Cyclotrimerization of 1,6-diynes

The metathesis of ene-ynamides has been investigated by Mori et al. and Hsung et al. [80]. Second-generation ruthenium catalysts and elevated temperatures were required to obtain preparatively useful yields. Witulski et al. published a highly regioselective cyclotrimerization of 1,6-diynes such as 98 and terminal alkynes using the first-generation ruthenium metathesis catalyst 9... 

Based on this work, Itoh and co-workers developed ruthenium(n)-catalyzed [2 + 2 + 2]-cyclotrimerizations of 1,6-diynes 174 and electron-deficient nitriles (Equation (34)),368>368a These partially intramolecular cycloadditions proceed through ruthenacycle intermediates as well. The importance of using electronically activated nitriles is underlined by the fact that acetonitrile and benzonitrile gave only very low yields. 

Rh(l)-catalyzed [2-I-2-I-2] cyclotrimerization of 1,6-diynes (e.g., 1391 and 1394) with monoynes (e.g., 1392) in combination with stereospecific Ag(i)-catalyzed aldimine (metallo)azomethine ylide — cycloaddition cascades affords rapid access to complex heterocyclic benzene derivatives 1393 and 1395 in one-pot processes with the generation of five new bonds, four stereocenters and three rings (Schemes 266 and 267) <2000T8967>. 

Axially chiral biaryls are an important class of molecules primarily because of their biological activity, as well as their use as chiral ligands. Although enantioselective cyclotrimerization of 1,6-diynes with alkynes or nitriles catalyzed by transition metals has been developed, it was difficult to realize the intermolecular cross-cyclotrimerization process with three alkynes. However, a cationic Rh-complex with (5)-H8-BINAP was found to catalyze effectively the regioselective and enantioselective intermolecular cross-cyclotrimerization of two alkynes 392 and 394 to give chiral biaryls 395 with 89-96% ee in good yields (Scheme 2-35). ... 

Various cyclohexadienes can be obtained through the rhodium-catalyzed cyclotrimerization of 1,6-diynes with alkenes [12] or 1,6-enynes with alkynes [13], Valorization of these cyclohexadienes was reported with the development of original tandem [2-I-2-I-2] cycloaddition/[4-l-2] Diels-Alder cascades. For example, Tanaka and coworkers recently achieved the construction of bridged polycyclic lactam products, by performing a [2-1-2-1-2] cycloaddition/[4-l-2] Diels-Alder cascade between... 

Ruthenium(ll)-catalyzed cycloadditions of diynes with bicycloalkenes illustrate the synthetic importance of ruthena-cyclopentatrienes as biscarbenoid intermediates.380 Reaction of 1,6-diyne 448 and biscyclic alkene 449 with ruthenium catalyst afforded a mixture of biscyclopropanation product 450 and cyclotrimerization product 451 (Scheme 113). 

Related co-cyclotrimerizations of two alkyne molecules with limited isocyanates have also been achieved using cobalt and nickel catalysts. With respect to intramolecular versions, two examples of the cobalt(I)-catalyzed cycloaddition of a,m-diynes with isocyanates have been reported to afford bicyclic pyri-dones only in low yields, although 2,3-dihydro-5(lff)-indolizinones were successfully obtained from isocyanatoalkynes and several silylalkynes with the same cobalt catalysis [19]. On the other hand, the ruthenium catalysis using Cp RuCl(cod) as a precatalyst effectively catalyzed the cycloaddition of 1,6-diynes 21 with 4 equiv. of isocyanates in refluxing 1,2-dichloroethane to afford bicyclic pyridones 25 in 58-93% yield (Eq. 12) [20]. In this case,both aryl and aliphatic isocyanates can be widely employed. 

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]. 

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]. 

As 1,/2-alkenes, 1,6-derivatives are used very frequently leading to five-membered heterocycles, while the use of 1,7-derivatives, which produce six-mem-bered heterocycles, is very rare. The reactions of 1,6-dienes, -enynes, and -diynes are classified into three groups (a) cycloisomerization, (b) tandem addition— cyclization, and (c) cycloaddition, such as the Pau-son—Khand reaction, cyclotrimerization, and the Diels—Alder reaction (Scheme 15).97 In these reactions five-membered heterocycles are constructed upon the carbon—carbon bond-forming processes. 

Nitrogen-containing 15-membered trialkyne macrocycles, such as l,6,ll-frw(aiylsulfonyl)-l,6,ll-triazacyclopentadeca-3,8,13-triynes and enediynes as 1,6,11-frw(arylsulfonyl)-1,6,11-triazacyclopentadeca-3-ene-8,13-diynes have been prepared and subjected to a [2+2+2]-cyclotrimerization process catalyzed by transition metal complexes, e.g., RhCl(CO)(PPh3)2 <05JOC2033>. The reaction of pemosylated diethylenetriamine and 2-substituted propan-1,3-... 

Heptadiyne leads to a polymer that possesses a system of conjugated double bonds (11-41) (153, 154). The structural assignment was based on chemical and spectroscopic evidence. However, its correctness was questioned by Hubert and Dale (68). These workers interpreted the polymerization of unconjugated diynes, HC=C(CH2) C CH, as a poly(cyclotrimerization) rather than a cyclopolymerization, The trimerization of monoacetylenes in the presence of Ziegler catalysts is well known (148). 

The regiochemical product distribution of the co-cyclization of two or three different alkynes occurs statistically. In some cases carefully controlled reaction conditions allow isolation of a main product from mixed cyclotrimerizations. For example, l,2,3,4-tetraphenyl-5,6-diethylbenzene can be obtained from cobalt-catalyzed reaction of tolane and 3-hexyne in good yield [62]. The first example of an intermolecular, regiospecific cross-benzannulation reaction catalyzed by Pd(PPh3)4 was reported by Yamamoto [63]. The reaction of 2-alky 1-but-l-ene-3-yne with disubstituted diynes leads exclusively in high yields to... 

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