电化学促进的镍催化的α-氰基乙酸酯的α-芳基化反应  

Nickel-Catalyzed a-Arylation of a-Cyanoacetates Enabled by Electrochemistry

作　　者：李子萌 李章健 Anat Milo 方萍 梅天胜 Zi-Meng Li;Zhang-Jian Li;Anat Milo;Ping Fang;Tian-Sheng Mei(State Key Laboratory of Organometallic Chemistry,Shanghai Institute of Organic Chemistry,University of Chinese Academy of Sciences,Chinese Academy of Sciences,Shanghai 200032,China;College of Chemistry and Materials Science,Sichuan Normal University,Chengdu 610068,China;Department of Chemistry,Ben-Gurion University of the Negev,Beer-Sheva 841051,Israel)

机构地区：[1]中国科学院上海有机化学研究所金属有机国家重点实验室,中国科学院大学,上海200032 [2]四川师范大学化学与材料科学学院,成都610068 [3]本·古里安大学化学部,贝尔谢巴841051

出　　处：《电化学（中英文）》2024年第5期11-24,共14页Journal of Electrochemistry

基　　金：This work was financially supported by the National Key R&D Program of China(No.2021YFA1500100);the NSF of China(Grants 21821002,21772222,and 91956112);the S&TCSM of Shanghai(Grants 20XD1425100 and 20JC1417100).

摘　　要：β-氨基酸在医药领域有着广泛的应用。本文利用镍催化的成对电解策略,发展了一种羰基α-芳基化反应,实现了α-芳基-α-氰基乙酸酯的合成。产物可通过简单还原制备α-芳基-β-氨基酸,具有极高的附加价值。在温和条件下,以缺电子芳基溴与α-氰基乙酸酯为底物,可以良好的收率获得目标产物,且具有较好的官能团兼容性。当芳基溴过于富电子时,目标产物发生自偶联。使用DFT计算了产物负离子的还原电势,表明了富电子芳基取代使产物还原电势降低,更易于在阳极发生氧化。通过电化学分析和机理实验,推测为烯醇负离子配体交换型机理而非自由基加成型机理。β-Amino acids have a wide range of applications in the field of pharmaceuticals.Utilizing a combination strategy of nickel catalysis and paired electrolysis,a catalyticα-arylation protocol of carbonyl compounds has been developed.This protocol affords various-aryl--cyanoacetates,which can be reduced to high-value-addedα-aryl-β-amino acids.The cross-coupling reaction of electron-deficient aryl bromides with-cyanoacetates achieves the expected products with good yields and functional group compatibility under mild conditions.Excessive electron-richness in initial aryl bromides facilitates the self-coupling of desired products.DFT calculations confirm that the presence of electron-rich aryl substitutions decreases the reduction potentials of the product anions,making them more susceptible to oxidation at the anode.Based on electroanalyses and mechanistic studies,it is proposed that the enolate intermediate,rather than the radical intermediate,participates in the catalytic cycle.

关 键 词：有机电合成 镍催化 成对电解 α-芳基化 DFT计算 

分 类 号：O625.636[理学—有机化学]