Photo-driven redox-neutral decarboxylative carbon-hydrogen trifluoromethylation of (hetero)arenes with trifluoroacetic acid

Jin Lin,Zhi Li,Yadong Li,Weiping Su,Jian Kan,Shijun Huang

doi:10.1038/ncomms14353

Abstract

Catalytic oxidative C–H bond functionalization reactions that proceed without requiring stoichiometric amounts of external oxidants or pre-functionalized oxidizing reagents could maximize the atom- and step-economy in chemical syntheses. However, such a transformation remains elusive. Here, we report that a photo-driven catalytic process enables decarboxylative C–H trifluoromethylation of (hetero)arenes with trifluoroacetic acid as a trifluoromethyl source in good yields in the presence of an external oxidant in far lower than stoichiometric amounts (for example, 0.2 equivalents of Na2S2O8) using Rh-modified TiO2 nanoparticles as a photocatalyst, in which H2 release is an important driving force for the reaction. Our findings not only provide an approach to accessing valuable decarboxylative C–H trifluoromethylations via activation of abundant but inert trifluoroacetic acid towards oxidative decarboxylation and trifluoromethyl radical formation, but also demonstrate that a photo-driven catalytic process is a promising way to achieve external oxidant-free C–H functionalization reactions.

Highlights

Catalytic oxidative C–H bond functionalization reactions that proceed without requiring stoichiometric amounts of external oxidants or pre-functionalized oxidizing reagents could maximize the atom- and step-economy in chemical syntheses
Minisci reactions have implied that trifluoroacetic acid (TFA) may act as a trifluoromethylating reagent via oxidative decarboxylation to generate trifluoromethyl radical[23,24,25]
The decarboxylative C–H trifluoromethylation mediated by a stoichiometric amount silver salt required 2 equivalents of K2S2O8 as oxidant and tolerated only a few electron-deficient substituted benzenes[25]

Summary

Introduction

Catalytic oxidative C–H bond functionalization reactions that proceed without requiring stoichiometric amounts of external oxidants or pre-functionalized oxidizing reagents could maximize the atom- and step-economy in chemical syntheses. Benefiting from the identification of various precursors that are capable of generating trifluoromethyl radicals through regular oxidation[19] or photoredox catalysis[20] under mild conditions, the radical-based reactions have evolved into an efficient approach to construct C-CF3 bonds In spite of these remarkable advances, the commonly used trifluoromethylating reagents are very expensive due to their timeconsuming and multistep syntheses, which prompt chemists to develop readily available, cost-effective surrogates of existing trifluoromethylating reagents. Our findings demonstrate that the underlying redox chemistry of natural photosynthesis can operate in C–H functionalization reactions, which may provide an opportunity to maximize the step- and atom-economy of such reactions

Methods

Results

Conclusion