LAUSR

The metal-catalyzed remote C–H functionalization of quinoline N-oxide was investigated systematically through density functional theory calculations. We found that the coordination of the N-oxide moiety to a metal center greatly lowered the barrier to C–H activation and made C8–H activation favorable, regardless of the metal center (Ir, Rh, or Pd). For IrIII and RhIII systems, the active catalyst was identified from several candidates as [Cp*M(OAc)]+ (M = Ir or Rh, Cp* = pentamethylcyclopentadienyl) because the N-oxide moiety in quinoline N-oxide can coordinate to the metal center in the [Cp*M(OAc)]+ system. The cleavage of the C8–H bond was favored over the C2–H cleavage because the transition state in the former case is a five-membered metallacycle, whereas that for the latter is a four-membered metallacycle. For the PdII system, the absence or presence of a phosphine ligand enabled C8–H or C2–H bond functionalization in quinoline N-oxide. This is attributed to the occurrence or not of the coordination of the N-oxide moiety to the Pd center. Acid additives play a key role in the catalytic cycle for IrIII-catalyzed C8 amidation because the protodemetalation step contributes to the overall rate-determining barrier, on the basis of an energetic span model.