Kinetic isotope and thermodynamic analysis of the nornicotine-catalyzed aqueous aldol reaction

A series of kinetic isotope effects and thermodynamic studies were performed to test key predictions of a computationally derived model for a nornicotine-catalyzed aqueous aldol reaction. The relative energies of the two computationally-derived transition states were challenged using the proton inventory, which demonstrated that a single water molecule from the solvent is involved in, or before, the rate-limiting step. These results suggest the importance of proton transfer in the aqueous aldol reaction and may assist the development of other aqueous organocatalytic processes. (c) 2005 Elsevier Ltd. All rights reserved.