Seyferth-Gilbert homologation

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.^[1][2] Dimethyl (diazomethyl)phosphonate 2 is often called the Seyferth-Gilbert reagent.^[3]

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

Additional recommended knowledge

Daily Sensitivity Test

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Reaction mechanism

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.

Bestmann modification

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.^[4][5]

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

References

1. ^ D. Seyferth, R. S. Marmor and P. Hilbert (1971). "Reactions of dimethylphosphono-substituted diazoalkanes. (MeO)2P(O)CR transfer to olefins and 1,3-dipolar additions of (MeO)2P(O)C(N2)R". J. Org. Chem. 36 (10): 1379-1386. doi:10.1021/jo00809a014.
2. ^ J. C. Gilbert and U. Weerasooriya (1982). "Diazoethenes: their attempted synthesis from aldehydes and aromatic ketones by way of the Horner-Emmons modification of the Wittig reaction. A facile synthesis of alkynes". J. Org. Chem. 47 (10): 1837-1845. doi:10.1021/jo00349a007.
3. ^ 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.
4. ^ 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.
5. ^ 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.

See also

• Corey-Fuchs reaction
• Horner-Wadsworth-Emmons reaction
• Wittig reaction