Cyclotrimerization

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.  

Rhodium also has been reported as a catalyst for [2-I-2-1-2] alkyne cycloaddition in water. Uozumi et al. explored the use of an amphiphihc resin-supported rhodium-phosphine complex as catalyst (Eq. 4.60). The immobilized rhodium catalyst was effective for the [2- -2- -2] cycloaddition of internal alkynes in water, although the yields of products were not satisfactory. 

Rhodium catalysis in an aqueous-organic biphasic system was highly effective for intramolecular [2- -2- -2] cyclotrimerization. It has been shown that the use of a biphasic system could control the concentration of an organic hydrophobic substrate in the aqueous phase, thus increasing the reaction selectivity. The intramolecular cyclization for 

Palladium has also been reported as an effective catalyst for [2-I-2-1-2] alkyne cyclotrimerization in water. Both aryl and alkylalkynes underwent 

Alkyne-nitrile cyclotrimerization is a powerful synthetic methodology for the synthesis of complex heterocyclic aromatic molecules. 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(I) 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. In addition, photocatalyzed [2+2+2] alkyne or alkyne-nitrile cyclotrimerization in water and cyclotrimerization in supercritical have been reported in recent years. 

The reactions that yield benzene rings can be categorized further into the following types according to the substrates involved (1) intermolecular cycloaddition of three alkynes (cyclotrimerization), (2) partially intramolecular cycloaddition ofdiynes with alkynes, and (3) fully intramolecular cyclotrimerization of triynes. In the next section, the synthetic routes to benzene derivatives using ruthenium-catalyzed cycloaddition are surveyed according to these classifications. Classic examples of [2 + 2 + 2] alkyne cycloadditions using stoichiometric ruthenium mediators are included since they provide useful information on the further development of ruthenium catalysis. 

Since the first reaction was discovered by Reppe and Schweckendiek [4], numerous transition metals have been used to promote alkyne [2 + 2 + 2] cycloadditions [1]. The majority of attention has focused on group 9 and 10 transition elements, including Co, Rh, Ni, and Pd. In comparison to these precedents, [2 + 2 + 2] alkyne cycloaddition reactions involving group 8 metals have been relatively neglected. However, over the past decade, there has been significant progress in efficient and selective [2 + 2 + 2] alkyne cycloadditions catalyzed by ruthenium. In this section we review the synthesis of benzene derivatives via alkyne [2 + 2 + 2] cycloaddition both stoichiometrically and catalytically. 

13) to deliver the corresponding benzene derivatives in moderate to excellent yields. The resulting ratios of the 1,3,5- and 1,2,4-substituted isomers 3 and 4 range from 7.3 1 to 1 16. In all cases except for entries 3, 8, and 9, the unsymmetrical 1,2,4-isomers 4 are the major products. Cyclofrimerization of DMAD is also catalyzed by complexes 6,11,14, and 15 to furnish mellitate 2 in 25 to 96% yields (entries 14 to 17). Overall, complexes featuring a substituted cyclopentadienyl ligand (e.g., 6 and 

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Pd-cataly2ed reactions of butadiene are different from those catalyzed by other transition metal complexes. Unlike Ni(0) catalysts, neither the well known cyclodimerization nor cyclotrimerization to form COD or CDT[1,2] takes place with Pd(0) catalysts. Pd(0) complexes catalyze two important reactions of conjugated dienes[3,4]. The first type is linear dimerization. The most characteristic and useful reaction of butadiene catalyzed by Pd(0) is dimerization with incorporation of nucleophiles. The bis-rr-allylpalladium complex 3 is believed to be an intermediate of 1,3,7-octatriene (7j and telomers 5 and 6[5,6]. The complex 3 is the resonance form of 2,5-divinylpalladacyclopentane (1) and pallada-3,7-cyclononadiene (2) formed by the oxidative cyclization of butadiene. The second reaction characteristic of Pd is the co-cyclization of butadiene with C = 0 bonds of aldehydes[7-9] and CO jlO] and C = N bonds of Schiff bases[ll] and isocyanate[12] to form the six-membered heterocyclic compounds 9 with two vinyl groups. The cyclization is explained by the insertion of these unsaturated bonds into the complex 1 to generate 8 and its reductive elimination to give 9. 

Dimethyl acetylenedicarboxylate (DMAD) (125) is a very special alkyne and undergoes interesting cyclotrimerization and co-cyclization reactions of its own using the poorly soluble polymeric palladacyclopentadiene complex (TCPC) 75 and its diazadiene stabilized complex 123 as precursors of Pd(0) catalysts, Cyclotrimerization of DMAD is catalyzed by 123[60], In addition to the hexa-substituted benzene 126, the cyclooctatetraene derivative 127 was obtained by the co-cyclization of trimethylsilylpropargyl alcohol with an excess of DMAD (125)[6l], Co-cyclization is possible with various alkenes. The naphthalene-tetracarboxylate 129 was obtained by the reaction of methoxyallene (128) with an excess of DMAD using the catalyst 123[62],... 

Butynediol is more difficult to polymerize than propargyl alcohol, but it cyclotrimerizes to hexamethylolbenzene [2715-91 -5] (benzenehexamethanol) with a nickel carbonyl—phosphine catalyst (64) with a rhodium chloride—arsine catalyst a yield of 70% is claimed (65). 

Other Methods. A variety of other methods have been studied, including phenol hydroxylation by N2O with HZSM-5 as catalyst (69), selective access to resorcinol from 5-methyloxohexanoate in the presence of Pd/C (70), cyclotrimerization of carbon monoxide and ethylene to form hydroquinone in the presence of rhodium catalysts (71), the electrochemical oxidation of benzene to hydroquinone and -benzoquinone (72), the air oxidation of phenol to catechol in the presence of a stoichiometric CuCl and Cu(0) catalyst (73), and the isomerization of dihydroxybenzenes on HZSM-5 catalysts (74). 

Mesitylene can be synthesized from acetone by catalytic dehydrocyclization (17). Similarly, cyclotrimerization of acetylenes has produced PMBs such as hexamethylbenzene (18). Durene has been recovered from Methanex s methanol-to-gasoline (MTG) plant in New Zealand (19). 

The formation of isocyanurates in the presence of polyols occurs via intermediate aHophanate formation, ie, the urethane group acts as a cocatalyst in the trimerization reaction. By combining cyclotrimerization with polyurethane formation, processibiUty is improved, and the friabiUty of the derived... 

Scheme 5.2-24 Biphasic, Fe-catalyzed cyclotrimerization of butadiene in [BMIM][BF4],...

Scheme 3. CpCo(CO)2-catalyzed cyclotrimerization of 7 with 8, and subsequent reactions of benzo-cyclobutene 9.

With respect to reaction mechanism, it is likely that CpCo(CO)2-mediated alkyne cyclotrimerizations proceed through discrete orga-nometallic intermediates and are therefore not concerted.12 A plausible mechanistic pathway for the CpCo(CO)2-catalyzed cyclotri-... 

Scheme 6. Vollhardt s tandem alkyne cyclotrimerization/o-quinodimethane cycloaddition strategy for polycycle synthesis.

Subphthalocyanines are the products of the cyclotrimerization of molecules like phthalonitriles or isoindolinediimines. The formation of structural isomers occurs if these precursors are un-symmetrically substituted at the benzene nucleus (see also p736). 

Moulijn et al. (33) studied the reactions of some linear alkynes over a W08-Si02 catalyst in a fixed-bed flow reactor. Besides metathesis, cyclotrimerization to benzene derivatives occurred. Thus, propyne yielded, in addition to metathesis products, a mixture of trimethylbenzenes. From this an indication of the mechanism of the metathesis of alkynes can be obtained. 

For the cyclotrimerization of alkynes, several mechanisms have been proposed. The most plausible ones are a concerted fusion of three ir-bonded alkyne molecules, and stepwise processes involving a cyclobutadiene complex or a five-membered metallocyclic intermediate (98). In the case of the cyclotrimerization of a-alkynes it is possible to discriminate between a reaction pathway via a cyclobutadiene complex and the other reaction pathways, by analysis of the products. If cyclotrimerization proceeds via a cyclobutadiene complex and if steric factors do not affect the reaction,... 

Because of the almost complete absence of the 1,2,3-isomer in the product mixture when propyne, 1-butyne, or 1-pentyne were passed over the W08-Si02 catalyst, it was concluded that cyclotrimerization over this catalyst does not occur via a cyclobutadiene complex (39). 

Since cyclotrimerization and metathesis of alkynes occur simultaneously, a common intermediate might be involved, which would mean that the metathesis of alkynes does not proceed via a cyclobutadiene complex. 

The metathesis of ene-ynamides has been investigated by Mori et al. and Hsung et al. [80]. Second-generation ruthenium catalysts and elevated temperatures were required to obtain preparatively useful yields. Witulski et al. published a highly regioselective cyclotrimerization of 1,6-diynes such as 98 and terminal alkynes using the first-generation ruthenium metathesis catalyst 9... 

In 1988, Linstrumelle and Huynh used an all-palladium route to construct PAM 4 [21]. Reaction of 1,2-dibromobenzene with 2-methyl-3-butyn-2-ol in triethylamine at 60 °C afforded the monosubstituted product in 63 % yield along with 3% of the disubstituted material (Scheme 6). Alcohol 15 was then treated with aqueous sodium hydroxide and tetrakis(triphenylphosphine)palladium-copper(I) iodide catalysts under phase-transfer conditions, generating the terminal phenylacetylene in situ, which cyclotrimerized in 36% yield. Although there was no mention of the formation of higher cyclooligomers, it is likely that this reaction did produce these larger species, as is typically seen in Stephens-Castro coupling reactions [22]. 

Whereas cyclotrimerization of phenylacetylene with uncomplexed PdCl2 provides only low yields of the unsymmetrical trimer, and polymers, on treatment of 3-hexyne with Pd/C and Me3SiCl 14 hexaethylbenzene 2165 is obtained in quantitative yield [78] (Scheme 13.23). 

Recently, it has been demonstrated that coordination vacancies on the surface metal cations are relevant to the unique redox reactivity of oxide surfaces]2]. Oxidation of fonnaldehyde and methyl formate to adsorbed formate intermediates on ZnO(OOOl) and reductive C-C coupling of aliphatic and aromatic aldehydes and cyclic ketones on 1102(001) surfaces reduced by Ar bombardment are observed in temperature-prognunmed desorption(TPD). The thermally reduced 1102(110) surface which is a less heavily damaged surface than that obtained by bombardment and contains Ti cations in the -t-3 and +4 states, still shows activity for the reductive coupling of formaldehyde to form ethene]13]. Interestingly, the catalytic cyclotrimerization of alkynes on TiO2(100) is also traced in UHV conditions, where cation coordination and oxidation states appear to be closely linked to activity and selectivity. The nonpolar Cu20( 111) surface shows a... 

Catalytic Formation of Carbon-Carbon Bonds in Ultrahigh Vacuum Cyclotrimerization of Alkynes on Reduced Ti02 Surfaces... 

We have previously demonstrated the stoichiometric cyclotrimerization of a variety of alkynes on reduced TiO2(001) surfaces in UHV using TPD [1,2]. A... 

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