title: Temporary intramolecular generation of pyridine carbenes in metal-free three-component C-H bond functionalisation/aryl-transfer reactions.
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.
authors: Aix Marseille Université, Centrale Marseille, CNRS, iSm2 UMR 7313, 13397, Marseille (France).
authors: Faisal
authors: F
authors: Nawaz
authors: Kishor
authors: K
authors: Mohanan
authors: Laurence
authors: L
authors: Charles
authors: Michel
authors: M
authors: Rajzmann
authors: Damien
authors: D
authors: Bonne
authors: Olivier
authors: O
authors: Chuzel
authors: Jean
authors: J
authors: Rodriguez
authors: Yoann
authors: Y
authors: Coquerel
keywords: CH activation; aromatic substitution; arynes; carbenes; multicomponent reactions