Cu-catalyzed Photoredox Chlorotrifluoromethylation of Polysubstituted Alkenes and Pharmacological Evaluation

Abstract

A visible-light-mediated chlorotrifluoromethylation catalyzed by Copper-based photoredox catalyst of internal alkenes is depicted. The reaction proceeds with total regioselectivity under mild reaction conditions using commercially available F3CSO2Cl as both the trifluoromethyl and chlorine source, leading to a synthesis of added-value chemicals with atom-economy. A vast array of internal alkenes was functionalized with decent to good yields highlighting a great tolerance to various functional groups. A radical process starting through 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 trifluoromethylatedamides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 as well as antifungal and antibacterial activity, against C. albicans, E. coli and S. aureus strains, respectively. Compounds 2a, 2m, 2n, and 2o demonstrated anticancer activity, while compounds 2a, 6g, and 6h exhibited weak antibacterial activity, underscoring the therapeutic promise of this class of molecules and suggesting opportunities for further optimization.