Document Detail


Stereocontrolled alkylative construction of quaternary carbon centers.
MedLine Citation:
PMID:  18788739     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Protocols for the stereodefined formation of alpha,alpha-disubstituted enolates of pseudoephedrine amides are presented followed by the implementation of these in diastereoselective alkylation reactions. Direct alkylation of alpha,alpha-disubstituted pseudoephedrine amide substrates is demonstrated to be both efficient and diastereoselective across a range of substrates, as exemplified by alkylation of the diastereomeric pseudoephedrine alpha-methylbutyramides, where both substrates are found to undergo stereospecific replacement of the alpha-C-H bond with alpha-C-alkyl, with retention of stereochemistry. This is shown to arise by sequential stereospecific enolization and alkylation reactions, with the alkyl halide attacking a common pi-face of the E- and Z-enolates, proposed to be opposite the pseudoephedrine alkoxide side chain. Pseudoephedrine alpha-phenylbutyramides are found to undergo highly stereoselective but not stereospecific alpha-alkylation reactions, which evidence suggests is due to facile enolate isomerization. Also, we show that alpha,alpha-disubstituted pseudoephedrine amide enolates can be generated in a highly stereocontrolled fashion by conjugate addition of an alkyllithium reagent to the s-cis-conformer of an alpha-alkyl-alpha,beta-unsaturated pseudoephedrine amide, providing alpha,alpha-disubstituted enolate substrates that undergo alkylation in the same sense as those formed by direct deprotonation. Methods are presented to transform the alpha-quaternary pseudoephedrine amide products into optically active carboxylic acids, ketones, primary alcohols, and aldehydes.
Authors:
David A Kummer; William J Chain; Marvin R Morales; Olga Quiroga; Andrew G Myers
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2008-09-13
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  130     ISSN:  1520-5126     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-10-01     Completed Date:  2008-12-22     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13231-3     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Alkylation
Amides / chemistry
Carbon / chemistry*
Models, Molecular
Molecular Structure
Stereoisomerism
Grant Support
ID/Acronym/Agency:
GM007598-30/GM/NIGMS NIH HHS; T32 GM007598/GM/NIGMS NIH HHS; T32 GM007598-30/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Amides; 7440-44-0/Carbon
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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