Origin of the diastereofacial selectivity in the nucleophilic addition to chiral acyclic ketones. An ab initio MO study

Abstract

Ab initio MO calculations were carried out, at the MP2/6-311G(d,p)//MP2/6-31G(d) level, to investigate the conformational Gibbs energy of alkyl 1-phenylethyl ketones, C6H5CHCH3COR, 1 (R = CH3, C2H5, i-C3H7, t-C4H9). Rotamers a and a′ whereby R is synclinal to C6H5 and the benzylic methyl group is nearly eclipsed to CO have been shown to be the most stable in every case. Rotamer a is stabilized by a 5-member CH/π hydrogen bond and is more abundant than a′, which is stabilized by a less effective 6-member CH/π bond. The diastereomeric ratio of the product secondary alcohols in the nucleophilic addition to 1 was estimated on the basis of the ground-state rotamer distribution. The Gibbs energy of the diastereomeric transition states was also calculated for a model reaction (C6H5CHCH3COR + LiH) at the same level of approximation. The transition-state geometries leading to the predominant product are similar to those of the ground-state conformation. In geometries leading to the minor product, the relevant torsion angles are twisted to avoid unfavourable steric interactions. The short CH/π and CH/O distances suggest that these weak hydrogen bonds are operating in stabilizing the transition structures. The above two methods gave results consistent with each other. The mechanism of 1,2-asymmetric induction can thus be explained on the basis of the simple premise that the geometry of the transition state resembles the ground-state conformation of the substrate and the nucleophilic reagent approaches from the less hindered side of the carbonyl π-face.