Stereoselective Mannich Reaction of α-Acetoxy-β-keto Esters with Isatin Imine: An Efficient Access to Vicinal Tetra-Substituted Stereocenters

Abstract

A highly diastereo- and enantioselective Mannich reaction of α-acetoxy-β-keto esters with isatin imine was developed. The quinine thiourea organocatalyst smoothly promoted the asymmetric Mannich reaction to furnish various 3-substituted-3-aminooxindole derivatives bearing two adjacent tetra-substituted stereocenters in up to 93 % yield, up to 98 % ee with >20 : 1 dr. The transition state structure and absolute configuration of the obtained product were predicted using DFT calculations, and results from single crystal X-ray analysis are in agreement with the DFT studies. © 2021 Wiley-VCH GmbH