Direct β-Alkylation of Ketones and Aldehydes via Pd-Catalyzed Redox Cascade

We report a direct beta-alkylation of ketones and aldehydes with simple alkyl bromides through a Pd-catalyzed redox-cascade strategy. The use of a Cu cocatalyst is important for improved efficiency. The reaction is redox-neutral, without the need for strong acids or bases. Both cyclic and acyclic ketones, as well as alpha-branched aldehydes, are suitable substrates for coupling with secondary and tertiary alkyl bromides. Concise formal synthesis of Zanapezil is achieved using this beta-alkylation method.