Origins of Stereoselectivity in the alpha-Alkylation of Chiral Hydrazones
Abstract
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 pi-face of the azaenolate. Although it was earlier
reported that use of ACC auxiliaries led to a-alkylated ketones with er values of
82:18 to 98:2, B3LYP calculations predict higher stereosclectivity. 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.
Type
Other articleSubject
lithio azaallylic systemsasymmetric-synthesis
acyclic ketones
enantioselective alkylation
organolithium compounds
ab-initio
density
cyclohexanone
solvation
anions
chemistry, organic
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https://hdl.handle.net/10161/4064Published Version (Please cite this version)
10.1021/jo1019877Citation
Krenske,Elizabeth H.;Houk,K. N.;Lim,Daniel;Wengryniuk,Sarah E.;Coltart,Don M.. 2010.
Origins of Stereoselectivity in the alpha-Alkylation of Chiral Hydrazones. Journal
of Organic Chemistry 75(24): 8578-8584.
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