CN113511966A - 三氟甲基取代二氢菲类化合物的合成方法 - Google Patents

三氟甲基取代二氢菲类化合物的合成方法 Download PDF

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CN113511966A
CN113511966A CN202110958508.2A CN202110958508A CN113511966A CN 113511966 A CN113511966 A CN 113511966A CN 202110958508 A CN202110958508 A CN 202110958508A CN 113511966 A CN113511966 A CN 113511966A
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刘丙贤
王娟娟
杨凌云
石雨佳
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Abstract

本发明提供了一种利用过渡金属催化合成三氟甲基取代二氢菲类化合物的方法，属于有机合成技术领域。以2‑联苯硼酸类化合物和α,β‑不饱和酮化合物为起始原料，在过渡金属铑催化剂和银盐氧化剂作用下，有机溶剂中加热反应得到三氟甲基取代二氢菲类化合物。在2‑联苯硼酸与三氟甲基取代烯酮环化偶联中，催化剂中庞大环戊二烯基配体(CptBu)能有效促进质子解前还原消除过程，获得[4+2]环化产物，而不是简单1,4‑加成产物，同时从2‑联苯硼酸与苯醌偶联中分离出来桥环，再次证明了反应经过两步Michael加成。本发明具有起始原料简单易制备、底物适用范围广、耐空气条件、产率高和操作简单等优点。

Description

三氟甲基取代二氢菲类化合物的合成方法
技术领域
本发明涉及有机合成技术领域，具体涉及三氟甲基取代二氢菲类化合物的合成方法。
背景技术
二氢菲类化合物可通过抑制NF-κB等通路有效地抑制炎症因子的产生，这类化合物结构存在于多种抗炎药物中，该类结构同时也具有良好的抗癌活性。而三氟甲基是一种有强吸电子性、强亲脂性的含氟基团，三氟甲基的引入经常可以增强药物分子的药物活性。
目前对于二氢菲类化合物研究开发相对并不充分，因此，开发三氟甲基取代二氢菲类化合物的高效合成方法对于药物先导化合物的筛选具有重要作用。
发明内容
为了克服上述技术缺陷，本发明提供了一种三氟甲基取代二氢菲类化合物及其制备方法和应用。本发明中，所述化合物结构新颖，具体结构为
Figure BDA0003220805890000011
在铑催化剂存在下，以2-联苯硼酸类化合物和α,β-不饱和酮化合物为起始原料，一步即可完成上述化合物合成，高产率得到三氟甲基取代二氢菲类化合物，合成方法目前尚未有报道。该方法具有如下优势：反应条件温和，成本低，反应收率高，产生的副产物少、反应路径合理，可高效制备该类型的化合物。
本发明所述一种三氟甲基取代二氢菲类化合物，具体结构如下：
Figure BDA0003220805890000012
其中：R1选自C1-C6烷基、卤素、C1-C6烷氧基、三氟甲基、硝基、腈基、C1-C4烷氧羰基中的一种或多种；R2选自苯基或取代苯基、萘基或取代萘基、噻吩基或取代噻吩基、呋喃基或取代呋喃基，取代基为C1-C6烷基、卤素、C1-C6烷氧基、三氟甲基、硝基、腈基、C1-C4烷磺酰基、C1-C4烷氧羰基中的一种或多种。
B结构中，
Figure BDA0003220805890000021
表示
Figure BDA0003220805890000022
本发明还提供了上述结构化合物的合成方法，包括如下步骤：以2-联苯硼酸类化合物1和α,β-不饱和酮化合物2A或2B为起始原料，在过渡金属铑催化剂和银盐氧化剂作用下，有机溶剂中加热反应分别得到三氟甲基取代二氢菲类化合物3A或3B。
反应方程式表示如下：
Figure BDA0003220805890000023
其中：R1选自C1-C6烷基、卤素、C1-C6烷氧基、三氟甲基、硝基、腈基、C1-C4烷氧羰基中的一种或多种；R2选自苯基或取代苯基、萘基或取代萘基、噻吩基或取代噻吩基、呋喃基或取代呋喃基，取代基为C1-C6烷基、卤素、C1-C6烷氧基、三氟甲基、硝基、腈基、C1-C4烷磺酰基、C1-C4烷氧羰基中的一种或多种；2B选自
Figure BDA0003220805890000024
进一步地，在上述技术方案中，所述铑催化剂为[CptBuRhI2]2或[Cp*RhCl2]2。
进一步地，在上述技术方案中，所述银盐氧化剂为醋酸银、碳酸银、氧化银中的一种或多种。
进一步地，在上述技术方案中，所述化合物1、化合物2、铑催化剂与银盐氧化剂摩尔比为1.0-1.5:1.0:0.04-0.10:1.0-2.0。
进一步地，在上述技术方案中，有机溶剂选自饱和烃类酯，例如乙酸乙酯、甲基叔丁酯、甲酸乙酯或苯甲酸叔丁酯等，优选溶剂为乙酸乙酯。
进一步地，在上述技术方案中，所述加热反应温度为60-90℃。
进一步地，在上述技术方案中，反应无需惰性气体保护，可在空气中直接进行。
进一步地，在上述技术方案中，得到的产物进一步衍生如下(以3aa为例)：
Figure BDA0003220805890000031
为了对反应机理进行研究，做了如下对比试验，结果如下：
Figure BDA0003220805890000032
根据以上对比试验结果，推测的可能反应机理如下：
Figure BDA0003220805890000033
本发明在得到上述化合物3最优条件下，2-联苯硼酸与活泼烯烃偶联反应得到环化产物和桥环化合物，具体如下：
Figure BDA0003220805890000041
发明有益效果
本发明可高选择性合成三氟甲基取代二氢菲类化合物，本发明的优势在于：首次合成此类化合物，反应条件温和，效率高，反应路径合理，后处理简单。
具体实施方式
以下通过实施例对本发明的上述内容做进一步详细说明，但不应该将此理解为本发明上述主题的范围仅限于以下的实施例，凡基于本发明上述内容实现的技术均属于本发明的范围。
反应条件优化试验：
反应条件探索试验：(以1a和2a在铑催化下生成3aa为例)典型操作为：将化合物1a(0.12mmol,1.2eq)、[CptBuRhI2]2(4.0mol％)、化合物2a(0.1mmol,1.0eq)和AgOAc(0.025mmol)、Ag2O(0.1mmol)、乙酸乙酯(1.0mL)混合后，反应管密封，升温至80℃反应，薄层板(TLC)监测原料2a完全消失(12h)；旋干溶剂，柱层析分离(石油醚/乙酸乙酯体积比15:1)，得到白色固体3aa。
反应方程式如下：
Figure BDA0003220805890000051
Figure BDA0003220805890000052
a反应条件:1a(0.1mmol),2a(0.1mmol),[CptBuRhI2]2(4mol％),氧化剂(x eq),溶剂(1mL),60℃,空气条件下反应12h,分离收率.b[Cp*RhCl2]2(4mol％)替代[CptBuRhI2]2.c括号内收率为非环化的1,4-加成副产物的收率.d80℃.e1a(0.12mmol).f无[CptBuRhI2]2.
如表所示，对反应的边界条件进行了探索，发现其他可能的反应条件下均以不同的收率得到目标产物。最终确定最佳反应条件为：在乙酸乙酯(EA)溶剂中，采用[CptBuRhI2]2为催化剂，在AgOAc和Ag2O存在下原料1a和2a以最优收率得到3aa。
在以上优化试验基础上，三氟甲基取代二氢菲类化合物3通用合成方法，典型操作如下：
Figure BDA0003220805890000053
在反应试管中，加入化合物1、化合物2(化合物1与化合物2摩尔比1.5-1.0:1.0)和[CptBuRhI2]2(1-10mol％)，在空气条件下，再加入有机溶剂，密封真空封管，置于80℃油浴中，搅拌至反应完毕。加水淬灭，乙醚萃取，合并乙醚层，减压除去有机溶剂得到粗产物，PE/EA硅胶柱层析纯化，得到化合物3。
实施例1
Figure BDA0003220805890000061
在25mL耐压管中，依次加入2-联苯硼酸(0.12mmol,24mg)、4,4,4-三氟-1-(对甲苯基)丁-2-烯-1-酮(0.1mmol,21.4mg)、[CptBuRhI2]2(0.004mmol,4.9mg)、AgOAc(0.025mmol,4.2mg)、Ag2O(0.1mmol,23.2mg)和EA(1.0mL),反应管密封，然后将该混合物于80℃加热搅拌反应12h。反应完成后，待反应完全后冷却到室温，旋干溶剂。加入去离子水与乙酸乙酯，水相萃取三次，合并有机相，用饱和食盐水反萃一次，无水硫酸钠干燥。旋干用柱层析分离(石油醚/乙酸乙酯＝15:1)，得白色固体3aa(34.2mg,94％)。该化合物的表征数据如下：1HNMR(600MHz,CDCl3)δ7.80–7.73(m,4H),7.34–7.31(m,1H),7.28–7.25(m,1H),7.19(d,J＝8.0Hz,2H),7.17–7.08(m,4H),5.08(s,1H),3.84(q,J＝9.4Hz,1H),2.32(s,3H).13C NMR(100MHz,CDCl3)δ196.0,144.6,134.9,134.3,132.6,131.3,130.7,129.8,129.7,129.6,128.9,128.7,128.3,128.0,126.4(d,J＝1.0Hz,1C),126.3(q,J＝281.8Hz,1C),124.2,124.1,45.9(d,J＝1.1Hz,1C),45.7(q,J＝27.3Hz,1C),21.8.19F NMR(376MHz,CDCl3)δ-70.09(d).HRMS(ESI-TOF)m/z:[M+Na]+Calcd for C23H17F3NaO+389.1124,Found:389.1124.
实施例2
采用
Figure BDA0003220805890000062
按实施例1所述方法，得白色固体3ab(23.0mg,55％,m.p.114-116℃).
Figure BDA0003220805890000063
该化合物表征数据如下：1H NMR(400MHz,CDCl3)δ7.86(d,J＝8.1Hz,2H),7.72–7.67(m,2H),7.27(d,J＝8.0Hz,2H),7.18(d,J＝8.8Hz,1H),7.13(d,J＝7.8Hz,1H),6.96(m,2H),5.10(s,1H),3.82(q,J＝9.4Hz,1H),2.40(s,3H),2.28(s,3H),2.27(s,3H).13C NMR(100MHz,CDCl3)δ196.1,144.5,137.7,137.4,132.5,132.3,131.9,131.8,130.5,130.4,130.1,129.8,129.4,129.0,126.4(q,J＝281.9Hz,1C),125.8,123.7,123.7,45.84,45.83(q,J＝27.1Hz,1C),21.8,21.2,21.1.19F NMR(376MHz,CDCl3)δ-70.06(d).[M+Na]+Calcd for C25H21F3NaO+417.1437,Found:417.1437.
实施例3
采用
Figure BDA0003220805890000071
按实施例1所述方法，得白色固体3ac(29.3mg,61％,m.p.105-106℃).
Figure BDA0003220805890000072
该化合物表征数据如下：1H NMR(400MHz,CDCl3)δ7.88(d,J＝8.1Hz,2H),7.77(d,J＝8.3Hz,1H),7.74(d,J＝8.3Hz,1H),7.43(dd,J＝8.3,1.9Hz,1H),7.35(dd,J＝8.2,1.9Hz,1H),7.31(d,J＝8.0Hz,2H),7.19(s,1H),7.13(d,J＝1.7Hz,1H),5.14(s,1H),3.91(q,J＝9.5Hz,1H),2.44(s,3H),1.31(s,9H),1.26(s,9H).13C NMR(100MHz,CDCl3)δ196.5,150.8,150.6,144.3,132.9,132.0,131.5,130.0,129.7,129.0,128.3,126.7,126.6,126.5(q,J＝281.8Hz,1C),125.7,125.6,123.5,123.4,45.9(q,J＝26.8Hz,1C),46.5,34.6,31.4,31.3,21.8.19F NMR(565MHz,CDCl3)δ-70.19(d).[M+Na]+Calcd for C31H33F3NaO+501.2376,Found:501.2373.
实施例4
采用
Figure BDA0003220805890000073
按实施例1所述方法，得白色固体3ad(25.1mg,29％,m.p.146-147℃).
Figure BDA0003220805890000081
该化合物表征数据如下：1H NMR(600MHz,CDCl3)δ7.87(d,J＝8.2Hz,2H),7.71(d,J＝8.7Hz,1H),7.69(d,J＝8.7Hz,1H),7.31(d,J＝8.0Hz,2H),6.95(dd,J＝8.7,2.7Hz,1H),6.88(dd,J＝8.6,2.6Hz,1H),6.73(d,J＝2.3Hz,1H),6.72(d,J＝2.6Hz,1H),5.09(s,1H),3.85(q,J＝9.4Hz,1H),3.79(s,3H),3.76(s,3H),2.44(s,3H).13CNMR(100MHz,CDCl3)δ196.0,158.9,158.7,144.6,132.6,131.3,129.8,129.0,127.7,127.3,127.0(d,J＝0.9Hz,1C),126.3(q,J＝282.2Hz,1C),124.7,124.6,116.7,115.19,115.16,113.9,55.42,55.35,46.2,46.0(q,J＝26.8Hz,1C),21.8.19F NMR(376MHz,CDCl3)δ-70.02(d).[M+Na]+Calcd for C25H21F3NaO+449.1335,Found:449.1331.
实施例5
采用
Figure BDA0003220805890000082
按实施例1所述方法，得白色固体3ab(32.6mg,83％,m.p.133-134℃).
Figure BDA0003220805890000083
该化合物表征数据如下：1H NMR(600MHz,CDCl3)δ7.88(d,J＝8.2Hz,2H),7.71(s,1H),7.69(s,1H),7.31(d,J＝8.0Hz,2H),7.12–7.05(m,4H),5.15(s,1H),3.90(q,J＝9.4Hz,1H),2.44(s,3H),2.43(s,3H),2.42(s,3H).13C NMR(100MHz,CDCl3)δ196.3,144.4,139.4,138.2,134.7,134.2,132.6,131.1,129.7,129.4,129.0,128.9,128.8,127.8,126.4(q,J＝281.7Hz,1C),124.9,124.8,123.6,45.6,45.4(q,J＝27.1Hz,1C),21.8,21.7,21.6.19F NMR(565MHz,CDCl3)δ-70.23(d).[M+Na]+Calcd for C25H21F3NaO+417.1437,Found:417.1432.
实施例6
采用
Figure BDA0003220805890000084
按实施例1所述方法，得白色固体3af(16.3mg,37％,m.p.140-141℃).
Figure BDA0003220805890000091
该化合物表征数据如下：1H NMR(400MHz,CDCl3)δ7.84(d,J＝8.2Hz,2H),7.80(d,J＝2.0Hz,1H),7.78(d,J＝2.0Hz,1H),7.32(d,J＝8.1Hz,2H),7.28–7.23(m,2H),7.17–7.14(m,2H),5.15(s,1H),3.91(q,J＝9.2Hz,1H),2.45(s,3H).13C NMR(100MHz,CDCl3)δ195.4,145.1,136.1,135.5,135.0,134.8,132.6,132.1,130.9,130.0,129.3,128.9,128.7,125.9(q,J＝281.1Hz,1C),124.9,124.6,124.5,45.23,45.20(q,J＝27.8Hz,1C),21.9.19F NMR(376MHz,CDCl3)δ-70.22(d).[M+Na]+Calcd for C23H15Cl2F3NaO+457.0344,Found:457.0341.
实施例7
采用
Figure BDA0003220805890000092
按实施例1所述方法，得白色固体3ag(14.4mg,29％,m.p.130-131℃).
Figure BDA0003220805890000093
该化合物表征数据如下：1H NMR(600MHz,CDCl3)δ8.12(s,2H),8.09(s,1H),7.85(d,J＝8.1Hz,2H),7.58(d,J＝7.8Hz,1H),7.55(d,J＝7.8Hz,1H),7.41–7.36(m,2H),7.34(d,J＝8.0Hz,2H),5.28(s,1H),4.02(q,J＝9.1Hz,1H),2.45(s,3H).13CNMR(150MHz,CDCl3)δ194.8,145.4,134.8,134.5,134.0,132.4(q,J＝32.7Hz,1C),132.1,131.8,131.4(q,J＝32.6Hz,1C),130.3,130.2,130.1,129.0,126.7,125.8(q,J＝3.5Hz,1C),125.6(q,J＝3.8Hz,1C),124.0(q,J＝272.4Hz,1C),123.9(q,J＝273.1Hz,1C),121.3(q,J＝3.9Hz,1C),121.2(q,J＝3.9Hz,1C),45.52,45.52(q,J＝27.7Hz,1C),21.9.19F NMR(376MHz,CDCl3)δ-62.80(d),-70.16(d).[M+Na]+Calcd for C25H15F9NaO+525.0871,Found:525.0871.
实施例8
采用
Figure BDA0003220805890000101
按实施例1所述方法，得白色固体3ah(25.1mg,38％,m.p.76-77℃).
Figure BDA0003220805890000102
该化合物表征数据如下：1H NMR(400MHz,CDCl3)δ7.72(d,J＝8.2Hz,2H),7.24–7.19(m,4H),7.13(d,J＝9.9Hz,1H),7.08(d,J＝10.1Hz,1H),7.04(m,1H),6.97(d,J＝7.4Hz,1H),5.07(s,1H),3.93(q,J＝9.2Hz,1H),2.36(s,3H).13C NMR(100MHz,CDCl3)δ195.0,159.8(d,J＝249.3Hz,1C),159.6(d,J＝246.8Hz,1C),144.8,134.5(d,J＝3.8Hz,1C),132.4,130.3,129.94(d,J＝9.2Hz,1C),129.85,129.6(d,J＝9.0Hz,1C),128.8,126.5(d,J＝2.8Hz,1C),125.7(q,J＝281.6Hz,1C),124.9(d,J＝2.8Hz,1C),119.7(d,J＝15.3Hz,1C),119.4(d,J＝14.9Hz,1C),117.8(d,J＝23.5Hz,1C),116.8(d,J＝23.7Hz,1C),47.0,46.3(q,J＝26.0Hz,1C),21.8.19F NMR(376MHz,CDCl3)δ-69.19(d),-104.97/-105.01(m),-105.25/-105.30(m),-105.90/-105.94(m),-106.18/-106.22(m).[M+Na]+Calcd for C23H15F5NaO+425.0935,Found:425.0936.
实施例9
采用
Figure BDA0003220805890000103
按实施例1所述方法，得白色固体3ai(11.1mg,26％,m.p.111-112℃).
Figure BDA0003220805890000104
该化合物表征数据如下：1H NMR(600MHz,CDCl3)δ7.86(d,J＝8.2Hz,2H),7.71(d,J＝8.7Hz,1H),7.68(d,J＝8.7Hz,1H),7.30(d,J＝8.1Hz,2H),6.95(dd,J＝8.7,2.6Hz,1H),6.87(dd,J＝8.6,2.7Hz,1H),6.72(d,J＝2.4Hz,1H),6.71(d,J＝2.6Hz,1H),5.09(s,1H),3.84(q,J＝9.6Hz,1H),3.79(s,3H),3.76(s,3H),2.44(s,3H).13CNMR(150MHz,CDCl3)δ196.0,158.9,158.7,144.6,132.6,131.3,129.8,129.0,127.9,127.7,127.3,127.0,126.3(q,J＝281.7Hz,1C),124.7,124.6,116.7,115.19,115.16,114.3,113.9,55.44,55.37,46.2,46.1(q,J＝27.1Hz,1C),21.8.19F NMR(376MHz,CDCl3)δ-70.04(d).[M+Na]+Calcd for C25H21F3Na O3 +449.1335,Found:449.1330.
实施例10
采用
Figure BDA0003220805890000111
按实施例1所述方法，得白色固体3ba(36.6mg,99％,m.p.93-94℃).
Figure BDA0003220805890000112
该化合物表征数据如下：1H NMR(400MHz,CDCl3)δ7.95–7.91(m,2H),7.85–7.80(m,2H),7.42–7.38(m,1H),7.36–7.32(m,1H),7.24–7.18(m,3H),7.17–7.10(m,3H),5.09(s,1H),3.88(q,J＝9.3Hz,1H).13C NMR(100MHz,CDCl3)δ194.9,166.0(d,J＝256.0Hz,1C),134.7,131.6(d,J＝3.0Hz,1C),131.5(d,J＝9.4Hz,2C),134.3,131.3,130.3,129.9,129.6,128.9,128.4,128.2,126.3(q,J＝1.0Hz,1C),126.2(q,J＝281.8Hz,1C),124.3,124.1,116.4,116.3(d,J＝21.9Hz,2C),116.2,46.1,45.6(q,J＝27.4Hz,1C).19F NMR(376MHz,CDCl3)δ-70.13(d),-104.17/-104.24(m).[M+Na]+Calcd forC22H14F4NaO+393.0873,Found:393.0872.
实施例11
采用
Figure BDA0003220805890000113
按实施例1所述方法，得白色固体3ca(33.5mg,87％,m.p.120-121℃).
Figure BDA0003220805890000114
该化合物的表征数据如下：1H NMR(400MHz,CDCl3)δ7.93–7.89(m,4H),7.57–7.46(m,3H),7.45–7.41(m,1H),7.35–7.27(m,3H),7.23(dd,J＝7.5,1.3Hz,1H),5.16(s,1H),3.97(q,J＝9.4Hz,1H).13C NMR(150MHz,CDCl3)δ195.4,140.1,134.7,134.3,133.6,131.3,130.2,130.1,129.9,129.7,129.4,128.9,128.4,128.2,126.4,126.2(q,J＝281.7Hz,1C),124.3,124.2,46.2(s,1H),45.5(q,J＝27.3Hz,1C).19F NMR(376MHz,CDCl3)δ-70.12(d).[M+Na]+Calcd for C22H14F3ClNaO+409.0577,Found:406.0572.
实施例12
采用
Figure BDA0003220805890000121
按实施例1所述方法，得白色固体3da(42.3mg,98％,m.p.123-125℃).
Figure BDA0003220805890000122
该化合物的表征数据如下：1H NMR(400MHz,CDCl3)δ7.77(m,2H),7.69(d,J＝8.6Hz,2H),7.54(d,J＝8.6Hz,2H),7.35–7.33(m,1H),7.287.31–7.26(m,1H),7.21–7.13(m,3H),7.09(d,J＝7.4Hz,1H),5.01(s,1H),3.83(q,J＝9.3Hz,1H).13C NMR(150MHz,CDCl3)δ195.6,134.7,134.3,134.1,132.4,131.3,130.2,130.1,129.9,129.7,128.9,128.8,128.4,128.2,126.4,126.2(q,J＝281.6Hz,1C),124.3,124.1,46.2,45.5(q,J＝27.4Hz,1C).19F NMR(376MHz,CDCl3)δ-70.06(d).[M+Na]+Calcd for C22H14F3BrNaO+453.0072,Found:453.0066.
实施例13
采用
Figure BDA0003220805890000123
按实施例1所述方法，得白色固体3ea(33.9mg,89％,m.p.165-167℃).
Figure BDA0003220805890000124
该化合物表征数据如下：1H NMR(600MHz,CDCl3)δ7.96(d,J＝8.7Hz,2H),7.87(d,J＝7.9Hz,1H),7.84(d,J＝7.9Hz,1H),7.43–7.41(m,1H),7.37–7.34(m,1H),7.25–7.21(m,2H),7.19(,2H),6.97(d,J＝8.7Hz,2H),5.15(s,1H),3.92–3.86(m,4H).13C NMR(100MHz,CDCl3)δ194.8,164.0,134.9,134.4,131.3,131.2,131.0,129.8,129.5,128.7,128.3,128.0,127.8,126.4,126.3(q,J＝281.6Hz,1C),124.2,124.1,114.3,55.7,45.9(q,J＝27.2Hz,1C),45.5.19F NMR(565MHz,CDCl3)δ-70.21(d).[M+Na]+Calcdfor C23H17F3NaO2 +405.1073,Found:405.1066.
实施例14
采用
Figure BDA0003220805890000131
按实施例1所述方法，得白色固体3fa(38.5mg,92％,m.p.95-97℃).
Figure BDA0003220805890000132
该化合物表征数据如下：1H NMR(400MHz,CDCl3)δ7.91(d,J＝8.2Hz,2H),7.84–7.76(m,2H),7.69(d,J＝8.2Hz,2H),7.43–7.36(m,1H),7.34–7.31(m,1H),7.25–7.15(m,3H),7.12(d,J＝7.4Hz,1H),5.06(s,1H),3.89(q,J＝9.3Hz,1H).13C NMR(150MHz,CDCl3)δ196.0,138.5,134.8(q,J＝33.0Hz,1C),134.6,134.3,131.3,129.9,129.8,129.6,129.1,129.0,128.5,128.3,126.2(d,J＝281.9Hz,1C),126.1(q,J＝4.0Hz,2C),124.4,124.2,123.6(q,J＝272.8Hz,1C),46.9,45.3(q,J＝27.5Hz,1C).19F NMR(376MHz,CDCl3)δ-63.18,-70.04(d).[M+Na]+Calcd for C23H14F6NaO+443.0841,Found:443.0834.
实施例15
采用
Figure BDA0003220805890000133
按实施例1所述方法，得白色固体3ga(14.7mg,35％,m.p.124-126℃).
Figure BDA0003220805890000134
该化合物表征数据如下：1H NMR(400MHz,CDCl3)δ8.30(d,J＝8.7Hz,2H),7.96(d,J＝8.7Hz,2H),7.88–7.82(m,2H),7.49–7.44(m,1H),7.41–7.36(m,1H),7.34–7.27(m,2H),7.25–7.21(m,1H),7.17(d,J＝7.5Hz,1H),5.07(s,1H),3.98(q,J＝9.3Hz,1H).13C NMR(100MHz,CDCl3)δ195.8,150.4,140.8,134.3,134.2,131.3,130.0,129.5,129.3,129.0,128.6,128.5,126.5,126.1(q,J＝281.5Hz,1C),124.6,124.2,124.1,47.4(d,J＝1.2Hz,1C),45.1(q,J＝27.5Hz,1C).19F NMR(376MHz,CDCl3)δ-69.94(d).[M+Na]+Calcd for C22H14F3NaO3 +420.0818,Found:420.0816.
实施例16
采用
Figure BDA0003220805890000141
按实施例1所述方法，得白色固体3ha(28.9mg,67％,m.p.150-151℃).
Figure BDA0003220805890000142
该化合物表征数据如下：1H NMR(400MHz,CDCl3)δ8.05(d,J＝8.5Hz,2H),7.98(d,J＝8.5Hz,2H),7.87–7.83(m,2H),7.48–7.44(m,1H),7.40–7.36(m,1H),7.33–7.29(m,2H),7.25–7.21(m,1H),7.18–7.16(m,1H),5.08(s,1H),3.97(q,J＝9.3Hz,1H),3.08(s,3H).13C NMR(100MHz,CDCl3)δ196.0,144.4,140.2,134.4,134.2,131.3,130.0,129.4,129.2,129.2,128.6,128.4,128.1,126.5,126.1(q,J＝281.8Hz,1C),124.5,124.2,47.3,45.1(q,J＝27.5Hz,1C),44.4.19F NMR(376MHz,CDCl3)δ-69.94(d).[M+Na]+Calcd for C23H17F3NaO3S+453.0743,Found:453.0741.
实施例17
采用
Figure BDA0003220805890000143
按实施例1所述方法，得白色固体3ia(18.4mg,47％,m.p.80-81℃).
Figure BDA0003220805890000144
该化合物表征数据如下：1H NMR(600MHz,CDCl3)δ7.86(d,J＝7.8Hz,1H),7.81(d,J＝7.7Hz,1H),7.48–7.43(m,2H),7.39–7.30(m,4H),7.28–7.26(m,1H),7.17–7.15(m,1H),7.12(d,J＝7.6Hz,1H),7.02(d,J＝7.4Hz,1H),4.79(s,1H),4.15(q,J＝9.6Hz,1H),1.81(s,3H).13C NMR(100MHz,CDCl3)δ201.5,137.9,137.0,134.4,133.9,131.4,130.6,130.6,129.7,128.7,128.3,128.2,127.5(d,J＝1.1Hz,1C),126.4(q,J＝281.3Hz,1C),126.2,125.4,124.1,124.0,50.6(d,J＝1.1Hz,1C),44.4(q,J＝27.5Hz,1C),19.3.19F NMR(376MHz,CDCl3)δ-69.80(d).[M+Na]+Calcd for C23H17F3NaO+389.1124,Found:389.1125.
实施例18
采用
Figure BDA0003220805890000151
按实施例1所述方法，得白色固体3ja(33.7mg,91％,m.p.113-115℃).
Figure BDA0003220805890000152
该化合物表征数据如下：1H NMR(400MHz,CDCl3)δ7.95–7.91(m,2H),7.85–7.80(m,2H),7.42–7.38(m,1H),7.36–7.32(m,1H),7.24–7.17(m,3H),7.15–7.11(m,3H),5.09(s,1H),3.87(q,J＝9.3Hz,1H).13C NMR(150MHz,CDCl3)δ197.5,195.0,166.1(d,J＝255.6Hz,1C),134.7,134.3,131.6(d,J＝3.1Hz,1C),131.5(d,J＝9.6Hz,1C),131.3,130.3,129.9,129.6,128.9,128.4,128.2,126.3,126.2(q,J＝281.5Hz,1C),124.3,124.1,116.3(d,J＝21.9Hz,1C),46.1,45.6(q,J＝27.4Hz,1C).19F NMR(376MHz,CDCl3)δ-70.13(d),-104.17/-104.24(m).[M+Na]+Calcd for C22H14F4NaO+393.0873,Found:393.0874.
实施例19
采用
Figure BDA0003220805890000153
按实施例1所述方法，得无色油状液体3ka(20.8mg,47％).
Figure BDA0003220805890000154
该化合物表征数据如下：1H NMR(400MHz,CDCl3)δ7.85(d,J＝7.9Hz,1H),7.78(d,J＝7.5Hz,1H),7.63(d,J＝7.9Hz,1H),7.49–7.42(m,3H),7.38–7.34(m,2H),7.33–7.28(m,1H),7.08–7.04(m,1H),6.90(d,J＝7.4Hz,1H),6.74(d,J＝7.7Hz,1H),4.64(s,1H),4.30(q,J＝9.7Hz,1H).13C NMR(100MHz,CDCl3)δ200.3,137.6(q,J＝2.1Hz,1C),134.0,133.9,131.7,131.3,130.8,130.0,129.7,129.0,128.9,128.5,128.2,127.7(q,J＝1.0Hz,1C),127.3,126.9(q,J＝32.1Hz,1C),126.6(q,J＝4.6Hz,1C),126.4(q,J＝281.2Hz,1H),124.13,124.11,123.6(q,J＝273.8Hz,1C),51.9,43.7(q,J＝27.6Hz,1C).19FNMR(376MHz,CDCl3)δ-57.93,-69.89(d).[M+Na]+Calcd for C23H14F6NaO+443.0841,Found:443.0844.
实施例20
采用
Figure BDA0003220805890000161
按实施例1所述的方法，得白色固体3la(36.2mg,99％,m.p.90-92℃).
Figure BDA0003220805890000162
该化合物表征数据如下：1H NMR(400MHz,CDCl3)δ7.80–7.75(m,2H),7.68(d,J＝6.7Hz,1H),7.62(s,1H),7.37–7.26(m,4H),7.20–7.10(m,4H),5.09(s,1H),3.86(q,J＝9.4Hz,1H),2.32(s,3H).13C NMR(100MHz,CDCl3)δ196.7,139.0,135.3,134.8,134.4,131.3,130.6,129.8,129.6,129.4,128.9,128.7,128.3,128.1,126.4,126.3(q,J＝281.9Hz,1C),125.9,124.2,124.1,46.1(d,J＝1.1Hz,1C),45.6(q,J＝27.2Hz,1C),21.5.19F NMR(376MHz,CDCl3)δ-70.11(d).[M+Na]+Calcd for C23H17F3NaO+389.1124,Found:389.1123.
实施例21
采用
Figure BDA0003220805890000163
按实施例1所述方法，得白色固体3ma(34.4mg,93％,m.p.72-74℃).
Figure BDA0003220805890000164
该化合物表征数据如下：1H NMR(400MHz,CDCl3)δ7.89–7.80(m,2H),7.76–7.71(m,1H),7.55–7.52(m,1H),7.51–7.40(m,2H),7.39–7.34(m,1H),7.31–7.20(m,4H),7.17(dd,J＝7.6,1.3Hz,1H),5.09(s,1H),3.92(q,J＝9.3Hz,1H).13C NMR(150MHz,CDCl3)δ195.4(d,J＝1.6Hz,1C),163.1(d,J＝249.4Hz,1C),137.5(d,J＝6.2Hz,1C),134.7,134.3,131.3,130.7(d,J＝7.7Hz,1C),130.0,129.9,129.7,129.0,128.4,128.2,126.2(q,J＝281.8Hz,1C),124.4,124.3(d,J＝3.3Hz,1C),124.2,120.6(d,J＝21.7Hz,1C),115.7(d,J＝22.2Hz,1C),46.5,45.4(q,J＝27.3Hz,1C).19F NMR(376MHz,CDCl3)δ-70.07(d),-110.66/-110.73(m).[M+Na]+Calcd for C22H14F4NaO+393.0873,Found:393.0873.
实施例22
采用
Figure BDA0003220805890000171
按实施例1所述方法，得淡黄色液体3na(27.5mg,71％).
Figure BDA0003220805890000172
该化合物表征数据如下：1H NMR(600MHz,CDCl3)δ7.86–7.83(m,3H),7.79(d,J＝7.8Hz,1H),7.55(d,J＝6.3Hz,1H),7.45–7.41(m,2H),7.38–7.35(m,1H),7.29–7.26(m,1H),7.24–7.22(m,2H),7.17(d,J＝7.4Hz,1H),5.08(s,1H),3.92(q,J＝9.3Hz,1H).13C NMR(100MHz,CDCl3)δ195.4,137.0,135.5,134.6,134.3,133.5,131.3,130.3,129.9,129.7,129.0,128.9,128.5,128.2,126.7,126.4(d,J＝1.1Hz,1C),126.2(q,J＝281.8Hz,1C),124.4,124.2,46.5(d,J＝1.1Hz,1C),45.4(q,J＝27.5Hz,1C).19F NMR(376MHz,CDCl3)δ-70.03(d).[M+Na]+Calcd for C22H14ClF3NaO+409.0577,Found:409.0577.
实施例23
采用
Figure BDA0003220805890000173
按实施例1所述方法，得白色固体3oa(38.0mg,88％,m.p.130-131℃).
Figure BDA0003220805890000174
该化合物表征数据如下：1H NMR(400MHz,CDCl3)δ7.99–7.98(m,1H),7.87–7.83(m,3H),7.71(d,J＝8.1Hz,1H),7.46–7.42(m,1H),7.39–7.35(m,2H),7.30–7.21(m,3H),7.18(d,J＝7.4Hz,1H),5.07(s,1H),3.92(q,J＝9.3Hz,1H).13C NMR(10MHz,CDCl3)δ195.3,137.2,136.4,134.6,134.3,131.8,131.3,130.6,129.9,129.84,129.75,129.0,128.5,128.3,127.1,126.4(d,J＝1.1Hz,1C),126.2(q,J＝281.9Hz,1C),124.4,124.2,123.5,46.5(d,J＝1.1Hz,1C),45.4(q,J＝27.4Hz,1C).19F NMR(376MHz,CDCl3)δ-70.14(d).[M+Na]+Calcd for C22H14BrF3NaO+453.0072,Found:453.0072.
实施例24
采用
Figure BDA0003220805890000181
按实施例1所述方法，得无色油状液体3pa(32.0mg,76％).
Figure BDA0003220805890000182
该化合物表征数据如下：1H NMR(600MHz,CDCl3)δ8.14(s,1H),8.10(d,J＝7.9Hz,1H),7.88(d,J＝7.6Hz,1H),7.87–7.84(m,2H),7.66–7.63(m,1H),7.48–7.45(m,1H),7.41–7.38(m,1H),7.33–7.30(m,1H),7.29–7.27(m,1H),7.26–7.24(m,1H),7.20(dd,J＝7.5,1.1Hz,1H),5.14(s,1H),3.96(q,J＝9.3Hz,1H).13C NMR(150MHz,CDCl3)δ195.4,136.1,134.6,134.3,131.73,131.72(q,J＝33.1Hz,1C),131.4,129.91,129.88(q,J＝3.4Hz,1C),129.8,129.72,129.65,129.1,128.5,128.3,126.4,126.2(q,J＝281.7Hz,1C),125.6(q,J＝3.5Hz,1C),124.5,124.2,123.6(q,J＝272.6Hz,1C),46.6,45.3(q,J＝27.5Hz,1C).19F NMR(565MHz,CDCl3)δ-62.92,-70.07(d).[M+Na]+Calcd for C23H14F6NaO+443.0841,Found:443.0841.
实施例25
采用
Figure BDA0003220805890000183
按实施例1所述方法，得白色固体3qa(30.0mg,73％,m.p.158-159℃).
Figure BDA0003220805890000184
该化合物表征数据如下：1H NMR(600MHz,CDCl3)δ7.81(d,J＝7.8Hz,1H),7.79(d,J＝7.8Hz,1H),7.68(dd,J＝8.4,1.9Hz,1H),7.38–7.35(m,1H),7.34(d,J＝1.9Hz,1H),7.31–7.29(m,1H),7.21–7.17(m,2H),7.17–7.14(m,1H),7.13(d,J＝7.7Hz,1H),6.90(d,J＝8.4Hz,1H),5.11(s,1H),3.90(s,3H),3.87–3.82(m,1H),3.77(s,3H).13C NMR(100MHz,CDCl3)δ194.9,153.8,149.6,134.9,134.4,131.4,131.0,129.8,129.5,128.7,128.3,128.0,127.9,126.4,126.3(q,J＝281.8Hz,1C),124.2,124.1,123.2,111.2,110.3,56.3,56.0,46.0(q,J＝27.2Hz,1C),45.3(s,1H).19F NMR(376MHz,CDCl3)δ-70.22(d).[M+Na]+Calcd for C24H19F3NaO3 +435.1178,Found:435.1169.
实施例26
采用
Figure BDA0003220805890000191
按实施例1所述方法，得白色固体3ra(33.4mg,83％,m.p.114-115℃).
Figure BDA0003220805890000192
该化合物表征数据如下：1H NMR(400MHz,CDCl3)δ8.52(s,1H),7.99(d,J＝7.8Hz,1H),7.95–7.83(m,5H),7.65–7.54(m,2H),7.45–7.41(m,1H),7.39–7.32(m,1H),7.27–7.19(m,4H),5.34(s,1H),4.01(q,J＝9.4Hz,1H).13C NMR(100MHz,CDCl3)δ196.4,135.8,134.8,134.4,132.6,132.5,131.4,130.6,130.4,129.8,129.7,129.1,129.0,128.8,128.4,128.1,128.0,127.2,126.5,126.4(q,J＝281.7Hz,1C),124.5,124.3,124.1,46.2,45.8(q,J＝27.2Hz,1C).19F NMR(376MHz,CDCl3)δ-70.09(d).[M+Na]+Calcd forC26H17F3NaO+425.1124,Found:425.1117.
实施例27
采用
Figure BDA0003220805890000193
按实施例1所述方法，得黄色油状液体3sa(33.8mg,99％).
Figure BDA0003220805890000194
该化合物表征数据如下：1H NMR(600MHz,CDCl3)δ7.88–7.82(m,2H),7.66(d,J＝1.1Hz,1H),7.45–7.37(m,3H),7.34–7.26(m,3H),7.11(d,J＝3.5Hz,1H),6.54(dd,J＝3.6,1.7Hz,1H),4.98(s,1H),4.00(q,J＝9.4Hz,1H).13C NMR(100MHz,CDCl3)δ185.1,151.2,146.9,134.6,134.3,131.3,,130.01,129.95,129.6,128.9,128.3,128.2,127.2(d,J＝1.0Hz,1C),126.2(q,J＝281.5Hz,1C),124.3,124.1,118.9,113.0,46.8,45.2(q,J＝27.4Hz,1C).19F NMR(376MHz,CDCl3)δ-70.11(d).[M+Na]+Calcd for C20H13F3NaO2 +365.0760,Found:365.0760.
实施例28
采用
Figure BDA0003220805890000201
按实施例1所述方法，得黄色油状液体3ta(4.0mg,16％).
Figure BDA0003220805890000202
该化合物表征数据如下：1H NMR(400MHz,CDCl3)δ7.84(d,J＝7.6Hz,1H),7.79(d,J＝7.6Hz,1H),7.41–7.20(m,5H),6.98(d,J＝7.6Hz,1H),3.93(d,J＝5.6Hz,1H),3.34–3.25(m,1H),2.60–2.55(m,1H),2.46–2.42(m,1H),2.04–1.99(m,1H),1.94–1.82(m,2H),1.81–1.75(m,1H).13C NMR(100MHz,CDCl3)δ212.6,138.0,133.6,133.0,132.5,128.4,128.3,128.0,127.8,127.7,127.6,124.3,124.1,54.7,43.7,39.2,28.1,25.6.[M+Na]+Calcd for C18H16NaO+271.1093,Found:271.1093.
实施例29
采用
Figure BDA0003220805890000203
按实施例1所方法，得白色固体3ua(7.8mg,30％,m.p.166-167℃).
Figure BDA0003220805890000204
该化合物表征数据如下：1H NMR(600MHz,CDCl3)δ7.92(d,J＝7.8Hz,2H),7.74(d,J＝7.4Hz,2H),7.43–7.33(m,4H),4.36(s,2H),3.00(s,3H).13C NMR(150MHz,CDCl3)δ177.3,131.2,130.1,128.8,128.5,127.0,123.5,43.4,25.7.[M+Na]+Calcd forC17H13NNaO2 +286.0838,Found:286.0830.
实施例30
采用
Figure BDA0003220805890000205
按实施例1所述方法，得白色固体3va(17.3mg,73％).
Figure BDA0003220805890000206
该化合物表征数据如下：1H NMR(400MHz,CDCl3)δ7.71(d,J＝7.6Hz,1H),7.58(d,J＝16.3Hz,1H),7.47–7.38(m,6H),7.35–7.30(m,2H),6.67(d,J＝16.3Hz,1H),2.56(q,J＝7.3Hz,2H),1.10(t,J＝7.3Hz,3H).13C NMR(150MHz,CDCl3)δ201.3,143.2,141.8,140.1,132.9,130.6,130.1,130.0,128.4,127.9,127.8,127.6,126.9,33.4,8.3.[M+Na]+Calcd for C17H16NaO+259.1093,Found:259.1093.
实施例31
采用
Figure BDA0003220805890000211
按实施例1所述方法，得白色固体3wa(24.3mg,93％,m.p.133-135℃).
Figure BDA0003220805890000212
该化合物表征数据如下：1H NMR(600MHz,CDCl3)δ7.66–7.61(m,2H),7.43–7.39(m,4H),7.31–7.27(m,2H),4.12(t,J＝6.0Hz,2H),3.15(dd,J＝18.6,5.3Hz,2H),3.00(dd,J＝18.9,6.9Hz,2H).13C NMR(150MHz,CDCl3)δ205.8,203.5,137.3,135.0,132.5,129.7,129.1,128.5,53.4,46.8.[M+Na]+Calcd for C18H14NaO2 +285.0886,Found:285.0881.
实施例32
采用
Figure BDA0003220805890000213
按实施例1所述方法，得黄色固体3xa(17.8mg,64％,m.p.139-140℃).
Figure BDA0003220805890000214
该化合物表征数据如下：1H NMR(400MHz,CDCl3)δ7.69–7.61(m,2H),7.45–7.38(m,4H),7.34–7.26(m,2H),4.18–4.17(m,1H),3.54(d,J＝8.0Hz,1H),3.25(dd,J＝19.1,3.1Hz,1H),3.21–3.13(m,1H),3.03(dd,J＝19.1,6.4Hz,1H),1.13(d,J＝6.8Hz,3H).13C NMR(150MHz,CDCl3)δ207.7,203.4,137.4,137.0,136.0,134.3,132.6,132.3,130.2,129.7,129.3,128.8,128.7,128.1,62.0,54.0,48.7,47.7,14.3.[M+Na]+Calcd forC19H16NaO2 +299.1043,Found:299.1038.
实施例33
采用
Figure BDA0003220805890000221
按实施例1所述方法，得黄色固体3ya(7.9mg,25％,m.p.136-137℃).
Figure BDA0003220805890000222
该化合物表征数据如下：1H NMR(400MHz,CDCl3)δ9.46–9.35(m,1H),8.89(d,J＝8.4Hz,1H),8.74–8.70(m,2H),7.81–7.69(m,4H),6.78(s,1H),1.45(s,9H).13CNMR(150MHz,CDCl3)δ190.7,189.2,158.5,134.3,133.5,133.0,132.8,129.5,129.22,129.17,128.7,128.4,128.1,127.0,126.8,123.0,122.8,35.6,29.6.[M+Na]+Calcd forC22H18NaO2 +337.1199,Found:337.1196.
实施例34
反应采用扩大规模试验，参考实施例1反应条件，仅仅反应规模扩大，结果如下：
Figure BDA0003220805890000223
实施例35
化合物3aa到4衍生化操作步骤：
将3aa(36.6mg，0.1mmol)和mCPBA(83.0mg，0.5mmol)溶解于CH2Cl2(1.0mL)中，然后加入磷酸盐缓冲液(pH＝7，0.4mL)和HFIP(1.0mL)，并在室温下剧烈搅拌36h。饱和硫代硫酸钠溶液(3.0mL)淬灭，二氯甲烷萃取，无水硫酸钠干燥，旋蒸后柱层析得到14.1mg黄色油状液体4，收率37％。1H NMR(600MHz,CDCl3)δ7.94(d,J＝7.8Hz,1H),7.89(d,J＝7.8Hz,1H),7.65(d,J＝8.2Hz,2H),7.61(d,J＝7.5Hz,1H),7.53–7.47(m,2H),7.41–7.34(m,3H),7.09(d,J＝8.2Hz,2H),6.52(d,J＝1.2Hz,1H),3.99(q,J＝9.1Hz,1H),2.32(s,3H).13C NMR(150MHz,CDCl3)δ165.7,144.1,134.2,134.1,131.7,131.0,130.6,130.4,129.9,129.7,129.1,128.5,128.3,127.0,126.9(q,J＝281.3Hz,1C),126.4,124.3,124.0,68.3(q,J＝1.9Hz,1C),48.1(q,J＝26.6Hz,1C),21.8.19F NMR(565MHz,CDCl3)δ-68.58(d).[M+Na]+Calcd for C16H10F3NaO2 +405.1073,Found:405.1073.
化合物3aa到6衍生化操作步骤：
将3aa(36.6mg，0.1mmol)溶解于干DCM(2.0mL)中，添加LiAlH4(29.0mg，0.1mmol)，并在80℃下搅拌反应4h，然后通过缓慢添加水(2.0mL)淬灭。用二氯甲烷萃取，无水硫酸钠干燥，旋蒸后柱层析得到中间产物5+5'。5+5'(35.6mg，0.1mmol)溶解于干DCM中，然后沿管壁缓慢加入三氟磺酸(15.0mg，0.1mmol)。反应在80℃下加热并搅拌12小时，然后冷却至室温。旋蒸后柱层析得到29.3mg黄色油状液体6，收率84％。1H NMR(600MHz,CDCl3)δ8.75(d,J＝8.0Hz,1H),8.73(d,J＝8.3Hz,1H),8.36(d,J＝8.2Hz,1H),8.10(d,J＝8.4Hz,1H),7.74–7.66(m,3H),7.55–7.52(m,1H),7.08(d,J＝8.0Hz,2H),7.03(d,J＝8.0Hz,2H),4.75(s,2H),2.31(s,3H).13C NMR(150MHz,CDCl3)δ137.0,136.2,135.6,131.9,131.0,130.6,129.4,128.6,127.89,127.86,127.6,127.3,127.1,127.0,126.03(q,J＝5.2Hz,1C),125.97(q,J＝277.8Hz,1C),124.5(q,J＝27.6Hz,1C),123.03,123.00,35.7(q,J＝4.8Hz,1C),21.1.19F NMR(56C5 MHz,CDCl3)δ-50.56.[M+Na]+Calcd for C16H10F3Na+373.1175,Found:373.1177.
化合物3aa到7衍生化操作步骤：
在惰性气体条件下，向甲基三苯基溴化膦(124.0mg，0.4mmol)、叔丁醇钾(44.9mg，0.4mmol)和THF(2.0mL)组成溶液中加入3aa(36.6mg，0.1mmol)。反应在30℃下加热并搅拌12小时，然后冷却至室温。乙酸乙酯萃取，无水硫酸钠干燥，旋蒸后柱层析得到29.2mg无色油状液体7，收率80％。1H NMR(400MHz,CDCl3)δ7.92–7.90(m,2H),7.50–7.48(m,2H),7.41–7.37(m,1H),7.36–7.31(m,2H),7.31–7.28(m,2H),7.28–7.25(m,2H),7.12(d,J＝7.5Hz,1H),5.14(s,1H),4.59(s,1H),4.39–4.34(m,1H),3.53(q,J＝9.8Hz,1H),2.45(s,3H).13CNMR(150MHz,CDCl3)δ148.1,137.9,137.3,135.0,134.9,134.1,131.8,129.9,129.6,129.4,128.5,128.2,127.9,127.1,126.7,126.6(q,J＝282.2Hz,1C),124.0,123.8,116.8,46.7(q,J＝26.2Hz,1C),42.6,21.3.19F NMR(376MHz,CDCl3)δ-69.96(d).[M+Na]+Calcdfor C24H19F3Na+387.1331,Found:387.1331.
上实施例描述了本发明的基本原理、主要特征及优点。本行业的技术人员应该了解，本发明不受上述实施例的限制，上述实施例和说明书中描述的内容只是说明本发明的原理，在不脱离本发明原理的范围下，本发明还会有各种变化和改进，这些变化和改进均落入本发明保护的范围内。

Claims (9)

1.一种含三氟甲基取代二氢菲类化合物，其特征在于，具体结构如下：
Figure FDA0003220805880000011
其中：R1选自C1-C6烷基、卤素、C1-C6烷氧基、三氟甲基、硝基、腈基、C1-C4烷氧羰基中的一种或多种；R2选自苯基或取代苯基、萘基或取代萘基、噻吩基或取代噻吩基、呋喃基或取代呋喃基，取代基为C1-C6烷基、卤素、C1-C6烷氧基、三氟甲基、硝基、腈基、C1-C4烷磺酰基、C1-C4烷氧羰基中的一种或多种；
B结构中，
Figure FDA0003220805880000012
表示
Figure FDA0003220805880000013
2.如权利要求1所述三氟甲基取代二氢菲类化合物的合成方法，其特征在于，包括如下步骤：以2-联苯硼酸类化合物1和α,β-不饱和酮化合物2A或2B为起始原料，在过渡金属铑催化剂和银盐氧化剂作用下，有机溶剂中加热反应分别得到三氟甲基取代二氢菲类化合物3A或3B；
Figure FDA0003220805880000014
其中：R1选自C1-C6烷基、卤素、C1-C6烷氧基、三氟甲基、硝基、腈基、C1-C4烷氧羰基中的一种或多种；R2选自苯基或取代苯基、萘基或取代萘基、噻吩基或取代噻吩基、呋喃基或取代呋喃基，取代基为C1-C6烷基、卤素、C1-C6烷氧基、三氟甲基、硝基、腈基、C1-C4烷磺酰基、C1-C4烷氧羰基中的一种或多种；2B选自
Figure FDA0003220805880000015
3.根据权利要求2所述三氟甲基取代二氢菲类化合物的合成方法，其特征在于：所述铑催化剂为[CptBuRhI2]2或[Cp*RhCl2]2。
4.根据权利要求2所述三氟甲基取代二氢菲类化合物的合成方法，其特征在于：所述银盐氧化剂为醋酸银、碳酸银、氧化银中的一种或多种。
5.根据权利要求2所述三氟甲基取代二氢菲类化合物的合成方法，其特征在于：所述化合物1、化合物2、铑催化剂与银盐氧化剂摩尔比为1.0-1.5:1.0:0.04-0.10:1.0-2.0。
6.根据权利要求2所述三氟甲基取代二氢菲类化合物的合成方法，其特征在于：有机溶剂选自饱和烃类酯。
7.根据权利要求6所述三氟甲基取代二氢菲类化合物的合成方法，其特征在于：有机溶剂为乙酸乙酯。
8.根据权利要求2所述三氟甲基取代二氢菲类化合物的合成方法，其特征在于：所述加热反应温度为60-90℃。
9.根据权利要求2所述三氟甲基取代二氢菲类化合物的合成方法，其特征在于：反应无需惰性气体保护，在空气中直接进行。
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