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

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• 作者：Jian-Biao Liu ; Xie-Huang Sheng ; Chuan-Zhi Sun ; Fang Huang ; De-Zhan Chen
• 刊名：ACS Catalysis
• 出版年：2016
• 出版时间：April 1, 2016
• 年：2016
• 卷：6
• 期：4
• 页码：2452-2461
• 全文大小：720K
• ISSN：2155-5435

文摘

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 → π*_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 Rh^III 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.