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

Site-selective trifluoromethylation of silyl dienol ethers derived from alpha,ss-unsaturated aldehydes, ketones, and amides was achieved for the first time in the remote gamma 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 center dot R-F radical sources enables the generalization of the reaction to other perfluoroalkyl groups (R-F = CF2H, C4F9). Importantly, an unprecedented enantioselective C(sp(3))-H perfluoroalkylation process is disclosed.

Automated summary

Site-selective trifluoromethylation of silyl dienol ethers derived from alpha,ss-unsaturated aldehydes, ketones, and amides was achieved for the first time in the remote gamma position. An unprecedented enantioselective C(sp(3))-H perfluoroalkylation process is disclosed.