Arynes, chemistry

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. 

This review covers the hterature up to the beginning of 1963. Papers published before the era of aryne chemistry that merely give incidental information on reactions which might proceed via hetarynes are not included. 

For synthetic aspects of aryne chemistry, see C. Grundmann, Arene und Arine, in Houben-Weyl, Methoden der Organischen Chemie, Vol. 5, C. Grundmann, Ed., Thieme, Stuttgart, 1981. 

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. 

Cramer, C. J. Bergman, aza-Bergman, and protonated aza-Bergman cyclizations and intermediate 2,5-arynes chemistry and challenges to computation, J. Am. Chem. Soc. 1998,120, 6261-6269. 

Two areas of aryne chemistry, aryne-metal complexes and aryne radical ions, have been omitted from this review. 

Since the aryne chemistry [82-84] is a very important synthetic tool for transformation of heteroaromatic A-oxides, the further studies expanding application of this methodology are expected to be done. 

Details of aryne chemistry that remain mysterious, particularly, reactions with pyridinium oxides and imides 13, 0116. 

Although acetonitrile is a common solvent in aryne chemistry, it is rarely involved as a reactant in the coupling reactions with arynes. Recently, a three-component coupling of arynes, N-heteroaromatic compounds, and nitriles was reported by Jeganmohan and Cheng (Scheme 12.18) [42] where the reachon was initiated by a nucleophilic attack of the N-heteroaromatic on the aryne, leading to a zwitterionic species 50. The zwitterion 50 then abstracted a proton from acetonitrile (or other nitrile) to afford intermediate 51, alongside anion 52. Anion 52... 

Sanz R (2008) Recent applications of aryne chemistry to organic synthesis. A review. Org Prep Proced Int 40 215-291. doi 10.1080/00304940809458089... 

The most recent review is by Kauffmann and Wirthwein in 1971 but intentionally slights five-membered hetarynes with one heteroatom in favor of their six-membered homologs. With the exception of Hoffmann s classic monograph on arynes in 1967, reviews devoted to general aryne chemistry " tend to neglect hetarynes. Considering the recent activity in this field it seems appropriate to review five-membered hetarynes at this time both as a summary of past research and as a stimulus to future research in this area. An attempt has been made to cover all pertinent literature and unpublished observations available to the author as of December 1981. ... 

As will be described in Section III investigations of the existence of five-membered hetarynes have relied heavily on analogies to the chemistry of the well-authenticated six-membered carbocyclic arynes. It will therefore be the purpose of this section to briefly review and update those aspects of aryne chemistry which have played an important role in this regard. For a more complete coverage of aryne chemistry the reader is referred to the several reviews previously cited and especially to the excellent monograph by Hoffmann. ... 

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. 

SCHEME 36 Synthesis of natural product glycozoline using aryne chemistry [61]. 

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