Enantioselective synthesis of tetrahydrofuran spirooxindoles via domino oxa-Michael/Michael addition reaction using a bifunctional squaramide catalyst

Abstract

An enantioselective approach for the synthesis of tetrahydrofuran spirooxindoles via domino oxa-Michael/Michael addition reaction of γ-hydroxyenones to isatylidene malononitriles, using a cinchona derived bifunctional squaramide catalyst has been developed. The methodology is the first success of enantioselective oxa-Michael addition to isatylidene malononitriles. The spiro products were obtained in excellent yields with moderate to good enantio- and diastereoselectivities. Scale-up of the reaction and synthetic transformation of the spiro product into structurally complex molecules have been performed.