A palladium-catalysed enolate alkylation cascade for the formation of adjacent quaternary and tertiary stereocentres.
The catalytic enantioselective synthesis of densely functionalised organic molecules containing all-carbon quaternary stereocentres is a challenge to modern chemical methodology research. The catalytically controlled asymmetric alpha-alkylation of ketones represents another difficult task and has been of major interest to our and other research groups in the past. We now report a palladium-catalyzed enantioselective process that addresses both problems at once 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 via conjugate addition of an in situ-generated palladium enolate to activated Michael acceptors. In other words, the CO(2)-moiety of the substrate is displaced by a C-C fragment in an asymmetric cut-and-paste reaction. The products are obtained in high yield, diastereomeric ratio, and enantiomeric excess.
Streuff
Jan
J
The Arnold and Mabel Beckman Laboratories of Chemical Synthesis, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
White
David E
DE
Virgil
Scott C
SC
Stoltz
Brian M
BM