Factors Controlling the Reactivity and Chemoselectivity of Resonance Destabilized Amides in Ni-Catalyzed Decarbonylative and Nondecarbonylative Suzuki-Miyaura Coupling.

N-Glutarimide amides have recently emerged as an exceptional group of compounds with unusually high reactivity in amide C-N bond activation. To understand the key factors that control the remarkable reactivity of these resonance destabilized amides, we explored the Ni-catalyzed decarbonylative and nondecarbonylative Suzuki-Miyaura coupling with N-glutarimide amides through density functional theory calculations. Two leading effects are responsible for the C-N cleavage activity of N-glutarimide amides, the coordinating N-substituents and the geometric twisting. The carbonyl substituent of the N-glutarimide amides provides crucial nickel-oxygen interaction, which essentially acts as a directing group to facilitate the formation of the reactive intermediate for the amide C-N bond cleavage. The geometric twisting weakens the resonance stability by removing the acyl-nitrogen conjugation, which lowers the energy penalty for the C-N bond stretch during oxidative addition. For the chemoselectivity of decarbonylation versus carbonyl retention, we found that the C-C reductive elimination for ketone formation is kinetically faster than that for biaryl formation, while ketone is thermodynamically less stable with respect to the decarbonylated biaryls. The computations also suggest that the nickel catalyst is able to promote the decarbonylation of biaryl ketones via an unexpected C-C bond activation.