Remote Radical Trifluoromethylation: A Unified Approach to the Selective Synthesis of γ-Trifluoromethyl α,β-Unsaturated Carbonyl Compounds

Marina Briand (1) , Linh Thai (1) , Flavien Bourdreux (1) , Nicolas Vanthuyne (2) , Xavier Moreau (1) , Emmanuel Magnier (1) , Elsa Anselmi (1) , Guillaume Dagousset (1)

1 ILV - Institut Lavoisier de Versailles
2 ISM2 - Institut des Sciences Moléculaires de Marseille

Site-selective trifluoromethylation of silyl dienol ethers derived from α,β-unsaturated aldehydes, ketones, and amides was achieved for the first time in the remote γ position. This photoredox catalyzed process is quite general to compounds bearing many functionalities and is applicable to the late-stage functionalization of biorelevant molecules. The use of S-perfluoroalkyl sulfoximines as ·RF radical sources enables the generalization of the reaction to other perfluoroalkyl groups (RF = CF2H, C4F9). Importantly, an unprecedented enantioselective C(sp3)–H perfluoroalkylation process is disclosed.

Domains: Chemical Sciences; Organic chemistry

Marina Briand, Linh Thai, Flavien Bourdreux, Nicolas Vanthuyne, Xavier Moreau, et al.. Remote Radical Trifluoromethylation: A Unified Approach to the Selective Synthesis of γ-Trifluoromethyl α,β-Unsaturated Carbonyl Compounds. Organic Letters, 2022, 24 (51), pp.9375-9380. ⟨10.1021/acs.orglett.2c03676⟩. ⟨hal-03936896⟩