Cyclotrimerization 1,3,5-trisubstituted benzene

Transition metal-catalyzed intermolecular [2 + 2 + 2] cyclotrimerization of alkynes to benzene derivatives has been extensively studied. In this section, the focus is on the cyclo-trimerizations of the substrates bearing three independent unsaturated bond components. The key issue with this type of process usually involves the challenge of controlling regioselectivity [1—1]. However, 1,3,5-trisubstituted benzene 44 can be obtained as the sole product in good yield when 3-butyn-2-one 43 is used as the substrate for the cyclotrimerization catalyzed by Rh2(pfb)4 (pfb=perfluorobutyrate) in the presence of EtsSiH under a CO atmosphere (Eq. 11) [30]. 

This mechanism is supported by the transformation of preformed metallacyclo-pentadienes with alkynes,73,76-78 and labeling experiments79 that excluded the involvement of cyclobutadiene intermediates. It also accounts for the observation that terminal alkynes yield 1,2,4- (and 1,3,5-) trisubstituted benzene derivatives as the main product but not 1,2,3 derivatives. In contrast with this picture in cyclotrimerization with PdCl2-based catalysts, stepwise linear insertion of alkynes takes place without the involvement of palladacyclopentadiene.80... 

Structural analysis of the homopolymers by spectroscopic methods confirmed that the diynes had undergone [2 + 2 + 2] polycyclotrimerizations by forming new benzene rings from their acetylenic triple bonds. The ratio of the 1,2,4- to 1,3,5-isomers of the trisubstituted benzene rings was estimated to be 2.2 1. Careful evaluation of the 111 NMR spectra unveiled that the number of terminal triple bonds in the final hb-PAs was much smaller than that in an ideal hyperbranched structure produced by the diyne polycyclotrimer-ization. This result suggests that intra-sphere ring formation might have been involved in the cyclotrimerization polymerization. 

Co2(CO)8 and Hg[Co(CO)j2 (41), i7T-CMCo CO)2 191), Co CO)aNO 192), Co2(CO)8(RCaR ) (193), and Co4(CO)io(RC2R ) 48). The trimeri-zation reactions with symmetrically disubstituted alkynes, RC=CR, lead inevitably to hexasubstituted benzenes. Unsymmetrical alkynes RC=CR are trimerized generally to 1,2,4- rather than 1,3,5-trisubstituted benzenes. These cyclotrimerization reactions can be achieved readily by... 

The metallacyclic compounds react with protic reagents to yield the corresponding substituted 1,3-butadienes and the iodination reactions give the 1,4-diiodo 1,3-butadiene derivatives (Scheme 122). Reactions with different unsaturated organic molecules have also been investigated. They catalyze the cyclotrimerization of a range of alkynes. Terminal alkynes with small substituents produce the 1,2,4-trisubstituted benzene, preferentially, in an exothermic reaction. The more bulky substrates BuTl CH and Me3SiC=CH react more slowly and only the symmetrical 1,3,5-isomer is produced (Scheme 122).174... 

When a monosubstituted acetylene RCsCH is heated with nickel or cobalt carbonyls, it gives the 1,2,4-trisubstituted benzene as major product, the 1,3,5-benzene as minor product, and little if any of the 1,2,3-isomer. Coordination of the metal with the triple bond has been considered to be involved [52]. Thus, in the transition-metal-catalyzed cyclotrimerization, the... 

Bis(ethene)(toluene)iron catalyses the cyclotrimerization of alkynes to derivatives of benzene terminal alkynes RC=CH (R = t -Bu, Ph or C02Me) yield mainly 1,2,4-trisubstituted benzenes 560, while dimethyl acetylenedicarboxylate furnishes the iron complex 561. ... 

Another type of benzannulation, which might be related to the benzannulation of conjugated enynes, is the Pd-catalyzed cyclotrimerization of 1,3-diynes (Scheme 1,3-Diynes cyclotrimerize in the presence of a Pd catalyst to give 1,3.5-trisubstituted benzene derivatives. In this reaction, too, the regioselectivity is perfectly controlled as shown in Scheme 4, and other products were never isolated. The reaction of various diynes is summarized in Table 7. Some functional groups such as olefins and ether linkages may be present in the side chain. An example for the cross-cyclotrimerization of a diyne and an aUcyne has also been reported (Scheme... 

A group of Chinese chemists proposed a new reaction for the cyclotrimerization of alkynes 2.26a-j catalyzed by InCls in the presence of 2-iodophenol (Scheme 2.11) [46]. This gave 1,3,5-trisubstituted benzenes and per-substituted benzenes 2.27a-j in excellent yields and complete stereoselectivity. This method provides a rapid synthesis of 1,3,5-trisubstituted benzenes (Table 2.1) obeying modern requirements of both green chemistry and industry [46]. 

The catalytic cyclotrimerization of alkynes to give substituted benzenes was investigated in supercritical water by the groups of Parsons [53a] and Dinjus [53b] using [CpCo(CO>2] as the catalyst. The reaction proceeded smoothly with 1-alkynes and phenylacetylene at T - 374 °C and p = 250 bar using substrate to catalyst ratios up to 35 1. The ratios of isomeric trisubstituted ben-... 

Cyclotrimerization of acetylenes to form benzene derivatives has probably been the most studied of all organometallic reactions of acetylenes. A few reviews of the subject have appeared (Hiibel, 1968 Bowden and Lever, 1968 Otsuka and Nakamura, 1976a Dickson and Fraser, 1974). The same or different acetylenes can be incorporated to produce several possible substitution patterns. Trimerization of symmetrical alkynes produces hexasub-stituted benzenes, while unsymmetrical alkynes may lead to 1,3,5- or 1,2,4-trisubstituted derivatives. 

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