In organic chemistry, an alkyne trimerisation is a [2+2+2] cycloaddition reaction in which three alkyne units () react to form a benzene ring. The reaction requires a metal catalyst. The process is of historic interest as well as being applicable to organic synthesis. Being a cycloaddition reaction, it has high atom economy. Many variations have been developed, including cyclisation of mixtures of alkynes and alkenes as well as alkynes and nitriles. Mechanism and stereochemistry 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 Reppe and Schweckendiek reported their wartime results showing that nickel compounds are effective catalysts: 3 RC2H -> C6R3H3 Since this discovery, many other cyclotrimerisations have been reported. 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. Starting from the metallacyclopentadiene intermediate, many pathways can be considered including metallocycloheptatrienes, metallanorbornadienes, and a more complicated structure featuring a carbenoid ligand. Catalysts used include cyclopentadienylcobalt dicarbonyl and Wilkinson's catalyst. Stereochemistry and regiochemistry Trimerisation of unsymmetrical alkynes gives two isomeric benzenes. For example, phenylacetylene affords both 1,3,5- and 1,2,4-. The substitution pattern about the product arene is determined in two steps: formation of the metallocyclopentadiene intermediate and incorporation of the third equivalent of alkyne. Steric bulk on the alkyne coupling partners and catalyst have been invoked as the controlling elements of regioselectivity. Chiral catalysts have been employed in combination with arynes to produce non-racemic atropisomeric products. 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. 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. 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. 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). For nickel catalysis, formation of larger rings