Direct Organocatalytic Asymmetric α-Chlorination of Aldehydes

Nis Halland, Alan Braunton, Stephan Bachmann, Mauro Marigo, and Karl Anker Jørgensen*
Danish National Research Foundation, Center for Catalysis, Department of Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark
J. Am. Chem. Soc., 2004, 126 (15), pp 4790–4791
DOI: 10.1021/ja049231m
Publication Date (Web): March 27, 2004
Copyright © 2004 American Chemical Society
*

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

, kaj@chem.au.dk

Abstract

Abstract Image

The direct organocatalytic enantioselective α-chlorination of aldehydes has been developed. The reaction proceeds for a series of different aldehydes with NCS as the chlorine source using easily available catalysts such as l-proline amide and (2R,5R)-diphenylpyrrolidine. The α-chloro aldehydes are obtained in up to 99% yield and up to 95% ee. The synthetic utility of the enantioselective α-chlorination of aldehydes is demonstrated by transformation of the α-chloro aldehydes to the corresponding α-chloro alcohols (>90% yield) by standard reduction and further transformation to both a terminal epoxide and amino alcohol, both obtained without loss of optical purity. Oxidation of the α-chloro aldehydes followed by esterification gave optically active α-chloro esters without loss of optical purity. It is demonstrated that these optically active α-chloro esters can be converted into nonproteinogenic amino acids in overall high yields, maintaining the enantiomeric excess obtained in the catalytic enantioselective α-chlorination step.

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History

  • Published In Issue April 21, 2004
  • Received February 12, 2004

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