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Origin of the π‐Facial Stereoselectivity in the Addition of Nucleophilic Reagents to Chiral Aliphatic Ketones as Evidenced by High‐Level Ab Initio Molecular‐Orbital Calculations
Author(s) -
Takahashi Osamu,
Yamasaki Katsuyoshi,
Kohno Yuji,
Ueda Kazuyoshi,
Suezawa Hiroko,
Nishio Motohiro
Publication year - 2006
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.200600204
Subject(s) - conformational isomerism , diastereomer , chemistry , ab initio , nucleophile , stereochemistry , molecular orbital , crystallography , stereoselectivity , alkyl , molecule , computational chemistry , organic chemistry , catalysis
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‐ C 6 H 11 CHCH 3 COR (R=Me, Et, i Pr, and t Bu). In each case, one of the equatorial conformations was shown to be the most stable. Conformers with the axial CHCH 3 COR group were also shown to be present in an appreciable concentration. Short CH⋅⋅⋅CO and CH⋅⋅⋅OC distances were found in each stable conformation. The result was interpreted on the grounds of CH⋅⋅⋅π(CO) and CH⋅⋅⋅O hydrogen bonds, which stabilize the geometry of the molecule. The ratio of the diastereomeric secondary alcohols produced in the nucleophilic addition to cyclo‐ C 6 H 11 CHCH 3 COR 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= t Bu. The energy of the diastereomeric transition states in the addition of LiH to cyclo‐ C 6 H 11 CHCH 3 COR was also calculated for R=Me and t Bu. The product ratio did not differ significantly in going from R=Me to t Bu 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 π‐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 π face.