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 eight-membered 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.