Scope and Mechanism of the Redox-Active 1,2-Benzoquinone Enabled Ruthenium-Catalyzed Deaminative α-Alkylation of Ketones with Amines
Scope and Mechanism of the Redox-Active 1,2-Benzoquinone Enabled Ruthenium-Catalyzed Deaminative α-Alkylation of Ketones with Amines
复制标题
氧化还原活性 1,2-苯醌钌催化酮与胺的脱氨 α-烷基化反应的范围和机制
DOI：
10.1021/acscatal.1c04732
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发表时间：
2021
期刊：
影响因子：
12.9
通讯作者：
Yi, Chae S.
中科院分区：
文献类型：
--
作者：
Kirinde Arachchige, Pandula T.;Handunneththige, Suhashini;Talipov, Marat R.;Kalutharage, Nishantha;Yi, Chae S.
研究发现，阳离子Ru-H配合物与3,4,5,6-四氯-1,2-苯醌反应原位形成的催化体系可介导酮与胺的区域选择性脱氨偶联反应，形成α-烷基化酮产物。发现苄基和脂肪族伯胺都是与酮进行偶联反应形成α-烷基化酮产物的合适底物。 PhCOCD3 与 4-甲氧基苄胺的偶联反应在烷基化产物的 α-CH2(41% D) 和 β-CH2(21%) 位置上显示出广泛的 H/D 交换。苯乙酮与对位取代的苄胺sp-X-C6H4CH2NH2(X = OMe, Me, H, F, Cl, CF3)反应得到的哈米特图显示，带有电子释放基团的胺底物具有很强的促进作用(ρ = -0.49 ± 0.1)。最显着的碳同位素效应是在苯乙酮与 4-甲氧基苄胺偶联反应的烷基化产物 (Cα= 1.020) 的 α-碳上观察到的。分离的亚胺底物的烷基化反应动力学得出经验速率定律：速率=k[Ru][亚胺]。通过阳离子Ru-H配合物与3,5-二叔丁基-1,2-苯醌和PCy3的反应合成了具有催化活性的Ru-儿茶酚配合物。对烷基化反应进行了 DFT 计算研究，揭示了通过形成具有中等活化能 (ΔG‡= 32–42 kcal/mol) 的 Ru(IV)-烷基物种来进行 [1,3]-碳迁移的逐步机制。基于这些实验和计算数据，已经编制了通过 Ru-烯胺中间体的分子内 [1,3]-烷基迁移进行催化烷基化反应的合理机制。
The catalytic system formedin situfrom the reaction of a cationic Ru–H complex with 3,4,5,6-tetrachloro-1,2-benzoquinone was found to mediate a regioselective deaminative coupling reaction of ketones with amines to form the α-alkylated ketone products. Both benzylic and aliphatic primary amines were found to be suitable substrates for the coupling reaction with ketones in forming the α-alkylated ketone products. The coupling reaction of PhCOCD3with 4-methoxybenzylamine showed an extensive H/D exchange on both α-CH2(41% D) and β-CH2(21%) positions on the alkylation product. The Hammett plot obtained from the reaction of acetophenone withpara-substituted benzylaminesp-X-C6H4CH2NH2(X = OMe, Me, H, F, Cl, CF3) showed a strong promotional effect by the amine substrates with electron-releasing groups (ρ = −0.49 ± 0.1). The most significant carbon isotope effect was observed on the α-carbon of the alkylation product (Cα= 1.020) from the coupling reaction of acetophenone with 4-methoxybenzylamine. The kinetics of the alkylation reaction from an isolated imine substrate led to the empirical rate law: rate =k[Ru][imine]. A catalytically active Ru–catecholate complex was synthesized from the reaction of the cationic Ru–H complex with 3,5-di-tert-butyl-1,2-benzoquinone and PCy3. The DFT computational study was performed on the alkylation reaction, which revealed a stepwise mechanism of the [1,3]-carbon migration stepviathe formation of a Ru(IV)-alkyl species with a moderate energy of activation (ΔG‡= 32–42 kcal/mol). A plausible mechanism of the catalytic alkylation reactionviaan intramolecular [1,3]-alkyl migration of an Ru-enamine intermediate has been compiled on the basis of these experimental and computational data.