Origins of stereoselectivity in the α-alkylation of chiral hydrazones

Krenske, Elizabeth H., Houk, K. N., Lim, Daniel, Wengryniuk, Sarah E. and Coltart, Don M. (2010) Origins of stereoselectivity in the α-alkylation of chiral hydrazones. Journal of Organic Chemistry, 75 24: 8578-8584. doi:10.1021/jo1019877

Author Krenske, Elizabeth H.
Houk, K. N.
Lim, Daniel
Wengryniuk, Sarah E.
Coltart, Don M.
Title Origins of stereoselectivity in the α-alkylation of chiral hydrazones
Journal name Journal of Organic Chemistry   Check publisher's open access policy
ISSN 0022-3263
Publication date 2010-12-17
Year available 2010
Sub-type Article (original research)
DOI 10.1021/jo1019877
Open Access Status DOI
Volume 75
Issue 24
Start page 8578
End page 8584
Total pages 7
Place of publication Washington, United States
Publisher American Chemical Society
Language eng
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 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.
Keyword Lithio azaallylic systems
Asymmetric synthesis
Acyclic ketones
Enantioselective alkylation
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID GM-36700
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
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