The effect of solvent on the stereoselectivity of reactions between hydroxyalkyl azides and ketones

• Published in: Journal of molecular structure. Theochem 2006-08, Vol.766 (2), p.105-112
• Main Authors: Manukyan, Anna K., Radkiewicz-Poutsma, Jennifer L.
• Format: Article
• Language: English
• Subjects: Cation-π interactions; CPCM; Diastereoselectivity; Schmidt reaction
• ISSN: 0166-1280; 1872-7999
• DOI: 10.1016/j.theochem.2006.04.008

Reactions between achiral 4-substituted cyclohexanones and chiral hydroxyalkyl azides can give asymmetric ring expansion products. Previously, we carried out quantum chemical calculations on the reactions involving 2-R-hydroxypropyl azides to determine the cause of the observed diastereoselectivities. We found that the axial/equatorial ratio of the chiral substituent in the resulting heterocyclohexyl intermediate was the controlling factor. However, our predicted product ratio for 2-phenylhydroxypropyl azide did not agree well with experiment. We attributed this problem to the lack of solvent in our calculations, since the phenyl axial/equatorial ratio was strongly influenced by a cation-π interaction, which should be shielded in solvent. Therefore, we have added solvent via the CPCM method to our previous calculations. We observed little change in the predicted selectivities for R=Me or i-Pr, which are close to their experimental values. For R=Ph, we now predict essentially no preference for either diastereomer, in agreement with experiment. Surprisingly, the charge–dipole interaction between the oxygen and N 2 + group was less affected by solvent than the cation-π interaction. In addition, a possible gas-phase electrostatic interaction between the methyl group (R=Me) and the cationic N 2 group was revealed.