Alkyne trimerisation

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.

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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].

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 ^[2]

The ligand L in the 18-electron compound CpCoL₂ (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 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 second oxidative addition 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 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(η⁴arene) complex and then a CpCo(η⁶arene) sandwich compound before eliminating benzene and CpCo.

Scope

The trimerisation can be extended to inclusion of benzyne.^[3] 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 tetrahydroanthracene compound.

In one study, a combination of a [2+2+2] trimerization and a [4+2] cycloaddition gives access to a Taxol analogue^[4] (Scheme 2 ^[5] ). 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 silicon tether.

Dicobalt octacarbonyl catalyzes the trimerization towards a hexakis(4-ferrocenylphenyl)benzene ^[6][7]:

References