Solvent-Tuned Photocatalytic (Phenylsulfonyl)difluoromethylation of Anilines: Selectivity and Postfunctionalization
Hang Zhang1, Long Xiao1, Huanyi Guo1
1Guizhou Provincial Key Laboratory of Innovation and Manufacturing for Pharmaceuticals, School of Pharmacy, Zunyi Medical University, Zunyi 563003, P. R. China.
Abstract:
The control of the ortho versus para 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 ortho-para 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 para:ortho ratio of up to 13.3:1. Conversely, switching to a 2:1 MeOH/DCM mixture as the solvent enables the ortho 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.
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