L-Proline-Catalyzed One-Pot Diastereoselective Synthesis of Cyclohexanols from β-Aryl-γ-nitroketones and α,β-Unsaturated Aldehydes: A New Route to 2,3,4,6-Tetrasubstituted Phenols

Abstract

A wide array of densely functionalized cyclohexanol derivatives having five contiguous chiral centers were efficiently achieved in good to high yields with high diastereoselectivities. The double C−C bonds forming reaction proceeds via a domino nitro-Michael/aldol reaction between several β-aryl-substituted-γ-nitroketones and a range of β-aryl-substituted acroleins as Michael acceptors catalyzed by L-proline as a naturally available, non-toxic, cheap organocatalyst. Several important features of this strategy include 100% atom-economical, high-efficiency, operational simplicity, and broad functional-group tolerance. Gratifyingly, one-pot conversion of cyclohexanols to a novel class of 2,3,4,6-tetrasubstituted phenols under metal-free conditions has been demonstrated. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim