CN102127001A - 一种合成2-烷基-4-吲哚基-4-芳基-2-丁烯酸乙酯衍生物的方法 - Google Patents
一种合成2-烷基-4-吲哚基-4-芳基-2-丁烯酸乙酯衍生物的方法 Download PDFInfo
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Abstract
一种合成顺式和反式的2-烷基-4-吲哚基-4-芳基-2-丁烯酸乙酯衍生物的方法,通过各种取代的2,3-联烯基亚砜和N吸电子基保护的吲哚及其衍生物在三氟醋酸中发生氢芳基化反应,生成一系列各种取代的顺式和反式的2-烷基-4-吲哚基-4-芳基-2-丁烯酸乙酯类衍生物,本方法操作简单,原料和试剂易得,反应具有较高的产率,可通过对温度和反应时间的调整有选择性地获得顺式或反式构型为主的产物,并通过柱层析对两者进行分离,产物易分离纯化,适用于合成各种取代的2-烷基-4-吲哚基-4-芳基-2-丁烯酸乙酯类化合物。
Description
技术领域
本发明涉及一种合成各种取代的2-烷基-4-吲哚基-4-芳基-2-丁烯酸乙酯类化合物的方法,即通过2,3-联烯酸酯和N吸电子基保护的吲哚及其衍生物在三氟醋酸中发生氢芳基化反应,生成一系列各种取代的2-烷基-4-吲哚基-4-芳基-2-丁烯酸乙酯的方法。
背景技术
2-烷基-4-吲哚基-4-芳基-2-丁烯酸乙酯是有机合成中重要的中间体之一,也是天然产物中常见的结构单元之一,在生物技术领域,医药及农药等方面有巨大的开发利用价值,特别是其含有较大的共轭结构,是潜在的良好发光材料,但文献中少见这类2-烷基-4-吲哚基-4-芳基-2-丁烯酸乙酯化合物的直接合成报道。先前,曾有文献报道过钯催化下在三氟醋酸中富电子芳环和2,3-联烯酸酯合成2-烷基-4,4-二芳基反-2-丁烯酸乙酯的反应(Chemistry, a European Journal, 2010, 16, 3910-3910),但这种方法中富电子芳环为苯环类化合物,需要使用钯催化剂,且只能得到顺式丁烯酸乙酯。本专利提供了一种利用N吸电子基保护的吲哚亲电性直接和2,3-联烯酸酯反应得到共轭基团更大的顺式反式可调控的2-烷基-4-吲哚基-4-芳基-2-丁烯酸乙酯的方法。
发明内容
本发明的目的就是提供一种在简单条件下利用氢芳基化反应有效的合成各种取代的2-烷基-4-吲哚基-4-芳基-2-丁烯酸乙酯衍生物的方法,反应可以直接对吲哚3位的碳氢键进行官能团化构建新的碳碳键,具有较好的底物普适性。
本发明提供合成2-烷基-4-吲哚基-4-芳基-2-丁烯酸乙酯的方法,由N吸电子基保护的吲哚和取代的吲哚化合物和2,3-联烯酸酯高区域和可调控的立体选择性地碳氢官能团化反应生成2-烷基-4-吲哚基-4-芳基-2-丁烯酸乙酯,反应式如下:
R1 =对甲苯磺酰基、乙酰基;R2=各种取代的苯基;R3=氢、甲基、甲氧基和溴;R4=烷基;其步骤是:
(1) 2,3-联烯酸酯2和N吸电子基保护的吲哚1在三氟醋酸中发生分子间的氢芳基化反应生成2-烷基-4-吲哚基-4-芳基-2-丁烯酸乙酯类化合物3:在一定温度下,将原料N吸电子基保护的吲哚1加入反应瓶内,三氟醋酸润洗2,3-联烯酸酯2加入,反应一定时间;
(2) 步骤1反应完全后,加入10mL饱和碳酸氢钠溶液淬灭反应,乙醚萃取,饱和碳酸氢钠洗涤至中性,无水硫酸钠干燥,过滤,浓缩,快速柱层析,获得产物2-烷基-4-吲哚基-4-芳基-2-丁烯酸乙酯类化合物3。
本发明的有机溶剂为:三氟醋酸。
本发明原料配比为:N吸电子基保护的吲哚1:2,3-联烯酸酯2: 三氟醋酸=0.3毫摩尔:0.36-0.45毫摩尔:1.5毫升。
本发明的N吸电子基保护的吲哚1:三氟醋酸=0.3毫摩尔:1.5毫升。
本发明的N吸电子基保护的吲哚1:2,3-联烯酸酯2=1:1.2-1.5。
本发明涉及一种各种取代的2-烷基-4-吲哚基-4-芳基-2-丁烯酸乙酯化合物的合成方法,即N吸电子基保护的吲哚和2,3-联烯酸酯在三氟醋酸中发生氢芳基化反应,生成一系列各种取代的2-烷基-4-吲哚基-4-芳基-2-丁烯酸乙酯类化合物,本方法操作简单,原料和试剂易得,反应产率较高,反应的区域选择性很好,产物双键的立体选择性可以通过反应时间和温度的变化得到一定的调控,能得到各种取代的双键顺式和反式的2-烷基-4-吲哚基-4-芳基-2-丁烯酸乙酯产物,产物易分离纯化,适用于合成各种取代的2-烷基-4-吲哚基-4-芳基-2-丁烯酸乙酯类化合物合成。
本发明克服了传统方法的弊端,具有以下优点:1)原料简单易得,制备方便;2)条件温和,操作性强;3)有一定的底物普适性,可以合成各种取代的2-烷基-4,4-二芳基反-2-丁烯酸乙酯;4)产物易分离纯化。
本发明适用于各种5位取代的N吸电子基保护的吲哚和4-芳基取代的2,3-联烯酸酯,并可以得到双键顺式和反式构型的两种丁烯酸乙酯化合物,是对以往反应的很大改进。
本发明创新点在于发展了一种N吸电子基保护的吲哚化合物和2,3-联烯酸酯的直接碳氢官能团化反应的方法学。
本方法所得的相应的2-烷基-4-吲哚基-4-芳基-2-丁烯酸乙酯的产率为42-78%。
具体实施方式
以下实施例有助于理解本发明,但不限于本发明的内容。
实施例1
向一反应管内加入N对甲苯磺酰胺基保护的吲哚(81.0 mg, 0.3 mmol),用滴管吸取2-甲基-4-(4-氟苯基)-2,3联烯丁酸乙酯(79.5 mg, 0.36 mmol), 用三氟乙酸1.5mL润洗加入体系。加料完毕后维持30度加热搅拌12小时。待体系稍微冷却到室温后,滴加饱和的碳酸氢钠水溶液淬灭反应并中和三氟乙酸溶剂。用乙醚萃取,饱和碳酸氢钠溶液洗有机相至中性,无水硫酸钠干燥,过滤,浓缩,快速柱层析,得主要产物为2-甲基-4-(3-(N-对甲苯磺酰基)吲哚基)-4-(4-氟苯基)顺-2-丁烯酸乙酯104.2mg,产率为71%,产物为液体。
1H NMR (300 MHz, CDCl3) δ 7.95 (d, J = 8.1 Hz, 1 H), 7.80-7.70 (m, 2 H), 7.33 (s, 1 H, CHN), 7.30-7.13 (m, 6 H), 7.13-7.05 (m, 1 H), 7.00-6.89 (m, 2 H), 6.24 (d, J = 10.2 Hz, 1 H), 5.97 (d, J = 10.2 Hz, 1 H), 4.19 (q, J = 7.1 Hz, 2 H), 2.34 (s, 3 H, CH3), 2.00 (d, J = 1.2 Hz, 3 H), 1.24 (t, J = 7.1 Hz, 3 H); 13C NMR (75 MHz, CDCl3 ) δ 167.5, 163.2, 160.0, 144.8, 141.2, 137.6 (d, J = 3.75 Hz), 135.6, 135.2, 129.8, 129.4 (d, J = 8.7 Hz), 128.3 (d, J = 233.9 Hz), 127.9, 124.8, 124.7, 123.5, 123.1, 120.4, 115.4 (d, J = 21.7 Hz), 113.7, 60.5, 40.6, 21.5, 20.9, 14.1; 19F NMR (282 MHz) δ -116.0; IR (neat) ν (cm-1) 2981, 2928, 1709, 1646, 1600, 1507, 1448, 1372, 1276, 1221, 1175, 1132, 1094, 1020; MS (70 eV, EI) m/z (%) 491 (M+, 57.89), 262 (100); HRMS Calcd for C28H26NO4SF (M+): 491.1567; Found: 491.1567.
实施例2
按实施例1所述的方法,不同的是所用底物和试剂为:N对甲苯磺酰胺基保护的吲哚(81.7 mg, 0.3 mmol)和2-甲基-4-(4-氯苯基)-2,3联烯丁酸乙酯(84.9 mg, 0.36 mmol),三氟醋酸(1.5 mL),20oC反应12小时,得到产物2-甲基-4-(3-(N-对甲苯磺酰基)吲哚基)-4-(4-氯苯基)顺-2-丁烯酸乙酯95.0 mg,产率62%,产物为液体。
1H NMR (300 MHz, CDCl3) δ 7.95 (d, J = 8.4 Hz, 1 H), 7.79-7.71 (m, 2 H), 7.34 (d, J = 1.2 Hz, 1 H), 7.30-7.12 (m, 8 H), 7.12-7.04 (m, 1 H), 6.24 (dd, J 1 = 10.2 Hz, J 2 = 1.5 Hz, 1 H), 5.98 (d, J = 10.2 Hz, 1 H), 4.19 (q, J = 7.1 Hz, 2 H), 2.32 (s, 3 H, CH3), 1.99 (d, J = 1.5 Hz, 3 H), 1.24 (t, J = 7.2 Hz, 3 H); 13C NMR (75 MHz, CDCl3 ) δ 167.4, 144.8, 140.8, 140.4, 135.5, 135.0, 132.4, 129.8, 129.2, 128.7, 128.1, 126.7, 124.7, 124.5, 123.5, 123.0, 120.4, 113.6, 60.5, 40.6, 21.5, 20.8, 14.1; IR (neat) ν (cm-1) 3051, 2980, 2927, 1712, 1644, 1597, 1489, 1447, 1372, 1276, 1219, 1188, 1175, 1132, 1092, 1016; MS (70 eV, EI) m/z (%) 509 (M+(37Cl), 30.13), 507 (M+(35Cl), 71.78), 278 (100); HRMS Calcd for C28H26NO4S35Cl (M+): 507.1271; Found: 507.1272.
实施例3
按实施例1所述的方法,不同的是所用底物和试剂为:N对甲苯磺酰胺基保护的吲哚(81.3 mg, 0.3 mmol)和2-甲基-4-(3-氯苯基)-2,3联烯丁酸乙酯(85.4 mg, 0.36 mmol),三氟醋酸(1.5 mL),60oC反应12小时,得到产物2-甲基-4-(3-(N-对甲苯磺酰基)吲哚基)-4-(3-氯苯基)顺-2-丁烯酸乙酯73.9 mg,产率48%,产物为白色固体。
1H NMR (300 MHz, CDCl3) δ 7.96 (dt, J 1 = 8.1 Hz, J 2 = 0.8 Hz, 1 H), 7.78-7.69 (m, 2 H), 7.34 (d, J = 1.2 Hz, 1 H), 7.31-7.16 (m, 7 H), 7.14-7.06 (m, 2 H), 6.24 (dq, J 1 = 10.2 Hz, J 2 = 1.5 Hz, 1 H), 5.99 (d, J = 10.2 Hz, 1 H), 4.20 (q, J = 7.1 Hz, 2 H), 2.33 (s, 3 H, CH3), 2.00 (d, J = 1.2 Hz, 3 H), 1.25 (t, J = 7.2 Hz, 3 H); 13C NMR (75 MHz, CDCl3 ) δ 167.4, 144.9, 144.0, 140.5, 135.5, 135.0, 134.4, 129.9, 129.84, 129.80, 128.4, 128.0, 127.0, 126.7, 126.1, 124.8, 124.5, 123.6, 123.2, 120.3, 113.7, 60.6, 40.9, 21.5, 20.9, 14.1; IR (KBr) ν (cm-1) 3065, 2980, 2927, 1711, 1645, 1594, 1572, 1494, 1474, 1448, 1372, 1276, 1219, 1173, 1133, 1092, 1020; MS (70 eV, EI) m/z (%) 509 (M+(37Cl), 30.06), 507 (M+(35Cl), 67.92), 278 (100); Anal. Calcd for C28H26ClNO4S: C, 66.20; H, 5.16; N, 2.76; Found: C, 66.14; H, 5.22; N, 2.67.
实施例4
按实施例1所述的方法,不同的是所用底物和试剂为:N对甲苯磺酰胺基保护的吲哚(80.5 mg, 0.3 mmol)和2-甲基-4-(4-溴苯基)-2,3联烯丁酸乙酯(101.4 mg, 0.36 mmol),三氟醋酸(1.5 mL),40oC反应15小时,得到产物2-甲基-4-(3-(N-对甲苯磺酰基)吲哚基)-4-(4-溴苯基)顺-2-丁烯酸乙酯95.5 mg,产率58%,产物为蜡状液体。
1H NMR (300 MHz, CDCl3) δ 7.94 (d, J = 8.4 Hz, 1 H), 7.74 (d, J = 8.4 Hz, 2 H), 7.38 (d, J = 8.4 Hz, 2 H), 7.32 (d, J = 0.9 Hz, 1 H), 7.30-7.19 (m, 3 H), 7.18-7.03 (m, 4 H), 6.22 (dd, J 1 = 10.2 Hz, J 2 = 1.2 Hz, 1 H), 5.95 (d, J = 9.9 Hz, 1 H), 4.19 (q, J = 7.1 Hz, 2 H), 2.35 (s, 3 H, CH3), 1.99 (d, J = 1.5 Hz, 3 H), 1.25 (t, J = 7.1 Hz, 3 H); 13C NMR (75 MHz, CDCl3 ) δ 167.4, 144.9, 140.9, 140.8, 135.5, 135.1, 131.7, 129.83, 129.78, 129.7, 128.3, 126.8, 124.8, 124.4, 123.5, 123.1, 120.7, 120.4, 113.7, 60.5, 40.8, 21.6, 20.9, 14.2; IR (neat) ν (cm-1) 2977, 2927, 2871, 1709, 1644, 1597, 1486, 1447, 1371, 1277, 1219, 1187, 1174, 1132, 1092, 1011; MS (70 eV, EI) m/z (%) 398 (M+-Ts(81Br), 100), 396 (M+-Ts(79Br), 100); Anal. Calcd for C28H26BrNO4S: C, 60.87; H, 4.74; N, 2.54; Found: C, 60.97; H, 4.89; N, 2.49.
实施例5
按实施例1所述的方法,不同的是所用底物和试剂为:N对甲苯磺酰胺基保护的吲哚(80.2 mg, 0.3 mmol)和2-甲基-4-(4-甲氧基苯基)-2,3联烯丁酸乙酯(105.9 mg, 0.46 mmol),三氟醋酸(1.5 mL),5oC反应0.5小时,得到产物2-甲基-4-(3-(N-对甲苯磺酰基)吲哚基)-4-(4-甲氧基苯基)顺-2-丁烯酸乙酯101.9 mg,产率68%,产物为白色固体。
1H NMR (300 MHz, CDCl3) δ 7.94 (d, J = 8.4 Hz, 1 H), 7.74 (d, J = 8.4 Hz, 2 H), 7.31 (d, J = 1.5 Hz, 1 H), 7.29-7.04 (m, 7 H), 6.86-6.76 (m, 2 H), 6.25 (dd, J 1 = 10.4 Hz, J 2 = 1.4 Hz, 1 H), 5.92 (d, J = 10.5 Hz, 1 H), 4.19 (q, J = 7.1 Hz, 2 H), 3.77 (s, 3 H), 2.35 (s , 3 H, CH3), 1.98 (d, J = 1.5 Hz, 3 H), 1.25 (t, J = 7.1 Hz, 3 H); 13C NMR (75 MHz, CDCl3 ) δ 167.6, 158.3, 144.8, 141.8, 135.5, 135.1, 133.9, 130.1, 129.8, 128.9, 127.3, 126.8, 125.3, 124.6, 123.4, 123.0, 120.6, 114.0, 113.6, 60.4, 55.2, 40.5, 21.6, 20.9, 14.2; IR (KBr) ν (cm-1) 3072, 3030, 2971, 2931, 2836, 1703, 1644, 1609, 1504, 1447, 1364, 1249, 1218, 1132, 1033; MS (70 eV, EI) m/z (%) 503 (M+, 59.41), 430 (100); Anal. Calcd for C29H29NO5S: C, 69.16; H, 5.80; N, 2.78; Found: C, 69.05; H, 5.87, N, 3.03.
实施例6
按实施例1所述的方法,不同的是所用底物和试剂为:N对甲苯磺酰胺基保护的吲哚(80.3 mg, 0.3 mmol)和2-甲基-4-(4-甲基苯基)-2,3联烯丁酸乙酯(98.2 mg, 0.45 mmol),三氟醋酸(1.5 mL),5oC反应0.5小时,得到产物2-甲基-4-(3-(N-对甲苯磺酰基)吲哚基)-4-(4-甲基苯基)顺-2-丁烯酸乙酯105.5 mg,产率73%,产物为液体。
1H NMR (300 MHz, CDCl3) δ 7.94 (d, J = 8.4 Hz, 1 H), 7.73 (d, J = 8.1 Hz, 2 H), 7.34 (s, 1 H), 7.29-7.15 (m, 4 H), 7.15-6.98 (m, 5 H), 6.28 (dd, J 1 = 10.2, J 2 = 1.4 Hz, 1H), 5.96 (d, J = 10.2 Hz, 1 H), 4.18 (q, J = 7.0 Hz, 2 H), 2.30 (s, 3 H), 2.29 (s, 3 H, CH3), 1.98 (s, 3 H), 1.23 (t, J = 7.1 Hz, 3 H); 13C NMR (75 MHz, CDCl3 ) δ 167.5, 144.7, 141.7, 138.7, 136.2, 135.4, 135.0, 130.1, 129.7, 129.3, 127.7, 127.4, 126.7, 125.2, 124.5, 123.3, 123.0, 120.5, 113.5, 60.3, 40.9, 21.4, 20.95, 20.88, 14.1; IR (neat) ν (cm-1) 3045, 3021, 2980, 2925, 1710, 1644, 1597, 1511, 1447, 1371, 1275, 1220, 1187, 1175, 1132, 1092, 1021; MS (70 eV, EI) m/z (%) 487 (M+, 2.79), 332 (M+-Ts, 81.03), 258 (100); Anal. Calcd for C29H29NO4S: C, 71.43; H, 5.99; N, 2.87; Found: C, 71.27; H, 6.19; N, 2.69.
实施例7
按实施例1所述的方法,不同的是所用底物和试剂为:N对甲苯磺酰胺基保护的吲哚(81.9 mg, 0.3 mmol)和2-甲基-4-(1-萘基)-2,3联烯丁酸乙酯(113.1 mg, 0.45 mmol),三氟醋酸(1.5 mL),5oC反应2.5小时,得到产物2-甲基-4-(3-(N-对甲苯磺酰基)吲哚基)-4-(1-萘基)顺-2-丁烯酸乙酯122.8 mg,产率78%,产物为白色固体。
1H NMR (300 MHz, CDCl3) δ 8.07 (d, J = 8.4 Hz, 1 H), 7.95 (d, J = 8.4 Hz, 1 H), 7.87 (d, J = 7.5 Hz, 1 H), 7.75 (d, J = 8.1 Hz, 1 H), 7.61 (d, J = 8.4 Hz, 2 H), 7.54-7.37 (m, 2 H), 7.37-7.29 (m, 1 H), 7.29-7.11 (m, 6 H), 7.10-7.02 (m, 1 H), 6.76 (d, J = 9.9 Hz, 1 H), 6.35 (dd, J 1 = 9.3 Hz, J 2 = 1.2 Hz, 1 H), 4.15 (q, J = 7.1 Hz, 2 H), 2.32 (s, 3 H, CH3), 2.01 (d, J = 0.6 Hz, 3 H), 1.13 (t, J = 7.1 Hz, 3 H); 13C NMR (75 MHz, CDCl3 ) δ 167.5, 144.6, 142.1, 138.1, 135.5, 134.9, 134.0, 131.6, 130.2, 129.7, 128.8, 128.4, 127.6, 126.7, 126.1, 126.0, 125.5, 125.0, 124.7, 124.2, 123.7, 123.2, 120.3, 113.7, 60.5, 37.5, 21.5, 20.9, 14.0; IR (KBr) ν (cm-1) 3066, 2971, 2927, 1715, 1643, 1597, 1509, 1447, 1367, 1275, 1221, 1188, 1175, 1130, 1092, 1020; MS (70 eV, EI) m/z (%) 523 (M+, 31.36), 266 (100); Anal. Calcd for C32H29NO4S: C, 73.40; H, 5.58; N, 2.67; Found: C, 73.24; H, 5. 84; N, 2.86.
实施例8
按实施例1所述的方法,不同的是所用底物和试剂为:N对甲苯磺酰胺基保护的吲哚(81.1 mg, 0.3 mmol)和2-甲基-4-苯基-2,3联烯丁酸乙酯(71.9 mg, 0.36 mmol),三氟醋酸(1.5 mL),10oC反应13小时,得到产物2-甲基-4-(3-(N-对甲苯磺酰基)吲哚基)-4-苯基顺-2-丁烯酸乙酯90.0 mg,产率64%,产物为液体。
1H NMR (300 MHz, CDCl3) δ 7.95 (d, J = 8.1 Hz, 1 H), 7.77-7.70 (m, 2 H), 7.35 (d, J = 0.9 Hz, 1 H), 7.32-7.16 (m, 9 H), 7.12-7.03 (m, 1 H), 6.29 (dd, J 1 = 10.2 Hz, J 2 = 1.5 Hz, 1 H), 5.99 (d, J = 10.2 Hz, 1 H), 4.19 (q, J = 7.2 Hz, 2 H), 2.31 (s, 3 H, CH3), 1.99 (d, J = 1.2 Hz, 3 H), 1.23 (t, J = 7.1 Hz, 3 H); 13C NMR (75 MHz, CDCl3 ) δ 167.5, 144.7, 141.8, 141.4, 135.5, 135.0, 130.0, 129.7, 128.6, 127.9, 127.7, 126.7, 125.0, 124.6, 123.5, 123.0, 120.5, 113.6, 60.4, 41.3, 21.4, 20.9, 14.1; IR (neat) ν (cm-1) 3063, 3028, 2977, 2928, 2868, 1712, 1645, 1598, 1494, 1447, 1372, 1276, 1219, 1174, 1131, 1092, 1021; MS (70 eV, EI) m/z (%) 473 (M+, 34.41), 244 (100); Anal. Calcd for C28H27NO4S: C, 71.01; H, 5.75; N, 2.96; Found: C, 70.70; H, 5. 88; N, 3.04.
实施例9
按实施例1所述的方法,不同的是所用底物和试剂为:N对甲苯磺酰胺基保护的吲哚(81.5 mg, 0.3 mmol)和2-乙基-4-苯基-2,3联烯丁酸乙酯(79.4 mg, 0.37 mmol),三氟醋酸(1.5 mL),10oC反应24小时,得到产物2-乙基-4-(3-(N-对甲苯磺酰基)吲哚基)-4-苯基顺-2-丁烯酸乙酯85.9 mg,产率59%,产物为液体。
1H NMR (300 MHz, CDCl3) δ 7.98-7.91 (m, 1 H), 7.76-7.68 (m, 2 H), 7.32-7.30 (m, 1 H), 7.32-7.16 (m, 9 H), 7.12-7.04 (m, 1 H), 6.19 (dt, J 1 = 10.2 Hz, J 2 = 1.2 Hz, 1 H), 5.84 (d, J = 10.2 Hz, 1 H), 4.19 (q, J = 7.0 Hz, 2 H), 2.42-2.28 (m, 5 H), 1.22 (t, J = 7.1 Hz, 3 H), 1.07 (t, J = 7.4 Hz, 3 H); 13C NMR (75 MHz, CDCl3 ) δ 167.7, 144.7, 141.9, 139.0, 135.5, 135.1, 134.3, 130.1, 129.7, 128.6, 127.9, 126.7, 125.2, 124.6, 123.6, 123.0, 120.5, 113.6, 60.3, 41.3, 27.7, 21.5, 14.1, 13.5; IR (neat) ν (cm-1) 3062, 3028, 2973, 2933, 2874, 1709, 1641, 1599, 1494, 1448, 1372, 1276, 1217, 1188, 1175, 1132, 1094, 1020; MS (70 eV, EI) m/z (%) 487 (M+, 0.95), 332 (M+-Ts, 100), 286 (M++1-Ts-OEt, 100), 258 (M++1-Ts-COOEt, 100); Anal. Calcd for C29H29NO4S: C, 71.43; H, 5.99; N, 2.87; Found: C, 71.57; H, 5.91; N, 2.85.
实施例10
按实施例1所述的方法,不同的是所用底物和试剂为:N对甲苯磺酰胺基保护的吲哚(80.3 mg, 0.3 mmol)和2-烯丙基-4-苯基-2,3联烯丁酸乙酯(83.3 mg, 0.37 mmol),三氟醋酸(1.5 mL),40oC反应15小时,得到产物2-烯丙基-4-(3-(N-对甲苯磺酰基)吲哚基)-4-苯基顺-2-丁烯酸乙酯61.7 mg,产率42%,产物为液体。
1H NMR (300 MHz, CDCl3) δ 7.86 (d, J = 8.4 Hz, 1 H), 7.64 (d, J = 8.1 Hz, 2 H), 7.23 (d, J = 0.9 Hz, 1 H), 7.20-7.06 (m, 9 H), 7.04-6.95 (m, 1 H), 6.19 (d, J = 10.2 Hz, 1 H), 5.85 (d, J = 10.5 Hz, 1 H), 5.82-5.67 (m, 1 H), 5.04-4.98 (m, 1 H), 4.97-4.93 (m, 1 H), 4.10 (q, J = 7.1 Hz, 2 H), 3.05-2.95 (m, 2 H), 2.24 (s, 3 H, CH3), 1.13 (t, J = 7.2 Hz, 3 H); 13C NMR (75 MHz, CDCl3 ) δ 167.1, 144.8, 141.6, 141.5, 135.5, 135.4, 135.0, 130.7, 130.0, 129.7, 128.6, 127.9, 126.8, 126.7, 125.0, 124.6, 123.5, 123.0, 120.4, 116.7, 113.6, 60.5, 41.3, 38.3, 21.5, 14.1; IR (neat) ν (cm-1) 3063, 3028, 2980, 2925, 1712, 1639, 1599, 1494, 1448, 1372, 1276, 1214, 1174, 1132, 1093, 1020; MS (70 eV, EI) m/z (%) 499 (M+, 25.68), 303 (100); HRMS Calcd for C30H29NO4S (M+): 499.1817; Found: 499.1816.
实施例11
按实施例1所述的方法,不同的是所用底物和试剂为:N乙酰基保护的吲哚(48.1 mg, 0.3 mmol)和2-甲基-4-(4-氟苯基)-2,3联烯丁酸乙酯(80.1 mg, 0.36 mmol),三氟醋酸(1.5 mL),20oC反应10小时,得到产物2-甲基-4-(3-(N-乙酰基)吲哚基)-4-(4-氟苯基)顺-2-丁烯酸乙酯65.4 mg,产率57%,产物为白色固体。
1H NMR (300 MHz, CDCl3) δ 8.51-8.32 (m, 1 H), 7.42-7.09 (m, 6 H), 7.05-6.83 (m, 2 H), 6.30 (d, J = 10.5 Hz, 1 H), 6.03 (d, J = 9.9 Hz, 1 H), 4.23 (q, J = 7.0 Hz, 2 H), 2.60 (s, 3 H), 2.01 (s, 3 H), 1.29 (t, J = 7.1 Hz, 3 H); 13C NMR (75 MHz, CDCl3 ) δ 168.3, 167.5, 163.2, 160.0, 141.2, 137.6 (d, J = 3.6 Hz), 136.2, 129.42 (d, J = 7.5 Hz), 129.41, 128.0, 125.3, 124.5, 122.5, 121.7 (d, J = 256.5 Hz), 116.5, 115.4 (d, J = 21.8 Hz), 60.5, 40.6, 24.0, 20.9, 14.2; 19F NMR (282 MHz) δ -116.0; IR (KBr) ν (cm-1) 2981, 2929, 1709, 1644, 1604, 1569, 1507, 1451, 1383, 1346, 1331, 1299, 1217, 1158, 1135, 1096, 1015; MS (70 eV, EI) m/z (%) 379 (M+, 46.99), 264 (100); Anal. Calcd for C23H22FNO3: C, 72.81; H, 5.84; N, 3.69; Found: C, 73.12; H, 5.75; N, 3.60.
实施例12
按实施例1所述的方法,不同的是所用底物和试剂为:N乙酰基保护的吲哚(49.9 mg, 0.31 mmol)和2-甲基-4-苯基-2,3联烯丁酸乙酯(74.6 mg, 0.37mmol),三氟醋酸(1.5 mL),10oC反应15小时,得到产物2-甲基-4-(3-(N-乙酰基)吲哚基)-4-苯基顺-2-丁烯酸乙酯69.5 mg,产率61%,产物为白色固体。
1H NMR (300 MHz, CDCl3) δ 8.49-8.34 (m, 1 H), 7.36-7.10 (m, 9 H), 6.33 (dq, J 1 = 10.4 Hz, J 2 = 1.4 Hz, 1 H), 6.04 (dd, J 1 = 10.2 Hz, J 2 = 0.9 Hz, 1 H), 4.23 (q, J = 7.1 Hz, 2 H), 2.61 (s, 3 H), 2.01 (d, J = 1.2 Hz, 3 H), 1.29 (t, J = 7.2 Hz, 3 H); 13C NMR (75 MHz, CDCl3 ) δ 168.4, 167.6, 142.0, 141.5, 136.2, 129.7, 128.7, 128.0, 127.9, 126.8, 125.2, 124.8, 123.4, 122.5, 120.1, 116.5, 60.5, 41.4, 24.1, 20.9, 14.2; IR (KBr) ν (cm-1) 3027, 2973, 2927, 2853, 1708, 1639, 1603, 1451, 1382, 1347, 1331, 1213, 1134, 1019; MS (70 eV, EI) m/z (%) 361 (M+, 57.40), 246 (100); Anal. Calcd for C23H23NO3: C, 76.43; H, 6.41; N, 3.88; Found: C, 76.19; H, 6.51; N, 4.26.
实例13
按实施例1所述的方法,不同的是所用底物和试剂为:N对甲苯磺酰基保护的吲哚(80.6 mg, 0.30 mmol)和2-甲基-4-(4-氯苯基)-2,3联烯丁酸乙酯(86.1 mg, 0.36mmol),三氟醋酸(1.5 mL),60oC反应12小时,得到产物2-甲基-4-(3-(N-对甲苯磺酰基)吲哚基)-4-(4-氯苯基)反-2-丁烯酸乙酯99.1 mg,产率66%,产物为白色固体。
1H NMR (300 MHz, CDCl3) δ 7.97 (d, J = 8.1 Hz, 1 H), 7.79-7.72 (m, 2 H), 7.35 (d, J = 1.2 Hz, 1 H), 7.31-7.19 (m, 5 H), 7.16-7.03 (m, 5 H), 5.07 (d, J = 9.9 Hz, 1 H), 4.22 (q, J = 7.0 Hz, 2 H), 2.33 (s, 3 H, CH3), 1.96 (d, J = 1.5 Hz, 3 H), 1.30 (t, J = 7.1 Hz, 3 H); 13C NMR (75 MHz, CDCl3 ) δ 167.6, 145.0, 140.6, 139.4, 135.5, 134.9, 132.8, 129.8, 129.5, 129.2, 129.1, 128.9, 126.7, 124.9, 123.7, 123.2, 123.1, 120.1, 113.7, 60.9, 41.2, 21.5, 14.2, 12.8; IR (KBr) ν (cm-1) 2981, 2928, 1710, 1647, 1597, 1490, 1447, 1371, 1276, 1225, 1188, 1175, 1123, 1093, 1015; MS (70 eV, EI) m/z (%) 507 (M+, 60.73), 278 (100); Anal. Calcd for C28H26ClNO4S: C, 66.20; H, 5.16; N, 2.76; Found: C, 66.03; H, 4.88; N, 2.48.
实例14
按实施例1所述的方法,不同的是所用底物和试剂为:N对甲苯磺酰基保护的吲哚(80.7 mg, 0.30 mmol)和2-甲基-4-(4-甲氧基苯基)-2,3联烯丁酸乙酯(103.9 mg, 0.45mmol),三氟醋酸(1.5 mL),40oC反应15小时,得到产物2-甲基-4-(3-(N-对甲苯磺酰基)吲哚基)-4-(4-甲氧基苯基)反-2-丁烯酸乙酯88.4 mg,产率59%,产物为白色固体。
1H NMR (300 MHz, CDCl3) δ 7.96 (d, J = 8.1 Hz, 1 H), 7.75 (d, J = 8.4 Hz, 2 H), 7.35-7.19 (m, 4 H), 7.18-7.03 (m, 5 H), 6.87-6.74 (m, 2 H), 5.03 (d, J = 9.6 Hz, 1 H), 4.21 (q, J = 7.1 Hz, 2 H), 3.78 (s, 3 H), 2.35 (s, 3 H, CH3), 1.96 (d, J = 1.2 Hz, 3 H), 1.31 (t, J = 7.1 Hz, 3 H); 13C NMR (75 MHz, CDCl3 ) δ 167.8, 158.5, 144.8, 141.6, 135.5, 135.0, 132.9, 129.8, 128.8, 128.2, 126.7, 124.7, 124.1, 123.6, 123.0, 120.3, 114.1, 113.7, 60.7, 55.1, 41.0, 21.5, 14.2, 12.7; IR (KBr) ν (cm-1) 2980, 2932, 2836, 1709, 1645, 1608, 1510, 1447, 1370, 1301, 1276, 1251, 1174, 1123, 1094, 1033; MS (70 eV, EI) m/z (%) 503 (M+, 5.82), 348 (100); Anal. Calcd for C29H29NO5S: C, 69.16; H, 5.80; N, 2.78; Found: C, 69.16; H, 5. 88; N, 3.09.
实例15
按实施例1所述的方法,不同的是所用底物和试剂为:N对甲苯磺酰基保护的吲哚(82.1 mg, 0.30 mmol)和2-甲基-4-(4-甲基苯基)-2,3联烯丁酸乙酯(98.1 mg, 0.45mmol),三氟醋酸(1.5 mL),40oC反应12小时,得到产物2-甲基-4-(3-(N-对甲苯磺酰基)吲哚基)-4-(4-甲基苯基)反-2-丁烯酸乙酯95.4mg,产率65%,产物为白色固体。
1H NMR (300 MHz, CDCl3) δ 7.96 (d, J = 8.1 Hz, 1 H), 7.74 (d, J = 8.4 Hz, 2 H), 7.34 (d, J = 0.9 Hz, 1 H), 7.30-7.02 (m, 10 H), 5.05 (d, J = 9.9 Hz, 1 H), 4.20 (q, J = 7.1 Hz, 2 H), 2.33 (s, 3 H, CH3), 2.30 (s, 3 H), 1.96 (d, J = 1.2 Hz, 3 H), 1.29 (t, J = 7.1 Hz, 3 H); 13C NMR (75 MHz, CDCl3 ) δ 167.8, 144.8, 141.5, 137.8, 136.6, 135.5, 135.0, 129.84, 129.77, 129.5, 128.4, 127.7, 126.7, 124.7, 124.0, 123.6, 123.1, 120.3, 113.7, 60.7, 41.5, 21.5, 21.0, 14.2, 12.7; IR (neat) ν (cm-1) 2981, 2925, 1709, 1646, 1597, 1511, 1494, 1447, 1370, 1276, 1226, 1188, 1175, 1130, 1095, 1021; MS (70 eV, EI) m/z (%) 487 (M+, 2.94), 332 (M+-Ts, 82.82), 258 (100); Anal. Calcd for C29H29NO4S: C, 71.43; H, 5.99; N, 2.87; Found: C, 71.48; H, 6.04; N, 2.76.
实例16
按实施例1所述的方法,不同的是所用底物和试剂为:N对甲苯磺酰基保护的吲哚(83.1 mg, 0.31 mmol)和2-甲基-4-(1-萘基)-2,3联烯丁酸乙酯(113.1 mg, 0.45mmol),三氟醋酸(1.5 mL),80oC反应3小时,得到产物2-甲基-4-(3-(N-对甲苯磺酰基)吲哚基)-4-(1-萘基)反-2-丁烯酸乙酯86.3mg,产率55%,产物为黄色固体。
1H NMR (300 MHz, CDCl3) δ 7.98 (d, J = 8.4 Hz, 1 H), 7.90 (d, J = 8.4 Hz, 2 H), 7.79 (d, J = 8.1 Hz, 1 H), 7.64 (d, J = 8.1 Hz, 2 H), 7.55-7.47 (m, 1 H), 7.46-7.39 (m, 1 H), 7.39-7.32 (m, 1 H), 7.32-7.03 (m, 8 H), 5.78 (d, J = 9.3 Hz, 1 H), 4.20 (q, J = 7.1 Hz, 2 H), 2.36 (s, 3 H, CH3), 2.00 (s, 3 H), 1.29 (t, J = 7.2 Hz, 3 H); 13C NMR (75 MHz, CDCl3 ) δ 167.7, 144.8, 142.0, 136.7, 135.6, 134.9, 134.0, 131.4, 130.0, 129.8, 129.4, 129.1, 127.9, 126.7, 126.2, 125.62, 125.58, 124.9, 124.6, 124.3, 123.24, 123.16, 120.1, 113.9, 60.9, 38.1, 21.5, 14.2, 13.0; IR (KBr) ν (cm-1) 3045, 2981, 2925, 1708, 1642, 1597, 1447, 1370, 1273, 1235, 1188, 1175, 1128, 1093, 1020; MS (70 eV, EI) m/z (%) 523 (M+, 2.64), 368 (100); Anal. Calcd for C32H29NO4S: C, 73.40; H, 5.58; N, 2.67; Found: C, 73.48; H, 5. 63; N, 2.71.
实例17
按实施例1所述的方法,不同的是所用底物和试剂为:N对甲苯磺酰基保护的吲哚(82.0 mg, 0.30 mmol)和2-甲基-4-苯基-2,3联烯丁酸乙酯(71.4 mg, 0.36 mmol),三氟醋酸(1.5 mL),80oC反应11小时,得到产物2-甲基-4-(3-(N-对甲苯磺酰基)吲哚基)-4-苯基反-2-丁烯酸乙酯82.5mg,产率58%,产物为白色固体。
1H NMR (300 MHz, CDCl3) δ 7.96 (d, J = 8.4 Hz, 1 H), 7.74 (d, J = 8.1 Hz, 2 H), 7.34 (d, J = 0.9 Hz, 1 H), 7.32-7.05 (m, 11 H), 5.09 (d, J = 9.6 Hz, 1 H), 4.22 (q, J = 7.1 Hz, 2 H), 2.35 (s, 3 H, CH3), 1.97 (d, J = 1.5 Hz, 3 H), 1.30 (t, J = 7.2 Hz, 3 H); 13C NMR (75 MHz, CDCl3 ) δ 167.8, 144.9, 141.4, 140.9, 135.6, 135.0, 129.8, 128.8, 128.7, 127.9, 127.1, 126.8, 124.8, 123.8, 123.1, 120.3, 113.8, 60.9, 41.9, 21.6, 14.3, 12.8; IR (KBr) ν (cm-1) 3063, 3028, 2981, 2928, 1763, 1712, 1646, 1598, 1494, 1447, 1371, 1276, 1226, 1188, 1174, 1123, 1094, 1021; MS (70 eV, EI) m/z (%) 473 (M+, 41.66), 244 (100); Anal. Calcd for C28H27NO4S: C, 71.01; H, 5.75; N, 2.96; Found: C, 70.70; H, 5. 98; N, 2.90.
实例18
按实施例1所述的方法,不同的是所用底物和试剂为:N乙酰基保护的吲哚(46.2 mg, 0.29 mmol)和2-甲基-4-(4-甲氧基苯基)-2,3联烯丁酸乙酯(104.0 mg, 0.45 mmol),三氟醋酸(1.5 mL),40oC反应20小时,得到产物2-甲基-4-(3-(N-乙酰基)吲哚基)-4-(4-甲氧基苯基)反-2-丁烯酸乙酯59.7mg,产率52%,产物为液体。
1H NMR (300 MHz, CDCl3) δ 8.52-8.34 (m, 1 H), 7.36-7.29 (m, 1 H), 7.26-7.06 (m, 6 H), 6.91-6.78 (m, 2 H), 5.11 (d, J = 10.2 Hz, 1 H), 4.21 (q, J = 7.1 Hz, 2 H), 3.79 (s, 3 H), 2.61 (s, 3 H, CH3), 2.02 (d, J = 1.5 Hz, 3 H), 1.29 (t, J = 7.1 Hz, 3 H); 13C NMR (75 MHz, CDCl3 ) δ 168.4, 167.9, 158.5, 141.7, 136.3, 133.0, 129.5, 128.9, 128.2, 125.3, 124.0, 123.4, 122.6, 119.8, 116.6, 114.2, 60.8, 55.2, 41.0, 24.1, 14.2, 12.8; IR (neat) ν (cm-1) 2980, 2933, 2836, 1708, 1646, 1608, 1583, 1510, 1451, 1382, 1346, 1331, 1248, 1215, 1177, 1121, 1109, 1033; MS (70 eV, EI) m/z (%) 391 (M+, 45.43), 303 (100); HRMS Calcd for C24H25NO4 (M+): 391.1784; Found: 391.1783.
实例19
按实施例1所述的方法,不同的是所用底物和试剂为:5-甲基-N对甲苯磺酰基保护的吲哚(85.7 mg, 0.30 mmol)和2-甲基-4-苯基-2,3联烯丁酸乙酯(72.1 mg, 0.36 mmol),三氟醋酸(1.5 mL),10oC反应11小时,得到产物2-甲基-4-(3-(5-甲基-N-乙酰基)吲哚基)-4-苯基顺-2-丁烯酸乙酯84.9 mg,产率58%,产物为液体。
1H NMR (300 MHz, CDCl3) δ 7.83 (d, J = 8.4 Hz, 1 H), 7.71 (d, J = 8.4 Hz, 2 H), 7.37-7.13 (m, 8 H), 7.06 (dd, J 1 = 8.6 Hz, J 2 = 1.4 Hz, 1 H), 6.98 (s, 1 H), 6.28 (dd, J 1 = 10.2 Hz, J 2 = 1.5 Hz, 1 H), 5.97 (d, J = 10.5 Hz, 1 H), 4.19 (q, J = 7.1 Hz, 2 H), 2.30 (s, 3 H), 2.26 (s, 3 H, CH3), 1.98 (d, J = 1.5 Hz, 3 H), 1.24 (t, J = 7.2 Hz, 3 H); 13C NMR (75 MHz, CDCl3 ) δ 167.5, 144.6, 141.9, 141.5, 135.0, 133.7, 132.6, 130.3, 129.7, 128.5, 127.8, 127.5, 126.6, 126.1, 124.9, 123.6, 120.2, 113.3, 60.4, 41.2, 21.4, 21.2, 20.9, 14.1; IR (neat) ν (cm-1) 3028, 2980, 2926, 1710, 1644, 1597, 1493, 1454, 1371, 1297, 1272, 1220, 1173, 1127, 1094, 1024; MS (70 eV, EI) m/z (%) 487 (M+, 62.62), 258 (100); HRMS Calcd for C29H29NO4S (M+): 487.1817; Found: 487.1831.
实例20
按实施例1所述的方法,不同的是所用底物和试剂为:5-甲基-N对甲苯磺酰基保护的吲哚(88.1 mg, 0.31 mmol)和2-甲基-4-苯基-2,3联烯丁酸乙酯(72.9 mg, 0.36 mmol),三氟醋酸(1.5 mL),60oC反应20小时,得到产物2-甲基-4-(3-(5-甲基-N-乙酰基)吲哚基)-4-苯基反-2-丁烯酸乙酯84.3 mg,产率56%,产物为液体。
1H NMR (300 MHz, CDCl3) δ 7.85 (d, J = 8.4 Hz, 1 H), 7.72 (d, J = 8.4 Hz, 2 H), 7.37-7.01 (m, 10 H), 6.94 (s, 1 H), 5.07 (d, J = 9.6 Hz, 1 H), 4.21 (q, J = 7.1 Hz, 2 H), 2.32 (s, 3 H), 2.27 (s, 3 H, CH3), 1.96 (d, J = 1.2 Hz, 3 H), 1.29 (t, J = 7.2 Hz, 3 H); 13C NMR (75 MHz, CDCl3 ) δ 167.8, 144.7, 141.5, 141.0, 134.9, 133.8, 132.8, 130.0, 129.7, 128.7, 128.5, 127.8, 126.9, 126.6, 126.2, 123.9, 123.7, 120.0, 113.4, 60.8, 41.8, 21.4, 21.3, 14.2, 12.7; IR (neat) ν (cm-1) 3028, 2981, 2925, 1709, 1647, 1597, 1493, 1454, 1370, 1275, 1228, 1173, 1150, 1124, 1094, 1032; MS (70 eV, EI) m/z (%) 487 (M+, 61.24), 258 (100); HRMS Calcd for C29H29NO4S (M+): 487.1817; Found: 487.1826.
实例21
按实施例1所述的方法,不同的是所用底物和试剂为:5-溴-N对甲苯磺酰基保护的吲哚(104.8 mg, 0.30 mmol)和2-甲基-4-苯基-2,3联烯丁酸乙酯(71.9 mg, 0.36 mmol),三氟醋酸(1.5 mL),10oC反应12小时,得到产物2-甲基-4-(3-(5-溴-N-乙酰基)吲哚基)-4-苯基顺-2-丁烯酸乙酯116.0 mg,产率70%,产物为白色固体。
1H NMR (300 MHz, CDCl3) δ 7.88-7.77 (m, 1 H), 7.71 (d, J = 8.4 Hz, 2 H), 7.41-7.31 (m, 3 H), 7.31-7.09 (m, 7 H), 6.25 (dd, J 1 = 10.2 Hz, J 2 = 1.5 Hz, 1 H), 5.95 (d, J = 10.2 Hz, 1 H), 4.20 (q, J = 7.1 Hz, 2 H), 2.33 (s, 3 H, CH3), 1.99 (d, J = 1.2 Hz, 3 H), 1.24 (t, J = 7.2 Hz, 3 H); 13C NMR (75 MHz, CDCl3 ) δ 167.4, 145.1, 141.4, 141.0, 134.7, 134.2, 131.8, 129.8, 128.7, 128.0, 127.8, 127.6, 126.9, 126.7, 124.7, 124.5, 123.1, 116.6, 115.0, 60.5, 41.1, 21.5, 20.8, 14.1; IR (KBr) ν (cm-1) 3063, 3028, 2980, 2927, 1710, 1645, 1597, 1493, 1443, 1374, 1295, 1258, 1219, 1174, 1126, 1024; MS (70 eV, EI) m/z (%) 553 (M+(81Br), 1.88), (M+ (79Br), 1.77), 91 (100); Anal. Calcd for C28H26BrNO4S: C, 60.87; H, 4.74; N, 2.54; Found: C, 60.84; H, 4.74, N, 2.60.
实例22
按实施例1所述的方法,不同的是所用底物和试剂为:5-溴-N对甲苯磺酰基保护的吲哚(104.1 mg, 0.30 mmol)和2-甲基-4-苯基-2,3联烯丁酸乙酯(72.1 mg, 0.36 mmol),三氟醋酸(1.5 mL),60oC反应20小时,得到产物2-甲基-4-(3-(5-溴-N-乙酰基)吲哚基)-4-苯基反-2-丁烯酸乙酯87.4 mg,产率53%,产物为白色固体。
1H NMR (300 MHz, CDCl3) δ 7.84 (d, J = 8.7 Hz, 1 H), 7.77-7.62 (m, 2 H), 7.40-7.33 (m, 2 H), 7.32-7.19 (m, 6 H), 7.19-7.12 (m, 2 H), 7.08 (dd, J 1 = 9.8 Hz, J 2 = 1.7 Hz, 1 H), 5.03 (d, J = 9.6 Hz, 1 H), 4.22 (q, J = 7.1 Hz, 2 H), 2.35 (s, 3 H, CH3), 1.95 (d, J = 1.5 Hz, 3 H), 1.30 (t, J = 7.2 Hz, 3 H); 13C NMR (75 MHz, CDCl3 ) δ 167.6, 145.2, 140.9, 140.5, 134.6, 134.3, 131.5, 129.9, 129.0, 128.9, 127.8, 127.2, 126.7, 124.9, 123.2, 122.9, 116.7, 115.2, 60.9, 41.6, 21.5, 14.2, 12.8; IR (KBr) ν (cm-1) 3087, 3063, 3028, 2981, 2927, 1710, 1648, 1597, 1493, 1443, 1373, 1281, 1227, 1174, 1125, 1096, 1031; MS (70 eV, EI) m/z (%) 553 (M+(81Br), 0.07), (M+ (79Br), 0.07), 91 (100); Anal. Calcd for C28H26BrNO4S: C, 60.87; H, 4.74; N, 2.54; Found: C, 61.04; H, 5.23; N, 2.28.
实例23
按实施例1所述的方法,不同的是所用底物和试剂为:5-甲氧基-N对甲苯磺酰基保护的吲哚(89.6 mg, 0.30 mmol)和2-甲基-4-苯基-2,3联烯丁酸乙酯(72.5 mg, 0.36 mmol),三氟醋酸(1.5 mL),40oC反应7小时,得到产物2-甲基-4-(3-(5-甲氧基-N-乙酰基)吲哚基)-4-苯基顺-2-丁烯酸乙酯77.3 mg,产率52%,产物为白色固体。
1H NMR (300 MHz, CDCl3) δ 7.83 (d, J = 9.0 Hz, 1 H), 7.69 (d, J = 8.1 Hz, 2 H), 7.37-7.13 (m, 8 H), 6.85 (dd, J 1 =8.9 Hz, J 2 = 2.6 Hz, 1 H), 6.61 (d, J = 2.1 Hz, 1 H), 6.26 (dd, J 1 = 10.4 Hz, J 2 = 1.4 Hz, 1 H), 5.92 (d, J = 10.2 Hz, 1 H), 4.19 (q, J = 7.2 Hz, 2 H), 3.62 (s, 3 H), 2.32 (s, 3 H), 1.99 (d, J = 1.2 Hz, 3 H), 1.24 (t, J = 7.2 Hz, 3 H); 13C NMR (75 MHz, CDCl3 ) δ 167.5, 156.0, 144.6, 141.7, 141.3, 135.0, 131.1, 130.2, 129.7, 128.6, 127.9, 127.7, 126.8, 126.6, 125.2, 124.3, 114.5, 113.4, 103.1, 60.4, 55.3, 41.4, 21.5, 20.9, 14.1; IR (KBr) ν (cm-1) 3085, 3062, 3028, 2981, 2958, 2931, 2835, 1711, 1644, 1611, 1597, 1492, 1472, 1449, 1370, 1280, 1219, 1173, 1135, 1093, 1033; MS (70 eV, EI) m/z (%) 503 (M+, 93.86), 274 (100); Anal. Calcd for C29H29NO5S: C, 69.16; H, 5.80; N, 2.78; Found: C, 69.11; H, 5.79, N, 2.86.
Claims (4)
1.一种合成各种取代顺式或反式的2-烷基-4-吲哚基-4-芳基-2-丁烯酸乙酯类化合物的方法,其特征是通过2,3-联烯酸酯2在三氟醋酸和N吸电子基保护的吲哚1发生氢芳基化反应,生成顺式和反式的2-烷基-4-吲哚基-4-芳基-2-丁烯酸乙酯3类化合物,反应式如下:
R1 =对甲苯磺酰基、乙酰基;R2=各种取代的苯基;R3=氢、甲基、甲氧基和溴;R4=烷基;其步骤是:
(1)、2,3-联烯酸酯2和N吸电子基保护的吲哚1在三氟醋酸中发生分子间的氢芳基化反应生成2-烷基-4-吲哚基-4-芳基-2-丁烯酸乙酯类化合物3:在一定温度下,将原料N吸电子基保护的吲哚1加入反应瓶内,三氟醋酸润洗2,3-联烯酸酯2加入,反应一定时间;
(2)、步骤1反应完全后,加入10mL饱和碳酸氢钠溶液淬灭反应,乙醚萃取,饱和碳酸氢钠洗涤至中性,无水硫酸钠干燥,过滤,浓缩,快速柱层析,获得产物2-烷基-4-吲哚基-4-芳基-2-丁烯酸乙酯类化合物3。
2.根据权利要求1所述的合成2-烷基-4-吲哚基-4-芳基-2-丁烯酸乙酯类化合物的方法,其特征是所述的N吸电子基保护的吲哚1可以带有5-溴,5-甲基或5-甲氧基取代基。
3.根据权利要求1所述的合成2-烷基-4-吲哚基-4-芳基-2-丁烯酸乙酯类化合物的方法,其特征是所述的N吸电子基保护的吲哚1:2,3-联烯酸酯2: 三氟醋酸=0.3毫摩尔:0.36-0.45毫摩尔:1.5毫升。
4.根据权利要求1所述的合成2-烷基-4-吲哚基-4-芳基-2-丁烯酸乙酯类化合物的方法,其特征是所述的N吸电子基保护的吲哚1:2,3-联烯酸酯2=1:1.2-1.5。
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CN104529868A (zh) * | 2014-12-10 | 2015-04-22 | 中国农业大学 | 2,3-二取代吲哚啉类衍生物及其制备方法 |
CN108912036A (zh) * | 2018-08-24 | 2018-11-30 | 南昌航空大学 | 一种烯烃1,4-双官能团化反应制备烯丙基吲哚类化合物的方法 |
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《Journal of Organometallic Chemistry》 20090215 Kristina L. Toups et al Gold(I)-catalyzed hydroarylation of allenes with indoles 571-575 1-4 , 第694期 2 * |
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CN104529868A (zh) * | 2014-12-10 | 2015-04-22 | 中国农业大学 | 2,3-二取代吲哚啉类衍生物及其制备方法 |
CN104529868B (zh) * | 2014-12-10 | 2016-08-17 | 中国农业大学 | 2,3-二取代吲哚啉类衍生物及其制备方法 |
CN108912036A (zh) * | 2018-08-24 | 2018-11-30 | 南昌航空大学 | 一种烯烃1,4-双官能团化反应制备烯丙基吲哚类化合物的方法 |
CN108912036B (zh) * | 2018-08-24 | 2021-06-25 | 南昌航空大学 | 一种烯烃1,4-双官能团化反应制备烯丙基吲哚类化合物的方法 |
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