Cyclodimerization of alkynes

Table 9.13 Rh(l)-Catalyzed cyclodimerization of alkynes with allylamine.

The sigma-complexes of cyclobutadienes and aluminium halides react with activated nitriles (e.g. EtOjCCN) to yield substituted pyridines. The sigma-complexes are themselves formed by aluminium-bromide-promoted cyclodimerization of alkynes (Scheme 3). In an extension of this work, Dewar-... 

S.8.2.7.4. Metallacyclopentadiene and Metallacyclopentene Complexes by Cyclodimerization of Alkynes with Alkynes or Alkenes... 

Likewise when two alkyne molecules coordinate to a transition metal such as Co(I) with subsequent coupling of the C-C bond, oxidative cyclization takes place to give a metallacyclopentadiene. Further reaction of another alkyne molecule with the metallacyclopentadiene followed by reductive elimination liberates benzene derivatives. Thus cyclotrimerization of three alkyne molecules catalyzed by a cobalt complex [40,41] can be performed. If a nitrile is used as the second component, pyridine derivatives are obtained catalytically as shown in Scheme 1.13 [42]. The catalytic cyclotrimerization and cyclodimerization of alkynes and conjugated enynes have found extensive applications in synthesis of complex cyclic compounds such as steroid derivatives [43]. 

In recent years, transition-metal-mediated inter- or intramolecular cyclodimerization of alkynes has received lots of attention [1, 2]. During the study of the mechanism of zirconium-mediated cyclodimerization of heteroaryl-substituted alkynes [1], the zirconium intermediate 10 was successfully isolated (Scheme 1). However, in the NMR spectral data, there was no resonance in the region of 70-100 ppm, which is... 

In this latter reaction mode, which is observed much more rarely than /3-dehydropal-ladation, a wide variety of ligands can be coupled to each other with the formation of new C—C, C—H, C— N, C—O, and C—Hal bonds. This section does not cover the numerous cascade couplings in which a number of successive intramolecular additions of 2 onto double bonds is eventually completed by /3-dehydropalladationt as well as the numerous [2 -I- 2 -I- 2] and [4 + 2] cyclotri- and cyclodimerizations of alkynes, enynes, and related compounds. " The Pd(0)-catalyzed Cope rearrangement also will not be considered here, as it proceeds via bis(i7 -allyl)palladium(ll) intermediates. The carbopalladation reactions of aUenes, which have been reviewed recently, are covered in Sect. IV.7. (For new examples see also refs. [10]-[12]). On the other hand, the numerous Pd-catalyzed formal [3 + 2] cycloadditions of trimethylenemethane (TMM) complexes may be classified as carbopalladations of alkenes without subsequent dehydropalladation. As the subject of this section has partially been covered in several newly published reviews, " the attention here will be on the most recent and interesting communications. 

The most common routes to this type of complex, cyclodimerization of alkynes on a platinum template or ligand substitution, are included in COMC (1995). ... 

The Cp Rh( 7 -N03)(0Tf)-mediated cyclodimerization of alkynes afforded the preparation of ( -cyclobuta-diene)-rhodium(l) intermediates 429 and 430, which were isolated and characterized. ... 

While one of the first preparations of a cyclobutadiene-metal complex involved the cyclodimerization of diphenylacetylene in the presence of Fe(CO)5 at high temperature212, the thermal reaction of alkynes with Fe(CO)s gives predominantly cyclopentadienone complexes (Section IV.E.l.b). The cyclization of alkynes by a wide variety of metal complexes has been reported (Scheme 59)l 5-21 A—222... 

The complex Re(CO)5(FBF3) also reacts with but-2-yne or pent-2-yne via cyclodimerization of the alkyne to give complexes with a coordinated methylenecyclobutene derivative.7... 

By using the hypersensitive molecular mechanistic probe 2-(2-methoxy-3-phenylcy-clopropyl)-5-methylhexa-2,4-diene in the 2 + 2-photocycloaddition of [60]fullerene, it was shown that the reaction proceeds via a biradical and not a dipolar intermediate.6 Zirconium-induced cyclodimerization of heteroaryl-substituted alkynes produces tetrasubstituted cyclobutenes with high regio- and stereo-selectivity.7 The ruthenium-... 

A similar reaction applied to propargyl alcohols in place of terminal alkynes led to the one-step catalytic head-to-head cyclodimerization of propargyl alcohols and to the formation of alkylidenecyclobutene derivatives [90] (Eq. 69). It was shown that the reaction occurs via cyclobutadieneruthenium and cy-clobutenylruthenium intermediates, dehydration and carboxylate addition. 

Nb and Ta alkyne complexes are of interest in part because they have found use in organic synthesis and cyclooligermerization (see Cyclodimerization -tri-merization Reactions) of alkynes. 

When the cation radical of this alkyne is generated by y radiolysis in a solid matrix at 77 K and then warmed to 150 K, the ESR spectrum of the 1,2,3,4-tetramethyl-1,3-butadiene cation radical is observed. An analogous intramolecular reaction was also observed even in a rigid matrix at 77 K. The feasibility of the cycloaddition step itself is therefore indicated, but little work has yet been done in respect of the aminium salt or PET induced cycloadditions of alkynes in solution at ambient or near-ambient temperatures. Whether a chain or catalytic alkyne cyclodimerization can be effected is yet unclear, as is the potential fate of the cyclobutadiene products. 

Cyclodimerization of disubstituted alkynes R C=CR" mediated by this type of precatalyst (Ln = La, Ce Y is unreactive) seems to be limited to alkynes bearing at least one a-methyl group (R ) and a small second alkyl group (eq. (6)) [97]. Already use of R" = Et, n-Pr results in formation of two isomers. For example, formation of l,2-dimethyl-3-ethylidenecyclobutene from excess 1- butyne is complete in ca. 10 h at 80 °C, giving a TOF of 2 h. Unprecedented propargylic metalation/alkyne insertion are the key steps of the proposed mechanistic cycle. 

An interesting cyclodimerization of internal alkynes is apparently proceeding via metallation in the propargylic position, followed by an insertion of a second alkyne molecule, intramolecular carbometallation and o-bond metathetical protonolysis (Fig. 24) [65]. The reaction is slow even at elevated temperatures and the insertion is not regioselective in case of unsymmetrical alkynes. More hindered substituents such as Bu are not tolerated as the reaction stops at the metallation step. The reaction is more of a fundamental interest, as the cyclization pattern is different from the most common [2 + 2] route of existing protocols of transition-metal (in particular cobalt)-catalyzed alkyne cyclodimerization, which are significantly more versatile and synthetically applicable [194],... 

Passarella D, Giardini A et al (2001) Cyclodimerization of indol-2-ylacetylenes. An example of intermolecular enyne-alkyne cycloaddition. J Chem Soc, Perkin Trans 1 127-129... 

The scope of the reaction discussed in Sect. B is somewhat limited since the only practical synthetic procedure consists of the cyclodimerization of the two identical enynes, and therefore the same substituents are attached at the phenyl group and the vinyl group of the reaction product. The attempted cross-annulation of conjugated enynes with alkynes or dienes turned out to be unsuccessful. However, the scope of the benzannulation reaction could be extended significantly by introducing conjugated... 

Despite the biological significance of the triazole moiety and the success of intermolecular triazole formation, intramolecular alkyne-azide couphng remains surprisingly Hmited. On a macromolecular scale, intramolecular triazole formation can occur on specially synthesized DNA molecules [93] by cyclodimerization of solid-phase bound suitably functionalized peptides [94] or on copper surfaces to induce adhesion [95]. There are just a few traditional examples on macrocycloadditions [96-98]. 

The precise mechanism of many oligomerization reactions remains open to discussion. We have already mentioned the question of whether cyclodimerization of butadiene, catalysed by nickel complexes, is a concerted or a stepwise process, of polymerization and then cyclization. The cyclo-trimerization of alkynes is often thought to proceed by co-ordination of three alkyne molecules to the metal catalyst, with a subsequent concerted cyclization step. Recent studies of the cyclotrimerization of hexafluorobut-2-yne in the presence of Ni(cod)j or of arsine complexes, however, suggest a stepwise process in which an intermediate (67) is formed, to which... 

Billing and Nilsson reported the cyclodimerization of a bifunctional molecnle 85 displaying both an azido- and an alkyne-group. A propynoyl-dipeptide was conpled to an azido-aminoglucopyranoside and cyclodimerized by CuAAC to afford 86 in decent yields (33-64%, Scheme 10.25). The prodncts were believed to be artificial receptor prototypes. A similar strategy was used to assemble macrocycle 87 containing two amino acid resi-... 

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