Using theozymes for designing transition‐state analogs for the intramolecular aldol reaction of δ‐diketones

Resumen

Abstract Two theozymes for the intramolecular aldol reaction of δ‐diketones have been studied using ab initio methods. The presence of both acid/base residues favors several steps of the aldol reaction. The appropriate positioning of these residues can accelerate one of two diastereromeric reaction pathways, the catalyzed aldol reaction being highly stereoselective. Analysis of the geometrical parameters, charge distribution, and the shape of molecular electrostatic potential for the corresponding acid/base catalyzed transition structure allows us to design adequate transition‐state analogs to favor a reactive channel of this intramolecular aldol reaction. © 2001 John Wiley & Sons, Inc. Int J Quant Chem 83: 338–347, 2001