Solvent-Tuned Photocatalytic (Phenylsulfonyl)difluoromethylation of Anilines: Selectivity and Postfunctionalization

The control of the <i>ortho</i> versus <i>para</i> selectivity in substitution reactions of aniline derivatives remains a fundamental challenge in organic synthesis. Herein, we report a photoredox-catalyzed synthesis of (phenylsulfonyl)difluoromethylated anilines. The <i>ortho</i>-<i>para</i> selectivity of this transformation is predominantly governed by the solvent choice. Using the reaction system with a 1:1 DMSO/DMA mixed solvent achieves a high <i>para</i>:<i>ortho</i> ratio of up to 13.3:1. Conversely, switching to a 2:1 MeOH/DCM mixture as the solvent enables the <i>ortho</i> isomer to be obtained highly selectively, even as the sole product. The practicality of this protocol is further evidenced by its application in diverse derivative syntheses. For example, the PhSO₂CF₂ group can be converted into CF₃ or CF₂H and the amino group can be transformed into iodo or alkynyl groups, among others.