Asymmetric synthesis of 1,2,3-trisubstituted indanes via an enantioselective copper(II)-catalyzed asymmetric nitroaldol reaction followed by an intramolecular Michael cyclization

Abstract

Herein we describe a novel approach for the synthesis of a chiral 1,2,3-trisubstituted indane, a privileged substructure in medicinal chemistry, via an enantioselective nitroaldol reaction and subsequent intramolecular Michael addition. The asymmetric copper(II)-catalyzed reactions of ortho-formyl cinnamates, ortho-formyl cinnamonitrile, or ortho-formyl α-benzalketones with nitromethane were carried out using the C1-symmetric chiral secondary diamine L1 as a ligand, which afforded the nitroaldol products in high yields (up to 92%) and with good to excellent enantioselectivities (up to 97%) under mild conditions. The notable effect of the base and the dosage of nitromethane on the reaction are also discussed.