Transition-Metal-Free Three-Component Chalcogen-Trifluoromethylation of Alkenes Enabled by a Catalytic Electron Donor-Acceptor Complex

Abstract

The transition metal-free chalcogen trifluoromethylation of alkenes represents a highly efficient transformation for the rapid generation of C(sp³)-rich aliphatic trifluoromethyl compounds. However, a unified methodology to achieve oxy-, thio-, and seleno-trifluoromethylation remains elusive yet highly desirable. In this study, we report a triarylamine-catalyzed three-component vicinal chalcogen-trifluoromethylation of alkenes under blue light irradiation without the need of transition metal catalyst. This reaction is broadly applicable to oxy, thio, and seleno nucleophiles, facilitating modular access to a diverse array of β-trifluoromethyl alcohols, ethers, thioethers, thiocyanates, and selenocyanates with good yields and predictable regioselectivities (61 examples). Additionally, we demonstrate its application in the late-stage modification of natural products and pharmaceutical compounds. Preliminary mechanistic studies suggest that a catalytic electron donor-acceptor (EDA) complex between triarylamine and the Umemoto reagent is key to enabling the radical/polar crossover process.

Keywords

Trifluoromethyl group / Electron donor-acceptor complex / Alkene difunctionalization / Radical/polar crossover / Chalcogen atom / Triarylamine / Multicomponent reactions / Photoredox catalysis / Alkenes / Synthetic methods

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