Cu-catalyzed photoredox chlorotrifluoromethylation of polysubstituted alkenes and pharmacological evaluation

Abstract

A visible-light-mediated chlorotrifluoromethylation catalyzed by a copper-based photo-redox catalyst of internal alkenes is reported. The reaction proceeds with complete regioselectivity under mild reaction conditions using commercially available F₃CSO₂Cl as both the trifluoromethyl and chlorine source, leading to the synthesis of added-value chemicals with atom-economy. A vast array of internal alkenes were functionalized in decent to good yields, highlighting a great tolerance to various functional groups. A radical process starting from a single electron reduction of F₃CSO₂Cl with an excited copper catalyst was evidenced, and the synthetic utility of our products was showcased by the synthesis of valuable molecules such as α-trifluoromethylated amides, α-trifluoromethylated-β-aminoamides, and trifluoromethyl alkenes. In addition, the library was evaluated in vitro for its cytotoxicity against lung carcinoma (A549) and colorectal adenocarcinoma (DLD-1) cell lines, and for its antifungal and antibacterial activities against C. albicans, E. coli and S. aureus strains, respectively. Compounds 2a, 2m, 2n, and 2o demonstrated anticancer activities, while compounds 2a, 6g, and 6h exhibited weak antibacterial activities, underscoring the therapeutic potential of this class of molecules and suggesting opportunities for further optimization.