Transition‐Metal‐Free C2‐Functionalization of Pyridines through Aryne Three‐Component Coupling

• Published in: Chemistry : a European journal Vol. 27; no. 55; pp. 13864 - 13869
• Main Authors: Guin, Avishek, Bhattacharjee, Subrata, Biju, Akkattu T.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 01.10.2021; Wiley Subscription Services, Inc
• Subjects: arynes; Carbonyl compounds; Carbonyls; Chemistry; Chemistry, Multidisciplinary; Coupling; Esters; Ketones; multicomponent coupling; Physical Sciences; pyridine; Pyridines; Science & Technology; Smiles rearrangement; transition-metal-free reactions; Smiles rearrangement; BENZYNES; multicomponent coupling; ARYLATION; pyridine; TERMINAL ALKYNES; transition-metal-free reactions; N-OXIDES; arynes; H BOND ADDITION; HETEROCYCLES; EMPLOYING ARYNES; REGIOSELECTIVE SYNTHESIS; GENERATION; MULTICOMPONENT REACTION
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202102005

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 SNAr process resembling the Smiles rearrangement affords the desired products. Getting into position: Aryne multicomponent coupling triggered by pyridines allows the broad‐scope synthesis of C2‐substituted pyridines bearing a −CF3 group by engaging α,α,α‐trifluoroacetophenones as the third component. Activated keto esters could also be used 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.