{ "id": "epvr1peer5", "slug": "carbometalation", "title": "Carbometalation", "updated": "2026-10-15", "topic_path": [ { "id": "physical", "label": "Physical world and mathematics", "api_url": "https://www.edgepedia.org/api/v1/topics/physical" }, { "id": "physical.chemistry", "label": "Chemistry", "api_url": "https://www.edgepedia.org/api/v1/topics/physical.chemistry" }, { "id": "physical.chemistry.methods", "label": "Chemical principles and methods", "api_url": "https://www.edgepedia.org/api/v1/topics/physical.chemistry.methods" }, { "id": "physical.chemistry.methods.chemical-synthesis", "label": "Chemical synthesis", "api_url": "https://www.edgepedia.org/api/v1/topics/physical.chemistry.methods.chemical-synthesis" }, { "id": "physical.chemistry.methods.chemical-synthesis.named-preparative-methods", "label": "Named synthetic methods", "api_url": "https://www.edgepedia.org/api/v1/topics/physical.chemistry.methods.chemical-synthesis.named-preparative-methods" }, { "id": "physical.chemistry.methods.chemical-synthesis.named-preparative-methods.alpha-2-to-he", "label": "Titles 2 to He", "api_url": "https://www.edgepedia.org/api/v1/topics/physical.chemistry.methods.chemical-synthesis.named-preparative-methods.alpha-2-to-he" } ], "geo": [ { "id": "geo.nongeo.t1800.physical.chemistry.methods.chemical-synthesis.named-preparative-methods", "label": "Non-geographic · 1800 to 1945: Named synthetic methods", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1800.physical.chemistry.methods.chemical-synthesis.named-preparative-methods", "path": [ { "id": "geo.nongeo", "label": "Non-geographic", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo" }, { "id": "geo.nongeo.t1800", "label": "Non-geographic · 1800 to 1945", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1800" }, { "id": "geo.nongeo.t1800.physical", "label": "Physical world and mathematics", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1800.physical" }, { "id": "geo.nongeo.t1800.physical.chemistry", "label": "Chemistry", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1800.physical.chemistry" }, { "id": "geo.nongeo.t1800.physical.chemistry.methods", "label": "Chemical principles and methods", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1800.physical.chemistry.methods" }, { "id": "geo.nongeo.t1800.physical.chemistry.methods.chemical-synthesis", "label": "Chemical synthesis", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1800.physical.chemistry.methods.chemical-synthesis" }, { "id": "geo.nongeo.t1800.physical.chemistry.methods.chemical-synthesis.named-preparative-methods", "label": "Named synthetic methods", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1800.physical.chemistry.methods.chemical-synthesis.named-preparative-methods" } ] }, { "id": "geo.nongeo.t1946.physical.chemistry.methods.chemical-synthesis.named-preparative-methods", "label": "Non-geographic · 1946 to 2000: Named synthetic methods", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1946.physical.chemistry.methods.chemical-synthesis.named-preparative-methods", "path": [ { "id": "geo.nongeo", "label": "Non-geographic", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo" }, { "id": "geo.nongeo.t1946", "label": "Non-geographic · 1946 to 2000", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1946" }, { "id": "geo.nongeo.t1946.physical", "label": "Physical world and mathematics", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1946.physical" }, { "id": "geo.nongeo.t1946.physical.chemistry", "label": "Chemistry", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1946.physical.chemistry" }, { "id": "geo.nongeo.t1946.physical.chemistry.methods", "label": "Chemical principles and methods", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1946.physical.chemistry.methods" }, { "id": "geo.nongeo.t1946.physical.chemistry.methods.chemical-synthesis", "label": "Chemical synthesis", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1946.physical.chemistry.methods.chemical-synthesis" }, { "id": "geo.nongeo.t1946.physical.chemistry.methods.chemical-synthesis.named-preparative-methods", "label": "Named synthetic methods", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1946.physical.chemistry.methods.chemical-synthesis.named-preparative-methods" } ] } ], "excerpt": "Carbometalation is an addition reaction in which the carbon–metal bond of an organometallic reagent adds across an alkene or alkyne, forming new carbon–carbon and carbon–metal bonds in one step.", "snippet": "Carbometalation is an addition reaction in which the carbon–metal bond of an organometallic reagent adds across an alkene or alkyne, forming new carbon–carbon and carbon–metal bonds in one step.", "node": "physical.chemistry.methods.chemical-synthesis.named-preparative-methods.alpha-2-to-he", "markdown": "# Carbometalation\n\nCarbometalation is an addition reaction in which the carbon–metal bond of an organometallic reagent adds across an alkene or alkyne, forming a new carbon–carbon bond and a new carbon–metal bond in a single step.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10795483/) The organometallic product is a versatile intermediate: it can be trapped with electrophiles, transmetalled to a transition metal for cross-coupling, or simply protonated, giving access to multisubstituted alkenes and alkanes that are difficult to assemble otherwise.[2](https://www.beilstein-journals.org/bjoc/articles/9/34)\n\n| Key fact | Detail |\n| --- | --- |\n| Bonds formed | One C–C bond and one C–M bond across a C=C or C≡C unit; the C–M product is then trapped by electrophiles or used in cross-coupling[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10795483/) • [2](https://www.beilstein-journals.org/bjoc/articles/9/34) |\n| Stereochemistry | Alkyne carboalumination and carbocupration proceed by syn-addition; carbozincation reaches syn:anti ratios above 98:2[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10795483/) • [3](https://pubs.rsc.org/en/content/articlehtml/2016/cs/c5cs00897b) • [4](https://www.russchemrev.org/RCR5158pdf) |\n| Zr-catalyzed methylalumination of alkynes (ZMA) | High regioselectivity and nearly perfect stereoselectivity for stereodefined alkene synthesis[5](https://pubs.acs.org/doi/abs/10.1021/acs.accounts.6b00338) |\n| ZACA reaction | Catalytic asymmetric carboalumination of terminal alkenes; tandem ZACA–cross-coupling sequences deliver chiral compounds of >99% ee[6](https://www.jstage.jst.go.jp/article/pjab/91/8/91_PJA9108B-05/_html/-char/en) |\n| Representative catalytic conditions | Ni(acac)2 (25 mol%) alkylzincation of diphenylacetylene in THF/NMP (3:1) at −35 °C for 3–18 h gives 98% of one isomer[4](https://www.russchemrev.org/RCR5158pdf) |\n| Representative yield | ZACA of 1,4-pentadiene with Me3Al and 5 mol% (−)-(NMI)2ZrCl2 gives 2-methyl-4-penten-1-ol in 80% yield based on Me3Al[7](https://www.sciencedirect.com/science/article/abs/pii/S0957416606000607) |\n\n## How it works\n\nThe reaction is an insertion of an unsaturated C–C bond into a C–M bond. For the group 13 reagents, the reactive species in uncatalyzed carboalumination is a tricoordinate, monomeric organoaluminum; its electrophilic attack on the alkene or alkyne is the rate-determining step and passes through a four-centered transition state. Lewis bases slow or inhibit the reaction because they coordinate to aluminum and deplete the monomeric species.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10795483/) Alkynes react faster than alkenes because the transition state for alkyne carbometalation develops less steric hindrance, and the addition is generally syn.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10795483/)\n\nIn the zirconium-catalyzed variant, interaction between the alkylalane and a 16-electron zirconocene derivative generates a bimetallic, strongly electrophilic reagent in which a Zrδ+–Cl–Alδ– contact is important; carbometalation then proceeds through an acyclic transition state rather than a cyclic one.[5](https://pubs.acs.org/doi/abs/10.1021/acs.accounts.6b00338) • [8](https://stats.iupac.org/publications/pac/2002/pdf/7401x0151.pdf) Regiochemistry follows sterics: with sterically distinct internal alkynes, aluminum is placed at the more congested carbon atom.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10795483/) In carbozincation of alkylarylacetylenes, zinc attaches to the aryl-bearing carbon, giving more than 99% of a single regioisomer for methyl- and ethyl-substituted alkynes.[4](https://www.russchemrev.org/RCR5158pdf) For catalytic acylzincation, density functional theory calculations show that acylmetallation is lower in energy than alkylmetallation, with favorable interaction energies lowering the transition state for the major regioisomer.[9](https://www.nature.com/articles/s44160-022-00208-z)\n\n## How it is done\n\nA classic carbocupration setup uses an ethylcopper reagent made in situ from equimolar EtMgBr and CuBr, which adds to n-hexyne in a low-polar solvent such as diethyl ether by regio- and stereospecific syn-addition; treatment of the resulting alkenylcopper with iodine gives the pure (E)-iodoolefin. Three features make this useful: addition outcompetes deprotonation of the terminal alkyne, the regio- and cis-selectivity are excellent, and the alkenylcopper intermediate can be trapped by many electrophiles or transmetalled for cross-coupling.[3](https://pubs.rsc.org/en/content/articlehtml/2016/cs/c5cs00897b)\n\nCatalytic carbozincation of diphenylacetylene is run with 25 mol% Ni(acac)2 in THF/NMP (3:1 v/v) at −35 °C for 3–18 h, giving an alkenylzinc compound as 98% of one isomer, which on hydrolysis yields a substituted stilbene; rhodium catalysis reduces the loading to 3 mol%.[4](https://www.russchemrev.org/RCR5158pdf) Uncatalyzed carboalumination needs forcing conditions; norbornadiene, for example, reacts at 80 °C through a four-membered-ring transition state followed by protonation.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10795483/) In ZACA chemistry, water, MAO, and IBAO serve as promoters to accelerate otherwise sluggish carboaluminations of unactivated terminal alkenes.[5](https://pubs.acs.org/doi/abs/10.1021/acs.accounts.6b00338)\n\n## Origin\n\nThe alkyne carbometallation chemistry that underlies most of these variants was consolidated in a review by Jean F. Normant and Alexandre Alexakis, \"Carbometallation (C-Metallation) of Alkynes: Stereospecific Synthesis of Alkenyl Derivatives\", published in Synthesis in 1981.[10](https://doi.org/10.1055/s-1981-29622) The individual named reactions discussed below are documented in the primary and review literature cited in their sections.\n\n## Variants\n\n**Carboalumination.** With Me3Al and Cp2ZrCl2, alkynes undergo Zr-catalyzed methylalumination (ZMA), a highly regioselective and nearly perfectly stereoselective route to stereodefined alkenes.[5](https://pubs.acs.org/doi/abs/10.1021/acs.accounts.6b00338) The asymmetric version applied to terminal alkenes is the ZACA reaction; cyclic carboalumination of alkynes and alkenes is known as cyclocarboalumination.[11](https://onlinelibrary.wiley.com/doi/10.1002/9780470682531.pat0834) Zirconocene-catalyzed methylalumination is also used for 1,2-bis-alkylation of alkynes, including diastereoselective reactions of cyclobutenes.[12](https://pubs.rsc.org/en/content/articlepdf/2017/sc/c6sc02617f)\n\n**Carbocupration.** The ethylcopper addition to terminal alkynes described above is one of the earliest controlled, single-stage carbometallations, but difficulties associated with methylcupration have limited its use in natural product synthesis.[3](https://pubs.rsc.org/en/content/articlehtml/2016/cs/c5cs00897b) • [8](https://stats.iupac.org/publications/pac/2002/pdf/7401x0151.pdf) Reagent choice matters: Gilman cuprates (R2CuLi) react with monosubstituted alkynes by deprotonation in THF rather than by addition.[3](https://pubs.rsc.org/en/content/articlehtml/2016/cs/c5cs00897b)\n\n**Carbozincation and carbomagnesiation.** Zirconocene-initiated addition of dialkylzinc compounds (Et2Zn, Me2Zn, Bun2Zn, EtZnCl) to alkynes was the first regio- and stereoselective synthesis of 1-alkenylzinc derivatives, with syn:anti ratios above 98:2.[4](https://www.russchemrev.org/RCR5158pdf) Transition-metal-catalyzed carbozincation and carbomagnesiation convert alkynes and alkenes directly into organozinc and organomagnesium reagents for electrophile trapping.[2](https://www.beilstein-journals.org/bjoc/articles/9/34) **Carboboration**, which forms C–C and C–B bonds in one operation, is much less common than hydroboration and generally requires a catalyst because the uncatalyzed background rate is slow.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10795483/)\n\n**ZACA.** The ZACA reaction (Zr-catalyzed asymmetric carboalumination) is a catalytic asymmetric C–C bond-forming reaction of terminal alkenes that requires no other functional group in the substrate; the chiral alkylaluminum products are transformed in situ.[6](https://www.jstage.jst.go.jp/article/pjab/91/8/91_PJA9108B-05/_html/-char/en) Its development depended on suppressing three competitive side reactions: cyclic carbometalation, hydrometalation, and alkene polymerization. This was achieved with the chiral zirconocene (−)-(NMI)2ZrCl2 as catalyst and a chlorinated hydrocarbon as solvent.[5](https://pubs.acs.org/doi/abs/10.1021/acs.accounts.6b00338) • [6](https://www.jstage.jst.go.jp/article/pjab/91/8/91_PJA9108B-05/_html/-char/en) In a representative run, 1,4-pentadiene (5 molar equivalents relative to Me3Al) with Me3Al and 5 mol% of (−)-(NMI)2ZrCl2 gave 2-methyl-4-penten-1-ol in 80% yield based on Me3Al.[7](https://www.sciencedirect.com/science/article/abs/pii/S0957416606000607)\n\n## Applications\n\nZr-catalyzed carboalumination of alkynes has become a standard route to stereodefined alkenes and has been applied to the synthesis of many dozens of complex natural products.[8](https://stats.iupac.org/publications/pac/2002/pdf/7401x0151.pdf) ZACA-based tandem processes extend this to asymmetric synthesis: one-pot ZACA–Pd-catalyzed vinylation gives one-step homologation to deoxypropionates,[5](https://pubs.acs.org/doi/abs/10.1021/acs.accounts.6b00338) and ZACA–lipase-catalyzed acetylation–cross-coupling sequences provide chiral organic compounds at >99% ee.[6](https://www.jstage.jst.go.jp/article/pjab/91/8/91_PJA9108B-05/_html/-char/en) The method has been used to modernize syntheses of natural products including deoxypolypropionates and isoprenoids, and to build all-carbon quaternary stereocenters.[13](https://www.arkat-usa.org/get-file/37396) • [5](https://pubs.acs.org/doi/abs/10.1021/acs.accounts.6b00338) Nickel-catalyzed acylzincation of ynamides, oxabicyclic alkenes, and α,β-unsaturated ketones with organozinc reagents under 1 atm of CO offers broad substrate scope, excellent functional group tolerance, and mild conditions.[9](https://www.nature.com/articles/s44160-022-00208-z)\n\n## Limitations and alternatives\n\nSeveral failure modes constrain the reaction. Terminal alkynes resist carboalumination and instead undergo metalation at the terminal C–H bond.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10795483/) Aluminum reagents bearing β-hydrogens, such as triisobutylaluminum, eliminate in situ to dialkylaluminum hydrides, which hydroaluminate rather than carboaluminate.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10795483/) Carboalumination can be reversible (decarboalumination), causing cis–trans isomerization of alkenes at elevated temperatures.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10795483/) In carbozincation of alkylarylacetylenes, regioselectivity falls as the alkyl chain lengthens; ethylzincation of octylphenylacetylene is non-regioselective.[4](https://www.russchemrev.org/RCR5158pdf)\n\nThe nearest alternative is hydroboration, the addition of an H–B bond across unsaturated carbon–carbon bonds. Catalyzed hydroboration is a syn-addition that gives anti-Markovnikov products with non-activated terminal alkenes, installing H and B rather than C and M.[14](https://beta.iopscience.iop.org/article/10.1070/RCR4916)\n\n## References\n\n1. [Uncatalyzed Carbometallation Involving Group 13 Elements: Carboboration and Carboalumination of Alkenes and Alkynes](https://pmc.ncbi.nlm.nih.gov/articles/PMC10795483/)\n2. [Recent advances in transition-metal-catalyzed intermolecular carbomagnesiation and carbozincation (Beilstein J. Org. Chem.)](https://www.beilstein-journals.org/bjoc/articles/9/34)\n3. [Copper mediated carbometalation reactions (Chemical Society Reviews)](https://pubs.rsc.org/en/content/articlehtml/2016/cs/c5cs00897b)\n4. [Catalytic carbozincation of acetylenic compounds catalyzed by transition metal complexes (Russian Chemical Reviews)](https://www.russchemrev.org/RCR5158pdf)\n5. [Zirconium-Catalyzed Asymmetric Carboalumination of Unactivated Terminal Alkenes (Acc. Chem. Res.)](https://pubs.acs.org/doi/abs/10.1021/acs.accounts.6b00338)\n6. [Catalytic enantioselective synthesis of chiral organic compounds of ultra-high purity of >99% ee (Proc. Japan Acad.)](https://www.jstage.jst.go.jp/article/pjab/91/8/91_PJA9108B-05/_html/-char/en)\n7. [Zirconium-catalyzed asymmetric carboalumination (ZACA reaction) of 1,4-dienes (Tetrahedron: Asymmetry)](https://www.sciencedirect.com/science/article/abs/pii/S0957416606000607)\n8. [Zirconium-catalyzed enantioselective carboalumination of 'unactivated' alkenes (Pure Appl. Chem. 2002)](https://stats.iupac.org/publications/pac/2002/pdf/7401x0151.pdf)\n9. [Nickel-catalysed regio- and stereoselective acylzincation of unsaturated hydrocarbons with organozincs and CO (Nature Synthesis)](https://www.nature.com/articles/s44160-022-00208-z)\n10. [Jean F. Normant, Alexandre Alexakis (1981). Carbometallation (C-Metallation) of Alkynes: Stereospecific Synthesis of Alkenyl Derivatives. Synthesis.](https://doi.org/10.1055/s-1981-29622)\n11. [Patai's Chemistry of Functional Groups chapter on carboalumination reactions](https://onlinelibrary.wiley.com/doi/10.1002/9780470682531.pat0834)\n12. [Zirconocene catalyzed diastereoselective carbometalation of cyclobutenes (Chemical Science)](https://pubs.rsc.org/en/content/articlepdf/2017/sc/c6sc02617f)\n13. [Discovery of ZACA reaction − Zr-catalyzed asymmetric carboalumination of alkenes (ARKIVOC)](https://www.arkat-usa.org/get-file/37396)\n14. [Catalysis and regioselectivity in hydrofunctionalization reactions of unsaturated carbon bonds. Part I](https://beta.iopscience.iop.org/article/10.1070/RCR4916)\n\n---\n*Topic: Encyclopedia › Physical world and mathematics › Chemistry › Chemical principles and methods › Chemical synthesis › Named synthetic methods › Titles 2 to He*\n\n*Initially written Sep 29, 2026 · Edited: Oct 15, 2026*\n\n*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*\n\nLicense: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license\n", "same_as": [], "url": "https://www.edgepedia.org/carbometalation", "markdown_url": "https://www.edgepedia.org/carbometalation.md", "license": { "name": "Edgepedia Community License 1.0", "url": "https://www.edgepedia.org/edgepedia/license", "summary": "Free with credit, commercial use included. AI training is open to everyone. For other uses, organizations over USD 100M in revenue or 100M monthly users license separately.", "spdx": "LicenseRef-Edgepedia-Community-1.0" }, "credit": "\"Carbometalation\", Edgepedia (EdgeChat), https://www.edgepedia.org/carbometalation. Edgepedia Community License 1.0.", "credit_md": "\"[Carbometalation](https://www.edgepedia.org/carbometalation)\", Edgepedia (EdgeChat), [https://www.edgepedia.org/carbometalation](https://www.edgepedia.org/carbometalation). [Edgepedia Community License 1.0](https://www.edgepedia.org/edgepedia/license).", "credit_html": "\"Carbometalation\", Edgepedia (EdgeChat), https://www.edgepedia.org/carbometalation. Edgepedia Community License 1.0.", "speakable": "Carbometalation is an addition reaction in which the carbon–metal bond of an organometallic reagent adds across an alkene or alkyne, forming new carbon–carbon and carbon–metal bonds in one step." }