Stereoselectivity of hydroxyethyl azide reactions

COMP 197

Donna G. Withrow, and Jennifer L. Poutsma. Department of Chemistry and Biochemistry, Old Dominion University, 4541 Hampton Boulevard, Norfolk, VA 23529
A modified Schmidt reaction was found by Jeffrey Aube and co-workers which showed experimentally that high diastereoselectivity was possible for the final lactam product (J. Am. Chem. Soc. 2003, 125, 7914-7922). Experimental observations for the hydroxyethyl azide reaction showed that the preferred product resulted from a syn conformation of the N2 and phenyl groups of the intermediate. Ab initio calculations were carried out to determine why this stereoselective preference is seen. Prior studies have been completed by Deborah Hewlett and Jennifer Poutsma on the stereoselectivity of hydroxypropyl azide reactions (J. Org. Chem. 2004, 69, 3439-3446). Experimental results by Aube and the ab initio calculations showed that the stereoselectivity was a result of a preference for the equatorial conformer in the intermediate. However, it was noted that when the phenyl group was in an axial position that there was a favored interaction with the N2 group and the stereoselectivy decreased. This was shown to be the direct result of a cation-pi interaction. This cation-pi interaction is believed to be the driving force in the preference of the hydroxyethyl azide reactions as well. Gas phase calculations completed thus far show a preference for the syn conformation resulting directly from electrostatics. This preference is higher than what is shown experimentally. The addition of solvent to the calculations is expected to bring the preference closer to what was seen experimentally. To further study this interaction the phenyl group will be replaced by a more negative methoxy group.