(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 organocobalt catalysts has been commercialized for the production of substituted pyridines. Cyclization involving substrates in which some or all of the alkyne units are tethered together can provide fused ring systems. The length of the tether(s) controls the sizes of the additional rings. Addition of a 1,5-diyne with an alkyne produces a benzocyclobutene, a strained structure that can then be induced to undergo further reactions. 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. Crowded triynes can cyclize to products exhibiting helical chirality. In one example remarkable for the formation of three new aromatic rings in one step, the triyne shown is transformed into the helical product via treatment with cyclopentadienylcobalt dicarbonyl. As of 2004, this process had yet to be rendered asymmetric, but the products could be separated through chiral HPLC. Cyclisation carried out with a diyne and a separate alkyne affords greater control. Using commercially available cyclopentadienylcobalt dicarbonyl, CpCo(CO)2, as catalyst, bis(trimethylsilyl)acetylene (BTMSA) will react with a diyne-1,2-disubstituted benzene to form an anthroquinone aromatic system: Benzyne, generated in situ from a benzene ring bearing ortho-distributed triflate and trimethylsilyl substituents, can be used to generate an aryne in place of an acetylene and combined with a suitable diyne. Such a benzene derivative reacts with 1,7-octadiyne in the presence of a suitable catalyst to generate a naphthalene system. This is an example of a hexadehydro Diels–Alder reaction. Trimerisation of three 2-butyne (dimethylacetylene) molecules yields hexamethylbenzene. The reaction is catalyzed by triphenylchromium tri-tetrahydrofuranate or by a complex of triisobutylaluminium and titanium tetrachloride. 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 Dötz reaction, palladium-catalyzed [4+2] benzannulation of enynes with alkynes, and Lewis-acid-mediated [4+2] cycloaddition of enynes with alkynes. Cyclization of transient benzyne species with alkynes, catalyzed by palladium, can also produce substituted aromatic compounds. Further reading References Carbon-carbon bond forming reactions Cycloadditions Multiple component reactions