Direct aldehyde homologation utilized to construct a conjugated-tetraene hydrocarbon insect pheromone.
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.
Petroski
Richard J
RJ
Crop Bioprotection Research Unit, National Center for Agricultural Utilization Research, Agricultural Research Service, U.S. Department of Agriculture, 1815 North University Street, Peoria, Illinois 61604, USA. petrosrj@ncaur,usda.gov
Bartelt
Robert J
RJ
D000447:Aldehydes / Q000138:chemical synthesis / Q000737:chemistry*; D000475:Alkenes / Q000138:chemical synthesis; D000818:Animals; D001517:Coleoptera / Q000737:chemistry*; D007202:Indicators and Reagents; D063065:Organophosphonates; D010675:Pheromones / Q000138:chemical synthesis*
C520887:(2E,4E,6E,8E)-3,5-dimethyl-7-ethyl-2,4,6,8-undecatetraene; D000447:Aldehydes; D000475:Alkenes; D007202:Indicators and Reagents; D063065:Organophosphonates; D010675:Pheromones