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

Angew Chem Int Ed Engl. 2023 Apr 24;62(18):e202215855. doi: 10.1002/anie.202215855. Epub 2023 Jan 25.

Abstract

A practical method for the efficient and enantioselective preparation of versatile ketones and aldehydes that contain an α-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.

Keywords: Allyl Addition; Copper; Enantioselective; Ketone; Quaternary Carbon.