title: Direct organocatalytic asymmetric alpha-chlorination of aldehydes.
abstract: The direct organocatalytic enantioselective alpha-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 alpha-chloro aldehydes are obtained in up to 99% yield and up to 95% ee. The synthetic utility of the enantioselective alpha-chlorination of aldehydes is demonstrated by transformation of the alpha-chloro aldehydes to the corresponding alpha-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 alpha-chloro aldehydes followed by esterification gave optically active alpha-chloro esters without loss of optical purity. It is demonstrated that these optically active alpha-chloro esters can be converted into nonproteinogenic amino acids in overall high yields, maintaining the enantiomeric excess obtained in the catalytic enantioselective alpha-chlorination step.
authors.affiliation: Danish National Research Foundation, Center for Catalysis, Department of Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark.
authors.forename: Nis
authors.initials: N
authors.lastname: Halland
authors.forename: Alan
authors.initials: A
authors.lastname: Braunton
authors.forename: Stephan
authors.initials: S
authors.lastname: Bachmann
authors.forename: Mauro
authors.initials: M
authors.lastname: Marigo
authors.forename: Karl Anker
authors.initials: KA
authors.lastname: Jørgensen