Trimerization of alkyne

Malacria and coworkers [274] used an intermolecular trimerization of alkynes to gain efficient access to the skeleton of the phyllocladane family. Thus, the Co-cata-lyzed reaction of the polyunsaturated precursor 6/4-4 gave 6/4-5 in 42% yield. Here, six new carbon-carbon bonds and four stereogenic centers are formed. The first step is formation of the cyclopentane derivative 6/4-6 by a Co-catalyzed Conia-ene-type reaction [275] which, on addition o f his( Iri me ill y I si ly 1) e thy ne (btmse), led to the benzocyclobutenes 6/4-7 (Scheme 6/4.2). The reaction is terminated by the addition of dppe and heating to reflux in decane to give the desired products 6/4-5 by an electrocyclic ring opening, followed by [4+2] cycloaddition. 

As shown in the two examples described here, formation of the benzene nucleus by trimerization of alkynes is usually catalyzed by a Co-complex. However, Und-heim and coworkers [276] have recently shown that a Ru "-complex can also be used. Reaction of the triyne 6/4-9, which was prepared from SchollkopPs bislactim ether 6/4-8 [277] with Grubbs I catalyst 6/3-13, led to 6/4-10 in an excellent yield of 90%. Hydrolysis of 6/4-10 gave the desired as-indacene-bridged bis(a-amino acid) derivative 6/4-11 (Scheme 6/4.3). 

Fig. 4. Generic mechanism for trimerization of alkynes to provide arenes by CpCoL2 catalysts (94).

The vapors of the transition metals are effective in promoting the catalytic trimerization of alkynes, e.g.,... 

Scheme 9.33 Synthesis of regioisomers by an iron-catalyzed trimerization of alkynes.

The trimerization of alkynes is a general and useful method for the preparation of aromatic compounds [152]. However, this method has serious limitations when three different alkynes are used, as numerous regioisomers may be formed. Taka-hashi and co-workers have reported the beginnings of a solution using zirconocy-clopentadienes prepared in situ from two different alkynes. Substituted arenes were obtained upon addition of a third alkyne to the organometallic complex in the presence of copper chloride [153] or a nickel complex [154], This approach is nevertheless limited by the fact that at least one of the alkynes must be symmetrical, and by... 

Few examples of such polymolecular processes are known, however. Trimerizations of alkynes appear to be 2 + 2 + 2 cycloadditions, but... 

A Co2(CO)8-catalyzed trimerization of alkyne 1 in refluxing dioxane gave (90%) a 1 3 ratio of the symmetrical and unsymmetrical polyethers 2 and 3 in an overall 40% conversion,... 

Photochemical trimerization of alkynes to give benzenes is, however, well documented. Benzene (and butadiyne) are the most abundant volatile products in... 

Trimerization of alkynes. Heating alkynes with Si Cl at 170-180° promotes the formation of substituted benzenes. 

The trimerization of alkynes to a Dewar benzene, which was found by Viehe s group, was developed by Schafer s group using a Lewis add as a catalyst. Thus, the treatment of 2-butyne with aluminum chloride gives hexamethyl Dewar benzene (7)9). Hexamethyl Dewar benzene is fairly stable and now commercially available. 

The strong forward donation-back donation of electrons (i.e., the Chatt model) between alkynes and ruthenium makes such a bond a very good ligand for Ru. Hence it is not surprising that reactions involving ruthenacyclopentadienes as intermediates, notably in the trimerization of alkynes to benzenes, occur readily. Intercepting the ruthenacyclopentadiene prior to its reaction with an additional alkyne, however, is rather rare. A unique juxtaposition of functionality occurs when a propargyl alcohol is the alkyne partner which allows such a diversion as shown in Scheme 1.3. 

The chelate function of the tertiary bis-phosphane then allows then the isolation of this 7 -arene complex, which represents a good model for the well-known Rh-catalyzed trimerization of alkynes. 

Mixtures of alkynes and cyclopentadiene with Co atoms yield a variety of air-stable organometallics . These result from hydrogen transfer from cyclopentadiene, dimerization or trimerization of alkyne, clustering of Co atoms and simple addition. The nature of the products implies that a variety of reactive intermediates must be formed en route. Table 1 shows the major products that are formed. 

Trimerization of alkynes to derivatives of benzene is promoted by [Co(pyridine)6]+ BPh4. In the presence of hydrogen the catalyst induces the formation of a mixture of the dienes 565-567 and the tributylbenzenes 568 and 569 from 1 -hexyne the composition of the mixture depends on the hydrogen pressure. ... 

Trimerizations of alkynes are also of interest and Ferris and Guillemin have demonstrated that irradiation of the alkyne 154 at 185 or 206 nm results in the formation of 1,3,5-tricyanobenzene. This product is also formed on irradiation at 254 nm, but then it is accompanied by 1,2,4-tricyanobenzene and tetracyanocyclo-octatetraene. 

A similar scheme is suggested by Bergman and collaborators for the trimerization of alkynes. The intermediate 41 has been isolated, characterized and shown to display catalytic activity. The authors suggest that the intermediate between 41 and hexamethylbenzene may well be the Diels-Alder adduct, 42. 

The ease of interaction of Ni(0) complexes with organic substrates has been shown to depend upon both the ligands on nickel and the solvent. The presence of a,a-bipyridyl with the Ni(0) complex and the alkyne led to the isolation of a nickelacyclopropene, an observation in accord with the recently proposed metallocyclic pathway for the Ni(0)-cata-lyzed trimerization of alkynes. Allylic and benzylic ethers and epoxides have been observed to undergo oxidative insertion of Ni(0) into their C-0 bonds with solvent (TMEDA > THE > Et O > CeHe) and ligand (EtsP > PhsP a,a-bipy > COD) effects consistent with an electron-transfer attack by Ni(0). With such sulfur heterocycles as dibenzothiophene, phenoxathiin, phenothiazine, and thian-threne, a 1 1 admixture of (COD)2Ni with a,a-bipyridyl gave as the principal product the desulfurized, ring-contracted cyclic product. 

Electrophilic aromatic substitution as a route to differentially substituted products is well established. The often forcing conditions, the incompatibility of this process with acid-sensitive functional groups, and the need for mild and selective syntheses have been the driving forces in the search for new methods of synthesis. A large range of methods has been developed over the past 20 years they include the trimerization of alkynes, the directed orfho-metallation, the benzannellation via metal carbenes, and transition metal-catalyzed carbon-carbon and carbon-heteroatom bond formation. Aromatic C-H activation, while still in its beginning stages, is another area of promise. 

More recently, Gevorgyan and Yamamoto proposed a Pd-catalyzed trimerization of alkynes as a sequential approach to the multisubstituted benzenes 17 and 18 (Scheme In the first step of the sequence, a donor alkyne 1 would undergo either homodimerization to produce 2 or cross-coupling with an acceptor alkyne 3 to form an enyne 4. Enynes 2 and 4, after completion of the first step of the sequence, would undergo [4 + 2] benzannelation with the enynophile 16 to afford the tetra- or pentasubsdtuted benzenes 17 and 18, respectively (Scheme 6) (for the Pd-catalyzed [4 + 2] benzannelation of conjugated enynes, see Sect. IV.10.2). 

Based on previous results for the 1 2 cross-trimerization of alkynes [50], Ogata, Fukuzawa et al. [51] developed the first 1 1 1 cross-trimerization of alkynes employing Ni(cod)j/2PPhj (10mol%) as the catalyst. A high... 

SCHEME3.29 Proposed mechanism for Ni-catalyzed 1 1 1 cross-trimerization of alkynes. 

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