Activation of Unstrained Ketone C(O)-C Bond: 1,2-Nucleophilic Addition Followed by β-Carbon Elimination Strategy

Transition-metal-catalyzed C-C bond activation has emerged as an increasingly effective method for reorganizing a molecular skeleton. Ketone, as a versatile functional molecule, has been extensively studied for the C-C bond activation reaction. However, most C-C bond activation of unstrained ketones generally follows an oxidative addition strategy, while a nucleophilic 1,2-addition of a carbonyl moiety followed by beta-C elimination strategy was less studied. Here a palladium-catalyzed C-C bond activation of an unstrained ketone enabled by a removable directing group through beta-C elimination to synthesize 2-arylpyridine is described. The protocol features wide substrate scope with yields up to 95%, good functional group tolerance, and functionality of natural products. The 2-arylpyridine N-oxide products can be easily converted to the corresponding 2-arylpyridines under mild reaction conditions.

Automated summary

This study presents a palladium-catalyzed C-C bond activation of an unstrained ketone enabled by a removable directing group through β-C elimination to synthesize 2-arylpyridine. The method demonstrates wide substrate scope with yields up to 95%, good functional group tolerance, and functionality of natural products. The 2-arylpyridine N-oxide products can be easily converted to the corresponding 2-arylpyridines under mild reaction conditions.