University of Redlands InSPIRe @ Redlands Undergraduate Honors Theses Theses, Dissertations, and Honors Projects 2015 Ozonolysis of silyl enol ethers: Synthesis of 3-silyloxy-1,2-and 3-alkyl-3-silyloxy-1,2-dioxolanes Katrina Wilson Follow this and additional works at: https://inspire.redlands.edu/cas_honors Part of the Medicinal-Pharmaceutical Chemistry Commons, Organic Chemistry Commons, and the Other Chemistry Commons Recommended Citation Wilson, K. (2015). Ozonolysis of silyl enol ethers: Synthesis of 3-silyloxy-1,2-and 3-alkyl-3-silyloxy-1,2-dioxolanes (Undergraduate honors thesis, University of Redlands). Retrieved from https://inspire.redlands.edu/cas_honors/123 This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License This material may be protected by copyright law (Title 17 U.S. Code). This Open Access is brought to you for free and open access by the Theses, Dissertations, and Honors Projects at InSPIRe @ Redlands. It has been accepted for inclusion in Undergraduate Honors Theses by an authorized administrator of InSPIRe @ Redlands. For more information, please contact [email protected]. Ozonolysis of silyl enol ethers: Synthesis of 3-silyloxy-1,2- and 3-alkyl-3-silyloxy-1,2-dioxolanes By: Katrina Wilson A thesis submitted to the Faculty of the Department of Chemistry at The University of Redlands in partial fulfillment of the requirements for a Bachelor of Science degree Department of Chemistry 2015 ii Abstract Katrina Wilson (B.S. Chemistry and Biology) Synthesis and Ozonolysis of Silyl Enol Ethers Thesis Directed by Dr. David Soulsby Silyl enol ethers are important synthetic intermediates that are used in a variety of reactions. The ozonolysis of silyl enol ethers to anomalous 1,2-dioxolane products has not yet been fully been explored. Though the synthesis of silyl enol ethers from aldehydes, ketones, and esters is relatively straightforward, the most commonly used methods still require air- or moisture-sensitive conditions and/or the use of toxic solvents. We have shown that silyl enol ethers can be easily synthesized from aldehydes and ketones under mild conditions and with a straightforward workup procedure in good to excellent yields. We ozonolyzed these silyl enol ethers to study their reactivity and found that unsubstituted and 1-substituted silyl enol ethers gave (3-alkyl)-3-silyloxy1,2-dioxolane products in excellent to moderate yields, respectively. However, alkyl substitution at the 2-position led to the formation of polymeric product. Finally, we investigated the reactions of these dioxolane products and found that they can undergo rearrangement to β-hydroxy esters via the addition of acid and diols via hydrogenation. iii Acknowledgments The University of Redlands has provided me with a wonderful place to learn and grow as an individual. Throughout my four years here, I have met many people who have contributed to my development as a chemist, and as a person, and I would like to thank them for influencing my life and career path and creating quite an unforgettable experience. First and foremost, I would like to express my deepest appreciation to Dr. David Soulsby for being such an incredible research advisor and mentor, and for pushing me to apply for honors. He has taught me everything I know about organic chemistry and 1H NMR, and has helped me with everything, from teaching me how to do various lab techniques, to editing, re- editing, and re-re-editing my thesis. His excitement for this project and patience with me has allowed me to thrive in the lab and as a student. I would also like to thank Dr. Lisa Olson, Dr. Tommi Cahill, and Dr. David Soulsby for being amazing and compassionate academic advisors and professors. Without their guidance and help I would not have been able to complete all three of my majors. I would also like to thank Dr. Teresa Longin, Dr. Sue Blauth, and Dr. Daniel Wacks for being on my honor’s committee, and a special thanks to Dr. Sue Blauth for being such a wonderful mentor and friend during summer research. Additionally I would like to thank Dr. Van Engelen, Dr. Aquaye, Dr. Lyons, Dr. Schrum, and Dr. Aronson for being such wonderful professors and for always answering all my endless questions. I would also like to thank Tavleen Kochar for putting up with me in everything that we did together, and to say thank you to Madison Michaud for teaching me how to be a mentor and making research fun and entertaining, and to all the seniors in the chemistry and biology departments. Finally, I would like to thank my family and friends both back home and in Redlands for always supporting me in everything that I do. iv Table of Contents Abstract........................................................................................................................................... ii Acknowledgements........................................................................................................................iii 1. Introduction.................................................................................................................................1 1.1 Organic Synthesis..........................................................................................................1 1.2 Structures and Synthesis of Silyl Enol Ethers...............................................................2 1.3 Synthesis Applications of Silyl Enol Ethers..................................................................6 1.4 Ozonolysis of Alkenes...................................................................................................7 1.5 Ozonolysis of Enol Ethers.............................................................................................9 1.6 Ozonolysis of Silyl Enol Ethers.....................................................................................7 2. Experimental Design and Data..................................................................................................14 2.1 Optimization of Synthesis of Silyl Enol Ethers from Aldehydes................................14 2.1.1 (Tert-butyldimethylsilyloxy)ethene..............................................................14 2.1.2 (Tert-butyldimethylsilyloxy)ethene..............................................................15 2.1.3 (Triisopropylsilysilyloxy)ethene...................................................................15 2.1.4 (Tert-butyldimethylsilyloxy)propene............................................................16 2.1.5 (Tert-butyldimethylsilyloxy)propene............................................................16 2.1.6 (Tert-butyldimethylsilyloxy)butylene...........................................................17 2.1.7 3-phenyl(tert-butyldimethylsilyloxy)propene...............................................18 2.1.8 3,7-dimethyl-1-(tert-butyldimethylsilyloxy)-1,6-octadiene..........................18 2.1.9 3,7-dimethyl-1-(tert-butyldimethylsilyloxy)-1,6-octadiene..........................19 2.2 Optimization of Synthesis of Silyl Enol Ethers from Ketones....................................19 2.2.1 1-(Tert-butyldimethylsilyloxy)-cyclohexene................................................19 2.2.2 2-(Tert-butyldimethylsilyloxy)-propene.......................................................20 2.2.3 Synthesis of 2-Triisopropylsilyloxypropene.................................................21 2.2.4 1-Triisopropylsilyloxystyrene.......................................................................21 2.2.5 Synthesis of (tert-butyldimethylsilyloxy)-1,3-dicyclohexene......................22 2.3 Ozonolysis of Silyl Enol Ethers..................................................................................23 2.3.1 3-(Tert-butylsilyloxy)-1,2-dioxolane............................................................23 2.3.2 3-Methyl-3-(trimethylsilyloxy)-1,2-dioxolane.............................................23 v 2.4 Further Reactions of Ozonolyzed Silyl Enol Ether Products..................................................24 2.4.1 Ring Opening of 3-Silyloxy-1,2-dioxolane..................................................24 2.4.2 Hydrogenation of 3-Methyl-3-silyloxy-1,2- dioxalane..................................25 3, Results and Discussion..............................................................................................................26 3.1 Synthesis of Silyl Enol Ethers from Aldehydes..........................................................26 3.2 Synthesis of Silyl Enol Ethers from Ketones..............................................................30 3.3 Ozonolysis of Silyl Enol Ethers...................................................................................33 3.4 Further Reactions of 3-Silyloxy-1,2-dioxolane Products............................................37 4. Conclusions................................................................................................................................38 5. Future Work...............................................................................................................................39 References......................................................................................................................................39 Appendix: 1H NMR Spectra .........................................................................................................41 vi Table of Figures Figure 1: The Generic Structure of a Silyl Enol Ether (R=alkyl)...................................................2 Figure 2: Kinetic versus Thermodynamic Silyl Enol Ether Formation of 2-methylcyclohexanone