Alkyne trimerisation

An alkyne trimerisation is a [2+2+2] 

Trimerisation of acetylene to benzene is highly exergonic, proceeding with a free energy change of 142 kcal/mol at room temperature. Kinetic barriers however prevent the reaction from proceeding smoothly. The breakthrough came in 1948, when Walter Reppe and W. J. Schweckendiek reported their wartime results showing that nickel compounds are effective catalysts:^[2][3]

${\displaystyle {\ce {3 RC2H -> C6R3H3}}}$

Since this discovery, many other cyclotrimerisations have been reported.^[4]

Mechanism

In terms of mechanism, the reactions begin with the formation of metal-alkyne complexes. The combination of two alkynes within the coordination sphere affords a metallacyclopentadiene.^[5] Starting from the metallacyclopentadiene intermediate, many pathways can be considered including metallocycloheptatrienes, metallanorbornadienes, and a more complicated structure featuring a carbenoid ligand.^[4]

Catalysts used include cyclopentadienylcobalt dicarbonyl and Wilkinson's catalyst.

Stereochemistry and regiochemistry

Trimerisation of unsymmetrical alkynes gives two isomeric benzenes. For example,

Chiral catalysts have been employed in combination with arynes to produce non-racemic atropisomeric products.^[6]

Scope and limitations

Catalysts for cyclotrimerisation are selective for triple bonds, which gives the reaction a fairly wide substrate scope. Many functional groups are tolerated. Regioselective intermolecular trimerization of unsymmetrical alkynes remains an unsolved problem.^[4]

Perhaps the most useful development in this area, at least from the commercial perspective is the cotrimerization of nitriles and alkynes. This reaction is a practical route to some substituted pyridines.^[7]

Some catalysts are deactivated by formation of stable, 18-electron η⁴-complexes. Cyclobutadiene, cyclohexadiene, and arene complexes have all been observed as off-cycle, inactivated catalysts.^[8] In addition to high-order polymers and dimers and trimers, which originate from low regio- and chemoselectivities, enyne side products derived from alkyne dimerisation have been observed. Rhodium catalysts are particularly adept at enyne formation (see below).^[9] For nickel catalysis, formation of larger rings (particularly cyclooctatetraene) can be a problem.

Synthetic applications

Alkyne trimerization is of no practical value, although the reaction was highly influential. The cotrimerization of alkynes and nitriles in the presence of

All three alkyne units can be tethered, leading to creation of three rings in a single step, with each of the two additional ring sizes controlled by the respective tether lengths.^[12]

Crowded triynes can cyclize to products exhibiting

Trimerisation of three

Trimerisation of three diphenylacetylene molecules yields hexaphenylbenzene. The reaction is catalyzed by dicobalt octacarbonyl.^[19]

Comparison with other methods

Cyclotrimerization presents an alternative to the functionalization of pre-formed aromatic compounds through electrophilic or nucleophilic substitution, the regioselectivity of which can sometimes be difficult to control.

Other methods for the direct formation of aromatic rings from substituted, unsaturated precursors include the

Further reading

• Musso, F.; Solari, E.; Floriani, C. (1997). "Hydrocarbon Activation with Metal Halides: Zirconium Tetrachloride Catalyzing the Jacobsen Reaction and Assisting the Trimerization of Alkynes via the Formation of η⁶-Arene−Zirconium(IV) Complexes". Organometallics. 16 (22): 4889.
  doi:10.1021/om970438g
  .
• Rodríguez, J. Gonzalo; Martín-Villamil, Rosa; Fonseca, Isabel (1997). "Tris(2,4-pentanedionato)vanadium-catalysed cyclotrimerization and polymerization of 4-(N,N-dimethylamino)phenylethyne: X-ray structure of 1,2,4-tris[4-(N,N -dimethylamino)phenyl]benzene". Journal of the Chemical Society, Perkin Transactions 1 (6): 945–948.
  ISSN 0300-922X
  .
• Sakurai, H.; Nakadaira, Y.; Hosomi, A.; Eriyama, Y.; Hirama, K.; Kabuto, C. (1984). "Chemistry of organosilicon compounds. 193. Intramolecular cyclotrimerization of macrocylic and acyclic triynes with Group 6 metal carbonyls. The formation of fulvene and benzene". J. Am. Chem. Soc. 106 (26): 8315.
  doi:10.1021/ja00338a063
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• Amer, I.; Bernstein, T.; Eisen, M.; Blum, J.; Vollhardt, K. P. C. (1990). "Oligomerization of alkynes by the RhCl₃-aliquat 336 catalyst system Part 1. Formation of benzene derivatives". J. Mol. Catal. 60 (3): 313.
  doi:10.1016/0304-5102(90)85254-F
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• Lee, C. L.; Hunt, C. T.; Balch, A. L. (1981). "Novel reactions of metal-metal bonds. Reactions of Pd₂{(C₆H₅)₂PCH₂P(C₆H₅)₂}₂Cl₂ with acetylenes, olefins, and isothiocyanates". Inorg. Chem. 20 (8): 2498.
  doi:10.1021/ic50222a026
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• Aalten, H. L.; van Koten, G.; Riethorst, E.; Stam, C. H. (1989). "The Hurtley reaction. 2. Novel complexes of disubstituted acetylenes with copper(I) benzoates having a reactive ortho carbon-chlorine or carbon-bromine bond. X-ray structural characterization of tetrakis(2-chlorobenzoato)bis(diethyl acetylenedicarboxylate)tetracopper(I)". Inorg. Chem. 28 (22): 4140.
  doi:10.1021/ic00321a020
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• Hardesty, J. H.; Koerner, J. B.; Albright, T. A.; Lee, G. B. (1999). "Theoretical Study of the Acetylene Trimerization with CpCo". J. Am. Chem. Soc. 121 (25): 6055.
  doi:10.1021/ja983098e
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• Ozerov, O. V.; Patrick, B. O.; Ladipo, F. T. (2000). "Highly Regioselective [2 + 2 + 2] Cycloaddition of Terminal Alkynes Catalyzed by η6-Arene Complexes of Titanium Supported by Dimethylsilyl-Bridgedp-tert-Butyl Calix[4]arene Ligand". J. Am. Chem. Soc. 122 (27): 6423.
  doi:10.1021/ja994543o
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