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

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.[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.

## Contents

* 1 Reaction mechanism
* 2 Bestmann modification
* 3 Improved in situ generation of the Ohira-Bestmann reagent
* 4 Other modifications
* 5 See also
* 6 References

## Reaction mechanism

Deprotonation of the Seyferth–Gilbert reagent A gives an anion B, which reacts with the ketone to form the oxaphosphetane 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

Ohira–Bestmann reagent

Names
IUPAC name

dimethyl (1-diazo-2-oxopropyl)phosphonate

Identifiers

CAS Number

* 90965-06-3 Y

3D model (JSmol)

* Interactive image

ChemSpider |

* 9281325

PubChem CID

* 11106189

UNII |

* 96G79J0LR6 Y

InChI

* InChI=1S/C5H9N2O4P/c1-4(8)5(7-6)12(9,10-2)11-3/h1-3H3

Key: SQHSJJGGWYIFCD-UHFFFAOYSA-N

* InChI=1/C5H9N2O4P/c1-4(8)5(7-6)12(9,10-2)11-3/h1-3H3

Key: SQHSJJGGWYIFCD-UHFFFAOYAK

SMILES

* O=P(OC)(OC)C(C(C)=O)=[N+]=[N-]

Properties

Chemical formula

| C5H9N2O4P
Molar mass | 192.11

Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Infobox references

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. Reaction of Bestmann's reagent with aldehydes gives terminal alkynes often in very high yield and fewer steps than the Corey–Fuchs reaction.[4][5]

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

## Improved in situ generation of the Ohira-Bestmann reagent

Safe and scalable synthesis of alkynes from aldehydes

Recently a safer and more scalable approach has been developed for the synthesis of alkynes from aldehydes. This protocol takes advantage of a stable sulfonyl azide, rather than tosyl azide, for the in situ generation of the Ohira−Bestmann reagent.[6]

## Other modifications

Another modification for less reactive aldehydes is made by replacement of potassium carbonate with caesium carbonate in MeOH and results in a drastic[quantify] yield increase.[7]

## See also

* Corey–Fuchs reaction
* Horner–Wadsworth–Emmons reaction
* Wittig reaction

## References

1. ↑ D. Seyferth; R. S. Marmor; 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; 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; 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; H. J. Bestmann (1996). "An Improved One-pot Procedure for the Synthesis of Alkynes from Aldehydes". Synlett 1996 (6): 521–522. doi:10.1055/s-1996-5474.
5. ↑ G. Roth; B. Liepold; S. Müller; H. J. Bestmann (2004). "Further Improvements of the Synthesis of Alkynes from Aldehydes". Synthesis 2004 (1): 59–62. doi:10.1055/s-2003-44346.
6. ↑ Jepsen, T.H, Kristensen, J.L. J. Org. Chem. 2014, "In Situ Generation of the Ohira–Bestmann Reagent from Stable Sulfonyl Azide: Scalable Synthesis of Alkynes from Aldehydes". http://pubs.acs.org/doi/abs/10.1021/jo501803f
7. ↑ Lidija Bondarenko; Ina Dix; Heino Hinrichs; Henning Hopf (2004). "Cyclophanes. Part LII:1 Ethynyl[2.2]paracyclophanes – New Building Blocks for Molecular Scaffolding". Synthesis 2004 (16): 2751–2759. doi:10.1055/s-2004-834872.

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* t
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Alkynes

* Ethyne ( C2H2 )
* Propyne ( C3H4 )
* Butyne ( C4H6 )
* 1
* 2
* Pentyne ( C5H8 )
* 1
* 2
* Hexyne ( C6H10 )
* Heptyne ( C7H12 )
* Octyne ( C8H14 )
* 2
* 4
* Nonyne ( C9H16 )
* Decyne ( C10H18 )
* 1
* 5

Preparations|

* Cracking
* [[Chemistry:DehydrogenatDehydrogenation]] of alkane]], alkene
* Alkylation of alkynyl anion
* Dehydrohalogenation of dihaloalkane
* Fritsch–Buttenberg–Wiechell rearrangement
* Corey–Fuchs reaction
* Seyferth–Gilbert homologation

Reactions|

* Deprotonation
* Hydrogenation
* Halogenation
* Hydration
* Hydroboration
* Hydrohalogenation
* Thiol-yne reaction
* Alkyne trimerisation
* Diels–Alder reaction
* Pauson–Khand reaction
* Azide-alkyne Huisgen cycloaddition
* Sonogashira coupling
* Cadiot–Chodkiewicz coupling
* Glaser coupling
* Favorskii reaction

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Topics in Organic Reactions

* Addition reaction
* Elimination reaction
* Polymerization
* Reagents
* Rearrangement reaction
* Redox reaction
* Regioselectivity
* Stereoselectivity
* Stereospecificity
* Substitution reaction

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