Aryl aryne formation

Hart, H., Harada, K. and Frank Du, C.-J. (1985) Synthetically useful aryl-aryl bond formation via Grignard generation and trapping of arynes. A one-step synthesis of p-terphenyl and unsymmetrical biaryls. The Journal of Organic Chemistry, 50, 3104-10. 

Figure 4.9 Decomposition of aryl complexes via (a) biaryl or (b) aryne formation...

The reaction proceeds by (1) organometallic exchange, followed by (2) aryne formation, and (3) a regiospecific nucleophilic addition of the aryl Grignard to the aryne. These steps can occur or recur in tandem fashion to form from one to six new carbon-carbon bonds in a single operation [33,34]. Subsequently, the method was extended to alkenyl and alkynyl Grignards [35 Eq. (13)] and trimethylsilylvinyl Grignards [36]. 

The animation of aryl chlorides is desirable due to their prevalence and lower costs as compared to aryl bromides and iodides. Aryl chlorides are less prone to oxidative addition to palladium(O) and therefore require more activating ligands. An early example of ArCl amination was reported by M. Beller and co-workers.52 They found a palladacycle derived from Pd(OAc)2 and (o-tol)3P, for example, trawj-di(p-acetato)-bis[o-(di-o-tolylphosphino)benzyl]dipalladium(II). This catalyst allows for the amination of electron deficient aryl chlorides (13) with piperidine in the presence of catalytic LiBr and KO/-Bu as the stoichiometric base. The high temperature required (135 °C) also gives rise to a minor amount of the meta aminated product 15, likely due to aryne formation. It is unclear from this example whether a true oxidative addition to the aryl chloride is occurring, or whether the para product 14 also results from aryne formation, as a 1 1 mixture of products 14 and 15 also results without palladacycle present. 

Beller et al. have reported a transition metal-free amination reaction of an aryl chloride in the presence of KOt-Bu by intermediate aryne formation (Equation 12.8) [10]. 

The second example of a cine-substitution of a thiophene involves the reaction of arylthiolates with 3,4-dinitrothiophene (331) or 3-nitro-4-phenylsul-fonylthiophene (332) to give the 2,4-substituted products 333. Both an elimination-addition mechanism via the aryne (334) or an abnormal addition-elimination (AEa) mechanism (Section II.2.A.e) via the Meisenheimer complex (335) have been considered for these reactions. The former is unlikely for several reasons including the lack of precedence for aryne formation from aryl nitro compounds (Section II. 1) under these reaction conditions and the fact that addition of the nucleophile ArS" to the aryne (334) would have to proceed via the 3-thienyl anion (336) rather than via a more stable 2-thienyl anion such as 320 as would be expected. Contrariwise, cine-substitution by the AEa mechanism is favored by the ability of the complex (335) to stabilize the negative charge by delocalization to both the NO2 group and the a position of the thiophene ring." As in the pyrrole series (Section III.2.B) the actual mechanism appears to be more complex, however, involving several addition and elimination steps via 337, which was recently isolated from the reaction (X = NO2) and shown to go to the product 333 under the reaction conditions. It therefore appears that neither of the cine-substitutions of thiophene described in this Section proceeds via an aryne intermediate. 

Franck, R.W., Yanagi, K., 1966. Aryne formation via a hindered aryl carbonium ion. Tetrahedron Letters 1966,2905. 

The first benzazetidine (243) was isolated from the photolysis of 3-phenyldihydroben-zotriazine (242) (66JA1580). Another route to benzazetidines involving formation of the N to aryl-C bond utilizes intramolecular nucleophilic substitution via aryne (287). It is not general, however, and is only satisfactory when R and/or are alkoxy groups. The reaction also fails for iV-alkylamines (78LA608). 

Most of the subsequent work on this reagent was concerned with the formation of aryl radicals (see review by Cadogan, 1971). However, 2-terf-butyl-A-nitrosoacet-anilide was found to decompose in benzene to give, instead of 2-tert-butylbiphenyl, as expected for a substitution of benzene by a 2-tert-butylphenyl radical, a mixture of isomeric tert-butylphenyl acetates. A careful reexamination (Cadogan and Hib-bert, 1964) suggested that the ratio of 2- and 3-tert-butylphenyl acetates was consistent with the involvement of 2-tert-butylbenzyne, i.e., the product of an ionic dediazoniation, as an intermediate. This was later confirmed by trapping experiments designed to detect aryne intermediates. 

An unusual domino process was observed by Biehl and coworkers [69] in the reaction of 2-bromo-l-naphthol 4-196 with arylacetonitriles in the presence of LDA or LiTMP by employing 3-thienylacetonitrile 4-197, the tetracyclic compound 4-200 was obtained in 57% yield (Scheme 4.43). The reaction probably includes the formation of an aryne and a ketenimine which undergo [2+2] cycloaddition to give 4-198, followed by rearrangement and allylic addition to the intermediately formed aryl cyano compound 4-199. 

Aromatic substitution, a quantitative treatment of directive effects in, 1, 35 Aromatic substitution reactions, hydrogen isotope effects in, 2, 163 Aromatic systems, planar and non-planar, 1, 203 Aryl halides and related compounds, photochemistry of, 20, 191 Arynes, mechanisms of formation and reactions at high temperatures, 6, I A-Se2 reactions, developments in the study of, 6,63... 

Much of the early work on arynes was undertaken using the aryl halide-strong base route (equation 6), but a variety of other procedures, discussed below, are also available. In practice, the choice of the method of generation is often governed by the nature of the reaction to be carried out subsequently. Since arynes are transitory intermediates used in situ, the conditions employed for their formation have... 

Some typical reactions of stannylanionoids which result in the formation of a C-Sn bond are shown in Table 4-1. Primary and secondary alkyl halides react mainly by substitution, but tertiary alkyl halides give mainly elimination. Aryl halides can also give arynes through elimination reactions. 

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