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Temporary Intramolecular Generation of Pyridine Carbenes in Metal‐Free Three‐Component CH Bond Functionalisation/Aryl‐Transfer Reactions

2013; Wiley; Volume: 19; Issue: 51 Linguagem: Inglês

10.1002/chem.201303359

1521-3765

Faisal Nawaz, Kishor Mohanan, Laurence Charles, Michel Rajzmann, Damien Bonne, Olivier Chuzel, Jean Rodriguez, Yoann Coquerel,

Catalytic C–H Functionalization Methods

Abstract Nucleophilic addition of pyridines to benzyne generates zwitterionic adducts that evolve by a rapid intramolecular proton shift to produce the corresponding pyridine carbenes, N ‐phenyl pyrid‐2‐ylidenes. In the presence of electrophilic ketones (isatin derivatives), the pyridylidenes can further react by an original bis‐arylation reaction of the carbonyl compounds involving a formal pyridine CH bond functionalisation. The overall transformation is an unprecedented three‐component reaction featuring a carbene intermediate. The mechanism of this transformation was examined in detail by using both experimental and theoretical approaches. It was found that the generation of N ‐phenyl pyrid‐2‐ylidene from pyridine and benzyne is energetically favoured, and that the corresponding carbene dimer can also form easily. Under the three‐component reaction conditions, the pyridylidene preferentially adds to the ketone group of the isatin derivative to produce a zwitterionic adduct amenable to an intramolecular aryl transfer reaction by a concerted nucleophilic aromatic substitution. This peculiar reactivity for a carbene was compared to possibly competitive known reactions of stable carbenes with carbonyl compounds, and the reaction was found to be under thermodynamic control. The reported method of generation of N ‐phenyl pyrid‐2‐ylidenes and their reactivity with carbonyl compounds unlock new perspectives in organic synthesis.