Direct aldehyde homologation utilized to construct a conjugated-tetraene hydrocarbon insect pheromone

J Agric Food Chem. 2007 Mar 21;55(6):2282-7. doi: 10.1021/jf063337e. Epub 2007 Feb 24.

Abstract

New phosphonate reagents were developed for the two-carbon homologation of aldehydes to methyl- or ethyl-branched unsaturated aldehydes and used in the practical synthesis of (2E,4E,6E,8E)-3,5-dimethyl-7-ethyl-2,4,6,8-undecatetraene (1), a pheromone of the beetle Carpophilus lugubris. The phosphonate reagents, diethyl ethylformyl-2-phosphonate dimethylhydrazone and diethyl 1-propylformyl-2-phosphonate dimethylhydrazone, contained a protected aldehyde group instead of the usual ester group. A homologation cycle entailed condensation of the reagent with the starting aldehyde, followed by removal of the dimethylhydrazone protective group with a biphasic mixture of dilute HCl and petroleum ether. This robust two-step process replaces the standard three-step aldehyde homologation route using ester-based Horner-Wadsworth-Emmons reagents. The new synthesis of compound 1 from (2E)-2-methyl-2-butenal was run on a 10-g scale and required just five steps (two cycles of condensation and deprotection, followed by a final Wittig olefination) instead of the usual seven. In addition, the Wittig olefination step was simplified and its E-isomer selectivity was improved. The overall yield for the entire synthetic pathway was increased from 20% to 37%, enhancing the commercial potential of Carpophilus pheromones.

MeSH terms

  • Aldehydes / chemical synthesis
  • Aldehydes / chemistry*
  • Alkenes / chemical synthesis
  • Animals
  • Coleoptera / chemistry*
  • Indicators and Reagents
  • Organophosphonates
  • Pheromones / chemical synthesis*

Substances

  • (2E,4E,6E,8E)-3,5-dimethyl-7-ethyl-2,4,6,8-undecatetraene
  • Aldehydes
  • Alkenes
  • Indicators and Reagents
  • Organophosphonates
  • Pheromones