Triynes intramolecular

The cyclization of the enediynes 110 in AcOH gives the cyclohexadiene derivative 114. The reaction starts by the insertion of the triple bond into Pd—H to give 111, followed by tandem insertion of the triple bond and two double bonds to yield the triene system 113, which is cyclized to give the cyclohexadiene system 114. Another possibility is the direct formation of 114 from 112 by endo-rype. insertion of an exo-methylene double bond[53]. The appropriately structured triyne 115 undergoes Pd-catalyzed cyclization to form an aromatic ring 116 in boiling MeCN, by repeating the intramolecular insertion three times. In this cyclization too, addition of AcOH (5 mol%) is essential to start the reaction[54]. 

In order to minimize the formation of side products, PAM 4 can be assembled via an intramolecular approach [23]. The Sonogashira protocol [15] and conversion of masked iodides [24] comprises most of the chemistry involved in Scheme 7. Using these proven methods, diyne 16 and subsequently triyne 17 can be prepared quickly. lodination, desilylation, and intramolecular alkynylation with Pd(dba)2 under high dilution conditions furnished 4 as the sole product. 

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. 

The reaction of triallylborane with silicon triyne 123 is interesting. A113B attacks both internal and external triple bonds giving rise to silole 124 and two heterocycles with bridgehead boron 125 and 126 in a 1 3 3 ratio as a result of competitive sequential reactions (Scheme 52). When 1,1-allylboration of the internal C C bond followed by intramolecular 1,1-vinyIboration takes place, the silole 124 is formed, while in another case 1,1-allylboration followed by a series of intramolecular 1,2-allylboration reactions leads to boron derivatives 125 and 126 <2002JOM(657)146>. 

Extensively developed by Ojima and co-workers, SiCaT and carbonylative silylcarbocyclization (CO-SiCaC) represent a rapid entry into polycyclic molecules of interest.271 For instance, the rhodium-catalyzed intramolecular SiCaT of triyne 441 afforded tricyclic compound 442 in high yield, accompanied by a small amount of cycloadduct 443 (Scheme 111).270... 

The intramolecular thermal cyclotrimerization of dodeca-1,6,11-triyne (110) at 450-600 °C afforded l,2,3,6,7,8-hexahydro[a5]indacene (112) and dehydro derivatives. An exothermic cycloaromatization mechanism has been proposed. An initial formation of a single bond gives diradical (111) which is then trapped by an alkyne. °... 

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. 

The Ir-MeDUPHOS catalyst also functioned efficiently in an intramolecular reaction, where triynes, which possessed ortho-substituted aryl groups on their termini, were transformed into ortho-diarylbenzene derivatives, which have adjacent two axial chiralities (Scheme 11.14) [22]. 

It is possible to carry out the [2+2+2] cyclotrimerization reaction in a regioselective manner by using a partially or completely intramolecular approach. Rhodium-catalyzed intramolecular cyclotrimerization of 1,6,11-triynes, which construct fused 5-6-5 ring-systems, has been studied extensively [33-36]. Cyclization of 1,6,11-triyne 47 catalyzed by RhCl(PPh3)3, gives the tricyclic benzene 48 in good yield (Eq. 14) [33a]. 

The problem of regioisomerism was avoided by utilizing intramolecular triynes such as 46 as substrates for the cyclotrimerization process. However, many diimines and pyridinimines seem to give very reactive complexes so that further developments can be envisaged. 

Intramolecular 2 + 2 + 2-cycloisomerizations of cyclic triynes and enediynes have been reported with RhCl(CO)(PPh3)2.126 The transition metal-catalysed rearrangement of alk-5-ynals to /-alkynyl ketones and cyclopent-l-enyl ketones was developed using [Rh(P(OPh)3)2]BF4 or Cu(OTf)2 as a catalyst and the effect of substituents on the partition to products was elaborated (Scheme 84).127... 

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. 

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. 

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 261 in which the alkyne linkages are properly spaced can undergo intramolecular cyclotrimerization to aromatics 262 and 263 in the presence of Ziegler-type catalysts-"h... 

An intramolecular cyclotrimerization has been reported by condensation of a diyne with an alkyne in the presence of a palladium, molybdenum, nickel, rhodium, iridium, or ruthenium catalyst. Triynes have been... 

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. ... 

The ifaodium-catalyzed intramolecular cyclotrimerization of 1,6,11-triyne 419, forming 5-6-5 fiised-ring system 420, has been extensively studied (Scheme 2-41, eq. i).[220b,276] reaction has also been used as the key step in the synthesis of a marine illudalane sesquiterpenoid, alcyopterosin E (423) (Scheme 2-41, eq. 2)P as well as in die asymmetric synthesis of chiral diphosphine ligands 425 (Scheme 2-41, eq. 3). ... 

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. 

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]. 

The sequential intramolecular hydroarylation of alkynes is applied to the synthesis of structurally complex extended x-systems. The gold-catalyzed sequential intramolecular hydroarylation of triynes followed by aromatization with DDQ proceeded to give triaryl-substituted diacenaphtho[l,2-y l, 2 -l] fluoranthenes, which can be used for organic light-emitting devices (Scheme 21.49) [55]. 

All three alkynes can be incorporated into a single molecule, making the reaction entirely intramolecular. This has been used in a synthesis of Cryptoacetalide 11.60 (Scheme 11.21). The triyne 11.58 was constructed by coupling a diyne 11.56 containing a carboxylic acid with an alkynol 11.57. A ruthenium catalyst was found to be most effective for the cyclotrimerization, combined with microwave heating. The synthesis was completed by deprotection and free-radical spiroketal formation. 

Scheme 9.5 Intramolecular Rh-catalyzed [2+2+2] cyclotrimerization of a triyne substrate leading to 6-oxa-allocolchicinoids, as described by Schmalz and coworkers [10].

In 2013, Yuan etal. [26] reported the Ru-catalyzed intramolecular [2+2+2] cydotrimerization followed by tandem cross-metathesis of triynes and enediynes using Grubbs ruthenium catalyst - Ru gen-1 - (Figure 9.4). The yields were good and the scope was broad. 

Complexation of triynes to Pd(0) has been reported to give homoleptic palladium alkyne complexes that show a trigonal-planar arrangement with all of the alkyne carbons and Pd in the same plane. Complex 73 is a macrocyclic complex synthesized by reaction of the triyne with Pd(PPh3)4- Due to coordination to the metal, the alkyne carbons are shifted to the center of the cycle and their substituents deviate from linearity by about 22°. Complex 74 undergoes clean intramolecular cyclization at room temperature upon addition of PPh3 (Equation (24)). No intermediate complexes were detected in the course of this reaction, which is an example of the important cycloisomerization of alkynes and enynes catalyzed, among other transition metal complexes, by Pd(0) derivatives. 

Two particular cyclization processes involving an intramolecular C(sp )-H insertion event as key step have been reported. While furan- and thiophene-containing diynes (73) have been found to cyclize to indane derivatives (74) under Au(I)-catalysis via a novel 6-endo dig mode, the synthesis of related indane derivatives (75) has been accomplished through Ag(I)-catalysed cyclization of acyclic triynes (76). Both cyclization processes rely on the generation of a rare 1,2-bis-carbene-carbenoid species as key intermediate (77), such intermediate appearing prone to undergo the intramolecular C-H insertion process. 

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]. 

Recently, Okamoto et al. reported that NHC-Fe species derived from FeCl2 or FeCla by in situ reduction with zinc powder in the presence of IMes or IPr were efficient catalysts for the intramolecular cyclotrimerisation of triynes into annulated benzenes (Equation (7.3)). Although no well-defined complex could be isolated from this mixture, its activity was preserved for a few days when kept under inert atmosphere. 

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