CN118047657A - 一种偕二氟烯烃类化合物及其制备方法 - Google Patents

一种偕二氟烯烃类化合物及其制备方法 Download PDF

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CN118047657A
CN118047657A CN202410030267.9A CN202410030267A CN118047657A CN 118047657 A CN118047657 A CN 118047657A CN 202410030267 A CN202410030267 A CN 202410030267A CN 118047657 A CN118047657 A CN 118047657A
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张譞
焦岩
李鑫
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Nanjing University of Information Science and Technology
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Abstract

本发明公开了一种偕二氟烯烃类化合物及其制备方法，其中，制备方法包括以下步骤：将醇和碱在四氢呋喃溶液中进行反应，然后加入二硫化碳，继续反应，得到中间体；将中间体、三氟甲基烯烃和还原剂加入到溶剂中，以蓝光照射进行反应，反应结束后分离，得到偕二氟烯烃类化合物。本发明所提供的制备方法，原料来源广泛，产物具有多样性，反应条件温和可控，绿色环保，无污染，实用性好。

Description

一种偕二氟烯烃类化合物及其制备方法
技术领域
本发明属于材料合成技术领域，具体涉及一种偕二氟烯烃类化合物及其制备方法。
背景技术
含氟化合物因其高渗透性、强吸电子性、热稳定性和高疏水疏油性而广泛应用于药物及其中间体(氧氟沙星)、农药(氯氟氰菊酯)、高性能材料(聚四氟乙烯)和表面活性剂(PFOS)等领域，例如已知的含氟上市药物据统计就已经有300多种，含氟农药有150多种。众多含氟化合物中，含有1,1-二氟乙烯(偕二氟乙烯)结构的化合物，以其独特的结构，良好的反应活性，可以作为高分子单体聚合成高分子材料，也可以作为羰基的生物电子等排体用于药物及其中间体设计，也可作为农药或者功能材料使用。比如瑞士诺华制药的专利(DengHaibing等，US11420970B1)报道的含偕二氟乙烯的化合物作为一种NSD2蛋白抑制剂，在抗肿瘤药物等相关领域具有良好的应用价值。
也有报道偕二氟烯烃类化合物可以用作治疗骨质疏松等疾病的候选药物(US20220332690A1)，一些化合物作为多巴胺受体拮抗剂，并有望用于精神类疾病的治疗(CN 114456149A)。作为有机合成中间体，偕二氟烯烃其可以用于氟代羧酸化合物的合成(Zhu C.等，Chem.Sci.,2019,10,6721-6726.)，二氟硫甲基酮或醇的制备(CN 114436919B)，氟代烯基醇的合成(CN 115448816 A)，是一种应用广泛的含氟化合物。目前偕二氟烯烃化合物的合成方法中，文献报道有以氟磺酰基二氟乙酸甲酯和苯甲醛反应制得(Thomoson,Charles S等，Journal of Fluorine Chemistry,2013,150,53-59)，以二氟氯乙酸钠和醛反应得到(Loska R等，Organic Letters,2013,15,5706-5709)，或者以三氟甲基烯烃和相应的给体化合物以加成脱氟反应得到偕二氟烯烃化合物(褚雪强等，CN 114409515 A；Lu X等，Chem.Sci.,2019,10,809-813；ZhouY等，US20190144469A1)，其中以三氟甲基烯烃为氟来源，该化合物容易制备，性质稳定，克服了前二者存在的试剂不好保存使用，反应产物单一等问题。三氟甲基苯乙烯可以和相应的烯烃，硫醇，二硼酸酯等反应生成偕二氟烯烃，具有反应物来源多元，产物种类丰富的特点。但是，作为有机物中常见的醇类化合物，在无催化剂、无金属参与下羟基碳的活化对三氟甲基烯烃的加成，尚未见研究。
发明内容
本发明的目的在于克服现有技术中的不足，提供一种偕二氟烯烃类化合物及其制备方法，原料来源广泛，产物具有多样性，反应条件温和可控，绿色环保，无污染，实用性好。
本发明提供了如下的技术方案：
第一方面，提供一种偕二氟烯烃类化合物的制备方法，包括以下步骤：
将醇和碱在四氢呋喃溶液中进行反应，然后加入二硫化碳，继续反应，得到中间体；
将中间体、三氟甲基烯烃和还原剂加入到溶剂中，以蓝光照射进行反应，反应结束后分离，得到偕二氟烯烃类化合物。
进一步的，所述醇为以下醇中的一种：
进一步的，所述醇和碱在四氢呋喃溶液中进行反应的温度为25℃，反应时间为30min。
进一步的，加入二硫化碳后继续反应的温度为0℃，反应时间为3h。
进一步的，所述三氟甲基烯烃为以下烯烃中的一种：
进一步的，所述还原剂为二环己基一苯基膦。
进一步的，所述蓝光为456nm蓝光，以蓝光照射进行反应的时间为12h。
进一步的，所述醇、碱和二硫化碳的摩尔比为1：1：3。
进一步的，所述中间体、三氟甲基烯烃和还原剂的摩尔比为1：1.2：1.2。
第二方面，提供一种偕二氟烯烃类化合物，采用第一方面所述方法制备得到。
与现有技术相比，本发明的有益效果是：
(1)本发明以醇为供体，三氟甲基烯烃为受体，加成脱氟合成偕二氟烯烃类化合物，原料来源广泛，产物具有多样性，实用性好；
(2)本发明的中间体、三氟甲基烯烃和还原剂以蓝光照射即可进行反应，无需任何催化剂和金属参与反应，也不需要使用加热装置，条件温和可控，绿色环保，无污染，实用性好；
(3)本发明提供的制备方法能够对一些药物分子如吉非罗齐、布洛芬、吲哚美辛、非诺贝特酸和非布索坦进行偕二氟烯烃修饰，产率高，有望应用于药物分子或者天然产物的结构改造。
附图说明
图1为本发明实施例中所采用的反应瓶和光化学反应器；
图2a、图2b和图2c分别为本发明实施例40中化合物5n的核磁共振氢谱、碳谱和氟谱图；
图3a、图3b和图3c为本发明实施例41中化合物5o的核磁共振氢谱、碳谱和氟谱图；
图4a、图4b和图4c为本发明实施例42中化合物5p的核磁共振氢谱、碳谱和氟谱图；
图5a、图5b和图5c为本发明实施例43中化合物5q的核磁共振氢谱、碳谱和氟谱图；
图6a、图6b和图6c为本发明实施例44中化合物5r的核磁共振氢谱、碳谱和氟谱图；
图7a、图7b和图7c为本发明实施例45中化合物5s的核磁共振氢谱、碳谱和氟谱图；
图8a、图8b和图8c为本发明实施例46中化合物5t的核磁共振氢谱、碳谱和氟谱图；
图9a、图9b和图9c为本发明实施例47中化合物5u的核磁共振氢谱、碳谱和氟谱图。
具体实施方式
下面结合附图对本发明作进一步描述。以下实施例仅用于更加清楚地说明本发明的技术方案，而不能以此来限制本发明的保护范围。
实施例1：制备2-(1,1-二氟-6-苯基己-1-烯-2-基)萘(化合物3a)
1.1磺原酸盐的制备
氮气保护下，在圆底烧瓶中先后加入10mmol的苯丙醇(1a)、10mmol的叔丁醇钾和100ml四氢呋喃，室温反应30min，0℃下加入30mmol的二硫化碳，继续搅拌反应3h，结束反应，减压蒸干，得到固体，乙醚洗涤，真空干燥得到磺原酸盐，反应式如下。淡黄色固体，2.34g，产率93％。1H NMR(400MHz,DMSO-D6)δ:7.28(t,J＝7.4Hz,2H),7.22-7.15(m,3H),4.18(t,J＝6.6Hz,2H),2.63(t,J＝7.9Hz,2H),1.93-1.85(m,2H)；13C NMR(100MHz,DMSO-D6)δ:141.7,128.3,125.7,70.0,31.9,30.3；无需提纯，直接投入下一步反应。
1.2偕二氟烯烃的制备
上述黄原酸盐0.30mmol，在氮气保护下，加入α-三氟甲基萘乙烯(2a)(80mg，0.36mmol)、还原剂二环己基一苯基膦(PhPCy2，98.8mg，0.36mmol)和溶剂丙酮/乙腈(5.4mL/0.6mL)，密封，室温下搅拌，以LEDS蓝光(456nm，the light intensity is 25％)照射12h进行反应，装置见附图1。反应结束，蒸干溶剂，硅胶柱层析得到化合物3a：2-(1,1-二氟-6-苯基己-1-烯-2-基)萘，反应式如下。
由1a和2a制备得到3a，产率86％，黄色油状物:1H NMR(400MHz,CDCl3)δ:7.87-7.79(m,4H),7.54-7.45(m,4H),7.29(t,J＝7.2Hz,2H),7.20(dd,J＝7.7Hz,7.0Hz,3H),2.63-2.56(m,4H),1.74-1.66(m,2H),1.53-1.46(m,2H)；13C NMR(100MHz,CDCl3)δ:153.8(dd,J＝285.1Hz,285.1Hz),142.3,133.2,132.4,131.1(t,J＝3.8Hz),128.3,128.2,128.0,127.9,127.6,127.3(t,J＝3.8Hz),126.2,126.1(t,J＝3.8Hz),126.0,125.7,92.4(dd,J＝12.9Hz,12.9Hz),35.5,30.7,27.4,27.2；19F NMR(376MHz,CDCl3)δ:-91.01(d,J＝43.4Hz),-91.40(d,J＝43.3Hz)。
实施例2：制备(5-(4-溴苯基)-1,1-二氟戊-1-烯-2-基)萘(化合物3b)
采用实施例1的方法，由1b和2a制备得到3b(结构式如上)，产率72％，白色固体:1HNMR(400MHz,CDCl3)δ:7.85-7.80(m,3H),7.71(s,1H),7.52-7.49(m,2H),7.41(dd,J＝8.6Hz,8.5Hz,3H),6.99(d,J＝8.4Hz,2H),2.61-2.52(m,4H),1.75-1.67(m,2H)；13C NMR(100MHz,CDCl3)δ:153.8(dd,J＝285.6Hz,285.6Hz),140.7,133.2,132.4,131.3,130.8(t,J＝3.8Hz),130.1,128.1,127.9,127.6,127.2(d,J＝3.4Hz),126.3,126.2,126.0(d,J＝2.9Hz),119.5,92.2(dd,J＝13.4Hz,13.4Hz),34.5,29.1,27.1；19F NMR(376MHz,CDCl3)δ:-90.75(d,J＝41.9Hz),-91.02(d,J＝43.4Hz)。
实施例3：制备(5-(4-甲氧基苯基)-1,1-二氟戊-1-烯-2-基)萘(化合物3c)
采用实施例1的方法，由1c和2a制备得到3c(结构式如上)，产率70％，无色油状物:1H NMR(400MHz,CDCl3)δ:7.85-7.81(m,3H),7.74(s,1H),7.52-7.43(m,3H),7.06(d,J＝8.7Hz,2H),6.83(d,J＝8.7Hz,2H),3.79(s,3H),2.62-2.53(m,4H),1.76-1.68(m,2H)；13CNMR(100MHz,CDCl3)δ:167.7,153.8(dd,J＝285.6Hz,285.6Hz),133.8,133.2,132.4,131.0(t,J＝3.4Hz),129.2,128.0,127.9,127.6,127.2(t,J＝3.4Hz),126.2,126.1,126.1,113.7,92.3(dd,J＝12.9Hz,12.9Hz),55.2,34.2,29.6,27.1；19F NMR(376MHz,CDCl3)δ:-90.86(d,J＝41.9Hz),-91.19(d,J＝41.9Hz)。
实施例4：制备2-(1,1-二氟-6-(4-(三氟甲基)苯基)己-1-烯-2-基)萘(化合物3d)
采用实施例1的方法，由1d和2a制备得到3d(结构式如上)，产率71％，无色油状物:1H NMR(400MHz,CDCl3)δ:7.86-7.75(m,4H),7.53-7.41(m,5H),7.22(d,J＝8.2Hz,2H),2.64-2.53(m,4H),1.70-1.63(m,2H),1.49-1.41(m,2H)；13C NMR(100MHz,CDCl3)δ:153.8(dd,J＝285.6Hz,285.6Hz),146.4,133.2,132.4,130.9,128.6,127.9(dt,J＝32.1Hz,25.4Hz),127.3(d,J＝3.4Hz),126.3,126.2,126.1(t,J＝3.4Hz),125.7(d,J＝270.7Hz),125.2(q,J＝3.4Hz),92.2(dd,J＝13.9Hz,13.9Hz),35.3,30.3,27.3,27.1；19F NMR(376MHz,CDCl3)δ:-62.13,-91.11(d,J＝43.3Hz),-91.30(d,J＝43.3Hz)。
实施例5：制备叔丁基(4-(5,5-二氟-4-(萘-2-基)戊-4-烯-1-基)苯基)氨基甲酸酯(化合物3e)
采用实施例1的方法，由1e和2a制备得到3e(结构式如上)，产率821％，白色固体:1H NMR(400MHz,CDCl3)δ:7.84-7.72(m,4H),7.52-7.47(m,2H),7.43(d,J＝8.6Hz,1H),7.25(d,J＝8.4Hz,2H),7.05(d,J＝8.6Hz,2H),6.45(s,1H),2.61-2.51(m,4H),1.74-1.66(m,2H),1.53(s,3H)；13C NMR(100MHz,CDCl3)δ:153.7(dd,J＝285.6Hz,285.6Hz),152.8,136.4,136.1,133.2,132.4,130.9(t,J＝3.4Hz),128.8,128.0,127.9,127.5,127.2(t,J＝3.4Hz),126.2,126.1,118.6,92.3(dd,J＝13.0Hz,13.0Hz),80.3,34.4,29.4,28.3,27.1；19F NMR(376MHz,CDCl3)δ:-90.85(d,J＝43.3Hz),-91.1(d,J＝43.3Hz)。
实施例6：制备4-(6,6-二氟-5-(萘-2-基)己-5-烯-1-基)吡啶(化合物3f)
采用实施例1的方法，由1f和2a制备得到3f(结构式如上)，产率52％，黄色油状物:1H NMR(400MHz,CDCl3)δ:7.44(d,J＝6.2Hz,2H),7.84-7.74(m,4H),7.51-7.40(m,3H),7.03(d,J＝6.3Hz,2H),2.57-2.51(m,4H),1.69-1.61(m,2H),1.48-1.40(m,2H)；13C NMR(100MHz,CDCl3)δ:153.8(dd,J＝285.6Hz,285.6Hz),151.1,149.6,133.2,132.4,130.8,128.1,127.8,127.6,127.3(t,J＝3.4Hz),126.3,126.2,126.0(t,J＝2.9Hz),123.8,92.1(dd,J＝13.4Hz,13.4Hz),34.7,29.4,27.3,27.0；19F NMR(376MHz,CDCl3)δ:-91.04(d,J＝43.3Hz),-91.23(d,J＝43.3Hz)。
实施例7：制备1-(5,5-二氟-4-(萘-2-基)戊-4-烯-1-基)-1H-吡唑(化合物3g)
采用实施例1的方法，由1g和2a制备得到3g(结构式如上)，产率35％，黄色油状物:1H NMR(400MHz,CDCl3)δ:7.84-7.79(m,3H),7.71(s,1H),7.51-7.48(m,3H),7.41(m,1H),7.30(d,J＝2.2Hz,1H),4.13(t,J＝7.0Hz,2H),2.54-24.9(m,2H),2.03-1.95(m,2H)；13CNMR(100MHz,CDCl3)δ:153.8(dd,J＝286.1Hz,286.1Hz),139.3,133.2,132.5,130.4(t,J＝3.4Hz),129.0,128.2,127.9,127.6,127.2(t,J＝3.8Hz),126.4,126.2,125.9(t,J＝3.4Hz),105.3,91.5(dd,J＝13.4Hz,13.4Hz),51.1,28.5,24.7；19F NMR(376MHz,CDCl3)δ:-90.03(d,J＝41.9Hz),-90.34(d,J＝41.9Hz)。
实施例8：制备2-(6,6-二氟-5-(萘-2-基)己-5-烯-1-基)噻吩(化合物3h)
采用实施例1的方法，由1h和2a制备得到3h(结构式如上)，产率41％，无色油状物:1H NMR(400MHz,CDCl3)δ:7.85-7.76(m,4H),7.50(td,J＝3.6Hz,8.7Hz,3H),7.10(d,J＝5.2Hz,1H),6.89(t,J＝5.2Hz,1H),6.74(d,J＝3.7Hz,1H),2.80(t,J＝7.6Hz,2H),2.57-2.53(m,2H),1.76-1.69(m,2H),1.53-1.45(m,2H)；13C NMR(100MHz,CDCl3)δ:153.8(dd,J＝285.6Hz,285.6Hz),145.2,133.2,132.4,131.0(t,J＝3.8Hz),128.0,127.9,127.6,127.3(t,J＝3.4Hz),126.6,126.2,126.1,124.0,122.9,92.3(dd,J＝13.4Hz,13.4Hz),31.0,29.5,27.3,27.1；19F NMR(376MHz,CDCl3)δ:-91.05(d,J＝43.3Hz),-91.32(d,J＝43.3Hz)。
实施例9：制备N-(6,6-二氟-5-(萘-2-基)己-5-烯-1-基)-N-苯基苯胺(化合物3i)
采用实施例1的方法，由1i和2a制备得到3i(结构式如上)，产率42％，无色油状物:1H NMR(400MHz,CDCl3)δ:7.85-7.72(m,4H),7.50(t,J＝4.8Hz,2H),7.39(d,J＝8.6Hz,1H),7.22(t,J＝7.4Hz,4H),6.96-6.88(m,6H),3.63(t,J＝7.5Hz,2H),2.52(t,J＝7.4Hz,2H),1.73-1.65(m,2H),1.47-1.40(m,2H)；13C NMR(100MHz,CDCl3)δ:153.8(dd,J＝285.1Hz,285.1Hz),147.9,133.2,132.4,130.9,129.2,128.1,127.9,127.6,127.3(t,J＝3.4Hz),126.3,126.1,121.1,120.8,92.3(dd,J＝13.4Hz,13.4Hz),51.8,27.4,26.7,25.1；19F NMR(376MHz,CDCl3)δ:-91.10(d,J＝43.3Hz),-91.34(d,J＝43.3Hz)。
实施例10：制备2-(1,1-二氟壬-1-烯-2-基)萘(化合物3j)
采用实施例1的方法，由1j和2a制备得到3j(结构式如上)，产率80％，无色油状物:1H NMR(400MHz,CDCl3)δ:7.86-7.79(m,4H),7.51-7.45(m,3H),2.54-2.49(m,2H),1.43-1.25(m,10H),0.88(t,J＝7.1Hz,3H)；13C NMR(100MHz,CDCl3)δ:153.8(dd,J＝285.1Hz,285.1Hz),133.3,132.4,131.3(t,J＝3.4Hz),128.0,127.9,127.6,127.3(t,J＝3.4Hz),126.2,126.0,92.6(dd,J＝12.5Hz,12.9Hz),31.8,29.0,28.9,27.8,27.7,22.6,14.0；19FNMR(376MHz,CDCl3)δ:-91.4(d,J＝44.8Hz),-91.71(d,J＝44.8Hz).。
实施例11：制备2-(1,1-二氟丙-1-烯-2-基)萘(化合物3k)
采用实施例1的方法，由1k和2a制备得到3k(结构式如上)，产率80％，无色油状物:1H NMR(400MHz,CDCl3)δ:7.85-7.78(m,4H).7.52-7.44(m,3H),2.52-2.47(m,2H),1.49-1.39(m,2H),0.93(t,J＝7.4Hz,3H)；13C NMR(100MHz,CDCl3)δ:153.9(dd,J＝285.6Hz,285.6Hz),133.2,132.4,131.3(t,J＝3.4Hz),128.0,127.9,127.6,127.3(t,J＝3.4Hz),126.2,126.0,92.3(dd,J＝12.9Hz,12.9Hz),29.6,20.9,13.4；19F NMR(376MHz,CDCl3)δ:-91.39(d,J＝44.8Hz),-91.61(d,J＝44.8Hz)。
实施例12：制备(E)-2-(1,1-二氟十三碳-1,7-二烯-2-基)萘(化合物3l)
采用实施例1的方法，由1l和2a制备得到3l(结构式如上)，产率49％，无色油状物:1H NMR(400MHz,CDCl3)δ:7.84-7.76(m,4H).7.50-7.42(m,3H),5.36-5.29(m,2H),2.53-2.49(m,2H),2.02-1.95(m,4H),1.43-1.24(m,10H),0.88(t,J＝7.1Hz,3H),13C NMR(100MHz,CDCl3)δ:153.8(dd,J＝285.1Hz,285.1Hz),133.3,132.4,131.2(t,J＝3.8Hz),130.3,129.3,128.0,127.9,127.6,127.3(t,J＝3.4Hz),126.2,126.2(t,J＝3.4Hz),126.0,92.5(dd,J＝12.9Hz,12.5Hz),31.5,29.4,29.0,27.6,27.3,27.1,26.8,22.5,14.0；19F NMR(376MHz,CDCl3)δ:-91.32(d,J＝44.8Hz),-91.61(d,J＝44.8Hz)。
实施例13：制备2-(1,1,7,7,7-五氟庚-1-烯-2-基)萘(化合物3m)
采用实施例1的方法，由1m和2a制备得到3m(结构式如上)，产率33％，无色油状物:1H NMR(400MHz,CDCl3)δ:7.86-7.76(m,4H),7.53-7.41(m,3H),2.57-2.52(m,2H),2.06-2.00(m,2H),1.64-1.56(m,2H),1.51-1.43(m,2H)；13C NMR(100MHz,CDCl3)δ:153.9(dd,J＝286.5Hz,285.6Hz),133.2,132.5,130.7,128.4,128.2,127.9,127.6,127.3(t,J＝3.4Hz),126.4,126.2,126.0(t,J＝3.4Hz),125.7,91.9(dd,J＝15.3Hz,15.3Hz),33.5(q,J＝287.5Hz),27.3,26.7,21.2,21.2；19F NMR(376MHz,CDCl3)δ:-66.30(t,J＝10.1Hz),-90.88(dd,J＝14.5Hz,14.4Hz)。
实施例14：制备2-(1,1-二氟-6-甲氧基己-1-烯-2-基)萘(化合物3n)
采用实施例1的方法，由1n和2a制备得到3n(结构式如上)，产率72％，无色油状物:1H NMR(400MHz,CDCl3)δ:7.85-7.79(m,4H),7.51-7.44(m,3H),3.34(ts,J＝6.6Hz,5H),2.58-2.53(m,2H),1.66-1.59(m,2H),1.52-1.45(m,2H)；13C NMR(100MHz,CDCl3)δ:153.8(dd,J＝285.6Hz,285.1Hz),133.2,132.4,131.0(t,J＝3.4Hz),128.0,127.9,127.6,127.3(t,J＝3.4Hz),126.2,126.1(t,J＝3.4Hz),126.0,92.4(dd,J＝12.5Hz,12.9Hz),72.4,58.5,28.9,27.5,24.4；19F NMR(376MHz,CDCl3)δ:-91.08(d,J＝43.3Hz),-91.4(d,J＝43.3Hz)。
实施例15：制备2-(1,1-二氟-4-苯基丁-1-烯-2-基)萘(化合物3o)
采用实施例1的方法，由1o和2a制备得到3o(结构式如上)，产率36％，白色固体:1HNMR(400MHz,CDCl3)δ:7.89-7.79(m,4H),7.55-7.46(m,3H),7.31(t,J＝7.6Hz,2H),7.24-7.16(m,3H),2.87-2.82(m,2H),2.74-2.71(m,2H)；13C NMR(100MHz,CDCl3)δ:153.9(dd,J＝286.1Hz,285.6Hz),133.3,132.5,130.8(t,J＝3.8Hz),128.4,128.3,128.1,127.9,127.6,127.4(t,J＝3.8Hz),126.3,126.2,126.1,92.0(dd,J＝12.9Hz,13.4Hz),34.0,29.7；19FNMR(376MHz,CDCl3)δ:-90.42(d,J＝41.9Hz),-91.06(d,J＝41.9Hz)。
实施例16：制备2-(3-环己基-1,1-二氟丙-1-烯-2-基)萘(化合物3p)
采用实施例1的方法，由1p和2a制备得到3p(结构式如上)，产率36％，白色固体:1HNMR(400MHz,CDCl3)δ:7.84-7.77(m,4H),7.51-7.43(m,3H),2.40-2.37(m,2H),1.74-1.58(m,5H),1.30-1.25(m,1H),1.15-1.0 4(m,3H),0.99-0.91(m,2H)；13C NMR(100MHz,CDCl3)δ:154.1(dd,J＝285.1Hz,285.1Hz),133.2,132.4,131.4,127.9,127.9,127.6,127.3(t,J＝3.4Hz),126.2(t,J＝3.4Hz),126.2,126.0,91.2(dd,J＝12.5Hz,12.0Hz),35.7,35.3,32.9,26.4,26.0；19F NMR(376MHz,CDCl3)δ:-90.82(d,J＝43.3Hz),-91.53(d,J＝43.3Hz)。
实施例17：制备2-(3-环庚基-1,1-二氟丙-1-烯-2-基)萘(化合物3q)
采用实施例1的方法，由1q和2a制备得到3q(结构式如上)，产率71％，白色固体:1HNMR(400MHz,CDCl3)δ:7.85-7.76(m,4H),7.50-7.42(dt,J＝3.7Hz,8.6Hz,3H),2.42-2.39(m,2H),1.72-1.68(m,2H),1.64-1.57(m,2H),1.53-1.42(m,5H),1.34-1.17(m,4H)；13C NMR(100MHz,CDCl3)δ:154.3(dd,J＝284.6Hz,284.6Hz),133.2,132.4,131.4(t,J＝4.3Hz),128.0,127.9,127.6,127.3(t,J＝2.9Hz),126.3(t,J＝3.4Hz),126.2,126.0,91.8(dd,J＝12.5Hz,12.5Hz),37.1,35.7,34.0,28.4,26.0；19F NMR(376MHz,CDCl3)δ:-91.13(d,J＝43.2Hz),-91.67(d,J＝43.3Hz)。
实施例18：制备4-(3,3-二氟-2-(萘-2-基)烯丙基)四氢-2H-吡喃(化合物3r)
采用实施例1的方法，由1r和2a制备得到3r(结构式如上)，产率49％，黄色油状物:1H NMR(400MHz,CDCl3)δ:7.87-7.77(m,4H),7.53-7.43(m,3H),3.93-3.89(m,2H),3.24(t,J＝11.8Hz,2H),2.48-2.45(m,2H),1.66-1.48(m,3H),1.39-1.32(m,2H)；13C NMR(100MHz,CDCl3)δ:154.2(dd,J＝285.1Hz,285.1Hz),133.2,132.4,131.1(t,J＝3.8Hz),128.1,127.9,127.6,127.3(t,J＝3.4Hz),126.3,126.2,126.0(t,J＝2.9Hz),90.5(dd,J＝12.9Hz,12.9Hz),67.7,34.8,33.2,32.6；19F NMR(376MHz,CDCl3)δ:-90.23(d,J＝41.9Hz),-90.81(d,J＝41.9Hz)。
实施例19：制备4-(3,3-二氟-2-(萘-2-基)烯丙基)哌啶-1-甲酸叔丁酯(化合物3s)
采用实施例1的方法，由1s和2a制备得到3s(结构式如上)，产率43％，无色油状物:1H NMR(400MHz,CDCl3)δ:7.85-7.76(m,4H),7.51-7.42(m,3H),4.20-3.87(m,2H),2.54(td,J＝12.5Hz,7.3Hz,4H),1.68-1.59(m,3H),1.44(s,9H),1.20-1.13(m,2H)；13C NMR(100MHz,CDCl3)δ:154.7,154.3(dd,J＝285.6Hz,285.6Hz),133.2,132.4,131.0(t,J＝3.8Hz),128.2,127.9,127.6,127.3(t,J＝3.4Hz),126.3,126.2,126.0(t,J＝3.4Hz),90.7(dd,J＝12.9Hz,12.9Hz),79.3,34.4,34.2,31.7,28.4；19F NMR(376MHz,CDCl3)δ:-90.17(d,J＝41.9Hz),-90.80(d,J＝41.9Hz)。
实施例20：制备2-(1,1-二氟-4-丙基庚-1-烯-2-基)萘(化合物3t)
采用实施例1的方法，由1t和2a制备得到3t(结构式如上)，产率79％，无色油状物:1H NMR(400MHz,CDCl3)δ:7.85-7.82(m,3H),7.77(s,1H),7.52-7.43(m,3H),2.45-2.42(m,2H),1.36-1.21(m,9H),0.87-0.80(m,6H)；13C NMR(100MHz,CDCl3)δ:154.1(dd,J＝286.1Hz,286.1Hz),133.2,132.4,131.4,127.9,127.8,127.6,127.4(t,J＝3.4Hz),126.2(t,J＝2.9Hz),126.1,126.0,91.8(dd,J＝14.4Hz,14.4Hz),35.3,35.0,32.1,19.4,14.4；19F NMR(376MHz,CDCl3)δ:-91.28,-91.30。
实施例21：制备2-(1,1-二氟-4,4-二甲基戊-1-烯-2-基)萘(化合物3u)
采用实施例1的方法，由1u和2a制备得到3u(结构式如上)，产率80％，白色固体:1HNMR(400MHz,CDCl3)δ:7.84-7.79(m,4H),7.50-7.44(m,3H),2.46(m,2H),0.83(s,9H)；13CNMR(100MHz,CDCl3)δ:154.6(dd,J＝286.5Hz,286.5Hz),133.2,133.1(t,J＝4.3Hz),132.3,127.8,127.6,127.4(t,J＝2.9Hz),126.5(t,J＝2.9Hz),126.2,125.9,91.2(dd,J＝12.5Hz,12.5Hz),41.2,32.8,29.7；19F NMR(376MHz,CDCl3)δ:-89.16(d,J＝40.4Hz),-92.00(d,J＝40.5Hz)。
实施例22：制备2-(1,1-二氟-4,4-二甲基-6-苯基己-1-烯-2-基)萘(化合物3v)
采用实施例1的方法，由1v和2a制备得到3v(结构式如上)，产率73％，白色固体:1HNMR(400MHz,CDCl3)δ:7.86-7.82(m,4H),7.52-7.47(m,3H),7.17-7.09(m,3H),6.88(dd,J＝2.1Hz,1.7Hz,2H),2.55(t,J＝2.5Hz,2H),2.50-2.45(m,2H),1.50-1.46(m,2H),0.89(s,6H)；13C NMR(100MHz,CDCl3)δ:154.6(dd,J＝287.0Hz,287.0Hz),142.9,133.3,133.0,132.4,128.2,128.0,127.8,127.6,127.5(t,J＝2.9Hz),126.5(t,J＝2.4Hz),126.3,126.0,125.5,90.1(dd,J＝13.4Hz,13.4Hz),44.5,39.1,35.5,30.6,27.4；19F NMR(376MHz,CDCl3)δ:-88.83(d,J＝40.4Hz),-91.45(d,J＝39.0Hz)。
实施例23：制备2-(1,1-二氟-3-(1-甲基环己基)丙基-1-烯-2-基)萘(化合物3w)
采用实施例1的方法，由1w和2a制备得到3w(结构式如上)，产率84％，白色固体:1HNMR(400MHz,CDCl3)δ:7.85-7.79(m,4H),7.52-7.46(m,3H),2.48(t,J＝2.6Hz,2H),1.43-1.29(m,5H),1.24-1.16(m,5H),0.80(s,3H)；13C NMR(100MHz,CDCl3)δ:154.6(dd,J＝286.5Hz,286.5Hz),133.3,132.3,127.9,127.8,127.6,127.4(t,J＝2.9Hz),126.6(t,J＝2.4Hz),126.1,125.9,90.7(dd,J＝12.9Hz,12.9Hz),40.4,38.0,35.2,26.2,24.6,22.0；19FNMR(376MHz,CDCl3)δ:-88.81(d,J＝40.4Hz),-91.76(d,J＝40.4Hz)。
实施例24：制备(3r，5r，7r)-1-(3,3-二氟-2-(萘-2-基)烯丙基)金刚烷(化合物3x)
采用实施例1的方法，由1x和2a制备得到3x(结构式如上)，产率84％，白色固体:1HNMR(400MHz,CDCl3)δ:7.84-7.79(m,4H),7.51-7.45(m,3H),2.33(t,J＝2.7Hz,2H),1.89-1.82(m,3H),1.64-1.51(m,6H),1.44-1.38(m,6H)；13C NMR(100MHz,CDCl3)δ:154.6(dd,J＝286.1Hz,286.1Hz),133.4,133.2,132.3,127.9,127.8,127.6,127.2(t,J＝3.4Hz),126.5(t,J＝2.9Hz),126.1,125.9,89.9(dd,J＝12.0Hz,12.5Hz),42.6,42.0,36.8,34.7,28.5；19F NMR(376MHz,CDCl3)δ:-88.37(d,J＝39.0Hz),-91.70(d,J＝40.5Hz)。
实施例25：制备7,7-二氟-6-(萘-2-基)庚-6-烯-2-(化合物3y)
采用实施例1的方法，由1y和2a制备得到3y(结构式如上)，产率45％，黄色油状物:1H NMR(400MHz,CDCl3)δ:7.85-7.78(m,4H),7.51-7.43(m,3H),3.73-3.72(m,1H),2.56-2.51(m,2H),1.52-1.41(m,4H),1.51(d,J＝6.2Hz,3H)；13C NMR(100MHz,CDCl3)δ:153.8(dd,J＝285.6Hz,285.6Hz),133.2,132.4,131.0(t,J＝3.4Hz),128.0,127.9,127.6,127.3(t,J＝3.4Hz),126.3,126.1,92.3(dd,J＝12.9Hz,12.9Hz),67.8,38.4,27.6,23.9,23.5；19FNMR(376MHz,CDCl3)δ:-91.06(d,J＝43.4Hz),-91.36(d,J＝43.3Hz)。
实施例26：制备7,7-二氟-2,4-二甲基-6-(萘-2-基)庚-6-烯-2-醇(化合物3z)
采用实施例1的方法，由1z和2a制备得到3z(结构式如上)，产率52％，黄色油状物:1H NMR(400MHz,CDCl3)δ:7.85-7.80(m,4H),7.52-7.46(m,3H),2.70-2.64(m,1H),2.37-2.31(m,1H),1.70-1.54(m,2H),1.40-1.34(m,1H),1.14(d,J＝4.9Hz,6H),0.99(d,J＝6.5Hz,3H)；13C NMR(100MHz,CDCl3)δ:154.4(dd,J＝284.6Hz,284.6Hz),133.3,133.2,133.0,132.7,132.4,131.1(t,J＝3.8Hz),129.0,128.7,128.4,128.0,127.9,127.6,127.4(t,J＝3.4Hz),126.5,126.3,126.2,126.1(t,J＝3.4Hz),126.0,91.7(dd,J＝12.5Hz,12.5Hz),71.4,71.2,51.0,49.8,49.3,37.9,36.2,30.2,30.0,29.9,29.8,27.7,26.6,25.8,23.2,21.4,20.6；19F NMR(376MHz,CDCl3)δ:-69.14(d,J＝10.1Hz),-90.59(d,J＝41.9Hz),-91.35(d,J＝41.9Hz)。
实施例27：制备7,7-二氟-2-甲基-6-(萘-2-基)庚-6-烯-2-醇(化合物5a)
采用实施例1的方法，由4a和2a制备得到5a(结构式如上)，产率67％，黄色固物:1HNMR(400MHz,CDCl3)δ:7.84-7.77(m,4H),7.51-7.43(m,3H),2.54-2.50(m,2H),1.54-1.43(m,4H),1.14(s,6H)；13C NMR(100MHz,CDCl3)δ:153.8(dd,J＝285.1Hz,285.1Hz),133.2,132.4,131.0(t,J＝3.8Hz),128.1,127.9,127.6,127.3(t,J＝3.4Hz),126.2,126.1(t,J＝3.4Hz),126.0,92.4(dd,J＝12.9Hz,12.9Hz),70.8,43.0,29.2,28.1,22.1；19F NMR(376MHz,CDCl3)δ:-91.06(d,J＝43.3Hz),-91.40(d,J＝43.4Hz)。
实施例28：制备1-(1,1-二氟-6-苯基己-1-烯-2-基)-4-(三氟甲基)苯(化合物5b)
采用实施例1的方法，由1a和2b制备得到5b(结构式如上)，产率64％，无色油状物:1H NMR(400MHz,CDCl3)δ:7.62(d,J＝8.4Hz,2H),7.41(d,J＝8.3Hz,2H),7.32-7.25(m,3H),7.20-7.12(m,3H),2.58(t,J＝7.9Hz,2H),2.48-2.43(m,2H),1.67-1.59(m,2H),1.44-1.37(m,2H)；13C NMR(100MHz,CDCl3)δ:153.8(t,J＝287.9Hz),142.1,137.5,129.4(q,J＝32.6Hz),128.5,128.3,125.8,125.4,122.7,91.7(dd,J＝12.0Hz,12.5Hz),35.4,30.6,27.1；19F NMR(376MHz,CDCl3)δ:-62.51,-89.55(d,J＝40.5Hz),-89.95(d,J＝39.0Hz)。
实施例29：制备4-(1,1-二氟-6-苯基己-1-烯-2-基)苯甲腈(化合物5c)
采用实施例1的方法，由1a和2h制备得到5c(结构式如上)，产率49％，无色油状物:1H NMR(400MHz,CDCl3)δ:7.64(d,J＝8.4Hz,2H),7.39(d,J＝8.2Hz,2H),7.08-7.25(m,2H),7.18(t,J＝7.1Hz,1H),7.13(d,J＝6.8Hz,2H),2.58(t,J＝7.8Hz,2H),2.47-2.42(m,2H),1.66-1.59(m,2H),1.43-1.36(m,2H)；13C NMR(100MHz,CDCl3)δ:153.9(dd,J＝287.8Hz,287.8Hz),142.0,138.7,132.2,128.8(t,J＝3.4Hz),128.3,125.8,118.7,110.9,91.7(dd,J＝11.5Hz,11.5Hz),35.4,30.5,27.1,26.9；19F NMR(376MHz,CDCl3)δ:-87.94(d,J＝36.1Hz),-88.49(d,J＝36.1Hz)。
实施例30：制备4-(1,1-二氟-6-苯基己-1-烯-2-基)苯甲酸甲酯(化合物5d)
采用实施例1的方法，由1a和2g制备得到5d(结构式如上)，产率80％，无色油状物:1H NMR(400MHz,CDCl3)δ:8.04(d,J＝8.6Hz,2H),7.38(d,J＝8.7Hz,2H),7.29-7.25(m,2H),7.18(td,J＝7.2Hz,6.8Hz,3H),3.93(s,3H),2.58(t,J＝7.9Hz,2H),2.49-2.44(m,2H),1.67-1.60(m,2H),1.45-1.38(m,2H)；13C NMR(100MHz,CDCl3)δ:166.7,153.8(dd,J＝286.6Hz,286.6Hz),142.2,138.5(t,J＝3.8Hz),129.7,128.8,128.3,128.2,128.1(t,J＝3.4Hz),125.7,92.0(dd,J＝12.5Hz,12.5Hz),52.1,35.4,30.6,27.2,27.0；19F NMR(376MHz,CDCl3)δ:-89.28(d,J＝39.0Hz),-89.52(d,J＝39.0Hz)。
实施例31：制备1-氯-4-(1,1-二氟-6-苯基己-1-烯-2-基)苯(化合物5e)
采用实施例1的方法，由1a和2d制备得到5e(结构式如上)，产率46％，无色油状物:1H NMR(400MHz,CDCl3)δ:7.34-7.26(m,4H),7.23-7.13(m,5H),2.58(t,J＝7.8Hz,2H),2.44-2.39(m,2H),1.67-1.59(m,2H),1.44-1.37(m,2H)；13C NMR(100MHz,CDCl3)δ:153.6(dd,J＝286.1Hz,286.1Hz),142.2,133.0,132.1,129.5(t,J＝3.4Hz),128.6,128.3,128.2,125.7,91.5(dd,J＝14.9Hz,14.9Hz),35.5,30.6,27.2,27.1；19F NMR(376MHz,CDCl3)δ:-90.82,-90.84。
实施例32：制备1-溴-4-(1,1-二氟-6-苯基己-1-烯-2-基)苯(化合物5f)
采用实施例1的方法，由1a和2e制备得到5f(结构式如上)，产率50％，无色油状物:1H NMR(400MHz,CDCl3)δ:7.49(d,J＝8.6Hz,2H),7.27(t,J＝7.2Hz,2H),7.20-7.12(m,5H),2.58(t,J＝7.5Hz,2H),2.43-2.38(m,2H),1.66-1.58(m,2H),1.43-1.36(m,2H)；13CNMR(100MHz,CDCl3)δ:153.5(dd,J＝286.5Hz,286.5Hz),142.2,132.6,131.6,129.9(t,J＝3.4Hz),128.3,128.2,125.7,121.1,91.5(dd,J＝14.4Hz,13.9Hz),35.4,30.6,27.2,27.1；19F NMR(376MHz,CDCl3)δ:-90.67(d,J＝43.3Hz),-90.83(d,J＝43.3Hz)。
实施例33：制备3-(1,1-二氟-6-苯基己-1-烯-2-基)吡啶(化合物5g)
采用实施例1的方法，由1a和2k制备得到5g(结构式如上)，产率71％，黄色油状物:1H NMR(400MHz,CDCl3)δ:8.56-8.51(m,2H),7.59(d,J＝8.0Hz,1H),7.30-7.10(m,6H),2.58(t,J＝7.8Hz,2H),2.46-2.41(m,2H),1.67-1.59(m,2H),1.45-1.38(m,2H)；13C NMR(100MHz,CDCl3)δ:153.8(dd,J＝287.0Hz,287.0Hz),149.2(t,J＝3.8Hz),148.3,142.1,135.5,129.7,128.3,125.7,123.3,89.7(dd,J＝12.9Hz,12.5Hz),35.4,30.6,27.1,27.0；19F NMR(376MHz,CDCl3)δ:-89.42(d,J＝40.4Hz),-90.14(d,J＝40.5Hz)。
实施例34：制备5-(1,1-二氟-6-苯基己-1-烯-2-基)嘧啶(化合物5h)
采用实施例1的方法，由1a和2l制备得到5h(结构式如上)，产率46％，黄色油状物:1H NMR(400MHz,CDCl3)δ:9.12(s,1H),8.68(s,1H),7.27(t,J＝7.6Hz,2H),7.19-7.12(m,3H),2.59(t,J＝7.7Hz,2H),2.47-2.43(m,2H),1.68-1.60(m,2H),1.47-1.39(m,2H)；13CNMR(100MHz,CDCl3)δ:157.1,155.8(t,J＝3.8Hz),154.2(dd,J＝293.2Hz,293.2Hz),141.8,128.3,128.2,128.0(t,J＝4.3Hz),125.9,87.2(dd,J＝12.5Hz,12.5Hz),35.4,30.5,27.0,26.3；19F NMR(376MHz,CDCl3)δ:-86.79(d,J＝36.1Hz),-87.95(d,J＝36.1Hz)，
实施例35：制备3-(1,1-二氟-6-苯基己-1-烯-2-基)喹啉(化合物5i)
采用实施例1的方法，由1a和2m制备得到5i(结构式如上)，产率76％，黄色油状物:1H NMR(400MHz,CDCl3)δ:8.88(t,J＝2.0Hz,1H),8.13-8.03(m,2H),7.81-7.71(m,2H),7.58(t,J＝8.2Hz,1H),7.26-7.11(m,5H),2.60-2.53(m,4H),1.70-1.63(m,2H),1.50-1.42(m,2H)；13C NMR(100MHz,CDCl3)δ:154.1(dd,J＝287.5Hz,287.5Hz),150.1,146.8,142.1,135.0,129.7,129.1,128.3,127.7,127.6,127.1,126.9(t,J＝4.3Hz),125.8,89.9(dd,J＝12.5Hz,12.9Hz),35.4,30.6,27.1；19F NMR(376MHz,CDCl3)δ:-89.01(d,J＝39.0Hz),-89.85(d,J＝40.4Hz)。
实施例36：制备2-(1,1-二氟-6-苯基己-1-烯-2-基)二苯并[b，d]呋喃(化合物5j)
采用实施例1的方法，由1a和2j制备得到5j(结构式如上)，产率76％，黄色油状物:1H NMR(400MHz,CDCl3)δ:8.00(d,J＝7.6Hz,1H),7.94(dd,J＝2.3Hz,2.4Hz,1H),7.63(d,J＝8.2Hz,1H),7.53-7.48(m,1H),7.41-7.35(m,3H),7.23(t,J＝7.6Hz,2H),7.18-7.11(m,3H),2.69-2.64(m,2H),2.57(t,J＝7.8Hz,2H),1.73-1.65(m,2H),1.47-1.39(m,2H)；13CNMR(100MHz,CDCl3)δ:156.0,153.9,153.5(dd,J＝286.1Hz,286.1Hz),142.4,128.3,128.2,127.8,127.3,125.6,124.5,124.1,122.8,122.7,120.7,120.0,118.3(dd,J＝1.9Hz,1.9Hz),111.8,88.1(dd,J＝14.9Hz,14.9Hz),35.5,30.6,27.3,27.2；19F NMR(376MHz,CDCl3)δ:-88.12(d,J＝40.4Hz),-91.63(d,J＝40.4Hz)。
实施例37：制备4-(1,1-二氟-6-苯基己-1-烯-2-基)苯甲醛(化合物5k)
采用实施例1的方法，由1a和2i制备得到5k(结构式如上)，产率43％，黄色油状物:1H NMR(400MHz,CDCl3)δ:10.01(s,1H),7.87-7.85(d,J＝8.3Hz,2H),7.47(d,J＝6.9Hz,2H),7.28-7.24(m,2H),7.19-7.12(m,3H),2.58(t,J＝7.8Hz,2H),2.50-2.45(m,2H),1.68-1.60(m,2H),1.46-1.38(m,2H)；13C NMR(100MHz,CDCl3)δ:191.6,153.9(dd,J＝287.0Hz,287.5Hz),142.1,140.2(t,J＝4.3Hz),135.1,129.8,128.7(t,J＝3.4Hz),128.3,125.8,92.1(dd,J＝11.5Hz,11.5Hz),35.4,30.6,27.2,27.0；19F NMR(376MHz,CDCl3)δ:-88.36(d,J＝37.6Hz),-88.74(d,J＝36.1Hz)。
实施例38：制备1-(1,1-二氟-6-苯基己-1-烯-2-基)-4-甲氧基苯(化合物5l)
采用实施例1的方法，由1a和2c制备得到5l(结构式如上)，产率66％，无色油状物:1H NMR(400MHz,CDCl3)δ:7.31-7.16(m,7H),6.94-6.90(m,2H),3.84(s,3H),2.60(t,J＝7.6Hz,2H),2.44-2.40(m,2H),1.69-1.61(m,2H),1.48-1.40(m,2H)；13C NMR(100MHz,CDCl3)δ:158.6,153.4(dd,J＝285.6Hz,285.6Hz),142.4,129.3(t,J＝3.4Hz),128.3,128.2,125.8,125.7,113.8,91.6(dd,J＝16.3Hz,15.8Hz),55.2,35.5,30.7,27.4.27.2；19FNMR(376MHz,CDCl3)δ:-92.59。
实施例39：制备1-(1,1-二氟-6-苯基己-1-烯-2-基)-4-甲基苯(化合物5m)
采用实施例1的方法，由1a和2b制备得到5m(结构式如上)，产率76％，无色油状物:1H NMR(400MHz,CDCl3)δ:7.29(t,J＝7.7Hz,2H),7.24-7.15(m,7H),2.60(t,J＝7.8Hz,2H),2.46-2.41(m,2H),2.38(s,3H),1.69-1.61(m,2H),1.48-1.41(m,2H)；13C NMR(100MHz,CDCl3)δ:153.5(dd,J＝285.1Hz,285.1Hz),142.4,136.9,130.6,129.1,128.3,128.2,128.1(t,J＝3.4Hz),125.7,92.0(dd,J＝14.9Hz,14.4Hz),35.5,30.7,27.4,27.2,21.1；19FNMR(376MHz,CDCl3)δ:-92.07,-92.10。
实施例40：制备3-(1,1-二氟-6-苯基己-1-烯-2-基)苯基-2-(1-(4-氯苯甲酰基)-5-甲氧基-2-甲基-1H-吲哚-3-基)乙酸盐(化合物5n)
采用实施例1的方法，由1a和2o制备得到5n(结构式如上)，产率66％，如图2a、图2b和图2c所示，绿色油状物:1H NMR(400MHz,CDCl3)δ:7.70(d,J＝8.6Hz,2H),7.49(d,J＝8.6Hz,2H),7.36-7.30(m,1H),7.28-7.24(m,2H),7.19-7.12(m,4H),7.08-6.99(m,3H),6.92(d,J＝9.0Hz,1H),6.72(dd,J＝2.6Hz,2.6Hz,1H),3.93(s,2H),3.84(s,3H),2.57(t,J＝7.8Hz,2H),2.47(s,3H),2.43-2.38(m,2H),1.66-1.58(m,2H),1.45-1.38(m,2H)；13C NMR(100MHz,CDCl3)δ:169.2,168.3,156.1,153.7(dd,J＝286.5Hz,286.5Hz),150.7,142.3,139.3,136.2,135.2,133.8,131.2,130.8,130.5,129.3,129.1,128.3,128.2,125.8,125.7,121.2(t,J＝3.8Hz),120.2,115.0,111.9,111.8,101.2,91.7(dd,J＝13.9Hz,13.9Hz),55.1,35.4,30.6,30.5,27.2,13.4；19F NMR(376MHz,CDCl3)δ:-90.33,-90.36。
实施例41：制备2-(4-(4-氯苯甲酰基)苯氧基)-N-(3-(1,1-二氟-6-苯基己-1-烯-2-基)苯基)-2-甲基丙酰胺(化合物5o)
采用实施例1的方法，由1a和2n制备得到5o(结构式如上)，产率79％，如图3a、图3b和图3c所示，绿色固体:1H NMR(400MHz,CDCl3)δ:8.32(s,1H),7.77(dd,J＝8.8Hz,8.7Hz,4H),7.51-7.44(m,4H),7.32(t,J＝8.0Hz,1H),7.27-7.23(m,2H),7.17-7.11(m,3H),7.08(d,J＝8.8Hz,3H),2.57(t,J＝7.8Hz,2H),2.44-2.39(m,2H),1.69(s,6H),1.66-1.58(m,2H),1.45-1.38(m,2H)；13C NMR(100MHz,CDCl3)δ:194.1,172.2,158.1,153.6(dd,J＝285.6Hz,285.6Hz),142.3,138.7,137.4,135.9,134.7(t,J＝2.9Hz),132.1,131.9,131.2,129.1,128.6,128.3,128.2,125.6,124.6(t,J＝3.4Hz),120.2,119.7(t,J＝3.4Hz),118.8,92.0(dd,J＝12.9Hz,12.9Hz),82.4,35.4,3.6,27.3,27.1,25.0；19F NMR(376MHz,CDCl3)δ:-90.94(d,J＝43.4Hz),-91.19(d,J＝43.3Hz)。
实施例42：制备2-(3-氰基-4-异丁氧基苯基)-N-(3-(1,1-二氟-6-苯基己-1-烯-2-基)苯基)-4-甲基噻唑-5-甲酰胺(化合物5p)
采用实施例1的方法，由1a和2p制备得到5p(结构式如上)，产率60％，如图4a、图4b和图4c所示，黄色固体:1H NMR(400MHz,CDCl3)δ:8.12(d,J＝2.3Hz,1H),8.06(dd,J＝2.4Hz,2.5Hz,1H),7.64(s,1H),7.54(d,J＝6.6Hz,2H),7.35(t,J＝8.8Hz,1H),7.26(t,J＝7.6Hz,2H),7.18-7.09(m,4H),7.02(d,J＝8.9Hz,1H),3.90(d,J＝6.5Hz,2H),2.78(s,3H),2.58(t,J＝7.8Hz,2H),2.46-2.41(m,2H),2.23-2.16(m,1H),1.67-1.59(m,3H),1.47-1.39(m,2H),1.10(d,J＝6.8Hz,6H)；13C NMR(100MHz,CDCl3)δ:164.9,162.4,159.8,157.1,153.6(dd,J＝285.6Hz,285.6Hz),142.3,137.5,134.8,132.5,131.9,129.2,128.3,128.2,125.7,125.6,124.9,120.1,119.3,115.4,112.6,102.8,92.0(dd,J＝12.9Hz,12.9Hz),75.7,35.4,30.6,28.1,27.3,27.2,19.0,17.5；19F NMR(376MHz,CDCl3)δ:-90.78(d,J＝43.3Hz),-91.03(d,J＝41.9Hz)。
实施例43：制备2-(1,1-二氟-3-((2S，5S)-2-异丙基-5-甲基环己基)丙基-1-烯-2-基)萘(化合物5q)
采用实施例1的方法，由4b和2a制备得到5q(结构式如上)，产率76％，如图5a、图5b和图5c所示，无色油状物:1H NMR(400MHz,CDCl3)δ:7.87-7.79(m,4H),7.5-7.44(m,3H),2.93-2.87(m,1H),2.16-2.05(m,2H),1.83-1.31(m,5H),1.25-1.08(m,2H),1.02-0.94(m,1H),0.92-0.88(m,3H),0.86(d,J＝6.5Hz,3H),0.82-0.79(m,2H),0.74(d,J＝6.6Hz,1H),0.67(d,J＝6.8Hz,3H)；13C NMR(100MHz,CDCl3)δ:154.1(dd,J＝284.6Hz,284.6Hz),133.3,133.2,132.5,132.4,131.3(t,J＝3.8Hz),127.9,127.8,127.6,127.5,127.3(t,J＝3.4Hz),126.3,126.2,126.0,91.4(dd,J＝12.9Hz,13.4Hz),47.6,40.5,37.8,36.8,35.8,35.2,32.8,32.4,31.2,29.3,26.6,26.0,25.1,24.1,23.7,22.8,21.7,21.5,20.6,15.2；19FNMR(376MHz,CDCl3)δ:-91.01(d,J＝43.3Hz),-91.25(d,J＝43.3Hz),-91.88(d,J＝44.8Hz),-92.24(d,J＝44.8Hz)。
实施例44：制备(S)-2-(1,1-二氟-5-(4-异丁基苯基)己-1-烯-2-基)萘(化合物5r)
采用实施例1的方法，由4c和2a制备得到5r(结构式如上)，产率74％，如图6a、图6b和图6c所示，无色油状物:1H NMR(400MHz,CDCl3)δ:7.86-7.79(m,3H),7.68(s,1H),7.53-7.48(m,2H),7.40(tt,J＝1.7Hz,1.8Hz,1H),7.08(d,J＝4.7Hz,4H),2.74-2.69(m,1H),2.49(d,J＝7.2Hz,3H),2.45-2.35(m,2H),1.92-1.86(m,1H),1.73-1.66(m,2H),1.24(d,J＝7.0Hz,3H),0.95(d,J＝6.5Hz,6H)；13C NMR(100MHz,CDCl3)δ:153.6(dd,J＝285.6Hz,285.6Hz),144.0,139.3,133.2,132.4,131.0(t,J＝3.8Hz),129.1,127.9,127.5,127.1(t,J＝3.4Hz),126.7,126.2,126.1(t,J＝3.4Hz),126.0,92.5(dd,J＝12.0Hz,12.5Hz),45.0,39.2,36.3,30.2,25.8,22.4,22.3；19F NMR(376MHz,CDCl3)δ:-90.78(d,J＝41.9Hz),-91.29(d,J＝43.3Hz)。
实施例45：制备(R)-2-(3-氰基-4-异丁氧基苯基)-N-(3-(1,1-二氟-5-(4-异丁基苯基)己-1-烯-2-基)苯基)-4-甲基噻唑-5-甲酰胺(化合物5s)
采用实施例1的方法，由4c和2p制备得到5s(结构式如上)，产率45％，如图7a、图7b和图7c所示，白色固体:1H NMR(400MHz,CDCl3)δ:8.12(m,2H),7.64-7.53(m,2H),7.44(s,1H),7.32(t,J＝8.0Hz,1H),7.04-7.00(m,6H),3.91(d,J＝6.5Hz,2H),2.78(s,3H),2.68-2.63(m,1H),2.42(d,J＝7.2Hz,2H),2.36-2.17(m,3H),1.86-1.79(m,1H),1.67-1.60(m,2H),1.22(d,J＝6.9Hz,3H),1.10(d,J＝6.8Hz,6H),0.89(d,J＝6.6Hz,6H)；13C NMR(100MHz,CDCl3)δ:164.9,162.5,159.7,156.9,153.4(dd,J＝287.0Hz,287.0Hz),143.9,139.3,137.5,134.7,132.5,131.9,129.1,129.0,126.6,125.7,125.6,124.8,120.1,119.2,115.4,112.6,102.9,92.1(dd,J＝15.8Hz,15.8Hz),45.0,39.1,36.2,30.2,28.1,25.7,22.3,22.2,19.0,17.5；19F NMR(376MHz,CDCl3)δ:-90.66。
实施例46：制备2-(8-(2,5-二甲基苯氧基)-1,1-二氟-5,5-二甲基辛-1-烯-2-基)萘(化合物5t)
采用实施例1的方法，由4d和2a制备得到5t(结构式如上)，产率47％，如图8a、图8b和图8c所示，无色油状物:1H NMR(400MHz,CDCl3)δ:7.87-7.80(m,4H),7.52-7.46(m,3H),7.05(d,J＝7.4Hz,1H),6.70-6.65(m,2H),3.93(t,J＝6.3Hz,2H),2.53-2.47(m,2H),2.34(s,3H),2.21(s,3H),1.76-1.68(m,2H),1.44-1.35(m,4H),0.94(s,6H)；13C NMR(100MHz,CDCl3)δ:157.1,153.5(dd,J＝285.6Hz,285.6Hz),136.4,133.3,132.4,131.2(t,J＝3.4Hz),130.3,128.0,127.9,127.6,127.1(t,J＝3.4Hz),126.2,126.0,126.0(t,J＝3.4Hz),123.5,120.6,111.9,93.1(dd,J＝12.9Hz,12.9Hz),68.4,39.8,37.6,32.5,27.0,24.2,22.6,21.4,15.8；19F NMR(376MHz,CDCl3)δ:-91.32(d,J＝43.3Hz),-91.54(d,J＝43.4Hz)。
实施例47：制备(R)-2-(4-(4-氯苯甲酰基)苯氧基)-N-(3-(1,1-二氟-5-(6-甲氧基萘-2-基)己-1-烯-2-基)苯基)-2-甲基丙酰胺(化合物5u)
采用实施例1的方法，由4e和2n制备得到5u(结构式如上)，产率35％，如图9a、图9b和图9c所示，无色油状物:1H NMR(400MHz,CDCl3)δ:8.30(s,1H),7.78(d,J＝8.8Hz,2H),7.72(d,J＝8.5Hz,2H),7.66(dd,J＝2.5Hz,2.6Hz,2H),7.50-7.43(m,5H),7.29(t,J＝7.9Hz,1H),7.25(dd,J＝1.8Hz,1.8Hz,1H),7.13-7.05(m,4H),7.00(d,J＝8.1Hz,1H),3.90(s,3H),2.84-2.79(m,1H),2.38-2.23(m,2H),1.77-1.70(m,2H),1.68(s,6H),1.28(d,J＝7.0Hz,3H)；13C NMR(100MHz,CDCl3)δ:194.2,172.2,158.1,157.2,156.3,153.4(dd,J＝287.0Hz,287.0Hz),141.8,138.7,137.4,135.9,134.7,133.2,132.2,132.0,131.2,129.1,129.0,128.6,126.9,126.0,125.1,124.5,120.2,119.7(t,J＝3.4Hz),118.8,118.6,105.6,92.1(dd,J＝17.3Hz,17.3Hz),82.4,55.3,39.4,36.0,25.9,25.0,22.0；19F NMR(376MHz,CDCl3)δ:-90.77。
前述实施例1～实施例47所涉及的原料醇和三氟甲基烯烃的结构式如下表1和表2所示。
表1实施例1～实施例47中醇的结构式
表2实施例1～实施例47中三氟甲基烯烃的结构式
以上所述仅是本发明的优选实施方式，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明技术原理的前提下，还可以做出若干改进和变形，这些改进和变形也应视为本发明的保护范围。

Claims (10)

1.一种偕二氟烯烃类化合物的制备方法，其特征在于，包括以下步骤：
将醇和碱在四氢呋喃溶液中进行反应，然后加入二硫化碳，继续反应，得到中间体；
将中间体、三氟甲基烯烃和还原剂加入到溶剂中，以蓝光照射进行反应，反应结束后分离，得到偕二氟烯烃类化合物。
2.根据权利要求1所述的偕二氟烯烃类化合物的制备方法，其特征在于，所述醇为以下醇中的一种：
3.根据权利要求1所述的偕二氟烯烃类化合物的制备方法，其特征在于，所述醇和碱在四氢呋喃溶液中进行反应的温度为25℃，反应时间为30min。
4.根据权利要求1所述的偕二氟烯烃类化合物的制备方法，其特征在于，加入二硫化碳后继续反应的温度为0℃，反应时间为3h。
5.根据权利要求1所述的偕二氟烯烃类化合物的制备方法，其特征在于，所述三氟甲基烯烃为以下烯烃中的一种：
6.根据权利要求1所述的偕二氟烯烃类化合物的制备方法，其特征在于，所述还原剂为二环己基一苯基膦。
7.根据权利要求1所述的偕二氟烯烃类化合物的制备方法，其特征在于，所述蓝光为456nm蓝光，以蓝光照射进行反应的时间为12h。
8.根据权利要求1所述的偕二氟烯烃类化合物的制备方法，其特征在于，所述醇、碱和二硫化碳的摩尔比为1：1：3。
9.根据权利要求1所述的偕二氟烯烃类化合物的制备方法，其特征在于，所述中间体、三氟甲基烯烃和还原剂的摩尔比为1：1.2：1.2。
10.一种偕二氟烯烃类化合物，其特征在于，采用权利要求1～9任一项所述方法制备得到。
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