可见光促进(氮杂)芳香胺与...氮乙酸乙酯的N-烷基化反应_赵亚婷.pdf

研究通讯 Communication *E-mail:WangQA; Received December 7,2022;published January 11,2023.Supporting information for this article is available free of charge via the Internet at http:/sioc-.Project supported by the National Natural Science Foundation of China(No.21901141)and the Start-up Funds of Quzhou University(No.BSYJ201714).国家自然科学基金(No.21901141)和衢州学院科研启动基金(No.BSYJ201714)资助项目.Acta Chim.Sinica 2023,81,111115 2023 Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences http:/sioc- 111 化 学 学 报 化 学 学 报 ACTA CHIMICA SINICA 可见光促进(氮杂)芳香胺与重氮乙酸乙酯的 N-烷基化反应 赵亚婷a,b,c 刘帆c 汪秋安*,a 夏吾炯*,c(a湖南大学化学化工学院 长沙 410000)(b衢州学院化学与材料工程学院 衢州 324000)(c哈尔滨工业大学(深圳)理学院 深圳 518055)摘要摘要 本工作利用可见光催化剂和 Lewis 酸双催化体系,在可见光条件下实现了重氮乙酸乙酯与苯胺衍生物或氮杂芳烃的 N-烷基化反应,合成了一系列-氨基酸类化合物.该反应条件温和,有良好的官能团兼容性和底物普适性.机理验证实验证明该反应涉及了自由基机理,由重氮烷在光催化剂作用下通过 proton-coupled electron transfer(PCET)过程形成了烷基自由基,并在 Lewis 酸催化作用下与胺发生自由基偶联反应形成 N-烷基化产物.这种新的催化机制进一步丰富了重氮化合物在可见光化学反应中的应用类型与范围.关键词关键词 可见光;重氮化合物;自由基;N-烷基化 Visible-Light-Promoted Visible-Light-Promoted N N-Alkylation Reactions of(aza)Aromatic Amines with-Alkylation Reactions of(aza)Aromatic Amines with Ethyl Diazoacetate Ethyl Diazoacetate Zhao,Yatinga,b,c Liu,Fanc Wang,Qiuan*,a Xia,Wujiong*,c(a College of Chemistry and Chemical Engineering,Hunan University,Changsha 410000)(b College of Chemical and Material Engineering,Quzhou University,Quzhou 324000)(c School of Science,Harbin Institute of Technology(Shenzhen),Shenzhen 518055)Abstract Unnatural-amino acid derivatives are greatly important in pharmaceuticals and biochemicals owing to their diverse biological activities,and usually serve as versatile building blocks in organic synthesis as well.A variety of ap-proaches have been developed to prepare-amino acid derivatives,among which NH insertion reactions of diazo com-pounds are considered to be one of the most direct methods.These NH insertion reactions typically proceed through car-bene active intermediates that derived from diazo compounds by UV-induction or metal catalysis.As a green and powerful avenue to organic synthesis,visible-light-mediated methodology has also been applied to NH insertion of diazo com-pounds principally through carbene intermediates.Due to the single reaction mechanism of these reactions,however,the scope of diazo compounds were limited to-aryl diazoacetates that can directly absorb the visible-light.Therefore,exploring new activation modes is conducive to expanding the applicable scope and reaction type of diazo compounds in visible-light-mediated reactions.Herein we report visible-light-promoted N-alkylation reactions of(aza)aromatic amines with ethyl diazoacetate based on the mechanism of proton-coupled electron transfer(PCET).A series of-amino acid derivatives were synthesized by the combination of photocatalyst and Lewis-acid catalyst.This method featured in mild reaction conditions,good functional group tolerance and wide range of substrate scope.Mechanism experiments indicated the reaction involved in radical intermediate rather than carbene that engaged in conventional NH insertion reactions.According to the fluores-cence quenching experiment,the alkyl radical intermediate was formed by the PCET step between ethyl diazoacetate and excited photocatalyst.And then radicals cross-coupling occurred under the coordination of Lewis-acid to produce the final N-alkylation products.This new catalytic strategy expands the applications of diazo compounds in visible-light chemical reactions.The general procedure for the visible-light-promoted N-alkylation reactions of(aza)aromatic amines with ethyl diazoacetate is as following:Aniline 1a(0.1 mmol),ethyl diazoacetate 2(0.2 mmol),Fe(OTf)2(0.02 mmol)and photocatalyst Ir(ppy)2(NCMe)2PF6(0.005 mmol)were dissolved in MeOH(2 mL).Then the mixture was degassed via a“freeze-pump-thaw”procedure(3 times).After that,the resulting mixture was stirred under irradiation of 30 W blue LEDs at room temperature.Upon reaction completion,the crude product was purified by flash chromatograph on silica gel to give the final product.Keywords visible-light;diazo compound;radical;N-alkylation DOI:10.6023/A22120490 化化 学学 学学 报报 研究通讯 112 http:/sioc- 2023 Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences Acta Chim.Sinica 2023,81,111115 1 引言-氨基酸及其衍生物是一类重要的化合物,能表现出多样的生物活性,在生命医药、农药等领域有广泛应用1.此外,它们还是一类用途广泛的有机合成中间体,可用来合成各种化工原料,如化妆品、食品添加剂等.因此,研究-氨基酸及其衍生物的合成在化学和生物学中具有重要意义.目前已经发展了多种制备-氨基酸及其衍生物的途径,而重氮化合物的 NH 插入反应被认为是最直接的合成方法之一2.重氮化合物是一种常见的卡宾前体,根据所含取代基的电子效应不同主要被划分为以下几种类型:供体/受体,双供体,双受体,受体,供体(如 图 1 所示),其中关于供体/受体型重氮化合物的应用最为普遍.重氮化合物可通过光诱导3、金属催化4、酸催化5、生物催化6等作用产生卡宾活性中间体,其中过渡金属催化的各类重氮化合物的NH插入反应研究已取得了显著进展,反应通过配体调控可获得良好的选择性和底物普适性(如图 2a 所示).然而,随着绿色化学理念深入人心,发展新的合成方法使这些化学转变在更温和、更绿色的反应条件下得以实现仍然是非常可取的.图图 1 重氮化合物的类型 Figure 1 Typical diazo compounds 可见光促进的化学反应具有绿色环保、操作简单、条件温和等优点,符合现代绿色可持续化学的要求.近年来,通过游离卡宾中间体的可见光促进重氮化合物的卡宾转移反应发展成一种实用、温和而有力的工具,已被有效地应用于环丙烷化反应、XH 插入反应、重排反应等3.然而,与发展成熟的过渡金属催化方法相比,可见光诱导重氮试剂的 NH 插入反应还处于发展早期.已报道文献中所使用的重氮试剂基本局限于-芳基重氮乙酸酯这类供体/受体型重氮烷,这类重氮化合物可直接吸收可见光并分解成卡宾中间体来参与反应(如