# Enyne metathesis
**Enyne metathesis** is an organic reaction in which an alkene and an alkyne undergo pi bond reorganization, catalyzed by a transition-metal carbene complex, to produce a conjugated 1,3-diene.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC2707033/) When the alkene and alkyne are in the same molecule, the intramolecular version is called ring-closing enyne metathesis (RCEYM or RCEM), a subclass of ring-closing metathesis that builds ring structures bearing 1,3-diene moieties that can be further functionalized.[2](https://pubs.rsc.org/en/content/articlelanding/2007/cs/b508899m) The intermolecular version is called cross enyne metathesis (CEM or EYCM).[3](https://pubs.acs.org/doi/10.1021/acsomega.9b03020)
| Key fact | Detail |
|---|---|
| Transformation | An alkene and an alkyne join to give a conjugated 1,3-diene by pi bond reorganization[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC2707033/) |
| Principal catalysts | Grubbs and Hoveyda-Grubbs ruthenium-alkylidene complexes, valued for functional group tolerance[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC2707033/) • [4](https://www.sciencedirect.com/science/article/abs/pii/S0022328X24001852) |
| Ring-closing variant | RCEYM forms carbocycles and heterocycles with 1,3-diene units; five- to nine-membered heterocycles were made with 1 mol % first-generation Grubbs catalyst at room temperature[2](https://pubs.rsc.org/en/content/articlelanding/2007/cs/b508899m) • [5](https://pmc.ncbi.nlm.nih.gov/articles/PMC5445882/) |
| Exo/endo selectivity | Small- to medium-sized rings generally follow the exo-mode pathway; macrocycles are commonly obtained by the endo-mode, which places one more carbon in the ring[6](https://pubs.rsc.org/en/content/articlehtml/2007/cs/b508899m) |
| Ethylene effect | Ethylene gas markedly raises yields for terminal-alkyne substrates; one substrate improved from 21% to 90% yield under ethylene with 1 mol % catalyst[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC5445882/) |
| Driving force | The reaction is atom economical and driven by the enthalpic stability of the conjugated diene product[7](https://www.sciencedirect.com/org/science/article/pii/S1860539721020375) |
| Applications | Key step in total syntheses including (-)-stemoamide, (+)-anatoxin-a, and the amphidinolides[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC5445882/) |
## Reaction types
Enyne metathesis is classified by the molecularity of the reacting partners. The intramolecular reaction of an enyne, a molecule containing both an alkene and an alkyne, is ring-closing enyne metathesis and affords a cyclic 1,3-diene; formally, a carbon-carbon bond forms between an olefinic and an alkynylic carbon.[6](https://pubs.rsc.org/en/content/articlehtml/2007/cs/b508899m) The intermolecular reaction between a separate alkene and alkyne is cross enyne metathesis.[3](https://pubs.acs.org/doi/10.1021/acsomega.9b03020) Related variants developed from the same chemistry include dienyne metathesis, which builds fused bicyclic or polycyclic compounds in one step, and ring-opening enyne metathesis of cycloalkene-ynes, in which ring-opening metathesis, ring-closing metathesis, and [cross metathesis](https://www.edgepedia.org/cross-metathesis) occur in one operation.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC5445882/)
**Tandem processes** exploit a capacity that distinguishes enyne metathesis from other metatheses: forming multiple C=C bonds and polycyclic systems in a single sequence. Reviews organize these as enyne metathesis/metathesis and enyne metathesis/nonmetathesis combinations, the latter pairing the metathesis with transformations such as Diels-Alder cycloaddition, Suzuki-Miyaura or Heck cross-couplings, aromatization, epoxidation, and hydroxylation.[8](https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/ejoc.201100438) • [7](https://www.sciencedirect.com/org/science/article/pii/S1860539721020375)
## Catalysts
The first enyne metathesis was reported by Katz using a Fischer tungsten-carbene complex, and Mori later reported a chromium-catalyzed version.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC5445882/) The field changed with the well-defined molybdenum and ruthenium carbene complexes introduced by Schrock in 1990 and Grubbs in 1992, after which synthetic applications expanded rapidly.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC5445882/)
**Grubbs ruthenium carbenes** became the standard catalysts for two reasons: they tolerate a wide range of functional groups, and they promote intermolecular enyne metathesis, which many other metal complexes do not.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC2707033/) This chemoselectivity for alkenes, known as functional group tolerance, is what makes the reaction usable in complex molecule synthesis, where delicate functionality must survive.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC2707033/) • [9](https://www.sciencedirect.com/science/article/abs/pii/S1381116906006418) Under Grubbs and Hoveyda-Grubbs catalysis the reaction proceeds under mild conditions with control over chemo-, regio-, and stereoselectivity.[4](https://www.sciencedirect.com/science/article/abs/pii/S0022328X24001852)
A distinct, non-carbene family of transformations also exists. Late transition metal salts can trigger enyne bond reorganization without metal carbenes: Trost pioneered Pd(II) salts, which coordinate the enyne, undergo oxidative cyclization to a metalacyclopentene, reductive elimination to a cyclobutene, and isomerizing ring opening to a diene; Fürstner proposed a Pt(II) mechanism based on π-alkyne activation.[6](https://pubs.rsc.org/en/content/articlehtml/2007/cs/b508899m) Whether a substrate undergoes cycloisomerization, ring-closing metathesis, or skeletal reorganization depends on the functional groups and their position on the substrate and on the catalyst type, including metal-carbene systems, non-carbene complexes of Ru, Pt, Pd, and In, and metal halides such as GaCl₃, InCl₃, and AuCl.[10](https://www.sciencedirect.com/science/article/pii/S0022328X25003705)
## Mechanism
Although enyne metathesis is closely related to alkene metathesis, its mechanism is less well understood.[6](https://pubs.rsc.org/en/content/articlehtml/2007/cs/b508899m) Two orders of bond engagement have been discussed. In the yne-then-ene pathway, the metal carbene first reacts with the alkyne through a [2+2] cycloaddition to give a metallacyclobutene, which opens to a metal vinyl carbene; that intermediate then reacts with the alkene through a metallacyclobutane to release the diene product and regenerate the catalyst.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC5445882/) In the ene-then-yne pathway, the alkene reacts first.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC5445882/)
**Computational evidence** favors the ene-then-yne order for ruthenium catalysis. The DFT study by Lippstreu and Straub concluded that the reaction proceeds via the alkene-first route and that the ruthenacyclobutene generated from an alkyne-first pathway is not a local minimum in the catalytic cycle.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC5445882/) A 2024 review of the ring-closing reaction notes that the metallacyclobut-2-ene intermediate has a lifetime of a molecular vibration and, rather than cycloreverting, undergoes conrotatory opening to a mixture of E- and Z-metal-vinylcarbenes.[4](https://www.sciencedirect.com/science/article/abs/pii/S0022328X24001852) Which double or triple bond enters the initiation step of precatalyst activation is determined by the catalyst and the substrate structure.[11](https://www.beilstein-journals.org/xiv/download/pdf/202084-pdf)
**Exo/endo selectivity** dictates the ring size of the product: endo-mode closure gives a ring with one carbon more than exo-mode closure. In formations of small- to medium-sized rings the reaction generally follows the exo-mode pathway, whereas macrocycles are commonly obtained by the endo-mode.[6](https://pubs.rsc.org/en/content/articlehtml/2007/cs/b508899m) Hansen and Lee argued that the ene-then-yne route explains this change more directly, because in that pathway the selectivity follows from the ring strain of the respective ruthenacyclobutene intermediates and the tether length dictates the course.[6](https://pubs.rsc.org/en/content/articlehtml/2007/cs/b508899m)
## The ethylene effect
In 1998 Mori investigated the effect of ethylene gas on ring-closing enyne metathesis and found that conversions of substrates with terminal alkynyl groups improved significantly under an ethylene atmosphere, while substrates with non-terminal alkynes were unaffected.[6](https://pubs.rsc.org/en/content/articlehtml/2007/cs/b508899m) The improvement is large in practice: the ring closure of enyne 11h, which gave only 21% yield under standard conditions because the product's alkene traps the catalyst as less active species, reached 90% yield with 1 mol % second-generation catalyst under ethylene gas.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC5445882/)
Mechanistically, ethylene keeps the ruthenium catalyst in an active state through formation of a ruthenacyclobutane, counteracting trapping of the catalyst in less active species derived from the product and ruthenium alkylidenes.[6](https://pubs.rsc.org/en/content/articlehtml/2007/cs/b508899m) [Isotopic labeling](https://www.edgepedia.org/isotopic-labeling) studies by Lloyd-Jones later provided evidence of an ene-then-yne pathway involving a second catalytic cycle under ethylene.[6](https://pubs.rsc.org/en/content/articlehtml/2007/cs/b508899m) The higher reactivity under ethylene has often been advantageous in natural product synthesis.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC5445882/) Ethylene is not an unqualified promoter, however; Gregg, Keister, and Diver reported an inhibitory effect of excess ethylene in enyne metathesis.[12](https://pmc.ncbi.nlm.nih.gov/articles/PMC6332380/)
Ethylene also serves as a reagent in cross enyne metathesis. A procedure developed by Mori in 1997 converts an alkyne and ethylene into a 1,3-diene, formally cleaving the double bond of ethylene and introducing each methylene onto an alkyne carbon; one example gave the diene in 62% yield at room temperature.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC5445882/)
## Applications in synthesis
[The 1](https://www.edgepedia.org/the-1),3-diene products are versatile building blocks, and the catalysts' tolerance of heteroatoms makes RCEYM suitable for constructing functionalized heterocycles for target-directed natural product synthesis.[6](https://pubs.rsc.org/en/content/articlehtml/2007/cs/b508899m) Mori's early work showed that five- to nine-membered heterocycles could be made from enynes with 1 mol % of first-generation [Grubbs catalyst](https://www.edgepedia.org/grubbs-catalyst) at room temperature in high yields.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC5445882/)
**Natural product total syntheses** use the reaction as a key step. The first total synthesis of a natural product by ring-closing enyne metathesis was that of (-)-stemoamide, in which ring closure of an ester-substituted enyne with 4 mol % catalyst gave the bicyclic intermediate in 87% yield.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC5445882/) The total synthesis of (+)-anatoxin-a was achieved by Martin and by Mori using the same strategy, with enyne metathesis constructing the azabicyclo[4.2.1]nonene ring system.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC5445882/) Cross enyne metathesis with ethylene has been used to introduce methylene units late in syntheses, as in the anolignans, and to build side chains in total syntheses of amphidinolide E and, by an intramolecular cross variant, amphidinolide K.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC5445882/) Tandem ring-closing/cross-metathesis sequences compress syntheses further, as in Martin's one-step preparation of 8-epi-xanthatin from a lactone precursor in the presence of excess methyl vinyl ketone.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC5445882/)
## References
1. [Steven T. Diver (2007). Ruthenium Vinyl Carbene Intermediates in Enyne Metathesis. Coordination Chemistry Reviews 251, 671-701.](https://pmc.ncbi.nlm.nih.gov/articles/PMC2707033/)
2. [Hélène Villar, Marcus Frings, Carsten Bolm (2007). Ring closing enyne metathesis: A powerful tool for the synthesis of heterocycles. Chemical Society Reviews 36, 55-66.](https://pubs.rsc.org/en/content/articlelanding/2007/cs/b508899m)
3. [Diversity-Oriented Approaches to Polycycles and Heterocycles via Enyne Metathesis and Diels-Alder Reaction as Key Steps. ACS Omega (2019).](https://pubs.acs.org/doi/10.1021/acsomega.9b03020)
4. [Carmen-Irena Mitan, Petru Filip, Lionel Delaude, Valerian Dragutan (2024). Mechanistic aspects of the ring-closing enyne metathesis catalyzed by ruthenium-alkylidene complexes. Journal of Organometallic Chemistry 1014, 123190.](https://www.sciencedirect.com/science/article/abs/pii/S0022328X24001852)
5. [Miwako Mori (2010). Recent Progress on Enyne Metathesis: Its Application to Syntheses of Natural Products and Related Compounds. Materials 3, 2087-2140.](https://pmc.ncbi.nlm.nih.gov/articles/PMC5445882/)
6. [Villar, Frings, Bolm (2007). Ring closing enyne metathesis, full text. Chemical Society Reviews 36, 55-66.](https://pubs.rsc.org/en/content/articlehtml/2007/cs/b508899m)
7. [Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules. ScienceDirect (2021).](https://www.sciencedirect.com/org/science/article/pii/S1860539721020375)
8. [Zhi-Gang Li and colleagues (2011). Enyne-Metathesis-Based Tandem Processes. European Journal of Organic Chemistry.](https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/ejoc.201100438)
9. [Metal carbenes in enyne metathesis: Synthetic and mechanistic studies. Journal of Molecular Catalysis A: Chemical (2006).](https://www.sciencedirect.com/science/article/abs/pii/S1381116906006418)
10. [Exploring relevant features of the mechanism of enyne cycloisomerization reaction and related processes catalyzed by metal-carbenes and metal halides. Journal of Organometallic Chemistry (2025).](https://www.sciencedirect.com/science/article/pii/S0022328X25003705)
11. [Ring closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans. Beilstein Journal of Organic Chemistry (2018).](https://www.beilstein-journals.org/xiv/download/pdf/202084-pdf)
12. [Preparation and Reaction Chemistry of Novel Silicon-Substituted 1,3-Dienes. PMC (2014).](https://pmc.ncbi.nlm.nih.gov/articles/PMC6332380/)
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*Topic: Encyclopedia › Physical world and mathematics › Chemistry › Organic substances › Organic reactions, structure and reference › Organic reactions and synthetic methods › C–C bond formation and coupling methods › Olefin and alkyne metathesis › Enyne metathesis*
*Initially written Sep 17, 2026 · Reviewed: Oct 15, 2026 · Edited: Oct 11, 2026; Oct 15, 2026 · Last review: Oct 15, 2026*
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