On the mechanism of catalytic enantioselective hetero-Diels-Alder reactions of carbonyl compounds catalyzed by chiral aluminum complexes - a concerted, step-wise or Mukaiyama-aldol pathway

摘要

The mechanism for the hetero-Diels-Alder reaction of benzaldehyde with Danishefsky's diene catalyzed by various types of achiral and chiral aluminum complexes has been studied from a theoretical point of view using semi-empirical and ab initio calculations. The uncatalyzed reaction proceeds as a concerted reaction with an unsymmetrical transition state. The catalytic reaction has been studied using first (MeO)(2)AlMe, followed by (S)-BINOL-AlMe as the catalysts, and the transition states and intermediates have been calculated for different reaction paths. The catalyst activates benzaldehyde making the carbon atom in the carbonyl, functionality more electrophilic. Attempts to calculate a concerted reaction path failed. However, a two-step process, the first step being a nucleophilic attack of the activated diene to the carbonyl carbon atom, with a transition-state energy of up to 13 kcal mol(-1), depending on the catalyst and calculation method used, was found to take place leading to an aldol-like local energy-minimum intermediate. The second step, the ring-closure, which has a significantly lower transit-ion-state energy leads to the hetero-Diels-Alder adduct. The mechanistic aspects of the catalytic hetero-Diels-Alder reaction is discussed on the basis of the calculations. (C) 2001 Elsevier Science Ltd. All rights reserved. [References: 44]