A Computational Mechanistic Study of Amidation of Quinoline N-Oxide: The Relative Stability of Amido Insertion Intermediates Determines the Regioselectivity

作者：Liu, Jian-Biao^*; Sheng, Xie-Huang; Sun, Chuan-Zhi; Huang, Fang; Chen, De-Zhan^*

来源：ACS Catalysis, 2016, 6(4): 2452-2461.

DOI：10.1021/acscatal.5b02938

• quinoline N-oxide
• site selectivity
• C-H activation
• metal effect
• activation energy
• oxidation state

The origin of site selectivity of quinoline N-oxide substrate in Ir(III)-catalyzed amidation with tosyl azide was investigated computationally. The reaction proceeds exclusively at the C8 position, instead of the C2 position, which has been reported previously in many other reactions. C2-Amidation is kinetically impossible under the reaction condition according to our calculations, with high apparent activation energy up to 51.1 kcal/mol. The high energetic span is caused by the deep-lying 5-membered amido insertion intermediate, in which a strong stabilization effect was observed due to n(N) -> pi(C=N)* delocalization. For C8-amidation, however, the 6-membered counterpart is relatively unstable, making the activation energy only about half the value of C2-amidation. Meanwhile, denitrogenation is found to be turnover limiting in the reaction. The oxidation state changes of the Ir center during the stepwise C-N bond formation were investigated, and a considerably higher effective oxidation state was found in the Ir-nitrenoid intermediate. The ineffective Rh-III catalyst was also studied. In comparison with the results of the Ir-III catalyst, the Rhin catalyst features higher energy profiles and higher apparent activation energies. A dual role of acetic acid additive participating both in the C-H activation and protodemetalation was also demonstrated.

• 出版日期2016-4
• 单位山东师范大学