Arynes, chemistry heterocyclic

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. 

Another important aspect of aryne chemistry that has found application in benzo-fused heterocycles synthesis is MCRs, which generally include the first addition of nucleophiles to arynes and subsequent interception of the aryl anion intermediate with other electrophiles. If the nucleophile and electrophile are not part of the same molecule, the overall process is a unique multicomponent coupling, where the aryne is inserted between the other two coupling partners to afford the final product 85 (Scheme 39). This highly efficient transition-metal-free methodology has been applied to the S5mthesis of valuable benzo-fused heterocycles and has foxmd application in natural product synthesis. 

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. 

While no concerted attempts to prepare selenaarynes have been reported, the chemistry of several potential precursors has been examined. The 2-lithio-3-bromo derivatives 490 and 491 react with electrophiles as expected for aryllithium reagents and show no tendency at —70°C to eliminate lithium bromide to form a 2,3-didehydroselenophene (492). Similar observations have been reported for the benzolog 493 and the possible aryne 2,3-didehydrobenzo[ft]selenophene 494. As in the corresponding sulfur and oxygen heterocycles, this unusual stability of the 2-lithio derivatives is probably related to the ability of the heteroatom to stabilize an adjacent carbanion. ... 

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