k PLACE IN RETURN BOX to remove this checkout from your record. TO AVOID FINES return on or before date due. Mkh‘flan State fix LIBRARY University V—fi * MSU In An Affirmative Action/Equal Opportunity Institution amnion l INTRAMOLECULAR PHOTOCYCLOADDITION OF 5-(P-ACETYLPHENYL)-1-PENTENES By Hadi Alehashem A DISSERTATION submitted to Michigan State University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Department of Chemistry 1992 ABSTRACT by Hadi Alehashem INTRAMOLECULAR PHOTOCYCLOADDITION OF 5-(p-ACETYLPHENYL)-1- PENTENES One of the major challenges in organic chemistry is the construction of eight-membered ring systems. These ring systems form the main skeleton of a variety of natural products. These products are usually prepared through multistep reactions which make their synthesis inconvenient. Simplified methods have been pursued by many chemists. Intramolecular photocycloadditions of p-substituted acetophenones in which a double bond is attached to the aromatic ring by a trimethylene chain were studied. The eight membered-rings obtained from this precursor have an all carbon skeleton, as required for a variety of natural products. The effect of a methylene group in place of an oxygen atom on the photoaddition and the nature of the photoproducts was also of interest. All irradiations were done with a Pyrex-filtered medium pressure mercury arc, so all wavelengths above 290 nm were available. Usually two isomeric photoproducts were identified from each ketone. One set was identified as derivatives of 4-trifluoroacetyI-cis-anti-tricyclo[6.3.0.01-8]undeca-2,5-diene and the other as derivatives of 4-trifluoroacetyl-cis-anti—tricyclo [6.3.0.035] undeca- 1,4-diene. The [2+2] ortho-photocycloaddition described in this thesis involves the rut“ triplet excited state of benzene‘. Two intermediates are involved in these reactions. An initial photocycloadduct, cyclohexadiene, is in thermal equilibrium with the corresponding cyclooctatriene? The cyclooctatriene then reacts photochemically to give the linear and the angular photoproducts. The angular photOproduct can undergo thermal rearrangements when heated in toluene or methanol. ln toluene, it undergoes a Cope rearrangement to form a product which is an epimer of the linear photoproduct. This diastereomeric product was identified as 4-trifluoroacetyl-cis-syn-tricyclo [6.3.0.03-6] undeca-1,4-diene. ln methanol at 50°C the angular photoproduct transforms to the 9-trifluoroacetyl- cis-antlltricyclo[6.3.0.01-7]undeca-8,1O-diene, presumably through the formation of cyclooctatriene. When irradiated this cyclohexadiene transforms to the angular and linear photoproducts as well as the starting ketone. This finding led to a better understanding of the overall mechanism of intramolecular photocycloaddition reactions. Finally, the stereochemistry of all photoproducts and their thermally rearranged products were studied by NOE. All photo and thermally rearranged products have cis cyclobutene rings. The structures of the linear photoproducts have the cyclobutene rings syn to the bridgehead group R3 (H or CH3), while in the thermally rearranged products the cyclobutene rings are anti to R3 (H or CH3). The angular photOproducts have the cyclobutene rings syn to the bridgehead R5 (H or CH3) group. ACKNOWLEDGMENT I wish to thank Professor Peter J. Wagner for his guidance, encouragement, financial support, and, most importantly, his friendship throughout the course of my graduate career. I would also like to thank my colleagues, friends, and the faculties of the chemistry department who made my stay at MSU an enjoyable one. Financial assistance and facilities prepared by the department of chemistry and from NSF and NIH awarded to Professor Wagner are also acknowledged. I would like to thank Professor Famum for critically reading the manscript. Finally, I would like to thank my wife and family for their encouragements and support. Table of Contents Chapter Page List of Tables Vlll List of Figures X List of Schemes Xlll Introduction 1 Results 23 Preparation of Ketones 23 Photocycloaddition 26 Photoproducts from 3-[4-(a, a, a—trifluoroacetyl)benzyloxy] propene (F011) 26 Chemical Yield Calculation of F011 29 Photoproducts from 3-[4-(a, a, a-trifluoroacetyI)benzyloxy]- 2-methyl propene(FO12) 30 Photoproducts from 3-[4-(0. a. a-trifluoroacetyl)benzyloxy]- 3-methyl-1-butene (F021) 35 Photolysis of 4-[4-(a,a,a-trifluoroacetyl)benzyloxy]-2methyl- 2-butene (F013) 43 Photolysis of 5-[4-(a, a, a-trifluoroacetylphenyl)]-1-pentene (FC11) 43 Photolysis of 5-(4-acetylphenyl)-1-pentene (A011) -------- 46 Photoproducts from 5-(4-acetyl-2-methoxyphenyl)-1- pentene (3-MOAC11) 49 meta-Photocycloadditions 52 meta-Photocycloaddition of 3-(p-acetylbenzyloxy)propene (A011) 52 meta-Photocycloaddition of 5-(4-acetylphenyI)-1-pentene (M311) 54 Thermal Rearrangements 58 Photolysis of Cyclohexadiene 76 NMR tube quantum yield of cyclohexadiene 79 Structural considerations 85 Vicinal Coupling Constants 87 Kinetic Results 38 Stern-Volmer quenching plots 38 Triplet Lifetime 88 Quantum Yield 88 Discussion 97 Stmctural considerations 97 Stereochemistries 99 Coupling Constants 105 Correlations between the %E and internuclear distances ------ 112 Alternative structures 124 1H NMR and chemical shifts of Geminal hydrogens of photoproducts and thermally rearranged products 124 Photochemistry 130 [2+2] ortho-photocycloaddition 130 Linear vs. angular photoproducts ' 132 meta-Photocycloaddition 1 34 Thermal Rearrangement 137 Cope rearrangement vs. cyclooctatriene formation ----- 140 Regioselectivity 1 40 VI Kinetic 1 41 Chemical yields 142 Quantum yield 143 Synthetic Application of Products from [2+2]-o-Photocycloaddition--147 Experimental 1 49 Purification and Preparation of Chemicals 149 Solvent and Additives 149 Internal Standards 1 5O Quenchers 150 Spectroscopic Data 150 Ketones 152 Photolysis Procedure 166 Glassware 166 Preparation of Solutions for Quenching Study ----------- 166 Degassing of Solutions 166 Irradiation of Ketones 167 NMR tube irradiation 167 Thermal Transformation . 168 Analysis 168 Response Factors 168 Quantum Yield Calculation 169 Chemical Yield Calculation 169 Molecular Mechanics Calculation 170 Appendix 194 Bibliography 225 VII Table 1 . 99.9991 11. 12. 13. 14. 15. 16. 17. 18. 19. List of Tables Page Chemical Yields of Photoproducts of 3-[4-(a, a, a-trifluoroacetyl) benzyloxylpropene (F011) 29 Chemical Yields of Photoproducts of 3-[4-(a, a, a-trifluoroacetyl) benzyloxyl-z-methyl propene (F012) 35 Chemical Yields of Photoproducts of 3-[4-(a, a, a-trifluoroacetyl) benzyloxy1-3-methyl-1 -butene (F021 ) 42 Chemical Yields of Photoproducts of 5-[4-(a, a, a-trifluoro acetylphenyl)]-1 -pentene (F01 1) 46 Quantum Weld of Photolysis of Cyclohexadiene at 290 nm------79 Quantum Weld of Photolysis of Cyclohexadiene at 334 nm ------ 80 th and Quantum Yields of Photoproducts 95 UV-Visible absorption Data for Ketones 96 Summary of NOE experiments of LFO11 and TAFO11-----------101 Summary of NOE experiments of LFO12 and TAFO12 ---------- 102 Summary of NOE experiments of LF021 and TAFOz1 --------- 102 Summary of NOE experiments of LFC11 and TAFC11 ---------- 103 Summary of NOE experiments of LAC11 103 Summary of NOE experiments of AFO11, AFO12 and AF021 104 Vicinal coupling constants 105 %NOE and internuclear distances 112 Minimized energies 95 Response Factors for Ketone F011 and Its Photoproducts ------ 197 Response Factors for Ketone F012 and Its Photoproducts ------- 199 VIII 20. 21 . 22. 23. 24. 25. 26. 27. 28. 29. 30. 31 . 32. 33. 34. 35. Response Factors for Ketone F021 and Its Photoproducts----200 Response Factors for Ketone F011 and Its Photoproducts---202 Response Factors for Ketone A011 and Its Photoproducts-«204 Response Factors for Ketone AC11 and Its Photoproducts-«205 206 Response Factor of o-methylvalerophenone Data of Quenching Study of Ketone F011 207 Data of Quenching Study of Ketone F012— Data of Quenching Study of Ketone F021 Data of Quenching Study of Ketone FC11 209 211 213 216 Data of Quenching Study of Ketone A011 218 Data of Quenching Study of Ketone AC11 Data of Chemical Yield Measurement of F021 Data of Chemical Yield Measurement of F011 Data of Chemical Yield Measurement of F012 Data of Chemical Yield Measurement of FC11 response Factors for Various Ketones and Their 220 221 222 223 224 Photoproducts List of Figures Figure P399 1. Homodecoupling Experiments of 9-trifluoroacetyl-cis-anri-3- oxatricyclo[7.2.0.01-5]undeca-7, 10-diene (AFO11) in CDCl3---------31 2. Homodecoupling Experiments of 10-trifluoroacetyl-cis-anti-S- oxatricyclo[7.2.0.03-7]undeca-7, 10—diene (LFO11) in CDCl3---------32 3. Homodecoupling Experiments of 5-methyl-9-trifluoroacetyl-cis-anti- 3-oxatricyclo[7.2.0.01v5]undeca-7, 10-diene (AFO12) in CDCI3 ------ 36 4. Homodecoupling Experiments of 3-methyI-10-trifluoroacetyl-cis-anti- 5-oxatricyclo[7.2.0.03.7]undeca-7, 10-diene (LFO12) in 0606 ------- 37 5. NOE Experiment of 5—methyl-9-trifluoroacetyl-cis-anti-a- oxatricyclo[7.2.0.01-5]undeca-7, 10-diene (AFO12) in CDCI3 -------- 38 6. NOE Experiment of 3-methyI-10-trifluoroacetyl-cis-anti-5- oxatricyclo[7.2.0.03-7]undeca-7, 10—diene (LFO12) in CDCl3-------39 7. Homodecoupling Experiments of 10-trifluoroacetyl-cis-anti-tricyclo [7.2.0.03-71undeca-7, 10-diene (LFC11) in CDCI3 47 8. Homodecoupling Experiments of 10-acetyl-cis-antlltricyclo [7.2.0.03-71undeca-7, 10-diene (LAC11) in CDCI3 50 9. NOE Experiment of 1O-acetyl-cis-antrltricyclope.0.03-7] undeca-7, IO-diene (LAC11) in CDCI3 51 10. Homodecoupling Experiments of 10-oxa-acetyl, tetracyclo [6.3.0.01-5.04-5]undeca-2-ene (MAO11) in 0605 55 11. Homodecoupling Experiments of 9-oxa-1-acetyl, tetracyclo [5.3.1 .01-5.O4-1 1]undeca-2-ene (RMAO11) in 0506 56 12. DEPT Experiments of RMAO11 in C6D5 57 13. 14. 15. 16. 17. 18 19. 20. 21. 22. 23. 1H NMR of 10-trifluoroacetyl-cis-antrl5-oxatricyclo[7.2.0.03-7] undeca-7, 10-diene (LFO11) and 10-trifluoro-cis-syn-5- oxatricyclo [7.2.0.03v7lundeca-7, 10-diene (TAFO11) in CDCl3----61 1H NMR of 3-methyl-10-trifluoroacetyl-cis-anti-5- oxatricyclo[7.2.0.03-7]undeca-7, 10-diene (LFO12) and 3- methy l-1 0-tn'fluoroacetyl-Qis-syn-S-oxatricyclow.2.0.03-7] undeca-7, 10-diene (‘I'AFO12) in 0506 63 Homodecoupling Experiments of 4,4—dimethyl-10-trifluoroacetyl-cis- syn-5-oxatricyclo[7.2.0.03-7]undeca-7. 10—diene (T AFO12) in CDCI3 64 NOE Experiments of TAFO12 in CsDe 65 1H NMR of 4,4-dimethyl-10-trifluoroacetyl-cis-ant135- oxatricyclo[7.2.0.03-7]undeca-7, 10-diene (LFOz1) and 4,4-dimethyl-1 0-trifluoroacetyl-cis-syn-5-oxatricyclo[7.2.0.03-7] undeca-7, 10-diene (1' AFOz1) in CDCls 68 1H NMR of 10-tn’fluoroacetyI-cis-anti-tricyclo[7.2.0.03.7] undeca-7, 10-diene (LFC11) and 10-trifluoroacetyl-cis-syn- tricyclo[7.2.0.03-7]undeca-7, 10-diene (T AFC11) in CDCla ----------- 71 Homodecoupling Experiments of 10-trifluoroacetyl-cis-syn-tricyclo- [7.2.0.03-71undeca-7, 10-diene (T AFC11) in 0506 72 NOE Experiment of 10-tn'fluoroacetyl-cis-syn-tricyclo[7.2.0.03-7] undeca-7, 10-diene (TAFC11) in CeDs 73 Homodecoupling Experiments of 9-trifluoroacetyI-cis-tricyclo [6.3.0.01-71undeca-8, 10-diene (CFC11) in CDCls 77 NOE Experiment of 9-trifluoroacetyl-cis-tricyclo[6.3.0.01-7] undeca-8, 10-diene (CFC11) in CDCI3 78 1H NMR's pf photolysis of CFC11 at >290 nm 81 XI 24. 25. 26. 27. 28. 29. 30. 31. 32. 1H NMR's of photolysis of CFC11 at >334 nm 82 UV-Visible Spectrum of Cyclohexadiene CFC11 in Benzene ------ 83 UV-Visible Spectrum of Acetophenone in Benzene 84 Stern-Volmer Plots of Quenching of 3-[4-(0t, a, a-trifluoroacetyl) benzyloxy]propene (F011) 89 Stern-Volmer plots of Quenching of 3-[4-(a. a. a-trifluoroacetyl) benzyloxy]-2-methyl propene (F012) 90 Stern-Volmer plots of Quenching of 3-[4-(a, a, a-trifluoroacetyl) benzyloxy]-3-methyl-1 -butene (F021) 91 Stern-Volmer Plots of Quenching of 3-(4-acetylbenzyloxy)propene (A011) 92 Stern-Volmer Plots of Quenching of 5-[4-(a, a, a-trifluoroacetyl phenyl)]-1 -propene (F01 1) 93 Stern-Volmer Plots of Quenching of 5-(4-acetylphenyl)-1-pentene (AC11) 94 33-38. Correlations between %E and internuclear distances for: LFO‘1 and AF011 115 LF012 and AF012 116 LFO21 and AF021 117 LFC11 and LAC11 118 TAFO11 and TAF012 119 TAF021 and TAFC11 ' 120 XII List of Schemes Scheme 1. PPNPS’IESPP 10. Results of NOE Experiments of CAFC11 Results of NOE Experiments of LF011 and AF011 Page 28 Results of NOE Experiments of LF012 and AF012 Results of NOE Experiments of LFO21 and AF021 34 41 Results of NOE Experiments of LFC11 Results of NOE Experiments of LAC11 45 49 Results of NOE Experiments of TAFO11 59 Results of NOE Experiments of TAFO12 Results of NOE Experiments of TAF021 57 Results of NOE Experiments of TAFC11 70 75 XIII INTRODUCTION Benzene rings can undergo efficient intramolecular photocycloaddition to double bonds when the two groups are separated by three atom tethers.“6 Fused ring systems obtained from these reactions have found utility in natural products synthesis].8 The benzene ring of a phenyl ketone can also undergo intramolecular [2+2] ortho photocycloaddition to the double bonds tethered ortho or para to the acyl group‘. This reaction involves the n, 16" triplet excited state of aromatic ketones.1 The bicyclooctadienes obtained in these reactions can undergo thermal transformation into a cyclooctatriene ring}.2 Eight-membered rings form the main skeleton of a variety of natural products.9 This new approach could provide a route to the synthesis of these natural products. Most of the earlier studies used ketones where the alkenes were attached to the aromatic ring by an oxygen atom. Since most of the natural products have mainly carbon skeletons, we chose to study the intramolecular reaction of phenyl ketone with alkenes utilizing only carbon tethers. I .uo: . lo: 1.:03009; 0.0.0.0 -eu.'-".o:| In studying the intramolecular quenching of m" triplets of phenyl alkyl ketones, Wagner and Nahm1-2 investigated ketones 1a and b. o RJ‘O-(Cth—CH =cr-I2 1: (a): R=CH3. (b): R: C4H9 In so doing, they discovered that an intramolecular CT interaction between the triplet excited state benzene and the double bond leads to the formation of photoproduct 2 (equation 1).1.2 In fact cyclohexadiene 3 was the first [2+2] photocycloadduct formed which then rearranged to cyclooctatriene 4 (equation 2). Photoproduct 2 was the result of secondary photolysis of cyclooctatriene 4. Formation of bicyclooctadiene 2 from cyclooctatriene 4 was demonstrated by photolysis of 4 which was the product of thermal ring opening 0 Kc???) fi. <1) 2 1a 250°C 3 4 of 2.1.2 The o-alkenoxyphenyl ketone 5 as well as its p-isomer undergo intramolecular [2+2] photocycloaddition as shown in equation 3. H3C 0 O A O 0" TC” h” @ ‘83 (a) 0 o m, O o 6 5 The bicyclooctadiene was transformed to all-cis cyclooctatriene 6 upon heating. Since the bicyclooctadiene has a cis- ring fusion, its thermal transformation to cyclooctatriene 6 was not a concerted electrocyclic reaction. Wagner has suggested that thermal ring opening of the cyclobutene results from the weakened character of the bridge C-C bond through conjugation with donor-acceptor.2 The zwitterion intermediate in equation 4 has been proposed for the thermal transformation of bicyclooctadiene to cyclooctatriene.2 O o 5 o \ [Is—L ”‘07—. ——> (4) In this thesis, the intramolecular charge transfer quenching of 1:, 16" lowest triplet excited states of p—substituted acetOphenones and trifluoroacetophenones bearing tethered terminal olefins is discussed. In particular, compounds in which the tether is connected to the benzene ring by carbon were studied. All of the earlier work used oxygen atoms which could perturb both the photochemistry and the subsequent thermal ring opening. El | I II'I' , Photocycloaddition of arenes to olefins has been widely studied. The arena-olefin cycloaddition provides a general approach for the synthesis of natural products10 and the construction of complex eight-membered ring systems1v9°v11 which form the main skeleton of a variety of natural products. Arenes have been shown to undergo a variety of transformations among which are ortho- and meta-cycloaddition reactions (Scheme 1).12 Addition of olefins to aromatic rings occurs by intermolecular and intramolecular mechanisms. Most commonly the S1 excited state of benzene and So of olefins are involved in these reactions.13.14 Scheme 1 O we 2» ho Ortho M913 Intramolecular versions of the arene-alkene photocycloaddition were also discovered by Morrison and co-workers.3-15 Intramolecular photocycloaddition takes place in bichromophoric molecules in which the arena and olefin chromophores are separated by three connecting atoms.45 The intramolecular meta or 1,3-photoaddition of olefins to arenes, involving the singlet excited state of benzene, has received the most attention (Scheme 2). This was due to the formation of a cycloadduct which could serve as a precursor to a variety of synthetically important ring systems.10 Scheme 2 It is known that meta cycloaddition is the usual outcome of irradiation of substituted benzenes with alkenesfifi‘18 Bryce-Smith and co-workers have found that meta cycloaddition is particularly favored when the difference between the ionization potentials of the arena and alkene is small.15‘18 This reaction is highly regioselective especially with substituted benzenesfi”:19 Gilbert studied the photoreactions of arenes having both electron-donor and electron-acceptor substituentsflov21 Irradiation of 2-, 3-, and 4- cyanoanisole with different ethenes led to the formation of 1:1 adducts. The photoreactions of the 2- and 3- isomers were generally less efficient and gave complex mixtures in low yields.20.21 The major products from the reactions of 4—cyanoanisole with the ethenes are shown in Scheme 3. The major product from the irradiation of this arena with cis-cyclooctene was the endo meta cycloadduct 7 (65%).21 Scheme 3 OMe cis-cyclooctene > NC 65% of adduct mixture OMe (CH2)6 hu 7 OMe ON C" ethyl vinyl ether 05‘ > CI + $- MeO NC oer 8 9 45% 25% The reaction mixture from irradiation of ethyl vinyl ether and 4- cyanoanisole was complex, but two major photoadducts (70%) were formed at <50% conversion. They were assigned structures 8 and 9, which are the products of ortho-additioan.21 In the case of cis-cyclooctene, the addition to 4-cyanoanisole in non- polar solvents is controlled by the methoxy substituent giving the 2,6-(mefa) adduct. For ethyl vinyl ether, the major mode of reaction reflects the cyano group exerting the stronger influence to promote the ortho cycloadditionfm21 Since the early discoveries of orth022'25 and metaZ5-27 photocycloadditions, several mechanisms have been proposed for these reactions. The mechanism in which an excited state intermediate (exciplex) is involved provides a rationalization in accord with the experimental evidence.1 .2339 In order to explain the high regioselectivities of photocycloadditions with donor (-OCH3) and acceptor (-CN) substituted benzenes, besides involvement of exciplex 10, the dipolar intermediate 11 has also been proposed (Scheme 4)5-16. As shown in scheme 4, donor (0) substituents Scheme 4 02>. + j££> 1 ,3-closure 1 .5-closure 6 5 CO *4 A 2 3 2 3 1 2 1 3 were preferentially located at position 1' of the meta adducts. whereas acceptor (A) substituents are generally placed at position 3' or 5230 The intramolecular [2+2] ortho photocycloaddition of o- and p- alkenoxyphenyl ketones was reported in 1987.1-2 Based on the dual 1,4- biradical and charge transfer nature of phenyl ketone 1r,n* triplets and also the preference for five-membered rings in olefin-CT interactions and in radical cyclization, Wagner and Sakamoto concluded that the addition takes place specifically at the para- carbon as shown in Scheme 5.31 Once the biradical is formed, it can cyclize to form the cyclohexadiene 14, or it can revert to the starting ketone. Reversion to the starting ketone is the cause for cis-trans isomerization of the substituted double bond.1 Scheme 5 3- ° °H2_.. ' W Hac’\©- ’KQv-O -CH2 h” M )‘Q'O’CHZZ— —>H30 Q o triplet //EXCIDIBX CH2 ‘ Hacofl A00 CH2 H30 0 biradical II II . I' , The primary photoadducts obtained by intramolecular ortho cycloaddition of alkenes to aromatics are thermally labile and are isomerized to new products upon heating. Thermal isomerization of the C3H1o isomers at 225°C has already been studied and is shown in equation 5.32 The photochemistry of the isomers mAA (5) 15 16 15-16 has also been reported and the main products have been characterized?”1| Gas phase photolysis of 15 produced the photoproducts shown in equation 6.32 hu.‘ + NW (6) 15 16 68% 32% After irradiation of 16 for a short period in the gas phase and in solution, the cyclooctatriene 15, benzene, and ethylene are observed “9+0" 0» 16 15 (equation 7).32 Orchard and Greathead studied the direct photolysis of bicyclo[4.2.0]octa-2,4-diene 16 in the gas phase at 280 and 300 nm in the presence of N2, He, 02, and No.33 Photolysis of 16 at 300 nm led to the formation of up to eight products, the major ones being cyclooctatriene 15, benzene and ethylene.33 Irradiating 16 at 280 nm gives two additional products, one of which was identified as 1, 3, 5, 7-octatetraene.33 This simply showed the wavelength dependency of the photolysis of 16. The general term "valence isomerization” has been introduced by Grob and Schiess for the transformation of 15 and 16 (equation 8).34 Cops and co- workers concluded that the two valence isomers 1 5 and 1 6 are in equilibrium»?5 Since the free energy of the monocyclic and bicyclic isomers are slightly different (AG for 15 -> 16 is approximately +1.5 kcaI/mole at 100°C),36 steric or electronic substituent effects are sufficient to shift the 5 6 100°C 3 2 1 a 0—» e- <— 3 3 4 6 7 2 1 5 15 16 85%, 150/0 equilibrium almost completely to one side or the other.36 Thus, chloro,37a bromo,37a acetoxy,37a or methoxy35 groups in the 7- or 8- positions stabilize 16. Bicyclooctadiene 16 with electronegative substituents in the 1- or 1- and 6- positions rearranges very easily to 15.35 This is due to the tendency of the substituents to enter into conjugation with the triene system and also to the unfavorable conformation of the two neighboring cis- substituents on the cyclobutene ring.35 When 15 is a trans-7,8-dimethyl cyclooctatriene, the population of the corresponding 16 is 94%.37b»c When 15 has methoxy groups in 7- and 8- positions, the population of the corresponding 16 is more than 95%_37b,c The cyclooctatriene is also favored in case of the isomeric pair bicyclo[4.2.0]octa-2,4-diene-7-one 19 and cycloocta-1,3,5-triene-7—one 18 (equation 9).38 Irradiation of cyclooctatrienone 18 produces the valence 10 isomer 17. This compound reverts to the eight-membered ring 18 upon heating (equation 9).36 O .. °«-—— our 21:: + (9) MO . O 17 18 19 Huisgen reported the equilibrium between cyclooctatrienes 21 and 23 with the corresponding cyclohexadienes, once the trans, cr's, cis, trans- decatetraene 20 was heated at 171°C (Scheme 6).39 The authors did not mention which isomer is favored. Scheme 6 \ CH3 {H H I H <— CH3 ' CHa . -——-> CCHa .‘ H ‘— . H g20 21 CH3 22 H CH3 '\ CH3 ,’ H I? / H 1"— CH3—> CH3 \ / (”'13—> ‘ CH3<— CH3 H ‘H 1'4 23 24 II |' ID 'I I' , When benzene is irradiated in the presence of an alkene, a number of processes can take place including ortho-, meta- and para- cycloaddition.12 Bryce-Smith noted that the reactions of benzene (IF. = 9.24 eV) with alkenes having I. P.'s between 8.65 and 9.60 W (A l. P. = 0.59 to -0.36 eV), generally proceed with meta-mode selectivity.40 In contrast, when the A I. P. between the 11 alkene and arena is greater than 10.60 eV, a situation which favors charge transfer, ortho- cycloaddition results.40 The r: orbitals of benzene are presented in Scheme 7. The orbitals are labelled according to their symmetries relative to a vertical plane of symmetry.“'1 It is important to know how each of the benzene HOMOs and LUMOs, if singly occupied, would best interact with the ethylene HOMO and LUMO. This is shown diagramatically in Scheme 7.42 In the ortho approach of ethylene to benzene, stabilization may be achieved either by interaction of the benzene A orbital with the ethylene 1r HOMO, or the benzene A' orbital with the ethylene n“ LUMO. Although generally of lesser significance, the ethylene HOMO might interact with S“ and the ethylene LUMO with S. For meta approach, the Scheme 7 Arene FMO's Alkene FMO's S. m ortho \ O \ 011110’ ” 1C 12 ethylene HOMO interacts with S and the ethylene LUMO interacts with A* as shown. The other two possible interactions are much weaker. Finally, in the para approach, the ethylene HOMO interacts with no filled orbitals, only with S*, while the ethylene LUMO can interact only with S.42 Frontier molecular orbital theory has been applied to the treatment of various substituted arenes and alkenes.42 Interaction of ethylene with donor- substituted benzene was calculated by this treatment to favor meta- over ortho- approach due to preferential stabilization of the S-> A' transition.42 The alkene in this case adds in a meta fashion preferentially across the donor group. Furthermore, for alkenes bearing an electron donating group (D) or for arena bearing an electron withdrawing group (A), charge-transfer is expected to become more important. When charge transfer is significant, ortho- addition is expected to predominate over meta42. Interaction between a benzene singlet state and an ethylene bearing electron donating groups is shown in Scheme 8.42 The interaction of one of the aromatic HOMOs with the n—bond HOMO will result in great stabilization due to 1.211 “— S¢+Ae_ + _— ....... ~19“: .2: ----------- 424114: Scheme 8 A+1r 13 the usual orbital mixing and because one electron is transferred from 1: to the lower energy A+1r orbital. The ortho cycloaddition is favored because the overlap of A with 11: in the ortho fashion is greater than that of S with 1c in the meta fashion.42 It 013 ol30 .ll..l..1.1 02000l0 <°lI<..'0= I ' Several intramolecular and intermolecular o-photocycloadditions have been reported. Wagner and Sakamoto reported the first example of intramolecular o-photocycloaddition of alkenes to 1r,1r* triplet naphthalenes for 1-butenoxy-2-acetonaphthones 25 (equation 10) and 2-butenoxy-1- acetonaphthones 27 (equation 11).43 The products formed upon photolysis of 25 and 27 at 313 nm were the cycloadducts 26 and 28, respectively. Compound 27c underwent only sis-trans isomerization of the double bond.43 .91 NR2 o 0 " . o 26' 25: - d): a: 0.23 a, R1=R2=H . b, R1=CH3, R2=H b- °-‘7 C,R1=H, 82:0sz C: 0.31 R R fnz “1:31 a 0 h 0 " .'o \ .. " O. (m 27: 28 a: R1=R2=H . . b: R1=CH3, R2=H (D. a. 0.01 c: R,=H, R2=C2H5 bi 0-04 14 Photolysis of 29 has been reported to give the ortho cycloadduct 30 (equation 12).44 The authors did not mention the excited state multiplicity of this reaction. (12) 29 30 Intramolecular photocycloaddition of alkenes to aromatics substituted by a cyano group in place of the acetyl group also lead to the formation of o- cycloadducts. Irradiation of compound 31 in benzene resulted in the rapid formation of two products 32 and 33 by intramolecular cyclization (equation 13). The initial ratio of 32:33 was 20:1, but after prolonged irradiation, 33 was the major product.45 (NH NC: ‘23—»: 005 o + O 313nm l benzene 31 32 33 Irradiation of bichromophoric compounds 34 (equation 14) and 36 (equation 15) gave ortho cycloadducts which have been identified as 35 and 37 respectively.45 Photolysis of bichromophoric compunds with no electron withdrawing group on the aromatic ring and having an enol ether also led to the formation of o-photocycloadduct. The bichromophore 38 gave the cycloadduct 39 when 15 CN CN go h” = 0‘ +20%minorproduct (14) , 3% benzene 313 nm ‘ O 34 35 CN 0Q hu : o (15) benzene OW 313nm 36 37 irradiated as 1% solutions in cyclohexane at 254 nm or wavelengths longer than 290 nm (equation 16).45 O /) (16) 38 39 When the bichromophoric compounds 40 (equation 17) and 42 (equation 18) were irradiated under the same condition, the intramolecular cycloadducts were identified as structure 41 and 43, respectively.46 Reactions 1618 take place from the singlet excited state of arenes.46 The formation of o-photocycloadducts depends on the polarity of the solvent. Gilbert reported that the photocycloadduct resulting from photolysis of 2-cyanoanisole and ethyl vinyl ether is the bicyclooctadiene 46 (equation19).47 16 (17) (18) This final product is the result of photolysis of cyclooctatriene 45.47 The original photocycloadduct is the bicyclohexadiene 44.47 The rate of adduct formation in this reaction is increased about two-fold on changing the solvent from cyclohexane to acetonitrile.47 The authors did not mention the excited state multiplicity of this reaction. QOM OMe (I + ol/e. lw fiCCIii Q0?" 2 (19) CN CN OE CNOEt Photolysis of pentafluorophenyl-a-allyl ether 47 at 254 nm in cyclohexane resulted in the formation of stable cyclohexadiene 48 (equation 20).48 The author did not mention the excited state multiplicity of this reaction. 17 F F F F 0 H Fee 6- ‘7 A 254nm >Ffi F F C6H12 F F 47 48 Direct eight-membered ring formation has already been reported. Photolysis of 6-phenyl-2-hexyne 49 at 254 nm in hexane led to the formation of cyclooctatetraene 50 (equation 21).49 This reaction took place from the singlet excited state of arene. Dorachzcrrzc-ccna fixing» (21) 49 5° Pirrung studied the intramolecular photocycloaddition of substituted 5- aryI-1-pentynes (equation 22).50 Irradiation of compound 51 led to the formation of cyclooctatetraene 52.50 The authors did not mention the excited state multiplicity of this reaction. Both triplet51 and singlet52 excited states can be involved in the photoaddition of triple bonds to the aromatic ring. O fl OH 51 52 TMS 18 Hexafluorobenzene 54 readily reacts with indene (53a) or 1,2- dihydronaphthalene (53b), to form only the 1:1 cycloadduct 55 (equation 23).53 The photocycloaddition of 53b was completely quenched by piperylene.53 Fcyclohexane (23) gfj+ 253. 7 nm (CH2)n F 0F 50 hr 53: a; n=1 54 55: 45% b; n=2 Hexafluorobenzene 54 also reacts with phenyl substituted acetylene 56 to form the corresponding hexafluorobicyclo [4.2.0] octatrienes 57 in high yield (equation 24).54 The photoaddition of 56 was completely quenched by piperylene.54 F QC- cn+ F F “’CEH‘Z phr- +P"F (24) F F 253.7 nm F 60 hrs 5 6 5 4 5 7 The intramolecular [2+2] regiospecific photoaddition of pentafluoropyridine 58 and 1-phenyl-2-tert-butylacetylene 59 has been reported to give products 60, 61 and 62 (Scheme 9).55 The authors did not mention the excited state multiplicity of this reaction. 19 Scheme 9 F F F/IET __>FN/FF FF mph'h— s1 F\NLW1ZWR FF 58 N’\R F\/Ph FF 62 W Some of the photoproducts obtained in this work underwent Cope rearrangement upon heating. Generally, 1,5-dienes can undergo this [3,3]- sigmatropic rearrangement .55 The transition state for Cope rearrangement can have either four-center, chair-like or six-center, boat-like geometries.57 A pictorial representation of these geometries is provided in Scheme 10. Two Scheme 10 227—» -'-:-: :_ six-center ovcrlappin g (boat form) four-center overlapping (chair form) 20 different arrangements are possible for the transition state of the rearrangement of flexible diallyl compounds:36 a quasi-boat form with two parallel allyl groups (six-center overlapping) and a quasi-chair form in which only the ends of the two allyl groups interact (four—center overlapping). Kineticfludx; When a particular excited state decays by competing reactions, all of which are kinetically first order, then the lifetime, I, can be defined as the reciprocal of the sum of all of the rate constants which depopulate the state (equation. 25).58-59 (25) a. Quantum yield: the quantum yield of formation or destruction of a given species is based on the number of molecules which are observed to undergo a given phenomenon per photon absorbed (equation 26).58.59 . _ moles of iven species formed or destroyed Quantum yield ‘ moles of path—owns absorbed by the system (26) or e = [P] (27) In equation 27, P is the concentration of photOproduct formed and la is the intensity of the light absorbed in Einstein litre mole-1. la may be related to the incident intensity, lo, through the Beer-Lambert law as shown in equation 2853.60. In this equation, 0 is the concentration of absorbing species (in 21 moles/liter), I is the path length (in cm), and ethe molar extinction coefficient (whose units are 1000 cm2/mole). Ia =10 (1 - 10m) (28) b. Stem-Volmer kinetics: The triplet lifetimes of ketones can be measured by a Stem-Volmer quenching study. Equation 29 is the Stern-Volmer equation.58-60 0 <1) T = 1 + kq‘li [Q] (29) In this equation, 0" and 0 are the quantum yields in the absence and presence of quencher, respectively. The symbol, kq, is the quenching rate constant by the quencher, 't is the triplet state lifetime, and [Q] is the concentration of quencher. A plot of 00/0 vs. [Q] gives a straight line with a slope of qu and an intercept of one. By measuring the kq‘l value from the slope of the straight line in a Stern-Volmer plot, 1: can be calculated (M=10X109 M' ‘8'1 in acetonitrile61 and 5X109 M'1S'1 in benzene62 at ambient temperature). Beseamluioals: One of the main objectives was to construct fused ring systems which could act as precursors for the synthesis of a variety of natural products. Since it was necessary to have a good understanding of the stereochemistry of the photoproducts obtained, the stereochemistry of all photoproducts and their thermal rearrangements were studied. 22 Application of any process or reaction toward further research and development cannot be accomplished without a good understanding of the mechanism of the process. Examination of the intramolecular photocycloaddition of aromatics-olefins in systems in which the olefinic tethers are connected to the benzene ring by carbon is useful in understanding the mechanism of these reactions. In fact, studying these reactions revealed the effect of oxygen conjugated with the aromatic ring on photocycloaddition reactions. 23 RESULTS AW [p - (a,a,a-Trifluoroacetyl) benzyloxy] propenes were prepared from 4- bromobenzyl bromide and the corresponding allyl alcohol as Shown in Scheme 11 : Scheme 1 1 F011 , F012, F021 , N33 0 3 cm, ”28' R as Fl, Ra 5 Eff“ "Na” 2,0405%” R R R2 213”ch R3 1) Mg / 5120 “V9, 2, We WAG/‘0 -78°C F011, F012, F021, F013 R1=R2=R3=R4=R5=H, 3 - [4-(a.a,a-trifluoroacetyl) benzyloxy] propene. R3=CH3, R1=R2=R4=R5=H, 3 - [4-(a,a,a-trifluoroacetyl) benzyloxy] -2- methylpropene. R1=R2=CH3, R3=R4=R5=H, 3 - [4-(a,a,a- trifluoroacetyl) benzyloxy] -3- methyl - 1- butane. F013, R4=R5=CH3, R1=R2=R3=H, 4- [4-(a,a,a-trifluoroacetyl) benzyloxy] -2- methyl-2- butene. 24 Reaction between the Grignard reagent of the corresponding bromobenzyloxy propane and ethyl trifluoroacetate produced (4-a,a,a- tritluoroacetylbenzyloxy) propenes.53-54 p—Bromobenzyloxypropenes were prepared by the 8N2 reaction between p-bromobenzyl bromide and the sodium salt of the corresponding allyl alcohol in THF.55 p-Bromobenzyl bromide was prepared by refluxing p-bromotoluene and N-bromosuocinimide in CCl4. 5-[4-(a, a, a—tritluoroacetyl)phenyl]-1-pentene FC11 was prepared by the reaction between ethyl trifluoroacetate and the Grignard reagent of 5-(4- bromophenyl)-1-pentene,‘53 which was prepared by the 8N2 reaction between 4-bromobutene‘56 and the Grignard reagent of 4-bromobenzyl bromide as shown in Scheme 12. Scheme 12 1) Mg / E120 2)HMPA Br-O-CHzBr = Br—OW 3) NB r 1) Mg / THF 0 u- F CW 2) CF3COzEt 3 -78°C Fc,1 3-(4-Acetylbenzyloxy) propene A011 was prepared by the reaction between the Grignard reagent of 3-(4-bromobenzyloxy) propene and acetic anhydride (equation 30).57 1 0 M 1) Mg / THF : M 30 3'00 2) (CH300)20 HaCWO ( ) '1 -78°C A01 25 5-(4-acetylphenyl)-1-pentene AC11 was prepared by the reaction between the Grignard reagent of 5-(4-bromophenyl)-1-pentene and acetic anhydride (equation 31).67 O 1) Mg/ IHF W / ’ RFD/\N 2) (CH300)2O "ac O (31) _7800 AC1 1 3-Methoxy-4-(1-pentenyl)acetophenone 3-MOAC11 was prepared in four steps from m—hydroxyacetophenone as shown in Scheme 13.6359 Scheme 13 rfi o O OHOH / W O O 3’2 > ——> ”SC 0 CGHG H30 toluene OH OH I ‘o flo 0 M01 “(2003 O er ~ 0 3, “ac“- acetone “30“- OH OMe O WVMQBV PdCIzldppf) “30+ / >- —> H3C 0 E120 OMe 3-MOAC11 *PdCl2(dppf): Dichloro-[1,1'-bis (diphenylphosphino)ferrocene] palladium (ll). 26 B Ell l ll'l" All photoirradiations were carried out in a Hanovia immersion well preparative apparatus using a Pyrex glass filter (wavelength above 295 nm).70 Usually a dilute solution of ketone (0.01 M) in argon bubbled, glass distilled Omnisolv benzene, Mg dried methanol, or distilled acetonitrile was irradiated. Purification of photoproducts was carried out by flash column chromatography on silica gel using hexane / ethyl acetate as eluent. All photoproducts were characterized by 1H NMR, 13C NMR, IR, mass spectrometry and UV-visible spectroscopy. The stereochemistry of photoproducts was studied by the Nuclear Overhauser Effect (NOE). The chemical yields of the photoproducts were measured by GC and or by 1H NMR based on the concentration of converted starting ketone. '...... ., on 1.. .. -' _. .._ ; 0:. .‘ ...;.; e Irradiation of a benzene solution of F011 (0.25 g ketone per 70 mL solvent). through a Pyrex filter led to the formation of two photoproducts based on GC analysis (Scheme 14). The two products were separated by gradient flash column chromatography on silica gel using hexane / ethyl acetate as eluent. Scheme 14 o \A F30 PC = 3 Pyrex H Hb'7\23 41 H “8 O'T-Hb Ha AFO1 1 , 9-trifluoroacetyl-cis-anti-3-oxatricyclo[7.2.0.01 o5]undeca-7,1 O-diene. LFO1 1 , 1 O-trifluoroacetyl-cis-antrls-oxatricyclon.2.0.03.7]undeca-7,1O-diene. 27 Photoproduct AFO11 showed the same molecular ion peak as that of the starting ketone. Its 13C NMR showed four vinyl carbons: one signal at 5 140.83 (C-11) and 136.03 (C-10) characteristic of vinyl carbons of cyclobutene71-72, and one signal at 5128.78 (C-7) and 123.78 (C-8) characteristic of vinyl carbons of cyclohexane.71 -72 The order of chemical shifts in 13C NMR was usually the same as the corresponding 1H NMR. The 1H NMR showed four vinyl protons: doublet at 5 6.33 (H-11) and 6.20 (H-10) coupled to each other (J=3.4 Hz) characteristic of vinyl protons of the cyclobutene.7‘-72 and two more vinyl protons, a multiplet at 5 5.98 (H-7) and a doublet at 5 5.83 (H-8) coupled to each other with J=10.3 Hz, characteristic of the vinyl protons of cyclohexene71v72. The vinyl proton at 5 5.98 (H-7) was also coupled with two allylic protons at 5 2.19 (H-6a,b) observed as a multiplet. The two allylic protons at 5 2.19 (H-6a,b) are coupled with the bridgehead proton at 5 2.43 (H-5), which is also coupled to the triplets at 5 3.94 (H-4a) and 3.58 (H-4b) with J=8.0 Hz. The triplet at 5 3.94 (H-4a) is also coupled with the triplet at 5 3.58 (H-4b) with J=8.0 Hz. The A8 quartets at 5 3.78 (H-2a) and 3.70 (H-2b) are coupled to each other with J=10.3 Hz. All of the above couplings have been confirmed by homodecoupling experiments (Figure 1). The stereochemistry of AFO11 has been established by NOE experiments, which showed an increase of H-11 (1.85%), H-7(0.51%), H-4a (4.45%) and H-2a (2.22%) when the bridgehead proton at 5 2.43 ( C-5, 100%) was irradiated. The relative enhancements of hydrogens, based on 100% enhancement of the irradiated hydrogen, are summarized in Scheme 15 (* shows the hydrogen which is irradiated). The IR spectrum of AFO11 showed a carbonyl signal at 1738 cm”. Photoproduct LFO11 showed the same molecular ion peak as the starting ketone (Scheme 14). Its 13C NMR showed four vinyl carbons: one signal at 5 155.65 (C11) and 140.46 (C10) characteristic of a cyclobutene 28 structure,72 and signals at 5 144.86 (C7) and 114.16 (Cg) were assigned to vinyl carbons of the cyclohexane ring.72»73 The 1H NMR showed two vinyl protons: a multiplet at 57.15 (H-11) which was weakly coupled with the bridgehead proton at 5 3.26 (H-1), and a multiplet at 5 5.81 (H-8) which was coupled with the bridgehead proton at 5 3.70 (H-9). The Scheme 15 E: 1 .9 :d2 3.20 LFO11 'E' is the percent enhancement in NOE experiment. 'd' is the distance between the two hydrogens in A0 as calculated with PCMODEL. bridgehead proton at 5 3.26 (H-1) was coupled with the protons at 5 2.19 (H-2a) and 1.18 (H-2b). The protons of H-2a,b were coupled with the bridgehead proton at 5 2.38 (H-3). The bridgehead proton at 5 2.38 (H-3) was coupled with the proton at 5 4.20 (H-4a) and 3.34 (H-4b) with J=8.57 Hz, and with the vinyl proton at 5 5.81 (H-8). The proton at 5 4.20 (H-4a) was coupled with the proton at 5 3.34 (H-4b) with J=8.57 Hz, which was also coupled with the bridgehead 29 proton at 5 3.70 (H-9) with J=4.96 Hz. The bridgehead proton at 5 3.70 (H-9) was coupled with the proton at 5 5.81 (H-8). The proton at 5 4.37 (H-Ba) was coupled with the proton at 5 4.25 (H-6b). All of the above couplings have been confirmed by homodecoupling experiments (Figure 2). The stereochemistry of LFO11 was established by Nuclear Overhauser Effect (NOE) experiments which showed a cis ring junction at H1-H9 , anti to H3 (Scheme 15). An increase in intensity of the bridgehead proton signal at 5 3.70 (H-9) was observed when the bridgehead proton at 5 3.26 (H-1, 100%) was irradiated, while the bridgehead proton at 5 2.38 (H-3) remained unchanged. The IR spectrum of LFO11 showed a carbonyl signal at 1711 cm'1. The chemical yields of photoproducts LFO11 and AFO11 were measured in benzene and are summarized in Table I. Table I: Chemical Yields of Products of Photocycloaddition of F011 Based on GC, Using C15H32 as Standard. Irradiation time % conversion % chemical %chemical (minutes) of yield of yield of F011 LFO11 AFO11 30 24.2 28.3 9.6 60 38.3 32.6 10.9 100 51.7 15.0 5.9 %Chemical yield of photoproducts is equal to the concentration of the photoproducts after irradiation divided by the concentration of reacted ketone. Concentration of reacted ketone is equal to the initial concentration of ketone minus the concentration of unreacted ketone. 30 The irradiation was performed in a small test tube sealed with a mbber septum. The test tube was deaerated before irradiation by bubbling with argon. An internal standard was included in the solution to allow for the quantitative analysis of the data. The irradiated ketone was analyzed by 60. Each time that irradiation was interrupted for GO analysis, the test tube was deaerated and sealed again for the continuation of irradiation. '|ooooo o, on ---':.A.‘.‘. .o. : 0:. .. .....,;I 000:]: LEQflLlrradiation of a benzene solution of F012 (0.60 g of ketone per 400 mL of solvent), through a Pyrex filter led to the formation of two photoproducts based on GC analysis (Scheme 16). The two products were separated by gradient column chromatography on silica gel using hexane / ethyl acetate as eluent. Scheme 16 F012 AF 01 2, 5-methyl-9-trifluoroacetyl-cis-anti-3-oxatricyclo[7.2.0.01.5]undeca-7,1 0 diene. LFO1 2, 3-methyl-1 0-tritluoroacetyl-cis-anti-5-oxatricyclo[7.2.0.03-7]undeca-7,1 0 diene. w.— 31 o_o>omeo-m-_Em 1&0- .980 5 2.9.5 229°258525.335 _boomo.o:_E.-m B mEoEanxo usaaoooooEoI 3 2:9“. 1.: J: 1; 31 A” an m N F P b h h h b r P P 3-: 3.3.: ‘3 . 32 .908 s :6"; 832.tnasocareoddd o_o>omeo-m-_Em-m_o-_38382.50F 3 3.5.5398 asaaooouoEoI ”N 239...... can 05 o.m n.m o.n n.n h h h b b lr b P 06 mi o.n n6 0.0 0.0 h (D P b + P b h (P1P h h L FL F D rib F P b P — P Firlrlb’b 1' F‘ b bL'blFL .. 2. a. 4 0.1 . 0.2 Oh serbp ——.1(_ 33 Photoproduct AFO12 showed the same molecular ion peak as that of the starting ketone. lts 13C NMR showed four vinyl carbons: one signal at 5138.60 (C11) and 136.25 (C10) characteristic of a cyclobutene structure, and one signal at 5128.98 (C7) and 122.73 (Ca) characteristic of cyclohexane vinyl carbons. The 1H NMR showed four vinyl protons: doublet at 5 6.27 (H-11) and 6.22 (H-10) coupled to each other (J=3.0 Hz) characteristic of vinyl protons of a cyclobutene ring and also two other vinyl protons at 5 5.92 (H-7), a multiplet, and at 5 5.73 (H-8), a doublet, coupled to each other (J=10.30 Hz) characteristic of vinyl protons of cyclohexane. The vinyl proton at 5 5.73 (H-8) has a weak allylic coupling with protons at 5 2.20 (H-6b) and 1.96 (H-6a). The vinyl proton at 5 5.92 (H-7) was coupled with protons at 5 2.20 (H-6b) and 1.96 (H-6a). The doublet at 5 3.50 (H-4a) was coupled to the doublet at 5 3.73 (H-4b) with J=8.05 Hz. The doublet at 5 3.98 (H-2a) was coupled with the doublet at 5 3.66 (H-2b) with J=10.78 Hz. The proton at 5 1.96 (H-6b) was coupled to the proton at 5 2.20 (H-6a) with J=17.07 Hz. The methyl protons appeared as a singlet at 5 1.06. Most of these decouplings have been confirmed by homodecoupling experiments (Figure 3). The chemical shifts of H-2a,b, H-4a,b and H-6a,b were all assigned based on NOE experiments (Figure 4). The stereochemistry of AFO12 has also been established based on NOE experiments, which showed an increase of H-11 (2.15%), H-2a (2.0%), H-4a (2.56%), H-6b(1.09%) and H- 6a (2.16%) when the bridgehead methyl group at Cs (100%) was irradiated (Scheme 17). The IR spectrum of AFO12 showed a carbonyl signal at 1738 cm”. Photoproduct LFO12 showed the same molecular ion peak as that of the starting ketone. Its 13C NMR showed four vinyl carbons, one signal at 5158.15 (C11) and 148.41 (C10) were characteristic of a cyclobutene system, and one 34 signal at 5141.24 (C7) and 113.91 (C3) were characteristic of a cyclohexane Scheme 17 vinyl carbon. 1H NMR showed two vinyl protons: a vinyl proton at 5 6.53 (H-11) which was coupled with the bridgehead proton at 5 2.54 (H-1), and a multiplet at 5 5.49 (H-8), coupled with the bridgehead proton at 5 3.22 (H-9). The H-8 proton also coupled with the proton at 5 4.22 (H-6a), which was coupled with the proton at 5 4.02 (H-6b) with J=13.5 Hz. The bridgehead proton at 5 3.22 (H- 9) was coupled with the bridgehead proton at 5 2.54 (H-t). The bridgehead proton at 5 2.54 (H-1) was weakly coupled with the proton at 5 1.38 (H-2a) and strongly with the hydrogen at 5 0.86 (H-2b). The doublet at 5 3.51 (H-4a) was coupled to the doublet at 5 3.04 (H-4b) with J=7.8 Hz. The proton at 5 1.38 (H- 2a) was coupled with the hydrogen at 5 0.86 (H-2b). All of the above couplings have been confirmed by homodecoupling experiments (Figure 5). The chemical shift of H-2a,b, H-4a,b and H-6a, b were all assigned based on NOE experiments. The stereochemistry of LFO12 has also been established by NOE 35 experiments (Figure 6) which showed a cis n‘ng junction at H1-H9 which was anti to H3. There was an increase in the vinyl proton of H-11 (1.6%) when the bridgehead methyl group was irradiated (100%) as shown in Scheme 17. The IR spectrum of LFO12 showed a carbonyl signal at 1709 cm'1. The chemical yields of photoproducts AF 012 and LFO12 were measured and are summarized in Table II. Table II. Chemical Yield of Products of Photocycloaddition of F012 Based on GC Using C17H36 as Standard. Irradiation time % conversion % chemical %chemical (minutes) of yield of yield of F012 LFO12 AFO12 3 3 1 6 .7 47.5 1 8 6 3 3 o 1 8 16 .9 1 08 54.2 5.2 15.4 .“ .. .. .1 m ml t P. . .. :1 ”I L H“. _ _ :1: erradiation of a benzene solution of F021 (1.0 g of ketone per 400 mL of solvent), through a Pyrex filter led to the formation of two major photoproducts based on GC analysis (Scheme 18). The two products were separated by gradient flash column chromatography on silica gel using hexane / ethyl acetate as eluent. 36 5.08 s 8.83 2.2.323825335 c.9853o-m-_Em-m_o._booman_E3-35656 .0 956598 05.3830on "a 059“. ton a N )- P p p b - b h L b t 37 some 5 a6“; 2.9.3FK88:areoddsoactfixo -m-_.cm-m_o._boomo.o:=E.o7352.5 B mcoetoaxo usaaoocuoEoI ”c 239.... 500 a N M V n — h b b b — .2 . A? 44111; «so: a... 3. 3. 8.: I... 9: :4. i {3.1: . a: - : n A" q . 11‘: 4 a— «t1 i ‘1 j . 38 .980 5 3.9.3 22325885 r.6.0.m£222.53-m-_boomeo=_§-m-_§oe-m B Emerges m02 ”m 23E Ecn w— o n m.~ om n.m oi mi o.m rim 9m IL 1. . . _ . . . t _ . r . _ . . . _ . p . . . . . . _ . . . . . . . . . _ . . . . . . . . . _ . s. = a. a . no.2 . a... 92 n: 3.: u 9... :i 8.3 “.2 39 .980 s 3.93 225-5F$885.23.“.«2205593 429392883355Essa.» .0 955:an moz a 2:9... 40 Scheme 18 O F021 AF021 LF021 AF021 , 4,4-dimethyI-9-trifluoroacetyl-cis-anti-S-oxatricyclo[7.2.0.01.5jundeca- 7,1 0-diene. LF021 , 4,4-dimethyl-10-trifluoroacetyI-cis-anti-5-oxatricyclo[7.2.0.03-7jundeca- 7,1 0-diene. Photoproduct AF021 showed the same molecular ion peak as that of the starting ketone. Its 13C NMR showed four vinyl carbons: one signal at 5 144.47 (C11) and 135.15 (C10) characteristic of a cyclobutene structure, and one signal at 5 130.75 (C7) and 125.22 (Ca) were assigned to vinyl carbons of cyclohexene ring. The 1H NMR showed four vinyl protons: a doublet at 5 5.94 (H-11) and 5.87 (H-10) with a coupling of 3.07 Hz characteristic of vinyl protons of cyclobutene ring, and two vinyl protons at 5 5.67 (H-7), a multiplet, and 5 5.54 (H-8), a doublet, with a coupling of 10.05 Hz characteristic of cyclohexene system. The vinyl proton at 5 5.67 (H-7) was coupled with protons at 5 1.65 (H- 6a) and 1.75 (H-6b). The allylic proton at 51.75 (H-6b) was coupled to the allylic proton at 5 1.65 (H-6a). The doublet at 5 3.93 (H-2b) was coupled to the doublet at 5 3.71 (H-2a) with J=10.12 Hz. The bridgehead proton at 5 1.49 (H-5) was coupled with the two protons at 5 1.75 (H-6b) and 1.65 (H-6a). All of the above couplings have been confirmed by homodecoupling experiments. The stereochemistry of AF021 has been established by NOE experiments which showed an increase of H-11 (2.57%), H-10 (0.89%), H-6b (1.78%), H-6a 41 (3.89%) and -CHaa (5.14%) when the bridgehead proton at 5 1.49 (H—5, 100%) was irradiated (Scheme 19). The IR spectrum of AF021 showed a carbonyl signal at 1738 cm'1. Photoproduct LF021 showed the same molecular ion peak as that of the starting ketone. Its 13C NMR showed four vinyl carbons: one peak at 5 155.24 (C11) and 145.17 (C10) characteristic of a cyclobutene structure and one signal at 5 140.12 (C7) and 113.80 (C3) were assigned to the vinyl carbons of cyclohexene. The 1H NMR showed two vinyl protons: one at 5 6.40 (H-11) which is weakly coupled to the bridgehead proton at 5 2.49 (H-t), and another one at 5 5.53 (H-8) had allylic coupling to the protons at 5 4.17 (H-6a) and 4.05 (H-6b). The protons at 5 4.17 (H-6a) and 4.05 (H-6b) were coupled to each other with J=13.65 Hz. The vinyl proton at 5 5.53 (H-8) was also coupled to the bridgehead proton at 3.22 (H-9) with J=4.60 Hz, which was coupled with the bridgehead proton at 5 2.49 (H-t). The bridgehead proton at 5 2.49 Scheme 19 d:2.45 d:4.70 E:O.9 15:17.0 “-85 O 42 (H-1) was coupled to the protons at 5 1.34 (H-2a) and 0.66 (H-2b). Protons at 5 1.34 (H-2a) and 0.66 (H-2b) were coupled to each other and also to the bridgehead proton at 5 1.85 (H3). All of the above couplings have been confirmed by homodecoupling experiments. The chemical shifts of H-2a, b, H- 6a, b and CH33,0 were all assigned based on NOE experiments. The stereochemistry of LF021 has also been established by NOE experiments which showed cis ring junction at H1- H9, anti to H3. An increase in intensity of vinyl proton H-11 (7.4%) was observed when the bridgehead proton H-3 (100%) was irradiated, while there was no enhancement of H-1 and H-9 (scheme 19). The IR spectrum of LF021 showed a carbonyl signal at 1709 cm’i. The chemical yields of photoproducts AF021 and LF021 were measured in benzene and are summarized in Table III. Table III. Chemical Cields of Products of Photocycloaddition of F021 Based on GC, Using C15H34 as Standard. Irradiation time % conversion % chemical %chemical (minutes) of yield of yield of F021 LF021 AF021 30 25.0 35.0 27.5 60 37.5 35.0 31.7 90 42.5 35.5 36.8 135 52.5 28.6 39.3 195 60.0 21.9 43.8 255 81.2 10.0 32.3 43 lo. . o ‘--‘0. 0‘ o-. to, : 0:. CAN-":1 --o :I: E943: Prolonged irradiation of a benzene solution of ketone F013 using Pyrex filter did not lead to the formation of any photoproduct. The 1H NMR of the crude photolyzed material after evaporation of benzene showed only the recovery of the starting material. no . ' . - - 0.0.0.110 .._ =1 . :1 --0:1 :1: F 'lrradiation of a benzene solution of FC11 (0.6 g of ketone per 400 mL solvent), through a Pyrex filter led to the formation of two major photoproducts based on GC analysis ( scheme 20). The two products were separated by gradient flash column chromatography on silica gel using hexane / ethyl acetate as eluent. Scheme 20 FC11 AFC11 I-FC11 AFC1 1, 9-tritluoroacetyl-cis-anti-tricyclo[7.2.0.01 v5jundeca-7,1 0-diene. LFC1 1 , 10-trifluoroacetyl-cis-anti-tricyclo[7.2.0.03,7]undeca-7,1 0-diene. Photoproduct AFC11 showed the same molecular ion peak as the starting ketone. Its 13C NMR showed four vinyl carbons: one vinyl carbon at 5 143.71 (C11) and 132.58 (C10) characteristic of vinyl carbons of a cyclobutene structure, and one signal at 5128.84 (C7) and 124.12 (C3) characteristic of vinyl carbons of the cyclohexene ring. The 1H NMR showed four vinyl protons: a doublet at 5 6.32 (H-11, J=3.02) and a doublet at 5 6.05-6.10 (H-10), coupled to 44 each other and are characteristic of vinyl protons of a cyclobutene ring. Two other vinyl protons appeared as a multiplet at 5 5.80-5.97 (H-7) and a doublet at 5 5.72 (H-8) coupled to each other with J=9.89 Hz characteristic of of a cyclohexene structure. Three protons at 51.99-2.13 (multiplet) were the two allylic protons (H-6a,b) and one bridgehead proton (H-5). There were six protons at 51.44-1.76 (multiplet) which were H-4a,b, H-3a,b and H-2a,b. The IR spectrum of AFC11 showed a carbonyl signal at 1736 cm°1. Photoproduct LFC11 showed the same molecular ion peak as that of the starting ketone. Its 13C NMR showed four vinyl carbons: one vinyl carbon at 5 140.06 (C7) and 114.49 (Ca) which were characteristic of the cyclohexene ring. Two vinyl carbon at 5156.02 (C11) and 149.40 (C10) were assigned to the cyclobutene structure. The 1H NMR showed two vinyl protons: a vinyl proton (figure 7) at 5 7.12-7.16 (H-11) which was weakly coupled with the bridgehead proton at 5 3.17-3.22 (H-1), which was coupled with the protons at 51.25-1.75 (H-2b) and 5 2.15-2.22 (H-2a). Another vinyl proton at 5 5.70 (H-8) which was coupled with the bridgehead proton at 5 3.62 (H-9). The proton at 5 222-2.30 (H-6a) was coupled to the protons at 5 2.30-2.38 (H-6b), 1.62-1.73 (H-5a) and 1.45-1.58 (H-5b). The proton at 5 215-222 (H-2a) was coupled to the protons at 5 3.17-3.22 (H-1) and 1.90-2.25 (H-3). The proton at 51.62-1.73 (H-5a) was coupled to the protons at 5 1.45-1.58 (H-5b), 1.15-1.22 (H-4a), 1.87-1.95 (H-5a), 222-2.27 (H-6a) and 2.27239 (H-6b). The proton at 5 1.45-1.58 (H-5b) was coupled to the protons at 5 1.15-1.22 (H-4a), 1.62-1.73 (H-5a), 1.85-1.90 (H-4b), 222-2.27 (H-6a) and 2.27-2.39 (H-6b). The proton at 51.15-1.22 (H-4a) was coupled to the protons at 5 1.45-1.58 (H-5b), 1.62-1.73 (H-5a), 1 85-190 (H-4b), 1.90-2.25 (H-3) and weakly to the protons at 51.25-1.75 (H-2b), 215-222 (H- 2a), 2.22-2.27 (H-6a) and 227-239 (H-6b). The proton at 5 1.25-1.75 (H-2b) was coupled to the protons at 5 190-225 (H-3), 2.15-2.22 (H-2a) and 3.17-3.22 45 (H-1). All of the above decouplings have been confirmed by homodecoupling experiments (Figure 7). The stereochemistry of LFC11 has been established by NOE experiments which showed cis- ring junction at H1-H9, syn to H3. An increase of the intensity of the bridgehead proton at 5 3.56-3.64 (H-9, 7.2%) was observed when the bridgehead proton at 53.17-3.22 (H-1, 100%) was irradiated. When H-11 was irradiated (100%), an enhancement of H-1 (2.6%) and H-3 (1.9%) was observed as shown in Scheme 21. The IR spectrum of LFC11 showed a carbonyl signal at 1709 cm'1. Scheme 21 The chemical yields of photoproducts LFC11 and AFC11 were measured in benzene and are summarized in Table IV. 46 Table IV. Chemical Yields of Products of Photocycloaddition of FC11 Based on GC, Using C14H30 as Standard. Irradiation time % conversion % chemical %chemical (minutes) of yield of yield of FC11 LFC11 AFC11 30 16.7 49.0 20.0 60 25.8 45.2 23.9 90 35.8 34.9 23.0 140 49.2 23.7 22.0 W11: Irradiation of AC11 in anhydrous methanol (0.5 g of ketone per 400 mL solvent), through a Pyrex filter led to the formation of two major photoproducts based on GC analysis (Scheme 22). The two products were separated by flash column chromatography on silica gel using hexane / ethyl acetate as eluent. Scheme 22 0 H30 Ac,1 AAC1 1 , 9-acetyI-cis-anti- tricyclo[7.2.0.01-5]undeca-7,10-diene. LAc1 1, 1 0-acetyI-cis-anti- tricyclo[7.2.0.03-7]undeca-7,10-diene. 47 5.58 s :92 2.22.2382:5393. 226E-_Em-m_o-_boomeoa_§-oP .o £58:on 353388080: K 959“. EGO N n V n O N llhllblllllrflb's‘hz » b b P h u p p p L p p L p P P P r b p k P , I I I 4A l I I i .I 8.: 8.: a: 2. 38.: I. a... I. 2.: . _ 1.1! I 14 J J 0" III-‘0‘] a] ‘OI-jfi‘ I I4 1 .F (J. (I «I I 1 Id 4 J I A" 3 It 4 1»: - Ill 1 I J n 141' q 111 11%1' J ‘ 1 "V 48 Photoproduct AAC11 could not be purified, and its crude proton NMR showed four vinyl protons: doublet at 5 6.27 (H-10, J=2.96 Hz) and 5 6.05 (H- 11, J=2.94 Hz) were coupled to each other are characteristic of vinyl protons of a cyclobutene stmcture. Two other vinyl protons, a doublet at 5 5.74 (H-8) and a multiplet at 5 5.41 (H-7) were assigned to vinyl protons of the cyclohexene ring. The methyl of acetyl group was at 5 2.30. Photoproduct LAC11 showed the same molecular ion peak as the starting ketone. Its 13C NMR showed four vinyl carbons: these vinyl carbons were at 5148.18, 147.02, 146.45 and 115.65. Its 1H NMR showed two vinyl protons: a vinyl proton at 5 6.75 (H-11) that was weakly coupled to the bridgehead proton at 5 2.99-3.04 (H-1) (Figure 9). Another vinyl proton at 5 5.70-5.73 (H-8) was coupled to the bridgehead protons at 5 3.46-3.50 (H-9) and 5 2.99304 (H-1) and weakly to the bridgehead proton at 5 224-2.31 (H-3). The bridgehead proton at 5 3.46-3.50 (H-9) was coupled to the bridgehead proton at 5 2.24-2.31 (H-3). The bridgehead proton at 5 2.99-3.04 (H-1) was coupled to the protons at 5 2.08-2.15 (H-2a) and 0.98-1.08 (H-2b), which was coupled to the protons at 5 208-215 (H-2a) and the bridgehead proton at 208-215 (H- 2a). All other protons are at 5 1.13-1.20 (H-5), 5 1.21-1.25 (H-5), 5 1.42-1.75 (H- 4a,b) and 5 1.88-2.02 (H-6a,b). All of the above couplings have been confirmed by homodecoupling experiments (Figure 8). The stereochemistry of LAC11 has been established by NOE experiments (Figure 9) which showed cis-ring junction at H1-H9, anti to H3. An increase of the intensity of the bridgehead proton at 5 299-304 (H-1) was observed when the bridgehead proton at 5 3.46- 3.50 (H-9) was irradiated (Scheme 23). An increase in the intensity of the bridgehead proton at 5 299-304 (H-1) was observed when the proton at 5 0.98- 1.08 (H-2b) was irradiated. There was no increase in the intensity of the proton 49 at 5 224-2.31 when the proton at 5 0.98-1.08 was irradiated. The IR spectrum of LAC11 showed a carbonyl signal at 1678 cm'1. Scheme 23 d:2.45 E:6.9 d:2.84 E:14.8 r\ H Hal-1b H HaHb “Hb “Hb Ha H Ha H‘ ' .' H Ha E:7.9 41.“): Ha Hb . d:2.49 “5:131 LAc,1 HIGH 100 0 -‘- = ”1|:I0.0|:| ”0:1:1: -1.0; Irradiation of 3-MOAC11 in anhydrous methanol (0.13 g of ketone per 400 mL solvent) through a Pyrex filter led to the formation of C-3-MOAC11 as the major photoproduct (Scheme 24). Qcheme 24 OCH3 3-M0Ac,1 C-3-MOAC11 C-3-MOAC11 , 1 1-methoxy-9-acetyl-cis-tricyclo[6.3.0.01-7]undeca-8, 10-diene The 1H NMR of C-3-MOAC11 in CDCI3 showed two vinyl protons. A doublet at 5 6.26 (H-8) with J=5.4 Hz and a singlet at 5 5.48 (H-10). There were 50 £4. 071?: $2 or: 11.. 3.08 s :65: Senstwmooncakeoémd o_o>oE-_Em-m_o-_boom-oF .o mucoEtoaxo usaaooocoEoI no 2:9... m n v n m _ p . p L — > ID L I h b 1P b h b h b h h b b b 1- b - w H: 9: 9: DY... 51 .980 s :65: 22.92.5885 PB.o«dosagezfiaazaooaé. B 2:55:85 moz a 23E p72 v. ‘0 52 two bridgehead protons, a multiplet at 5 3.02 (H-7) and a multiplet at 5 2.92 (H- 5). The methoxy group was at 5 3.58, and the methyl of acetyl group was at 5 2.28. The remaining protons appeared as a multiplet from 5 1.40 to 2.08. B IEII I III , WW1]. Irradiation of 0.25 g of ketone A011 in a 400 mL immersion well equipped with a Pyrex filter and Hanova mercury lamp in Mg dried methanol for 48.0 hrs led to the formation of two major photoproducts based on GC analysis (Scheme 25). The two major photoproducts were separated by gradient flash column chromatography on silica gel using hexane / ethyl acetate as eluent. Scheme 25 Ao,1 MAO1 1 : 10-oxa-4-acetyl, tetracyclo[6,3,0,01 -5,04-6]undeca-2-ene RMAO1 1 : 9-oxa—1-acetyl, tetracyclo[5,3,1 ,01-504v11jundeca-2-ene Product MAO11 showed the same molecular ion peak as the starting ketone. Its 13C NMR showed vinyl carbons at 5134.0 and 124.7. The 1H NMR showed two vinyl as doublets at 5 5.69 (H-3) and 5.10 (H-2). The two vinyl protons were coupled to each other with J=5.5 Hz, characteristic of vinyl protons of a cyclopentene ring. The proton at 5 3.74 (H-11) was coupled with the proton 53 at 5 3.64 (H-1 1) with J=8.8 Hz. The triplet at 5 3.68 (H-9) was coupled with the proton at 5 3.30-3.38 (H-9) and with the bridgehead proton at 5 1.87-1.97 (H-8) with J=8.0 Hz. The proton at 5 3.30-3.38 (H-9) was coupled with the bridgehead proton at 5 187-197 (H-8) with J=10.4 Hz. The bridgehead proton at 5 2.66 (H- 5) was coupled to the bridgehead proton at 5 2.37 (H-6) with J=6.81 Hz, which was coupled to the proton at 51.42 (H-7a) with J=1.5 Hz and to the proton at 5 1.38 (H-7b) with J=5.7 Hz. The bridgehead proton at 5 1.87-1.97 (H-8) was coupled with the proton at 51.42 (H-7a) with J=5.4 Hz. All of the above decouplings have been confirmed by homodecoupling experiments (Figure 10). Photoproduct RMAO11 showed the same molecular ion peak as that of the starting ketone. Its 13C NMR showed vinyl carbons at 5 133.77 and 125.59. The 1H NMR showed two vinyl protons: one at 5 5.56 (H-2) was coupled to the vinyl proton at 5 5.33 (H-3) with J=5.8 Hz and to the bridgehead proton at 5 215-219 (H-5) with J=1.2 Hz characteristic of cyclobutene ring. Another vinyl proton at 5 5.33 (H-3) was coupled to the bridgehead proton at 5 224-2.30 (H-4) with J=2.3. The proton at 5 4.59 (H-10) was coupled to the doublet at 5 4.0 (H- 10). The proton at 5 3.41 (H-8) was coupled to the proton at 5 2.92-3.00 (dd, H- 8) and to the bridgehead proton at 5 2.57-2.70 (H-7) with J=7.2 Hz. The proton at 5 2.92-3.00 (H-8) was coupled to the bridgehead proton at 5 257-270 (H-7) with J=11.7 Hz, which was coupled to the protons at 5 0.98-1.07 (H-6) and 5 1.23-1.33 (H-6). The bridgehead proton at 5 224-2.30 (H-4) was coupled to the bridgehead proton at 5 215-219 (H-5) and to the protons at 5 098-107 (H-6) and 1.23133 (H-6). The proton at 5 098-107 (H-6) was coupled to the proton at 5 1.23-1.33 (H-6). All of the above decouplings has been confirmed by homodecoupling experiments (Figure 11).DEPT74 (Distortionless Enhancement by Polarization Transfer) experiment of RMAO11 confirmed the presence of nine protonated carbons (5 -CH, 1 -CH3 and 3 -CH2, Figure 12). 54 - - - - ' Irradiation of A011 in anhydrous methanol (0.25 g of ketone per 400 mL of solvent) through a Pyrex filter led to the formation of two major products (Scheme 26). The two photoproducts were separated by gradient column chromatography on silica gel using hexane I ethyl acetate as eluent. Scheme 26 H36 0 H30 0’ \ _'“’_, pyrex methanol A011 MAC1 1, 4-acetyl,tetracyclo[6.3.0.01 ,5.04,6]undeca-2-ene RMAC1 1, 1 -acetyl,tetracyclo[5.3.1 .01 ,5.04,1 1]undeca-2-ene While photoproduct MAC11 could not be purified, product RMAC11 was characterized based on its 1H and 130 NMR. The 1H NMR showed two vinyl protons: one at 5 5.40 with J=5.82 and 2.28, and the second vinyl proton was at 5 5.34 with J = 5.85 and 1.14 Hz. The methyl group was at 5 1.55, and all other protons were at 5 0.80-0.95 (1 H, m), 1.05-1.25 (2H, m), 1.43-1.52 (1 H, m), 1.65-1.75 (1H,m), 1.80-2.0 (3H, m), 2.27-2.50 (3H, m). Further support for structure RMAC11 arose from its 130 NMR which showed vinyl carbons at 5 135.56 and 124.60. The remaining carbons were at 5 206.72 (C=O), 67.68, 44.39, 28.09, 27.77, 22.08 and 21.95. 55 .5050 s :65: 55-9885 5.5.».66.0320695. .589 7966 F .0 2:68:35 uc_.a:oooooEoI ”3 239“. sac . N m v n 0 _. h .1.-rinibr _ P > P F b n > I. P p b p h n p b h r p b . P b .51. 411114.13 56 .88 a. $5525 55-9885 : v.36. S. F.m.m_o_o>oa:o. ._boom-p.mxo-m .0 3:58:36 asaaoooooEoI ”3 2:9". 4 . .lfi . . . a. 1.... . 4" 44 . Wifi 4 l fl 4 o of a . _ IIJI. : 3!. o . 57 .88 5 $6525 25.3..- 885: .843. 5320598. .558- 7965 a 252.85 two ”N. 9.3.... inn ON on 0' on 00 0h 00 om 00“ On « can on“ av. can on. i.) u gives-st. — a. 53 unarmeLBearranoements: Upon heating in toluene-ds or in methanol-d4 the angular photoproducts underwent thermal rearrangement to form new products. The progress of all rearrangements were followed by 1H NMR. 1H NMR showed the formation of only one product with complete disappearance of the starting compound. W11: A solution of AFO11 in toluene-da (one drop of compound per 1.0 mL solvent) in an NMR tube was heated at 100°C for 12.0 hrs to give the thermally rearranged product. This product possessed an NMR spectrum nearly identical to that of LAFO11 (Figure 13) as shown in Scheme 27. Bicyclooctadiene TAFO11 was the only product detected by 1H NMR. Scheme 27 F30 o 100°C toluene-da AFO11 TAFO1 1 , 10-trifluoroacetyl-cis-syn-S-oxatricyclo[7.2.0.03v7jundeca-7,1O-diene. Product TAFO11 showed the same molecular ion peak as that of the starting ketone. Its 13C NMR (CDCI3) showed four vinyl carbons: one signal at 5 158.47 (C11) and 145.67 (C10) characteristic of a cyclobutene structure, and the signals at 5142.57 (C7) and 115.25 (C3) were assigned to vinyl carbons of 59 cyclohexene ring. The 1H NMR showed two vinyl protons: one vinyl proton at 5 6.41 (H-11), which was weakly coupled to the bridgehead proton at 5 2.34 (H- 1), which was coupled to the bridgehead proton at 5 3.18 (H-9) and to the hydrogens at 51.48 (H-2b) and 0.50 (H-2a). A second vinyl proton at 5 5.57 (H- 8) was coupled with the bridgehead proton at 5 3.18 (H-9) and to the protons at 5 4.14 (H-6b) and 3.97 (H-6a). Protons at 51.48 (H-2b) and 0.50 (H-2a) were coupled to the bridgehead proton at 5 2.09 (H-3), which was coupled with the protons at 5 3.86 (H-4b) and 2.96 (H-4a) with J=8.45 Hz. The proton at 5 1.48 (H-2b) was coupled to the hydrogen at 5 0.50 (H-2a). The two protons at 5 3.86 (H-4b) and 2.96 (H-4a) were coupled to each other with J=8.4 Hz. Protons at 5 4.14 (H-6b) and 3.97(H-6a) were coupled to each other with J=13.2 Hz. All of the above decouplings have been confirmed by homodecoupling experiments. The stereochemistry of TAFO11 has been established by NOE experiments which showed a cis ring junction at H1-H9, syn to H3 (Scheme 28). An Scheme 28 d:2.45 E: 3-7\ 0 IIII-I I n) E:5.1 “ Hb . q / d.2.47 Ha TAFO11 increase in intensity of the bridgehead proton H-1 (2.6%) was observed when the bridgehead proton H-3 (100%) was irradiated. When the bridgehead proton H-1 (100%) was irradiated, an enhancement of bridgehead protons H-9 (8.7%) 60 and H-3 (4.6%) were observed as shown in Scheme 28. The IR spectrum of TAFO11 showed a carbonyl signal at 1709 cm'1. WW2; The thermally rearranged product formed upon heating AFO12 in toluene-d3 (one drop of compound per 1.0 mL of solvent) for 10 hrs at 100°C is the linear bicyclooctadiene TAFO12 (Scheme 29). This product has an NMR spectrum nearly identical to that of LFO12 (Figure 14). The bicyclooctadiene TAFO12 was the only product detected by 1H NMR. Scheme 29 F30 0 100°C _Fac toluene-dB \o—- CH3 AFO12 TAFO12, 3-methyI-10-trifluoroacetyl-cis-syn-S-oxatricyc|o[7.2.0.03-7jundeca 7,1 0-diene. Product TAFO12 showed the same molecular ion peak as that of the starting ketone. Its 13C NMR showed four vinyl carbons: one signal at 8 158.17 (C11) and 148.38 (C10) characteristic of vinyl carbons of cyclobutene ring. Two other peaks at 5141.23 (C7) and 113.93 (Ca) were characteristic of vinyl carbons of cyclohexene structure. The 1H NMR (Figure 15) showed two vinyl .908 s 29.3 as. :9... a 522 I a. 23m 5 a Q '- )‘N m 61 If 0 Q... 2 I 9.8 «III }IIPIJ WILIJ can . m a > IF 5 L. b L h D h F F L b P L l\l .\\l 62 protons: one vinyl proton at 5 6.48 (H-11) weakly coupled to the bridgehead proton at 5 2.53 (H-1), which was coupled with the bridgehead protons at 5 3.17 (H-9), 1.39 (H-2b) with J=8.2 Hz and 5 0.73 (H-2a) with J=12.1 Hz. The second vinyl proton at 5 5.47 (H-8) was coupled with the bridgehead proton at 5 3.17 (H-9) and with protons at 5 4.24 (H-6b) and 3.97 (H-6a). The two protons at 5 1.39 (H-2b) and 0.73 (H-2a) were coupled to each other with J=12.1 Hz. The protons at 5 4.24 (H-6b) and 3.97 (H-6a) were coupled to each other with J=13.5 Hz. Protons at 5 3.53 (H-4b) and 3.09 (H-4a) were coupled with J=8.2 Hz. The methyl protons appear as a singlet at 5 0.83. All of the above couplings have been confirmed by homodecoupling experiments. The stereochemistry of TAFO12 has been established by NOE experiments which showed cis ring junction at H1-H9, syn to H3 (Scheme 30). Irradiation of the bridgehead proton at 5 2.53 (H-1, 100%) caused an enhancement of the bridgehead proton at 5 3.17 (H-9, 3.7%) and the methyl protons at 5 0.83. When the methyl protons at 5 0.83 were irradiated an increase in the intensity of the signals of the bridgehead protons at 5 3.17 (H-9, 0.7%) and 2.53 (H-1, 3.2%) were observed. The IR . spectrum of TAF021 showed a carbonyl signal at 1707 cm'1. Scheme 30 d:5.19 d:2.90 63 .88 519.3 use «.9... 3 E22 1. .3 23E \.. \ 0.. s. eon . a m .908 s 5.92: 8%-..F.588:83352055995 -c>m-m_o._boomEo:=E.o _-_>£oE_o.¢.v .0 2:58:83 9.3383080: "mp 2:9... bl P - IF L f f 2 t . P b n 4% .1: o... v n h P h D P P b P P .5 5. u r b P P L fifififififi 4% _II 65 .88 s 8.92: 8%.2 $8523.33... 0.26:836-..“-cam-m_o._aoomeoa_§.o SEES...” .o «Ecstoaxo mOz no. 959“. 66 W1: The thermally rearranged product formed upon heating of AF021 in toluene-d3 (one drop of compound per 1.0 mL of solvent) for 6 hrs at 100°C (scheme 31) was the linear bicyclooctadiene TAF021. Compound TAF021 has an NMR spectrum nearly identical to that of LAF021 (Figure 17). The bicyclooctadiene TAF021 was the only product detected by 1H NMR. Scheme 31 F30 O I. 100°C ‘ toluene-d3 \ H O CHaa'l CH3” TAF021 AF021 TAF021 ,4,4-dimethyl-10-trifluoroacetyl-cis-syn-S-oxatricyclo[7.2.0.03-7]undeca- 7,1 0-diene. Product TAF021 showed the same molecular ion peak as that of the starting ketone. Its 13C NMR showed four vinyl carbons: one vinyl carbon at 5 158.12 (C11) and 146.63 (C10) characteristic of a cyclobutene structure. Two signals at 5 142.57 (C7) and 114.80 (Ca) were assigned to vinyl carbons of the cyclohexene ring. The 1H NMR showed two vinyl protons: one vinyl proton at 5 7.19 (H-11) weakly coupled to the bridgehead protons at 5 3.62 (H-9) and 3.18 (H-1), which was coupled to the protons at a 3.62 (H-9), 2.10 (H-2b) and 1.09 (H-2a). The second vinyl proton at 5 5.75 (H-8) was coupled with the bridgehead proton at 5 3.62 (H-9). The bridgehead proton at 5 2.37 (H-3) was 67 coupled with the protons at 5 2.10 (H-2b) and to the vinyl proton at 5 5.74 (H-8), which was coupled to the bridgehead proton at 5 3.62 (H-9) and to the allylic protons at 5 4.34 (H-6b) and 4.24 (H-6a). Protons at 5 4.34 (H-6b) and 4.24 (H- 6a) were also coupled to each other. The two methyl groups were at 51.31 (- CH3a) and 0.96 (~CH3b). All coupling has been confirmed by homodecoupling experiments. The chemical shifts of H-2a, b, H-6a, b, -CH3a and -CH3b were all assigned based on NOE experiments. The stereochemistry of TAF021 has been established by NOE experiments which showed a cis ring junction at H1- H9, syn to H3 (Scheme 32). An increase of the intensity of the bridgehead protons at 5 3.62 (H-9) and 2.18 (H-3) was observed when the bridgehead proton at 5 3.18 (H-1) was irradiated. The intensity in the vinyl proton at 5 7.19 (H-11) and the proton at 5 2.37 (H-2b) were increased when the proton at 5 3.18 (H-1) was irradiated. An increase of the intesity of the protons at 5 3.18 (H-1) and 5 2.10 (H-2b) and the methyl group of -CH3a was observed when the bridgehead proton at 5 2.37 (H-3) was irradiated (Scheme 32). The IR spectrum of TAF021 showed a carbonyl signal at 1707 cm-1. Scheme 32 d:2.45 E:10.6 68 .908 c. 39.3 as. 2.9... 5 $2 1. E 2.6.“. "N hbrpbb-ppmpb-IPP. 69 WW When a solution of AFC11 in toluene-d8 (one drop of compound per 1.0 mL of solvent) in an NMR tube was heated at 100°C for 2.5 hrs, AFC11 underwent thermal transformation through Cope rearrangement to provide TAFC11 (Scheme 33). Product TAFC11 has an NMR spectrum identical to that of LFC11 (Figure 18). The bicyclooctadiene TAFC11 was the only product detected by 1H NMR. Scheme 33 F30 0 100°C toluene-d3= LH AFC11 TAFC1 1 , 10-trifluoroacetyI-cis-syn-tricyclo[7.2.0.03»7]undeca-7,10-diene. Product TAFC11 showed the same molecular ion peak as the starting ketone. Its 13C NMR showed four vinyl carbons: one vinyl carbon at 5 158.62 (C11) and 146.63 (C10) which were characetristic of a cyclobutene stmcture. One peak at 5 142.58 (C7) and 115.81 (C3) which were characteristic of the cyclohexene ring. The 1H NMR showed two vinyl protons (Figure 18): one vinyl proton at 5 6.52-6.54 (H-11) was coupled to the bridgehead proton at 5 2.47- 2.52 (H-1), weakly coupled to the bridgehead proton at 5 331-338 (H-9). The second vinyl proton at 5 5.77-5.79 (H-8) was coupled to the bridgehead proton at 5 3.31-3.38 (H-9), weakly coupled to the allylic protons at 5 2.06-2.15 and 1.96-2.06 (H-6a, b) and to the bridgehead proton at 5 331-338 (H-9). The bridgehead proton at 5 3.31338 (H-9) was coupled to the bridgehead proton at 5 2.47-2.52 (H-1), and also weakly to the proton at 5 1.96-2.06 (H-6b). The 7O bridgehead proton at 5 2.47-2.52 was coupled to the protons at 5 1.74-1.80 (H- 2b) and 5 0.64-0.73 (H-2a). The bridgehead proton at 5 1.84-1.93 (H-3) was coupled to the protons at 51.74-1.80 (H-2b), 1.60-1.66 (H-4b), 1.27-1.38 (H-5a) and 064-073 (H-2a). The proton at 51.60-1.66 (H-4b) was coupled to the protons at 51.41-1.49 (H-5b), 1.27-1.38 (H-5a) and to the bridgehead proton at 51.84-1.93 (H-3). The proton at 5 1.41-1.49 (H-5b) was coupled to the protons at 51.60-1.66 (H-4b), 1.27-1.38 (H-5a), 0.83-0.92 (H-4a), 206-2.15 (H-6a) and 1.96-2.06 (H-6b). The proton at 51.27-1.38 (H-5a) was coupled to the protons at 5 1.60-1.66 (H-4a), 1.41-1.49 (H-5b), 0.83-0.92 (H-4a), 2.06-2.15 (H-6a) and 1.96-2.06 (H-6b). The proton at 5 0.83-0.92 (H-4a) was coupled to the protons at 51.60-1.66 (H-4b), 1.41-1.49 (H-5b), 1.27-1.38 (H-5a) and weakly to the bridgehead proton at 51.84-1.93 (H-3). The proton at 5 0.64073 (H-2a) was coupled to the protons at 51.74-1.80 (H-2b), 1.84-1.93 (H-3) and to the bridgehead proton at 5 247-252 (H-1). All of the above couplings have been confirmed by homodecoupling experiments (Figure 19). The stereochemistry of TAFC11 has been established by NOE experiments which showed cis ring Shame 34 d:2.45 .908 c. :2: 2o 19...... 522 I. no. 23.... v... n a . a .19“ m m w m m . rLlrLthlrrrlrLLirL. ELlrlrLlhlrlrbLLLlhlLLlrrrrrlPLlrLlrplrLlrrlerer .rlrLlrbI.LI—Llhra . .r .. .. r; FLIPIPLLIFI < 19.: I - I . 71 72 .550 c. €92: 2.2.9....A-o8....c_..r.no.o.~<.. 0.0.6...-c>m-m_o-_boomo.o:_==.oF .o EcoEcoaxo asaaoocooEoI .9 9591.. n v r. L P b P h p P P b P b P) L) P b F F r F P h r P o F I.) b b P P F b Ifi : fl 4 91 3.1 ’ I _ IIII'I .. . i. .. 33...: f I I. 3 . 73 .88 s 392: 25.2.5 . .momncardodfl.to.o>oE-c>m-m_o._booa203:5...p .0 525598 mOz .8 2:9... can on Tu ON mm on ad 0' 0' on an on no F|br F F P F D F F b F \PL F r FL F P x— F FL F b by F F hi. F F F D h. r F .Fr FL F’F D \F b D F F F bLL b F P r F P P b F Fl 3 I. 9: 3.8.... .3 z ‘ . .x a... 9: .1 a: as: O...— 3.: v nvn- n. .- ~ n Q .6 .6? LI. WILJ «II } «LJ .— .- ’t L > [hr - F .3 1. : - 1 1 - 74 junction at H1-H9. syn to H3 (Scheme 34, Figure 20). An increase of the intensity of the bridgehead protons H-9 (11.1%) and 1.84-1.93 H-3 (5.4%) was observed when the bridgehead proton H-1 (100%) was irradiated. The IR spectrum of TAFO11 showed a carbonyl signal at 1707 cm'l. Wlmmm When a solution of AFC11 in methanol-d4 in an NMR tube (one drop compound per 1.0 mL solvent) was heated at 50°C for 30 hrs. AFC11 was transformed to CFC11 (Scheme 35). Scheme 35 methanol-d4 ll 50°C, 30h CAFC1 1 , 9-trifluoroacetyl-cis-anti-tricyclo[6.3.0.O1 -7]undeca-8,1 O-diene. Product CFC11 showed the same molecular ion peak as the starting ketone. Its 130 NMR showed four vinyl carbons: signals at 8 145.33 (Ce), 145.29 (C9). 134.07 (C10) and 115.96 (C1 1) were characteristic of a cyclohexadiene structure. The 1H NMR showed three vinyl protons: one vinyl proton at 8 6.88-6.91 (H-8) which was weakly coupled to vinyl protons at 8 6.23- 6.27 (H-10) and 5.57-5.61 (H-11) with J=0.9 Hz. The vinyl proton at 8 6.23-6.27 (H-tO) was also coupled to the vinyl proton at 8 5.57-5.61 (H-11) with J=6.0 Hz. 75 The third vinyl proton at 8 6.88-6.91 (H-8) was coupled to the bridgehead proton at 8 2.84-2.93 (H-7). The bridgehead proton at 8 2.92-2.99 (H-5) was coupled to the protons at 8 1.62-1.71 (H-4a), 1.86-1.96 (H-4b), 1.94-2.03 (H-6a) and 2.35- 2.46 (H-6b). The proton at 81.62-1.71 (H-4a) was coupled to the protons at 8 1.86-1.96 (H-4b), 2.03-2.14 (H-3b) and 1.28-1.34 (H-3a). The proton at 8 2.04- 2.14 (H-3b) was coupled to the protons at 81.28-1.34 (H-3a). 1.44-1.49 (H-2b), 1.62-1.71 (H-4a), 1.70-1.75 (H-2a) and 1.86-1.96 (H-4b). The proton at 81.28- 1.34 (H-3a) was coupled to the protons at 8 2.04-2.14 (H-3b), 1.86-1.96 (H-4b), 1.70-1.75 (H-2a) and 1.44-1.49 (H-2b). All of the above couplings have been confirmed by homodecoupling experiments (Figure 21). The stereochemistry of CFC11 has been established by NOE experiments (Figure 22) which showed cis ring junction at C1-C7 (Scheme 36). The proton at C5 is anti to the one at C7. An increase of the intensity of the bridgehead proton at 8 2.92-2.99 (H-5) was observed when the proton at 8 2.35-2.46 (H-6b) was irradiated (Scheme 36). The IR spectrum of CFC11 showed a carbonyl signal at 1707 cm“. Scheme 36 76 The thermally rearranged product formed upon heating of neat LAC11 in a sealed test tube at 190°C was the cyclohexadiene TLAC11 (Scheme 37). Scheme 37 TLAC11 TLAC1 1 , 9-acetyl-cis-anfi-tricyclo[6.3.0.01 ,7]undeca-8,10-diene. Product TLAC11 which was formed in only 30% when neat LAC11 was heated at 190°C for one minute was characterized by its 1H NMR. 1H NMR showed three vinyl protons, one was a broad doublet at 8 6.57 (J=5.3 Hz), another proton was a dd at 8 6.32 (J=9.9, 1.3 Hz). The third vinyl proton was also a dd at 8 5.47 with J=10.1 and 1.2 Hz. mmaLBcauarmmanoflLAQlLA solution of TLAC11 in an NMR tube in toluene d3 was heeated for six hrs. Follow up of the process by 1H NMR did not show the formation of any new product and the starting material was recovered intact. 77 [an 0+. m N... .980 s 2.80. 22.-25-885 r.Po.o.m.a0.96586-38883:; .0 358398 3.3388050: ”pm 959“. . o.~ n.~ Om , n.n 9' mi 0.0 n.n o .0 n.@ OS bthPhFhrFLleb .‘ 4) 11.11.11 I a... a... o... 2. . 2.: a... ;N.1;O.Z :4. 7N8 .908 s €96. 2% -o 3-88:8.Ed.».ao_o>u_...2o.588§_§.m .0 3:35:85 32 ”mm 2:9“. :8 m. 9... m.~ 9n 0n 9' n6 6...» a.» ad ad P F F F PL F F F n r F F F F rF F F F — +L’ + F .- F F F F by by F F 1F by! F F F F — F F F F b F L F F b F F F l? - F P F 1.... - :11 2. 0.... v.3 5.8 n3..wx «4. .qx .4. 3.: w \ O-d. (0.0 2.. 3 92 0...? . . . . . . .. .. . . 79 DEIII'DICII I' CEEI' Photolysis of cyclohexadiene CFC11 in a quartz cell using a Pyrex filter led to the formation of products FC11, LFC11 and AFC11 (Scheme 38). When the irradiation was carried out in an NMR tube, LFC11 and AFC11 were the minor products (Figure 23). When the NMR tube irradiation was carried out at A > 334 (Uranium glass filter), only A011 and LAC11 were formed (Figure 24). Scheme 38 hu Pyrex CBDS : F011 4' LFC11 + AFC11 Wm; A benzene solution of CFC11 and methyl benzoate in an NMR tube was irradiated. and the progress of the reaction was followed by 1H NMR. Valerophenone was used as an actinometer. and octyl benzoate was the internal standard for the actinometer. In this experiment F011 was the major product. The quantum yields obtained are summarized in Table V. \ Table V: Quantum Yield of Photolysis of CFC11 at it > 290 nm. Execursor Fromm—MW CFC11 F011 45 0.55 CFC11 F011 80 0.82 80 W: This experiment was performed the same way as the above experiment, but a Uranium filter was used in place of a Pyrex. In this experiment, only ketone FC11 and the bicyclooctadiene LFC11 were formed. Quantum yields for the formation of ketone F611 and bicyclooctadiene LFC11 are summarized in Table VI. Table VI: Quantum Yield of Photolysis of CFC11 at it >334 nm. E Ell II'I'I'I' QI'II CFC11 AF11 30 0.83 CFC11 LAF11 30 0.19 CFC11 AF1‘I 60 0.86 CFC11 LAF11 60 0.24 2 ”1H?“ 5 | [EEC I The UV-visible spectrum of cyclohexadiene CFC11 was recorded in benzene and is shown in Figure 25. In Figure 25 the UV-visible spectrum of ketone F611 is also shown for comparison. The UV-Visible spectrum of acetophenone was also recorded under similar condition for comparison and is shown in Figure 26. 81 .980 s 5.65 msec c. 19.83 8.38:. .o =39 s. as «.80 s a. .63 82885.08 3 E22 :22“. .8 2:9... 5.... v. .1rtt..—I.L..ILllrllLll.rllrL1.lr-lllhIIH.1L;L. 11L L1H-1.11.FIL:1FIIFI.I_. .....1..1 —1.IL. {flirt}. .. a. p 9.0 .< < 3. 1| . } ‘11» t {11" ‘1111 . . . . . ... . . . . . . gimme ._ o 2 ___oo o. m m . 1 m toning . tunic m to“. 829. ”m 82 .9; t a. E: can a 8.8.3:. .23 a. can 5.3.3:. 228 .3 meme 5 2823 .382 65 :95 82855.26 .0 $.22 :. new 2:9... xaq. v m m m m ~FP»>~»PF-—p.~bWP-p?~p[._1rp.p-prLIP—prb.LhCPILl.P_—ppub—.ppFLLFh.ppn>~FpPpppr—Pppp—Fkb. g < < < . m m m a. . . Swen—.2: 52: .m 19.02 :3. m n v m. I I, o N m rhp>Fbppunpbpp—.ppunr-bprpprrphppbpprtbpp—bh-ppprbuhpp.ppp»L-P~5»»—.F-pbpub o o m. a. to“... no 0 to“. 823 no SAHP? REF 3 300.200 1.3430 Ill +0.000 T . 0 I (3,311.» 1. 1 _ A no! L {l I \\\\“ +0.0“ :t_ . - - , NH 200.0 58.0(NH/DIU.) 400.0 22:20 4x13 '92 [ 400.0Hn 0.05§§] sane: 33?.2NN 1.8620 353.6NH 0.3900 +2-aan $1 L A :— \ I S 0 500 \\ i tnxDIu )l \\ l I I l i B \ i 1 l * 1 I \ . +9.96“: & 3¥ - J N" 300.0 28.8(NH/DIU.) 400.0 6=23 9x23 '92 [_fl86.@NM 0.0135 Figure 25: UV-Visible spectra of (A) cyclohexadiene CFC11 in benzene (6.20X10'4M, 0-2160); (B) ketone F011 in benzene (1 .20X10'2 M, 0337-88, 3353-32). 84 snap REF: -320.0Nn 0.1150 ¥__ +2 .000 F l - 4 *1 ‘r 1, 323?3.1. 3 ~ 11 .1 ~m—‘ \ g0.oen . \\J""t-—======J '— 209.0 50.0(HH/DIO+)- Q.’f 4/13 -92 400.02KIIIEIIILIL Figure 26: UV-Visible spectrum of acetophenone in benzene (9.0 x 10-4 M, 0-128) 85 ESIIIC'II" There is a good agreement between the spectroscopic data and the structures assigned to the linear and angular photoproducts and also the corresponding thermally rearranged products. The 1H NMR of all linear photoproducts and thermally rearranged products showed two vinyl protons one of which was characteristic of the cyclobutene ring and the other was characteristic of a cyclohexene ring. The proton NMR's of the angular photoproducts showed four vinyl protons, two of which were characteristic of a cyclobutene ring and the other two were characteristic of a cyclohexene ring. 13C NMR's of all linear and angular photoproducts and also the thermally rearranged products clearly showed four vinyl carbons characteristic of both cyclobutene and cyclohexene rings. (a) 1H NMR: The vinyl protons of the angular photoproducts (in CDCI3) showed signals from 856-64. The order of chemical shifts and signal multiplicities were the same for all of the vinyl protons of these photoproducts. The 1H NMR's of all linear photoproducts (in CDCI3) showed signals corresponding to vinyl protons with comparable chemical shifts. The B-vinyl protons of conjugated carbonyl groups showed signals at about 8 7.1-7.3 and the signals due to the vinyl protons of cyclohexadienes appeared at 8 565.8 for all linear products. The 1H NMR of all thermally rearranged products (in CDCI3) showed signals due to the vinyl protons of cyclobutenyl ketones at about 8 7.2 and also signals due to the vinyl protons of cyclohexenes at about 8 56-58. The chemical shifts corresponding to the vinyl protons of the linear photoproducts and those of thermally rearranged products were comparable. These 86 similarities in both chemical shifts and multiplicities were consistent with the hypothesis that these products were indeed diastereomers. (b) IR: The IR spectra of all angular photoproducts showed signals due to carbonyl absorption at about 1738 cm'1 and strong C-O-C stretching at 1150 cm'l. The IR spectra of all linear photoproducts showed signals characteristic of carbonyl absorption at about 1710 cm'1. The difference between the carbonyl signals linear and angular photoproducts were due to the conjugation of the carbonyl group in the linear photoproducts. This conjugation shifted the signals due to carbonyl absorption toward the lower wavenumber.72 The angular photoproducts showed signals due to C-Q-C stretching at about 1150 cm"1 which was similar to those of the angular photoproducts. The IR spectra of all thermally rearranged products showed C=O absorption signals at about 1707 cm'1 and a C-Q-C stretching at about 1153 cm'1. The low wavenumber of the carbonyl signals of the thermally rearranged products were due to the conjugation of the 0:0 groups. (c) 130 NMR: The 13C NMR of the angular photoproducts showed signals at approximately 8136.00 and 140.00 which were characteristic of cyclobutene ring71-72 and at 8 123.00 and 128.00 which were characteristic of cyclohexene structure.71:72 The linear photoproducts showed signals at approximately 8 145.00 and 158.00 which were characteristic of cyclobutene ring71-72 and at 8 115.00 and 142.00 which were characteristic of cyclohexene structure.72-73 The 13C NMR of all thermally rearranged products showed signals at approximately 8 146.00 and 158.00 which were characteristic of cyclobutene ring71-72 and at 8 142.00 and 115.00 which were characteristic of the 87 cyclohexene structure.72-73 Compounds bearing a trifluoroacetyl group showed a quartet for the carbonyl carbon with J=37 Hz and a quartet for the -CF3 group with J=290 Hz. E1!" ID I' C II' The vicinal coupling constants for hydrogen atoms connected by six electrons (3J) have been calculated from the dihedral angle (Jpc) using the Karplus equation (equation 32).75 These coupling constants are listed in Table XV. The dihedral angles were calculated using PCMODEL for different conformers after optimization (PCMODEL, MMX). In equation 32, o is the dihedral angle in degrees. The constants are A=4.22, Ba-O.5 and C=4.5 c.p.s. JH-H-=A+BCOS¢+CCOS 2¢ (32) Besides the linear and angular photoproducts and thermally rearranged products, the vicinal coupling constants of bicyclooctadienes with a trans- cyclobutene of the type shown in scheme 39 were also calculated for comparison. Scheme 39 1-TAFO11 88 WW Degassed and vacuum-sealed benzene or methanol solutions (2.8 mL) of ketone (0.02 M) containing various concentrations of 2,5-dimethyl-2,4- hexadiene and a standard were irradiated using a pyrex filter in a merry-go- round apparatus at room temperature. The degassing process was performed by three freeze-thaw cycles prior to irradiation. lrradiations were continued to approximately 10% conversion of ketone. Degassed benzene solution of 0.1 M o-methylvalerophenone as an actinometer was irradiated along with ketones. Stern-Volmer plots of ¢°l¢ versus quencher concentration were treated as linear with slope = M1. ZI'III'II' The slope of a linear Stern-Volmer plot was equal to qu where kq was the rate constant of quenching of tn‘plet ketone and 1: was its lifetime. The value of kq was estimated to be 5.0 X 109 M45“1 in benzene61 and 7.5 X 109 M’1S'1 in methanol.75 unamumlields The quantum yields for formation of cycloadducts were measured by parallel irradiation of a degassed benzene solution containing 0.1 M o- methylvalerophenone actinometer (¢=0.016)77 and 0.01 M of n-C15H32 as standard or 0.1 M valerophenone actinometer (=0.33)61 and 0.01 M of n- C15H34. In the case of o-methylvalerophenone, equation 67 was used to calculate the quantum yield of photoproduct formation. 89 (Do/(b 0 f I r I I F f I ' 1 0.00 0.01 0.02 0.03 0.04 0.05 0.06 [Q] 1M Figure 27. Stern-Volmer Plots of 3-[4-(a,a,0r-trifluoroacetyl)benzyony]propene (F011) with 2,5-dimethyl-2,4-hexadiene. (e) LFO11, qu=35.0 and (Cl) AFO11, kqt=12.3. 90 (Do/(b 0 . 1 [QLM Figure 28.Stern-Volmer plots of 3-[4-(a,a,a-trifluoroacetyl)benzyloxy]-2 -methyl propene (F012) with 2,5-dimethyl-2,4-hexadiene. (0) LFO12 and(0) AFO12, kqt=26.5. 91 (Do/(I) 0.0 0.1 0.2 0.3 0.4 0.5 0.6 [QJMXIO Figure 29.8tern-Volmer plots of 3-[4-(a,a,0t-trifluoroacetyl)benzyloxy]-3- methyl-1-butene (F021) with 2,5-dimethyI-2,4-hexadiene. (0) LF021 and (Cl) AF021, kqt=7.0. 92 (Do/(D 0. 0.00 0.01 0.02 0.03 0.04 [QJM Figure 30.Stern-Volmer plots of 3-(4-acetylbenzyloxy)propene (A011) with 2,5-dimethyl-2,4-hexadiene. (o) RMAO11 and (D) MA011. 93 (Do/<1) 01 ' Tfi I V I r l ' I 0.00 0.01 0.02 0.03 0.04 0.05 [QlM Figure 31. Stern-Volmer plot 5 of 5-(4-(a,a,a-trifluoroacetylphenyl)]- 1 -propene(FC11) with 2,5-dimethyl-2,4-hexadiene. (0) AFC11, kqt=17.62 and (Cl) LFC11. 94 (Do/(b 0.00 0.02 0.04 0.06 0.08 0.10 0.12 [QJM Figure 32. Stern-Volmer plots of 5-(4-acetylphenyl)-1-pentene (A011) with 2,5-dimethyI-2,4-hexadiene. (O) LAC11, kqt=7.9 and (Cl) AAC1‘I, kq1=4.3. 95 Table VII. Results of Stern-Volmer Quenching of Various Ketones by 2,5-dimethyl-2,4-hexadiene in Benzene (0.02 M) at 25°C. Keton Photoproducts Solvent kq‘l: 1/0 (Dproducts 5‘1 X 10'8 F011 AFO11 CsHe 12.3 4.1 0.017 LFO1 1 CeHe 35.0 1.4 0.045 F012 AFQ12 CeHs 26.5 1.8 0.021 LFO12 CsHe ------ ----- 0.026 F021 AF021 CeHe 7.0 5.8 0.005 LF021 CeHa 0.0087 FC1 1 AFC11 C6H5 17.6 2.8 0.0034 LFC1 1 CeHe ------ ----- 0.0064 MOAC1 1 MAO11 CH30H -------- ----- 0.0024 RMAO1 1 CH30H ------- ----- 0.0089 AC1 1 AAC11 CH30H 4.3 17.5 --------- LAC11 CH30H 7.9 9.5 0.0071 96 Table VIII. UV-visible Absorption Data for Various Ketones. Ketones 1:, 10* 8313 8240 n, 11* Max (8) 71mm) F011 280 (5300) 443 120 355 (33) F012 280 (5300) 453 113 356 (31) F021 280 (6700) 576 158 354 (28) FC11 280 (9300) 542 194 354 (33) A011 280 (1000) 55 2 357 (11) A011 280 (1100) 84 0 360 (22) 3-MOAC11 300 (2700) 3020 103 371 (16) 97 DISCUSSION | El | I C . I I' The photocycloaddition reaction of ketones F011, F012, F021, and FC11 led to the formation of both angular (A800) and linear (LBCO) bicyclooctadienes as shown in Scheme 40. The bicyclooctadiene TABCO is the thermally rearranged product of ABCO. Scheme 40 F011, F012, F021, Fc,1 _"_”.. Spectroscopic data clearly supported the structures suggested in scheme 40. As representative structures, compounds AFO11, LFO12 and TAFO12 can be correlated from their spectroscopic data. The 1H NMR of compound AFO11 (Figure 1) showed two methylene groups alpha to oxygen. The hydrogens of one of the methylene groups appeared as a triplet. This is due to the coupling with the bridgehead proton which is confirmed by the decoupling experiment (Figure 1). There are four vinyl protons in this conformer 98 characteristic of four- and six-membered rings based on their coupling AFO,1 constants (J values). In order to satisfy the structural formula of AFO11 there should be a furan type five-membered ring in the molecule. Structure AFO11 is the only possible conformer with complete satisfaction of the spectroscopic data and decoupling experiments (Figure 1). 1H NMR of LFO12 (Figure 5) showed two vinyl protons and its 130 NMR showed four vinyl carbons. The 1H NMR showed two methylene groups alpha to oxygen. Hydrogens of one of the methylene groups appeared as doublets and those of the second methylene group appeared also as doublets with fine allylic coupling. These allylic couplings disappeared when the upfield vinyl proton was irradiated. According to decoupling experiments this vinyl proton was coupled to a bridgehead proton. IR spectrum of LFO12 showed a carbonyl signal characteristic of a conjugated carbonyl group. The vinyl proton 99 conjugated with the carbonyl group appeared at 6 6.53. This downfield vinyl proton is weakly coupled to a bridgehead proton which is not the one coupled with the vinyl proton at higher field. Based on these data one can have the following fragments in the structure of LFO12. The two bridgehead protons 0 H H H H F36 I 0 -CH2' H H H H were coupled to each other (Figure 5) and had different chemical shifts. This confirmed that one bridgehead proton should be doubly allylic and the second one should be mono allylic. The upfield bridgehead group was coupled with the methylene group which is part of the six-membered ring. The above evidence strongly agrees with structure LFO12. Compound TAFO12 was the result of thermal rearrangement of AFO12. It's 1H and 13C NMR's are similar to LFO12 as shown in Figure 14. In fact the two conformers are diastereomers. Using an argument similar to the one used for LFO12, one can come to the conclusion that conformer TAFO12 has the same structural skeleton as that of LFO12. WISH! The stereochemistry of bicyclooctadienes ABCO, LBCO and TABCO were determined to be as shown in Scheme 40 based on NOE experiments. In these structures the cyclobutene rings have cis geometry which is syn to the bridgehead R3 (CH3 or H) group. The NOE experiments of the bicyclooctadienes showed an enhancement of the signal due to H11 of ABCO when the R3 group (H or CH3) irradiated. In the case of LEGO NOE 100 experiments showed no enhancement of the R3 group (H or CH3) upon irradiation of the bridgehead proton H1 and only Hg was enhanced. In bicyclooctadiene TABCO the cyclobutene ring has cis geometry which is trans to the bridgehead group R3. One might argue that, in LBCO, the H1 and the bridgehead group R3 may be too far apart to interact. The fact that the NOE experiments of TABCO showed an enhancement of the R3 signal when H1 was irradiated, confirmed that the two bridgehead groups H1 and R3 of LBCO can interact if they are cis. Three dimensional structures of products LFO11, AFO11 and TAFO11 are shown in Scheme 41 for visualization. These structures were saved and printed from MOPAC format after optimazation. Scheme 41 101 These three dimensional structures were optimized by molecular modeling techniques (PCMODEL, MMX). For a better understanding of the Stereochemistries of photoproducts and thermally rearranged products, it is more convenient to compare their NOE results. a: LFO11 and TAFO11: The key NOE experiments for these two conformers are summarized in Table IX. Table IX: Results of NOE Experiments of LFO11 and TAFO11 * Indicates the Hydrogens which are Saturated Ht-Ha‘ H3‘-H11 H1'-H9 LFO11 d(A°): 3.96 3.20 2.78 %E: 0.0 1.9 7.9 TAFO11 d(A°): 2.95 4.84 2.45 %E: 2.6 0.0 8.7 As shown in Table IX for photoproduct LFO11 there was no enhancement of the bridgehead hydrogen H1 when H3 was irradiated, while there is an enhancement of H1 of TAFO11 upon irradiation of H3. This clearly demonstrates that the two bridgehead protons H1 and H3 are trans for LFO11 and cis for TAFO11. Irradiation of the bridgehead proton H3 of LFO11 caused an enhancement of H11 while there was no enhancement of H11 for TAFO11 when H3 was irradiated (table IX). This clearly demonstrates that the cyclobutene ring must be cis to H3 of LFO11 and trans to H3 of TAFO11. For both LFO11 and TAFO11 an enhancement of the bridgehead protons Hg was observed upon irradiation of H1. This simply confirms that the bridgehead hydrogens H1 and H9 are cis to each other for both conformers. 102 b: LFO12 and TAFO12: The key NOE experiments for these two conformers are summarized In Table X. Table X: Results of NOE Experiments of LFO12 and TAFO12 H1-CH3' CH3'-H11 H1.-H9 LFO12 d(A°): 4.59 3.59 2.43 %E: 0.0 1.5 10.5 TAFO12 d(A°): 3.28 5.19 2.49 %E: 0.8 0.0 3.7 As shown in Table X, the same conclusion for LFO12 and TAFO12 can be drawn based on the arguments used above for LFO11 and TAFO11. c: LF021 and TAF021: The key NOE experiments for these conformers are summarized in Table XI. The same conclusion can be drawn for conformers LFOz‘I and TAF021 based on the arguments used above. Table XI: Results of NOE Experiments of LF021 and TAF021 H1-H3' H3'-H11 H1'-H9 LF021 d(A°): 3.86 3.12 2.45 %E 0.0 3.5 17.0 TAF021 d(A°): 2.90 5.05 2.45 %E: 3.6 0.0 10.6 103 d: LFC11 and TAFC11: The key NOE experiments for these conformers are shown in Table XII. Table XII: Results of NOE Experiments of LFC11 and TAFC11 H1-Ha’ H3'-H11 H1'-H9 LFC11 d(A°): 3.91 3.19 2.45 %E 0.0 1.9 7.2 TAFC11 d(A°): 2.86 5.04 2.45 %E: 3.5 0.0 10.5 Using the same arguments as used for the above compounds one comes to the conclusion that the two bridgehead hydrogens H1 and H3 are trans for LFC11 and cis for TAFC11. The bridgehead hydrogen H3 is cis to the cyclobutene ring for LFC11 and trans for TAFC11 as shown in Table XII. e: LAC11: The key NOE experiments for this photoproduct are summarized in Table XIII. Table XIII: Results of NOE Experiments of LAC11 H1-H3' H3"-H11 H1'—H9 LAC11 d(A°): 4.20 ------ 2.45 %E 0.0 ----- - 5.9 As shown in Table XIII there is no enhancement of H3 when H1 is saturated, while H9 is enhanced upon irradiation of H1. Therefore the 104 conformer LAC11 must have the same stereochemistry as those of the previous linear photoproducts. f: AFO11, AFO12 and AF021: The key NOE experiments for these photoproducts are summarized in Table XIV. Table XIV: Results of NOE Experiments of AFO11, AFO12 and AF021(R: CH3 or H) H11-85* 85'-H10 AFO1 1 d(A°): 2.91 4.97 %E 1.8 0.0 AFO1 2 d(A°): 3.32 4.01 %E: 2.2 0.36 AF021 d(A°): 2.92 4.70 %E: 2.6 0.9 As shown in Table XIV it is clear that when the bridgehead group R5 (methyl or hydrogen) is irradiated an enhancement of H11 is observed for all three photoproducts. For photoproducts AFO12 and AF021 the vinyl proton H10 is also enhanced upon irradiation of R5. This clearly demonstrates that the cyclobutene rings are all cis and syn to the bridgehead group R5. 105 W Although the NOE experiments clearly supported the stereochemistries suggested, this can further be verified by calculating the vicinal coupling constants."5 The vicinal coupling constants obtained from 1H NMR (Jobs) and PCMODEL calculations (Jpc) for the proposed structures and their trans isomers (eg. t-LFO11) are listed in Table XV. In Table XV, besides the Jobs and Jpc, the J values for the dihedral angles at the two extremes (Jmod) are also listed for LFO11, TAFO11 and AFO11. These dihedral angles were estimated from the molecular models and are not accurate. They only show the angle limit within which the calculated angles should fall. In Table XV asterisks show the key coupling constant experiments. Table XV: The Dihedral Angles of Vicinal Hydrogens; Jpc: Coupling Constants based on Dihedral Angles Calculated from PCMODEL; Jmod: Coupling Constants Based on Dihedral Angles Estimated from Molecular Models; Jobs is the Coupling Constant Observed by 1H NMR (Asterisks Shows the Key Coupling Constant Experiments). Cmpds hydrogens angle (deg) angle (deg) Jpc Jmod Jobs PCMODEL Molecular Model LFO11 H1-H11' 58.58 4560 0.74 4.0-1.7 1.20 H1-Hga" 52.81 120-60 2.71 2.2-1.7 4.20 H1-H2b' 53.77 10-(-90) 1.25 8.0-0.3 1.20 H1-H9 8.50 30-10 8.03 5.9-8.0 6.00 Hg-Ha’ 37.04 6010 5.05 1.780 4.95 Table XV (cont'd) 106 Cmpds hydrogens angle (deg) angle (deg) Jpc Jmod Jobs PCMODEL molecular Mel 14.5011 H1-H11 82.54 0.19 1.20 H1-H23 176.46 9.18 4.20 H1-H2b 56.43 2.19 1.20 H1-H9 166.28 8.59 5.00 H9-Ha 98.79 0.01 4.95 TAFO11 H1-H11' 53.72 5090 1.25 1.7-0.3 0.84 H1412; 34.38 30-(-50) 5.44 5.9-1.7 4.47 H1-H2b 153.13 150-90 7.33 81-03 11.4 H1-H9 3.38 0—0 8.18 8.28.2 8.24 Hg-Hg" 52.57 90-45 1.39 0.3-4.0 2.23 t-TAFO11 H1-H11 79.98 0.10 0.84 H1-Hza 53.57 1.28 4.47 111-sz 174.89 9.15 11.4 H1-Hg 167.98 8.82 8.24 Hg-Hs 88.15 0.29 2.23 LFO1 2 H1 -H1 1 64.47 1.98 small H1-Hza' 174.02 7.75 6.95 H1 -H2b 55.92 3.09 1 .67 H1-H9’ 41.54 5.00 5.70 Hg-Hg“ 18.70 7.44 5.85 {A Table XV 107 t-LFO1 2 TAFO12 H1-H11' t-TAFO12 LF021 (cont'd) Cmpds hydrogens angle (deg) angle (deg) Jpc Jmod Jobs PCMODEL Molecular Model H1-H11 80.17 0.11 small H1-H23 170.96 8.99 6.95 H1 -H2b 53.09 3.27 1 .67 H1-H9 23.56 6.82 5.70 Hg-Ha 104.27 0.39 5.86 65.66 1 .04 1 .12 1114-123" 151.23 7.08 7.40 111-1121; 33.35 5.58 4.47 H1 -H9 0.50 8.22 12.1 Hg-Ha" 65.88 1.02 2.24 1114-111 80.50 0.12 1.12 H1-Hza 176.59 9.19 7.40 H1 -H2b 63.96 1 .23 4.47 H1 -H9 169.36 8.90 12.1 Hg-Ha 88.14 0.29 2.24 H1-H1 1 66.26 0.98 small H1-Hza' 65.02 1.01 1.67 H1 -H2b 48.62 3.32 6.42 H9413" 28.93 6.17 5.59 113-H2; 39.98 4.62 5.30 157.98 7.91 12.3 H3-H25’ 108 Table XV (cont'd) Cmpds hydrogens angle (deg) angle (deg) Jpc Jmod Jobs PCMODEL Molecular Model f-LF021 H1-H11 35.57 5.26 small H1-Hza 70.12 0.59 1.57 111-sz 45.83 3.59 5.42 Hg-Ha 103.54 0.33 5.59 H3-Hza 18.09 7.37 5.30 H3-H2b 92.87 0.24 12.3 TAF021 H1-H11' 66.55 0.94 1.12 111-112;; 34.90 5.35 5.70 111-sz 62.52 1.41 4.19 H1-H9 0.50 8.22 12.3 H9413" 66.28 0.98 2.23 H3-H2b 178.09 9.21 7.82 f—TAF021 H1-H11 79.80 0.09 1.12 H1-Hza 63.38 1.31 6.70 H1-H2b 175.97 9.18 4.19 H1-H9 167.76 8.80 12.3 H9-H3 88.71 0.28 2.23 H3—sz 164.31 8.54 7.82 LFC11 H1-H11 59.45 0.65 small H1-H2b' 55.41 2.34 5.76 H1-H9' 13.15 7.75 5.04 119-113* 32.89 5.55 4.94 Ha-sz‘ 173.91 9.12 12.0 109 Table XV (cont'd) Cmpds hydrogens angle (deg) angle (deg) Jpc Jmod Jobs PCMODEL Molecular t-LFC11 H1-H11 83.22 0.21 small H1-H2b 57.34 2.07 5.76 H1-H9 166.48 8.72 5.04 Hg-Ha 97.50 0.07 4.94 H3-H2b 97.07 0.08 12.0 TAFC11 H1-H11' 76.40 0.98 1.00 H1-Hza 66.87 0.91 4.50 H1-H2b’ 35.19 5.30 4.00 H1 -H9 19.89 7.21 11.0 Hg-Hg’ 40.31 4.57 2.50 Ha-Hza' 114.84 1.52 4.00 H3-H2b 4.87 8.16 6.00 t-TAFC11 H1-H11 82.28 0.19 1.00 H1 -Hza 175.98 9.18 4.50 H1 -H2b 63.02 1.34 4.00 H1 -H9 167.92 8.82 1 1 .0 Hg-Ha 89.97 0.28 2.50 H3-Hza 160.60 8.20 4.00 H3-H2b 40.20 4.59 6.00 LAC11 H1-H11 69.19 0.68 small H1412; 51.71 1.50 1.39 H1-H2b' 55.39 2.34 5.86 H1-H9' 12.90 7.78 4.88 Hg-Ha' 32.64 5.68 4.50 H3-Hza' 55.94 2.25 1.57 H3-H2b’ 173.93 9.12 1 1 .4 Table XV (cont'd) Cmpds hydrogens angle (deg) angle (deg) Jpc Jmod Jobs PCMODEL Molecular Model t-LAC11 H1-H11 79.02 0.05 small H1 -H23 54.47 2.44 1 .39 H1-H2b 173.09 9.01 5.86 H1-H9 163.10 8.44 4.88 H9-H8 103.37 0.32 4.60 H3-H23 100.67 0.12 1.67 H3-H2b 18.09 7.37 1 1.4 AFO11 H5-H4a' 35.69 90-(-45) 5.25 0.3-4.0 7.80 H5-H4b' 156.67 90-170 7.77 0.3-8.1 7.80 H7-Hea 71.95 120-(-30) 0.42 2.2-6.9 4.46 Hy-Heb‘ 45.05 30120 3.86 5.9-2.2 4.46 t-AFO11 H5-H4a 51.60 2.88 7.80 H5-H4b 178.1 3 9.20 7.80 H7-H6a 103.23 0.30 4.46 H7-H5b 14.29 7.69 4.46 AFO12 H7-H5a 29.20 6.14 5.60 H7-H5b 87.90 0.29 3.90 t-AFO12 H7-Hea 27.35 5.38 5.60 H7-H5b 89.83 0.28 3.90 AF021 H5-Hea 61.15 1.58 6.04 H5-H5b" 178.84 9.22 8.73 H7-H5a" 32.23 5.74 5.50 H7-H5b 86.24 0.27 3.79 111 Table xv (cont'd) Cmpds hydrogens angle (deg) angle (deg) Jpc Jmod Jobs PCMODEL Molecular Model t—AF021 H5-Hea 9.87 8.06 6.04 Hs-Heb 104.55 0.41 . 8.73 H7—Hea 90.83 0.27 5.50 H7—H5b 20.32 7.16 3.79 As shown in Table XV there is better agreement between the observed 3J values and the calculated 3J values for the stereochemistries consistent with NOE experiments than for the conformers with trans cyclobutene rings. This clearly supports the cis geometry for the cyclobutene rings and makes the possibility of trans geometry very unlikely. The 3J values estimated from equation 32 are comparable with the observed coupling constants. Equation 32 does not predict the variablity of the observed coupling constants.75 For a perfect result, factors such as the effect of electron orbital and dipolar electron spin terms, and the consideration of ionic and other perturbations should be introduced.75 The most reliable results using equation 32 are to be expected from the comparison of closely related species.75 112 III II. II II IIIDE' ll'l , Bell and Saunders73 argued that for similar molecules the measured NOE's should be directly proportional to 1/d6 in which d is the intemuciear distance. They found a good correlation between NOE and 1/d6 for a variety of compounds. They also found a straight line when they constructed a plot of %E against intemuciear distance.78 Plots of %E against internuclear distances in Table XVI for the compounds studied are shown in Figures 3338. Table XVI: % NOE's and 1/r5 Values for the Products Studied. compound proton proton %NOE d 1/d6 minted—observed LangstroM) LFO1 1 H1 H9 7.9 2.45 0.0046 H3 H23 0.17 2.52 0.0039 H3 H43 6.4 2.47 0.0044 H1 H 2b 5.1 2.49 0.0042 H1 H23 2.1 2.62 0.0031 H1 H11 3.1 3.14 0.0019 H3 H11 1.9 3.20 0.0010 AFO11 H5 H11 1.8 2.91 0.0048 H5 H23 2.2 4.12 0.0002 H5 H43 4.4 2.38 0.0068 LFO12 H1 H9 10.5 2.43 0.0048 CH3 H1 1 1.5 3.59 0.0005 CH3 H2a 2.3 3.14 0.0010 H48 3.1 3.07 0.0012 Table XVI (cont'd) compound proton AFO12 LF021 AF021 LFC11 LAC11 113 proton %NOE d 1/d6 mutated—9W (mm) CH3 H10 0.36 4.01 0.0002 CH3 H1 1 2.2 3.32 0.0008 CH3 H43 2.6 2.93 0.0016 CH3 H65 1.1 4.00 0.0002 CH3 H63 2.2 3.09 0.001 1 H1 H9 17 2.45 0.0046 H1 H11 7.4 2.83 0.0019 H3 H11 3.5 3.12 0.0010 H1 H23 4.1 2.62 0.0031 H1 H25 6.8 2.43 0.0048 H1 CH35 1.9 5.27 0.0000 H5 H10 0.9 4.70 0.0001 H5 H11 2.6 2.92 0.0016 H5 H55 1.8 2.58 0.0034 H5 H63 3.9 2.36 0.0058 H1 H9 7.2 2.42 0.0050 H1 H11 3.8 2.88 0.0018 H1 H25 4.3 2.49 0.0042 H3 H11 1.9 3.19 0.0009 H1 H9 6.9 2.45 0.0046 H1 H11 14.8 2.84 0.0019 H1 CH3 1.9 5.04 0.0001 H1 H25 4.0 2.54 0.0037 H25 H1 7.9 2.49 0.0042 H25 H23 13.1 2.61 0.0032 Table XVI (cont'd) compound proton TAFO11 TAFO12 TAF021 TAFC11 proton %NOE d 1/d5 Mam—observed (8005mm) H1 H9 8.7 2.45 0.0046 H1 H11 4.4 2.89 0.0017 H1 H3 3.3 2.96 0.0015 H3 H25 3.0 2.56 0.0036 H3 H45 5.1 2.47 0.0044 H3 H1 2.6 2.96 0.0015 H1 H9 3.7 2.49 0.0042 H1 H11 2.8 2.90 0.0017 H1 H25 3.6 2.53 0.0038 CH3 H1 0.8 3.28 0.0008 CH3 H45 1.7 2.97 0.0014 CH3 H55 0.5 3.42 0.0006 H1 H9 10.6 2.45 0.0046 H1 H25 4.8 2.44 0.0047 H1 H11 4.3 2.87 0.0018 H1 H3 3.6 2.82 0.0020 H1 H23 1.2 3.11 0.0011 H1 H9 10.6 2.45 0.0046 H1 H11 4.3 2.84 0.0019 H1 H25 4.8 2.50 0.0041 H1 H23 1.2 2.61 0.0032 H1 H3 3.6 3.89 0.0003 %E 115 8'—a q l 6-1 0 4-1 I Column1 1 a O Column3 2-1 I . . . o-—n . . . 2 3 4 5 Internucleer distance (angstrom) Figure 33: Plots of %E against intemuciear distance for LFO11 (CI) and AFO11(O). %E 116 O 1 #1.. Internuclear distance (angstrom) Figure 34: Plots of intemuciear distance for LFO12 (D) and AFO12 (O). %E 117 20 10" a a ' e 1 . . . e . a e 0 T t I V T V 2 3 4 5 6 Internuclear distance (angstrom) Flgure 35: Plots of %E against intemuciear distance for LF021 (Cl) and AF021 (O). %E 118 20 e e 10" e a e ‘ a a e o I V I I r 2 3 4 5 6 lnternuclear distance (mum) Flgure 36: Plots of %E against intemuciear distance for LFC11 (Cl) and LAC11 (O). %E 119 10 J I 8.1 61-1 .1 I 4‘ .. I - 1 . I . O 2" . ° e Internuclear dlstance (angstmm) Figure 37: Plots of %E against intemuciear distance for TAFO11 (Cl) and TAFO12 (O). %E 120 12 10‘ 8.1 a l "I O .1 Internuclear distance (mum) Figure 38: Plots of %E against intemuciear distance for TAF021 (Cl) and TAFC11 (O). 121 As shown in Figures 33-38 there is not a good correlation between the %E and the internuclear distances. In most of the cases only a few points correlate well. The correlation is much better for the angular photoproducts than for the linear photoproducts and thermally rearranged products. This could depend on the number of ring junctions in the molecules. As the numbers of ring junctions increases the stereochemistry of the molecule will be more complex and other factors could then contribute to the NOE measurements. As an example let us examine the NOE studies of photoproduct LFO12. As shown in this scheme there is an enhancement of H11 when the bridgehead CH3 is irradiated while there is no enhancement of H1 upon irradiation of CH3. The interesting point is the shorter internuclear distance between H1 and CH3 compared to H11 and CH3. As shown, the two bridgehead groups H1 and CH3 are trans to each other and this could be a reason for the zero enhancement of H1 when the CH3 group is irradiated. In another words, the orientation of the interacting groups in NOE experiments should be an important factor for efficient enhancement. Therefore the NOE effect may depend upon the angle between the CH bond vectors. Most of the systems studied by Bell and Saunders78 had C-H bonds with parallel vectors or vectors with angles less than 90°. They only studied proton systems of molecules having unequivocal and fairly rigid structures.73 Rigidity of systems studied should be an important 122 factor in NOE study. The angular photoproducts are more rigid than the linear ones based on the moecular models. This could be a reason for a better correlation between %E and the internuclear distances for these compounds. For a given compound the ratio of %E for two internuclear distances should be proportional to the ratio of their 1/r5. As can be seen from Table XVII, there are some cases for which this correlation exists, but this is not We for all %E and m“. This could again be due to the comlexity of the compound studied. There are other reasons for the deviation from linearity when %E was plotted against the internuclear distance. One reason may be due to the enhancement of signals too close to the irradiation frequency since partial direct saturation may occur. When the bridgehead proton H3 of TAFO11 was irradiated, the increase in the intensity of the bridgehead proton H1 was 2.6%. The increase in the intensity of the bridgehead proton H3 of TAFO11 was 3.3% when the bridgehead proton H1 was irradiated. The difference in the percent enhancement of the two bridgehead hydrogens could be due to the involvement of factors other than distances in the NOE experiments. Both NOE experiments and decoupling constant calculations clearly supported the structures suggested. As can be seen from the results, the calculated coupling constants showed a better correlation for the linear products. In the case of NOE the correlation was better for the angular photoproducts. In fact the two experiments were complementary of each other. A better conclusion could be drawn if both were applied to a series of closely related compounds. Finally the minimum energies of different conformers with both cis and trans cyclobutenes were calculated by PCMODEL (MMX) after optimization. The structures were created in PCMODEL and were fully optimized. The minimum energies were displayed in the upper right corner of the screen after 123 optimization. These energy values are shown in Table XVII. As shown, the minimum energy of the conformers with cis cyclobutenes were much lower than those with trans cyclobutenes. Table XVII. Minimized Energy of Different Conformers and their trans lsomers. Cis-Compounds Minimum Trans-Compounds Minimum Energy Energy LFO11 74.51 t-LFO11 318.95 LFO12 76.79 t-LFO12 319.45 LF021 78.45 t-LF021 321.58 LFC11 73.17 f-LFC11 317.98 LAC11 45.06 t-LAC11 116.22 TAFO11 74.96 f-TAFO11 314.82 TAFO12 76.06 f-TAFO12 317.22 TAF021 77.62 t-TAF021 411.86 TAFC11 74.44 t-TAFC11 312.28 AF 01 1 68.25 t-AFO11 88.86 AFO12 70.39 t-AFO12 91.40 AF021 71.29 t-AF021 93.24 AFC11 67.61 t-AFC11 89.85 124 5 Eli I' | . , The angular photoproducts and the linear photoproducts and thermally rearranged products cannot have the stereochemistries shown in Scheme 42. In the angular conformers shown in Scheme 42 there should not be any enhancement of H11 when H5 is irradiated because they are trans to each other. Similarly, for the linear conformer in Scheme 42, the vinyl proton H11 is trans to H3 and should not get enhanced when H3 is irradiated and this is not consistent with the observed NOE results. Scheme 42 L 3410 1:1,. it 0 -= l-_ a 0.00:0 010””. 01 :10 a: AFO12: Assignment of the hydrogens of the 02 and C4 methylene groups of AFO12 have been made by a combination of selective decoupling and NOE experiments as shown in Figures 3 and 4. Based on the homodecoupling experiments (Figure 3), when the doublet at 8 3.89 was irradiated, the doublet at 8 3.66 collapsed to a singlet. Therefore, the proton responsible for the AB quartet at 8 3.89 and 3.66 were geminal and so were those which gave the AB quartet at 6 3.73 and 3.50. A task remains to differentiate between the hydrogens of the 02 and C4 methylene groups. As shownin Figure 4, the NOE experiment showed interaction between the bridgehead methyl group and the 125 protons at 8 3.89 and 3.50. These two protons were syn with the bridgehead Ha F15 AFO12 methyl group. Since there was a stronger interaction between the proton at 8 3.50 and the methyl group, the two protons at 8 3.50 and 3.73 belonged to the methylene group of C4 and the protons at 83.66 and 3.89 were those from the methylene group of C2. NOE experiments also showed a greater enhancement of the proton at 8 1.96 compared to the one at 8 2.20. This confirmed that the signal at 8 1.96 belonged to the C6 proton which was syn with the CH3 group. A similar strategy was used to assign the methylene groups of AFO11, AF021 and AFC11. b: LFO12: The assignment of the methylene groups of 02, C4 and C5 have also been made by a combination of NOE (Figure 6) and homodecoupling experiments (Figure 5). The homodecoupling experiments of LFO12 showed 126 two geminal protons at 8 4.22 and 4.02 and also at 8 3.51 and 3.04. The NOE experiment showed a stronger enhancement of the proton at 8 3.51 in comparison to the one at 8 4.22 when the bridgehead methyl group is irradiated (figure 6). Therefore, the two doublets at 8 4.22, and 4.02 belong to the hydrogens of C6, and the doublets at 8 3.51 and 3.04 belong to the hydrogens of C4. NOE experiments (figure 6) also showed a greater enhancement of the doublet at 8 1.38 compared to the quartet at 8 0.86 which belongs to the methylene group of C2. The doublet at 8 1.38 belongs to one of the 02 hydrogens which was syn with the bridgehead methyl group. Another interesting point in the NOE experiments of LFO12 was the enhancement of the quartet at 8 0.86 (H25) when the bridgehead proton at 8 0.87 (H1) was irradiated. Similarly, the stereochemistry and differentiation of the methylene groups of LFO11, “0:1 and LFC11 can also be worked out using the above arguments. c: LAC11: The assignment of the C2, C4, C5 and Cs methylene groups have been made by a combination of NOE (Figure 9) and homodecoupling experiments (Figure 8). The multiplets at 8 1.03 and 2.11 were decoupled when the bridgehead proton at 8 3.02 (H1) was irradiated (figure 9). This means that the protons at 8 1.03 and 2.11 were those of the 02 methylene group. NOE experiments(figure 9) showed an enhancement of the multiplet at 8 1.03 when 127 the bridgehead proton at 8 3.02 (H1) was irradiated (Figure 9). Therefore, the multiplet at 8 1.03 belongs to one of the methylene protons of C2 which was syn with the bridgehead proton of H1 and was specified by H25. Consequently, the multiplet at 8 2.11 was from H23. Irradiation of the vinyl proton at 8 5.71 (H3) decoupled the multiplet at 8 1.88-2.02 (Figure 8). Therefore, the two allylic protons of Ce were at 81.88-2.02. Irradiation of the allylic protons of Ce decoupled the multiplets at 8 1.42-1.75. The multiplets at 8 1.42-1.75 should be due to the methylene protons of C5. Irradiation of the proton at 8 1.13-1.25 enhanced the signals at 8188-202 and 1.42-1.75 (H53,5) (Figure 9). This means that the multiplet at 81.13-1.25 belongs to H43, and the multiplets at 8 188-202 belong to the bridgehead proton H3 and the methylene protons of H45. d: TAFO12: The assignment of the C2, C4 and 06 methylene groups of TAFO12 have been made by a combination of selective decoupling (Figure 15) and NOE experiments (Figure 16). Irradiation of the bridgehead proton at 8 2.53 (H1) decoupled the two protons at 81.39 and 0.73 (H235) as shown in Figure 15. The NOE experiments showed stronger enhancement of the proton TAFO12 at 81.39 compared to that of 8 0.73 when the bridgehead proton at 8 2.53 was irradiated (Figure 16). Therefore the proton at 81.39 was syn with the 128 bridgehead proton at 8 2.53 and belongs to H25. The proton at 8 0.73 was assigned to H23, which was anti to the bridgehead proton at 8 2.53. The protons responsible for the AB quartet at 8 4.24 and 3.97 were the methylene protons of C5. An NOE experiment also showed an enhancement of the allylic proton at 8 4.24 when H1 was irradiated (Figure 16). It follows that the signal at 8 4.24 belongs to H5 which was syn with the bridgehead methyl group. Consequently, the signal at 8 3.97 was that of H53. The protons responsible for the AB quartet at 8 3.53 and 3.09 were the methylene protons of C4. Enhancement of the doublet at 8 3.53 upon irradiation of the bridgehead methyl group showed that this signal belong to H45. Therefore, the doublet at 8 3.09 belongs to H43. A similar strategy was used to assign the methylene protons of TAFO11 and TAF021. e: TAFC11: Assignment of the protons of the 02, C4, Cs and Cs methylene groups have been made by a combination of decoupling and NOE experiments (Figures 19 and 20). An enhancement of the protons at 8 1.77 and 0.68 was observed when the bridgehead proton at 82.50 was irradiated (figure 20). Therefore, the two protons at 81.77 and 0.68 were those of the C2 methylene group. The proton at 8 1.77 was enhanced to a greater extent and was therefore the H25 proton. The signal at 8 0.68 was assigned to H23 proton. Irradiation of 129 the bridgehead proton at 81.88 (figure 19), decoupled the protons at 8 1.77 (H25), 0.68 (H23), 1.63 and 0.87. Consequently, the two protons at 8 1.63 and 0.87 belong to the methylene group C4. Irradiation of the proton at 8 0.87 decoupled the two protons at 81.45 and 1.32. Therefore, the protons at 8 1.45 and 1.32 belong to the methylene group 05. When the vinyl proton at 8 5.78 was irradiated the signals at 8 2.10 and 2.01 were decoupled. Therefore, the two protons at 8 2.10 and 2.01 belong to the allylic methylene Ce. f: CFC11: Assignment of the methylene groups of CFC11 have been made by a combination of NOE and homodecoupling experiments (figures 21 and 22). Homodecoupling experiments showed that the vinyl proton at 8 6.90 and also the protons at 8 2.40 and 1.98 were decoupled when the bridgehead proton at 8 2.88 was irradiated. Consequently, the bridgehead proton at 8 2.88 was H-7 and the protons at 81.98 and 2.40 were H-6a,b. Irradiation of the vinyl proton at 8 2.95 (H-5) decoupled the protons at 8 2.40, 1.98, 1.91 and 1.66, therefore, the two protons at 8 1.91 and 1.66 were H-4a and b. Irradiation of the proton at 8 1.30 decoupled the protons at 8 1.46, 1.91, 1.66, 1.72 and 2.09. This means that the proton at 8 1.30 belongs to H-3. A similar effect was observed when the proton at 8 2.09 was irradiated, therefore this proton should also be H-3. Consequently, the protons at 8 1.66 and 1.91 were H-4. NOE experiments 130 showed an enhancement of the protons at 8 2.40, 2.09 and 1.66 when the bridgehead proton H-5 was irradiated (Figure 22). Therefore, these protons were syn to the bridgehead proton H-5. W [2 2] II El I I III The intramolecular [2+2] o-photocycloaddition of alkenes to aromatics separated by three atom tethers takes place as shown in Scheme 43.1-2 A cyclohexadiene (CI-ID) is the first photoadduct which forms. This cycloadduct then thermally transforms to a cyclooctatriene (COTR) which can further react photochemically to form the bicyclooctadienes ABCO and LBCO. Scheme 43 X30 0 0 \4 Y flu pyrex X=H, F Y x30? + x30 . a‘ H \ .= Y—-' H O ABCO LBCO The cyclohexadienes of the ketones in Scheme 43 are in thermal equilibrium with the corresponding cyclooctatrienes. For the ketones in 131 Scheme 43 the equilibrium favors the cyclohexadiene more than the cyclooctatriene and only a small amount of cyclooctatriene is formed. The existing equilibrium between the cyclohexadiene CFC11 (CI-ID: Ya-CH2, X=F) and the corresponding cyclooctatriene is supported by the high molar absorptivity of CFC11 in benzene (e =- 2160 at 1:3280 nm) compared with that of the acetophenone (e . 128 at 328 nm; nan). The high molar absorptivity of CFC11 is in fact characteristic of 11,111 excitation of the corresponding cyclooctatriene which is in equilibrium with the cyclohexadiene. The concentration of cyclooctatriene in equilibrium with the corresponding cyclohexacfiene is so low ( > 5%) that it cannot be detected by 1H NMR. Upon photolysis, the cyclooctatriene is transformed to the bicyclooctadienes as shown in Scheme 43. Consumption of cyclooctatrienes due to their transformation to the corresponding bicyclooctadienes shifts the equilibrium from cyclohexadiene to cyclooctatriene. The cyclohexadienes can undergo fast transformation to the starting ketone as well as to the linear and angular bicyclooctadienes upon absorption of light. While irradiation of CFC11 at 290 nm (Pyrex filter) produced both linear and angular bicyclooctadienes and the starting ketone (Scheme 38), irradiation at 334 nm (Uranium filter) produced only the linear bicyclooctadiene as well as the starting ketone. This showed the wavelength dependency of the photocycloaddition reactions. It is possible that the two bicyclooctadienes were formed from different excited states of the cyclooctatriene. The cyclooctatriene exists in a boat conformation (Scheme 43) and the chromophore conjugated with the carbonyl group presumably forms the lowest excited state. The nature of these excited states is in fact a subject of further investigation. Once the cyclooctatriene is formed it can undergo a photochemical [2+2] disrotatory ring closure reaction between the conjugated dienes to produce the 132 cyclobutenes as shown in Scheme 44. In these concerted reactions the exo Scheme 44 0 H1 Y= 0, CH2; X=H, F ring closure is preferred over the endo. In case of the angular bicyclooctadienes there will be an interaction between the bridgehead hydrogen, the five-membered ring, and the acetyl group if an endo ring closure is going to take place. For the linear bicyclooctadienes the endo ring closure creates a transition state in which the bridgehead hydrogen, the allylic hydrogen, and the vinyl hydrogen H1 will have an axial conformation based on molecular models. This increases the barrier for rotation, where for an exo ring closure this high barrier does not exist. WW Formation of both linear and angular photoproducts have been reported as the result of disrotatory electrocyclization of each diene unit in cyclooctatrienes.1.2184 Ketones in which the alkenes are attached to the aromatic ring by an oxygen anchor usually gave the angular photoproduct upon irradiation. Those in which the alkene, are attached to the aromatic ring by a methylene group gave both angular and linear photoproducts. It seems that this selectivity depends on the electron deficiency of the eight-membered cyclooctatriene intermediate. For a better understanding of this process let us 133 examine the cyclooctatrienes shown in Scheme 45 and compare their photochemistry with those shown in Scheme 46. Scheme 45 H3C o Scheme 46 X 0 x30 0 A011: X3C C III! + NC F011, __> _-’ Fc,1 x x 0 x30 COTR 31:5,1; x=o, Y=F LFo,1: X=O, Y=F X=O, CH2 AFC11:X= CH2. Y=F LFC11: X=CH2. Y=F =H1 F Ac11: X=CH2, =H LAC11. XBCHZ, Y=H Cyclooctatriene CK-ll is more electron deficient than CK-I and COTR. The electron deficiency of the cyclooctatriene CK-II compared to CK-1 is due to the presence of an electron withdrawing (CN) group as well as an acetyl group conjugated with the 1: system. The difference in electron deficiency of cyclooctatrienes COTR with cyclooctatriene CK-I is due to the presence of an electron donating group conjugated with the 1: system of CK-l. Both angular and linear bicyclooctadienes are formed from electron deficient cyclooctatrienes CK-Il34 and COTR. Cyclooctatriene CK-I gave only the angular photoproduct. 134 This is because CK-l is less electron deficient than CK-Il and COTR. The electron deficiency of CK-l is due to the conjugation of the electron donating oxygen with the acetyl group through the n system. Further support for the effect of electron deficiency of the cyclooctatriene on the regioselectivity of ring closure reactions came by comparing the chemical yields of photoproducts of ketones F011 and F011 as shown in tables I and IV. For the ketone F011 the ratio of chemical yield of linear to angular photoproduct (LFO11:AFO11) is 3:1 and for ketone FC11 the ratio of LFC11:AFO11 is 25:1. The cyclooctatriene of ketone F011 is more electron deficient compared to that of F011. This could be a reason for the excess formation of LFO11 compared to LFC11. Winn Ketones A011 and A011 showed two different modes of photocycloaddition reactions. In earlier studies photolysis of both AC11 and A011 led to the formation of products which were the results of intramolecular meta cycloaddition (Schemes 25 and 26). Later their photolysis led to the formation of o-photocycloadducts similar to those of trifluoroacetophenones (Scheme 22). Irradiation of ketones A011 and AC11 in methanol led to the formation of two photocycloadducts. 13C NMR of these products showed two vinyl carbons and the 1H NMR confirmed the presence of two vinyl protons. These data are consistent with the photocycloadducts which arose from meta- photocycloaddition as shown in Schemes 25 and 26. Spectroscopic data confirmed that meta-cycloadducts are the result of 1,3— and 2,4-intramolecular meta-addition of the double bond to the aromatic ring. 135 Two meta-cycloadducts are formed from 1.3-photocycloaddition of double bonds to the aromatic rings. These adducts for ketones A011 and AC11 are shown in Scheme 47. Several 1,3-Photocycloadducts have already been reported (Scheme 2).13-27.79 Scheme 47 o 3 4 ’\ H30 / yrex A011: X=O MAX1‘I: X=O,CH2 MAX123 X=O,CH2 AC11: XSCHZ Structures RMAX11 are presumably the rearranged products of the initial 2,4-m-photocycloadduct M1AX11 as shown in Scheme 48. This transformation may be a concerted process through 1.3-sigmatropic rearrangement. It has been reported that the 1.3-adduct shown in Scheme 49 undergoes sigmatropic rearrangement upon heating.80 Scheme 48 O O =(\ hp 0: 2 XW H3C X —* H30 4 Y H30 X A011: X=O M1Ax11: X=O,CH2 RMAX11: X=O,CH2 AC11: X=CH2 Scheme 49 9.4“.” 136 Examples of intramolecular meta photocycloaddition forming 2,4- photoadducts have been reported (Scheme 50).19-81 Two intramolecular 2,4- photoadducts are possible for ketones A011 and AC11 as shown in Scheme 51. Scheme 50 hu . .. —* CD _ v Scheme 51 A011: X=O AC1 12 X=CH2 M1AX11: X=O,CH2 M1AX12: X=O,CH2 Product M1AX12 which could also form through vinyl-cyclopropyl rearrangement of M1AX11 as shown in Scheme 52 is highly strained and can Scheme 52 M,Ax,1: X=O,CH2 MiAX12= X=O.CH2 not be built by molecular models. All of the reported 2,4-meta photocycloadducts”:81 have structures similar to M1AX11 (Scheme 50).“9-31 A careful comparison of the proton NMR's of MAO11 and RMAO11 showed that the methyl of MAO11 appeared as a singlet at 8 1.70, while that of the RMAO11 appeared at 8 1.35. If the rearranged product had the structures 137 shown in Scheme 51, then there is no reason for the upfield shift of the methyl group of the rearranged products. In the rearranged products shown in Scheme 50, based on molecular models, the methyl group is located right above the shielding region of the double bond which could account for the upfield shift of the methyl group in 1H NMR. The 1H NMR of RMAX11 showed two vinyl protons. One at 8 5.56 with J=5.8 and 1.2. The second vinyl proton at 8 5.33 with J=5.8 and 2.3. The coupling constants 1.2 and 2.3 are due to the coupling between the vinyl protons and the bridgehead allylic proton. The reasons for the duality in the photocycloaddition reactions of A011 and A011 are not known. ortho-Photocycloaddition takes place from the triplet excited state of benzenefiv2 The presence of a small amount of triplet quencher as impurity in the starting ketones or in the solvent might shift the mode of addition from triplet to singlet position. WW Photoproducts AFO11, AFO12, AF021 and AFC11 underwent thermal transformations through Cope rearrangement to form products other than cyclooctatrienes. The corresponding linear bicyclooctadienes LFO11, LFO12, LFOz1 and LFC11 were stable under similar conditions. Thermal transformation through Cope rearrangement is symmetry allowed}36 This rearrangement for AFO11 is shown in Scheme 52. The transition state for this rearrangement resembles a chair type conformation. It is interesting that the stereochemistries at the ring junctions of the products shown in Scheme 53 are all syn and completely consistent with the observed stereochemistry established from spectroscopic data. 138 Scheme 53 H H TAFO11 TAFO11 Thermal rearrangements of bicycloheptadienone BCHD-I are shown in Scheme 54.82 When BCHD-l was heated at 187°C two thermally rearranged products were formed, the triene l-IT which was the minor product and the bicycloheptadiene BCHD—ll which was major. In the thermal rearrangement of BCHD-l at 187°C there is no reason for the discrimination between products HT and BCHD-ll if the reaction is going to proceed through a diradical intermediate. In fact, if there is going to be any discrimination it should favor the formation of HT rather than BCHD-ll because not only is heptatriene HT highly conjugated, but it is less strained compared to bicycloheptadiene BCI-ID-ll. The thermal transformation of BCHD-I to BCHD-ll resembles that of AFO11 to TAFO11 shown in Scheme 27 and this latter rearrangement presumably does not take place through a diradical intermediate. 139 Poor resolution of the signals in 1H NMR of the angular photoproduct AFC11 (Scheme 43; A800: X=F; Y=CH2) made the NOE experiment impossible and its stereochemistry could not be determined. Once AFC11 Scheme 54 O OMe 0 gm .. , 6 HT BCHD-II undenlvent Cope rearrangement upon heating in toluene, the separation of the signals in the 1H NMR of the product was resolved enough to make it possible to study its stereochemistry. This thermally rearranged product showed the same stereochemistry as TAFO11 (Scheme 27). Consequently, the angular bicyclooctadiene AFC11 should have the same stereochemistry as that of the AFO11. When phot0product AFC11 was heated at 50°C in methanol it rearranged to the cyclohexadiene CFC11. This transformation takes place presumably through the formation of cyclooctatriene followed by a 61: electron disrotatory ring closure to the cyclohexadiene as shown in Scheme 55. 140 Scheme 55 O F C 0 3 AFC11 metILanol F30 50 C 30 h _ CFC11 It has been observed that angular bicyclooctadienes having an oxygen conjugated with the bridge bond underwent rearrangement to the corresponding cyclooctatriene in the presence of a catalytical amount of p- toluenesulfonic acid in benzene“. Thermal transformation of AFC11 to CFC11 in methanol is slow and presumably is acid catalyzed. There is always a trace amount of acid present in commercially available methanol which may catalyze this transformation. 9 g B I D I I I . E I. _ While angular photoproducts having an oxygen conjugated with the bridge bond gave an eight-membered ring cyclooctatriene upon heating, those without the oxygen underwent Cope rearrangement to a linear bicyclooctadiene. This thermally produced product is a diastereomer of the corresponding linear photoproduct. Two products can be formed through thermal ring opening. The formation of an eight-membered ring, presumably through a zwitterionic intermediate‘ and the concerted Cope rearrangement. The formation of the eight-membered ring is favored when there is an electron withdrawing or donating group conjugated with the bridge bond of the angular bicyclooctadiene. In the absence of such conjugation the concerted Cope rearrangement is preferred. 141 III B . I I. .I Ketone 3-MOAC11 underwent Q-photocycloaddition to the corresponding cyclohexadiene as shown in Scheme 24. In this reaction the addition took place at the unsubstituted side of the benzene ring. The [2+2] photocycloaddition involves the approach and interaction of the double bond with the excited state benzene ring which leads to the exciplex formation.1 This interaction presumably takes place through a charge transfer process in which the alkene is the donor and the aromatic ring is the acceptor.1 The addition takes place at the more positive side of the benzene ring depending on the nature of the substituents.84 When there is a methoxy group at the meta position of the acetyl group, the unsubstituted side of the benzene ring is the preferred side for the addition.84 The cyclohexadiene shown in Scheme 56 does not open to the corresponding cyclooctatriene and no angular or linear photocycloadducts of Scheme 56 o \ 00H3 H30 LHaC 0.. OCH3 the type shown in Scheme 41 is observed upon photolysis of 3-MOAC11. Transformation of the cyclohexadiene to the corresponding cyclooctatriene presumably involves the formation of a biradical followed by an electron transfer to form the zwitterionic intermediate of the type shown in Scheme 57. For the cyclohexadiene in Scheme 56 the presence of a donor 142 Scheme 57 H3C 0 'Hac 0 H30 0 H c 0 \ 3 O O O O conjugated with the bridge bond opposes the electron transfer process. Since no zwitterionic intermediate is formed, there is no cyclooctatriene present and consequemly no angular or linear photoproducts are formed. I I I? I. It is well known that photocycloaddition reactions occur from the 11:, n“ triplet of the aromatic ring.1 In most cases the Stern-Volmer plots of relative quantum yields versus the quencher concentrations showed a linear correlation. In the cases of photoproducts AFO12, LF021 and LFC11 the Stern-Volmer plots were not linear and indeed they were curved. This is possibly due to the involvement of more than one excited state in the photolysis.‘58 Presumably in the case of the curved Stern-Volmer plots both of the intermediates involved in the excited states are quenched. Formation of both the angular and the linear photoproducts from the ketones take place through a multistep process in which several intermediates are included. For complete understanding of these reactions stepwise quenching studies should be performed. Formation of photoproducts MAO11 and RMAO11 cannot be quenched by 2,5-dimethyl-2,4-hexadiene. This is due to the involvement of a singlet excited state. Further support for the involvement of a singlet excited state in formation of MAO11 and RMAO11 comes from the fact that these are the products of meta addition which usually takes place from the singlet excited state. 143 Formation of photocycloadducts of ketones with a trifluoroacetyl group para to the alkene tether is much faster than those with acetyl groups. This is due to the inductive effect of fluorine with strong withdrawing power. In ketones with a trifluoroacetyl group the difference in the ionization potential of the double bond and the benzene ring increases because the benzene ring is more positive. This facilitates the exciplex formation and consequently the formation of the cyclohexadiene adducts. The fast formation of cycloadducts from ketones bearing trifluoroacetyl groups support the idea of involvement of a charge transfer process in ortho-photocycloaddition reactions. Chemical yields: Linear Stern-Volmer plots are obtained in the quenching study of LFO11 and AFO11 (Figure 33), AFO12 (Figure 34), AF021 (Figure 35) and AFC11 (Figure 36). In the case of LFO12 (figure 34), LF021 (Figure 35) and LFC11 (Figure 36) the results of a quenching study led to curved Stern-Volmer plots. There is a correlation between the Stern-Volmer plots obtained and the chemical yields calculated. In case where both the linear and angular photoproducts showed a linear Stern-Volmer plot, the ratio of their chemical yields stayed almost the same as long as the photolysis was going on. However, when the linear product has a curved Stern-Volmer plot, the ratio of the two photoproducts changes as the irradiation continues. The chemical yield is higher for the photoproducts with curved Stern-Volmer plots at the beginning, but lower at the end. This is presumably due to the involvement of two triplet excited states in the formation of phot0products and, in the case of linear photoproducts, both excited states get quenched. This suggests that the angular and linear cyclooctadienes are not formed from the same excited state. The chemical yields of the linear photoproducts were high at the early stage of irradiation and decreased dramatically with continued irradiation as shown in tables l-IV. This is not the case for the angular photoproducts. Their 144 chemical yields stayed more or less the same with prolonged irradiation. The only structural difference between linear and angular photoproducts shown in Scheme 14 is that in the linear case the carbonyl group is conjugated with the cyclobutene double bond. This enone chromophore can absorb light and undergo reactions characteristic of conjugated enones. For example, it can add to the double bond of the cyclohexene ring and the sequence can lead to polymerization. Irradiation of the benzene solution of the linear photoproduct in an NMR tube did not lead to the formation of a specific, identifiable product based on 1H NMR. The only change observed in the 1H NMR before and after irradiation was that the baseline of the 1H NMR became noisy and broad peaks appeared in the upfield region. This is presumably due to the formation of several secondary products from prolonged irradiation of the linear photoproduct, this is the main reason for the disappearance of these photoproducts. Quantum yields: Quantum yields for the phot0products formed from the ketones having alkyl tethers (Scheme 43) are lower than those in which the ketone is tethered by an oxygenJ.2 It has been suggested that the formation of cyclooctatrienes from the corresponding cyclohexadienes involves a zwitterionic intermediate of the type shown in Scheme 57.2 When there is an oxygen conjugated with the bridge bond, cyclooctatriene formation is faster due to resonance stabilization (Scheme 54). Although the cyclohexadiene with an oxygen tether might undergo a reverse reaction to the starting ketone upon photolysis, resonance stabilization and faster formation of the cyclooctatriene will reduce the extent of the reverse reaction. Hence, the concentration of the cyclooctatriene increases which 145 results in higher quantum and chemical yields of the corresponding bicyclooctadiene. Phenyl ketones have two low lying triplets n,11* and 11,111. The energies of these two excited triplets are affected by ring substituents. Atoms like oxygen, lower the 11,11* triplet energy level relative to n.11*. Since intramolecular photocycloaddition involves charge transfer quenching of the 11,111 triplet excited state of benzene by the alkene, the presence of an oxygen atom conjugated with aromatic ring will increase the 11,n:* population which will increase the probability of the exciplex formation from the excited state and cause an increase in the quantum yield. In the presence of an alkyl tether the 11, 11* population is lower and the probability of exciplex formation decreases and this reduces the quantum yields. It has been observed that the quantum yields of addition for the ketones tethered by all carbon atoms ( F011; Scheme 43; Y=CH2, X=F) are lower than those having oxygen (Scheme 43; Y=O, X=F). For photocycloaddition a preferred orientation of the double bond and the the benzene ring is required.12 Once this orientation is achieved for ketone FC11, the carbon tether will have the conformation shown in Scheme 58. Since ketone F011 has a comparable rate constant to F011, F012, and F021, (T able IX) the gauche interaction Scheme 58 If H l ”‘1 @ x30 X=F, H O 146 between the methylene group is not significant in the formation of the biradical. The energy for the most stable conformers of the biradicals formed from FC11 and F011 are comparable based on molecular model calculations. This is in agreement with the idea that formation of these biradiacals is the rate determinig step.31 F30 F3C o . o - . BRF011 BRFC11 The dihedral angles between the radical centers of BRFO11 and BRFC11 were calculated by molecular mechanics (PC Model) to be about 750. Formation of the four-membered ring requires a proper orientation of the two radical centers. This demands a rotation towards minimization of the dihedral angles. During this rotation there is a conformation for BRFC11 in which all of the methylene groups of the five-membered ring are gauche. This rotation for BRFC11 requires a higher barrier compared to that of BRFO11. This high barrier could be the reason for the low quantum yield of the photoproducts formation from F011. In the case of F021 based on the molecular models the proper orientation of the two radical centers creates a conformation in which one of the methyl groups of the five-membered ring is gauche with the methylene radical. This could account for the lower quantum yields of the photoproducts formed from F021 compared with those of F011. 147 Synthetic application of products from [2+2] ortho-photocycloaddition The linear bicyclooctadienes TAFC11 and LAC11 find utility in the synthesis of natural products having four-, five-, and six-membered ring systems. Among these are the metabolites of the fungus stereum purpureum which causes silver leaf disease on plum, apple, and other fruit trees. Ayer and co-workers reported the isolation of sterpuric acid XI, hydroxysterpuric acid XII, sterpurene-3, 12, 14-triol XIII, and 1-sterpurene XIX from the natural metabolism of fungus stereum purpureum (Scheme 59).35.86 Scheme 59 H CH3 HOOC .’ -----I H30 """‘ OH H3 XI '1' CH3 HOHzC ACOHzc - lea-- .1.,5 .13.; .9...) OH CHZOAc XIII XIX The sterpurenes, which are constructed of four-, five-, and six- membered ring systems, constitute natural products of a new structural type. Their framework can be prepared by photolysis of the corresponding ketone. The four-, five- , and six-membered ring photoproducts can then be converted to the corresponding sterpurene by established chemistry. The route for the photosynthesis of these 148 by established chemistry. The route for the photosynthesis of these systems is shown in scheme 60.87 Scheme 60 R-H2C R / O O H3COf% CF3 h" ,. CF3 A ’ 3 R'-H2C OTBDMS ”300366 R. OTBDMS < a: R=R'=H 3 b: R=-OTBDMS, R'=H c: R=H, R'=-OTBDMS R c c H CHZ-(r; H30020’ 0 m, “3 02 )(IFIflngFa Dibal _ CF = H3C ’ ”30 OTBDlelS 58:39” RI CH -R CH -R — -2 - HOHZC [221-(2:1: 5H HOHZC 2| Bu4N+F _ -° 3 > H3C '7 H3C OTBDMS ‘002 CSJgPMS THF CHz-R' CHZ-R H CHz-R HOH2C 2] selective HOOCWI ’- HaC 0H [0] “30 OH XIII CH?“ CH?“ xr: R=R'=H . . XII: R=OH, R'=H selectlve acylatlon CH3 AcOHZC ...I H3C OH CHzoAC XIX 149 EXPERIMENTAL EE'flI'I I’ll'l S I I I I ll Benzene: One gallon of reagent grade, thiophene free, benzene was repeatedly stirred with 150 ml portions of concentrated sulfuric acid for about 24 hrs until the acid layer remained colorless (about 5 times). The benzene layer was washed twice with 500 ml portions of distilled water followed by 200 mL portions of saturated aqueous sodium bicarbonate until the aqueous phase became neutral or basic. The benzene layer was then dried over magnesium sulfate, and filtered into a 5 liter round bottom flask. Anhydrous phosphorus pentoxide was then added and the solution was refluxed overnight. The benzene was then distilled through a one meter column packed with stainless steel helicies at a rate of 50 mL per hour. The first and the last 10% were discarded and only the middle fraction was collected.88 Methanol: Super dry methanol was obtained by the method of Lund and Bjerrum.88 In a dry 2.0 liter round-bottom flask equipped with magnetic stirrer and double surface condenser under argon was placed 5.0 g of Mg turning, 0.5 g of iodine and about 50 ml of commercial absolute methanol. The mixture was warmed until the red color of iodine disappeared. When all of the magnesium has been converted into methanolate, 800 ml of commercial absolute methanol added and the mixture was refluxed for 2 h. The methanol was then distilled directly into a 1000 mL round bottom flask and the middle fraction was collected (ignoring the first and the last 10%).‘39 Ethanol: Super dry ethanol was obtained by the same method used to dry methanol.89 150 12.—[WEB Tetradecane: Tetradecane (Columbia Organic) was washed with sulfuric acid and distilled (b.p. 119.12°C at 10 Torr). Pentadecane: Pentadecane (Columbia Organic) was washed with sulfuric acid and distilled (b.p. 131°C at 10 Torr). Hexadecane: Hexadecane (Aldrich) was purified by washing with sulfuric acid followed by distillation (b.p. 105°C at 10 Torr). Heptadecane: Heptadecane (Chemical Sample Company) was purified by washing with sulfuric acid followed by distillation (b.p. 158°C at 8 Torr). All the above were purified by professor P. J. Wagner. Docosane: Docosane (Aldrich) was used as received. 2.0119an1: 2,5-DlmethyI-2,4-hexadIene: 2.5-Dimethyl-2,4-hexadiene (Aldrich) was allowed to sublime in the refrigerator and the sublimate was used. Ethyl sorbate: Ethyl sorbate (Aldrich) was used as received. WW aLEmtanslMB A Varian Gemini 300 was used to record NMR spectra of most of the synthetically prepared compounds and the ketone precursors. For the photoproducts usually a Varian VXR-300 was used. The VXR-500 was employed if a higher resolution was required. Both Varian VXR-300 and 500 were used for NOE experiments. Usually CDCI3 (dried by storing over anhydrous CaCl2) and CsD5 were used as a solvent to prepare NMR samples in eight inch 527-PP type or seven inch Norell 505-P NMR tubes. The 1H- 151 signals of the solvent at 8 7.24 (chloroform) and 8 7.15 (benzene) were used as a reference. W All 13C NMR spectra were obtained in CDCI3 using a Varian Gemini- 300. The signal of CDCI3 at 8 77 was used as a reference. '!!l| v‘ I |-1!'°Il S I Shimadzu uv-visible recording spectrophotometer, uv-160, was used to record absorption spectra. Usually a dilute solution (10'4 M) of a ketone was used in 1 cm Beckman quartz cels in spectrometric grade benzene or acetonitrile. A blank cell filled with pure solvent was used for background correction. W13 All IR spectra were obtained using a Nicolet lR/42 Fourier Transform spectrometer. The spectra were recorded by a Hewlett-Packard colorpro recorder. CCI4 was used as solvent for all samples in a 0.025 mm Z12308-0 Aldrich IR cell. The background correction was made by first recording the spectrum of the pure solvent. 2.111139351139113 Low resolution mass spectra were obtained on a Finnigan 4000 GC/MS or a JEOL JMS-HX110 mass spectrometer at the MSU-NIH mass spectrometry facility at the Department of Biochemistry. High resolution mass spectra were also obtained on a JEOL JMS—HX1 10 mass spectrometer. The following atomic 152 masses were used for C, H, O and Fin order to obtain the high resolution mass spectra. C: 12.000000; H: 1.007825; 0: 15.994920; F: 18.998400. nLlSetcnas; West” In a 1-L round bottom flask equipped with reflux condenser and magnetic stirrer was placed 25.6 g. (0.15 moles) of p- bromotoluene, 25.8 g. (0.145 mole, Aldrich Chemical Company) of N- bromosuccinimide, 1.0 g of benzoyl peroxide (Aldrich Chemical Company) and 90 mL of dry carbon tetrachloride. This mixture was refluxed until a severe exothermic reaction began at which point the yellowish reaction mixture turned white. Refluxing was continued for an additional hour and the hot reaction mixture was filtered through a sintered glass funnel into a 250 mL round bottom flask. The solid residue on the tunnel was washed with 2x30 mL of hot carbon tetrachloride. Evaporation of the solvent under reduced pressure gave a yellowish solid. Recrystallization of the yellowish solid from absolute ethanol (30 mL) gave 28.9 g (77.06% yield, including second crop) of white needles (mp: 57-57.5 ° C). ‘H-NMR: 8 7.45(d, 2H, J=7.8), 7.24(d,2H, J=7.8), 4.42(s,2H); 13CmNMl-‘l: 8136.72, 131.91, 130.62, 128.08, 32.36; IR: 1716.9, 1489.2, 1360.0, 1219.2, 1070.6, 1014.7, 827.6 cm‘1; MS (tn/e) 250(M+), 169, 90, 89, 63, 50, 44. W63 13.8 g. (0.3 moles: 17.5mL) of ethyl alcohol was added dropwise to a 100 mL round bottom flask containing 22.8g. (0.2 moles, EM Science) of trifluoroacetic acid at 0°C. This was followed by dropwise addition of 23.5 mL of concentrated H2SO4 while cooling. The mixture was then 153 refluxed for 0.5 h and the product distilled from the concentrated H2804 through a 20 cm Vigreux column. Fractional distillation was carried out at 61°C (atmospheric pressure): Yield=23.5 g (82.7%). 1H-NMR: 8 4.39(q, 2H, J=7.17), 1.37(t, 3H, J=7.18); 13C-NMR: 8 157.52(q,C=0, J= 42.3), 114.52(q, J= 283.9), 64.30,13.71; IR: 2988.1, 1788.2(C=0), 1346.5, 1225.0, 1174.8, 1143.9, 1010.8, 856.5 cm“. MS(m/e) 143(M++1), 115. 99, 59, 59, 50, 47, 43. W653 In a 100 mL three neck round bottom flask equipped with reflux condenser, mechanical stirrer and serum cap, 3.0 g. (0.125 mol of 80% oil dispersion, Aldrich Chemical Company) of sodium hydride was washed with anhydrous pentane (3x15 mL). Then 30 mL THF, freshly distilled from sodium was added, followed by careful dropwise addition of 2.99 (0.05 moles ) of allyl alcohol (Aldrich Chemical Company) under argon. The resulting mixture was refluxed for 2 h until H2 evolution has ceased. HMPA (22.5 mL, Janssen Chimica) was added to the warm mixture at once followed by careful addition of 12.5 g ( 0.05 moles ) of p-bromobenzyl bromide at such a rate to maintain a gentle reflux. The reaction mixture was then refluxed for an additional 3 h, cooled and quenched with 10% HCI (30 mL). The aqueous layer was extracted with pentane (3 X 30 mL). The combined organic extracts were washed with 10% HCI (30 mL), saturated NaHCOa (30 mL), H20 (30 mL) and saturated NaCI solution (30 mL) and dried over MgSO4. Solvent was removed by rotary evaporation and the cmde product distilled under reduced pressure to give 8.3 g (73.2%) of the product. b.p: 84-86°C/0.4 mm. 1H NMR: 8 7.45 (d, 2H, J=8.3), 7.20(d, 2H, J=8.52), 5.93 (m, 1H), 5.24 (m,2H), 4.45 (s,2H), 4.00 (d, 2H, J=5.55). ‘30 NMR: 8137.33, 134.48, 131.46, 129.29, 127.54, 121.41, 117.33, 71.28, 71.23. IR: 3089.3, 3014.3, 2974.4, 2924.5, 2859.9, 1595.3, 1489.2, 154 1405.3, 1355.1, 1089.9. 1072.5, 1012.8, 927.9 cm'1. MS (m/e) 225 (MM). 184,169,91,90,77. Was“ This ether was made from p- bromobenzyl bromide (10 g, 0.04 moles), 2-methylallyl alcohol (2.88 g, 0.04 moles, Aldrich Chemical Company), sodium hydride (3.09 of 80% oil dispersion) in 30 mL of THF and using 18 mL of HMPA by the method as used for the preparation of 3-(p-bromobenzyloxy)-1-propene. The yield was 7.7 g (79.9%). b.p: 929800 I 0.45mm. 1H NMR: 87.45(d, 2H, J=8.34), 7.20(d, 2H, J=8.61), 4.97(s,1H), 4.91(s,1H), 4.42(s,2H), 3.90(s,2H), 1.74(s, 3H). 13C: 8 141.92, 137.44, 131.60, 121.34, 112.51, 74.19, 70.99, 19.50. IR: 3082.6, 2974.4, 2918.7, 2855.0, 1700.7, 1600.8, 1489.2, 1089.8, 1072.4, 1012.8, 904.7 cm-l. MS (m/e) 242(M++1), 185, 172, 169, 90.77.55. W553 This ether was made from p- bromobenzylbromide (25 g, 0.1 moles), 2-methyI-3-butene-2-ol (9.5 g, 0.11 moles, Aldrich Chemical Company), sodium hydride (2.9 g, .12 mol of 80% oil dispersion) in 70 mL of THF using 45 mL of HMPA by the method as used for 3- (p-bromobenzyloxy)-1-propene. The yield was18.1 g (72.4%). b.p: 75°C/0.25 mmHg. 1H NMR: 87.43(d, 2H, J=8.46), 7.19 (d,2H,J=8.52), 5.88 (q, 1H, J=17.64, 10.79), 5.18(ddd, 2H, J=17.64, 10.74), 4.30 (s, 2H), 1.34 (S,6H). 130 NMR: 8143.59, 138.69, 131.27, 128.96, 120.84, 114.25, 75.80, 64.21, 25.90. IR: 3096.0, 2982.3, 2936.8, 3901.4, 1489.2, 1377.4, 1151.6, 1072.6, 1012.8, 1003.1, 925.9 cm-l. MS(m/e) 256(M++1), 241, 169, 90, 70. 155 W551 This ether was made from p- bromobenzyl bromide (15.0 g, 0.06 mol), 3-methyl-2-butene-1-ol (5.16 g, 0.06 moles, Aldrich Chemical Company), sodium hydride (1.569, 0.065 moles of 80% oil dispersion) in 45 mL of THF using 27 mL of HMPA by the method as used for 3-(p—bromobenzyloxy)-1-propene. The yield was 9.9 g (64.70%). bp: 106-116°C/0.4 mmHg. 1H NMR: 8 7.44(d, 2H, J=8.46), 7.20(d, 2H, J=8.67), 5.36(m, 1H), 4.42(s,2H), 3.97(d,2H, J=6.96), 1.74(s, 3H), 1.63(s, 3H). 13C NMR: 8137.61, 137.52, 131.41, 129.38, 121.32, 120.78, 71.18, 66.65, 25.80, 18.05. IR: 2974.4, 2930.2, 2856.9, 1489.2, 1115.0, 1072.6, 1012.8 cm“. MS (mle) 254( MM), 171, 90, 85, 77, 70, 63, 57. Wilt“ In a 100 ml— ""99 neck flask equipped with a dropping funnel, magnetic stirrer and serum cap, was placed 2.13 g (15 mmoles) of ethyl trifluoroacetate in 15 mL of sodium dried diethyl ether. The flask was cooled to -78°C (dry ice-acetone bath). The Grignard reagent of 3-(p-bromobenzyloxy)-1-propene (prepared by refluxing a solution of 3.0 g (13.2 mmoles) of the bromide and 0.34 g (14 mmoles) of magnesium turnings in 15 mL of sodium dried THF for one hour) was added dropwise over a period of 15 minutes. The acetone-dry ice bath was removed and the reaction mixture was warmed to about 5°C and quenched with 30 mL of saturated NH4CI. The organic layer was separated and the aqueous layer extracted with 2 X 30 mL of ether. The combined organic layers was successively washed with 30 mL of saturated sodium bicarbonate and water, dried over anhydrous MgSO4. Removal of solvent by rotary evaporation gave a yellowish residue. Distillation under reduced pressure gave 2.0 g (62%) of a colorless liquid which was less than 90% pure by GC (b.p: 73°C at 0.2 mmHg). Further purification of the product was achieved by column chromatograhpy 156 using silica gel (35X3 cm), hexane! ethyl acetate as eluent. The column was packed using 97.5:2.5% of hexane/ethyl acetate. The crude product was then transferred to the column and eluted with hexane/ethyl acetate (100 mL of 97.5:2.5, 200 mL of 95.0:5.0, 200 mL of 92.5:7.5 and finally with 90.0:10.0). Evaporation of solvent by rotary evaporator gave a clear liquid residue which was pure based on 1H NMR. 1H NMR: 8 8.04 (d, 2H, J=8.46), 7.51(d, 2H, J=8.07), 5.95(ddt, 1H, J: 17.30, 10.40, 5.50). 5.32 (ddt, 1H, J: 17.2, 1.6, 1.5), 5.23 (ddt, 1H, J=- 10.4, 1.0, 1.3) , 4.60 (s, 2H), 4.06 (dt, 2H, J=5.76, 1.40). 13C NMR: 8 180.15 (quartet, J: 37.5), 146.96, 134.17, 130.26, 129.02, 127.53, 117.60, 116.68 (quartet, J: 289.5), 71.68, 71.01. IR: 3094.3, 3019.8, 2959.4, 2929.5, 2856.9, 1720.7 (C=O), 1610.8, 1419.8, 1359.0, 1205.7, 1174.5, 1149.7, 1093.8, 941.4 cm“. Low resolution MS (mle) 244( 11+), 203, 200, 175, 159, 118, 105, 90, 41. High resolution MS (FAB): MH+1 at 245.07876 (calculated mass: 245.07894). '1. ,5 -' .., : .., .. --,,.. ....,; . 6411115 compound was prepared from the Grignard reagent of 3-(p-bromobenzyloxy)-2- methyl-1-propene (made by refluxing a mixture of 5.3 g (22 mmoles) of the corresponding bromide and 0.6 g of Mg turnings in 30 mL of sodium dried THF for one hour) and 3.6 g of ethyl trifluoroacetate in 25 mL of sodium dried ether. The procedure used was that for the preparation of F011. The product was purified over silica gel (45X3.5 cm) using hexane/ethyl acetate as eluent. The column was packed with 97.5:2.5% of hexane/ethyl acetate and after transferring the crude product was eluted with 97525 (200 mL), 95:5 (300 mL), 92.5:7.5 (300 mL) and finally with 90:10 of hexane/ethyl acetate. A pale yellow liquid which was pure enough based on 1H NMR was obtained. Yield: 3.8 g ( 66.9%). 1H NMR: 8 8.04( d, 2H, J=7.98), 7.51( d, 2H, J=8.16), 5.00( s,1H). 157 4.94(s, 1H), 4.57(s, 2H), 3.96(s,2H), 1.76(s, 3H). 130 NMR: 8180.64 (quartet, J=35.2), 147.45, 141.98, 130.527, 129.22, 127.71, 115.88 (quartet, J=291.0), 112.90, 74.54, 70.71.1912. IR: 3082.27, 2979.43, 2924.48, 2849.54, 1722.55, 1620.83, 1205.55, 1174.89, 1149.72, 941.38 cm'1. MS (m/e) 258(M+), 229, 203, 187, 159, 118.90.56.41. High resolution MS (FAB): MH+1 at 259.09434 (calculated mass: 259.09459). --._..,.-' ... . .z, ., --,,.. --. H. e -54 This compound was prepared from the Grignard reagent of 3-(p-bromobenzyloxy)-3- methyl-l-butene (made by refluxing a mixture of 7.0 g (27.4 mmoles) of the corresponding bromide and 0.9 g of Mg turnings in 40 mL of sodium dried THF for one hour) and 4.0 g of ethyl trifluoroacetate in 30 mL of sodium dried ether. The procedure is exactly the same as the one used to prepare F011. Purification of the product over silica gel using hexane/ethyl acetate took place the same way as that of the F012 to give a colorless liquid which was highly pure based on 1H NMR. Yield: 5.1 g (68.4%). 1H NMR: 8 8.02(d, 2H, J=8.24), 7.50 (d, 2H, J=8.08), 5.88(dd, 1H, J=17.65, 10.70). 5.19(dd, 1H, J: 17.50, 1.10), 5.16 (dd, 1H, J= 10.70, 1.10), 4.46(s, 2H), 1.36(s, 6H). 130 NMR: 8180.10 (quartet, J= 34.50), 148.53, 143.26, 130.15, 128.55, 127.30, 115.61 (quartet, J= 289.50), 114.56, 76.15, 64.13, 25.86. IR: 2982.3, 1720.7 (C=O), 1610.8. 1377.4, 1205.7, 1149.7, 1084.1, 941.4 om-1. Low resolution MS (m/e) 272(M+), 257, 187, 159, 118, 90, 59. High resolution MS (FAB): MH+1 at 273.1097. Calculated mass: 273.11024). -- o,o_o-' es.~ : 0:. e. ”11:. --e :1: O '64 This compound was prepared from the Grignard reagent of 4-(p-bromobenzyloxy)-2- methyl-2-butene (made by refluxing a mixture of 8.0 g (31.27 mmoles) of the 158 corresponding bromide and 1.0 g of Mg turnings in 40 mL of sodium dried THF for one hour) and 5.4 g of ethyltrifluoroacetate in 35 mL of sodium dried ether. The procedure used was that for the preparation of F011. Purification of the product over silica gel using hexane / ethylacetate eluent (starting from 2.5% ethyl acetate and increasing its concentration up to 10%) gave a colorless liquid which was pure based on 1H NMR. Yield: 5.9 g. (69.15%). 1H NMR: 8 8.03 (d, 2H, .1.-7.74), 7.50(d, 2H, J=8.16), 5.30 (m, 1H, J: 6.96, 1.41), 4.57(s,2H), 4.03(d, 2H, J=7.14), 1.75(bs, 3H), 1.65(bs, 3H). 13C NMR: 8 180.18 (quartet, J: 35.02), 147.32, 137.91, 129.84, 128.51, 127.22, 120.07, 116.24 (quartet, J: 289.5), 70.48, 66.71 ,25.37, 17.63. IR: 2974.6, 2934.1, 2858.9, 1720.7 (C=O), 1610.8, 1576.0, 1551.0, 1253.9, 1205.7, 1174.8, 1149.7, 1115.0, 1086.1, 1007.0, 980.0, 941.4 cm'1. Low resolution MS (m/e) 272 (M1), 257, 203, 188, 159, 118, 85, 69, 57. W65 In a 500 mL three neck round bottom flask equipped with magnetic stirrer, serum cap and reflux condenser was placed 5.0 g of Mg turnings and 25.0 g (0.1 moles) of p—bromobenzyl bromide in 250 mL of sodium dried ether. This mixture was refluxed with stirring for one hour after which the formation of the Grignard reagent was complete. The reagent was transferred through a canula to another 500 mL three neck flask equipped with mechanical stirrer, reflux condenser and serum cap. Sufficient HMPA was added until the red color of the solution persisted. This was followed by cautious dropwise addition of 13.5 9 (0.0.1 moles) of neat 4-bromobutene. The mixture was then refluxed for two hour and quenched with 100 mL of 10% HCI. The ethereal layer was separated and the organic layer extracted with 2X100 mL pentane. The combined organic extracts were washed with HCI (100 mL, 10%), saturated NaHCOa (100 mL) and water (100 mL). Evaporation of solvent 159 after drying over anhydrous MgSO4 gave a greenish residue. Recrystallization of the greenish residue from absolute ethanol gave the 1,2-diphenyl ethane as a solid precipitate which was collected by suction filtration. The filtrate was concentrated and the residue was distilled under reduced pressure to give 11.8 g (52.4%) of a colorless semi-solid (bp: 707500 at .25 mmHg). 1H: 8 7.38(d, 2H, J=7.62), 7.03(d, 2H, J=8.04), 5.72-5.90 (m, 1H), 4.90-5.05 (m, 2H), 2.55 (t, 2H, J=7.92), 2.05 (q, 2H, J=7.14), 1.57 (ft, 2H, .1.-.741); 13c NMR: 8141.34, 138.30, 131.29 (20), 130.20 (2C), 119.37, 114.91, 34.63, 33.10, 30.40: IR: 3614.8, 3083.3, 2934.1, 2860.8, 1647.8, 1489.2, 1404.4, 1072.6, 1012.8, 991.5, 914.4, 829.5 orn-l; MS (m/e) 224(M+), 184, 171, 159. 145. 115, 104, 91, 77. 53. 51 . W“ This compound was prepared from the Grignard reagent of 5-(p-bromophenyl)-1-pentene (made by refluxing a mixture of 4.9 g (20.9 mmoles) of the corresponding bromide and 0.52 g of Mg turnings in 40 mL of sodium dried THF for one hour) and 3.2 g of ethyl trifluoroacetate in 25 mL of sodium dried ether. The procedure was that for preparation of F011. Chromatography of the crude product over silica gel (45X3.5 cm) using hexane I ethyl acetate (97512.5) gave 2.89 (55.4%) of a pale yellow liquid residue which was pure enough for photolysis based on 1H NMR. 1H NMR: 8 7.98(d, 2H, J=8.61), 7.33(d, 2H, J-8.76), 5.73-5.87(ddt,1 H, J- 17.10. 10.25, 6.59), 5.02 (ddt, 1H, J= 17.10, 1.80, 1.80), 4.99 (ddt, 1H, J- 10.19, 1.95, 1.04), 270(1, 2H, J=7.47), 2.09(dddt, 2H, J=7.63, 7.63. 1.34, 1.34), 1.74(tt. 2H, J=7.63, 7.50); 13c NMR: 8 180.09(q, J= 34.50)), 151.40, 137.92, 130.33, 129.21, 127.59, 116.74(q, J: 290.35), 115.25, 35.44, 33.10, 29.95; IR: 2936.0. 2862.7, 1718.8, 1641.6, 1608.8, 1419.8, 1338.8, 1207.6, 1192.0, 1174.8. 1149.7, 991.5, 941.4, 915.3 om-i; Low resolution MS (m/e) 242(M+), 200, 188, 160 173, 159, 145, 131, 119, 104.91.77.55; High resolution MS (FAB): MH+1 at 243.0999 (calculated mass: 243.09967). WWW” In a 100 mL three neck round bottomed flask equipped with magnetic stirrer, dropping funnel and mbber septum was placed 7.149 (0.07 mmoles) of acetic anhydride in 18 mL of sodium dried ether. The flask was cooled down to -78°C (acetone-dry ice bath) and 35 mmoles of the Grignard reagent of 3-(p-bromobenzyloxy)-1-propene (prepared by refluxing 8.09. of 3-(p-bromobenzyloxy)-1-propene and 1.09 of Mg turnings in 40 mL of sodium dried THF) was added dropwise over a period of 30 minutes. After two hours of stirring the cooling bath was removed and the mixture was quenched with 50 mL of saturated ammonium chloride. The aqueous layer was extracted with 2X30 mL of ether. The combined organic layers was washed successively with saturated NaHCOa (50 mL), water (50 mL) and brine (50 mL) and dried over anhydrous M9804. Evaporation of the solvent by rotary evaporation gave a yellowish residue. This was purified by column chromatography using silica gel (35X3 cm) and hexane / ethyl acetate (95/5%) to give 3.59 (52%) of product which was pure based on 1H NMR. 1H NMR: 8 7.92 (d, 2H, J= 8.25), 7.42 (d, 2H, J= 8.04), 5.92 (ddt, 1H, J= 17.28, 10.44, 5.49), 5.30 (ddt, 1H, J= 17.25, 1.65, 1.59), 5.21 (ddt, 1H, J= 10.43, 1.40, 1.38), 4.55 (s, 2H), 4.03 (dd, 2H, J: 5.57, 1.53), 2.58 (s, 2H). 130 NMR: 6 197.85 (C=O), 143.88, 136.36, 134.38, 128.48, 127.36, 117.45, 71.47, 71.36, 26.65. IR: 2854.5, 1689.9 (C=O), 1610.8, 1411.00, 1358.1, 1265.5, 1093.8, 1015.3, 926.4 om-i. Low resolution MS (m/z) 190 (M+), 175, 149, 133, 118, 105, 89, 63. High resolution MS (El): M+ at 190.0995 (calculated mass: 190.09939). 161 W57 This compound was made from the Grignard reagent of 5- (p-bromophenyl)-1-pentene (made by refluxing a mixture of 2.25 g (10 mmoles) of the corresponding bromide and 0.25 g of Mg turnings in 15 mL of sodium dried THF for one hour) and 2.12 g (20 mmoles, 2 mL) of anhydrous acetic anhydride in 6 mL of sodium dried ether. The procedure was that for preparation of A011. Purification of the crude product over silica gel using hexane/ethyl acetate (95/5) gave 76.8% yield (liquid) which was 98% pure based on GC. This could be further purified by chromatography over Alumina using hexane / ethyl acetate (97.5/2.5). 1H NMR: 8 7.86(d, J=8.31, 2H), 7.24 (d, J=8.40, 2H), 5.80(ddt, 1H, J= 17.06, 10.22, 6.60), 5.01 (ddt, 1H, J: 17.00, 1.71, 1.80), 4.97 (ddt, 1H, J: 10.14, 0.88), 2.66(t, 2H, J=7.65), 2.56(s, 3H), 2.07(td, 2H J=6.86, 7.62) 1.71 (ft, 2H J=7.55, 7.55); 13c NMR: 8198.47, 148.68, 138.50, 135.29, 128.90, 128.75, 115.213, 35.04, 32.93, 29.95, 26.27; IR (neat) 3076.8, 3001.6, 2976.5, 2932.2, 2858.9, 1684.1 (C=O), 1641.6, 1606.9, 1570.3, 1684.1, 1641.6, 1606.9, 1570.3, 1414.0, 1358.1, 1304.0, 1267.4, 1182.5, 1120.8, 1074.5, 1016.6, 993.5, 956.8, 912.4, 843.0, 816.0; low resolution MS (m/z) 188 (M1), 173, 146, 131, 105, 91, 77, 55, 43; high resolution MS (FAB): MH’r1 at 189.12837 (calculated mass: 189.127945). msuxdmxxacntnnnnnuasdinxnlnn In a 250 mL round bottom flask equipped with Dean-Stark trap and reflux condenser attached to a drying tube was placed 12.0 9 (88.24 mmole) of 3-hydroxyacetophenone, 14.5 mL of ethylene glycol and 0.27 g of p—toluenesulfonic acid in 125 mL of benzene. This mixture was refluxed for 24 h. Another 0.5 g of p-toluenesulfonic acid was added and refluxing was continued for another 15 h, after which the reaction was complete. After cooling to room temperature the solution was transferred to a separatory funnel and the bottom oily layer separated. The organic layer was 162 washed with 20 mL of saturated NaHC03 followed by 20 mL of water and dried over anhydrous M9804. Evaporation of solvent by rotary evaporation gave a yellow solid. Recrystallization of the solid from hexane/ethyl acetate gave 9.9 9 (62.6%) of light brown needles m. p. 85-85.5°C. 1H NMR: 8 7.20 (t, J=7.8, 1H), 7.03 (ddd, J=7.8 and 1.2, 1H), 6.94 (dd, J=1.2, 1H), 6.74 (ddd, J=8.1 and 1.2, 1H), 4.02(m, 2H), 3.76(m, 2H), 1.63(s, 3H), OH shows a broad signal at 4.72; 130 NMR: 8155.62, 145.08, 129.64, 117.64, 114.82, 112.30, 108.74, 64.43, 27.46; IR: absence of carbonyl functional group and presence of -OH group at 3600 cm“; M8 (m/z) 180 (M1), 166, 165, 149, 133, 122, 121, 107, 93, 87, 77, 65, 43. W69 In a 500 mL three neck round bottom flask equipped with dropping funnel, mechanical stirrer and low temperature thermometer was placed 115 mL of dry toluene and 7.7 9 (105.5 mmole) of t-butylamine. After the flask was cooled to -20 to -30°C in an isopropanol-dry ice bath, 8.44 (52.7 mmole) of Br2 was added over a period of 10 minutes. The solution was then cooled to -75°C by adding more dry ice and 9.5 9 (52.77 mmole) of m-hydroxyacetophenone-l ,3-dioxolane dissolved in 200 mL of CH2CI2 was added over a period of 5 minutes. The reaction mixture was then allowed to warm to room temperature over a period of 5-6 h. The solution was then filtered and the filtrate evaporated under vacuum to give a yellow solid. Chromatography using hexane/ethyl acetate (starting with 1% ethyl acetate and increasing its concentration up to 5%) gave 7.0 g (51.2%) of the product, m. p. 909200. 1H NMR: 87.41 (d, J=8.4, 1H), 7.13 (d, J=2.1, 1H), 5.92 (dd, J=8.4 and 2.1, 1H), 5.49 (s, 1H), 4.01 (m, 2H), 3.76 (m, 2H)1.61(s, 3H); 13C NMR: 8152.07, 145.25, 131.84, 118.93, 113.25, 109.48, 108.21, 64.50, 27.38. IR: 3528.2, 2988.0, 2953.3, 2888.9, 1577.9, 1481.5, 1433.3, 1375.4, 1313.7, 163 1292.5, 1217.2, 1199.9, 1186.4, 1041.7, 1024.3 and 875.8 cm-1; MS (m/z) 258 (MM), 245, 243, 201, 199, 171, 143, 119, 92, 87, 43. Wan. In a 100 mL round bottom flask equipped with reflux condenser and magnetic stirrer was placed a solution of 2.8 g (10.8 mmole) of p-bromo-m-hydroxyacetophenone-1,3-dioxane, 3.0 g of anhydrous K2003 and 1 mL of methyl iodide in 45 mL of dry acetone. This solution was refluxed for 6 h, cooled to room temperature and filtered. The filtrate was concentrated by rotary evaporation to give 2.65 9 (89.8%) of pure product as white crystals (m.p: 55.5-57.5°C). In cases where purification was necessary, the crude product can be recrystallized from hexane/ethyl acetate (95/5), using 10 mL of solvent per 5.0 g of cmde product. 1H NMR: 8 7.47 (d, J=8.12, 1H), 7.01(d, .1.-155. 1H), 5.94 (dd, J=8.21 and 1.92, 1H), 4.02 (m, 2H), 3.89 (s, 3H), 3.75 (m, 2H), 1.52 (s, 3H); 130 NMR: 8155.67, 144.46, 133.00, 118.73, 110.92, 109.00, 108.42, 64.47, 56.20, 27.56. IR: 2999, 2972, 2939, 2085, 1575, 1548, 1485, 1468, 1404, 1383, 1292, 1268, 1217, 1200, 1129, 1100, 1038, 1021 cm-1; MS (m/z) 272 (M+1+), 259, 215, 185, 170, 87, 78,63. 51, 49. WW“ To a suspension of 0.95 9 (3.60 mmol) of dichlorobis(acetonitrile)palladium(ll) in 36 mL of benzene, in a 100 mL three- neck flask under Argon, was added with stirring a solution of 1.99 g (3.6 mmol) of 1,1'-bis(diphenylphosphino)ferrocene (dppf, Aldrich Chemical Company) in 36 mL of benzene. After the solution was stirred at room temperature for 12 h, a reddish brown precipitate was collected by suction filtration using a M size pyrex Buchner funnel. The precipitate was washed with benzene and dried 164 under vacuum to give a 100% yield of PdCl2(dppf): mp 274-275°C dec; 1H NMR: 6 4.13-4.23, 4.304.41 (m, 8 H), 7.25-7.50, 7.58-8.00 (m, 20 H). - - - - - - - 1,);69 In atwo neck round bottom flask equipped with magnetic stirrer and serum cap was placed 0.07 g (0.097 mmol) of PdCl2(dppf). This flask was degassed and filled with Argon three times. Then 2.65 g (9.7 mmol) of p-bromo-m-methoxyacetophenone-1,3- dioxolane in 5 mL of sodium dried ether was transferred by syringe to the solution at -78°C (acetone and dry ice bath). The Grignard reagent from 5- bromopentene (prepared by refluxing 2.9 g, 19.4 mmol, of 5-bromopentene and 0.5 9 of magnesium turnings in 30 mL of sodium dried ether for 1 h) was then transferred through a cannula. The acetone-dry ice bath was then removed and the solution was stirred at room temperature for 24 h. After cooling in an ice bath the solution was quenched with saturated NH4CI (the solution was red at this point). The other layer was separated and the aqueous layer extracted with 2X50 mL of ether. Evaporation of other under reduced pressure gave a brown residue. THF (45 mL) and 5% HCI (22 mL) were added and the mixture stirred overnight at room temperature. The organic layer was then separated and the aqueous layer extracted with 2X30 mL of ether. The combined organic layers were washed with 40 mL of saturated NaHC03 and water, and dried over anhydrous M9804. The solvent was evaporated under vacuum by rotary evaporator and the brownish residue was chromatographed over silica gel (30X3 cm) using hexane/ethyl acetate (after packing the column with hexane it was eluted with 100 mL of 99: 1.0, 100 mL of 98:2, 100 mL of 97:3, 100 mL of 96:4 and finally with 95:5.0% of hexane/ethyl acetate) to give the product in 50% yield which was pure enough for photolysis (pale yellow liquid) based on 1H NMR. 1H NMR: 8 7.46 (dd, 1H, J=7.54, 1.62), 7.43 (d, 1H, J= 1.43), 7.20 (d, 165 1H, J= 7.5), 5.83 (ddt, 1H, J= 17.10, 10.23, 6.62), 5.02 (ddt, 1H, J: 17.30, 1.90, 1.54), 4.95 (ddt, J= 10.20, 2.05, 1.22), 3.81 (s, 3H), 2.67 (t, J=7.5, 2H), 2.59 (s, 3H), 2.11 (q, J=8.4, 2H), 1.65 (m, 2H); 130 NMR: 6197.87, 157.57, 138.50. 137.14, 135.33, 129.55, 121.50, 114.68, 108.77, 55.42, 33.53. 29.85, 28.61, 25.55; IR: 3084.3, 2999.4, 2955.4, 2859.5, 2834.50, 1686.0, 1604.9, 1500.8, 1454.2, 1412.1, 1354.2, 1284.8, 1259.3, 1224.9, 1039.8, 914.4, 879.5 cm": MS (m/z) 218 (M+), 203, 175, 153, 150, 135, 128, 121, 115. 105, 91, 77, 55, 51, 43; high resolution MS: MH+ at 219.13905 (calculated mass: 218.138515). 155 EhotnlttsinEmcnduLe: 33W Glassware used for photolysis were ”type A" volumetric flasks, 5 cm syringes with stainless steel needles, pipettes and 13X100 mL pyrex test tubes. The test tubes were heated with a natural gas/oxygen tourch (about 5 cm from the top) and stretched to a 16.5 cm length. All glassware used for photolysis was carefully cleaned by first rinsing three times with acetone and then with distilled water followed by boiling in distilled water overnight in a pyrex jar containing Alconox. The process of rinsing and boiling in distilled water was repeated four times. Finally the glassware was rinsed three times with distilled water and dried in an oven at 150°C. I , E I. I I I. Stock solutions of ketone, standard and quencher were prepared by directly weighing them into separate volumetric flasks and diluting to the mark. These stock solutions were further diluted by transferring a known volume into a series of 10 mL volumetric flasks, using pipettes. Finally 2.80 ml of the dilute solutions were transferred to the photolysis tubes, using the 5.0 mL syringes. , D . i I I. The test tubes were attached to a degassing cow containing twelve # 00 rubber stoppers, each with one hole. The degassing cow was attached to a diffusion pump and oil pump through a glass manifold. The samples were then frozen by slowly immersing them into a liquid nitrogen bath. They were then exposed to the vacuum for 10 minutes. The vacuum stopcocks were then 167 closed and the solutions were allowed to thaw at room temperature. This freeze-pump-thaw cycle was repeated three times. finally, the solutions were frozen and evacuated for another 5 minutes and sealed with an oxygen/natural gas torch under vacuum. I' I I. I. [IE I All sealed tubes were irradiated in parallel with an actinometer in a merry-go-round apparatus immersed in a water bath at 25°C. A Hanova 450 W medium pressure mercury lamp cooled by a water condenser was used as a light source. Since irradiation at 313 nm (the 313 nm emission band was isolated by passing the UV light through an aqueous solution of 0.002 M of potassium chromate and 1% potassium carbonate) was not efficient, therefore the tubes were irradiated at > 290 nm using pyrex filter. Preparative scale photolysis were carried out in a 450 ml preparative apparatus, using a Hanova medium mercury lamp and pyrex filter. Usually 0.5 g of ketones dissolved in special grade benzene or methanol were irradiated at room temperature. Photolysis were also performed by preparing 0.02 M solution of ketone in 1.0 ml of deuterated solvent in a NMR tube. The samples were bubbled with argon before irradiation. The progress of reactions were frequently checked by NMR. 'IIIIBII I I. I. NMR tubes for irradiation were prepared by making a 0.02 M solution of a photoirradiation precursor in a deuterated solvent. The NMR tube was then sealed by a rubber septum and degassed by bubbling argon through a needle. The degassed NMR tube was irradiated by hanging to the outside wall of an 168 immersion well. The progress of the reactions for all NMR tube irradiations were checked by 1H NMR. nLIhnnnaLIrnstotmatins All thermal transformations were carried out in NMR tubes in toluene-da or methanol-d4 as solvents. The solutions in toluene-da were heated by dipping the NMR tube in boiling water, and the solutions in methanol-d4 were heated in a 50°C water bath (the water bath of the rotary evaporator was used). In both cases the progress of reaction was frequently checked by 1H NMR. LAnaIILsIs All post-irradiation analysis have been performed using gas-liquid chromatography using either a Varian aerograph-1400 chromatograph with 15 m megabore DB-l column or 15 and 30 m megabore DB-wax, and or a Varian- 3400 gas chromatography with megabore DB-210 column. The chromatograms were recorded by a Hewlett-Packard 3392A or 3393A integrator. All of the chromatographs were equipped with flame ionization detectors using hydrogen and compressed air and Helium as a carrier gas. 00 conditions for individual experiments are listed in the appendix. Wm Response factor for photoprecursor ketones, photoproducts and o- methylacetophenone were obtained by gas chromatography using equation 33. Astd [photo] RF. = — X -— (33) Aphoto [Std] 169 Three different stock solutions of photoproducts, starting ketones and a standard were prepared and the response factors were calculated based on the chromatograms obtained. The reported response factors are in fact the average of the calculated R1 values. I , Q I . I I I I I. o-Methylvaler0phenone was used to determine the amount of photons absorbed by ketones. A degassed solution of 0.1 M of actinometer and 0.01 M of n-C15H32 in benzene was irradiated in parallel with the ketones. The concentration of o-methylacetophenone was then calculated from its response factor using the above equation. By knowing the quantum yield for the formation of o-methylacetophenone (41:0.016)" and using the equation 34, quantum yield for photoproducts were calculated.5&59 [PTOdUCti o= x 0.016 (34) [o-methylacetophenone] When valerophenone with quantum yield of 0.33 is used as the actinometer,61 then the quantum yield of photoproducts formation were calculated by equation 35. [product 6: l x 0.33 (35) [acetophenone] "DI . I'll I ll' , Chemical yields for the‘photoproducts were calculated using GC. A benzene solution of the ketone photoprecursor and an internal standard in a 170 small test tube (sealed by rubber septum) was irradiated through Pyrex filter. The solution was degassed by bubbling with argon for 10 minutes prior to irradiation and its 00 chromatogram was recorded. The solution was then irradiated and chromatograms of the irradiated solution were recorded at several time intervals between irradiation. After each analysis the solution was sealed by rubber septum and degassed by bubbling with argon and irradiated. Concentrations of the photoproducts were calculated by using the response factors. By knowing the concentration of unreacted ketone and calculating the concentration of the converted ketone, the % chemical yield was determined using equation 36. Concentration of Photoproduct Chemical Yield = , x 100 (36) Concentration of Converted ketone Concentrations of photoproducts were measured by GC analysis of the irradiated solution from equation X. Concentration of unreacted ketone was also calculated from equation X. Concentration of converted ketone can then be figured out from equation 37. Concentration of converted = Original concentration - Concentration of unreacted (37) ketone of ketone ketone llll llll . Clll" A molecular Modeling software, PCMODEL distributed by Serena Software, was used to calculate the minimum energy of different conformers. The MMX mode of the PCMODEL was used for this purpose. All structures were drawn in PCMODEL and were fully optimized. The minimum energy of the molecules with no hydrogen. Then hydrogens were added and the minimization continued. The minimum energy appeared in the upper right side of the screen were recorded. 1 71 LEnmnlxsis 'ton to 01111.1.-' 00-. =1 0:1 0. ore-:1: 013A solution of 0.25 g of ketone F011 in 70 mL of Omnisolv benzene (EM Science) in a 100 mL Pyrex test tube sealed with rubber septum was deaerated by bubbling with argon for 10 minutes. This test tube was irradiated for 15 hrs by attaching to the outside wall of an immersion well equipped with Pyrex filter and Hanova mercury lamp. Two photoproducts were formed based on GC analysis (GC: 08-1; 15 m). After evaporation of solvent by rotary evaporator at 40°C, the two products were purified by gradient flash column using silica gel (40 cm, Aldrich grade 60, 230-400 mesh) and hexane/ethyl acetate. Pressure was applied to increase the elution rate to one drop per second. In a 60x2 cm column packed with hexane, elution started with 99/1% hexane/ethyl acetate (100 mL) and then the ratio increased to 97.5:2.5% until all of the starting ketone eluted from the column. The ratio of hexane/ethyl acetate was changed to 95:5 (200 mL) and 92.5:7.5 until the first photoproduct started to elute from the column. Then 90:10 ratio of hexane/ethyl acetate was used to complete the separation. The angular photoproduct was eluted first from the column followed by the linear one. These products are 9-trifluoroacetyl-cis-anti-3- oxatricyclo[7.2.0.0‘-5] undeca-7,10-diene (AF011) and 10-trifluoroacetyl-cis- anti-5-oxatricyclo[7.2.0.03-7] undeca-7,10-diene (LF011). W11; 1H NMR (vxn 300, CDCI3) 6 6.33 (d, 1H, J=2.79), 5.20 (m, 1H, J=3.07), 5.98 (td, 1H, 1:10.33, 4.45), 5.83 (d, 1H, J=10.33), 3.94 (t, 1H, J=7.82), 3.78 (d, 1H, J=10.33), 3.70 (d, 1H, 3:10.33), 3.58 (t, 1H, J=8.1), 2.43 (m, 1H), 2.19 (m, 2H); 13C NMR (Gemini 300, CDCI3) 8192.05 (q, C=0, J=33.82), 140.83, 136.03, 128.78, 123.78, 116.01 (quartet, CF3, J=276.3), 71.24, 71.19, 61.67, 60.18, 40.93, 23.33; FT-lR (CCI4) 3039.5, 2919.5, 2849.5, 172 1738.1 (C=O), 1307.9, 1261.6, 1207.6, 1153.6, 1136.2, 1064.8, 924.0 cm-I; M8, m/e 244 (M1), 215, 203, 187, 118, 86, 57. The stereochemistry of AF011 has been established by Nuclear Overhauser Effect (NOE) which showed an increase of H11 (1.85%), H7 (0.51%), H43 (4.45%) and H23 (2.22%) when the bridgehead proton at 8 2.43 ( H5, 100%) was irradiated. W11; 1H NMR (vxn 300, 00013) 6 7.15 (t, 1H, J=1.5), 5.81 (m, 1H, J=5.7, 2.4), 4.37 (d, 1H, J=13.26), 4.25 (d, 1H, J=13.20), 4.20 (t, 1H, J=8.37), 3.70 (m, 1H, J=4.96), 3.34 (t, 1H, J=8.77), 3.26 (ddt, 1H, J=6.00, 4.20, 1.20), 2.38 (m, 1H), 2.19 (ddd, 1H, J=13.2, 5.4, 1.5), 1.18 (ddd, 1H, J=12.45, 5.4, 1.5); 130 NMR: 8175.54 (quartet, C=O), 155.56, 144.86, 140.46, 116.14(quartet, CF3), 114.16, 73.63, 70.34, 40.80, 39.59, 36.17, 27.57; FT-IR: 2929.5, 2849.5, 1711.1(c.=0), 1587.6, 1221.1, 1155.6, 1115.0, 1053.3, 926.0 cm'1; M8 (m/e) 244 (M1), 229, 214, 203, 187, 175, 145, 117, 91, 57. The stereochemistry of LFO11 has been established by Nuclear Overhauser Effect (NOE) experiments which showed a cis ring junction at H1-Hg , anti to H3. An increase in intensity of the bridgehead proton signal at 8 3.70 (Hg) was observed when the bridgehead proton at 8 3.26 (H1, 100%) was irradiated, while the bridgehead proton at 8 2.38 (H3) was unchanged. W11 In two different 10 mL volumetric flasks solutions of 0.24 M of ketone F011 (needs 0.593 g / 10 mL) and 0.0104 M of C15H32 (needs 0.0221 g / 10 mL) were prepared in benzene. In another 50 mL volumetric flask a solution of 0.10 M (needs 0.5589 g / 50 mL) of quencher (2,5-dimethyl-2,4-hexadiene) was also prepared. Using a pipet,1.0 mL of each of the ketone F011 and standard solutions were transferred to nine 10 mL volumetric flasks. While the 173 concentration of quencher was zero in the first flask, known amount of quencher were added to remaining flasks. The volume of quencher in flasks 2-9 was 2.0, 2.5, 3.0. 3.5, 4.0, 5.0, 6.0 and 7.0 mL. All flasks were filled up to the mark by benzene. A known volume (2.8 mL) from each of the above solutions was transferred to nine different stretched test tubes. The new solutions were degassed. After sealing, the degassed test tubes were irradiated using Pyrex filter (by removing the potassium chromate solution) for 5.0 hrs in a merry-go- round. The degassed solution of actinometer (2.8 mL) was irradiated in parallel with the samples in merry-go-round and the results were analyzed by GC. '1...” e1 e||10_oA-. to. :1 0:. e. “11:. eee:|: £9421; A solution of 0.60 g of ketone F012 in a 400 mL immersion well containing omnisolv benzene (about 400 mL), equipped with Pyrex filter and Hanova mercury lamp was irradiated for 12.0 hrs under argon atmosphere. Two photoproducts were formed based on GC analysis (GC: DB-wax, 15 m). After evaporation of solvent by rotary evaporator at 40°C, the crude product was chromatographed by gradient flash column using silica gel (40 cm, Aldrich grade 60, 230-400 mesh) and hexane/ethyl acetate. Pressure was applied to increase the elution rate to one drop per second. The column (60X2.5 cm) was packed in hexane and after transferring the crude product to the column was eluted with 982% of hexane/ethyl acetate until all of the starting ketone was removed from the column. The ratio of hexane/ethyl acetate then changed to 95:5% until the first photoproduct started eluting and then changed to 92.5:7.5 until the separation was complete. The angular photoproduct was eluted first followed by the linear one. These products are 5-methyl-9-trifluoroacetyl-cis- 174 anti-3-oxatricyclo[7.2.0.0‘v5] undeca-7,10 diene AFO12 and 3-methyI-10- trifluoroacetyl-cis-anti-S-oxatricyclo [7.2.0.03-7] undeca-7,10-diene LFO12. W 1H NMR (Gemini 300, CDCI3) 8 6.27 (d, 1H, J=3.03), 6.22 (dd, 1H, J=3.02, 0.99), 5.92 (ddd, 1H, J=10.16, 5.60, 3.90), 5.73 (d, 1H, J=10.44), 3.89 (d, 1H, J=10.71), 3.73 (d. 1H, J=8.01), 3.66 (d, 1H, J=10.86), 3.50 (d, 1H, J=8.10), 2.20 (ddd, 1H, J=17.07, 5.22, 1.37), 1.96 (ddd, 1H, J=17.07, 3.85, 2.28), 1.06 (s, 3H); 13C NMR 8192.37 (quartet, C=O), 138.60, 136.25, 128.98, 122.73, 115.86 (quartet, -CF3), 77.29, 71.20, 64.65, 61.19, 43.70, 31.11, 22.40; FT -IR (CCI4) 3044.3, 2966.1, 2932.8, 2874.5, 1738.1 (C=O), 1307.9, 1226.9, 1207.6, 1151.7, 1064.8, 1053.3, 939.4 cm"; M8 (m/e) 258 (M‘l'), 243, 228, 213, 200, 187, 159, 131, 115, 105, 96, 91, 77, 41. The stereochemistry of AFO12 has been established by Nuclear Overhauser Effect (NOE) experiment (figure 4) which showed an increase of H11 (2.15%), H23 (2.0%), H43 (2.56%), H55 (1.09%) and H53 (2.16%) when the bridgehead methyl group at C5 (109%) was irradiated. W12; 1H NMR, a: (VXR 300, C5D5) 8 6.53 (bs, 1H), 5.49 (td, 1H, J=5.86, 2.23), 4.22 (d, 1H, J=13.5), 4.02 (d, 1H, J=13.5), 3.51 (d, 1H, J=7.8), 3.22 (t, 1H, J=5.7), 3.04 (d, 1H, J=7.8), 2.54 (m, 1H), 1.38 (dd, 1H, J=14.1, 1.67), 0.87 (s, 3H), 0.86 (dd, 1H, J=13.40, 5.97); o: (Gemini 300. CDCI3) 6 7.28 (bs, 1H), 5.79 (td, 1H, J=5.83, 2.05), 4.57 (ddd, 1H, J=13.19, 2.26, 1.04), 4.27 (d, 1H, J=13.19), 3.73 (d, 1H, J=7.97), 3.71 (t, 1H, J=4.94), 3.39 (m, 1H), 3.30 (d, 1H, =7.96), 2.08 (dd, 1H, J=13.80, 1.65), 1.52 (dd, 1H, J=13.95, 7.14), 1.10 (s, 3H); 13C NMR (Gemini 300, CDCI3) 8 174.85 (C=O, quartet, J=36.80) 158.78, 147.03, 140.18, 116.04 (-CF3, quartet, J=289.50) 114.51, 81.72, 69.87, 41.87, 41.02, 40.27, 34.10, 24.14; FT-IR (Nicolet IR / 42) 2966.1, 2924.5, 2849.5, 1709.15, 175 1598.8, 1250.0. 1217.2, 1172.9, 1151.5, 1057.1, 925.5 om-l; M8 (m/e) 258 (M1), 229, 213, 201, 187, 159, 131, 91, 77, 41. The stereochemistry of LF012 has been established by Nuclear Overhauser Effect (NOE) experiment (figure 6) which showed a cis ring junction at H1-H9 which was anti to CH3 group- There was an increase in the vinyl proton of H11 (1 .6%) when the bridgehead methyl group was irradiated (100%). An increase in the bridgehead proton Hg was observed when the bridgehead proton H1 was irradiated. W Similar procedure as that used for ketone F011 was employed in the quenching study of ketone F012. C17H35 was used as internal standard and 2.5-dimethyl-2,4-hexadiene as quencher. Concentration of stock solution of F012: 0.23 M (0.588 g/ 10 mL). Concentration of stock solution of standard: 0.012 M (0.277 g / 10 mL). Concentration of stock solution of quencher: 0.20 M (1.11 g / 50 mL). The above stock solutions were diluted as before. Volume of quencher in each flask was as follow: 0.0, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 6.0 and 7.0 mL. The degassed solutions were irradiated for 45 hrs using a Pyrex filter (by removing the potassium chromate filter) in a merry-go-round. The irradiated solutions were analyzed by GC. ”1000 ss 01 01111111 es. : 0:1 0,-1-1'1 --e :1: £921; A solution of 1.0 g of ketone F021 in a 400 mL immersion well containing Omnisolv benzene (about 400 mL), equipped with Pyrex filter and Hanova 176 mercury lamp was irradiated for 12.0 hrs under argon atmosphere. Two photoproducts were formed based on GC analysis (GC: DB-210; 15m). After evaporation of solvent by rotary evaporator at 40°C, two products were separated by gradient flash column using silica gel (30 cm, aldrich grade 60, 230-400 mesh) and hexane/ethyl acetate. Pressure was applied to increase the elution rate to one drop per second. The column (50X3 cm) was packed with hexane and was eluted first with 982% of hexane/ethyl acetate (200 mL), the ratio was then changed to 96:4% until all of the starting ketone was eluted. The ratio of hexane/ethyl acetate was then changed to 94:6% (200 mL) and 92:8% until the first photoproduct started to elute from the column. Finally 90:10% of hexane/ethyl acetate was used to complete the separation. The linear photoproduct eluted first from the column followed by the angular one. The two photocycloadducts are 4,4-dimethyl-9-trifluoroacetyl-cis-anti-3- oxatricyclo[7.2.0.0‘-5]-undeca-7,10-diene (AF021) and 4,4-dimethyl-10- trifluoroacetyl-cis-antI-S-oxatricyclo[72.0.03-7]undeca-7,1 0 diene (LF021). W 1H NMR, a: (VXR 300, C5D5) 8 5.94 (m, 1H), 5.87 (dddd, 1H, J=2.52, 1.25, 1.25, 1.25), 5.57 (ddd, 1H, J=9.95, 5.50, 3.79), 5.54 (d, 1H, J=10.05), 3.93 (d, 1H, J=10.05), 3.71 (d, 1H, J=10.20), 1.75 (dddd, 1H, J=16.41, 8.73, 3.69, 2.53), 1.65 (dddd, 1H, J=16.64, 5.77, 5.77, 2.50), 1.49 (dd, 1H, J=8.73, 6.04), 0.97 (s, 3H), 0.96 (s, 3H); b: (Gemini 300, CDCI3) 8 6.46 (m, 1H), 6.23 (dddd, 1H, J=2.82, 1.31, 1.31, 1.31), 6.08 (ddd, 1H, 9.98, 5.65, 3.85), 5.82 (d, 1H, 9.89), 3.86 (d, 1H, J=10.44), 3.81 (d, 1H, J=10.32), 2.18 (dddd, 1H, J=16.26, 5.99, 5.99, 1.25), 2.05 (dddd, 1H, J=16.21, 7.14, 4.67, 2.47), 1.92 (dd. 1H), 1.22 (s, 3H), 1.17 (s, 3H); 130 NMR (Gemini 300, CDCI3) 8 191.11 (q, C=O), 144.47, 135.15, 130.75, 125.22, 115.66 (q, -CF3), 82.35, 68.96, 62.74, 61.62, 50.39, 28.58, 23.38 (2C's); IR (CCI4) 2976.5, 2941.8, 2876.2, 1738.1 177 (C=O), 1387.7, 1307.9, 1207.5, 1155.5, 1055.2, 1032 cm-1.; MS (m/e) 272 (M1), 214, 145, 91, 59. The stereochemistry of AF021 has been established by NOE experiment which showed an increase of H11 (2.57%), H10 (0.89%), H55 (1.78%), H53 (3.89%) and CH343 (5.14%) when the bridgehead proton at 8 1.49 (H5, 100%) was irradiated. WWI-£921; 1H NMR, a: (vxn 300. 0605) 6 6.40 (m, 1H), 5.53 (dddd. 1H, J=5.59, 2.23, 3.08, 2.51), 4.17 (m, 1H, J=13.64), 4.05 (m, 1H, J=13.67), 3.22 (m, 1H), 2.49 (m, 1H), 1.85 (m, 1H), 1.34 (ddd, 1H, J=13.11, 5.30, 1.67), 1.24 (s, 3H). 0.82 (s, 3H), 0.66 (ddd, 1H, J=12.56, 12.29, 6.42); b: (Gemini 300, CDCI3) 8 7.18 (broad s, 1H), 5.78 (m, 1H), 4.35 (d, 1H, J=13.52), 4.27 (d, 1H, J=12.88), 3.68 (m, 1H), 3.30 (m, 1H), 2.08 (m, 1H), 2.00 (ddd, 1H, 0:522, 1.55, 1.55), 1.32 (s, 3H), 1.22 (m, 1H), 1.00 (s, 3H); 13C NMR (Gemini 300, CDCI3, figure 39) 8 175.04 (C=O), 155.24, 145.17, 140.12, 116.61, 113.80, 82.13, 67.72, 45.73, 40.80, 39.73, 27.03, 25.58, 21.35; Mass (m/e) 272 (M1), 214, 187, 145, 117, 91, 69; FT-IR (CCI4) 2976.5, 2943.5, 2812.3, 1709.2, 1582.3, 1367.7, 1244.2. 1225.9, 1153.5, 1043.52 cm'1. The stereochemistry of LF021 has been established by NOE experiments which showed cis ring junction at H1- H9, anti to H3. An increase in intensity of vinyl proton H11 (7.4%) was observed when the bridgehead proton H-3 (100%) was irradiated, while there was no enhancement of H1 and H9. WW Similar procedure as that used for compound F011 was employed in the quenching study of F021 using C16H34 as internal standard and 2,5-dimethyl- 2,4-hexadiene as quencher. Concentration of stock solution of F021: 0.20 M (0.55 g l 10 mL). 178 Concentration of stock solution of standard: 0.0055 M (0.012 g / 10 mL). Concentration of stock solution of quencher: 0.20 M (1.10 g / 50 mL). The above stock solutions were diluted in benzene as before. Volume of quencher in each flask was as follow: 0.0, 1.0, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0 and 6.0 mL. The degassed solutions were irradiated for 2.0 hrs using a Pyrex filter in merry- go-round (by removing the potassium chromate solution). The solutions were analyzed by GC. to . ' . - - ._ ._ t- r' . .. :1 n=1 - «:1 :t- 11; Asolution of 0.60 g of ketone FC11 in a 400 mL immersion well containing Omnisolv benzene (about 400 mL), equipped with Pyrex filter and Hanova mercury lamp was irradiated for 4.0 hrs under argon atmosphere. Two major photoproducts were formed based on GC analysis (GC: DB-1; 15 m). After evaporation of solvent by rotary evaporator at about 40°C, two products were separated by flash column using silica gel (30 cm, Aldrich grade 60, 230-400 mesh) and hexane/ethyl acetate. Pressure was applied to increase the elution rate to one drop per second. The column (50X3 cm) was packed with 97.5:2.5% hexane/ethyl acetate and was eluted with the same ratio of solvents. Photoproduct AFC11 was eluted first followed by a mixture of starting ketone and the photoproduct LFC11. Photoproduct LFC11 was further purified by flash column chromatography using silica gel (40x2 cm) and hexane/ethyl acetate (97.5:2.5%, 100 mL) followed by 95:5% hexane/ethyl acetate. Photoproduct LFC11 eluted first from the column followed by the starting ketone. solvent mixture. The two photoproducts are 9-trifluoroacetyl-cis-anti- .908 s such. oce_?o..s.8eo==r.eo.o.~.n 5.58:86-25-29.285252.561.362.5466 £22 on. an 2:9... 9.... 3&3 we we 03 o~« « o2 8. L...prhnp—bin-phhb bubPPpb-h P-nppb-ppb-p-LPLbL—hpbbupppP Fbprbp.h-—b»--PP+P. 5 il 179 it 1 ii. i _. 1 ii I 1-. 134-14. .14 J a. (1 180 tricyclo[7.2.0.0‘v5]undeca-7,10-diene (AFC11) and 10-trifluoroacetyl-cis—anti— tricyclo[7.2.0.03-7jundeca-7,10-diene (LFC1 1). W 1H NMR (Gemini 300, CDCI3) 8 6.32 (m, 1H), 6.07 (dd, 1H, J=2.75, 1.25), 5.88 (td, 1H, J=9.89, 4.67), 5.71 (d, 1H, J=9.89), 2.05-2.13 (m, 2H), 1.98-2.06(m, 1H), 1.66-1.77 (m, 2H), 1.44-1.63 (m, 4H); 13C NMR (Gemini 300, CDCI3) 8192.45, 143.71, 132.58, 128.84, 124.12, 115.82, 63.96, 60.63. 41 .52, 32.26, 28.91, 26.45, 21.44; FT-IR (0014) 3029.4, 2959.2, 2872.4, 1735.2, 1309.8, 1230.7, 1207.6, 1180.6, 1149.7, 1088.0, 891.2, 881.6, 854.6: MS (m/e) 242 (M1), 227, 214, 200, 188, 173, 155, 145, 131, 120, 105, 91, 79, 67, 55. W11; 1H NMR (vxn 500, 00013) 87.14 (m, 1H), 5.59 (m, 1H), 3.60 (dd, 1H, J=5.04, 4.94), 3.20 (m, 1H), 2.20-2.38 (m, 2H), 2.18 (dd, 1H, J=13.17, 4.94), 1.82-2.03 (m, 2H), 1.53-1.70 (m, 1H), 1.48-1.59 (m, 1H), 1.15- 1.25 (m, 1H), 1.10 (ddd, 1H, J=12.2, 12.03. 5.75); 130 NMR (Gemini 300. 00013) 6 175.13 (q), 155.02, 149.40, 140.06, 115.09 (q), 114.49, 41.84, 40.45, 37.05, 33.21, 31.75, 31.41, 24.55; FT-IR (CCI4) 2955.32, 2930.24, 2864.41, 2844.57, 1709.2, 1585.7, 1446.0, 1346.1, 1259.7, 1252.0, 1221.1, 1205.7. 1194.1, 1171.0, 1151.6, 1113.1, 1064.8 cm'1;MS (m/e) 242 (M+), 227, 200, 173, 145, 145, 117, 91, 67. The stereochemistry of LFC11 has been established by NOE experiments which showed cis ring junction at H1-H9, syn to H3. An increase of the intensity of the bridgehead proton at 8 3.56-3.64 (H9, 7.2%) was observed when the bridgehead proton at 8 3.17-3.22 (H1, 100%) irradiated. When H11 was irradiated (100%) there was an enhancement of H1 (2.6%) and H3 (1 .9%). 181 W). Similar procedure as that used for F011 was employed in the quenching study of F021 using C14H30 as internal standard and 2,5-dimethyl- 2,4-hexadiene as quencher. Concentration of stock solution of F011: 0.20 M (0.48 g / 10 mL). Concentration of stock solution of standard: 0.019 M (0.37 g / 10 mL). Concentration of stock solution of quencher: 0.10 M (0.56 g / 50 mL). The above stock solutions were diluted in benzene as before. Volume of quencher in each flask was as follow: 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5 and 4.0 mL. The degassed solutions were irradiated for 90 hrs using a Pyrex filter in merry-go-round (by removing the potassium chromate filter). The solutions were analyzed by GC. WW1]; In a 400 ml immersion well equipped with Pyrex filter and Hanova mercury lamp 0.50 g of ketone AC11 was irradiated in M9 dried methanol (under argon atmosphere) for 48 hrs after which a major product was formed (based on 1H NMR). Alter evaporation of solvent by rotary evaporator at 40°C photoproducts were separated by gradient flash column on silica gel (40 cm, Aldrich grade 60, 230- 400 mesh) using hexane/ethyl acetate as eluent. Pressure was applied to increase the elution rate to one drop per second. The column (50x2 cm) was packed with hexane and after transferring the crude product to the column was eluted first with 150 mL of hexane and then a mixture of hexane and ethyl acetate. The ratio of hexane/ethyl acetate was initially 99:1 (100 mL) and then changed to 98:2 until the starting ketone and the photoproduct AAC11 started 182 to elute. The ratio of hexane/ethyl acetate was then changed to 97:3 (100 mL), 96:4 (100 mL) and finally to 95:5 until the separation was complete. The two photoproducts are 9-acetyl, tricyclo[7.2.01-5]undeca-7,10-diene AAC11 and 10- acetyl, tricyclo [7.2.03-7] undeca-7,10-diene LAC11. Photoproduct AAC11 was eluted first from the column as a mixture with the starting ketone followed by the photoproduct LAC11. WM: could not be further purified and its proton NMR showed four vinyl protons. Two, both doublets, occur at 8 6.27 (H10, J=2.96) and 8 6.05 (H11, J=2.94). There are two other vinyl protons, a doublet at 8 5.74 (H3) and a multiplet at 8 5.41 (H7). The methyl of acetyl group is at 8 2.30. 13591331931111.35th NMR (vxrt 300, 00013) 6 5.75 (m, 1H), 5.76 (m, 1H), 3.48 (ddd, 1H, J=4.88, 4.60, 0.84), 3.02 (tdd, 1H, J=5.86, 4.19, 1.39), 2.18-2.32 (m, 2H), 2.15 (s, 3H), 2.12 (ddd, 1H, J=12.84, 5.02, 1.57), 1.87-2.07 (m, 2H), 1.43-1.58 (m, 1H), 1.58-1.73 (m, 2H), 1.13-1.25 (m, 1H), 1.04 (ddd, 1H, J=12.76, 11.45, 5.59); 13C NMR (CDCI3)8194.09 (C=O), 148.18, 147.02, 146.45, 115.65, 40.03. 39.27. 35.84. 33.25, 31.77, 31.70, 25.52, 24.68: FT-IR (0014) 2954.4, 2925.4, 2889.5, 2844.4, 1678.3, 1594.4, 1359.0, 1234.6, 1129.5, 853.61; MS (m/e) 188 (M1'), 173, 160, 145, 131, 117, 105, 91, 77, 65, 51. The stereochemistry of LAC11 has been established by NOE experiments which showed cis-ring junction at 01-09, anti to 03. An increase of the intensity of the bridgehead proton at 8 2.99-3.04 (H1) was observed when the bridgehead proton at 8 346-350 (Hg) was irradiated. When the proton at 8 0.98-1.08 (H25) was irradiated there was an increase in the intensity of the bridgehead proton at 8 2.99-3.04 (H1). When the proton at 8 0.98-1.08 (H25) was irradiated the bridgehead proton at 8 2.24-2.31 was unchanged. 183 W11 Similar procedure as that used for F011 was employed in the quenching of AC11 using C24H50 as internal standard and 2,5-dimethyl-2,4 hexadiene as quencher in benzene/methanol (80/20). The degassed solutions were irradiated for 3.5 hrs by hanging them to the outside wall of an immersion-well, using Pyrex filter. The solutions were analyzed by GC. 'to . ' . - --. : - -n: to. 01:1 - --:t :t: '11.; 11;,lna400 mL immersion well equipped with Pyrex filter and Hanova mercury lamp 0.13 g of ketone 3-MOAC11 was irradiated in acetonitrile (under argon atmosphere) for 24.0 hrs. The proton NMR of the crude showed the formation of only one major product. After evaporation of solvent by rotary evaporator at 40°C, the crude photoproduct was separated by gradient flash column chromatography. Pressure was applied to increase the elution rate to one drop per second. The column was packed with silica gel (28X1.5 cm) in hexane and was first eluted with 100 mL of hexane. Then hexane/ethyl acetate was used to elute the column. The ratio of hexane/ethyl acetate was as: 99:1 (50 mL), 98:2 (50 mL), 97:3 (50 mL), 96:4 (50 mL) and finally 95:5 until the separation was complete. The starting ketone was eluted first followed by the photoproduct. The major product formed is the 11-methoxy-9-acetyl-cis-tricyclo[6.3.0.01-7]undeca-8,10- diene (C-3-MOAC11). 1H NMR (VXR 300, CDCI3) 8 6.26 (d, 1H, J=5.40), 5.48 (s, 1H), 3.58 (s, 3H), 3.40 (m, 1H), 2.92 (m, 1H), 2.30 (m, 1H), 2.28 (s, 3H), 1.86- 2.05 (m, 2H), 1.80 (m, 1H), 1.56 (m, 1H), 1.54 (m, 1H), 1.44 (m, 1H), 1.28 (m. 1H). 184 WW1]; In a 400 mL immersion well equipped with Pyrex filter and Hanova mercury lamp 0.25 g of ketone A011 was irradiated in M9 dried methanol (about 400 mL, under argon atmosphere) for 48.0 hrs. After evaporation of solvent by rotary evaporator at 40°C two photoproducts were separated by gradient column chromatography. The column (50X3 cm) was packed with silica gel (30X3 cm) in hexane. Elution began with pure hexane (100 mL) and then hexane/ethyl acetate. The ratio of hexane/ethyl acetate was as: 99:1 (200 mL), 98:2 (200 mL), 97:3 (200 mL), 96:4 (200 mL), 95:5 (200 mL), 94:5 (200 mL), 93:7 (200 mL), 92:8 (200 mL) and 90:10. Two major photoproducts were identified based on GC analysis (GC: DB-wax, 15 m). These photoproducts which are the result of meta- photocycloaddition of the double bond to the aromatic ring are 10-oxa-4-acetyl, tetracyclo [6,3,0,01-5,04-5]undeca-2-ene MAO11 and 9-oxa-1-acetyl, tetracyclo [5,3,1.01-5,04-"jundeca-2-ene RMAO11. Photoproduct MAO11 eluted first from the column after the starting ketone, followed by photoproduct RMAO11. Wmm NMR, a: (Gemini 300, C505) 8 5.68 (d, 1H, J=5.40), 5.09 (d, 1H, J=5.70), 3.75 (d, 1H, J=8.85), 3.68 (t, 1H, J=8.0), 3.54 (d, 1H, J=8.85), 3.36 (d, 1H), J=8.09), 3.32 (d, 1H, J=8.06), 2.66 (d, 1H, J=6.81), 2.37 (dd, 1H, J=6.78, 1.59), 1.92 (dddd, 1H, J=9.65, 7.70, 4.58, 0.79), 1.70 (s, 3H), 1.42 (ddd, 1H, J=14.29, 5.41, 1.58), 1.38 (dd, 1H, J=14.39, 5.41); b: (VXR 300. CDCI3) 8 5.96 (d, 1H, J=5.40), 5.55 (d, 1H, J=5.10), 3.96 (dd, 1H, J=9.00, 3.00). 3.89 (t, 1H, J=8.10), 3.85 (dd, 1H, J=8.10, 1.20). 3.54 (AB quartet, 1H, 1:10.20. 8.10), 2.97 (d, 1H, J=6.60), 2.65 (dd, 1H, J=5.70, 5.70). 2.36 (m, 1H), 2.17(s. 3H), 1.91 (dd, 1H, J=14.40, 5.86), 1.80 (ddd, 1H, J=14.40, 6.75, 1.20); 13C NMR (VXR 300, CDCI3) 8 204.5, 134.0, 124.7, 72.0, 70.8, 69.3, 58.6, 54.0, 53.2, 42.2, 27.7 and 25.0; MS (m/e) 190 (W), 149, 131, 115, 103, 91, 77, 65, 55, 51, 43. 185 W1]; 1H NMR, a: (Gemini 300, C5D5) 8 5.56 (dd, 1H, J=5.83, 1.15), 5.33 (dd, 1H, J=5.83, 2.32), 4.59 (d, 1H, J=7.69), 3.99 (d, 1H, J=7.66), 3.41 (t, 1H, J=7.34), 2.90 (AB quartet, 1H, J=11.68, 7.28), 2.54 (dtt, 1H, J=11.63, 11.63, 7.25), 2.27 (ddd, 1H, J=8.07, 5.04, 2.0), 2.17 (ddd, 1H, J=8.02, 2.38, 1.15), 1.40 (s, 3H), 1.28 (ddd, 1H, 1:122, 5.10, 7.18), 1.03 (ddd, J=11.82, 11.82, 2.05); o: (vxn 300, CDCI3) 6 5.75 (dd, 1H, J=5.70, 2.40), 5.70 (dd, 1H, =5.70, 0.90), 4.32 (d, 1H, J=7.80), 3.85 (d, 1H, J=7.50), 3.55 (t, 1H, J=7.10), 2.95-3.13 (m, 2H), 2.92 (ddd, 1H, J=7.88, 5.30, 1.80), 2.78 (ddd, 1H, J=7.80. 2.10, 1.20), 1.89 (s, 3H), 1.83 (dd, 1H, J=11.99, 6.29), 1.39 (dt, 1H, J=12.30, 1.80); 130 NMR (vxn 300, CDCI3) 6204.30, 133.75, 125.55, 77.14, 68.06, 65.47, 54.35, 57.80, 44.85, 43.97, 25.29, 20.14; MS (m/e) 190 (W), 159, 145, 129, 117, 105, 91, 77, 55, 43: DEPT: 1(-CH3), 3 (-CH2) and 5 (-0H). WM Similar procedure as that used for compound F011 was employed in the quenching study of A011. The internal standard was C22H45 with 2,5- dimethyI-2,4-hexadiene as quencher in benzene-methanol (80 / 20). The degassed solutions were irradiated for 4.0 hrs by hanging them to the outside wall of immersion-well, using Pyrex filter. The solutions were analyzed by GC. WW: "I a 400 mL immersion well equipped with Pyrex filter and Hanova mercury lamp 0.25 g of ketone AC11 was irradiated in M9 dried methanol (about 400 mL, under argon atmosphere) for 48 hrs. After evaporation of solvent by rotary evaporator at 40°C, the photoproducts were chromatographed by flash column using silica gel and 186 hexane/ethyl acetate the same way as of that of the A011. Two photoproducts were forme based on GC analysis (GC: DB-wax; 15 m). These photoproducts which were the result of meta-photocycloaddition of the double bond to the aromatic ring were 4-acetyl, tetracyclo[6.3.0.01-5.04-5]undeca-2-ene (MAC11) and 1-acetyl,tetracyclo[5.3.1.015.04-11]undeca-2-ene (RMAC11). Photoproduct MAC11 was eluted first along with the starting ketone (both have the same R; values) followed by the photoproduct RMAC11. While photoproduct MAC11 could not be further purified, product RMAC11 was characterized based on its 1H and 13C NMR. 1H NMR a: (Gemini 300, 0503) 6 5.40 (dd, 1H, J=5.82, 2.28), 5.34 (dd, 1H, J=5.85, 1.14), 1.55 (s, 3H), 0.80-0.95 (m, 1H), 1.05-1.25 (m, 2H), 1.43-1.52 (m, 1H), 1.55-1.75 (m, 1H), 1.80-2.0 (m, 3H), 2.27-2.50 (m, 3H); 5: (Gemini 300, 00013) d 5.54 (dd, 1H, J=5.60, 2.10). 5.55 (dd, 1H, J=5.65, 1.40), 2.79 (dd, 1H, J=7.06, 7.06), 2.67 (d, 1H, J=8.47), 2.57 (m, 1H), 2.27 (AB quartet, 1H, J=9.88, 8.19), 2.00-2.18 (m, 2H), 1.96 (s, 3H), 1.65-1.78 (m, 2H), 1.35 (m, 1H), 1.20 (ddd, 1H, J=10.59. 10.59, 2.80), 1.40 (m, 1H). 13C NMR (CDCI3) 8206.72 (C=O), 135.56, 124.60, 67.68, 67.47, 57.14, 54.60, 44.90, 44.39, 28.09, 26.69, 22.08, 21.94. 1:11- :.t-to:tt:t o 't-' 00- ‘\"0.-I01 o It mm W A solution of AF011 in toluene-da (one drop of compound per 1.0 mL of toluene—dg) in an NMR tube was heated at 100°C (immersed in boiling water) for 12.0 hrs to give the thermally rearranged product 10- trifluoroacetyl-cis-syn-S-oxatricyclo [7.2.0.03-7jundeca-7,10-diene(TAFO1 1 ). The progress of the rearrangement was followed by 1H NMR until it was complete and there was no starting material left. 1H NMR showed the formation of only one product. The toluene d3 solution was then transferred to a 25 mL round bottomed flask and the solvent was evaporated under reduced pressure 187 at about 50°C using rotary evaporator. Deuterated benzene was added (1.0 mL) to the residue and solution transferred to an NMR tube for spectroscopic analysis. Transferring of the rearranged product from C505 to CDCI3 took place the same way as going from toluene to benzene. 1H NMR, a: (VXR 300. C505) 8 6.41 (m, 1H), 5.57 (dt, 1H, J=2.24, 2.24), 4.14 (ddddd, 1H, J=13.4, 1.68, 1.68, 1.68, 1.68), 3.97 (m, 1H), 3.86 (dd, 1H, J=1-8.38, 8.10), 3.18 (m, 1H), 2.95 (dd, 1H, J=8.66, 8.66), 2.34 (dddd, 1H, J=11.16, 7.81, 4.47, 0.84), 2.09 (m, 1H), 1.48 (ddd, 1H, J=12.28, 7.96, 4.20), 0.50 (A8 quartet, 1H, J=23.45, 11.45) b: (vxn 300, CDCI3) 6 7.20 (m, 1H), 5.82 (dddd, 1H, J=2.23, 2.23, 2.23, 2.23), 4.35 (ddddd, 1H, J=13.12, 1.68, 1.68, 1.68, 1.68), 4.22 (d, 1H, J=13.12), 4.15 (dd, 1H, J=8.38, 8.10), 3.65 (m, 1H), 3.24 (dd, 1H, J=8.93, 8.66), 3.22 (dddd, 1H, J=11.45, 8.24, 4.47, 0.84), 2.68 (m, 1H), 2.30 (ddd, 1H, J=12.28, 7.95, 4.47), 1.10 (AB quartet, 1H, J=23.44, 11.45); 130 NMR (Gemini 300, CDCI3) d 176.08(quartet, 0:0, 3:35.15) 158.47, 145.57, 142.57, 115.15 (quartet, -0F3, 32239.55), 115.25, 73.48, 59.79, 41.63, 40.09, 39.58, 29.27; FT-IR (0014) 2964.4, 2932.2, 2860.8, 1709.15, 1585.69, 1358.1, 1259.7, 1205.7, 1153.6, 1059.3, 955.45, 922.1, 868.1 cm-i; MS (m/e) 244 (W), 215. 203, 187, 175, 147, 129, 117, 105, 86, 57 cm“. The stereochemistry of TAFO11 has been established by NOE experiments which showed a cis ring junction at H1-H9, syn to H3. An increase in intensity of the bridgehead proton H-l (2.6%) was observed when the bridgehead proton H3 (100%) was irradiated. When the bridgehead proton H1 (100%) was irradiated, there was an enhancement of both bridgehead protons of H9 (8.7%) and H3 (4.6%). 188 m... ........... . .... -- .' . .. .. - .., . t 1.51 W A solution of AFO12 in toluene-da in an NMR tube (one drop compound per 1.0 mL of solvent) was heated at 100°C (immersed in boiling water) for 10.0 hrs. to give the thermally rearranged product of 3- methyl-1 0-trifluoroacetyl-cis-syn-S-oxatricyclo[7.2.0.03-7jundeca-7,1 0-diene (TAFO12). Follow up of the transformation and transferring the rearranged product to 0505 was the same as that of the TAFO11. 1H NMR, 3: (VXR 300, 0505) 86.48 (m, 1H), 5.47 (dt, 1H, J=2.24, 1.95), 4.24 (ddd, 1H, J=13.68, 3.36, 2.23), 3.97 (ddd, 1H, J=13.41, 2.24, 0.56), 3.53 (d, 1H, J=8.37), 3.17 (dddd, 1H, J=3.34, 2.84, 3.07, 3.35). 3.09 (d, 1H, J=8.09), 2.53 (dddd, 1H, J=12.08, 7.40, 4.47, 1.12), 1.39 (AB quartet, 1H, J=12.28, 8.24), 0.83 (s, 3H), 0.73 (dd, J=11.72, 11.72); h: (vxn 300, 00013) 6 7.21 (m, 1H), 5.69 (dt, 1H, J=2.23, 1.95), 4.45 (ddd, 1H, J=13.40, 3.63, 2.24), 4.24 (dddd, 1H, J=13.40, 2.23, 1.96, 0.56), 3.76 (d, 1H, J=8.37), 3.67 (m, 1H), 3.36 (d, 1H, J=8.10), 3.34 (m, 1H, J=4.46, 1.12), 2.10 (A8 quartet, 1H, J=12.29, 8.24), 1.28 (dd, 1H, J=12.00, 11.73), 1.15 (s, 3H); 130 NMR (Gemini 300, 00013) 6 175.94 (quartet, C=O), 158.17, 148.38, 141.23, 115.99 (q), 113.93, 80.42, 59.51, 43.79, 41 .15, 39.02, 34.93, 23.08; FT- IR (CCI4) 2966.9, 2932.2, 2858.9, 1707.2, 1583.8, 1451.0, 1351.1, 1251.9. 1207.5, 1182.5, 1153.5, 1115.9, 1080.3, 1057.1, 922.1, 868.1 cm-i; M8 (m/e) 258 (M1), 243, 219, 200, 187, 159, 131, 115, 105, 96, 91, 83, 77, 41. The stereochemistry of TAFO12 has been established by NOE experiments (figure 16) which showed cis ring junction at H1-H9, syn to CH3 group. An increase in intensity of signals of the bridgehead proton at 8 3.17 (H9, 3.7%) and the methyl protons at 8 0.83 was observed when the bridgehead proton at 8 2.53 (H1, 100%) was irradiated. When the methyl protons at 8 0.83 (1005) were irradiated an increase in the intensity of the signals of the bridgehead protons at 8 3.17 (H9, 0.7%) and 2.53 (H1, 3.2%) was observed. 189 1:11. :.tr=t-:tt:t . . ' 011:: --t' - 03°13\ - --.- t-t - l l 1 W502]; A solution of AF021 in toluene-d3 was heated at 100°C (immersed in boiling water) in an NMR tube for 6 hrs to give the thermally rearranged product of 4,4-dimethyl-10-trifluoroacetyI-cis-syn-5- oxatricyclo[7.2.0.03-7]undeca-7,10-diene (TAFOzt). Follow up of the transformation and transferring of the rearranged product from toluene-d3 to deuterated chloroform was the same as that of the AFO11. 1H NMR (VXR 300, CDCI3) 8 7.19 (m, 1H), 5.74 (dddd, 1H, J=2.23, 2.23, 2.23, 2.51 , ), 4.34 (ddddd, 1H, J=13.68, 1.95, 1.40, 1.95, 1.68), 4.24 (ddt, 1H, J=13.67, 3.07, 2.23), 3.62 (m, 1H), 3.18 (dddd, 1H, J=12.28, 6.70, 4.47, 1.12), 2.37 (m, 1H), 2.10 (ddd, 1H, J=12.28, 7.82, 4.19), 1.31 (s, 3H), 1.09 (AB quartet, 1H, 1:23.32, 12.00); 130 NMR (Gemini 300, CDCI3, figure 35)8176.10, 158.12, 146.63, 142.57, 114.80, 116.00, 81.90, 67.25, 49.10, 41.74, 40.19, 27.59, 27.04, 21.06; FT-IR (CCI4) 2974.6, 2864.7, 1707.2, 1583.8, 1367.1, 1207.6, 1153.58, 1091.8, 1035.9. 871.9 cm-i; MS (m/e) 272 (M+), 214, 145, 117, 91, 59, 59. The stereochemistry of TAF021 has been established by NOE experiments which showed cis ring junction at H1-H9, syn to H3. An increase of the intensity of the bridgehead protons at 8 3.62 (H9) and 2.18 (H3) was observed when the bridgehead proton at 8 3.18 (H1) was irradiated. The intensity of the vinyl proton at 8 7.19 (H11) and the proton at 8 2.37 (H25) were increased when the proton at 8 3.18 (H1) was irradiated. An increase of the intesity of the protons at 8 3.18 (H1) and 8 2.10 (H25) and the methyl hydrogens of CH33 were observed when the bridgehead proton at 8 2.37 (H3) was irradiated. IhntmalJnaLanntnnLnLnotonmductnfimLmolunnfln When a solution of one drop of 9-trifluoroacetyl, tricyclo [7.2.0.01-5jundeca-7,10-diene AFC11 in 1.0 mL toluene-d8 in an NMR tube is heated at 100°C (immersed in boiling 190 .908 5 $5928 2552.085 23.8.6.3. 5.585566-5556.38526256235554.: 5 :22 on ”o: 28E 2%. cm ow 8 2: 02 o: 8‘ .L—ppr-ppp-Prbb-npbP-P- .b-pb-npb—pnnpnbpbp—pb-b—b-uu—sr-pp-uh.—.. h- 4 if j 1 iii) it i iiii .jdtfiianl I 114111 ii i1_1 191 water) for 2.5 hrs it underwent thermal transformation through Cope rearrangement to 10-trifluoroacetyl-cis-syn—tricyclo [7.10.0.03-7]undeca-7,10- diene (TAFC11). Follow up of the transformation and transferring of the rearranged product to deuterated benzene solution for spectrosc0pic study was exactly the same as that of the TAFO11. Product TAFC11 is characterized by spectroscopic data as follows: 1H NMR, a: (VXR 500, C605) 8 6.53 (m, 1H), 5.78 (dddd, 1H, J=2.50, 2.25, 2.25, 2.00), 3.34 (m, 1H), 2.50 (dddd, 1H, J=11.00. 8.00, 4.50, 1.00), 2.10 (m, 1H), 2.02 (m, 1H), 1.89 (m, 1H), 1.76 (ddd, 1H, J=10.00, 6.00, 4.00), 1.63 (m, 1H), 1.45 (m, 1H), 1.33 (m, 1H), 0.87 (dddd, 1H, J=12.12, 9.75, 7.00, 10.00). 0.68 (A8 quartet, J=24.50, 11.00); b: (VXR 500, 00013) 5 7.18 (m. 1H), 5.70 (dddd, 1H, J=2.24, 2.24, 2.10. 1.95), 3.60 (m, 1H), 3.16 (dddd, 1H, J=11.02, 7.12, 4.74, 1.12), 2.21-2.33 (m, 3H), 1.33-1.97 (m, 1H), 1.50-1.74 (m, 3H), 0.97-1.26 (m, 2H); 13C NMR (Gemini 300. CDCI3) 5 176.08 ( quartet, C=O), 158.62, 149.55, 142.58, 116.08, 115.81, 42.25, 41 .07. 39.89. 32.95 (2C's), 31.15. 24.81; FT-IR (CCI4) 2957.2, 2936.0, 2891.7, 2860.8, 1707.2, 1583.8, 1296.3, 1253.9, 1205.7, 1180.6, 1151.6, 1109.21. 1088.0. 970.3, 868.1 cm"; MS (m/e) 242 (m), 27. 213, 200, 188, 173, 155, 145, 131, 120, 105, 91, 79, 67, 55. The stereochemistry of TAFC11 has been established by NOE experiments which showed cis- ring junction at H1-H9, syn to H3. An increase of the intensity of the bridgehead protons H9 (11.1%) and 1.84-1.93 H3 (5.4%) was observed when the bridgehead proton H1 (100%) was irradiated. Wlmmmm When a solution of 9-trifluoroacetyl-cis-anri-tricyclo [7.2.0.01,5]undeca-7,10-diene AFC11 in methanol-d4 in a NMR tube (one drop of compound per 1.0 mL methanol-d4) was heated at 50°C water bath (the water bath of a rotary 192 evaporator setup was used) for 30 hrs it underwent transformation to 9- trifluoroacetyl-cis-anti-tricyclo [6.3.0.01-7]undeca-8,1O-diene (CFC11). The progress of this transformation was followed by 1H NMR until it was complete and there was no starting material left. The solvent was evaporated the same and the product was transferred to an NMR tube in CDCI3 for spectroscopic analysis, the same way as that of the TAFO11. 1H NMR (VXR 500, CDCI3) 8 6.90 (m, 1H). 6.25 (dd, 1H, .1.-40.01, 1.40). 5.60 (dd, 1H, J=10.01, 1.16), 2.95 (m, 1H), 2.88 (m, 1H), 2.40 (ddd, 1H, J=12.34. 9.67, 7.50), 2.09 (m, 1H), 1.98 (ddd, 1H, J=12.24, 4.32, 7.49), 1.91 (m, 1H), 1.72 (dd, 1H, J=13.37, 6.71), 1.68 (ddd, 1H, J=19.96, 13.11, 6.99), 1.46 (AB quartet, 1H, J=13.37. 6.47), 1.30 (ddd, 1H, J=12.75, 12.75, 6.58) ; 13C NMR (Gemini 300, CDCI3)8179.65, 145.33, 145.29, 134.07, 116.59 (q). 115.96, 53.21, 46.78, 40.56, 35.81, 35.78, 33.79. 25.58; MS (m/e) 242 (11+), 200, 173, 159, 131, 115, 91, 55; FT-IR (CCI4) 2849.5, 1707.2, 1585.9, 1322.0, 1201.8, 1170.9, 1149.7 cm“. The stereochemistry of CAFC11 has been established by NOE experiments (figure 22) which showed cis cyclobutene ring. The bridgehead proton H5 was anti to the bridgehead proton H7. An increase of the intensity of the bridgehead proton at 5 2.92-2.99 (H5) was observed when the proton at 8 235-246 (Heb) was irradiated. W: A drop of photonroduct LAC11 was dissolved in about 2 mL of benzene and was transferred to a stretched test tube. The solvent was then evaporated by a rotary evaporator at about 40°C and the test tube was sealed after degassing. The sealed test tube containing the neat product was then heated for one minut at 190°C by dipping in a graphite bath on a hot plate. The tube was opened and its 1H NMR was recorded in CDCI3. The NMR of the crude showed the formation of the corresponding 193 cyclohexadiene. 1H NMR (Gemini 300, CDCI3) 5 6.57 (broad d, 1H, J= 5.34), 6.31 (dd, 1H, J=9.93, 1.32), 5.47 (dd, 1H, J=10.08, 1.20). WWWMMEhL W: In a NMR tube was placed 0.0023 g (0.014 M) of CFC11 and 0.0013 g (0.014 M) of methyl benzoate (as internal standard) in 0.70 mL of deuterated benzene. The tube was degassed by bubbling with argon and the 1H NMR spectrum of the sample was recorded. The tube was then irradiated using Pyrex filter. The 1H NMR of the irradiated sample was recorded after 45 and 80 min of irradiation. Two NMR tubes containing actinometer were also irradiated in parallel with CFC11 (actinometer: 0.12 M of valerophenone; internal standard: 0.0057 M of octyl benzoate, both in benzene). The actinometer was analyzed by h.p.l.c. using hexane (97%) and ethyl acetate (3%) at x = 270 nm and flow rate of 1.0 mL/min. By calculating the concentration of ketone A011 from the 1H NMR spectrum and that of the acetophenone by h.p.l.c. analysis, the quantum yield for the formation of ketone A011 from CAC11 was determined. In this experiment ketone AC11 is the major product. A very small amount of bicycloocadiene LAC11 and AAC11 also were formed. W: This experiment was performed the same way as the above experiment, but using a Uranium filter in place of Pyrex. The concentration of methyl benzoate was 0.0095 M (0.0013 g / 1.0 mL) and that of the ketone was 0.0010 M in 1.0 mL of deuterated benzene. Concentration of octyl benzoate was 0.0064 M and that of the valerophenone was 0.10 M. Photolysis of CAC11 at 334 nm led to the formation of ketone A011 and bicyclooctadiene LAC11. The AAC11 is not formed in this photolysis. 194 APPENDIX 195 Nuclear Overhauser Enhancement (NOE) The following parameters have been used for all NOE experiments (11 = 40 DS = 4 gain = 25 temp = 25 def = 5 nt = 64 or 128 ii = 'y' d1: Length of the first delay Description: This is the delay used to allow recovery of magnetization back to equilibrium. Limits: 0 to 8190 seconds; smallest value is 0.2 ps. bs: Block size Description: As data are acquired, the bs parameter directs the acquisition computer to periodically store the data on the disk, from where it can be accessed by the host computer. Limits: bs = 1 to 32767 gain: Receiver gain Description: gain = x sets receiver gain, where x is a value from 0 to 59. gain = 'n' enables Autogain, in which the gain is automatically adjusted at the start of acquisition for an optimum value. After the acquisition is finished setting gain = 'y' then allows the value of gain to be read. temp: Sample temperature Description: Temperature of sample, entered in degree celsius (00). Temp = 'n' instructs the acquisition system. Limits: -150°C to +200°C, in steps of 0.1°C. dpwr: Decoupler power with linear Amplifiers Description: On systems equipped with a linear amplifier on the decoupler channel, the decoupler power is under computer control. Limits:dpwr can be given values from 0 to 63. nt: Description: Limits: il: Description: 196 Number of Transients The number of transients to be acquired, i. e. , the number of repetitions or "scans” performed to make up the experiment. To set up an indefinite acquisition, set nt to a very large number, e. g. , 1eq. nt = 1 t0 1eq lnterleave arrayed and 20 Experiments Experimental interleaving, which is turned on with il = 'y', applies only to arrayed experiments. ii = 'n' turns off the interleaving. When interleaving is active, bs transients are performed for each member of the array, followed by bs more transients for each member of the array, and so on until nt transients have been collected for each member of the array. Thus, il will only be of relevance if bs < nt. 197 MW The response factors for the ketones and photoproducts were measured by preparing a stock solution of the compounds and an internal standard. Two to three solutions were usually prepared and the analysis was performed by GC. Table XVIII. Response factors of 3-(p-trifluoroacetylbenzyloxy)-1-propene (F011) and its photoproducts using C15H32 as a standard. 800.31.; [F011] = 0.0022 M (0.0027 g I 5 mL) [AFO11] = 0.0015 M (0.0018 g / 5 mL) [standard] = 0.0010 M (0.0011 g / 5 mL) GC: Column: DB-l (15 m); temperature: detector: 210°C; flow rate: He, 30 mL / min. Run #2: [F011] = 0.0022 M (0.0027 g / 5 mL) [LFO11] = 0.0022 M (0.0022 g / 5 mL) [standard] = 0.0021 (0.0022 g I 5 mL) GC: same as run #1. Run #3: [F011] = 0.0024 M (0.0029 g I 5 mL) [AFO11] = 0.0016 M (0.0020 g / 5 mL) [LFO11] = 0.0022 M (0.0027 g / 5 mL) [standard] = 0.0023 M (0.0024 g / 5 mL) GC: same as run #1. Rf=1.55 Rf =2.19 120°C; injector: 170°C; Rf =1.45 Rf = 2.02 Rf=1.75 Rf = 2.12 Rf = 2.49 198 Table XVIII (cont'd) Run ff 4: [F011] = 0.0023 M (0.0023 g / 5 mL) R1 = 1.63 [AFO11] = 0.0017 M (0.0017 g / 5 mL) F11 = 2.04 [LFO11] = 0.0015 M (0.0018 g / 5 mL) R; = 2.16 [standard] a 0.0024 M (0.0025 g / 5 mL) GC: same as mn #1. 199 Table XIX. Response factors of 3-(p-trifluoroacetylbenzyloxy)-2-methyl-1- propene (F012) and its photoproducts using C17H36 as a standard. Bum [F012] . 0.0017 M (0.0043 g / 10 mL) R; = 1.37 [AFO12] = 0.0020 M (0.0053 g / 10 mL) R] = 1.77 [LFO12] = 0.0014 M (0.0035 g / 10 mL) Rf = 2.21 [standard] = 0.0014 M (0.0035 g / 10 mL) GC: Column: DB-wax; temperature: 130°C; injector: 150°C; detector: 230°C; flow rate: He, 30 mL/ min. 8140.22: [F012] = 0.0029 M (0.0037 g / 5 mL) R]: 1.56 [AFO12] = 0.0020 M (0.0026 g I 5 mL) R]: 2.12 [LFO12] = 0.0020 M (0.0026 g / 5 mL) R] = 2.35 [standard] = 0.0020 M (0.0024 g / 5 mL) GC: same as mn #1. Hum [F012] = 0.0024 M (0.0031 g / 5 mL) R; = 1.72 [AFO12] = 0.0022 M (0.0022 g / 5 mL) R; = 2.27 [LFO12] = 0.0026 M (0.0028 g / 5 mL) R]: 2.50 [standard] = 0.0026 M (0.0031 g / 5 mL) GC: same as n.1n #1. 200 Table XX. Response factors of 3-(p-trifluoroacetylbenzyloxy)-3-methyl-1- butene (F021) and its photoproducts using C15H34 as a standard. Bum [AF021] = 0.0014 M R. = 2.43 [LF021] = 0.0017 M R] = 2.45 [standard] = 0.00095 M GC: Column: DB-210; temperature: initial 90°C and final 115°C; temperature change in oC I minute :20; injector: 180°C; detector: 230°C; flow rate: He, 30 mL per min. Run #2: [AF021] = 0.0024 M R; = 2.00 [LF021] = 0.0027 M R] = 2.34 [standard] = 0.00088 M GC: same as mn #1. Run #3: [AF021] = 0.00081 M R; = 1.87 [standard] = 0.0016 M GC: same as mn #1. Run #4: [F021] = 0.0038 M R; = 1.51 [standard] = 0.0021 M GC: same as run #1. 201 Table XX (cont'd) Run #5: [F021] = 0.0074 M R": 1.53 [standard] = 0.0057 M GC: same as mn #1. Run #6: [F021] = 0.0074 M R; = 1,43 [standard] = 0.0039 M GC: same as m #1. 202 Table XXI Response factors of 4-(1-pentenyl)trifluoroacetophenone (F011) and its photoproducts using C14H30 as a standard. Run #1 [F011] = 0.0022 M (0.0027 g / 5 mL) R; = 1.21 [AFC11] = 0.0023 M (0.0028 g / mL) R; = 1.70 [standard] = 0.0016 M (0.0016 g / 5 mL) GC: Column: DB-1; temperature: 110°C; injector: 160°C; detector: 230°C; flow rate: He, 30 mL/ min. Run #2 [FC11] = 0.0021 M (0.0025 g / 5 mL) R; = 1.40 [AFC11] = 0.0021 M (0.0025 g / 5 mL) R;= 1.60 [standard] a 0.0014 M (0.0014 g / 5 mL) GC: same as mm #1. Run #3 [FC11] = 0.0021 M (0.0025 g / 5 mL) R; = 1.42 [AFC11] = 0.0018 M (0.0022 g / 5 mL) R; = 1.68 [standard] = 0.0013 M GC: same as an #1. Run #4 [LFC11] = 0.0019 M (0.0023 g / 5 mL) R;-_- 1.61 [standard] = 0.0024 M (0.0024 g / 5 mL) GC: same as mn #1. 203 Table XXI (cont'd) Run #5 [LFC11] = 0.0017 M (0.0021 g / 5 mL) R; = 1.60 [standard] = 0.0023 M (0.0023 g l 5 mL) GC: same as run #1. Run #6 [LFC11] = 0.0024 M (0.0029 g I 5 mL) R;= 1.58 [standard] = 0.0021 M (0.0021 g / 5 mL) GC: same as mn #1. 204 Table XXII Response factors of 3-(p-acetylbenzyloxy)-1~propene (A011) and its photoproducts using 022H46 as a standard. Run #1 [A011] = 0.0024 M Rf: 1.99 [MAO11] = 0.0018 M n; = 1.93 [standard] = 0.00077 M GC: Column: DB-wax; temperature: 160°C; injector: 150°C; detector: 230°C; flow rate: He, 30 mL/ min. Run #2 [A011] = 0.0023 M R;= 2.09 [RMAO11] = 0.0019 M R;= 3.33 [standard] = 0.00098 M GC: same as run #1. 205 Table XXIII Response factors of 4-(1-pentenyl)acetophenone (AC11) and its photoproducts using C24H50 as a standard. Run #1 [A011] = 0.0022 M R;= 1.28 [LAC11] a 0.0020 M R;= 3.57 [standard] = 0.0014 M GC: Column: DB-wax; temperature 150°C; injector: 160°C; detector: 230°C; flow rate: He, 30 mL/ min. Run #2 [A011] = 0.0019 M R;=1.40 [LAC11] = 0.0030 M R;= 3.33 [standard] = 0.0012 M GC: same as mn #1. 206 Table XXIV Response factor of o-methylacetophenone using C15H32 as a standard. Run #1 [o-MACP] = 0.012 M R; .-.1 .73 [standard] a: 0.0042 M GC: Column: DB-wax; temperature: 100°C; injector: 180°C; detector: 230°C; flow rate: He, 30 mL/ min. Run #2 [o-MACP] = 0.010 M R; = 1.63 [standard] = 0.0042 M GC: same as run #1. Run #3 [o-MACP] a 0.0098 M R; = 1.67 [standard] = 0.0050 M GC: same as mn #1. 207 Table XXV Quenching of AFO11 and LF011 formation upon photolysis of 3-(p-trifluoroacetylbenzyloxy)-1-propene F011 with 2,5-Dimethyl-2,4-Hexadiene in Benzene. Irradiation time: 15.0 hrs W R; = 2.12 qu = 12.29 M" one" = 0.017 102X[Q] (AFO11/std)A [AFO11] «>010 M area ratio M 0 0.228 0.0036 1.00 2.03 0.172 1.33 2.53 0.179 1.27 3.04 0.172 1.32 3.55 0.157 1.46 4.05 0.149 1.53 6.08 0.140 2.06 [ketone] = 0.024 M, wavelength = >290 nm (by removing the potassium chromate filter), column: DB-1; 120°C; injector: 160°C; detector: 230°C; flow rate: He, 30 mL I min, internal standard: C15H32, [standard] = 0.0010 M._irradiation time: 5 hrs. LEhomnmnucLLfith Concentration of ketone, wavelength, type of column, internal standard, cocentration of standard and irradiation time were exactly the same as that of AFO11. 208 Table xxv (cont,d) a; = 2.23 kqx = 35.02 m-1 cm," = 0.045 102x10] (LFO11/std)A [LFO11] owe M area ratio M 0 1.143 0.0096 1.00 2.03 0.644 1.77 2.53 0.660 1.73 3.04 0.567 2.01 3.55 0.515 2.22 4.05 0.488 2.24 6.08 0.321 3.56 Actinometer: [o-MVP] = 0.10 M, R;= 1.67, wavelength = >290 nm, GC: column: DB-wax; 100°C; injector: 180°C; detector: 230°C; flow rate: He, 30 mL/ min., internal standard: C15H32, [standard] = 0.011 M (o-MAP/std)A [o-MAP] la area ratio M Einstein litre/mole 0.18 0.0034 0.21 209 Table XXVI Quenching of the formation of AFO12 and LFO12 upon photolysis of 3-(p-trifluoroacetylbenzyloxy)-2-methyl-1-propene F012 with 2,5-Dimethyl-2,4-Hexane in Benzene. Irradiation time: 12.0 hrs W R; = 2.05 (Daron = 0.021 102x10] (AFO12/std)A [AFO12] 00/0 M area ratio M 0 0.586 0.014 1.00 4.00 0.559 1.05 5.00 0.503 1.17 6.00 0.443 1.32 7.00 0.382 1.54 8.00 0.341 1.72 10.00 0.233 2.52 12.00 0.167 3.52 [ketone] = 0.023 M, wavelength = >290 nm (by removing the potassium chromate filter), column: DB-wax; 130°C; injector: 1500C; detector: 23000; flow rate: He, 30 mL/ min, internal standard: C17H36, [standard] a 0.012 M. W Concentration of ketone, wavelength, type of column, internal standard, concentration of standard and irradiation time were exactly the same as that of AFO12. 210 Table XXVI (cont,d) R1 = 2.35 kg? = 26.52 ‘DLFO12 = 0.026 102x10] (LFO12/std)A [LFO1 2] com M area ratio M 0 0.640 0.018 1.00 5.00 0.268 2.38 6.00 0.242 2.65 7.00 0.232 2.76 8.00 0.202 3.17 Actinometer: [o-MVP] = 0.10 M (R; = 1.67), wavelength = >290 nm ( by removing the potassium chromate filter), GC: column: DB-wax; 100°C; injector: 18000; detector: 23000; flow rate: He, 30 mL/ min, internal standard: C15H32, [standard] = 0.011 M (o-MAP/std)A [o-MAP] Ia area ratio M Einstein litre/mole 0.592 0.011 0.68 21 1 Table XXVII. Quenching of AF021 and LF021 formation upon photolysis of 3-(p-trifluoroacetylbenzyloxy)-3-methyl-1-butene F021 with 2,5-Dimethyl-2,4-Hexadiene in Benzene. Irradiation time: 12.0 hrs W R; = 2.10 w = 7.02 M-1 M=021 = 0.0050 1OX[Q] (AF021/std)A [AF021] (Do/Cb M area ratio M 0 0.635 0.0050 1 2.01 0.286 2.22 3.02 0.200 3.17 4.02 0.173 3.67 5.05 0.146 4.34 5.53 0.133 4.76 6.03 0.120 5.30 [ketone] = 0.020 M, wavelength = >290 nm (by removing the potassium chromate filter), GC:column: DB-210; initial = 90°C, final =115°C; column hold time: 2 minutes; column rate per minute: 20°C; detector: 230°C; injector: 180°C; flow rate: He, 30 mL/ min, internal standard: C16H34, [standard] = 0.00037 M, irradiation time: 2 hrs W Concentration of ketone, wavelength, type of column, internal standard, concentration of standard and irradiation time were exactly the same as that of AF021 . Table XXVII (cont'd) R; = 2.50 ¢LF021 = 0.0087 1OX[Q] (LF021/std)A [LF021] (Do/(b M area ratio M O 0.931 0.0087 1.00 2.01 0.340 2.73 3.01 0.237 3.93 4.02 0.167 5.57 4.52 0.138 6.76 5.05 0.101 9.18 Actinometer: 212 [o-MVP] = 0.10 M (R; = 1.67), wavelength = >290 nm (by removing the potassium chromate filter), GC: column: DB-wax; 100°C; injector: 180°C; detector: 230°C; flow rate: 30 mLI min, internal standard: C15H32, [standard] = 0.011_M (o-MAP/std)A [o-MAP] Ia area ratio M Einstein litre/mole 0.087 0.0016 0.10 21 3 Table XXVlll. Quenching of AFC11 and LFC11 formation upon photolysis of 4-(1-pentenyl)trifluoroacetophenone FC11 with 2,5-Dimethyl- 2,4-Hexadiene in Benzene. Irradiation time: 4.0 hrs a. Photoproduct AFC11: R; = 1.66 K]! = 17.62 ¢AFC11 = 0.0034 103x10] (AFC11Istd)A [AFC11] ¢°I290 nm (by removing the potassium chromate filter), GC:column: DB-t; 110°C; injector: 160°C; detector: 230°C; flow rate: He, 30 mL/ min, internal standard: C14H30, [standard] = 0.0019 M, irradiation time: 90 hrs 214 Table XXVIII (cont,d) WM Concentration of ketone, wavelength, type of column, internal standard, concentration of standard and irradiation time were exactly the same as that of AFC11. R;= 1.60 Chute" = 0.0064 103x101 (LFC11/std)A [LFC11] com M area ratio M 0 0.977 0.0029 1.00 5.04 0.754 1.30 10.08 0.619 1.58 15.12 0.504 1.94 20.16 0.373 2.63 25.20 0.320 3.06 30.24 0.26 3.70 35.28 0.233 4.20 40.32 0.187 5.23 Actinometer: [o-MVP] = 0.10 M (R; = 1.67), wavelength = >290 nm (by removing the potassium chromate filter), GC:column: DB-wax; 100°C; injector: 180°C; detector: 230°C; flow rate: He, 30 mL/ min, internal standard: C15H32, [standard] = 0.010 M 215 Table XXVIII (cont'd) (o-MAP/std)A [o-MAP] Ia area ratio M Einstein litre/mole 0.42 0.0073 0.46 216 Table XXIX. Quenching of MAO11 and RMAO11 formation upon photolysis of 3-(p-acetylbenzyloxy)-1-propene A011 with 2,5-Dimethyl-2,4- Hexadiene in Methanol. Irradiation time: 48.0 hrs W R; =1.93 omm; = 0.0024 103x10] (MAO11lstd)A [MAo;1] 00/0 M area ratio M 0 1.444 0.0012 1.00 1.20 1.830 0.79 14.60 1.723 0.84 19.80 1.855 0.78 30.40 2.240 0.65 [ketone] = 0.020 M, wavelength = >290 nm (by removing the potassium chromate filter), GC:column: DB-wax; 160°C; injector: 15000; detector: 2300C; flow rate: He, 30 mL/ min, internal standard: 022H46, [standard] = 0.00042 M, irradiation time: 4 hrs WM]; Concentration of ketone, wavelength, type of column, internal standard, concentration of standard and irradiation time were exactly the same as that of MAO11. 217 Table XXIX (cont'd) R1 = 3.30 (Daqu-n = 0.0089 103x10] (RMAO11/std)A [RMAO11] d>°l¢ M area ratio M 0 3.091 0.0089 1.00 1.20 3.120 0.99 14.60 4.175 0.74 19.80 4.248 0.73 30.40 5.597 0.55 Actinometer: [o-MVP] = 0.10 M (R; = 1.67), wavelength = >290 nm (by removing the potassium chromate filter), GC:column: DB-wax; 100°C; injector: 180°C; detector: 230°C; flow rate: 30 mL/ min, internal standard: C15H32, [standard] = 0.013 M (o-MAP/std)A [o-MAP] la area ratio M Einstein litre/mole 0.31 0.0076 0.48 218 Table XXX. Quenching of AAC11 and LAC11 formation upon photolysis of 4-(1-pentenyl)acetophenone AC11 with 2,5-DimethyI-2,4- Hexadiene in Benzene. Irradiation time: 48.0 hrs WM qu = 4.32 102xm] (AAC11/std)A 0% M area ratio 0 0.149 1.00 2.00 0.124 1 .21 4.00 0.113 1.32 6.00 0.102 1.46 10.00 0.0822 1.82 [ketone] = 0.021 M, wavelength = >290 nm (by removing the potassium chromate filter), GC:column: DB-wax; 150°C; injector: 160°C; detector: 230°C; flow rate: He, 30 mL/ min, internal standard: C24H50, [standard] = 0.00094 M, irradiation time: 3.5 hrs W11; Concentration of ketone, wavelength, type of column, internal standard, concentration of standard and irradiation time were exactly the same as that of AAC11. 219 Table XXX (cont'd) R1 = 3.45 kq‘t: = 7.91 ¢LAC11 = 0.0071 102x10] (LAC1 1/std)A [LAC1 1] 00/5 M area ratio M 0 0.466 0.0015 1.00 2.00 0.438 1.06 4.00 0.413 1.13 6.00 0.353 1.32 10.00 0.332 1.40 Actinometer: [o-MVP] = 0.10 M (R; = 1.67), wavelength = >290 nm (by removing the potassium chromate filter), GC:column: DB—wax; 100°C; injector: 180°C; detector: 230°C; flow rate: 30 mLI min, internal standard: C15H32, [standard] = 0.0089 M (o-MAPIstd)A [o-MAP] la area ratio M Einstein litre/mole 0.23 0.0034 0.21 220 CI 'l'll |||' W: In a small Pyrex test tube a benzene solution of 0.016 M (0.044 g I 10 mL) of ketone F021 and 0.0062 M of C15H34 (0.014 g I 10 mL) as internal standard was irradiated after bubbling with argon. The pre— and post- irradiated solutions were analyzed by GC (column: DB-210, 90-115°C; rate of temperature increase: 20°C I min; initial hold time: 2.0 min; injector: 180°C; detector: 230°C). The solution was analyzed after 30, 60, 90, 135, 195 and 255 min of irradiation and the chemical yield were 35.0, 35.0, 35.3, 28.6, 21.9 and 10% for LF021 and 27.5, 31.7, 36.8, 39.3, 43.8 and 32.3% for AF021 respectively. Response factors for F021, LF021 and AF021 are 1.28, 2.50 and 2.10 respectively. Each time that irradiation was interrupted for GC analysis, the test tube was septum sealed and deaerated with argon for the continuation of irradiation. The data for this calculation is summarized in Table XXXI. Table XXXI. Data For Chemical Yield Calculation Of F021. As; is the area of the standard in GC chromatogram. Irradiation time Concentration Ast/Aketone As;IAL1=021 As;IAA1=oz1 mules gt rematona 0 0 0.45 ----------------- - 30 0.0040 M 0.67 10.70 11.66 60 0.0060 M 0.76 7.32 6.87 90 0.0068 M 0.86 6.43 5.20 135 0.0084 M 1.03 6.49 3.78 195 0.0096 M 1.24 7.27 3.07 255 0.013 M 1.70 11.49 3.00 221 Initial concentration of ketone: 0.016 M Concentration of standard (C16H34): 0.0062 M GC: DB-210; 15 m; temp: 90-115°C; rate of temperature increase: 20°C/minute; injector temperature: 180°C; detector temperature: 230°C; carrier gas: He 30 mL./minute. W11: In a small Pyrex test tube a benzene solution of 0.012 M (0.029 g I 10 mL) of ketone F011 and 0.0077 M of C15H32 (0.016 g I 10 mL) as internal standard was irradiated after bubbling with argon the same way as for the ketone F021. The results were analyzed by GC (column: DB-1, 120°C; injector: 150°C; detector: 230°C; flow rate: 30 mLImin). The solution was analyzed after 30. 60 and 100 min of irradiation and the chemical yields were 28.3, 32.6 and 15% for LFO11 and 9.6, 10.9 and 5.9% for AFO11 respectively. Response factors for F011, LFO11 and AFO11 are 1.87, 2.23 and 2.12 respectively. The data for this calculation is summarized in Table XXXII. Table XXXII. Data For Chemical Weld Calculation Of F011. As; is the area of the standard in 60 chromatogram. Irradiation time Concentration As;IAke;one As;IA1_1=o11 As;IAA;=o1; minutes of rem 0 0 1.20 ------- - -------- - 30 0.0029 M 1.58 20.76 57.16 60 0.0046 M 1.95 11.12 32.62 90 0.0062 M 2.48 9.70 22.98 Initial concentration of ketone: 0.012 M Concentration of standard (C15H32): 0.0077 M GC: DB-1; 15 m; temp: 120°C; injector temperature: 180°C; detector temperature: 230°C; carrier gas: He 30 mLIminute. 222 W In a small test tube a benzene solution of 0.012 M (0.031 g I 10 mL) of ketone F012 and 0.0029 M (0.0070 gI 10 mL) of C17H35 as internal standard was irradiated after bubbling with argon the same way as for the ketone F021. The results were analyzed by GC (column: DB-wax, 125°C; injector: 150°C; detector: 230°C; flow rate: 30 mLImin). The solution was analyzed after 33, 63 and 108 min of irradiation and the chemical yields were 47.5, 18 and 5.2% for LFO12 and 18, 16.9 and 15.4% for AFO12 respectively. Response factors for F012, LFO12 and AFO12 are 1.83, 2.35 and 2.05 respectively. The data for this calculation is summarized in Table XXXIII. Table XXXIII. Data For Chemical Yield Calculation Of F012. As; is the area of the standard in CC chromatogram. Irradiation time Concentration As;IA1;e;o;;9 As;/ALpo;2 As;/AA;:o;2 mjmJes of raagtedjetone 0 0 0.44 -------- ---------- 33 0.0020 M 0.53 7.16 16.29 66 0.0036 M 0.63 10.53 9.72 121 0.0065 M 0.96 20.20 5.80 Initial concentration of ketone: 0.012 M Concentration of standard (C17H35): 0.0029 M GC: DB-wax; 15 m; temp: 125°C; injector temperature: 180°C; detector temperature: 230°C; carrier gas: He 30 mUminute. “M11; In a small Pyrex test tube a benzene solution of 0.012 M (0.028 g I 10 mL) of ketone FC11 and 0.0036 M (0.0071 g I 10 mL) of C14H30 as internal standard was irradiated after bubbling with argon the same way as for the ketone F021. The results were analyzed by GC (column: DB-1, 110°C; 223 injector: 160°C; detector: 230°C; flow rate: 30 mLImin). The solution was analyzed after 30, 60, 90 and 140 min of irradiation and the chemical yields were 49, 45.2, 34.9 and 23.7% for LFC11 and 20, 23.9, 23.0 and 22.0% for AFC11 respectively. Response factors for F011, LFC11 and AFC11 are 1.38, 1.60 and 1.66 respectively. The data for this calculation is summarized in Table XXXIV. Table XXXIV. Data For Chemical Yield Calculation Of FC11. As; is the area of the standard in CC chromatogram. Irradiation time Concentration As;/Ake;o;;e As;/A1_1=c;1 As;IAA;:c1 1 minutes Missions 0 0 0.42 ------- - --------- 30 0.0020 M 0.48 5.90 14.74 60 0.0032 M 0.56 3.97 8.10 90 0.0043 M 0.64 3.73 6.06 140 0.0059 M 0.81 4.06 4.55 Initial concentration of ketone: 0.012 M Concentration of standard (C14H30): 0.0036 M GC: 08-1; 15 m; temp: 110°C; injector temperature: 180°C; detector temperature: 230°C; carrier gas: He 30 mLIminute. 224 Table XXXV. Response Factors for various ketones and their photoproducts. 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