16H24OSi, 260.1596]. Preparation of (2-cyclohexyl-3,6-dihydro-2H-pyran-4-yl)dimethyl(phenyl)silane (3.1k) Following General Procedure F, diene 3.12k (87 mg, 0.265 mmol, 1 equiv) in benzene (5.3 mL), and second-generation Grubbs catalyst (9 mg, 0.011 mmol, 0.04 equiv) at 80 ºC for 1 h, followed by silica gel chromatography (35% CH2Cl2 in hexanes) afforded dihydropyran 3.1k as a colorless oil (82.3 mg, 0.262 mmol, 99% isolated yield). 1H NMR (500 MHz, CDCl3)  7.48 (m, 212 2 H), 7.35 (m, 3 H), 6.01 (m, 1 H), 4.25–4.15 (m, 2 H), 3.14 (ddd, J = 3.5, 5.5, 10.0 Hz, 1 H), 2.03 (m, 1 H), 1.99–1.92 (m, 2 H), 1.70 (m, 2 H), 1.62 (m, 2 H), 1.33 (m, 1 H), 1.25–1.11 (m, 3 H), 0.96 (m, 2 H), 0.32 (s, 6 H). 13 C NMR (126 MHz, CDCl3)  137.7, 136.5, 134.7, 134.0 (2 C), 129.0, 127.8 (2 C), 77.9, 67.5, 42.8, 29.4, 29.0, 28.5, 26.6, 26.2, 26.1, -3.8, -3.9. IR (neat) 2924, 2853, 1427, 1246, 1126, 835 cm-1. HRMS (EI) m/z 300.1893 [(M)+; calcd for C19H28OSi, 300.1909]. Preparation of (2-cyclopropyl-3,6-dihydro-2H-pyran-4-yl)dimethyl(phenyl)silane (3.1l) Following General Procedure F, diene 3.12l (82 mg, 0.286 mmol, 1 equiv) in benzene (5.7 mL), and second-generation Grubbs catalyst (9.7 mg, 0.0114 mmol, 0.04 equiv) at 80 ºC for 1 h, followed by silica gel chromatography (20–25% CH2Cl2 in hexanes) afforded dihydropyran 3.1l as a colorless oil (63 mg, 0.243 mmol, 85% isolated yield).1H NMR (600 MHz, CDCl3)  7.48 (m, 2 H), 7.34 (m, 3 H), 5.99 (m, 1 H), 4.26 (m, 1 H), 4.18 (m, 1 H), 2.75 (ddd, J = 3.0, 7.8, 9.6 Hz, 1 H), 2.17–2.11 (m, 1 H), 2.09–2.05 (m, 1 H), 0.87 (m, 1 H), 0.51 (m, 1 H), 0.45 (m, 1 H), 0.33 (s, 6 H), 0.33 (overlapped) 0.17 (m, 1 H). 13C NMR (151 MHz, CDCl3)  137.6, 136.2, 134.6, 134.0 (2 C), 129.0, 127.8 (2 C), 77.9, 67.2, 31.9. 15.7, 2.8, 1.8, -3.8, -3.9. IR (neat) 3070, 3007, 2957, 1427, 1248, 1122, 817 cm-1. HRMS (EI) m/z 258.1429 [(M)+; calcd for C16H22OSi, 258.1440]. 213 Preparation of (2-cyclopropyl-3,6-dihydro-2H-pyran-4-yl)triethylsilane (3.1m) Following General Procedure F, diene 3.12m (106 mg, 0.398 mmol, 1 equiv) in benzene (8 mL), and second-generation Grubbs catalyst (13.6 mg, 0.016 mmol, 0.04 equiv) at 80 ºC for 1 h, followed by silica gel chromatography (20–25% CH2Cl2 in hexanes) afforded dihydropyran 3.1m as a colorless oil (81.6 mg, 0.342 mmol, 86% isolated yield). 1H NMR (500 MHz, CDCl3)  5.90 (m, 1 H), 4.25 (m, 1 H), 4.17 (m, 1 H), 2.74 (m, 1 H), 2.13 (m, 1 H), 2.04 (m, 1 H), 0.91 (t, J = 8.0 Hz, 9 H), 0.90 (m, heavily overlapped, 1 H), 0.57 (q, J = 8.0 Hz, 6 H), 0.53–0.48 (m, 2 H), 0.34 (m, 1 H), 0.20 (m, 1 H). 13C NMR (126 MHz, CDCl3)  135.4, 133.5, 78.0, 67.2, 32.6, 15.7, 7.4, 2.9, 2.3, 1.8. IR (film) 3082, 3007, 2953, 1124, 1018, 731 cm-1. HRMS (EI) m/z 238.1763 [(M)+; calcd for C14H26OSi, 238.1753]. Preparation of (2-(3-chlorophenyl)-3,6-dihydro-2H-pyran-4-yl)(ethyl)dimethylsilane (3.1n) Following General Procedure F, diene 3.12n (123 mg, 0.398 mmol, 1 equiv) in benzene (8 mL), and second-generation Grubbs catalyst (13.5 mg, 0.016 mmol, 0.04 equiv) at 80 ºC for 1 h, followed by silica gel chromatography (30% CH2Cl2 in hexanes) afforded dihydropyran 3.1n as a colorless oil (93.8 mg, 0.334 mmol, 84% isolated yield). 1H NMR (500 MHz, CDCl3)  7.36 (t, J 214 = 1.5 Hz, 1 H), 7.27–7.21 (m, 3 H), 6.01 (m, 1 H), 4.44 (dd, J = 5.5, 8.0 Hz, 1 H), 4.36 (q, J = 2.5 Hz, 2 H), 2.23 (m, 2 H), 0.91 (t, J = 8.0 Hz, 3 H), 0.54 (q, J = 8.0 Hz, 2 H), 0.03 (s, 6 H). 13C NMR (126 MHz, CDCl3)  145.0, 135.6, 134.4, 134.3, 129.6, 127.4, 126.0, 123.9, 74.9, 67.6, 34.6, 7.4, 6.0, -4.8. IR (film) 3013, 2953, 2820, 1126, 835 cm-1. HRMS (EI) m/z 280.1064 [(M+); calcd for C15H21OSiCl, 280.1050]. Preparation of 2-(4-(triethylsilyl)-3,6-dihydro-2H-pyran-2-yl)pyridine (3.1o) Following General Procedure F, diene 3.12o (334 mg, 1.1 mmol, 1 equiv) in benzene (40 mL), and second-generation Grubbs catalyst (38 mg, 0.044 mmol, 0.04 equiv) at 80 ºC for 1 h, followed by silica gel chromatography (30% CH2Cl2 in hexanes) afforded dihydropyran 3.1o as a colorless oil (302 mg, 1.09 mmol, 99% isolated yield). 1H NMR (500 MHz, CDCl3) δ 8.55 (ddd, J = 5.7, 1.8, 0.8 Hz, 1H), 7.69 (td, J = 7.7, 1.8 Hz, 1H), 7.47 (d, J = 7.8 Hz, 1H), 7.17 (ddd, J = 7.6, 4.8, 1.2 Hz, 1H), 6.03 (q, J = 2.7 Hz, 1H), 4.61 (dd, J = 10.4, 3.3 Hz, 1H), 4.43 (dt, J = 4.6, 2.3 Hz, 2H), 2.44 (dq, J = 16.5, 2.2 Hz, 1H), 2.29 (ddq, J = 16.8, 9.8, 3.1 Hz, 1H), 0.92 (t, J = 7.9 Hz, 9H), 0.60 (q, J = 7.9 Hz, 6H). 13 C NMR (126 MHz, CDCl3) δ 161.9, 148.8, 136.7, 135.2, 133.7, 122.2, 120.0, 76.3, 67.6, 33.6, 7.3, 2.2. HRMS (ESI) m/z 274.1627 [(M – H)+; calcd for C16H24NOSi, 274.1627]. 215 Synthesis of dimethyl(2-(naphthalen-2-yl)-3,6-dihydro-2H-pyran-4-yl)(phenyl)silane (3.1p) Following General Procedure F, diene 3.12p (932 mg, 2.5 mmol, 1 equiv) in benzene (80 mL), and second-generation Grubbs catalyst (85 mg, 0.044 mmol, 0.04 equiv) at 80 ºC for 1 h, followed by silica gel chromatography (40% CH2Cl2 in hexanes) afforded dihydropyran 3.1p as a colorless oil (492 mg, 1.40 mmol, 56% isolated yield). 1H NMR (500 MHz, C6D6) δ 7.76 (s, 1H), 7.63 – 7.55 (m, 3H), 7.47 (dq, J = 5.4, 2.1 Hz, 2H), 7.44 (dd, J = 8.5, 1.7 Hz, 1H), 7.25 – 7.13 (m, 5H), 5.91 (tt, J = 3.2, 1.5 Hz, 1H), 4.53 (dd, J = 10.0, 3.3 Hz, 1H), 4.27 (dtd, J = 17.2, 3.1, 1.0 Hz, 1H), 4.19 (dddd, J = 17.2, 4.0, 3.2, 1.8 Hz, 1H), 2.43 (dddt, J = 16.7, 10.0, 3.9, 2.7 Hz, 1H), 2.30 (dtt, J = 17.1, 3.3, 1.2 Hz, 1H), 0.26 (s, 3H), 0.25 (s, 3H). 13 C NMR (126 MHz, C6D6) δ 141.4, 138.0, 137.5, 135.4, 134.7, 134.3, 133.7, 129.9, 128.72, 128.66, 128.62, 128.4, 126.5, 126.2, 125.1, 125.0, 76.1, 68.0, 35.6, -3.4, -3.5. IR (neat) 3057, 2955, 2818, 1427, 1248, 1115, 815 cm-1. HRMS (EI) m/z 344.1580 [(M)+; calcd for C23H24OSi, 344.1596]. 216 Table 3.1: Conditions for ring closing metathesis Entry S.M Cat. (mol %) Add. Solvent Temp (°C) Time (h) % Conv 1 S2-q A (0.04) None benzene 80 1 0 2 S2-q A (0.04) None benzene 80 12 0 3 S2-q A (0.04) None toluene 110 12 0 4 S2-q A (0.04) None DCM 25 24 0 5 S2-q B (0.04) None toluene 60 12 0 6 S2-r A (0.04) None benzene 80 1 5a 7 S2-r A (0.04) TMSCl 1,2-DCE 90 °C 4 20a a The product was not isolated but analyzed as a mixture with the starting material. S.M. = starting material, Cat. = catalyst, Add. = additive. Cat. A = Grubbs II, cat. B = Hoveyda-Grubbs II. DCM = dichloromethane. TMSCl = chlorotrimethylsilane. 1,2-DCE = 1,2-dichloroethane 217 3.10.3. Wittig rearrangements of 4-silyl-6-aryl dihydropyrans 3.1 – general procedure G Freshly prepared and purified dihydropyran 3.1 was dissolved in THF under nitrogen (concentration = 0.08 M, unless otherwise noticed) and the solution cooled down at –78 ºC (dry ice/acetone bath). n-Butyllithium (1.2 equiv, 1.6 M in hexanes) or sec-butyllithium (1.2 equiv, 1.4 M in cyclohexane) was added dropwise (1 drop/second) to give a colored solution. After the indicated time (~3 hours or ~10 minutes, respectively) the reaction was quenched by adding NH4Cl (sat), diluted with water and diethyl ether. The aqueous phase was extracted with diethyl ether three times. Combined organic extracts were washed with water, and brine. The solution was dried over MgSO4, filtered, concentrated in a rotavap at room temperature (or lower) and the residue purified by column chromatography (5-10% EtOAc in hexanes) to afford the aldehyde and or alcohol as colorless oils. 3.10.4. Wittig rearrangements of 4-silyl-6-alkyl dihydropyrans 3.1 – general procedure H Freshly prepared and purified 3.1 was dissolved in THF under nitrogen (concentration = 0.08 M, unless otherwise noticed) and the solution cooled down at –78 ºC (dry ice/acetone bath). 218 n-Butyllithium (1.2 equiv, 1.6 M in hexanes) or sec-butyllithium (1.2 equiv, 1.4 M in cyclohexane) was added dropwise (1 drop/second) with stirring to give a colored solution. After ~25 minutes the temperature was raised to –10 ºC (unless otherwise indicated). After the indicated time (1.5-3 hours) the reaction was cooled down at –78 ºC and quenched by adding NH4Cl (sat), diluted with water and diethyl ether. The aqueous phase was extracted with diethyl ether three times. Combined organic extracts were washed with water, and brine. The solution was dried over MgSO 4, filtered, concentrated in a rotavap at room temperature (or lower) and the residue purified by column chromatography (4-5% EtOAc in hexanes) to afford the aldehyde as a colorless oil. Preparation of 2-(1-(dimethyl(phenyl)silyl)-2-phenylcyclopropyl)acetaldehyde (3.2a) Following General Procedure G, dihydropyran 3.1a (89 mg, 0.302 mmol, 1 equiv) in THF (3.8 mL) and n-butyllithium (0.23 mL, 0.36 mmol, 1.2 equiv) at –78 ºC for 3 h, followed by workup and silica gel chromatography (5% EtOAc in hexanes) afforded silylcyclopropane 3.2a as a colorless oil (70.7 mg, 0.242 mmol, 80% isolated yield, dr = 1.0:0.3). 1H NMR (500 MHz, CDCl3) mixture of diastereomers (1.0:0.3 ratio)  9.67 (t, J = 2.0 Hz, 1 H), 9.33 (dd, J = 2.0, 2.5 Hz, 0.3 H), 7.55 (m, 0,6 H), 7.38 (m, 0,9 H), 7.33–7.17 (m, 10.9 H), 7.10 (m, 0.6 H), 2.66 (dd, J = 2.0, 17.0 Hz, 1 H), 2.25 (dd, J = 6.0, 8.0 Hz, 0.3 H, partially overlapped), 2.22 (dd, J = 6.0, 8.0 Hz, 1 H), 2.18 (dd, J = 3.0, 17.5 Hz, 0.3 H), 2.01 (dd, J = 2.0, 17.0 Hz, 1 H), 1.79 (dd, J = 2.0, 17.5 Hz, 0.3 H), 1.39 (dd, J = 4.5, 6.0 Hz, 1 H), 1.16 (dd, J = 5.5, 8.0 Hz, 0.3 H), 1.09 (t, J = 5.0 Hz, 0.3 H), 0.93 (dd, J = 4.5, 8.5 Hz, 1 H), 0.36 (s, 0.9 H), 0.35 (s, 0.9 H), 0.08 (s, 3 H), -0.23 (s, 3 H). 13C 219 NMR (126 MHz, CDCl3) major diastereomer  202.7, 139.1, 137.9, 134.0, 129.9, 129.0, 128.0, 127.7, 126.5, 53.2, 29.4, 15.7, -2.8, -3.4. Minor diastereomer (a substituted aromatic carbon could not be located)  203.2, 137.8, 134.1 (2 C), 129.5, 129.3 (2 C), 128.2 (2 C), 127.9 (2 C), 126.4, 45.1, 24.9, 10.3, -4.35, -4.43. IR (neat) 3063, 2956, 1722, 1496. 1427, 1250, 1111, 816 cm-1. HRMS (EI) m/z 294.1430 [(M)+; calcd for C19H22OSi, 294.1440]. Preparation of 2-(1-(ethyldimethylsilyl)-2-phenylcyclopropyl)acetaldehyde (3.2b) Following General Procedure G, dihydropyran 3.1b (38 mg, 0.154 mmol, 1 equiv) in THF (1.9 mL) and sec-butyllithium (0.16 mL, 0.23 mmol, 1.5 equiv) at –78 ºC for 40 minutes, followed by workup and silica gel chromatography (5% EtOAc in hexanes) afforded silylcyclopropane 3.2b as a colorless oil (70.7 mg, 0.123 mmol, 80% isolated yield, crude dr = 1.0:0.26, isolated dr = 1.0:0.3). Mixture of diastereomers (1.0:0.3 ratio) 1H NMR 600 MHz, CDCl3)  9.90 (dd, J = 1.8, 6.0 Hz, 1 H), 9.50 (dd, J = 2.4, 6.0 Hz, 0.3 H), 7.29 (m, 2 H), 7.24 (m, 2.6 H), 7.17 (m, 1.9 H), 2.74 (dd, J = 6.0, 16.8 Hz, 1 H), 2.19 (m, 1.6 H), 2.01 (dd, J = 1.8, 16.8 Hz, 1 H), 1.80 (dd, J = 2.4, 17.4 Hz, 0.3 H), 1.24 (dd, J = 4.8, 6.0 Hz, 1 H), 1.13 (dd, J = 5.4, 7.8 Hz, 0.3 H), 1.07 (t, J = 5.4 Hz, 0.3 H), 0.97 (t, J = 7.8 Hz, 0.9 H), 0.86 (dd, J = 4.8, 8.4 Hz, 1.3 H), 0.76 (t, J = 7.8 Hz, 3 H), 0.56 (q, J = 7.8 Hz, 0.6 H), 0.26 (m, 2 H), 0.00 (s, 1.8 H), -0.32 (s, 3 H), -0.42 (s, 3 H). 13C NMR (126 MHz, CDCl3) Major diastereomer:  202.9, 139.4, 129.9 (2 C), 127.9 (2 C), 126.4, 53.4, 29.4, 15.3, 9.9, 7.3, 6.6, -3.8, -4.0. Minor diastereomer:  203.4, 138.1, 129.4 (2 C), 128.2 (2 C), 126.4, 45.4, 24.7, 13.7, 9.1, 7.4, 5.8, -5.0, -5.1. IR (film) 3059, 2955, 1724, 1454, 1250, 814 220 cm-1. HRMS (EI) m/z 246.1431 [(M)+; calcd for C15H22OSi, 246.1440]. Preparation of 2-(2-phenyl-1-(triethylsilyl)cyclopropyl)acetaldehyde (3.2c) Following General Procedure G, dihydropyran 3.1c (89 mg, 0.324 mmol, 1 equiv) in THF (4 mL) and sec-butyllithium (0.27 mL, 0.389 mmol, 1.2 equiv) at –78 ºC for 1 h, followed by workup and silica gel chromatography (5% EtOAc in hexanes) afforded silylcyclopropane 3.2c as a colorless oil (62 mg, 0.227 mmol, 70% isolated yield, crude dr = 11:1, isolated dr > 20:1). 1H NMR (500 MHz, CDCl3)  9.90 (dd, J = 2.5, 3.0 Hz, 1 H), 7.30 (m, 2 H), 7.24 (m, 2 H), 7.18 (m, 1 H), 2.72 (dd, A of ABX system, J = 2.5, 17.0 Hz, 1 H), 2.14 (dd, J = 6.0, 8.0 Hz, 1 H), 2.04 (dd, B of ABX system, J = 2.0, 17.0 Hz, 1 H), 1.32 (dd, J = 4.5, 5.5 Hz, 1 H), 0.91 (dd, J = 4.5, 8.0 Hz, 1 H), 0.78 (t, J = 8.0 Hz, 9 H), 0.30 (m, 3 H), 0.15 (m, 3 H). 13C NMR (126 MHz, CDCl3)  203.2, 139.4, 129.7 (2 C), 127.9 (2 C), 126.4, 53.6, 28.7, 15.7, 9.4, 7.5, 3.2. IR (film) 3060, 2956, 1725, 1450, 1250, 814 cm-1. HRMS (EI) m/z 274.1747 [(M)+; calcd for C17H26OSi, 274.1753]. Preparation of 2-(1-(dimethyl(phenyl)silyl)-2-(p-tolyl)cyclopropyl)acetaldehyde (3.2d) Following General Procedure G, dihydropyran 3.1d (108 mg, 0.35 mmol, 1 equiv) in THF 221 (4.5 mL) and sec-butyllithium (0.3 mL, 0.42 mmol, 1.2 equiv) at –78 ºC for 10 minutes, followed by workup and silica gel chromatography (5% EtOAc in hexanes) afforded silylcyclopropane 3.2d as a colorless oil (93.7 mg, 0.305 mmol, 87% isolated yield, crude dr = 1.0:0.3, isolated dr = 1.0:0.4). Mixture of diastereomers (1:0.4 ratio) 1H NMR (500 MHz, CDCl3)  9.67 (t, J = 2.0 Hz, 1 H), 9,34 (t, J = 2.0 Hz, 0.4 H), 7.55 (m, 0.8 H), 7.39–7.27 (m, 6.2 H), 7.14 (d, J = 8.0 Hz, 2 H), 7.05 (m, 2.8 H), 6.99 (d, J = 8.0 Hz, 0.8 H), 2.64 (dd, J = 2.0, 17.0 Hz, 1 H), 2.33 (s, 2 H), 2.30 (s, 0.8 H), 2.22–2.16 (m, 1.8 H), 1.99 (dd, J = 2.0, 17.5 Hz, 1 H), 1.81 (dd, J = 2.0, 17.5 Hz, 0.4 H), 1.38 (t, J = 4.5 Hz, 1 H), 1.14 (dd, J = 5.0, 8.0 Hz, 0.4 H), 1.07 (t, J = 5.5 Hz, 0.4 H), 0.92 (dd, J = 4.5, 8.0 Hz, 1 H), 0.36 (s, 1.2 H), 0.35 (s, 1.2 H), 0.10 (s, 3 H), -0.21 (s, 3 H). 13C NMR (126 MHz, CDCl3) Major diastereomer:  202.6, 138.0, 135.97, 135.96, 134.1, 134.0 (2 C), 129.7 (2 C), 128.6 (2 C), 127.7 (2 C), 53.2, 29.0, 21.1, 15.7, 10.3, -2.7, -3.4. Minor diastereomer (one aromatic carbon could not be located):  203.2, 136.8, 135.94, 134.6, 129.4, 129.2 (2 C), 129.0 (2 C), 128.9 (2 C), 127.9 (2 C), 45.1, 24.5, 21.0, 13.9, 9.3, -4.2, -4.4. IR (film) 3033, 2954, 1719, 1490, 1250, 830 cm-1. HRMS (EI) m/z 308.1591 [(M+); calcd for C20H24OSi, 308.1596]. Preparation of 2-(1-(benzyldimethylsilyl)-2-(p-tolyl)cyclopropyl)acetaldehyde (3.2e) Following General Procedure G, dihydropyran 3.1e (78 mg, 0.242 mmol, 1 equiv) in THF (3 mL) and sec-butyllithium (0.18 mL, 0.254 mmol, 1.05 equiv) at –78 ºC for 15 minutes, followed by workup and silica gel chromatography (5% EtOAc in hexanes) afforded silylcyclopropane 3.2e as a colorless oil (71.7 mg, 0.223 mmol, 92% isolated yield, crude dr = 1.0:0.5, isolated dr = 222 1.0:0.24). Mixture of diastereomers (1.0:0.24 ratio) 1H NMR (500 MHz, CDCl3)  9.90 (dd, J = 2.0, 2.5 Hz, 1 H), 7.20 (d, J = 8.0 Hz, 2 H), 7.12 (t, J = 7.5 Hz, 2 H), 7.07 (d, J = 8.0 Hz, 2 H), 7.00 (t, J = 7.5 Hz, 1 H), 6.78 (m, 2 H), 2.79 (dd, A of ABX system, J = 3.0, 17.5 Hz, 1 H), 2.32 (s, 3 H), 2.18 (m, 1 H), 2.04 (dd, B of ABX system, J = 2.5, 17.5 Hz, 1 H), 1.86 (d, C of CDX system, J = 13.5 Hz, 1 H), 1.80 (dd, D of CDX system, J = 13.5 Hz, 1 H), 1.22 (t, J = 5.5 Hz, 1 H), 0.86 (dd, J = 5.0, 8.5 Hz, 1 H), -0.32 (s, 3 H), -0.45 (s, 3 H). 13C NMR (126 MHz, CDCl3) major diastereomer  202.8, 139.7, 136.2, 136.1, 129.8 (2 C), 128.7 (2 C), 128.2 (2 C), 128.0 (2 C), 124.0, 53.4, 29.3, 24.8, 21.1, 15.5, 9.8, -3.3, -3.6. IR (film) 3024, 2957, 2720, 1722, 1493, 1250, 827 cm-1. HRMS (EI) m/z 231.1197 [(M-C7H7)+; calcd for C14H19OSi, 231.1205]. The minor diastereomer was also partially purified as the major component. (1.0:0.2 ratio) 1H NMR (500 MHz, CDCl3)  9.50 (dd, J = 2.0, 3.0 Hz, 1 H), 7.21 (t, J = 7.5 Hz, 2 H), 7.07 (m, 3 H), 7.02 (m, 2 H), 6.98 (d, J = 8.0 Hz, 2 H), 2.32 (s, 3 H), 2.18 (m, 4 H), 1.87 (dd, J = 2.0, 17.5 Hz, 1 H), 1.12 (dd, J = 5.5, 8.0 Hz, 1 H), 1.05 (t, J = 5.5 Hz, 1 H), -0.01 (s, 3 H), -0.02 (s, 3 H). 13C NMR (126 MHz, CDCl3)  203.3, 139.5, 136.0, 134.6, 129.3 (2 C), 128.9 (2 C), 128.3 (4 C), 124.2, 45.4, 24.6, 24.2, 21.0, 13.9, 8.9, -4.5, -4.7. IR (film) 3025, 2956, 2720, 1722, 1493, 1251, 827 cm-1. HRMS (EI) m/z 231.1209 [(M-C7H7)+; calcd for C14H19OSi, 231.1205]. Preparation of 2-(1-(ethyldimethylsilyl)-2-(o-tolyl)cyclopropyl)acetaldehyde (3.2f) Following General Procedure G, dihydropyran 1f (95 mg, 0.365 mmol, 1 equiv) in THF (4.6 mL) and sec-butyllithium (0.3 mL, 0.438 mmol, 1.2 equiv) at –78 ºC for 13 minutes, followed 223 by workup and silica gel chromatography (5% EtOAc in hexanes) afforded silylcyclopropane 2f as a colorless oil (86.5 mg, 0.332 mmol, 91% isolated yield, crude dr = 8.3:1.0, isolated dr = 20:1). 1 H NMR (500 MHz, CDCl3)  9.88 (t, J = 2.5 Hz, 1 H), 7.12–7.05 (m, 4 H), 2.56 (dd, J = 2.5, 16.5 Hz, 1 H), 2.37 (overlapped, dd, J = 3.0, 16.5 Hz, 1 H), 2.37 (s, 3 H), 1.95 (dd, J = 6.0, 8.0 Hz, 1 H), 1.37 (dd, J = 5.0, 6.0 Hz, 1 H), 0.97 (dd, J = 5.0, 8.5 Hz, 1 H), 0.76 (t, J = 8.0 Hz, 3 H), 0.26 (m, 2 H), -0.30 (s, 3 H), -0.39 (s, 3 H). 13C NMR (126 MHz, CDCl3)  202.8, 138.8, 137.5, 129.7, 128.3, 126.6, 125.3, 53.5, 29.0, 20.1, 14.7, 10.3, 7.3, 6.8, -3.7, -3.9. IR (film) 3029, 2953, 1722, 1124, 830 cm-1. HRMS (EI) m/z 260.1605 [(M+); calcd for C16H24OSi, 260.1596]. Synthesis of 2-(1-(ethyldimethylsilyl)-2-(3-methoxyphenyl)cyclopropyl)acetaldehyde (3.2g) Following General Procedure G, dihydropyran 3.1g (68.9 mg, 0.249 mmol, 1 equiv) in THF (3.1 mL) and sec-butyllithium (0.2 mL, 0.274 mmol, 1.1 equiv) at –78 ºC for 30 minutes, followed by workup and silica gel chromatography (5-10% EtOAc in hexanes) afforded silylcyclopropane 3.1g as a colorless oil (41.7 mg, 0.152 mmol, 61% isolated yield, crude dr = 2:1, isolated dr = 1.1:1.0). Mixture of diastereomers (cis/trans 1.1:1) 1H NMR (500 MHz, CDCl3)  9.89 (t, J = 2.5 Hz, 1.1 H), 9.51 (dd, J = 2.0, 3.0 Hz, 1 H), 7.18 (t, J = 8.0 Hz, 1 H), 7.15 (t, J = 8.0 Hz, 1.1 H), 6.87 (m, 2.1 H), 6.71 (m, 4.2 H), 3.78 (s, 3.3H), 3.77 (s, 3 H), 2.74 (dd, J = 3.0, 17.5 Hz, 1.1 H), 2.23–2.13 (m, 3.1 H), 2.01 (dd, t, J = 2.0, 17 Hz, 1.1 H), 1.83 (dd, t, J = 2.5, 17.5 Hz, 1 H), 1.22 (dd, J = 4.5, 5.5 Hz, 1.1 H), 1.12 (dd, J = 5.0, 8.0 Hz, 1 H), 1.05 (t, J = 5.5 Hz, 1 H), 0.97 (t, J = 8.0 Hz, 3 H), 0.86 (m, 1.1 H), 0.77 (t, J = 8.0 Hz, 3.3 H), 0.55 (q, J = 8.0 Hz, 2 H), 0.28 224 (m, 2.2 H), 0.00 (s, 6 H), -0.29 (s, 3.3 H), -0.39 (s, 3.3 H). 13C NMR (126 MHz, CDCl3) major diastereomer  202.9, 159.3, 141.1, 128.9, 121.8, 115.5, 112.0, 29.5, 15.5, 9.9, 7.3, 6.7, -4.0, -5.0. Minor diastereomer  203.5, 159.5, 139.8, 129.2, 122.3, 115.5, 111.4, 24.8, 13.9, 9.1, 7.4, 5.8, - 3.7, -5.2. IR (film) 2955, 1722, 1601, 1255, 1045, 835 cm-1. HRMS (EI) m/z 276.1550 [(M)+; calcd for C16H24O2Si, 276.1546] Preparation of 2-(1-(dimethyl(phenyl)silyl)-2-ferrocenylcyclopropyl)acetaldehyde (3.2h) Following General Procedure G, dihydropyran 3.1h (117 mg, 0.291 mmol, 1 equiv) in THF (3.6 mL) and sec-butyllithium (0.25 mL, 0.349 mmol, 1.2 equiv) at –78 ºC for 10 minutes, followed by workup and silica gel chromatography (5% EtOAc in hexanes) afforded silylcyclopropane 3.2h as an orange oil (80.3 mg, 0.201 mmol, 69%, isolated yield, crude dr = 9.4:1, isolated dr = 1.0:0.1). Mixture of diastereomers (1.0:0.1 ratio) 1H NMR (500 MHz, CDCl3) major diastereomer:  9.53 (t, J = 7.0 Hz, 1 H), 7.31 (m, 2 H), 7.28 (m, 3 H), 4.30 (m, 1 H), 4.09 (m, 1 H), 4.08 (s, 5 H), 3.92 (m, 1 H), 3.76 (m, 1 H), 2.42 (dd, A of ABX system, J = 2.0, 17.0 Hz, 1 H), 1.97 (dd, B of ABX system, J = 2.0, 17.0 Hz, 1 H), 1.93 (dd, J = 6.5, 9.0 Hz, 1 H), 1.03 (d, J = 4.5, 6.0 Hz, 1 H), 0.87 (dd, J = 5.0, 8.5 Hz, 1 H), 0.06 (s, 3 H), -0.04 (s, 3 H). 13C NMR (126 MHz, CDCl3)  202.8, 138.1, 134.2 (2 C), 129.0, 127.6 (2 C), 86.5, 70.1, 69.3, 68.7 (5 C), 68.2, 66.0, 53.3, 24.9, 16.8, 11.2, - 2.5, -2.9. IR (film) 3091, 2988, 1722, 1427, 1250, 1107, 816 cm-1. HRMS (EI) m/z 402.1093 [(M+); calcd for C23H26OSiFe, 402.1102]. 225 Preparation of 2-(1-(ethyldimethylsilyl)-2-(thiophen-2-yl)cyclopropyl)acetaldehyde (3.2i) Following General Procedure G, dihydropyran 3.1i (39.5 mg, 0.157 mmol, 1 equiv) in THF (2 mL) and sec-butyllithium (0.25 mL, 0.344 mmol, 2.2 equiv) at –78 ºC for 1 h, followed by workup and silica gel chromatography (5% EtOAc in hexanes) afforded silylcyclopropane 3.2i as a colorless oil (28 mg, 0.112 mmol, 71% isolated yield, crude dr = 1.0:0.5, isolated dr = 1.0:0.5). Mixture of diastereomers (trans/cis 1.0:0.5). 1H NMR (500 MHz, CDCl3)  9.84 (dd, J = 2.0, 3.0 Hz, 0.5 H), 9.57 (dd, J = 2.0, 3.0 Hz, 1 H), 7.10 (m, 1.5 H), 6.90 (dd, J = 3.5, 5.0 Hz, 1.0 H), 0.87 (dd, J = 3.5, 5.0 Hz, 0.5 H), 6.81 (dt, J = 1.5, 3.5 Hz, 0.5 H), 6.73 (dt, J = 1.5, 3.5 Hz, 1 H), 2.65 (dd, A of ABX system, J = 3.0, 17.5 Hz, 0.5 H), 2.30 (dd, C of CDX system, J = 3.0, 17.5 Hz, 1 H), 2.24 (dd, J = 5.5, 7.0 Hz, 1 H), 2.14 (dd, J = 6.0, 7.5 Hz, 0.5 H), 2.02 (dd, B of ABX system, J = 2.0, 17.0 Hz, 0.5 H), 1.95 (dd, D of CDX system, J = 2.0, 17.5 Hz, 1 H), 1.25 (m, 1.5 H), 1.01 (t, J = 5.0 Hz, 1 H), 1.00 (m, 0.5 H), 0.97 (t, J = 8.0 Hz, 3 H), 0.81 (t, J = 8.0 Hz, 1.5 H), 0.54 (q, J = 8.0 Hz, 2 H), 0.40–0.28 (m, 1 H), -0.01 (s, 3 H), 0.02 (s, 3 H), -0.21 (s, 1.5 H), -0.32 (s, 1.5 H). 13 C NMR (126 MHz, CDCl3) major diastereomer:  203.2, 142.6, 126.9, 126.0, 124.1, 19.2, 16.4, 10.1, 7.4, 5.8, -5.0, -5.3. Minor diastereomer:  202.7, 144.1, 126.5, 126.2, 124.0, 23.3, 17.6, 11.2, 7.3, 6.4, -4.0, -4.3. IR (film) 2953, 1722, 1250, 833 cm-1. HRMS (EI) m/z 252.1001 [(M)+; calcd for C13H20OSiS, 252.1004]. 226 Preparation of 2-(1-(dimethyl(phenyl)silyl)-2-propylcyclopropyl)acetaldehyde (3.2j) Following general procedure H, dihydropyran 3.1j (82.8 mg, 0.318, 1 equiv), in THF (4 mL) and sec-butyllithium (0.27 mL, 0.381 mmol, 1.2 equiv) at –78 ºC and warming to –10 ºC for 2 h, followed by aqueous workup and silica gel chromatography (5% EtOAc in hexanes) afforded silylcyclopropane 3.2j as a colorless oil (68.6 mg, 0.316 mmol, 83% isolated yield, crude dr = 4.3:1.0, isolated dr = 1.0:0.2). Mixture of diastereomers (cis/trans = 1.0:0.2 ratio). 1H NMR (600 MHz, CDCl3) major diastereomer (cis):  9.53 (t, J = 2.4 Hz, 1 H), 7.50 (m, 2 H), 7.34 (m, 3 H), 2.41 (dd, A of ABX system, J = 2.4, 16.8 Hz, 1 H), 1.80 (dd, B of ABX system, J = 2.4, 17.4 Hz, 1 H), 1.56 (m, 1 H), 1.38 (m, 2 H), 1.11 (m, 1 H), 0.88 (t, J = 7.2 Hz, 3 H), 0.81 (m, 1 H), 0,61 (dd, C of CDX system, J = 4.2, 8.4 Hz, 1 H), 0.56 (dd, D of CDX system, J = 4.2, 5.4 Hz, 1 H), 0.36 (s, 3 H), 0.32 (s, 3 H). Minor diastereomer (trans):  9.50 (t, J = 2.4 Hz, 1 H), 7.48 (m, 2 H), 2.38 (dd, A of ABX system, J = 3.0, 17.4 Hz, 1 H), 2.23 (dd, B of ABX system, J = 2.4, 17.4 Hz, 1 H), 0.24 (s, 6 H), all other protons are overlapped with major diastereomer, presumably at 7.34 (3 H), 1.38 (4 H), 0.92–079 (6 H). 13C NMR (151 MHz, CDCl3) mixture of diastereomers (cis / trans = 1.0:0.2 ratio), Major (cis) diastereomer:  203.3, 138.4, 134.1 (2 C), 129.1, 127.8 (2 C), 53.4, 33.5, 26.0, 23.3, 17.9, 13.9, 6.4, -1.4, -2.1. IR (neat) 3070, 2957, 2872, 1725, 1427, 1251, 1111, 816 cm-1. HRMS (EI) m/z 260.1590 [(M)+; calcd for C16H24OSi, 260.1596]. 227 Preparation of 2-(2-cyclohexyl-1-(dimethyl(phenyl)silyl)cyclopropyl)acetaldehyde (3.2k) Following general procedure H, dihydropyran 3.1k (67 mg, 0.223, 1 equiv), in THF (2.8 mL) and n-butyllithium (0.28 mL, 0.446 mmol, 2 equiv) at –78 ºC and warming to –10 ºC for 2 h, followed by aqueous workup and silica gel chromatography (5% EtOAc in hexanes) afforded silylcyclopropane 3.2k as a colorless oil (50.4 mg, 0.170 mmol, 76% isolated yield, crude dr = 1.6:1.0, isolated dr = 1.0:0.6). Mixture of diastereomers (~1:0.6 ratio). 1H NMR (500 MHz, CDCl3)  9.54 (dd, J = 2.0, 3.0 Hz, 1 H), 9.47 (dd, J = 2.0, 3.0 Hz, 0.6 H), 7.49 (m, 3.2 H), 7.34 (m, 4.8 H), 2.54 (dd, J = 3.0, 17.0 Hz, 1 H), 2.50 (22, J = 3.5, 17.5 Hz, 0.6 H), 2.06 (dd, J = 2.0, 17.0 Hz, 0.6 H), 1.84 (m, 1 H), 1.75–1.56 (m, 8.80 H), 1.17–0.93 (m, 8.64 H), 0.89–0.80 (m, 2 H), 0.70 (m, 13 1 H), 0.63–0.52 (m, 3.2 H), 0.38 (s, 3 H), 0.31 (s, 3 H), -0.23 (d, 3.6 H). C NMR (126 MHz, CDCl3)  203.9, 203.7, 138.2, 137.1, 134.1, 134.0, 129.3, 129.1, 127.8, 127.7, 53.2, 44.5, 39.1, 37.6, 34.3, 33.43, 33.41, 33.38, 33.3, 26.6, 26.4, 26.33, 26.31, 26.30, 26.0, 25.9, 16.7, 14.1, 6.8, 5.3, -1.4, -2.2, -4.6, -4.7. HRMS (EI) m/z 300.1909 [(M)+; calcd for C19H28OSi, 300.1909]. Preparation of 2-(2-(dimethyl(phenyl)silyl)-[1,1'-bi(cyclopropan)]-2-yl)acetaldehyde (3.2l) Following general procedure H, dihydropyran 3.1l (66.8 mg, 0.257, 1 equiv), in THF (3.2 228 mL) and sec-butyllithium (0.22 mL, 0.309 mmol, 1.2 equiv) at –78 ºC and warming to –10 ºC for 2.5 h, followed by aqueous workup and silica gel chromatography (5% EtOAc in hexanes) afforded silylcyclopropane 3.2l as a colorless oil (51.6 mg, 0.188 mmol, 73% isolated yield, crude dr = 1:1, isolated dr = 1:1). Mixture of diastereomers (1:1 ratio) 1H NMR (600 MHz, CDCl3)  9.58 (t, J = 3.0 Hz, 1 H), 9.49 (t, J = 2.4 Hz, 1 H), 7.54 (m, 2 H), 7.47 (m, 2 H), 7.34 (m, 6 H), 2.49 (dd, A of ABX system, J = 2.4, 17.4 Hz, 1 H), 2.40 (dd, B of ABX system, J = 2.4, 18.0 Hz, 1 H), 2.36 (dd, C of CDX system, J = 2.4, 16.8 Hz, 1 H), 1.81 (dd, D of CDX system, J = 2.4, 16.8 Hz, 1 H), 0.78–0.72 (m, 2 H), 0.71 (t, J = 4.8 Hz, 1 H), 0.61–0.57 (m, 2 H), 0.54–0.43 (m, 6 H), 0.40 (s, 3 H), 0.37 (m, 3 H), 0.31 (t, J = 4.8 Hz, 1 H), 0.26 (m, 1 H), 0.23 (s, 3 H), 0.22 (s, 3 H), 0.21 (m, overlapped with Me singlet at 0.22, 1 H), 0.17–0.12 (m, 2 H). 13C NMR (151 MHz, CDCl3)  204.0, 203.1, 138.3, 137.1, 134.2 (2 C), 134.0 (2 C), 129.3, 129.1, 127.83 (2 C), 127.80 (2 C), 53.1, 45.5, 29.8, 23.2, 17.3, 14.7, 11.9, 9.5, 7.3, 6.7, 6.1, 6.0, 5.3, 4.5, -1.9, -2.2, -4.52, -4.55. IR (neat) 3071, 3000, 2959, 2816, 1722, 1427, 1250, 1113, 815 cm-1. HRMS (EI) m/z 258.1440 [(M)+; calcd for C16H22OSi, 258.1440]. Preparation of 2-(2-(triethylsilyl)-[1,1'-bi(cyclopropan)]-2-yl)acetaldehyde (3.2m) Following general procedure H, dihydropyran 3.1m (69.5 mg, 0.292, 1 equiv), in THF (3.6 mL) and sec-butyllithium (0.25 mL, 0.35 mmol, 1.2 equiv) at –78 ºC and warming to –10 ºC for 3 h, followed by aqueous workup and silica gel chromatography (3.5% EtOAc in hexanes) afforded silylcyclopropane 3.2m as a colorless oil (52.4 mg, 0.219 mmol, 75% isolated yield, crude dr = 229 1.5:1.0, isolated dr = 1.0:0.7). Mixture of diastereomers (1:0.7 ratio, relative stereochemistry was not assigned) 1H NMR (600 MHz, CDCl3) (1:0.7 ratio)  9.79 (t, J = 2.5 Hz, 0.7 H), 9.68 (dd, J = 2.5, 3.5 Hz, 1 H), 2.49 (dd, A of ABX system, J = 2.5, 17.0 Hz, 0.7 H), 2.42 (dd, C of CDX system, J = 3.0, 16.5 Hz, 1 H), 2.40 (dd, B of ABX system, J = 2.5, 17.0 Hz, 0.7 H), 1.77 (dd, D of CDX system, J = 2.5, 17.0 Hz, 1 H), 0.97 (t, J = 8.0 Hz, 9 H), 0.92 (t, J = 8.0 Hz, 6.3 H), 0.74 (dd, J = 4.5, 8.0 Hz, 0.7 H), 0.69–0.60 (m, heavily overlapped with SiCH2, not quantified), 0.60 (q, J = 8.0 Hz, 6 H), 0.52–0.47 (m, ~6 H), 0.46 (q, J = 8.0 Hz, 4.2 H), 0.37 (m, 1 H), 0.28–0.17 (m, ~4 H). 13 C NMR (126 MHz, CDCl3) major diastereomer:  203.9, 53.5, 29.2, 17.4, 12.2, 7.6, 6.0, 5.3, 4.5, 3.7. Minor diastereomer:  204.5, 46.2, 22.8, 14.5, 9.6, 7.4, 6.5, 5.6, 4.3, 2.2. IR (film) 3078, 2999, 2953, 1724, 1458, 1018, 733 cm-1. HRMS (EI) m/z 238.1756 [(M)+; calcd for C14H26OSi, 238.1753]. Preparation of 2-(2-(3-chlorophenyl)-1-(ethyldimethylsilyl)cyclopropyl)acetaldehyde (2n), 5-(3-chlorophenyl)-3-(ethyldimethylsilyl)cyclopent-2-en-1-ol (3n), and 1-(3-chlorophenyl)-3-(ethyldimethylsilyl)cyclopent-3-en-1-ol (4n) Following General Procedure G, dihydropyran 3.1n (90 mg, 0.32 mmol, 1 equiv) in THF (4 mL) and sec-butyllithium (0.24 mL, 0.336 mmol, 1.05 equiv) at –78 ºC for 15 minutes, followed by workup and silica gel chromatography (6–15% EtOAc in hexanes) afforded silylcyclopropane 3.2n (16.4 mg, 0.0544 mmol, 17% isolated yield, crude dr = 5.4:1, isolated dr = 1.0:0.12), 230 secondary alcohol 3.3n (49.7 mg, 0.173 mmol, 54% isolated yield, dr = 20:1), and tertiary alcohol 3.4n (6.3 mg, 0.0192 mmol, 6% isolated yield), all as colorless oils, together with unreacted 3.1n (21.5 mg, 0.074 mmol, 23% recovery). Spectroscopic data for 3.2n: mixture of diastereomers (cis / trans = 1.0:0.12 ratio) 1H NMR (600 MHz, CDCl3) major (cis) diastereomer:  9.87 (dd, J = 1.8, 3.0 Hz, 1 H), 7.28 (m, 1 H), 7.21 (m, 1 H), 7.19–7.15 (m, 2 H), 2.78 (dd, J = 2.4, 17.4 Hz, 1 H), 2.12 (dd, J = 6.6, 8.4 Hz, 1 H), 2.00 (dd, J = 1.8, 17.4 Hz, 1 H), 1.20 (dd, J = 5.4, 6.0 Hz, 1 H), 0.87 (dd, J = 5.4, 8.4 Hz, 1 H), 0.77 (t, J = 7.8 Hz, 3 H), 0.26 (m, 2 H), -0.31 (s, 3 H), -0.41 (s, 3 H). Minor (trans) diastereomer:  9.51 (dd, J = 1.8, 3.0 Hz, 0.15 H), 7.20–7.14 (m, heavily overlapped with major diastereomer, 0.45 H), 7.03 (m, 0.15 H), 2.17 (m, 0.30 H), 1.79 (dd, J = 1.8, 17.4 Hz, 0.15 H), 1.14 (dd, J = 5.4, 7.8 Hz, 0.15 H), 1.03 (t, J = 5.4 Hz, 0.15 H), 0.96 (t, J = 7.8 Hz, 0.45 H), 0.55 (q, J = 7.8 Hz, 0.30 H), 0.01 (s, 0.9 H). 13C NMR (151 MHz, CDCl3) major diastereomer  202.4, 141.8, 133.8, 129.9, 129.2, 128.2, 126.6, 53.3, 29.0, 15.5, 10.2, 7.3, 6.7, -3.7, -3.9. IR (film) 3422, 3061, 2955, 2876, 1724, 1250, 814 cm-1. HRMS (EI) m/z 228.1042 [(M)+; calcd for C15H21OSiCl, 280.1050]. Spectroscopic data for 3.3n: 1H NMR (600 MHz, CDCl3)  7.22 (t, J = 1.8 Hz, 1 H), 7.20 (d, J = 7.2 Hz, 1 H), 7.17 (m, 1 H), 7.11 (m, 1 H), 5.99 (q, J = 1.8 Hz, 1 H), 4.83 (m, 1 H), 3.12 (m, 1 H), 2.95 (ddt, J = 1.8. 8.4, 16.8 Hz, 1 H), 2.41 (ddt, J = 1.8, 6.6, 16.8 Hz, 1 H), 1.80 (s, 1 H), 0.95 (t, J = 7.8 Hz, 3 H), 0.60 (q, J = 7.8 Hz, 2 H), 0.09 (s, 6 H). 13C NMR (151 MHz, CDCl3)  147.5, 146.3, 141.8, 134.3, 129.8, 127.3, 126.4, 125.4, 86.4, 54.9, 43.0, 7.4, 6.6, -4.2, -4.3. IR (film) 3352, 2955, 1458, 1250, 1089, 837 cm-1. HRMS (EI) m/z 263.1019 [(M-OH)+; calcd for C15H20SiCl, 263.1023]. Spectroscopic data for 3.4n: 1H NMR (600 MHz, CDCl3)  7.49 (t, J = 1.8 Hz, 1 H), 7.34 (ddd, J = 1.2, 1.8, 7.8 Hz, 1 H), 7.24 (m, 1 H), 7.20 (ddd, J = 1.2, 2.4, 7.8 Hz, 1 H), 6.01 (m, 1 H), 231 2.97 (dq, J = 1.8, 18.0 Hz, 1 H), 2.87 (m, 1 H), 2.80–2.75 (m, 2 H), 2.04 (s, 1 H), 0.94 (t, J = 7.8 Hz, 3 H), 0.58 (q, J = 7.8 Hz, 2 H), 0.08 (s, 6 H). 13 C NMR (151 MHz, CDCl3)  149.0, 142.3, 137.8, 134.1, 129.4, 126.8, 125.4, 123.1, 82.9, 53.9, 52.4, 7.4, 6.7, -4.11, -4.13. IR (film) 3397, 3031, 2955, 1253, 839 cm-1. HRMS (EI) m/z 263.1009 [(M-OH)+; calcd for C15H20SiCl, 263.1023]. Preparation of trans-5-(pyridin-2-yl)-3-(triethylsilyl)cyclopent-2-en-1-ol (3.3o), cis-5-(pyridin-2-yl)-3-(triethylsilyl)cyclopent-2-en-1-ol (3.3o’), and 6-(pyridin-2-yl)-4-(triethylsilyl)-5,6-dihydro-2H-pyran-2-one (3.5o) Following General Procedure G, dihydropyran 3.1o (248 mg, 0.90 mmol, 1 equiv) in THF (15 mL) and 1.4M sec-butyllithium (1.9 mL, 2.7 mmol, 3.0 equiv) at –78 ºC for 2 hours, followed by workup and silica gel chromatography (35% EtOAc in hexanes) afforded silylcyclopentenols 3.3o (56 mg, 0.198 mmol, 22% isolated yield, dr = 20:1), 3.3o′ (29 mg, 0.099 mmol, 11% isolated yield, dr = 20:1), and lactone 3.5o (40 mg, 0.144 mmol, 16% isolated), all as colorless oils. Spectroscopic data for 3.3o: 1H NMR (500 MHz, CDCl3) δ 8.54 (ddd, J = 4.9, 1.9, 0.9 Hz, 1H), 7.62 (td, J = 7.7, 1.9 Hz, 1H), 7.21 (d, J = 7.8 Hz, 1H), 7.14 (ddd, J = 7.6, 4.9, 1.2 Hz, 1H), 6.07 (dt, J = 2.7, 1.6 Hz, 1H), 5.14 (dq, J = 7.0, 1.9 Hz, 1H), 3.36 (td, J = 8.3, 6.9 Hz, 1H), 2.94 (ddt, J = 15.8, 8.3, 1.6 Hz, 1H), 2.59 (ddt, J = 15.8, 8.5, 2.3 Hz, 1H), 0.96 (t, J = 7.9 Hz, 9H), 0.64 (q, J = 8.0 Hz, 6H). 13C NMR (126 MHz, CDCl3) δ 162.9, 149.1, 143.8, 143.3, 136.5, 122.0, 121.4, 84.7, 57.0, 41.0, 7.4, 2.9. HRMS (ESI) m/z 274.1630 [(M – H)+; calcd for C16H24NOSi, 274.1627]. Spectroscopic data for 3.3o′: 1H NMR (500 MHz, CDCl3) δ 8.58 (ddd, J = 4.9, 1.8, 0.9 Hz, 232 1H), 7.71 (td, J = 7.7, 1.8 Hz, 1H), 7.49 – 7.46 (m, 1H), 7.20 (ddd, J = 7.6, 4.9, 1.2 Hz, 1H), 6.09 (td, J = 2.8, 1.2 Hz, 1H), 5.54 (t, J = 2.1 Hz, 1H), 5.02 (dd, J = 11.2, 3.2 Hz, 1H), 3.13 (s, 1H), 2.44 (ddd, J = 17.5, 3.2, 1.2 Hz, 1H), 2.25 (dddd, J = 17.5, 11.1, 2.8, 1.5 Hz, 1H), 0.94 (t, J = 7.9 Hz, 9H), 0.63 (q, J = 8.1 Hz, 6H). 13 C NMR (126 MHz, CDCl3) δ 161.2, 149.0, 139.3, 136.8, 134.2, 122.4, 120.5, 89.6, 69.6, 33.2, 7.3, 2.2. HRMS (ESI) m/z 276.1787 [(M + H)+; calcd for C16H26NOSi, 276.1784]. Spectroscopic data for 3.5o: 1H NMR (500 MHz, CDCl3) δ 8.56 (dt, J = 4.9, 1.3 Hz, 1H), 7.75 (td, J = 7.7, 1.8 Hz, 1H), 7.59 (d, J = 7.9 Hz, 1H), 7.26 – 7.22 (m, 1H), 6.27 (dd, J = 2.4, 1.1 Hz, 1H), 5.49 (dd, J = 10.6, 4.1 Hz, 1H), 2.88 (ddd, J = 18.1, 4.1, 1.1 Hz, 1H), 2.67 (ddd, J = 18.1, 10.7, 2.4 Hz, 1H), 0.92 (t, J = 7.9 Hz, 9H), 0.69 (q, J = 7.6 Hz, 6H). 13C NMR (126 MHz, CDCl3) δ 162.5, 160.9, 158.0, 149.0, 137.0, 128.1, 123.0, 120.5, 79.2, 32.5, 7.1, 1.8. HRMS (ESI) m/z 290.1579 [(M + H)+; calcd for C16H24NO2Si, 290.1576]. Preparation of (E)-3-(dimethyl(phenyl)silyl)-5-(naphthalen-2-yl)pent-3-enal (3.6p), and (E)-3-(dimethyl(phenyl)silyl)-5-(naphthalen-2-yl)pent-4-enal (3.7p) Following General Procedure G, dihydropyran 3.1p (150 mg, 0.44 mmol, 1 equiv) in THF (15 mL) and 1.4M sec-butyllithium (0.63 mL, 0.88 mmol, 2.0 equiv) at –78 ºC for 2 hours, followed by workup and silica gel chromatography (5% EtOAc in hexanes) afforded aldehydes 3.6p (39.2 mg, 0.114 mmol, 26% isolated yield), 3.7p (20 mg, 0.057 mmol, 13% isolated yield) all as colorless oils. 233 Spectroscopic data for 3.6p: 1H NMR (500 MHz, CDCl3) δ 9.47 (t, J = 2.2 Hz, 1H), 7.86 – 7.77 (m, 3H), 7.64 – 7.60 (m, 1H), 7.57 – 7.52 (m, 2H), 7.50 – 7.45 (m, 2H), 7.43 – 7.35 (m, 3H), 7.32 (dd, J = 8.4, 1.8 Hz, 1H), 6.42 (tt, J = 7.0, 1.1 Hz, 1H), 3.65 (d, J = 7.0 Hz, 2H), 3.37 (dd, J = 2.2, 1.0 Hz, 2H), 0.42 (s, 6H). 13C NMR (126 MHz, CDCl3) δ 199.2, 144.9, 137.2, 137.1, 134.0, 133.6, 132.1, 130.8, 129.3, 128.2, 127.9, 127.6, 127.5, 127.1, 126.5, 126.1, 125.4, 44.9, 35.7, -3.3. HRMS (ESI) m/z 344.1593 [(M)+; calcd for C23H24OSi, 344.1596]. Spectroscopic data for 3.7p: 1H NMR (500 MHz, CDCl3) δ 9.67 (t, J = 2.1 Hz, 1H), 7.80 – 7.73 (m, 3H), 7.61 (s, 1H), 7.56 – 7.51 (m, 2H), 7.49 (dd, J = 8.5, 1.8 Hz, 1H), 7.47 – 7.37 (m, 5H), 6.39 (d, J = 15.9 Hz, 1H), 6.25 (dd, J = 15.9, 8.2 Hz, 1H), 2.65 – 2.43 (m, 3H), 0.39 (s, 6H). 13 C NMR (126 MHz, CDCl3) δ 202.9, 136.1, 135.0, 134.0, 133.6, 132.6, 130.3, 129.6, 128.9, 128.1, 128.0, 127.8, 127.6, 126.2, 125.5, 125.2, 123.3, 42.7, 27.7, -4.5, -5.3. HRMS (ESI) m/z 345.1676 [(M + H)+; calcd for C23H25OSi, 345.1675]. 3.10.5. Rearrangement of 6-phenyl-5,6-dihydropyran The 6-phenyl-5,6-dihydropyran (3.5) was synthesized following three steps from benzaldehyde (see the scheme below): 234 Preparation of 1-phenylbut-3-en-1-ol (3.13) Following a reported procedure61 with a slight modification, commercial zinc dust (3.92 g, 60 mmol, 2.0 equiv.) was weighed into a dry 250 mL round bottomed flask equipped with a magnetic stir bar. The flask was capped with a rubber septum and purged with nitrogen for approximately 5 minutes. Freshly distilled THF (80 mL) was added into the flask followed by 3.9 mL of allyl bromide (5.45g, 45 mmol, 1.5 equiv). The resulting mixture was stirred at room temperature for 30 minutes after which 2.9 mL of benzaldehyde (3.18 g, 30 mmol, 1.0 equiv.) was added dropwise. The resulting mixture was stirred at room temperature for 1 h then quenched by addition of 10 mL of saturated aqueous ammonium chloride solution. The mixture was diluted with 20 mL of diethyl ether and 10 mL of water, respectively. The layers were separated, and the aqueous layer was extracted with diethyl ether (20 mL x 3). The combined organic layers were washed with 10 mL saturated aqueous ammonium chloride, (10 mL x 2) water and 10 mL of saturated aqueous sodium chloride solution then dried over anhydrous magnesium sulfate. Filtration and concentration under reduced pressure afforded homoallylic alcohol 3.13 as a yellow oil (4.17 g, 28.2 mmol, 94% crude yield) which was used in the next step without further purification. 1H NMR (500 MHz, CDCl3) δ 7.36 (d, J = 4.4 Hz, 4H), 7.29 (ddd, J = 8.8, 4.9, 3.9 Hz, 1H), 5.88 – 5.76 (m, 1H), 5.21 – 5.11 (m, 2H), 4.73 (dd, J = 7.6, 5.3 Hz, 1H), 2.57 – 2.46 (m, 2H), 2.27 (s, 1H). 13C NMR (126 MHz, CDCl3) δ 143.8, 134.4, 128.3, 127.5, 125.8, 118.3, 73.3, 43.7. IR (neat) 3342, 3054, 1638, 1507, 1270, 1124, 1042, 817, 744 cm–1. Spectroscopic data were 235 in agreement with those reported in literature.62 Preparation of (1-(allyloxy)but-3-en-1-yl)benzene (3.14) To a dry 250 mL round bottomed flask fitted with a magnetic stir bar was weighed 1.73 g of sodium hydride (60% w/w suspension in mineral oil, 75 mmol, 3.0 equiv). The flask was sealed with a rubber septum and purged with nitrogen. Freshly distilled THF (40 mL) was then added to the flask via syringe. This was followed by addition of 4.3 mL of allyl bromide (6.05 g, 50 mmol, 2.0 equiv). The mixture was cooled to 0 °C using ice bath. To the cold suspension, 3.71 g of homoallylic 3.13 (25 mmol, 1.0 equiv) was added in a dropwise manner. After complete addition, the resulting mixtrure was allowed to warm up slowly to room temperature while stirring. The reaction was quenched after 5 hours by addition of 10 mL of saturated ammonium chloride solution. This was followed by addition of 20 mL of diethyl ether and 10 mL of water. The layers were separated, and the aqueous layer was extracted with diethyl ether (20 mL x 3). The combined organic layers were washed with 10 mL saturated ammonium chloride, (10 mL x 2) water and 10 mL of saturated sodium chloride solution then dried over anhydrous magnesium sulfate. Filtration and concentration under reduced pressure followed by a flash column chromatography purification (40% CH2Cl2 in hexanes) afforded 4.12 g, 22 mmol (88% isolated yield) of 3.14. 1H NMR (500 MHz, CDCl3) δ 7.39 – 7.34 (m, 2H), 7.34 – 7.27 (m, 3H), 5.91 (dddd, J = 17.3, 10.4, 6.0, 5.1 Hz, 1H), 5.80 (ddt, J = 17.2, 10.2, 7.0 Hz, 1H), 5.26 (dq, J = 17.3, 1.7 Hz, 1H), 5.17 (dq, J = 10.4, 1.4 Hz, 1H), 5.10 – 5.00 (m, 2H), 4.35 (dd, J = 7.5, 5.9 Hz, 1H), 3.94 (ddt, J = 12.8, 5.1, 1.6 Hz, 1H), 3.79 (ddt, J = 12.8, 6.1, 1.4 Hz, 1H), 2.67 – 2.57 (m, 1H), 2.44 (dddt, J = 14.3, 7.2, 5.9, 1.3 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 141.9, 134.9, 134.8, 128.3, 127.5, 126.7, 116.8, 116.7, 81.1, 236 69.4, 42.6. Spectroscopic data were in agreement with those reported in literature.63 Preparation of 2-phenyl-3,6-dihydro-2H-pyran (3.8) A dry 250 mL round bottomed flask fitted with a magnetic stir bar was sealed with a rubber septum and cooled under nitrogen. 136 mg (0.16 mmol, 0.008 equiv) of Grubbs catalyst 2 nd generation was weighed into a vial and dissolved in dry dichloromethane (5 mL). The solution was transferred by means of syringe into the flask and additional 125 mL of dry dichloromethane added. This was followed by addition of 3.8 g (20 mmol, 1.0 equiv) of 3.14 in 20 mL dry dichloromethane. The resulting mixture was stirred under nitrogen for 12 hours after which the dichloromethane was removed by rotorvap under reduced pressure. The crude material was purified by flash column chromatography (40% CH2Cl2 in hexanes) to give 3.17 g, 19.8 mmol (99% isolated yield) of dihydropyran 3.8. 1H NMR (500 MHz, CDCl3) δ 7.44 – 7.35 (m, 4H), 7.33 – 7.27 (m, 1H), 5.95 (ddt, J = 9.9, 5.4, 2.2 Hz, 1H), 5.84 (dtt, J = 10.9, 3.1, 1.5 Hz, 1H), 4.58 (dd, J = 10.3, 3.5 Hz, 1H), 4.45 – 4.34 (m, 2H), 2.45 – 2.34 (m, 1H), 2.33 – 2.22 (m, 1H). 13C NMR (126 MHz, CDCl3) δ 142.5, 128.3, 127.4, 126.4, 125.8, 124.4, 75.6, 66.5, 32.8. HRMS (APCI) m/z 160.0836 [(M)+; calcd for C11H12O, 160.0888]. 237 Preparation of 2-(2-phenylcyclopropyl)acetaldehyde (3.15) by Wittig rearrangement of 6-phenyl-5,6-dihydro-2H-pyran (3.8) Following General Procedure G, dihydropyran 3.8 (321 mg, 2.0 mmol, 1 equiv) in THF (40 mL) and sec-butyllithium (1.4 M in pentane) (1.7 mL, 2.4 mmol, 1.2 equiv) at –78 ºC for 1 hour, followed by workup and silica gel chromatography (5% EtOAc in hexanes) afforded cyclopropane 3.15 (34.5 mg, 0.22 mmol, 11% isolated yield, dr = 4:1) and 161 mg, 1.0 mmol (50% of recovered starting material) 3.8. Spectroscopic data for compound 3.15: 1H NMR (500 MHz, C6D6) δ 9.28 (t, J = 1.9 Hz, 1H), 7.11 – 7.05 (m, 2H), 7.03 – 6.97 (m, 1H), 6.91 – 6.83 (m, 2H), 1.75 (ddd, J = 17.1, 6.9, 2.0 Hz, 1H), 1.67 (ddd, J = 17.0, 7.1, 2.0 Hz, 1H), 1.27 (dt, J = 9.1, 4.9 Hz, 1H), 0.93 – 0.85 (m, 1H), 0.66 (dt, J = 8.5, 5.1 Hz, 1H), 0.34 (dt, J = 8.6, 5.2 Hz, 1H). 13 C NMR (126 MHz, C6D6) δ 200.2, 143.1, 128.9, 126.6, 126.3, 48.3, 23.1, 16.6, 15.6. HRMS (APCI) m/z 161.0948 [(M + H)+; calcd for C11H13O, 161.0966]. 3.10.6. Derivatization of 2-(2-phenyl-1-(triethylsilyl)cyclopropyl)acetaldehyde (3.2c) 238 Preparation of (E)-1-(2,4-dinitrophenyl)-2-(2-(2-phenyl-1-(triethylsilyl)cyclopropyl) ethylidene)hydrazine (3.16) Compound 3.16 was prepared from aldehyde 3.2c (dr > 20:1) utilizing the following procedure: To a 5 mL conical vial with a vane magnetic stir bar was weighed 50 mg (0.25 mmol, 1.0 equiv) of 2,4-dinitrophenylhydrazine (DNPH). A solution of ethanol/water (5:2), 2 mL was added to the vial followed by 13.4 µL of concentrated sulfuric acid (0.25 mmol, 1.0 equiv) and the resulting mixture stirred for about 5 minutes to make a homogeneous solution. Compound 3.2c (68.7 mg, 0.25 mmol, 1.0 equiv) in 1 mL ethanol was added dropwise to the vial and the mixture stirred for additional 10 minutes resulting in the formation of a deep orange precipitate. The mixture was filtered, and the residue rinsed with 10 mL solution of ethanol/water (5:2). The residue was dried for 12 hours under high vacuum to give 107 mg, 0.235 mmol (94% crude yield) of 3.16 as a single diastereomer. This product was recrystallized in ethanol/dichloromethane (4:1) and its crystal structure solved by X-ray crystallography and the results deposited to the Cambridge Crystallographic Data Centre and assigned CCDC 2031553. Spectroscopic and melting point data for compound 3.16: mp 115.5 to 117.0 °C; 1H NMR (500 MHz, DMSO-d6) δ 11.52 (s, 1H), 8.86 (d, J = 2.7 Hz, 1H), 8.37 (dd, J = 9.7, 2.7 Hz, 1H), 8.29 (dd, J = 7.2, 4.6 Hz, 1H), 7.91 (d, J = 9.7 Hz, 1H), 7.34 (d, J = 7.1 Hz, 2H), 7.27 (t, J = 7.5 Hz, 2H), 7.18 (t, J = 7.3 Hz, 1H), 2.74 (dd, J = 14.8, 7.3 Hz, 1H), 2.19 (t, J = 7.1 Hz, 1H), 2.04 (dd, J = 14.7, 4.7 Hz, 1H), 1.30 (dd, J = 5.9, 4.5 Hz, 1H), 0.97 (dt, J = 8.2, 4.8 Hz, 1H), 0.73 (t, J = 7.9 Hz, 9H), 0.30 (dq, J = 15.8, 7.9 Hz, 3H), 0.14 (dq, J = 15.7, 7.9 Hz, 3H). 13 C NMR (126 MHz, DMSO-d6) δ 154.6, 144.8, 139.6, 136.6, 129.9, 129.6, 128.8, 127.8, 126.3, 123.2, 116.3, 42.2, 27.5, 15.3, 12.2, 7.5, 2.8. IR (neat) 3291, 3107, 2951, 2872, 1614, 1588, 1519, 1496, 1426, 1324, 1308, 1281, 1222, 1138, 1071 cm-1. HRMS (ESI) m/z 455.2118 [(M + H)+; calcd for C23H31N4O4Si, 455.2115]. 239 REFERENCES (1) Felkin, H.; Tambute, A. 1,4-Alkyl shifts in the Wittig rearrangement of alkyl allyl ethers. 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A scalable membrane pervaporation approach for continuous flow olefin metathesis. Org. Process Res. Dev. 2020, 24, 2298. 244 APPENDIX Crystallographical information of compound 3.16 Crystal structure, Chirality not determined, but Regio-stereo chemistry is observed. Crystal data and experimental Figure 3.2: Crystal structure of compound 3.16 Experimental. Single yellow needle crystals of 3.16 used as received. A suitable crystal with dimensions 0.21 × 0.05 × 0.03 mm3 was selected and mounted on a nylon loop with paratone oil on a XtaLAB Synergy, Dualflex, HyPix diffractometer. The crystal was kept at a steady T = 100.00(10) K during data collection. The structure was solved with the ShelXT (Sheldrick, 2015) solution program using dual methods and by using Olex2 (Dolomanov et al., 2009) as the graphical interface. The model was refined with ShelXL 2018/3 (Sheldrick, 2015) using full matrix least squares minimisation on F2. Crystal data. C23H30N4O4Si, Mr = 454.60, monoclinic, P21/c (No. 14), a = 18.5519(12) Å, b = 7.2993(5) Å, c = 18.8084(12) Å, b = 114.662(8)°, a = g = 90°, V = 2314.6(3) Å3, T = 100.00(10) K, Z = 4, Z' = 1, m(Cu Ka) = 1.204, 14074 reflections measured, 4597 unique (Rint = 0.0666) which were used in all calculations. The final wR2 was 0.2855 (all data) and R1 was 0.1072 (I≥2 s(I)). 245 Table 3.2: Crystal data Compound 3.16 Formula C23H30N4O4Si CCDC 2031553 Dcalc./ g cm-3 1.305 m/mm-1 1.204 Formula Weight 454.60 Colour yellow Shape needle Size/mm3 0.21×0.05×0.03 T/K 100.00(10) Crystal System monoclinic Space Group P21/c a/Å 18.5519(12) b/Å 7.2993(5) c/Å 18.8084(12) a/° 90 b/° 114.662(8) g/° 90 V/Å3 2314.6(3) Z 4 Z' 1 Wavelength/Å 1.54184 Radiation type Cu Ka Qmin/° 4.725 Qmax/° 77.629 Measured Refl's. 14074 Indep't Refl's 4597 Refl's I≥2 s(I) 3836 Rint 0.0666 Parameters 296 Restraints 0 Largest Peak 0.802 Deepest Hole -0.396 GooF 1.185 wR2 (all data) 0.2855 wR2 0.2802 R1 (all data) 0.1193 R1 0.1072 246 Structure quality indicators Reflections: Refinement: Figure 3.3: Structure quality indicators A yellow needle-shaped crystal with dimensions 0.21×0.05×0.03 mm3 was mounted on a nylon loop with paratone oil. Data were collected using a XtaLAB Synergy, Dualflex, HyPix diffractometer equipped with an Oxford Cryosystems low-temperature device, operating at T = 100.00(10) K. Data were measured using w scans of 1.0° per frame for 4.3/17.4 s using Cu Ka radiation (micro- focus sealed X-ray tube, 50 kV, 1 mA). The total number of runs and images was based on the strategy calculation from the program CrysAlisPro (Rigaku, V1.171.40.84a, 2020). The actually achieved resolution was Q = 77.629. Cell parameters were retrieved using the CrysAlisPro (Rigaku, V1.171.40.84a, 2020) software and refined using CrysAlisPro (Rigaku, V1.171.40.84a, 2020) on 4376 reflections, 31 % of the observed reflections. Data reduction was performed using the CrysAlisPro (Rigaku, V1.171.40.84a, 2020) software which corrects for Lorentz polarization. The final completeness is 98.70 out to 77.629 in Q CrysAlisPro 1.171.40.84a (Rigaku Oxford Diffraction, 2020) Numerical absorption correction based on gaussian integration over a multifaceted crystal model Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm. The structure was solved in the space group P21/c (# 14) by using dual methods using the ShelXT (Sheldrick, 2015) structure solution program. The structure was refined by Least Squares using version 2018/2 of XL (Sheldrick, 2008) incorporated in Olex2 (Dolomanov et al., 2009). All non- hydrogen atoms were refined anisotropically. Hydrogen atom positions were calculated geometrically and refined using the riding model, except for the hydrogen atom on the non-carbon atom(s) which were found by difference Fourier methods and refined isotropically when data permits. CCDC 2031553 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures. Model has Chirality at C1 (Centro SPGR) R Verify. Model has Chirality at C2 (Centro SPGR) S Verify. In this centrosymmetric space group this means both, R,S and S,R confirmations are observed in the crystal studied. There is a single molecule in the asymmetric unit, which is represented by the reported sum formula. In other words: Z is 4 and Z' is 1. 247 Figure 3.4: Crystal structure of 3.16 showing hydrogen bonding Figure 3.5: Model has Chirality at C1 (Centro SPGR) R Verify. Model has Chirality at C2 (Centro SPGR) S Verify. In this centrosymmetric space group this means both, R,S and S,R confirmations are observed in the crystal studied 248 Figure 3.6: The following hydrogen bonding interactions with a maximum D-D distance of 2.9 Å and a minimum angle of 120 ° are present in 3.16: N2–O1: 2.634 Å Figure 3.7: The p-p interactions of 3.16. plane 2 to #2@3_676 (1-X,2-Y,1-Z): The angle between these two planes is 0.000 °, the centroid-centroid distance is 3.817 Å and the shift distance is 1.962 Å 249 Figure 3.8: Packing diagram of 3.16 Data Plots: Diffraction data Figure 3.9: Data plots: Diffraction data 250 Figure 3.9 (cont’d) 251 Data Plots: Refinement and data Figure 3.10: Data plots: Refinement and data Table 3.3: Reflection statistics Total reflections (after 14898 Unique reflections 4597 filtering) Completeness 0.933 Mean I/s 10.59 hklmax collected (22, 8, 23) hklmin collected (-23, -9, -16) hklmax used (21, 9, 23) hklmin used (-23, 0, 0) Lim dmax collected 100.0 Lim dmin collected 0.77 dmax used 17.09 dmin used 0.79 Friedel pairs 525 Friedel pairs merged 1 Inconsistent 29 Rint 0.0666 equivalents Rsigma 0.0642 Intensity transformed 0 Omitted reflections 0 Omitted by user 12 (OMIT hkl) Multiplicity (4557, 2079, 970, 341, Maximum multiplicity 13 210, 109, 27, 2) Removed systematic 812 Filtered off 0 absences (Shel/OMIT) 252 Table 3.4: Fractional atomic coordinates (×104) and equivalent isotropic displacement parameters (Å2×103) for 3.16. Ueq is defined as 1/3 of the trace of the orthogonalised Uij Atom x y z Ueq Si1 8542.1(8) 6859(2) 8121.6(8) 24.8(4) O1 4210(2) 7872(7) 5945(2) 36.5(10) O2 3309(2) 8675(7) 4812(2) 37.0(10) O3 3938(3) 9804(8) 2654(3) 48.3(13) O4 5030(3) 8764(8) 2654(3) 46.1(12) N1 6295(3) 5659(7) 6397(3) 31.3(11) N2 5580(3) 6558(8) 6070(3) 31.3(11) N3 3985(3) 8173(7) 5231(3) 31.6(11) N4 4574(3) 8999(8) 2970(3) 34.0(12) C1 7861(3) 5142(8) 8281(3) 27.2(12) C2 7564(3) 5259(9) 8922(3) 29.8(13) C3 8222(3) 3977(9) 9013(3) 31.9(13) C4 7281(3) 4185(9) 7533(3) 31.7(13) C5 6530(3) 5230(9) 7122(3) 30.8(13) C6 5309(3) 7133(8) 5315(3) 29.8(12) C7 4551(3) 7906(8) 4893(3) 27.8(12) C8 4302(3) 8517(9) 4124(4) 31.2(13) C9 4816(3) 8320(9) 3766(3) 32.2(13) C10 5557(3) 7522(9) 4157(4) 33.9(13) C11 5800(3) 6939(9) 4907(3) 32.4(13) C12 7683(3) 6914(9) 9425(3) 29.6(12) C13 7321(3) 8549(9) 9101(3) 29.3(13) C14 7407(3) 10100(9) 9561(4) 35.0(14) C15 7883(4) 10015(10) 10365(4) 36.3(14) C16 8242(4) 8385(10) 10681(4) 36.0(14) C17 8146(3) 6835(9) 10229(3) 30.7(13) C18 7928(3) 8512(9) 7331(3) 30.3(12) C19 8372(4) 10119(9) 7168(4) 35.0(14) C20 9204(3) 5423(9) 7794(3) 31.0(13) C21 9739(4) 4081(9) 8418(4) 34.7(14) C22 9201(3) 8121(9) 9039(4) 33.2(13) C23 9973(3) 8892(10) 9031(4) 36.7(14) 253 Table 3.5: Anisotropic Displacement Parameters (×104) for 3.16. The anisotropic displacement factor exponent takes the form: -2p2[h2a*2 × U11+ ... +2hka* × b* × U12] Atom U11 U22 U33 U23 U13 U12 Si1 24.6(7) 30.9(8) 26.2(7) -0.4(6) 17.9(6) -0.6(6) O1 32(2) 53(3) 35(2) -1(2) 23.3(18) 0(2) O2 26(2) 51(3) 42(2) 4(2) 21.0(18) 4.1(19) O3 34(2) 75(4) 40(2) 11(2) 20(2) 10(2) O4 44(2) 69(3) 39(2) 0(2) 31(2) 2(2) N1 26(2) 35(3) 35(3) -3(2) 16(2) -1(2) N2 25(2) 40(3) 33(3) 0(2) 16(2) 5(2) N3 29(2) 36(3) 40(3) -1(2) 25(2) -1(2) N4 29(2) 45(3) 33(3) -1(2) 18(2) -3(2) C1 25(3) 33(3) 31(3) 1(2) 20(2) -1(2) C2 28(3) 40(3) 30(3) 2(2) 21(2) -2(2) C3 34(3) 36(3) 32(3) 4(3) 20(2) 0(3) C4 29(3) 36(3) 36(3) -1(3) 20(2) -4(3) C5 29(3) 37(3) 35(3) -7(3) 22(2) -6(2) C6 29(3) 33(3) 35(3) -5(2) 21(2) -6(2) C7 24(3) 30(3) 36(3) -3(2) 20(2) -2(2) C8 25(3) 33(3) 40(3) -2(3) 18(2) -2(2) C9 31(3) 37(3) 36(3) -2(3) 22(2) -8(3) C10 29(3) 43(4) 40(3) -5(3) 24(3) -4(3) C11 25(3) 41(4) 38(3) -7(3) 20(2) -4(3) C12 24(3) 41(3) 33(3) 4(3) 22(2) 0(2) C13 25(3) 45(4) 30(3) 6(3) 23(2) 3(2) C14 32(3) 40(3) 47(3) 8(3) 30(3) 5(3) C15 35(3) 45(4) 38(3) -8(3) 25(3) -5(3) C16 36(3) 48(4) 30(3) -3(3) 19(3) -1(3) C17 29(3) 43(4) 29(3) 4(3) 21(2) 1(3) C18 29(3) 36(3) 34(3) 2(2) 21(2) 3(2) C19 40(3) 39(4) 36(3) 6(3) 25(3) 2(3) C20 26(3) 40(3) 33(3) 2(3) 18(2) -1(2) C21 34(3) 38(4) 41(3) 0(3) 25(3) 5(3) C22 28(3) 43(4) 38(3) -6(3) 23(2) -5(3) C23 28(3) 47(4) 40(3) -5(3) 19(3) -8(3) 254 Table 3.6: Bond Lengths in Å for 3.16 Atom Atom Length/Å Si1 C1 1.890(6) Si1 C18 1.885(6) Si1 C20 1.901(6) Si1 C22 1.887(6) O1 N3 1.249(6) O2 N3 1.227(6) O3 N4 1.227(7) O4 N4 1.233(6) N1 N2 1.374(7) N1 C5 1.285(8) N2 C6 1.361(8) N3 C7 1.450(6) N4 C9 1.458(8) C1 C2 1.524(7) C1 C3 1.516(8) C1 C4 1.537(8) C2 C3 1.491(8) C2 C12 1.492(9) C4 C5 1.490(8) C6 C7 1.412(8) C6 C11 1.422(7) C7 C8 1.394(8) C8 C9 1.385(8) C9 C10 1.388(9) C10 C11 1.358(9) C12 C13 1.380(9) C12 C17 1.396(8) C13 C14 1.394(9) C14 C15 1.398(9) C15 C16 1.372(10) C16 C17 1.381(9) C18 C19 1.536(8) C20 C21 1.533(8) C22 C23 1.545(8) 255 Citations CrysAlisPro (ROD), Rigaku Oxford Diffraction, Poland (?). CrysAlisPro Software System, Rigaku Oxford Diffraction, (2020). O.V. Dolomanov and L.J. Bourhis and R.J. Gildea and J.A.K. Howard and H. Puschmann, Olex2: A complete structure solution, refinement and analysis program, J. Appl. Cryst., (2009), 42, 339-341. Sheldrick, G.M., Crystal structure refinement with ShelXL, Acta Cryst., (2015), C71, 3-8. Sheldrick, G.M., ShelXT-Integrated space-group and crystal-structure determination, Acta Cryst., (2015), A71, 3-8. 256 Copies of NMR spectra 257 7.239 10.0 7.238 4.545 4.537 4.533 9.0 4.525 4.520 4.299 4.296 4.294 8.0 4.292 4.289 4.239 4.238 4.235 7.0 4.232 4.198 4.197 4.195 4.194 6.0 4.190 4.189 4.173 4.172 5.0 4.171 4.169 258 1.00 4.168 f1 (ppm) 1.11 4.166 1.20 2.599 5.03 2.598 4.0 1.79 2.596 2.593 2.592 2.591 2.587 3.0 2.586 2.584 2.16 2.583 0.92 2.582 0.84 2.581 2.0 2.579 2.578 2.242 2.241 2.234 1.0 2.233 2.069 2.068 2.063 2.062 0.0 2.058 2.057 91.82 28.19 81.08 77.26 77.00 76.75 70.60 68.45 68.20 68.10 68.04 67.03 65.76 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 f1 (ppm) 259 3.045 3.042 3.036 3.033 9.5 2.529 2.527 2.523 2.521 2.520 8.5 2.517 2.514 2.512 2.483 7.5 2.481 2.478 2.476 2.470 2.468 6.5 2.464 2.049 2.047 2.044 2.042 2.039 5.5 4.5 2.004 1.017 260 1.001 f1 (ppm) 0.547 0.546 0.544 0.543 0.542 3.5 0.540 0.537 1.00 0.536 0.535 0.533 1.08 0.530 2.5 1.10 0.529 0.89 0.526 0.82 0.524 0.521 1.5 0.519 0.517 0.94 0.351 0.348 1.98 0.345 0.5 0.98 0.256 0.97 0.251 0.248 0.246 0.244 -0.5 81.00 27.13 16.76 77.26 77.00 76.75 2.90 74.59 70.52 2.53 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 f1 (ppm) 261 262 263 10.0 7.547 7.543 7.537 7.535 9.0 7.528 7.372 7.368 7.298 7.284 8.0 7.269 1.79 7.240 2.74 7.234 1.87 7.214 2.95 7.213 7.0 7.198 7.196 5.846 5.843 5.840 6.0 5.631 1.00 5.629 0.99 5.625 5.624 5.0 4.549 264 4.543 4.537 f1 (ppm) 0.95 4.529 4.523 4.518 4.0 2.601 2.595 2.594 2.573 2.565 3.0 2.455 2.453 1.00 2.433 1.00 2.426 2.405 2.0 0.86 1.947 1.0 0.430 5.20 0.421 0.0 7.373 7.372 7.360 7.359 7.350 7.336 7.320 7.272 7.258 7.244 7.240 3.83 5.767 147.44 200 190 180 170 160 150 140 130 120 110 100 90 0.82 5.765 145.54 5.764 144.05 5.762 137.62 5.759 133.88 5.758 129.96 5.756 129.27 5.542 128.28 5.541 127.96 1.03 5.539 127.33 1.00 5.536 125.68 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 5.535 5.534 2.611 0.95 2.610 265 2.608 2.607 f1 (ppm) 2.604 2.603 2.601 80 77.25 2.600 77.00 2.452 76.75 70 72.16 2.450 2.432 2.430 60 2.424 1.00 2.404 1.00 50 2.110 47.01 0.83 2.108 2.106 40 2.104 0.950 30 0.935 0.934 0.919 20 2.84 0.632 1.76 0.617 10 0.601 0.585 0 -2.90 5.25 0.584 -2.99 f1 (ppm) 0.107 7.364 7.363 7.361 7.359 7.349 7.347 7.336 7.334 7.268 7.258 7.256 7.240 4.01 200 190 180 170 160 150 140 130 120 110 100 90 7.239 1.19 5.826 148.21 5.823 144.15 5.821 5.819 5.532 128.69 5.531 128.37 5.530 127.42 1.00 5.529 125.77 5.528 1.00 5.527 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 5.526 2.427 2.411 266 0.99 2.126 0.960 f1 (ppm) 0.958 0.950 0.946 80 77.25 0.945 77.00 0.941 76.75 70 72.20 0.939 0.933 0.932 60 0.674 1.00 0.673 50 0.671 47.06 1.00 0.97 0.670 0.662 40 0.660 0.658 30 0.656 0.649 0.647 20 8.83 0.644 0.643 10 7.33 5.65 0.636 6.88 0.634 0 0.631 -3.65 0.629 -3.73 f1 (ppm) 7.687 7.683 10.0 7.677 7.675 7.668 7.511 7.507 9.0 7.501 7.500 7.499 7.497 5.984 200 190 180 170 160 150 140 130 120 110 100 90 8.0 141.555 5.981 1.79 138.593 5.979 2.70 136.854 5.976 136.169 5.973 134.812 7.0 5.761 133.895 5.759 128.841 5.758 128.824 5.755 127.965 5.753 127.706 6.0 0.99 5.752 0.99 4.676 4.671 5.0 4.669 4.664 267 4.657 f1 (ppm) 4.652 f1 (ppm) 0.99 4.649 4.645 77.254 2.700 80 77.000 4.0 2.698 76.747 2.697 70 72.129 2.695 71.219 2.692 2.691 60 3.0 2.689 1.00 2.688 50 1.04 2.603 2.94 2.601 0.85 2.599 40 2.0 2.583 2.582 30 2.580 2.573 21.162 1.0 2.553 20 15.635 2.455 4.99 2.452 10 2.061 2.056 0 -3.332 0.0 0.572 -3.362 0.562 -3.669 7.529 7.526 7.516 7.513 9.5 7.240 7.228 7.227 7.227 7.226 8.5 7.161 7.158 7.146 147.48 200 190 180 170 160 150 140 130 120 110 100 90 7.129 141.12 0.95 7.128 7.5 1.13 137.66 7.127 136.94 0.97 7.126 0.95 133.88 7.124 129.79 5.827 129.22 6.5 5.824 128.95 5.822 127.93 5.820 125.63 1.01 5.817 5.581 0.97 5.580 5.5 4.5 5.578 0.98 5.576 268 5.575 5.573 f1 (ppm) f1 (ppm) 4.971 4.959 77.25 4.954 80 77.00 2.383 76.75 2.366 70 72.03 3.5 2.359 2.351 2.351 60 2.350 2.5 1.00 2.343 50 3.99 2.048 46.88 0.89 0.954 40 0.941 0.940 1.5 0.927 30 0.641 0.628 20 21.07 2.90 0.615 1.89 0.601 0.5 0.127 10 0.122 5.41 0 0.119 -2.90 0.117 -2.98 0.114 -0.5 -10 7.273 7.271 7.258 7.256 7.252 6.952 6.951 6.948 6.947 6.934 6.820 6.817 200 190 180 170 160 150 140 130 120 110 100 90 6.813 148.38 1.06 6.804 1.93 142.28 6.802 134.19 0.95 6.799 130.29 6.797 128.81 5.777 127.11 5.775 126.32 5.772 125.31 1.00 5.769 1.00 5.766 5.550 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 5.548 5.547 5.544 269 0.99 5.542 5.541 f1 (ppm) 4.706 3.818 77.21 3.02 2.616 80 77.00 2.614 76.79 2.612 70 68.45 2.610 2.609 2.607 60 2.450 1.00 2.449 50 1.00 2.431 45.42 0.93 2.429 2.422 40 2.402 2.099 30 2.094 0.958 20 19.24 2.90 0.942 0.927 1.94 0.639 10 7.33 0.624 6.88 5.74 0.608 0 -3.65 0.591 f1 (ppm) -3.73 0.115 10.0 7.539 7.534 7.528 7.527 7.520 9.0 7.361 7.357 7.356 7.348 5.797 8.0 5.794 159.721 5.791 200 190 180 170 160 150 140 130 120 110 100 90 1.83 5.788 2.76 5.785 148.193 5.574 145.910 7.0 5.572 5.571 5.568 129.378 5.567 128.657 5.565 6.0 4.277 118.125 0.97 4.157 112.840 0.97 4.157 111.313 4.156 5.0 4.155 4.153 270 4.152 f1 (ppm) 0.96 4.150 f1 (ppm) 0.94 4.149 1.79 4.085 4.082 80 77.254 4.0 4.50 77.000 0.92 4.081 4.078 76.746 70 72.117 4.070 4.015 3.0 4.015 60 4.012 55.224 1.10 4.011 50 1.00 4.010 46.996 4.009 2.0 4.008 40 0.92 4.005 2.500 30 2.498 2.449 1.0 2.448 20 2.430 2.429 10 7.332 5.80 1.862 6.885 1.855 0 0.0 0.403 -3.638 0.394 -3.723 7.240 10.0 7.232 7.229 7.222 7.219 9.0 6.967 6.965 6.964 6.963 6.959 8.0 6.952 200 190 180 170 160 150 140 130 120 110 100 90 6.949 6.942 5.759 147.262 0.87 5.756 137.978 5.754 133.949 7.0 1.94 5.751 129.173 5.748 129.153 5.532 127.883 5.531 5.529 6.0 5.527 1.00 5.525 1.00 5.524 5.0 5.005 0.99 4.987 271 4.986 93.333 f1 (ppm) 2.724 f1 (ppm) 2.722 2.721 77.254 2.719 80 77.000 4.0 2.716 76.746 2.714 70 68.300 2.712 68.113 2.711 67.704 2.608 60 67.608 3.0 2.606 66.754 1.01 2.604 50 65.696 1.00 2.589 45.137 2.587 0.90 40 2.585 2.0 2.577 2.559 30 2.178 2.172 0.941 20 1.0 3.10 0.925 0.909 10 2.01 0.604 0.602 0 0.588 -2.826 6.15 0.0 0.094 -2.917 10.0 7.507 7.503 7.497 7.488 7.348 9.0 7.344 7.338 7.334 5.784 5.782 8.0 5.779 5.776 200 190 180 170 160 150 140 130 120 110 100 90 1.86 5.572 147.95 2.87 5.571 147.57 5.569 7.0 5.567 5.565 5.564 128.90 3.486 126.53 2.395 124.37 6.0 2.393 123.51 1.00 2.392 0.97 2.390 2.388 5.0 2.386 2.367 272 2.366 f1 (ppm) 2.364 f1 (ppm) 2.363 2.360 77.25 4.0 2.359 80 77.00 2.357 76.75 2.153 70 0.97 68.48 2.151 2.135 3.0 2.133 60 2.131 2.125 50 0.99 2.124 46.83 1.00 2.105 1.501 40 2.0 1.370 1.338 30 1.05 1.334 2.95 1.248 1.08 0.851 20 1.0 2.67 0.840 0.837 10 7.32 5.03 0.823 6.84 0.392 0 0.388 -3.69 0.0 -3.76 0.383 10.0 7.500 7.499 7.496 7.480 7.344 9.0 7.340 7.329 5.811 5.809 5.808 8.0 5.806 5.803 1.88 5.802 200 190 180 170 160 150 140 130 120 110 100 90 2.84 5.565 147.81 5.563 7.0 5.559 137.77 5.558 133.80 2.761 129.44 2.758 129.16 2.754 127.89 6.0 2.519 1.00 2.518 0.98 2.516 2.514 5.0 2.513 2.511 273 2.316 f1 (ppm) 2.315 f1 (ppm) 2.297 2.296 4.0 2.288 80 77.25 2.287 77.00 2.269 76.75 2.267 70 69.28 1.582 3.0 0.806 60 0.95 0.789 1.00 0.448 1.00 0.440 50 0.432 44.98 2.0 0.430 40 39.14 0.414 1.05 0.413 0.375 30 0.212 1.0 0.210 20 18.81 0.86 0.202 1.88 13.97 0.201 5.37 0.193 10 0.96 -0.006 -2.87 0.0 0.87 -0.015 0 -2.93 -0.016 7.240 5.764 5.763 5.760 5.757 5.756 5.460 5.458 5.454 5.452 2.936 2.933 2.930 200 190 180 170 160 150 140 130 120 110 100 90 2.920 2.549 147.51 2.524 137.77 2.523 133.84 2.521 129.34 2.519 129.15 2.518 127.85 1.02 2.516 2.515 1.01 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 2.285 2.284 2.266 2.264 274 2.256 2.236 f1 (ppm) 0.923 0.908 0.892 77.25 80 77.00 0.884 0.873 76.75 0.613 70 74.54 0.608 0.96 0.598 60 0.592 1.00 0.583 0.576 50 1.00 0.567 44.30 0.560 40 0.514 0.504 0.496 30 0.486 0.478 20 10.18 17.34 0.469 5.29 0.354 2.29 10 0.343 2.87 0.90 0.335 2.23 0.88 0 0.184 -2.85 f1 (ppm) 0.176 -2.93 10.0 7.355 7.351 7.350 7.347 7.240 9.0 7.230 7.229 7.226 7.218 7.216 8.0 7.215 7.214 200 190 180 170 160 150 140 130 120 110 100 90 7.213 0.85 7.212 2.89 5.747 146.22 7.0 5.745 5.744 5.741 5.739 128.83 5.738 6.0 5.736 1.01 5.543 1.02 5.541 5.540 5.0 5.537 5.536 275 5.534 f1 (ppm) 0.98 4.681 f1 (ppm) 4.668 4.661 4.0 2.574 77.25 80 77.00 2.572 2.571 76.75 2.568 70 74.21 2.567 3.0 2.565 60 2.378 1.01 2.378 1.00 2.358 50 0.87 2.357 44.63 2.0 2.350 40 2.131 0.932 0.917 30 0.916 1.0 2.71 0.901 20 0.612 17.41 1.74 0.596 0.595 10 7.30 5.06 0.581 2.95 0.0 0.091 0 2.24 0.084 147.89 146.19 134.27 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 129.63 129.11 127.50 125.96 123.92 276 77.25 77.00 76.75 71.52 f1 (ppm) 47.09 7.32 40 30 20 10 6.87 0 -3.65 -3.74 277 278 279 7.517 7.502 7.347 7.345 7.343 7.272 7.257 7.240 7.144 7.141 7.127 5.693 5.690 1.78 5.687 2.72 5.481 1.94 5.479 0.95 5.474 1.88 5.165 5.162 5.131 5.128 5.090 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.90 5.086 1.00 5.069 0.99 5.065 0.95 4.207 280 4.197 0.96 4.191 4.180 3.764 3.753 0.98 3.741 3.738 0.98 3.731 0.98 3.728 3.549 3.546 3.537 3.534 1.00 3.520 0.98 3.508 2.648 2.638 2.636 2.621 2.619 2.416 2.414 2.405 2.403 0.357 f1 (ppm) 5.14 0.355 10.0 7.331 7.316 7.302 7.279 7.265 9.0 7.247 5.585 5.582 5.579 5.576 8.0 5.573 146.29 5.375 142.39 200 190 180 170 160 150 140 130 120 110 100 90 5.374 138.31 5.372 134.98 5.19 134.01 5.370 7.0 5.368 129.20 5.366 128.95 5.216 128.18 5.212 127.74 5.182 127.37 6.0 5.178 126.81 0.98 116.51 0.98 5.126 0.97 5.123 1.01 5.122 5.0 1.00 5.121 5.119 281 5.102 f1 (ppm) 5.101 f1 (ppm) 0.97 5.100 5.099 80.68 4.0 4.362 80 77.25 1.00 77.00 1.00 4.351 3.856 70 76.75 3.855 69.38 3.845 3.0 3.845 60 3.737 1.00 3.725 50 0.96 3.712 44.69 3.700 40 2.0 2.636 0.904 0.889 30 0.888 0.873 20 1.0 2.91 0.566 0.550 1.76 0.535 10 0.534 0.532 0 -2.92 0.0 5.15 0.038 -2.92 0.024 7.331 7.316 7.303 7.284 7.271 7.247 5.649 5.646 5.643 5.360 5.355 5.216 5.212 200 190 180 170 160 150 140 130 120 110 100 90 4.95 5.181 147.23 5.178 142.50 5.120 135.01 5.119 128.25 5.117 127.56 5.116 127.43 5.099 126.92 0.89 5.098 0.98 5.096 116.63 0.99 5.095 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 0.94 4.382 0.93 4.371 4.366 282 4.355 3.846 f1 (ppm) 0.99 3.836 3.734 3.732 80 77.25 0.99 3.722 77.00 1.00 3.720 76.75 2.613 70 69.50 2.611 2.595 60 2.395 1.00 2.386 50 2.384 0.98 0.911 44.50 0.897 40 0.895 0.880 30 0.607 0.606 0.604 20 8.05 0.592 0.588 10 7.35 5.30 0.577 6.81 0.572 0 0.561 -3.72 0.555 -3.75 f1 (ppm) 7.518 10.0 7.509 7.503 7.345 7.341 7.333 9.0 7.096 7.080 7.039 7.039 7.023 8.0 5.702 200 190 180 170 160 150 140 130 120 110 100 90 5.700 1.86 5.697 2.93 144.93 5.694 142.56 1.98 5.479 7.0 2.01 135.01 5.477 128.38 5.473 128.25 5.471 127.43 5.165 126.94 5.131 6.0 5.088 116.59 0.93 5.086 1.02 5.067 1.01 5.065 5.0 0.99 4.189 283 0.99 4.178 f1 (ppm) 4.172 f1 (ppm) 4.162 3.760 81.01 1.00 3.737 80 77.25 4.0 3.734 77.00 1.00 3.727 76.75 3.724 70 1.00 69.49 3.541 3.538 60 3.0 3.529 3.526 1.02 3.503 50 1.00 3.501 44.54 3.05 2.633 40 2.0 2.409 2.407 2.398 30 2.397 2.380 20 2.378 1.0 2.369 2.368 10 7.33 2.318 2.84 5.21 0 2.316 0.361 0.0 10.0 7.165 7.161 7.146 7.061 7.058 9.0 7.045 6.971 6.956 5.877 5.865 8.0 5.643 146.39 5.640 139.33 5.637 200 190 180 170 160 150 140 130 120 110 100 90 138.34 5.64 5.383 136.97 0.92 5.380 135.06 7.0 1.85 5.376 134.01 5.226 129.07 5.222 128.92 5.191 128.88 5.130 127.71 6.0 0.87 5.127 126.76 0.97 5.109 116.45 0.97 4.363 0.93 4.353 0.93 4.347 5.0 4.336 284 3.880 f1 (ppm) 3.873 0.95 f1 (ppm) 3.870 3.858 80.45 4.0 0.97 3.854 80 77.25 0.99 3.848 77.00 3.844 76.75 3.737 70 69.26 3.734 3.0 3.725 60 1.00 3.722 1.01 3.712 2.94 3.709 50 1.91 3.696 44.68 2.0 2.670 40 2.654 2.641 30 2.625 2.412 21.12 1.0 2.402 20 2.383 2.373 10 2.338 5.83 2.133 0.0 0.026 0 -2.89 0.007 -2.91 7.415 10.0 7.412 7.399 7.396 7.205 7.204 9.0 7.203 7.202 7.201 7.149 8.0 7.146 7.134 200 190 180 170 160 150 140 130 120 110 100 90 146.84 0.93 7.113 140.03 0.94 7.112 139.32 0.95 7.110 137.15 7.0 0.92 7.109 135.05 7.107 129.00 5.420 128.28 5.415 128.17 5.211 128.05 6.0 5.208 126.86 0.89 5.177 0.98 123.94 5.174 116.64 0.97 5.118 0.93 5.117 5.0 0.94 5.116 285 5.115 f1 (ppm) 0.98 5.098 f1 (ppm) 5.096 5.094 80.99 4.0 4.653 80 77.25 0.99 4.645 77.00 0.99 4.636 76.75 70 4.628 69.38 3.848 3.0 3.838 60 3.708 1.00 3.696 1.10 50 3.683 2.85 3.671 44.40 2.0 2.536 40 2.353 2.304 30 0.916 25.40 0.900 20 21.14 1.0 2.68 0.884 0.582 1.72 0.567 10 0.551 2.33 0.550 -3.52 0.0 2.29 0.054 0 -3.53 0.046 7.240 10.0 7.224 7.208 6.861 6.847 9.0 6.843 6.801 6.799 6.785 6.781 8.0 5.603 5.600 200 190 180 170 160 150 140 130 120 110 100 90 5.598 147.77 5.595 140.82 1.28 5.592 135.20 7.0 1.93 5.381 135.17 0.96 5.379 130.27 5.378 127.13 5.375 126.98 5.374 126.22 6.0 5.372 126.18 0.93 5.220 116.53 1.00 5.217 1.00 5.186 0.96 5.182 5.0 0.96 5.123 286 5.120 f1 (ppm) 5.119 f1 (ppm) 0.98 5.102 5.099 77.57 4.0 0.99 5.098 80 77.25 3.04 4.350 77.00 1.02 4.340 70 76.75 4.334 69.40 4.324 3.0 3.871 60 3.861 1.04 3.795 50 1.00 3.743 3.730 43.22 2.0 2.614 40 2.613 2.406 30 0.906 0.890 20 19.27 1.0 0.875 3.05 0.568 1.94 0.553 10 7.37 0.538 6.78 0.536 0 5.85 0.040 -3.75 0.0 -3.78 0.029 9.5 7.564 7.557 8.5 7.357 7.355 159.69 7.353 200 190 180 170 160 150 140 130 120 110 100 90 7.349 1.75 7.344 147.24 7.5 2.85 7.344 144.32 7.240 5.850 135.00 5.844 129.23 5.562 127.52 6.5 5.556 5.185 119.38 5.181 116.66 1.14 5.150 112.86 0.91 5.146 112.22 0.93 5.5 4.5 1.00 5.070 1.00 5.067 287 5.049 5.046 f1 (ppm) f1 (ppm) 4.090 7.17 3.983 81.02 4.82 3.892 80 77.25 1.11 3.881 77.00 0.88 3.867 76.75 3.5 3.857 70 69.56 3.685 3.674 60 3.660 55.20 2.16 3.649 2.5 2.741 50 2.712 44.47 2.664 40 2.644 1.5 2.614 30 20 0.5 0.422 4.73 10 7.35 0.414 6.82 0 -3.71 -3.73 -0.5 7.240 10.0 7.227 6.935 6.928 6.925 6.918 9.0 6.903 6.902 6.901 6.900 5.594 8.0 5.591 200 190 180 170 160 150 140 130 120 110 100 90 5.588 5.586 147.08 1.66 5.583 138.33 0.97 5.375 135.37 7.0 0.92 5.374 134.01 5.372 129.06 5.370 128.38 5.368 127.83 6.0 5.366 0.92 5.234 116.12 1.01 5.231 0.99 5.200 0.98 5.197 5.0 0.98 5.144 288 5.143 f1 (ppm) 0.94 5.141 77.25 f1 (ppm) 5.140 77.00 5.123 76.75 4.0 0.99 5.122 80 76.06 1.02 5.121 69.21 5.119 70 68.57 4.656 68.36 4.644 67.82 3.0 4.643 60 67.14 1.01 4.642 66.13 1.00 4.640 50 4.629 3.946 42.06 2.0 3.936 40 3.808 3.796 30 0.905 0.889 1.0 0.873 20 3.15 0.568 2.00 0.553 10 0.00 0.552 6.03 0.537 0.0 0 -2.69 0.041 -2.75 0.032 7.508 10.0 7.504 7.504 7.498 7.496 7.489 9.0 7.339 7.338 7.334 7.328 7.326 8.0 7.324 200 190 180 170 160 150 140 130 120 110 100 90 7.323 1.86 5.748 146.721 2.80 5.745 146.373 5.742 7.0 5.739 134.774 5.736 127.741 5.492 126.189 5.491 125.285 5.489 124.722 6.0 5.486 117.031 0.88 5.485 1.00 5.483 0.99 5.186 5.0 0.90 5.182 289 0.91 5.152 f1 (ppm) 5.148 f1 (ppm) 5.088 5.087 77.255 5.085 80 77.001 4.0 1.00 5.084 76.746 0.97 5.067 70 76.282 5.065 69.394 5.064 0.97 3.813 60 3.0 3.805 3.802 50 3.776 44.809 1.00 3.768 3.765 40 0.99 2.0 1.331 1.329 30 1.326 1.324 20 3.52 1.321 1.0 0.97 1.209 2.74 0.812 10 7.339 0.797 6.797 5.23 0.783 0 -3.729 0.379 -3.768 0.0 0.366 7.512 10.0 7.505 7.497 7.341 7.339 9.0 7.336 7.335 7.330 5.779 5.777 5.775 8.0 5.772 200 190 180 170 160 150 140 130 120 110 100 90 5.771 1.94 5.496 147.23 2.90 5.495 138.14 5.490 135.53 7.0 5.489 133.94 5.180 128.98 5.179 128.89 5.177 127.74 5.146 6.0 5.142 116.25 1.94 5.076 1.01 5.074 0.94 5.073 5.0 0.92 5.072 290 5.055 f1 (ppm) 5.054 f1 (ppm) 5.051 3.793 77.87 3.792 80 77.25 4.0 3.782 77.00 2.03 3.771 70 76.75 3.770 69.90 3.760 3.758 60 3.0 1.00 3.023 3.015 50 2.291 1.98 2.290 41.37 2.289 40 2.0 36.00 2.287 2.279 30 4.36 2.278 2.02 2.276 5.22 2.275 20 18.54 1.0 1.609 14.11 1.101 10 1.084 5.41 1.079 0 -2.71 0.386 -2.92 0.0 0.373 7.506 10.0 7.503 7.490 7.326 7.325 7.323 9.0 7.321 7.314 5.835 5.818 5.802 8.0 5.799 5.797 200 190 180 170 160 150 140 130 120 110 100 90 1.88 5.487 2.79 5.482 147.49 5.198 138.28 7.0 5.195 135.70 5.169 133.94 5.166 128.95 5.082 128.79 5.081 127.72 6.0 5.080 1.94 115.97 5.079 1.01 5.065 0.95 5.064 5.0 0.95 5.063 291 5.062 f1 (ppm) 4.054 f1 (ppm) 4.045 4.033 82.34 0.99 4.024 80 77.25 4.0 3.768 77.00 1.00 3.759 76.75 3.747 70 71.07 3.738 3.0 2.601 60 2.593 1.00 2.443 1.04 2.442 50 1.02 2.430 40.77 2.0 2.429 40 38.03 2.404 29.22 2.403 30 27.39 2.397 26.62 2.395 20 26.49 1.0 0.94 0.741 26.42 0.98 0.727 5.79 0.488 10 1.03 0.360 1.04 0.356 0.93 0.355 0 -2.71 0.0 -2.86 0.241 5.890 10.0 5.878 5.861 5.750 5.747 5.744 9.0 5.374 5.369 5.242 5.239 5.213 8.0 5.210 5.105 5.103 5.088 146.96 5.085 138.44 7.0 4.178 135.69 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 4.169 133.98 4.157 128.90 4.148 128.83 3.946 127.68 6.0 0.93 3.937 115.97 1.02 3.925 1.02 3.916 5.0 0.96 2.791 0.96 2.783 292 2.418 f1 (ppm) 2.416 2.405 2.404 82.24 1.00 77.21 2.374 4.0 1.01 2.372 77.00 2.370 76.79 2.366 69.72 2.364 3.0 0.920 1.00 0.907 0.894 f1 (ppm) 1.03 1.05 0.830 0.816 42.04 0.606 40 2.0 0.593 0.580 30 0.579 0.567 20 8.77 1.0 0.565 15.05 1.19 0.552 5.92 10 0.423 4.42 0.94 0.416 1.27 0.99 0 0.366 -2.72 0.99 0.0 0.357 -2.80 0.94 0.084 -10 7.266 10.0 7.262 7.261 7.260 7.259 7.245 9.0 7.244 7.240 7.231 7.230 7.226 8.0 7.222 200 190 180 170 160 150 140 130 120 110 100 90 7.153 7.139 3.02 5.568 145.60 0.95 5.566 7.0 5.563 135.69 5.388 5.387 127.96 5.382 6.0 5.381 0.91 5.221 116.07 0.99 5.218 1.00 5.187 0.98 5.183 5.0 0.95 5.139 293 5.119 f1 (ppm) 4.342 f1 (ppm) 4.331 0.99 4.326 82.28 4.0 4.315 80 77.21 1.02 3.858 77.00 1.02 3.848 76.79 3.737 70 69.85 3.725 3.0 3.711 60 3.699 1.04 2.603 2.602 50 1.00 2.588 41.94 2.0 2.587 40 2.374 2.373 2.363 30 2.362 1.0 0.560 20 2.79 15.16 0.545 1.77 0.544 7.34 0.530 10 4.40 0.528 2.96 0.0 5.06 0.035 0 1.42 0.022 200 190 180 170 160 150 140 130 120 110 100 90 146.84 144.77 134.68 134.22 129.58 127.92 127.60 126.98 125.07 116.90 294 f1 (ppm) 80.54 80 77.25 77.00 70 76.75 69.69 60 50 44.35 40 30 20 10 7.33 6.79 0 -3.74 -3.76 295 296 297 7.517 10.0 7.513 7.507 7.505 7.497 7.358 9.0 7.354 7.348 7.347 7.345 7.344 8.0 7.326 7.322 1.73 7.321 6.24 7.315 0.96 7.313 7.0 7.262 7.257 7.250 7.246 0.93 7.244 6.0 7.242 7.240 6.111 5.0 6.109 6.106 298 6.103 f1 (ppm) 6.101 0.94 4.492 1.99 4.485 4.472 4.0 4.465 4.411 4.409 4.406 4.403 3.0 4.402 4.399 4.397 0.97 4.394 1.00 2.315 2.0 2.310 2.295 2.290 2.264 1.0 2.262 2.261 2.260 5.17 2.256 2.253 0.0 0.359 0.358 7.384 10.0 7.381 7.380 7.369 7.367 7.364 9.0 7.358 7.356 7.348 7.346 7.344 8.0 7.342 200 190 180 170 160 150 140 130 120 110 100 90 7.339 142.70 3.48 7.330 137.40 0.88 7.328 136.11 7.326 135.09 7.0 7.265 133.96 7.263 129.12 6.044 128.33 6.042 127.83 0.87 6.039 127.41 6.0 6.036 125.85 6.034 4.497 5.0 4.477 4.397 299 4.394 f1 (ppm) 4.392 0.83 f1 (ppm) 4.390 2.01 4.388 4.385 80 77.25 4.0 77.00 4.382 4.381 76.75 2.268 70 75.63 2.265 67.72 3.0 2.262 60 0.947 0.945 50 1.00 0.935 1.03 0.931 0.929 40 2.0 0.915 34.51 0.913 30 0.571 0.568 0.555 20 1.0 2.55 0.553 1.75 0.056 10 0.054 0.051 0 4.58 0.049 -3.86 0.0 -3.98 0.048 7.377 10.0 7.376 7.363 7.360 7.357 7.343 9.0 7.342 7.342 7.328 7.326 200 190 180 170 160 150 140 130 120 110 100 90 7.281 8.0 7.278 7.266 142.93 7.264 135.88 3.74 7.250 134.56 0.89 6.035 128.36 7.0 6.033 127.39 6.031 125.85 6.029 6.027 6.026 6.0 0.98 6.024 6.023 6.022 5.0 4.490 4.483 f1 (ppm) 300 4.469 f1 (ppm) 4.463 80 77.25 0.95 4.412 77.00 2.06 4.408 76.75 4.407 70 75.69 4.0 4.405 67.69 4.402 4.400 60 2.309 2.288 50 3.0 2.246 2.243 2.241 40 2.239 34.76 1.00 0.99 2.236 30 2.0 2.234 0.952 20 0.936 0.920 0.620 10 7.36 1.0 0.619 6.08 8.36 0.604 0 5.43 0.602 -4.76 0.588 0.572 0.0 0.571 10.0 7.512 7.508 7.503 7.500 7.499 9.0 7.497 7.495 7.493 7.356 7.352 8.0 7.349 7.342 1.83 7.341 2.76 7.339 1.83 7.241 7.0 1.84 7.240 7.223 142.90 7.211 135.49 7.207 133.94 7.134 128.35 0.96 6.0 7.131 127.39 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 7.119 125.85 7.117 7.116 5.0 7.115 7.114 301 6.101 f1 (ppm) 6.098 1.00 1.97 6.096 6.095 4.0 6.093 6.092 77.25 6.090 77.00 4.459 76.74 4.452 75.69 4.439 67.76 3.0 4.432 4.395 3.96 4.391 1.00 4.388 2.0 4.385 4.383 35.29 4.379 4.376 2.314 1.0 2.244 2.241 2.239 f1 (ppm) 7.38 5.27 2.237 2.234 2.28 0 0.0 0.356 0.353 -10 7.240 10.0 7.233 7.217 7.201 7.186 7.158 9.0 7.144 7.142 7.081 7.079 7.065 8.0 6.997 6.995 200 190 180 170 160 150 140 130 120 110 100 90 6.993 139.77 3.51 137.47 1.90 6.981 6.979 137.03 7.0 0.98 136.15 1.82 6.978 6.976 135.16 6.016 133.96 6.013 129.10 1.10 6.010 128.99 6.0 6.007 127.82 4.407 125.82 4.400 5.0 4.386 4.380 302 4.370 f1 (ppm) 4.367 f1 (ppm) 3.28 4.365 4.363 4.0 4.360 80 77.25 4.358 77.00 4.354 76.75 2.332 70 75.49 2.252 67.70 3.0 2.245 60 2.238 2.224 50 3.00 2.218 1.26 2.141 2.0 3.09 2.114 40 2.112 34.51 2.110 30 2.108 2.106 21.09 1.0 2.103 20 2.076 2.072 10 0.055 5.85 0.054 0 0.0 0.039 -3.85 0.037 -3.98 7.500 10.0 7.497 7.485 7.482 7.285 7.283 9.0 7.263 7.260 7.207 7.205 7.203 8.0 7.191 200 190 180 170 160 150 140 130 120 110 100 90 7.183 0.97 7.181 139.83 1.17 7.180 139.80 2.10 7.178 137.05 7.0 6.086 135.51 6.083 135.17 6.080 129.02 4.707 128.16 0.99 4.700 125.75 6.0 4.687 124.09 4.680 4.443 5.0 4.441 4.438 303 4.436 f1 (ppm) 1.00 4.434 f1 (ppm) 2.10 4.431 4.429 77.25 2.378 80 4.0 77.00 2.286 76.75 2.284 70 75.47 2.281 67.71 0.991 0.989 60 3.0 0.975 0.973 50 3.12 0.959 2.38 0.958 0.628 40 2.0 34.85 0.627 0.613 30 0.611 25.01 0.597 20 21.12 1.0 2.92 0.595 0.580 1.82 0.094 10 0.092 0.090 0 5.26 -4.48 0.0 0.085 0.083 -4.64 7.273 10.0 7.270 7.259 7.256 7.252 7.240 9.0 6.953 6.952 6.949 6.948 200 190 180 170 160 150 140 130 120 110 100 90 8.0 6.946 6.945 140.863 6.938 136.169 6.936 134.557 1.28 6.826 134.515 7.0 1.97 6.822 130.199 0.96 6.819 127.185 6.809 126.287 6.807 125.438 6.804 6.0 0.98 6.802 6.039 6.037 304 6.034 5.0 6.031 4.480 f1 (ppm) 4.473 f1 (ppm) 1.00 4.461 4.453 80 77.254 2.10 76.999 4.395 4.0 4.391 76.746 3.16 70 72.665 4.389 4.386 67.875 4.384 60 4.379 3.0 3.815 50 2.307 2.302 1.02 2.287 40 1.10 2.282 33.216 2.0 2.266 30 2.262 2.258 2.255 20 19.108 0.944 1.0 3.08 0.928 10 7.364 0.913 6.126 2.04 -4.753 0.584 0 0.568 -4.778 6.12 0.552 0.0 0.049 0.047 7.552 10.0 7.546 7.545 7.543 7.540 7.539 9.0 7.536 7.376 7.373 159.755 7.371 200 190 180 170 160 150 140 130 120 110 100 90 7.369 8.0 7.366 7.240 144.596 1.90 6.072 2.79 6.071 135.880 6.069 134.499 7.0 4.328 129.355 4.322 4.315 118.162 4.220 113.109 0.94 4.218 111.150 6.0 4.216 4.214 4.212 5.0 4.149 4.125 f1 (ppm) 305 4.123 f1 (ppm) 1.19 4.121 0.74 4.119 80 77.254 0.80 4.117 77.000 1.33 76.746 4.115 70 4.0 1.91 4.113 75.612 1.06 67.684 4.111 4.30 4.109 60 4.091 55.245 4.089 50 3.0 4.089 4.087 4.085 40 2.00 4.083 34.800 4.060 30 2.0 4.057 4.054 20 4.052 2.351 2.348 10 7.370 1.0 2.346 6.072 2.343 0 2.340 -4.753 5.62 0.397 0.394 0.0 0.391 7.247 10.0 7.245 7.240 7.237 7.235 6.991 9.0 6.990 6.986 6.984 6.983 6.982 8.0 6.969 6.962 200 190 180 170 160 150 140 130 120 110 100 90 80 6.959 1.98 6.952 137.53 0.89 6.007 136.13 7.0 0.92 6.006 134.86 6.004 133.94 6.002 129.14 5.999 127.84 0.94 5.997 6.0 4.782 4.780 4.774 5.0 4.773 4.763 306 4.762 f1 (ppm) 0.93 88.76 4.761 4.755 77.21 1.99 77.00 4.754 f1 (ppm) 4.371 76.79 4.0 4.369 71.72 4.368 70 68.56 4.365 67.95 4.364 60 67.59 4.362 67.55 3.0 66.81 4.347 50 4.344 66.39 1.01 4.341 1.00 2.388 40 2.386 2.0 32.39 0.936 30 0.921 0.905 0.584 20 1.0 0.568 2.93 0.552 10 1.97 0.537 0.536 0 0.054 -3.94 5.88 0.048 -3.98 0.0 0.041 -10 10.0 7.493 7.488 9.0 7.486 7.349 7.346 7.341 7.339 8.0 6.029 200 190 180 170 160 150 140 130 120 110 100 90 6.026 2.02 6.023 3.04 6.021 145.925 6.019 7.0 6.017 135.254 4.220 134.421 4.216 126.461 4.212 124.605 1.00 4.211 123.727 6.0 4.207 4.202 3.424 5.0 3.420 3.413 307 3.410 f1 (ppm) 3.408 f1 (ppm) 3.402 2.07 3.400 1.976 80 77.254 4.0 1.973 77.000 1.971 76.746 70 71.444 1.00 1.969 1.968 67.305 1.965 60 3.0 1.961 1.957 50 1.496 1.399 1.377 40 2.0 2.07 1.363 34.371 1.260 30 4.80 1.256 1.251 0.904 20 1.0 3.38 0.893 0.892 10 7.352 0.880 6.046 5.93 0.333 0 0.329 -4.761 0.0 0.326 -4.775 7.486 10.0 7.471 7.346 7.342 7.336 7.332 9.0 6.016 6.014 6.011 4.245 4.211 8.0 4.190 4.188 200 190 180 170 160 150 140 130 120 110 100 90 1.82 4.186 2.77 4.156 4.152 137.69 7.0 3.158 136.32 3.152 134.66 3.145 133.96 3.138 129.02 3.132 127.77 6.0 0.99 3.125 3.118 2.026 5.0 2.019 2.006 308 1.962 f1 (ppm) 1.928 f1 (ppm) 1.899 2.09 1.895 1.705 80 77.21 4.0 1.699 77.00 1.693 76.79 1.634 70 73.27 1.615 67.07 1.00 1.605 60 3.0 1.345 1.339 50 1.332 1.182 1.03 1.175 40 2.0 38.07 2.04 1.155 2.12 32.43 1.150 30 2.11 1.107 1.03 1.011 3.59 0.963 20 18.69 1.0 2.05 14.09 0.958 0.958 10 0.945 5.33 0.937 0 -3.85 0.0 0.321 0.318 -3.95 7.490 10.0 7.487 7.480 7.474 7.345 7.344 9.0 7.342 7.340 7.333 5.992 5.990 8.0 5.988 4.253 1.91 4.249 2.80 4.244 4.198 137.74 7.0 4.196 136.47 4.194 134.67 4.193 133.96 4.191 129.01 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 4.189 127.77 6.0 0.98 2.763 2.755 2.753 5.0 2.750 2.747 309 2.739 f1 (ppm) 2.734 2.082 1.04 0.887 77.92 1.06 0.879 77.25 4.0 0.874 77.00 0.866 76.75 0.865 67.47 0.521 0.514 3.0 0.512 1.00 0.505 0.465 0.460 42.76 1.04 0.457 29.44 2.0 1.06 0.453 28.99 0.451 28.54 0.443 26.59 0.328 26.19 0.323 26.09 1.0 1.19 0.172 0.99 0.170 f1 (ppm) 1.03 0.164 6.70 0.162 0 0.96 0.156 -3.80 0.0 0.155 -3.90 7.240 10.0 5.911 5.909 5.907 5.904 5.902 9.0 5.900 5.898 4.239 4.235 4.232 8.0 4.229 4.196 4.194 4.192 4.190 137.63 7.0 4.188 136.16 4.186 134.64 2.745 133.96 2.743 129.04 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 2.738 127.79 6.0 0.99 2.736 2.719 2.071 5.0 2.069 2.066 310 2.062 f1 (ppm) 0.923 0.907 1.01 0.891 77.95 1.06 0.591 77.21 4.0 0.576 77.00 0.560 76.79 0.544 67.25 0.543 0.533 3.0 0.530 1.00 0.525 0.523 0.514 1.06 0.512 2.0 1.05 0.507 0.505 31.93 0.485 0.477 0.355 1.0 10.12 15.69 0.346 6.41 0.336 f1 (ppm) 1.91 0.329 2.82 1.06 0.203 0 1.75 1.04 0.195 -3.83 0.0 0.185 -3.95 10.0 7.365 7.363 7.361 9.0 7.360 7.358 7.240 7.239 7.231 8.0 7.230 7.228 200 190 180 170 160 150 140 130 120 110 100 90 0.89 7.226 3.08 7.224 6.022 7.0 6.019 6.017 135.44 6.014 133.50 6.012 0.99 6.009 6.0 6.007 6.004 4.455 4.444 5.0 4.439 311 4.428 f1 (ppm) 4.369 1.00 4.364 f1 (ppm) 2.14 4.359 4.0 4.353 77.99 2.245 80 77.25 2.240 77.00 2.238 70 76.75 2.237 67.19 3.0 2.234 2.231 60 2.228 2.226 50 2.08 2.223 2.0 2.218 0.925 40 0.912 32.56 0.909 30 0.894 1.0 2.79 0.566 0.550 20 15.70 1.86 0.534 0.518 10 7.36 0.034 2.86 5.29 0.032 2.29 0.0 0 1.78 0.027 144.988 135.581 134.437 134.268 129.611 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 127.440 126.017 123.903 312 77.254 77.001 76.745 74.906 67.592 34.629 f1 (ppm) 7.366 6.031 0 -4.773 -10 313 9.6783 9.6742 0.74 9.6699 7.3849 0.21 7.3810 7.3181 7.3161 7.3125 7.3096 7.3035 7.3024 0.57 7.3000 0.97 7.2986 3.25 7.2962 7.85 7.2876 0.75 7.2857 0.65 7.2753 7.2743 7.2723 7.2706 7.2584 7.2555 7.2442 7.2428 7.2399 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 314 7.2381 7.2315 7.2296 7.2157 7.2139 2.6857 2.6811 2.6510 2.6463 2.0236 1.00 2.0198 1.26 1.9888 0.32 1.9850 1.00 1.4054 0.27 1.3960 1.05 1.3936 0.30 1.3841 0.31 0.9444 1.02 0.9349 0.9278 0.9183 1.64 0.3577 2.53 0.3485 2.41 0.0795 -0.2321 f1 (ppm) 202.6650 9.5 8.5 139.0611 210 200 190 180 170 160 150 140 130 120 110 100 90 137.9252 134.1037 7.5 134.0383 129.9075 129.3344 129.0180 6.5 128.2137 127.9792 127.9482 127.7036 126.4788 5.5 4.5 f1 (ppm) 315 f1 (ppm) 80 77.2540 76.9996 3.5 76.7452 70 60 2.5 53.2340 50 45.1036 40 1.5 30 29.3888 24.8788 20 0.5 15.7025 10 10.2810 -2.8324 0 -3.4254 -0.5 -4.3500 1 2 3 4 -4.4260 9.904 9.901 203.44 10.0 0.89 9.899 202.95 9.896 0.27 7.302 7.301 9.0 7.291 7.289 7.288 7.287 7.260 8.0 7.243 7.241 7.240 2.03 7.230 139.40 2.64 7.227 138.06 7.0 1.97 7.170 129.90 7.169 129.35 7.158 128.21 7.157 127.94 2.763 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 126.43 6.0 2.759 126.36 2.735 2.730 5.0 2.186 2.031 316 2.028 f1 (ppm) 2.002 1.257 1.249 77.21 4.0 1.247 77.00 1.239 76.79 0.987 0.974 0.961 3.0 0.877 53.39 1.00 0.869 45.42 0.865 29.40 1.59 0.863 24.72 1.00 0.855 15.34 2.0 0.28 0.775 13.72 1.21 0.764 9.89 0.30 0.763 9.06 0.29 0.762 7.44 0.89 0.749 7.26 1.0 1.18 0.276 6.64 2.93 0.263 f1 (ppm) 5.79 0.61 0.260 -3.78 1.85 0.246 0 -4.00 1.69 0.004 -4.99 0.0 2.60 -0.315 -5.15 2.62 -0.424 -10 9.9047 203.37 0.57 7.3066 7.3049 7.3037 7.3020 7.2938 7.2920 7.2899 7.2883 7.2870 7.2855 7.2562 210 200 190 180 170 160 150 140 130 120 110 100 90 7.2544 2.25 7.2418 1.59 7.2400 1.85 7.2252 139.62 2.7363 2.7025 129.92 2.6969 128.08 2.0570 126.59 1.3336 1.3238 1.3215 1.3119 1.0095 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 317 1.0083 1.0061 1.0000 f1 (ppm) 0.9934 0.9193 77.41 0.9097 80 77.16 0.7927 76.91 0.7907 70 0.7766 0.7747 60 1.00 0.7610 53.81 0.7590 50 1.02 0.3209 1.09 0.3064 0.3050 40 0.2929 1.09 0.2908 30 28.89 2.56 0.2770 1.66 0.2750 9.63 0.1727 20 0.1707 15.88 3.38 0.1565 10 7.68 2.90 0.1547 3.36 0.1406 0 0.1247 f1 (ppm) 9.679 9.674 0.77 9.670 203.19 202.67 9.5 9.345 0.34 7.562 7.555 7.389 7.385 8.5 7.339 7.335 7.332 138.06 0.94 7.327 136.77 1.47 7.322 7.5 5.28 7.320 135.98 135.96 2.11 7.314 135.95 3.06 7.297 134.63 1.00 7.285 134.11 7.147 6.5 7.135 134.04 129.75 7.131 129.43 7.054 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 129.20 7.038 128.97 5.5 7.009 128.92 6.992 128.64 2.662 4.5 2.657 318 127.92 127.66 2.627 f1 (ppm) 2.622 2.334 2.297 2.207 77.26 2.202 77.00 2.198 76.75 3.5 2.191 2.185 2.017 0.95 2.013 3.25 1.982 53.16 2.5 1.45 1.978 45.10 1.99 1.388 29.04 1.00 1.379 24.53 0.41 1.376 21.07 1.5 0.97 1.367 20.96 0.45 1.067 15.68 0.47 0.930 13.85 1.23 0.921 10.26 0.914 9.26 0.5 0.905 f1 (ppm) -2.73 2.56 0.362 -3.40 2.58 0.352 0 2.45 -4.33 0.101 -4.41 -0.206 -10 -0.5 9.905 9.901 210 0.69 9.900 202.77 9.896 9.5 0.13 190 7.212 8.5 7.196 7.133 170 7.118 7.103 7.084 7.5 1.95 7.069 1.55 7.018 150 139.67 1.87 7.017 136.20 1.35 7.002 136.09 1.58 6.988 129.83 6.5 6.788 130 128.74 6.787 128.24 6.773 128.04 6.772 123.99 2.813 5.5 4.5 2.807 110 90 2.778 2.773 2.315 319 f1 (ppm) 2.313 f1 (ppm) 2.203 2.191 77.25 2.187 77.00 2.175 76.75 3.5 2.171 70 2.057 2.053 1.00 2.023 53.36 2.019 2.5 2.98 1.870 50 1.45 1.843 1.02 1.811 1.14 1.784 0.97 1.228 30 1.5 1.03 29.27 1.218 24.77 0.26 1.216 21.08 0.23 1.206 15.54 1.29 0.872 10 9.75 0.5 0.862 0.856 0.846 -3.29 2.50 -0.324 -3.56 1.99 -0.451 -10 -0.5 9.504 9.500 9.499 9.495 9.5 0.91 7.226 203.32 7.212 7.211 7.196 7.082 8.5 7.078 7.077 7.062 7.060 7.5 7.029 2.07 7.028 3.01 7.027 1.97 7.026 2.04 7.013 139.45 6.5 7.011 136.04 7.010 134.55 6.990 129.26 6.974 128.93 2.304 2.220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 128.30 124.23 5.5 4.5 2.218 2.214 2.212 2.192 320 f1 (ppm) 2.188 2.185 2.183 2.179 2.178 77.25 3.5 2.172 77.00 2.165 76.75 1.892 0.20 1.888 0.38 1.858 2.5 2.91 1.854 4.00 1.136 0.22 1.134 1.12 1.125 45.43 0.15 1.5 1.124 1.11 1.120 1.12 1.118 1.109 24.56 1.108 24.18 0.5 1.064 20.99 1.052 2.89 1.041 13.85 2.93 f1 (ppm) 8.93 -0.011 -0.021 0 -4.50 -0.5 -4.73 9.889 0.85 9.884 202.78 9.878 9.5 7.121 7.120 8.5 7.108 7.075 7.063 2.577 2.573 7.5 2.544 2.540 4.49 2.390 138.81 2.384 137.51 2.366 129.72 6.5 2.357 128.28 2.351 126.60 2.332 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 125.33 1.965 1.953 1.949 5.5 4.5 1.937 321 1.386 1.384 f1 (ppm) 1.376 1.374 1.372 77.25 1.364 77.00 1.362 76.75 3.5 0.989 0.979 0.972 0.962 0.779 53.54 2.5 1.06 0.765 4.80 0.763 1.00 0.749 0.747 0.323 1.5 0.308 29.04 1.05 0.278 20.09 1.23 0.262 14.73 3.05 0.259 10.25 0.243 0.5 f1 (ppm) 7.28 0.229 1.93 6.74 0.213 0 -3.69 2.54 -0.295 -3.86 2.63 -0.390 -10 -0.5 9.898 9.894 210 0.90 9.893 203.48 9.889 202.92 9.5 0.72 9.516 9.514 190 7.177 7.169 7.153 8.5 7.137 6.866 170 6.863 6.861 159.49 6.735 159.33 7.5 6.719 1.94 6.714 150 2.03 6.696 141.08 3.31 3.783 139.79 6.5 3.774 129.18 2.763 130 128.91 2.758 122.33 2.729 121.79 2.724 115.51 2.175 115.47 5.5 4.5 2.031 110 90 112.04 2.027 322 111.35 1.848 1.236 f1 (ppm) 1.227 f1 (ppm) 1.225 1.215 77.25 2.72 1.048 77.00 2.13 0.986 76.75 3.5 0.971 70 55.18 0.955 55.13 0.868 53.37 1.17 0.865 45.42 2.5 2.70 0.859 50 29.48 1.15 0.851 24.78 1.00 0.842 15.50 1.23 0.792 13.86 0.94 0.776 9.93 1.5 0.95 0.760 30 9.13 0.560 2.34 7.45 1.52 0.544 7.30 2.94 0.298 6.66 1.73 0.285 10 5.79 0.5 2.25 0.283 -3.73 4.32 0.268 -3.96 2.73 -0.002 -4.99 2.44 -0.285 -5.15 -0.392 -10 -0.5 9.534 9.529 202.83 9.525 7.314 9.5 0.77 7.310 0.07 7.310 7.283 7.282 7.267 8.5 7.240 4.302 4.300 4.297 7.5 4.295 5.18 4.292 4.097 4.095 138.08 4.093 134.23 6.5 4.090 128.97 4.088 127.60 4.085 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 4.078 3.919 3.918 5.5 4.5 3.916 3.915 323 3.765 3.764 86.47 f1 (ppm) 0.93 3.762 77.26 0.97 3.761 77.00 4.02 3.760 76.75 0.91 3.759 70.06 0.94 2.441 69.34 3.5 2.436 68.70 2.406 68.20 2.402 66.04 1.985 53.29 2.5 1.00 1.981 0.09 1.951 0.11 1.946 2.07 1.933 1.928 1.5 1.041 0.11 1.032 24.93 0.98 1.029 16.84 1.10 1.020 11.24 0.09 0.888 0.5 0.878 0.49 f1 (ppm) 2.52 0.871 2.51 0.862 0 -2.52 0.064 -2.86 -0.044 -0.5 9.845 203.24 9.843 202.72 0.45 9.577 0.81 9.574 9.5 9.572 9.568 7.110 7.107 7.099 8.5 7.097 6.909 6.902 6.899 7.5 6.892 1.20 6.809 144.11 0.90 6.736 142.58 0.46 6.734 126.86 0.45 6.731 126.46 6.5 0.89 6.729 126.16 6.727 2.289 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 126.01 124.10 2.287 124.03 2.283 2.282 5.5 4.5 1.974 1.970 324 1.939 1.935 f1 (ppm) 1.263 1.261 77.25 1.256 77.00 1.255 76.75 1.254 3.5 1.252 1.246 1.245 0.57 52.73 1.029 0.98 45.44 2.5 1.018 0.91 23.28 1.007 0.52 19.16 0.986 0.57 17.65 0.970 1.00 16.45 0.954 11.20 1.5 1.34 0.827 10.14 1.11 0.811 7.40 2.74 0.795 7.31 1.44 0.569 6.45 1.98 0.554 5.77 0.5 1.24 0.538 f1 (ppm) -4.04 5.13 -0.011 0 -4.29 1.36 -0.017 -4.97 1.35 -0.210 -5.31 -0.317 -0.5 9.529 10.0 9.525 203.29 9.521 0.79 9.500 0.17 7.511 7.508 9.0 7.507 7.501 7.495 7.346 7.342 8.0 7.338 7.335 2.41 2.436 3.69 2.431 2.407 7.0 2.403 138.36 1.819 134.12 1.815 129.08 1.790 127.83 1.786 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 6.0 1.568 1.557 1.556 5.0 1.408 1.396 325 1.383 f1 (ppm) 1.371 1.131 1.120 77.21 4.0 1.110 77.00 1.096 76.79 0.903 0.891 0.888 3.0 0.879 53.40 0.866 0.825 1.20 0.821 0.19 0.811 2.0 1.00 0.802 1.09 0.797 33.46 2.72 0.620 26.01 1.01 0.613 23.27 4.36 0.606 17.94 1.0 1.15 0.599 13.89 0.96 0.568 f1 (ppm) 6.43 0.95 0.561 -1.45 2.77 0.559 0 -2.08 0.552 2.63 0.0 0.363 -10 0.320 203.88 9.551 203.68 9.547 9.545 0.78 9.541 9.5 0.48 9.472 9.468 9.466 9.461 7.501 8.5 7.495 7.489 7.486 7.475 7.5 3.31 7.470 138.27 4.84 7.347 137.09 7.345 134.10 7.340 134.08 7.334 129.29 6.5 7.331 129.11 2.560 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 127.82 2.554 127.79 2.526 2.522 2.520 5.5 4.5 2.083 77.25 2.079 326 77.00 1.639 76.75 f1 (ppm) 1.635 53.19 1.605 44.47 1.601 39.07 1.103 37.57 1.100 34.28 3.5 1.098 33.44 1.095 33.42 0.962 33.39 0.872 33.31 0.858 26.58 2.5 1.69 0.819 26.39 0.818 26.34 0.63 0.812 26.31 1.15 0.811 26.29 9.30 0.803 26.03 1.5 10.02 0.802 25.95 0.76 0.584 16.70 1.49 0.576 14.10 0.99 0.573 6.76 3.52 0.565 5.33 0.5 0.551 f1 (ppm) 2.70 -1.48 2.74 0.379 0 -2.23 3.44 0.310 -4.58 0.233 -4.65 0.230 -0.5 203.96 203.10 9.588 9.583 9.579 0.81 9.494 9.5 0.80 9.490 9.486 7.535 7.480 7.347 8.5 7.345 7.344 7.342 7.338 138.30 1.89 7.336 137.05 7.5 2.07 7.334 134.17 5.83 2.513 134.02 2.509 129.28 2.484 129.09 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 6.5 2.479 127.84 2.415 127.80 2.411 2.375 2.370 2.346 5.5 4.5 2.342 1.832 327 1.828 1.804 77.21 f1 (ppm) 1.800 77.00 0.767 76.79 0.760 0.742 53.13 0.713 45.50 3.5 0.706 29.78 0.704 23.25 0.697 17.34 0.610 14.74 1.00 0.603 11.92 2.5 2.01 0.597 9.49 0.589 7.32 0.529 6.67 0.98 0.525 6.14 1.5 1.91 0.522 5.99 0.95 0.398 5.30 1.87 0.368 f1 (ppm) 4.54 6.11 0.321 -1.95 2.87 0.313 0 -2.24 0.5 2.90 0.305 -4.52 0.98 0.227 -10 -4.54 1.29 0.218 5.91 0.153 2.00 0.144 -0.5 9.800 9.794 210 204.51 0.64 9.793 203.84 0.85 9.789 9.5 9.688 9.686 190 9.683 9.681 9.680 8.5 9.677 2.472 170 2.467 2.436 7.5 2.429 2.415 150 2.410 2.402 2.396 6.5 1.791 1.786 130 1.758 1.753 0.980 0.965 5.5 4.5 0.949 110 90 0.931 328 0.915 0.900 f1 (ppm) 0.628 f1 (ppm) 0.612 0.611 77.24 0.597 76.99 0.596 76.74 3.5 0.595 70 0.512 53.51 0.484 46.17 0.469 0.75 0.468 29.23 2.5 50 1.72 0.452 22.83 17.38 0.437 14.49 0.436 1.00 12.19 0.276 9.57 1.5 0.266 30 0.257 7.59 7.42 9.61 0.213 6.49 8.45 0.208 5.99 20.38 0.206 10 0.5 1.05 0.203 5.24 4.44 4.41 0.202 3.73 0.192 2.16 0.182 0.176 -10 -0.5 9.881 9.878 0.76 202.40 9.877 0.09 9.874 9.5 7.286 7.285 7.283 7.240 8.5 7.219 7.218 7.208 7.206 7.178 7.5 0.91 7.166 0.99 7.165 2.32 7.163 141.78 2.804 133.80 2.800 129.95 6.5 2.775 129.21 2.771 128.22 2.147 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 126.62 2.137 5.5 2.134 2.133 4.5 2.132 2.123 329 2.122 f1 (ppm) 2.029 2.026 2.000 77.21 1.997 77.00 1.221 76.79 3.5 1.213 1.212 1.204 1.00 0.969 53.34 2.5 0.956 0.23 0.888 0.95 0.879 1.03 0.874 0.11 0.866 1.5 1.01 0.791 29.03 0.14 0.777 0.12 0.764 0.38 0.300 15.51 1.07 0.287 10.21 0.5 2.89 0.274 f1 (ppm) 7.27 0.26 0.260 6.69 1.92 0.247 0 -3.72 0.69 0.003 -3.91 2.63 -0.296 -10 -0.5 2.64 -0.397 7.225 7.224 7.216 7.209 9.5 7.195 7.176 7.160 7.117 7.102 8.5 5.990 5.987 5.986 5.982 7.5 5.979 147.50 4.840 2.64 146.25 4.836 0.94 141.79 4.829 134.30 3.124 129.76 6.5 3.110 127.30 3.096 126.43 2.975 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 125.43 0.91 2.971 2.954 2.942 5.5 4.5 2.938 2.934 330 0.93 2.925 f1 (ppm) 2.921 2.438 86.40 2.434 77.21 2.433 77.00 2.424 76.79 3.5 2.420 2.419 0.95 2.401 1.00 2.400 54.95 2.387 2.5 0.98 2.386 1.828 42.99 0.956 0.89 0.941 0.940 1.5 0.940 0.924 0.615 2.67 0.614 1.75 0.601 f1 (ppm) 7.36 0.5 0.599 6.55 0.598 0 4.91 0.585 -4.23 0.583 -4.25 0.091 -10 -0.5 10.5 7.499 7.499 7.496 7.496 9.5 7.493 7.354 7.352 7.351 7.349 8.5 7.341 7.340 7.339 7.338 0.84 7.336 7.5 0.93 7.248 148.97 1.57 7.247 142.35 0.92 7.244 137.80 7.243 134.12 7.235 129.41 6.5 7.212 126.79 7.210 125.37 0.89 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 7.208 123.13 7.206 7.197 5.5 4.5 6.011 6.010 331 6.009 6.008 f1 (ppm) 2.980 82.92 2.954 77.25 2.953 77.00 2.951 76.75 2.864 3.5 2.863 1.00 2.862 1.01 2.861 2.07 2.859 53.89 2.799 52.42 2.5 2.779 0.89 2.778 2.037 0.950 1.5 0.937 0.937 0.924 2.86 0.604 1.88 0.591 7.44 0.578 f1 (ppm) 0.5 6.73 0.565 5.43 0.086 0 -4.11 0.085 -4.12 0.083 -10 -0.5 332 333 334 335 336 337 338 339 340 341 CHAPTER 4. A [1,2]-WITTIG / m-CPBA TRIGGERED [1,2]-CARBON-TO-CARBON SILYL MIGRATION APPROACH TO α-SILYL-β-HYDROXY CYCLOPENTANONES AND CYCLOHEXANONES 4.1. Introduction The most explored [1,2]-silyl migrationinvolves the migration of the silicon group from carbon to oxygen (Brook rearrangement)1-3 or its reverse reaction (retro-Brook rearrangement).4-9 In contrast, the [1,2]-carbon-to-carbon silyl migration has remained largely unexplored. Reported examples of such [1,2]-carbon-to-carbon silyl migration involve the use of protic acids to trigger the migration.10-16 Other examples involve alkynyl silanes or silyl propagylic systems that are catalyzed by Lewis acids17,18 and/or transition metals.19-25 With recent work from our lab on Wittig rearrangements of silyldihydropyrans,26,27 we were looking to investigate the utility of the products formed. The [1,2]-silyl migration from carbon to carbon to generate α-silyl aldehydes (Scheme 4.1a)28 and ketones (Scheme 4.1b)29,30 has been previously reported and takes place via epoxide derivatives of acyclic α-silyl allylic alcohols. Scheme 4.1: [1,2]-carbon-to-carbon silyl migration triggered by epoxidation 342 In our quest to functionalize the olefin of the [1,2]-Wittig rearrangement products by epoxidation we saw an unexpected rearrangement involving a [1,2]-carbon-to-carbon silyl shift. We were interested to learn the generality of such migration in the context of the cyclic systems accessible by [1,2]-Wittig ring contraction of silyl cyclic ethers. 4.2. Synthesis of 2-silyl-6-aryl-5,6-dihydro-2H-pyrans The 2-silyl-6-aryl-5,6-dihydro-2H-pyrans were synthesized following our earlier reported protocol.26 The synthesis began by allylation of benzaldehydes followed by conversion of the resulting homoallylic alcohols 4.1 to trichloroacetimidates 4.2. The trichloroacetimidates were then coupled with α-hydroxy allyl silanes 4.3 in the presence of catalytic amount of a Lewis acid to form diastereomeric dienes 4.4. For most of the compounds reported herein, the syn diastereomer exhibited a lower Rf value than its anti counterpart (dichloromethane/hexanes). The syn/anti dienes were then subjected to ring closing metathesis using Grubbs 2nd generation catalyst leading to 2- silyl-6-aryl-5,6-dihydro-2H-pyrans 4.5. The cis/trans diastereomers of pyrans 4.5 were separable by column chromatography. Generally, the trans diastereomer has lower Rf value than its cis counterpart (dichloromethane/hexanes). The relative stereochemistry of the dihydropyrans was determined by 1H NMR NOESY experiments. 343 Scheme 4.2: Synthesis of 2-silyl-6-aryl-5,6-dihydro-2H-pyrans 4.3. Wittig rearrangements of 2-silyl-6-aryl-5,6-dihydro-2H-pyrans Since the trans diastereomers have been shown to be more reactive, 26 they were subjected to Wittig rearrangement using n-butyllithium, whereas the cis diastereomers were reacted with sec- butyllithium resulting in the stereoconvergent [1,2]- and [1,4]-Wittig rearrangement products (Table 4.1). 344 Table 4.1: Wittig rearrangement of 2-silyl-6-aryl-5,6-dihydro-2H-pyrans Entry Substrate Ar SiR3 R′ % (4.6) % (4.7) 1 4.5aa C6H5 SiMe3 H 65b n.d 2 4.5b 4-Cl-C6H4 SiMe3 H 56 21 3 4.5c 4-CF3-C6H4 SiMe3 H 70 n.d. 4 4.5d 1-Naph SiMe3 H 81 n.d. 5 4.5e 4-Ph-C6H4 SiMe3 H 75 n.d. 6 4.5f 2-Naph SiEt3 H 73 17 7 4.5g 4-Cl-C6H6 SiMe2Ph H 37 n.d. 8 4.5h 4-OMe-C6H6 SiMe3 Me 85 n.d. 9 4.5i 4-Cl-C6H6 SiMe3 Me 63 n.d. a Reaction performed on a 1:1 mixture of diastereomers as follows: 0.6 equiv n-BuLi added at –78 °C and stirred at –78 °C for 15 minutes, then 0.5 equiv sec-BuLi was added at –78 °C and stirred at room temperature for 3 hours after the cold bath was removed. b4.6a and 4.6a′ were formed. n.d. Not detected. It is also worth noting that we were looking at the substrates that would favor [1,2]- over [1,4]-Wittig rearrangements 345 4.4. The [1,2]-carbon-to-carbon silyl migration in cyclic system triggered by epoxidation 4.4.1. [1,2]-carbon-to-carbon silyl migration of silylcyclopentenols 4.6a and 4.6a′ Having the starting materials in hand, we began by subjecting cyclopentenol 4.6a to m-CPBA and NaHCO3 leading to the formation of cyclopentanone 4.8a as a single diastereomer in 83% yield. (Scheme 4.4, substrate 4.6a). Given that we were unable to detect any epoxide intermediate in the reaction and determine the stereoselectivity of this step, we questioned whether epimerization of the benzylic position might have taken place. To test this, we subjected an epimer of 4.6a (4.6a′), with aryl and hydroxy groups cis to each other, to our conditions that led to silyl migration with the resulting β-hydroxy and α-aryl in cis relationship (Scheme 4.4, substrate 4.6a′). Scheme 4.3: [1,2]-carbon-to-carbon silyl migration of cyclopentenol 1a and 1a′ a Reaction conducted in absence of NaHCO3 Although the substrates employed in Scheme 4.3 were racemic, the relative stereochemistry of the diastereomeric products suggests that the epoxidation step is stereoselective and takes place syn to the tertiary hydroxyl group. In addition, the [1,2]-silyl migration leading to epoxide ring opening appears to occur in a syn fashion, in such a way that the relative stereochemistry of the silyl and aryl groups is conserved. 346 4.4.2. Substrate scope for [1,2]-carbon-to-carbon silyl migration in silylcyclopentenols We next explored the substrate scope of this transformation (Scheme 4.4). We started by modifying the substituents of the aromatic appendage. Incorporating electron withdrawing groups at the para position of the phenyl ring resulted in higher yields (>98%). Employing a sterically hindered aryl group (1-naphthyl) also led to higher yield (99%) of cyclopentanone 4.8d as a single diastereomer. Scheme 4.4: Substrate scope for [1,2]-carbon-to-carbon silyl migration in silylcyclopentenols a Reaction conducted in absence of NaHCO3 Modifying the substituents on silicon to triethyl and dimethylphenyl groups respectively also 347 resulted in higher yields and greater diastereoselectivity (compounds 4.8e and 4.8f). We then explored the substrates with a methyl group at the olefin carbon proximal to silicon with varying aryl groups. All these resulted in high yields (compounds 4.8g, 4.8h and 4.8i). It is worth noting that compounds 4.8b through 4.8e did not require further purification by column chromatography or crystallization. 4.4.3. Substrate scope for [1,2]-carbon-to-carbon silyl migration in silylcyclohexenols Next, we evaluated the behavior of analogous silyl cyclohexenols that were synthesized through [1,2]-Wittig rearrangement of 2-trimethylsilyl-2,5,6,7-tetrahydro-7-aryl-oxepins (see Chapter 2). The 6-aryl-2-trimethylsilylcyclohex-2-en-1-ols were then exposed to the standard conditions for silyl migration (m-CPBA and NaHCO3). This resulted in the formation of α- trimethylsilyl-β-hydroxy-6-arylcyclohexan-1-ones in high yields and high diastereoselectivities (Scheme 4.5). Scheme 4.5: Substrate scope for [1,2]-carbon-to-carbon silyl migration in silylcyclohexenols a Reaction performed on a mixture of diastereomers 4.5. Proposed reaction mechanism for the silyl migration Mechanistically, the stereoselective epoxidation of the double bond by m-CPBA could be 348 controlled by intramolecular hydrogen bond interactions with the tertiary allylic alcohol.31-33 Furthermore, the epoxide opening may be triggered by the ring strain from a fused oxirane and the cyclopentane or cyclohexane skeleton. Since the same has also been seen in acyclic systems, 28-30 the ring opening could also be as a result of the ability of the silicon atom to stabilize the development of positive charge at a beta carbon atom, also known as the β-silicon effect or silicon hyperconjugation.34-46 The silyl shift appears to be caused by a pinacol-type rearrangement,47 resulting in carbonyl formation.48-55 We therefore propose that after stereoselective epoxidation, the epoxide opens up leading to the formation of a carbocation β to silyl group. This carbocation is then intramolecularly attacked by silicon through hyperconjugation resulting in silylium ion. Intramolecular proton abstraction from the alcohol by the resulting alkoxide followed by carbon oxygen double bond formation with concerted opening of the silyl heterocyclic ring furnishes the observed product. We were unable to observe the epoxide intermediate in all the substrates herein. Thus, if this isomerization is a stepwise (epoxide formation and then ring opening to give a tertiary carbocation followed by silyl migration) or a concerted process (simultaneous epoxidation/silyl migration) is unknown at this point (Scheme 4.6). 349 Scheme 4.6: Proposed mechanistic pathways of the silyl shift a Allylic alcohol directed epoxidation 4.6. Conclusion In summary, a novel protocol to access α-silyl β-hydroxy cyclopentanones and cyclohexanones by [1,2]-Wittig rearrangement followed by [1,2]-carbon-to-carbon silyl migration has been developed. This transformation occurs with high yields and excellent diastereoselectivities and is independent of the substitution at the aromatic group and more importantly, alkyl substitution at the olefin is not a requirement. The reaction proceeded with poor yields in the absence of sodium bicarbonate (NaHCO3). The purity of m-CPBA also played an important role in the conversion of the starting material into the desired products. Column chromatography could not be used to purify the products which had epimerizable proton at the carbon bearing the silyl group. In such cases, recrystallization was helpful. Lastly, from the mechanistic standpoint, whether this transformation occurs in a concerted or stepwise version is unknown at the moment. 4.7. Experimental section 4.7.1. General information Unless otherwise noted, all reactions were run under a positive atmosphere of nitrogen in oven- 350 dried or flame-dried round-bottomed flasks or conical vials or disposable drum vials capped with rubber septa. Solvents were removed by rotary evaporation under reduced pressure at temperatures lower than 45 ºC. Column chromatography was run on 230–400 mesh silica gel. Tetrahydrofuran and diethyl ether were distilled from sodium-benzophenone ketyl; dichloromethane, benzene, trimethylsilyl chloride were distilled from calcium hydride. Trimethylsilyltrifluoromethane sulfonate (TMSOTf) was redistilled and stored under nitrogen at –10 °C before the reaction. Triethylsily chloride, dimethylphenylsilyl chloride, tert-butyllithium (1.7 M in pentane) and BF3•OEt2 were used as received. n-Butyllithum (1.6 M or 2.5 M in hexanes) and sec-butyllithium (1.4 M in cyclohexane) were purchased from Aldrich and their concentration calculated by titration with diphenylacetic acid (average of three runs). 1H NMR spectra was collected in 500 MHz and 600 MHz Varian instruments using CDCl3 as solvent, which was referenced at 7.26 ppm (residual chloroform proton) and 13C NMR spectra was collected in CDCl3 at 126 MHz or 151 MHz and referenced at 77.0 ppm. High-resolution mass spectrometric analysis was run in TOF instruments. 4.7.2. Synthesis of 2-Silyl-5,6-Dihydropyrans 4.7.2.1. Preparation of aryl homoallylic alcohols 4.1 – peneral procedure A Following a reported procedure56 with a slight modification, commercial zinc dust (5.23 g, 80 mmol, 2.0 equiv.) was weighed into a dry 250 mL round-bottomed flask equipped with a magnetic stir bar. The flask was capped with a rubber septum and purged with nitrogen for approximately 5 minutes. Freshly distilled THF (100 mL) was added into the flask followed by 5.2 mL of allyl 351 bromide (7.26g, 60 mmol, 1.5 equiv). The resulting mixture was stirred at room temperature for 30 minutes after which the desired aryl aldehyde (40 mmol, 1.0 equiv.) was added dropwise. The resulting mixture was stirred at room temperature for 1 h then quenched by addition of 20 mL of saturated aqueous ammonium chloride solution. The mixture was diluted with 40 mL of diethyl ether and 20 mL of water, respectively. The layers were separated, and the aqueous layer was extracted with diethyl ether (40 mL x 3). The combined organic layers were washed with 20 mL saturated aqueous ammonium chloride, (20 mL x 2) water and 20 mL of saturated aqueous sodium chloride solution then dried over anhydrous magnesium sulfate. Filtration and concentration under reduced pressure afforded aryl homoallylic alcohol 4.1 which was typically used in the next step without need for further purification. 4.7.2.2. Preparation of trichloroacetimidates 4.2 – general procedure B Following our reported procedure with a slight modification, 26 to a dry 250 mL round- bottomed flask fitted with a magnetic stir bar and sealed with a rubber septum was added 60 mL of dry dichloromethane under nitrogen. The desired homoallylic alcohol 4.1 (20 mmol, 1.00 equiv) in dichloromethane (20 mL) was then transferred into the flask. This was followed by addition of 0.54 mL of 1,8-Diazabicyclo(5.4.0)undec-7-ene (DBU) (0.55 g, 3.6 mmol, 0.18 equiv.). After stirring for 5 minutes, the solution was cooled to 0 °C on an ice bath. This was followed by dropwise addition of 2.8 mL of tricchloroacetonitrile (4.04 g, 28 mmol, 1.40 equiv.). After 12 hours, the resulting dark brown mixture was filtered through a plug of silica (5 cm thick) to remove 352 the dark residue. The filtrate was concentrated, and the crude mixture subjected to column chromatography (EtOAc/hexanes) to afford the desired trichloroacetimidate 4.2. 4.7.2.3. Alternative preparation of trichloroacetimidates 4.2 – general procedure C26 Following our reported procedure,26 240 mg of sodium hydride 60% w/w dispersion in mineral oil (6 mmol, 0.18 equiv) was weighed into a dry 100 mL round-bottomed flask fitted with a magnetic stir bar and 20 mL of freshly distilled diethyl ether was added into the flask. The flask was sealed with a rubber septum and purged with nitrogen. The resulting grey suspension was cooled on an ice bath and the desired homoallylic alcohol 4.1 (30 mmol, 1.00 equiv) in dry diethyl ether (20 mL) was then transferred into the flask slowly resulting in a fizzy reaction. The mixture was stirred at 0 °C for 10 minutes. This was followed by dropwise addition of 4.2 mL of trichloroacetonitrile (6.06 g, 42 mmol, 1.40 equiv.). The mixture turned dark brown after complete addition of the trichloroacetonitrile. The mixture was stirred at 0 °C for 20 minutes and then the ice bath was removed, and the mixture stirred at room temperature for 1 hour. The diethyl ether was then removed by rotorvap and methanol (0.25 mL, 6.0 mmol, 0.18 equiv.) in 15 mL pentane was added to the crude mixture. The mixture was further diluted with 40 mL pentane and filtered through a plug of celite (5 cm thick). The filtrate was concentrated, and the crude mixture subjected to column chromatography (EtOAc/hexanes) to afford the desired trichloroacetimidate 4.2. 353 4.7.2.4. Preparation of α-hydroxy allyl silanes 4.3 – general procedure D26 A solution of the corresponding allylic alcohol in THF was cooled at −78 °C, and n- butyllithium (1.6 M or 2.5 M in hexanes) was added dropwise over 5 min. After 30 min the corresponding chlorosilane was added dropwise via syringe. After the resulting solution was stirred for a given amount of time (see individual compounds procedure below), sec-butyllithium or tert-butyllithium (see below for details) was added dropwise over 30−60 min, and then the reaction was kept at the indicated temperature. 4.7.2.5. Preparation of diastereomeric dienes 4.4 – general procedure E26 A dry 250 mL round-bottomed flask with a magnetic stir bar was sealed with a rubber septum and purged with nitrogen. A solution of the corresponding allylic alcohol 4.3 (10 mmol, 1 equiv) in 20 mL hexanes was transferred into the flask followed by a solution of the corresponding trichloroacetimidate 4.2 (15 mmol, 1.5 equiv.) in 20 mL hexanes. An additional 40 mL of hexanes was then added into the flask and the resulting mixture was cooled on ice bath to 0 °C while stirring. To the cold solution was added appropriate Lewis acid: BF3•OEt2 (0.12 mL, 1 mmol, 0.1 354 equiv.) or TMSOTf (0.18 mL, 1 mmol, 0.1 equiv.). After complete addition, a thick precipitate was formed. The mixture was stirred at 0 °C to room temperature for 6 hours and filtered through a plug of celite (5 cm thick) and the filtrate was transferred into a separating funnel. The filtrate was then washed with saturated solution of aqueous sodium bicarbonate (50 mL x 3), water (50 mL x 2) and brine (50 mL) respectively. The organic layer was dried over anhydrous sodium sulfate and then filtered. The filtrate was concentrated under reduced pressure to afford diene 4.4 as a mixture of diastereomers. The resulting crude reaction mixture was purified by column chromatography (dichloromethane/hexanes). It is important to note that some diastereomers were separable by column chromatography and hence only one of them (syn) was taken to the next step (RCM). The diastereomers that could not be separated by column chromatography were taken to the next step as a mixture. The stereochemistry of these diastereomers were determined after the RCM reaction: syn diastereomers underwent RCM to form cis dihydropyrans or tetrahyrooxepins and vice versa. It is also worth noting that for most of the compounds reported herein, the syn diastereomer exhibited lower Rf value than its anti counterpart (dichloromethane/hexanes). 4.7.2.6. Preparation of dihydropyrans 4.5 and via RCM – general procedure F26 To a dry 250 mL round-bottomed flask with a magnetic stir bar was weighed 170 mg of Grubbs catalyst 2nd generation (0.2 mmol, 0.04 equiv.) and the flask was sealed with a rubber septum and purged with nitrogen. This was followed by addition of 80 mL of dry dichloromethane and corresponding diene (5 mmol, 1.0 equiv) as a solution in 20 mL dry dichloromethane as a single 355 diastereomer (syn) or as a mixture of diastereomers (syn:anti = 1:1). The resulting mixture was stirred at room temperature for 12 hours. The mixture was concentrated under reduced pressure to afford dihydropyran 4.5. The resulting crude reaction mixture was purified by column chromatography (dichloromethane/hexanes). The cis and trans diastereomers were separable by column chromatography. The stereochemistry of these diastereomers were determined by 1D NOESY experiment. It is also worth noting that for most of the compounds reported here the trans diastereomer has lower Rf value than its cis counterpart (dichloromethane/hexanes). Synthesis of 1-phenylbut-3-en-1-ol (4.1a) Following general procedure A, commercial zinc dust (3.92 g, 60 mmol, 2.0 equiv), allyl bromide (3.9 mL, 45 mmol, 1.5 equiv), benzaldehyde (3.18 g, 30 mmol, 1.0 equiv.) and THF (80 mL) homoallylic alcohol 4.1a was obtained as a yellow oil (4.17 g, 94%) which was used in the next step without further purification. 1H NMR (500 MHz, CDCl3)  = 7.36 (d, J = 4.4 Hz, 4H), 7.29 (ddd, J = 8.8, 4.9, 3.9 Hz, 1H), 5.88 – 5.76 (m, 1H), 5.21 – 5.11 (m, 2H), 4.73 (dd, J = 7.6, 5.3 Hz, 1H), 2.57 – 2.46 (m, 2H), 2.27 (s, 1H). 13C NMR (126 MHz, CDCl3)  = 143.8, 134.4, 128.3, 127.5, 125.8, 118.3, 73.3, 43.7. IR (FTIR, film, cm -1) ṽ = 3342, 3054, 1638, 1507, 1270, 1124, 1042, 817, 744. 4.1a is a known compound and spectroscopic data are in agreement with those reported in literature.57 356 Synthesis of 1-(4-chlorophenyl)but-3-en-1-ol (4.1b) Following general procedure A, commercial zinc dust (5.88 g, 90 mmol, 1.8 equiv), allyl bromide (6.5 mL, 75 mmol, 1.5 equiv), 4-chlorobenzaldehyde (7.02 g, 50 mmol, 1.0 equiv.) and THF (100 mL) homoallylic alcohol 4.1b was obtained as a yellow oil in THF (13 g, ~100 %) which was used in the next step without further purification. 1H-NMR (500 MHz, CDCl3)  = 7.32 (d, J = 8.6 Hz, 2H), 7.27 (d, J = 8.5 Hz, 2H), 5.81 – 5.72 (m, 1H), 5.19 – 5.15 (m, 1H), 5.14 (q, J = 1.3 Hz, 1H), 4.70 (dd, J = 7.6, 5.3 Hz, 1H), 2.60 (s, 1H), 2.53 – 2.48 (m, 1H), 2.48 – 2.42 (m, 1H). 13C NMR (126 MHz, CDCl3)  = 142.0, 133.8, 133.1, 128.5, 127.2, 118.8, 72.6, 43.7. IR (FTIR, film, cm-1) ṽ = 3348, 3077, 2905, 1640, 1492, 1090, 1012, 916, 824. 4.1b is a known compound and spectroscopic data are in agreement with those reported in literature.57 Synthesis of 1-(4-(trifluoromethyl)phenyl)but-3-en-1-ol (4.1c) Following general procedure A, commercial zinc dust (13.08 g, 200 mmol, 2.0 equiv), allyl bromide (13 mL, 150 mmol, 1.5 equiv), 4-trifluoromethylbenzaldehyde (17.41 g, 100 mmol, 1.0 357 equiv.) and THF (200 mL) homoallylic alcohol 4.1c was obtained as a yellow oil in THF (27.84 g, quantitative yield) which was used in the next step without further purification. 1H-NMR (500 MHz, CDCl3)  = 7.60 (d, J = 8.1 Hz, 2H), 7.46 (d, J = 8.5 Hz, 2H), 5.83 – 5.73 (m, 1H), 5.19 (h, J = 1.8 Hz, 1H), 5.16 (tq, J = 3.2, 1.4 Hz, 1H), 4.79 (dd, J = 8.1, 4.7 Hz, 1H), 2.53 (dddt, J = 14.0, 13 6.2, 4.7, 1.3 Hz, 1H), 2.45 (dtt, J = 14.1, 7.9, 1.1 Hz, 1H), 2.32 (s, 1H). C NMR (126 MHz, CDCl3)  = 147.7 (d, J = 1.4 Hz), 133.7, 129.7 (q, J = 32.4 Hz), 126.1, 125.3 (q, J = 3.8 Hz), 124.2 (q, J = 271.9 Hz), 119.2, 72.5, 43.9. 4.1c is a known compound and spectroscopic data are in agreement with those reported in literature.57 Synthesis of 1-(naphthalen-1-yl)but-3-en-1-ol (4.1d) Following general procedure A, commercial zinc dust (11.77 g, 180 mmol, 2.0 equiv), allyl bromide (13 mL, 150 mmol, 1.5 equiv), 1-naphthaldehyde (15.62 g, 100 mmol, 1.0 equiv.) and THF (200 mL) homoallylic alcohol 4.1d was obtained as a yellow oil in THF (39.11 g, quantitative yield) which was used in the next step without further purification. 1H-NMR (500 MHz, CDCl3)  = 8.11 – 8.04 (m, 1H), 7.90 (dd, J = 8.1, 1.6 Hz, 1H), 7.80 (dt, J = 8.1, 1.1 Hz, 1H), 7.67 (dt, J = 7.2, 1.0 Hz, 1H), 7.56 – 7.47 (m, 3H), 5.94 (dddd, J = 16.9, 10.2, 7.6, 6.5 Hz, 1H), 5.52 (dd, J = 8.4, 4.1 Hz, 1H), 5.27 – 5.17 (m, 2H), 2.77 (dddt, J = 14.3, 6.7, 4.1, 1.4 Hz, 1H), 2.62 (dtt, J = 14.3, 8.6, 1.1 Hz, 1H), 2.37 (s, 1H). 13C NMR (126 MHz, CDCl3)  = 139.3, 134.7, 133.7, 130.2, 128.9, 127.9, 126.0, 125.5, 125.4, 122.9, 122.8, 118.3, 69.9, 42.8. 4.1d is a known compound and 358 spectroscopic data are in agreement with those reported in literature.58 Synthesis of 1-(naphthalen-2-yl)but-3-en-1-ol (4.1f) Following general procedure A, commercial zinc dust (5.23 g, 80 mmol, 2.0 equiv), allyl bromide (5.2 mL, 60 mmol, 1.5 equiv), 2-naphthaldehyde (6.25 g, 40 mmol, 1.0 equiv.) and THF (100 mL) homoallylic alcohol 4.1f was obtained as a yellow oil in THF (9.64 g, quantitative yield) which was used in the next step without further purification. 1H-NMR (500 MHz, CDCl3)  = 7.87 – 7.82 (m, 3H), 7.81 (s, 1H), 7.54 – 7.45 (m, 3H), 5.84 (ddt, J = 17.1, 10.1, 7.1 Hz, 1H), 5.25 – 5.13 (m, 2H), 4.91 (dd, J = 7.7, 5.2 Hz, 1H), 2.68 – 2.55 (m, 2H), 2.27 (s, 1H). 13C{1H}-NMR (126 MHz, CDCl3)  = 141.2, 134.3, 133.2, 132.9, 128.2, 127.9, 127.6, 126.1, 125.8, 124.5, 124.0, 118.5, 73.3, 43.7. IR (FTIR, cm-1) ṽ = 3342, 3054, 1638, 1507, 1270, 1124, 1042, 817, 744. S1-f is a known compound and spectroscopic data are in agreement with those reported in literature.57 Synthesis of 1-(4-methoxyphenyl)but-3-en-1-ol (4.1h) 359 Following general procedure A, commercial zinc dust (5.88 g, 90 mmol, 1.8 equiv), allyl bromide (6.5 mL, 60 mmol, 1.5 equiv), 6.1 mL of p-anisaldehyde (6.81 g, 50 mmol, 1.0 equiv.) and THF (80 mL) homoallylic alcohol 4.1h was obtained as a yellow oil in THF (13.44 g, quantitative yield) which was used in the next step without further purification. 1H-NMR (500 MHz, CDCl3)  = 7.27 (d, J = 8.4 Hz, 2H), 6.87 (d, J = 8.8 Hz, 2H), 5.78 (ddt, J = 17.3, 10.2, 7.1 Hz, 1H), 5.17 – 5.09 (m, 2H), 4.66 (t, J = 6.6 Hz, 1H), 3.79 (s, 3H), 2.53 – 2.44 (m, 2H), 2.23 (s, 1H). 13C NMR (126 MHz, CDCl3, ppm)  = 158.9, 136.0, 134.6, 127.0, 118.1, 113.7, 72.9, 55.2, 43.6. IR (FTIR, cm-1) ṽ = 3395, 2933, 2835, 1610, 1510, 1242, 1173, 1032, 829. 4.1h is a known compound and spectroscopic data are in agreement with those reported in literature. 57 Synthesis of 1-phenylbut-3-en-1-yl 2,2,2-trichloroacetimidate (4.2a) Following general procedure B, 1-phenylbut-3-en-1-ol 4.1-a (2.23 g, 15 mmol, 1.0 equiv), DBU (0.4 mL, 2.7 mmol, 0.18 equiv), trichloroacetonitrile (2.1 mL, 21 mmol, 1.4 equiv.) and dichloromethane (40 mL), 1-phenylbut-3-en-1-yl 2,2,2-trichloroacetimidate 4.1a was obtained as a dark brown oil in dichloromethane (4.5 g, ~100 %) which was used in the next step without further purification. 1H-NMR (500 MHz, CDCl3)  = 8.30 (s, 1H), 7.45 – 7.40 (m, 2H), 7.37 (ddd, J = 7.7, 6.7, 1.3 Hz, 2H), 7.34 – 7.29 (m, 1H), 5.90 (dd, J = 7.9, 5.4 Hz, 1H), 5.83 (ddt, J = 17.2, 10.2, 6.9 Hz, 1H), 5.14 (dq, J = 17.2, 1.6 Hz, 1H), 5.10 (ddt, J = 10.2, 2.1, 1.1 Hz, 1H), 2.81 (dddt, J = 14.7, 8.0, 6.8, 1.3 Hz, 1H), 2.66 (dddd, J = 14.5, 6.9, 4.1, 1.3 Hz, 1H). 13C NMR (126 MHz, CDCl3)  = 161.5, 139.6, 133.0, 128.4, 128.0, 126.2, 118.2, 91.6, 80.1, 41.0. 4.1a is a known 360 compound and spectroscopic data are in agreement with those reported in literature. 59 Synthesis of 1-(4-chlorophenyl)but-3-en-1-yl 2,2,2-trichloroacetimidate (4.2b) Following general procedure B, 1-(4-chlorophenyl)but-3-en-1-ol 4.1b (14.61 g, 80 mmol, 1.0 equiv), DBU (2.15 mL, 14.4 mmol, 0.18 equiv), trichloroacetonitrile (11.2 mL, 112 mmol, 1.4 equiv.) and dichloromethane (200 mL), 1-(4-chlorophenyl)but-3-en-1-yl 2,2,2- trichloroacetimidate 4.2b was obtained as a dark brown oil in dichloromethane (29 g, quantitative yield) which was used in the next step without further purification. 1H-NMR (500 MHz, CDCl3)  = 8.31 (s, 1H), 7.34 (s, 4H), 5.86 (dd, J = 7.8, 5.6 Hz, 1H), 5.79 (ddt, J = 17.1, 10.2, 6.9 Hz, 1H), 5.17 – 5.06 (m, 2H), 2.78 (dddt, J = 14.6, 8.0, 6.8, 1.3 Hz, 1H), 2.62 (dddt, J = 14.2, 7.0, 5.6, 1.2 Hz, 1H). 13C NMR (126 MHz, CDCl3)  = 161.3, 138.1, 133.7, 132.6, 128.6, 127.7, 118.6, 91.5, 79.3, 40.8. 4.2b is a known compound and spectroscopic data are in agreement with those reported in literature.59 Synthesis of 1-(4-(trifluoromethyl)phenyl)but-3-en-1-yl 2,2,2-trichloroacetimidate (4.2c) Following general procedure C, 1-(4-trifluoromethylphenyl)but-3-en-1-ol 4.1c (10.81 g, 50 mmol, 1.0 equiv), NaH 60% w/w dispersion in mineral oil (400 mg, 10 mmol, 0.20 equiv), 361 trichloroacetonitrile (5.51 mL, 55 mmol, 1.1 equiv.) and diethyl ether (15 mL), 18.5 g, 51 mmol (quantitative yield) of 1-(4-(trifluoromethyl)phenyl)but-3-en-1-yl 2,2,2-trichloroacetimidate 4.2c was obtained as a yellow oil after column chromatography, Rf = 0.3 (5% EtOAc in hexanes). 1H NMR (500 MHz, CDCl3)  = 8.34 (s, 1H), 7.63 (d, J = 8.1 Hz, 2H), 7.53 (d, J = 8.1 Hz, 2H), 5.93 (dd, J = 7.7, 5.5 Hz, 1H), 5.80 (ddt, J = 17.2, 10.3, 7.0 Hz, 1H), 5.18 – 5.09 (m, 2H), 2.79 (dddt, J 13 = 14.6, 8.0, 6.8, 1.3 Hz, 1H), 2.65 (dddt, J = 14.1, 6.9, 5.5, 1.3 Hz, 1H). C NMR (126 MHz, CDCl3, ppm)  =161.4, 143.6 (d, J = 1.3 Hz), 132.4, 130.2 (q, J = 32.5 Hz), 126.5, 125.5 (q, J = 3.8 Hz) 124.0 (q, J = 272.2 Hz), 118.9, 91.4, 79.3, 40.8. 4.2c is a known compound and spectroscopic data are in agreement with those reported in literature.59 Synthesis of 1-(naphthalen-1-yl)but-3-en-1-yl 2,2,2-trichloroacetimidate (4.2d) Following general procedure C, 1-(naphthalen-1-yl)but-3-en-1-ol 4.1d (9.9 g, 50 mmol, 1.0 equiv), NaH 60% w/w dispersion in mineral oil (400 mg, 10 mmol, 0.20 equiv), trichloroacetonitrile (5.51 mL, 55 mmol, 1.1 equiv.) and diethyl ether (15 mL), 16.86 g, 49 mmol (98% isolated yield) of 1-(naphthalen-1-yl)but-3-en-1-yl 2,2,2-trichloroacetimidate 4.2d was obtained as a yellow oil after column chromatography, Rf = 0.4 (30% DCM in hexanes). 1H NMR (500 MHz, CDCl3)  = 8.36 (s, 1H), 8.20 (d, J = 8.5 Hz, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.85 (d, J = 8.2 Hz, 1H), 7.73 (d, J = 7.1 Hz, 1H), 7.60 (ddd, J = 8.4, 6.8, 1.5 Hz, 1H), 7.57 – 7.48 (m, 2H), 6.73 (dd, J = 8.2, 4.8 Hz, 1H), 5.96 (ddt, J = 17.1, 10.2, 6.9 Hz, 1H), 5.21 (dq, J = 17.1, 1.6 Hz, 1H), 5.15 (dt, J = 10.3, 1.4 Hz, 1H), 2.97 (dddt, J = 15.0, 8.2, 6.8, 1.3 Hz, 1H), 2.89 (dddt, J = 362 14.6, 7.3, 4.8, 1.3 Hz, 1H). 13 C NMR (126 MHz, CDCl3)  = 161.5, 135.5, 133.7, 133.4, 130.1, 128.9, 128.5, 126.3, 125.6, 125.3, 123.5, 123.0, 118.1, 91.7, 77.5, 40.5. MS (GC/MS): m/z (%) = 181 (12.5) [M – Cl3CCONH]+: C14H13 HRMS (ESI), m/z [M + H]+ calcd for C16H15Cl3NO: 342.0219 found: 342.0227. Synthesis of 1-(naphthalen-2-yl)but-3-en-1-yl 2,2,2-trichloroacetimidate (4.2f) Following general procedure B, 1-(naphthalen-2-yl)but-3-en-1-ol 4.1f (5.95 g, 30 mmol, 1.0 equiv), DBU (0.81 mL, 5.4 mmol, 0.18 equiv), trichloroacetonitrile (4.21 mL, 42 mmol, 1.4 equiv.) and dichloromethane (80 mL), 11.04 g, 32 mmol (quantitative yield) of 1-(naphthalen-2-yl)but-3- en-1-yl 2,2,2-trichloroacetimidate 4.2f was obtained as a yellow oil after column chromatography, Rf = 0.3 (4% EtOAc in hexanes). 1H NMR (500 MHz, CDCl3)  = 8.33 (s, 1H), 7.90 (s, 1H), 7.89 – 7.83 (m, 3H), 7.56 (dd, J = 8.5, 1.8 Hz, 1H), 7.54 – 7.46 (m, 2H), 6.08 (dd, J = 7.9, 5.5 Hz, 1H), 5.87 (ddt, J = 17.1, 10.2, 6.9 Hz, 1H), 5.17 (dq, J = 17.1, 1.5 Hz, 1H), 5.12 (ddt, J = 10.2, 2.0, 1.1 Hz, 1H), 2.92 (dddt, J = 14.7, 8.0, 6.8, 1.3 Hz, 1H), 2.76 (dddt, J = 14.2, 6.9, 5.6, 1.3 Hz, 1H). 13C NMR (126 MHz, CDCl3)  = 161.5, 136.9, 133.1, 133.02, 133.00, 128.3, 128.1, 127.7, 126.2, 126.1, 125.5, 124.0, 118.3, 91.7, 80.2, 40.9. 4.2f is a known compound and spectroscopic data are in agreement with those reported in literature.26 363 Synthesis of 1-(4-methoxyphenyl)but-3-en-1-yl 2,2,2-trichloroacetimidate (4.2h) Following general procedure C, 1-(4-methoxyphenyl)but-3-en-1-ol 4.1h (8.9 g, 50 mmol, 1.0 equiv), NaH 60% w/w dispersion in mineral oil (360 mg, 9 mmol, 0.18 equiv), trichloroacetonitrile (5.51 mL, 55 mmol, 1.1 equiv.) and diethyl ether (15 mL), 15.86 g, 49 mmol, (98% crude yield) of 1-(4-methoxyphenyl)but-3-en-1-yl 2,2,2-trichloroacetimidate 4.2h which was used in the next step without further purification. It is worth noting that compound 4.2h is unstable on silica and it breaks down to the starting alcohol. 1H NMR (500 MHz, CDCl3)  = 8.27 (s, 1H), 7.35 (d, J = 8.5 Hz, 2H), 6.90 (d, J = 8.8 Hz, 2H), 5.87 – 5.76 (m, 2H), 5.13 (dq, J = 17.2, 1.6 Hz, 1H), 5.09 (ddt, J = 10.3, 2.1, 1.1 Hz, 1H), 3.81 (s, 3H), 2.80 (dddt, J = 14.7, 8.0, 6.8, 1.3 Hz, 1H), 2.62 (dddt, J = 14.2, 7.0, 5.7, 1.3 Hz, 1H). 13 C NMR (126 MHz, CDCl3)  = 161.5, 159.3, 133.2, 131.6, 127.7, 118.1, 113.7, 91.7, 79.9, 55.2, 40.9. 4.2h is a known compound and spectroscopic data are in agreement with those reported in literature.26 Synthesis of 1-(trimethylsilyl)prop-2-en-1-ol (4.3a) Following general procedure D, a solution of allyl alcohol (3.49 g, 60 mmol, 1 equiv.) in THF (150 mL) was cooled to −78 °C. n-BuLi (2.5 M in hexanes, 26.4 mL, 66 mmol, 1.1 equiv.) was 364 added dropwise and the mixture stirred at –78 °C for 1 h. Freshly distilled chlorotrimethylsilane (7.6 mL, 60 mmol, 1 equiv.) was then added slowly from a syringe and the resulting mixture was stirred at –78 °C for 1.5 hours resulting in the formation of a white suspension. This was followed by addition of tert-BuLi (1.7 M in pentane, 43 mL, 72 mmol, 1.2 equiv.) dropwise via cannula and the reaction stirred for an additional 1.5 hours at –78 °C. The reaction was quenched by the addition of aqueous NH4Cl and diluted with Et2O, and the mixture was warmed to room temperature. After the layers were separated, the aqueous phase was washed with Et 2O (3 × 50 mL). Then all the organic phases were combined, washed with H2O (50 mL) and brine (50 mL) respectively, and dried over anhydrous MgSO4. After filtration and concentration, the residue was purified by column chromatography, Rf = 0.5 (30% Et2O in pentane) to afford 5.17 g, 47.4 mmol, (79% isolated yield) of compound 4.3a as a colorless liquid. 1H NMR (500 MHz, CDCl3)  = 6.03 (ddd, J = 17.1, 10.7, 5.3 Hz, 1H), 5.07 (ddd, J = 17.2, 2.1, 1.5 Hz, 1H), 4.99 (dt, J = 10.8, 1.8 Hz, 1H), 4.02 (dt, J = 5.3, 2.1 Hz, 1H), 1.42 (s, 1H), 0.04 (s, 9H). 13C NMR (126 MHz, CDCl3)  = 139.9, 109.4, 69.0, -4.3. IR (FTIR, film, cm-1) ṽ = 3405, 2956, 1632, 1247, 895. 4.3a is a known compound and spectroscopic data are in agreement with those reported in literature.60 Synthesis of 2-methyl-1-(trimethylsilyl)prop-2-en-1-ol (4.3b)61 Following general procedure D, a solution of 2-methylprop-2-en-1-ol (4.33 g, 60 mmol, 1 equiv.) in THF (110 mL) was cooled to −78 °C. n-BuLi (2.5 M in hexanes, 26.4 mL, 66 mmol, 1.1 equiv.) was added dropwise and the mixture stirred at –78 °C for 1 h. Freshly distilled 365 chlorotrimethylsilane (7.6 mL, 60 mmol, 1 equiv.) was then added slowly from a syringe and the resulting mixture was stirred at –78 °C for 1.5 hours resulting in the formation of a white suspension. This was followed by addition of tert-BuLi (1.7 M in pentane, 45.9 mL, 78 mmol, 1.3 equiv.) dropwise via cannula and the reaction warmed up slowly to –35 °C and stirred at this temperature for an additional 3.5 hours. The reaction was cooled down to –78 °C and quenched by the addition of 4.5 mL acetic acid solution in 10 mL THF and the cold bath was removed. The reaction mixture was diluted with saturated aqueous NaHCO3 (50 mL) solution and pentane (150 mL. After the layers were separated organic phase was washed with H2O (50 mL x 3) and brine (50 mL) respectively and dried over anhydrous MgSO4. After filtration and concentration, the residue was purified by column chromatography, Rf = 0.4 (15% Et2O in hexanes) to afford 5.37 g, 37.2 mmol, (62% isolated yield) of compound 4.3b as a pale-yellow liquid. 1H NMR (500 MHz, C6D6)  = 4.85 (tq, J = 1.7, 0.8 Hz, 1H), 4.74 (h, J = 1.4 Hz, 1H), 3.63 (d, J = 1.4 Hz, 1H), 1.57 (dt, J = 1.5, 0.6 Hz, 3H), 1.00 (s, 1H), 0.08 (s, 9H). 13C NMR (126 MHz, C6D6)  = 148.6, 106.6, 71.4, 20.8, -3.3. 4.3b is a known compound.61 Synthesis of 1-(triethylsilyl)prop-2-en-1-ol (4.3c) Following general procedure D, a solution of allyl alcohol (1.16 g, 20 mmol, 1 equiv.) in THF (35 mL) was cooled to −78 °C. n-BuLi (2.5 M in hexanes, 10 mL, 24 mmol, 1.2 equiv.) was added dropwise and the mixture stirred at –78 °C for 1 h. Chlorotriethylsilane (3.7 mL, 22 mmol, 1.1 equiv.) was then added slowly from a syringe and the resulting mixture was stirred at –78 °C to 366 room temperature for 18 hours resulting in the formation of a white suspension. The mixture was cooled back to –78 °C followed by dropwise addition of sec-butyllithium (1.4 M in cyclohexane, 18.6 mL, 26 mmol, 1.3 equiv.) and the reaction stirred for an additional 2 hours at –78 °C to –50 °C. The reaction mixture was cooled back to –78 °C and quenched by the addition of aqueous NH4Cl and diluted with Et2O, and the mixture was warmed to room temperature. After the layers were separated, the aqueous phase was washed with Et2O (3 × 20 mL). Then all the organic phases were combined, washed with H2O (20 mL) and brine (20 mL) respectively, and dried over anhydrous MgSO4. After filtration and concentration, the residue was purified by column chromatography, Rf = 0.3 (15% Et2O in hexanes) to afford 2.97 g, 17.2 mmol, (86% isolated yield) of compound 4.3c as a colorless liquid. 1H NMR (500 MHz, CDCl3)  = 6.07 (ddd, J = 17.1, 10.7, 5.2 Hz, 1H), 5.09 (ddd, J = 17.2, 2.2, 1.6 Hz, 1H), 4.97 (ddd, J = 10.7, 2.1, 1.6 Hz, 1H), 4.18 (dt, J = 5.2, 2.1 Hz, 1H), 1.30 (s, 1H), 0.98 (t, J = 8.0 Hz, 9H), 0.62 (qd, J = 8.0, 1.6 Hz, 6H). 13C NMR (126 MHz, CDCl3)  = 140.4, 109.0, 67.4, 7.4, 1.5. 4.3c is a known compound and spectroscopic data are in agreement with those reported in literature. 60 Synthesis of 1-(dimethyl(phenyl)silyl)prop-2-en-1-ol (4.3d) Following general procedure D, a solution of allyl alcohol (1.16 g, 20 mmol, 1 equiv.) in THF (35 mL) was cooled to −78 °C. n-BuLi (2.5 M in hexanes, 10 mL, 24 mmol, 1.2 equiv.) was added dropwise and the mixture stirred at –78 °C for 1 h. chlorodimethyl(phenyl)silane (3.7 mL, 22 mmol, 1.1 equiv.) was then added slowly from a syringe and the resulting mixture was stirred at – 367 78 °C to room temperature for 18 hours resulting in the formation of a white suspension. The mixture was cooled back to –78 °C followed by dropwise addition of sec-butyllithium (1.4 M in cyclohexane, 18.6 mL, 26 mmol, 1.3 equiv.) and the reaction stirred for an additional 2 hours at – 78 °C to –50 °C. The reaction mixture was cooled back to –78 °C and quenched by the addition of aqueous NH4Cl and diluted with Et2O, and the mixture was warmed to room temperature. After the layers were separated, the aqueous phase was washed with Et 2O (3 × 20 mL). Then all the organic phases were combined, washed with H2O (20 mL) and brine (20 mL) respectively, and dried over anhydrous MgSO4. After filtration and concentration the residue was purified by column chromatography, Rf = 0.4 (15% Et2O in hexanes) to afford 2.73 g, 14.2 mmol, (71% isolated yield) of compound 4.3d as a colorless liquid. 1H NMR (500 MHz, CDCl3)  = 7.64 – 7.56 (m, 2H), 7.45 – 7.36 (m, 3H), 6.01 (ddd, J = 17.1, 10.7, 5.2 Hz, 1H), 5.08 (dt, J = 17.2, 1.8 Hz, 1H), 5.02 (dt, J = 10.7, 1.7 Hz, 1H), 4.23 (dt, J = 5.1, 2.0 Hz, 1H), 1.43 (s, 1H), 0.37 (s, 3H), 0.35 (s, 3H). 13C NMR (126 MHz, CDCl3)  = 139.3, 136.0, 134.2, 129.5, 127.8, 110.0, 68.4, -5.8, -6.1. 4.3d is a known compound and spectroscopic data are in agreement with those reported in literature.62,63 368 Synthesis of syn/anti-trimethyl(2-methyl-1-((1-phenylbut-3-en-1-yl)oxy)allyl)silane (syn/anti-4.4a) Compound 4.4a was prepared following general procedure E, a solution of 2-methyl-1- (trimethylsilyl)prop-2-en-1-ol 4.3b (2.47 g, 17.1 mmol, 1 equiv.) and 1-phenylbut-3-en-1-yl 2,2,2- trichloroacetimidate 4.2a (10.0 g, 34.18 mmol, 2.0 equiv.), TMSOTf (0.46 mL, 2.6 mmol, 0.15 equiv.) and cyclohehane (80 mL) for 12 hour followed by workup, concentration and column chromatography, Rf for syn/anti-4.4d = 0.6 (10% DCM in hexanes) afforded 1.64 g, 6 mmol (35% isolated yield) inseparable mixture of diastereomers of compound 4.4d (syn:anti = 1:1) as colorless liquid. 1H NMR (500 MHz, CDCl3)  = 7.35 – 7.26 (m, 8H), 7.26 – 7.20 (m, 2H), 5.81 (ddt, J = 17.2, 10.2, 7.1 Hz, 1H), 5.74 – 5.63 (m, 1H), 5.03 – 4.95 (m, 4H), 4.87 – 4.81 (m, 1H), 4.69 (dddd, J = 6.6, 3.2, 1.8, 0.8 Hz, 3H), 4.34 (dd, J = 6.4, 5.4 Hz, 1H), 4.30 (dd, J = 7.7, 5.8 Hz, 1H), 3.79 (s, 1H), 3.33 (s, 1H), 2.59 – 2.52 (m, 2H), 2.52 – 2.45 (m, 1H), 2.40 – 2.33 (m, 1H), 1.70 – 1.63 (m, 3H), 1.53 (dd, J = 1.4, 0.8 Hz, 3H), 0.09 (s, 9H), 0.00 (s, 9H). 13C NMR (126 MHz, CDCl3)  = 145.0, 144.4, 143.4, 142.3, 135.5, 134.6, 128.1, 127.8, 127.5, 127.4, 126.8, 126.6, 116.9, 116.4, 369 109.9, 109.5, 80.0, 79.1, 77.8, 75.4, 43.0, 40.5, 20.4, 20.3, -3.0, -3.2. Syn-4.4b and anti-4.4b are known compounds and spectroscopic data are in agreement with those reported in literature.26 Synthesis of syn/anti-(1-((1-(4-chlorophenyl)but-3-en-1-yl)oxy)allyl)trimethylsilane (syn/anti-4.4b) Compound 4.4b was prepared following general procedure E with slight modification to minimize formation of the side product 4.10b resulting from elimination. A solution of 1- (trimethylsilyl)prop-2-en-1-ol 4.3a (1.96 g, 15 mmol, 1 equiv.) and 1-(4-chlorophenyl)but-3-en-1- yl 2,2,2-trichloroacetimidate 4.2b (4.91 g, 15 mmol, 1.0 equiv) in dichloromethane (100 mL) was cooled to −78 °C. TMSOTf (0.27 mL, 1.5 mmol, 0.1 equiv.) was added dropwise and the mixture stirred at –78 °C for 6 hours. The rubber septum was removed, and 5 g of sodium bicarbonate was poured into the flask. The dry ice-acetone bath was removed, and the mixture was allowed to warm up to room temperature. The mixture was filtered and concentrated under reduced pressure to remove dichloromethane. Hexanes was then added to the resulting mixture resulting in the formation of white precipitate. Subsequent filtration and concentration furnished a residue which was purified by column chromatography, Rf for 4.10b = 0.8 and Rf for syn/anti-4.4b = 0.6 (5% 370 DCM in hexanes) to afford 2.15 g, 7.35 mmol, (49% isolated yield) inseparable mixture of diastereomers of compound 4.4b (syn:anti = 1:1) as colorless liquid and 1.26 g, 7.65 mmol (51% isolated yield) elimination side product (E)-1-(buta-1,3-dien-1-yl)-4-chlorobenzene 4.10b (E:Z > 99:1). Spectroscopic data for syn:anti-4.4b: 1H NMR (500 MHz, CDCl3)  = 7.30 (d, J = 8.4 Hz, 2H), 7.27 (d, J = 8.6 Hz, 2H), 7.23 (d, J = 8.5 Hz, 2H), 7.18 (d, J = 8.4 Hz, 2H), 5.82 – 5.60 (m, 4H), 5.06 – 4.95 (m, 6H), 4.90 (dt, J = 17.2, 1.7 Hz, 1H), 4.85 (dt, J = 10.6, 1.6 Hz, 1H), 4.42 (dd, J = 7.6, 5.9 Hz, 1H), 4.35 (t, J = 6.1 Hz, 1H), 3.80 (dt, J = 7.2, 1.5 Hz, 1H), 3.38 (dt, J = 7.5, 1.3 Hz, 1H), 2.56 – 2.46 (m, 2H), 2.40 (dddt, J = 14.3, 7.3, 6.2, 1.2 Hz, 1H), 2.36 – 2.28 (m, 1H), 0.06 (s, 9H), -0.01 (s, 9H). 13C NMR (126 MHz, CDCl3)  = 142.1, 140.9, 137.6, 137.3, 134.9, 134.3, 133.0, 132.5, 128.7, 128.3, 128.0, 127.9, 117.2, 116.8, 113.1, 112.1, 80.3, 78.5, 75.9, 73.1, 42.9, 41.3, -3.8, -4.0. Syn-4.4b and anti-4.4b are known compounds and spectroscopic data are in agreement with those reported in literature.26 Spectroscopic data for 4.10b: 1H NMR (500 MHz, CDCl3)  = 7.33 (d, J = 8.6 Hz, 2H), 7.29 (d, J = 8.6 Hz, 2H), 6.76 (ddd, J = 15.2, 10.2, 0.9 Hz, 1H), 6.55 – 6.46 (m, 2H), 5.36 (dd, J = 16.4, 1.6 Hz, 1H), 5.24 – 5.19 (m, 1H). 13C NMR (126 MHz, CDCl3)  = 136.8, 135.6, 133.1, 131.4, 130.1, 128.7, 127.5, 118.2. 4.10b is a known compound and spectroscopic data are in agreement with those reported in literature.64 371 Synthesis of syn/anti-(1-((1-(4-trifluromethylphenyl)but-3-en-1-yl)oxy)allyl) trimethylsilane (syn/anti-4.4c) Compound 4.4c was prepared following general procedure E with slight modification to minimize formation of the side product as a result of elimination. A solution of 1- (trimethylsilyl)prop-2-en-1-ol 4.3a (2.61 g, 20 mmol, 1 equiv.) and 1-(4- trifluoromethylphenyl)but-3-en-1-yl 2,2,2-trichloroacetimidate 4.2c (10.1 g, 28 mmol, 1.4 equiv.) in dichloromethane (100 mL) was cooled to −78 °C. TMSOTf (0.36 mL, 2.0 mmol, 0.1 equiv.) was added dropwise and the mixture stirred at –78 °C for 6 hours. The rubber septum was removed and 7 g of sodium bicarbonate was poured into the flask. The dry ice-acetone bath was removed and the mixture was allowed to warm up to room temperature. The mixture was filtered and concentrated under reduced pressure to remove dichloromethane. Hexanes was then added to the resulting mixture resulting in the formation of white precipitate. Subsequent filtration and concentration furnished a residue which was purified by column chromatography, Rf for 4.10c = 0.7 and Rf for syn/anti-4.4c = 0.5 (100% hexanes) to afford 2.2 g, 6.6 mmol (33% isolated yield) inseparable mixture of diastereomers of compound 4.4c (syn:anti = 1:1) as colorless liquid and 372 1.72 g, 8.7 mmol (31% isolated yield based on the starting trichloroacetimidate) elimination side product (E)-1-(buta-1,3-dien-1-yl)-4-trifluoromethylbenzene 4.10c (E:Z > 99:1). Spectroscopic data for syn:anti-4.4c: 1H NMR (500 MHz, CDCl3)  = 7.59 (d, J = 8.1 Hz, 2H), 7.56 (d, J = 8.1 Hz, 2H), 7.41 (d, J = 8.3 Hz, 2H), 7.37 (d, J = 8.1 Hz, 2H), 5.83 – 5.61 (m, 4H), 5.06 (ddd, J = 10.6, 2.0, 1.2 Hz, 1H), 5.03 – 4.96 (m, 5H), 4.91 (dt, J = 17.2, 1.8 Hz, 1H), 4.87 (ddd, J = 10.6, 2.0, 1.4 Hz, 1H), 4.52 (dd, J = 7.6, 5.8 Hz, 1H), 4.45 (t, J = 6.0 Hz, 1H), 3.83 (dt, J = 7.3, 1.5 Hz, 1H), 3.39 (dt, J = 7.6, 1.3 Hz, 1H), 2.57 – 2.48 (m, 2H), 2.48 – 2.41 (m, 1H), 2.35 (dddt, J = 14.1, 7.1, 5.8, 1.2 Hz, 1H), 0.08 (s, 9H), 0.01 (s, 9H). 13C NMR (126 MHz, CDCl3)  = 147.69 (d, J = 1.2 Hz), 146.65 (d, J = 1.2 Hz), 137.5, 137.2, 134.6, 134.0, 130.0 –128.7 (m, 2C), 127.7 –123.2 (m, 2C), 127.5, 126.7, 125.12 (q, J = 3.8 Hz), 124.85 (q, J = 3.8 Hz), 117.5, 117.0, 113.3, 112.4, 80.2, 78.7, 76.1, 73.5, 42.9, 41.2, –3.8, –4.0. Syn-4.4c and anti-4.4c are known compounds and spectroscopic data are in agreement with those reported in literature. 26 Spectroscopic data for 4.10c: 1H NMR (500 MHz, CDCl3)  = 7.57 (d, J = 8.2 Hz, 2H), 7.49 (d, J = 8.2 Hz, 2H), 6.87 (dd, J = 15.7, 10.5 Hz, 1H), 6.62 – 6.49 (m, 2H), 5.42 (d, J = 16.9 Hz, 1H), 5.28 (d, J = 10.0 Hz, 1H). 13C NMR (126 MHz, CDCl3)  = 140.58 (q, J = 1.3 Hz), 136.7, 132.0, 131.2, 129.25 (q, J = 32.4 Hz), 126.5, 125.55 (q, J = 3.9 Hz), 124.21 (q, J = 271.7 Hz), 119.4. 4.10c is a known compound and spectroscopic data were in agreement with those reported in literature.65 373 Synthesis of syn/anti-trimethyl(1-((1-(naphthalen-1-yl)but-3-en-1-yl)oxy)allyl)silane (syn/anti-4.4d) Compound 4.4d was prepared following general procedure E, a solution of 1- (trimethylsilyl)prop-2-en-1-ol 4.3a (2.61 g, 20 mmol, 1 equiv.) and 1-(naphthalen-1-yl)but-3-en- 1-yl 2,2,2-trichloroacetimidate 4.2d (9.6 g, 28 mmol, 1.4 equiv.), TMSOTf (0.36 mL, 2.0 mmol, 0.1 equiv.) and hexanes (50 mL) for 12 hour followed by workup, concentration and column chromatography, Rf for syn/anti-4.4d = 0.6 (10% DCM in hexanes) afforded 2.11 g, 6.8 mmol (34% isolated yield) inseparable mixture of diastereomers of compound 4.4d (syn:anti = 1:1) as colorless liquid. 1H NMR (500 MHz, CDCl3)  = 8.22 (d, J = 6.8 Hz, 1H), 8.12 (d, J = 8.1 Hz, 1H), 7.92 – 7.86 (m, 2H), 7.80 (d, J = 8.2 Hz, 1H), 7.77 (d, J = 8.2 Hz, 1H), 7.67 – 7.63 (m, 1H), 7.57 – 7.46 (m, 7H), 5.94 (ddt, J = 17.4, 10.4, 7.2 Hz, 1H), 5.89 – 5.80 (m, 2H), 5.69 (ddd, J = 17.6, 10.5, 7.4 Hz, 1H), 5.31 – 5.23 (m, 1H), 5.14 (t, J = 6.0 Hz, 1H), 5.12 – 4.96 (m, 7H), 4.93 374 (dt, J = 17.2, 1.7 Hz, 1H), 4.80 (dt, J = 10.5, 1.6 Hz, 1H), 3.95 (dt, J = 7.4, 1.4 Hz, 1H), 3.52 (dt, J = 7.8, 1.3 Hz, 1H), 2.78 – 2.64 (m, 3H), 2.60 (dddt, J = 14.0, 7.4, 5.1, 1.2 Hz, 1H), 0.13 (s, 9H), 0.04 (s, 9H). 13 C NMR (126 MHz, CDCl3)  = 139.5, 137.8, 137.7, 135.7, 135.2, 133.8, 133.7, 131.5, 130.4, 128.8, 128.7, 127.7, 127.3, 125.6, 125.5, 125.4, 125.29, 125.28, 125.1, 124.3, 123.7, 116.7, 116.3, 113.6, 112.2, 78.8, 76.6, 73.4, 42.4, 41.3, -3.7, -3.9. IR (FTIR, cm-1) ṽ = 3072, 3050, 2955, 2899, 1639, 1626, 1509, 1413, 1246, 909, 837, 775. HRMS (ESI), m/z [M + H]+ calcd for C20H27OSi: 311.1826; found: 311.1837. Synthesis of syn/anti-(1-((1-([1,1'-biphenyl]-4-yl)but-3-en-1-yl)oxy)allyl)trimethylsilane (syn/anti-4.4e) Compound 4.4e was prepared as per the following procedure: A mixture of syn/anti-4.4b (dr = 1:1) (390 mg, 1.3 mmol, 1.0 equiv), phenylboronic acid (240 mg, 1.97 mmol, 1.5 equiv) and K3PO4.2H2O (652 mg, 2.6 mmol, 2.0 equiv) in toluene (2 mL) was degassed (3-freeze-pump-thaw actions) and then a solution of Pd(OAc)2 (3 mg, 0.013 mmol, 0.01 equiv) and S-PHOS (10.8 mg, 0.026 mmol, 0.02 equiv) in THF (1 mL) was added resulting In formation of red solution. The resulting mixture was heated in an oil bath at 100 °C for 4.5 hours. The reaction mixture was concentrated and the residue subjected to column chromatography to give a total of 161 mg, 0.478 375 mmol (37% isolated yield) of partially separable mixture of diastereomers. Rf value for syn-4.4e = 0.36 and Rf value for trans-4.4e = 0.40. Spectroscopic data for syn-S4-e: 1H NMR (600 MHz, CDCl3)  = 7.62 (dd, J = 8.3, 1.1 Hz, 2H), 7.56 (d, J = 8.2 Hz, 2H), 7.48 – 7.43 (m, 2H), 7.39 (d, J = 8.1 Hz, 2H), 7.37 – 7.33 (m, 1H), 5.84 – 5.69 (m, 2H), 5.09 – 5.01 (m, 2H), 4.98 (dt, J = 17.2, 1.8 Hz, 1H), 4.90 (dt, J = 10.6, 1.7 Hz, 1H), 4.47 (t, J = 6.1 Hz, 1H), 3.87 (dt, J = 7.1, 1.5 Hz, 1H), 2.62 – 2.55 (m, 1H), 2.55 – 2.47 (m, 1H), 0.11 (s, 9H). 13C -NMR (151 MHz, CDCl3)  = 142.7, 141.1, 139.7, 137.9, 134.8, 128.7, 127.0, 127.0, 127.0, 126.6, 117.0, 112.0, 80.6, 75.7, 41.4, -3.7. Syn-4.4e is a known compound and spectroscopic data are in agreement with those reported in literature.26 Spectroscopic data for anti-4.4e: 1H NMR (600 MHz, CDCl3)  = 7.64 (d, J = 7.7 Hz, 2H), 7.59 (d, J = 8.1 Hz, 2H), 7.46 (t, J = 7.8 Hz, 2H), 7.39 – 7.32 (m, 3H), 5.87 (ddt, J = 17.2, 10.2, 7.0 Hz, 1H), 5.79 (ddd, J = 17.5, 10.6, 7.4 Hz, 1H), 5.10 – 5.00 (m, 4H), 4.52 (dd, J = 7.8, 5.7 Hz, 1H), 3.52 (d, J = 7.4 Hz, 1H), 2.63 – 2.56 (m, 1H), 2.45 – 2.38 (m, 1H), 0.04 (s, 9H). 13C NMR (151 MHz, CDCl3)  = 141.6, 141.0, 140.2, 137.6, 135.4, 128.7, 127.7, 127.2, 127.0, 126.8, 116.5, 112.9, 78.9, 72.9, 43.07, -4.0. Trans-S4-e is a known compound and spectroscopic data are in agreement with those reported in literature.26 376 Synthesis of syn/anti-triethyl(1-((1-(naphthalen-2-yl)but-3-en-1-yl)oxy)allyl)silane (syn/anti-4.4f) Compound 4.4f was prepared following general procedure E with slight modification to minimize formation of the side product as a result of elimination. A solution of 1- (triethylsilyl)prop-2-en-1-ol 4.3c (2.59 g, 15 mmol, 1 equiv.) and 1-(naphthalen-2-yl)but-3-en-1- yl 2,2,2-trichloroacetimidate 4.2f (6.17 g, 18 mmol, 1.2 equiv.) in dichloromethane (120 mL) was cooled to −78 °C. TMSOTf (0.28 mL, 1.5 mmol, 0.1 equiv.) was added dropwise and the mixture stirred at –78 °C for 6 hours. The rubber septum was removed and 7 g of sodium bicarbonate was poured into the flask. The dry ice-acetone bath was removed and the mixture was allowed to warm up to room temperature. The mixture was filtered and concentrated under reduced pressure to remove dichloromethane. Hexanes was then added to the resulting mixture resulting in the formation of white precipitate. Subsequent filtration and concentration furnished a residue which 377 was purified by column chromatography, Rf for anti-4.4f = 0.6 and Rf for syn-4.4f = 0.4 (10% DCM in hexanes) to afford a total of 2.48 g, 7.1 mmol (47% isolated yield) of partially separable mixture of diastereomers of compound 4.4f (syn:anti = 1:1) as colorless liquid Spectroscopic data for syn-4.4f: 1H NMR (500 MHz, CDCl3)  = 7.86 – 7.79 (m, 3H), 7.74 (s, 1H), 7.51 – 7.43 (m, 3H), 5.80 – 5.68 (m, 2H), 5.05 – 4.93 (m, 3H), 4.82 (dt, J = 10.5, 1.6 Hz, 1H), 4.55 (t, J = 6.2 Hz, 1H), 4.08 (dt, J = 7.4, 1.5 Hz, 1H), 2.65 (dddt, J = 14.4, 7.3, 6.0, 1.3 Hz, 1H), 2.58 – 2.48 (m, 1H), 1.04 (t, J = 7.9 Hz, 9H), 0.68 (qd, J = 7.9, 2.6 Hz, 6H). 13C NMR (126 MHz, CDCl3)  = 141.2, 138.3, 134.7, 133.1, 132.7, 127.9, 127.6, 127.5, 125.7, 125.4, 125.3, 125.0, 116.9, 111.9, 81.2, 74.5, 41.4, 7.5, 1.8. Syn-4.4f is a known compound and spectroscopic data are in agreement with those reported in literature.26 Spectroscopic data for anti-4.4f: 1H-NMR (500 MHz, CDCl3)  = 7.88 – 7.81 (m, 3H), 7.67 (s, 1H), 7.52 – 7.44 (m, 3H), 5.91 – 5.78 (m, 2H), 5.10 – 4.97 (m, 4H), 4.63 (dd, J = 7.8, 5.7 Hz, 1H), 3.62 (dt, J = 7.7, 1.4 Hz, 1H), 2.64 (dddt, J = 14.1, 8.0, 6.8, 1.3 Hz, 1H), 2.45 (dddt, J = 14.2, 7.1, 5.7, 1.2 Hz, 1H), 0.92 (t, J = 7.9 Hz, 9H), 0.59 (qd, J = 7.9, 3.7 Hz, 6H). 13C NMR (126 MHz, CDCl3)  = 139.7, 137.9, 135.4, 133.10, 133.05, 128.0, 127.8, 127.7, 126.6, 125.9, 125.6, 125.1, 116.5, 112.9, 79.1, 71.5, 42.9, 7.4, 1.6. Anti-4.4c is a known compound and spectroscopic data are in agreement with those reported in literature.26 378 Synthesis of syn/anti-(1-((1-(4-chlorophenyl)but-3-en-1-yl)oxy)allyl) dimethyl(phenyl)silane (syn/anti-S4-g) Compound 4.4c was prepared following general procedure E, a solution of 1- (dimethyl(phenyl)silyl)prop-2-en-1-ol 4.3d (2.40 g, 13.5 mmol, 1 equiv.) and 1-(4- chlorophenyl)but-3-en-1-yl 2,2,2-trichloroacetimidate 4.2b (6.18 g, 18.9 mmol, 1.4 equiv.), BF3•OEt2 (0.17 mL, 1.35 mmol, 0.1 equiv.) and hexanes (80 mL) for 12 hour followed by workup, concentration and column chromatography, Rf for syn/anti-4.4g = 0.6 (20% DCM in hexanes) afforded a total of 3.76 g, 10.5 mmol (78% isolated yield) inseparable mixture of diastereomers of compound 4.4g (syn:anti = 1:1) as colorless liquid. Spectroscopic data for syn/anti-4.4g: 1H-NMR (500 MHz, CDCl3, ppm)  = 7.64 – 7.58 (m, 2H), 7.53 (dt, J = 6.5, 1.6 Hz, 2H), 7.43 – 7.33 (m, 6H), 7.26 (d, J = 8.4 Hz, 2H), 7.21 – 7.16 (m, 4H), 6.96 (d, J = 8.4 Hz, 2H), 5.82 – 5.53 (m, 5H), 5.05 (dt, J = 10.6, 1.4 Hz, 1H), 5.03 – 4.88 (m, 6H), 4.86 (dt, J = 10.6, 1.7 Hz, 1H), 4.43 (dd, J = 7.6, 5.8 Hz, 1H), 4.28 (t, J = 6.1 Hz, 1H), 3.99 379 (dt, J = 7.0, 1.5 Hz, 1H), 3.58 (dt, J = 7.4, 1.3 Hz, 1H), 2.54 – 2.41 (m, 2H), 2.39 – 2.28 (m, 2H), 0.39 (s, 3H), 0.35 (s, 3H), 0.32 (s, 3H), 0.28 (s, 3H). 13C NMR (126 MHz, CDCl3)  = 141.8, 140.5, 137.2, 136.8, 136.7, 136.6, 134.8, 134.4, 134.3, 134.2, 132.8, 132.5, 129.23, 129.15, 128.6, 128.21, 128.00, 127.95, 127.6, 127.5, 117.2, 116.8, 113.7, 112.6, 80.4, 78.5, 75.4, 72.7, 42.9, 41.3, -5.28, -5.31, -5.7, -6.3. 4.4g is a known compound and spectroscopic data are in agreement with those reported in literature.26 Synthesis of syn/anti-(1-((1-(4-methoxyphenyl)but-3-en-1-yl)oxy)-2-methylallyl)trimethyl silane (syn/anti-4.4h) Compound 4.4h was prepared following general procedure E, a solution of 2-methyl-1- (trimethylsilyl)prop-2-en-1-ol 4.3b (1.44 g, 10 mmol, 1 equiv.) and 1-(4-methoxyphenyl)but-3- en-1-yl 2,2,2-trichloroacetimidate 4.2h (4.84 g, 15 mmol, 1.5 equiv.), BF3•OEt2 (0.12 mL, 1.0 mmol, 0.1 equiv.) and hexanes (80 mL) for 12 hour followed by workup, concentration and column chromatography, Rf for anti-4.4h = 0.7 and Rf for syn-4.4h = 0.6 (15% DCM in hexanes) afforded 380 a total of 1.15 g, 3.8 mmol (38% isolated yield) partially separable mixture of diastereomers of compound 4.4h as colorless liquid. Spectroscopic data for syn-4.4h: 1H NMR (500 MHz, CDCl3)  = 7.22 (d, J = 8.5 Hz, 2H), 6.84 (d, J = 8.7 Hz, 2H), 5.68 (ddt, J = 17.3, 10.3, 7.0 Hz, 1H), 5.01 – 4.94 (m, 2H), 4.68 (ddt, J = 7.9, 2.2, 1.1 Hz, 2H), 4.28 (t, J = 6.0 Hz, 1H), 3.80 (s, 3H), 3.76 (s, 1H), 2.59 – 2.49 (m, 1H), 2.49 – 2.41 (m, 1H), 1.53 (t, J = 1.1 Hz, 3H), 0.08 (s, 9H). 13 C NMR (126 MHz, CDCl3)  = 158.4, 145.1, 135.5, 134.8, 127.7, 116.8, 113.1, 109.3, 79.7, 77.6, 55.1, 40.5, 20.3, -3.0. Syn-4.4h is a known compound and spectroscopic data are in agreement with those reported in literature. 26 Spectroscopic data for anti-4.4h: 1H-NMR (500 MHz, CDCl3)  = 7.17 (d, J = 8.6 Hz, 2H), 6.87 (d, J = 8.7 Hz, 2H), 5.80 (ddt, J = 17.3, 10.2, 7.1 Hz, 1H), 5.03 – 4.94 (m, 2H), 4.81 (dq, J = 2.8, 1.5 Hz, 1H), 4.68 (dt, J = 2.2, 1.0 Hz, 1H), 4.25 (dd, J = 7.7, 6.0 Hz, 1H), 3.82 (s, 3H), 3.31 (s, 1H), 2.54 (dddt, J = 13.8, 7.9, 6.8, 1.2 Hz, 1H), 2.34 (dddt, J = 13.7, 7.3, 6.1, 1.2 Hz, 1H), 1.68 – 1.61 (m, 3H), -0.01 (s, 8H). 13C NMR (126 MHz, CDCl3)  = 158.9, 144.4, 135.7, 134.3, 128.6, 116.3, 113.4, 109.8, 78.4, 75.0, 55.1, 43.0, 20.4, -3.2. Anti-4.4h is a known compound and spectroscopic data are in agreement with those reported in literature.26 381 Synthesis of syn/anti-(1-((1-(4-chlorophenyl)but-3-en-1-yl)oxy)-2-methylallyl)trimethyl silane (syn/anti-S4-i) Compound 4.4i was prepared following general procedure E, a solution of 2-methyl-1- (trimethylsilyl)prop-2-en-1-ol 4.3b (1.44 g, 10 mmol, 1 equiv.) and 1-(4-chlorophenyl)but-3-en- 1-yl 2,2,2-trichloroacetimidate 4.2b (4.58 g, 14 mmol, 1.4 equiv.), BF3•OEt2 (0.12 mL, 1.0 mmol, 0.1 equiv.) and hexanes (60 mL) for 12 hour followed by workup, concentration and column chromatography, Rf for anti/syn-4.4i = 0.4 (100% hexanes) afforded a total of 1.80 g, 5.8 mmol (58% isolated yield) inseparable mixture of diastereomers of compound 4.4i as colorless liquid. Spectroscopic data for syn/anti-4.4i: 1H NMR (500 MHz, CDCl3)  = 7.32 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.6 Hz, 2H), 7.24 (d, J = 8.5 Hz, 2H), 7.20 (d, J = 8.4 Hz, 2H), 5.79 (ddtd, J = 14.3, 10.6, 7.1, 2.4 Hz, 1H), 5.66 (ddt, J = 16.5, 10.7, 7.1 Hz, 1H), 5.19 – 5.12 (m, 1H), 5.03 – 4.95 (m, 4H), 4.84 (dq, J = 2.8, 1.5 Hz, 1H), 4.72 (qd, J = 1.6, 0.9 Hz, 1H), 4.68 (ddq, J = 4.2, 2.1, 0.9 Hz, 2H), 4.36 – 4.27 (m, 2H), 3.79 (s, 1H), 3.30 (s, 1H), 2.57 – 2.50 (m, 2H), 2.50 – 2.42 (m, 1H), 2.35 382 13 (dddt, J = 13.8, 7.3, 6.1, 1.2 Hz, 1H), 1.66 (s, 3H), 1.54 (s, 3H), 0.10 (s, 9H), 0.02 (s, 9H). C NMR (126 MHz, CDCl3)  = 144.7, 144.1, 141.8, 140.8, 135.0, 134.0, 133.0, 132.4, 128.9, 128.3, 128.0, 127.9, 117.3, 116.8, 110.1, 109.7, 79.2, 78.3, 77.9, 75.6, 42.9, 40.3, 20.4, 20.3, -3.0, -3.2. MS (GC/MS): m/z (%) = 308 (0.02) [M]+, 143 (33), 141 (100), 113 (25), 77 (65). Synthesis of cis/trans-trimethyl(3-methyl-6-phenyl-5,6-dihydro-2H-pyran-2-yl)silane (cis/trans-4.5a) Compound 4.5a was prepared following general procedure F: Grubbs catalyst 2nd generation (37 mg, 0.043 mmol, 0.04 equiv.) and syn/anti-trimethyl(2-methyl-1-((1-phenylbut-3-en-1- yl)oxy)allyl)silane, syn:anti = 1:2, 4.4a (297 mg, 1.08 mmol, 1 equiv.) and dichloromethane (11 mL) for 5 hours followed by concentration and column chromatography, Rf for cis-4.5a = 0.7 and Rf for trans-4.5b = 0.4 (10% and 30% DCM in hexanes) afforded a total of 248 mg, 1.00 mmol (93% isolated yield) fully separable mixture of diastereomers of compound 4.5a as colorless liquid. Spectroscopic data for cis-4.5a: 1H NMR (500 MHz, CDCl3)  = 7.40 – 7.31 (m, 4H), 7.29 – 7.24 (m, 1H), 5.52 – 5.47 (m, 1H), 4.56 (dd, J = 8.0, 5.2 Hz, 1H), 4.06 – 4.01 (m, 1H), 2.40 – 2.27 (m, 2H), 1.66 (dt, J = 2.6, 1.3 Hz, 3H), 0.16 (s, 9H). 13C NMR (126 MHz, CDCl3)  = 144.0, 135.3, 128.1, 126.8, 125.6, 117.0, 74.9, 74.3, 34.2, 20.0, -2.6. Cis-4.5a is a known compound and spectroscopic data are in agreement with those reported in literature.26 Spectroscopic data for trans-4.5a: 1H NMR (500 MHz, CDCl3)  = 7.38 – 7.27 (m, 5H), 5.52 – 5.45 (m, 1H), 4.55 (dd, J = 8.0, 5.3 Hz, 1H), 4.03 (d, J = 2.8 Hz, 1H), 2.36 – 2.30 (m, 2H), 1.67 383 – 1.64 (m, 3H), 0.16 (s, 9H). 13C NMR (126 MHz, CDCl3)  = 142.7, 135.4, 128.2, 127.2, 126.0, 115.8, 75.0, 72.9, 32.1, 20.4, -1.4. HRMS (ESI), m/z [M – H–]+ calcd for C15H21OSi: 245.1362; found: 245.1353. Synthesis of cis/trans-(6-(4-chlorophenyl)-5,6-dihydro-2H-pyran-2-yl)trimethylsilane (cis/trans-4.5b) Compound 4.5b was prepared following general procedure F: Grubbs catalyst 2nd generation (170 mg, 0.2 mmol, 0.04 equiv.) and syn/anti-(1-((1-(4-chlorophenyl)but-3-en-1- yl)oxy)allyl)trimethylsilane, syn:anti = 1:1, 4.4b (1.47 g, 5 mmol, 1 equiv.) and dichloromethane (100 mL) for 12 hours followed by concentration and column chromatography, Rf for cis-4.5b = 0.7 and Rf for trans-4.5b = 0.4 (10% and 30% DCM in hexanes) afforded a total of 1.16 g, 4.35 mmol (87% isolated yield) fully separable mixture of diastereomers of compound 4.5b as colorless liquid. Spectroscopic data for cis-4.5b: 1H NMR (500 MHz, CDCl3)  = 7.36 – 7.27 (m, 4H), 5.85 – 5.77 (m, 2H), 4.38 (dd, J = 10.1, 3.1 Hz, 1H), 4.18 (dddd, J = 5.0, 3.6, 2.2, 1.5 Hz, 1H), 2.26 – 2.19 (m, 1H), 2.17 – 2.08 (m, 1H), 0.10 (s, 9H). 13C NMR (126 MHz, CDCl3,)  = 142.5, 132.6, 128.3, 128.1, 127.0, 120.4, 74.7, 71.7, 34.0, -4.0. Cis-4.5b is a known compound and spectroscopic data are in agreement with those reported in literature. 26 Spectroscopic data for trans-4.5b: 1H NMR (500 MHz, CDCl3)  = 7.33 – 7.29 (m, 4H), 5.85 – 5.76 (m, 2H), 4.72 (dd, J = 6.4, 4.5 Hz, 1H), 4.01 – 3.97 (m, 1H), 2.47 – 2.40 (m, 1H), 2.39 – 384 2.32 (m, 1H), 0.10 (s, 9H). 13 C NMR (126 MHz, CDCl3)  = 140.5, 132.9, 128.3, 128.2, 128.0, 119.7, 71.6, 69.7, 29.9, -3.1. Trans-4.5b is a known compound and spectroscopic data are in agreement with those reported in literature.26 Synthesis of cis/trans-(6-(4-trifluoromethylphenyl)-5,6-dihydro-2H-pyran-2-yl)trimethyl silane (cis/trans-4.5c) Compound 4.5c was prepared following general procedure F: Grubbs catalyst 2nd generation (204 mg, 0.24 mmol, 0.04 equiv.) and syn/anti-(1-((1-(4-trifluorophenyl)but-3-en-1- yl)oxy)allyl)trimethylsilane, syn:anti = 1:1, 4.4c (1.97 g, 6 mmol, 1 equiv.) and dichloromethane (100 mL) for 12 hours followed by concentration and column chromatography, Rf for cis-4.5c = 0.7 and Rf for trans-4.5c = 0.4 (10% and 30% DCM in hexanes) afforded a total of 1.74 g, 1.89 mmol (96% isolated yield) fully separable mixture of diastereomers of compound 4.5c as colorless liquids. Spectroscopic data for cis-4.5c: 1H-NMR (500 MHz, CDCl3)  = 7.60 (d, J = 8.1 Hz, 2H), 7.48 (d, J = 8.0 Hz, 2H), 5.89 – 5.78 (m, 2H), 4.47 (dd, J = 10.3, 3.1 Hz, 1H), 4.20 (dddd, J = 5.0, 3.5, 2.3, 1.6 Hz, 1H), 2.31 – 2.24 (m, 1H), 2.19 – 2.11 (m, 1H), 0.12 (s, 9H). 13C NMR (126 MHz, CDCl3)  = 148.0 (t, J = 1.4 Hz), 129.2 (q, J = 32.1 Hz), 128.1, 125.9, 125.1 (q, J = 3.8 Hz), 120.7,74.8, 71.7, 34.0, -4.0. Cis-4.5c is a known compound and spectroscopic data are in agreement with those reported in literature.26 Spectroscopic data for trans-4.5c: 1H NMR (500 MHz, CDCl3)  = 7.61 (d, J = 8.1 Hz, 2H), 7.52 (d, J = 8.1 Hz, 2H), 5.87 – 5.78 (m, 2H), 4.80 (dd, J = 6.6, 4.5 Hz, 1H), 4.04 (dddd, J = 3.4, 385 2.6, 1.8, 0.6 Hz, 1H), 2.52 – 2.45 (m, 1H), 2.43 – 2.35 (m, 1H), 0.12 (s, 9H). 13C NMR (126 MHz, CDCl3)  = 146.2 (d, J = 1.5 Hz), 129.4, (q, J = 32.2 Hz), 128.3, 126.8, 125.15 (q, J = 3.8 Hz), 119.6,71.7, 70.0, 30.1, -3.1. Trans-4.5c is a known compound and spectroscopic data are in agreement with those reported in literature.26 Synthesis of cis/trans-trimethyl(6-(naphthalen-1-yl)-5,6-dihydro-2H-pyran-2-yl)silane (cis/trans-4.5d) Compound 4.5d was prepared following general procedure F: Grubbs catalyst 2nd generation (204 mg, 0.24 mmol, 0.04 equiv.) and syn/anti-trimethyl(1-((1-(naphthalen-1-yl)but-3-en-1- yl)oxy)allyl)silane, syn:anti = 1:1, 4.4d (1.9 g, 6 mmol, 1 equiv.) and benzene (100 mL) at 85 °C for 1 hour followed by concentration and column chromatography, Rf for cis-4.5d = 0.7 and Rf for trans-4.5d = 0.4 (20% DCM in hexanes) afforded a total of 1.66 g, 5.88 mmol (98% isolated yield) fully separable mixture of diastereomers of compound 4.5d as colorless liquid. Spectroscopic data for cis-4.5d: 1H NMR (500 MHz, CDCl3)  = 7 8.11 (d, J = 8.9 Hz, 1H), 7.88 (d, J = 9.4 Hz, 1H), 7.79 (d, J = 8.2 Hz, 1H), 7.67 (d, J = 7.1 Hz, 1H), 7.50 (tddd, J = 10.2, 8.4, 3.8, 2.3 Hz, 3H), 5.97 – 5.85 (m, 2H), 5.13 (dd, J = 9.9, 3.3 Hz, 1H), 4.33 (tdd, J = 4.0, 2.3, 1.2 Hz, 1H), 2.52 – 2.36 (m, 2H), 0.17 (s, 9H). 13C NMR (126 MHz, CDCl3)  = 139.6, 133.6, 130.6, 128.7, 128.0, 127.5, 125.59, 125.56, 125.2, 123.7, 123.0, 121.5, 73.5, 72.0, 33.4, -3.9. IR (FTIR, cm-1) ṽ = 3049, 3027, 2954, 2897, 1510, 1385, 1336, 1245, 1061, 837, 773. MS (GC/MS): m/z (%) = 282 (5) [M]+, 281 (7.5) [M – H]+ , 192 (32), 191 (21), 141 (17.5), 73 (100). HRMS 386 (ESI), m/z [M – H–]+ calcd for C18H21OSi: 281.1362; found: 281.1360. Spectroscopic data for trans-4.5d: 1H NMR (500 MHz, CDCl3)  = 8.33 (d, J = 8.3 Hz, 1H), 7.89 (d, J = 7.8 Hz, 1H), 7.81 (d, J = 8.2 Hz, 1H), 7.58 (d, J = 7.1 Hz, 1H), 7.56 – 7.48 (m, 2H), 7.48 – 7.43 (m, 1H), 5.95 (dq, J = 10.6, 3.8 Hz, 1H), 5.84 (dq, J = 10.3, 2.0 Hz, 1H), 5.55 (t, J = 5.1 Hz, 1H), 3.78 (p, J = 3.2 Hz, 1H), 2.72 (ddtd, J = 17.6, 5.3, 3.5, 1.9 Hz, 1H), 2.61 – 2.52 (m, 1H), 0.09 (s, 9H). 13C NMR (126 MHz, CDCl3)  = 136.7, 133.9, 131.7, 128.6, 128.3, 128.1, 125.8, 125.4, 125.0, 124.5, 124.4, 120.4, 70.0, 68.3, 29.7, -3.3. IR (FTIR, cm-1) ṽ = 3050, 3027, 2953, 2898, 1509, 1336, 1245, 1048, 838, 774. HRMS (ESI), m/z [M + H]+ calcd for C18H23OSi: 283.1518; found: 283.1518. Synthesis of cis/trans-(6-([1,1'-biphenyl]-4-yl)-5,6-dihydro-2H-pyran-2-yl)trimethylsilane (cis/trans-4.5e) Compound 4.5e was prepared following general procedure F: Grubbs catalyst 2nd generation (16 mg, 0.02 mmol, 0.04 equiv.) and syn/anti-(1-((1-([1,1'-biphenyl]-4-yl)but-3-en-1- yl)oxy)allyl)trimethylsilane, syn:anti = 2:1, 4.4e (161 mg, 0.48 mmol, 1 equiv.) and CH2Cl2 (5 mL) at room temperature for 3 hours followed by concentration and column chromatography, Rf for cis-4.5e = 0.7 and Rf for trans-4.5e = 0.4 (25% DCM in hexanes) afforded a total of 92 mg, 0.30 mmol (63% isolated yield) fully separable mixture of diastereomers of compound 4.5e as colorless liquid. Spectroscopic data for cis-4.5e: 1H NMR (500 MHz, CDCl3)  = 7.65 – 7.58 (m, 4H), 7.50 – 7.43 (m, 4H), 7.39 – 7.34 (m, 1H), 5.94 – 5.80 (m, 2H), 4.49 (dd, J = 9.8, 3.4 Hz, 1H), 4.24 (tdd, 387 J = 3.9, 2.2, 1.2 Hz, 1H), 2.36 – 2.22 (m, 2H), 0.16 (s, 9H). 13 C NMR (126 MHz, CDCl3)  = 143.1, 141.2, 139.9, 128.7, 128.1, 127.1, 127.1, 126.9, 126.1, 121.1, 75.2, 71.7, 34.1, -4.0. Cis- 4.5e is a known compound and spectroscopic data are in agreement with those reported in literature.26 Spectroscopic data for trans-4.5e: 1H NMR (500 MHz, CDCl3)  = 7.62 – 7.57 (m, 4H), 7.49 – 7.46 (m, 2H), 7.44 (dddd, J = 7.4, 6.1, 1.3, 0.6 Hz, 2H), 7.37 – 7.32 (m, 1H), 5.89 – 5.79 (m, 2H), 4.81 (t, J = 5.6 Hz, 1H), 4.08 (q, J = 2.9 Hz, 1H), 2.54 – 2.42 (m, 2H), 0.14 (s, 9H). 13C NMR (126 MHz, CDCl3)  = 141.2, 141.0, 140.1, 128.7, 128.2, 127.2, 127.09, 127.05, 127.0, 120.0, 72.1, 70.0, 30.2, -2.9. Trans-4.5e is a known compound and spectroscopic data are in agreement with those reported in literature.26 Synthesis of cis/trans-triethyl(6-(naphthalen-2-yl)-5,6-dihydro-2H-pyran-2-yl)silane (cis/trans-4.5f) Compound 4.5f was prepared following general procedure F: Grubbs catalyst 2nd generation (102 mg, 0.12 mmol, 0.04 equiv.) and syn/anti-triethyl(1-((1-(naphthalen-2-yl)but-3-en-1- yl)oxy)allyl)silane, syn:anti = 1:1, 4.4f (1.06 g, 3 mmol, 1 equiv.) and benzene (100 mL) at 85 °C for 1 hour followed by concentration and column chromatography, Rf for cis-4.5f = 0.7 and Rf for trans-4.5f = 0.4 (10% and 20% DCM in hexanes) afforded a total of 883 mg, 2.52 mmol (84% isolated yield) fully separable mixture of diastereomers of compound 4.5f as colorless liquid. Spectroscopic data for cis-4.5f: 1H NMR (500 MHz, CDCl3)  = 7.88 – 7.82 (m, 3H), 7.81 (s, 388 1H), 7.51 (dd, J = 8.5, 1.7 Hz, 1H), 7.49 – 7.42 (m, 2H), 5.94 – 5.87 (m, 1H), 5.82 (ddt, J = 10.4, 5.3, 2.6 Hz, 1H), 4.57 (dd, J = 9.0, 4.3 Hz, 1H), 4.41 (tdd, J = 4.3, 3.1, 2.2 Hz, 1H), 2.40 – 2.25 (m, 2H), 1.06 (t, J = 8.0 Hz, 9H), 0.72 (q, J = 7.8 Hz, 6H). 13C NMR (126 MHz, CDCl3)  = 141.5, 133.2, 132.7, 128.7, 128.0, 127.8, 127.6, 125.8, 125.5, 124.3, 124.1, 120.7, 75.9, 70.3, 34.0, 7.6, 1.9. Cis-4.5f is a known compound and spectroscopic data are in agreement with those reported in literature.26 Spectroscopic data for trans-4.5f: 1H NMR (500 MHz, CDCl3)  = 7.87 – 7.83 (m, 3H), 7.82 (s, 1H), 7.56 (dd, J = 8.5, 1.8 Hz, 1H), 7.51 – 7.44 (m, 2H), 5.88 – 5.79 (m, 2H), 4.94 (t, J = 5.3 Hz, 1H), 4.18 (td, J = 3.6, 1.8 Hz, 1H), 2.63 – 2.48 (m, 2H), 1.01 (t, J = 7.9 Hz, 9H), 0.68 (qd, J = 8.0, 1.2 Hz, 6H). 13C NMR (126 MHz, CDCl3)  = 139.4, 133.2, 132.7, 129.0, 128.1, 127.8, 127.6, 125.8, 125.6, 125.3, 125.1, 119.4, 72.4, 67.6, 29.9, 7.5, 2.5. Trans-4.5f is a known compound and spectroscopic data are in agreement with those reported in literature.26 Synthesis of cis/trans- (6-(4-chlorophenyl)-5,6-dihydro-2H-pyran-2-yl)dimethyl(phenyl) silane (cis/trans-4.5g) Compound 4.5g was prepared following general procedure F: Grubbs catalyst 2nd generation (200 mg, 0.2 mmol, 0.026 equiv.) and syn/anti-(1-((1-(4-chlorophenyl)but-3-en-1- yl)oxy)allyl)dimethyl(phenyl)silane, syn:anti = 1:1, 4.4g (3.21 g, 9 mmol, 1 equiv.) and benzene (200 mL) at 85 °C for 2 hours followed by concentration and column chromatography, Rf for cis- 4.5g = 0.7 and Rf for trans-4.5g = 0.4 (30% DCM in hexanes) afforded a total of 2.96 g, 8.28 mmol (92% isolated yield) fully separable mixture of diastereomers of compound 4.5g as colorless 389 liquids. Spectroscopic data for cis-4.5g: 1H NMR (500 MHz, CDCl3)  = 7.67 – 7.61 (m, 2H), 7.44 – 7.36 (m, 3H), 7.36 – 7.32 (m, 2H), 7.32 – 7.29 (m, 2H), 5.81 (t, J = 1.9 Hz, 2H), 4.45 – 4.40 (m, 2H), 2.28 – 2.21 (m, 1H), 2.18 – 2.10 (m, 1H), 0.43 (s, 3H), 0.42 (s, 3H). 13C NMR (126 MHz, CDCl3)  = 142.4, 136.5, 134.2, 132.6, 129.3, 128.3, 127.74, 127.71, 127.0, 121.3, 74.9, 71.3, 33.9, -5.2, -6.0. MS (GC/MS): m/z (%) = 328 (1.5) [M]+, 250 (4), 135 (100), 107 (7), 75 (18). HRMS (ESI), m/z [M – H–]+ calcd for C19H20ClOSi: 327.0972; found: 327.0963. Spectroscopic data for trans-4.5g: 1H NMR (500 MHz, CDCl3)  = 7.63 – 7.56 (m, 2H), 7.45 – 7.36 (m, 3H), 7.32 (d, J = 8.5 Hz, 2H), 7.26 (d, J = 8.5 Hz, 2H), 5.87 – 5.78 (m, 2H), 4.63 (t, J = 5.6 Hz, 1H), 4.30 – 4.24 (m, 1H), 2.42 – 2.29 (m, 2H), 0.44 (s, 3H), 0.42 (s, 3H). 13C NMR (126 MHz, CDCl3)  = 140.4, 136.7, 134.1, 132.8, 129.3, 128.3, 128.0, 127.82, 127.80, 120.2, 71.5, 69.6, 30.0, -4.5, -4.7. Trans-4.5g is a known compound and spectroscopic data are in agreement with those reported in literature.26 Synthesis of trans-(6-(4-methoxyphenyl)-3-methyl-5,6-dihydro-2H-pyran-2-yl)trimethyl silane (trans-4.5h) Compound 4.5h was prepared following general procedure F: Grubbs catalyst 2nd generation (51 mg, 0.06 mmol, 0.04 equiv.) and syn-(1-((1-(4-methoxyphenyl)but-3-en-1-yl)oxy)-2- methylallyl)trimethylsilane, syn-4.4h (457 mg, 1.5 mmol, 1 equiv.) and benzene (40 mL) at 85 °C for 2 hours followed by concentration and column chromatography, Rf for trans-4.5h = 0.5 (30% DCM in hexanes) afforded a total of 377 mg, 1.37 mmol (91% isolated yield) of compound trans- 390 4.5h as a colorless liquid. 1H NMR (500 MHz, CDCl3)  = 7.29 (d, J = 8.7 Hz, 2H), 6.88 (d, J = 8.7 Hz, 2H), 5.48 (ddq, J = 5.0, 3.4, 1.5 Hz, 1H), 4.50 (dd, J = 8.9, 4.2 Hz, 1H), 4.00 (s, 1H), 3.80 (s, 3H), 2.38 – 2.24 (m, 2H), 1.65 (s, 3H), 0.16 (s, 9H). 13C NMR (126 MHz, CDCl3)  = 158.8, 135.4, 134.9, 127.3, 115.9, 113.6, 74.9, 72.6, 55.2, 32.0, 20.4, -1.4. Trans-4.5h is a known compound and spectroscopic data are in agreement with those reported in literature. 26 Synthesis of cis/trans-(6-(4-chlorophenyl)-3-methyl-5,6-dihydro-2H-pyran-2-yl)trimethyl silane (cis/trans-4.5i) Compound 4.5i was prepared following general procedure F: Grubbs catalyst 2nd generation (70.04 mg, 0.083 mmol, 0.03 equiv.) and syn/anti-(1-((1-(4-chlorophenyl)but-3-en-1-yl)oxy)-2- methylallyl)trimethylsilane, syn:anti = 1:1, 4.4i (850 mg, 2.75 mmol, 1 equiv.) and dichloromethane (40 mL) at room temperature for 12 hours followed by concentration and column chromatography, Rf for cis-4.5i = 0.7 and Rf for trans-4.5i = 0.4 (20% DCM in hexanes) afforded a total of 763 mg, 2.70 mmol (98% isolated yield) fully separable mixture of diastereomers of compound 4.5i as colorless liquid. Spectroscopic data for cis-4.5i: 1H NMR (500 MHz, CDCl3)  = 7.33 – 7.27 (m, 4H), 5.85 – 5.77 (m, 2H), 4.38 (dd, J = 10.1, 3.1 Hz, 1H), 4.18 (dtd, J = 5.0, 2.7, 1.5 Hz, 1H), 2.26 – 2.19 (m, 1H), 2.13 (dddt, J = 14.8, 8.3, 2.7, 1.6 Hz, 1H), 0.10 (s, 9H). 13 C NMR (126 MHz, CDCl3)  = 142.5, 132.6, 128.2, 128.1, 127.0, 120.8, 74.7, 71.6, 34.0, -4.0. IR (FTIR, cm-1) ṽ = 3057, 2953, 1492, 1380, 1243, 1012, 813. MS (GC/MS): m/z (%) = 280 (0.02) [M]+, 208 (6), 68 (100). Spectroscopic data for trans-4.5i: 1H NMR (500 MHz, CDCl3)  = 7.35 – 7.29 (m, 4H), 5.84 391 – 5.76 (m, 2H), 4.72 (dd, J = 6.4, 4.5 Hz, 1H), 4.01 – 3.96 (m, 1H), 2.47 – 2.40 (m, 1H), 2.39 – 2.32 (m, 1H), 0.10 (s, 9H). 13 C NMR (126 MHz, CDCl3)  = 140.5, 132.9, 128.3, 128.2, 128.1, 119.7, 71.6, 69.8, 30.0, -3.0. IR (FTIR, cm-1) ṽ = 3056, 2952, 1492, 1380, 1242, 1012, 812. MS (GC/MS): m/z (%) = 280 (0.015) [M]+, 208 (5.8), 68 (100). 4.7.3. Wittig rearrangements of trans-2-silyl-5,6-dihydro-6-aryl-(2H)-pyrans trans-4.5: general procedure G Following our reported procedure,8 freshly prepared and purified trans-2-silyl-5,6-dihydro-6- aryl-(2H)-pyran 4.5 was dissolved in THF under nitrogen (concentration 0.08 M, unless otherwise noted) and the solution cooled at −78 °C (dry ice/acetone bath), n-butyllithium (1.2 equiv, 1.6 M or 2.5 M in hexanes) was added dropwise (1 drop/s) to give a colored solution. The reaction was quenched after the indicated time (10−30 min) by adding saturated NH4Cl(aq) and diluted with H2O and diethyl ether. The aqueous phase was extracted with diethyl ether three times. Combined organic extracts were washed with saturated NH4Cl(aq), H2O, and brine. The solution was dried over magnesium sulfate, filtered, quickly concentrated in a rotovap at temperatures lower than 45 °C. Column chromatography with EtOAc in hexanes afforded cyclopentenol 4.6. Other products including the ones resulting from [1,4]-Wittig rearrangement (4.7) were also observed (see individual substrate). 392 Synthesis of 2-methyl-5-phenyl-1-(trimethylsilyl)cyclopent-2-en-1-ol (4.6a), –OH and phenyl trans to one another and (4.6a′), –OH and phenyl cis Following general procedure G with slight modification, 370 mg of cis-trimethyl(3-methyl-6- phenyl-5,6-dihydro-2H-pyran-2-yl)silane, cis-4.5a and 370 mg of trans-trimethyl(3-methyl-6- phenyl-5,6-dihydro-2H-pyran-2-yl)silane, trans-4.5a were weighed into a 20 mL vial respectively making a mixture of 1:1 cis:trans diastereomeric ratio (740 mg, 3.0 mmol, 1.0 equiv). This was dissolved in 20 mL dry THF and the resulting solution was transferred into a 100 mL round bottom flask via syringe. Additional 20 mL of THF was transferred into the flask and the resulting mixture was cooled to –78 °C on an acetone/dry-ice bath. This was followed by dropwise addition of 0.72 mL of n-butyllithium, 2.5 M in hexanes (1.8 mmol, 0.6 equiv.). The resulting mixture was stirred at –78 °C for 15 minutes (approximate time taken by the trans diastereomer to react), then 3.22 mL of sec-butyllithium, 1.4 M in cyclohexane (4.5 mmol, 1.5 equiv.) was added to the flask at – 78 °C. The solution turned dark purple after complete addition of sec-butyllithium. The mixture was stirred at –78 °C for 1.5 hours after which the cold bath was removed, and the mixture allowed to warm up to room temperature. The mixture was stirred at room temperature for additional 3 hours and then cooled down to –78 °C and quenched by 10 mL water. The cold bath was removed again, and the mixture allowed to warm up to room temperature and diluted with diethyl ether. The resulting mixture was transferred into a separating funnel and the layers were separated. The aqueous layer was extracted with diethyl ether (25 mL x 3). The combined organic layers were washed with brine and dried over anhydrous MgSO4. The mixture was filtered, and the filtrate was 393 concentrated on a rotavapor under reduced pressure to give crude reaction mixture. Further purification by column chromatography, Rf for 4.6a′ = 0.71 and Rf for 4.6a = 0.44 (10% EtOAc in hexanes) furnished 287 mg, 1.2 mmol (40% isolated yield) of 4.6a as a colorless liquid and 185 mg, 0.75 mmol (25% isolated yield) of 4.6a′ as a colorless liquid. Spectroscopic data for 4.6a: 1H NMR (500 MHz, CDCl3): δ = 7.46 – 7.40 (m, 2H), 7.34 – 7.28 (m, 2H), 7.28 – 7.23 (m, 1H), 5.67 (dp, J = 3.2, 1.6 Hz, 1H), 3.44 (dd, J = 10.6, 7.6 Hz, 1H), 2.72 – 2.63 (m, 1H), 2.46 (dddt, J = 15.4, 7.7, 3.1, 1.5 Hz, 1H), 1.80 (dt, J = 2.9, 1.5 Hz, 3H), 1.47 (s, 1H), -0.27 (s, 9H). 13C NMR (126 MHz, CDCl3): δ = 145.6, 140.8, 128.6, 128.1, 126.7, 124.7, 84.8, 61.7, 32.8, 14.6, -2.2. 29Si NMR (99 MHz, CDCl3): δ = 1.44. 4.6a is a known compound and the spectroscopic data are in agreement with those reported in the literature.26 Spectroscopic data for 4.6a′: 1H NMR (500 MHz, CDCl3): δ = 7.34 – 7.28 (m, 2H), 7.26 – 7.20 (m, 3H), 5.57 (dq, J = 3.2, 1.7 Hz, 1H), 3.71 (dt, J = 8.2, 1.6 Hz, 1H), 2.73 – 2.64 (m, 1H), 2.54 (ddq, J = 16.8, 3.4, 1.7 Hz, 1H), 1.75 (dt, J = 3.0, 1.6 Hz, 3H), 0.82 (s, 1H), 0.15 (s, 9H). 13C NMR (126 MHz, CDCl3): δ = 144.2, 141.5, 128.6, 128.5, 126.8, 123.6, 81.6, 51.0, 38.6, 14.3, - 3.2. 29Si NMR (99 MHz, CDCl3, ppm): δ = 4.01. HRMS (ESI): m/z [M – OH]+ calcd for C15H21Si: 229.1413; found: 229.1406. Synthesis of 5-(4-chlorophenyl)-1-(trimethylsilyl)cyclopent-2-en-1-ol (4.6b) and 2-(2-(4-chlorophenyl)cyclopropyl)-1-(trimethylsilyl)ethan-1-one (4.7b) Following general procedure G, compounds 4.6b and 4.7b were prepared from trans-(6-(4- chlorophenyl)-5,6-dihydro-2H-pyran-2-yl)trimethylsilane, trans-4.5b (534 mg, 2.0 mmol, 1.0 394 equiv.), n-butyllithium 2.5 M in hexanes (1.0 mL, 2.4 mmol, 1.2 equiv.) and THF (25 mL) for 15 minutes. The reaction was quenched by adding water instead of saturated NH4Cl(aq). Workup, concentration and column chromatography, Rf for 4.7b = 0.7 and Rf for 4.6b = 0.3 (10% EtOAc in hexanes) furnished 297 mg, 1.12 mmol (56% isolated yield) of 4.6b as a yellow liquid and 111 mg, 0.42 mmol of 4.7b (21% isolated yield) as a colorless liquid. Spectroscopic data for 4.6b: 1H NMR (500 MHz, CDCl3): δ = 7.35 (d, J = 8.3 Hz, 2H), 7.27 (d, J = 8.5 Hz, 2H), 5.99 (ddd, J = 5.8, 2.9, 2.0 Hz, 1H), 5.77 (ddd, J = 5.8, 2.3, 1.4 Hz, 1H), 3.41 (dd, J = 10.2, 8.2 Hz, 1H), 2.72 – 2.59 (m, 2H), 1.52 (s, 1H), -0.27 (s, 9H). 13C NMR (126 MHz, CDCl3): δ = 139.0, 137.4, 132.3, 130.4, 129.8, 128.2, 84.2, 59.3, 35.3, -3.4. 4.6b is a known compound and the spectroscopic data are in agreement with those reported in the literature.26 Spectroscopic data for 4.6b: 1H NMR (500 MHz, CDCl3): δ = 7.20 (d, J = 8.5 Hz, 2H), 7.01 (d, J = 8.4 Hz, 2H), 2.69 (dd, J = 6.7, 1.1 Hz, 2H), 1.60 (dt, J = 8.9, 4.9 Hz, 1H), 1.27 (dtdd, J = 8.6, 6.7, 5.7, 4.5 Hz, 1H), 0.94 (dt, J = 8.6, 5.2 Hz, 1H), 0.76 (dt, J = 8.6, 5.4 Hz, 1H), 0.20 (s, 9H). 13 C NMR (126 MHz, CDCl3): δ = 247.1, 141.4, 131.0, 128.3, 127.4, 53.0, 22.2, 16.7, 15.5, -3.2. HRMS (APCI): m/z [M + H]+ calcd for C14H20ClOSi: 267.0972; found: 267.0967. Synthesis of 5-(4-trifluorophenyl)-1-(trimethylsilyl)cyclopent-2-en-1-ol (4.6c) Following general procedure G, compound 4.6c was prepared from trans-(6-(4- trifluorophenyl)-5,6-dihydro-2H-pyran-2-yl)trimethylsilane trans-4.5c (841 mg, 2.8 mmol, 1.0 equiv.), n-butyllithium 2.5 M in hexanes (1.4 mL, 3.36 mmol, 1.2 equiv.) and THF (40 mL) for 20 minutes. Workup, concentration and column chromatography, Rf = 0.5 (20% EtOAc in hexanes) 395 furnished 578 mg (70%) of 4.6c as a yellow liquid. Compound 4.6c is very unstable and upon storage at –15 °C slowly converts to 4-(4-(trifluoromethyl)phenyl)-3-(trimethylsilyl)cyclopent-2- en-1-one 4.11c. Spectroscopic data for 4.6c: 1H NMR (500 MHz, CDCl3): δ = 7.57 (d, J = 8.8 Hz, 2H), 7.54 (d, J = 8.8 Hz, 2H), 6.01 (ddd, J = 5.8, 2.9, 1.9 Hz, 1H), 5.79 (ddd, J = 5.8, 2.3, 1.3 Hz, 1H), 3.50 (dd, J = 10.3, 8.0 Hz, 1H), 2.75 (ddt, J = 15.8, 10.3, 2.1 Hz, 1H), 2.66 (dddd, J = 15.9, 8.0, 2.9, 1.3 Hz, 1H), 1.56 (s, 1H), -0.29 (s, 9H). 13C NMR (126 MHz, CDCl3): δ = 144.75 (d, J = 1.4 Hz), 137.4, 130.4, 128.8, 129.02 (q, J = 32.4 Hz), 124.97 (q, J = 3.8 Hz), 124.28 (q, J = 271.8 Hz), 84.2, 59.7, 35.1, -3.5. 4.6c is a known compound and the spectroscopic data are in agreement with those reported in the literature.26 Spectroscopic data for 4.11c 1H NMR (500 MHz, CDCl3): δ = 7.57 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 6.52 (d, J = 1.9 Hz, 1H), 4.26 (dt, J = 7.0, 2.1 Hz, 1H), 2.89 (dd, J = 19.2, 7.1 Hz, 1H), 2.28 (dd, J = 19.1, 2.3 Hz, 1H), -0.05 (s, 9H). 13C NMR (126 MHz, CDCl3): δ = 209.9, 185.0, 146.5 (d, J = 1.6 Hz), 142.3, 129.6 (q, J = 32.6 Hz), 128.0, 125.8 (q, J = 3.8 Hz), 124.0 (q, J = 272.1 Hz), 50.3, 45.4, -1.8. 19F NMR (470 MHz, CDCl3, ppm): δ = -62.47. Synthesis of 5-(naphthalen-1-yl)-1-(trimethylsilyl)cyclopent-2-en-1-ol (4.6d) Following general procedure G, compound 4.6c was prepared from trans-(6-naphthalen-1-yl)- 5,6-dihydro-2H-pyran-2-yl)trimethylsilane trans-4.5d (701 mg, 2.48 mmol, 1.0 equiv.), n- butyllithium 2.5 M in hexanes (1.24 mL, 2.98 mmol, 1.2 equiv.) and THF (40 mL) for 20 minutes. Workup, concentration and column chromatography, Rf = 0.4 (10% EtOAc in hexanes) furnished 396 568 mg, 2.01 mmol (81% isolated yield) of 4.6d as a yellow liquid. 1H NMR (500 MHz, CDCl3): δ = 8.62 (d, J = 8.5 Hz, 1H), 7.86 (d, J = 8.0 Hz, 1H), 7.78 (d, J = 8.2 Hz, 1H), 7.63 (d, J = 7.2 Hz, 1H), 7.51 (dddd, J = 22.6, 8.0, 6.8, 1.3 Hz, 2H), 7.45 (t, J = 7.7 Hz, 1H), 6.10 (ddd, J = 5.7, 2.9, 1.9 Hz, 1H), 5.81 (ddd, J = 5.8, 2.4, 1.3 Hz, 1H), 4.47 (dd, J = 10.0, 8.1 Hz, 1H), 3.04 (ddt, J = 16.0, 10.0, 2.1 Hz, 1H), 2.81 (dddd, J = 16.2, 8.1, 2.8, 1.3 Hz, 1H), 1.72 (s, 1H), -0.43 (s, 9H). 13C NMR (126 MHz, CDCl3): δ = 137.4, 136.2, 134.0, 133.8, 130.8, 128.6, 127.4, 125.8, 125.5, 124.98, 124.97, 124.1, 86.0, 53.8, 37.4, -3.6. IR (FTIR, cm–1): ṽ = 3423, 3046, 2952, 1508, 1396, 1244, 832, 777. MS (GC/MS): m/z (%) = 282 (20) [M]+, 191 (25), 165 (18), 73 (100). HRMS (ESI): m/z [M – H–]+ calcd for C18H21OSi: 281.1362; found: 281.1353. Synthesis of 5-([1,1'-biphenyl]-4-yl)-1-(trimethylsilyl)cyclopent-2-en-1-ol (4.6e) Following general procedure G, compound 4.6e was prepared from trans-(6-([1,1'-biphenyl]- 4-yl)-5,6-dihydro-2H-pyran-2-yl)trimethylsilane trans-4.5e (67 mg, 0.22 mmol, 1.0 equiv.), sec- butyllithium 1.4 M in cyclohexane (0.46 mL, 0.66 mmol, 3.0 equiv.) and THF (2.4 mL) for 3 hours. Workup, concentration and column chromatography, Rf = 0.4 (10% EtOAc in hexanes) furnished 51 mg, 0.165 mmol (75% isolated yield) of 4.6e as a white solid. 1H NMR (500 MHz, CDCl3): δ = 7.66 – 7.62 (m, 2H), 7.58 (d, J = 8.3 Hz, 2H), 7.50 (d, J = 8.0 Hz, 2H), 7.48 – 7.43 (m, 2H), 7.38 – 7.33 (m, 1H), 6.04 (ddd, J = 5.8, 2.9, 1.9 Hz, 1H), 5.82 (ddd, J = 5.8, 2.3, 1.3 Hz, 1H), 3.52 (dd, J = 10.3, 7.9 Hz, 1H), 2.81 (ddt, J = 16.0, 10.3, 2.1 Hz, 1H), 2.70 (dddd, J = 16.0, 8.0, 2.9, 1.3 Hz, 1H), 1.58 (s, 1H), -0.23 (s, 9H). 13C NMR (126 MHz, CDCl3): δ = 140.9, 139.6, 397 137.3, 130.5, 128.9, 128.7, 127.1, 126.9, 126.8, 84.5, 59.7, 35.4, -3.4. 4.6e is a known compound and the spectroscopic data are in agreement with those reported in the literature.26 Synthesis of 5-(naphthalen-2-yl)-1-(triethylsilyl)cyclopent-2-en-1-ol (4.6f) and 2-(2-(naphthalen-2-yl)cyclopropyl)-1-(triethylsilyl)ethan-1-one (4.7f) Following general procedure G, compounds 4.6f and 4.7f were prepared from trans-triethyl(6- (naphthalen-2-yl)-5,6-dihydro-2H-pyran-2-yl)silane trans-4.5f (650 mg, 2.0 mmol, 1.0 equiv.), n- butyllithium 2.5 M in hexanes (1.0 mL, 2.4 mmol, 1.2 equiv.) and THF (25 mL) for 15 minutes. The reaction was quenched by adding water instead of saturated NH4Cl(aq). Workup, concentration and column chromatography, Rf for 4.7f = 0.7 and Rf for 4.6f = 0.3 (10% EtOAc in hexanes) furnished 473 mg, 1.46 mmol (73% isolated yield) of 4.6f as a yellow liquid and 110 mg, 0.34 mmol of 4.7f (17% isolated yield) as a colorless liquid. Spectroscopic data for 4.6f: 1H NMR (500 MHz, CDCl3): δ = 7.88 – 7.76 (m, 4H), 7.64 (dd, J = 8.5, 1.7 Hz, 1H), 7.51 – 7.41 (m, 2H), 6.03 (ddd, J = 5.8, 2.9, 1.9 Hz, 1H), 5.91 (ddd, J = 5.8, 2.3, 1.3 Hz, 1H), 3.60 (dd, J = 10.0, 7.7 Hz, 1H), 2.90 (ddt, J = 16.0, 9.9, 2.1 Hz, 1H), 2.76 (dddd, J = 16.0, 7.8, 2.9, 1.3 Hz, 1H), 1.55 (s, 1H), 0.80 (t, J = 8.0 Hz, 9H), 0.28 (qd, J = 7.9, 1.9 Hz, 6H). 13 C NMR (126 MHz, CDCl3): δ = 138.5, 138.3, 133.3, 132.5, 130.5, 127.9, 127.7, 127.6, 127.4, 126.2, 125.8, 125.3, 85.9, 60.6, 35.8, 7.8, 2.3. 4.6f is a known compound and the spectroscopic data are in agreement with those reported in the literature. 26 Spectroscopic data for 4.7f: 1H NMR (500 MHz, CDCl3): δ = 7.82 – 7.70 (m, 3H), 7.54 (s, 1H), 7.46 – 7.36 (m, 2H), 7.23 (dd, J = 8.6, 1.8 Hz, 1H), 2.80 (dd, J = 17.2, 6.2 Hz, 1H), 2.65 (dd, 398 J = 17.2, 7.0 Hz, 1H), 1.81 (dt, J = 9.2, 4.9 Hz, 1H), 1.51 – 1.44 (m, 1H), 1.12 (dt, J = 8.6, 5.1 Hz, 1H), 0.99 (t, J = 7.9 Hz, 8H), 0.83 (dt, J = 8.6, 5.3 Hz, 1H), 0.80 – 0.70 (m, 7H), 0.47 (qd, J = 8.3, 7.9, 3.7 Hz, 1H). 13C NMR (126 MHz, CDCl3): δ = 247.1, 140.4, 133.5, 131.9, 127.8, 127.5, 127.2, 125.9, 124.91, 124.86, 123.9, 54.8, 22.8, 16.5, 15.7, 7.3, 2.1. 4.7f is a known compound, and the spectroscopic data are in agreement with those reported in the literature. 26 Synthesis of 5-(4-chlorophenyl)-1-(dimethyl(phenyl)silyl)cyclopent-2-en-1-ol (4.6g) Following general procedure G, compound 4.6g was prepared from trans- (6-(4- chlorophenyl)-5,6-dihydro-2H-pyran-2-yl)dimethyl(phenyl)silane trans-4.5g (987 mg, 3.0 mmol, 1.0 equiv.), n-butyllithium 2.5 M in hexanes (1.5 mL, 3.6 mmol, 1.2 equiv.) and THF (10 mL) for 10 minutes. Workup, concentration and column chromatography, Rf = 0.4 (10% EtOAc in hexanes) furnished 362 mg, 1.11 mmol (37% isolated yield) of 4.6g as a yellow liquid. 1H NMR (500 MHz, CDCl3, ppm): δ = 7.37 – 7.32 (m, 1H), 7.32 – 7.25 (m, 4H), 7.21 – 7.14 (m, 4H), 6.01 (ddd, J = 5.7, 2.9, 1.9 Hz, 1H), 5.76 (ddd, J = 5.8, 2.4, 1.3 Hz, 1H), 3.42 (dd, J = 10.3, 7.8 Hz, 1H), 2.57 (dddd, J = 15.8, 7.8, 2.9, 1.3 Hz, 1H), 2.48 (ddt, J = 15.9, 10.4, 2.2 Hz, 1H), 1.63 (s, 1H), 0.07 (s, 3H), 0.01 (s, 3H). 13 C NMR (126 MHz, CDCl3): δ = 138.5, 137.4, 136.5, 134.3, 132.3, 130.9, 129.9, 129.0, 127.9, 127.3, 84.2, 59.0, 35.3, -4.9, -5.2. 4.6g is a known compound and the spectroscopic data are in agreement with those reported in the literature. 26 399 Synthesis of 5-(4-methoxyphenyl)-2-methyl-1-(trimethylsilyl)cyclopent-2-en-1-ol (4.6h) Following general procedure G, compound 4.6h was prepared from trans-(6-(4- methoxyphenyl)-3-methyl-5,6-dihydro-2H-pyran-2-yl)trimethylsilane trans-4.5h (276 mg, 1.0 mmol, 1.0 equiv.), n-butyllithium 2.5 M in hexanes (0.5 mL, 1.2 mmol, 1.2 equiv.) and THF (10 mL) for 20 minutes. Workup, concentration and column chromatography, Rf = 0.4 (10% EtOAc in hexanes) furnished 236 mg, 0.85 mmol (85% isolated yield) of 4.6h as a yellow liquid. 1H NMR (500 MHz, CDCl3): δ = 7.32 (d, J = 8.5 Hz, 2H), 6.85 (d, J = 8.7 Hz, 2H), 5.65 (dp, J = 3.3, 1.6 Hz, 1H), 3.80 (s, 3H), 3.36 (dd, J = 10.6, 7.6 Hz, 1H), 2.60 (ddp, J = 15.6, 10.4, 2.5 Hz, 1H), 2.43 (dddt, J = 12.3, 6.1, 3.1, 1.5 Hz, 1H), 1.78 (dt, J = 2.8, 1.5 Hz, 3H), 1.41 (s, 1H), -0.27 (s, 9H). 13C NMR (126 MHz, CDCl3): δ = 158.5, 145.6, 132.9, 129.5, 124.7, 113.4, 84.8, 61.0, 55.2, 33.1, 14.6, -2.2. 4.6h is a known compound and the spectroscopic data are in agreement with those reported in the literature.26 Synthesis of 5-(4-chlorophenyl)-2-methyl-1-(trimethylsilyl)cyclopent-2-en-1-ol (4.6i) and 4-(4-chlorophenyl)-2-methyl-3-(trimethylsilyl)cyclopent-2-en-1-ol (4.12i) Following general procedure G, compounds 4.6i and 4.12i were prepared from trans-(6-(4- chlorophenyl)-3-methyl-5,6-dihydro-2H-pyran-2-yl)trimethylsilane, trans-4.5i (617 mg, 2.2 400 mmol, 1.0 equiv.), n-butyllithium 2.5 M in hexanes (1.06 mL, 2.64 mmol, 1.2 equiv.) and THF (30 mL) for 15 minutes. Workup, concentration and column chromatography, Rf for 4.6i = 0.6 and Rf for 4.12i = 0.3 (15% EtOAc in hexanes) furnished 388 mg, 1.386 mmol (63% isolated yield) of 4.6i as a yellow liquid and 37 mg, 0.132 mmol of 4.12i (6% isolated yield) as a colorless liquid. Compound 4.12i might have been formed from 4.6i during the workup. Spectroscopic data for 4.6i: 1H NMR (500 MHz, CDCl3): δ = 7.33 (d, J = 8.6 Hz, 2H), 7.25 (d, J = 8.5 Hz, 2H), 5.63 (dp, J = 3.3, 1.6 Hz, 1H), 3.36 (dd, J = 10.6, 7.6 Hz, 1H), 2.61 – 2.52 (m, 1H), 2.41 (dddt, J = 15.3, 7.6, 3.1, 1.5 Hz, 1H), 1.76 (dt, J = 2.9, 1.5 Hz, 3H), 1.45 (s, 1H), -0.29 (s, 9H). 13C NMR (126 MHz, CDCl3): δ = 145.7, 139.4, 132.3, 129.9, 128.1, 124.6, 84.7, 60.9, 32.8, 14.5, -2.1. IR (FTIR, cm–1): ṽ = 3416, 3092, 3069, 2955, 1490, 1401, 1249, 1091, 1012, 822. MS (GC/MS): m/z (%) = 280 (15) [M]+, 263 (15), 169 (35), 97 (15), 73 (100). HRMS (ESI): m/z [M – OH]+ calcd for C15H20ClSi: 263.1023; found: 263.1010. Spectroscopic data for 4.12i: 1H NMR (500 MHz, CDCl3): δ = 7.21 (d, J = 8.5 Hz, 2H), 6.97 (d, J = 8.4 Hz, 2H), 4.82 (tdt, J = 7.2, 2.0, 1.0 Hz, 1H), 4.00 (ddt, J = 7.6, 3.7, 1.7 Hz, 1H), 2.09 (ddd, J = 6.8, 5.2, 2.2 Hz, 2H), 1.97 (dd, J = 1.7, 1.0 Hz, 3H), 1.70 (s, 1H), -0.06 (s, 9H). 13C NMR (126 MHz, CDCl3): δ = 153.1, 145.1, 140.7, 131.5, 128.7, 128.4, 82.0, 53.6, 45.1, 14.3, -0.5. IR (FTIR, cm–1): ṽ = 3400, 2957, 1489, 1249, 1090, 823. HRMS (ESI): m/z [M – OH]+ calcd for C15H20ClSi: 263.1023; found: 263.1005. 4.7.4. The [1,2]-carbon-to-carbon silyl migration (1.0 mmol scale) – general procedure H 401 A dry 50 mL round-bottom flask fitted with a magnetic stir bar was charged with 193 mg (2.3 mmol, 2.3 equiv) of NaHCO3. The flask was sealed with a rubber septum and kept under positive atmosphere of nitrogen gas. An amount corresponding to 1.0 mmol of alcohol from procedure I (starting material) was dissolved in 5 mL of dry CH2Cl2, and the solution transferred into the flask via syringe. An additional 5 mL of dry CH2Cl2 was added into the flask via syringe. Into a separate vial, 302.5 mg of 77% w/w m-CPBA (1.35 mmol, 1.35 equiv) was weighed and 5 mL dry CH2Cl2 transferred into the vial to dissolve the m-CPBA. The resulting solution was transferred into the flask via syringe. The resulting mixture (in the flask) was stirred for 1–3 hours monitoring by TLC. Typically, formation of a white suspension indicated the end of the reaction. The reaction mixture was transferred into a separating funnel and diluted with 50 mL CH2Cl2. The mixture was washed with 20 mL saturated Na2SO3(aq), 20 mL saturated NaHCO3(aq) and 20 mL water respectively. The aqueous layers were combined and extracted with CH2Cl2 (30 mL X 2). All the organic layers were combined and washed with 20 mL saturated NaCl(aq) and dried over anhydrous Na2SO4. Filtration and concentration of the filtrate under reduced pressure afforded the desired product. In most cases, purification by column chromatography was not necessary. Synthesis of 3-hydroxy-2-methyl-5-phenyl-2-(trimethylsilyl)cyclopentan-1-one (4.8a) Applying general procedure H to NaHCO3, (6.5 mg, 0.09 mmol, 1.2 equiv.), 2-methyl-5- phenyl-1-(trimethylsilyl)cyclopent-2-en-1-ol 4.6a (16 mg, 0.064 mmol, 1.0 equiv), m-CPBA (77% w/w, 15.7 mg, 0.08 mmol, 1.1 equiv.), and DCM (2 mL) afforded 14 mg, 0.053 mmol (83% crude yield) of 4.8a as a white solid. No further purification was necessary judging by the 1H and 13C 402 NMR analysis of the crude reaction mixture. The crystal structure of compound 4.8a was solved by X-ray crystallography and the results deposited to the Cambridge Crystallographic Data Centre and assigned CCDC 2175610. 1H NMR (600 MHz, CDCl3): δ = 7.35 – 7.31 (m, 2H), 7.31 – 7.28 (m, 2H), 7.25 – 7.22 (m, 1H), 4.57 (d, J = 4.1 Hz, 1H), 3.78 (dd, J = 12.6, 8.5 Hz, 1H), 2.52 (ddd, J = 13.6, 8.6, 1.3 Hz, 1H), 2.42 (ddd, J = 13.6, 12.5, 4.2 Hz, 1H), 1.75 (s, 1H), 1.30 (s, 3H), 0.06 (s, 9H). 13C NMR (151 MHz, CDCl3): δ = 218.1, 137.0, 128.4, 127.8, 126.7, 72.5, 50.7, 50.1, 36.7, 13.8, -2.3. Synthesis of epi-3-hydroxy-2-methyl-5-phenyl-2-(trimethylsilyl)cyclopentan-1-one (4.8a′) Applying general procedure H to NaHCO3, (96.6 mg, 1.15 mmol, 2.30 equiv.), epi-2-methyl- 5-phenyl-1-(trimethylsilyl)cyclopent-2-en-1-ol 4.6a′ (123.2 mg, 0.5 mmol, 1.0 equiv), m-CPBA (77% w/w, 151.3 mg, 0.68 mmol, 1.35 equiv.), and DCM (8 mL) afforded after workup 130 mg, 0.495 mmol (99% crude yield) 4.8a′ as a white solid. The crystal structure of compound 4.8a′ was solved by X-ray crystallography and the results deposited to the Cambridge Crystallographic Data Centre and assigned CCDC 2158501. 1H NMR (500 MHz, CDCl3): δ = 7.35 – 7.28 (m, 2H), 7.27 – 7.20 (m, 3H), 4.54 (dd, J = 5.7, 4.8 Hz, 1H), 3.39 (dd, J = 9.9, 8.2 Hz, 1H), 2.75 (ddd, J = 13.9, 9.9, 5.8 Hz, 1H), 2.19 (ddd, J = 13.9, 8.2, 4.8 Hz, 1H), 1.24 (s, 3H), 0.14 (s, 9H). 13C NMR (126 MHz, CDCl3): δ = 218.3, 139.2, 128.6, 128.4, 126.7, 72.7, 53.9, 49.8, 38.6, 12.2, -3.6. 29Si NMR (99 MHz, CDCl3): δ = 6.79. HRMS (ESI): m/z [M + Na]+ calcd for C15H22NaO2Si: 285.1287; found: 285.1282. 403 Synthesis of 5-(4-chlorophenyl)-3-hydroxy-2-(trimethylsilyl)cyclopentan-1-one (4.8b) Applying general procedure H to NaHCO3, (116 mg, 1.38 mmol, 2.30 equiv.), 5-(4- chlorophenyl)-1-(trimethylsilyl)cyclopent-2-en-1-ol 4.6b (160 mg, 0.6 mmol, 1.0 equiv), m-CPBA (77% w/w, 182 mg, 0.81 mmol, 1.35 equiv.), and DCM (10 mL) afforded 170 mg, 0.6 mmol (100% crude yield) of 4.8b as a white solid. No further purification was necessary judging by the 1H and 13 C NMR analysis of the crude reaction mixture. 1H NMR (500 MHz, CDCl3): δ = 7.29 (d, J = 8.5 Hz, 2H), 7.16 (d, J = 8.3 Hz, 2H), 4.68 (d, J = 3.9 Hz, 1H), 3.79 (dd, J = 12.5, 8.3 Hz, 1H), 2.49 (dddd, J = 13.6, 8.2, 3.0, 1.2 Hz, 1H), 2.30 (dd, J = 3.0, 1.6 Hz, 1H), 2.26 (ddd, J = 13.6, 12.7, 4.1 Hz, 1H), 2.03 (s, 1H), 0.12 (s, 9H). 13C NMR (126 MHz, CDCl3): δ = 215.5, 135.6, 132.7, 129.3, 128.6, 70.2, 54.0, 50.4, 38.9, -1.6. MS (GC/MS): m/z (%) = 282 (0.08) [M]+, 192 (45), 157 (20), 129 (100). Synthesis 5-(4-trifluoromethylphenyl)-3-hydroxy-2-(trimethylsilyl)cyclopentan-1-one (4.8c) Applying general procedure H to NaHCO3, (193 mg, 2.3 mmol, 2.30 equiv.), 5-(4- trifluoromethylphenyl)-1-(trimethylsilyl)cyclopent-2-en-1-ol 4.6c (301 mg, 1.0 mmol, 1.0 equiv), m-CPBA (77% w/w, 303 mg, 1.35 mmol, 1.35 equiv.), and DCM (10 mL) afforded 309 mg, 0.98 mmol (98% crude yield) of 4.8c as a white solid. No further purification was necessary judging by the 1H and 13C NMR analysis of the crude reaction mixture. 1H NMR (500 MHz, CDCl3): δ = 7.58 404 (d, J = 8.1 Hz, 2H), 7.34 (d, J = 8.1 Hz, 2H), 4.70 (d, J = 3.8 Hz, 1H), 3.89 (dd, J = 12.8, 8.2 Hz, 1H), 2.53 (dddd, J = 13.5, 8.2, 3.0, 1.1 Hz, 1H), 2.36 – 2.28 (m, 2H), 2.15 (s, 1H), 0.13 (s, 9H). 13 C NMR (126 MHz, CDCl3): δ = 215.1, 141.2 (d, J = 1.5 Hz), 129.1 (q, J = 32.4 Hz), 128.3, 125.4 (q, J = 3.8 Hz), 70.2, 54.1, 50.9, 38.7, -1.6. MS (GC/MS): m/z (%) = 316 (0.12) [M]+, 240 (35), 212 (100), 115 (35) Synthesis of 3-hydroxy-5-(naphthalen-1-yl)-2-(trimethylsilyl)cyclopentan-1-one (4.8d) Applying general procedure H to NaHCO3, (193 mg, 2.3 mmol, 2.30 equiv.), 5-(naphthalen- 1-yl)-1-(trimethylsilyl)cyclopent-2-en-1-ol 4.6d (283 mg, 1.0 mmol, 1.0 equiv), m-CPBA (77% w/w, 300 mg, 1.34 mmol, 1.34 equiv.), and DCM (10 mL) afforded 285 mg, 0.96 mmol (96% crude yield) of 4.8d as a white solid. No further purification was necessary judging by the 1H and 13 C NMR analysis of the crude reaction mixture. 1H NMR (500 MHz, CDCl3): δ = 8.04 (d, J = 8.5 Hz, 1H), 7.85 (dd, J = 7.4, 2.0 Hz, 1H), 7.76 (d, J = 8.2 Hz, 1H), 7.54 – 7.46 (m, 2H), 7.45 – 7.40 (m, 1H), 7.21 (d, J = 7.1 Hz, 1H), 4.71 – 4.62 (m, 2H), 2.63 (dddd, J = 13.6, 8.2, 3.0, 1.2 Hz, 1H), 2.40 (dd, J = 3.1, 1.6 Hz, 1H), 2.30 (td, J = 13.2, 4.1 Hz, 1H), 2.22 (s, 1H), 0.20 (s, 8H). 13C NMR (126 MHz, CDCl3): δ = 216.5, 134.4, 134.0, 132.7, 128.7, 127.5, 126.0, 125.7, 125.3, 123.9, 123.8, 70.5, 54.6, 47.8, 40.2, -1.5. MS (GC/MS): m/z (%) = 298 (0.03) [M]+, 208 (100), 179 (80), 165 (70), 152 (45), 128 (20), 89 (30). HRMS (ESI): m/z [M – OH]+ calcd for C18H21OSi: 281.1356; found: 281.1360. 405 Synthesis of 5-([1,1'-biphenyl]-4-yl)-3-hydroxy-2-(trimethylsilyl)cyclopentan-1-one (4.8e) Applying general procedure H to NaHCO3, (8.7 mg, 0.1 mmol, 1.2 equiv.), 5-([1,1'-biphenyl]- 4-yl)-1-(trimethylsilyl)cyclopent-2-en-1-ol (4.6e) (26.5 mg, 0.086 mmol, 1.0 equiv), m-CPBA (77% w/w, 21.2 mg, 0.095 mmol, 1.1 equiv.), and DCM (10 mL) afforded 25.1 mg, 0.077 mmol (90% crude yield) of 4.8d as a white solid. No further purification was necessary judging by the 1 H and 13C NMR analysis of the crude reaction mixture. 1H NMR (600 MHz, CDCl3): δ = 7.58 – 7.55 (m, 4H), 7.45 – 7.41 (m, 2H), 7.36 – 7.32 (m, 1H), 7.30 (d, J = 8.1 Hz, 2H), 4.73 (d, J = 3.9 Hz, 1H), 3.89 (dd, J = 12.6, 8.2 Hz, 1H), 2.58 – 2.52 (m, 1H), 2.38 (td, J = 13.1, 4.1 Hz, 1H), 2.35 – 2.32 (m, 1H), 1.74 (s, 1H), 0.17 (s, 9H). 13C NMR (151 MHz, CDCl3): δ = 215.7, 140.9, 139.8, 136.4, 128.7, 128.4, 127.3, 127.2, 127.0, 70.5, 54.0, 51.0, 39.3, -1.5. Synthesis of 3-hydroxy-5-(naphthalen-2-yl)-2-(triethylsilyl)cyclopentan-1-one (4.8f) Applying general procedure H to NaHCO3, (174 mg, 2.07 mmol, 2.30 equiv.), 5-(naphthalen- 2-yl)-1-(triethylsilyl)cyclopent-2-en-1-ol 4.6f (292 mg, 0.9 mmol, 1.0 equiv), m-CPBA (77% w/w, 274 mg, 1.22 mmol, 1.35 equiv.), and DCM (10 mL) afforded 308 mg (quantitative yield) of 4.8f as a white solid. No further purification was necessary judging by the 1H and 13C NMR analysis of the crude reaction mixture. 1H NMR (500 MHz, CDCl3): δ = 7.87 – 7.77 (m, 3H), 7.67 (s, 1H), 406 7.51 – 7.43 (m, 2H), 7.41 (d, J = 8.5 Hz, 1H), 4.73 (d, J = 4.0 Hz, 1H), 4.00 (dd, J = 12.7, 8.2 Hz, 1H), 2.60 – 2.51 (m, 1H), 2.49 – 2.41 (m, 2H), 2.14 – 1.98 (m, 1H), 0.97 (t, J = 7.9 Hz, 9H), 0.68 (q, J = 7.7 Hz, 6H). 13C NMR (126 MHz, CDCl3): δ = 216.2, 134.8, 133.3, 132.4, 128.0, 127.7, 127.5, 126.5, 126.3, 125.9, 125.6, 70.3, 51.2, 50.7, 38.9, 7.3, 3.3. IR (FTIR, cm–1): ṽ = 3463, 2952, 2933, 2899, 2873, 1697, 1415, 1242, 1115, 1011, 802, 740. HRMS (ESI): m/z [M + H]+ calcd for C21H29O2Si: 341.1937; found: 341.1934. Synthesis of 5-(4-chlorophenyl)-2-(dimethyl(phenyl)silyl)-3-hydroxycyclopentan-1-one (4.8g) Applying general procedure H to NaHCO3, (174 mg, 2.07 mmol, 2.30 equiv.), 5-(4- chlorophenyl)-1-(dimethyl(phenyl)silyl)cyclopent-2-en-1-ol 4.6g (296 mg, 0.9 mmol, 1.0 equiv), m-CPBA (77% w/w, 274 mg, 1.22 mmol, 1.35 equiv.), and DCM (10 mL) afforded 307 mg, 0.99 mmol (99% crude yield) of 4.8g as a white solid. Attempted further purification by column chromatography, Rf = 0.6 (50% EtOAc in hexanes) led to some of the product to undergo epimerization at the carbon bearing the silyl group followed by subsequent Peterson olefination. Spectroscopic data for 4.8g: 1H NMR (500 MHz, CDCl3): δ = 7.46 – 7.40 (m, 3H), 7.38 – 7.32 (m, 2H), 7.17 (d, J = 8.5 Hz, 2H), 6.73 (d, J = 8.5 Hz, 2H), 4.68 (d, J = 3.6 Hz, 1H), 3.70 (dd, J = 12.7, 8.1 Hz, 1H), 2.47 (dd, J = 3.0, 1.5 Hz, 1H), 2.29 (dddd, J = 13.5, 8.2, 3.0, 1.3 Hz, 1H), 1.95 (td, J = 13.1, 4.1 Hz, 1H), 1.55 (s, 1H), 0.49 (s, 3H), 0.45 (s, 3H). 13C NMR (126 MHz, CDCl3): δ = 215.1, 135.4, 135.3, 134.0, 132.5, 130.0, 129.3, 128.4, 128.3, 70.3, 53.6, 50.7, 38.3, -3.2, -3.6. IR (FTIR, cm–1): ṽ = 3426, 2957, 1708, 1491, 1250, 1044, 789, 699. MS (GC/MS): m/z (%) = 344 (0.02) [M]+,271 (100), 193 (90), 89 (35). 407 Spectroscopic data for 4.12g (Peterson olefination product): 1H NMR (500 MHz, CDCl3): δ = 7.87 (dt, J = 5.6, 2.7 Hz, 1H), 7.30 (d, J = 8.5 Hz, 2H), 7.08 (d, J = 8.4 Hz, 2H), 6.30 (dt, J = 5.7, 2.1 Hz, 1H), 3.53 (dd, J = 7.0, 2.6 Hz, 1H), 3.26 (ddt, J = 19.6, 7.1, 2.5 Hz, 1H), 2.78 (dq, J = 19.6, 2.5 Hz, 1H). 13C NMR (126 MHz, CDCl3): δ = 209.1, 164.1, 137.6, 133.4, 133.0, 132.8, 132.5, 50.1, 38.5. MS (GC/MS): m/z (%) = 192 (0.1) [M]+, 178 (100), 115 (65), 75 (75). Synthesis 3-hydroxy-5-(4-methoxyphenyl)-2-methyl-2-(trimethylsilyl)cyclopentan-1-one (4.8h) Applying general procedure H to NaHCO3, (135 mg, 1.61 mmol, 2.30 equiv.), 5-(4- methoxyphenyl)-2-methyl-1-(trimethylsilyl)cyclopent-2-en-1-ol 4.6h (194 mg, 0.7 mmol, 1.0 equiv), m-CPBA (77% w/w, 212 mg, 0.91 mmol, 1.35 equiv.), and DCM (10 mL) afforded after column chromatography, Rf = 0.5 (40% EtOAc in hexanes) 194 mg, 0.67 mmol (95% isolated yield) of 4.8h as a white solid. 1H NMR (500 MHz, CDCl3, ppm): δ = 7.21 (d, J = 8.8 Hz, 2H), 6.87 (d, J = 8.8 Hz, 2H), 4.55 (d, J = 3.9 Hz, 1H), 3.78 (s, 3H), 3.71 (dd, J = 12.6, 8.5 Hz, 1H), 2.48 (ddd, J = 13.7, 8.6, 1.3 Hz, 1H), 2.36 (ddd, J = 13.5, 12.6, 4.2 Hz, 1H), 1.93 (s, 1H), 1.29 (s, 3H), 0.05 (s, 9H). 13C NMR (126 MHz, CDCl3): δ = 218.6, 158.3, 129.1, 128.7, 113.8, 72.4, 55.2, 50.6, 49.4, 36.8, 13.8, -2.3. HRMS (ESI): m/z [M + H]+ calcd for C16H25O3Si: 293.1573; found: 293.1567. 408 Synthesis of 5-(4-chlorophenyl)-3-hydroxy-2-methyl-2-(trimethylsilyl)cyclopentan-1-one (4.8i) Applying general procedure H to NaHCO3, (212 mg, 2.53 mmol, 2.30 equiv.), 5-(4- chlorophenyl)-2-methyl-1-(trimethylsilyl)cyclopent-2-en-1-ol 4.6i (309 mg, 1.1 mmol, 1.0 equiv), m-CPBA (77% w/w, 333 mg, 1.49 mmol, 1.35 equiv.), and DCM (10 mL) afforded 321 mg, 1.08 mmol (98% crude yield) of 4.8i as a white solid. 1H NMR (500 MHz, CDCl3): δ = 7.30 (d, J = 8.6 Hz, 2H), 7.25 (d, J = 8.6 Hz, 2H), 4.56 (d, J = 3.9 Hz, 1H), 3.74 (dd, J = 12.6, 8.5 Hz, 1H), 2.51 (ddd, J = 13.6, 8.5, 1.2 Hz, 1H), 2.36 (ddd, J = 13.5, 12.6, 4.2 Hz, 1H), 1.78 (s, 1H), 1.29 (s, 3H), 0.04 (s, 9H). 13C{1H} NMR (126 MHz, CDCl3): δ = 217.6, 135.4, 132.5, 129.0, 128.5, 72.3, 50.9, 49.3, 36.4, 13.7, -2.3. IR (FTIR, cm–1): ṽ = 3435, 2975, 2953, 2895, 1696, 1487, 1444, 1405, 1251, 1012, 836, 820. HRMS (ESI): m/z [M + H]+ calcd for C15H22ClO2Si: 297.1078; found: 297.1077. Synthesis of 6-(4-chlorophenyl)-3-hydroxy-2-(trimethylsilyl)cyclohexan-1-one (4.9a) Applying general procedure H to NaHCO3, (193 mg, 2.3 mmol, 2.30 equiv.), 4'-chloro-2- (trimethylsilyl)-1,2,5,6-tetrahydro-[1,1'-biphenyl]-2-ol 2.5b (281 mg, 1.0 mmol, 1.0 equiv), m- CPBA (77% w/w, 303 mg, 1.35 mmol, 1.35 equiv.), and DCM (10 mL) afforded after workup and recrystallization (50% EtOAc in hexanes) 321 mg, 0.93 mmol (93% crude yield) of 4.9a as white 409 crystals. The crystal structure of compound 4.9a was solved by X-ray crystallography and the results deposited to the Cambridge Crystallographic Data Centre and assigned CCDC 1890864. 1 H NMR (500 MHz, CDCl3): δ = 7.30 (d, J = 8.4 Hz, 2H), 7.06 (d, J = 8.4 Hz, 2H), 4.53 (dq, J = 3.3, 1.6 Hz, 1H), 3.32 (dd, J = 13.2, 5.2 Hz, 1H), 2.62 (t, J = 2.0 Hz, 1H), 2.53 – 2.42 (m, 1H), 2.11 – 1.97 (m, 3H), 1.95 (s, 1H), 0.18 (s, 9H). 13C NMR (126 MHz, CDCl3): δ = 208.8, 137.8, 132.6, 130.1, 128.5, 70.3, 57.1, 56.6, 30.8, 28.0, -1.4. Synthesis of 3-hydroxy-6-(4-methoxyphenyl)-2-(trimethylsilyl)cyclohexan-1-one (4.9b) Applying general procedure H to NaHCO3, (58 mg, 0.7 mmol, 2.30 equiv.), 6- (methoxyphenyl-2-yl)-1-(trimethylsilyl)cyclohex-2-en-1-ol (2.5c), dr = 2:1, (83 mg, 0.3 mmol, 1.0 equiv), m-CPBA (77% w/w, 92 mg, 0.4 mmol, 1.35 equiv.), and DCM (5 mL) afforded after workup 89 mg (quantitative crude yield) of 4.9b as a mixture of diastereomers (dr = 2:1). 1H NMR (500 MHz, CDCl3): δ = 7.15 (d, J = 8.7 Hz, 2H), 7.05 (d, J = 8.7 Hz, 2H), 6.90 – 6.83 (m, 4H), 4.53 (h, J = 1.5 Hz, 1H), 4.27 (dt, J = 5.8, 4.1 Hz, 1H), 3.79 (s, 3H), 3.79 (s, 3H), 3.67 (dd, J = 8.0, 6.3 Hz, 1H), 3.30 (dd, J = 13.2, 5.2 Hz, 1H), 2.62 (t, J = 1.9 Hz, 1H), 2.52 – 2.43 (m, 1H), 2.38 (dt, J = 4.6, 1.4 Hz, 1H), 2.37 – 2.30 (m, 1H), 2.20 – 2.12 (m, 1H), 2.12 – 1.85 (m, 7H), 0.18 (s, 9H), -0.03 (s, 9H). 13 C NMR (126 MHz, CDCl3): δ = 210.6, 209.5, 158.5, 158.4, 131.4, 129.9, 129.7, 129.1, 113.84, 113.77, 70.5, 70.2, 57.1, 56.4, 55.22, 55.20, 54.4, 52.9, 31.0, 30.6, 28.2, 24.3, -1.37, -1.4. HRMS (ESI): m/z [M + H]+ calcd for C16H25O3Si: 293.1573; found: 293.1571. 410 Synthesis of 3-hydroxy-6-(4-methoxyphenyl-3-d)-2-(trimethylsilyl)cyclohexan-1-one (4.9b-d1) Applying general procedure H to NaHCO3, (135 mg, 1.6 mmol, 2.30 equiv.), 4'-methoxy-2- (trimethylsilyl)-1,2,5,6-tetrahydro-[1,1'-biphenyl]-3'-d-2-ol (2.5c-d1), dr = 12:1, (194 mg, 0.7 mmol, 1.0 equiv), m-CPBA (77% w/w, 212 mg, 0.95 mmol, 1.35 equiv.), and DCM (10 mL) afforded after workup 199 mg, 0.679 mmol (97% crude yield) of 4.9b-d1, dr = 12:1. A portion of the crude material was recrystallized in a mixture of hexanes and EtOAc (1:1) to give a single diastereomer of 4.9b-d1. 1H NMR (500 MHz, CDCl3): δ = 7.05 (dq, J = 4.4, 2.3 Hz, 2H), 6.87 (d, J = 9.1 Hz, 1H), 4.52 (dq, J = 3.3, 1.5 Hz, 1H), 3.79 (s, 3H), 3.30 (dd, J = 13.2, 5.3 Hz, 1H), 2.62 (t, J = 2.0 Hz, 1H), 2.55 – 2.41 (m, 1H), 2.23 – 1.93 (m, 4H), 0.18 (s, 9H). 13 C NMR (126 MHz, CDCl3): δ = 209.6, 158.3, 131.4, 129.7, 129.6, 113.8, 70.4, 57.1, 56.4, 55.2, 30.9, 28.2, -1.4. 29Si NMR (99 MHz, CDCl3): δ = 2.24. HRMS (ESI): m/z [M + H]+ calcd for C16H24DO3Si: 294.1630; found: 294.1628. Synthesis of 3-hydroxy-6-(naphthalen-2-yl)-2-(trimethylsilyl)cyclohexan-1-one (4.9c) Applying general procedure H to NaHCO3, (155 mg, 1.84 mmol, 2.30 equiv.), 6-(naphthalen- 2-yl)-1-(trimethylsilyl)cyclohex-2-en-1-ol (2.5d), dr = 4:1, (237 mg, 0.8 mmol, 1.0 equiv), m- 411 CPBA (77% w/w, 242 mg, 1.08 mmol, 1.35 equiv.), and DCM (10 mL) afforded after workup 242 mg, 0.784 mmol (98% crude yield) of 4.9c as a mixture of diastereomers (dr = 4:1). A portion of the crude material was recrystallized in a mixture of ethyl acetate and hexanes (1:1). The resulting crystals were for the major diastereomer which crushed out as brown crystals of a single diastereomer. 1H NMR (500 MHz, CDCl3): δ = 7.86 – 7.75 (m, 3H), 7.59 (s, 1H), 7.49 – 7.41 (m, 2H), 7.28 (dd, J = 8.5, 1.7 Hz, 1H), 4.57 (t, J = 2.2 Hz, 1H), 3.53 (dd, J = 13.1, 5.5 Hz, 1H), 2.67 (d, J = 1.8 Hz, 1H), 2.62 (td, J = 12.9, 4.6 Hz, 1H), 2.18 – 2.02 (m, 3H), 1.88 (s, 1H), 0.22 (s, 9H). 13 C NMR (126 MHz, CDCl3): δ = 209.1, 137.1, 133.5, 132.6, 127.8, 127.7, 127.6, 127.23, 127.19, 125.8, 125.5, 70.5, 57.4, 57.2, 30.9, 28.1, -1.3. IR (FTIR, cm–1): ṽ = 3434, 3055, 3021, 2938, 2923, 2882, 2863, 1665, 1336, 1287, 1251, 1147, 1074, 956, 836, 740. HRMS (ESI): m/z [M + H]+ calcd for C19H25O2Si: 313.1624; found: 313.1623. 412 REFERENCES (1) Brook, A. G. Isomerism of some α-hydroxysilanes to silyl ethers. J. Am. Chem. Soc. 1958, 80, 1886. (2) Brook, A. G. Molecular rearrangements of organosilicon compounds. Acc. Chem. Res. 1974, 7, 77. (3) Page, P. C. B.; Klair, S. S.; Rosenthal, S. 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A suitable crystal with dimensions 0.29 × 0.19 × 0.04 mm3 was selected and mounted on a nylon loop with paratone oil on a XtaLAB Synergy, Dualflex, HyPix diffractometer. The crystal was kept at a steady T = 99.99(10) K during data collection. The structure was solved with the ShelXT (Sheldrick, 2015) solution program using dual methods and by using Olex2 1.5 (Dolomanov et al., 2009) as the graphical interface. The model was refined with ShelXL 2018/3 (Sheldrick, 2015) using full matrix least squares minimisation on F2. Crystal data. C15H22O2Si, Mr = 262.41, monoclinic, P21/n (No. 14), a = 6.40749(6) Å, b = 23.6316(2) Å, c = 9.64907(10) Å, b = 93.6810(8)°, a = g = 90°, V = 1458.04(2) Å3, T = 99.99(10) K, Z = 4, Z' = 1, m(Cu Ka) = 1.355, 14998 reflections measured, 2900 unique (Rint = 0.0328) which were used in all calculations. The final wR2 was 0.0844 (all data) and R1 was 0.0324 (I≥2 s(I)). 418 Table 4.2: Crystal data Compound 4.8a′ Formula C15H22O2Si CCDC 2158501 Dcalc./ g cm-3 1.195 m/mm-1 1.355 Formula Weight 262.41 Color colourless Shape block-shaped Size/mm3 0.29×0.19×0.04 T/K 99.99(10) Crystal System monoclinic Space Group P21/n a/Å 6.40749(6) b/Å 23.6316(2) c/Å 9.64907(10) a/° 90 b/° 93.6810(8) g/° 90 V/Å3 1458.04(2) Z 4 Z' 1 Wavelength/Å 1.54184 Radiation type Cu Ka Qmin/° 3.741 Qmax/° 77.169 Measured Refl's. 14998 Indep't Refl's 2900 Refl's I≥2 s(I) 2729 Rint 0.0328 Parameters 171 Restraints 0 Largest Peak 0.359 Deepest Hole -0.263 GooF 1.054 wR2 (all data) 0.0844 wR2 0.0828 R1 (all data) 0.0342 R1 0.0324 419 Structure quality indicators Reflections: Refinement: Figure 4.2: Structure quality indicators A colourless block-shaped-shaped crystal with dimensions 0.29×0.19×0.04 mm3 was mounted on a nylon loop with paratone oil. Data were collected using a XtaLAB Synergy, Dualflex, HyPix diffractometer equipped with an Oxford Cryosystems low-temperature device, operating at T = 99.99(10) K. MSU Data were measured using w scans using Cu Ka radiation (micro-focus sealed X-ray tube, 50 kV, 1 mA). The total number of runs and images was based on the strategy calculation from the program CrysAlisPro 1.171.41.123a (Rigaku OD, 2022). The achieved resolution was Q = 77.169. Cell parameters were retrieved using the CrysAlisPro 1.171.41.123a (Rigaku OD, 2022) software and refined using CrysAlisPro 1.171.41.123a (Rigaku OD, 2022) on 9207 reflections, 61 % of the observed reflections. Data reduction was performed using the CrysAlisPro 1.171.41.123a (Rigaku OD, 2022) software which corrects for Lorentz polarization. The final completeness is 100.00 out to 77.169 in Q CrysAlisPro 1.171.41.123a (Rigaku Oxford Diffraction, 2022) Numerical absorption correction based on gaussian integration over a multifaceted crystal model Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm. The structure was solved in the space group P21/n (# 14) by using dual methods using the ShelXT (Sheldrick, 2015) structure solution program. The structure was refined by Least Squares ShelXL incorporated in Olex2 software program. All non-hydrogen atoms were refined anisotropically. Hydrogen atom positions were calculated geometrically and refined using the riding model, except for the hydrogen atom on the non-carbon atom(s) which were found by difference Fourier methods and refined isotropically when data permits. CCDC 2158501 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures. There is a single molecule in the asymmetric unit, which is represented by the reported sum formula. In other words: Z is 4 and Z' is 1. 420 Figure 4.3: Drawing of molecule 4.8a′ with labeled heteroatoms Figure 4.4: Drawing of molecule 4.8a′ with labeling scheme. although crystal is in the Centro-symmetric space group. Model has Chirality at C1 S, Model has Chirality at C2 (Centro SPGR) R; Model has Chirality at C4 (Centro SPGR) R Verify 421 Figure 4.5: The following hydrogen bonding interactions with a maximum D-D distance of 3.1 Å and a minimum angle of 110 ° are present in 4.8a′: O1–O2_1: 2.766 Å Figure 4.6: Packing diagram of 4.8a′ Data Plots: Diffraction Data Figure 4.7: Data plots: Diffraction data 422 Figure 4.7 (cont’d) 423 Data plots: Refinement and data Figure 4.8: Data plots: Refinement and data Table 4.3: Reflection statistics Total reflections (after 15216 Unique reflections 2900 filtering) Completeness 0.942 Mean I/s 28.51 hklmax collected (3, 28, 12) hklmin collected (-7, -28, -11) hklmax used (7, 28, 12) hklmin used (-7, 0, 0) Lim dmax collected 100.0 Lim dmin collected 0.77 dmax used 11.82 dmin used 0.79 Friedel pairs 1065 Friedel pairs merged 1 Inconsistent 1 Rint 0.0328 equivalents Rsigma 0.0224 Intensity transformed 0 Omitted reflections 0 Omitted by user 0 (OMIT hkl) Multiplicity (2746, 1774, 1016, Maximum multiplicity 17 548, 292, 196, 88, 39, 12, 1) Removed systematic 218 Filtered off 0 absences (Shel/OMIT) Selected crystal pictures Figure 4.9: Selected crystal pictures 424 Table 4.4: Fractional atomic coordinates (×104) and equivalent isotropic displacement parameters (Å2×103) for 4.8a′. Ueq is defined as 1/3 of the trace of the orthogonalised Uij Atom x y z Ueq Si1 5412.1(5) 5875.8(2) 2579.5(3) 16.40(11) O1 1373.5(13) 7131.8(4) 3587.1(10) 19.4(2) O2 5249.2(15) 7133.1(4) 641.8(9) 25.0(2) C1 3755.8(17) 6557.1(5) 2397.3(12) 14.4(2) C2 3185.8(17) 6783.0(5) 3819.5(12) 15.0(2) C3 5083.5(18) 7140.1(5) 4360.9(12) 16.3(2) C4 6153.3(18) 7355.3(5) 3070.5(12) 16.2(2) C5 5059.6(18) 7028.5(5) 1861.9(12) 16.2(2) C6 1877.2(18) 6417.1(5) 1378.6(13) 18.2(3) C7 6148.2(18) 7987.9(5) 2829.4(12) 16.5(2) C8 4333.8(19) 8310.1(5) 2918.8(14) 21.1(3) C9 4372(2) 8891.3(6) 2701.3(14) 24.4(3) C10 6212(2) 9157.6(6) 2383.6(14) 25.2(3) C11 8012(2) 8841.1(6) 2295.0(13) 23.7(3) C12 7983.4(19) 8260.2(5) 2515.9(12) 19.3(3) C13 7676(2) 5928.8(6) 3893.8(14) 22.7(3) C14 6373(2) 5707.3(6) 841.9(14) 26.3(3) C15 3645(2) 5300.8(6) 3150.7(16) 28.2(3) Table 4.5: Anisotropic displacement parameters (×104) for 4.8a′. The anisotropic displacement factor exponent takes the form: -2p2[h2a*2 × U11+ ... +2hka* × b* × U12] Atom U11 U22 U33 U23 U13 U12 Si1 16.73(18) 13.66(18) 18.89(19) -0.61(12) 1.90(12) 0.52(11) O1 16.9(4) 21.6(5) 19.9(5) -4.7(4) 2.3(3) 3.4(3) O2 37.6(5) 21.8(5) 16.3(5) 0.0(4) 6.7(4) -8.8(4) C1 15.4(5) 14.1(6) 13.8(5) 0.3(4) 0.8(4) -0.2(4) C2 15.9(5) 14.0(6) 15.4(6) -0.1(4) 1.7(4) 0.7(4) C3 19.2(6) 14.7(6) 15.0(6) -0.1(4) -0.3(4) -0.8(4) C4 15.0(5) 15.9(6) 17.5(6) -0.5(4) 0.9(4) -0.5(4) C5 17.6(5) 13.9(6) 17.2(6) -0.1(4) 3.0(4) 1.2(4) C6 18.6(6) 18.8(6) 16.9(6) -0.8(5) -0.9(4) -1.2(4) C7 20.1(6) 15.9(6) 13.2(5) -1.1(4) -1.0(4) -2.3(4) C8 19.7(6) 19.1(6) 24.2(6) 0.8(5) -0.7(5) -1.8(5) C9 27.4(7) 19.7(7) 25.6(7) 0.8(5) -1.6(5) 3.7(5) C10 39.4(8) 15.0(6) 20.7(6) 0.9(5) -1.4(5) -4.2(5) C11 29.5(7) 21.7(7) 20.2(6) -0.4(5) 3.3(5) -9.6(5) C12 21.2(6) 21.2(6) 15.7(6) -1.6(5) 2.2(4) -3.0(5) C13 21.2(6) 21.9(7) 24.8(7) 0.7(5) -0.7(5) 3.9(5) C14 26.8(7) 26.7(7) 25.4(7) -6.6(5) 2.7(5) 4.9(5) C15 26.7(7) 17.0(6) 41.1(8) 4.5(6) 2.8(6) -1.1(5) 425 Table 4.6: Bond lengths in Å for 4.8a′ Atom Atom Length/Å Si1 C1 1.9302(12) Si1 C13 1.8689(13) Si1 C14 1.8659(14) Si1 C15 1.8741(14) O1 C2 1.4299(14) O2 C5 1.2167(15) C1 C2 1.5381(16) C1 C5 1.5037(16) C1 C6 1.5404(16) C2 C3 1.5433(16) C3 C4 1.5455(16) C4 C5 1.5305(16) C4 C7 1.5130(16) C7 C8 1.3970(17) C7 C12 1.3906(17) C8 C9 1.3898(19) C9 C10 1.388(2) C10 C11 1.382(2) C11 C12 1.3896(19) 426 Table 4.7: Bond angles in ° for 4.8a′ Atom Atom Atom Angle/° C13 Si1 C1 113.84(5) C13 Si1 C15 107.84(6) C14 Si1 C1 107.91(6) C14 Si1 C13 109.72(6) C14 Si1 C15 110.49(7) C15 Si1 C1 107.01(6) C2 C1 Si1 111.65(8) C2 C1 C6 115.04(9) C5 C1 Si1 109.57(8) C5 C1 C2 102.61(9) C5 C1 C6 111.63(10) C6 C1 Si1 106.34(8) O1 C2 C1 107.29(9) O1 C2 C3 110.62(9) C1 C2 C3 105.35(9) C2 C3 C4 106.72(9) C5 C4 C3 104.05(9) C7 C4 C3 116.90(10) C7 C4 C5 112.64(10) O2 C5 C1 125.11(11) O2 C5 C4 124.44(11) C1 C5 C4 110.44(10) C8 C7 C4 121.51(11) C12 C7 C4 119.81(11) C12 C7 C8 118.68(12) C9 C8 C7 120.43(12) C10 C9 C8 120.33(13) C11 C10 C9 119.50(12) C10 C11 C12 120.38(12) C11 C12 C7 120.68(12) 427 Table 4.8: Torsion angles in ° for 4.8a′ Atom Atom Atom Atom Angle/° Si1 C1 C2 O1 -157.81(7) Si1 C1 C2 C3 84.30(9) Si1 C1 C5 O2 88.25(13) Si1 C1 C5 C4 -90.80(10) O1 C2 C3 C4 -88.74(11) C1 C2 C3 C4 26.88(12) C2 C1 C5 O2 -153.01(12) C2 C1 C5 C4 27.94(11) C2 C3 C4 C5 -9.65(12) C2 C3 C4 C7 115.23(11) C3 C4 C5 O2 169.31(11) C3 C4 C5 C1 -11.63(12) C3 C4 C7 C8 -46.77(16) C3 C4 C7 C12 132.98(11) C4 C7 C8 C9 179.60(12) C4 C7 C12 C11 -179.81(11) C5 C1 C2 O1 84.93(10) C5 C1 C2 C3 -32.97(11) C5 C4 C7 C8 73.66(14) C5 C4 C7 C12 -106.58(12) C6 C1 C2 O1 -36.50(13) C6 C1 C2 C3 -154.39(10) C6 C1 C5 O2 -29.28(16) C6 C1 C5 C4 151.67(10) C7 C4 C5 O2 41.74(16) C7 C4 C5 C1 -139.20(10) C7 C8 C9 C10 0.4(2) C8 C7 C12 C11 -0.04(18) C8 C9 C10 C11 -0.5(2) C9 C10 C11 C12 0.3(2) C10 C11 C12 C7 -0.02(19) C12 C7 C8 C9 -0.16(18) 428 Table 4.9: Hydrogen fractional atomic coordinates (×104) and equivalent isotropic displacement parameters (Å2×103) for 4.8a′. Ueq is defined as 1/3 of the trace of the orthogonalised Uij Atom x y z Ueq H1 1160(30) 7293(8) 4300(20) 37(5) H2 2918.1 6465.78 4470.56 18 H3A 6066.73 6906.39 4951.14 20 H3B 4620.53 7462.89 4918.67 20 H4 7644.54 7228.26 3159.86 19 H6A 2378.83 6319.69 470.41 27 H6B 950.92 6746.65 1282.43 27 H6C 1106.54 6095.74 1734.89 27 H8 3065.66 8130.8 3129.68 25 H9 3132.55 9107.3 2770.38 29 H10 6233.34 9554.51 2228.3 30 H11 9276.76 9021.76 2081.83 28 H12 9230.1 8046.79 2452.04 23 H13A 8530.96 5585.71 3860.43 34 H13B 7158.42 5969.13 4822.53 34 H13C 8526.92 6259.24 3687.77 34 H14A 7187.58 6027.02 520.06 39 H14B 5177.97 5637.08 178.99 39 H14C 7259.43 5369.18 914.01 39 H15A 4479.27 4966.18 3419.7 42 H15B 2630.72 5202.86 2384.79 42 H15C 2901.18 5432.54 3946.23 42 429 Table 4.10: Hydrogen bond information for 4.8a′ D H A d(D-H)/Å d(H-A)/Å d(D-A)/Å D-H-A/deg O1 H1 O21 0.81(2) 1.99(2) 2.7659(13) 161.8(19) –––– 1 -1/2+x,3/2-y,1/2+z Citations CrysAlisPro (Rigaku, V1.171.41.123a, 2022) CrysAlisPro (ROD), Rigaku Oxford Diffraction, Poland (?). O.V. Dolomanov and L.J. Bourhis and R.J. Gildea and J.A.K. Howard and H. Puschmann, Olex2: A complete structure solution, refinement and analysis program, J. Appl. Cryst., (2009), 42, 339-341. Sheldrick, G.M., Crystal structure refinement with ShelXL, Acta Cryst., (2015), C71, 3-8. Sheldrick, G.M., ShelXT-Integrated space-group and crystal-structure determination, Acta Cryst., (2015), A71, 3-8. 430 Crystallographic document of 4.9a Structure from thin plate, shows some disorder in the SiMe3 portion, but the stereochemistry of the diastereomer is determined, both enantiomers are present in the crystal. Figure 4.10: Crystal structure of compound 4.9a Experimental. Single colourless plate-shaped crystals of 4.9a were used as received. A suitable crystal 0.34×0.20×0.02 mm3 was selected and mounted on a nylon loop with paratone oil on a Bruker APEX-II CCD diffractometer. The crystal was kept at a steady T = 173(2) K during data collection. The structure was solved with the XT (Sheldrick, 2015) structure solution program using the Intrinsic Phasing solution method and by using Olex2 (Dolomanov et al., 2009) as the graphical interface. The model was refined with version 2018/3 of ShelXL (Sheldrick, 2015) using Least Squares minimization. Crystal data. C15H21ClO2Si, Mr = 296.86, monoclinic, P21/n (No. 14), a = 6.4892(6) Å, b = 22.023(2) Å, c = 11.0546(11) Å, β = 94.8430(10)°, α = γ = 90°, V = 1574.2(3) Å3, T = 173(2) K, Z = 4, Z' = 1, µ(MoKα) = 0.315, 12974 reflections measured, 2988 unique (Rint = 0.0378) which were used in all calculations. The final wR2 was 0.1393 (all data) and R1 was 0.0509 (I > 2(I)). 431 Table 4.11: Crystal data Compound 4.9a CCDC 1890864 Formula C15H21ClO2Si Dcalc./ g cm-3 1.253 -1 µ/mm 0.315 Formula Weight 296.86 Color colourless Shape plate 3 Size/mm 0.34×0.20×0.02 T/K 173(2) Crystal System monoclinic Space Group P21/n a/Å 6.4892(6) b/Å 22.023(2) c/Å 11.0546(11) α/° 90 β/ ° 94.8430(10) γ/° 90 3 V/Å 1574.2(3) Z 4 Z' 1 Wavelength/Å 0.710730 Radiation type MoK Θmin/° 1.849 Θmax/° 25.703 Measured Refl. 12974 Independent Refl. 2988 Reflections with I 2231 > 2(I) Rint 0.0378 Parameters 201 Restraints 0 Largest Peak 0.503 Deepest Hole -0.384 GooF 1.047 wR2 (all data) 0.1393 wR2 0.1267 R1 (all data) 0.0691 R1 0.0509 432 Structure iuality indicators Reflections: Refinement: Figure 4.11: Structure quality indicators A colourless plate-shaped crystal with dimensions 0.34×0.20×0.02 mm3 was mounted on a nylon loop with paratone oil. Data were collected using a Bruker APEX-II CCD diffractometer equipped with an Oxford Cryosystems low-temperature device, operating at T = 173(2) K. Data were measured using ϕ and ω scans of -0.50° per frame for 299.33 s using MoK radiation (sealed tube, 50 kV, 40 mA). The total number of runs and images was based on the strategy calculation from the program COSMO (BRUKER, V1.61, 2009). The actually achieved resolution was Θ = 25.703. Cell parameters were retrieved using the SAINT (Bruker, V8.34A, after 2013) software and refined using SAINT (Bruker, V8.34A, after 2013) on 4999 reflections, 39 % of the observed reflections. Data reduction was performed using the SAINT (Bruker, V8.34A, after 2013) software which corrects for Lorentz polarization. The final completeness is 100.00 out to 25.703 in SADABS-2014/5 (Bruker,2014/5) was used for absorption correction. wR2(int) was 0.0586 before and 0.0488 after correction. The Ratio of minimum to maximum transmission is 0.8603. The /2 correction factor is 0.00150. The structure was solved in the space group P21/n (# 14) by Intrinsic Phasing using the XT (Sheldrick, 2015) structure solution program. The structure was refined by Least Squares using version 2018/3 of XL (Sheldrick, 2015) incorporated in Olex2 (Dolomanov et al., 2009). All non- hydrogen atoms were refined anisotropically. Hydrogen atom positions were calculated geometrically and refined using the riding model, except for the Hydrogen atom on the nitrogen atom which was found by difference Fourier methods and refined isotropically. β CCDC 1890864 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures. There is a single molecule in the asymmetric unit, which is represented by the reported sum formula. In other words: Z is 4 and Z' is 1. 433 Figure 4.12: Drawing of 4.9a with representative atoms Figure 4.13: Model has Chirality at C1 (Centro SPGR) R Verify; Model has Chirality at C3 (Centro SPGR) S Verify; Model has Chirality at C6 (Centro SPGR) S Verify 434 Figure 4.14: Drawing of 4.9a Figure 4.15: The following hydrogen bonding interactions with a maximum D-D distance of 2.9 Å and a minimum angle of 120 ° are present in 4.9a: O2–O1_1: 2.765 Å 435 Figure 4.16: Packing diagram of 4.9a Data Plots: Diffraction Data Figure 4.17: Data plots: Diffraction data 436 Data Plots: Refinement and Data Figure 4.18: Data plots: Refinement and data Table 4.12: Reflection statistics Total reflections (after 13207 Unique reflections 2988 filtering) Completeness 1.0 Mean I/σ 15.77 hklmax collected (7, 26, 13) hklmin collected (-7, -26, -13) hklmax used (7, 26, 13) hklmin used (-7, 0, 0) Lim dmax collected 100.0 Lim dmin collected 0.36 dmax used 11.02 dmin used 0.82 Friedel pairs 5258 Friedel pairs merged 1 Inconsistent 0 Rint 0.0378 equivalents Rsigma 0.0318 Intensity transformed 0 Omitted reflections 0 Omitted by user 0 (OMIT hkl) Multiplicity (9289, 1854, 70) Maximum multiplicity 10 Removed systematic 233 Filtered off 0 absences (Shel/OMIT) Images of the crystal on the diffractometer Figure 4.19: Images of the crystal on the diffractometer 437 Table 4.13: Fractional atomic coordinates (×104) and equivalent isotropic displacement parameters (Å2×103) for 4.9a. Ueq is defined as 1/3 of the trace of the orthogonalised Uij Atom x y z Ueq Cl1 2851(2) 4768.2(4) 6691.2(8) 100.7(4) Si1 6323.1(11) 8825.0(3) 5073.8(7) 45.7(2) O1 7102(3) 7491.2(8) 6575.6(13) 43.3(4) O2 10432(2) 7651.3(8) 3777.8(14) 44.1(4) C1 7880(3) 8094.2(10) 4911.5(19) 33.5(5) C2 6865(3) 7568.5(10) 5476.5(19) 33.6(5) C3 5430(3) 7168.3(10) 4666(2) 35.7(5) C4 6340(4) 7041.4(11) 3447(2) 39.9(6) C5 6904(4) 7630.2(11) 2838.0(19) 40.2(6) C6 8530(3) 7981.9(11) 3626.4(19) 35.3(5) C7 4784(4) 6583.3(11) 5254(2) 40.3(6) C8 2744(4) 6391.5(12) 5093(2) 49.2(6) C9 2146(5) 5831.8(14) 5525(3) 60.2(8) C10 3595(6) 5471.4(13) 6132(3) 62.5(8) C11 5619(5) 5644.3(13) 6322(3) 64.0(8) C12 6215(5) 6204.1(12) 5873(2) 51.8(7) C13 4312(6) 8926.7(19) 3748(4) 70.7(12) C13B 6760(20) 9400(6) 3999(15) 70.7(12) C14 8236(7) 9442.7(18) 4983(4) 73.6(13) C14B 7290(30) 9181(8) 6693(13) 78(5) C15 5170(11) 8818(2) 6506(5) 111(3) C15B 3560(20) 8679(6) 5240(20) 95(7) 438 Table 4.14: Anisotropic displacement parameters (×104) 4.9a. The anisotropic displacement factor exponent takes the form: -2π2[h2a*2 × U11+ ... +2hka* × b* × U12]$ Atom U11 U22 U33 U23 U13 U12 Cl1 186.6(12) 55.6(5) 61.4(5) 9.1(4) 18.8(6) -49.9(6) Si1 55.6(5) 36.3(4) 46.7(4) 3.8(3) 13.4(3) 6.0(3) O1 50.8(10) 53.2(11) 27.1(8) 7.2(7) 10.3(7) 4.3(8) O2 39.0(9) 63.8(11) 30.8(8) -2.8(8) 10.3(7) 7.3(8) C1 34.6(11) 38.4(12) 28.2(11) 0.5(9) 7.0(9) 1.9(10) C2 32.7(12) 38.2(12) 31.1(11) 3.6(9) 10.0(9) 8.3(9) C3 34.8(12) 37.7(13) 35.3(12) 5.0(9) 7.3(9) 2.0(10) C4 48.4(14) 42.0(14) 29.6(12) 0.5(10) 5.0(10) -5.6(11) C5 48.0(14) 46.6(14) 26.0(11) 4.4(10) 3.2(10) -3.5(11) C6 40.3(12) 39.8(13) 26.8(11) 4.0(9) 7.8(9) 0.1(10) C7 49.5(14) 38.4(13) 35.1(12) 1.4(10) 15.8(10) -0.4(11) C8 56.7(16) 46.4(15) 45.9(14) -2.7(12) 13.5(12) -6.0(12) C9 72.7(19) 55.9(18) 54.7(17) -6.2(14) 20.6(15) -21.2(16) C10 104(3) 40.7(16) 45.3(16) -0.6(12) 24.0(16) -22.8(16) C11 95(2) 45.4(17) 51.6(17) 13.0(13) 9.1(16) 4.1(16) C12 61.8(17) 42.7(15) 52.0(15) 10.1(12) 10.2(13) 2.2(12) C13 67(2) 55(2) 88(3) 2(2) -2(2) 15.3(19) C13B 67(2) 55(2) 88(3) 2(2) -2(2) 15.3(19) C14 89(3) 42(2) 87(3) -7(2) -2(2) 0(2) C14B 90(11) 83(11) 59(9) -35(8) -10(8) 30(9) C15 187(7) 77(3) 83(4) 21(3) 84(4) 70(4) C15B 48(8) 33(7) 210(20) -17(10) 32(11) 2(6) 439 Table 4.15: Bond lengths in Å for 4.9a Atom Atom Length/Å Cl1 C10 1.750(3) Si1 C1 1.917(2) Si1 C13 1.892(4) Si1 C13B 1.776(15) Si1 C14 1.850(4) Si1 C14B 2.006(13) Si1 C15 1.807(4) Si1 C15B 1.847(13) O1 C2 1.224(2) O2 C6 1.431(3) C1 C2 1.494(3) C1 C6 1.536(3) C2 C3 1.518(3) C3 C4 1.541(3) C3 C7 1.518(3) C4 C5 1.520(3) C5 C6 1.522(3) C7 C8 1.387(4) C7 C12 1.386(4) C8 C9 1.389(4) C9 C10 1.363(5) C10 C11 1.366(4) C11 C12 1.396(4) 440 Table 4.16: Bond angles in ° for 4.9a Atom Atom Atom Angle/° C1 Si1 C14B 106.5(4) C13 Si1 C1 111.19(15) C13B Si1 C1 114.8(5) C13B Si1 C14B 105.2(8) C13B Si1 C15B 113.7(8) C14 Si1 C1 104.54(16) C14 Si1 C13 107.0(2) C15 Si1 C1 109.55(16) C15 Si1 C13 111.7(3) C15 Si1 C14 112.6(3) C15B Si1 C1 112.8(4) C15B Si1 C14B 102.4(9) C2 C1 Si1 110.93(14) C2 C1 C6 115.28(18) C6 C1 Si1 114.20(15) O1 C2 C1 120.0(2) O1 C2 C3 121.6(2) C1 C2 C3 118.23(18) C2 C3 C4 111.10(18) C7 C3 C2 114.71(19) C7 C3 C4 111.12(18) C5 C4 C3 110.92(19) C4 C5 C6 111.19(18) O2 C6 C1 105.99(17) O2 C6 C5 110.94(19) C5 C6 C1 112.36(18) C8 C7 C3 119.9(2) C12 C7 C3 121.7(2) C12 C7 C8 118.2(2) C7 C8 C9 121.2(3) C10 C9 C8 119.0(3) C9 C10 Cl1 119.3(3) C9 C10 C11 121.8(3) C11 C10 Cl1 118.9(3) C10 C11 C12 118.9(3) C7 C12 C11 120.9(3) 441 Table 4.17: Hydrogen fractional atomic Coordinates (×104) and equivalent isotropic displacement parameters (Å2×103) for 4.9a. Ueq is defined as 1/3 of the trace of the orthogonalised Uij Atom x y z Ueq H2 10915.64 7610.88 3101.1 66 H1 9203 8159.27 5426.81 40 H3 4136.26 7407.92 4470.65 43 H4A 7589.06 6784.64 3589.99 48 H4B 5314.99 6816.39 2904.89 48 H5A 5649.47 7883.61 2683.25 48 H5B 7441.42 7537.68 2046.5 48 H6 8779.35 8381.02 3232.94 42 H8 1737.16 6647.54 4680.66 59 H9 748.55 5702.08 5398.98 72 H11 6603.92 5387.82 6751.76 77 H12 7620.93 6326.8 5992.76 62 H13A 4992.41 8934.14 2989.88 106 H13B 3573.51 9309.95 3839.56 106 H13C 3327.57 8588.59 3728.08 106 H13D 8255.56 9458.59 3967.81 106 H13E 6132.1 9780.36 4239.55 106 H13F 6147.94 9277.1 3196.09 106 H14A 9210.09 9435.85 5710.1 110 H14B 7518.71 9834.57 4929.13 110 H14C 8992.71 9384.82 4260.84 110 H14D 6986.93 8898.16 7338.5 117 H14E 6576.98 9566.59 6803.47 117 H14F 8786.9 9252.73 6728.92 117 H15A 4045.06 8519.58 6470.27 167 H15B 4620.13 9221.41 6665.2 167 H15C 6220.55 8707.45 7158.11 167 H15D 2887.08 8536.91 4460.84 142 H15E 2892.3 9054.56 5477.09 142 H15F 3426.12 8367.89 5859.76 142 Table 4.18: Hydrogen bond information for 4.9a D H A d(D-H)/Å d(H-A)/Å d(D-A)/Å D-H-A/deg O2 H2 O11 0.84 1.93 2.765(2) 178.2 –––– 1 1/2+x,3/2-y,-1/2+z 442 Table 4.19: Atomic occupancies for all atoms that are not fully occupied in 4.9a Atom Occupancy C13 0.776(4) H13A 0.776(4) H13B 0.776(4) H13C 0.776(4) C13B 0.224(4) H13D 0.224(4) H13E 0.224(4) H13F 0.224(4) C14 0.776(4) H14A 0.776(4) H14B 0.776(4) H14C 0.776(4) C14B 0.224(4) H14D 0.224(4) H14E 0.224(4) H14F 0.224(4) C15 0.776(4) H15A 0.776(4) H15B 0.776(4) H15C 0.776(4) C15B 0.224(4) H15D 0.224(4) H15E 0.224(4) H15F 0.224(4) Citations COSMO-V1.61 - Software for the CCD Detector Systems for Determining Data Collection Parameters, Bruker axs, Madison, WI (2000). O.V. Dolomanov and L.J. Bourhis and R.J. Gildea and J.A.K. Howard and H. Puschmann, Olex2: A complete structure solution, refinement and analysis program, J. Appl. Cryst., (2009), 42, 339-341. Sheldrick, G.M., Crystal structure refinement with ShelXL, Acta Cryst., (2015), C27, 3-8. Software for the Integration of CCD Detector System Bruker Analytical X-ray Systems, Bruker axs, Madison, WI (after 2013). 443 Copies of NMR spectra 444 445 446 447 448 449 450 451 452 453 454 455 456 457 458 459 460 461 462 463 464 465 466 467 468 469 470 471 472 473 474 475 476 477 478 479 480 481 482 483 484 485 486 487 488 489 490 491 492 493 494 495 496 497 498 499 500 501 502 503 504 505 506 507 508 509 510 511 512 513 514 515 516 517 518 519 520 521 522 523 524 525 526 527 528 529 530 531 532 533 534 535 536 537 538 539 540 541 542 543 544 545 546 547 548 549 550 551 552 553 554 555 556 557 558 559 560 561 562 563 564 565 566 567 568 569 570 571 572 573 574 575 576 577 578 579 580 581 582 583 584 585 586 587 588 589 590 591 592 593 594 595 596 597 598 599 600 CHAPTER 5. SERENDIPITOUS [1,2]-CARBON-TO-CARBON SILYL MIGRATION IN α-HYRDOXY ALLYL SILANES: ACCESS TO α-SILYL ALKANALS 5.1. Introduction As we have seen in chapter 4, carbon to carbon silyl migration is rare compared to carbon to oxygen (Brook rearrangement)1-4 or oxygen to carbon (retro-Brook rearrangement)5-10 silyl shifts. Aldehydes and ketones with a silyl group at the α-position are good precursors for vinyl silyl ethers,11 aldol reactions,12 α-amino ketones,13 and Peterson olefinations14,15 (Scheme 5.1) Scheme 5.1: Selected synthetic applications of α-silyl ketones and aldehydes Despite their synthetic usefulness, few methods of accessing α-silyl ketones and aldehydes have been reported. Example of these methods are lithiation followed by silyl vinylation, 11 601 synthesis from 3-silyl-2,3-epoxy alcohols,16 and catalytic asymmetric Roskamp reaction17 (Scheme 5.2). Scheme 5.2: Selected syntheses of α-silyl ketones and aldehydes 5.2. Serendipitous [1,2]-carbon-to-carbon silyl migration During preparation of one of the intermediates for Wittig rearrangement in Chapter 4 (Scheme 5.3), a peak at around 9.5 ppm in 1H NMR corresponding to an aldehyde was observed (Figure 5.1). Scheme 5.3: Synthesis of 2-methyl-1-(trimethylsilyl)prop-2-en-1-ol 4.3b by retro-Brook rearrangement 602 Figure 5.1: 1H NMR of crude reaction mixture At first, the peak was thought to be from a byproduct or impurity in the crude reaction mixture. After purification by column chromatography, the peak remained as a ~1:1 mixture with the compound of interest (Figure 5.2). 603 Figure 5.2: 1H NMR of purified material in CDCl3 At a glance, it was unclear whether this unknown compound had the same Rf value as the compound of interest or if it was being formed from that compound in the NMR tube. To further investigate this, the sample in the NMR tube was left overnight (~12 hours) and resubmitted for NMR analysis the following day. Surprisingly, the aldehyde peak had increased in intensity, overshadowing the compound of interest (Figure 5.3). 604 Figure 5.3: 1H NMR of purified material in CDCl3 after 12 hours Having determined that the unknown compound was being formed from the compound of interest, we embarked on deducing its structure. It turned out to be 2-methyl-2- (trimethylsilyl)propanal, which is formed as a result of an irreversible [1,2]-carbon-to-carbon silyl migration of 2-methyl-1-(trimethylsilyl)prop-2-en-1-ol (Scheme 5.4). Scheme 5.4: The [1,2]-carbon-to-carbon silyl migration of 2-methyl-1-(trimethylsilyl)prop-2-en-1-ol Although this rearrangement looks trivial, we were surprised to find only one report of such migration in the literature (Scheme 5.5).18 In this paper, the authors stated, “This unusual rearrangement reaction was NOT appreciably accelerated by the presence of acids (HCl gas, TsOH), and was completely inhibited by weak bases (pyridine, Et3N) and even THF. We are not 605 aware of a precedent for this rearrangement process.” Scheme 5.5: Silyl migration of compound 5.2 in DCM With this information, we decided to do further experiments to determine why this migration was occurring. Knowing that over many months of storage at room temperature, deuterated chloroform can become acidic,19 we acquired the 1H NMR in deuterated chloroform that was stored over K2CO3. Compound 5.1a did not form immediately, but the transformation of compound 4.3b to 5.1a slowly occurred. Thus, the chloroform stored over K2CO3 only slows the reaction but it does not stop the process. Notably even with new bottle of chloroform, the aldehyde was formed overnight. However, compound 4.3b was stable in deuterated benzene and the aldehyde was not formed even after weeks (Figure 5.4). Figure 5.4: 1H NMR of purified material in C6D6 606 5.3. Substrate scope for [1,2]-carbon-to-carbon silyl migration Next, we looked at the substrate scope of this migration. We began by modifying the substituents on silicon: Moving from trimethyl to triethyl, tripropyl and diphenyl methyl groups all effected the migration in varying amount of time (Scheme 5.6, substrates 5.1b – 5.1d). Having an isopropyl group in place of methyl at the olefin carbon proximal to silicon also worked well (Scheme 5.6, substrates 5.1e and 5.1f). Finally, [1,2]-silyl migration also occurred on a trisubstituted olefin 5.1g. Scheme 5.6: Substrate scope for [1,2]-carbon to carbon migration in NMR tube a Conversion (y%) was determined by 1H NMR integration We then tested the importance of having an alkyl substituent on the olefin carbon β to silicon. The silyl migration was not observed in compounds 4.3a and 5.3 even after days of sitting in NMR tube with CDCl3 as a solvent (Scheme 5.7). 607 Scheme 5.7: Substrate scope limitation When a mixture of 5.3 and 5.1f was dissolved in CDCl3 from a bottle that contained K2CO3, both alcohols could be observed at time zero. After 18 hours, alcohol 5.1f had converted to aldehyde 5.2f while alcohol 5.3 remained unchanged. On the fifth day, alcohol 5.1f had completely transformed to aldehyde 5.2f while silyl migration was not detected on alcohol 5.3. (Figure 5.5) Figure 5.5: 1H NMR of compounds 5.1f and 5.3 over time 608 5.4. Proposed reaction mechanism of the [1,2]-carbon-to-carbon silyl migration With the above observations of importance of having the alkyl group at the olefin carbon β to the silyl group, we propose that this reaction is acid catalyzed and proceeds by the olefin abstracting proton followed by subsequent silyl migration which is facilitated by carbonyl formation (Scheme 5.8). Scheme 5.7: Proposed reaction mechanism of the silyl shift 5.5. Attempted mechanistic investigation of the [1,2]-carbon-to-carbon silyl migration To investigate whether the proposed mechanism is concerted or stepwise. Compound 5.1f was studied since the silyl migration would create a new stereogenic center. An enantiomerically enriched 5.1f will lead to 5.2f with inversion / retention of stereochemistry (concerted) or erosion of stereochemistry (stepwise) with carbocation intermediate (Scheme 5.8). Scheme 5.8: Reaction design to investigate mechanistic pathways With the above idea, we began with synthesizing the enantiomerically enriched 5.1f by first oxidizing the racemic 5.1f followed by asymmetric reduction of the resulting acyl silane 5.4f using Corey-Bakshi-Shibata (CBS) catalyst36 to generate 5.1f* (Scheme 5.9). 609 Scheme 5.9: Synthesis of enantioenriched 5.1f With compound 5.1f* at hand, we subjected it to conditions leading to [1,2]-carbon-to-carbon silyl shift. Unfortunately, attempts to derivatize the resulting aldehyde with the purpose of determining absolute stereochemistry were unsuccessful. Aldehyde 5.2f was reacted with 2,4- dinitrophenyl hydrazine with intention of forming 2,4-dinitrophenyl hydrazone (5.5), but instead, desilylated hydrazone 5.6 was formed (Scheme 5.10). The proposed mechanism is shown in Scheme 5.11. Scheme 5.10: Attempted derivatization of 5.2f 610 Scheme 5.11: Proposed reaction mechanism for the formation of the observed product 5.6 Whether the mechanism of the [1,2]-carbon to carbon silyl migration is stepwise (involving carbocation formation) or concerted is not known at this time. Formation of carbocation intermediate is more likely since it would be doubly stabilized: a tertiary carbocation 20-22 and β to silicon.23-35 Further investigations will be performed by others. 5.6. Unexpected SN2-like reaction between the O-silylated 2-phenylprop-2-en-1-ol and butyl lithiums Knowing the importance of having a substituent other than proton on the olefin carbon β to silicon, we embarked on synthesizing substrates containing aromatic groups at this position. In our 611 quest to expand the substrate scope of the silyl migration, we saw an unexpected transformation involving SN2-like reaction between the O-silylated 2-phenylprop-2-en-1-ol and butyl lithiums (Scheme 5.12). To the best of our knowledge, this reaction had no literature precedence. Use of tert-butyllithium and sec-butyllithium resulted in the formation of products 5.8a and 5.8b in high yields. However, when we employed n-butyllithium, product 5.8c was formed as a mixture with desilylated alcohol 5.9h which could have resulted from unreacted starting material during workup. Lastly, there exists a challenge to access molecules with all C-sp3 quaternary center by C−C coupling reactions.37-50 This discovery will be helpful in accessing such products. Scheme 5.12: Unexpected SN2-like reactions a The product was formed as a mixture with 2-phenyl ally alcohol 5.7. Conclusion In summary, we have serendipitously discovered an irreversible [1,2]-carbon-to-carbon silyl migration leading to α-silylated alkanals. This migration proceeds even when the substituents on silicon are modified but requires an alkyl group at the olefin carbon β to silicon. Preliminary studies have also shown that the migration is acid catalyzed. Further experimental studies to determine the mechanistic pathway of this migration are 612 underway. Lastly, we have seen unexpected SN2-like reaction between the O-silylated 2- phenylprop-2-en-1-ol and butyl lithiums in attempted retro-Brook rearrangement to expand the substrate scope. This reaction not only takes place on an in situ generated O-Silylated alcohol but also occurs when the O-silyl alcohol is prepared separately. 5.8. Experimental section 5.8.1. General information Unless otherwise noticed all reactions were run under a positive atmosphere of nitrogen in oven- dried (at least 4 hours) or flame-dried round bottom flasks or disposable drum vials capped with rubber septa. Solvents were removed by rotary evaporation at temperatures lower than 45 ºC. Column chromatography was run on 230–400 mesh silica gel. Tetrahydrofuran and diethyl ether were distilled from sodium-benzophenone ketyl; dichloromethane and trimethylsilyl chloride were distilled from calcium hydride. Triethylsilyl chloride, tripropylsilyl chloride, and diphenylmethylsilyl chloride were used as received. n-Butyllithum (2.5 M in hexanes) and sec- butyllithium (1.4 M in cyclohexane) were purchased from Aldrich and their concentration calculated by titration with diphenylacetic acid (average of three runs). 1H NMR spectra was collected in 500 MHz Varian instruments using CDCl3 as solvent, which was referenced at 7.26 ppm (residual chloroform proton) and 13C NMR spectra was collected in CDCl3 at 126 MHz or 151 MHz and referenced at 77.0 ppm. Another deuterated solvent used for NMR analysis was benzene (referenced at 7.16 for 1HNMR and 128.39 for 13 CNMR). High resolution mass spectrometric (HRMS) analysis was run in TOF instruments. 613 5.8.2. Synthesis of ally alcohols 5.9 from propargyl alcohols: General procedure A Following a reported procedure,51 for a 50 mmol scale reaction, to a dry 500 mL 3-neck round bottomed flask fitted with a magnetic stir bar was weighed 4.01 g of magnesium powder (165 mmol, 3.3 equiv), 3 crystals of iodine and 125 mL of freshly distilled dry THF. The two side necks of the flask were sealed with rubber septa and a reflux condenser was attached to the middle neck and the whole system purged with nitrogen after placing an oil bath was placed underneath the flask. On a separate 250 mL round bottomed flask a solution corresponding to 150 mmol (3.0 equiv) of alkyl/aryl halide in 100 mL dry THF was prepared. The 250 mL flask was sealed with a rubber septum and purged with nitrogen. The 250 mL flask was then connected to the 500 mL flask via canula. The alkyl/aryl halide solution was transferred in a dropwise manner for ~30 minutes to the 500 mL flask via canula while stirring and monitoring both the temperature of the oil bath and the reaction mixture in the 500 mL flask. After complete addition, the temperature of the oil bath had risen to 35 – 40 °C. The canula was removed and the oil bath was heated to 75 °C to allow the Grignard reagent to form over 1.5 hours. The heat was then turned off and the reaction mixture allowed to cool down to room temperature slowly without removing the oil bath. This was followed by addition of 1.43 g of copper (I) iodide (7.5 mmol, 0.15 equiv) which was done by removing one of the side neck rubber septum, quickly adding the CuI and replacing the septum fast enough to minimize contact with air. The resulting mixture was stirred at room temperature for 30 minutes after which 2.91 mL (50 mmol, 1 equiv) of propargyl alcohol as a solution in 25 614 mL dry THF was added dropwise via syringe. After complete addition, the mixture was heated to 75 °C and stirred at this temperature for 24 hours. This was followed by turning off the heat and allowing the mixture to cool to room temperature. The oil bath was removed and replaced with an ice bath to cool down the mixture further to 0 °C. The mixture was quenched by slow addition of 80 mL of water. The reaction mixture was transferred to a 1000 mL separatory funnel and diluted with 100 mL ethyl ether. The layers were separated, and the aqueous layer was extracted with ether (80 mL X 3). Combined organic layers were washed with 80 mL water and 80 mL brine respectively then dried over anhydrous magnesium sulfate. The mixture was filtered, and the filtrate was concentrated on a rotorvap under reduced pressure to afford allyl alcohol 5.9 which was purified by column chromatography (Hexanes/EtOAc). 5.8.3. Preparation of α-hydroxy allyl silanes 4.3 – general procedure B:52 A solution of the corresponding allylic alcohol in THF was cooled at −78 °C, and n- butyllithium (1.6 M or 2.5 M in hexanes) was added dropwise over 5 min. After 30 min the corresponding chlorosilane was added dropwise via syringe. After the resulting solution was stirred for a given amount of time (see individual compounds procedure below), sec-butyllithium or tert-butyllithium (see below for details) was added dropwise over 30−60 min, and then the reaction was kept at the indicated temperature. 615 Synthesis of 3-methyl-2-methylenebutan-1-ol (5.9e) and (E)-4-methylpent-2-en-1-ol (5.10) Following the general procedure A with slight modification compounds 5.9e and 5.10 were synthesized from 8.00 g (330 mmol, 3.3 equiv) of magnesium, 28 mL (300 mmol, 3.0 equiv) of isopropyl bromide, 2.86 g CuI (15 mmol, 0.15 equiv) and 5.85 mL (100 mmol, 1.0 equiv) of propargyl alcohol: After reflux (formation of the Grignard reagent) the Grignard reagent was allowed to cool down to around 40 degrees Celsius. On a separate flask, copper (I) iodide and propargyl alcohol were stirred at 0 °C in THF (100 mL). The Grignard reagent was transferred to this flask via cannula and the reaction proceeded at room temperature for 24 hours and then quenched at minus 10 degrees Celsius, worked up and solvent evaporated. Purification by column chromatography (30% Et2O in hexanes) afforded total of 7428 mg, 74 mmol (74% isolated yield) of 5.9e and 5.10, as a 5:1 mixture: a 74% yield. 803 mg of another side product 5.11 was also formed (see structure below). Spectroscopic data for 5.9e: 1H NMR (500 MHz, CDCl3) δ 4.97 (q, J = 1.5 Hz, 1H), 4.86 (p, J = 1.2 Hz, 1H), 4.08 (t, J = 1.3 Hz, 2H), 2.29 (hept, J = 6.4 Hz, 1H), 2.18 (s, 1H), 1.04 (d, J = 6.9 Hz, 6H). 13C NMR (126 MHz, CDCl3) δ 155.1, 106.8, 64.7, 30.9, 21.7. Spectroscopic data were similar to those reported in the literature. 53 The minor product 5.10 spectroscopic data also matched the literature report.54 616 Spectroscopic data for (E)-2-isopropyl-4-methylenepent-2-ene-1,5-diol 5.11: 1H NMR (500 MHz, CDCl3) δ 5.33 (dt, J = 10.2, 1.1 Hz, 1H), 5.26 (q, J = 1.5 Hz, 1H), 4.91 (dd, J = 1.9, 1.0 Hz, 1H), 4.10 – 4.06 (m, 2H), 4.02 (d, J = 1.1 Hz, 2H), 3.43 (s, 2H), 2.48 (dp, J = 10.1, 6.6 Hz, 1H), 0.92 (d, J = 6.7 Hz, 6H). 13C NMR (126 MHz, CDCl3) δ 146.2, 138.4, 136.2, 114.7, 67.4, 65.6, 27.9, 23.1. Synthesis of (E)-2-methylbut-2-en-1-ol (5.9g) Following procedure A: This time around having the propargyl alcohol and CuI in a 500 mL RB flask at 0 °C, MeMgCl as a solution in THF (3M) was added. Accidentally, the flask cracked while quenching and spilled the reaction mixture in the hood. A small amount of the reaction mixture was recovered and worked up. Purification by column chromatography afforded 731 mg as a mixture of 5.9g and the starting propargyl alcohol (5.9g 66% W/W with but-2-yn-1-ol). Spectroscopic data for 5.9g: 1H NMR (500 MHz, CDCl3) δ 5.46 (q, J = 6.8 Hz, 1H), 3.96 (s, 2H), 2.14 (s, 2H), 1.63 (s, 3H), 1.59 (d, J = 6.7 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 135.3, 120.5, 68.8, 13.2, 13.0. Spectroscopic data were similar to those reported in the literature.55 617 Synthesis of 2-phenylprop-2-en-1-ol (5.9h) Applying procedure A to 4 g (165 mmol, 3.3 equiv) of magnesium, 15.8 mL (150 mmol, 3.0 equiv) of bromobenzene, 1.43 g CuI (7.5 mmol, 0.15 equiv) and 2.88 mL (50 mmol, 1.0 equiv) of propargyl alcohol, alcohol 5.9h was prepared in quantitative yield: 1H NMR (500 MHz, CDCl3) δ 7.48 – 7.43 (m, 2H), 7.40 – 7.34 (m, 2H), 7.34 – 7.29 (m, 1H), 5.48 (q, J = 1.0 Hz, 1H), 5.36 (q, J = 1.4 Hz, 1H), 4.53 (dd, J = 1.5, 0.9 Hz, 2H), 2.22 (s, 1H). 13C NMR (126 MHz, CDCl3) δ 147.1, 138.4, 128.4, 127.8, 126.0, 112.5, 64.7. Spectroscopic data were similar to those reported in the literature.56 Attempted synthesis of 2-benzylprop-2-en-1-ol (5.9i) Applying general procedure A to 3.65 g (150 mmol, 3.0 equiv) of magnesium, 16.04 mL (135 mmol, 2.7 equiv) of benzyl bromide, 1.43 g CuI (7.5 mmol, 0.15 equiv) and 2.88 mL (50 mmol, 1.0 equiv) of propargyl alcohol, compound 5.9i could not be obtained. Instead, 1,2-diphenylethane 5.12i was formed in quantitative yield. Spectroscopic data for 5.12i: 1H NMR (500 MHz, CDCl3) δ 7.42 – 7.34 (m, 4H), 7.33 – 7.25 (m, 6H), 3.03 (s, 4H). 13C NMR (126 MHz, CDCl3) δ 141.7, 128.4, 128.3, 125.9, 37.9. Spectroscopic data were similar to those reported in the literature.57 618 Synthesis of 2-methyl-1-(triethylsilyl)prop-2-en-1-ol (5.1b) Following general procedure B, a solution of 1.26 mL 2-methyl allyl alcohol (1081.7 mg, 15 mmol, 1 equiv.) in THF (25 mL) was cooled to −78 °C. n-BuLi (2.4 M in hexanes, 7.5 mL, 18 mmol, 1.2 equiv.) was added dropwise and the mixture stirred at –78 °C for 1 h. Chlorotriethylsilane (2.52 mL, 15 mmol, 1.0 equiv.) was then added slowly from a syringe and the resulting mixture was stirred at –78 °C to room temperature for 18 hours resulting in the formation of a white suspension. The mixture was cooled back to –78 °C followed by dropwise addition of sec-butyllithium (1.4 M in cyclohexane, 12.9 mL, 18 mmol, 1.2 equiv.) and the reaction stirred for an additional 2 hours at –78 °C to –50 °C. The reaction mixture was cooled back to –78 °C and quenched by the addition of aqueous NH4Cl and diluted with Et2O, and the mixture was warmed to room temperature. After the layers were separated, the aqueous phase was washed with Et2O (3 × 20 mL). Then all the organic phases were combined, washed with H2O (20 mL) and brine (20 mL) respectively, and dried over anhydrous MgSO4. After filtration and concentration, the residue was purified by column chromatography, Rf = 0.3 (15% Et2O in hexanes) to afford 1.4 g, 7.5 mmol (50% isolated yield) of compound 5.1b as a colorless liquid. 1H NMR (500 MHz, C6D6) δ 4.88 (tq, J = 1.7, 0.8 Hz, 1H), 4.74 (h, J = 1.3 Hz, 1H), 3.80 (s, 1H), 1.61 (dt, J = 1.3, 0.7 Hz, 3H), 1.23 (s, 1H), 1.02 (t, J = 7.9 Hz, 9H), 0.65 (qd, J = 14.9, 7.6 Hz, 6H). 13C NMR (126 MHz, C6D6) δ 149.4, 107.1, 70.1, 21.0, 8.1, 2.8. 619 Synthesis of 2-methyl-1-(tripropylsilyl)prop-2-en-1-ol (5.1c) Following general procedure B, a solution of 0.84 mL 2-methyl allyl alcohol (721.1 mg, 10 mmol, 1 equiv.) in THF (25 mL) was cooled to −78 °C. n-BuLi (2.4 M in hexanes, 5 mL, 12 mmol, 1.2 equiv.) was added dropwise and the mixture stirred at –78 °C for 1 h. Chlorotripropylsilane (2.2 mL, 10 mmol, 1.0 equiv.) was then added slowly from a syringe and the resulting mixture was stirred at –78 °C to room temperature for 18 hours resulting in the formation of a white suspension. The mixture was cooled back to –78 °C followed by dropwise addition of sec-butyllithium (1.4 M in cyclohexane, 8.6 mL, 12 mmol, 1.2 equiv.) and the reaction stirred for an additional 2 hours at –78 °C to –50 °C. The reaction mixture was cooled back to –78 °C and quenched by the addition of aqueous NH4Cl and diluted with Et2O, and the mixture was warmed to room temperature. After the layers were separated, the aqueous phase was washed with Et 2O (3 × 20 mL). Then all the organic phases were combined, washed with H2O (20 mL) and brine (20 mL) respectively, and dried over anhydrous MgSO4. After filtration and concentration, the residue was purified by column chromatography (10% Et2O in hexanes) to afford 491 mg, 2.2 mmol (22% isolated yield) of compound 5.1c as a colorless liquid. 1H NMR (500 MHz, C6D6) δ 4.89 (tt, J = 1.7, 0.7 Hz, 1H), 4.75 (p, J = 1.4 Hz, 1H), 3.80 (s, 1H), 1.63 (dd, J = 1.6, 0.7 Hz, 3H), 1.42 (dddd, J = 14.4, 12.8, 11.1, 7.3 Hz, 6H), 1.01 (t, J = 7.3 Hz, 9H), 0.97 (s, 1H), 0.74 – 0.59 (m, 6H). 13C NMR (126 MHz, C6D6) δ 149.4, 107.2, 70.5, 21.1, 19.3, 18.3, 14.7. 620 Synthesis of 2-methyl-1-(methyldiphenylsilyl)prop-2-en-1-ol (5.1d) Following general procedure B, a solution of 1.26 mL 2-methyl allyl alcohol (1081.7 mg, 15 mmol, 1 equiv.) in THF (25 mL) was cooled to −78 °C. n-BuLi (2.4 M in hexanes, 7.5 mL, 18 mmol, 1.2 equiv.) was added dropwise and the mixture stirred at –78 °C for 1 h. Chloromethyldiphenylsilane (3.15 mL, 15 mmol, 1.0 equiv.) was then added slowly from a syringe and the resulting mixture was stirred at –78 °C to room temperature for 18 hours resulting in the formation of a white suspension. The mixture was cooled back to –78 °C followed by dropwise addition of sec-butyllithium (1.4 M in cyclohexane, 12.9 mL, 18 mmol, 1.2 equiv.) and the reaction stirred for an additional 2 hours at –78 °C to –50 °C. The reaction mixture was cooled back to –78 °C and quenched by the addition of aqueous NH4Cl and diluted with Et2O, and the mixture was warmed to room temperature. After the layers were separated, the aqueous phase was washed with Et2O (3 × 20 mL). Then all the organic phases were combined, washed with H2O (20 mL) and brine (20 mL) respectively, and dried over anhydrous MgSO4. After filtration and concentration, the residue was purified by column chromatography (12% Et2O in hexanes) to afford 391 mg, 1.5 mmol (10% isolated yield) of compound 5.1d as a colorless liquid. 1H NMR (500 MHz, C6D6) δ 7.73 – 7.64 (m, 2H), 7.61 – 7.54 (m, 2H), 7.21 – 7.10 (m, 6H), 4.86 (dq, J = 1.7, 0.9 Hz, 1H), 4.72 13 (h, J = 1.4 Hz, 1H), 4.22 (s, 1H), 1.34 (s, 3H), 1.21 (s, 1H), 0.55 (s, 3H). C NMR (126 MHz, C6D6) δ 148.3, 136.1, 135.8, 135.8, 130.1, 128.5, 128.4, 108.7, 70.8, 21.6, -6.1. 621 Synthesis of 3-methyl-2-methylene-1-(trimethylsilyl)butan-1-ol (5.1e) and (E)-4-methyl-1- (trimethylsilyl)pent-2-en-1-ol (5.13) Following general procedure B, a solution of 3-methyl-2-methylenebutan-1-ol 5.9e and (E)- 4-methylpent-2-en-1-ol 5.10e (501 mg, 5.0 mmol, 1 equiv.) in THF (10 mL) was cooled to −78 °C. n-BuLi (2.4 M in hexanes, 2.5 mL, 12 mmol, 1.2 equiv.) was added dropwise and the mixture stirred at –78 °C for 1 h. Chlorotrimethylsilane (0.65 mL, 5.0 mmol, 1.0 equiv.) was then added slowly from a syringe and the resulting mixture was stirred at –78 °C for 1.5 hours resulting in the formation of a white suspension. This was followed by dropwise addition of tert-butyllithium (1.6 M in pentane, 4.4 mL, 7.0 mmol, 1.4 equiv.) and the reaction stirred for an additional 1.5 hours at –78 °C and quenched by the addition of aqueous NH4Cl and diluted with Et2O, and the mixture was warmed to room temperature. After the layers were separated, the aqueous phase was washed with Et2O (3 × 20 mL). Then all the organic phases were combined, washed with H2O (20 mL) and brine (20 mL) respectively, and dried over anhydrous MgSO4. After filtration and concentration, the residue was purified by column chromatography (10% Et2O in hexanes) to afford 51 mg, 0.3 mmol (6% isolated yield) of compound 5.1e as a colorless liquid. The very low isolated yield could be attributed to impure starting material. Alcohol 5.13 was observed in crude reaction mixture but could not be isolated. Spectroscopic data for 5.1e: 1H NMR (500 MHz, C6D6) δ 4.94 (dd, J = 1.5, 1.0 Hz, 1H), 4.82 (q, J = 1.0 Hz, 1H), 3.74 (s, 1H), 1.86 (hept, J = 6.7 Hz, 1H), 1.03 (d, J = 6.8 Hz, 3H), 0.98 (d, J = 6.8 Hz, 4H), 0.92 (s, 1H), 0.09 (s, 9H). 13C NMR (126 MHz, C6D6) δ 160.6, 103.1, 70.5, 32.0, 24.4, 21.7, -3.00. 622 Synthesis of 3-methyl-2-methylene-1-(triethylsilyl)butan-1-ol (5.1f) and (E)-4-methyl-1- (triethylsilyl)pent-2-en-1-ol (5.3) Following general procedure B, a solution of 3-methyl-2-methylenebutan-1-ol 5.9e and (E)- 4-methylpent-2-en-1-ol 5.10e (4.01 g, 40 mmol, 1 equiv.) in THF (80 mL) was cooled to −78 °C. n-BuLi (2.5 M in hexanes, 19.2 mL, 48 mmol, 1.2 equiv.) was added dropwise and the mixture stirred at –78 °C for 1 h. Chlorotriethylsilane (8.4 mL, 50 mmol, 1.25 equiv.) was then added slowly from a syringe and the resulting mixture was stirred at –78 °C to room temperature for 18 hours resulting in the formation of a white suspension. The mixture was cooled back to –78 °C followed by dropwise addition of sec-butyllithium (1.4 M in cyclohexane, 39.3 mL, 55 mmol, 1.38 equiv.) and the reaction stirred for an additional 2 hours at –78 °C to –30 °C. The reaction mixture was cooled back to –78 °C and quenched by the addition of aqueous NH4Cl and diluted with Et2O, and the mixture was warmed to room temperature. After the layers were separated, the aqueous phase was washed with Et2O (3 × 20 mL). Then all the organic phases were combined, washed with H2O (20 mL) and brine (20 mL) respectively, and dried over anhydrous MgSO4. After filtration and concentration, the residue was purified by column chromatography (15% Et2O in hexanes) to afford a colorless liquid 4037 mg, 18.8 mmol (47% isolated yield) of compounds 5.1f and 5.3 as 2:1 mixture. This mixture was further purified by column chromatography (2.5% Et2O in hexanes) to afford both compound 5.1f and 5.3 as pure compounds. Spectroscopic data of 5.1f in C6D6: 1H NMR (500 MHz, C6D6) δ 4.99 (dd, J = 1.6, 1.0 Hz, 1H), 4.83 (q, J = 1.0 Hz, 1H), 3.94 (t, J = 1.3 Hz, 1H), 1.91 (heptd, J = 6.8 Hz, 1H), 1.08 – 1.01 623 (m, 12H), 1.00 (d, J = 6.8 Hz, 3H), 0.95 (s, 1H), 0.74 – 0.60 (mq 6H). 13C NMR (126 MHz, C6D6) δ 161.0, 103.3, 68.8, 31.7, 24.4, 21.9, 8.2, 2.8. Spectroscopic data of 5.1f in CDCl3 stored over K2CO3: 1H NMR (500 MHz, CDCl3) δ 4.90 (dd, J = 1.6, 0.9 Hz, 1H), 4.83 (q, J = 0.9 Hz, 1H), 4.04 (t, J = 1.2 Hz, 1H), 1.94 (heptd, J = 6.8, 1.0 Hz, 1H), 1.21 (s, 1H), 1.09 (d, J = 6.8 Hz, 3H), 1.05 (d, J = 6.8 Hz, 3H), 0.98 (t, J = 8.0 Hz, 9H), 0.62 (qd, J = 7.9, 3.0 Hz, 6H). 13C NMR (126 MHz, CDCl3) δ 160.1, 102.7, 68.3, 31.2, 23.9, 21.2, 7.5, 1.9. Spectroscopic data of 5.3: 1H NMR (500 MHz, CDCl3) δ 5.58 (ddd, J = 15.4, 6.7, 1.2 Hz, 1H), 5.45 (ddd, J = 15.4, 6.6, 1.6 Hz, 1H), 4.06 (ddd, J = 6.6, 1.6, 0.9 Hz, 1H), 2.29 (dqt, J = 13.4, 6.7, 1.1 Hz, 1H), 1.25 (s, 1H), 1.03 – 0.91 (m, 18H), 0.59 (qd, J = 8.0, 1.7 Hz, 6H). 13 C NMR (126 MHz, CDCl3) δ 134.1, 128.8, 66.7, 31.0, 22.6, 7.4, 1.6. Synthesis of 3-methyl-2-methylene-1-(triethylsilyl)butan-1-ol (5.1g) and (E)-4-methyl-1-(triethylsilyl)pent-2-en-1-ol (5.14) Following general procedure B, to a 50 mL round bottom flask was weighed 600 mg of (E)- 2-methylbut-2-en-1-ol 5.9g 66% W/W with but-2-yn-1-ol (a total of 7.51 mmol, 1 equiv). 20 mL of freshly distilled THF was added to the flask, purged with nitrogen and the solution was cooled to −78 °C. n-BuLi (2.4 M in hexanes, 3.75 mL, 9.0 mmol, 1.2 equiv.) was added dropwise and the mixture stirred at –78 °C for 1 h. Chlorotriethylsilane (1.4 mL, 8.3 mmol, 1.1 equiv.) was then added slowly from a syringe and the resulting mixture was stirred at –78 °C to room temperature 624 for 18 hours resulting in the formation of a white suspension. The mixture was cooled back to –78 °C followed by dropwise addition of sec-butyllithium (1.4 M in cyclohexane, 6.4 mL, 9 mmol, 1.2 equiv.) and the reaction stirred for an additional 2 hours at –78 °C to –30 °C. The reaction mixture was cooled back to –78 °C and quenched by the addition of aqueous NH4Cl and diluted with Et2O, and the mixture was warmed to room temperature. After the layers were separated, the aqueous phase was washed with Et2O (3 × 20 mL). Then all the organic phases were combined, washed with H2O (20 mL) and brine (20 mL) respectively, and dried over anhydrous MgSO 4. After filtration and concentration, the residue was purified by column chromatography (10% Et2O in hexanes) to afford 463 mg, 2.31 mmol of 5.1g (50% based on starting alcohol 5.10g) and 102 mg, 0.55 mmol of 5.14 (19% based on starting propargyl alcohol) as colorless liquids. Spectroscopic data of 5.1g: 1H NMR (500 MHz, C6D6) δ 5.31 (qt, J = 6.7, 1.3 Hz, 1H), 3.81 (s, 1H), 1.56 (dt, J = 6.7, 1.3 Hz, 3H), 1.53 (s, 3H), 1.04 (t, J = 7.9 Hz, 9H), 0.86 (s, 1H), 0.65 (qq, J = 16.0, 7.9 Hz, 6H). 13 C NMR (126 MHz, C6D6) δ 140.0, 116.1, 71.5, 14.9, 13.5, 8.2, 3.0. Spectroscopic data for 5.14: 1H NMR (500 MHz, CDCl3) δ 4.17 (q, J = 2.7 Hz, 1H), 1.86 (d, J = 2.5 Hz, 3H), 1.42 (s, 1H), 1.00 (t, J = 8.0 Hz, 9H), 0.68 (q, J = 8.0 Hz, 6H). 13C NMR (126 MHz, CDCl3) δ 83.8, 79.8, 54.6, 7.3, 3.8, 1.6. 4.7.3. The [1,2]-carbon to carbon silyl migration: general procedure C Alcohol 5.1 was dissolved in CDCl3 and the solution transferred into NMR tube. The reaction in the NMR tube was monitored by NMR analysis until over 90% conversion had been achieved, 625 obtaining aldehyde 5.2. Synthesis of 2-methyl-2-(trimethylsilyl)propanal (5.2a) Aldehyde 5.2a was synthesized from alcohol 4.3b following general procedure C in 97% conversion after 12 hours: 1H NMR (500 MHz, CDCl3) δ 9.56 (s, 1H), 1.19 (s, 6H), 0.06 (s, 9H). 13 C NMR (126 MHz, CDCl3) δ 206.8, 42.1, 17.3, -4.2. Synthesis of 2-methyl-2-(triethylsilyl)propanal (5.2b) Aldehyde 5.2b was synthesized from alcohol 5.1b following general procedure C in 92% conversion after 48 hours: 1H NMR (500 MHz, CDCl3) δ 9.59 (s, 1H), 1.21 (s, 6H), 0.97 (t, J = 7.9 Hz, 9H), 0.65 (q, J = 7.9 Hz, 6H). 13C NMR (126 MHz, CDCl3) δ 206.3, 43.0, 18.2, 7.7, 1.8. Synthesis of 2-methyl-2-(tripropylsilyl)propanal (5.2c) Aldehyde 5.2c was synthesized from alcohol 5.1c following general procedure C in 95% conversion after 72 hours: 1H NMR (500 MHz, CDCl3) δ 9.56 (s, 1H), 1.38 – 1.27 (m, 6H), 1.19 (s, 6H), 0.95 (t, J = 7.2 Hz, 9H), 0.64 – 0.58 (m, 6H). 13C NMR (126 MHz, CDCl3) δ 206.4, 42.8, 626 18.7, 18.3, 17.6, 13.5. Synthesis of 2-methyl-2-(methyldiphenylsilyl)propanal (5.2d) Aldehyde 5.2d was synthesized from alcohol 5.1d following general procedure C in 97% conversion after 96 hours: 1H NMR (500 MHz, CDCl3) δ 9.64 (s, 1H), 7.64 – 7.59 (m, 4H), 7.46 – 7.38 (m, 6H), 1.32 (s, 6H), 0.70 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 206.7, 135.2, 133.2, 129.8, 128.0, 41.9, 18.5, -6.3. Synthesis of 2,3-dimethyl-2-(trimethylsilyl)butanal (5.2e) Aldehyde 5.2e was synthesized from alcohol 5.1e following general procedure C in 95% conversion after 24 hours. NMR analysis was done on a mixture of 5.1e:5.2e (1.4:1) 1H NMR (500 MHz, CDCl3) δ 9.53 (s, 1H), 4.85 (dt, J = 1.5, 0.8 Hz, 1H), 4.83 (q, J = 0.9 Hz, 1H), 3.90 (s, 1H), 2.53 (hept, J = 6.8 Hz, 1H), 1.94 (h, J = 6.8 Hz, 1H), 1.27 (s, 2H), 1.10 – 1.02 (m, 12H), 1.00 (d, J = 7.0 Hz, 4H), 0.85 (d, J = 6.9 Hz, 3H), 0.08 (s, 9H), 0.05 (s, 9H). 13C NMR (126 MHz, CDCl3) δ 207.0, 160.1, 102.5, 70.2, 50.9, 31.5, 29.4, 23.8, 21.0, 19.6, 19.2, 8.8, -2.3, -3.6. 627 Synthesis of 2,3-dimethyl-2-(triethylsilyl)butanal (5.2f) Aldehyde 5.2f was synthesized from alcohol 5.1f following general procedure C in 100% conversion after 72 hours: 1H NMR (500 MHz, CDCl3) δ 9.56 (s, 1H), 2.50 (hept, J = 6.9 Hz, 1H), 1.04 (s, 3H), 1.00 (d, J = 7.0 Hz, 3H), 0.96 (t, J = 7.9 Hz, 9H), 0.82 (d, J = 6.8 Hz, 3H), 0.66 (qd, J = 7.9, 3.4 Hz, 6H). 13C NMR (126 MHz, CDCl3) δ 206.1, 52.3, 29.5, 19.6, 19.4, 9.4, 7.8, 3.0. 29 Si NMR (99 MHz, CDCl3) δ 8.71. Synthesis of 2-methyl-2-(triethylsilyl)butanal (5.2g) Aldehyde 5.2g was synthesized from alcohol 5.1g following general procedure C in 100% conversion after 144 hours: 1H NMR (500 MHz, CDCl3) δ 9.57 (s, 1H), 2.16 (dq, J = 13.9, 7.0 Hz, 1H), 1.53 (dq, J = 14.7, 7.4 Hz, 1H), 1.15 (s, 3H), 0.96 (t, J = 7.9 Hz, 9H), 0.82 (t, J = 7.4 Hz, 3H), 0.64 (q, J = 8.1 Hz, 6H). 13C NMR (126 MHz, CDCl3) δ 206.5, 48.3, 24.5, 13.2, 9.9, 7.7, 1.8. 5.8.4. Synthesis of enantioenriched 5.1f Compound 5.1f* was synthesized from 5.1f in two steps as indicated on scheme 5.9. 628 Synthesis of 3-methyl-2-methylene-1-(triethylsilyl)butan-1-one (5.4f) Following a reported procedure; a dry 100 mL round bottom flask fitted with a magnetic stir bar was sealed with a rubber septum and cooled under nitrogen. 25 mL of dry DCM was then added to the flask via syringe followed by 1.04 mL trifluoroacetic anhydride (7.5 mmmol, 1.5 equiv). The mixture was cooled on a dry ice-acetone bath to –78 °C followed by dropwise addition of 0.71 mL of DMSO (10 mmol, 2.0 equiv). After complete addition of DMSO, the resulting mixture was stirred at –78 °C for additional 30 minutes after which a solution of α- hydroxyallylsilane 5.1f 1072.1 mg in dry DCM (5.0 mmol, 1.0 equiv) was added dropwise and resulting solution stirred at –78 °C for one hour. This was followed by slow addition of 2.09 mL of freshly distilled triethylamine (15 mmol, 3.0 equiv) and the resulting mixture stirred at –78 °C for another one hour. The reaction mixture was quenched with water and allowed to warm up slowly to room temperature. The layers were separated and the aqueous phase was extracted twice with DCM. The combined organic phases were dried over anhydrous magnesium sulfate filtered and concentrated in vacuo followed by column chromatography (5% EtOAc in hexanes) to afford 722 mg, 3.4 mmol (68% isolated yield) of 5.4f as a colorless oil and 95 mg of 5.1f (9% recovery). Spectroscopic data for 5.4f: 1H NMR (500 MHz, CDCl3) δ 5.94 (d, J = 1.2 Hz, 1H), 5.88 (s, 1H), 2.83 (hept, J = 6.9, 1.2 Hz, 1H), 0.98 – 0.89 (m, 15H), 0.76 (qd, J = 7.8, 1.1 Hz, 6H). 13C NMR (126 MHz, CDCl3) δ 237.9, 161.5, 124.7, 26.1, 21.6, 7.3, 3.8. 29Si NMR (99 MHz, CDCl3) δ -0.88. 629 Synthesis of (S)-3-methyl-2-methylene-1-(triethylsilyl)butan-1-ol (5.1f*) Following a reported procedure,58 to a solution of 659 mg 5.4f (3.1 mmol, 1.0 equiv) in 10 mL of freshly distilled anhydrous THF was added 2 g of 4Å molecular sieves at room temperature under nitrogen atmosphere and the mixture stirred at room temperature for 2 h. To the mixture was added 4.3 g (R)-CBS as a solution in 5 mL dry THF 5(15.5 mmol, 5.0 equiv) and reaction mixture was cooled to –30 °C and stirred at this temperature for 10 min. This was followed by dropwise dropwise addition of 1.5 mL BH3•SMe2 (15.5 mmol, 5.0 equiv) at –30 °C. The resulting mixture was stirred at –30 °C for 15 min, quenched with MeOH and saturated NH4Cl, and extracted with Et2O (20 mL x 2). The combined organic layers were washed with brine, dried over MgSO4, and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (30% Et2O in hexanes) to give 165 mg, 0.78 mmol of 5.1f* (25% isolated yield) as a colorless oil. The optical purity and absolute configuration of 5.1f* were not determined experimentally but compared to similar structures in the literature. 58 The other spectral data were identical with those of 5.1f. Synthesis of 2,3-dimethyl-2-(triethylsilyl)butanal (5.2f*?) 630 Aldehyde 5.2f*? was synthesized from alcohol 5.1f* following general procedure C in 100% conversion after 72 hours: Spectroscopic data was identical to those of 5.2f. Attempted derivatization of 5.2f*?: Synthesis of (E)-1-(2,3-dimethylbutylidene)-2-(2,4- dinitrophenyl)hydrazine Compound 5.6 was synthesized following the same procedure for the synthesis of 3.16 in Chapter 3. Spectroscopic data for 5.6: 1H NMR (500 MHz, CDCl3) δ 11.00 (s, 1H), 9.11 (d, J = 2.6 Hz, 1H), 8.29 (ddd, J = 9.6, 2.6, 0.8 Hz, 1H), 7.93 (d, J = 9.6 Hz, 1H), 7.46 (dd, J = 6.1, 0.7 Hz, 1H), 2.41 (h, J = 7.0 Hz, 1H), 1.90 – 1.78 (m, J = 6.8 Hz, 1H), 1.16 (d, J = 6.8 Hz, 3H), 0.98 (d, J = 2.7 Hz, 3H), 0.97 (d, J = 2.7 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 156.3, 145.2, 137.6, 129.9, 128.7, 123.5, 116.6, 43.0, 31.6, 20.1, 19.5, 14.3. Compound 5.6 is known.59 Synthesis of trimethyl((2-phenylallyl)oxy)silane (5.7) To a 100 mL round bottom flask was weighed 1342 mg ally alcohol 5.9h (10 mmol, 1.0 equiv) and 50 mL of dry THF added. The flask was sealed with a rubber septum and purged with nitrogen. This was followed by addition of 0.89 mL of pyridine (11 mmol, 1.1 equiv) and the resulting mixture stirred in dry THF for 5 minutes. This was followed by addition of 1.27 mL of TMSCl 631 (10 mmol, 1.0 equiv) and the resulting mixture stirred for an additional one hour at room temperature. The THF was removed by rotavap and the resulting residue diluted with hexanes. The mixture was filtered, and the filtrate was concentrated under reduced pressure to give the expected product. The product was further purified by column chromatography (10% EtOAc in hexanes) to give 2046 mg, 9.9 mmol (99% isolated yield) of 5.7. 1H NMR (500 MHz, CDCl3) δ 7.49 – 7.41 (m, 2H), 7.39 – 7.33 (m, 2H), 7.33 – 7.27 (m, 1H), 5.47 (q, J = 1.4 Hz, 1H), 5.41 (q, J = 1.7 Hz, 1H), 4.54 (t, J = 1.5 Hz, 2H), 0.19 (s, 9H). 13C NMR (126 MHz, CDCl3) δ 146.8, 139.0, 128.3, 127.6, 126.0, 111.9, 64.3. Spectroscopic data were in agreement with those reported in the literature.60 5.8.5. Unexpected SN2-like reactions: general procedure D To a 50 mL round bottom flask was added as a solution of 5.7 in 12 mL dry THF. The mixture was cooled to –78 °C then butyllithium was added dropwise resulting in a colored solution. The mixture was stirred at –78 °C for two hours then quenched with saturated ammonium chloride solution and diluted with 20 mL of ether 10 mL of water. The layers were separated and the aqueous layer was extracted with ether (20 mL X 3). Combined organics were washed with saturated ammonium chloride, water and brine respectively and then dried over anhydrous magnesium sulfate. Filtration and concentration gave the substitution product. 632 Synthesis of (4,4-dimethylpent-1-en-2-yl)benzene 5.8a Applying general procedure D to silyl ether 5.7 412.72 mg (2.0 mmol, 1.0 equiv) and 1.5 mL of tert-butyllithium (1.6 M in pentane, 2.4 mmol, 1.2 equiv), compound 5.8a was synthesized in quantitative yield: 1H NMR (500 MHz, CDCl3) δ 7.44 – 7.38 (m, 2H), 7.36 – 7.30 (m, 2H), 7.29 – 7.24 (m, 1H), 5.28 (d, J = 2.1 Hz, 1H), 5.05 (dd, J = 2.0, 0.9 Hz, 1H), 2.50 (s, 2H), 0.84 (s, 9H). 13 C NMR (126 MHz, CDCl3) δ 147.6, 143.7, 128.1, 126.9, 126.5, 116.3, 48.9, 31.7, 30.1. Spectroscopic data were in agreement with those reported in the literature.61 Synthesis of (4-methylhex-1-en-2-yl)benzene 5.8b Applying general procedure D to silyl ether 5.7 412.72 mg (2.0 mmol, 1.0 equiv) and 1.71 mL of sec-butyllithium (1.4 M in cyclohexane, 2.4 mmol, 1.2 equiv). After workup and column chromatography (1.5% EtOAc in hexanes), compound 5.8b was synthesized in 292.81 mg, 1.68 mmol (84% isolated yield): 1H NMR (500 MHz, CDCl3) δ 7.45 – 7.40 (m, 2H), 7.37 – 7.26 (m, 3H), 5.29 (d, J = 1.8 Hz, 1H), 5.06 (q, J = 1.2 Hz, 1H), 2.62 (ddd, J = 14.1, 5.8, 1.3 Hz, 1H), 2.25 (ddd, J = 14.0, 8.3, 1.0 Hz, 1H), 1.52 – 1.43 (m, 1H), 1.22 – 1.14 (m, 1H), 0.89 (t, J = 7.4 Hz, 3H), 0.85 (d, J = 6.6 Hz, 4H), 0.80 (ddd, J = 14.1, 7.0, 2.1 Hz, 1H). 13 C NMR (126 MHz, CDCl3) δ 147.8, 141.5, 128.2, 127.2, 126.3, 113.6, 43.0, 32.6, 29.4, 18.9, 11.3. Spectroscopic data were in 633 agreement with those reported in the literature.62 Synthesis of hept-1-en-2-ylbenzene 5.8c Applying general procedure D to silyl ether 5.7 412.72 mg (2.0 mmol, 1.0 equiv) and 1 mL of n-butyllithium (2.4 M in cyclohexane, 2.4 mmol, 1.2 equiv). After workup compound 5.8c and 5.9h as a mixture 100% conversion by NMR of the crude material: 1H NMR (500 MHz, CDCl3) δ 7.51 – 7.43 (m, 4H), 7.42 – 7.28 (m, 6H), 5.51 (q, J = 1.0 Hz, 1H), 5.38 (q, J = 1.4 Hz, 1H), 5.31 (d, J = 1.5 Hz, 1H), 5.10 (q, J = 1.4 Hz, 1H), 4.56 (dd, J = 1.6, 0.9 Hz, 2H), 2.57 – 2.50 (m, 1H), 1.91 (s, 1H), 1.55 – 1.44 (m, 2H), 1.43 – 1.31 (m, 4H), 0.98 – 0.86 (m, 4H). 13C NMR (126 MHz, CDCl3) δ 148.7, 147.2, 141.4, 138.4, 128.5, 128.2, 127.9, 127.2, 126.0, 126.0, 112.5, 111.9, 64.9, 35.3, 31.5, 27.9, 22.4, 14.0. Spectroscopic data of 5.8c were in agreement with those reported in the literature.63 634 REFERENCES (1) Brook, A. G. Isomerism of some α-hydroxysilanes to silyl ethers. J. Am. 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Nickel-catalyzed enantioselective hydrovinylation of silyl-protected allylic alcohols: An efficient access to homoallylic alcohols with a chiral quaternary center. Sci. China Chem. 2010, 53, 1899. (61) Chen, H.; Jia, X.; Yu, Y.; Qian, Q.; Gong, H. Nickel-catalyzed reductive allylation of tertiary alkyl halides with allylic carbonates. Angew. Chem. Int. Ed. 2017, 129, 13103. (62) Chen, X.; Luo, X.; Wang, P. Electrochemical-induced radical allylation via the fragmentation of alkyl 1,4-dihydropyridines. Tetrahedron Lett. 2022. 91, 153646. (63) Lu, P.; Ren, X.; Xu, H.; Lu, D.; Sun, Y.; Lu, Z. Iron-catalyzed highly enantioselective hydrogenation of alkenes. J. Am. Chem. Soc. 2021, 143, 12433. 639 APPENDIX Copies of NMR spectra 640 641 642 643 644 645 646 647 648 649 650 651 652 653 654 655 656 657 658 659 660 661 662 663 664 665 666 667 668 669 670 671 672 673 674 675 676 677 678 679 680 681 682 683 684 685 686 687 688 689 690 691 692 693 694 695 CHAPTER 6. FUTURE WORK 6.1. Future work on Wittig rearrangements 6.1.1. Wittig rearrangement on a contracted ring So far, we have seen the Wittig rearrangement of dihydropyrans and tetrahydrooxepins whereby regioselectivity is controlled by having a silyl group either at the 2- or 4-position.The future work on Wittig rearrangements will entail reducing the ring system to 2-silyl-2,5- dihydrofuran 6.1. This might lead to formation of 2-silylcyclobutenols 6.2 via [1,2]-Wittig rearrangement and/or the two ring opened products 6.3 and 6.4 (Scheme 6.1). Scheme 6.1: Proposed Wittig rearrangement of 2-silyl-2,5-dihydrofuran The above transformation has not been able to be accomplished due to difficulties in accessing the dihydrofuran via ring closing metathesis. This problem was solved in 2005 by Grubbs (Hong, S. H.; Sanders, D. P.; Lee, C. W.; Grubbs, R. H. Prevention of undesirable isomerization during olefin metathesis. J. Am. Chem. Soc. 2005, 127, 17160). 6.1.2. Use of other heteroatoms on Wittig rearrangement All the Wittig rearrangements discussed in this dissertation use oxygen as the heteroatom. The future work will involve the use of other atoms in place of oxygen (Scheme 6.2). 696 Scheme 6.2: Proposed Wittig rearrangement on a six-member ring with other heteroatoms 6.2. Future Work on silyl migrations For silyl migrations, future work will involve use of other electrophiles apart from m-CPBA (Scheme 6.3a). For the acid catalyzed silyl migration, future work will entail the use of Lewis acid (Scheme 6.3b). Lastly, for the unusual SN2-like reaction, the future work will involve expanding the substrate scope by modifying the aromatic ring and/or use of other alkyl/aryl lithiums in place of butyllithiums (Scheme 6.3c). Scheme 6.3: Future work on silyl migrations 697