A Photochemical Organocatalytic Strategy for the α-Alkylation of Ketones by using Radicals

Reported herein is a visible-light-mediated radical approach to the alpha-alkylation of ketones. This method exploits the ability of a nucleophilic organocatalyst to generate radicals upon S(N)2-based activation of alkyl halides and blue light irradiation. The resulting open-shell intermediates are then intercepted by weakly nucleophilic silyl enol ethers, which would be unable to directly attack the alkyl halides through a traditional two-electron path. The mild reaction conditions allowed functionalization of the alpha position of ketones with functional groups that are not compatible with classical anionic strategies. In addition, the redox-neutral nature of this process makes it compatible with a cinchona-based primary amine catalyst, which was used to develop a rare example of enantioselective organocatalytic radical alpha-alkylation of ketones.