| Seyferth–Gilbert homologation | |
|---|---|
| Named after | Dietmar Seyferth John C. Gilbert |
| Reaction type | Homologation reaction |
| Identifiers | |
| Organic Chemistry Portal | seyferth-gilbert-homologation |
| RSC ontology ID | RXNO:0000387 |
TheSeyferth–Gilbert homologation is achemical reaction of anarylketone1 (oraldehyde) with dimethyl (diazomethyl)phosphonate2 andpotassium tert-butoxide to give substitutedalkynes3.[1][2] Dimethyl (diazomethyl)phosphonate2 is often called theSeyferth–Gilbert reagent.[3]
This reaction is called ahomologation because the product has exactly one additionalcarbon more than the starting material.
Deprotonation of the Seyferth–Gilbert reagentA gives an anionB, which reacts with the ketone to form theoxaphosphetaneD. Elimination of dimethylphosphateE gives thevinyldiazo-intermediateFa andFb. The generation ofnitrogen gas gives avinylcarbeneG, which via a1,2-migration forms the desired alkyneH.
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| Names | |
|---|---|
| IUPAC name dimethyl (1-diazo-2-oxopropyl)phosphonate | |
| Identifiers | |
3D model (JSmol) | |
| ChemSpider | |
| UNII | |
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| Properties | |
| C5H9N2O4P | |
| Molar mass | 192.11 |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
The dimethyl (diazomethyl)phosphonate carbanion can be generatedin situ from dimethyl-1-diazo-2-oxopropylphosphonate (also called theOhira-Bestmann reagent) by reaction withmethanol andpotassium carbonate as the base by cleavage of theacetyl group asmethyl acetate. Reaction of Bestmann's reagent with aldehydes gives terminal alkynes often in very high yield and fewer steps than theCorey–Fuchs reaction.[4][5]
The use of the milder potassium carbonate makes this procedure much more compatible with a wide variety offunctional groups.
Traditional syntheses of the Ohira−Bestmann reagent use the rather explosivetosyl azide, but betterdiazo transfer agents are available.[6]
Another modification for less reactive aldehydes is made by replacement of potassium carbonate withcaesium carbonate in MeOH and results in a drastic[quantify] yield increase.[7]
