Ab initio approach to understanding the stereoselectivity of reactions between hydroxyalkyl azides and ketones

A new stereoselective version of the Schmidt reaction has been discovered by Aubé and co-workers (J. Am. Chem. Soc. 2003, 125, 7914-7922). Quantum chemical calculations reported in this paper were carried out to examine the observed diastereoselectivities. The azide attack step is found to be reversible, but a thermodynamic preference for the equatorial attack product is observed. The final stereoselectivity of the reaction is determined by the axial/equatorial ratio of the chiral substituent in the resulting intermediate. In the case of 2-R-hydroxypropyl azides, interesting axial/equatorial preferences are observed. In particular, the phenyl substituent shows a preference for the axial position resulting from a novel interaction with a N(2) cationic group.