Dynamic Kinetic Asymmetric Allylation of Ketones: Stereodivergent Synthesis of E - or Z -Substituted α,β-Stereogenic Tertiary Alcohols

Despite the widespread occurrence of enantiomerically enriched tertiary alcohols in bioactive molecules and pharmaceuticals, efficient methods for preparing optically pure α,β-stereogenic tertiary alcohols remain scarce. Here, we report a dynamic kinetic asymmetric allylation of readily available racemic ketones with 2-aza-1,4-dienes. Notably, through the judicious selection of chiral ligands for copper catalysts, both E- and Z-isomers can be accessed with high efficiency and stereocontrol. Density functional theory (DFT) calculations reveal that ligand-controlled face-selective attacks via distinct allylcopper intermediates dictate the stereodivergent E/Z selectivity. This reaction achieves excellent diastereo- and enantioselectivity, accommodates a broad range of heterocyclic substrates, and exhibits extensive functional group tolerance. We demonstrate the utility of this protocol by modifying Profen-type drugs and rapidly synthesizing complex drug molecules. This study provides a versatile and efficient route to diverse chiral tertiary alcohols, offering a powerful tool for pharmaceutical assembly.