三氟乙酸钯催化吲哚与芳基硼酸偶联反应机理的理论研究

Theoretical Study on the Mechanism of Coupling Reaction of Indole with Aryl Group Catalyzed by Palladium Trifluoroacetate

金属钯催化偶联反应在现代有机合成中起着至关重要的作用。为了对其机理进行详细探索,以目前在药物合成和化工生产中非常热门的吲哚与芳基硼酸偶联反应作为研究对象,选取三氟乙酸钯作为催化剂,采用密度泛函理论(density functional theory,DFT)中的贝克三重杂化泛函及李-杨-帕尔的局部密度近似(Baker′s triple hybrid functional and Li-Yang-Parr′s local density approximation,B3LYP)方法,通过计算,对钯催化无外加配体的吲哚与芳基硼酸偶联反应提出如下反应机理:第一步,三氟乙酸钯与芳基硼酸反应生成芳基钯中间体;第二步,芳基钯中间体作为亲电试剂进攻吲哚的C-3位;第三步,芳基钯从吲哚的C-3位迁移到C-2位;第四步,三氟乙酸的配位三氟乙酸根开环夺走吲哚上的氢质子;第五步,金属钯还原消除,并在空气作用下被氧化为三氟乙酸钯,催化剂被复原。该研究可拓展至其他芳基配体,为合成复杂分子提供新方法。

Metal palladium catalyzed coupling reaction plays an important role in modern organic synthesis.In this paper,the coupling reaction of indole with arylboronic acid,which is very popular in the drug synthesis and chemical production at present,is taken as the research object,palladium trifluoroacetate is selected as the catalyst,and its mechanism is explored in detail by the Baker′s triple hybrid functional and Li-Yang-Parr′s local density approximation(B3LYP)method in density functional theory(DFT).Through density functional theory calculation,the following mechanism was proposed for palladium catalyzed coupling reaction of indole with arylboronic acid without external ligand.Step 1:palladium trifluoroacetate reacted with arylboronic acid to form aryl palladium intermediate.Step 2:aryl palladium intermediates act as electrophilic reagents to attack the C-3 position of indole.Step 3:the aromatic palladium migrates from the C-3 position of indole to the C-2 position.Step 4:the coordination of trifluoroacetic acid on trifluoroacetic acid takes away the hydrogen proton on indole by opening the ring.Step 5:the metal palladium is reduced and eliminated,and oxidized to palladium trifluoroacetate under air oxidation,and the catalyst is restored.This study can be extended to other aryl ligands,providing new method for synthesizing complex molecules.