Alkyne trimerisation
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2008-06-23T02:57:16Z
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An '''alkyne trimerisation''' reaction is a [[cycloaddition|2+2+2]] cyclization [[organic reaction|reaction]] where three [[alkyne]] [[molecule]]s react to form a [[benzene]] compound. The reaction is 'pseudo' [[pericyclic]] since it has not been observed to occur without the assistance of metal catalysis; and the metal catalyst assembles the ring stepwise via intermediates which are not directly in between (in a geometric sense) the starting material and products.
In the example of [[phenylacetylene]] a simple [[catalyst]] system of [[cobalt(II) bromide]] / [[zinc]] / [[zinc iodide]] suffices to obtain 99% [[chemical yield]] and 97% [[regioselectivity]] in favor of the ortho substituted reaction product '''1''' <ref>{{cite journal | title = A simple cobalt catalyst system for the efficient and regioselective cyclotrimerisation of alkynes | author = Gerhard Hilt , Thomas Vogler, Wilfried Hess, Fabrizio Galbiati | journal = [[Chemical Communications]] | year = 2005 | volume = 2005 | issue = 11 | pages = 1474–1475 | doi = 10.1039/b417832g}}</ref>.
[[image:Alkyne trimerisation.gif|center|Scheme 1. Alkyne trimerization]]
==Mechanism==
The [[reaction mechanism]] for trimerization is fairly well understood. A 2007 mechanism consistent with [[in silico]] and experimental data is depicted below for a [[cobaltocene]] catalyst <ref>''Cobalt-Catalyzed Cyclotrimerization of Alkynes: The Answer to the Puzzle of Parallel Reaction Pathways'' Nicolas Agenet, Vincent Gandon, K. Peter C. Vollhardt, Max Malacria, and Corinne Aubert [[J. Am. Chem. Soc.]]; '''2007'''; 129(28) pp 8860 - 8871; (Article) {{DOI|10.1021/ja072208r}}</ref>
[[Image:AlkynetrimerizationMechanism.png|500px|center|Alkyne trimerization mechanism Agenet 2007]]
The [[ligand]] L in the [[electron counting|18-electron compound]] CpCoL<sub>2</sub> ('''A''') can be [[triphenylphosphine]] or [[carbon monoxide]]. These ligands are replaced by the alkyne in two steps forming first '''B''' and then '''C''' which enters the [[catalytic cycle]] by [[oxidative coupling]] to the 16 VE ''cobaltacyclopentadiene'' [[metallacycle]] '''D'''. This compound forms in its [[diradical|singlet state]] and therefore first relaxes to the [[triplet state]]. This intermediate coordinates to another equivalent of ligand to form '''E''' and then forms cobaltanorbornene '''F''' (see: [[norbornadiene]]) on accepting an alkyne unit in one [4+2]cycloaddition step. In the final step [[benzene]] is liberated in a [[reductive elimination]] with formation of CpCoL which can re-enter the cycle by accepting two units of alkyne. When the ligand is less of a sigma donor such as [[ethylene]] or [[tetrahydrofuran|THF]] (as a solvent) or when the alkyne is electron-poor as in butynedioic acid a different cycle takes over where another alkyne unit and not a ligand adds to intermediate '''D'''. In the remainder of this cycle (not depicted) the new intermediate forms an CpCo(η<sup>4</sup>arene) complex and then a CpCo(η<sup>6</sup>arene) [[sandwich compound]] before eliminating benzene and CpCo.
==Scope==
The trimerisation can be extended to inclusion of [[benzyne]].<ref>{{cite journal | title = Nickel-catalyzed cocyclotrimerization of arynes with diynes; a novel method for synthesis of naphthalene derivatives | author = Jen-Chieh Hsieh and Chien-Hong Cheng | journal = [[Chemical Communications]] | year = 2005 | volume = 2005 | issue = 19 | pages = 2459–2461 | doi = 10.1039/b415691a}}</ref> Benzyne is generated [[in situ]] from a [[benzene]] compound with a [[triflate]] and a [[trimethylsilyl]] [[substituent]] in the [[ortho-]] positions and reacts with a di-yne such as 1,7-octadiyne and with a [[nickel(II) bromide]] / [[zinc]] catalyst system (NiBr<sub>2</sub> [[1,2-Bis(diphenylphosphino)ethane|bis(diphenylphosphino) ethane]] / Zn) to the corresponding [[naphthalene]] derivative.
[[Image:AlkyneTrimerizationInvolvingAnAryne.png|400px|Alkyne trimerization involving an aryne]]
In the [[catalytic cycle]] elementary zinc serves to reduce nickel(II) to nickel(0) to which can then coordinate two alkyne bonds. A [[cyclometalation]] step follows to the nickelcyclopentadiene intermediate and then coordination of the [[benzyne]] which gives a [[CH activation|C-H insertion reaction]] to the nickelcycloheptatriene compound. [[Reductive elimination]] liberates the tetrahydroanthracene compound.
In one study, a combination of a [2+2+2] trimerization and a [[Diels-Alder reaction|[4+2] cycloaddition]] gives access to a [[taxol total synthesis|Taxol]] analogue<ref>{{cite journal | author = G. Chouraqui, M. Petit, P. Phansavath, C. Aubert and M. Malacria | title = From an Acyclic, Polyunsaturated Precursor to the Polycyclic Taxane Ring System: The [4+2]/[2+2+2] and [2+2+2]/[4+2] Cyclization Strategies | year = 2006 | journal = [[European Journal of Organic Chemistry]] | volume = 2006 | issue = 6 | pages = 1413–1421 | doi = 10.1002/ejoc.200500762}}</ref> (''Scheme 2'' <ref>Reaction sequence: a] CpCo(CO)<sub>2</sub>, [[xylene]], [[photochemistry|irradiation]] b] desilylation by [[Tetra-n-butylammonium fluoride]] c] intramolecular ring closure by [[butyllithium]] (oxygen nucleophile) and [[tosyl chloride]] (tosyl [[leaving group]]) e] desilylation by [[Tetra-n-butylammonium fluoride]] e] [[organic oxidation|oxidation]] [[IBX acid]] to ketone f] [[enolate]] formation with [[Sodium bis(trimethylsilyl)amide|NaHMDS]] followed by [[selenation]] with phenylseleniumchloride g] selenium oxidation and elimination with [[sodium periodate]] h] [[Diels-Alder reaction]] with [[boron trifluoride]]</ref> ). In this reaction sequence the trimerization takes place in [[xylene]] with catalyst the [[cobaltocene]] CpCo(CO)<sub>2</sub> (one Cp unit replaced by two [[metal carbonyl|carbonmonoxide ligand]]s) and with irradiation. The two main components are held together by a temporary [[silicon tether]].
[[Image:Taxol framework Chouraqui.png|center|600px|Scheme 2. Taxol framework Ref. Chouraqui 2006]]
[[Dicobalt octacarbonyl]] catalyzes the trimerization towards a hexakis(4-ferrocenylphenyl)benzene <ref>{{cite journal | author = V. J. Chebny, D. Dhar, S. V. Lindeman and R. Rathore | title = Simultaneous Ejection of Six Electrons at a Constant Potential by Hexakis(4-ferrocenylphenyl)benzene | year = 2006 | journal = [[Org. Lett.]] | volume = 8 | issue = 22 | pages = 5041–5044 | doi=10.1021/ol061904d}}</ref><ref>In a [[redox reaction]] the six [[ferrocene]] substituents lose an electron each at one and the same potential.</ref>:
[[Image:HexaferrocenylbenzeneFromAlkyne.png|center|400px|Scheme 3. Hexakis(4-ferrocenylphenyl)benzene]]
==References==
<div class="references-small"><references/></div>
[[Category:Carbon-carbon bond forming reactions]]
[[Category:Cycloadditions]]
[[Category:Multiple component reactions]]