Electrochemical meta-C−H Sulfonylation of Pyridines with Nucleophilic Sulfinates

Abstract

Considering the indispensable significance and utilities of meta-substituted pyridines in medicinal, chemical as well as materials science, a direct meta-selective C − H functionalization of pyridines is of paramount importance, but such reactions remain extremely limited and highly challenging. In general, established methods for meta C − H functionalization of pyridines rely on the utilization of tailored electrophilic reagents to realize the intrinsic polarity match. Herein, we report a complementary electrochemical methodology; diverse nucleophilic sulfinates allow unprecedented meta-sulfonylation of pyridines through a redox-neutral dearomatization-rearomatization strategy by a tandem dearomative cycloaddition/hydrogen-evolution electrooxidative C − H sulfonation of the resulting oxazino-pyridines/acid-promoted rearomatization sequence. Besides, several salient features, including exclusive regiocontrol, remarkable substrate/functional group compatibility, scale-up potential, and facile late-stage modification, have been demonstrated, which further contributes to the practicality and adaptability of this approach.