The effect of hydrogen bond donors in asymmetric organocatalytic conjugate additions

Abstract

A series of primary amine organocatalysts with various hydrogen bond donors were prepared and examined in the conjugate addition of isobutyraldehyde and acetone to trans-β-nitrostyrene and (E)-methyl 2-oxo-4-phenylbut-3-enoate. The effect of N-H acidity and hydrogen-bonding modes of the catalysts on the catalytic activity and enantioselectivity was studied. The experimental results did not support a general correlation of N-H acidity and hydrogen-bonding modes with catalytic activity and enantioselectivity. The catalysts with double hydrogen-bonding interactions provided better catalytic activities and enantioselectivities than the catalysts with single hydrogen-bonding interactions for the reaction of trans-β-nitrostyrene. The catalyst with the most acidic N-H bond showed the best catalytic activity and enantioselectivity for the reaction of (E)-methyl 2-oxo-4-phenylbut-3-enoate. These results suggest that the effect of hydrogen bond donors in organocatalytic reactions may be highly dependent on the substrates and the reaction conditions. © 2009 Elsevier Ltd. All rights reserved.