【吲哚衍生物去芳构化概述4000字】

III吲哚衍生物去芳构化概述1.1多环体系的吲哚衍生物\o"添加到收藏夹"近年来，由于吲哚去芳构化反应之后得到的化合物在癌症、炎症和高血压等疾病的治疗中发挥了一定的生物活性，使该生物碱被开发为极具研究前景的治疗药物。ADDINEN.CITE<EndNote><Cite><Author>Roche</Author><Year>2015</Year><RecNum>62</RecNum><DisplayText><styleface="superscript">[1]</style></DisplayText><record><rec-number>62</rec-number><foreign-keys><keyapp="EN"db-id="afv0av224a9rt7e5rrtxs55hzreedt0vze9f"timestamp="1620006263">62</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Roche,S.P.</author><author>Tendoung,J.J.Y.</author><author>Treguier,B.</author></authors></contributors><titles><title>Advancesindearomatizationstrategiesofindoles</title><secondary-title>Tetrahedron</secondary-title></titles><periodical><full-title>Tetrahedron</full-title><abbr-1>Tetrahedron</abbr-1></periodical><pages>3549-3591</pages><volume>71</volume><number>22</number><dates><year>2015</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>0040-4020</isbn><accession-num>WOS:000355051000003</accession-num><urls><related-urls><url><GotoISI>://WOS:000355051000003</url></related-urls></urls><electronic-resource-num>10.1016/j.tet.2014.06.054</electronic-resource-num></record></Cite></EndNote>[1]2012年，Horrocks制备了一组新的合成吲哚异喹啉，并评估了其抗疟疾药物的潜力，同时研究了化学空间三个不同区域的结构-活性关系，发现产生的铅化合物的活性与已知的抗疟疾天然产物二氢氨基苯甲磺酸具有相似的活性，该化合物具有吲哚异喹啉模板结构。ADDINEN.CITE<EndNote><Cite><Author>Horrocks</Author><Year>2012</Year><RecNum>8</RecNum><DisplayText><styleface="superscript">[2]</style></DisplayText><record><rec-number>8</rec-number><foreign-keys><keyapp="EN"db-id="afv0av224a9rt7e5rrtxs55hzreedt0vze9f"timestamp="1619944285">8</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Horrocks,Paul</author><author>Fallon,Samantha</author><author>Denman,Laura</author><author>Devine,Oliver</author><author>Duffy,LiamJ.</author><author>Harper,Anthony</author><author>Meredith,Emma-Louise</author><author>Hasenkamp,Sandra</author><author>Sidaway,Adam</author><author>Monnery,Daniel</author><author>Phillips,TheresaR.</author><author>Allin,StevenM.</author></authors></contributors><titles><title>Synthesisandevaluationofanovelseriesofindoloisoquinolinesassmallmoleculeanti-malarialleads</title><secondary-title>Bioorganic&MedicinalChemistryLetters</secondary-title></titles><periodical><full-title>Bioorganic&MedicinalChemistryLetters</full-title></periodical><pages>1770-1773</pages><volume>22</volume><number>4</number><keywords><keyword>Indoloisoquinoline</keyword><keyword>Anti-malarial</keyword><keyword>Naturalproduct</keyword><keyword>Malaria</keyword><keyword>Dihydrousambarensine</keyword></keywords><dates><year>2012</year><pub-dates><date>2012/02/15/</date></pub-dates></dates><isbn>0960-894X</isbn><urls><related-urls><url>/science/article/pii/S0960894X11017525</url></related-urls></urls><electronic-resource-num>/10.1016/j.bmcl.2011.12.071</electronic-resource-num></record></Cite></EndNote>[2](图1-1A)2014年，Pereira发现一种神经毒性的现象会导致N-甲基-D-天冬氨酸受体(NMDAR)激活加剧，进而致使神经元死亡。这些受体与多种神经系统疾病(如阿尔茨海默病和帕金森病)有关，因此是一个重要的治疗靶点。他描述了色氨酸衍生恶唑哌啶酮内酰胺作为NMDA受体拮抗剂的对映体研究。ADDINEN.CITE<EndNote><Cite><Author>Pereira</Author><Year>2014</Year><RecNum>10</RecNum><DisplayText><styleface="superscript">[3]</style></DisplayText><record><rec-number>10</rec-number><foreign-keys><keyapp="EN"db-id="afv0av224a9rt7e5rrtxs55hzreedt0vze9f"timestamp="1619945466">10</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Pereira,N.A.L.</author><author>Sureda,F.X.</author><author>Esplugas,R.</author><author>Perez,M.</author><author>Amat,M.</author><author>Santos,M.M.M.</author></authors></contributors><titles><title>Tryptophanol-derivedoxazolopiperidonelactams:IdentificationofahitcompoundasNMDAreceptorantagonist</title><secondary-title>Bioorganic&MedicinalChemistryLetters</secondary-title></titles><periodical><full-title>Bioorganic&MedicinalChemistryLetters</full-title></periodical><pages>3333-3336</pages><volume>24</volume><number>15</number><dates><year>2014</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0960-894X</isbn><accession-num>WOS:000339228700022</accession-num><urls><related-urls><url><GotoISI>://WOS:000339228700022</url></related-urls></urls><electronic-resource-num>10.1016/j.bmcl.2014.05.105</electronic-resource-num></record></Cite></EndNote>[3](图1-1B)图1-1多环异吲哚化合物的功能Fig.1-1Functionsofpolycyclicisoindoles2015年，Pereira报告了一类新型的潜在的抗疟疾化合物，其中包含吲哚并吲哚酮骨架。ADDINEN.CITE<EndNote><Cite><Author>Pereira</Author><Year>2015</Year><RecNum>11</RecNum><DisplayText><styleface="superscript">[4]</style></DisplayText><record><rec-number>11</rec-number><foreign-keys><keyapp="EN"db-id="afv0av224a9rt7e5rrtxs55hzreedt0vze9f"timestamp="1619946026">11</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Pereira,N.A.L.</author><author>Monteiro,A.</author><author>Machado,M.</author><author>Gut,J.</author><author>Molins,E.</author><author>Perry,M.J.</author><author>Dourado,J.</author><author>Moreira,R.</author><author>Rosenthal,P.J.</author><author>Prudencio,M.</author><author>Santos,M.M.M.</author></authors></contributors><titles><title>EnantiopureIndolizinoindoloneswithinvitroActivityagainstBlood-andLiver-StageMalariaParasites</title><secondary-title>Chemmedchem</secondary-title></titles><periodical><full-title>Chemmedchem</full-title></periodical><pages>2080-2089</pages><volume>10</volume><number>12</number><dates><year>2015</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>1860-7179</isbn><accession-num>WOS:000366511000013</accession-num><urls><related-urls><url><GotoISI>://WOS:000366511000013</url></related-urls></urls><electronic-resource-num>10.1002/cmdc.201500429</electronic-resource-num></record></Cite></EndNote>[4](图1-1C)这些新颖的对映纯吲哚并吲哚酮通过(S)-或(R)-色氨酸和2-酰基苯甲酸的环缩合反应，然后通过分子内α-酰胺基烷基化合成，具有良好至优异的收率和出色的非对映选择性。新化合物显示出对人类疟疾寄生虫，恶性疟原虫的红细胞阶段和啮齿类寄生虫伯氏疟原虫的肝脏阶段有希望的活性。(S)-色氨酸-异吲哚啉酮被认为是寻找新型抗疟疾的有前途的起始支架，结合了对寄生虫生命周期两个阶段的出色活性以及低细胞毒性以及体外优异的代谢和化学稳定性。2007年，Lubbers报告了一系列与环噻啶2具有DNA促旋酶抑制活性的结构相关的新型2,3-二氢异吲哚-1-酮的设计和合成。在这个系列中，一些化合物对革兰氏阳性细菌菌株显示出有希望的抗菌活性。ADDINEN.CITE<EndNote><Cite><Author>Lubbers</Author><Year>2007</Year><RecNum>12</RecNum><DisplayText><styleface="superscript">[5]</style></DisplayText><record><rec-number>12</rec-number><foreign-keys><keyapp="EN"db-id="afv0av224a9rt7e5rrtxs55hzreedt0vze9f"timestamp="1619948012">12</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Lubbers,T.</author><author>Angehrn,P.</author><author>Gmunder,H.</author><author>Herzig,S.</author></authors></contributors><titles><title>Design,synthesis,andstructure-activityrelationshipstudiesofnewphenolicDNAgyraseinhibitors</title><secondary-title>Bioorganic&MedicinalChemistryLetters</secondary-title></titles><periodical><full-title>Bioorganic&MedicinalChemistryLetters</full-title></periodical><pages>4708-4714</pages><volume>17</volume><number>16</number><dates><year>2007</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0960-894X</isbn><accession-num>WOS:000248877800057</accession-num><urls><related-urls><url><GotoISI>://WOS:000248877800057</url></related-urls></urls><electronic-resource-num>10.1016/j.bmcl.2006.12.065</electronic-resource-num></record></Cite></EndNote>[5](图1-1D)综上，含有吲哚结构的多元环体系在生物医药领域多元化的用途，也促使有机化学领域的科学家对多元环吲哚体系的合成开始深层次的探究。近年来，有很多的通过去芳构化反应构建多元环吲哚体系的方法研究报道。1.2吲哚衍生物去芳构化1.2.1金属催化的去芳构化反应2016年，Lin课题组在上述反应的基础上提出了一例钯催化分子内氧化heck去芳构化反应，反应以N-噻唑甲酰基吲哚为底物，生成含C2-杂季碳中心和C3-环外双键的噻唑并吡咯烷酮化合物ADDINEN.CITE<EndNote><Cite><Author>Gao</Author><Year>2016</Year><RecNum>19</RecNum><DisplayText><styleface="superscript">[6]</style></DisplayText><record><rec-number>19</rec-number><foreign-keys><keyapp="EN"db-id="afv0av224a9rt7e5rrtxs55hzreedt0vze9f"timestamp="1619963949">19</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Gao,Shang</author><author>Yang,Chi</author><author>Huang,Yue</author><author>Zhao,Lei</author><author>Wu,Xiaoming</author><author>Yao,Hequan</author><author>Lin,Aijun</author></authors></contributors><titles><title>Pd(II)-catalyzedintramolecularoxidativeHeckdearomativereaction:approachtothiazole-fusedpyrrolidinoneswithaC-2-azaquarternarycenter</title><secondary-title>Organic&BiomolecularChemistry</secondary-title></titles><periodical><full-title>Organic&BiomolecularChemistry</full-title></periodical><pages>840-843</pages><volume>14</volume><number>3</number><dates><year>2016</year><pub-dates><date>2016</date></pub-dates></dates><isbn>1477-0520</isbn><accession-num>WOS:000368687600006</accession-num><urls><related-urls><url><GotoISI>://WOS:000368687600006</url></related-urls></urls><electronic-resource-num>10.1039/c5ob01970b</electronic-resource-num></record></Cite></EndNote>[6]。该反应的特点是在原有的吲哚结构上引入具有潜在生物活性的噻唑基团，且反应避免了对底物进行预活化的步骤，直接通过噻唑环上C5-H活化得到钯中间体。醋酸银有助于实现零价钯到活性物种二价钯的氧化，使反应在较低催化量的钯催化剂下顺利进行。(图1-2)图1-2Pd催化N-酰基噻唑吲哚的氧化heck去芳构化Fig.1-2PdcatalyticdearomatizationofN-acylthiazoleindolebyheckoxidation2018年，You课题组报道了醋酸钯催化N-(卤代苯甲酰)-2,5-二甲基吡咯的不对称分子内去芳构化反应，该反应在手性膦配体和钯的共同作用下，通过heck反应以良好的收率和对映选择性得到含环外双键和一个季碳中心的吡咯衍生物ADDINEN.CITE<EndNote><Cite><Author>Yang</Author><Year>2018</Year><RecNum>20</RecNum><DisplayText><styleface="superscript">[7]</style></DisplayText><record><rec-number>20</rec-number><foreign-keys><keyapp="EN"db-id="afv0av224a9rt7e5rrtxs55hzreedt0vze9f"timestamp="1619964170">20</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Yang,P.</author><author>You,S.L.</author></authors></contributors><titles><title>Palladium-CatalyzedAsymmetricIntramolecularDearomativeHeckReactionofPyrroleDerivatives</title><secondary-title>OrganicLetters</secondary-title></titles><periodical><full-title>OrganicLetters</full-title><abbr-1>Org.Lett.</abbr-1></periodical><pages>7684-7688</pages><volume>20</volume><number>23</number><dates><year>2018</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>1523-7060</isbn><accession-num>WOS:000452930100074</accession-num><urls><related-urls><url><GotoISI>://WOS:000452930100074</url></related-urls></urls><electronic-resource-num>10.1021/lett.8b03425</electronic-resource-num></record></Cite></EndNote>[7]。(图1-3)图1-3Pd催化吡咯的heck去芳构化Fig.1-3Pdcatalyticpyrroleheckdearomatization烷基取代的炔烃是大量生物活性分子和材料中的常见结构。2016年，Jia设想用末端炔来捕捉芳基钯物种对吲哚上双键配位迁移后生成的苄基钯物种，构建一个新的C(sp3)-C(sp),实现N-酰基吲哚的芳基化炔基化同时去芳构化反应ADDINEN.CITE<EndNote><Cite><Author>Liu</Author><Year>2016</Year><RecNum>21</RecNum><DisplayText><styleface="superscript">[8]</style></DisplayText><record><rec-number>21</rec-number><foreign-keys><keyapp="EN"db-id="afv0av224a9rt7e5rrtxs55hzreedt0vze9f"timestamp="1619964471">21</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Liu,R.R.</author><author>Xu,T.F.</author><author>Wang,Y.G.</author><author>Xiang,B.</author><author>Gao,J.R.</author><author>Jia,Y.X.</author></authors></contributors><titles><title>Palladium-catalyzeddearomativearylalkynylationofindoles</title><secondary-title>ChemicalCommunications</secondary-title></titles><periodical><full-title>ChemicalCommunications</full-title></periodical><pages>13664-13667</pages><volume>52</volume><number>94</number><dates><year>2016</year></dates><isbn>1359-7345</isbn><accession-num>WOS:000388958400005</accession-num><urls><related-urls><url><GotoISI>://WOS:000388958400005</url></related-urls></urls><electronic-resource-num>10.1039/c6cc06262h</electronic-resource-num></record></Cite></EndNote>[8]。同年，Liang课题组报道了一例在钯催化下，以一系列苯丙炔酸或烷基丙炔酸为炔基化试剂ADDINEN.CITE<EndNote><Cite><Author>Chen</Author><Year>2016</Year><RecNum>22</RecNum><DisplayText><styleface="superscript">[9]</style></DisplayText><record><rec-number>22</rec-number><foreign-keys><keyapp="EN"db-id="afv0av224a9rt7e5rrtxs55hzreedt0vze9f"timestamp="1619964843">22</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Chen,S.</author><author>Wu,X.X.</author><author>Wang,J.</author><author>Hao,X.H.</author><author>Xia,Y.</author><author>Shen,Y.</author><author>Jing,H.W.</author><author>Liang,Y.M.</author></authors></contributors><titles><title>Palladium-CatalyzedIntramolecularDearomatizationofIndolesviaDecarboxylativeAlkynylTermination</title><secondary-title>OrganicLetters</secondary-title></titles><periodical><full-title>OrganicLetters</full-title><abbr-1>Org.Lett.</abbr-1></periodical><pages>4016-4019</pages><volume>18</volume><number>16</number><dates><year>2016</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1523-7060</isbn><accession-num>WOS:000381847500021</accession-num><urls><related-urls><url><GotoISI>://WOS:000381847500021</url></related-urls></urls><electronic-resource-num>10.1021/lett.6b01711</electronic-resource-num></record></Cite></EndNote>[9]，这一类试剂同样能捕捉该底物经历去芳构化后得到的苄基钯物种，再脱去一分子二氧化碳，能高效合成目标产物。(图1-4)图1-4Pd催化吡咯的heck去芳构化Fig.1-4Pdcatalyticpyrroleheckdearomatization2017年，Yin课题组巧妙地选用了3-酰胺取代的N-烷基吲哚为底物，在不同的催化体系下以中等至优秀的产率得到去芳构化并且双键碳上C-3芳基化，C2-烷氧基化的双官能团产物或C-2芳基化的产物ADDINEN.CITE<EndNote><Cite><Author>Xu</Author><Year>2017</Year><RecNum>23</RecNum><DisplayText><styleface="superscript">[10]</style></DisplayText><record><rec-number>23</rec-number><foreign-keys><keyapp="EN"db-id="afv0av224a9rt7e5rrtxs55hzreedt0vze9f"timestamp="1619965091">23</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Xu,X.B.</author><author>Liu,J.C.</author><author>Lu,L.</author><author>Wang,F.R.</author><author>Yin,B.L.</author></authors></contributors><titles><title>Pd-catalyzedregioselectiveintramoleculardirectarylationof3-indolecarboxamides:accesstospiro-indoline-3,3'-oxindolesand5,11-dihydro-6H-indolo3,2-cquinolin-6-ones</title><secondary-title>ChemicalCommunications</secondary-title></titles><periodical><full-title>ChemicalCommunications</full-title></periodical><pages>7796-7799</pages><volume>53</volume><number>55</number><dates><year>2017</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>1359-7345</isbn><accession-num>WOS:000411278200023</accession-num><urls><related-urls><url><GotoISI>://WOS:000411278200023</url></related-urls></urls><electronic-resource-num>10.1039/c7cc02256e</electronic-resource-num></record></Cite></EndNote>[10]。去芳构化过程经历了芳基钯物种的迁移插入，产生的中间体与烷基醇反应得到烷氧基钯物种，随即还原消除得到3-芳基化-2-烷氧基化产物；而C-2芳基化反应是在酰胺作导向基，先经历了C(sp2)-H的活化，接着发生亲电芳环取代反应。(图1-5)图1-5Pd催化3-酰胺取代吲哚的C-3去芳构化反应或C-2芳基取代反应Fig.1-5PdcatalyzedC-3dearomatizationorC-2arylsubstitutionof3-amide-substitutedindoles除了通过heck反应，形成螺环或并环吲哚啉类衍生物外，吲哚类化合物可以在钯催化下异构化，与亲电试剂反应得到C3-官能团且去芳构化的化合物。2011年，Sankey课题组选用2-氯苯基胺取代的吲哚为底物，在钯催化下，发生去芳构化得到目标化合物，ADDINEN.CITE<EndNote><Cite><Author>Bedford</Author><Year>2011</Year><RecNum>24</RecNum><DisplayText><styleface="superscript">[11]</style></DisplayText><record><rec-number>24</rec-number><foreign-keys><keyapp="EN"db-id="afv0av224a9rt7e5rrtxs55hzreedt0vze9f"timestamp="1619965249">24</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Bedford,R.B.</author><author>Fey,N.</author><author>Haddow,M.F.</author><author>Sankey,R.F.</author></authors></contributors><titles><title>Remarkablyreactivedihydroindoloindolesviapalladium-catalyseddearomatisation</title><secondary-title>ChemicalCommunications</secondary-title></titles><periodical><full-title>ChemicalCommunications</full-title></periodical><pages>3649-3651</pages><volume>47</volume><number>12</number><dates><year>2011</year></dates><isbn>1359-7345</isbn><accession-num>WOS:000288085600097</accession-num><urls><related-urls><url><GotoISI>://WOS:000288085600097</url></related-urls></urls><electronic-resource-num>10.1039/c0cc05033d</electronic-resource-num></record></Cite></EndNote>[11]。(图1-6)图1-6Pd催化2-胺基吲哚去芳构化反应Fig.1-6Pdcatalyzeddearomatizationof2-aminoindole2012年，You课题组选用C-3取代吲哚作为底物，在钯和膦配体作用下发生分子内去芳构化芳基化反应，在C-3位上形成一个新的季碳中心ADDINEN.CITE<EndNote><Cite><Author>Wu</Author><Year>2012</Year><RecNum>32</RecNum><DisplayText><styleface="superscript">[12]</style></DisplayText><record><rec-number>32</rec-number><foreign-keys><keyapp="EN"db-id="afv0av224a9rt7e5rrtxs55hzreedt0vze9f"timestamp="1619968364">32</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Wu,K.J.</author><author>Dai,L.X.</author><author>You,S.L.</author></authors></contributors><titles><title>Palladium(0)-CatalyzedDearomativeArylationofIndoles:ConvenientAccesstoSpiroindolenineDerivatives</title><secondary-title>OrganicLetters</secondary-title></titles><periodical><full-title>OrganicLetters</full-title><abbr-1>Org.Lett.</abbr-1></periodical><pages>3772-3775</pages><volume>14</volume><number>14</number><dates><year>2012</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>1523-7060</isbn><accession-num>WOS:000306536500053</accession-num><urls><related-urls><url><GotoISI>://WOS:000306536500053</url></related-urls></urls><electronic-resource-num>10.1021/ol301663h</electronic-resource-num></record></Cite></EndNote>[12]。不同的R基团变换对反应的可行性都没有影响，能以中等至良好的收率得到一系列五元或六元螺环吲哚化合物。推测的机理与上一篇Sankey课题组的去芳构化机理类似，零价钯先与溴苯氧化加成得到二价钯中间体，吲哚未经保护的N-H在碱的作用下脱去质子生成的亲核试剂进攻Pd(II)中间体，形成一个含钯七元环，通过还原消除得到C-3去芳构化螺环吲哚亚胺化合物。(图1-7)图1-7Pd催化3-烷基苯基吲哚去芳构化反应Fig.1-7Pdcatalyzeddearomatizationof3-alkylphenylindoles2016年，Yao课题组报道了钯催化下吲哚与内炔烃发生烯丙基化去芳构化ADDINEN.CITE<EndNote><Cite><Author>Gao</Author><Year>2016</Year><RecNum>33</RecNum><DisplayText><styleface="superscript">[13]</style></DisplayText><record><rec-number>33</rec-number><foreign-keys><keyapp="EN"db-id="afv0av224a9rt7e5rrtxs55hzreedt0vze9f"timestamp="1619968733">33</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Gao,S.</author><author>Wu,Z.J.</author><author>Fang,X.X.</author><author>Lin,A.J.</author><author>Yao,H.Q.</author></authors></contributors><titles><title>Palladium-CatalyzedDearomativeAllylicAlkylationofIndoleswithAlkynesToSynthesizeIndolenineswithC3-QuarternaryCenters</title><secondary-title>OrganicLetters</secondary-title></titles><periodical><full-title>OrganicLetters</full-title><abbr-1>Org.Lett.</abbr-1></periodical><pages>3906-3909</pages><volume>18</volume><number>15</number><dates><year>2016</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1523-7060</isbn><accession-num>WOS:000381236300100</accession-num><urls><related-urls><url><GotoISI>://WOS:000381236300100</url></related-urls></urls><electronic-resource-num>10.1021/lett.6b01947</electronic-resource-num></record></Cite></EndNote>[13]，该反应过程中无需外加氧化剂氧化烯丙基C-H，底物结构中无需引入离去基团，步骤和原子经济性高。(图1-8)图1-8Pd催化烯丙基化去芳构化Fig.1-8PdcatalyzedAllylationanddearomatization2011年，Movassaghi报道了一例3-溴环色氨酸的傅克芳基化反应，从相应的色氨酸底物两步得到芳基化的吡咯啉吲哚啉ADDINEN.CITE<EndNote><Cite><Author>Kim</Author><Year>2011</Year><RecNum>31</RecNum><DisplayText><styleface="superscript">[14]</style></DisplayText><record><rec-number>31</rec-number><foreign-keys><keyapp="EN"db-id="afv0av224a9rt7e5rrtxs55hzreedt0vze9f"timestamp="1619968209">31</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Kim,J.</author><author>Movassaghi,M.</author></authors></contributors><titles><title>ConciseTotalSynthesisandStereochemicalRevisionof(+)-NaseseazinesAandB:RegioselectiveArylativeDimerizationofDiketopiperazineAlkaloids</title><secondary-title>JournaloftheAmericanChemicalSociety</secondary-title></titles><periodical><full-title>JournaloftheAmericanChemicalSociety</full-title></periodical><pages>14940-14943</pages><volume>133</volume><number>38</number><dates><year>2011</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0002-7863</isbn><accession-num>WOS:000295604400026</accession-num><urls><related-urls><url><GotoISI>://WOS:000295604400026</url></related-urls></urls><electronic-resource-num>10.1021/ja206743v</electronic-resource-num></record></Cite></EndNote>[14]。吡咯吲哚啉骨架是一类很重要的生物碱结构，广泛存在于有生物活性的天然产物和药物中。为了能更方便更高效地获得这一类重要化合物，科学家们发展了一些芳基化-环化串联反应。2012年，Reisman报道了一例铜催化N-对甲苯磺酰基保护的色胺在温和的条件下发生C3-芳基化-亲核环化串联反应生成一系列吡咯啉并吲哚啉化合物ADDINEN.CITE<EndNote><Cite><Author>Kieffer</Author><Year>2012</Year><RecNum>29</RecNum><DisplayText><styleface="superscript">[15]</style></DisplayText><record><rec-number>29</rec-number><foreign-keys><keyapp="EN"db-id="afv0av224a9rt7e5rrtxs55hzreedt0vze9f"timestamp="1619967504">29</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Kieffer,M.E.</author><author>Chuang,K.V.</author><author>Reisman,S.E.</author></authors></contributors><titles><title>Acopper-catalyzedarylationoftryptaminesforthedirectsynthesisofarylpyrroloindolines</title><secondary-title>ChemicalScience</secondary-title></titles><periodical><full-title>ChemicalScience</full-title></periodical><pages>3170-3174</pages><volume>3</volume><number>11</number><dates><year>2012</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>2041-6520</isbn><accession-num>WOS:000311068100006</accession-num><urls><related-urls><url><GotoISI>://WOS:000311068100006</url></related-urls></urls><electronic-resource-num>10.1039/c2sc20914d</electronic-resource-num></record></Cite></EndNote>[15]。通过实验现象他们发现使用醋酸铜作催化剂可使反应体系较干净方便后续纯化，但三氟甲磺酸铜可用来催化活性较低的均三甲苯取代的碘盐。巧妙地在选择不同的铜催化剂催化反应可进一步提高反应的效率和化学选择性。反应经历了Cu(I)/Cu(III)的转化过程，磺酰胺基团可能作为配体与Cu(III)配位，有利于发生亲核芳基化反应的同时生成亚胺中间体，磺酰胺对亚胺中间体进行亲核加成，进行还原消除后就可以转化为目标产物和Cu(I)。(图1-9)图1-9铜催化色胺的芳基化环化去芳构化反应Fig.1-9coppercatalyzedarylation,cyclizationanddearomatizationoftryptaminesReisman在全合成NaseseazinesAandB的工作中选用含二酮哌嗪的吲哚为底物ADDINEN.CITE<EndNote><Cite><Author>Kieffer</Author><Year>2013</Year><RecNum>65</RecNum><DisplayText><styleface="superscript">[16]</style></DisplayText><record><rec-number>65</rec-number><foreign-keys><keyapp="EN"db-id="afv0av224a9rt7e5rrtxs55hzreedt0vze9f"timestamp="1620006857">65</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Kieffer,MadeleineE.</author><author>Chuang,KangwayV.</author><author>Reisman,SarahE.</author></authors></contributors><titles><title>Copper-CatalyzedDiastereoselectiveArylationofTryptophanDerivatives:TotalSynthesisof(+)-NaseseazinesAandB</title><secondary-title>JournaloftheAmericanChemicalSociety</secondary-title></titles><periodical><full-title>JournaloftheAmericanChemicalSociety</full-title></periodical><pages>5557-5560</pages><volume>135</volume><number>15</number><dates><year>2013</year><pub-dates><date>2013/04/17</date></pub-dates></dates><publisher>AmericanChemicalSociety</publisher><isbn>0002-7863</isbn><urls><related-urls><url>/10.1021/ja4023557</url></related-urls></urls><electronic-resource-num>10.1021/ja4023557</electronic-resource-num></record></Cite></EndNote>[16]，在铜催化下和二芳基碘盐反应能以优秀的收率和极好的非对映选择性得到一系列含二酮哌嗪的含氮并环结构。二亚胺型配体能有效提高反应的收率和C-3芳基化/C-2芳基化比例。(图1-10)图1-10铜催化含二酮哌嗪结构的色胺的芳基化环化去芳构化反应Fig.1-10coppercatalyzedarylation,cyclizationanddearomatizationoftryptaminescontainingdiketopiperazinestructure2012年，MacMillan实现了3-乙酰胺吲哚和二芳基碘盐在铜催化下发生高对映选择性的C-3芳基化-环化ADDINEN.CITE<EndNote><Cite><Author>Zhu</Author><Year>2012</Year><RecNum>28</RecNum><DisplayText><styleface="superscript">[17]</style></DisplayText><record><rec-number>28</rec-number><foreign-keys><keyapp="EN"db-id="afv0av224a9rt7e5rrtxs55hzreedt0vze9f"timestamp="1619967403">28</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Zhu,S.L.</author><author>MacMillan,D.W.C.</author></authors></contributors><titles><title>EnantioselectiveCopper-CatalyzedConstructionofArylPyrroloindolinesviaanArylation-CyclizationCascade</title><secondary-title>JournaloftheAmericanChemicalSociety</secondary-title></titles><periodical><full-title>JournaloftheAmericanChemicalSociety</full-title></periodical><pages>10815-10818</pages><volume>134</volume><number>26</number><dates><year>2012</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0002-7863</isbn><accession-num>WOS:000305863900026</accession-num><urls><related-urls><url><GotoISI>://WOS:000305863900026</url></related-urls></urls><electronic-resource-num>10.1021/ja305100g</electronic-resource-num></record></Cite></EndNote>[17]。他们推测在反应过程中底物上的羰基和配体同时与铜催化剂配位，因此设计了3-乙酰胺作为底物。通过筛选发现，二芳基碘六氟砷盐能有效提高了反应的立体选择性和效率。(图1-11)图1-11铜催化3-乙酰胺吲哚的不对称芳基化环化Fig.1-11asymmetricarylationandcyclizationof3-acetamidoindolecatalyzedbycopper2016年，Li课题组报道了一例使用铜催化金进行催化，所使用的氧化剂为叔丁基过氧化氢，使底物2-甲酰胺吲哚发生氧化去芳构化螺环化反应ADDINEN.CITE<EndNote><Cite><Author>Kong</Author><Year>2016</Year><RecNum>25</RecNum><DisplayText><styleface="superscript">[18]</style></DisplayText><record><rec-number>25</rec-number><foreign-keys><keyapp="EN"db-id="afv0av224a9rt7e5rrtxs55hzreedt0vze9f"timestamp="1619967149">25</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Kong,L.K.</author><author>Wang,M.D.</author><author>Zhang,F.F.</author><author>Xu,M.R.</author><author>Li,Y.Z.</author></authors></contributors><titles><title>Copper-CatalyzedOxidativeDearomatization/SpirocyclizationofIndole-2-Carboxamides:Synthesisof2-Spiro-pseudoindoxyls</title><secondary-title>OrganicLetters</secondary-title></titles><periodical><full-title>OrganicLetters</full-title><abbr-1>Org.Lett.</abbr-1></periodical><pages>6124-6127</pages><volume>18</volume><number>23</number><dates><year>2016</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>1523-7060</isbn><accession-num>WOS:000389396100040</accession-num><urls><related-urls><url><GotoISI>://WOS:000389396100040</url></related-urls></urls><electronic-resource-num>10.1021/lett.6b03131</electronic-resource-num></record></Cite></EndNote>[18]，不同的取代基团替换都不影响其可以高效高产率地得到一系列C2-螺环-吲哚啉衍生物。作者推测底物在铜和氧化剂的作用下先生成3-酮-2-亚胺中间体，接着与N上相连的苯基发生亲电芳环取代，得到螺环化合物。(图1-12)图1-12铜催化2-甲酰胺吲哚的氧化芳基化去芳构化反应Fig.1-12coppercatalyzedoxidativearylationanddearomatizationof2-formamidoindole2012年，Wang组使用Acylindoles与Grignard试剂进行亲核型反应，可有效提供顺式或反式取代的二氢吲哚，具体取决于不同的淬灭步骤。其机理为烯醇化物中间体可以被芳基酰氯捕获，以提供具有高立体选择性的带有季碳中心的二氢吲哚。相反，使用苄基溴作为亲电试剂会导致吲哚环断裂。该方法可以通过用一锅法用DDQ氧化可将二氢吲哚产物轻松转化为吲哚。ADDINEN.CITE<EndNote><Cite><Author>Wang</Author><Year>2012</Year><RecNum>14</RecNum><DisplayText><styleface="superscript">[19]</style></DisplayText><record><rec-number>14</rec-number><foreign-keys><keyapp="EN"db-id="afv0av224a9rt7e5rrtxs55hzreedt0vze9f"timestamp="1619960724">14</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Wang,Lu</author><author>Shao,Yushang</author><author>Liu,Yuanhong</author></authors></contributors><tit