Effect of solvent on the stereoselectivity of reactions between hydroxyalkyl azides and ketones

COMP 226

Anna K. Manukyan, amanukya@odu.edu and Jennifer Radkiewicz-Poutsma, jradkiew@odu.edu. Department of Chemistry and Biochemistry, Old Dominion University, 4541 Hampton Blvd, Norfolk, VA 23529
Recently, a new diastereoselective reaction resulting in an N-hydroxyalkyl lactam was discovered. The starting materials, a hydroxyalkyl azide and a substituted cyclohexanone, form a hemiketal. The azide then attacks the carbonyl carbon giving an intramolecular Schmidt reaction. This process has the potential to be an important tool for synthesis. Thus, we have uesd ab initio calculations to explore the stereoselectivity of this modified Schmidt reaction. A preference for the N2+ leaving group was observed for the heterosubstituted cyclohexane intermediate. Results concerning the effect of solvent on our calculations and the effect of phenyl substituents on the cation-π interaction will be presented. Preliminary calculations on the mechanism of the Schmidt reaction will also be discussed.