A PTC-catalyzed diastereoselective Mannich reaction to access indanone-based α-amino acid derivatives
Lei Yang1, Yu-Ting Hou1,2, Wan-Yu Wei1,2
1Innovation Research Center of Chiral Drugs, Institute for Advanced Study, Chengdu, University, Chengdu 610106, China. zhaojianqiang@cdu.edu.cn.
Abstract:
We herein disclose a phase-transfer-catalyzed diastereoselective Mannich reaction between β,γ-alkynyl-α-ketimines and in situ generated 1-hydroxy isobenzofulvene anions from 2-alkylidene-1-indanones, enabling the formation of indanone-based α-amino acid derivatives with good results (up to 93% yield with >20 : 1 dr in all cases). The protocol is characterized by mild reaction conditions, broad substrate tolerance, and excellent diastereoselectivity. The practicality of the methodology is underscored by a gram-scale experiment and the coupling of the product with structurally complex pharmaceuticals. Notably, this work represents the first example of a reaction of 1-hydroxyl isobenzofulvene anions with imines.
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