Copper-catalyzed highly switchable defluoroborylation and hydrodefluorination of 1-(trifluoromethyl)alkynes

Abstract

CF2-containing compounds hold significant potential in drug discovery, organic synthesis, and materials science. However, synthesizing various CF2-containing building blocks from a single compound remains challenging. Here, we present a Cu-catalyzed, switchable defluoroborylation and hydrodefluorination of trifluoromethylated alkynes, yielding four types of CF2-containing compounds. The chemo- and regio-selective sp2/sp3 1,2-diborylation and sp2 monoborylation of 1-(trifluoromethyl)alkynes are controlled by adjusting the solvent and ligand quantity. Additionally, altering the base allows selective generation of gem-difluoroalkenes or difluoromethylalkenes. Notably, our method prevents over-defluorination of the CF3 group on unsaturated C-C bonds during nucleophilic additions, preserving the pharmaceutically valuable CF2 group. Experimental data and density functional theory (DFT) calculations elucidate the regioselectivities of Cu-Bpin addition and the regulatory role of the ligand in selective deborylation processes.