Copper–Catalyzed Thiocarbonylation and Thiolation of Alkyl Iodides

In the present study, an efficient Cu-catalyzed transthiolation of alkyl iodides has been developed. Notably, in the presence of CO, thioesters could also be obtained with copper and cobalt as...

Copper-Catalyzed Difluoromethylation of Alkyl Halides Enabled by Aryl Radical Activation of Carbon–Halogen Bonds

The engagement of unactivated alkyl halides in copper-catalyzed cross-coupling reactions has been historically challenging, due to their low reduction potential and the slow oxidative addition of copper(I) catalysts. In this work, we report a novel strategy that leverages the halogen abstraction ability of aryl radicals, thereby engaging a diverse range of alkyl iodides in copper-catalyzed Negishi–type cross-coupling reactions at room temperature. Specifically, aryl radicals generated via copper catalysis efficiently initiate the cleavage of the carbon–iodide bonds of alkyl iodides. The alkyl radicals thus generated enter the copper catalytic cycles to couple with a difluoromethyl zinc reagent, thus furnishing the alkyl difluoromethane products. This unprecedented Negishi–type difluoromethylation approach has been applied to the late-stage modification of densely functionalized pharmaceutical agents and natural products.

Copper-Catalyzed Difluoromethylation of Alkyl Halides Enabled by Aryl Radical Activation of Carbon–Halogen Bonds

The engagement of unactivated alkyl halides in copper-catalyzed cross-coupling reactions has been historically challenging, due to their low reduction potential and the slow oxidative addition of copper(I) catalysts. In this work, we report a novel strategy that leverages the halogen abstraction ability of aryl radicals, thereby engaging a diverse range of alkyl iodides in copper-catalyzed Negishi–type cross-coupling reactions at room temperature. Specifically, aryl radicals generated via copper catalysis efficiently initiate the cleavage of the carbon–iodide bonds of alkyl iodides. The alkyl radicals thus generated enter the copper catalytic cycles to couple with a difluoromethyl zinc reagent, thus furnishing the alkyl difluoromethane products. This unprecedented Negishi–type difluoromethylation approach has been applied to the late-stage modification of densely functionalized pharmaceutical agents and natural products.