ARS | Publication request: New phosphonate reagents for aldehyde homologation

Submitted to: Synthetic Communications
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 17, 2007
Publication Date: November 1, 2007
Citation: Petroski, R.J. 2007. New phosphonate reagents for aldehyde homologation. Synthetic Communications. 37(21):3841-3854.

Interpretive Summary: There is a continuing need to develop more efficient pest and weed control strategies. The use of insect pheromones has become an important part of the process because of cost savings and selectivity. Difficulties occur when the chemical synthesis of the pheromone substances is lengthy or expensive. This paper describes how to shorten a commonly used linear synthetic sequence from three expensive steps to just two much less expensive steps, in response to the expressed needs of our customers and stakeholders. These results are important to scientists, especially those in industry, because synthetic pathways must be economical and capable of scale-up in order to be commercially viable.

Technical Abstract: New phosphonate reagents were developed for the two-carbon homologation of aldehydes to unbranched- or methyl-branched unsaturated aldehydes. The phosphonate reagents, diethyl methylformyl-2-phosphonate dimethylhydrazone and diethyl ethylformyl-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 1 M HCL and petroleum ether. This robust two-step process worked with aliphatic, alpha,beta-unsaturated and aromatic aldehydes. Isolated yields for the condensation step ranged from 77-89 percent, and yields for the deprotection step ranged from 81-96 percent.