Enantioselective Intermolecular Reductive Aldol Reaction to Ketones

Significance

The authors have developed a CuF-chiral bisphosphine-catalyzed intermolecular reductive aldol coupling with simple ketones. (EtO)₃SiH is used as the stoichiometric reductant. While the use of prochiral ketones (e.g., acetophenone) gave very low de and ee values, the use of symmetrical ketones gave much better results (up to 76% ee). Due to similar results obtained with the preformed silyl ketene acetals, the authors propose that in both cases, an in situ formed chiral copper enolate is responsible for the stereoselectivity.