Heterocyclic arynes

The heterocyclic aryne (trithiadiazepyne) 12.18, generated by treatment of the monobromo derivative of 12.16 with a strong base, can be trapped as a Diels-Alder adduct with furan (Scheme 12.3). ... 

Similar alkene formations via dealkoxycarbonylation and denitration have been reported for the synthesis of novel heterocycles. Heterocyclic nitro compounds such as 4-nitroisoxazole undergo the Diels-Alder reaction subsequent dealkoxycarbonylation and denitration give the products, which are regarded as the Diels-Alder adducts of five-membered heterocyclic arynes (Eq. 7.142).121... 

A common synthetic use of heterocyclic carbanions is as precursors of heterocyclic arynes (hetarynes), although the intermediacy of the latter species can often only be inferred from the structure of the isolated products [65AG(E)543, 65AHC(4)121 67MI1 71AG(E)20 82T427], However,... 

For a nice review on heterocyclic arynes, seeM. G. Reinecke, Hetarynes. Tetrahedron, 1982 38, All. 

Lester Friedman and Frauds M. Logullo prepared substituted benzynes by diazotizing substituted anthranilic acid. This is a mild, room-temperature reaction which permits simultaneous reactions of the benzynes with suitable acceptors to prepare halogen. —NO , — ClL. and —OCH3 derivatives. They have also prepared new heterocyclic arynes, such as 3-pyridine from 3-amino-isonicotinic add. 

Arynes and hetarynes (heterocyclic arynes)67-72 such as 25 and 26 are named benzyne or dehydrobenzene and 3,4-pyridyne or 3,4-dehydropyridine, respectively. 

Prior to 1960 little work had been done on reactions of heterocyclic compounds involving hetarynes, i.e. intermediates with a triple bond in the nucleus containing the hetero atom. Since then interest in hetarynes has grown and investigations in this area are developing rapidly using information available from carbocyclic aryne chemistry. Therefore, a short survey of the chemistry of arynes is presented before summarizing typical problems encountered in hetaryne chemistry. 

Heterocyclic compounds may show a higher tendency than carbocycles to react with nucleophiles according to the addition-elimination mechanism than via arynes. 

Despite the fact that the history of hetarynes is older than that of the benzynes (cf. 2), physical data on these compounds are scarce. Numerous trapping experiments furnished evidence for the formation of brradicaloid intermediates in the field of five-membered heterocycles (didehydrofurans, -thiophenes, and -pyrroles)." Direct spectroscopic data on these species, however, do not exist, which may be attributable to the increased ring strain in the five-membered o-arynes, associated with a strong tendency to undergo ring-opening reactions. 

Just as in phenyl halides, the halogen can be replaced by hydrogen, by a metal, or be coupled. Two of the four mechanisms of such nucleophilic substitutions are also familiar from benzene chemistry via arynes and by the SRN1 mechanism. However, of the two further mechanisms of nucleophilic replacement, the ANRORC is unique to heterocycles, and SAE reactions occur only with strongly activated benzenoid systems. 

The very reactive arynes have also been used as dienophiles in Diels-Alder cycloadditions with vinyl heterocycles and are included here, after the acetylenic esters, because of the similarity of their reactive functions. This reaction is of considerable importance because of its application in the synthesis of polycyclic compounds. 

Accordingly, nine aromatic and two heterocyclic anhydrides were pyrolyzed in admixture with pyridine under standardized conditions, and the relative amounts of aryne or heteroaryne produced were determined by analysis of the reaction products (Fields and Meyerson,... 

While not formal carbanions, arynes have been found to react with electrophilic centers. The first report of an aryne reacting with an epoxide has been published. While the yield of this reaction is not good, it suggests that this could be a viable route for the synthesis of benzofused heterocyclic ring systems <07SL1308>. 

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