Pd(0)-Catalyzed Chemo-, Diastereo-, and Enantioselective α-Quaternary Alkylation of Branched Aldehydes

Quaternary carbon stereocenters are ubiquitous in a wide variety of organic compounds and drug molecules. Highly enantioselective construction of such quaternary carbon centers poses a singular challenge due to the steric repulsion between the four different carbon substituents. Herein, we report a novel strategy to control the enantioselective construction of chiral α-quaternary aldehydes from racemic α-branched aldehydes. Distinct from the established chiral α-quaternary aldehyde synthesis, this project employed a chiral π-allyl–Pd complex neighboring the enolate to determine both the enantio- and diastereoselectivity. The synthetic utility of the products has been highlighted by a series of derivatizations, and the potential of this method has been extended to the synthesis of chiral α-quaternary ketones. Furthermore, this reaction exemplifies the themes of step and atom economy, in addition to the principles of diversity-oriented synthesis.