A palladium-catalysed enolate alkylation cascade for the formation of adjacent quaternary and tertiary stereocentres

The catalytic enantioslective synthesis of densely functionalized organic moleucles that contain all-carbon quaternary stereocentres is a challenge to modern chemical methodology. The catalytically controlled, asymmetric alpha-alkylation of ketones represents another difficult task and is of major interest to our and other research groups. We report here a palladium-catalysed enantioselective process that addresses both problems simultaneously and allows the installation of vicinal all-carbon quaternary and tertiary stereocentres at the alpha-carbon of a ketone in a single step. This multiple bond-forming process is carried out on readily available beta-ketoester starting materials and proceeds by conjugate addition of a palladium enolate, generated in situ, to activated Michael acceptors. As a result, the CO2 moiety of the substrate is displaced by a C-C fragment in an asymmetric cut-and-paste reaction with high yield, diastereomeric ration and enantiomeric excess.