Modular Multicomponent Cascade Synthesis of Benzo[b]thiophene-Fused N,O-Heterocycles from 1,2-Benzisothiazoles, Benzolactones and Aldehydes

Abstract

A modular, metal-free multicomponent cascade reaction for the synthesis of benzo [b]thiophene-fused seven-, or eightmembered N,O-heterocyclic compounds from 1,2-benzisothiazoles, benzolactones, and aldehydes has been developed. Notably, 1,2-benzisothiazoles were employed as novel sulfuration reagents in multicomponent reactions for the first time.The regioselectivity of this modular transformation is controlled by the in situ ring-opening of 1,2-benzisothiazoles with benzolactones, a process involving N-S bond cleavage and decarboxylation. This modular multicomponent cascade reaction proceeds under mild conditions, exhibits broad substrate tolerance, and enables the one-step formation of new C-C, C-S, C-N, and C-O bonds. Moreover, the successful scale-up synthesis and efficient late-stage modification of pharmaceutical molecules highlight the synthetic utility of this method.