Insight into the Mechanism and Regioselectivity of Pd(OAc)2-Catalyzed C-O Bond Activation via a β-O Elimination Approach: A Computational Study.
Insight into the Mechanism and Regioselectivity of Pd(OAc)2-Catalyzed C-O Bond Activation via a β-O Elimination Approach: A Computational Study.
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DOI：
10.1021/acs.jpca.1c05412
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发表时间：
2021-10
期刊：
影响因子：
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通讯作者：
Junxia Yang;Yan Zhang;Ruyu Zhu;Ying Xue
中科院分区：
文献类型：
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作者：
Junxia Yang;Yan Zhang;Ruyu Zhu;Ying Xue
采用密度泛函理论研究了Pd（OAc）2催化的4-苯氧基-N-（喹啉-8-基）丁酰胺与N-甲基吲哚反应中碳氧键活化的区域选择性机理和起源.该反应依次经历了C-H活化、β-O消除、新C-C键形成的核钯化和原钯化四个主要阶段。在β-O消除步骤中有两种可能的C-O键断裂形式，在关键的核钯化步骤中有六种亲核攻击反应通道，因此共考虑了六种途径。计算结果表明，共同的第一步（C-H键活化步骤）通过协调的金属化去质子化（CMD）机制发生。核钯化是所有六个反应途径的速率决定步骤。结果还表明，整个反应的最有利途径是在第二阶段脱除苯酚，在第三阶段N-甲基吲哚的氢原子进攻中间体乙酸酯基的氧原子的途径（记为路径b1）。根据非共价相互作用（NCI）和约化密度梯度（RDG）的分析，最有利的反应途径得益于其关键过渡态的强吸引相互作用和弱排斥相互作用。此外，结构，自然键轨道电荷，和过渡态的能量分析揭示了区域选择性的起源。这很好地解释了实验现象，有利于今后设计类似反应的新策略。
The density functional theory investigations were carried out to elucidate the mechanism and the origin of regioselectivity for the Pd(OAc)2-catalyzed carbon-oxygen bond activation in the reaction between 4-phenoxy-N-(quinolin-8-yl) butanamide and N-methylindole. The reaction proceeded through four main stages in succession: C-H activation, β-O elimination, nucleo-palladation of the new C-C bond formation, and proto-depalladation steps. A total of six pathways were considered since there were two possible forms of C-O bond breaking in the β-O elimination step and six reaction channels of nucleophilic attack in the crucial nucleo-palladation step. The computational results indicate that the common first step (C-H bond activation step) occurs via a concerted metalation deprotonation (CMD) mechanism. The nucleo-palladation was the rate-determining step for all six reaction pathways. The results also show that the most favorable pathway for the whole reaction is the one (denoted as path b1) in which phenol was removed in the second stage and the hydrogen atom of N-methylindole attacked the oxygen atom of acetate group of the intermediate in the third stage. According to the analyses of noncovalent interaction (NCI) and the reduced density gradient (RDG), the most favored pathway benefits from the strong attractive interaction and weak repulsive interaction in its key transition state. Furthermore, structural, natural bond orbital charge, and energy analyses of the transition states reveal the origin of the regioselectivity. This is a good explanation of the experimental phenomenon and benefits future design of a new strategy for a similar reaction.