The Utilization of Sulfinimines (N-Sulfinyl Imines) in the Asymmetric Synthesis of Substituted Pyrrolidines

Abstract

The objective of this research was the development of new methods for the asymmetric synthesis of nitrogen containing compounds. As one part of this goal, 3,4-dihydroxyprolines and their derivatives were prepared from sulfinimines (N-sulfinyl imines). During this project new methods were developed for asymmetric hydroxylation and decarboxylation of 3-oxo-2-carboxylate pyrroldines. The application of this new methodology was realized by the total synthesis of the α- and β-glycosidases inhibitor (+)-lentginosine. It was also found that electrophiles regioselectively add to the 4-position of 3-oxo-2-carboxylate-5-substituted pyrrolidines. The addition is accomplished through lithium diisopropyl amide generation of the pyrrolidine dianion. This addition was also compatible with 3-oxo-2-phosophono-5-substituted pyrroldines. Furthermore air oxidation of these pyrrolidines give the corresponding pyrroles. This procedure represents the first general preparation procedure for 2-phonopyrroles, which have been examined as HIV protease inhibitors. A range of β-amino carbonyl compounds were prepared from N-sulfinyl β-amino Weinreb amides in a concise and efficient procedure. A general method for the preparation of a variety of β-amino carbonyl compounds arose from the addition of an assortment of organometallic reagents to the Weinreb amides. The N-sulfinl β-amino Weinreb amides are prepared by reaction of the potassium enolate of N-methoxy-N-methylacetamide with sulfinimines or lithium N,O-dimethylhydroxylamine with N-sulfinyl β-amino esters.