The direct C2-functionalization of pyridines through a transition-metal-free protocol by using aryne multicomponent coupling is demonstrated. The reaction allowed a broad-scope synthesis of C2-substituted pyridine derivatives bearing the -CF3 group in good yields with α,α,α-trifluoroacetophenones as the third component. Activated keto esters could also be employed as the third component in this formal 1,2-di(hetero)arylation of ketones. Performing the reaction under dilute conditions inhibited the competing pyridine-aryne polymerization pathway. Nucleophilic attack by the initially generated pyridylidene intermediate on the carbonyl followed by an SN Ar process resembling the Smiles rearrangement affords the desired products.
Keywords: Smiles rearrangement; arynes; multicomponent coupling; pyridine; transition-metal-free reactions.
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