Enantioselective Synthesis of 1,3-Benzothiazine Derivatives: An Organocatalytic Chemoselective Approach

Abstract

Herein, a highly chemoselective 1,2-addition of thiols with 2-isothiocyanatochalcones followed by an enantioselective intramolecular thia-Michael addition cascade has been established to construct enantioenriched [1,3]-benzothiazine derivatives for the first time. The cinchona-derived squaramide catalyst provides good to excellent yield and enantioselectivity of the products with broad substrate adaptability. Furthermore, this strategy has been extended to the diphenylphosphine oxide nucleophile to access enantioenriched organophosphorus-substituted [1,3]-benzothazines. A scale-up reaction and synthetic transformation have demonstrated the viability of this protocol.