Ruthenium-NHC Catalyzed α‑Alkylation of Methylene Ketones Provides Branched Products through Borrowing Hydrogen Strategy

The α-alkylation of a broad range of methylene ketones was achieved using a ruthenium­(II)-NHC catalyst under borrowing hydrogen conditions. Primary alcohols served as alkylating agents and could be used in a one-to-one stoichiometry with respect to the ketone. The selectivity of the process for methyl over branched ketones enabled a one-pot double alkylation protocol utilizing two different alcohols with a single catalyst. Moreover, this methodology could be applied directly to the one-step synthesis of donepezil, the best-selling drug for the treatment of Alzheimer’s disease.