[4+2] CYCLOADDITIONS OF IMINOACETONITRILES: A GENERAL STRATEGY FOR THE SYNTHESIS OF QUINOLIZIDINES, INDOLIZIDINES, AND PIPERIDINES By

Iminoacetonitriles participate as reactive dienophiles in intermolecular and intramolecular DielsAlder cycloadditions leading to quinolizidines, indolizidines, and piperidines. The resultant aamino nitrile cycloadducts are versatile synthetic intermediates which can be further elaborated by stereoselective alkylation, reduction, reductive cyclization, and Bruylants reactions. The first part of this thesis describes the full details of our studies on the synthesis of iminoacetonitriles, the scope of their Diels-Alder reactions, and the synthetic elaboration of the a-amino nitrile cycloadducts to provide access to a variety of substituted quinolizidine and indolizidine derivatives. The second part of this thesis reports on the total synthesis of quinolizidine (-)217A and our efforts directed toward the total synthesis of indolizidine (-)-235B'. Thesis Supervisor: Rick L. Danheiser Title: Professor of Chemistry Acknowledgments All acknowledgments must begin with my thesis advisor Rick Danheiser. I will forever be grateful to Rick for allowing me to join his laboratory and helping me become a better chemist. I continue to be amazed not only be the extent of his knowledge, but also by his ability to explain complex topics in a simple and straightforward manner. Besides being a great advisor, Rick has also been a great friend. I will definitely miss our weekly (sometimes daily) discussions about the Red Sox and Patriots. Also, I would like to thank Rick for being an amazing pitcher the past three years on Toxic Waste. Without his consistent domination on the mound, we never would have won three straight MIT softball championships. I would also like to thank my thesis committee members Greg Fu and Tim Jamison for their helpful suggestions and comments pertaining to this thesis. Special thanks go to Greg Fu for his helpful advice and support during my time at MIT. No one goes through graduate school alone, and I would be remiss for not thanking my fellow coworkers. First, I would like to thank David Amos for taking me under his wing my first semester and teaching me how to be a successful organic chemist. Next, I would like to thank Xiao Yin Mak for being a great friend and an even better bench mate. I will definitely miss seeing her on a daily basis. I would also like to thank my "IAN partner" Mandeep Virdi. The opportunity to mentor her the past four years has been an amazing experience that I will never forget. I also owe a debit of gratitude to Xiao Yin and Mandeep for helping me write and prepare this thesis. Next, I would like to thank a few group members who were instrumental in making the Danheiser lab a terrific working environment. First, I would like to thank Charnsak Thongsornkleeb (a.k.a Touch), Josh Dunetz, and Aimee Crombie for creating an extremely friendly and open atmosphere in the laboratory. Martin Hayes and Wes Austin deserve a thank you for helping make Toxic Waste (and MIT NERC) the most feared softball team in the Northeast. I also want to thank Tammy Lam and Jenny Fong for all their help over the past few years. I wish our two new first-years, Shaun Fontaine and Julia Robinson, good luck as they begin their journey in the Danheiser lab. Lastly, I would like to thank Javier Horta for his amazing BBQs. There are several individuals at MIT outside of the Danheiser group that deserve recognition. First, I would like to thank all the members of "Noon Ball." There is no way I would have survived graduate school without basketball. I would also like to thank PJ (Kelvin Billingsley) and Matt Hill for being my "BFF's." Chris Clough and Kyle Proffitt were two amazing roommates and I will never forget our time together, especially our first few months in Boston. Lastly, I would like to thank all the members of Toxic Waste and Gashouse for the numerous championships we won over the past four years. I owe a debt of gratitude to my parents for their unending support and encouragement. Thank you so much! You are wonderful parents and I wouldn't be where I am today without your love and support. Last, but not least, I would like to thank Venda, Coors, and Coconut for their friendship and love. Coors has been my best friend for the past seven years and I would not have survived graduate school without his companionship. Most importantly, I would like to thank my girlfriend, Venda, for her love and support, and I am looking forward to starting a new life with her in New Jersey.