Copper‐Mediated C6‐Selective Dehydrogenative Heteroarylation of 2‐Pyridones with 1,3‐Azoles

Abstract

A copper-mediated C6-selective dehydrogenative heteroarylation of 2-pyridones with 1,3-azoles has been developed. The reaction proceeded smoothly by twofold C-H cleavage even in the absence of noble-metal catalysts. The observed site selectivity was directed by a pyridyl substituent on the nitrogen atom of the pyridone ring. This directing group was readily removed after the coupling event, thus leading to 2-pyridone derivatives with a free N-H group. Moreover, in some cases, catalytic turnover of the Cu salt was also possible with the ideal terminal oxidant: molecular oxygen in air.

Solvent‐Controlled Rhodium‐Catalyzed C6‐Selective C−H Alkenylation and Alkylation of 2‐Pyridones with Acrylates

“…To date, the C3, C4, C5, and C6‐selective C−H functionalizations have been reported under various transition metal catalyses. Our group has also focused on the site‐selective C−H functionalization of 2‐pyridones and developed the C3‐selective alkylation and arylation, and C6‐selective alkylation, (hetero)arylation, and borylation . As part of this research project, we herein wish to report a Cp*Rh(III)‐catalyzed C6‐selective C−H coupling of 2‐pyridones with acrylates via pyridine‐directed C−H cleavage (Scheme ): the reaction in DMF efficiently occurs to deliver the corresponding C−H alkenylation products in good yields (left).…”

Recent Advances in Copper-mediated Direct Biaryl Coupling

“…27 Also in this case, the molecular oxygen works well as the effective terminal oxidant and makes the reaction catalytic in copper. This is the single successful example of the highly C6-selective direct arylation of 2-pyridones.…”

Transition Metal Mediated C–H Activation of 2‐Pyrones, 2‐Pyridones, 2‐Coumarins and 2‐Quinolones

“…Hirano and Miura have developed a pyridine‐directed, copper‐mediated dehydrogenative C6‐heteroarylation of 2‐pyridones with 1,3‐azoles (Scheme ) . Importantly, the directing group can be removed after the coupling event.…”

“…Hirano and Miura have developed a pyridine-directed, coppermediated dehydrogenative C6-heteroarylation of 2-pyridones with 1,3-azoles (Scheme 33). [47] Importantly, the directing group can be removed after the coupling event. The authors also disclosed that in some cases, the use of molecular oxygen in air as the terminal oxidant makes the reaction catalytic in copper.…”