Addition of Arynes

Lieb and Martin were also able to add arynes 112 to 2.4,6-tiiphenyl-X -phosphorins the yields are better with 2.4.6-tri-tert-butyl-X -phosphorin. Here again 1,4 addition takes place with the formation of the 1-phosphabarfelenesiii. The arynes were generated either from 2-fluorophenylmagnesium bromide or penta-chlorophenyl-lithium. The reaction of the more nucleophilic 2.4.6-tri-tert-butyl-X -phosphorin with benzene-diazonium carboxylate also leads to 1,4 addition. The structure of the benzo-phosphabarrelenes 113a-d is supported by analytical and spectroscopic data (Table 16). 

Attempts to thermally split off acetylenes from 113 in the hope of forming phosphanaphthalenes failed. 

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Table 4 Palladium(II)-catalyzed cocyclo addition of arynes and alkynes...

Arynes can be added under mild conditions and rapid reaction times to azides through fluoride-promoted o-elimination. The addition of arynes to azides has been already shown by Huisgen and Wittig, respectively. Recently, 0-(trimethylsilyl)phenyltriflate and various fluoride sources in combination with a complementary crown ether were used for the [3 + 2]-cycloaddition with functionalized azides (Scheme 9.5). ... 

Addition of Arynes. Arynes generated from the decomposition of ortAo-trimethylsilylaryl triflates upon treatment with CsF have been reacted with the title compound to give 3-(2-hydroxyphenyl)pyridine in very good yields. The reaction is mostly selective, although the introduction of hindrance or... 

A transition-metal-free approach for the efficient synthesis of benzofurans was developed by Liang, Li, and coworkers by the addition of arynes to iodonium ylides (Scheme 34) [57]. The reaction proceeds via the addition of iodonium ylide 79 to arynes generating the alkoxy ylide 80, which undergoes intramolecular cyclization followed by release of iodobenzene affords the product. CsF was used for the generation of arynes and the reaction proceeds under mild conditions, and using this method, the synthesis of various of functionalized benzofurans can be achieved. 

X. Huang, T. Zhang, Cascade nucleophilic addition-cyclic Michael addition of arynes and phenols/anilines bearing ortho a,p-unsaturated groups fecile synthesis of 9-functionalized xanthenes/acridines, J. Org. Chem. 75 (2010) 506-509. 

An unusual case of addition of a carbanion to an unconjugated carbon-carbon double bond is shown in Scheme 47a. The subsequent transfer of the amide group is also noteworthy (80CC1042). The intramolecular addition of a carbanion to an aryne is a more widely established process. Such reactions have been applied to the synthesis of indoles (Scheme 47b) (75CC745> and oxindoles (Scheme 47c) (63JOC1,80JA3646). 

Arynes are intermediates in certain reactions of aromatic compounds, especially in some nucleophilic substitution reactions. They are generated by abstraction of atoms or atomic groups from adjacent positions in the nucleus and react as strong electrophiles and as dienophiles in fast addition reactions. An example of a reaction occurring via an aryne is the amination of o-chlorotoluene (1) with potassium amide in liquid ammonia. According to the mechanism given, the intermediate 3-methylbenzyne (2) is first formed and subsequent addition of ammonia to the triple bond yields o-amino-toluene (3) and m-aminotoluene (4). It was found that partial rearrangement of the ortho to the meta isomer actually occurs. 

The scope of heteroaryne or elimination-addition type of substitution in aromatic azines seems likely to be limited by its requirement for a relatively unactivated leaving group, for an adjacent ionizable substituent or hydrogen atom, and for a very strong base. However, reaction via the heteroaryne mechanism may occur more frequently than is presently appreciated. For example, it has been recently shown that in the reaction of 4-chloropyridine with lithium piperidide, at least a small amount of aryne substitution accompanies direct displacement. The ratio of 4- to 3-substitution was 996 4 and, therefore, there was 0.8% or more pyridyne participation. Heteroarynes are undoubtedly subject to orientation and steric effects which frequently lead to the overwhelming predominance of... 

A Diels-Alder reaction of arynes with 1,2,4-triazines 102 allows the preparation of isoquinolines substituted with electron-withdrawing groups in the nitrogen-containing ring. The isoquinoline-1-carboxylic esters bearing additional substituents are of particular interest because they are not readily available by the usual routes [100,101] (Scheme 2.42). 

One of the most interesting reactions of this type involves the intramolecular addition of the organolithium derivative to the aryne (13) which is derived from the dilithio-compound (12) 28>. This leads to the remarkably stable organolithium compound (14) which reacts with water to form the expected heptafluorobiphenylene, and with bromine to form 1-bromoheptafluorobiphenylene. 

The loss of proton from (93) could be concerted with, or followed by, loss of Cle to yield the aryne intermediate (97). The latter has two alternative positions (cf. 101 b/c) which eNH2 could attack, product formation then being completed by abstraction of a proton from the solvent NH3 the net effect is of the formal addition of NH3 in two alternative ways round. We should not expect the relative proportions of the two alternative products to be the same because (97) is... 

Bailey s group has elaborated a fourfold anionic domino approach leading to a N-allyl-3,4-disubstituted indoline 2-582 from 2-580 (Scheme 2.131) [300]. The central step is the formation of an aryne by treatment of 2-fluoro-N,N-diallylaniline (2-580) with nBuLi followed by a regioselechve intermolecular addition of nBuLi to give 2-581. This then cyclizes to afford a new lithiated species which is intercepted by added TMSCI. 

Arylindoles from o-nitrostilbenes and triethyl phosphite, 48,115 Arynes, addition of side-chain carban-ions, 48, 55 Azelaic acid, 45, 31... 

Benzenesulfonic anhydride, 46, 88 Benzocyclobutenes, 1-substituted, from addition of a side-chain carban-ion to an aryne bond, 48, 55 Benzofuran, 46,28 Benzoic acid, 2-phenylethyl ester,... 

Cyclization by addition of a side-chain carbanion to an aryne bond has been proposed as the method of choice for synthesis of the versatile 1-substituted benzocyclobutene system.7 This general procedure now has been modified to permit convenient large-scale preparations utilizing a commercially available base, a minimum amount of liquid ammonia, and distillation for isolation of the product. 

The nucleophilic addition of the mesoionic compound 41 was further investigated upon addition to arynes <20030BC978> (Scheme 8). In this case the process stops at a single addition of the anion to the aryne to form 45 and workup under aqueous conditions led to the formation of the tetrazolium-5-olate 46. 

Via aryne intermediates The aryne is formed in two steps, the first being a het-erolytic dediazoniation, followed by a heterolytic dissociation of a substituent (H, COO etc.) in one of the o-positions relative to the diazonio group (I)n + DN/). The (metastable) aryne reacts rapidly by addition of a Brpnsted acid (H2O, HC1 etc.). 

Another route to anthraquinones has been devised which relies on the addition of carbanions (22) derived from phthalides to arynes (81JCS(P1)2120). For the formation of anthraquinone (23) itself, phthalide was treated with 2.2 equivalents of lithium diisopropyl-amide in THF. Bromobenzene was then added and the reaction mixture warmed to room... 

It seems that the repulsive steric interactions play a more dominant role in regioselectivity of aryne reactions than is sometimes realized. In fact, it has been argued that in nucleophilic addition to arynes, the transition state is reached early, while the incipient bond is still very much extended. Consequently, steric effects were considered not to be of great importance.80 81 It should, however, be noted that the dehydro bond orbitals are so oriented that the optimal approach trajectory for the nucleophile lies in the... 

In addition of organometallic reagents to some arynes, prior counterion complexation with the substituent can direct the incoming group to the ortho position (kinetic control). Addition of alkyllithiums to oxazolinyl (OXZ) aryne (51) to give the ortho product (52) is explained in this manner. In contrast, lithium dialkylcuprates add to the aryne (51) exclusively at the meta position. This is ascribed to thermodynamic control of the reaction, which results in the formation of the more ligated and stable adduct (S3).i2 Control of nucleophilic addition to arynes by complex-induced proximity effects has not been explored with substituents other than OXZ,83 but has considerable synthetic potential if it can be achieved, say through solvent manipulation. 

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