Cyclic amines and amides through molybdenum-catalyzed asymmetric olefin metathesis: A total synthesis of quebrachamine

Chapter 1. We have exploited the sensitivity of chiral Mo-based metathesis catalysts to both the sterics and electronics of an olefin substrate in order to accomplish the selective coupling of terminal alkenes with strained norbornyl ethers. The overall intermolecular cross-metathesis likely occurs through a ring-opening of the strained bicycle with a Mo-alkylidene derived from the donor olefin cross partner. The resulting functionalized cyclopentanes are formed with high enantioselectivity and complete stereocontrol across the disubstituted double bond. Mechanistic studies indicate that the ether substituent protecting the norbornyl alkene is essential for reaction efficiency.*; Chapter 2. Methods for the asymmetric synthesis of cyclic amines and amides through catalytic olefin metathesis are presented. To provide a context for our work with chiral Mo catalysts, a brief overview of contributions centered on the use of achiral Ru and Mo complexes for the preparation of N-containing heterocycles is also included. Our initial success in developing a protocol for the ARCM (asymmetric ring-closing metathesis) of aniline-derived amines has been extended to the preparation of optically enriched cyclic amides, carbamates and lactams. Our strategy explores several issues of practicality including protecting group removal, olefin substitution and subsequent functionalization. Efforts in this area have laid the groundwork for the application of ARCM to the synthesis of naturally occurring alkaloids.*; Chapter 3.{09}The exploration of several synthetic routes focused on the use olefin metathesis to secure the heterocyclic ring system of Aspidosperma alkaloid quebrachamine is summarized. These efforts have culminated in an efficient eleven step sequence to the amine target without the use of protecting groups. Our strategy owes its brevity to the application of four mild and efficient transition metal (Rh, Ru, Pd, and Mo) catalyzed reactions. Key features of our approach include: (i) Rh-catalyzed cyclopropenation of a diazocarbonyl bearing alpha-protons, (ii) the ring-opening metathesis chemistry of a spirocyclic cyclopropene to access the requisite quaternary carbon center with gem-divinyl substituents and (iii) the use of an uncommon, yet highly convergent medium ring synthesis through ring expansion.*; *Please refer to dissertation for diagrams.