Copper(I)-Catalyzed Asymmetric Synthesis of α-Allenylamines and β-Lactams through Regioselective Mannich-Type Reactions
Feng Zhong, Wen‐Jun Yue, Xing‐Hao Yin, Hongming Zhang, Liang Yin
Abstract
Herein, a copper(I)-catalyzed alkynylogous Mannich-type reaction is developed, which starts from pyrazoleamides of alkynyl-substituted acetic acids and provides an array of chiral α-allenylamine derivatives in high regio-, diastereo-, and enantioselectivities. This reaction enjoys broad substrate scopes on both pyrazoleamides and N-Boc-aldimines. Moreover, a copper(I)-catalyzed cascade cyclization of pyrazoleamides of but-2-ynoic acid is disclosed, which involves an α-selective Mannich-type reaction as a key step and delivers a series of chiral β-lactams containing a pyrazole moiety in high enantioselectivity. In light of some mechanism studies, the deprotonation step is found as the rate-determining step in this cyclization. Propargyl copper(I) species are proposed as the operating nucleophiles in both reactions. Finally, the synthetic utility of the alkynylogous product is demonstrated by the transformations of the product to chiral α,β-unsaturated lactones. Furthermore, a gram-scale preparation of chiral β-lactam and its following transformations proved its synthetic versatility.