The effect of hydrogen bond donors in asymmetric organocatalytic conjugate additions

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-beta-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-beta-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. (C) 2009 Elsevier Ltd. All rights reserved.