Cyclotrimerization 2 + 2 + 2-, cobalt

Yong et al. developed a cobalt-catalyzed [2+2+2] cyclotrimerization of terminal alkynes in good yields in aqueous media (80/20 mixture of water and ethanol) at room temperature. A cyclopentadienyl cobalt complex bearing a pendant phosphine ligand was used as a catalyst (Eq. 4.59). The cyclotrimerization of internal alkynes resulted in lower yields and required an elevated temperature, most likely due to steric interactions. For example, cyclotrimerization of 2,5-dimethyl-3-hexyne gave hexaisopropylbenzene in 51% yield and the reaction of diphenylethyne resulted in a 47% yield of hexaphenylbenzene.112... 

Alkyne-nitrile cyclotrimerization is a powerful synthetic methodology for the synthesis of complex heterocyclic aromatic molecules.118 Recently, Fatland et al. developed an aqueous alkyne-nitrile cyclotrimerization of one nitrile with two alkynes for the synthesis of highly functionalized pyridines by a water-soluble cobalt catalyst (Eq. 4.62). The reaction was chemospecific and several different functional groups such as unprotected alcohols, ketones, and amines were compatible with the reaction.119 In addition, photocatalyzed [2+2+2] alkyne or alkyne-nitrile cyclotrimerization in water120 and cyclotrimerization in supercritical H2O110121 have been reported in recent years. 

Scheme 9. Cobalt-catalyzed cyclotrimerization of propargylated glycosides.90...

Novel transition metal-mediated strategies were also well represented this past year. Takahashi and co-workers reported a s nickel-catalyzed reaction between azaziconacyclopentadienes (9) and alkynes to form pyridines (10) of varying substitution patterns <00JA4994>. This methodology, a formal cyclotrimerization, is also noteworthy since two different alkynes can be used. In similar fashion, Eaton reported an aqueous, cobalt(II) catalyzed cyclotrimerization between two identical acetylenes and one nitrile to afford substituted pyridines . 

Comparison of the different types of cobalt catalysts shows that the in situ system [Eq.(2)] is most accessible while the Rep-, R(ind)-, and bori-ninato ligands having electron-withdrawing substitutents are the most active. The difference between the 14e" and the 12e core complexes makes itself apparent in the chemoselectivity of the reaction. Catalysts containing a 14-electron core favor pyridine formation, whereas those containing a 12-electron core (i.e., the rj -allylcobalt systems) favor the formation of benzene derivatives by cyclotrimerization of the alkynes. For example, in the reaction of propyne and propionitrile at 140°C in the presence of a 12-electron system (5), a 2 1 ratio of benzene to pyridine product is formed, whereas a catalyst containing the cpCo moiety (a 14-electron system) leads (under identical conditions) to the predominant formation of pyridine derivatives (84HCA1616). 

The cobalt catalyzed cocyclization of alkynes with heterofunctional substrates is not limited to nitriles. cpCo-core complexes are capable of co-oligomerizing alkynes with a number of C,C, C,N or C,0 double bonds in a Diels-Alder-type reaction. Chen, in our laboratories, has observed that these cycloadditions are best performed with the help of stabilizers such as ketones or acetic esters that are weakly coordinated to the cobalt and prevent the alkynes from being cyclotrimerized at the metal center... 

These results can be summarized as follows (1) the cobalt-mediated pyridine formation and alkyne cyclotrimerization depend on the square of the alkyne concentration and are independent of the nitrile concentration (2) a common cobaltacydopentadiene intermediate is responsible for both the pyridine and the benzene formation and may be regarded as a key intermediate for both hetero- and carbocyclic pathways. 

Reactions involving the [4 + 1 + 1] principle, an example of which is shown in equation (136), are rather uncommon and of strictly limited utility [3 + 2 + 1] and [2 + 2 + 2] processes, on th,e other hand, are well known. Representative [3 + 2+1] three-bond formation processes are given in equations (137)—(141), from which it can be seen that the common situation is where ammonia, a substituted amine or formamide constitutes the one-atom fragment. Many [2 + 2 + 2] atom fragment syntheses are known and some are familiar reactions. Thus, the cobalt(I)-catalyzed condensation of nitriles and isocyanates with alkynes gives pyridines and 2-pyridones, often in excellent yield (e.g. equation 142), while the cyclotrimerizations of nitriles, imidates, isocyanates, etc., are well established procedures for the synthesis of 1,3,5-triazine derivatives (e.g. equation 143). Further representative examples are given in equations (144)-(147), and the reader is referred to the monograph chapters for full discussion of these and other [2 + 2 + 2] processes. Examination of the... 

It appears difficult to propose a unified mechanism to explain all experimental observations of the cyclotrimerization of acetylene. The most common pathway, studied mainly with cobalt complexes,72 73 involves a metallacyclopentadiene intermediate ... 

The enantiomeric purity of the 3-pinanecarbaldehyde corresponds to the a-pinane utilized (70-85%). Enantiomerically pure aldehyde can be obtained by the acid-catalyzed trimerization of the aldehyde, with only one enantiomer being preferentially cyclotrimerized to a crystalline compound.2311 Cleavage of the trimer results in enantiomerically pure aldehyde. If cobalt catalysts are employed in the cyclization, rearrangement to the bomane structure takes place (equation 9).25... 

Cyclotrimerization of triynes has been reported using cobalt or iron complexes of NHCs without CO and Cp ligands.31 Benzannulated compounds have been isolated with up to quantitative yields. 

Vollhardf s group adopted the cobalt-catalyzed photochemical cyclotrimerization of alkynes for the rapid construction of a novel class of helicenes, helical [n]phe-... 

Related co-cyclotrimerizations of two alkyne molecules with limited isocyanates have also been achieved using cobalt and nickel catalysts. With respect to intramolecular versions, two examples of the cobalt(I)-catalyzed cycloaddition of a,m-diynes with isocyanates have been reported to afford bicyclic pyri-dones only in low yields, although 2,3-dihydro-5(lff)-indolizinones were successfully obtained from isocyanatoalkynes and several silylalkynes with the same cobalt catalysis [19]. On the other hand, the ruthenium catalysis using Cp RuCl(cod) as a precatalyst effectively catalyzed the cycloaddition of 1,6-diynes 21 with 4 equiv. of isocyanates in refluxing 1,2-dichloroethane to afford bicyclic pyridones 25 in 58-93% yield (Eq. 12) [20]. In this case,both aryl and aliphatic isocyanates can be widely employed. 

Substituted phthalides can be prepared in a [2+2+2] cycloaddition of two molecules of methyl propiolate with propargyl alcohol. This cyclotrimerization, which is catalyzed by a cobalt(ll)-DPPE complex in the presence of catalytic amounts of zinc, affords the reaction products in acceptable to good yields (Equation 150) <2005CC4955>. 

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