Origins of stereoselectivity in the α-alkylation of chiral hydrazones.
Density functional theory calculations and experiment reveal the origin of stereoselectivity in the deprotonation-alkylation of chiral N-amino cyclic carbamate (ACC) hydrazones. When the ACC is a rigid, camphor-derived carbamate, the two conformations of the azaenolate intermediate differ in energy due to conformational effects within the oxazolidinone ring and steric interactions between the ACC and the azaenolate. An electrophile adds selectively to the less-hindered π-face of the azaenolate. Although it was earlier reported that use of ACC auxiliaries led to α-alkylated ketones with er values of 82:18 to 98:2, B3LYP calculations predict higher stereoselectivity. Direct measurement of the dr of an alkylated hydrazone prior to removal of the auxiliary confirms this prediction; the removal of the auxiliary under the reported conditions can compromise the overall stereoselectivity of the process.
Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, United States.
Elizabeth H
EH
Krenske
K N
KN
Houk
Daniel
D
Lim
Sarah E
SE
Wengryniuk
Don M
DM
Coltart
D000478:Alkylation; D002164:Camphor / Q000737:chemistry*; D002219:Carbamates / Q000737:chemistry*; D006835:Hydrazones / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D013237:Stereoisomerism
D002219:Carbamates; D006835:Hydrazones; D007659:Ketones; D002164:Camphor