Phosphoramidite Gold(I)-Catalyzed Diastereo- and Enantioselective Synthesis of 3,4-Substituted Pyrrolidines

Abstract

In this article the utility of phosphoramidite ligands in enantioselective Au^I catalysis was explored in the development of highly diastereo- and enantioselective Au^I-catalyzed cycloadditions of allenenes. A Au^I-catalyzed synthesis of 3,4-disubstituted pyrrolidines and γ-lactams is described. This reaction proceeds through the enantioselective Au^I-catalyzed cyclization of allenenes to form a carbocationic intermediate that is trapped by an exogenous nucleophile, resulting in the highly diastereoselective construction of three contiguous stereogenic centers. A computational study (DFT) was also performed to gain some insight into the underlying mechanisms of these cycloadditions. The utility of this new methodology was demonstrated through the formal synthesis of (−)-isocynometrine.