Deprotonation of the Seyferth–Gilbert reagent A gives an anion B, which reacts with the ketone to form the oxaphosphetaneD. Elimination of dimethylphosphate E gives the vinyldiazo-intermediate Fa and Fb. The generation of nitrogen gas gives a vinylcarbeneG, which via a 1,2-migration forms the desired alkyne H.
The mechanism of the Seyferth–Gilbert homologation
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]
Bestmann's reagent
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 reagentedit
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 modificationsedit
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]
^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.
^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.
^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.
^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.
^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. S2CID 98558022.
^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
^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.
December 20, 2023
seyferth, gilbert, homologation, chemical, reaction, aryl, ketone, aldehyde, with, dimethyl, diazomethyl, phosphonate, potassium, tert, butoxide, give, substituted, alkynes, dimethyl, diazomethyl, phosphonate, often, called, seyferth, gilbert, reagent, named, . 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 Seyferth Gilbert homologationNamed after Dietmar Seyferth John C GilbertReaction type Homologation reactionIdentifiersOrganic Chemistry Portal seyferth gilbert homologationRSC ontology ID RXNO 0000387 The Seyferth Gilbert homologationThis 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 ReferencesReaction mechanism editDeprotonation 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 nbsp The mechanism of the Seyferth Gilbert homologationBestmann modification editOhira Bestmann reagent nbsp NamesIUPAC name dimethyl 1 diazo 2 oxopropyl phosphonateIdentifiersCAS Number 90965 06 3 nbsp Y3D model JSmol Interactive imageChemSpider 9281325PubChem CID 11106189UNII 96G79J0LR6 nbsp YInChI InChI 1S C5H9N2O4P c1 4 8 5 7 6 12 9 10 2 11 3 h1 3H3Key SQHSJJGGWYIFCD UHFFFAOYSA NInChI 1 C5H9N2O4P c1 4 8 5 7 6 12 9 10 2 11 3 h1 3H3Key SQHSJJGGWYIFCD UHFFFAOYAKSMILES O P OC OC C C C O N N PropertiesChemical formula C5H9N2O4PMolar mass 192 11Except 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 nbsp Bestmann s reagentThe 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 edit nbsp Safe and scalable synthesis of alkynes from aldehydesRecently 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 editAnother 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 editCorey Fuchs reaction Horner Wadsworth Emmons reaction Wittig reactionReferences edit D Seyferth R S Marmor amp 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 J C Gilbert amp 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 D G Brown E J Velthuisen J R Commerford R G Brisbois amp 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 Muller B Liepold G Roth amp 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 G Roth B Liepold S Muller amp H J Bestmann 2004 Further Improvements of the Synthesis of Alkynes from Aldehydes Synthesis 2004 1 59 62 doi 10 1055 s 2003 44346 S2CID 98558022 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 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 Retrieved from https en wikipedia org w index php title Seyferth Gilbert homologation amp oldid 1173124871 Bestmann modification, wikipedia, wiki, book, books, library,
