A Computational Mechanistic Study of Metal-Catalyzed Remote C-H Functionalizations - Insights into the Origin of Regioselectivity and the Role of Acid

作者：Xu, Yilu; Yang, Shengwen; Du, Lijuan; Li, Juan^*

来源：European Journal of Organic Chemistry, 2017, 2017(2): 381-388.

DOI：10.1002/ejoc.201601111

• Density functional calculations
• C-H activation
• Regioselectivity
• Nitrogen heterocycles
• Reaction mechanisms

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 Ir-III and Rh-III 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 Pd-II 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 Ir-III-catalyzed C8 amidation because the protodemetalation step contributes to the overall rate-determining barrier, on the basis of an energetic span model.

• 出版日期2017-1-10
• 单位暨南大学