苯并环庚烯酮类化合物的合成方法
阅读说明：本技术 苯并环庚烯酮类化合物的合成方法 (Method for synthesizing benzocycloheptenone compounds ) 是由 刘丙贤 王娟娟 杨凌云 石雨佳 于 2021-08-19 设计创作，主要内容包括：本发明公开了一种过渡金属催化合成苯并环庚烯酮类化合物的方法,属于有机合成技术领域。以2-联苯硼酸类化合物和二取代环丙烯酮类化合物为起始原料,在过渡金属铑催化剂和银盐氧化剂作用下,有机溶剂中加热搅拌反应得到苯并环庚烯酮类化合物。本发明具有起始原料简单易制备、底物适用范围广和操作简单等优点,环丙烯酮三元环在反应过程中开环重新生成七元环,为一步合成复杂多环化合物提供了有益的借鉴。(The invention discloses a method for synthesizing benzocycloheptenone compounds by transition metal catalysis, belonging to the technical field of organic synthesis. The preparation method comprises the steps of taking 2-biphenyl boric acid compounds and disubstituted cyclopropenone compounds as initial raw materials, and heating and stirring the initial raw materials in an organic solvent to react under the action of a transition metal rhodium catalyst and a silver salt oxidant to obtain the benzocycloheptenone compounds. The invention has the advantages of simple and easy preparation of the starting material, wide application range of the substrate, simple operation and the like, and the ring-opening of the three-membered ring of the cyclopropenone in the reaction process regenerates the seven-membered ring, thereby providing a beneficial reference for synthesizing the complex polycyclic compound in one step.)
技术领域
本发明涉及有机合成技术领域，具体涉及苯并环庚烯酮类化合物的合成方法。
背景技术
环庚烯酮及衍生物作为重要有机骨架广泛存在于天然产物及药物分子中。苯并环庚烯酮类化合物是一类包含有一个七元的环状结构的特殊化合物，该类结构大多具有抗真菌、抗细菌、抗病毒及抗肿瘤等生物活性。
目前对于环庚烯酮及衍生物研究开发相对并不充分，因此，开发苯并环庚烯酮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，本发明提供了一种苯并环庚烯酮类化合物及其制备方法。本发明中化合物苯并环庚烯酮类结构新颖，在铑催化剂和银盐氧化剂存在下，以2-联苯硼酸类化合物和二取代环丙烯酮化合物为起始原料，一步即可完成，高产率得到苯并环庚烯酮类化合物。该合成方法目前尚未有报道。该方法具有如下优势：本发明可以通用，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。
本发明所述苯并环庚烯酮类化合物，具体结构如下：
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C1-C6烷基、苯基或取代苯基，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。
本发明还提供了上述苯并环庚烯酮类化合物的合成方法，包括如下步骤：以2-联苯硼酸类化合物1和二取代环丙烯酮类化合物2为起始原料，在过渡金属铑催化剂和银盐氧化剂作用下，有机溶剂中加热搅拌反应得到苯并环庚烯酮类化合物3。
合成路线如下：
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C1-C6烷基、苯基或取代苯基，取代苯基中取代基为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。
进一步地，在上述技术方案中，所述铑催化剂为[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、苯甲酸银、硫酸银、硝酸银、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1.0-1.5:1.0:0.02-0.10:0.5-2.0。
进一步地，在上述技术方案中，有机溶剂选自非质子极性溶剂。所述非质子性极性溶剂优选自乙酸乙酯、甲苯、二氯乙烷或丙酮。
进一步地，在上述技术方案中，所述加热反应温度为40-80℃。
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。
根据试验结果，推测可能反应机理如下：
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)：
发明有益效果
本发明可以高选择性合成苯并环庚烯酮类化合物，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
反应条件的探索试验：(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,1.5eq)、[Cp*RhCl2]2(4.0mol％)、化合物2a(0.1mmol,1.0eq)和各种银盐以及相应常用溶剂，反应管密封，升温至40-80℃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(洗脱剂：石油醚/二氯甲烷体积比1:1)，得到白色固体3aa。反应方程式如下：
a反应条件：1a(0.1mmol),2a(0.1mmol),[Cp*RhCl2]2(4mol％),氧化剂(x eq),溶剂(1mL),60℃空气氛围下反应12h,分离收率。
在以上优化试验基础上，苯并环庚烯酮类化合物3通用合成方法，典型操作如下：
在反应试管中，化合物1、化合物2(化合物1与化合物2摩尔比为1.2:1.0)和[Cp*RhCl2]2(4mol％)，在空气条件下，再加入1.0mL乙酸乙酯，密封真空封管，置于60℃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/DCM硅胶柱层析纯化，得到化合物3。
实施例1
在25mL耐压管中，依次加入2-联苯硼酸1a(0.15mmol,30.0mg)、2,3-二苯基环丙烷-2-烯-1-酮2a(0.1mmol,20.6mg)、[Cp*RhCl2]2(0.004mmol,2.5mg)、AgOAc(0.2mmol,33.4mg)和乙酸乙酯(1.0mL),反应管密封，然后将该混合物60℃加热搅拌反应12h。冷却到室温，旋干溶剂。加入去离子水和乙酸乙酯，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。旋干柱层析分离(石油醚/二氯甲烷＝1:1)，得白色固体3aa(32.2mg,90％)。1H NMR(600MHz,CDCl3)δ7.88(d,J＝7.8Hz,1H),7.72(dd,J＝8.0,1.1Hz,1H),7.65–7.63(m,1H),7.45–7.43(m,1H),7.40–7.37(m,1H),7.34(dd,J＝7.6,1.2Hz,1H),7.26–7.20(m,3H),7.14–7.08(m,7H),6.99–6.96(m,2H).13C NMR(150MHz,CDCl3)δ197.9,144.2,142.6,141.8,141.1,137.8,137.2,136.4,136.1,134.2,133.8,131.7,131.4,131.0,130.8,130.1,129.4,129.2,129.1,128.9,128.7,128.5,128.4,127.8,127.7,127.6,125.7.[M+Na]+Calcd for C27H18NaO+381.1250,Found:381.1245.
实施例2
采用按实施例1所述方法，得白色固体3ab(24.5mg,62％,m.p.224-225℃).
1H NMR(600MHz,CDCl3)δ7.90(d,J＝7.9Hz,1H),7.74(dd,J＝7.9,0.9Hz,1H),7.69–7.66(m,1H),7.49–7.46(m,1H),7.45–7.41(m,1H),7.35(dd,J＝7.6,1.0Hz,1H),7.28–7.20(m,3H),7.10(dd,J＝8.0,1.0Hz,1H),6.98–6.91(m,2H),6.90–6.78(m,4H).13C NMR(150MHz,CDCl3)δ198.7,162.1(d,J＝247.3Hz,1C),161.9(d,J＝247.9Hz,1C),144.4,141.9,141.0,137.7,137.1(d,J＝3.7Hz,1C),136.8,136.4,132.8(d,J＝7.9Hz,1C),132.0(d,J＝7.9Hz,1C),131.8,131.7(d,J＝3.3Hz,1C),131.2,130.9,128.8,128.4(d,J＝7.5Hz,1C),127.4,125.6,115.2(d,J＝21.8Hz,1C),114.9(d,J＝21.1Hz,1C).19F NMR(376MHz,CDCl3)δ-114.15/-114.22(m),-114.44/-114.51(m).[M+Na]+Calcd forC27H16F2NaO+417.1563,Found:417.1561.
实施例3
采用按实施例1所述方法，得白色固体3ac(30.8mg,80％).
1H NMR(600MHz,CDCl3)for the diastereoisomersδ7.89(m,2H),7.80–7.77(m,1H),7.75–7.74(m,1H),7.70–7.68(m,3H),7.53–7.50(m,2H),7.48–7.40(m,4H),7.29–7.17(m,5H),7.14–7.00(m,8H),7.00–6.91(m,4H),6.87–6.80(m,2H),6.74(s,1H),2.50(s,2.5H),1.85(s,2.5H),1.67(s,3H),1.65(s,3H).13C NMR(150MHz,CDCl3)forthe diastereoisomersδ198.3,197.6,171.3,145.1,144.3,143.8,143.3,140.2,139.3,137.7,137.4,137.3,137.0,136.4,136.2,136.1,135.7,135.6,135.0,132.8,132.0,131.2,131.1,130.8,130.7,130.6,130.2,130.1,130.0,129.6,129.0,128.6,128.5,128.4,128.1,128.0,127.7,127.6,127.4,126.5,125.8,125.2,125.0,124.8,60.5,21.3,21.2,19.9,19.7,14.4.[M+Na]+Calcd for C29H22NaO+409.1563,Found:409.1561.
异构体为非对映异构体，分别为该异构体比例为1：1.2，且无法区分主要化合物结构，不能通过柱层析分离。
实施例4
采用按实施例1所述方法，得白色固体3ad(33.6mg,79％).
1H NMR(600MHz,CDCl3)for the diastereoisomersδ7.90–7.89(m,1H),7.81–7.74(m,2H),7.74–7.70(m,1H),7.59–7.50(m,2H),7.48–7.44(m,2H),7.36–7.16(m,5H),7.12–7.00(m,4H).13C NMR(150MHz,CDCl3)for the diastereoisomersδ196.9,195.3,144.4,143.6,143.1,142.5,142.2,141.9,139.4,138.2,138.03,137.96,137.1,136.9,135.8,135.2,134.6,134.3,134.2,133.7,133.0,132.9,132.8,131.5,131.3,131.1,130.3,130.1,130.0,129.4,129.33,129.29,129.21,129.15,129.1,128.9,128.8,128.6,128.4,128.3,127.8,127.6,127.2,126.6,126.5,126.3,125.54,125.49.[M+Na]+Calcd for C27H16Cl2NaO+449.0470,Found:449.0467.该产物是与实施例3类似的非对映异构体，比例为1：1.9，不能通过柱层析分离。
实施例5
采用按实施例1所述方法，得白色固体3ae(34.5mg,67％).
1H NMR(400MHz,CDCl3)for the diastereoisomersδ7.90–7.87(m,1H),7.80–7.75(m,1H),7.72–7.68(m,1H),7.63–7.37(m,5H),7.35–7.14(m,4H),7.09–6.95(m,3H).13C NMR(100MHz,CDCl3)for the diastereoisomersδ196.8,194.9,144.7,144.1,143.8,143.7,143.1,141.2,139.7,139.3,138.5,138.3,137.3,137.1,137.0,135.9,134.7,134.6,133.7,133.3,132.7,132.5,132.4,131.52,131.46,131.2,131.0,130.14,130.05,129.8,129.4,129.33,129.30,129.23,129.18,129.0,128.7,128.6,128.4,128.33,128.25,127.8,127.6,127.3,127.0,126.9,126.8,126.03,125.96,124.5,124.2,123.3,122.7.[M+Na]+Calcd for C27H16Br2NaO+538.9440,Found:538.9438.该产物是与实施例3类似的非对映异构体，比例为1：1.9，异构体不能通过柱层析分离。
实施例6
采用按实施例1所述方法，得白色固体3af(30.6mg,57％,m.p.139-140℃).
1H NMR(400MHz,CDCl3)δ7.83(d,J＝7.8Hz,1H),7.68(d,J＝7.8Hz,1H),7.64–7.60(m,1H),7.48–7.34(m,2H),7.30(d,J＝7.5Hz,1H),7.23–7.18(m,1H),7.10–6.98(m,5H),6.92(s,1H),6.83(d,J＝7.3Hz,1H).13C NMR(150MHz,CDCl3)δ197.9,144.2,142.6,141.8,141.1,137.8,137.2,136.4,136.1,134.2,133.8,131.7,131.4,131.0,130.8,130.1,129.4,129.2,129.1,128.9,128.7,128.5,128.4,127.8,127.7,127.6,125.7.[M+Na]+Calcd for C27H14Cl2NaO+449.0470,Found:449.0472.
实施例7
采用按实施例1所述的方法，得白色固体3ag(28.4mg,98％,m.p.55-57℃).
1H NMR(400MHz,CDCl3)δ7.73(d,J＝7.8Hz,1H),7.65–7.54(m,3H),7.49–7.42(m,2H),7.40–7.32(m,2H),2.73–2.48(m,4H),1.54–1.27(m,4H),0.91(t,J＝7.3Hz,3H),0.76(t,J＝7.4Hz,3H).13C NMR(100MHz,CDCl3)δ201.9,145.0,144.4,140.6,137.01,136.96,136.6,131.0,130.7,128.2,127.9,127.6,127.5,127.1,125.3,34.9,34.2,22.9,22.3,14.4,14.0.[M+Na]+Calcd for C21H22Na O+313.1563,Found:313.1563.
实施例8
采用按实施例1所述方法，得白色固体3ba(23.7mg,60％,m.p.184-185℃).
1H NMR(400MHz,CDCl3)δ7.44–7.40(m,1H),7.35–7.31(m,1H),7.25–7.19(m,3H),7.15–7.10(m,7H),7.05–6.95(m,3H),6.91(d,J＝8.0Hz,1H).13C NMR(100MHz,CDCl3)δ197.9,161.4(d,J＝1.7Hz,1C),160.3(d,J＝243.3Hz,1C),159.9(d,J＝244.9Hz,1C),158.9,147.8(d,J＝1.6Hz,1C),144.1,139.9(d,J＝2.2Hz,1C),139.8(d,J＝1.8Hz,1C),140.1,134.9,131.0,130.7(d,J＝8.4Hz,1C),130.0,129.2(d,J＝9.1Hz,1C),128.0(d,J＝11.0Hz,1C),127.6(d,J＝4.3Hz,1C),126.9(d,J＝3.0Hz,1C),120.0,119.9(d,J＝2.9Hz,1C),117.9(d,J＝22.1Hz,1C),117.1(d,J＝15.7Hz,1C),115.1(d,J＝1.0Hz,1C),114.9(d,J＝1.3Hz,1C).19F NMR(376MHz,CDCl3)δ-108.46/-108.50(m),-108.60/-108.64(m),-108.75/-108.79(m),-108.89/-108.93(m).[M+Na]+Calcd for C27H16F2NaO+417.1061,Found:417.1055.
实施例9
采用按实施例1所述方法，得白色固体3ca(37.1mg,96％,m.p.166-168℃).
1H NMR(600MHz,CDCl3)δ7.67(s,1H),7.52(s,1H),7.24–7.22(m,4H),7.09–7.07(m,6H),7.01(dd,J＝8.2,1.3Hz,1H),6.98–6.93(m,3H),2.51(s,3H),2.41(s,3H).13C NMR(150MHz,CDCl3)δ198.7,142.21,142.20,141.8,141.6,141.2,138.0,137.7,136.6,136.3,134.6,132.0,131.10,131.08,130.4,129.2,129.0,128.2,127.8,127.6,127.01,126.98,125.9,21.9,21.5.[M+Na]+Calcd for C29H22NaO+409.1563,Found:409.1554.
实施例10
采用按实施例1所述方法，得白色固体3da(20.0mg,51％).
1H NMR(400MHz,CDCl3)for the regioismersδ7.52–7.26(m,3H),7.18–6.91(m,10H),6.91–6.73(m,3H).13C NMR(100MHz,CDCl3)for theregioismersδ198.2,194.7,164.2(d,J＝250.8Hz),161.4(d,J＝249.5Hz),161.2(d,J＝252.8Hz),156.4(d,J＝253.0Hz),144.5,142.7(d,J＝0.9Hz,1H),141.4(d,J＝2.9Hz),140.5,140.2(d,J＝3.0Hz),138.9(d,J＝2.6Hz),138.8(d,J＝2.8Hz),138.7,138.4(d,J＝3.2Hz),138.3(d,J＝3.1Hz),134.5,134.4,134.2,134.0(d,J＝3.3Hz),133.9,131.7(d,J＝17.3Hz),131.4(d,J＝8.5Hz),131.2,130.1,130.0,129.6(d,J＝10.3Hz),129.5(d,J＝2.1Hz),128.2,128.0,127.8(d,J＝9.3Hz),127.70(d,J＝7.4Hz),127.68,127.4(d,J＝42.2Hz),126.0(d,J＝3.2Hz),125.8(d,J＝11.0Hz),124.3(d,J＝3.6Hz),116.7(d,J＝22.7Hz),116.2(d,J＝23.0Hz),115.71(d,J＝40.2Hz),115.71(d,J＝2.7Hz),115.4(d,J＝4.0Hz),115.1(d,J＝5.7Hz).19F NMR(376MHz,CDCl3)δ-101.40/-101.44(m),-108.27/-108.33(m),-112.44/-112.50(m),-119.17/-119.20(m).(The fluorine spectru m showsthat the ratio of products is 1:1.1)[M+Na]+Calcd for C27H16F2NaO+417.1061,Found:417.1054.该产物为区域异构体，比例为1：1.1，无法通过柱层析分离。
实施例11
采用按实施例1所述方法，得白色固体3ea(42.3mg,99％).
1H NMR(400MHz,CDCl3)δ7.85(d,J＝1.8Hz,1H),7.69(d,J＝2.1Hz,1H),7.44(dd,J＝8.2,1.8Hz,1H),7.29(d,J＝8.2Hz,1H),7.26–7.18(m,3H),7.17–7.09(m,6H),7.06(d,J＝8.6Hz,1H),6.95–6.93(m,2H).13C NMR(150MHz,CDCl3)δ197.3,143.0,142.8,140.9,140.7,137.8,137.3,136.7,135.9,135.4,134.0,133.7,131.0,130.2,130.1,129.0,128.5,128.1,128.0,127.8,127.6,127.5,127.4.[M+Na]+Calcd forC27H16Cl2NaO+449.0470,Found:449.0460.
实施例12
采用按实施例1所述方法，得白色固体3fa(48.9mg,99％,m.p.162-163℃).
1H NMR(400MHz,CDCl3)δ8.24(s,1H),8.06(s,1H),7.83(d,J＝7.9Hz,1H),7.59(d,J＝8.1Hz,1H),7.53(d,J＝7.9Hz,1H),7.40–7.31(m,3H),7.24–7.21(m,6H),7.05–7.04(m,2H).13C NMR(100MHz,CDCl3)δ197.4,147.0,144.2,140.7,140.1,136.8,135.7,134.7,133.2(q,J＝32.9Hz,1C),132.9,131.0,130.1,130.3(q,J＝32.9Hz,1C),128.3,128.0,127.9,127.4(q,J＝3.9Hz,1C),126.4,125.7(q,J＝3.5Hz,1C),125.6(q,J＝3.7Hz,1C),124.6(q,J＝3.5Hz,1C),123.8(q,J＝272.9Hz,1C).19F NMR(376MHz,CDCl3)δ-62.55,-62.63.[M+Na]+Calcd for C29H16F6NaO+517.0998,Found:517.1000.
实施例13
采用按实施例1所述的方法，得白色固体3ga(46.5mg,99％,m.p.200-201℃).
1H NMR(400MHz,CDCl3)δ7.85(d,J＝8.3Hz,1H),7.73–7.66(m,2H),7.43(dd,J＝8.3,2.0Hz,1H),7.39(d,J＝2.0Hz,1H),7.33(d,J＝3.6Hz,1H),7.31(d,J＝2.4Hz,1H),7.17–7.08(m,7H),7.00(d,J＝3.6Hz,1H),6.98(d,J＝2.3Hz,1H),1.35(s,9H),1.16(s,9H).13C NMR(150MHz,CDCl3)δ199.3,151.1,149.6,144.0,142.8,142.2,141.7,136.7,136.5,134.9,133.9,131.1,130.6,130.2,129.1,128.5,128.4,127.7,127.6,126.98,126.96,125.3,122.5,35.0,34.6,31.4,31.1.[M+Na]+Calcd for C35H34NaO+493.2502,Found:493.2495.
实施例14
采用按实施例1所述方法，得白色固体3ha(48.9mg,99％).
1H NMR(400MHz,CDCl3)δ8.03(d,J＝8.3Hz,1H),7.92(d,J＝8.3Hz,1H),7.85(d,J＝8.3Hz,1H),7.71–7.60(m,2H),7.41(s,1H),7.28–7.23(m,2H),7.21–7.07(m,6H),6.96–6.94(m,2H).13C NMR(150MHz,CDCl3)δ196.9,144.8,144.0,141.0,139.9,139.3,138.30,138.26,134.9,131.5,131.3(q,J＝33.8Hz,1C),130.9,130.4(q,J＝32.9Hz,1C),130.2,129.6,129.0(q,J＝3.6Hz,1C),128.4,128.0,127.9,127.7(q,J＝3.3Hz,1C),124.7(q,J＝3.4Hz,1C),123.7(q,J＝272.6Hz,1C),123.6(q,J＝272.4Hz,1C),123.0(q,J＝3.9Hz,1C).19F NMR(376MHz,CDCl3)δ-62.59,-62.93.[M+Na]+Calcd forC29H16F6NaO+517.0998,Found:517.0997.
实施例15
采用按实施例1所述方法，得黄色液体3ia(37.0mg,96％).
1H NMR(600MHz,CDCl3)δ7.78(d,J＝8.1Hz,1H),7.63(d,J＝8.1Hz,1H),7.46(d,J＝8.0Hz,1H),7.28–7.27(m,2H),7.22(d,J＝8.0Hz,1H),7.17(s,1H),7.14–7.11(m,6H),7.00–6.99(m,2H),6.92(s,1H),2.39(s,3H),2.24(s,3H).13C NMR(150MHz,CDCl3)δ198.8,159.2,157.8,144.8,142.19,142.17,141.3,137.9,136.3,131.7,131.0,130.7,130.4,130.0,129.5,127.9,127.6,127.2,127.1,118.7,116.5,114.6,108.8,55.7,55.3.[M+Na]+Calcd for C29H22NaO+409.1563,Found:409.1563.
实施例16
采用按实施例1所述方法，得黄色液体3ja(35.8mg,86％).
1H NMR(600MHz,CDCl3)δ7.75(d,J＝8.7Hz,1H),7.61(d,J＝8.8Hz,1H),7.27–7.24(m,2H),7.18(dd,J＝8.7,2.8Hz,1H),7.12–7.10(m,6H),6.99–6.95(m,3H),6.84(d,J＝2.8Hz,1H),6.59(d,J＝2.7Hz,1H),3.80(s,3H),3.62(s,3H).13C NMR(150MHz,CDCl3)δ198.8,159.2,157.8,144.8,142.19,142.17,141.3,137.9,136.3,131.7,131.0,130.7,130.4,130.0,129.5,127.9,127.6,127.2,127.1,118.7,116.5,114.6,108.8,55.7,55.3.[M+Na]+Calcd for C29H22NaO3 +441.1461,Found:441.1459.
实施例17
采用按实施例1所述方法，得无色液体3ka(42.3mg,99％).
1H NMR(600MHz,CDCl3)δ7.79(d,J＝8.5Hz,1H),7.66–7.60(m,2H),7.38(dd,J＝8.5,2.2Hz,1H),7.34(d,J＝2.2Hz,1H),7.25–7.24(m,2H),7.19–7.09(m,7H),7.00–6.94(m,2H).13C NMR(150MHz,CDCl3)δ197.1,145.2,143.4,140.9,140.2,138.7,135.2,135.03,134.97,133.9,133.7,131.9,131.6,131.2,131.0,130.2,130.0,128.5,128.2,127.9,127.7,127.6,125.4.[M+Na]+Calcd for C27H21Cl2NaO+449.0470,Found:449.0467.
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：
实施例35
化合物3aa到4衍生化操作步骤：
将3aa(35.8mg，0.1mmol)溶解于干燥DCM(1.0mL)中，添加LiAlH4(29.0mg，0.1mmol)，并在80℃将反应混合物搅拌4h，然后缓慢添加水(2.0mL)使其淬灭。首先用硅藻土过滤反应混合物，旋蒸后柱层析得到35.5mg无色油状液体4，收率99％。1H NMR(400MHz,CDCl3)for major productδ7.77(dd,J＝7.9,1.1Hz,1H),7.74–7.68(m,1H),7.45–7.41(m,3H),7.20–7.16(m,4H),7.09-7.07(m,2H),7.03–6.99(m,3H),6.96-6.92(m,2H),6.86–6.79(m,2H),5.09(d,J＝6.9Hz,1H),2.14(d,J＝7.4Hz,1H).13C NMR(151MHz,CDCl3)formixturesδ145.6,144.6,144.0,142.9,142.8,141.7,141.5,139.7,139.0,138.8,138.2,136.0,135.9,135.7,135.2,134.3,131.6,131.5,131.4,131.1,130.7,130.3,130.0,129.6,129.0,128.9,128.00,127.95,127.9,127.8,127.6,127.42,127.38,127.2,127.0,126.8,126.60,126.58,126.4,120.4,79.0,70.6.[M+Na]+Calcd for C27H20NaO+383.1406,Found:383.1406.产物为非对映异构体，比例为1：3，无法通过柱层析分离。
化合物3aa到5衍生化操作步骤：
将5aa(35.8mg，0.1mmol)、mCPBA(83.0mg，0.5mmol)、CF3COOH(16μL，0.2mmol)溶解在CH2Cl2(1.0mL)中，在80℃下加热并搅拌15小时，然后冷却至室温。旋蒸后柱层析得到20.1mg黄色油状液体5，收率54％。1H NMR(600MHz,CDCl3)δ8.37(d,J＝8.0Hz,1H),7.71–7.68(m,1H),7.63–7.61(m,1H),7.59(d,J＝7.6Hz,1H),7.55(d,J＝7.7Hz,1H),7.51–7.46(m,2H),7.40–7.33(m,4H),7.28(d,J＝7.8Hz,1H),7.19–7.15(m,4H),7.11(d,J＝7.8Hz,1H),6.66(d,J＝7.9Hz,1H).13C NMR(150MHz,CDCl3)δ197.1,168.0,141.8,140.2,137.8,135.5,134.9,133.6,133.0,131.9,130.0,129.94,129.87,129.5,129.2,129.0,128.9,128.6,128.4,128.2,128.1,127.5,127.1,91.8.[M+Na]+Calcd for C27H18NaO3 +413.1148,Found:413.1146.
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。
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