Catalytically generated acyl triazoliums as versatile acylating reagents and progress toward the total synthesis of okilactomycin

Abstract

The first chapter of this dissertation describes the development of reactions involving the NHC-catalyzed acylation of carbon and nitrogen nucleophiles. The overall goal of this work was to expand the scope of the NHC-redox reaction manifold and improve its applicability to the synthesis of products that would be useful to the organic chemistry community. An efficient and simple procedure for the preparation of amides from amine hydrochloride salts and α,β-unsaturated aldehydes was developed. This procedure was then applied to the asymmetric synthesis of α-fluoroamides which are valuable building blocks for the preparation of fluorinated compounds that are highly sought after in pharmaceutical, material, and agrichemical applications. The second chapter describes efforts toward the total synthesis of the complex polyketide natural product okilactomycin, enabled by the rhodium-catalyzed desymmetrization of 3,5-dimethylglutaric anhydride developed previously by our group. Progress includes construction of the entire carbon skeleton in two fragments, poised to be unified and elaborated to the natural product by closely precedented steps. This progress demonstrates the potential of the catalytic, enantioselective desymmetrization of anhydrides to build complexity in rapid fashion.