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

Safe Weighing Range Ensures Accurate Results

What is the Correct Way to Check Repeatability in Balances?

Weighing the right way

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