CN115286560A - 一种吲哚亚胺并环戊烯类化合物的合成方法 - Google Patents

一种吲哚亚胺并环戊烯类化合物的合成方法 Download PDF

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CN115286560A
CN115286560A CN202210903667.7A CN202210903667A CN115286560A CN 115286560 A CN115286560 A CN 115286560A CN 202210903667 A CN202210903667 A CN 202210903667A CN 115286560 A CN115286560 A CN 115286560A
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张祥志
邱宗旺
彭金宝
李保琼
朱志强
刘宏福
张艺瑞
吴腾飞
马炯冬
钟燕桂
蔡思琪
张梓旋
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Wuyi University
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Abstract

本发明公开了一种吲哚亚胺并环戊烯类化合物的合成方法。本发明的合成方法以2‑吲哚甲醇类化合物和炔丙醇类化合物为原料，经催化反应得到吲哚亚胺并环戊烯类化合物。本发明的合成方法起始原料廉价易得，操作方便，适用的官能团范围广，产率良好，是一种简洁、高效的合成方法，为吲哚亚胺并环戊烯类化合物在天然色素和生物碱类药物分子合成等领域的应用提供技术支持。

Description

一种吲哚亚胺并环戊烯类化合物的合成方法
技术领域
本发明属于有机合成技术领域，具体涉及一种吲哚亚胺并环戊烯类化合物的合成方法。
背景技术
吲哚亚胺并环戊烯类骨架结构广泛存在于天然色素和药物分子中，也是生物碱的重要组成部分，在天然色素和生物碱类药物分子合成、发光材料中有一定的潜在应用。目前这类骨架结构的合成方法比较匮乏，具有上述骨架结构的化合物的合成方法被文献报道出来的十分有限。如：1991年，Eastwood等通过快速真空热解的方式获得茚并[1,2-b]吲哚类化合物(Moffat M.R，Eastwood F.W,Coulston K.J,Brown R.F.C.TetrahedronLett.1991,32,801)。2011年，Martensson等用2-(1H-吲哚-3-基)乙酸作为起始原料历经9步实现了伪枝藻素的全合成(Ekebergh A,Karlsson I,Mete R,Pan Y,Borje A,Martensson J.Org.Lett.2011,13,4458)。2016年，Schneider等使用吲哚和天竺葵素两个关键前体化合物，通过生物合成的方式合成了独特的吲哚生物碱Nudicaulins(WarskulatA.C,Tatsis E.C,Dudek B,Kai M,Lorenz S,Schneider B.ChemBioChem.2016,17,318.)。2018年，Schneider等又通过化学途径合成了一种糖苷配基类化合物(Dudek B；SchnurrerF,Dahse H.-M,Paetz C,Warskulat A.C,Wiegel C,Voigt K,Schneider B.Molecules2018,23,3357.)。现有吲哚亚胺并环戊烯的合成方法存在路线长，操作复杂，催化剂不经济或不易得，官能团局限，产物收率低等方面的问题。目前还有待开发操作简单，原料廉价易得，官能团适用范围广，收率高的吲哚亚胺并环戊烯类化合物的合成方法。
发明内容
针对上述现有制备技术的缺陷，本发明的目的在于提供一种吲哚亚胺并环戊烯类化合物的合成方法。本发明的制备方法操作简单，原料廉价易得，适用的化合物官能团范围广，收率高。
为此，本发明的技术方案包括：
一种吲哚亚胺并环戊烯类化合物的合成方法，包括以下步骤：将2-吲哚甲醇类化合物和炔丙醇类化合物在溶剂中混合，经催化剂催化反应得到吲哚亚胺并环戊烯类化合物，反应式如下所示：
Figure BDA0003769687860000021
其中，R为苯基或取代苯基，所述的取代苯基上的取代基为卤素、烷基、烷氧基、羟基、三氟甲基中的至少一种；
R1为苯基或取代苯基，所述的取代苯基上的取代基为卤素、烷基、烷氧基、三氟甲基中的至少一种；
R2为苯基、取代苯基、杂环芳基、烷基中的任意一种，所述的取代苯基上的取代基为卤素、烷基、烷氧基、三氟甲基中的至少一种；所述的杂环芳基为含杂原子的环状基团，所述的杂原子为O、S、N、P、Si中的至少一种；
R3为苯基或取代苯基，所述的取代苯基上的取代基为卤素、烷基、烷氧基、三氟甲基、苯基中的至少一种；
R4为氢原子、卤素原子、烷基、烷氧基、三氟甲基中的至少一种。
作为本发明进一步优选的实施方式，所述R2为环丙基、叔丁基、噻吩基中的一种；所述R4为氟原子、氯原子、溴原子、甲基、甲氧基中的至少一种；
R为取代苯基时，所述的取代苯基上的取代基为甲基、甲氧基、氟原子、氯原子、溴原子中的至少一种；
R1为取代苯基时，所述的取代苯基上的取代基为甲基、甲氧基、氟原子、氯原子、溴原子中的至少一种；
R2为取代苯基时，所述的取代苯基上的取代基为甲基、乙基、正丁基、叔丁基、甲氧基、氟原子、氯原子中的至少一种；
R3为取代苯基时，所述的取代苯基上的取代基为氟原子、氯原子、甲基、叔丁基、甲氧基中的至少一种。
作为本发明进一步优选的实施方式，所述的吲哚亚胺并环戊烯类化合物包括如下3a～3p、4a～4t结构式中的任意一种：
Figure BDA0003769687860000031
Figure BDA0003769687860000041
作为本发明优选的实施方式，所述的反应的温度为50℃～120℃，所述的反应的时间为10min～1440min。
作为本发明进一步优选的实施方式，所述的反应的温度为50℃～100℃，所述的反应的时间为20min～240min。
作为本发明优选的实施方式，所述的催化剂包括三氟甲磺酸锌、三氟甲磺酸铋、三氟甲磺酸镱、双三氟甲烷磺酰亚胺银、三氟甲磺酸钪中的至少一种。
作为本发明进一步优选的实施方式，所述的催化剂为三氟甲磺酸钪，使用该催化剂反应的效率更高。
作为本发明优选的实施方式，所述的溶剂包括甲苯、氯苯、乙腈、1,4-二氧六环、三氯甲烷、四氢呋喃、乙醇、乙酸乙酯、N,N-二甲基甲酰胺、二甲基亚砜、丙酮中的至少一种。
作为本发明进一步优选的实施方式，所述溶剂为甲苯，使用该溶剂反应效率更高。
作为本发明优选的实施方式，所述的2-吲哚甲醇类化合物、炔丙醇类化合物、催化剂的摩尔比为1：(1-3)：(0.1-1)。
作为本发明进一步优选的实施方式，所述的2-吲哚甲醇类化合物、炔丙醇类化合物、催化剂的摩尔比为1：1.5：0.2。
作为本发明优选的实施方式，所述的溶剂的浓度为0.5-3mol/L。
作为本发明进一步优选的实施方式，所述的溶剂的浓度为1mol/L。
作为本发明优选的实施方式，所述吲哚亚胺并环戊烯类化合物经催化反应合成后，还需经硅胶柱进行层析分离，层析分离是的流动相成分为石油醚和乙酸乙酯的混合液，两者的体积比5:1。
炔丙醇类化合物是一种具有羟基和炔基两种官能团的有机化合物，其双官能团性质使其能够引发一系列的串联环化反应。2-吲哚甲醇是一种独特的亲核试剂，酸性条件下可以作为3C合成子发生环加成反应。在本发明当中，炔丙醇类化合物作为2C合成子，2-吲哚甲醇类化合物作为3C合成子，炔丙醇类化合物与2-吲哚甲醇类化合物在路易斯酸催化剂的作用下，发生形式[2+3]环化串联去芳构化合成了吲哚亚胺并环戊烯类化合物。
与现有合成方案相比，本发明的有益效果为：
(1)本发明可在仅廉价的金属催化剂的作用下将2-吲哚甲醇类化合物和炔丙醇类化合物一步合成吲哚亚胺并环戊烯类化合物。
(2)本发明的合成方法操作简单、步骤少，产率良好(产率可在29～93％)，无需氧化剂，除了最终产物外，一系列转化过程中的中间体均无需分离和纯化，所用的合成原料廉价易得，为吲哚亚胺并环戊烯类化合物提供了一种经济、简洁和高效的制备方法。
(3)本发明的合成方法适用的官能团范围广，进一步丰富了吲哚亚胺并环戊烯类化合物，为吲哚亚胺并环戊烯类化合物在天然色素和生物碱类药物分子合成等领域的应用提供技术支持，对该类化合物及其下游产品的工艺开发具有良好的借鉴价值。
附图说明
图1本发明实施例10产物3j的1H NMR谱图。
图2本发明实施例10产物3j的13C NMR谱图。
图3本发明实施例12产物3l的1H NMR谱图。
图4本发明实施例12产物3l的13C NMR谱图。
图5本发明实施例15产物3o的1H NMR谱图。
图6本发明实施例15产物3o的13C NMR谱图。
图7本发明实施例4产物3d的1H NMR谱图。
图8本发明实施例4产物3d的13C NMR谱图。
图9本发明实施例31产物4o的1H NMR谱图。
图10本发明实施例31产物4o的13C NMR谱图。
图11本发明实施例23产物4g的1H NMR谱图。
图12本发明实施例23产物4g的13C NMR谱图。
具体实施方式
下面将结合实施例对本发明的技术方案做进一步说明，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。实施例中使用的原料均可通过商业途径获得，所使用的方法如无特别指明，均为本领域的常规方法。
本发明当中，吲哚亚胺并环戊烯类化合物的反应式如下：
Figure BDA0003769687860000061
其中的化合物1代表2-吲哚甲醇类化合物，化合物2代表为炔丙醇类化合物，化合物3代表吲哚亚胺并环戊烯类化合物。具体的步骤可参见实施例1～36。
实施例1-16
实施例1-16的吲哚亚胺并环戊烯类化合物的合成路径如下所示：
Figure BDA0003769687860000071
其中的化合物1代表2-吲哚甲醇类合物，化合物2a代表炔丙醇类化合物，化合物3代表吲哚亚胺并环戊烯类化合物。
具体地，以化合物实施例4的化合物3d、实施例10的化合物3j、实施例12的化合物3l、实施例15的化合物3o为代表详细地描述吲哚亚胺并环戊烯类化合物的合成过程，其余的化合物相应地改变原料及反应时间。
实施例4吲哚亚胺并环戊烯类化合物3d的合成，具体反应式如下：
Figure BDA0003769687860000072
在15mL耐压管中依次加入搅拌子、2-吲哚甲醇类合物(75.6mg,0.2mmol)、炔丙醇类化合物(85.2mg,0.2mmol)、三氟甲磺酸钪(19.6mg,0.04mmol)和甲苯(2mL)，反应体系置于100℃下反应30min。反应体系直接利用硅胶(200-300目)柱层析(流动相成分为石油醚：乙酸乙酯＝5:1)分离得到黄色固体(116.5mg,产率：93％)。
实施例10吲哚亚胺并环戊烯类化合物3j的合成，具体如下：
Figure BDA0003769687860000073
在15mL耐压管中依次加入搅拌子、2-吲哚甲醇类合物(73.7mg,0.2mmol)、炔丙醇类化合物(85.2mg,0.2mmol)、三氟甲磺酸钪(19.6mg,0.04mmol)和甲苯(2mL)，反应体系置于100℃下反应2h。反应体系直接利用硅胶(200-300目)柱层析(流动相成分为石油醚：乙酸乙酯＝5:1)分离得到黄色固体吲哚亚胺并环戊烯类化合物(105mg,产率：85％)。
实施例12吲哚亚胺并环戊烯类化合物3l的合成，具体如下：
Figure BDA0003769687860000081
在15mL耐压管中依次加入搅拌子、2-吲哚甲醇类合物(82.3mg,0.2mmol)、炔丙醇类化合物(85.2mg,0.2mmol)、三氟甲磺酸钪(19.6mg,0.04mmol)和甲苯(2mL)，反应体系置于100℃下反应50min。反应体系直接利用硅胶(200-300目)柱层析(流动相成分为石油醚：乙酸乙酯＝5:1)分离得到黄色固体吲哚亚胺并环戊烯类化合物(105.6mg,产率：80％)。
实施例15吲哚亚胺并环戊烯类化合物3o的合成，具体如下：
Figure BDA0003769687860000082
在15mL耐压管中依次加入搅拌子、2-吲哚甲醇类合物(65.5mg,0.2mmol)、炔丙醇类化合物(85.2mg,0.2mmol)、三氟甲磺酸钪(19.6mg,0.04mmol)和甲苯(2mL)，反应体系置于100℃下反应30min。反应体系直接利用硅胶(200-300目)柱层析(流动相成分为石油醚：乙酸乙酯＝5:1)分离得到黄色固体吲哚亚胺并环戊烯类化合物(52.9mg,产率：46％)。
实施例1-16的吲哚亚胺并环戊烯类化合物汇总
1、实施例1-6合成得到的吲哚亚胺并环戊烯类化合物3a～3f结构式如下：
Figure BDA0003769687860000083
其中，X为取代基，化合物3a～3f中的X分别为H、F、Cl、Br、Me、MeO。
2、实施例7和8合成得到的吲哚亚胺并环戊烯类化合物3g和3h结构式如下：
Figure BDA0003769687860000091
其中，X为取代基，化合物3g和3h中的X分别为F、MeO。
3、实施例9-16合成得到的吲哚亚胺并环戊烯类化合物3i～3p结构式分别如下：
Figure BDA0003769687860000092
实施例1～16的反应时间、产率及合成的产物3a-3p的光谱数据如下：
实施例1的反应时间为30min，产率为87％；产物3a：1H NMR(500MHz,CDCl3)δ7.64(d,J＝7.5Hz,1H),7.60–7.54(m,2H),7.49(d,J＝7.8Hz,1H),7.42–7.34(m,4H),7.29–7.23(m,1H),7.20–7.04(m,9H),7.01(t,J＝7.3Hz,1H),6.95(t,J＝7.5Hz,1H),6.88–6.80(m,5H),6.77(t,J＝7.8Hz,2H),6.57(d,J＝7.2Hz,2H).13C{1H}NMR(126MHz,CDCl3)δ188.4,162.9,156.9,152.2,148.0,142.4,142.02,141.97,141.9,141.8,135.3,130.8,129.7,129.6,129.2,129.0,128.6,127.9,127.6,127.4,127.2,126.7,126.2,125.2,123.8,123.0,120.9,62.3.IR:
Figure BDA0003769687860000093
Figure BDA0003769687860000094
HRMS(ESI)m/z:[M+H]+calcd for C42H30N 548.2373；found:548.2371；
实施例2的反应时间为30min，产率为91％；产物3b：1H NMR(500MHz,CDCl3)δ7.57–7.48(m,2H),7.42–7.33(m,5H),7.32(dd,J＝8.6,2.5Hz,1H),7.22–7.06(m,9H),7.00–6.92(m,2H),6.88–6.81(m,5H),6.78(t,J＝7.8Hz,2H),6.57(d,J＝7.2Hz,2H).13C{1H}NMR(126MHz,CDCl3)δ188.41,188.38,160.9,159.01,158.98,158.0,152.0,149.0,142.2,141.8,141.7 141.6,141.5,135.0,130.8,129.5,129.2,128.9,128.8,128.1,127.7,127.5,127.4,127.2,126.9,126.3,126.23,126.15,121.14,121.07,116.0,115.8,110.2,110.0,62.4.19F NMR(471MHz,CDCl3)δ-119.2.IR:
Figure BDA0003769687860000101
Figure BDA0003769687860000102
HRMS(ESI)m/z:[M+H]+calcd for C42H29FN 566.2279；found:566.2275；
实施例3的反应时间为20min，产率为83％；产物3c：1H NMR(500MHz,CDCl3)δ7.57(d,J＝2.0Hz,1H),7.55–7.51(m,2H),7.40–7.33(m,5H),7.23–7.17(m,3H),7.16–7.07(m,7H),6.96(t,J＝7.5Hz,1H),6.87–6.81(m,5H),6.78(t,J＝7.8Hz,2H),6.57(dd,J＝8.2,1.1Hz,2H).13C{1H}NMR(126MHz,CDCl3)δ188.7,161.3,158.5,152.0,149.3,142.2,141.8,141.6,141.1,135.0,130.8,129.5,129.3,129.20,129.17,129.0,128.9,128.1,127.7,127.6,127.4,127.2,126.9,126.6,126.3,122.9,121.5,62.4.IR:
Figure BDA0003769687860000103
Figure BDA0003769687860000104
HRMS(ESI)m/z:[M+H]+calcd for C42H29ClN 582.1983；found:582.1979；
实施例4的反应时间为30min，产率为93％；产物3d：1H NMR(500MHz,CDCl3)δ7.72(d,J＝1.6Hz,1H),7.57–7.51(m,2H),7.39–7.30(m,6H),7.19(t,J＝7.5Hz,2H),7.17–7.05(m,7H),6.95(t,J＝7.5Hz,1H),6.87–6.80(m,5H),6.77(t,J＝7.8Hz,2H),6.57(dd,J＝8.0,1.1Hz,2H).13C{1H}NMR(126MHz,CDCl3)δ188.6,161.6,158.6,152.0,149.3,142.1,141.7,141.5,140.9,134.9,132.0,130.8,129.4,129.1,129.0,128.8,128.1,127.7,127.5,127.4,127.2,127.1,126.9,126.3,125.7,122.0,117.0,62.4.IR:
Figure BDA0003769687860000105
Figure BDA0003769687860000106
HRMS(ESI)m/z:[M+H]+calcd for C42H29BrN626.1478；found:626.1472；
实施例5的反应时间为30min，产率为87％；产物3e：1H NMR(500MHz,CDCl3)δ7.60–7.52(m,2H),7.43(s,1H),7.41–7.32(m,5H),7.17(t,J＝7.5Hz,2H),7.15–7.04(m,8H),6.94(t,J＝7.5Hz,1H),6.88–6.79(m,5H),6.76(t,J＝7.8Hz,2H),6.57(dd,J＝8.1,1.1Hz,2H),2.27(s,3H).13C{1H}NMR(126MHz,CDCl3)δ187.8,160.9,156.2,152.3,147.6,142.4,142.1,142.00,141.95,135.4,133.4,130.8,130.4,129.5,129.2,129.0,128.5,127.9,127.6,127.30,127.26,127.2,126.7,126.1,125.3,123.6,120.4,62.2,21.4.IR:
Figure BDA0003769687860000111
Figure BDA0003769687860000112
HRMS(ESI)m/z:[M+H]+calcd for C43H32N 562.2529；found:562.2524；
实施例6的反应时间为20min，产率为63％；产物3f：1H NMR(500MHz,CDCl3)δ7.57–7.52(m,2H),7.42–7.33(m,5H),7.22(d,J＝2.6Hz,1H),7.20–7.05(m,9H),6.99–6.92(m,1H),6.88–6.79(m,6H),6.77(t,J＝7.8Hz,2H),6.56(dd,J＝8.2,1.1Hz,2H),3.73(s,3H).13C{1H}NMR(126MHz,CDCl3)δ187.0,156.8,152.2,142.4,142.0,135.3,130.8,129.5,129.2,128.9,128.6,127.9,127.6,127.4,127.2,126.7,126.2,120.8,114.3,109.8,77.3,77.2,77.0,76.8,62.3,55.8.IR:
Figure BDA0003769687860000113
HRMS(ESI)m/z:[M+H]+calcd for C43H32NO 578.2478；found:578.2472；
实施例7的反应时间为3h，产率为78％；产物3g：1H NMR(500MHz,CDCl3)δ7.60–7.51(m,3H),7.36(d,J＝7.1Hz,4H),7.22–7.04(m,10H),6.96(t,J＝7.4Hz,1H),6.84(s,5H),6.78(t,J＝7.7Hz,2H),6.74–6.69(m,1H),6.57(d,J＝7.5Hz,2H).13C{1H}NMR(126MHz,CDCl3)δ190.3,165.0,164.7,164.6,163.1,156.8,151.9,148.3,142.3,141.9,141.6,141.0,135.2,130.8,129.5,129.2,128.9,128.7,128.0,127.7,127.5,127.4,127.2,126.8,126.4,123.6,123.5,121.4,110.7,110.5,108.8,108.6,62.4.19F NMR(471MHz,CDCl3)δ-109.8.IR:
Figure BDA0003769687860000114
Figure BDA0003769687860000115
HRMS(ESI)m/z:[M+H]+calcd for C42H29FN 566.2279；found:566.2273；
实施例8的反应时间为2h，产率为53％；产物3h：1H NMR(500MHz,CDCl3)δ7.57–7.51(m,3H),7.41–7.35(m,4H),7.19–7.05(m,10H),6.94(t,J＝7.4Hz,1H),6.88–6.79(m,5H),6.77(t,J＝7.7Hz,2H),6.57(d,J＝8.2Hz,3H),3.78(s,3H).13C{1H}NMR(126MHz,CDCl3)δ189.9,165.1,161.7,154.4,152.0,146.7,142.5,142.1,141.9,141.7,135.5,130.8,129.6,129.3,128.9,128.8,128.5,128.4,128.33,128.27,127.8,127.6,127.3,127.22,127.19,127.16,126.64,126.59,126.2,123.7,117.9,110.3,106.4,62.3,55.5.IR:
Figure BDA0003769687860000121
Figure BDA0003769687860000122
HRMS(ESI)m/z:[M+H]+calcd for C43H32NO 578.2478；found:578.2474；
实施例9的反应时间为1h，产率为76％；产物3i：1H NMR(500MHz,CDCl3)δ7.66(d,J＝7.6Hz,1H),7.59–7.51(m,2H),7.48(d,J＝7.7Hz,1H),7.38–7.23(m,6H),7.16(t,J＝7.4Hz,2H),7.10(t,J＝7.3Hz,1H),7.05–6.96(m,2H),6.90–6.76(m,10H),6.58(d,J＝7.3Hz,2H).13C{1H}NMR(126MHz,CDCl3)δ187.9,162.8,162.3,160.3,156.6,151.8,148.2,142.0,141.9,141.7,137.60,137.57,135.0,131.7,131.0,130.9,130.7,129.9,129.0,128.9,128.8,128.6,128.24,128.21,127.9,127.6,127.5,127.44,127.38,127.3,127.1,126.0,125.1,124.0,123.1,120.9,114.6,114.5,61.0.19F NMR(471MHz,CDCl3)δ-116.2.IR:
Figure BDA0003769687860000123
Figure BDA0003769687860000124
HRMS(ESI)m/z:[M+H]+calcd for C42H28F2N 584.2184；found:584.2178；
实施例10的反应时间为2h，产率为85％；产物3j：1H NMR(500MHz,CDCl3)δ7.66(d,J＝7.6Hz,1H),7.57–7.51(m,2H),7.49(d,J＝7.8Hz,1H),7.32–7.25(m,5H),7.17(t,J＝7.3Hz,2H),7.15–7.07(m,5H),7.07–6.98(m,2H),6.88–6.80(m,7H),6.57(d,J＝7.3Hz,2H).13C{1H}NMR(126MHz,CDCl3)δ187.3,162.6,156.7,151.2,148.5,141.9,141.8,141.7,140.2,134.9,132.4,130.7,130.0,129.0,128.9,128.0,127.9,127.6,127.44,127.38,127.2,125.0,124.2,123.2,120.9,61.3.IR:
Figure BDA0003769687860000125
Figure BDA0003769687860000126
HRMS(ESI)m/z:[M+H]+calcd for C42H28Cl2N 616.1593；found:616.1589；
实施例11的反应时间为1h，产率为76％；产物3k：1H NMR(500MHz,CDCl3)δ7.62(d,J＝7.6Hz,1H),7.57–7.52(m,2H),7.47(d,J＝7.7Hz,1H),7.29–7.20(m,6H),7.15(t,J＝7.4Hz,2H),7.12–7.05(m,1H),6.99(td,J＝7.6,0.9Hz,1H),6.97–6.90(m,5H),6.86–6.80(m,5H),6.77(t,J＝7.8Hz,2H),6.58(dd,J＝8.2,1.1Hz,2H),2.24(s,6H).13C{1H}NMR(126MHz,CDCl3)δ188.7,163.1,156.6,152.4,147.5,142.4,142.1,141.9,138.9,135.6,135.4,130.8,129.6,129.4,129.2,128.9,128.5,128.3,127.8,127.3,127.2,127.0,126.6,125.3,123.6,122.9,120.8,61.8,20.9.IR:
Figure BDA0003769687860000127
Figure BDA0003769687860000131
HRMS(ESI)m/z:[M+H]+calcd for C44H34N 576.2686；found:576.2684；
实施例12的反应时间为50min，产率为80％；产物3l：1H NMR(500MHz,CDCl3)δ7.65(d,J＝7.5Hz,1H),7.57(d,J＝7.3Hz,2H),7.51(d,J＝6.1Hz,1H),7.33–7.23(m,5H),6.88–6.79(m,7H),7.01(t,J＝7.4Hz,1H),6.93(t,J＝7.4Hz,1H),6.88–6.78(m,5H),6.75(t,J＝7.7Hz,2H),6.57(d,J＝7.4Hz,2H),1.26(s,18H).13C{1H}NMR(126MHz,CDCl3)δ188.8,163.1,156.7,152.6,148.6,147.4,142.5,142.1,141.9,138.8,135.5,130.8,129.6,129.2,129.0,128.5,127.8,127.3,127.2,127.0,126.4,125.4,124.4,123.6,123.0,120.8,61.8,34.2,31.3.IR:
Figure BDA0003769687860000132
Figure BDA0003769687860000133
HRMS(ESI)m/z:[M+H]+calcd for C50H46N 660.3625；found:660.3621；
实施例13的反应时间为2h，产率为67％；产物3m：1H NMR(500MHz,CDCl3)δ7.63(d,J＝7.4Hz,1H),7.57–7.52(m,2H),7.48(d,J＝7.8Hz,1H),7.30–7.24(m,6H),7.16(t,J＝7.4Hz,2H),7.13–7.05(m,1H),7.03–6.92(m,2H),6.87–6.77(m,7H),6.70–6.63(m,4H),6.60(dd,J＝8.2,1.3Hz,2H),3.73(s,6H).13C{1H}NMR(126MHz,CDCl3)δ188.8,163.1,157.8,156.5,152.6,147.5,142.4,142.1,141.8,135.4,134.2,130.8,130.5,129.6,129.2,128.9,128.5,127.9,127.30,127.25,127.1,126.7,125.3,123.7,123.0,120.8,113.1,61.0,55.2.IR:
Figure BDA0003769687860000134
Figure BDA0003769687860000135
HRMS(ESI)m/z:[M+H]+calcd for C44H34NO2 608.2584；found:608.2580；
实施例14的反应时间为3h，产率为74％；产物3n：1H NMR(500MHz,CDCl3)δ7.68(d,J＝7.5Hz,1H),7.64–7.58(m,2H),7.57–7.46(m,9H),7.45–7.34(m,8H),7.34–7.24(m,3H),7.21–7.14(m,2H),7.10(t,J＝7.4Hz,1H),7.06–6.95(m,2H),6.94–6.85(m,2H),6.85–6.76(m,5H),6.65(d,J＝7.3Hz,2H).13C{1H}NMR(126MHz,CDCl3)δ188.2,163.1,156.7,152.1,147.9,142.2,142.1,142.0,141.0,138.9,135.3,130.7,129.9,129.8,129.2,129.0,128.7,127.9,127.4,127.17,127.16,127.1,126.9,126.7,126.4,125.3,123.9,123.1,120.9,61.9.IR:
Figure BDA0003769687860000136
Figure BDA0003769687860000137
HRMS(ESI)m/z:[M+H]+calcd for C54H38N 700.2999；found:700.2996；
实施例15的反应时间为20min，产率为46％；产物3o：1H NMR(500MHz,CDCl3)δ7.64(d,J＝7.5Hz,1H),7.58–7.52(m,2H),7.48(d,J＝7.8Hz,1H),7.30–7.19(m,4H),7.19–7.14(m,4H),7.10(t,J＝7.4Hz,1H),7.07–6.98(m,3H),6.95(s,1H),6.90(d,J＝7.5Hz,2H),6.87–6.75(m,7H),6.59(d,J＝7.3Hz,2H),2.20(s,6H).13C{1H}NMR(126MHz,CDCl3)δ188.6,163.1,156.8,152.4,147.6,142.5,142.0,141.8,141.7,136.8,135.5,130.8,130.6,129.6,129.3,128.9,128.5,127.9,127.5,127.32,127.27,127.02,126.99,126.73,126.67,125.3,123.7,123.0,120.9,62.2,21.5.IR:
Figure BDA0003769687860000141
Figure BDA0003769687860000142
HRMS(ESI)m/z:[M+H]+calcd for C44H34N 576.2686；found:576.2682；
实施例16的反应时间为40min，产率为29％；3p：1H NMR(500MHz,CDCl3)δ7.64(d,J＝7.5Hz,1H),7.59–7.52(m,2H),7.48(d,J＝7.8Hz,1H),7.31–7.23(m,1H),7.16(t,J＝7.4Hz,2H),7.13–6.91(m,9H),6.89–6.78(m,7H),6.69–6.61(m,4H),3.67(s,6H).13C{1H}NMR(126MHz,CDCl3)δ188.1,163.0,158.8,156.7,152.0,147.8,143.2,142.3,142.0,141.9,135.3,130.8,129.7,129.2,129.0,128.6,128.5,127.9,127.4,127.1,126.7,125.3,123.8,123.0,122.2,120.9,115.8,112.0,62.3,55.1.IR:
Figure BDA0003769687860000143
Figure BDA0003769687860000144
HRMS(ESI)m/z:[M+H]+calcd for C44H34NO2 608.2584；found:608.2575。
实施例17-36
实施例17-36当中的吲哚亚胺并环戊烯类化合物的合成路径如下所示：
Figure BDA0003769687860000145
其中，化合物1a代表2-吲哚甲醇类合物，化合物2代表炔丙醇类化合物，化合物4代表吲哚亚胺并环戊烯类化合物。
具体地，以化合物4g和4o为代表详细地描述实施例17-36吲哚亚胺并环戊烯类化合物的合成过程，其余的化合物相应地改变原料及反应时间。
实施例23吲哚亚胺并环戊烯类化合物4g的合成，具体反应式如下：
Figure BDA0003769687860000151
在15mL耐压管中依次加入搅拌子、2-吲哚甲醇类合物(59.8mg,0.2mmol)、炔丙醇类化合物(94mg,0.2mmol)、三氟甲磺酸钪(19.6mg,0.04mmol)和甲苯(2mL)，反应体系置于100℃下反应40min。反应体系直接利用硅胶(200-300目)柱层析(流动相成分为石油醚：乙酸乙酯＝5:1)分离得到黄色固体吲哚亚胺并环戊烯类化合物(100.5mg,产率：87％)。
实施例31吲哚亚胺并环戊烯类化合物4g的合成，具体反应式如下：
Figure BDA0003769687860000152
在15mL耐压管中依次加入搅拌子、2-吲哚甲醇类合物(59.8mg,0.2mmol)、炔丙醇类化合物(93.7mg,0.2mmol)、三氟甲磺酸钪(19.6mg,0.04mmol)和甲苯(2mL)，反应体系置于100℃下反应30min。反应体系直接利用硅胶(200-300目)柱层析(流动相成分为石油醚：乙酸乙酯＝5:1)分离得到黄色固体吲哚亚胺并环戊烯类化合物(92.1mg,产率：80％)。
实施例17-36的吲哚亚胺并环戊烯类化合物汇总
1、实施例17-23合成得到的吲哚亚胺并环戊烯类化合物4a～4g结构式分别如下：
Figure BDA0003769687860000153
其中，R1为取代基，化合物4a～4g中的R1分别为4-FC6H4、F、4-ClC6H4、4-EtC6H4、4-MeC6H4、4-n-BuC6H4、4-t-BuC6H4、4-MeOC6H4。
2、实施例24-36合成得到的吲哚亚胺并环戊烯类化合物4h～4t结构式分别如下：
Figure BDA0003769687860000161
实施例17～36的反应时间、产率及产物4a～4t的光谱数据如下：
实施例17的反应时间为30min，产率为76％；产物4a：1H NMR(500MHz,CDCl3)δ7.59(d,J＝7.6Hz,1H),7.57–7.50(m,2H),7.49(d,J＝7.8Hz,1H),7.41–7.33(m,4H),7.27(td,J＝7.7,1.0Hz,1H),7.16–7.05(m,6H),7.01(t,J＝7.5Hz,1H),6.95(t,J＝7.4Hz,1H),6.92–6.81(m,7H),6.77(t,J＝7.7Hz,2H),6.57(d,J＝8.0Hz,2H).13C{1H}NMR(126MHz,CDCl3)δ188.3,163.3,163.0,161.3,155.4,152.1,148.0,142.2,142.0,141.8,141.7,131.42,131.39,130.92,130.85,130.8,129.9,129.5,129.2,127.6,127.48,127.45,127.2,126.8,126.3,125.1,123.9,122.8,121.0,115.1,115.0,62.3.19F NMR(471MHz,CDCl3)δ-111.3.IR:
Figure BDA0003769687860000171
Figure BDA0003769687860000172
HRMS(ESI)m/z:[M+H]+calcd for C42H29FN 566.2279；found:566.2273；
实施例18的反应时间为30min，产率为68％；产物4b：1H NMR(500MHz,CDCl3)δ7.57(d,J＝7.5Hz,1H),7.53–7.42(m,3H),7.41–7.32(m,4H),7.28(td,J＝7.7,1.1Hz,1H),7.18–7.06(m,8H),7.02(td,J＝7.6,1.1Hz,1H),7.00–6.89(m,2H),6.91–6.81(m,4H),6.78(t,J＝7.8Hz,2H),6.57(dd,J＝8.2,1.1Hz,2H).13C{1H}NMR(126MHz,CDCl3)δ188.4,163.0,155.0,152.0,148.0,142.2,142.1,141.69,141.65,134.2,133.8,130.7,130.2,130.0,129.5,129.1,128.1,127.6,127.51,127.47,127.2,126.8,126.3,125.0,123.9,122.9,121.0,62.3.IR:
Figure BDA0003769687860000173
Figure BDA0003769687860000174
HRMS(ESI)m/z:[M+H]+calcd for C42H29ClNO 582.1983；found:582.1978；
实施例19的反应时间为30min，产率为84％；产物4c：1H NMR(500MHz,CDCl3)δ7.68(d,J＝7.3Hz,1H),7.52–7.44(m,3H),7.42–7.32(m,4H),7.25(td,J＝7.7,1.1Hz,1H),7.17–7.03(m,6H),7.01(td,J＝7.6,0.9Hz,1H),6.99–6.90(m,3H),6.86–6.79(m,5H),6.76(t,J＝7.8Hz,2H),6.57(dd,J＝8.2,1.1Hz,2H),2.53(q,J＝7.6Hz,2H),1.15(t,J＝7.6Hz,3H).13C{1H}NMR(126MHz,CDCl3)δ188.4,162.9,157.1,152.3,147.9,145.0,142.3,142.1,141.9,141.5,132.5,130.8,129.6,129.5,129.21,129.15,127.6,127.4,127.21,127.15,126.6,126.1,125.3,123.7,123.0,120.8,62.3,28.8,15.5.IR:
Figure BDA0003769687860000175
Figure BDA0003769687860000176
HRMS(ESI)m/z:[M+H]+calcd for C44H34N 576.2686；found:576.2685；
实施例20的反应时间为40min，产率为83％；产物4d：1H NMR(500MHz,CDCl3)δ7.67(d,J＝7.5Hz,1H),7.51–7.42(m,3H),7.42–7.33(m,4H),7.24(td,J＝7.7,1.3Hz,1H),7.16–7.03(m,6H),7.00(t,J＝7.3Hz,1H),6.97–6.89(m,3H),6.86–6.79(m,J＝3.0Hz,5H),6.76(t,J＝7.7Hz,2H),6.57(dd,J＝8.0,1.4Hz,2H),2.23(s,3H).13C{1H}NMR(126MHz,CDCl3)δ188.4,162.9,157.1,152.2,147.9,142.4,142.1,141.9,141.4,138.6,132.3,130.8,129.53,129.45,129.2,129.0,128.5,127.5,127.2,127.1,127.0,126.6,126.1,125.3,123.6,123.0,120.8,62.3,21.3.IR:
Figure BDA0003769687860000181
Figure BDA0003769687860000182
HRMS(ESI)m/z:[M+H]+calcd for C43H32N 562.2529；found:562.2524；
实施例21的反应时间为30min，产率为82％；产物4e：1H NMR(500MHz,CDCl3)δ7.68(d,J＝7.4Hz,1H),7.53–7.44(m,3H),7.44–7.32(m,4H),7.24(td,J＝7.7,1.0Hz,1H),7.17–7.03(m,6H),7.00(td,J＝7.6,1.1Hz,1H),6.98–6.90(m,3H),6.88–6.78(m,5H),6.76(t,J＝7.8Hz,2H),6.60–6.54(m,2H),2.50(t,J＝7.5Hz,2H),1.58–1.44(m,2H),1.33–1.22(m,2H),0.94(t,J＝7.3Hz,3H).13C{1H}NMR(126MHz,CDCl3)δ188.4,162.9,157.2,152.3,147.8,143.6,142.4,142.1,141.9,141.4,132.5,130.8,129.5,129.4,129.2,129.0,128.0,127.5,127.2,127.1,126.6,126.1,125.3,123.6,123.0,120.8,62.3,35.4,33.3,22.0,13.9.IR:
Figure BDA0003769687860000183
Figure BDA0003769687860000184
HRMS(ESI)m/z:[M+H]+calcd for C46H38N 604.2999；found:604.2996；
实施例22的反应时间为30min，产率为87％；产物4f:1H NMR(500MHz,CDCl3)δ7.71(d,J＝7.3Hz,1H),7.53–7.45(m,3H),7.41–7.34(m,4H),7.32–7.22(m,1H),7.18–7.04(m,8H),7.03(td,J＝7.5,0.9Hz,1H),6.98–6.91(m,1H),6.84–6.73(m,7H),6.57(dd,J＝8.3,1.3Hz,2H),1.25(s,9H).13C{1H}NMR(126MHz,CDCl3)δ188.5,162.9,157.0,152.4,151.6,147.8,142.3,142.1,141.9,141.4,132.1,130.8,129.6,129.5,129.2,129.0,127.6,127.2,126.6,126.1,125.4,124.8,123.7,123.1,120.8,62.3,34.6,31.0.IR:
Figure BDA0003769687860000185
Figure BDA0003769687860000186
HRMS(ESI)m/z:[M+H]+calcd for C46H38N 604.2999；found:604.2998；
实施例23的反应时间为20min，产率为63％；产物4g:1H NMR(500MHz,CDCl3)δ7.70(d,J＝7.5Hz,1H),7.56–7.51(m,2H),7.49(d,J＝7.8Hz,1H),7.39–7.34(m,4H),7.30–7.23(m,1H),7.15–7.04(m,6H),7.03(td,J＝7.6,0.9Hz,1H),6.99–6.91(m,1H),6.90–6.79(m,5H),6.77(t,J＝7.8Hz,2H),6.72–6.66(m,2H),6.57(dd,J＝8.1,1.2Hz,2H),3.76(s,3H).13C{1H}NMR(126MHz,CDCl3)δ188.3,162.9,159.8,156.9,152.3,147.9,142.5,142.2,142.0,140.9,130.9,130.8,129.6,129.4,129.3,127.7,127.6,127.3,127.20,127.17,126.7,126.1,125.4,123.6,122.9,120.8,113.5,62.4,55.3.IR:
Figure BDA0003769687860000191
Figure BDA0003769687860000192
HRMS(ESI)m/z:[M+H]+calcd for C43H32NO 578.2478；found:578.2473；
实施例24的反应时间为20min，产率为65％；产物4h：1H NMR(500MHz,CDCl3)δ7.56(td,J＝7.4,1.8Hz,2H),7.50–7.30(m,5H),7.30–7.25(m,1H),7.20–7.07(m,7H),7.07–6.97(m,2H),6.97–6.81(m,6H),6.80–6.72(m,3H),6.57(d,J＝7.5Hz,2H).13C{1H}NMR(126MHz,CDCl3)δ188.5,163.1,159.1,157.1,151.7,149.9,147.7,143.2,141.7,141.6,130.8,130.7,130.5,130.4,130.3,130.0,129.6,128.9,128.4,127.6,127.4,127.2,126.6,126.2,125.0,123.9,123.8,123.64,123.61,123.4,120.9,115.9,115.8,62.2.19FNMR(471MHz,CDCl3)δ-108.4.IR:
Figure BDA0003769687860000193
HRMS(ESI)m/z:[M+H]+calcd for C42H29FN 566.2279；found:566.2276；
实施例25的反应时间为1h，产率为85％；产物4i：1H NMR(500MHz,CDCl3)δ8.11(d,J＝7.6Hz,1H),7.50(d,J＝7.8Hz,1H),7.36(d,J＝7.3Hz,4H),7.34–7.24(m,3H),7.14–7.02(m,7H),6.99–6.90(m,6H),6.81–6.73(m,3H),6.60(d,J＝8.0Hz,2H).13C{1H}NMR(126MHz,CDCl3)δ188.3,162.7,152.5,149.1,147.6,143.2,142.2,141.9,139.8,136.7,131.8,130.6,129.7,129.5,128.6,127.6,127.4,127.3,127.1,126.9,126.2,124.8,123.8,123.7,120.9,62.9.IR:
Figure BDA0003769687860000194
Figure BDA0003769687860000195
HRMS(ESI)m/z:[M+H]+calcd for C40H28NS 554.1937；found:554.1934；
实施例26的反应时间为30min，产率为50％；产物4j：1H NMR(500MHz,CDCl3)δ7.81(d,J＝7.6Hz,1H),7.52(d,J＝7.7Hz,1H),7.34–7.20(m,7H),7.18–6.89(m,11H),6.74(s,4H),1.31(s,9H).13C{1H}NMR(126MHz,CDCl3)δ188.5,176.7,162.3,153.9,146.8,145.6,143.0,142.6,142.2,132.1,130.1,128.72,128.70,128.24,128.16,127.4,126.9,126.0,125.6,125.5,123.4,120.7,65.7,37.4,31.0.IR:
Figure BDA0003769687860000196
Figure BDA0003769687860000197
HRMS(ESI)m/z:[M+H]+calcd for C40H34N 528.2686；found:528.2682；
实施例27的反应时间为20min，产率为50％；产物4k：1H NMR(500MHz,CDCl3)δ7.61(d,J＝7.5Hz,1H),7.46(d,J＝7.7Hz,1H),7.33–7.18(m,11H),7.13–7.00(m,7H),6.97–6.89(m,1H),6.76(t,J＝7.8Hz,2H),6.56(dd,J＝8.2,1.1Hz,2H),1.45–1.36(m,3H),0.95–0.85(m,2H).13C{1H}NMR(126MHz,CDCl3)δ188.4,167.2,162.4,154.6,145.8,144.0,142.0,141.8,138.7,130.4,129.6,129.2,128.6,128.02,128.00,127.5,127.2,126.7,126.0,124.4,123.9,123.5,120.7,62.1,16.1,13.0.IR:
Figure BDA0003769687860000201
Figure BDA0003769687860000202
HRMS(ESI)m/z:[M+H]+calcd for C39H30N 512.2373；found:512.2368；
实施例28的反应时间为20min，产率为74％；产物4l：1H NMR(500MHz,CDCl3)δ7.64(d,J＝7.5Hz,1H),7.55(d,J＝7.0Hz,2H),7.48(d,J＝7.8Hz,1H),7.38(d,J＝7.5Hz,4H),7.31–7.08(m,10H),7.02(t,J＝7.5Hz,1H),6.79(dd,J＝8.4,5.3Hz,2H),6.59–6.44(m,6H).13C{1H}NMR(126MHz,CDCl3)δ188.2,163.1,162.9,162.8,160.91,160.85,155.9,153.0,145.2,142.3,141.7,138.32,138.29,137.9,137.8,135.1,132.5,132.4,131.0,130.9,130.0,1295,128.9,128.8,128.1,127.8,1265,125.1,124.0,123.1,121.0,114.5,114.4,114.3,114.2,62.3.19F NMR(471MHz,CDCl3)δ-113.7,-114.6.IR:
Figure BDA0003769687860000203
Figure BDA0003769687860000204
HRMS(ESI)m/z:[M+H]+calcd for C42H28F2N 584.2184；found:584.2178；
实施例29的反应时间为20min，产率为53％；产物4m:1H NMR(500MHz,CDCl3)δ7.64(d,J＝7.4Hz,1H),7.55–7.49(m,2H),7.48(d,J＝7.8Hz,1H),7.41–7.33(m,4H),7.27(td,J＝7.7,1.1Hz,1H),7.24–7.19(m,3H),7.19–7.09(m,6H),7.02(td,J＝7.6,0.9Hz,1H),6.83–6.70(m,6H),6.52–6.46(m,2H).13C{1H}NMR(126MHz,CDCl3)δ188.0,163.1,155.5,153.5,144.6,142.5,141.5,140.3,140.0,134.9,133.5,133.1,131.9,130.5,130.1,129.5,128.9,128.8,128.2,127.8,127.6,127.5,126.5,125.1,124.0,123.2,121.0,62.3.IR:
Figure BDA0003769687860000205
Figure BDA0003769687860000206
HRMS(ESI)m/z:[M+H]+calcd for C42H28Cl2N 616.1593；found:616.1589；
实施例30的反应时间为20min，产率为43％；产物4n:1H NMR(500MHz,CDCl3)δ7.63(d,J＝6.7Hz,1H),7.58–7.44(m,3H),7.42–7.31(m,3H),7.30–7.07(m,10H),7.06–6.84(m,6H),6.67(d,J＝7.9Hz,2H),6.43(d,J＝7.9Hz,2H).13C{1H}NMR(126MHz,CDCl3)δ187.9,163.1,155.4,153.5,144.6,142.6,141.5,140.6,140.3,134.9,132.1,130.7,130.52,130.46,130.1,129.5,128.9,128.8,128.2,127.8,126.6,125.1,124.0,123.2,121.9,121.4,121.0,62.3.IR:
Figure BDA0003769687860000211
Figure BDA0003769687860000212
HRMS(ESI)m/z:[M+H]+calcd forC42H28Br2N 706.0563；found:706.0561；
实施例31的反应时间为20min，产率为80％；产物4o：1H NMR(500MHz,CDCl3)δ7.64(d,J＝7.5Hz,1H),7.60–7.51(m,2H),7.48(d,J＝7.8Hz,1H),7.38(d,J＝7.1Hz,4H),7.24(td,J＝7.7,1.2Hz,1H),7.19–7.04(m,9H),6.99(t,J＝7.5Hz,1H),6.71(d,J＝8.0Hz,2H),6.59(t,J＝7.8Hz,4H),6.46(d,J＝8.0Hz,2H),2.16(s,3H),2.04(s,3H).13C{1H}NMR(126MHz,CDCl3)δ188.6,162.9,157.3,151.8,148.4,142.0,141.5,139.7,139.3,137.1,136.5,135.5,130.8,129.6,129.4,129.2,129.0,128.1,127.9,127.8,127.5,126.1,125.3,123.6,122.9,120.8,62.3,21.0,20.9.IR:
Figure BDA0003769687860000213
Figure BDA0003769687860000214
HRMS(ESI)m/z:[M+H]+calcd for C44H34N 576.2686；found:576.2678；
实施例32的反应时间为30min，产率为75％；产物4p：1H NMR(500MHz,CDCl3)δ7.67(d,J＝7.5Hz,1H),7.61–7.55(m,2H),7.48(d,J＝7.8Hz,1H),7.43–7.34(m,4H),7.24(td,J＝7.7,1.2Hz,1H),7.19(t,J＝7.5Hz,2H),7.17–7.05(m,7H),7.00(td,J＝7.5,1.0Hz,1H),6.75(d,J＝8.7Hz,2H),6.51(d,J＝8.7Hz,2H),6.38–6.29(m,4H),3.65(s,3H),3.58(s,3H).13C{1H}NMR(126MHz,CDCl3)δ188.6,162.8,159.0,158.9,158.7,157.5,151.4,147.8,142.1,141.1,137.6,135.5,135.4,134.8,132.4,131.6,130.8,129.5,129.3,129.0,128.5,128.4,128.3,128.2,127.9,127.5,127.3,126.1,125.3,123.6,122.8,120.7,113.8,113.4,112.7,112.5,62.4,55.2,55.10,55.07.IR:
Figure BDA0003769687860000215
Figure BDA0003769687860000216
HRMS(ESI)m/z:[M+H]+calcd for C44H34NO2 608.2584；found:608.2578；
实施例33的反应时间为30min，产率为77％，顺反异构体的比例为1.1:1；产物4q:1H NMR(500MHz,CDCl3)δ7.64(dd,J＝7.5,2.8Hz,1H),7.61–7.52(m,2H),7.48(d,J＝7.8Hz,1H),7.45–7.34(m,4H),7.26(t,J＝7.6Hz,1H),7.25–7.05(m,9H),7.04–6.93(m,2H),6.83(s,2H),6.83–6.75(m,2H),6.60–6.42(m,4H).13C{1H}NMR(126MHz,CDCl3)δ188.3,188.2,163.01,162.99,162.8,162.7,160.82,160.75,156.5,156.2,152.6,152.5,146.6,146.5,142.2,142.13,142.11,141.8,141.7,138.50,138.47,138.04,138.02,135.2,132.5,132.4,131.0,130.9,130.8,129.81,129.79,129.5,129.2,128.9,128.7,128.6,128.1,127.9,127.8,127.7,127.6,127.5,127.4,127.3,126.9,126.4,126.3,125.18,125.16,123.9,123.1,120.9,114.3,114.21,114.17,114.0,62.3.19F NMR(471MHz,CDCl3)δ-114.0,-114.9.IR:
Figure BDA0003769687860000221
HRMS(ESI)m/z:[M+H]+calcd for C42H29FN 566.2279；found:566.2271；
实施例34的反应时间为15min，产率为68％，顺反异构体的比例为1.1:1；产物4r:1H NMR(500MHz,CDCl3)δ7.64(t,J＝6.6Hz,1H),7.58–7.50(m,2H),7.48(dd,J＝7.7,1.9Hz,1H),7.43–7.33(m,4H),7.26(td,J＝7.7,1.0Hz,1H),7.25–7.05(m,9H),7.01(t,J＝7.5Hz,1H),6.99–6.88(m,3H),6.83(s,2H),6.78(t,J＝7.8Hz,1H),6.73–6.65(m,1H),6.58–6.52(m,1H),6.45(d,J＝8.5Hz,1H).13C{1H}NMR(126MHz,CDCl3)δ188.3,188.2,163.1,156.28,156.25,155.98,155.95,152.9,152.8,146.30,146.25,146.2,142.33,142.29,141.73,141.68,141.65,141.4,141.3,141.0,135.1,132.21,132.19,130.81,130.78,130.7,130.4,130.3,129.94,129.91,129.88,129.6,129.53,129.50,129.2,129.0,128.72,128.67,128.6,128.2,128.0,127.77,127.75,127.68,127.66,127.6,127.5,127.4,127.0,126.9,126.5,126.33,126.30,125.2,124.0,123.1,121.68,121.65,121.14,121.11,120.9,62.3.IR:
Figure BDA0003769687860000222
Figure BDA0003769687860000223
HRMS(ESI)m/z:[M+H]+calcd for C42H29BrNO 626.1478；found:626.1469；
实施例35的反应时间为15min，产率为82％，顺反异构体的比例为1.3:1；产物4s:1H NMR(500MHz,CDCl3)δ7.65(t,J＝7.5Hz,1H),7.60–7.54(m,2H),7.48(d,J＝7.8Hz,1H),7.44–7.33(m,4H),7.25(td,J＝7.7,1.1Hz,1H),7.24–7.04(m,9H),7.04–6.93(m,2H),6.88–6.80(m,3H),6.81–6.72(m,2H),6.57(dd,J＝8.2,1.3Hz,1H),6.53–6.47(m,1H),6.38–6.28(m,2H),3.61(d,J＝35.1Hz,3H).13C{1H}NMR(126MHz,CDCl3)δ188.54,188.50,162.9,158.9,158.7,157.1,152.1,151.6,148.0,147.8,142.7,142.1,142.0,141.9,141.6,135.5,135.4,135.1,134.7,132.2,130.9,130.7,129.54,129.51,129.3,129.0,128.5,128.4,127.9,127.8,127.6,127.5,127.4,127.3,127.1,126.7,126.2,126.1,125.28,125.25,123.7,122.9,120.8,112.8,112.6,62.5,62.3,55.11,55.09.IR:
Figure BDA0003769687860000231
Figure BDA0003769687860000232
HRMS(ESI)m/z:[M+H]+calcd for C43H32NO 578.2478；found:578.2470；
实施例36的反应时间为3h，产率为34％，顺反异构体的比例为1.2:1；产物4t：1HNMR(500MHz,DMSO-d6)δ9.34(d,J＝18.4Hz,1H),7.64(td,J＝22.9,22.0,7.6Hz,3H),7.47–7.02(m,16H),6.97(t,J＝7.5Hz,1H),6.87(s,2H),6.78(t,J＝7.7Hz,1H),6.68(d,J＝8.1Hz,1H),6.51(d,J＝7.6Hz,1H),6.33(d,J＝8.1Hz,1H),6.25(d,J＝8.0Hz,1H),6.18(d,J＝8.1Hz,1H).13C NMR{1H}(126MHz,DMSO)δ188.3,162.4,158.2,158.0,157.0,156.7,151.0,150.2,148.6,148.5,142.8,142.2,142.1,140.2,140.1,135.0,134.9,133.3,132.7,132.2,130.8,130.4,129.6,129.5,129.4,129.3,129.0,128.9,128.8,128.7,128.0,127.6,127.5,127.4,127.3,127.0,126.7,126.2,125.0,124.9,123.9,122.74,122.70,120.4,114.2,113.8,61.8,61.7,40.0,39.8,39.7,39.5,39.3,39.2,39.0.IR:
Figure BDA0003769687860000233
Figure BDA0003769687860000234
HRMS(ESI)m/z:[M+H]+calcd for C42H30NO 564.2322；found:564.2317。
实施例37
在15mL耐压管中依次加入搅拌子、2-吲哚甲醇类合物(75.6mg,0.2mmol)、炔丙醇类化合物(93.72mg,0.22mmol)、三氟甲磺酸钪(19.6mg,0.04mmol)和甲苯(1mL)，反应体系置于80℃下反应3h。反应体系直接利用硅胶(200-300目)柱层析(流动相成分为石油醚：乙酸乙酯＝5:1)分离得到黄色固体(产率：81％)。
实施例38
在15mL耐压管中依次加入搅拌子、2-吲哚甲醇类合物(75.6mg,0.2mmol)、炔丙醇类化合物(93.72mg,0.22mmol)、三氟甲磺酸钪(19.6mg,0.04mmol)和甲苯(1mL)，反应体系置于50℃下反应24h。反应体系直接利用硅胶(200-300目)柱层析(流动相成分为石油醚：乙酸乙酯＝5:1)分离得到黄色固体(产率：44％)。
实施例37和38的反应式如下所示：
Figure BDA0003769687860000241
以上所述，仅是本发明的代表性实例，并非对本发明做任何形式上的限制，故凡未脱离本发明技术方案的内容，依据本发明的技术实质对以上实施例的任何的简单修改、等同变化与修饰，均仍属于本发明技术方案的范围内。

Claims (10)

1.一种吲哚亚胺并环戊烯类化合物的合成方法，其特征在于，包括以下步骤：将2-吲哚甲醇类化合物和炔丙醇类化合物在溶剂中混合，经催化剂催化反应得到吲哚亚胺并环戊烯类化合物，反应式如下所示：
Figure FDA0003769687850000011
其中，R为苯基或取代苯基，所述的取代苯基上的取代基为卤素、烷基、烷氧基、羟基、三氟甲基中的至少一种；
R1为苯基或取代苯基，所述的取代苯基上的取代基为卤素、烷基、烷氧基、三氟甲基中的至少一种；
R2为苯基、取代苯基、杂环芳基、烷基中的任意一种，所述的取代苯基上的取代基为卤素、烷基、烷氧基、三氟甲基中的至少一种；所述的杂环芳基为含杂原子的环状基团，所述的杂原子为O、S、N、P、Si中的至少一种；
R3为苯基或取代苯基，所述的取代苯基上的取代基为卤素、烷基、烷氧基、三氟甲基、苯基中的至少一种；
R4为氢原子、卤素原子、烷基、烷氧基、三氟甲基中的至少一种。
2.如权利要求1所述吲哚亚胺并环戊烯类化合物的合成方法，其特征在于，
所述R2为环丙基、叔丁基、噻吩基中的一种；所述R4为氟原子、氯原子、溴原子、甲基、甲氧基中的至少一种；
R为取代苯基时，所述的取代苯基上的取代基为甲基、甲氧基、氟原子、氯原子、溴原子中的至少一种；
R1为取代苯基时，所述的取代苯基上的取代基为甲基、甲氧基、氟原子、氯原子、溴原子中的至少一种；
R2为取代苯基时，所述的取代苯基上的取代基为甲基、乙基、正丁基、叔丁基、甲氧基、氟原子、氯原子中的至少一种；
R3为取代苯基时，所述的取代苯基上的取代基为氟原子、氯原子、甲基、叔丁基、甲氧基中的至少一种。
3.如权利要求1或2所述吲哚亚胺并环戊烯类化合物的合成方法，其特征在于，所述的反应的温度为50℃～120℃。
4.如权利要求1或2所述吲哚亚胺并环戊烯类化合物的合成方法，其特征在于，所述反应的时间为10min～1440min。
5.如权利要求4所述的合成方法，其特征在于，所述反应的时间为20min～240min。
6.如权利要求1或2所述吲哚亚胺并环戊烯类化合物的合成方法，其特征在于，所述的催化剂包括三氟甲磺酸锌、三氟甲磺酸铋、三氟甲磺酸镱、双三氟甲烷磺酰亚胺银、三氟甲磺酸钪中的至少一种。
7.如权利要求6所述吲哚亚胺并环戊烯类化合物的合成方法，其特征在于，所述的催化剂为三氟甲磺酸钪。
8.如权利要求1或2所述吲哚亚胺并环戊烯类化合物的合成方法，其特征在于，所述的溶剂包括甲苯、氯苯、乙腈、1,4-二氧六环、三氯甲烷、四氢呋喃、乙醇、乙酸乙酯、N,N-二甲基甲酰胺、二甲基亚砜、丙酮中的至少一种。
9.如权利要求8所述吲哚亚胺并环戊烯类化合物的合成方法，其特征在于，所述的溶剂为甲苯。
10.如权利要求1或2所述吲哚亚胺并环戊烯类化合物的合成方法，其特征在于，所述的2-吲哚甲醇类化合物、炔丙醇类化合物、催化剂的摩尔比为1：(1-3)：(0.1-1)。
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