Highly Diastereoselective Lithiation and Substitution of an (S)-Prolinyl Thiocarbamate via Sterically Homogeneous Lithio(thiocarbamate): Synthesis of Enantiomerically Pure Prolinethiols

Highly diastereoselective lithiation–substitution reactions of an (S)‐proline derived S‐alkyl thiocarbamate was accomplished. The configuration of the predominant alkyllithium species and the stereochemical course of the electrophilic substitution reactions are deduced by a combination of X‐ray crys...

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Bibliographic Details
Published in:Chemistry : a European journal 2007-01, Vol.13 (22), p.6419-6429
Main Authors: Sonawane, Ravindra P., Mück-Lichtenfeld, Christian, Fröhlich, Roland, Bergander, Klaus, Hoppe, Dieter
Format: Article
Language:English
Subjects:
carbamates
chiral auxiliaries
configuration analysis
lithium
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Summary:Highly diastereoselective lithiation–substitution reactions of an (S)‐proline derived S‐alkyl thiocarbamate was accomplished. The configuration of the predominant alkyllithium species and the stereochemical course of the electrophilic substitution reactions are deduced by a combination of X‐ray crystal structure analysis, NMR spectroscopic studies, deuteration/dedeuteration experiments, and quantum chemical calculations. The lithium intermediate (S,S)‐9 was found to be kinetically and thermodynamically favoured, whereas (S,R)‐9 rapidly epimerizes. A stereohomogeneous α‐thiocarbanion: An (S)‐prolinol‐derived thiocarbamate 1 is deprotonated with high diastereoselectivity to form the (S,S)‐lithium compound 2, which is substituted by several electrophiles with retention of the configuration.
ISSN:0947-6539
1521-3765
DOI:10.1002/chem.200601853