Anions reaction with benzyne

Strong base treatment of the spiro salt 49 gives a benzyne (107) from which the isolated products were produced by further reaction. For example, with n-butyllithium and furan in tetrahydrofuran, 108 is produced after hydrogenation and acid treatment via 109. Reaction with phenyllithium gives 110 (R == Ph and Me) by subsequent addition of phenyl or methyl anion to the benzyne, respectively, and 110 (R = I) by subsequent reaction with iodine anion. Similarly the 9,9-diphenyl salt 111 gives 112 with phenyllithium. Pyrolysis of the spiro salt 49 gives 50. 

Bromobenzyl 2-fluorophenyl thioether, derived from 2-fluorothiophenol and 2-bromobenzyl bromide, is a source of a benzyne through reaction with /-butyllithium. Simultaneously, the bromobenzyl moiety generates the tethered aryllithium 405 and an intramolecular anionic cyclisation is promoted. The sequence is completed by the addition of an electrophilic species leading to 1-substituted b/Z-dibenzol //]thiopyrans (Scheme 121) <2002CEJ2034>. 

In an interesting new application, benzynes have been generated from the 2-fluoroalkylanines 78, and underwent anionic cyclization, followed by reaction with electrophiles to furnish a variety of 4-substituted indoles 79 <02CEJ2034>. 

It has been found that benzo[c ]-l,3-azasilolines (141) can be prepared by the intermolecular reaction of A,A-dimethyl-2-triorganosilylethylamines (137) with benzyne in the presence of excess -butyllithium <76JOCi962>. It is postulated that deprotonation of the first betaine intermediate (138) with butyllithium affords the second intermediate (139) which undergoes silyl rearrangement with loss of ethylene. Cyclization of the resultant aromatic anion (140) onto silicon with concomitant loss of an R group then gives the heterocycle (141) (Scheme 15). 

The use of sodium amide or potassium amide in liquid ammonia with bromo- or chlorobenzene leads inevitably to the capture of benzyne by its reaction with ammonia. However, the utility of bromo- or chlorobenzene as a benzyne precursor is extended to ethereal solvent systems by employing the conjugate base of a hindered secondary amine (diisopropylamine, 2,2,6,6-tetramethylpiperidine) which can be formed in situ from the amine and alkyllithium. Alternatively, butyllithium itself is used with the halogeno-benzene, and pentafluorobenzene and butyllithium are the usual source of tetrafluorobenzyne. In all of these reactions the aryne is generated by decomposition of an o-halogenoaryl anion at temperatures below 0°C. 

Grignard reagents are also shown to undergo anionic 1,3-cycloadditions with benzyne, leading to the fused system (33), but the reaction competes with nucleophilic addition and [2-1-2] cycloaddition reactions. 

A final example of aryne formation involves the reaction of o-phenylene carbonate (90) with phosphines. An analogous reaction with thiocarbonates (91) fails as does generation of the anion of 2-phenyl-1,3-benzodioxole (92), which had been expected to lose benzoate ion to give benzyne. ... 

Stoltz et al. [53] and Ramtohul et al. [54] independently and almost simultaneously reported an isoquinoline synthesis via the reaction of A -acetylenamines with benzynes (Scheme 16, route b Scheme 18). In this reaction, intermediary A -acetylimines underwent nucleophilic attack of the aryl anions to give the corresponding isoquinolines after aromatization. The carbonyl carbon on the nitrogen atom was incorporated into the 1-position of the resulting isoquinolines. 

The photoinitiated reaction of haloarenes with the anion CHjCONMej followed by addition of methyl iodide is an approach to the synthesis of aryl propionic acids. The acids are obtained by hydrolysis. Competition with the benzyne mechanism (i.e., the reaction of the former anion with 4-bromo-2-fluorobiphenyl) and addition to the carbonyl group (when the same anion reacts with m-chloroben-zophenone) are responsible for the low yields of substitution from the amide derivatives of fluorobi-prophen and ketoprophen, respectively. ... 

A variation of the halide affinity approach was used by Riveros et al. in the investigation of the enthalpy of formation of o-benzyne. Reaction of bromo- or iodobenzene with base in an ICR leads predominantly to the formation the expected M-1 anion, but also leads to the formation of solvated halide ions (Eq. 5.15). By using substrates with known halide affinities, it was possible to assign limits to the enthalpy of formation of the benzyne product. Ultimately, the experiment is comparable to that outlined in Eq. 5.14, although the acidity and halide affinity measurements are made in a single step. 

Dehydrobenzene or benzyne 158 can be trapped by all manner of species. 1,2-Dehydro-o-carborane 159 has been shown to undergo many of the same reactions as its two-dimensional relative, 1,2-dehydrobenzene. Although dehydroaromatic molecules can be formed in a variety of ways, synthetic pathways to 1,2-dehydro-o-carborane are quite limited. An effective procedure reported so far78 first forms the dianion by deprotonation of o-carborane with 2 equiv. of butyllithium. Precipitated dilithium carborane is then treated with 1 equiv. of bromine at 0°C to form the soluble bromo anion 160. Thermolysis of 160 with anthracene, furan, and thiophene as substrates leads to the adducts 161-164.79 80 1,2-Dehydro-o-carborane reacts with norbomadiene to give both homo 2+4 and 2+2 addition, leading to three products 165-167, in a 7 1 ratio79. An acyclic diene, 2,3-dimethyl-... 

Scheme 3.37 describes gas-phase generation of m-benzyne anion (the distonic anion-biradical) from m-bis(trimethylsilyl) benzene (Wenthold et al. 1994, 1996 Wenthold and Squires 1998). The same anion-biradical is formed from isophthalic acid under the same conditions (Reed et al. 2000). Particularly, the reaction of m-bis(trimethylsilyl) benzene with fluoride ion, followed by treatment of the formed trimethylsilyl phenyl anion with fluorine in helium, produces the anion-biradical mentioned. The latter is transformed into the corresponding nitro benzoate anion through the addition of CO2 and NO2 (Scheme 3.37). 

However, this achievement was then marred by an unfortunate error. The calcium salt of 4-fluorobenzoic acid was heated in admixture with calcium hydroxide, and fluorobenzene was claimed to be formed by decarboxylation. Later, it was shown16 that the product, a solid, was phenol. It had been analyzed only for carbon and hydrogen content an early warning to all workers in fluorine chemistry of the need for quantitative assays for fluorine in their products. Being more activated than fluorobenzene towards nucleophilic attack, the fluorobenzoate anion itself probably lost fluorine before decarboxylation occurred. A benzyne-type process seems to be a less likely reaction pathway. 

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