I. Stereoselective Construction of Polycyclic Architectures: Enantioselective Catalytic Transannular Ketone-Ene Reactions and an Enantioselective Total Synthesis of (+)-Reserpine II. Synthesis of Chiral Bisthioureas for Anion-Abstraction Catalysis

The research presented herein explores three aspects of asymmetric catalysis: (1) the development of new catalytic enantioselective reactions, (2) the application of stereoselective catalysis to natural product total synthesis, and (3) the design and synthesis of new chiral catalysts.;In Chapter 1, an asymmetric transannular ene reaction of electronically unactivated ketones is reported. The transformation is catalyzed by a new chromium(III) tridentate Schiff-base catalyst and provides access to trans-decalinol frameworks in high diastereo- and enantioselectivity.;A convergent total synthesis of indole alkaloid (+)-reserpine is presented in Chapter 2. The synthesis uses two key catalytic asymmetric methods: an oligomeric Co(salen)-catalyzed enantioselective kinetic resolution of terminal epoxides and a catalyst-controlled diastereoselective primary aminothiourea-catalyzed formal aza-Diels-Alder reaction. These methods enabled an enantioselective synthesis of the classic target and addressed the historically problematic C3 stereocenter of the molecule. Through the investigation of various synthetic routes we were able to access two unnatural diastereomers of methyl reserpate: 16-epi-(+)-methyl reserpate and 15,16-di-epi-(+)-methyl reserpate.;Chapter 3 describes the syntheses of rationally designed bisthioureas for anion-abstraction catalysis. Recent mechanistic investigations have led to the identification of productive and nonproductive thiourea dimerization modes in the context of an asymmetric alkylation of alpha-chloroethers. Based on this work, we synthesized covalently tethered thioureas that enforce proximity of the hydrogen bond donor moieties for cooperative electrophile activation while disfavoring nonproductive self-aggregation. Significant enhancements in reactivity are obtained with the bisthioureas relative to analogous monomeric thioureas in the model reaction.