Highly Enantioselective Construction of Fully Substituted Stereocenters Enabled by <i>In Situ</i> Phosphonium-Containing Organocatalysis

Abstract

We present, herein, an important and practical class of bifunctional in situ phosphonium-containing organocatalysis and its initial application in highly efficient and enantioselective construction of N-containing fully substituted stereocenters through an asymmetric decarboxylative transformation between cyclic ketimines and β-keto acids. With this catalytic protocol, a variety of optically active cyclic tertiary amine derivatives were readily synthesized in high yields with excellent enantioselectivities (99.0 to >99.9% ee) under very low catalyst loading (0.5 mol %). The success of gram-level preparation and synthetic transformations proves the potential of this catalytic strategy for practical applications. Mechanistic investigation, including control experiments, in situ NMR analysis, and ESI-HRMS characterization of intermediates, provides insights into the mechanism.