Document Detail

Stereocontrolled alkylative construction of quaternary carbon centers.
MedLine Citation:
PMID:  18788739     Owner:  NLM     Status:  MEDLINE    
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.
David A Kummer; William J Chain; Marvin R Morales; Olga Quiroga; Andrew G Myers
Related Documents :
15844999 - Total syntheses of yingzhaosu a and of its c(14)-epimer including the first evaluation ...
17985899 - Mo-catalyzed regio-, diastereo-, and enantioselective allylic alkylation of 3-aryloxind...
20000669 - Allylcopper intermediates with n-heterocyclic carbene ligands: synthesis, structure, an...
20527739 - Rhenium-catalyzed synthesis of indenones by novel dehydrative trimerization of aryl ald...
12375959 - Highly stereoselective addition of stannylcuprates to alkynones.
18385839 - Urea derivatives are highly active catalysts for the base-mediated generation of termin...
1061139 - Structure of the iron complex in methemerythrin.
24046589 - Bis(μ-6-meth-oxy-2-{[(3-oxidoprop-yl)imino]-meth-yl}phenolato)nickel(ii) methanol mono...
10219879 - Reorientation of the acetyl group of the photoactive bacteriopheophytin in reaction cen...
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    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Amides / chemistry
Carbon / chemistry*
Models, Molecular
Molecular Structure
Grant Support
Reg. No./Substance:
0/Amides; 7440-44-0/Carbon

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

Previous Document:  Nanoscale organization of thiol and arylsulfonic acid on silica leads to a highly active and selecti...
Next Document:  Stereospecific total synthesis of somocystinamide A.