Cyclotrimerization benzynes

Dibromopyrrole 1084 (R = Br) and benzyne generated from anthranilic acid and isoamyl nitrile gave dibromo-derivative 1086, the metallation of which led to product 1087 (Scheme 211) <20050L1003>, which was later successfully used in a cyclotrimerization reaction. 

In 1998, Guitian, Perez and co-workers reported that the cyclotrimerization of benzyne (1) to triphenylene (56) is efficiently catalyzed by palladium(O) complexes (Scheme 11) [39]. This was the first time an aryne had been the substrate in a metal-catalyzed process. The success of the reaction was based on a judicious choice of the reaction conditions, particularly with regard to the catalytic system and the method of generating the aryne. Some significant results of this seminal study are shown in Table 1. After some preliminary experiments in which nickel complexes were used as catalysts (entry 1), it was found that nucleophilic palla-dium(O) complexes efficiently promote the desired [2+2+2] cycloaddition of the strongly electrophilic substrate 1 (entries 2-6) [40]. At the same time, a systematic study of benzyne generation conditions showed that Kobayashi s method... 

Triphenylene is not isolated in significant yields in the absence of the metal catalyst (entry 7), and when 55 is treated with Pd(PPh3)4 in the absence of fluoride it is recovered unchanged (entry 8), providing good evidence of the intermediacy of benzyne as the reactive species in the cyclotrimerization reaction. 

For the palladium-catalyzed cyclotrimerization of arynes, a mechanism similar to the accepted mechanism for [2+2+2] cycloaddition of alkynes may be proposed (Scheme 15). Though it has not been studied in depth, some experimental results support it. Firstly, aryne-forming conditions are necessary for the reaction to proceed (see Table 1, entry 8) no reaction of trifiate 55 takes place at room temperature in the presence of the catalyst if fluoride is absent, which rules out a mechanism initiated by the oxidative addition of the aryl trifiate to palladium. Data obtained in the closely related cocycloadditions of benzyne with alkynes, discussed below, hkewise point to benzyne as the reactive species. Secondly, the benzyne-palladium complex 67 is a plausible initial intermediate because the ability of group 10 metals to coordinate benzyne is well known (see Sect. 1.2.2), and although benzyne complexes of palladium have eluded isolation (apparently because of their instability) [7,26], they may well be able to exist as transient intermediates in a catalytic cycle such as that shown in Scheme 15. Thirdly, it is known that benzyne complex 34 can form metallacy-cles similar to 68, albeit with dcpe as hgand instead of PPhj [26]. 

Recently, the Yamamoto group and the Guitian group as pioneers in this field have developed efficient Pd-catalyzed reactions of arynes, particularly cyclotrimerization and cocyclization with alkynes, offering useful synthetic methods for polycyclic aromatic compounds [78]. The Spanish group reported that the cyclotrimerization of benzyne, generated from 251, occurred in situ at room temperature in the presence of Pd(PPh3)4 in MeCN, and obtained triphenylene (253) in 83 % yield [79]. 

The first example of a transition metal-catalyzed cycUzation of arynes was reported in 1998 [112], when benzyne generated from o-(trimethylsilyl)phenyl triflate was shown to undergo cyclotrimerization in the presence of a catalytic amount of Pd(PPh3)4 to afford triphenylene (208) (Scheme 12.60). 

Polycyclic Arenes. Trimethylsilylphenyl triflates have found widespread use as benzyne precursors in the preparation of polycyclic arenes. Triphenylenes are made via paUadium-catalyzed [2 + 2 + 2] cyclotrimerization of arynes, by paUadium-catalyzed annulation of the aryne and 2-halobiaryls, or via carbopalladation/carbocycUzation of arynes with substituted iodobenzenes (eq 2). All three approaches furnish substituted triphenylenes in high reported yields. Substituted phenanthrenes or naphthalenes are similarly prepared using 2-(trimethylsilyl) phenyl triflate as an aryne precursor. Treatment of the reagent with fluoride, a palladium catalyst, and a deactivated alkene, allyl halide, or internal aIk5Tie provides 9-substituted or 9,... 

The first metal-catalyzed reaction of arynes was described by Guitian in the late 1990s consisting in the cyclotrimerization of benzyne to yield triphenylene 100 (Scheme 12.51) [89]. These and other authors have extended this process to the trimerization of a variety of arynes, leading to polycyclic aromatic hydrocarbons (PAHs). 

The fused system 3,4-bis(trimethylsilyl)benzocyclobutene (7) has been obtained by cyclotrimerization of the alkyne l-trimethylsilylhexa-l,5-diyne in the presence of dicarbonyl(cyclopentadienyl)cobalt and converted (by Bu"Li) into l,2-dihydrocyclobuta[c]benzyne, which was trapped as the adduct (8). 

---