Enantioselective Copper-Catalyzed Intermolecular Cyanobenzoyldifluoromethylation of Alkenes: Access to Chiral ß-Difluoroacyl Nitriles.

A novel asymmetric copper-catalyzed intermolecular cyanobenzoyldifluoromethylation of alkenes with iododifluoromethyl ketones and TMSCN has been reported, which provides a particularly valuable route to access chiral ß-difluoroacyl nitriles with excellent enantioselectivities. The method permits the efficient cyanation of varied ß-difluoroacyl-benzylic radicals in mild conditions with high functional group tolerance. The reaction proceeds through a radical pathway. In order to get insight into the stereochemical outcome, computational mechanistic studies were conducted.

Nickel-Catalyzed Coupling Reaction of α-Bromo-α-fluoroketones with Arylboronic Acids toward the Synthesis of α-Fluoroketones.

A nickel-catalyzed coupling reaction of α-bromo-α-fluoroketones with arylboronic acids was reported, which provides an efficient pathway to access 2-fluoro-1,2-diarylethanones in high yields. We also disclosed the synthesis of the monofluorination agents α-bromo-α-fluoroketones by using a trifluoroacetate release protocol. Mechanistic investigation indicated that a monofluoroalkyl radical is involved in the catalytic circle. Moreover, an important medical intermediate of flindokalner was synthesized via a nickel-catalyzed coupling reaction of α-bromo-α-fluoro-2-indolone and boronic ester.