The Seyferth-Gilbert homologation is a the chemical reaction of an aryl ketone 1 (or aldehyde) with dimethyl (diazomethyl)phosphonate 2 and potassium tert-butoxide to give substituted alkynes 3. Dimethyl (diazomethyl)phosphonate 2 is often called the Seyferth-Gilbert reagent.
Deprotonation of the Seyferth-Gilbert reagent A give an anion B which reacts with the ketone to form the oxaphosphatane D. Elimination of dimethylphosphate E gives the vinyl diazo-intermediate Fa and Fb. The generation of nitrogen gas gives a vinyl carbene G which via a 1,2-migration forms the desired alkyne H.
Dimethyl (diazomethyl)phosphonate can be generated in situ from dimethyl-1-diazo-2-oxopropylphosphonate (also called Bestmann's reagent) by reaction with methanol and potassium carbonate. Reaction of Bestmann's reagent with aldehydes gives terminal alkynes often in very high yield.
The use of the milder potassium carbonate makes this procedure much more compatible with a wide variety of functional groups.
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- D. G. Brown, E. J. Velthuisen, J. R. Commerford, R. G. Brisbois and T. H. Hoye (1996). "A Convenient Synthesis of Dimethyl (Diazomethyl)phosphonate (Seyferth/Gilbert Reagent)". J. Org. Chem. 61 (7): 2540–2541. doi:10.1021/jo951944n.
- S. Müller, B. Liepold, G. Roth and H. J. Bestmann* (1996). "An Improved One-pot Procedure for the Synthesis of Alkynes from Aldehydes". Synlett (06): 521–522. doi:10.1055/s-1996-5474.
- G. Roth, B. Liepold, S. Müller and H. J. Bestmann (2004). "Further Improvements of the Synthesis of Alkynes from Aldehydes". Synthesis (1): 59–62. doi:10.1055/s-2003-44346.