Origin of the pi-facial stereoselectivity in the addition of nucleophilic reagents to chiral aliphatic ketones as evidenced by high-level ab initio molecular-orbital calculations.
Ab initio molecular-orbital (MO) calculations were carried out, at the MP2/6-311++G(d,p)//MP2/6-31G(d) level, to investigate the conformational Gibbs energy of alkyl 1-cyclohexylethyl ketones, cyclo-C6H11CHCH3-CO-R (R = Me, Et, iPr, and tBu). In each case, one of the equatorial conformations was shown to be the most stable. Conformers with the axial CHCH3COR group were also shown to be present in an appreciable concentration. Short C-H...C=O and C-H...O=C distances were found in each stable conformation. The result was interpreted on the grounds of C-H...pi(C=O) and C-H...O hydrogen bonds, which stabilize the geometry of the molecule. The ratio of the diastereomeric secondary alcohols produced in the nucleophilic addition to cyclo-C6H11CHCH3-CO-R was estimated on the basis of the conformer distribution. The calculated result was consistent with the experimental data previously reported: the gradual increase in the product ratio (major/minor) along the series was followed by a drop at R = tBu. The energy of the diastereomeric transition states in the addition of LiH to cyclo-C6H11CHCH3-CO-R was also calculated for R = Me and tBu. The product ratio did not differ significantly in going from R = Me to tBu in the case of the aliphatic ketones. This is compatible with the above result calculated on the basis of the conformer distribution. Thus, the mechanism of the pi-facial selection can be explained in terms of the simple premise that the geometry of the transition state resembles the ground-state conformation of the substrates and that the nucleophilic reagent approaches from the less-hindered side of the carbonyl pi face.
Takahashi
Osamu
O
Department of Chemistry, Graduate School of Science, Hiroshima University, Kagamiyama, Higashi-Hiroshima 739-8526, Japan. shu@hiroshima-u.ac.jp
Yamasaki
Katsuyoshi
K
Kohno
Yuji
Y
Ueda
Kazuyoshi
K
Suezawa
Hiroko
H
Nishio
Motohiro
M