Enantioselective (3+2) Cycloaddition–Rearrangement Strategy to Access Benzo[ d ]isothiazole‐Containing Polyheterocycles

Comprehensive Summary Benzo[ d ]isothiazole motif has emerged as a privileged structure in medicinal chemistry and agricultural science. However, conventional synthetic methods are plagued by tedious multistep procedures, low atom economy and harsh reaction conditions, rendering the development of a facile and convenient approach for the synthesis of compounds containing a benzo[ d ]isothiazole moiety highly desirable. We herein present a one‐pot enantioselective protocol that integrates a dearomative (3+2) cycloaddition of 2‐nitrobenzofurans with 2‐( N ‐2,2,2‐trifluoroethyl)benzothiophene‐derived ketimines and a subsequent DPPH‐mediated rearrangement. This methodology affords an efficient route to enantiomerically pure benzo[ d ]isothiazole‐containing polyheterocyclic derivatives in excellent outcomes (up to 95% yield, > 20 : 1 dr and 99% ee). The synthetic utility of this protocol is further substantiated by scale‐up synthesis, downstream transformations, as well as late‐stage modification of biologically active molecules.