A Lewis Acid-Controlled Enantiodivergent Epoxidation of Aldehydes

Two epoxidation catalysts, one of which consists of two VANOL ligands and an aluminum and the other that consists of two VANOL ligands and a boron, were compared. Both catalysts are highly effective in the catalytic asymmetric epoxidation of a variety of aromatic and aliphatic aldehydes with diazoacetamides, giving high yields and excellent asymmetric inductions. The aluminum catalyst is effective at 0 °C and the boron catalyst at -40 °C. Although both the aluminum and boron catalysts of (R)-VANOL give very high asymmetric inductions (up to 99% ee), they give opposite enantiomers of the epoxide. The mechanism, rate- and enantioselectivity-determining step, and origin of enantiodivergence are evaluated using density functional theory calculations.