Highly Enantioselective Construction of Fully Substituted Stereocenters Enabled by <i>In Situ</i> Phosphonium-Containing Organocatalysis
Hongkui Zhang, Chunhui Jiang, Jian‐Ping Tan, Huilin Hu, Yayun Chen, Xiaoyu Ren, Hong‐Su Zhang, Tianli Wang
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.