Transition Metal Catalyzed [2+2+2] Cycloaddition and Application in Organic Synthesis

Abstract

The [2+2+2] cycloaddition strategy is complementary to the well known Diels-Alder reaction for the generation of polycyclic compounds. This [2+2+2] approach is atom-economical and, with the availability of new catalysts to effect the [2+2+2] cycloaddition reaction, synthesis of a wide variety of highly functionalized polycycles is possible. This review deals with some recent advances relating to [2+2+2] cycloaddition reactions involving the syntheses both of polycycles

[2+2+2] Cycloaddition Reactions Catalyzed by Transition Metal Complexes

“…Kotha and co-workers have reviewed the synthesis of benzene derivatives by the cyclotrimerization of three alkyne functionalities utilizing transition metal systems as catalysts. [1] Their review is divided into: (a) intermolecular reactionsin which the three pi (alkyne) systems are part of three different molecules, (b) partially intermolecular reactions -two pi systems are connected, and (c) totally intramolecular reactions -all three alkyne moieties are present in the same molecule. They have also discussed the application of the [2 + 2 + 2] cycloaddition reaction in the synthesis of amino acids, peptides, and natural products.…”

“…[1][2][3] The [2 + 2 + 2] cycloaddition reaction is remarkable in terms of its ability to utilize various unsaturated substrates such as alkynes, diynes, alkenes, imines, isocyanates, isothiocyanates, and CO 2 in the synthesis of a broad variety of highly substituted cyclic molecules such as benzenes, pyridines, pyridones, 1,3-cyclohexadienes, pyrones, thiopyridones and cyclohexanes. Multisubstituted benzenes and pyridines have traditionally been synthesized by aromatic electrophilic substitution (AES) reactions and a variety of metal-mediated coupling reactions.…”

A General Approach to Chemo‐ and Regioselective Cyclotrimerization Reactions

“…The [2+2+2] cyclotrimerization reaction is an efficient tool for the construction of carbo-and heterocyclic structures. [1,2] Traditionally, the most commonly used catalyst systems are based on cobalt and rhodium. These catalysts, in conjunction with a partially intramolecular reaction using tethered alkynes, have led to several practical applications of the [2+2+2] cyclotrimerization in the construction of fused pyridine and benzene molecules, including several total syntheses.…”

“…Mechanistic explanations of nonthermal microwave effects are still in their infancy [6,8,16] and we are currently investigating the details of the observed rate enhancements. A possible explanation could be the lowering of activation barriers in the multistep cyclotrimerization mechanism [1,2] through specific dipole-dipole interactions of the electric field induced by microwave irradiation of polar intermediates (for example, metallacyclopentadienes) or polar transition states. Through this methodology, we have demonstrated the potential to employ microwave irradiation in the activation of a catalyst system for new synthetic transformations.…”

“…The cyclotrimerization was performed in nonpolar toluene as the solvent at 110 8C with 10 mol % [CpCo(CO) 2 ] under microwave irradiation (300 W) for 10 min. After removal of the protecting group with TFA, 3 was obtained in 46 % yield (similar results have recently been observed by others [9,10] ).…”