Photoredox Activation of Anhydrides for the Solvent-Controlled Switchable Synthesis of gem-Difluoro Compounds
Abstract
The incorporation of the gem-difluoromethylene (CF2) group into organic frameworks is highly sought due to the influence of this unit on the physicochemical and pharmacological properties of molecules. Herein we report an operationally simple, mild, and switchable protocol to access various gem-difluoro compounds that employs chlorodifloroacetic anhydride (CDFAA) as a low-cost and versatile fluoroalkylating reagent. Detailed mechanistic studies revealed that electron-transfer photocatalysis triggers mesolytic cleavage of a C-Cl bond generating a gem-difluoroalkyl radical. In the presence of alkene, this radical species acts as a unique intermediate that, under solvent-controlled reaction conditions, delivers a wide range of gem-difluorinated gamma-lactams, gamma-lactones, and promotes oxy-perfluoroalkylation. These protocols are flow- and batch-scalable, possess excellent chemo- and regioselectivity, and can be used for the late-stage diversification of complex molecules. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000572438Publication status
publishedExternal links
Journal / series
Angewandte Chemie. International EditionVolume
Pages / Article No.
Publisher
Wiley-VCHSubject
Anhydrides; gem-Difluoro Compounds; Late-Stage Functionalization; Photoredox; Radical MechanismsMore
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