Theoretical investigation of Prolyl‐Histidine‐catalyzed intermolecular aldol reaction

Abstract

AbstractThe mechanism of aldol reaction of acetone and benzaldehyde catalyzed by Prolyl‐Histidine dipeptide was studied using density functional theory (DFT) method at ωB97XD/6‐31G(d,p) level. The calculated results indicated that this reaction consisted of the following processes: (I) the formation of alcohol intermediate with acetone and Pro‐His by water assistance; (II) the formation of enamine by alcohol dehydration; (III) the formation of imine complexes by electrophilic addition of enamine and benzaldehyde; and (IV) the formation of aldol products by imine complex combining with water to obtain S or R type products after removing the catalyst. The calculated results show that the generation of enamine is the rate‐determining step, and the main product is cis‐enamine with a free energy barrier of 19.6 kcal/mol. The calculated enantiomeric excess (ee) value of aldol product is 100%.