Nickel-Catalyzed Hydrogen-Borrowing Strategy for α-Alkylation of Ketones with Alcohols: A New Route to Branched gem-Bis(alkyl) Ketones

The alpha-alkylation of ketones using an earth-abundant and nonprecious NiBr2/L1 system is reported. This nickel-catalyzed reaction could be performed in gram scale and successfully applied in the synthesis of donepezil (Alzheimer's drug) and functionalization of steroid hormones and fatty acid derivatives. Synthesis of N-heterocycles, methylation of ketones, and one-pot double alkylation to bis-hetero aryl ketones using two different alcohols with a single catalyst broadens the scope of the catalytic protocol. Preliminary mechanistic studies using defined Ni-H species and deuterium-labeling experiments established the participation of the borrowing-hydrogen strategy.