Reppe alkyne cyclotrimerization

What is Reppe alkyne cyclotrimerization?

The conversion of acetylene to benzene was first reported by Bertholet in 1866 at temperatures over 400 °C. However, it was Reppe who discovered in 1949 the Ni(II) complex catalyzed [2+2+2] cyclotrimerization of alkynes, which is commonly known as the Reppe alkyne cyclotrimerization.

Reppe alkyne cyclotrimerization - general reaction scheme
Reppe alkyne cyclotrimerization

Reppe alkyne cyclotrimerization is a highly convergent and atom-economic approach to benzene derivatives. When acetylene is used as the alkyne source, it is specifically called the metal-catalyzed acetylene trimerization or acetylene cyclotrimerization. Reppe alkyne cyclotrimerization is a highly exothermic transformation that liberates a large amount of energy. However, without a catalyst, the activation energy required for this transformation is exceedingly high, making the pure trimerization of alkyne useless for organic synthesis.

The transition metal complex catalysis makes this reaction remarkably easy and tolerable for a wide variety of functional groups. Conjugated alkynes are more reactive than unconjugated ones, and among the transition metals, the complexes from group VIII elements such as Co, Rh, Ni, and Pd have the highest activities. Cobalt complexes are almost always the first choice. Ni complexes are less reactive than their cobalt analogs but are the only ones successfully used in asymmetric reactions. Pd is the most active element among Ni, Pd, and Pt. The Rh-related Grubbs catalyst is almost as effective as cobalt catalyst, but the corresponding reaction takes place via a completely different mechanism.

Other metal complexes, such as Copper complex, Iridium complex, tantalum-η2-alkyne complexes, titanium complexes, chromium (VI) complex, dirhodaborane, Grubbs catalyst or Wilkinson’s catalyst, metal cluster, and metal porphyrin complexes, have also been successfully used for this reaction. Enamine-directed and microwave-promoted non-metal-catalyzed alkyne cyclotrimerization have also been developed.

When Reppe alkyne cyclotrimerization involves three different asymmetric alkynes, the regioselectivity is unpredictable, generating as many as 38 different isomers. Recent developments have improved the regioselectivity by using a partial or total intramolecular version of cyclotrimerization using a silyl or borate tether. Cyclotrimerization through titanium metalation, known as metalative Reppe reaction, converts three different asymmetric alkynes into single aromatic compounds.