Hydrolysis and retro‐aldol cleavage of ethyl threo‐2‐(1‐adamantyl)‐3‐hydroxybutyrate: competing reactions

Abstract

AbstractThe hydrolysis of ethyl threo‐2‐(1‐adamantyl)‐3‐hydroxybutyrate (1) and the parent ester ethyl 3‐hydroxybutyrate (4) has been studied experimentally and computationally. In the hydrolysis of threo‐ester 1 with 2 M NaOH, predominantly retro‐aldol product was observed, whereas the hydrolyzed product was present in a minor amount. When the reaction is carried out under the same conditions with the parent ester ethyl 3‐hydroxybutyrate (4), hydrolyzed product is exclusively observed. The competitive pathways, namely hydrolysis and the retro‐aldol reaction for 1 and 4 were investigated using DFT calculations in the both gas and solvent phase. The calculated results in the solvent phase at B3LYP/6–31 + G* level revealed that the formation of retro‐aldol products is kinetically preferred over the hydrolysis of threo‐ester 1 in the presence of a base. However, the parent ester 4 showed that the retro‐aldol process is less favored than the hydrolysis process under similar conditions. The steric effect imposed by the bulky adamantyl group to enhance the activation barriers for the hydrolysis of the ethyl threo‐2‐(1‐adamantyl)‐3‐hydroxybutyrate (1) was further supported by the calculations performed with tert‐butyl group at the α‐carbon atom of ethyl 3‐hydroxybutyrate (7). Copyright © 2010 John Wiley & Sons, Ltd.