Photocatalytic defluoroalkylation and hydrodefluorination of trifluoromethyls using o-phosphinophenolate

Can Liu,Ni Shen,Rui Shang

doi:10.1038/s41467-022-28007-2

Abstract

Under visible light irradiation, o-phosphinophenolate functions as an easily accessible photoredox catalyst to activate trifluoromethyl groups in trifluoroacetamides, trifluoroacetates, and trifluoromethyl (hetero)arenes to deliver corresponding difluoromethyl radicals. It works in relay with a thiol hydrogen atom transfer (HAT) catalyst to enable selective defluoroalkylation and hydrodefluorination. The reaction allows for the facile synthesis of a broad scope of difluoromethylene-incorporated carbonyl and (hetero)aromatic compounds, which are valuable fluorinated intermediates of interest in the pharmaceutical industry. The ortho-diphenylphosphino substituent, which is believed to facilitate photoinduced electron transfer, plays an essential role in the redox reactivity of phenolate. In addition to trifluoromethyl groups, pentafluoroethyl groups could also be selectively defluoroalkylated.

Highlights

Under visible light irradiation, o-phosphinophenolate functions as an accessible photoredox catalyst to activate trifluoromethyl groups in trifluoroacetamides, trifluoroacetates, and trifluoromethylarenes to deliver corresponding difluoromethyl radicals
Among the various photocatalysis-enabled methods of activating inert bonds, the direct selective C–F activation6–11 of trifluoromethyl groups to deliver corresponding difluoromethyl radicals is an ideal transformation for the synthesis of difluoromethylene-incorporated compounds, which are valuable fluorinated intermediates in the pharmaceutical industry12–14
While the photocatalysts prevalently used in these transformations are precious metal-based polypyridyl complexes and π-conjugated organic dyes, we conceived that anionic phenolate19–23, which has strong reductive potential in its excited state, may work as a suitable catalyst for selective C–F functionalization of trifluoromethyls over a broad scope of substrates

Summary

Introduction

O-phosphinophenolate functions as an accessible photoredox catalyst to activate trifluoromethyl groups in trifluoroacetamides, trifluoroacetates, and trifluoromethyl (hetero)arenes to deliver corresponding difluoromethyl radicals. While the photocatalysts prevalently used in these transformations are precious metal-based polypyridyl complexes and π-conjugated organic dyes, we conceived that anionic phenolate19–23, which has strong reductive potential in its excited state, may work as a suitable catalyst for selective C–F functionalization of trifluoromethyls over a broad scope of substrates. The ortho-PPh2 substituent redshifts the absorption of the ground state anion (PO–) from the ultraviolet to visible light range.

Results

Conclusion