Nickel-Catalyzed Hydrotrifluoroalkylation of Alkynes to Construct Allylic Trifluoromethyl Terminal Alkenes.

Herein, we describe a nickel-catalyzed hydrotrifluoroalkylation of terminal alkyne for the synthesis of a manifold allylic trifluoromethyl terminal alkene. The combination of nitrogen and phosphine ligands, especially electron-rich ones, plays an indispensable role in the course of the reaction, promoting the reactivity to a remarkable level, demonstrating high efficiency, broad substrate scope, and favorable functional group compatibility. The strategy provides a facile method for the synthesis of diversified allylic CF3-containing drugs and bioactive molecules.

Asymmetric construction of allylicstereogenic carbon center featuring atrifluoromethyl group via enantioselective reductive fluoroalkylation.

Emerging as a powerful tool for lead optimization in pharmaceutical research and development, to develop the facile, general protocols that allows the incorporation of fluorine-containing motif in drug candidates has accumulated enormous research interest in recent years. Among these important motifs, the incorporation of strategic motif CF3 on aliphatic chain especially with the concomitant construction of trifluoromethylated alkanes bearing a CF3-substituted stereogenic carbon, is of paramount importance. Herein, we disclose an asymmetric nickel-catalyzed reductive trifluoroalkylation of alkenyl halides for enantioselective syntheses of diverse α-trifluoromethylated allylic alkanes, offering a general protocol to access the trifluoromethyl analogue to chiral α-methylated allylic alkanes, one of the most prevalent key components among natural products and pharmaceuticals. Utilities of the method including the application of the asymmetric trifluoroalkylation on multiple biologically active complex molecules, derivatization of transformable alkenyl functionality were demonstrated, providing a facile method in the diversity-oriented syntheses of CF3-containing chiral drugs and bioactive-molecules.