New Phosphonate Reagents for Aldehyde Homologation

Abstract

New phosphonate reagents were developed for the two‐carbon homologation of aldehydes to unbranched or methyl‐branched unsaturated aldehydes. The phosphonate reagents, diethyl methylformylphosphonate 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, α,β‐unsaturated and aromatic aldehydes. Isolated yields for the condensation step ranged from 77% to 89%, and yields for the deprotection step ranged from 81% to 96%.

Keywords:

• aldehyde homologation
• diethyl ethylformyl‐2‐phosphonate dimethylhydrazone
• diethyl methylformylphosphonate dimethylhydrazone

Acknowledgments

I thank Karl Vermillion and David Weisleder of National Center for Agricultural Utilization Research (NCAUR) for acquisition of NMR data, Robert J. Bartelt for helpful discussions, and the University of Illinois, School of Chemical Sciences, Mass Spectrometry Laboratory, for acquisition of HRMS data.