Theoretical Investigation on the Oxazaborolidine-Ketone Interaction in Small Model Systems

The reductions of ketones by borane (BH3) with the Corey, Bakshi and Shibata (CBS) catalyst are important tools in asymmetric synthesis. Since substantial differences emerged depending on the method and basis set adopted in a theoretical study of the acetophenone reduction, the weak interaction responsible for the formation of the acetophenone-CBS complex was studied in model systems, with the aim to find the best compromise between quality of the description and computational costs. The major chosen model contained the most important elements of the acetophenone-CBS-BH3 complexes, that is the 1,3,2-oxazaborolidine ring with both a molecule of BH3 and acetone, the smallest possible ketone, coordinated to it. The effect of basis set and method on the description of the ketone-oxazaborolidine interaction along the B···O approaching path was investigated with several methods (HF, DFT-B3LYP, MP2) and basis sets (3-21G, 6-31G, 6-31G*, 6-31G**, 6-31+G**), taking into account basis set superposition errors, which can be significant even in the case of interactions involving two relatively large systems. Due to the remarkable structural changes occurring in the process, the effects of geometry deformation were also considered. The complexation of acetone is basically due to the electrostatic interaction between a Lewis acid/base couple, respectively the endocyclic boron and the carbonyl oxygen. Thus the electronic density drawn away from the C=O double bond makes the carbon atom more subject to hydride transfer, while the presence of the ring keeps the system rigid. The MP2 results turn out to be the closest to the QCISD(T) ones from QCISD(T)/6-31G*//HF/6-31G* calculations. In order to better analyze the nature of the interactions taking place in the complex, several dimers, smaller than the aforementioned model, were also considered. The solvent (tetrahydrofuran) effect on the adduct stability as well as on the association energy in the polarizable continuum model framework was taken into account at the 6-31G* level.