Triynes, 2 + 2 + 2-cycloaddition

As complex 40 proved to be active in cycloaddition reactions and is isoelectronic to Rh(+1), which is a potent catalyst for [2 + 2 + 2] cycloadditions [20, 21], it was expected that 40 might also be active in those reactions, which is indeed the case. Triyne 54 could be converted to the [2 + 2 + 2]-cycloaddition product 55 in good yield (eq. 3 in Scheme 11). Mechanistically, this reaction is also assumed to proceed via a metallacyclic intermediate. 

Cycloaddition of aUcynes catalysed by transition metals is one of the most efficient and valuable ways to prepare benzene and pyridine systems [12], Among the possible catalytic systems able to catalyse this reaction, cobalt and iron complexes containing NHCs as ligands have shown high catalytic activity in the intramolecular cyclotrimerisation of triynes 36 (Scheme 5.10) [13]. The reaction was catalysed with low loading of a combination of zinc powder and CoC or FeClj with two or three equivalents of IPr carbene, respectively. 

Two precedent examples had been reported of the enantioselective [2+2+2] cycloaddition of alkynes. In one case, an enantioposition-selective intermolecular reaction of a triyne with acetylene generated an asymmetric carbon at the benzylic position of a formed benzene ring [19]. In the other case, an intramolecular reaction of a triyne induced helical chirality [20]. Both reactions were developed by chiral Ni catalysts. 

Cyclization of triynes to benzenes,4 Wilkinson s catalyst catalyzes [2 + 2+2]cycloaddition of 1,6-heptadiynes with monoynes to form substituted benzenes. Intramolecular [2+2 + 2]cycloaddition of triynes is also possible with this catalyst. 

This [2+2 + 2]cycloaddition is useful for synthesis of highly substituted aromatic compounds since substitution reactions with arenes are seldom regiospecific. An example is the synthesis of calomelanolactone (2) from triyne l.5... 

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]. 

In a study of rhodium-catalyzed [2 + 2 + 2] cycloadditions of alkynes <88JCS(P1)1357>, the intramolecular [2 + 2 + 2] cycloaddition of4,9-dioxadodeca-l,6,12-triyne catalyzed by Wilkinson s catalyst [(PPh3)3RhCl] over a prolonged period of time gave the dihydropyrano- and tetrahydrofuro-fused 6-6-5 tricyclic benzene derivative (67) in moderate yield (Equation (38)). It should be noted that an analogous bis-tetrahydrofuro-fused 5-6-5 tricyclic compound could be prepared (74%) under similar conditions, but after only 3 h at room temperature. 

Several groups have developed the combination two or more PKR or PK-type reactions in the same reaction step. The multiplication of the synthetic power of this transformation has found immediate application for the synthesis of natural [S.5.5.5] systems called fenestranes. Starting materials have been enediynes that give two [2 + 2 + 1] cycloadditions. The extension of the reaction to triynes has led to interesting tandem processes that may include [2 + 2 + 2] cyclizations. Other cycloadditions like the Diels-Alder have also been combined with the PK. 

Cobalt catalyzed double [2 + 2 + 1] cycloaddition reactions of branched triynes 169 have led to novel [5.5.5.6] tetracyclic dienone systems 172, instead of the expected [S.5.5.5] systems 173. These substrates underwent first... 

In previous works this group had observed a competition between the PKR and a [2 + 2 + 2] cyclization in the second reaction step of three triple bonds. Thus, when reacting linear triynes 174 under catalytic, high CO pressure, cobalt mediated PKR conditions, they obtained mixtures of products 175 coming from two [2 + 2 + 1] cycloadditions, and 176 from a [2 + 2 + 1]/ [2 + 2 + 2] tandem reaction. When the triple bonds were ether linked, the latter was the favored reaction, while with substrates lacking oxygen atoms, the iterative PKRs was the major pathway (Scheme 51) [166]. When the reaction was performed intramolecularly between a diyne and an alkyne, the only reaction products were the result of a [2 + 2 + 1 ]/[2 + 2 + 2] tandem cycloaddition [167,168]. 

Triynes 24 derived from l-iodo-2-naphthol by repetitive Sonogashira couplings afford the helically chiral heptacyclic derivatives 25 through a [2+2+2] cycloaddition catalysed by Rh(II) complexes both yields and ee are good. In some instances, the alternative ladder-type... 

If cyclonona-l,4,7-triyne were subjected to cyclization, MNDO RHF calculations have suggested that its valence isomer, triscyclopropabenzene (1) (J//f 947 KJmol" ) might be formed via an allowed [ 2s -t- + 2j] cycloaddition process. 

Early attempts to synthesize the intriguing cyclonona-l,4,7-triyne molecule, 1 [1], grew from a recognition that the in-plane p-orbitals of the three acetylenes around its perimeter should encroach upon each other s space while the out-of-plane p-orbitals should consitute an essentially ideal trishomobenzene. The tantalizing prospect that a [2 + 2 + 2] cycloaddition requiring very little atomic motion might transform this monocylic triyne into tricyclopropabenzene (2, Fig. 9-1) added further incentive to prepare 1. 

The bismuthonium ylide 519 is converted into the annelated furans 522 on treatment with terminal alkynes in the presence of copper(I) chloride. It is suggested that the process involves the carbene 520 and the diradical 521. Intramolecular [2 + 2 + 2] cycloaddition of the triyne 523 mediated by tris(triphenylphosphine)rhodium(I) chloride gives the tetrahydrofuranobenzofuran 524. ... 

Roulland and coworkers utilized a [2-t2-t2] cycloaddition and an RCM-aromatization strategy in an innovative approach to the central core of the landomycinone natnral prodncts [46]. As shown in Scheme 17.24, the triyne 124 was successfully cycUzed with the catalyst RhCl(PPhj)j to afford compound 125, after which vinyUithium addition resulted in the hemiketal diene 126. Immediate... 

A mechanism has been proposed by Blechert for this metathesis cascade, which involved the formation of a number of carbon-carbon bonds (in principle, a ruthenium-mediated [2-I-2+2] cycloaddition is also plausible for this transformation [49]). This postulated mechanism, as shown for the conversion of triyne 141 into the substituted aromatic system 142, is depicted in Scheme 17.27 [50]. Initially, complex 1-Ru adds to the less hindered acetylene of 141 to afford the vinyl carbene complex 143, which then undergoes an intramolecular metathesis reaction to afford 144 via 145. The conjugated complex 144 can then undergo a further RCM reaction to yield the product 142. 

Substituted tetraphenylenes are known as interesting biaryl-based chiral cyclic scaffolds. The cationic rhodium(l)/Cy-BINAP or QuinoxP complex-catalyzed enantioselective double homo-[2+2+2] cycloaddition of triynes afforded chiral tetraphenylenes with high enantioselec-tivity (Scheme 21.20) [24]. 

The intramolecular [2+2+2] cycloaddition of triynes affords tricyclic compounds, which are not readily accessible by other methods. The double [2+2+2] cycloaddition of a diphenylphosphinoyl-substituted hexayne proceeded in the presence of the cationic rhodium(I)/tol-BINAP catalyst to give the corresponding Cj-symmetric axially chiral biaryl bisphosphine oxide with high enantioselectivity (Scheme 21.24) [28]. 

Interesting planar chiral tripodal cyclophanes have also been synthesized with high enantioselectivity by the cationic rhodium(I)/Me-Duphos complex-catalyzed [2+2+2] cycloaddition of branched triynes (Scheme 21.25) [29]. 

The intramoleeular [2+2+2] cycloaddition of triynes is particularly effective for the synthesis of helicenes and helicene-like molecules. For example, the novel direct synthesis of fully... 

Regarding the construction of helical chirality through intramolecular cycloaddition of designed triynes, the Ni(cod)2/(7 )-Quinap catalytic system has shown nice efficiency and allows the straightforward preparation of dibenzo[6]helicenes (Scheme 7.3) [7]. 

A rhodium-catalyzed cycloisomerization reaction of triyne 137 to 141 involves cleavage of the C=C triple bond (Scheme 7.49) [68]. The following reaction pathway is proposed initially, oxidative cyclization produces the rhodacycle 138, which then undergoes reductive elimination. The rhodium cyclobutadiene complex 139 is thus generated, and then undergoes oxidative addition to produce the rhodacycle 140. This isomerization from 138 to 140 would reduce the steric congestion of the heUcal structure. Subsequently, a cycloaddition reaction between the rhodacycle and the pendant alkyne moiety takes place to afford 141. 

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