A Catalytic Method for the Enantioselective Synthesis of α-Quaternary Ketones, α-Ketoesters and Aldehydes

A practical method for the efficient and enantioselective preparation of versatile ketones and aldehydes that contain an alpha-quaternary stereocenter is described. Reactions utilize simple carboxylic acid or ester starting materials, a monodentate chiral phosphine, and afford a variety of aryl, alkenyl, alkynyl, and alkyl-substituted ketone and aldehyde products in 25-94 % yield and 90 : 10 to >99 : 1 enantiomeric ratio. Reactions proceed by acyl substitution with in situ formed chiral allylic nucleophiles, and display selectivity and conversion dependence on a protic additive. The utility of the approach is demonstrated through several product transformations.

Automated summary

A practical method is presented for the preparation of versatile ketones and aldehydes containing an alpha-quaternary stereocenter. The method utilizes simple starting materials and a chiral phosphine catalyst, and provides a variety of substituted ketone and aldehyde products in good yield and high enantiomeric excess. The reactions proceed via acyl substitution with chiral allylic nucleophiles, and show selectivity and conversion dependence on a protic additive. The utility of this approach is demonstrated through several product transformations.