Aryne cyclization

Carbanions derived from side chain tertiary amides have also been cyclized to provide isoquinolones and isoindoles (equation 36).125 126 While benzyne intermediacy in the formation of the former is likely, the latter seems to arise through a SrnI reaction pathway. Synthesis of indole from the meta bromo compound (87), on the other hand, clearly involves an aryne cyclization. 27 A more versatile route to indoles is based on intramolecular addition of aminyl anions to arynes (equation 38).128 A somewhat similar dihydroindole preparation constitutes the first step in a synthesis of lycoranes (equation 39).129 The synthesis of (88) also falls in the same category of reactions, but it is noteworthy because only a few examples of ring closure of heteroarynes are mentioned in literature.27 28... 

Benzoxazoles. - Both o- and m-halogenobenzanilides (413) are converted into the amidines (415) by potassium amide in liquid ammonia these are formed by aryne cyclization to 2-phenylbenzoxazole (414) and subsequent aminoly-sis." The conversion of acetophenone oxime into 2-methylbenzoxazole by the action of phosphorus oxychloride involves a Beckmann rearrangement. Pyrolysis of aryl azidoformates, ArOaCNa, gives benzoxazol-2-ones. The azide (416) is converted into the benzoxazole (417) on heating. The... 

A number of examples of the aryne cyclization route have appeared. Treatment of the appropriately substituted halobenzene (45) with potassium amide in liquid ammonia affords 2-methylisoindole in 89% yield.74 A rationalization of the reaction is shown in Scheme 7. This route has been... 

In addition to the aforementioned intramolecular indoUzations involving aryne cyclizations, tntcrmolecu-lar reactions of arynes leading to indoles have been described. 

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. 

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. 

It has been shown that, in the presence of lithium diethylamide at —70 °C, bromoben-zoic acids form arynes which may react with arylacetonitriles to yield, predominantly, 2-cyanobenzoic acids. The reaction of alkyl and aryl isocyanides with benzyne may yield benzamide derivatives, showing their ability to act as charge-reversed equivalents to isocyanates. The generation and cyclization of a benzyne-tethered alkyllithium have been reported, and lead to a convenient synthetic route for 4-substituted indans. ... 

Diels-Alder reaction of 3-vinylindole 131 with aryne in the presence of air gives, besides primary Diels-Alder product 132, the methyl 12-methyl-12H-[3]-benzoxepino[l,2-l7]indole-5-carboxylate 135. This can be explained by the formation of 1,2-dioxetane 133, its cyclo reversion and final intramolecular cyclization of dienol 134 or its tautomers (Scheme 26 (1996JCS(P1)1767)). 

An interesting route to 98 was suggested by Cramer et al. " cyclization of isonitrile 110 could lead to 98 in a rearrangement analogous to the Bergman cyclization. The activation enthalpy for the only slightly exothermic reaction was estimated at 18 kcal/mol. However, this novel access to m-arynes could not be realized experimentally so far. 

Cramer, C. J. 1998. Bergman, Aza-Bergman, and Protonated Aza-Bergman Cyclizations and Intermediate 2,5-Arynes Chemistry and Challenges to Computation. 1. Am. Chem. Soc.. 120. 6261. 

If the moeity adding to the aryne carries a suitably placed electrophilic center, cyclization with the initially formed anion can occur as observed in the synthesis of dibenzothiophene (60).92 Of wider synthetic import in this context is enolate addition to arynes. Here, after the initial ring closure many types of products can be formed (Scheme ll).35 However, with some substrates, a particular reaction course can predominate 93 94 for example, reaction of cyclodecanone with bromobenzene provides an efficient method for benzo-annulation and ring expansion. Similarly, high yields of benzocyclobutenols can be obtained from the monoketals of ot-diketones.9s... 

Methyl thiosalicylate provides both electrophilic and nucleophilic sites for annulation of arynes generated from silylaryl triflates in the presence of CsF. An initial intermolecular nucleophilic coupling to afford a diaryl sulfide 529 is followed by an intramolecular electrophilic cyclization and thioxanthones result. The use of THF as solvent suppresses the competitive proton abstraction which leads to methyl 2-thiophenoxybenzoate (Scheme 211) <2005OL4273>. 

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