Alkynes cyclotrimerization and

Yamamoto Y (2005) Recent advances in intramolecular alkyne cyclotrimerization and its applications. Curr Org Chem 9 503-519... 

In addition to 6, different ruthenium complexes have been investigated as catalysts for alkyne cyclotrimerizations and cyclocotrimerization of alkynes with nitriles. Among them, Grubbs-type carbene complexes are of particular importance since they catalyze inter- and intramolecular metathesis-cascade cyclotrimerizations under mild conditions. In addition, they have good tolerance toward a variety of functional groups. 

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],... 

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-... 

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,... 

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 observation of negative apparent activation energy can most simply be interpreted in terms of the competition between the adsorption and desorption of methylacetylene on the surface. This qualitative explanation is illustrated in Figure 3, where the steady-state production of trimethylbenzene is compared with the TPD trace of methylacetylene. The fall off in steady state cyclotrimerization rate matches the tail of the desorption spectrum and illustrates the role of reactant desorption at higher temperatiu-es controlling the availability of alkyne monomers and thus the overall cyclotrimerization rate in this temperatime/pressure regime. 

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

S. K. Das and R. Roy, Mild Ruthenium-catalyzed intermolecular alkyne cyclotrimerization, Tetrahedron Lett., 40 (1999) 4015 -018. 

Saaby S, Baxendale IR, Ley SV (2005) Non-metal-catalysed intramolecular alkyne cyclotrimerization reactions promoted by focused microwave heating in batch and flow modes. Org Biomol Chem 3 3365-3368... 

A plausible mechanism for the cyclotrimerization includes initial oxidative cyclization between the less-hindered alkyne terminus and the ketone carbonyl group to form an oxaruthenacyclopentene intermediate. The insertion of the second alkyne terminus into the C-Ru bond, followed by reductive elimination, affords the 277-pyran compounds. 

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. 

Inter- and intramolecular alkyne cyclotrimerizations of 57 catalyzed by RhCl(PPh3)3 af ford substituted carbazoles that are relevant to natural product and drug-related synthe-... 

Rhodium-catalyzed alkyne cyclotrimerization is also applicable to the synthesis of a polyalkyne substrate bearing ether-linked 1,6-diyne moieties 59, which is easily prepared by Pd-Cu-catalyzed Sonogashira couphng reactions. These reactions provide a novel and efficient synthetic route to oligophenylene 60, which bears benzodihydrofur-an moieties (Scheme 7.17) [40]. 

A combination of the alkyne cyclotrimerization catalyzed by RhCl(PPh3)3 with a 1,3-dipolar cycloaddition provides rapid access to 3-dihydroindenylmethyl-3,7-diaza[3.3.0]-octane 61 in excellent yield thus five new bonds, four stereocenters, and three rings are created in a one-pot operation (Scheme 7.18) [41]. 

Crossed-alkyne cyclotrimerizations between the diynes 580 and the monoalkynes 581 with a catalytic amount of RhClfPPhsls afforded substituted carbazoles 582. The high efficiency of the carbazole formation could be rationalized by the conformational restrictions present in the diynes 580 (561) (Scheme 5.27). 

Witulski and Alayrac reported the synthesis of clausine C (clauszoline-L) (101) by a rhodium-catalyzed alkyne cyclotrimerization of diyne 1014 and propiolic ester 635 (561). Analogous to the hyellazole (245) synthesis (see Scheme 5.75), the diyne precursor 1014 required for this key cyclotrimerization reaction was obtained starting from readily available 2-iodo-5-methoxyaniline. Using Wilkinson s catalyst, [RhClfPPhsls], crossed-alkyne cyclotrimerization of 1014 and 635 led to N-tosylclausine C (1015) in 78% yield in an isomeric ratio of 3.8 1. Finally, deprotection of the tosyl group with TBAF in refluxing TFIF afforded clausine C (clauszoline-L) (101) (561) (Scheme 5.147). 

When desired vinylidene-mediated pathways are not sufficiently favorable. Group 9 metal catalysts can access a set of typical side-reaction pathways. Alkyne dimerization to give conjugated enynes or higher oligomers is often observed. Polysubstituted benzenes resulting from [2 + 2 + 2] alkyne cyclotrimerization are also common coproducts. Fortunately, the selectivity of rhodium and iridium catalysts can often be modulated by the variation of spectator ligands. 

Intramolecular [2+2+2] cyclotrimerizations of diynes and triynes possessing heteroatom tethers furnish benzoheterocycles. The cyclization of triynes 88 using the Grubbs catalyst 76 proceeds via cascade metathesis as shown in Eq. (35) to yield a tricyclic product 89 [88]. This novel type of catalytic alkyne cyclotrimerization can be applied to the cycloaddition of 1,6-diynes with monoalkynes [89]. 

Particularly important advances have been made recently in the chemistry of M2(OR)6 compounds. Many examples of simple crosswise addition of a R C CR" molecule to M2(OR)6, in the presence of pyridine, have been observed. The products differ in the details of structure and composition depending on the nature of R, R, and R", and on whether M is Mo or W, but in each case there is a quasitetrahedral M2Q cluster in which an M=M bond (2.55 to 2.66 A in length) is present. These simple adducts will react further with alkynes to give products in which two or more alkyne molecules have been linked, as in (18-C-XXIII). Further reaction affords alkyne cyclotrimerization products (substituted benzenes). 

Arene complexes are usually prepared by the following methods (i) metal vapor synthesis (see Metal Vapor Synthesis of Transition Metal Compounds).(ii) AEAIX3 reduction of a metal halide in the presence of the arene and (hi) alkyne cyclotrimerization (see Cyclodimerization -tri-merization Reactions). Synthetic procedmes to obtain r] -arene derivatives have been reviewed by Pampaloni and Calderazzo. Over the past ten years, studies in this... 

A wide variety of homogeneous and heterogeneous catalysts are available for alkyne cyclotrimerization. As a result, numerous mechanistic pathways have been established for the different versions of this process, each characteristic of the metals involved in the system. The most common involves the intermediacy of metallacyclopentadienes, derived as already shown from any number of metal fragments and two alkynes. Upon opening a vacant coordination site, these systems may readily complex a third alkyne, which may insert to give a transient metallacycloheptatriene from which the benzene product is ultimately released via reductive elimination of the metal (Scheme 24). ... 

As is clear from the introductory discussion, most, if not all, of the d-block transition metals are expected to participate in reactions that are related to those discussed here. In addition to the Co-based methodology mentioned earlier, some related reactions of Pd and are known. Also related are the cyclization reactions of metal-carbene complexes containing Cr, Mo, W and other transition metals with alkynes and alkenes and a recently reported Nb- or Ta-promoted diyne-alkyne cyclization reaction, which appears to be closely related to a number of previously developed alkyne cyclotrimerization reactions, such as those catalyzed by Co. Investigations of reactions involving other transition metals may prove to be important especially from the viewpoint of developing asymmetric and catalytic procedures. 

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