Alkyne trimerisation

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An alkyne trimerisation reaction is a [2+2+2] cyclization reaction where three alkyne molecules 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 [1].

Scheme 1. Alkyne trimerization

The trimerisation can be extended to inclusion of benzyne [2]. 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 (NiBr2 bis(diphenylphosphino) ethane / Zn) to the corresponding naphthalene derivative. 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 C-H insertion reaction to the nickelcycloheptatriene compound. Reductive elimination liberates the naphthalene compound.

In one study [3] a combination of a [2+2+2]trimerization and a [4+2]cycloaddition gives access to a Taxol analogue (Scheme 2 [4] ). In this reaction sequence the trimerization takes place in xylene with catalyst the cobaltocene CpCo(CO)2 (one Cp unit replaced by two carbonmonoxide ligands) and with irradiation. The two main components are held together by a temporary silyl tether.

Scheme 2. Taxol framework Ref. Chouraqui 2006

Dicobalt octacarbonyl catalyzes the trimerization towards a hexakis(4-ferrocenylphenyl)benzene [5] [6]:

Scheme 3. Hexakis(4-ferrocenylphenyl)benzene


[edit] References

  1. ^ A simple cobalt catalyst system for the efficient and regioselective cyclotrimerisation of alkynes Gerhard Hilt , Thomas Vogler, Wilfried Hess, Fabrizio Galbiati Chemical Communications, 2005, (11), 1474 Abstract
  2. ^ Nickel-catalyzed cocyclotrimerization of arynes with diynes; a novel method for synthesis of naphthalene derivatives Jen-Chieh Hsieh and Chien-Hong Cheng Chemical Communications, 2005, (19), 2459 - 2461 Abstract
  3. ^ 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 Gaëlle Chouraqui, Marc Petit, Phannarath Phansavath, Corinne Aubert, Max Malacria European Journal of Organic Chemistry Volume 2006, Issue 6 , Pages 1413 - 1421 Abstract
  4. ^ Reaction sequence: a] CpCo(CO)2, xylene, 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] oxidation IBX acid to ketone f] enolate formation with NaHMDS followed by selenation with phenylseleniumchloride g] selenium oxidation and elimination with sodium periodate h] Diels-Alder reaction with boron trifluoride
  5. ^ Simultaneous Ejection of Six Electrons at a Constant Potential by Hexakis(4-ferrocenylphenyl)benzene Vincent J. Chebny, Dwairath Dhar, Sergey V. Lindeman, and Rajendra Rathore Org. Lett.; 2006; 8(22) pp 5041 - 5044; (Letter) DOI:10.1021/ol061904d
  6. ^ In a redox reaction the six ferrocene substituents lose an electron each at one and the same potential.
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