Design and application of chiral sulfinyl imine ligands and synthetic applications of N-sulfinyl metalloenamine-based diastereoselective reactions

N-tert-Butanesulfinyl imines and their derivatives have become increasingly useful for the asymmetric synthesis of small molecules. N-tert-Butanesulfinyl imines possess several features that render them ideal for a variety of applications, including facile synthesis, excellent stability, high stereoselectivity imparted by the tert-butyl group, and mild cleavage of the tert-butanesulfinyl moiety. Work in our group has demonstrated their versatility as intermediates in the preparation of chiral amines, as well as their incorporation into a highly selective chiral ligand scaffold for enantioselective catalysis. This dissertation describes advances in both applications of N-tert-butanesulfinyl imine derivatives.;Chapter 1 details the design and development of a novel phosphine-containing sulfinyl imine ligand scaffold. The P, N-sulfinyl imine ligands were successfully applied to two important asymmetric transformations, with high enantioselectivities obtained in both Pd-catalyzed allylic alkylations and Ir-catalyzed olefin hydrogenations. A set of sterically and electronically diverse ligands was prepared, and interesting structure-activity relationship data was obtained for three positions on the ligand scaffold.;Chapter 2 describes applications of metalloenamines derived from N-tert-butanesulfinyl aldimines toward asymmetric syntheses of biologically relevant molecules. Highly diastereoselective self-condensation reactions of N-tert-butanesulfinyl aldimines were developed, which represent the first demonstration of stereoselective aldimine self-condensation. The intermolecular self-condensation reaction was applied to the efficient asymmetric synthesis of a drug candidate, while the intramolecular variant allowed for rapid synthesis of a useful cyclic beta-amino acid. Key to both of these syntheses was a novel, microwave-assisted conversion of sulfinyl imines to nitriles.;Metalloenamines derived from N-tert-butanesulfinyl amidines have also proven extremely useful for chiral amine synthesis. Chapter 3 describes the development of a highly diastereoselective aldol-type addition of metalloenamines derived from sulfinyl amidines. This was applied in studies toward the first synthesis of the complex natural product 10-formamido-4-amorphene.