Aromatic substitution, carbene synthesis

Electrophilic aromatic substitution as a route to differentially substituted products is well established. The often forcing conditions, the incompatibility of this process with acid-sensitive functional groups, and the need for mild and selective syntheses have been the driving forces in the search for new methods of synthesis. A large range of methods has been developed over the past 20 years they include the trimerization of alkynes, the directed orfho-metallation, the benzannellation via metal carbenes, and transition metal-catalyzed carbon-carbon and carbon-heteroatom bond formation. Aromatic C-H activation, while still in its beginning stages, is another area of promise. 

In contrast to considerations of 50 years ago, today carbene and nitrene chemistries are integral to synthetic design and applications. Always a unique methodology for the synthesis of cyclopropane and cyclopropene compounds, applications of carbene chemistry have been extended with notable success to insertion reactions, aromatic cycloaddition and substitution, and ylide generation and reactions. And metathesis is in the lexicon of everyone planning the synthesis of an organic compound. Intramolecular reactions now extend to ring sizes well beyond 20, and insertion reactions can be effectively and selectively implemented even for intermolecular processes. 

Other copper-based heterogeneous methodologies recently reported afford 1,2,3-triazoles from organic halides, aromatic terminal aUcynes, and sodium azide [70], As illustrated in Scheme 3.37, Wan and Cai described the efficient and green synthesis of 1,4-substituted 1,2,3-triazoles 71 catalyzed by silica-immobilized A-heterocyclic carbene-Cu(I) 72 (Scheme 3.37). 

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