Catalyst-free photochemical fluorination of C-H bonds of aromatic carbonyl compounds

A wide range of organic molecules can participate in hydrogen atom transfer (HAT) processes as both HAT-donors and photo-HAT-acceptors simultaneously. Therefore, it opens the possibilities to exclude catalysts for C-H functionalization in such cases. This is the underlying idea of the presented catalyst-free C-H bond fluorination approach. We demonstrated that broad range of aryl alkyl ketones can be efficiently fluorinated with Selectfluor-based reagents at benzylic position under UV-A irradiation without any added catalyst. The selectivity of mono- and difluorination can be controlled by con-trolling the excess of fluorinating reagent. Additionally, we propose an analogue of Selectfluor reagent - F-TEDA-TFSI with much greater solubility in acetonitrile which makes our protocol solvent-economical. By the same manner benzaldehydes can be transformed to corresponding benzoyl fluorides with almost quantitative yields. The protocol was successfully applied in late-stage fluorination of complex molecules Tonalide and Tolperisone. Kinetic measurements demonstrated zero-order kinetics which indicates that light flux is the limiting factor. A tentative mechanism was proposed based on the selectivity of fluorination of primary, secondary, and tertiary benzylic C-H bonds.