The FeCl3-Catalyzed Synthesis of Pyrans, Furans and Pyrrolines and Progress Towards the Total Synthesis of Isopalhinine A

Abstract

Part 1 of this dissertation describes developments in carbonyl-olefin metathesis. This transformation is made possible by the Lewis acid FeCl3, an inexpensive, Earth abundant, and environmentally benign late transition metal. This reaction platform serves to minimize some drawbacks of the well-developed olefin-olefin metathesis strategy, which is frequently accompanied with prerequisite olefination of carbonyls, and the use of more expensive metal complexes. Carbonyl-olefin metathesis has been demonstrated to be tolerant of common functional groups, and can be performed on sterically encumbered carbonyls. The first transformation described is the use of FeCl3 to generate chiral pyrrolines via carbonyl-olefin metathesis. Important considerations to the development of this transformation were the maintenance of chirality throughout the synthetic sequence and the modulation of Lewis basicity of the given substrates. In the following chapters the utility of FeCl3 is elaborated towards the synthesis of pyrans or furans from γ,δ-unstaturated carbonyls. Part 2 of this dissertation pertains to the synthesis of Lycopodium alkaloids. This class of natural products have been subject to decades of synthetic efforts. Despite modern advances of chemical technology the synthesis of these heavily bridged and polycyclic secondary metabolites remains a challenge. Herein is disclosed recent efforts towards the synthesis of a common core intermediate to access multiple palhinine and isopalhinine natural products. Key transformations include a stereoselective reductive aldol and an acyloin condensation of inequivalent carbonyls.