Catalysts cyclotrimerization

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],... 

Electron-deficient acetylenes 96 and 98 form 97 and 99, respectively, in poor yields with the assistance of Rh2(pfb)4 (Equation (19)). When Rh4(CO)i2 is used as the catalyst, cyclotrimerization of these acetylenes proceeds even in the presence of Me2PhSiH under GO pressure. ... 

In each of the alkyne metatheses outlined here, the byproduct is the volatile 2-butyne. The alkyne metathesis can only be carried out on internal alkynes, since the metathesis catalysts cyclotrimerize terminal alkynes such as 11 to benzene derivatives. In this context, it may prove useful that readily-available terminal alkynes such as 14 are easily isomerized specifically to methyl alkynes such as 15... 

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. 

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). 

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. 

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). 

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]. 

Steady-state molecular beam studies of the reaction of methylacetylene on reduced Ti02 (001) surfaces were undertaken to determine whether this reaction could be performed catalytically under UHV conditions. A representative experiment is presented in Figure 1. Prior to each experiment, the surface was sputtered and annealed to a temperature between 400 K and 550 K surfaces prepared in this manner have the highest fraction of Ti(+2) sites (ca. 30% of all surface cations) of any surface we have been able to create by initial sputtering [3]. Thus these are the surfaces most active for cyclotrimerization in TPD experiments [1]. Steady-state production of trimethylbenzene (as indicated by the m/e 105 signal detected by the mass spectrometer) was characterized by behavior typical of more traditional catalysts a jump in activity upon initial exposure of the crystal to the molecular beam, followed by a decay to a lower, constant level of activity over a longer time scale. Experiments of up to 6 hours in duration showed... 

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... 

Palladium has also been reported as an effective catalyst for [2+2+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.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. 

Among the most exciting frontiers in boratabenzene chemistry is the development of transition metal-boratabenzene complexes as catalysts. As early as 1984, it had been demonstrated that these adducts can accelerate useful reactions— specifically, Bonnemann established that (C5H5B-Ph)Co(cod) serves as a catalyst for pyridine-forming cyclotrimerization reactions of alkynes and nitriles.39... 

Following these investigations, Das and Roy first reported a Grubbs -catalyzed version of these intermolecular cyclotrimerizations, using 2-propynyl derivatives and a ruthenium carbenoid catalyst, which thus afforded mixtures of regioisomeric aryl... 

The cyclotrimer products are liberated in subsequent, consecutive substitution steps with new butadiene, which is an exothermic reaction (AH) for expulsion of all-t-CDT by three /ran.v-butadienes along 8b —> l b. This process, however, is endergonic by 7 kcal mol-1 (AG) after entropic costs are taken into account. Therefore, 7b and 8b (stabilized by donors) are indicated to be likely candidates for isolable intermediates of the catalytic process, while the active catalyst l b, the intermediate species 2b, in particular, and other species will not be present in a sufficient concentration, since they are either too reactive or thermodynamically too unfavorable, for experimental characterization. Overall, the cyclotrimerization process is driven by a strong thermodynamic force with an exothermicity of —44.6 kcal mol-1 (AH for the process without a catalyst) for the fusion of three trans-butadiene to afford the favorable all-t-CDT. 

Unlike nickel catalysts, palladium catalysts undergo neither cyclodimerization nor cyclotrimerization to form COD or CDT. Only one paper by Chepaikin and Khidekel reported that a mixture of divinylcyclobu-tanes was obtained from butadiene using palladium salts with noncom-plexing anions such as perchlorate and boron tetrafluoride (15). This is a big difference between the catalyses of palladium and nickel. 

Witulski introduced a novel protocol for crossed alkyne cyclotrimerizations of systems such as 87 mediated by Grubb s catalyst to produce 4,6-disubstituted indolines 88 <00CC1965>. Interestingly, use of Wilkinson s catalyst [RhCl(PPhj)3] allows for the regioselective synthesis of the corresponding 4,5-substituted isomers. 

The rhodium-catalyzed cyclization/hydrosilylation of internal diyne proceeds efficiently with high stereoselectivity (Scheme 106). However, terminal diynes show low reactivity to rhodium cationic complexes. Tolerance of functionalities seems to be equivalent between the rhodium and platinum catalysts. The bulkiness of the hydrosilane used is very important for the regioselectivity of the rhodium-catalyzed cyclization/hydrosilylation. For example, less-hindered dimethylethylsilane gives disilylated diene without cyclization (resulting in the double hydrosilylation of the two alkynes), and /-butyldimethylsilane leads to the formation of cyclotrimerization compound. 

Ruthenium(ll)-catalyzed cycloadditions of diynes with bicycloalkenes illustrate the synthetic importance of ruthena-cyclopentatrienes as biscarbenoid intermediates.380 Reaction of 1,6-diyne 448 and biscyclic alkene 449 with ruthenium catalyst afforded a mixture of biscyclopropanation product 450 and cyclotrimerization product 451 (Scheme 113). 

Under supercritical C02 at 102 °G, the [2 + 2 + 2]-cyclotrimerization of 3-hexyne with C02 was achieved by use of Ni(cod)2/dppb as a catalyst system (Scheme 27).39,40 In the case of diynes, the intramolecular cyclization/carboxyla-tion took place under high pressure and high temperature (Scheme 28).41,41a... 

Given the commercial availability of alkynes as two-carbon components, the intermolecular [5 + 2]-cycloaddition of alkynes and VCPs represents a potentially practical route to seven-membered rings. However, initial attempts at an intermolecular [5 + 2]-reaction of alkynes and VCPs with modified Wilkinson s catalysts led to cyclotrimerization of the alkynes and/or isomerization of the VCPs. The first intermolecular [5 + 2]-cycloaddition of alkynes was realized... 

The patent literature contains several references to the use of sulfoxide complexes, usually generated in situ, as catalyst precursors in oligomerization and polymerization reactions. Thus, a system based upon bis(acrylonitrile)nickel(0> with added Me2SO or EtgSO is an effective cyclotrimerization catalyst for the conversion of butadiene to cyclo-1,5,-9-dodecatriene (44). A similar system based on titanium has also been reported (407). Nickel(II) sulfoxide complexes, again generated in situ, have been patented as catalyst precursors for the dimerization of pro-pene (151) and the higher olefins (152) in the presence of added alkyl aluminum compounds. 

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