Enantioselective Synthesis of Hydrothiazole Derivatives via an Isocyanide-Based Multicomponent Reaction

Abstract

Catalytic asymmetric synthesis of hydrothiazole derivatives was developed via a well-organized formal [2 + 1 + 2] cycloaddition reaction triggered by asymmetric addition of isocyanide to alkylidene malonate. Various chiral hydrothiazole derivatives were readily provided in good yield with high enantioselectivity (up to 98% yield, 98.5:1.5 er) utilizing a chiral Mg(OTf)₂/<i>N</i>,<i>N'</i>-dioxide complex as the catalyst under mild conditions. Based on the experimental studies and the structure of the catalyst, a possible catalytic cycle was proposed to elucidate the reaction process and activation mode.