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

26 February 2024, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

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.

Keywords

fluorination
photoinitiated
hydrogen atom transfer
proton-coupled electron transfer

Supplementary materials

Title
Description
Actions
Title
Experimental and spectral details, calculation of metric
Description
Description of experimental setup, optimization data, spectral data for products, calculation and comparison of VTY metric, kinetics data.
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