Keinicke, Lise Edelmann1; Fristrup, Peter1; Norrby, Per-Ola1; Madsen, Robert1
1 Department of Chemistry, Technical University of Denmark2 Department of Organic Chemistry, Technical University of Denmark3 Centre for Catalysis and Sustainable Chemistry, Department of Chemistry, Technical University of Denmark
A new protocol for the synthesis of vicinal amino alcohols is described. The method employs a Barbier-type reaction between an imine and 3-benzoyloxyallyl bromide in the presence of zinc metal. The addition products are debenzoylated to afford amino alcohols in good yields and with diastereomeric ratios greater than 85:15 in favor of the anti isomer. A Hammett study has been performed which strongly indicates that the allylation does not follow a radical mechanism, but instead an organometallic reagent is formed which subsequently reacts with the imine. A computational study based on this mechanism reproduces the observed diastereoselectivity with high accuracy, but only when a sufficiently large portion of the substrate is included.
Journal of the American Chemical Society, 2005, Vol 127, Issue 45, p. 15756-15761