CN106674280A - 一种膦氧基吲哚化合物及其衍生物的制备方法 - Google Patents

一种膦氧基吲哚化合物及其衍生物的制备方法 Download PDF

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CN106674280A
CN106674280A CN201611169250.3A CN201611169250A CN106674280A CN 106674280 A CN106674280 A CN 106674280A CN 201611169250 A CN201611169250 A CN 201611169250A CN 106674280 A CN106674280 A CN 106674280A
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diazonium
methyl
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phosphine
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江俊
吴毅
王立升
刘扬
杨华
刘旭
王坚毅
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Abstract

一种膦氧基吲哚化合物及其衍生物的制备方法，步骤如下：称取1eq重氮吲哚化合物并溶解于有机溶剂，浓度为0.3～0.5mol/L，得到重氮溶液；在烧瓶中加入1～1.2eq的膦氧基化合物和0.05～0.10eq的六氟磷酸乙腈铜，加入有机溶剂，溶液中膦氧基化合物的浓度为0.3～0.5mol/L；将重氮溶液缓慢滴加入圆底烧瓶中，反应得到粗产物，将粗产物用体积比为乙酸乙酯：石油醚＝6～3∶1的溶液进行柱层析，即得。本发明采用金属催化、一步直接构建C(sp2)‑P键的路线，反应条件温且能实现克量级反应，能快速简单的合成出一系列膦氧基吲哚衍生物，提供多样性的化合物骨架，对新药筛选和制药工艺有很大的意义。

Description

一种膦氧基吲哚化合物及其衍生物的制备方法
技术领域
本发明涉及一种膦氧基吲哚化合物及其衍生物的制备方法，该膦氧基吲哚衍生物具有光学活性，属于药物合成化学技术领域。
背景技术
3-苯基膦氧基吲哚衍生物在生物制药上已经被报道起到了重要的作用(Chem.Rev.2011,111(12),7981-8006)。近期的研究发现，含膦取代的有机化合物表现出特别的生物活性和化学性质(Org.Lett.2006,8(23),5291-5293)，这就导致了其在有机合成、材料化学和药物化学上有广泛的应用。此外，吲哚骨架是许多常见的具有值得关注的药物价值和生物活性的天然物结构的重要组成部分(J.Nat.Prod.2014,77(9),2068-2080)。最近，有文章报道，3-苯基膦氧基吲哚衍生物在抑制HIV-1病毒(IDX 899)的复制起到了非同一般的效果(J.Med.Chem.2011,54(1),392-395)。尽管现如今能够高效合成芳基和杂芳基有机膦化合物，但是，3-苯基膦氧基吲哚衍生物的构建方法目前还鲜少有报道。
重氮化合物是直接构建碳-杂(C-X)键的最有效的方法(Chem.Soc.Rev.2013,42(12),4918-4931)，然而，相比于显著的X-H插入反应，由于膦的高配位性极易导致金属催化剂毒化，导致P-H插入反应的难度明显增大(Chem.Rev.1994,94(4),1091-1160)。近期研究发现了由三氮唑生成金属氮杂环卡宾，其具有新颖的反应性和合成前景，已成为一个越来越有价值的中间体(Angew.Chem.,Int.Ed.2012,51,862)。Fokin，Gevorgyan，Davies，Sarpong，Shi以及其他研究团队极大的推动了新型的氮杂乙烯卡宾中间体的发展，尤其是在金属氮杂乙烯卡宾直接构建C(sp2)-X键提供了简便的办法。此外，近期有报道通过2-亚胺-3-吲哚重氮化合物在金属催化下，产生金属吲哚氮杂乙烯卡宾作为活性中间进一步生成3-取代吲哚衍生物(Org.Lett.2014,16(19),5096-5099)。尽管在氮杂乙烯卡宾的插入反应中已取得了显著的进步，但是通过金属氮杂乙烯卡宾进行P-H插入反应构建吲哚3号位的C(sp2)-P键还没有被报道。
发明内容
本发明的目的是公开一种原料价廉易得，操作简单，高收率的光学活性膦氧基吲哚化合物。
为了实现上述目的，本发明采用了以下技术方案：
一种膦氧基吲哚化合物及其衍生物的制备方法，用重氮吲哚化合物和膦氧基化合物在六氟磷酸四乙腈铜的催化下，实现P-H插入反应，得到膦氧基吲哚化合物及其衍生物，具体步骤如下：
(1)先称取1eq重氮吲哚化合物，将重氮吲哚化合物溶解于有机溶剂中，浓度控制为0.3～0.5mol/L，得到重氮溶液；
(2)在一个圆底烧瓶中加入1～1.2eq的膦氧基化合物和0.05～0.10eq的六氟磷酸乙腈铜，加入有机溶剂，控制溶液中膦氧基化合物的浓度为0.3～0.5mol/L；
(3)将重氮溶液缓慢滴加入圆底烧瓶中，在1～2小时滴加结束，搅拌反应1-12小时，得到粗产物，
(4)将粗产物用体积比为乙酸乙酯：石油醚＝1:6～3的溶液进行柱层析，得到所述膦氧基吲哚化合物及其衍生物。
进一步的，所述有机溶剂为三氯甲烷。
进一步的，所述重氮吲哚化合物由相应的吲哚和叠氮化合物制备得到。
进一步的，所述重氮化合物为N-(1-甲基吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺、N-(1-乙基吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺、N-(1-异丙基吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺、N-(1-苄基吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺、N-(1-烯丙基吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺、N-(1-甲基-5-甲基-吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺、N-(1-甲基-5-氟-吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺、N-(1-甲基-5-氯-吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺、N-(1-甲基-5-溴-吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺、N-(1-甲基吲哚-2-亚基-3-重氮)-4-溴苯磺酰胺、N-(1-甲基吲哚-2-亚基-3-重氮)-2,4,6-三异丙基苯磺酰胺、N-(1-甲基吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺、N-(1-甲基-5-甲氧基吲哚-2-亚基-3-重氮)-2,4,6-三异丙基苯磺酰胺、N-(1-甲基-5-氟吲哚-2-亚基-3-重氮)-2,4,6-三异丙基苯磺酰胺、N-(1-甲基-5-氯吲哚-2-亚基-3-重氮)-2,4,6-三异丙基苯磺酰胺以及N-(1-甲基-5-溴吲哚-2-亚基-3-重氮)-2,4,6-三异丙基苯磺酰胺中的任意一种。
进一步的，所述膦氧基化合物为二苯基膦氧、二(4-甲氧基苯基)膦氧、二(2-甲基苯基)膦氧、二(4-氟苯基)膦氧、二(3,5-双三氟甲基苯基)膦氧、9,10-二氢-9-氧杂-10-磷杂菲-10-氧化物、苯基膦酸乙酯以及苯基膦酸薄荷酯中的任意一种。
与现有技术相比较，本发明具备的有益效果：
本发明公开了一种通过2-亚胺-3-重氮吲哚以及膦氢化合物作为反应底物，合成一系列3-苯基膦氧基吲哚衍生物的新型合成策略。在这个反应中，2-亚胺-3-重氮吲哚作为重要的α-亚胺金属卡宾前体。这个方法的特色就是提供一种通过金属催化，一步直接构建C(sp2)-P键的路线。该反应具有操作简单，反应条件温和且能实现克量级反应。
本发明所用的原料，重氮化合物、膦氢化合物、有机溶剂和催化剂廉价易得，因此本发明合成膦氧基吲哚衍生物成本低廉。
本发明合成路线简单，一步构建目标产物。
本发明具有原子经济性，高选择性，高收率等，符合绿色化学的要求。
本发明能快速简单的合成出一系列膦氧基吲哚衍生物，提供多样性的化合物骨架，对新药筛选和制药工艺有很大的意义。
具体实施方式
实施例1
称取二苯基膦氧(0.2mmol)以及六氟磷酸四乙腈铜(3.72mg，0.01mmol)于圆底烧瓶中，加入0.8mL三氯甲烷，置于5050℃油浴中；再取N-(1-甲基吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺(0.2mmol)溶于0.8mL三氯甲烷，并通过蠕动泵1小时注入反应体系中，注入完毕后，继续搅拌1小时后，再通过柱层析(石油醚：乙酸乙酯＝3:1)分离得到产物3a。收率82％。
1H NMR(600MHz,Chloroform-d)δ10.21(s,1H),7.53–7.46(m,3H),7.43(d,J＝8.3Hz,1H),7.41–7.30(m,8H),7.29–7.25(m,1H),6.99(t,J＝7.6Hz,1H),6.78(d,J＝8.0Hz,1H),6.73(d,J＝8.1Hz,2H),4.03(s,3H),2.08(s,3H)；13C NMR(151MHz,Chloroform-d)δ143.65,143.15(d,J＝12.5Hz),136.75(d,J＝11.2Hz),134.23,133.29(d,J＝109.5Hz),131.73(d,J＝2.7Hz),131.39(d,J＝11.0Hz),129.03,128.26(d,J＝12.7Hz),128.01,126.97(d,J＝9.9Hz),122.56,121.73,119.75,110.61,90.24(d,J＝125.1Hz),32.40,21.70；31P NMR(243MHz,CDCl3)δ28.18。
实施例2
称取二苯基膦氧(0.2mmol)以及六氟磷酸四乙腈铜(3.72mg，0.01mmol)于圆底烧瓶中，加入0.8mL三氯甲烷，置于5050℃油浴中；再取N-(1-乙基吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺(0.2mmol)溶于0.8mL三氯甲烷，并通过蠕动泵1小时注入反应体系中，注入完毕后，继续搅拌1小时后，再通过柱层析(石油醚：乙酸乙酯＝3:1)分离得到产物3b。收率76％。
1H NMR(600MHz,Chloroform-d)δ10.24(s,1H),7.55–7.47(m,5H),7.40–7.30(m,8H),7.24(t,J＝7.4Hz,1H),6.99–6.94(m,1H),6.76(d,J＝8.0Hz,1H),6.72(d,J＝8.0Hz,2H),4.71–4.63(m,2H),2.07(s,3H),1.56(t,J＝7.2Hz,3H)；13C NMR(151MHz,Chloroform-d)δ143.61,142.63(d,J＝12.3Hz),135.74(d,J＝11.2Hz),134.12,133.31(d,J＝109.5Hz),131.72(d,J＝2.7Hz),131.42(d,J＝11.0Hz),128.99,128.26(d,J＝12.6Hz),128.11,127.49(d,J＝9.9Hz),122.45,121.56,119.96,111.20,90.69(d,J＝124.5Hz),40.18,21.70,14.40；31P NMR(243MHz,CDCl3)δ28.33。
实施例3
称取二苯基膦氧(0.2mmol)以及六氟磷酸四乙腈铜(3.72mg，0.01mmol)于圆底烧瓶中，加入0.8mL三氯甲烷，置于5050℃油浴中；再取N-(1-异丙基吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺(0.2mmol)溶于0.8mL三氯甲烷，并通过蠕动泵1小时注入反应体系中，注入完毕后，继续搅拌1小时后，再通过柱层析(石油醚：乙酸乙酯＝3:1)分离得到产物3c。收率71％。
1H NMR(600MHz,Chloroform-d)δ10.27(s,1H),7.72(d,J＝8.4Hz,1H),7.55–7.45(m,4H),7.40–7.30(m,8H),7.20(t,J＝7.5Hz,1H),6.94(t,J＝7.6Hz,1H),6.77(d,J＝8.0Hz,1H),6.71(d,J＝8.0Hz,2H),5.61–5.51(m,1H),2.07(s,3H),1.76(d,J＝7.0Hz,6H)；13C NMR(151MHz,Chloroform-d)δ143.58,142.44(d,J＝12.3Hz),134.34(d,J＝11.0Hz),134.05,133.33(d,J＝109.5Hz),131.67(d,J＝2.6Hz),131.43(d,J＝10.9Hz),128.97,128.28,128.20,128.11,121.89,121.14,120.26,113.48,90.35(d,J＝124.8Hz),49.24,21.71,21.21；31P NMR(243MHz,CDCl3)δ28.37。
实施例4
称取二苯基膦氧(0.2mmol)以及六氟磷酸四乙腈铜(3.72mg，0.01mmol)于圆底烧瓶中，加入0.8mL三氯甲烷，置于5050℃油浴中；再取N-(1-苄基吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺(0.2mmol)溶于0.8mL三氯甲烷，并通过蠕动泵1小时注入反应体系中，注入完毕后，继续搅拌1小时后，再通过柱层析(石油醚：乙酸乙酯＝3:1)分离得到产物3d。收率58％。
1H NMR(600MHz,Chloroform-d)δ10.31(s,1H),7.58–7.49(m,4H),7.45–7.34(m,8H),7.34–7.30(m,2H),7.29–7.24(m,2H),7.17–7.09(m,3H),6.94(t,J＝7.5Hz,1H),6.78(d,J＝8.0Hz,1H),6.75(d,J＝8.1Hz,2H),5.88(s,2H),2.09(s,3H)；13C NMR(151MHz,Chloroform-d)δ143.72,143.31(d,J＝12.4Hz),136.88,136.14(d,J＝11.0Hz),134.12,133.25(d,J＝109.6Hz),131.81(d,J＝2.6Hz),131.42(d,J＝10.9Hz),129.04,128.62,128.34(d,J＝12.7Hz),128.21,127.47,127.41,126.74,122.69,121.82,119.93,112.07,91.56(d,J＝123.4Hz),48.82,21.73；31P NMR(243MHz,CDCl3)δ28.31。
实施例5
称取二苯基膦氧(0.2mmol)以及六氟磷酸四乙腈铜(3.72mg，0.01mmol)于圆底烧瓶中，加入0.8mL三氯甲烷，置于5050℃油浴中；再取N-(1-烯丙基吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺(0.2mmol)溶于0.8mL三氯甲烷，并通过蠕动泵1小时注入反应体系中，注入完毕后，继续搅拌1小时后，再通过柱层析(石油醚：乙酸乙酯＝3:1)分离得到产物3e。收率79％。
1H NMR(600MHz,Chloroform-d)δ10.26(s,1H),7.56–7.46(m,5H),7.41–7.31(m,8H),7.21(t,J＝7.7Hz,1H),6.96(t,J＝7.6Hz,1H),6.76(d,J＝8.0Hz,1H),6.72(d,J＝8.1Hz,2H),6.17–6.08(m,1H),5.31(d,J＝11.1Hz,1H),5.25–5.19(m,3H),2.07(s,3H)；13CNMR(151MHz,Chloroform-d)δ143.66,142.85(d,J＝12.4Hz),136.43(d,J＝11.1Hz),134.04,133.53,133.22(d,J＝109.6Hz),131.76(d,J＝2.7Hz),131.40(d,J＝10.9Hz),129.00,128.29(d,J＝12.7Hz),128.14,127.30(d,J＝9.8Hz),122.52,121.74,119.84,117.45,111.91,91.00(d,J＝123.9Hz),48.15,21.70；31P NMR(243MHz,CDCl3)δ28.27。
实施例6
称取二苯基膦氧(0.2mmol)以及六氟磷酸四乙腈铜(3.72mg，0.01mmol)于圆底烧瓶中，加入0.8mL三氯甲烷，置于5050℃油浴中；再取N-(1-甲基-5-甲基-吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺(0.2mmol)溶于0.8mL三氯甲烷，并通过蠕动泵1小时注入反应体系中，注入完毕后，继续搅拌1小时后，再通过柱层析(石油醚：乙酸乙酯＝3:1)分离得到产物3f。收率53％。
1H NMR(600MHz,Chloroform-d)δ10.19(s,1H),7.54–7.45(m,4H),7.41–7.29(m,9H),7.08(d,J＝8.4Hz,1H),6.73(d,J＝8.1Hz,2H),6.54–6.51(m,1H),4.00(s,3H),2.22(s,3H),2.08(s,3H)；13C NMR(151MHz,Chloroform-d)δ143.58,142.99(d,J＝12.7Hz),135.06(d,J＝11.4Hz),134.26,133.36(d,J＝109.4Hz),131.67(d,J＝2.7Hz),131.41(d,J＝10.9Hz),131.17,129.01,128.23(d,J＝12.6Hz),128.00,127.19(d,J＝9.8Hz),124.07,119.50,110.25,89.58(d,J＝125.5Hz),32.40,21.69,21.53；31P NMR(243MHz,CDCl3)δ28.39。
实施例7
称取二苯基膦氧(0.2mmol)以及六氟磷酸四乙腈铜(3.72mg，0.01mmol)于圆底烧瓶中，加入0.8mL三氯甲烷，置于5050℃油浴中；再取N-(1-甲基-5-氟-吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺(0.2mmol)溶于0.8mL三氯甲烷，并通过蠕动泵1小时注入反应体系中，注入完毕后，继续搅拌1小时后，再通过柱层析(石油醚：乙酸乙酯＝3:1)分离得到产物3g。收率74％。
1H NMR(600MHz,Chloroform-d)δ10.19(s,1H),7.53–7.48(m,4H),7.37–7.32(m,9H),7.02–6.95(m,1H),6.75(d,J＝8.0Hz,2H),6.38(dd,J＝9.5,2.5Hz,1H),4.01(s,3H),2.09(s,3H)；13C NMR(151MHz,Chloroform-d)δ158.70(d,J＝237.6Hz),144.12(d,J＝12.4Hz),143.77,134.25,133.19,132.91(d,J＝109.5Hz),131.91(d,J＝2.7Hz),131.33(d,J＝10.9Hz),129.07,128.38(d,J＝12.7Hz),127.95,127.42(t,J＝10.0Hz),111.49(d,J＝9.7Hz),110.87(d,J＝26.0Hz),105.07(d,J＝25.0Hz),90.51(d,J＝129.3Hz),32.65,21.70；31P NMR(243MHz,CDCl3)δ27.89；19F NMR(565MHz,CDCl3)δ-120.59。
实施例8
称取二苯基膦氧(0.2mmol)以及六氟磷酸四乙腈铜(3.72mg，0.01mmol)于圆底烧瓶中，加入0.8mL三氯甲烷，置于5050℃油浴中；再取N-(1-甲基-5-氯-吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺(0.2mmol)溶于0.8mL三氯甲烷，并通过蠕动泵1小时注入反应体系中，注入完毕后，继续搅拌1小时后，再通过柱层析(石油醚：乙酸乙酯＝3:1)分离得到产物3h。收率65％。
1H NMR(600MHz,Chloroform-d)δ10.23(s,1H),7.56–7.47(m,4H),7.39–7.31(m,9H),7.20(dd,J＝8.7,2.0Hz,1H),6.75(d,J＝8.0Hz,2H),6.68(d,J＝1.9Hz,1H),4.01(s,3H),2.09(s,3H)；13C NMR(151MHz,Chloroform-d)δ144.10(d,J＝12.3Hz),143.80,135.16(d,J＝10.9Hz),134.21,132.86(d,J＝109.8Hz),131.95(d,J＝2.7Hz),131.33(d,J＝11.0Hz),129.09,128.41(d,J＝12.7Hz),127.95,127.91,127.51,122.98,119.02,111.67,90.21(d,J＝124.2Hz),32.63,21.70；31P NMR(243MHz,CDCl3)δ27.80。
实施例9
称取二苯基膦氧(0.2mmol)以及六氟磷酸四乙腈铜(3.72mg，0.01mmol)于圆底烧瓶中，加入0.8mL三氯甲烷，置于5050℃油浴中；再取N-(1-甲基-5-溴-吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺(0.2mmol)溶于0.8mL三氯甲烷，并通过蠕动泵1小时注入反应体系中，注入完毕后，继续搅拌1小时后，再通过柱层析(石油醚：乙酸乙酯＝3:1)分离得到产物3i。收率59％。
1H NMR(600MHz,Chloroform-d)δ10.25(s,1H),7.56-7.47(m,4H),7.40-7.29(m,10H),6.83(d,J＝1.8Hz,1H),6.75(d,J＝8.0Hz,2H),4.00(s,3H),2.09(s,3H)；13C NMR(151MHz,Chloroform-d)δ143.99(d,J＝12.3Hz),143.80,135.46(d,J＝10.9Hz),134.24,132.86(d,J＝109.9Hz),131.95(d,J＝2.7Hz),131.33(d,J＝11.0Hz),129.09,128.53(d,J＝9.5Hz),128.41(d,J＝12.7Hz),127.94,125.57,122.04,115.09,112.07,90.16(d,J＝124.4Hz),32.60,21.71；31P NMR(243MHz,CDCl3)δ27.79。
实施例10
称取二苯基膦氧(0.2mmol)以及六氟磷酸四乙腈铜(3.72mg，0.01mmol)于圆底烧瓶中，加入0.8mL三氯甲烷，置于5050℃油浴中；再取N-(1-甲基吲哚-2-亚基-3-重氮)-4-溴苯磺酰胺(0.2mmol)溶于0.8mL三氯甲烷，并通过蠕动泵1小时注入反应体系中，注入完毕后，继续搅拌1小时后，再通过柱层析(石油醚：乙酸乙酯＝3:1)分离得到产物3j。收率65％。
1H NMR(600MHz,Chloroform-d)δ10.31(s,1H),7.55(m,2H),7.49-7.43(m,3H),7.40-7.35(m,8H),7.30-7.27(m,1H),7.06-7.03(m,2H),7.02-6.99(m,1H),6.79(d,J＝8.0Hz,1H),4.02(s,3H).；13C NMR(151MHz,Chloroform-d)δ142.44(d,J＝12.5Hz),136.72(d,J＝11.1Hz),136.21,132.97(d,J＝109.7Hz),132.22(d,J＝2.7Hz),131.64,131.21(d,J＝11.0Hz),129.55,128.55,128.46,126.88(d,J＝9.8Hz),122.81,121.93,119.83,110.68,90.71(d,J＝124.5Hz),32.36；31P NMR(243MHz,CDCl3)δ28.37。
实施例11
称取二苯基膦氧(0.2mmol)以及六氟磷酸四乙腈铜(3.72mg，0.01mmol)于圆底烧瓶中，加入0.8mL三氯甲烷，置于5050℃油浴中；再取N-(1-甲基吲哚-2-亚基-3-重氮)-4-三氟甲基苯磺酰胺(0.2mmol)溶于0.8mL三氯甲烷，并通过蠕动泵1小时注入反应体系中，注入完毕后，继续搅拌1小时后，再通过柱层析(石油醚：乙酸乙酯＝3:1)分离得到产物3k。收率70％。
1H NMR(600MHz,Chloroform-d)δ10.44(s,1H),7.80–7.78(m,2H),7.52–7.48(m,2H),7.47–7.44(m,1H),7.39–7.32(m,8H),7.31–7.27(m,1H),7.22(d,J＝8.3Hz,2H),7.01(t,J＝7.6Hz,1H),6.79(d,J＝8.0Hz,1H),4.04(s,3H)；13C NMR(151MHz,Chloroform-d)δ142.16(d,J＝12.2Hz),140.95,136.73(d,J＝11.1Hz),134.51,134.29,133.11(d,J＝109.8Hz),132.24(d,J＝2.7Hz),131.18(d,J＝11.0Hz),128.75,128.44(d,J＝12.7Hz),126.80(d,J＝9.7Hz),125.38(d,J＝3.7Hz),122.91,122.00,119.87,110.71,90.73(d,J＝124.1Hz),32.40；31P NMR(243MHz,CDCl3)δ28.53；19F NMR(565MHz,CDCl3)δ-62.87。
实施例12
称取二苯基膦氧(0.2mmol)以及六氟磷酸四乙腈铜(3.72mg，0.01mmol)于圆底烧瓶中，加入0.8mL三氯甲烷，置于5050℃油浴中；再取N-(1-甲基吲哚-2-亚基-3-重氮)-2,4,6-三异丙基苯磺酰胺(0.2mmol)溶于0.8mL三氯甲烷，并通过蠕动泵1小时注入反应体系中，注入完毕后，继续搅拌1小时后，再通过柱层析(石油醚：乙酸乙酯＝6:1)分离得到产物3l。收率88％。
1H NMR(600MHz,Chloroform-d)δ10.45(s,1H),7.55–7.46(m,6H),7.41(d,J＝8.3Hz,1H),7.38–7.33(m,4H),7.24(t,J＝7.4Hz,1H),7.07(s,2H),7.02–6.98(m,1H),6.85(d,J＝8.0Hz,1H),3.96(s,3H),3.94–3.87(m,2H),2.90–2.85(m,1H),1.25(d,J＝6.9Hz,6H),1.11(d,J＝6.7Hz,12H)；13C NMR(151MHz,Chloroform-d)δ153.04,151.11,143.58(d,J＝12.6Hz),136.62(d,J＝11.3Hz),133.62,133.04(d,J＝42.4Hz),131.83(d,J＝2.7Hz),131.66(d,J＝11.0Hz),128.28(d,J＝12.6Hz),127.06(d,J＝10.0Hz),123.85,122.29,121.59,119.57,110.29,90.31(d,J＝125.9Hz),33.96,32.23,30.51,24.81,23.48；31P NMR(243MHz,CDCl3)δ28.55。
实施例13
称取二(4-甲氧基苯基)膦氧(0.2mmol)以及六氟磷酸四乙腈铜(3.72mg，0.01mmol)于圆底烧瓶中，加入0.8mL三氯甲烷，置于5050℃油浴中；再取N-(1-甲基吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺(0.2mmol)溶于0.8mL三氯甲烷，并通过蠕动泵1小时注入反应体系中，注入完毕后，继续搅拌1小时后，再通过柱层析(石油醚：乙酸乙酯＝3:1)分离得到产物3m。收率88％。
1H NMR(600MHz,Chloroform-d)δ10.38(s,1H),7.53–7.50(m,2H),7.42(d,J＝8.3Hz,1H),7.31–7.23(m,5H),6.99(t,J＝7.6Hz,1H),6.84–6.81(m,4H),6.79–6.76(m,3H),4.01(s,3H),3.83(s,6H),2.10(s,3H)；13C NMR(151MHz,Chloroform-d)δ162.18,143.60,142.93(d,J＝12.6Hz),136.72(d,J＝11.1Hz),134.29,133.28(d,J＝12.4Hz),128.95,128.06,127.05(d,J＝9.6Hz),125.18(d,J＝116.1Hz),122.39,121.58,119.79,113.71(d,J＝13.7Hz),110.51,91.13(d,J＝125.3Hz),55.27,32.36,21.48；31P NMR(243MHz,CDCl3)δ27.17。
实施例14
称取二(2-甲基苯基)膦氧(0.2mmol)以及六氟磷酸四乙腈铜(3.72mg，0.01mmol)于圆底烧瓶中，加入0.8mL三氯甲烷，置于5050℃油浴中；再取N-(1-甲基吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺(0.2mmol)溶于0.8mL三氯甲烷，并通过蠕动泵1小时注入反应体系中，注入完毕后，继续搅拌1小时后，再通过柱层析(石油醚：乙酸乙酯＝3:1)分离得到产物3n。收率71％。
1H NMR(600MHz,Chloroform-d)δ10.41(s,1H),7.55-7.49(m,2H),7.45-7.35(m,3H),7.26-7.14(m,3H),7.07-7.01(m,2H),6.88(m,3H),6.66(d,J＝8.0Hz,2H),6.48(d,J＝8.0Hz,1H),4.04(s,3H),2.36(s,6H),2.05(s,3H)；13C NMR(151MHz,Chloroform-d)δ143.39,142.89(d,J＝12.9Hz),136.50(d,J＝10.9Hz),134.53,132.20,131.73,131.54,128.80,127.84,126.84(d,J＝9.4Hz),125.39(d,J＝13.7Hz),122.48,121.62,119.44,110.34,90.60(d,J＝123.3Hz),32.04,21.70,21.14；31P NMR(243MHz,CDCl3)δ33.51。
实施例15
称取二(4-氟苯基)膦氧(0.2mmol)以及六氟磷酸四乙腈铜(3.72mg，0.01mmol)于圆底烧瓶中，加入0.8mL三氯甲烷，置于5050℃油浴中；再取N-(1-甲基吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺(0.2mmol)溶于0.8mL三氯甲烷，并通过蠕动泵1小时注入反应体系中，注入完毕后，继续搅拌1小时后，再通过柱层析(石油醚：乙酸乙酯＝3:1)分离得到产物3o。收率57％。
1H NMR(600MHz,Chloroform-d)δ10.04(s,1H),7.51–7.44(m,3H),7.40–7.33(m,4H),7.31–7.26(m,1H),7.07–6.98(m,5H),6.78(d,J＝8.1Hz,2H),6.71(d,J＝8.0Hz,1H),4.03(s,3H),2.13(s,3H)；13C NMR(151MHz,Chloroform-d)δ164.92(dd,J＝253.8,3.1Hz),143.89,143.15(d,J＝12.8Hz),136.76(d,J＝11.3Hz),134.31,133.89(dd,J＝12.6,8.8Hz),129.24(d,J＝107.0Hz),128.98,128.05,126.71(d,J＝10.0Hz),126.37,122.42(d,J＝118.5Hz),119.34,115.76(dd,J＝21.4,13.9Hz),110.85,89.92(d,J＝127.5Hz),32.44,21.50；31P NMR(243MHz,CDCl3)δ26.34；19F NMR(565MHz,CDCl3)δ-106.27。
实施例16
称取二(3,5-双三氟甲基苯基)膦氧(0.2mmol)以及六氟磷酸四乙腈铜(3.72mg，0.01mmol)于圆底烧瓶中，加入0.8mL三氯甲烷，置于5050℃油浴中；再取N-(1-甲基吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺(0.2mmol)溶于0.8mL三氯甲烷，并通过蠕动泵1小时注入反应体系中，注入完毕后，继续搅拌1小时后，再通过柱层析(石油醚：乙酸乙酯＝3:1)分离得到产物3p。收率86％。
1H NMR(600MHz,Chloroform-d)δ9.48(s,1H),8.06(s,2H),7.91–7.80(m,4H),7.59–7.47(m,3H),7.38(t,J＝7.8Hz,1H),7.13(t,J＝7.3Hz,1H),6.79(d,J＝8.0Hz,2H),6.70(d,J＝8.0Hz,1H),4.09(s,3H),1.98(s,3H)；13C NMR(151MHz,Chloroform-d)δ144.03(d,J＝13.8Hz),143.80,136.90(d,J＝12.2Hz),136.03,135.31,134.15,132.63(d,J＝13.0Hz),132.40(d,J＝12.8Hz),132.17(d,J＝12.8Hz),131.05(d,J＝11.8Hz),128.98,128.21,126.15,125.76(d,J＝10.4Hz),123.79,123.40,123.12,121.59,118.15,111.66,86.41(d,J＝132.6Hz),32.66,21.13；31P NMR(243MHz,CDCl3)δ23.60；19F NMR(565MHz,CDCl3)δ-63.15。
实施例17
称取9,10-二氢-9-氧杂-10-磷杂菲-10-氧化物(0.2mmol)以及六氟磷酸四乙腈铜(3.72mg，0.01mmol)于圆底烧瓶中，加入0.8mL三氯甲烷，置于5050℃油浴中；再取N-(1-甲基吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺(0.2mmol)溶于0.8mL三氯甲烷，并通过蠕动泵1小时注入反应体系中，注入完毕后，继续搅拌1小时后，再通过柱层析(石油醚：乙酸乙酯＝3:1)分离得到产物3q。收率67％。
1H NMR(600MHz,Chloroform-d)δ9.37(s,1H),8.08–7.98(m,2H),7.79(d,J＝8.3Hz,2H),7.64(t,J＝7.7Hz,1H),7.44(d,J＝8.3Hz,1H),7.38(t,J＝7.7Hz,1H),7.33–7.29(m,3H),7.26(t,J＝7.7Hz,1H),7.18–7.13(m,1H),7.08(d,J＝7.9Hz,1H),6.93(t,J＝7.5Hz,1H),6.64(dd,J＝15.1,7.2Hz,1H),6.60(d,J＝8.0Hz,1H),4.06(s,3H),2.45(s,3H)；13C NMR(151MHz,Chloroform-d)δ148.98(d,J＝8.1Hz),144.41,143.77(d,J＝18.3Hz),136.75(d,J＝13.2Hz),135.23(d,J＝6.0Hz),134.64,132.88(d,J＝2.2Hz),130.59(d,J＝13.7Hz),130.32,129.64,128.89,127.77(d,J＝15.0Hz),126.52(d,J＝10.3Hz),125.44(d,J＝137.1Hz),125.04,124.57,123.61(d,J＝9.8Hz),123.06,122.11,121.97(d,J＝11.7Hz),120.55(d,J＝5.9Hz),119.64,110.63,88.76(d,J＝176.5Hz),32.59,21.79；31P NMR(243MHz,CDCl3)δ21.39。
实施例18
称取苯基膦酸乙酯(0.2mmol)以及六氟磷酸四乙腈铜(3.72mg，0.01mmol)于圆底烧瓶中，加入0.8mL三氯甲烷，置于5050℃油浴中；再取N-(1-甲基吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺(0.2mmol)溶于0.8mL三氯甲烷，并通过蠕动泵1小时注入反应体系中，注入完毕后，继续搅拌1小时后，再通过柱层析(石油醚：乙酸乙酯＝3:1)分离得到产物3r。收率42％。
1H NMR(600MHz,Chloroform-d)δ9.65(s,1H),7.55(d,J＝8.1Hz,2H),7.49–7.43(m,3H),7.41–7.32(m,3H),7.32–7.25(m,2H),7.20(t,J＝7.6Hz,1H),6.87(d,J＝8.1Hz,2H),4.01(s,3H),3.90–3.82(m,1H),3.66–3.56(m,1H),2.15(s,3H),1.20(t,J＝7.1Hz,3H)；13C NMR(151MHz,Chloroform-d)δ143.93,143.20(d,J＝17.1Hz),136.69(d,J＝12.1Hz),134.47,132.39(d,J＝152.1Hz),131.52(d,J＝2.9Hz),130.17(d,J＝11.3Hz),129.26,128.10,128.01(d,J＝14.2Hz),126.76(d,J＝9.2Hz),122.93,122.12,119.96,110.61,90.29(d,J＝155.8Hz),60.89(d,J＝6.1Hz),32.57,21.62,16.36(d,J＝7.0Hz)；31PNMR(243MHz,CDCl3)δ31.55。
实施例1～18中，非光学活性的膦氧基吲哚化合物的反应方程式是：
实施例19
称取实施例1的产物3a(0.1mmol)，在0℃环境下，加入浓硫酸0.5mL，在室温下反应2h。随后反应液冷却至0℃，加入约50mL冰水萃灭，再缓慢加入饱和NaHCO3溶液10mL。之后用CHCl3(20ml×3)萃取。有机相用无水硫酸钠干燥，过滤，旋干，再通过柱层析(二氯甲烷：甲醇＝3:1)分离得到产物4a。收率91％。
1H NMR(600MHz,Chloroform-d)δ7.80–7.73(m,4H),7.55–7.50(m,2H),7.46–7.40(m,4H),7.14(d,J＝8.1Hz,1H),7.06–7.01(m,1H),6.92–6.86(m,1H),6.64(d,J＝7.8Hz,1H),5.74(s,2H),3.56(s,3H)；13C NMR(151MHz,Chloroform-d)δ154.28(d,J＝13.7Hz),135.17,135.10,134.61(d,J＝107.7Hz),131.67(d,J＝10.8Hz),128.83(d,J＝11.4Hz),128.40(d,J＝12.3Hz),120.81,119.29,117.66,107.95,76.02(d,J＝136.5Hz),27.95；31PNMR(243MHz,CDCl3)δ29.13。
实施例19中，产物的衍生的反应方程式是：
实施例20
称取苯基膦酸薄荷酯(0.2mmol)(RP/SP>99/1)以及六氟磷酸四乙腈铜(7.45mg，0.02mmol)于圆底烧瓶中，加入0.8mL三氯甲烷，置于5050℃油浴中；再取N-(1-甲基吲哚-2-亚基-3-重氮)-2,4,6-三异丙基苯磺酰胺(0.2mmol)溶于0.8mL三氯甲烷，并通过蠕动泵1小时注入反应体系中，注入完毕后，继续搅拌8～12小时后，再通过柱层析(石油醚：乙酸乙酯＝6:1)分离得到产物5a。收率51％，dr>20:1。
1H NMR(600MHz,Chloroform-d)δ10.31(s,1H),7.59–7.52(m,2H),7.43(t,J＝7.0Hz,1H),7.36–7.29(m,3H),7.26–7.20(m,2H),7.18(s,2H),7.06(t,J＝7.5Hz,1H),4.30–4.20(m,1H),4.09–4.02(m,2H),3.85(s,3H),2.99–2.90(m,1H),2.38(d,J＝12.6Hz,1H),1.9–1.85(m,1H),1.66–1.56(m,2H),1.48–1.26(m,15H),1.06(d,J＝6.7Hz,6H),0.93(d,J＝6.4Hz,3H),0.92–0.82(m,2H),0.69(d,J＝7.0Hz,3H),0.09(d,J＝6.8Hz,3H)；13CNMR(151MHz,Chloroform-d)δ153.36,151.24,143.16(d,J＝16.5Hz),136.46(d,J＝12.2Hz),133.66(d,J＝150.7Hz),133.50,131.54(d,J＝2.7Hz),130.90(d,J＝11.1Hz),128.12(d,J＝13.9Hz),126.76(d,J＝9.9Hz),124.05,122.37,121.38,119.92,109.83,91.79(d,J＝156.1Hz),77.40(d,J＝7.1Hz),48.83(d,J＝6.6Hz),44.01,34.13,34.10,32.07,31.56,30.36,25.10,24.79(d,J＝20.4Hz),23.57(d,J＝15.6Hz),22.64,22.09,21.02,14.80；31P NMR(243MHz,CDCl3)δ29.32。
实施例21
称取苯基膦酸薄荷酯(0.2mmol)(RP/SP>99/1)以及六氟磷酸四乙腈铜(7.45mg，0.02mmol)于圆底烧瓶中，加入0.8mL三氯甲烷，置于5050℃油浴中；再取N-(1-甲基-5-甲氧基吲哚-2-亚基-3-重氮)-2,4,6-三异丙基苯磺酰胺(0.2mmol)溶于0.8mL三氯甲烷，并通过蠕动泵1小时注入反应体系中，注入完毕后，继续搅拌8～12小时后，再通过柱层析(石油醚：乙酸乙酯＝6:1)分离得到产物5b。收率56％，dr>20:1。
1H NMR(600MHz,Chloroform-d)δ10.18(s,1H),7.58–7.53(m,2H),7.45–7.41(m,1H),7.33–7.29(m,2H),7.21(dd,J＝8.9,1.7Hz,1H),7.17(s,2H),6.86(dd,J＝8.9,2.5Hz,1H),6.66(d,J＝2.4Hz,1H),4.29–4.22(m,1H),4.09–4.03(m,2H),3.80(s,3H),3.67(s,3H),2.98–2.90(m,1H),2.40(d,J＝12.6Hz,1H),1.98–1.90(m,1H),1.66–1.61(m,1H),1.61–1.56(m,1H),1.49–1.25(m,15H),1.07(d,J＝6.7Hz,6H),0.93(d,J＝6.5Hz,3H),0.91–0.82(m,2H),0.72(d,J＝7.0Hz,3H),0.09(d,J＝6.8Hz,3H)；13C NMR(151MHz,Chloroform-d)δ155.14,153.35,151.26,143.06(d,J＝16.5Hz),133.63(d,J＝150.3Hz),133.43,131.54(d,J＝2.8Hz),131.47(d,J＝12.2Hz),130.92(d,J＝11.0Hz),128.10(d,J＝13.8Hz),127.41(d,J＝9.6Hz),124.03,111.82,110.57,102.50,91.59(d,J＝156.6Hz),77.30(d,J＝7.1Hz),55.63,48.86(d,J＝6.6Hz),44.06,34.14,34.10,32.13,31.54,30.32,25.18,24.81(d,J＝14.6Hz),23.56(d,J＝16.1Hz),22.65,22.09,21.05,14.76；31PNMR(243MHz,CDCl3)δ29.19。
实施例22
称取苯基膦酸薄荷酯(0.2mmol)(RP/SP>99/1)以及六氟磷酸四乙腈铜(7.45mg，0.02mmol)于圆底烧瓶中，加入0.8mL三氯甲烷，置于5050℃油浴中；再取N-(1-甲基-5-氟吲哚-2-亚基-3-重氮)-2,4,6-三异丙基苯磺酰胺(0.2mmol)溶于0.8mL三氯甲烷，并通过蠕动泵1小时注入反应体系中，注入完毕后，继续搅拌8～12小时后，再通过柱层析(石油醚：乙酸乙酯＝6:1)分离得到产物5c。收率51％，dr>20:1。
1H NMR(600MHz,Chloroform-d)δ10.30(s,1H),7.52(dd,J＝13.3,7.6Hz,2H),7.47–7.43(m,1H),7.34–7.30(m,2H),7.26(dd,J＝9.0,4.2Hz,1H),7.18(s,2H),6.99–6.95(m,1H),6.88(dd,J＝9.5,2.4Hz,1H),4.27–4.20(m,1H),4.06–4.01(m,2H),3.84(s,3H),3.00–2.91(m,1H),2.35(d,J＝12.7Hz,1H),1.90–1.84(m,1H),1.66–1.57(m,2H),1.44–1.27(m,15H),1.06(d,J＝6.7Hz,6H),0.92(d,J＝6.4Hz,3H),0.90–0.83(m,2H),0.73(d,J＝7.0Hz,3H),0.15(d,J＝6.7Hz,3H)；13C NMR(151MHz,Chloroform-d)δ158.72(d,J＝237.1Hz),153.48,151.23,144.18(d,J＝16.3Hz),133.40,133.27(d,J＝150.8Hz),132.93(d,J＝11.9Hz),131.74(d),130.82(d,J＝11.1Hz),128.24(d,J＝13.9Hz),127.30(t,J＝10.1Hz),124.10,110.71(d,J＝9.7Hz),110.52(d,J＝26.0Hz),105.30(d,J＝24.8Hz),92.16(d,J＝160.3Hz),77.57(d,J＝7.1Hz),48.78(d,J＝6.5Hz),43.96,34.10,34.08,32.37,31.58,30.39,25.20,24.79(d,J＝18.7Hz),23.56(d,J＝17.5Hz),22.62,22.06,21.03,14.78；31P NMR(243MHz,CDCl3)δ28.70；19F NMR(565MHz,CDCl3)δ-121.62。
实施例23
称取苯基膦酸薄荷酯(0.2mmol)(RP/SP>99/1)以及六氟磷酸四乙腈铜(7.45mg，0.02mmol)于圆底烧瓶中，加入0.8mL三氯甲烷，置于5050℃油浴中；再取N-(1-甲基-5-氯吲哚-2-亚基-3-重氮)-2,4,6-三异丙基苯磺酰胺(0.2mmol)溶于0.8mL三氯甲烷，并通过蠕动泵1小时注入反应体系中，注入完毕后，继续搅拌8～12小时后，再通过柱层析(石油醚：乙酸乙酯＝6:1)分离得到产物5d。收率48％，dr>20:1。
1H NMR(600MHz,Chloroform-d)δ10.33(s,1H),7.54–7.49(m,2H),7.47–7.44(m,1H),7.35–7.30(m,2H),7.26(dd,J＝9.4,1.8Hz,1H),7.21–7.16(m,4H),4.23–4.16(m,1H),4.05–3.99(m,2H),3.84(s,3H),2.97–2.91(m,1H),2.37–2.33(m,1H),1.92–1.85(m,1H),1.66–1.57(m,2H),1.44–1.26(m,15H),1.05(d,J＝6.8Hz,6H),0.92(d,J＝6.4Hz,3H),0.89–0.83(m,2H),0.74(d,J＝7.0Hz,3H),0.14(d,J＝6.9Hz,3H)；13C NMR(151MHz,Chloroform-d)δ153.52,151.22,144.18(d,J＝16.3Hz),134.86(d,J＝11.8Hz),133.33,133.24(d,J＝151.3Hz),131.77,130.76(d,J＝11.1Hz),128.27(d,J＝14.0Hz),127.72(d,J＝9.4Hz),127.25,124.11,122.72,119.38,110.92,91.70(d,J＝155.4Hz),77.77(d,J＝7.2Hz),48.79(d,J＝6.7Hz),43.95,34.10,34.05,32.37,31.58,30.39,25.27,24.79(d,J＝14.0Hz),23.55(d,J＝17.1Hz),22.62,22.05,21.05,14.75；31P NMR(243MHz,CDCl3)δ28.67。
实施例24
称取苯基膦酸薄荷酯(0.2mmol)(RP/SP>99/1)以及六氟磷酸四乙腈铜(7.45mg，0.02mmol)于圆底烧瓶中，加入0.8mL三氯甲烷，置于5050℃油浴中；再取N-(1-甲基-5-溴吲哚-2-亚基-3-重氮)-2,4,6-三异丙基苯磺酰胺(0.2mmol)溶于0.8mL三氯甲烷，并通过蠕动泵1小时注入反应体系中，注入完毕后，继续搅拌8～12小时后，再通过柱层析(石油醚：乙酸乙酯＝6:1)分离得到产物5e。收率52％，dr>20:1。
1H NMR(600MHz,Chloroform-d)δ10.34(s,1H),7.54–7.49(m,2H),7.48–7.44(m,1H),7.36(d,J＝1.9Hz,1H),7.35–7.31(m,3H),7.21(dd,J＝8.6,1.7Hz,1H),7.18(s,2H),4.22–4.16(m,1H),4.05–4.00(m,2H),3.84(s,3H),2.97–2.92(m,1H),2.38–2.33(m,1H),1.93–1.86(m,1H),1.66–1.57(m,2H),1.45–1.25(m,15H),1.05(d,J＝6.8Hz,6H),0.92(d,J＝6.4Hz,3H),0.91–0.85(m,2H),0.76(d,J＝7.1Hz,3H),0.13(d,J＝6.8Hz,3H)；13C NMR(151MHz,Chloroform-d)δ153.54,151.22,144.08(d,J＝16.4Hz),135.17(d,J＝11.7Hz),133.32,133.22(d,J＝151.4Hz),131.80(d,J＝2.8Hz),130.75(d,J＝11.1Hz),128.28(d,J＝14.0Hz),128.27,125.34,124.11,122.41,114.85,111.33,91.59(d,J＝155.1Hz),77.81(d,J＝7.2Hz),48.79(d,J＝6.7Hz),43.97,34.11,34.06,32.35,31.59,30.39,25.29,24.79(d,J＝12.6Hz),23.55(d,J＝17.0Hz),22.63,22.05,21.08,14.76；31P NMR(243MHz,CDCl3)δ28.69。
实施例25
称取苯基膦酸薄荷酯(0.2mmol)(RP/SP>99/1)以及六氟磷酸四乙腈铜(7.45mg，0.02mmol)于圆底烧瓶中，加入0.8mL三氯甲烷，置于5050℃油浴中；再取N-(1-苄基吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺(0.2mmol)溶于0.8mL三氯甲烷，并通过蠕动泵1小时注入反应体系中，注入完毕后，继续搅拌8～12小时后，再通过柱层析(石油醚：乙酸乙酯＝6:1)分离得到产物5f。收率42％，dr>20:1。
1H NMR(600MHz,Chloroform-d)δ10.06(s,1H),7.71(d,J＝8.0Hz,2H),7.58–7.54(m,1H),7.39–7.31(m,9H),7.27–7.21(m,3H),7.13(t,J＝7.5Hz,1H),7.01(d,J＝8.0Hz,2H),6.24(d,J＝16.4Hz,1H),5.64(d,J＝16.4Hz,1H),4.15–4.06(m,1H),2.39–2.33(m,1H),2.26(s,3H),1.81–1.74(m,2H),1.72–1.68(m,1H),1.65–1.60(m,1H),1.52–1.33(m,2H),1.01(d,J＝6.5Hz,3H),0.91(m,2H),0.67(d,J＝7.0Hz,3H),0.04(d,J＝6.8Hz,3H)；13CNMR(151MHz,Chloroform-d)δ144.04,142.87(d,J＝16.7Hz),136.76,135.97(d,J＝11.8Hz),134.26,133.20(d,J＝150.1Hz),131.47(d,J＝2.8Hz),130.32(d,J＝11.7Hz),129.31,128.50,128.43,127.97(d,J＝14.2Hz),127.44,127.24(d,J＝9.1Hz),126.93,122.86,121.58,120.62,111.76,92.54(d,J＝155.1Hz),77.73(d,J＝7.2Hz),48.91,48.51(d,J＝6.4Hz),44.07,34.02,31.68,24.96,22.65,22.02,21.66,20.74,14.73；31P NMR(243MHz,CDCl3)δ31.31。
实施例20～25中，具有光学活性的膦氧基吲哚化合物的反应方程式是：
实施例26
一种膦氧基吲哚化合物及其衍生物的制备方法，用重氮吲哚化合物和膦氧基化合物在六氟磷酸四乙腈铜的催化下，实现P-H插入反应，得到膦氧基吲哚化合物及其衍生物，具体步骤如下：
(1)先称取1eq重氮吲哚化合物，将重氮吲哚化合物溶解于有机溶剂中，浓度控制为0.3mol/L，得到重氮溶液；
(2)在一个圆底烧瓶中加入1eq的膦氧基化合物和0.08eq的六氟磷酸乙腈铜，加入有机溶剂，控制溶液中膦氧基化合物的浓度为0.3mol/L；
(3)圆底烧瓶置于55℃油浴中，将重氮溶液缓慢滴加入圆底烧瓶中，在2小时滴加结束，搅拌反应12小时，得到粗产物，
(4)将粗产物用体积比为乙酸乙酯：石油醚＝1:6的溶液进行柱层析，得到所述膦氧基吲哚化合物及其衍生物。

Claims (5)

1.一种膦氧基吲哚化合物及其衍生物的制备方法，其特征在于，用重氮吲哚化合物和膦氧基化合物在六氟磷酸四乙腈铜的催化下，实现P-H插入反应，得到膦氧基吲哚化合物及其衍生物，具体步骤如下：
(1)先称取1eq重氮吲哚化合物，将重氮吲哚化合物溶解于有机溶剂中，浓度控制为0.3～0.5mol/L，得到重氮溶液；
(2)在一个圆底烧瓶中加入1～1.2eq的膦氧基化合物和0.05～0.10eq的六氟磷酸乙腈铜，加入有机溶剂，控制溶液中膦氧基化合物的浓度为0.3～0.5mol/L；
(3)圆底烧瓶置于50～55℃油浴中，将重氮溶液缓慢滴加入圆底烧瓶中，在1～2小时滴加结束，搅拌反应1-12小时，得到粗产物，
(4)将粗产物用体积比为乙酸乙酯：石油醚＝1:6～3的溶液进行柱层析，得到所述膦氧基吲哚化合物及其衍生物。
2.如权利要求1所述的膦氧基吲哚化合物及其衍生物的制备方法，其特征在于，所述有机溶剂为三氯甲烷。
3.如权利要求1所述的膦氧基吲哚化合物及其衍生物的制备方法，其特征在于，所述重氮吲哚化合物由相应的吲哚和叠氮化合物制备得到。
4.如权利要求1所述的膦氧基吲哚化合物及其衍生物的制备方法，其特征在于，所述重氮化合物为N-(1-甲基吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺、N-(1-乙基吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺、N-(1-异丙基吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺、N-(1-苄基吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺、N-(1-烯丙基吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺、N-(1-甲基-5-甲基-吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺、N-(1-甲基-5-氟-吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺、N-(1-甲基-5-氯-吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺、N-(1-甲基-5-溴-吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺、N-(1-甲基吲哚-2-亚基-3-重氮)-4-溴苯磺酰胺、N-(1-甲基吲哚-2-亚基-3-重氮)-2,4,6-三异丙基苯磺酰胺、N-(1-甲基吲哚-2-亚基-3-重氮)-4-甲基苯磺酰胺、N-(1-甲基-5-甲氧基吲哚-2-亚基-3-重氮)-2,4,6-三异丙基苯磺酰胺、N-(1-甲基-5-氟吲哚-2-亚基-3-重氮)-2,4,6-三异丙基苯磺酰胺、N-(1-甲基-5-氯吲哚-2-亚基-3-重氮)-2,4,6-三异丙基苯磺酰胺以及N-(1-甲基-5-溴吲哚-2-亚基-3-重氮)-2,4,6-三异丙基苯磺酰胺中的任意一种。
5.如权利要求1所述的膦氧基吲哚化合物及其衍生物的制备方法，其特征在于，所述膦氧基化合物为二苯基膦氧、二(4-甲氧基苯基)膦氧、二(2-甲基苯基)膦氧、二(4-氟苯基)膦氧、二(3,5-双三氟甲基苯基)膦氧、9,10-二氢-9-氧杂-10-磷杂菲-10-氧化物、苯基膦酸乙酯以及苯基膦酸薄荷酯中的任意一种。
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