STUDY OF DIFFERENT ROUTES TO DEVELOP ASYMMETRIC DOUBLE DECKER SILSESQUIOXANE (DDSQ) By Gayanthi Kumari Attanayake A THESIS Submitted to Michigan State University in partial fulfillment of the requirements for the degree of Chemistry Master of Science 2015 ABSTRACT STUDY OF DIFFERENT ROUTES TO DEVELOP ASYMMETRIC DOUBLE DECKER SILSESQUIOXANE (DDSQ) By Gayanthi Kumari Attanayake Silsesquioxane cages can be considered as well - defined nanosized molecules and have attracted widening interests due to their possible use as components of resourceful inorganic/organic hybrid materials, 1,2 as well as their applications in optics, catalysis, polymers and electronics. Double - decker silsesquioxa ne (DDSQ) nanoparticles have attracted much attention recently due to the ease of which these particles can be incorporated into polymeric materials and their unique capability to reinforce polymers. 3,4 These systems are of high interest to scientists, due to their unique chemical and physical properties . 5,6,7 For example, the United States Air Force and NASA use DDSQ incorporated polymers as thermoset material and fla me retardants. This thesis discussed mainly three projects. One project centered on the research to improve and optimize the synthetic routes for a large scale synthesis of DDSQ functionalized oligoimides. The second project discussed is on the synthesis of a novel ( phenylethynyl)phenyl DDSQ oligomer that can be used for high temperature application. The main project was on studies of different routes to an asymmetric DDSQ cage. DDSQ molecules possess a higher symmetr y. Breaking the symmetry and selective functionalization of the DDSQ molecule would be highly desirable to fine tune the physical properties. Different routes were studied to develop an asymmetric DDSQ cage. iii ACKNOWLEDGEMENTS I would like to extend my deepest gratitude to my research advisor, Professor , Robert E. Maleczka, Jr. for his encouragement and spontaneous willingness to answer my numerous questions. I realize that it would not be possible to accomplish this project without the efforts of my research advisor. I would like to thank our collaborator, Professor Andree Lee, Department of Chemical Engineering & Material Science, M ichigan State University. I would also like to thank the members o f the committee Dr. M. Smith, Dr. X. Hu ang, Dr. J. Tepe for their continuous involvement in the project. I would like to thank the Department of Chemistry at Michigan State University for providing me the opportunity to complete my M.S degree thesis work , I would like to respectfully thank all the faculty members and staff in the Department of Chemistry at MSU. My sincere thank s goes to Dr. Holmes and Dr. Li for their help and suggestion s related to NMR experiments. Thanks to my group members and friends for their kind cooperation throughout my study at MSU. Special thanks goes to my family members for their unconditional help throughout my life. iv TABLE OF CONTEN T S LIST OF FIGURES ..... ... ........... i v ...ix KEY TO ABBREVIATI .... ..... ... ........ x i ..... ... ............ . 1 1.1 B ackground 1 1.2 Pendant - like s .... ..... .. ............ 3 1.3 Bead - 4 1.4 ... .... 5 1.5 Objec 7 CHAPTER 2: ROUTES TOWARDS THE SYNTHESIS OF DDSQ 8 FUNCTIONALIZED OLIGOIMDES 2.1 .. ... .............. 8 2.2 ... 9 2.3 Conclusi 12 2.4 Experimen 13 2.4.1 General material and methods ... ... ............ 13 2.4.3 Studies about different route to synthesize DDSQ functionalized oligoimides ... ............ 14 2.4.4 Synthesis of (Para)Methyl - dichlorosilane .. . ............ 14 2.4.5 Synthesis of (Meta)Methyl - dichlorosilane .. ........... . 15 2.4.6 CHAPTER 3 : SYNTHESIS OF NOVEL (PHENYLETHYNYL) PHENYL DDSQ OLIGOMERS ... ........... . 19 3.1 Introduc .. ............ 19 3.2 Optimization of conditions to synthesize 1 - bromo - 4 - (phenylethynyl)benzene 21 3.3 Optimization of conditions to synthesize (phenylethynyl)phenyl 2 1 Dic hlorosilane 3.4 Synthesis of phenylethynyl(phenyl) DDSQ one - pot route . 22 3.5 Pd catalyzed silylation of aryl halides with dihydro DDSQ or T7(iBu) cage 24 3.6 Conclus ... .. ........... . 26 3.7 Experimental .. .. ............ 27 3.7.1 Synthesis of bromo - 4 - (phenylethynyl)benzene ... . 27 3.7.2 Synthesis of dichloro(methyl)(4 - (phenylethynyl)phenyl) silane ... .. .......... . . 28 3.7.3 Synthesis of phenylethynyl(phenyl) DDSQ one - pot route 28 3.7.4 Pd catalyzed silylation of aryl halides with T7(iBu) cage ... ... ............. 31 v 3.7.5 Pd catalyzed silylation of aryl halides with DDSQ(Me)(H) cage .. 32 CHAPTER 4: DEVELOPMENT OF ASYMMETRIC DDSQ MOLECULE BY 34 MONOPROTECTING HYDROXYL GROUP 34 4.2 Monoprotection ............ 36 4.3 Synthesis of DDSQ(Me)(OH) and Monoprotection 36 4.4 Synthesis of DDSQ(Me)(Hydroxopropyl) a nd Monoprotection 38 4.5 Conclusio ............ 41 41 4.6.1 Monoprotection using NaH .. ............ 41 4.6.2 Synthesis of DDSQ(Me)(OH) .. ............ 42 4.6.3 Monoprotection of DDSQ(Me)(OH) using NaH ............ 44 4.6.4 Synthesis of DDSQ(Me)(Hydroxopropyl) 45 4.6.5 Monoprotection of DDSQ(Me)(Hydroxopropyl) using NaH 47 CHAPTER 5: DEVELOPMENT OF ASYMMETRIC DDSQ MOLECULE BY 49 USING IMMOBILIZED SURFACE 5.1 Intr 49 5.2 Development of asymmetric DDSQ using Red - Sil immobilized surface .. ............ 50 5.2.1 Quantitative estimation of Si - H on the surface of Red - Sil 52 5.2.2 Studies of different routes to attach the DDSQ cage to the Red - Sil surface 53 60 ............ 60 5.2.5 Experimental section 60 - 60 5.2.5.2 Quantitative estimation of Si - H on the surface of Red - Sil 62 5.2.5.3 Development of asymmetric DDSQ Method A .. . ............ ..63 5.2.5.4 Development of asymmetric DDSQ Method B 64 5.2.5.5 Development of asymmetric DDSQ Method C ............ 65 5.3 Development of asymmetric DDSQ using Merrifield resin .. . ............ 68 APPENDIX ... .........70 REFERENCES ... .130 vi LIST OF FIGURES Figure 1.1 A common POSS material: a fully condensed cage with eigh 1 methyl groups (Me 8 T 8 ) Figure 1.2 Example of monofunc tionalized, corner - Figure 1.3 Example of a difunctionalized SQ from a disilanol (R= cyclopentyl) 5 (POSS - polyimide copolymer ) Figure 1.4 Double - 5 Figure 1.6 cis and trans isomers of DDSQ molecule 6 Figure 5.3 Structure of silic 51 Figure S1 (Para) Methyl - di - chloro silane - 29 Si NMR 71 Figure S2 (Para) Methyl - di - chloro silane 1 H NMR .72 Figure S3 (Meta) Methyl - di - chloro silane - 29 Si NMR 73 Figure S4 (Meta) Methyl - di - chloro silane 1 H NMR 74 Figure S5 1 H NMR 75 Figure S6 29 Si NMR ..76 Figure S7 29 Si NMR ..77 Figure S8 1 H NMR 78 Figure S9 29 Si NMR ..79 Figure S10 1 H NMR ..80 Figure S11 1 H NMR 81 Figure S12 29 Si NMR .82 Figure S13 DDSQ (Me)(OH) 29 Si NMR .84 Figure S14 DDSQ (Me)(OH) 1 H NMR 86 vii Figure S15 DDSQ (Me)(OH) 29 Si NMR 87 Figure S16 DDSQ (Me)(OH) 1 H NMR .. 88 Figure S17 DDSQ (Me)(H) 1 H NMR .. 89 Figure S18 DDSQ (Me)(H) 29 Si NMR 90 Figure S19 DDSQ (Me)(di(trimethylsilyl)oxypropyl) 1 H NMR .. 92 Figure S20 DDSQ (Me)(di(trimethylsilyl)oxypropyl) 29 Si NMR Figure S21 DDSQ (Me)(Hydroxopropyl) 1 H NMR Figure S22 DDSQ (Me)(Hydroxopropyl) 29 Si NMR Figure S23 DDSQ (Me)(Hydroxopropyl) 1 H NMR Figure S24 DDSQ (Me)(Hydroxopropyl) 29 Si NMR Figure S25 13 C NMR Figure S26 1 H NMR Figure S27 1 H NMR Figure S28 13 C NMR Figure S29 1 H NMR Figure S30 29 Si NMR 108 Figure S31 1 H NMR Figure S32 29 Si NMR Figure S33 1 H NMR Figure S34 13 C NMR Figure S35 29 Si NMR Figure S36 1 H NMR Figure S37 29 Si NMR viii Figure S38 1 H NMR Figure S39 29 Si NMR Figure S40 29 Si NMR Figure S41 1 H NMR 119 Figure S42 29 Si NMR Figure S43 1 H NMR Figure S44 SS 29 Si NMR Figure S45 SS 13 C NMR ..123 Figure S46 SS 29 Si NMR Figure S47 SS 29 Si NMR Figure S48 SS 29 Si NMR Figure S49 SS 29 Si NMR Figure S50 13 C NMR Figure S51 1 H NMR ix LIST OF SCHEMES Scheme 1.5 Capping reaction of DDSQ molecule . 6 Scheme 2.1 Synthesis of DDSQ(m/p)(Me)(PEPI) ...... 10 Scheme 2.2 Three different routes to synthesiz .11 Scheme 2.3 Synthesis of DDSQ (m/p)(Me)(PEPI) ...... ........14 Scheme 2.4 Synthesis of (Para)Methyl - dichloro silane capping agent .....14 Scheme 2.5 Synthesis of (Meta )Methyl - dichloro silane capping agent . Scheme 3.1 Synthesis of (phenylethynyl)phenyl DDSQ 20 Scheme 3.2 Synthesis of 1 - bromo - 4 - ( phenylethynyl 21 Scheme 3.3 S ynthes is of (phenylethynyl)phenyl dichlo ..... 22 Scheme 3.4 Synthesis of phenylethynyl(phenyl) DDSQ one - 23 Scheme 3.5 Pd catalyzed silylation of aryl halides with T7(iBu) cage 25 Scheme 3.6 Pd catalyzed silylation of aryl halides with DDSQ - H cage 26 Scheme 3.7 Synthesis of bromo - 4 - 27 Scheme 3.8 Synthesis of dichloro(methyl)(4 - . . 28 Scheme 3.9 Synthesis of phenylethynyl(phenyl) DDSQ one - 30 Scheme 3.10 Pd catalyzed silylation of aryl halides with T7(iBu) cage Scheme 3.11 Pd catalyzed silylation of aryl halides with DDSQ(Me)(H) cage 32 Scheme 4.1 Asymmetric DDSQ synthesis by using monoprotection .. . .. 3 5 Scheme 4.2 The chemistry developed by McDougal and coworkers to 35 monoprotect the symmetric diol Scheme 4.3 Monoprotection of symmetric DDSQ . 36 Scheme 4.4 Monoprotection of symmetric DDSQ(Me)(OH) 3 7 x Scheme 4.5 Closing of DDSQ cage using trichloro silane capping agent 38 Scheme 4.6 Synthesis of DDSQ(Me)(Hydroxopropyl) 39 Scheme 4.7 Mono protection of DDSQ(Me)(Hydroxopropyl) ...... .40 Scheme 4.8 Monoprotection of symmetric DDSQ 41 Scheme 4.9 Synthesis of DDSQ (Me)(OH) 42 Scheme 4.10 Mono protection of DDSQ (Me)(OH) using NaH 44 Scheme 4.11 Synthesis of DDSQ(Me)(Hydroxopropyl) 45 Scheme 4.12 Monoprotection of symmetric DDSQ ..... 47 Scheme 5.1 Synthesis of asymmetric DDSQ cage using immobilized reagents 50 Scheme 5.2 Synthesis of Re d - 51 Scheme 5.4 Ag + reduction by silyl h ydrides .53 Scheme 5.5 Development of asymmetric DDS Q 54 Scheme 5.6 Development of asymmetric DDSQ . 56 Scheme 5.7 Synthesis of DDSQ 57 Scheme 5.8 Development of asymmetric DDSQ 58 Scheme 5.9 d - . 61 Scheme 5.10 Ag + reduction by sily 62 Scheme 5.11 Development of asymmetri c DDSQ .. 64 Scheme 5.12 Development of asymmetric DDSQ - H ..... 65 Scheme 5.13 Development of asymmetric DDSQ - H ..... 67 Scheme 5.14 Merrifield Resin ..... 68 Scheme 5.15 Synthesis of asymmetric DDSQ cage using immobilized reagents 69 xi KEY TO ABBREVIATIONS DDSQ = Double Decker Silsesquioxane POSS = Polyhedral Oligomeric Silsesquioxane PEPI = Phenylethynyl Pthalic Imide PEPA = Phenylethynyl Pthalic Anhydride SQ = Silsesquioxane Tg = Glass transition temperature Td = Decompostion Temperature TGA = Thermo Gravimetric Analysis CP = Cross Polarization 1 CHAPTER 1 : INTRODUCTION 1.1 Background The chemistry of organo - functionalized silsesquioxane has emerged as a fascinating new field of modern technology. Silsesquioxane materials are a class of organosilicon compound with the formula (RSiO 1.5 ) n, functional group. Silsesquioxanes can have various geometrical structural orders, including random, ladder and cage structures; the latter are also known as polyhedral oligomeric silsesq uioxanes (POSS). 1 The first synthesis of a POSS cage was developed in the 1946 when Scott 1 isolated the highly symmetric Me 8 T 8 . The most common POSS cage is the T 8 (e.g., Me 8 T 8 in Figure 1.1), although other cages with well - defined geometries include n = 6 , 10, 12, 14, 16 and 18. 2,3 Figure 1.1 A common POSS material: a fully condensed cage with eight methyl groups (Me 8 T 8 ). These POSS cages can be considered as well - defined nanosized molecules (1 - 3 nm) and have attracted widening interest due to their possible use as components of resourceful inorganic/organic hybrid materials such as li quid crystals, porous materials and catalytic chemistry. 4,5 Okubo et al . developed hierarchial micr o - mesoporus silica that has been synthesized by solid - phase conversion of molecular crystals of an alkoxy derivatives of cubic silsesquioxane as a molecular building unit. 5 Poly ( L - lysine) dendrimers with POSS core were synthesize via Cu - catalyzed azidealk yne cycloaddition click chemistry by Gu et al . 5 It is a facile approach to prepare 2 peptide dendrimers with perfect architecture. He et al. designed POSS based thermo - responsive amphiphilic hybrid copolymers for thermally denatured protein protection applic ations. 5 Organic inorganic hybrid materials are attracting considerable interest because they offer the opportunity to develop high - performance materials that combine many desirable properties of conventional organic and inorganic components, such as ther mal stability, solubility, lower dielectric property and processability. 6 The silica core confers rigidity and thermal stability that provides mechanical and thermal properties surpassing typical organic compounds. POSS cages can be easily incorporated in to polymeric matrices to prepare novel polymer hybrids with promising properties, such as thermal and flammability resistance, solubility, oxidation resistance, decreased viscosity and excellent dielectric properties. 7 - 11 In the literature, the POSS - contai ning thermosetting polymers such as polyimide, 12 polyurethane, 13 poly(methyl methacrylate), 14 polybenzoxazines 15 and poly(ethylene imine) 16 have been prepared by the use of POSS cages. The US Air Force has identified the thermal stability of POSS incorpora ted polymers and using as thermoset material. NASA is also researching their properties as flame retardants and atomic oxygen resistance materials and considering using these materials as film coatings for cabin items during space missions (POSS cages form a glassy, passivating SiO 2 layer that prevents further decay of the underlying polymer in the presence of atomic oxygen / Low Earth Orbit condition simulations). The addition of POSS cages into organic monomers and polymers has been recognized to increase the decomposition temperature (T d ). During the degradation, the organic groups of POSS initially damage rapidly and form an active char - like coating on top of the Si - O cage, providing extra protection. 17 This is specifically useful in increasing t he limiting oxygen intake (LOI), or the 3 volume fraction of oxygen necessary for a material to sustain combustion, 18 for flame retardant applications. Each silicon atom is covalently bonded to an organic peripheral group, which allows these molecules to in teract with themselves or other organics in the medium. This property increases the solubility and processability of the polymer. These peripheral groups can be modified to make the Silsesquioxane (SQ) cage reactive. One of the major focus of POSS/polyme r research over the last two decades has been in the covalent incorporation of POSS moieties into a polymeric architecture, either during synthesis or network formation, with the goal of improving the thermal/thermo - oxidative performance of the resultant h ybrid system. The core tenet of this approach is that the inclusion of well - defined nano - scale silica (in the form of a functional POSS) as a chain segment, pendant, or crosslinking moiety will impart a range of physical and chemical improvements to the po lymeric system that will in turn, make the system more thermally and ox idatively resistant. SQ cage s have been attached to polymer s in three different ways; pendent - like, bead - like and beads on chain like structures. 1.2 Pendant - like structure Pendant - like structures are synthesized by corner capping, which is the most common method for modifying one of the peripheral groups on a cage - like SQ. This structure is also known as a monofunctionalized SQ (Figure 1.2). 4 Figure 1.2. Example of monofunctionalized, corner - capped SQs. 1.3 Bead - like structure To achieve a bead - like structure, two reactive moieties must be present on two silicon atoms. Difunctional SQs are mostly used for spacecraft applications. SQ cages incorporated into the polyimide Kapton ® (Figure 1.3) provide additional protection in lower Earth orbit from atomic oxygen. Polymers based on SQs have demonstrated 10 times higher durability than neat Kapton ® , which has t he highest resistance of conventional polymers towards active atomic oxygen. Similar to thermal degradation, when these SQs are exposed to atomic oxygen, their organic groups degrade and a silica (SiO 2 ) layer is preserved, providing protection from degrada tion. 19 This silica layer protects the underlying polymer from further degradation. The erosion yield of the SQ - Kapton ® is as low as ~ 0.01 that of neat Kapton ® , depending on the weight % of SQ in the polymer. 5 Figure 1.3. Example of a difunctionalized SQ from a disilanol (R= cyclopentyl) (POSSpolyimide copolymer). 1.4 Beads on a chain type of structure, called double - decker silsesquioxane (DDSQ) cages (Figure 1.4). 20 DDSQ is to form a cage - like structure. The only DDSQ molecule available to date has only phenyl (Ph) moieties attached to the tetrasilanol structure. Since its introduction in 2004, DDSQ has attracted researchers to explore the development of polymerizable SQ mono mers with an architecture where the inorganic SQ cage can easily become part of the linear backbone of the resulting polymers. 21 Figure 1.4. Double - Decker Silsesquioxane (DDSQ) 6 Scheme 1.5. Capping reaction of DDSQ molecule. These DDSQ cages can be closed via a capping agent like aminophenyl (X) dichloroalkyl (R) silane (Scheme 1.5). During the capping reaction, DDSQ cages generate cis and trans isomers (Figure 1.6). These two isomers of DDSQ exhibit different physical properties, such as melting point and solubility. Figure 1.6. cis and trans isomers of DDSQ molecule. Depending on the capping agent, different functionalized DDSQ compounds can be synthesized. This is particularly important in terms of reactive functional groups attached to a POSS core, e.g. vinyl, amino, epoxy, methacryloxy, and chloropropyl groups. 22 The development of new and e icient methods for DDSQ synthesis with variou s functional groups can open up new possible applications. 7 1.5 Objectives DDSQ molecules exhibit a high symmetry. One of the major goals of the proposed work is to synthesize asymmetric DDSQ molecules that are scientifically innovative. It can be evisioned that functionality, and hopefully physical properties will be improved by attaching two different functional groups to the asymmetric sites of the DDSQ molecule. However, with the higher symmetry of the DDSQ molecule, asymmetric functional group manipulation is challenging. Other than the above mentioned goal, synthesis of a novel DDSQ analog and optimization of the route to existing functionalized DDSQ oligoimides were carried out. The main objectives of the work carried out can be summarized as follows. 1. Study different routes to synthesize DDSQ functionalized oligoimides. 2. Synthesis of novel phenyl ethynyl (phenyl) DDSQ oligomers 3. Study different routes to synthesize asymmetric DDSQ molecules 8 CHAPTER 2 : ROUTES TOWARDS THE SYNTHESIS OF DDSQ FUNCTIONALIZED OLIGOIMDES 2.1 Introduction Polyimides are among the most successful commercial thermoset (synthetic materials that strengthen when heated, but cannot successfully be remolded when reheated) polymers, due to their excellent thermal stability and mechanical properties. They are widely used as coatings for microelectronic devices, integrated circuit fabrication, and high - temperature materials for the aerospace industry. Despite their wide use, polyimides are not without shortcomings. Due to their higher viscosity properties, in order to process and fabricate the structural composites, disadvantageous higher pressures are required. Therefore, research on polyimides is directed towards decreasing the visco sity without sacrificing desired characteristics. One method is to incorporate DDSQ as the backbone for these polyimides, 29,30,31 which interrupt the interlayer interactions of polymer layers that facilitate the reduction of the viscosity. Another disadv antage of polyimides is the small processing window, as the solid to liquid phase transition (319 - 349 °C) of polyamides is so close to the curing reaction (350 - 371 °C) (toughening or hardening of a polymer material by cross - linking of polymer chains). Ther efore, considerable efforts have been made to address these issues and to design polyimides with the desired properties. The incorporation of the DDSQ cages decreases the glass transition temperature (170 °C) (hard and relatively brittle state into a molte n or rubber - like state) by breaking the interlayer interactions, while maintaining higher thermomechanical features of the polyimide. 9 In order to overcome these issues and to improve the properties, our group previously attempted to synthesize a function alized DDSQ with phenylethynylphthalic (PEPI) anhydride (PEPI - DDSQ oligoimides). According to the previous studies, mixtures of six - isomers of DDSQ(m/p)(Me)(PEPI), which includes the asymmetric mixture of stereo - ( cis and trans ) and regio - (para - and met a - ) isomers, exhibit lower viscosity. 2.2 Optimization of synthetic routes However the attempted synthesis possessed several disadvantages such as diminished yields and being time intensive. In this work, extensive research was carried out to overcome the above mentioned drawbacks by improving and optimizing the synthetic routes for a large scale synthesis. Scheme 2.1 shows the novel synthetic route of DDSQ(m/p)(Me)(PEPI) compound. The end product contains 6 isomers of DDSQ(m/p - PEPI)(Me) ( cis and trans isomers of DDSQ(mPEPI)(Me), cis and trans isomers of DDSQ(p - PEPI)(Me) and ( c is and trans isomers of DDSQ(m/p - PEPI )(Me)). As shown in the Scheme 2.1 , DDSQ(m/p - PEPI)(Me) was synthesized using meta - and para - aminophenyl methyl dichlorosilane as the capping agent. First, the capping agent 3 was synthesized by reacting a 50:50 mixture of (3(bis(trimethylsilyl)amino)phenyl) magnesium bromide 1 (meta) and (4(bis(trimethylsilyl)amino)phenyl) magnesium bromide 1 (para) with methyl trichlorosilane 2 . Then capping agent 3 was reacted with DDSQ cage 4 and PEPA 5 to synthe size the DDSQ(m/p - PEPI )(Me) in 69% yield. 10 Scheme 2.1. Synthesis of DDSQ(m/p)(Me)(PEPI). 11 Scheme 2.2. Three different routes to synthesize DDSQ (m/p)(Me)(PEPI). The novel synthetic route was revealed by doing a systematic study of the previous synthetic route. Scheme 2.2 summarizes the previous and current attempts that were made to synthesize DDSQ(m/p)(Me)(PEPI). According to Path A (blue color route), meta - and para - aminophenyl methyl dichlorosilane capping agents 1 were reacted with DDSQ and DDSQ(m/pAP)(Me) (protected amine) 2 was synthesized. Then the amine group of 2 was deprotected and DDSQ(m/p - AP)(Me) (deprotected amine) 3 was synthesized. After that, 3 was reacted with PEPA and DDSQ(m/p)(Me)(PEPI) 4 was obtained with 53 % yield. According to Path B (green color route), meta - and para - aminophenyl methyl dichlorosilane capping agents 1 were reacted with DDSQ and DDSQ(m/p - AP)(Me) (protected amine) 2 was synthesized. Then 2 was directly reacted with PEPA and DDSQ(m/p)(Me)(PEPI) 4 was synthesized with 42% yield. The third route, Path C (red color route) was performed without isolating DDSQ(m/p - AP)(Me) 2 or 3 . According to Path C (red color route), meta - and para - aminophenyl methyl dichlorosilane 64% 53% 64% 12 capping agents 1 were reacted with DDSQ and PEPA to synthesis DDSQ(m/p)(Me)(PEPI) 4 with 69% yield. 2.3 Conclusion These studies concluded that Path A , the previously reported synthesis yielded about 50% o f the desired compound, but also required seven days for the completion of the synthesis. In the novel synthetic route Path B , it was anticipated that the overall yield could be enhanced by avoiding the isolation of pure deprotected amine. Nevertheless, no such improvement was observed. Then the studies were directed towards the total one pot synthetic route Path C , which avoids the tedious separation of the intermediate analogs. To our delight, not only Path C avoid tedious isolations of intermediates, it also enhanced the overall yield to about 70%. Moreover, we were able to decrease the time required from seven days to three days in the overall synthetic process. The novel improved synthetic route enabled us to efficiently synthesize about 50 g of the D DSQ(m/p - AP)(Me) molecule, which was sent to our collaborator as well as our funding source, the United State Air Force Research Institute, to explore further research avenues. 13 2.4 Experimental section 2.4.1 General materials and methods Octaphenyl(Ph8tetrasilanol POSS) (DDSQ) was obtained from Hybrid Plastics (Hattiesburg, MS). Tetrahydrofuran (THF), hexanes, diethyl ether, magnesium turnings, triethylamine,trichloro methylsilane, 3 - [bis (trimethylsilyl)amino]phenyl - magnesium chloride, an d 4[bis(trimethylsilyl)amino]phenyl (bromo)magnesium were obtained from Sigma - Aldrich. Phenylethynylphthalic anhydride (PEPA) was obtained from Chriskev Company. The solvents were distilled under nitrogen and degassed using Freeze - Pump - Thaw methods. All re actions were carried out under an N 2 atmosphere, unless otherwise noted. 2.4.2 NMR spectroscopy NMR spectra were recorded at 25 ºC on Agilent DDR2 500 MHz NMR spectrometer (500 MHz ( 1 H) and 1 00 MHz ( 29 Si)). 1 H NMR data were acquired using a recycle delay of 20 s and 32 scans. The 1 H NMR chemical shifts were referenced to that of residual protonated solvent in CDCl 3 (7.24 ppm). 29 Si NMR data were acquired using a recycle delay of 20 s. 29 Si NMR spectra were referenced against the lock solvent using vendor supplied lock referencing. 13 C NMR data were acquired using a recycle delay of 1 s and 256 scans. 14 2.4.3 Studies about different route to synthesize DDSQ functionalized oligoimides . Scheme 2.3. Synthesis of DDSQ( m/p)(Me)(PEPI). 2.4.4 Synthesis of (Para)Methyl - dichlorosilane Scheme 2.4. Synthesis of (Para)Methyl - dichlorosilane capping agent. Under a nitrogen atmosphere a solution of 0.5M (4(bis(trimethylsilyl)amino)phenyl) magnesium bromide (30 mL, 15 mmol ) in THF was added dropwise to a stirred solution of trichloromethyl silane (2.12 g, 18 mmol) and THF (5 mL). The solution was stirred for 20 h at 25 64% 53% 64% 15 °C and then purified by fractional distillation (120 °C, 0.1 Hgmm) to obtain (N - trimethylsilyl)2 - aniline - 4(dichloromethylsilane) (3.95 g, 11.26 mmol, 75 % yield) as a colorless liquid. 29 Si NMR (100 MHz, CDCl 3 1 H NMR (500 MHz, CDCl 3 (2H, multiplet), 7.01 (2H, multiplet), 1.02 (3H, CH 3 , singlet), 0.10 (18H, TMS , singlet) (Figure S2). 2.4.5 Synthesis of (Meta)Methyl - dichlorosilane Scheme 2.5. Synthesis of (Meta)Methyl - dichlorosilane capping agent. Under a nitrogen atmosphere a solution of 1M (3(bis(trimethylsilyl )amino)phenyl) magnesium bromide (15 mL, 15 mmol) in THF was added dr opwise to a stirred solution of trichloromethylsilane (2.71 g, 18.5 mmol) and THF (5 mL). The solution was stirred for 20 h at 25 °C and then purified by fractional distillation (110 °C, 0.1 Hgmm) to obtain (N - trimethylsilyl)2 - aniline - 4(dichloromethylsilane) (3.85 g, 11.2 mmol, 75 % yield) as a colorless liquid. 29 Si NMR (100 MHz, CDCl 3 1 H NMR (500 MHz, CDCl 3 , J = 7.67 Hz ), 7 .33 (1H, triplet , J = 6.39 Hz ), 7.27 (1H, singlet), 7.08 (1H, doublet , J = 8.95 Hz ), 1.04 (6H, CH 3 , singlet), 0.11 (18 H, TMS, singlet) (Figure S4). 16 2.4.6 Synthesis of DDSQ(m/p)(Me)(PEPI) using path A A solution of (N - trimethylsilyl)2 - aniline - 3( dichloromethylsilane) (1 .00 g, 2.85 mmol, 1equiv), (N - trimethyl silyl)2 - aniline - 4 - (dichloromethylsilane) (1 .00 g, 2.85 mmol, 1 equiv), and triethyl amine (1.16 g, 11.5 mmol, 4 equiv) in THF (14 mL) was added dropwise into a stirred solution of Ph8t etrasi lanol - POSS (3.02 f g, 2.82 mmol, 0.98 equiv) at 25 °C THF (40 mL). After 30 minutes, the HNEt 3 Cl (1.43g, 10.5 mmol) precipitate was separated by filtration, and the solvent was removed from the filtrate under vacuum. To the resultant residue diethyl ether ( 5 mL) was added followed by acidified methanol, which gave a white suspension that was stirred at 25 °C for 20 h. The heterogeneous mixture was filtered, and the precipitate was dried under nitrogen to yield compound DDSQ diamine (de - p rotected), (2.2 0 g, 1 .65 mmol, 58 % yield). Under a nitrogen atmosphere, a well - stirred solution of DDSQ diamine (deprotected) (2.2 0 g, 1.65 mmol) and PEPA (1.2 0 g, 4.83 mmol) in anhydrous THF (28 mL) and toluene (28 mL) was stirred at room temperature (25 °C) for 1 h. The so lution was heated to 60 °C for 2 h and refluxed at 115 °C for 20 h. Solvent was removed under vacuum and subsequently washed and precipitated with methanol. The product (PEPI) was filtered and dried. (2.3 0 g, 1.3 0 mmol, 79 % yield). 29 Si NMR (100 MHz, CDCl 3 - 31.20, - 31.46, - 77.34, - 77.92, - 78.03, - 78.63, - 78.69, - 78.75, - 79.06, - 79.17, - 79.23, - 79.35 (Figure S6 ). 1 H NMR (500 MHz, CDCl 3 - 7.03 (64H, overlapping multiplets), 0.58 - 0.56 (6H, o verlapping singlets) (Figure S5 ). 17 2.4.7 Synthesis of DDSQ(m/p)(Me)(PEPI) using path B A solution of (N - trimethylsilyl)2 - aniline - 3(dichloromethylsilane) (1 .00 g, 2.85 mmol, 1equiv), (N - trimethyl silyl)2 - aniline - 4 - (dichloromethylsilane) (1 .00 g, 2.85 mmol, 1 equiv), and triethylamine (1.164 g, 11.5 mmol, 4 equiv) in THF (14 mL) was added dropwise into a stirred solutio n of Ph8tetrasilanol - POSS (3.02 g, 2.82 mmol, 0.98 equiv) at 25 °C THF (40 mL). After 30 minutes, the HNEt 3 Cl (1.42g, 10.4 mmol) precipitate was separated by filtration, and the solvent was removed from the filtrate under vacuum. To the resultant residue diethyl ether (5 mL) was added, which gave a white suspension that was stirred at 25 °C for 20 h. The heterogeneous mixture was filtered, and the precipitate was dried un der nitrogen to yield compound DDSQ diamine (protected), (2.65 g, 1.98 mmol, 70 % yield). Under a nitrogen atmosphere, a well - stirred solution of DDSQ diamine (protected) (2.2 0 g, 1.65 mmol) and PEPA (1.2 0 g, 4.83 mmol) in anhydrous THF (28 mL) and toluene (28 mL) was stirred at room temperature (25 °C) for 1 h. The solution was heated to 60 °C for 2 h and refluxed at 115 °C for 20 h. Solvent was removed under vacuum and subsequently washed and precipitated with methanol. The product (PEPI) was fi lte red and dried. (1.75 g, 0.97 mmo l, 59 % yield). 29 Si NMR (100 MHz, CDCl 3 - 31.08, - 31.33, - 77.21, - 77.79, - 77.90, - 78.49, - 78.55, - 78.61, - 78.92, - 7 9.03, - 79.09, - 79.21 (Figure S7 ). 1 H NMR (500 MHz, CDCl 3 - 7.22 (64H, overlapping multiplets), 0 .57 - 0.56 (6H, o verlapping singlets) (Figure S8 ). 2.4.8 Synthesis of DDSQ(m/p)(Me)(PEPI) using path C A solution of (N - trimethylsilyl)2 - aniline - 3(dichloromethylsilane) (1 .00 g, 2.85 mmol, 1equiv), (N - trimethyl silyl)2 - aniline - 4 - (dichloromethylsilan e) (1 .00 g, 2.85 mmol, 1 equiv), and triethyl a - 18 - mine (1.16 g, 11.5 mmol, 4 equiv) in THF (14 mL) was added dropwise into a stirred solution of Ph8t etrasilanol - POSS (3.02 g, 2.82 mmol, 0.98 equiv) at 25 °C THF (40 mL). After 30 minutes, the HNEt 3 Cl (1.43g, 10.5 0 mmol) precipitate was separated by filtration, and the solvent was removed from the filtrate under vacuum. To the resultant residue PEPA (1.2 g, 4.83 mmol), THF 28 mL and toluene 28 mL were added. Reaction mixture was stirred at room temperature (25 °C) for 1 h. The solution was heated to 60 °C for 2 h and refluxed at 115 °C for 20 h (under nitrogen atmosphere). Solvent was removed under vacuum and subsequently washed and precipitated with methanol. The product (PEPI) was filtered and dried (3.60 g, 2.00 mmol, 70 % yield). 29 Si NMR (100 MHz, CDCl 3 - 31.28, - 31.54, - 77.38, - 77.96, - 78.07, - 78.67, - 78.73, - 78.82, - 79.10, - 7 9.21, - 79.27, - 79.39 (Figure S9 ). 1 H NMR (500 MHz, CDCl 3 - 7.24 (64H, overlapping multiples ), 0.57 - 0.56 (6H, o verlapping singlets) (Figure S10 ). 19 CHAPTER 3 : SYNTHESIS OF NOVEL (PHENYLETHYNYL)PHENYL DDSQ OLIGOMERS 3.1 Introduction Oligomers and polymers containing phenylethynyl groups have received considerable attention in high temperature applications. Upon thermal cure, the phenylethynyl group undergoes a complex reaction involving chain extension, branching and crosslinking to afford materials exhibiting a favorable combinat ion of physical and mechanical properties . 40 In the past, high temperature application has concentrated on silsesquioxane incorporated imide oligomers. In the present work, phenylethynyl functionality was considered and DDSQ incorporated phenylethynyl ol igomers were synthesized. The development of (phenylethynyl)phenyl DDSQ novel molec ule was illustrated in (Scheme 3.1 ). As shown in S cheme 3.1, first di - halide benzene 1 was reacted with phenyl acetylene 2 to form halogen 4 - (phenylethynyl) benzene 3 based on S onogashira coupling. Then the Grignard reaction was performed to form 4 . The treatment of one equivalent of methyl trichlorosilane 5 with 4 caused the formation of dichloro(methyl)(4 - (phenylethynyl)phenyl silane 6. After that half an equivalent of DDSQ 7 was reacted with one equivalent of capping agent 6 to form the (phenylethynyl)phenyl DDSQ 8 . 20 Scheme 3.1. Synthesis of (phenylethynyl)phenyl DDSQ 21 3.2 Optimization of conditions to synthesize 1 - bromo - 4 - (phenylethynyl)benzene Scheme 3.2. Synthesis of 1 - bromo - 4 - (phenylethynyl)benzene The synthesis of halogen 4 - (phenylethynyl) benzene 3 is depicted in Scheme 3.2. A mild protocol for the copper - free Sonogashira coupling of bromo - 4 - iodo benzene 1 with phenyl acetylene 2 i n water under aerobic conditions has been used in this synthesis. 41 The use of 1 mol % PdCl 2 in the presence of pyrrolidine allows the coupling reac tion to proceed at 50 °C with 81 % yield. 3.3 Optimization of conditions to synthesize (phenylethynyl)phenyl dichlorosilane Then the synthesis of (phenylethynyl)phenyl dichlorosilane capping agent 2 was carried out as shown in Scheme 3.3. The fractional distillation and Kugelroher distillation were performed to obtain the purified dichlorosilane capping agent . According to NMR studies (Figure S31) the (phenylethynyl)phenyl dichlorosilane was observed in the distilled product with some byproducts. Further purification of the distilled p roduct from those byproducts failed. These observation confirmed that purification of dichlorosilane capping agent was difficult. 81% 22 Scheme 3.3. Synthesis of (phenylethynyl)phenyl dichlorosilane capping agent 3.4 Synthesis of phenylethynyl(phenyl) DDSQ one pot route In order to avoid the tedious purif ication steps in this synthetic procedure, attempts were made for a one p ot synthesis. According to S cheme 3.4, the crude product of dichlorosilane capping agent 4 was introduced in to the DDSQ 5 under basic condition s . The desired product was not observed in the one pot synthesis even with the use of excess or one equivalent of methyltrichlorosilane. All these studies confirmed that, dichlorosilane capping agent shoul d be purified to avoid other reactions. Otherwise trichlorosilane will react with DDSQ and disrupt the reaction. Therefore the one pot route was optimized by the use of 0.9 equivalent s of methyltrichlorosilane and the dichlorosilane capping agent was obtained without any of the previously obtained undesired byproduc ts (Figure S29). W ithout any further purification the dichlorosilane capping agent was reacted with DDSQ for 24 h at room temperature. To our delight (phenylethynyl)phenyl DDSQ was synthesized th rough this one - pot route in 70% yield. 23 Scheme 3.4. Synthesis of phenylethynyl(phenyl) DDSQ one pot route 24 3.5 Pd catalyzed silylation of aryl halides with dihydro DDSQ or T7(iBu) cage In our efforts to explore novel synthetic approaches towards the synthesis of (phenylethynyl)phenyl DDSQ oligomers, a new approach based on Pd catalyzed silylation of aryl halide s was carried out. O rganosilicon reagents have played an increasingly important role in Pd(0) - catalyzed cross coupling s with organohalides. To the best of our knowledge, Pd catalyzed silylation has been developed for DDSQ molecule s and we were interested in doing as well as the synthesis of (phenylethynly)phenyl DDSQ molecule through such a novel route. For the preliminary studies, corner capped T7 - iBu POSS cage was selected . First, Pd catalyzed silylation chemistry was tested with the simple structure skeleton corner capped T7 - iBu cage. According to the S cheme 3.5, first T7 - iBu cage 1 was reacted with trichlorosilane (HSiCl 3 ) to obtain the hydrogen substituted closed T8 cag e 2 in 82% yield. Then Pd catalyzed reaction was performed between aryl halide 3 and T8 cage 2 . Phenyl substituted T8 cage 4 was obtained in 64% yield. Wi th these positive data and inferences in hand we elaborated our work towards the complex DDSQ molecule . 25 Scheme 3.5. Pd catalyzed silylation of aryl halides with T7(iBu) cage. As shown in Scheme 3.6, the reaction between DDSQ 1 and methyldichlorosilane can was carried out to prepare the DDSQ(Me)(H) 2 . Then two equivalent s of iodo benzene 3 were reacted with DDSQ(Me)(H) 2 using Pd catalyst . Even though this chemistry worked for T7(iBu) cage, it was not applicable to the DDSQ - H cage. The major products were iodo benzene and decomposed DDSQ cage. 1.5 mmol % Pd 2 (dba) 3 26 Scheme 3.6. Pd catalyzed silylation of aryl halides with DDSQ - H cage. 3.6 Conclusion The novel ( phenylethynyl)phenyl DDSQ oligomer was successfully synthesized through a one pot route with 70% yield. This synthesis avoids the tedious separation tech niques, fractional distillation or kugelroher distillation. This novel oligomer will be characterized using TGA (Thermal gravimetric Analysis) and DSC (Differential Scanning Calorimetry) for future studies. A n ew approach based on Pd catalyzed silylation of aryl halide was carried out to develop (phenylethynyl)phenyl DDSQ oligomer. Even though Pd catalyzed silylation of aryl halides was successful for T7(iBu) cage, this chemistry was not applicable for DDSQ - H cage as it showed decomposition duri ng the reaction. 1.5 mmol % Pd 2 (dba) 3 27 3.7 Experimental Section 3.7.1 Synthesis of bromo - 4 - (phenylethynyl)benzene Scheme 3.7. Synthesis of bromo - 4 - (phenylethynyl)benzene. Pd(Cl) 2 (0.1 mmol, 0.02 g), bromo - 4 - iodobenzene (10 mmol , 2.83 g), water (12.50 mL) and pyrrolidine (50 mmol, 4.15 mL) were charged into a flas k equipped with a stir bar. The reaction mixture was heated at 50 °C for 5 min. Afterward phenylactylene (12 mmol, 1.30 mL) was added and the mixture stirred at 50 °C fo r 24 h. After vigorous stirring, the reaction mixture was extracted with ethyl acetate (3 X 10 mL). The extracted solution was dried over anhydrous sodium sulf ate (Na 2 SO 4 ). The solvent was removed under vaccum and the residue was purified by flash chromato graphy on silica gel (hexane) give the product as a w hite solid (7.20 mmol, 2.40 g , 81% yield). 1 H NMR (500 MHz, CDCl 3 7.47 (4H, multiples), 7.39 - 7.34 (5H, multiplet) (Figure S26) ppm. 13 C NMR (125 MHz, CDCl 3 2.8, 122.5, 122.2, 90.4, 88.3 ppm (m.p 83 - 85 °C) (Figure 25). 28 3.7.2 Synthesis of dichloro(methyl)(4 - (phenylethynyl)phenyl) silane Scheme 3.8. Synthesis of dichloro(methyl)(4 - (phenylethynyl)phenyl) silane. Bromo - 4 - (phenylethynyl)benzene (10 mmol, 2.56 g) was charged into a flask equipped with a stir bar, Mg turnings (12 mmol, 0.26 g) and THF (5 mL). Reaction was carried out at 25 °C for 24 h under a n itrogen environment. After the G rignard reaction, the crude product was charged into a f lask equipped wi th a stir bar, methyl trichloro sil ane (12 mmol, 1.4 mL) and THF ( 5 mL). The reaction was performed at 25 °C for 48 h under a nitrogen environment. The product was purified by fractional distillation or Kugelrohr distillation (Figure S29) . 3.7.3 Synthesis of phenylethynyl(phenyl) DDSQ one - pot route Bromo - 4 - (phenylethynyl)benzene (10 mmol, 2.56 g) was charged into a flask equipped with a stir bar, Mg turnings (12 mmol, 0.26 g) and THF (5 mL). Reaction was carried out at 25 °C for 24 h under a nitrogen environment. 1 H NMR (500 MHz, CDCl 3 7.44 (4H, multiplet), 7.00 6.99 (5H, multiplet) ppm (Figure S27). 13 C NMR (125 MHz, CDCl 3 109.6, 92.4, 89.6 ppm (Figure S 28). 29 After the G rignard reaction, the cru de product was charged to the flask equipped with a sti r bar, methyl trichloro silane (12 mmol, 1.4 mL) and THF ((5 mL). The reaction was performed at 25 °C for 48 h under a nitrogen environment. 1 H NMR (500 MHz, CDCl 3 7.08 7.0 5 (5H, multiplet) ppm (Figure S30) . 29 Si NMR (100 MHz, CDCl 3 (Figure S 29). Dichloro(methyl)(4 - (phenylethynyl)phenyl) silane was charged into a flask equipped with a stirbar, DDSQ (5 mmol, 5. 30 g), THF (20 mL) and triethyl amine (NEt 3 ) (20 mmol, 2.02 mL). The reaction was performed at 25 °C for 24 h under a nitrogen environment. After 24 h, the HNEt 3 Cl precipitate was separated by filtration, and the solvent was removed from the filtrate under vacuum. The residue was purified by flash chromatography on silica gel ( hexane: dichloromethane 80:20). 1 H NMR (500 MHz, CDCl 3 7.20 (58 H, multiplet), 0. 55 (5H, singlet) ppm (Figure S35 ). 29 Si NMR (10 0 MHz, CDCl 3 - 32.40, - 78.59, - 79.34, - 79.65, - 79.88 ppm (Figure S33 ) (dichloro - DDSQ) . 13 C NMR ( 125 MHz, CDCl 3 130.86, 1 28.34, 127.87, 127.71, 127.62, 124.87 , 123.24, 90.22, 89.44 ppm (Figure S34) (diphenylethyne). 30 Scheme 3.9. Synthesis of phenylethynyl(phenyl) DDSQ one - pot route. 31 3.7.4 Pd cat alyzed silylation of aryl halides with T7(iBu) cage Scheme 3.10. Pd catalyzed silylation of aryl halides with T7(iBu) cage. Pd 2 (dba) 3 (0.015 mmol, 0.013 g) and P(o - tol) 3 (0.06 mmol, 0.018 g) were placed in a round bottom flask capped with a rubber septum. The flask was flushed with nitrogen and the n charged with NMP (4 mL). Iodo benzene (1.0 0 mmol, 0.10 mL), i - Pr 2 NEt (3 .00 mmol, 0.54 mL), and T7(iBu) 1 (1.5 0 mmol, 1.05 g) were added successively. The reaction mixtu re was th en stirred at r.t. for 24 h. When the reaction was complete, Et 2 O (10 mL) was added; the organic phase was washed with H 2 O (3 × 15 mL) to remove NMP and dried over Na 2 SO 4 . The solvent was removed 1.5 mmol % Pd 2 (dba) 3 32 under reduced pressure and the residue was purified by flash column chromatography (hexane CH 2 Cl 2 , 3:1) to give the desired product with 67 % yield ( 0.67 mmol, 0.70 g) 1 H NMR (500 MHz, CDCl 3 7.71 (2H, multiplet), 7.34 (1H, mult iplet), 7.12 7.10 (2H, multiplet ), 1.9 - 1.87 (1H, m ultiplet), 1 - 0.98 (38H, multiplet), 0.67 - 0.62 (13H, multiplet ) ppm (Figure S38). 29 Si NMR (100 MHz, CDCl 3 - 66.74, - 67.85, - 67.87 ppm (Figure S39) . 3.7.5 Pd catalyzed silylation of aryl halides with DDSQ(Me)(H) cage Scheme 3.11. Pd catalyzed silylation of aryl halides with DDSQ(Me)(H) cage. 1.5 mmol % Pd 2 (dba) 3 33 Pd 2 (dba) 3 (0.015 mmol, 0.013 g) and P(o - tol) 3 (0.06 mmol, 0.018 g) were placed in a round bottom flask capped with a rubber septum. The flask was flushed with nitrogen and the n charged with NMP (4 mL). Iodo benzene (2.0 0 mmol, 0.20 mL), i - Pr 2 NEt (3 .00 mmol, 0.54 mL), and DDSQ(Me)(H) (1 .00 mmol, 1.54 g) were added successively. The reaction mixture was th en stirred at r.t. for 24 h. When the reaction was complete, Et 2 O (10 mL) was added; the organic phase was washed with H 2 O (3 × 15 mL) to remove NMP and dried over Na 2 SO 4 . The solvent was removed under reduced pressure and the residue was purified by flash column chromatography (hexane CH 2 Cl 2 , 3:1) . 34 CHAPTER 4 : DEVELOPMENT OF ASYMMETRIC DDSQ MOLECULE BY MONOPROTECTING HYDROXYL GROUP 4.1. Introduction As stated earlier, DDSQ molecules possess a higher symmetry. Breaking the symmetry and selective functionalization of the DDSQ molecule will be highly desirable to fine tune the physical properties. DDSQ molecules possess four symmetrical hydroxyl groups at each corner. One of the approaches to achieve an asymmetric DDSQ molecule 7 is the protection of one hydroxyl group and subsequently closing the DDSQ cage 2 with the first capping agent 3 (Scheme 4.1 ). Then the hydroxyl group of 4 can be deprotected and a different second capping agent 6 can be incorporated to close the DDSQ molecule 5 . As shown in Scheme 4.2 , McDougal and coworkers studied the monoprotection of diol systems. This was anticipated to incorporate in the current asymmetric synthesis of DDSQ molecules. 32 The source of this selectivity may reside in the properties of the monosodium salt 2 of the diol 1 . Treatment of the diol 1 with 1 equivalent of NaH causes the formation of a voluminous precipitate. They observed that the solubility of the monosodium salt of the diol 2 wa s considerably less soluble in this solvent system. Upon the addition of silylating agent ( t BDMSCl), the small amou nt of dissolved monosodium salt 2 wa s silylated. As more salt slowly was going into solution, the rate of silylation of salt wa s faster than the backward reaction. 35 Scheme 4.1 . Asymmetric DDSQ synthesis by using monoprotection. Scheme 4.2. The chemistry developed by McDougal and coworkers to monoprotect the symmetric diol 36 4.2 Monoprotection of DDSQ Scheme 4.3. Monoprotection of symmetric DDSQ. As shown in Scheme 4.3, the Mc Dougal chemistry was applied to DDSQ in an attempt to synthesize a monoprotected cage. Though we expected to achieve the monoprotected DDSQ molecule with the use of the chemistry developed by McDougal and coworkers, the desir ed product was not observed. According to the NMR analysis (Figure S11 and S12 ) and mass spectrum, the major product was the diprotected hydroxyl group containing DDSQ molecule. Though various reaction conditions like variable temperatures, reaction time, and base were tested to get the expected monoprotected DDSQ molecule, all efforts were unsuccessful. 4.3 Synthesis of DDSQ(Me)(OH) and Monoprotection As it was challenging to achieve the monoprotection of this tetrasilanol system, a simplified diol sys tem was synthesized by using the cap ping agent as shown in Scheme 4.4 These capping agents have two hydroxyl groups and now the DDSQ molecule is turned into a simplified diol structure . As shown in Scheme 4.4, the DDSQ(Me)(OH) 2 was synthesized by reacting with MeSiCl 3 and DDSQ 1 followed by hydrolysis in 80% yield. Then, the monoprotection conditions were applied for this diol 2 . 37 Scheme 4.4. Monoprotection of symmetric DDSQ(Me)(OH). Even in the simplified diol DDSQ system, desired monoprotection of the hydroxyl group was not o bserved. NMR studies (Figure S1 5 and S16 ) concluded, that the reaction conditions provided the diprotected DDSQ(Me)(OH) molecule. According to the literature, the DDSQ cage is closed using dichlorosilane as the capping agent. During this project a novel approach was disco vered to clos e the DDSQ cage. I found that DDSQ cages can be closed using trichlorosilane and then the remaining Cl atom can be converted to a stable functional group (Scheme 4.5). 38 Scheme 4.5. Closing of DDSQ cage using trichlorosilane capping agent According to th e literature, 32 applied always for carbinol system without any issue. Nevertheless, for silanol, this chemistry was not applicable the same way. Therefore, the DDSQ cage was c losed with a capping agent that had a hydroxyl group on the carbon atom. 4.4 Synthesis of DDSQ(Me)(Hydroxopropyl) and Monoprotection DDSQ(Me)(Hydroxopropyl) was synthesized using hydrosilation chemistry. 33 As shown in Scheme 4.6, the silylation reaction between DDSQ 1 and methyldichlorosilane was carried ou t to prepare the DDSQ(Me)(H) 2 . The hydrosilylation reaction between 2 and allyloxytrimethylsilane 3 was performed to a ord DDSQ(Me)((trimethylsilyl)oxypropyl) 4 . The deprotection reaction of 4 with MeOH and MeSiCl 3 was carried out to a ffo rd DDSQ(Me)( Hydroxypropyl) 5 in 36% yield. After that, monoprotection of 39 Scheme 4.6. Synthesis of DDSQ(Me)( Hydroxopropyl) 40 Scheme 4.7. Monoprotection of DDSQ(Me)(Hydroxopropyl). Based on 29 Si NMR and 1 H NMR, (Figure S23 and S2 4 ) two different proton environments can be observed. If DDSQ(Me)(Hydroxopropyl) was monoprotected, two different proton environments should be present in the NMR. A h igh reso lution mass spectrum was acquired for further c onfirmation. Even though NMR showed two different proton environments, desired monoprotection of the hydroxyl group was not observed in mass spectrum. According to the mass spectrum, diprotected product and starting material were present . Two different proton environments were observed due to starting material and diprotected material. The monoprotection conditions were not successfully applicable for this carbinol system. 41 4.5 Conclusion Monoprotection of diols were studied to develop a route to an asymmetric DDSQ molecule. The possi bility of monoprotection among the four hydroxyl groups was difficult. Therefore the structure was simplified using a closed DDSQ cage with two hydroxyl groups that was tested to do monoprotection. However, the diol monoprotection conditions were not succe ssfully applicable for our disilanol syste m. Therefore, monoprotection was tested for the DDSQ(Me) (Hydroxoprop - yl) (carbinol system). Nevertheless the monoprotection conditions were not successfully applicable for the carbinol system. Possibly the MacDougal chemistry was not applicable for bulky skeleton molecules. Therefore future studies will be focused on development of a different route to synthesize an asymmetric DDSQ cages. 4.6 Experimental Section 4.6.1 Monoprotecton using NaH Scheme 4.8. Monoprotection of symmetric DDSQ. Sodium hydride (NaH 60% dispersion in mineral oil) was washed with hexane and suspended in THF (0.27 g, 6.75 mmol, 1 .20 equiv) was suspended in THF (11 mL) after being washed with hexane. The Ph8tetrasilanol - POSS (5.98 g, 5.6 mmol, 1 equiv) was added to this 42 reaction solutio n at room temperature and the mixture stirred for 45 min. The tert - b utyldimethylsilyl chloride ( t BDMSCl) (0.84 g, 5.6 0 mmol, 1 equiv) was then added, and vigorous stirring was continued for 45 min. The mixture was poured into ether (100 mL), washed with 10 % aqueous K 2 CO 3 (10 mL) and brine solution (10 mL), dried using anhydrous Na 2 SO 4 and concentrated in vacuo (3.0 0 g, 2.53 mmol, 45 % yield). 29 Si NMR ( 100 MHz, CDCl 3 (2Si), - 77.34 (2Si), - 78.42 (2Si), - 78.92 (2Si), - 79.12 (2Si) (Figure S12 ). 1 H NMR (500 MHz, CDCl 3 - 7.09 (40H, overlapping multiplets), 0.90 (15H, singlet), 0.08 (10H, singlet) (Figure S11 ). 4.6.2 Synthesis of DDSQ(Me)(OH) Scheme 4.9. Synthesis of DDSQ(Me)(OH) 43 A mixture containing Ph8tetrasilanol - POSS (2.65 g, 2.48 mmol, 1 equiv) and trimethylamine (Et 3 N) (1.14g, 11.26 mmol, 4.5 equiv) and 100 mL of THF was placed under an Ar atmosphere in a Schlenk bomb flask fitted with a plug valve. Then flask was placed in a n ice bath and methyltrichloro silane (MeSiCl 3 ) (0.74 g, 4.96 mmol, 2equiv) was added drop wise. The suspension was stirred for 24 h at room temperature and filtered through a glass frit (of triethylammonium chloride salt). The precipitate was washed wit h THF (3 × 5 mL) and solvent evaporated. The crude conden sation product (DDSQ(Me)(Cl)), was dissolved in THF (1.5 mL) and chloroform (4 mL), water (4 mL) and diluted HCl (0.5 mL) over a 90 min period. The aqueous layer was separated and extracted twice with chloroform. The combined organic layers were extracted with water first, then with diluted HCl, water, saturated brine and then dried with MgSO 4 . After filtration, the solvent was removed under vacuum to obtain the product (DDSQ(Me)(OH)), in the form of a white residue. (1.8 0 g, 1.60 mmol, 64 % yield). 29 Si NM R ( 100 MHz, CDCl 3 53.99 (2Si), - 78.57 (4Si), - 79.03 (1Si), - 79.13 (2Si), - 79.23 (1Si) (Figure S13 ). 1 H NMR (500 MHz, CDCl 3 - 7.19 (40H, overlapping multiplet) , 0.35 (6H, singlet) (Figure S14 ). 44 4.6.3 M o noprotection of DDSQ(Me)(OH) using NaH Scheme 4.10. Monoprot ection of DDSQ(Me)(OH) using NaH Sodium hydride (Na H 60% dispersion in mineral oil) was washed with hexane and suspended in THF (32.00 mg, 0.80 mmol, 1 equiv) was suspended in THF (1 mL) a fter being washed with hexane. The DDSQ(Me)(OH) (1.0 0 g, 0.8 0 mmol, 1 equiv) was added to this reaction solution at room temperature and stirred for 45 min. The tert - Butyldimethylsilyl chloride ( t BDMS) (0.13 g, 5.6 0 mmol, 1 equiv) was then added, and vigor ous stirring was continued for 45 min. The mixture was poured into ether (20 mL), washed with 10% aqueous K 2 CO 3 (10 mL) and brine solution (10 mL), dried using anhydrous Na 2 SO 4 and concentrated in vacuo to afford (0.03 g, 0.35 mmol, 44 %). 29 Si NMR ( 100 MHz, CDCl 3 - 54.13 (2Si) - 78.64 (4Si), - 78.79 (1Si), - 79.18 (2Si), - 79.39 (1Si) (Figure S15 ). 1 H NMR (500 MHz, CDCl 3 - 7.22 (40H, overlapping multiplets), 0.94 (15H, singlet), 0.38 (6H, singlet), 0.12 (10H, singlet) (Figure S16 ). 45 4.6.4 Synthesis of DDSQ(Me)(Hydroxopropyl) Scheme 4.11. Synthesis of DDSQ(Me)(Hydroxopropyl) Ph8tetrasilanol - POSS (11.60 g, 10.0 mmol) and triethylamine (4.13 mL, 41.2 mmol ) were charged to a flask equipped with a magnetic stirrer, 100 mL of anhydrous tetrahydrofuran were added with vigorous stirring. The flask was immersed in an ice - water bath and purged with highly pure nitrogen for one hour. After that, methyldichlorosila ne (3.45 g, 30.0 mmol) dissolved in 10 mL tetrahydrofuran were added dropwise within 30 min. The reaction was performed at 0 °C for 4 hours and at room temperature for 20 hours. The insoluble sol ids were removed by a filtration and the solvents together wi th other volatile compounds were eliminated via rotary evaporation to a ord the white solids. The solids were washed with 100 mL of methanol thrice and dried in vacuo 46 at 40 °C for 24 hours; the product (DDSQ (Me)(H)) (8.50 g, 7.36 mmol ) was obtained with 74% yield. 29 Si NMR ( 100 MHz, CDCl 3 Si) and ). 1 H NMR (500 MHz, CDCl 3 7.16 (40 H, multiplet), 4.99 (2H, singlet ) , 0.37 (6H, singlet ) (Figure S17 ). To a flask equipped w ith a magnetic stirrer, DDSQ(Me)(H)) (1.55 g, 1.34 mmol), anhydrous toluene (7 mL) and allyloxytrimethylsilane (2.35 g, 14.47 mmol) were charged. The flask was connected to a Schlenk line to degas with a repeated exhausting - refilling process with highly pu re nitrogen and then Karstedt catalyst [Pt] (two drops) was added with vigorous stirring. The hydrosilylation was performed at 95 °C for 36 hours to ensure that the reaction went onto completion. The solvent and excess allyloxytrimethylsilane were removed via rotary evaporation to a ord the solids with 90 % yield (1.7 0 g, 1.20 mmol). 29 Si NMR ( 100 MHz, CDCl 3 ). 1 H NMR (500 MHz, CDCl 3 7.23 (40H, multiplet), 3.50 (4H, triplet , J = 6.71 Hz ), 1.68 (4H, multiplet), 0.78 (4H, triplet, J = 5.48 Hz), 0.36 (6H, singlet) 0.06 (19H, singlet) (Figure S20). To a flask equipped with a magnetic stirrer, DDSQ(Me)(trimethyl silyl)oxypropyl) (6.00 g, 4.24 mmol) and dichloromethane (90 mL) were charged and then 90 mL of methanol was added with vigorous stirring. Thereafter, methyltrichlorosilane (1.360 g, 12.52 mmol) was added dropwise within 30 min using a syringe. The reaction was performed at room temperature for 5 hours. The solvents and the excess methyltrichlorosilane were removed via rotary evaporation. The resulting product was obtained via recrystallization from the mixture of THF with hexane (50/50 by vol.). After being dried in a vacuum oven at 40 °C for 24 hours, the product (2.10 g, 1.67 mmol) was obtained with 39 % yield (overall yield = 36%). 29 Si NMR (100 MHz, CDCl 3 ). 1 H NMR (500 47 MHz, CDCl 3 7.22 (40H, multiple t) 3.48 (4H, triplet , J = 6.51 Hz ), 1.68 (4H, multiplet), 0.78 (4H, triplet , J = 5.72 ), 0.35 (6H, singlet) (Figure S21 ). 4.6.5 Monoprotection of DDSQ(Me)(Hydroxopropyl) using NaH Scheme 4.12. Monoprotection of symmetric DDSQ. So dium hydride (NaH 60% dispersion in mineral oil) was washed with hexane and suspended in THF (11.20 mg, 0.28 mmol, 1 equiv ) was suspended in THF (1 mL) after being washed with hexane. The DDSQ(Me)(Hydroxypropyl) (0.35 g, 0.28 mmol, 1 equiv) was added to this reaction solution at room temperature and stirred for 45 min. The tert Butyldimethylsilyl chloride ( t BDMSCl) (0.04 g, 0. 28 mmol, 1 equiv) was then added, and vigorous stirring was continued for 45 min. The mixture was poured into ether (20 mL), washed with 10% aqueous K 2 CO 3 (10 mL) and brine solution (10 mL), dried using anhydrous Na 2 SO 4 and concentrated in vacuo to afford (0.14 g, 0.11 mmol, 39 % yield). 29 Si NMR ( 100 MHz, CDCl 3 (1Si), - 48 17.57 (1Si), - 17.65 (1Si), - 78.17 (1Si) - 78.54 (1Si), - 78.90 (1Si), - 79.23 (2Si), - 79.36 (1Si), - 79.46 (2Si) (Figure S24 ). 1 H NMR (500 MHz, CDCl 3 - 7.20 (40H, overlapping mu ltiplets), 3.41 (2H, triplet , J = 7.21 Hz ) 3.35 (2H, triplet , J = 6.56 Hz ), 1.61 (2H, multiplet), 1.48 (2H, multiplet), 0.89 (8H, singlet), 0.72 (2H, triplet , J = 6.91 ), 0.59 (2H, triplet , J = 6.42 ), 0.31 (3H, singlet), 0.19 (3H, singlet) , 0.07 (6H, singlet) (Figure S23 ). 49 CHAPTER 5 : DEVELOPMENT OF ASYMMETRIC DDSQ MOLECULE BY USING IMMOBILIZED SURFACE 5.1 Introduction Another approach to synthesize asymmetric DDSQ can be proposed using surfacesupported or immobilized reagent s . According to the Scheme 5.1 one side of the DDSQ cage can be blocked using the immobilized reagent 3 . DDSQ cage can be anchored to the immobilized surface with the use of a linkage (structure 4 ). The f ormerly open side of the DDSQ cage 4 can be closed using 1 equ iv alence of alkyl/aryl dichloro silane 5 . Afterward the one side closed DDSQ cage 6 can be cleaved from the immobilized surface to synthesize DDSQ cage 7 . By adding another 1 equivalence of a different alkyl/aryl dichloro silane capping agent 8 can close the open side of the DDSQ cage 7 to synthesize an asymmetric DDSQ cage 9 . Different surface immobilized reagents such as "Red - Sil" (Reducing Silica) and Merrifield immobilized reagent was explored . 50 Scheme 5.1. Synthesis of asymmetric DDSQ cage using immobilized reagents. 5.2 Development of asymmetric DDSQ using Red - Sil immobilized surface Red - Sil surface synthesized by modifying the surface of silica gel using trichlorosilane (Scheme 5.2). First the dried silica gel 1 was treated with trichlorosilane in methylene chloride with pyridine to remove the hydrogen chloride formed. There are three different surface modifications that can be formed dur ing this reaction. Those can be represented as surface 5 , 6 and 51 7 . After washing with methanol and dichloromethane Red - Sil surfaces were modified as surface 10 , 11 and 12 . 29 Si cross polarization (CP) solid state NMR was used to identify the nature of SiH functional group on the surface of the resulting product. Scheme 5.2 . Synthesis of Red - Sil. Figure 5.3 . Structure of silica gel. The 29 Si solid - state CP NMR spectrum of the original and unreacted silica gel showed the three different types of Si atoms (a - c) present in the silica gel (Figure 5.3). The 29 Si CP NMR 52 spectrum of t he Red - Sil (Figure S44 ) showed the presence of two new signals a - 77 and - 87 ppm in addition to the signals from the silicon atoms already present in the backbone of silica gel. The signal related to silicon atom c (Figure 5.3) had disappeared after treatment, and the intensity of the signal related to silicon atom b was sharply reduced. This is indicative of the reaction of the trichlorosilane with the pendant hydroxyl groups present on the silica gel. As shown in Scheme 5.2 there can be three different modes of attachment of trichlorosilane to the surface of the s ilica g el, giving rise to species A - C - 77 and - 87 ppm in the 29 Si NMR spectrum belong to Si atoms bearing hydrogen - SiH and - Si(OCH 3 ) n H groups respectively. 5.2.1 Quantitative estimation of Si - H on the surface of Red - Sil For any surface - immobilized reagent to be synthetically useful, it is essential to know the amount of the active species or functional groups present on the surface of the supporting material. Silver ions (Ag + ) reduction by silyl hydrides, used as the quantita tive method for determination the concentration of immobilized silyl hydrides (Scheme 5.4). 38 The stoichiometry of the reduction of silver ions by Si - H was confirmed by the reaction of a known amount of trimethoxysilane with a known excess of aqueous silve r nitrate solution. It was found that 1 equivalent of silver nitrate was needed to oxidize 1 equivalent of trimethoxysilane. 38 The excess of silver ions can be quantitatively recovered as AgCl precipitate by using diluted HCl solution. This confirmed the o ne electron nature of this reduction reaction. The following relationships were used to calculate the concertation of active surface - immobilized SiH functions on the sample. 53 Scheme 5.4. Ag + reduction by silyl hydrides Moles of AgCl (1.39 mmol ) = Moles of unchanged AgNO 3 Moles of original AgNO (3.75 mmol) - Moles of unchanged AgNO 3 (1.39 mmol) = Moles of AgNO 3 consumed (2.35 mmol ) Moles of AgNO 3 consumed = Moles of SiH present (2.35 mmol) 1g of Red - Sil = 2.35 mmol of Si - H Repeated analyses of material obtained by using the same amount of silica gel and trichlorosilane consistently yielded 2.35 mmol of SiH/g of silica gel product. 5.2.2 Studies of different routes to attach the DDSQ cage to the Red - Sil surface A reagent can be anchored onto a solid surface either by covalent bonding or through ionic interaction between the surface functional groups and reagent. 39 Various methods w ere tested to attach the DDSQ cage to the Red - Sil surface. 54 Scheme 5.5. Development of asymmetric DDSQ Method A 55 One route, method A i s described in Scheme 5.5. Red - Sil surface 2 undergo es hydrosilylation with propargylic chloride 1 to modify the Red - Sil surface to structure 3 . The surface reaction of this reagent 3 with the DDSQ 4 would be expected to react at only one of the silanols and formed structure 5 . Afterward the open side of the DDSQ cage 5 can be closed using 1 equivalence of alkyl/aryl dichloro silane 6 . One side closed DDSQ cage 7 can be cleaved from the immobilized surface to synthesize DDSQ cage 8 . Adding another 1 equivalence of a different alkyl/aryl dichloro silane capping agent can close t he open side of the DDSQ cage 8 to synthesize an asymmetric DDSQ cage. Solid state 29 Si CP NMR and 13 C CP NMR were studied for the method A. 29 Si CP NMR (Figure S46 ) of DDSQ attached Red - Sil surface (Scheme 5.5 - 77.9 ppm in addition to the signals from the silicon atoms already present in the backbone of silica gel - 103 and - 112 ppm) and Red - Sil Si - 70.4 and - 83.5 ppm) - 77.9 ppm was due to Si atoms of DDSQ cage. A nother route (Method B) is desc ribed in S cheme 5.6. "Red - Sil" 2 could be made to undergo dehydrogenation of a propargyl hydroxide 1 with diethyl hydroxylamine (Et 2 NOH). The surface reaction of this reagent 3 with the dihydro DDSQ (DDSQ(Me)(H)) 4 would be expected to react at only one si de (synthesis of DDSQ(Me)(H) will be des cribed in Scheme 5.7 ) Then DDSQ(Me)(H) 4 will be immobilized and site isolated. Afterward, the DDSQ(Me)(H) cage 5 would be cleaved by ozonolysis from the Red - Sil to synthesize an asymmetric DDSQ cage 6 . 56 Scheme 5.6. Development of asymmetric DDSQ Method B DDSQ(Me)(H) 3 was synthesized by reacting DDSQ 1 with methyl dichlorosilane (MeSiCl 2 H) capping agent 2 (Scheme 5.7). 57 Solid state 29 Si CP NMR and 13 C CP NMR were studied for the method B. 29 Si CP NMR (Figure S47 ) of DDSQ attached Red - Sil surface - 80.8 ppm in addition to the signals from the silicon atoms already present in the backbone of silica gel - 103 and - - 80.8 ppm was due to Si atoms of DDSQ(Me)(H) cage. The peak of DDSQ (Me)(H) had low intensity when compared with peaks intensities of method A . It was concluded that DDSQ(Me)(H) attachment to the Red - Sil surface was not efficient in method B. 58 Scheme 5.8. Develo pment of asymmetric DDSQ Method C Another attempt of attachment of DDSQ c age in to the Red - Sil surface i s illustrated in Scheme 5.8. In method B , hydrosilylation was performed first to connect the propargylic alcohol 1 in to the Red - Sil surface 2 . As s hown in the Scheme 5.8 , DDSQ(Me)(H) 4 can be anchored onto the modified Red - Sil surface 3 via dehydrogenation. According to the solid state 29 Si CP NMR (Figure S48 ) the DDSQ(Me)(H) attachment to the Red - Sil surface was more effective when compared with me thod A and method B. The peak around - 80 ppm was more intense compared with other two methods. 59 Solid state CP NMR studies confirmed the attachment of propargylic alcohol to the Red - Sil surface (Scheme 5.8). Solid state 29 Si CP NMR (Figure S49 ) showed a less intense for peak at 77 and - 87 p pm compared with the (Figure S44 ) unmodified Red - Sil surface. The peaks were less intense due to removal of hydrogen of the Si - H group of Red - Sil surface. Generally solid - state NMR of dilute nuclei, such as 13 C, 29 Si, and 15 N (isotopic abundance of 1.1%, 4.7%, and 0.03%, respectively), suffers from low sensitivity. Cross - polarization (CP ) overcomes this common problem in the NMR of solids. Cross polarization from abundant nuclei like 1 H, 19 F and 31 P can be transferred to dilute or rare nuclei like 13 C, 15 N, 29 Si in order to enhance signal to noise ratio. Cross polari zation can be reduced due to loss of hydrogen from the Si - H fragment. Therefore the intensity will be reduced. This is indicative of th e reaction of the propargylic chloride with the pendant Si - H groups present on the Red - Sil surface. Solid state CP 13 C NMR (Figure S50 ) exhibits the allylic efficiency o f DDSQ cage attachment to the modified Red - Sil surface. The higher peak intensity of DDSQ cage in solid state 29 Si CP NMR (Figure S48 ) was concluded the efficiency of DDSQ cage attachment compared to the method s A and B. According to these comparison stud ies, method C provides a better route to attach the DDSQ onto the Red - Sil surface. The challenging part is detachment of the DDSQ cage from the Red - Sil surface. Ozonolysis was carried out to detach the DDSQ cage. Before the ozonolysis , DDSQ cage stabil ity was checked under an ozone environment. DDSQ cage w as stable after ozone purging, b ut the de tachment was not successful by ozononlysis . May be the reductive workup of the ozonolysis wa s really slow or ozonolysis did not occur . Therefore another approach for the detachment will be considered in future. 60 5.2.3 Conclusion According to the solid state NMR studies significantly DDSQ was attached through the method C when compared with method s A and B. Nevertheless the challenging part of detachment was not successful through the ozonolysis. Therefore in the future, other approach es will be considered for the detachment. 5.2.4 Future studies Cross metathesis was considered for the detachment of the DDSQ cage from the Red - Sil surface. According to the liter ature, the Grubbs catalyst generation 1 (G1) (Pcy 3 ) 2 (Cl) 2 Ru=CHPh is using for cross metathesis of vinyl silane. 42 We were interested about using this chemistry in our situation to detach the DDSQ cage from the Red - Sil surface. Future studies will be focuse d on cross metathesis to detach the DDSQ cage from the immobilized surface. 5.2.5 Experimental section - Dried silica gel (8.00 g) was transferred into a three - necked 500 mL flask equipped with an addition funnel. Freshly di stilled trichlorosilane (25 mL, 0.24 mol) in 160 mL of dry CH 2 Cl 2 was added to silica gel under an argon atmosphere. The reaction mixture was cooled to - 78 °C with dry ice and acetone. Pyridine (60 mL, 0.74 mol) was added slowly dropwise from an additional funnel to the reaction mixture at - 78 °C with intermittent stirring. A thick precipitate of pyridinium chloride formed in the reaction flask. An additional (80 mL) portion of dry CH 2 Cl 2 was added to the reaction mixture, and the mixture was stirred at roo m temperature under argon for 24 h. The reaction mixture was then again cooled to - 78 °C, and dry methanol (80 mL) was added to slowly to the mixture dropwise. The reaction mixture filtered on a Buchner funnel, and 61 the silica gel was washed further with 20 0 mL of dry methanol to dissolve and remove the pyridinium chloride precipitate. Finally, the silica gel was washed with CH 2 Cl 2 (125 mL). This modified silica ge l product was product was dried to afford 29 Si NMR (CP) (79 MHz, CDCl 3 - 77.0 (SiH), - 87.0 ( SiH(OCH 3 ), - 103.7, and - 112.9 ppm. 13 C NMR (CP) (100 MHz, CDCl 3 - 48.2 ppm. Scheme 5.9 . - 62 5.2.5.2 Quantitative estimation of Si - H on the surface of Red - Sil Scheme 5.10 . Ag + reduction by silyl hydride. The following procedure for the estimation of silyl hydirdes on the surface of silica gel is representative. S ilver nitrate (3.75 mmol, 0.64 g) was dissolved in distilled water (50 mL) in a volumetric flask. Silica gel immobli zed silyl hydride (1.00 g) was placed in a 250 mL round - bottom flask. The silver nitrate solution made as above was added to the silica gel. The volumetric flask was rinsed with distilled water (20 mL), and the washings were added to the silica gel. An imm ediate bl a ck precipitate was observed after the addition of silver nitrate solution to the silica gel immobilized silyl hydirde. The solution was covered to exclude light and stirred with a magnetic stirrer for 24 h, and the solution was then filtered thro ugh a Buchner funnel. The silica g el was washed with distilled wa ter (50 mL) to remove traces of unchanged silver nitrate. Five drops of 1% HNO 3 solution w ere added to the filtrate. The solution was then warmed to 50 - 60 °C. Silver chloride was precipitate d out by adding 0.2 M aqueous HCl solution dropwise to the filtrate (unchanged silver nitrate solution). During the precipitation the temperature was kept at around 50 - 60 °C. The pr ecipitate was allowed to settle in the flask in a dark place for 2 h at ro om temperature. The supernatant liquid was tested for further precipitation with aqueous HCl solution. The precipitate was allowed to settle in the flask in a dark place overnight. The silver chloride precipitate was filtered and washed with 1% HNO 3 (20 - 25 mL) solution. This was followed by washing with distilled water (100 mL). The precipitate was dried and then weighed. Silver ion analysis showed 2.35 mmol of SiH/g of silica gel. 63 5.2.5.3 Development of asymmetric DDSQ Method A H ydrosilylation, was carried out in an argon environment. Propa r gylic chloride (3.00 mmol, 0.23 mL) and Red - Sil (1.00 g) were charged to a flask w ith toluene (20.00 mL) and K arst edt catalyst (Pt catalyst ) (two drops). The reaction was performed at 90 °C for 36 h. After vigorou s stirring, the solvent was removed using filtration. Then propargylic alcohol attached Red - Sil (species 3) solid powder was dried and weighed (1.21 g). 29 Si NMR (CP) (79 MHz, CDCl 3 ) - 75.6 (SiH), - 86.3 (SiH(OCH 3 ), - 102.7, and - 112.0 ppm. 13 C NMR (CP) (100 MHz, CDCl 3 127.4 (allylic C), 59.3 (C - Cl), 43.1 (OCH 3 ) ppm. Propagylic chloride attached Red - Sil solid powder was charged in to a flask equipped with a stir bar, DDSQ (3 mmol, 3.15 g), triethylamine (NEt 3 ) (3 mmol, 0.30 mL) and CH 2 Cl 2 (35.00 mL). The reaction was performed at 25 °C for 24 h. After vigoruos stirring, the solvent was removed using filtration. Then DDSQ attached Red - Sil (species 3) solid powder was dried and weighed (1.73 g). 29 Si NMR (CP) (80 MHz, CDCl 3 - 78.9 (DDSQ - Si), - 102.9, a nd - 112.7 ppm. 64 Scheme 5.11 . Development of asymmetric DDSQ Method A. 5.2.5.4 Development of asymmetric DDSQ Method B First step of this method B was dehydrogenation. The e xperiment was carried out in a nitrogen environment. Propargylic alcohol (3.00 mmol, 0.17 mL) and Red - Sil (1.00 g) were added to toluene (5.00 mL) and the mixture was heated at 60 °C. A solution of diethylhydroxyl amine (Et 2 NOH) (10 µL) in toluene (10.00 mL) was added as the catalyst. Partial geletation was occurred in the flask while the mixture was heated at 60 °C. After vigoruos stirring for two days, the solvent was removed using filtration. Then propargylic alcohol attached Red - Sil (species 3) solid powder was dried and weighed (1.13 g). Then hydrosilylation was carried out in an argon environment. Propargylic alcohol attached Red - Sil solid powder was charged in to a flask equipped with a stir bar, dihydro D DSQ 65 (DDSQ - H) (3 mmol, 5.40 g), K arst edt catalsyt (Pt catalsyt) (two drops) and toluene (20 mL). The rea ction was performed at 90 °C for 36 h. Solvent was eliminated via filtration. DDSQ - H attached Red - Sil solid powder was dried and weighed (1.38 g). 29 Si NMR (CP) (79 MHz, CDCl 3 - 80.8 (DDSQ - H - Si), - 93.3, - 103.1, and - 112.4 ppm. Scheme 5.12 . Development of asymmetric DDSQ - H Method B. 5.2.5.5 Development of asymmetric DDSQ Method C H ydrosilylation, was carried out in an argon environment. Propargylic alcohol (3.00 mmol, 0.17 mL) and Red - Sil (1.00 g) were charged in to a fla sk with toluene (20.00 mL) and K arstedt catalyst (Pt catalyst) (two drops). The reaction was performed at 90 °C for 36 h. After vigorous 66 stirring, the solvent was removed using filtration. Then propargylic alcohol attached Red - Sil (species 3) solid powder was dri ed and weighed (1.18 g). The second step, dehydrogenation was carried out in a nitrogen environment. Propargylic chloride attached Red - Sil solid powder (1.00 g) was charged in to a flask equipped with a stir bar, and DDSQ - H (3 mmol, 5.40 g), and toluene (5.00 mL). A solution of diethylhydroxyl amine (Et 2 NOH) (10 µL) in toluene (10.00 mL) was added as the catalyst. Partial gelation occurred in the flask while the mixture was heated at 60 °C. After vigorous stirring for two days, the solvent was removed using filtration. Then DDSQ - H attached Red - Sil (species 3) solid p owder was dried and weighed (1.3 3 g). 29 Si NMR (CP) (79 MHz, CDCl 3 - 66.3, - 72.8, - 73.7, - 80.0 (DDSQ - H - Si), 103.1, and - 112.5 ppm. The fin al step ozonolysis was performed to cleave the linkage between Red - Sil and DDSQ cage. The solid powder (spe cies 4) (1.80 g) was charged into a flask equipped with a stir bar and anhydrous CH 2 Cl 2 (10.00 mL). Ozone was bubbled through the solution at - 78 °C until the blue color persisted. Then solution was purged with oxygen for 10 min and triphenyl phosphine (PPh 3 ) (0.63 g) was added. The reaction was allowed to warm to room temperature and stirred overnight. After filtration, filtrate was concentrated thr ough the vacuum rotavap. 67 Scheme 5.13 . Development of asymmetric DDSQ - H Method C. 68 5.3 Development of asymmetric DDSQ using Merrifield resin. In future studies another immobilized surface will be studied. Merrifield resin, which was originally extensively investigated for peptide and other oligomer synthesis. Merrifield resin is a polystyrene resin based on a copolymer of styrene and chloromethy lstyrene, which is also crosslinked with divinylbenzene. 40 Merrifield resin, which was originally extensively investigated for peptide synthesis . Scheme 5.14 . Merrifield Resin 69 Scheme 5.15 . Synthesis of asymmetric DDSQ cage using immobilized reagents. As shown in Scheme 5.15 , DDSQ cage 2 can be anchored into the Merrifield resin 1 through the chloromethylated bond. The advantage over the Red - Sil surface is, DDSQ cage can be anchored direct ly to the solid surface without any linkage. After the attachment, the open side of DDSQ cage 3 can be closed using a capping agent 4 . Through the hydrogenolysis the DDSQ cage can be detach from the immobilized surface. The future studies will be focused on this route to develop asymmetric DDSQ molecule. 70 APPENDIX 71 Figure S1 (Para) Methyl - di - chloro silane - 29 Si NMR 72 Figure S2 (Para) Methyl - di - chloro silane 1 H NMR 73 Figure S3 (Meta) Methyl - di - chloro silane - 29 Si NMR 74 Figure S4 (Meta) Methyl - di - chloro silane 1 H NMR 75 Figure S5 DDSQ(m/p)(Me)(PEPI) (Path A) 1 H NMR 76 Figure S6 DDSQ(m/p)(Me)(PEPI) (Path A) 29 Si NMR 77 Figure S7 DDSQ(m/p)(Me)(PEPI) (Path B) 29 Si NMR 78 Figure S8 DDSQ(m/p)(Me)(PEPI) (Path B) 1 H NMR 79 Figure S9 DDSQ(m/p)(Me)(PEPI) (Path C) 29 Si NMR 80 Figure S10 DDSQ(m/p)(Me)(PEPI) (Path C) 1 H NMR 81 Figure S11 Mono - protection of DDSQ using NaH 1 H NMR 82 Figure S12 Mono - protection of DDSQ using NaH 29 Si NMR 83 Figure S12 (cont d) 84 Figure S13 DDSQ (Me)(OH) 29 Si NMR 85 Figure S13 (cont d) 86 Figure S14 DDSQ (Me)(OH) 1 H NMR 87 Figure S15 Mono - protection of DDSQ (Me)(OH) 29 Si NMR 88 Figure S16 Mono - protection of DDSQ (Me)(OH) 1 H NMR 89 Figur e S17 DDSQ (Me)( H) 1 H NMR 90 Figur e S18 DDSQ (Me)( H) 29 Si NMR 91 Figur e S18 (cont d) 92 Figur e S19 DSQ (Me)( di(trimethylsilyl)oxypropyl ) 1 H NMR 93 Figur e S20 DDSQ (Me)( di(trimethylsi lyl)oxypropyl ) 29 Si NMR 94 Figur e S20 (cont d) 95 Figur e S21 DDSQ (Me)( Hydroxopropyl) 1 H NMR 9 6 Figur e S22 DDSQ (Me)( Hydroxopropyl) 29 Si NMR 97 Figur e S22 (cont d) 98 Figur e S23 Mono - protection of DDSQ (Me)( Hydroxopropyl) 1 H NMR 99 Figur e S24 Mono - protection of DDSQ (Me)( Hydroxopropyl) 29 Si NMR 100 Figur e S24 (cont d) 101 Figur e S24 (cont d) 102 Figur e S24 (cont d) 103 Figur e S25 Phenylethynyl(phenyl) bromide 13 C NMR 104 Figur e S26 Phenylethynyl(phenyl) bromide 1 H NMR 105 Figur e S27 Phenylethynyl(phenyl) Gri gnard bromide 1 H NMR 106 Figur e S28 Phenylethynyl(phenyl) Grignard bromide 13 C NMR 107 Figur e S29 Phenylethynyl(phe nyl) (methyl) dichloro silane before distillation 1 H NMR 108 Figur e S30 Phenylethynyl(phe nyl) (methyl) dichloro silane before distillation 29 Si NMR 109 Figur e S31 distilled product by Kugelrohr distillation 1 H NMR 110 Figur e S32 distilled product by Kugelrohr distillation 29 Si NMR 111 Figur e S33 (phenylacetylene)phenyl DDSQ oligomer 1 H NMR 112 Figur e S34 (phenylacetylene)phenyl DDSQ oligomer 13 C NMR 113 Figur e S35 (phenylacetylene)phenyl DDSQ oligomer 29 Si NMR 114 Figur e S36 Si - H T7(iBu) 1 H NMR 115 Figur e S37 Si - H - T7(iBu) 29 Si NMR 116 Figur e S38 Ph - T7(iBu) 1 H NMR 117 Figur e S39 Ph - T 7(iBu) 29 Si NMR 118 Figur e S40 H - T7(Ph) 29 Si NMR 119 Figur e S41 H - T7(Ph) 1 H NMR 120 Figur e S42 Decomposed DDSQ cage 29 Si NMR 121 Figur e S43 Iodo benzene 1 H NMR 122 Figur e S44 Red - Sil SS 29 Si NMR 123 Figur e S45 Red - Sil SS 13 C NMR 124 Figur e S46 DDSQ attached Red - Sil Method A SS 29 Si NMR 125 Figur e S47 DDSQ attached Red - Sil Method B SS 29 Si NMR 126 Figur e S48 DDSQ attached Red - Sil Method C SS 29 Si NMR 127 Figur e S49 Propargylic alcohol attached Red - Sil Method C SS 29 Si NMR 128 Figur e S50 Propargylic alcohol attached Red - Sil Method C 1 3 C NMR Figur e S52 DDSQ attached Red - Sil Method C 29 Si NMR 129 Figur e S51 After ozonolysis 1 H NMR 130 REFERENCES 131 REFERENCES 1) (a) Harrison, P.G. 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