The Role of Menthyl Group in Catalyzed Asymmetric Diels−Alder Reactions. A Combined Quantum Mechanics/Molecular Mechanics Study

Abstract

The asymmetric Diels−Alder reactions of cyclopentadiene with the complex dienophiles AlCl3−menthyl acrylate and menthoxyaluminum dichloride−acrolein have been studied by means of combined Quantum Mechanics/Molecular Mechanics calculations. The part of the system involved in the reaction has been described using the AM1 method, whereas the MM3 force field has been used in order to account for interactions with the menthyl substituent. We focus our attention on the screening effect produced by the menthyl group, which may be placed in the dienophile or the catalyst. A reaction model has been proposed for the cycloaddition between cyclopentadiene and acrolein catalyzed by menthoxyaluminum dichloride, presenting different geometrical features from those proposed for an analogous reaction. Results indicate that the menthyl group adopts a stacked conformation preferentially, in contrast with previous Molecular Mechanics studies of similar systems. The weak steric hindrance of this conformation allows us to explain the rather low screening effect of the menthyl group. Finally, our results show that the use of the combined AM1/MM3 methodology avoids the artifactual stabilizations of nonbonded hydrogen atom pairs found in full AM1 calculations.