CN114105855A - 一种在吲哚c2位引入异戊烯基的方法 - Google Patents

一种在吲哚c2位引入异戊烯基的方法 Download PDF

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CN114105855A
CN114105855A CN202010895165.5A CN202010895165A CN114105855A CN 114105855 A CN114105855 A CN 114105855A CN 202010895165 A CN202010895165 A CN 202010895165A CN 114105855 A CN114105855 A CN 114105855A
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陈庆安
呼延成
季定纬
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Dalian Institute of Chemical Physics of CAS
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Abstract

本发明涉及一种在吲哚C2位引入异戊烯基的方法。具体为，以吲哚和2‑甲基‑3‑丁烯‑2‑醇为原料，在酸催化剂下，可以在吲哚C2位高选择性引入异戊烯基。本发明有以下优点，首次发展了催化方法，体系简单，无需当量的促进剂；异戊烯基前体商业可得，价格便宜；不需要对吲哚NH进行保护；副产物是水，体系绿色；色氨酸衍生物都是合适的底物，可以两步合成天然产物。

Description

一种在吲哚C2位引入异戊烯基的方法
技术领域
本发明涉及一种在吲哚C2位引入异戊烯基的方法。具体为，以吲哚和2-甲基-3-丁烯-2-醇为原料，在酸催化剂下，可以在吲哚C2位高选择性引入异戊烯基。本发明有以下优点，首次发展了催化方法，体系简单，无需当量的促进剂；异戊烯基前体商业可得，价格便宜；不需要对吲哚NH进行保护；副产物是水，体系绿色；色氨酸衍生物都是合适的底物，可以两步合成天然产物。
背景技术
异戊烯基取代的吲哚是一类重要的天然产物核心骨架(式1)，例如，从烟曲霉中分离的tryprostatins A和B是由L-色氨酸和L-脯氨酸组合而成，在吲哚骨架C2位连有异戊烯基。Terpeptin和Asterriquinone E分别是色氨酸、色醇衍生物，在C2位都连有异戊烯基。异戊烯基的存在可以增强化合物的亲脂性，使得化合物能够更容易地穿过脂溶性的细胞膜与靶蛋白相结合，从而有助于提升化合物本身所具有的活性。因此，探索简单、高效的催化体系来实现在吲哚骨架上引入异戊烯基，具有重要的研究意义。
Figure BDA0002658211380000011
式1.含有异戊烯基的吲哚生物碱
通过文献检索发现(式2)，Danishefsky课题组首先以吲哚和过量tBuOCl反应，然后再和BCl3、异戊烯基锡反应在C2位引入异戊烯基(S.J.Danishefsky et al,J.Am.Chem.Soc.,1996,118,12463；J.Am.Chem.Soc.,1999,121,11964.)。另一种方法是先和异戊烯基溴反应，在氮原子上连接异戊烯基，然后在过量BF3作用下，异戊烯基重排到C2位(A.M.Lobo et al,Tetrahedron Lett.,2000,41,3611；Org.Biomol.Chem.,2006,4,3966.)。这些方法所用的异戊烯基前体，大多都需要从相应的醇预先制备得到，增加了合成步骤，且和吲哚衍生物反应后还会产生对环境不利的废弃物。此外，这些过程都是化学计量的反应，需要加入过量的促进剂，通过分步法实现。
Figure BDA0002658211380000021
式2.文献中报道的吲哚C2位异戊烯基化反应
本专利首次开发出了一种催化方法实现吲哚的C2位高选择性引入异戊烯基。异戊烯基前体商业可得，价格便宜；不需要对吲哚NH进行保护；副产物是水，体系绿色；色氨酸衍生物都是合适的底物，可以两步合成天然产物。
发明内容
本发明目的，开发一种催化方法实现吲哚的C2位高选择性引入异戊烯基。
本发明是通过以下技术方案实现的：
吲哚(1或2或3)和2-甲基-3-丁烯-2-醇(4)在酸催化下，可以在C2位引入异戊烯基，反应式如下所示：
Figure BDA0002658211380000022
具体操作步骤如下：
在氩气或氮气气氛下，依次加入吲哚(1或2或3)和酸催化剂，然后加入溶剂溶解，最后加入2-甲基-3-丁烯-2-醇(4)，反应，点板监测反应体系，反应结束后，旋干溶剂，柱层析(流动相：石油醚/乙酸乙酯＝10/1v/v)得到目标产物(5或6或7)C2位引入异戊烯基的吲哚。
化合物1或2或3的苯环取代基Z可以是氢、C1-C8烷基、C1-C8烷氧基、苯氧基、苯基、对甲氧基苯基、苄基、对甲氧基苄基、萘基、醛基、酯基、酰基、-F、-Cl、-Br、-NO2中的一种或二种以上，其个数为1、2、3或4个；
化合物1或2或3的氮上PG可以是氢、C1-C8烷基、苯基、对甲氧基苯基、苄基、对甲氧基苄基、磺酰基、酯基、叔丁氧基羰基、苄氧基羰基、9-芴基甲氧基羰基中的一种；
化合物1或2或3的R可以是氢、C1-C8烷基、C1-C8烷氧基、苯基、对甲氧基苯基、苄基、对甲氧基苄基、醛基、酰基、磺酰基、酯基、叔丁氧基羰基、苄氧基羰基、9-芴基甲氧基羰基、-F、-Cl、-Br中的一种；
化合物2的X可以是CH2、O、NH、S中的一种；
化合物3的R’可以是氢、C1-C8烷基、C1-C8烷氧基、苯基、对甲氧基苯基、苄基、对甲氧基苄基、醛基、酰基、磺酰基、酯基、叔丁氧基羰基、苄氧基羰基、9-芴基甲氧基羰基、-F、-Cl、-Br中的一种；
其中上面所述酯基是甲酯、乙酯、丙酯、丁酯、苯酯、苄酯中的一种或二种以上。
所用酸催化剂为下述中的一种或二种以上：樟脑磺酸、对甲苯磺酸、苯磺酸、三氟乙酸、三氟甲磺酸、苯甲酸、邻苯二甲酸、对苯二甲酸、金刚烷甲酸、磷酸二苯酯、磷酸二苄酯、脯氨酸、三乙基硼、三氟化硼乙醚、三(五氟苯基)硼、二乙基锌、氯化铝、氯化锌、氯化铁、氯化镧、氯化铟、三甲基铝、二甲基氯化铝、高氯酸镁、双(三氟甲基磺酰)亚胺镁、双(三氟甲基磺酰)亚胺钙、三氟甲磺酸铜、三氟甲磺酸钪、三氟甲磺酸锌、三氟甲磺酸铁、三氟甲磺酸镱、三氟甲磺酸钐、三氟甲磺酸铝、三氟甲磺酸铟、Amberlyst-15、Amberlyst-36、Nafion，其中，优选催化剂是氯化铝。
催化剂与吲哚的摩尔比为0.001-1，优选范围为0.1-0.4。
所用溶剂为，以甲醇、乙醇、乙腈、甲苯、氯苯、环己烷、四氢呋喃、2-甲基四氢呋喃、1,4-二氧六环、乙二醇二甲醚、二氯甲烷、二氯乙烷、乙酸乙酯、N,N-二甲基甲酰胺、二甲亚砜、N-甲基吡咯烷酮、氯化1-乙基-3-甲基咪唑、氯化1-丁基-3-甲基咪唑中的一种或二种以上为溶剂。
吲哚在溶剂中浓度范围0.01-1.5mol/L，优选0.2-1.0mol/L。
2-甲基-3-丁烯-2-醇用量是吲哚摩尔量的0.5-10倍之间，优选1.5-3倍。
反应温度在25-120℃之间，优选60-80℃；反应时间在0.5-36h之间，优选12-24h。
本发明具有如下优点：
本发明有以下优点，首次发展了催化方法，体系简单，无需当量的促进剂；异戊烯基前体商业可得，价格便宜；不需要对吲哚NH进行保护；副产物是水，体系绿色；色氨酸衍生物都是合适的底物，可以两步合成天然产物。因此，本专利在合成异戊烯基化吲哚类生物碱方面有着潜在的应用前景。
具体实施方式
下面将以具体的实施例来对本发明加以说明，但本发明的保护范围不局限于这些实例。
1.酸催化色醇和2-甲基-3-丁烯-2-醇的反应
在2.0mL封管中，加入色醇2a(0.2mmol,32.2mg)和酸催化剂(色醇2a用量的10mol％)，用0.2mL溶剂溶解，然后加入2-甲基-3-丁烯-2-醇(色醇2a用量的3.0equiv,60μL)，在一定温度下反应24h，结束后加入萘作为内标，HPLC检测目标产物6a收率。
Figure BDA0002658211380000051
表1.催化剂、溶剂和温度等因素对反应的影响
Figure BDA0002658211380000052
Figure BDA0002658211380000061
由表1结果可以看出，布朗斯特酸如樟脑磺酸、三氟乙酸、三氟甲磺酸、苯甲酸等都可以促进反应的进行，但酸性太弱(苯甲酸)、太强(三氟甲磺酸)，目标产物的收率都不高。路易斯酸如氯化锌、氯化铝、三氟甲磺酸盐类等也是有效的催化剂，氯化铝给出较好的结果(实施例9)。通过溶剂的筛选发现，在醚类溶剂四氢呋喃、2-甲基四氢呋喃、二氧六环中，收率较高，但2-甲基四氢呋喃是一种绿色溶剂，因此，选择2-甲基四氢呋喃作为最佳溶剂(实施例29)。温度调节发现，80℃是最合适的温度(实施例33)，高温下原料烯丙醇会发生自聚，收率下降(实施例34-36)；而低温下，反应活性不够，原料转化不完，收率低(实施例37,38)。
2.底物类型
在2.0mL封管中，加入吲哚1或2或3(0.4mmol)和氯化铝(10mol％)，用0.4mL2-甲基四氢呋喃溶解，然后加入2-甲基-3-丁烯-2-醇4(3.0equiv,120μL)，在80℃下反应24h，结束后，直接用柱层析分离，流动相为石油醚/乙酸乙酯体积比10:1。
具体代表性底物反应：
Figure BDA0002658211380000062
Figure BDA0002658211380000063
7.3Hz,2H),2.98(t,J＝6.5Hz,2H),1.77(s,3H),1.75(s,3H).
13C NMR(100MHz,CDCl3)δ135.79,135.38,134.75,128.89,121.28,120.47,119.43,118.19,110.56,106.92,62.97,27.78,25.86,25.22,18.01.
HRMS calculated for C15H20NO[M+H]+230.1539,found 230.1541.
Figure BDA0002658211380000071
Figure BDA0002658211380000072
1H),7.07(s,1H),6.91–6.81(m,1H),5.30(t,J＝7.4Hz,1H),5.09(s,2H),3.81(t,J＝6.4Hz,2H),3.46(d,J＝7.4Hz,2H),2.94(t,J＝6.5Hz,2H),1.77(s,3H),1.75(s,3H).
13C NMR(100MHz,CDCl3)δ153.33,137.85,136.74,134.88,130.69,129.40,128.61,127.87,127.73,120.38,111.81,111.20,106.89,102.38,71.20,62.94,27.84,25.90,25.34,18.03.
HRMS calculated for C22H26NO2[M+H]+336.1958,found 336.1959.
Figure BDA0002658211380000073
Figure BDA0002658211380000074
7.3Hz,2H),2.94(t,J＝6.5Hz,2H),1.78(s,3H),1.76(s,3H).
13C NMR(100MHz,CDCl3)δ157.98(d,J＝234.1Hz),137.76,135.25,131.81,129.41(d,J＝9.4Hz),120.08,111.07(d,J＝9.7Hz),109.38(d,J＝26.1Hz),107.41(d,J＝4.5Hz),103.32(d,J＝23.4Hz),62.87,27.79,25.91,25.34,18.05.
HRMS calculated for C15H19FNO[M+H]+248.1445,found 248.1447.
Figure BDA0002658211380000075
Figure BDA0002658211380000076
1H),3.80(t,J＝6.5Hz,2H),3.46(d,J＝7.3Hz,2H),2.92(t,J＝6.5Hz,2H),1.77(s,3H),1.74(s,3H).
13C NMR(100MHz,CDCl3)δ137.37,135.27,133.69,130.09,125.13,121.43,119.99,117.73,111.51,106.98,62.86,27.66,25.88,25.25,18.03.
HRMS calculated for C15H19ClNO[M+H]+264.1150,found 264.1150.
Figure BDA0002658211380000081
Figure BDA0002658211380000082
3.50(d,J＝7.2Hz,2H),2.98(t,J＝6.5Hz,2H),2.46(s,3H),1.77(s,6H).
13C NMR(100MHz,CDCl3)δ135.55,134.90,134.66,128.41,122.07,120.65,119.75,116.00,107.58,63.04,27.95,25.89,25.34,18.09,16.73.
HRMS calculated for C16H22NO[M+H]+244.1696,found 244.1698.
Figure BDA0002658211380000083
Figure BDA0002658211380000084
3H),3.53(t,J＝7.7Hz,2H),3.48(d,J＝6.8Hz,2H),3.36(s,3H),3.02(t,J＝7.7Hz,2H),1.79(s,3H),1.71(s,3H).
13C NMR(100MHz,CDCl3)δ137.07,136.82,132.50,127.91,121.58,120.82,118.89,118.19,108.78,107.25,73.52,58.73,29.76,25.78,25.22,24.10,18.12.
HRMS calculated for C17H24NO[M+H]+258.1852,found 258.1856.
Figure BDA0002658211380000085
Figure BDA0002658211380000086
(t,J＝7.6Hz,2H),3.39(d,J＝6.8Hz,2H),3.11(t,J＝7.7Hz,2H),1.63(s,3H),1.55(s,3H).
13C NMR(100MHz,CDCl3)δ138.72,138.35,136.99,136.72,132.56,128.69,128.43,128.21,127.72,127.56,127.13,125.94,121.82,121.12,119.19,118.33,109.34,108.21,73.12,71.13,46.67,25.60,25.49,24.18,18.03.
HRMS calculated for C29H32NO[M+H]+410.2478,found 410.2476.
Figure BDA0002658211380000091
Figure BDA0002658211380000092
(t,J＝6.6Hz,2H),3.42(d,J＝6.3Hz,1H),3.04(t,J＝6.6Hz,1H),1.66(s,3H),1.59(s,3H).
13C NMR(100MHz,CDCl3)δ138.22,137.62,136.89,133.05,128.75,128.19,127.23,125.95,121.59,121.39,119.42,118.37,109.48,107.57,63.27,46.76,28.24,25.63,24.16,18.10.
HRMS calculated for C22H26NO[M+H]+320.2009,found 320.2008.
Figure BDA0002658211380000093
Figure BDA0002658211380000094
(t,J＝7.4Hz,1H),5.26(t,J＝6.9Hz,1H),4.33(t,J＝5.9Hz,1H),3.40(d,J＝7.2Hz,2H),3.21(q,J＝6.5Hz,2H),2.91(t,J＝6.7Hz,2H),2.38(s,3H),1.78(s,3H),1.75(s,3H).
13C NMR(100MHz,CDCl3)δ143.31,136.94,135.80,135.32,135.18,129.70,128.34,127.13,121.46,120.15,119.61,117.89,110.63,106.49,43.35,25.90,25.19,24.66,21.63,18.07.
HRMS calculated for C22H27N2O2S[M+H]+383.1788,found 383.1787.
Figure BDA0002658211380000095
Figure BDA0002658211380000096
7.2Hz,1H),3.51(q,J＝6.4Hz,2H),3.45(d,J＝7.3Hz,2H),2.93(t,J＝6.6Hz,2H),1.88(s,3H),1.78(s,3H),1.76(s,3H).
13C NMR(175MHz,CDCl3)δ170.16,135.42,135.38,134.88,128.78,121.37,120.41,119.54,118.06,110.64,107.92,40.20,25.92,25.17,24.16,23.49,18.05.
HRMS calculated for C17H23N2O[M+H]+271.1805,found 271.1808.
Figure BDA0002658211380000101
Figure BDA0002658211380000102
7.18–7.04(m,2H),6.21(s,1H),5.23(t,J＝7.1Hz,2H),3.73(q,J＝6.4Hz,2H),3.44(d,J＝7.2Hz,2H),3.06(t,J＝6.6Hz,2H),1.70(s,3H),1.69(s,3H).
13C NMR(100MHz,CDCl3)δ167.53,135.55,135.42,134.96,134.79,131.39,128.77,128.58,126.98,121.44,120.27,119.60,118.14,110.68,107.89,40.62,25.83,25.17,24.14,17.97.
HRMS calculated for C22H25N2O[M+H]+333.1961,found 333.1965.
Figure BDA0002658211380000111
Figure BDA0002658211380000112
1H),3.38(d,J＝7.2Hz,2H),3.33–3.16(m,2H),2.83(t,J＝6.3Hz,2H),1.71(s,3H),1.68(s,3H),1.36(s,9H).
13C NMR(100MHz,CDCl3)δ156.07,135.36,134.72,128.75,121.24,120.56,119.39,118.20,110.50,108.03,79.10,41.10,28.56,25.90,25.16,24.67,18.02.
HRMS calculated for C20H29N2O2[M+H]+329.2224,found 329.2226.
Figure BDA0002658211380000113
Figure BDA0002658211380000114
Hz,1H),5.36(t,J＝7.1Hz,1H),3.59(d,J＝7.3Hz,2H),1.79(s,3H),1.73(s,3H).
13C NMR(100MHz,CDCl3)δ135.48,135.30,135.08,134.80,129.68,128.60,128.10,125.97,121.67,120.57,120.06,119.07,114.09,110.58,25.94,25.75,18.07.
HRMS calculated for C19H20N[M+H]+262.1590,found 262.1587.
Figure BDA0002658211380000115
Figure BDA0002658211380000116
5.23(t,J＝5.9Hz,1H),3.70(s,3H),3.56(d,J＝6.3Hz,2H),1.73(s,3H),1.70(s,3H).
13C NMR(100MHz,CDCl3)δ136.91,136.79,135.85,133.12,129.95,128.56,127.15,125.88,121.49,121.39,119.75,119.10,114.23,108.90,29.93,25.82,24.58,18.13.
HRMS calculated for C20H22N[M+H]+276.1747,found 276.1747.
Figure BDA0002658211380000121
Figure BDA0002658211380000122
2.21(s,3H),1.74(s,3H),1.70(s,3H).
13C NMR(100MHz,CDCl3)δ170.22,136.45,135.87,132.97,131.32,123.91,122.87,121.65,118.48,115.61,114.98,27.37,26.43,25.79,18.21,8.87.
HRMS calculated for C16H20NO[M+H]+242.1539,found 242.1541.
Figure BDA0002658211380000123
Figure BDA0002658211380000124
3H),3.43(d,J＝7.1Hz,2H),3.24(d,J＝5.2Hz,2H),1.79(s,3H),1.76(s,3H),1.41(s,9H).
13CNMR(100MHz,CDCl3)δ172.95,155.22,136.19,135.26,135.08,129.04,121.35,120.36,119.56,118.27,110.48,105.25,79.82,54.26,52.39,28.44,27.30,25.92,25.18,18.04.
HRMS calculated for C22H31N2O4[M+H]+387.2278,found 387.2277.
Figure BDA0002658211380000125
Figure BDA0002658211380000126
(m,1H),3.59–3.51(m,1H),3.48(d,J＝7.2Hz,2H),2.94(d,J＝6.9Hz,2H),2.52(s,1H),1.79(s,3H),1.77(s,3H),1.42(s,9H).
13C NMR(100MHz,CDCl3)δ156.43,135.71,135.32,135.05,129.10,121.36,120.37,119.62,118.34,110.49,106.90,79.71,64.87,53.43,28.50,25.92,25.25,22.48,18.06.
HRMS calculated for C21H31N2O3[M+H]+359.2329,found 359.2281.
Figure BDA0002658211380000131
Figure BDA0002658211380000132
＝18.3,5.2Hz,1H),3.79(d,J＝18.1Hz,1H),3.47(t,J＝6.1Hz,2H),3.34–3.22(m,1H),3.19–3.09(m,1H),1.79(s,3H),1.76(s,3H),1.41(s,9H),1.22(t,J＝7.1Hz,3H).
13C NMR(175MHz,CDCl3)δ172.01,169.37,155.48,136.24,135.31,135.18,128.83,121.49,120.26,119.76,118.43,110.52,105.66,80.10,61.56,55.09,41.61,28.43,28.32,25.95,25.19,18.08,14.23.
HRMS calculated for C25H36N3O5[M+H]+458.2649,found 458.2645.
Figure BDA0002658211380000133
Figure BDA0002658211380000134
3.74–3.68(m,1H),3.68–3.64(m,1H),3.63–3.55(m,1H),3.48(t,J＝7.2Hz,2H),2.96(dd,J＝15.1,11.4Hz,1H),2.38–2.29(m,1H),2.11–1.98(m,2H),1.96–1.85(m,1H),1.79(s,3H),1.76(s,3H).
13C NMR(100MHz,CDCl3)δ169.46,165.93,136.54,135.64,135.58,128.13,122.01,120.06,119.84,117.88,110.92,104.80,59.42,54.72,45.56,28.51,25.89,25.75,25.27,22.80,18.13.HRMS calculated for C21H26N3O2[M+H]+352.2020,found352.2015.

Claims (10)

1.一种在吲哚C2位引入异戊烯基的方法，其特征在于：
吲哚(1或2或3)和2-甲基-3-丁烯-2-醇(4)在酸催化下，可以在C2位引入异戊烯基，具体过程为：
在惰性气氛下，于溶剂和酸催化剂存在下，吲哚(1或2或3)和2-甲基-3-丁烯-2-醇(4)反应，得到C2位引入异戊烯基的吲哚。
2.根据权利要求1所述的方法，其特征在于：
反应式如下所示：
Figure FDA0002658211370000011
3.根据权利要求1或2所述的方法，其特征在于：
具体操作步骤如下：
在氩气或氮气气氛下，依次加入吲哚(1或2或3)和酸催化剂，然后加入溶剂溶解，最后加入2-甲基-3-丁烯-2-醇(4)，反应，点板监测反应体系，反应结束后，旋干溶剂，柱层析(流动相：石油醚/乙酸乙酯＝10/1v/v)得到目标产物(5或6或7)C2位引入异戊烯基的吲哚。
4.根据权利要求2所述的方法，其特征在于：
化合物1或2或3的苯环取代基Z可以是氢、C1-C8烷基、C1-C8烷氧基、苯氧基、苯基、对甲氧基苯基、苄基、对甲氧基苄基、萘基、醛基、酯基、酰基、-F、-Cl、-Br、-NO2中的一种或二种以上，其个数为1、2、3或4个；
化合物1或2或3的氮上PG可以是氢、C1-C8烷基、苯基、对甲氧基苯基、苄基、对甲氧基苄基、磺酰基、酰基、酯基、叔丁氧基羰基、苄氧基羰基、9-芴基甲氧基羰基中的一种；
化合物1或2或3的R可以是氢、C1-C8烷基、C1-C8烷氧基、苯基、对甲氧基苯基、苄基、对甲氧基苄基、醛基、酰基、磺酰基、酯基、叔丁氧基羰基、苄氧基羰基、9-芴基甲氧基羰基、-F、-Cl、-Br中的一种；
化合物2的X可以是CH2、O、NH、S中的一种；
化合物3的R’可以是氢、C1-C8烷基、C1-C8烷氧基、苯基、对甲氧基苯基、苄基、对甲氧基苄基、醛基、酰基、磺酰基、酯基、叔丁氧基羰基、苄氧基羰基、9-芴基甲氧基羰基、-F、-Cl、-Br中的一种；
其中上面所述酯基是甲酯、乙酯、丙酯、丁酯、苯酯、苄酯中的一种或二种以上。
5.根据权利要求1-3任一所述的方法，其特征在于：
所用酸催化剂为下述中的一种或二种以上：樟脑磺酸、对甲苯磺酸、苯磺酸、三氟乙酸、三氟甲磺酸、苯甲酸、邻苯二甲酸、对苯二甲酸、金刚烷甲酸、磷酸二苯酯、磷酸二苄酯、脯氨酸、三乙基硼、三氟化硼乙醚、三(五氟苯基)硼、二乙基锌、氯化铝、氯化锌、氯化铁、氯化镧、氯化铟、三甲基铝、二甲基氯化铝、高氯酸镁、双(三氟甲基磺酰)亚胺镁、双(三氟甲基磺酰)亚胺钙、三氟甲磺酸铜、三氟甲磺酸钪、三氟甲磺酸锌、三氟甲磺酸铁、三氟甲磺酸镱、三氟甲磺酸钐、三氟甲磺酸铝、三氟甲磺酸铟、Amberlyst-15、Amberlyst-36、Nafion，其中，优选催化剂是氯化铝。
6.根据权利要求5所述的方法，其特征在于：
催化剂与吲哚的摩尔比为0.001-1，优选范围为0.1-0.4。
7.根据权利要求1-3任一所述的方法，其特征在于：
所用溶剂为，以甲醇、乙醇、乙腈、甲苯、氯苯、环己烷、四氢呋喃、2-甲基四氢呋喃、1,4-二氧六环、乙二醇二甲醚、二氯甲烷、二氯乙烷、乙酸乙酯、N,N-二甲基甲酰胺、二甲亚砜、N-甲基吡咯烷酮、氯化1-乙基-3-甲基咪唑、氯化1-丁基-3-甲基咪唑中的一种或二种以上为溶剂。
8.根据权利要求7所述的方法，其特征在于：
吲哚在溶剂中的浓度范围0.01-1.5mol/L，优选0.2-1.0mol/L。
9.根据权利要求1-3任一所述的方法，其特征在于：
2-甲基-3-丁烯-2-醇用量是吲哚摩尔量的0.5-10倍之间，优选1.5-3倍。
10.根据权利要求1-3任一所述的方法，其特征在于：
反应温度在25-120℃之间，优选60-80℃；反应时间在0.5-36h之间，优选12-24h。
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