Seyferth–Gilbert homologation

The Seyferth–Gilbert homologation is a chemical reaction of an aryl ketone 1 (or aldehyde) with dimethyl (diazomethyl)phosphonate 2 and potassium tert-butoxide to give substituted alkynes 3.

[3] This reaction is called a homologation because the product has exactly one additional carbon more than the starting material.

The generation of nitrogen gas gives a vinyl carbene G, which via a 1,2-migration forms the desired alkyne H. The dimethyl (diazomethyl)phosphonate carbanion can be generated in situ from dimethyl-1-diazo-2-oxopropylphosphonate (also called the Ohira-Bestmann reagent) by reaction with methanol and potassium carbonate as the base by cleavage of the acetyl group as methyl acetate.

[4][5] The use of the milder potassium carbonate makes this procedure much more compatible with a wide variety of functional groups.

Recently a safer and more scalable approach has been developed for the synthesis of alkynes from aldehydes.