Transition metal-free photochemical C-F activation for the preparation of difluorinated-oxindole derivatives

Abstract

The development of strategies for single and selective C-F bond activation represents an important avenue to overcome limitations in the synthesis of valuable fluorine-containing compounds. The synthetic and medicinal research communities would benefit from new routes that access such relevant molecules in a simple manner. Herein we disclose a straightforward and mechanistically distinct pathway to generate gem-difluoromethyl radicals and their installation onto N-arylmethacrylamides for the preparation of valuable difluorinated oxindole derivatives. To achieve operational simplicity, the use of a readily available benzenethiol as a photocatalyst under open-to-air conditions was developed, demonstrating the facile multigram preparation of the targeted fluorinated molecules. Additionally, dispersion-corrected density functional theory (DFT) and empirical investigations provide a new basis to support the proposed reaction pathway, indicating that arene thiolate is an efficient organophotocatalyst for this transformation.