A PTC-catalyzed diastereoselective Mannich reaction to access indanone-based α-amino acid derivatives.

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.