Submitted to: American Chemical Society National Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 9/1/2005
Publication Date: 6/22/2006
Citation: Petroski, R.J., Bartelt, R.J. 2006. New phosphonate reagents for aldehyde homologation [abstract]. American Chemical Society National Meeting. Paper No. 539.
Technical Abstract: The usual scheme of aldehyde homologation to alpha,beta-unsaturated aldehydes by Horner-Wadsworth-Emmons (R) condensations with phosphonate esters, such as triethyl-2-phosphonoacetate or triethyl-2-phosphonopropionate, involves three steps. The phosphonate condensation step results in extension of the carbon chain by two carbons, with an (E) double bond, introduction of an alpha-alkyl branch, such as methyl from the use of the methyl-branched phosphonate, and a functional group (an ester) is placed on the end of the chain. In the second step, the ester is reduced to an alpha,beta-unsaturated alcohol. In the third step, the alpha,beta-unsaturated alcohol is partially oxidized to an alpha,beta-unsaturated aldehyde. One way to shorten this three-step scheme would be to keep the terminal functional group in the oxidation state of an aldehyde, thus obviating the reduction and partial oxidation steps; however, direct use of an aldehyde phosphonate results in substantial self condensation. Aldehyde homologation was accomplished by preparation and use of aldehyde phosphonates, protected as aldehyde dimethylhydrazones. The reaction conditions involve formation of the phosphonate yield with lithium diisopropylamide in dry THF at 25 degrees C and adding the aldehyde starting material. The reaction mixture is stirred at 25 degrees C overnight under an inert atmosphere to afford the desired aldehyde dimethylhydrazone products in greater than 90% yield after workup. Liberation of the free aldehydes was accomplished with 50% aqueous glyoxylic acid at 25 degrees C for one to two days. Deprotection yields were greater than 85%. This new protocol should replace the usual Horner-Wadsworth-Emmons aldehyde homologation scheme.