Catalyst acidity sets enantioselectivity

Efforts to design better asymmetric catalysts that rely on hydrogen bonding to activate their substrates will get a leg up from a new study of the effect of catalyst acidity on such reactions (Angew. Chem. Int. Ed., DOI: 10.1002/anie.200700298). Hydrogen bonding, a common mode of substrate activation in enzymes, only recently has been exploited in synthetic asymmetric catalysts. Hoping to better understand the role hydrogen bonding plays in these reactions, Matthew S. Sigman and Katrina H. Jensen of the University of Utah systematically compared the activity of oxazoline catalysts of varying acidity in a hydrogen-bond-catalyzed hetero-Diels-Alder reaction between a diene and benzaldehyde. They found that both the reaction rate and the enantioselectivity are linearly correlated to the catalyst's acidity. That enantioselectivity directly tracks catalyst acidity "is especially exciting because it provides the basis for the design of new asymmetric catalysts," the researchers note. They're now working to determine what gives rise to this effect.