CN110204491A

CN110204491A - 一种手性3,4-二氢异喹啉酮化合物的合成方法

Info

Publication number: CN110204491A
Application number: CN201910524966.8A
Authority: CN
Inventors: 王治明; 丁寒锋; 孙嫚嫚; 张永刚; 吴海建; 李金山
Original assignee: Zhejiang University ZJU; Taizhou University
Current assignee: Zhejiang University ZJU; Taizhou University
Priority date: 2019-06-18
Filing date: 2019-06-18
Publication date: 2019-09-06
Anticipated expiration: 2039-06-18
Also published as: CN110204491B

Abstract

本发明公开了一种手性3,4‑二氢异喹啉酮化合物的合成方法，包括：在钯催化剂、手性配体、氧化剂和碱的作用下，N‑苯甲酰基磺酰胺类化合物与共轭二烯类化合物在有机溶剂中发生不对称C‑H官能化串联反应，反应完全后经过后处理得到所述的手性3,4‑二氢异喹啉酮化合物。该合成方法反应原料简单，同时，具有较高的收率和选择性。

Description

一种手性3,4-二氢异喹啉酮化合物的合成方法

技术领域

本发明属于有机合成领域，具体涉及一种手性3,4-二氢异喹啉酮化合物的合成方法。

背景技术

手性异喹啉化合物以及它们的衍生物是一类非常重要的化合物，在药物化学和材料化学中都有重要的应用。其中手性3,4-二氢异喹啉酮骨架广泛存在于很多有生物活性的天然产物和药物分子中。传统方法中，手性3,4-二氢异喹啉酮骨架都是以相应的手性胺为原料，通过分子内的Bischler-Napieralski反应，Pomeranz-Fritsch-Bobbitt反应，Friedel-Crafts反应或Heck反应来构建。这些方法的主要缺陷是合成步骤多、起始原料和试剂相对较贵，因此从简单易得的消旋原料出发，通过不对称的方法合成手性3,4-二氢异喹啉酮化合物成为研究的主要任务。然而，目前这方面的报道还很少。2017和2018年报导了两种手性环戊二烯銠催化的酰胺与烯烃的[4+2]环加成反应合成手性3,4-二氢异喹啉酮的方法，但是銠催化剂比较昂贵且较难合成。因此发展从简单易得的原料出发，以不对称串联反应的模式合成手性3,4-二氢异喹啉酮化合物的方法仍然很有必要。

在过去的十几年中，钯催化的烯烃的C-H官能化反应已经成为构建C-C键和C-X键的非常高效和原子经济性的方法，尤其是与苯甲酰胺化合物的串联环化反应。尽管有这么大的进展，钯催化苯甲酰胺化合物与烯烃以C-H官能化的方式构建3,4-二氢异喹啉酮化合物还是一种挑战。主要是因为金属钯中间体与双键发生氧化加成后容易马上发生β-H消除反应，生成C-H烯基化产物，或者继续发生aza-Wacker-type环化或Michael加成反应生成五元环状化合物，从而得不到想要的六元环状化合物。目前，仅2011年Booker-Milburn课题组报道过一例钯催化N-烷氧基苯甲酰胺与1,3-共轭二烯成功合成3,4-二氢异喹啉酮化合物的方法。但是产率都相对较低、底物范围也没法拓展、且不是不对称的方法。受以N-苯磺酰基为导向基团，芳胺或芳酰胺与1,3-共轭二烯通过钯催化的sp2C-H官能化/分子内N-烯丙基化的方式合成六元环的反应的启发，我们推测，通过仔细删选不对称的反应体系，可以以N-磺酰基苯甲酰胺和1,3-共轭二烯为原料，通过钯催化的sp2C-H官能化/分子内N-烯丙基化的方式成功实现手性3,4-二氢异喹啉酮化合物的合成。因此我们报道了这篇钯催化不对称C-H官能化串联反应合成手性3,4-二氢异喹啉酮化合物的方法。

发明内容

本发明提供了一种手性3,4-二氢异喹啉酮化合物的合成方法，该合成方法反应原料简单，同时，具有较高的收率和选择性。

一种手性3,4-二氢异喹啉酮化合物的合成方法，包括：

在钯催化剂、手性配体、氧化剂和碱的作用下，N-苯甲酰基磺酰胺类化合物与共轭二烯类化合物在有机溶剂中发生不对称C-H官能化串联反应，反应完全后经过后处理得到所述的手性3,4-二氢异喹啉酮化合物；

所述的N-苯甲酰基磺酰胺类化合物的结构如式(II)所示：

所述的共轭二烯类化合物的结构如式(III)所示：

所述的手性3,4-二氢异喹啉酮化合物的结构如式(I)所示：

式(I)～(III)中，R选自三氟甲基、取代或者未取代的芳基，所述芳基上的取代基选自C₁～C₅烷基、硝基或三氟甲基；

R¹选自H、C₁～C₅烷基、C₁～C₅烷氧基、卤素中的一个或者多个；

R²选自H、烷氧羰基、取代或者未取代的苯基，所述苯基上的取代基选自H、C₁～C₅烷基、C₁～C₅烷氧基、卤素中的一个或者多个。

作为优选，R选自三氟甲基、萘基、取代或者未取代的苯基，该苯基上的取代基选自甲基、硝基或三氟甲基。

作为优选，R¹选自H、甲基、甲氧基、F、Cl、Br中的一个或者多个。

作为优选，R²选自H、乙氧羰基、取代或者未取代的苯基，所述苯基上的取代基选自H、甲基、甲氧基、F、Cl、Br中的一个或者多个。

作为优选，所述的手性配体为L1～L9中的一个：

作为进一步的优选，所述的手性配体为L5。

作为优选，所述的有机溶剂为三氟甲苯。

作为优选，所述的氧化剂为2,6-二甲氧基-1,4-苯醌、2,5-二甲氧基-1,4-苯醌、苯醌或碳酸银，反应在空气氛围下进行；作为进一步的优选，所述的氧化剂为2,6-二甲氧基-1,4-苯醌。

作为优选，所述的碱为二异丙基乙胺。

作为优选，反应温度为80～90℃。

作为优选，所述的手性3,4-二氢异喹啉酮化合物为化合物3a～3bf中的一种；

化合物3a～3bf的结构如下：

同现有技术相比，本发明的有益效果体现在：

本发明所用的原料便宜易得，操作简单，同时，反应的收率高，原子经济性好，并且得到的产品具有较高的选择性。

具体实施方式

实施例1～23

操作方式如下：10ml史莱克管中加入取代的化合物1a(0.1mmol)，三氟乙酸钯(0.01mmol)，手性配体(0.012mmol)，氧化剂(0.03mmol)，碱(0.02mmol)，加入0.2毫升有机溶剂。然后80度敞口搅拌反应10分钟。加入取代的1-苯丁二烯2a(0.2mmol)。80度搅拌反应48小时。将反应体系冷却至室温，用石油醚/乙酸乙酯＝5/1或3/1过柱得到目标产品，反应条件和反应结果见表1，反应式如下：

^a反应条件:1a(0.1mmol),2a(0.2mmol),Pd(TFA)₂(0.01mmol),配体(0.012mmol),碱(0.02mmol)和氧化剂(0.03mmol)在PhCF₃(0.2ml)空气氛围下反应48h.^b分离收率.^c HPLC监测.^d氧气氛围下.^eDIPEA＝N，N-二异丙基乙胺.^fDABCO＝1,4-二氮杂二环[2.2.2]辛烷.^gDBU＝1,8-二氮杂二环十一碳-7-烯.^h2,6-DMBQ＝2,6-二甲氧基-1,4-苯醌.ⁱ 2,5-DMBQ＝2,5-二甲氧基-1,4-苯醌.^j 3.0mmol投料量。

实施例24～54

操作方式如下：10ml史莱克管中加入取代的化合物1(0.1mmol)，三氟乙酸钯(0.01mmol)，手性配体L5(0.012mmol)，2,6-二甲氧基-1,4-苯醌(0.03mmol)，N，N-二异丙基乙胺.(0.02mmol)，加入0.2毫升三氟甲苯。然后80度敞口搅拌反应10分钟。加入化合物2(0.2mmol)。80度搅拌反应48小时。将反应体系冷却至室温，用石油醚/乙酸乙酯＝5/1或3/1过柱得到目标产品，反应式、反应条件和反应结果如下：

实施例55

25ml史莱克管中加入1a(918mg，3mmol)，三氟乙酸钯(99.7mg，0.3mmol)，L5(97.9mg，0.36mmol)，2,6-二甲氧基-1,4-苯醌(151.2mg，0.9mmol)，二异丙基乙胺(77.4mg，0.6mmol)，加入6毫升三氟甲苯。然后80度敞口搅拌反应10分钟。加入2a(780mg，6mmol)。80度搅拌反应48小时。将反应体系冷却至室温，用石油醚/乙酸乙酯＝5/1过柱得到目标产品3a(100.2mg，收率77％，94:6e.r.)。

部分产物的表征数据如下：

(S,E)-2-((4-Nitrophenyl)sulfonyl)-3-styryl-3,4-dihydroisoquinolin-1(2H)-o ne(3a):淡黄色固体；36mg；83％产率；94:6e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝50/50,254nm UV检测器,1.0mL/min,t_R＝15.8min(major)and t_R＝40.0min(minor)]；mp＝198–199℃；[α]_D ²⁰＝+78.8(c＝1.0,CH₂Cl₂)；¹HNMR(400MHz,CDCl₃)δ8.29–8.24(m,4H),7.99(d,J＝7.9Hz,1H),7.53(t,J＝7.5Hz,1H),7.36(t,J＝7.6Hz,1H),7.31–7.20(m,6H),6.71(d,J＝15.7Hz,1H),6.01(dd,J＝15.8,8.1Hz,1H),5.71–5.66(m,1H),3.73(dd,J＝16.3,5.9Hz,1H),3.10(dd,J＝16.4,2.0Hz,1H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ162.91,150.46,144.69,136.81,135.15,134.58,134.39,130.83,129.10,128.79,128.68,128.37,127.83,127.17,126.59,125.32,123.67,58.01,34.85；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₃H₁₈N₂O₅SNa)457.0834,测量值：457.0836.

(S,E)-6-Methyl-2-((4-nitrophenyl)sulfonyl)-3-styryl-3,4-dihydroisoquinoli n-1(2H)-one(3b):淡黄色固体；35.8mg；80％yield；92:8e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝50/50,254nm UV检测器,1.0mL/min,t_R＝18.9min(major)and t_R＝50.7min(minor)]；mp＝180–181℃；[α]_D ²⁰＝+210.2(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.29–8.23(m,4H),7.86(d,J＝8.0Hz,1H),7.31–7.27(m,3H),7.22–7.20(m,2H),7.15(d,J＝8.0Hz,1H),7.02(s,1H),6.70(d,J＝15.7Hz,1H),6.01(dd,J＝15.8,8.1Hz,1H),5.68–5.64(m,1H),3.68(dd,J＝16.2,5.9Hz,1H),3.03(dd,J＝16.3,2.0Hz,1H),2.37(s,3H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ162.97,150.39,145.57,144.81,136.80,135.19,134.45,130.81,129.17,128.96,128.79,128.75,128.65,126.58,125.44,124.49,123.65,58.08,34.86,21.79；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₄H₂₀N₂O₅SNa)471.0991,测量值：471.0991.

(S,E)-6-Ethyl-2-((4-nitrophenyl)sulfonyl)-3-styryl-3,4-dihydroisoquinolin-1(2H)-one(3c):淡黄色固体；35.1mg；76％yield；93:7e.r.；[DaicelCHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝50/50,254nm UV检测器,1.0mL/min,t_R＝17.6min(major)and t_R＝49.5min(minor)]；mp＝137–139℃；[α]_D ²⁰＝+117.1(c＝0.9,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.28–8.23(m,4H),7.89(d,J＝8.1Hz,1H),7.33–7.17(m,6H),7.04(s,1H),6.71(d,J＝15.7Hz,1H),6.02(dd,J＝15.7,8.1Hz,1H),5.69–5.65(m,1H),3.70(dd,J＝16.2,5.9Hz,1H),3.05(dd,J＝16.3,2.0Hz,1H),2.66(q,J＝7.6Hz,2H),1.23(t,J＝7.6Hz,3H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ162.97,151.67,150.38,144.83,136.91,135.22,134.45,130.80,129.25,128.79,128.65,127.76,127.58,126.59,125.53,124.67,123.65,58.10,34.91,28.99,14.93；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₅H₂₂N₂O₅SNa)485.1147,测量值：485.1147.

(S,E)-6-(Tert-butyl)-2-((4-nitrophenyl)sulfonyl)-3-styryl-3,4-dihydroisoqui nolin-1(2H)-one(3d):淡黄色固体；39.7mg；81％yield；93.5:6.5e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝50/50,254nm UV检测器,1.0mL/min,t_R＝15.3min(major)and t_R＝47.9min(minor)]；mp＝110–112℃；[α]_D ²⁰＝+147.4(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.29–8.23(m,4H),7.90(d,J＝8.4Hz,1H),7.37(d,J＝8.4Hz,1H),7.32–7.22(m,5H),7.20(s,1H),6.73(d,J＝15.7Hz,1H),6.03(dd,J＝15.7,8.2Hz,1H),5.69–5.65(m,1H),3.72(dd,J＝16.2,5.9Hz,1H),3.07(dd,J＝16.4,2.0Hz,1H),1.31(s,9H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ162.90,158.55,150.37,144.84,136.59,135.25,134.47,130.79,128.98,128.81,128.65,126.61,125.63,125.19,125.17,124.38,123.64,58.18,35.28,35.12,31.00；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₇H₂₆N₂O₅SNa)513.1460,测量值：513.1461.

(S,E)-6-Methoxy-2-((4-nitrophenyl)sulfonyl)-3-styryl-3,4-dihydroisoquino lin-1(2H)-one(3e):淡黄色固体；28.8mg；62％yield；93:7e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝50/50,254nm UV检测器,1.0mL/min,t_R＝22.9min(major)and t_R＝63.4min(minor)]；mp＝69–70℃；[α]_D ²⁰＝+109.56(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.28–8.22(m,4H),7.93(d,J＝8.7Hz,1H),7.32–7.27(m,3H),7.22–7.20(m,2H),6.85–6.82(m,1H),6.70(d,J＝19.3Hz,1H),6.68(s,1H),6.02(dd,J＝15.8,8.2Hz,1H),5.67–5.63(m,1H),3.84(s,3H),3.69(dd,J＝16.3,5.9Hz,1H),3.03(dd,J＝16.3,2.0Hz,1H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ164.37,162.60,150.35,144.93,139.25,135.18,134.46,131.53,130.77,128.80,128.67,126.58,125.41,123.64,119.69,113.63,113.16,58.03,55.60,35.22；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₄H₂₀N₂O₆SNa)487.0940测量值：487.0944.

(S,E)-7-Methyl-2-((4-nitrophenyl)sulfonyl)-3-styryl-3,4-dihydroisoquinoli n-1(2H)-one(3f):淡黄色固体；35.8mg；80％yield；91:9e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝50/50,254nm UV检测器,1.0mL/min,t_R＝17.8min(major)and t_R＝55.3min(minor)]；mp＝180–181℃；[α]_D ²⁰＝+160.75(c＝0.8,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.29–8.23(m,4H),7.78(s,1H),7.34–7.27(m,4H),7.22–7.20(m,2H),7.12(d,J＝7.7Hz,1H),6.70(d,J＝15.7Hz,1H),6.01(dd,J＝15.7,8.1Hz,1H),5.68–5.64(m,1H),3.67(dd,J＝16.2,5.9Hz,1H),3.06(dd,J＝16.3,1.9Hz,1H),2.33(s,3H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ163.15,150.40,144.73,137.75,135.28,135.18,134.46,133.80,130.83,129.34,128.79,128.65,128.28,126.86,126.58,125.41,123.65,58.12,34.44,21.02；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₄H₂₀N₂O₅SNa)471.0991,测量值：471.0991.

(S,E)-8-Methyl-2-((4-nitrophenyl)sulfonyl)-3-styryl-3,4-dihydroisoquinoli n-1(2H)-one(3g):淡黄色固体；32.2mg；72％yield；90:10e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝50/50,254nm UV检测器,1.0mL/min,t_R＝12.2min(major)and t_R＝31.2min(minor)]；mp＝147–148℃；[α]_D ²⁰＝+174.03(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.30–8.25(m,4H),7.35(t,J＝7.6Hz,1H),7.31–7.23(m,5H),7.14(d,J＝7.7Hz,1H),7.06(d,J＝7.5Hz,1H),6.73(d,J＝15.7Hz,1H),6.02(dd,J＝15.8,7.8Hz,1H),5.64–5.60(m,1H),3.66(dd,J＝16.0,5.8Hz,1H),3.07(dd,J＝16.0,2.1Hz,1H),2.54(s,3H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ163.26,150.33,145.16,142.92,137.82,135.38,134.51,133.30,131.72,130.46,128.74,128.55,126.64,126.45,125.36,125.34,123.74,57.38,35.76,22.73；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₄H₂₀N₂O₅SNa)471.0991,测量值：471.0994.

(S,E)-6,8-Dimethyl-2-((4-nitrophenyl)sulfonyl)-3-styryl-3,4-dihydroisoqui nolin-1(2H)-one(3h):淡黄色固体；34.2mg；74％yield；91:9e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝50/50,254nm UV检测器,1.0mL/min,t_R＝13.7min(major)and t_R＝36.1min(minor)]；mp＝194–195℃；[α]_D ²⁰＝+54.6(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.29–8.24(m,4H),7.35–7.24(m,5H),6.94(s,1H),6.86(s,1H),6.72(d,J＝15.7Hz,1H),6.03(dd,J＝15.8,7.8Hz,1H),5.62–5.69(m,1H),3.62(dd,J＝15.9,5.8Hz,1H),3.00(dd,J＝16.0,2.2Hz,1H),2.50(s,3H),2.31(s,3H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ163.28,150.28,145.31,144.22,142.92,137.90,135.45,134.37,132.55,130.43,128.73,128.51,127.16,126.64,125.54,123.70,122.68,57.41,35.75,22.64,21.46；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₅H₂₂N₂O₅SNa)485.1147,测量值：485.1146.

(S,E)-6-Fluoro-2-((4-nitrophenyl)sulfonyl)-3-styryl-3,4-dihydroisoquinoli n-1(2H)-one(3i):淡黄色固体；19.4mg；43％yield；81:19e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝50/50,254nm UV检测器,1.0mL/min,t_R＝14.2min(major)and t_R＝36.5min(minor)]；mp＝174–175℃；[α]_D ²⁰＝+107.4(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.29–8.24(m,4H),8.01(dd,J＝8.8,5.6Hz,1H),7.32–7.27(m,3H),7.23–7.20(m,2H),7.04(td,J＝8.5,2.5Hz,1H),6.94(dd,J＝8.5,2.4Hz,1H),6.70(d,J＝15.7Hz,1H),5.99(dd,J＝15.7,8.0Hz,1H),5.70–5.67(m,1H),3.72(dd,J＝17.0,5.3Hz,1H),3.09(dd,J＝16.5,2.0Hz,1H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ166.22(d,J＝256.1Hz),162.00,150.48,144.50,140.00(d,J＝9.4Hz),134.95,134.82,132.21(d,J＝10.0Hz),130.87,128.84,128.82,126.61,124.86,123.71,123.51(d,J＝2.7Hz),115.47(d,J＝22.1Hz),115.35(d,J＝22.2Hz),57.91,34.93；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₃H₁₇N₂O₅SFNa)475.0740,测量值：475.0746.

(S,E)-6-Chloro-2-((4-nitrophenyl)sulfonyl)-3-styryl-3,4-dihydroisoquinoli n-1(2H)-one(3j):淡黄色固体；21.5mg；46％yield；86.5:13.5e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝50/50,254nm UV检测器,1.0mL/min,t_R＝14.9min(major)and t_R＝34.8min(minor)]；mp＝220–222℃；[α]_D ²⁰＝+244.2(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.29–8.24(m,4H),7.92(d,J＝8.4Hz,1H),7.35–7.20(m,7H),6.69(d,J＝15.7Hz,1H),5.97(dd,J＝15.7,8.0Hz,1H),5.70–5.67(m,1H),3.70(dd,J＝16.4,5.9Hz,1H),3.08(dd,J＝16.8,2.0Hz,1H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ162.13,150.52,144.40,140.86,138.49,134.90,134.88,130.90,130.67,128.85,128.44,128.37,126.61,125.61,124.76,123.72,57.90,34.71；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₃H₁₇N₂O₅SClNa)491.0444,测量值：491.0444.

(S,E)-6-Bromo-2-((4-nitrophenyl)sulfonyl)-3-styryl-3,4-dihydroisoquinoli n-1(2H)-one(3k):淡黄色固体；16.9mg；33％yield；89:11e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝50/50,254nm UV检测器,1.0mL/min,t_R＝16.0min(major)and t_R＝35.9min(minor)]；mp＝201–202℃；[α]_D ²⁰＝+208.5(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.28–8.24(m,4H),7.84(d,J＝8.4Hz,1H),7.50(d,J＝8.4z,1H),7.42(s,1H),7.32–7.26(m,3H),7.23–7.20(m,2H),6.69(d,J＝15.7Hz,1H),5.97(dd,J＝15.7,8.0Hz,1H),5.70–5.66(m,1H),3.71(dd,J＝16.4,5.9Hz,1H),3.07(dd,J＝16.4,2.0Hz,1H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ162.28,150.52,144.38,138.55,134.90,131.41,131.35,130.90,130.67,129.64,128.85,126.62,126.05,124.75,123.73,57.91,34.63；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₃H₁₇N₂O₅SBrNa)534.9939,测量值：534.9941.

(S,E)-7-Fluoro-6-methoxy-2-((4-nitrophenyl)sulfonyl)-3-styryl-3,4-dihydr oisoquinolin-1(2H)-one(3l):淡黄色固体；26.0mg；54％yield；91:9e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝50/50,254nm UV检测器,1.0mL/min,t_R＝18.9min(major)and t_R＝45.4min(minor)]；mp＝175–176℃；[α]_D ²⁰＝+100.0(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.28–8.23(m,4H),7.67(d,J＝11.2Hz,1H),7.32–7.28(m,3H),7.24–7.21(m,2H),6.74–6.69(m,2H),6.01(dd,J＝15.7,8.2Hz,1H),5.68–5.64(m,1H),3.93(s,3H),3.69(dd,J＝16.5,6.0,1H),3.02(dd,J＝16.4,2.0Hz,1H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ161.75,152.77,151.59(d,J＝257.6Hz),150.45,144.58,135.00,134.74,134.51(d,J＝3.5Hz),130.86,128.86,128.84(d,J＝4.0Hz),126.58,125.02,123.67,119.65(d,J＝6.5Hz),116.34(d,J＝40Hz),112.02(d,J＝1.2Hz),58.11,56.41,34.81；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₄H₁₉N₂O₆FSNa)505.0846,测量值：505.0854.

(S,E)-3-(4-Methylstyryl)-2-((4-nitrophenyl)sulfonyl)-3,4-dihydroisoquinoli n-1(2H)-one(3m):淡黄色固体；36.7mg；82％yield；92.5:7.5e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝50/50,254nm UV检测器,1.0mL/min,t_R＝16.1min(major)and t_R＝46.1min(minor)]；mp＝189–190℃；[α]_D ²⁰＝+103.0(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.29–8.23(m,4H),7.98(d,J＝7.8Hz,1H),7.53(t,J＝7.5Hz,1H),7.35(t,J＝7.6Hz,1H),7.23(d,J＝7.5Hz,1H),7.12–7.07(m,4H),6.68(d,J＝15.7Hz,1H),5.94(dd,J＝15.7,8.2Hz,1H),5.69–5.64(m,1H),3.72(dd,J＝16.3,5.9Hz,1H),3.09(dd,J＝16.3,2.0Hz,1H),2.32(s,3H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ162.93,150.42,144.70,138.77,136.90,134.57,134.37,132.31,130.86,129.49,129.09,128.39,127.79,127.15,126.51,124.12,123.65,58.20,34.93,21.26；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₄H₂₀N₂O₅SNa)471.0991,测量值：471.0993.

(S,E)-3-(4-Methoxystyryl)-2-((4-nitrophenyl)sulfonyl)-3,4-dihydroisoquin olin-1(2H)-one(3n):淡黄色固体；32.1mg；69％yield；92:8e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝50/50,254nm UV检测器,1.0mL/min,t_R＝25.7min(major)and t_R＝59.1min(minor)]；mp＝141–142℃；[α]_D ²⁰＝+178.0(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.29–8.22(m,4H),7.98(d,J＝7.9Hz,1H),7.53(t,J＝7.5Hz,1H),7.36(t,J＝7.6Hz,1H),7.23(d,J＝7.6Hz,1H),7.16–7.14(m,2H),6.82–6.80(m,2H),6.67(d,J＝15.7Hz,1H),5.85(dd,J＝15.7,8.3Hz,1H),5.67–5.63(m,1H),3.80(s,3H),3.72(dd,J＝16.3,5.8Hz,1H),3.08(dd,J＝16.3,2.0Hz,1H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ162.94,159.99,150.42,144.74,136.94,134.34,134.18,130.84,129.09,128.39,127.90,127.78,127.16,123.63,122.81,114.17,58.31,55.33,35.01；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₄H₂₀N₂O₆SNa)487.0940,测量值：487.0943.

(S,E)-3-(4-Fluorostyryl)-2-((4-nitrophenyl)sulfonyl)-3,4-dihydroisoquinoli n-1(2H)-one(3o):淡黄色固体；35.7mg；79％yield；88:12e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝50/50,254nm UV检测器,1.0mL/min,t_R＝19.9min(major)and t_R＝39.7min(minor)]；mp＝163–164℃；[α]_D ²⁰＝+76.2(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.27–8.26(m,4H),7.98(d,J＝7.9Hz,1H),7.54(t,J＝7.5Hz,1H),7.37(t,J＝7.6Hz,1H),7.25–7.18(m,3H),7.00–6.94(m,2H),6.69(d,J＝15.7Hz,1H),5.94(dd,J＝15.8,8.1Hz,1H),5.69–5.65(m,1H),3.72(dd,J＝16.3,5.9Hz,1H),3.10(dd,J＝16.3,2.0Hz,1H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ162.85,162.84(d,J＝247.3Hz),150.47,144.67,136.71,134.43,133.40,131.30(d,J＝3.4Hz),130.78,129.12,128.37,128.27(d,J＝8.0Hz),127.88,127.13,125.04(d,J＝2.3Hz),123.70,115.80(d,J＝21.6Hz),57.91,34.80；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₃H₁₇N₂O₅SFNa)475.0740,测量值：475.0743.

(S,E)-3-(4-Chlorostyryl)-2-((4-nitrophenyl)sulfonyl)-3,4-dihydroisoquinoli n-1(2H)-one(3p):淡黄色固体；34.2mg；73％yield；92.5:7.5e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝50/50,254nm UV检测器,1.0mL/min,t_R＝18.8min(major)and t_R＝37.2min(minor)]；mp＝170–171℃；[α]_D ²⁰＝+115.6(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.29–8.25(m,4H),7.98(d,J＝7.9Hz,1H),7.54(t,J＝7.5Hz,1H),7.37(t,J＝7.6Hz,1H),7.26–7.23(m,3H),7.17–7.13(m,2H),6.68(d,J＝15.7Hz,1H),6.01(dd,J＝15.8,8.0Hz,1H),5.69–5.65(m,1H),3.71(dd,J＝16.3,5.9Hz,1H),3.10(dd,J＝16.4,2.0Hz,1H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ162.82,150.48,144.63,136.64,134.46,134.42,133.61,133.32,130.77,129.13,128.98,128.36,127.92,127.83,127.10,125.96,123.72,57.81,34.72；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₃H₁₇N₂O₅SClNa)491.0444,测量值：491.0443.

(S,E)-3-(4-Bromostyryl)-2-((4-nitrophenyl)sulfonyl)-3,4-dihydroisoquinoli n-1(2H)-one(3q):淡黄色固体；30.3mg；59％yield；91.5:8.5e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝50/50,254nm UV检测器,1.0mL/min,t_R＝19.9min(major)and t_R＝38.9min(minor)]；mp＝174–175℃；[α]_D ²⁰＝+64.4(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.30–8.25(m,4H),7.98(d,J＝7.8Hz,1H),7.54(t,J＝7.5Hz,1H),7.41–7.35(m,3H),7.24(d,J＝7.5Hz,1H),7.09(d,J＝8.4Hz,2H),6.66(d,J＝15.7Hz,1H),6.02(dd,J＝15.7,7.9Hz,1H),5.69–5.65(m,1H),3.71(dd,J＝16.3,6.0Hz,1H),3.09(dd,J＝16.3,2.0Hz,1H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ162.82,150.48,144.63,136.64,134.46,134.42,133.61,133.32,130.77,129.13,128.98,128.36,127.92,127.83,127.10,125.96,123.72,57.81,34.72；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₃H₁₇N₂O₅SBrNa)534.9939,测量值：534.9937.

(S,E)-3-(3-Bromostyryl)-2-((4-nitrophenyl)sulfonyl)-3,4-dihydroisoquinoli n-1(2H)-one(3r):淡黄色固体；33.8mg；66％yield；91.5:8.5e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝50/50,254nm UV检测器,1.0mL/min,t_R＝17.1min(major)and t_R＝36.4min(minor)]；mp＝96–97℃；[α]_D ²⁰＝+32.8(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.30–8.25(m,4H),7.99(d,J＝7.8Hz,1H),7.54(t,J＝7.5Hz,1H),7.39–7.35(m,3H),7.24(d,J＝7.6Hz,1H),7.17–7.11(m,2H),6.63(d,J＝15.7Hz,1H),6.03(dd,J＝15.8,7.8Hz,1H),5.69–5.66(m,1H),3.71(dd,J＝16.3,6.0Hz,1H),3.10(dd,J＝16.4,2.0Hz,1H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ162.80,150.51,144.61,137.29,136.54,134.49,133.02,131.50,130.77,130.29,129.33,129.17,128.35,127.96,127.11,127.00,125.39,123.75,122.93,57.65,34.65；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₃H₁₇N₂O₅SBrNa)534.9939,测量值：534.9945.

(S,E)-3-(2-Methylstyryl)-2-((4-nitrophenyl)sulfonyl)-3,4-dihydroisoquinoli n-1(2H)-one(3s):淡黄色固体；35.8mg；80％yield；96:4e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝50/50,254nm UV检测器,1.0mL/min,t_R＝15.8min(major)and t_R＝33.0min(minor)]；mp＝134–135℃；[α]_D ²⁰＝+48.2(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.31–8.27(m,4H),7.98(d,J＝7.8Hz,1H),7.52(t,J＝15.1Hz,1H),7.35(t,J＝7.6Hz,1H),7.23(d,J＝7.6Hz,1H),7.24–7.06(m,4H),6.94(d,J＝15.6Hz,1H),5.90(dd,J＝15.6,7.6Hz,1H),5.72–5.69(m,1H),3.72(dd,J＝16.3,5.8Hz,1H),3.12(dd,J＝16.3,2.0Hz,1H),2.22(s,3H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ162.97,150.47,144.79,136.81,135.85,134.43,134.36,132.43,130.74,130.53,129.03,128.47,128.35,127.82,127.26,126.74,126.19,125.48,123.74,57.99,34.89,19.58；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₄H₂₀N₂O₅SNa)471.0991,测量值：471.0999.

(S,E)-3-(2-Methoxystyryl)-2-((4-nitrophenyl)sulfonyl)-3,4-dihydroisoquin olin-1(2H)-one(3t):淡黄色固体；29.6mg；64％yield；95:5e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝50/50,254nm UV检测器,1.0mL/min,t_R＝20.8min(major)and t_R＝54.8min(minor)]；mp＝126–127℃；[α]_D ²⁰＝+167.0(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.33–8.31(m,2H),8.24–8.22(m,2H),7.98(d,J＝7.9Hz,1H),7.52(t,J＝7.5Hz,1H),7.35(t,J＝7.6Hz,1H),7.26–7.22(m,2H),7.10(d,J＝7.7Hz,1H),7.07(d,J＝15.8Hz,1H),6.86(d,J＝8.4Hz,1H),6.83(t,J＝7.6Hz,1H),5.95(dd,J＝15.8,8.5Hz,1H),5.71–5.67(m,1H),3.80(s,3H),3.73(dd,J＝16.0,5.6Hz,1H),3.10(dd,J＝16.3,2.0Hz,1H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ162.99,156.84,150.38,144.66,137.08,134.31,131.03,129.82,129.08,128.42,127.73,127.18,126.80,125.52,124.17,123.57,120.65,110.94,58.57,55.46,35.02；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₄H₂₀N₂O₆SNa)487.0940,测量值：487.0944.

(S,E)-2-((4-Nitrophenyl)sulfonyl)-3-(2-(trifluoromethoxy)styryl)-3,4-dihyd roisoquinolin-1(2H)-one(3u):淡黄色固体；40.4mg；78％yield；95:5e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝50/50,254nm UV检测器,1.0mL/min,t_R＝10.3min(major)and t_R＝19.7min(minor)]；mp＝76–77℃；[α]_D ²⁰＝+55.0(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.31–8.26(m,4H),7.98(d,J＝7.5Hz,1H),7.53(t,J＝7.5Hz,1H),7.36(t,J＝7.6Hz,1H),7.31–7.16(m,5H),6.89(d,J＝15.8Hz,1H),6.08(dd,J＝15.9,7.6Hz,1H),5.75–5.70(m,1H),3.73(dd,J＝16.3,5.8Hz,1H),3.12(dd,J＝16.4,2.0Hz,1H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ162.84,150.50,144.61,136.63,134.41,130.78,129.72,129.10,128.69,128.61,128.30,127.87,127.43,127.18,127.12,127.03,123.70,121.54,120.38(q,J＝257.0Hz),57.70,34.66；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₄H₁₇N₂O₆F₃SNa)541.0657,测量值：541.0665.

(S,E)-3-(2-Fluorostyryl)-2-((4-nitrophenyl)sulfonyl)-3,4-dihydroisoquinoli n-1(2H)-one(3v):淡黄色固体；34.8mg；77％yield；96:4e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝50/50,254nm UV检测器,1.0mL/min,t_R＝20.4min(major)and t_R＝38.5min(minor)]；mp＝180–181℃；[α]_D ²⁰＝+86.8(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.32–8.26(m,4H),7.99(d,J＝7.9Hz,1H),7.53(t,J＝7.5Hz,1H),7.36(t,J＝7.6Hz,1H),7.26–7.15(m,3H),7.05–7.00(m,2H),6.81(d,J＝15.9Hz,1H),6.08(dd,J＝15.9,7.9Hz,1H),5.72–5.68(m,1H),3.73(dd,J＝16.3,5.9Hz,1H),3.12(dd,J＝16.4,1.9Hz,1H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ162.86,160.27(d,J＝248.7Hz),150.50,144.61,136.72,134.41,130.84,130.02(d,J＝8.4Hz),129.14,128.34,128.21(d,J＝5.2Hz),127.86,127.70(d,J＝3.4Hz),127.23(d,J＝3.2Hz),127.15,124.29(d,J＝3.5Hz),123.71,123.07(d,J＝12.0Hz),115.96(d,J＝21,7Hz),58.04,34.75；HRMS(ESI-TOF)m/z calcd for[M+Na]⁺(C₂₃H₁₇N₂O₅SFNa)475.0740,测量值：475.0746.

(S,E)-3-(2-Chlorostyryl)-2-((4-nitrophenyl)sulfonyl)-3,4-dihydroisoquinoli n-1(2H)-one(3w):淡黄色固体；36.5mg；78％yield；94.5:5.5e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝50/50,254nm UV检测器,1.0mL/min,t_R＝17.9min(major)and t_R＝35.2min(minor)]；mp＝153–154℃；[α]_D ²⁰＝+61.4(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.34–8.25(m,4H),7.99(d,J＝7.7Hz,1H),7.53(t,J＝7.5Hz,1H),7.38–7.33(m,2H),7.26–7.07(m,5H),5.97(dd,J＝15.7,8.0Hz,1H),5.75–5.72(m,1H),3.74(dd,J＝16.3,5.8Hz,1H),3.13(dd,J＝16.4,2.1Hz,1H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ162.85,150.50,144.58,136.75,134.43,133.51,133.31,130.92,130.90,129.89,129.64,129.14,128.39,128.21,127.87,127.19,126.99,126.91,123.72,57.80,34.71；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₃H₁₇N₂O₅SClNa)491.0444,测量值：491.0453.

(S,E)-3-(2-Bromostyryl)-2-((4-nitrophenyl)sulfonyl)-3,4-dihydroisoquinoli n-1(2H)-one(3x):淡黄色固体；34.9mg；68％yield；98:2e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝50/50,254nm UV检测器,1.0mL/min,t_R＝17.9min(major)and t_R＝35.9min(minor)]；mp＝240–241℃；[α]_D ²⁰＝+76.0(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.34(d,J＝9.0Hz,2H),8.27(d,J＝9.0Hz,2H),7.99(d,J＝7.8Hz,1H),7.56–7.52(m,2H),7.36(t,J＝7.6Hz,1H),7.26–7.09(m,4H),7.05(d,J＝15.6Hz,1H),5.93(dd,J＝15.6,8.0Hz,1H),5.75–5.72(m,1H),3.74(dd,J＝16.3,5.8Hz,1H),3.13(dd,J＝16.4,2.0Hz,1H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ162.84,150.51,144.56,136.72,135.28,134.42,133.49,133.13,130.94,129.86,129.17,128.38,128.29,127.88,127.61,127.20,127.09,123.77,123.72,57.67,34.69；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₃H₁₇N₂O₅SBrNa)534.9939,测量值：534.9945.

(S,E)-3-(2-Bromo-5-methoxystyryl)-2-((4-nitrophenyl)sulfonyl)-3,4-dihydr oisoquinolin-1(2H)-one(3y):淡黄色固体；33.6mg；62％yield；98:2e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝50/50,254nm UV检测器,1.0mL/min,t_R＝20.6min(major)and t_R＝41.9min(minor)]；mp＝152–153℃；[α]_D ²⁰＝+75.6(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.35–8.27(m,4H),7.99(d,J＝7.7Hz,1H),7.54(t,J＝7.5Hz,1H),7.43–7.41(m,1H),7.36(t,J＝7.6Hz,1H),7.25(d,J＝7.6Hz,1H),6.98(d,J＝15.6Hz,1H),6.71–6.68(m,2H),5.90(dd,J＝15.6,7.9Hz,1H),5.75–5.70(m,1H),3.77–3.72(m,4H),3.12(dd,J＝16.4,2.0Hz,1H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ162.83,158.90,150.52,144.53,136.67,135.99,134.44,133.69,133.47,130.95,129.18,128.39,128.37,127.90,127.18,123.73,115.05,114.35,113.12,57.64,55.55,34.65；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₄H₁₉N₂O₆SBrNa)565.0045,测量值：565.0051.

(S,E)-Ethyl3-(2-((4-nitrophenyl)sulfonyl)-1-oxo-1,2,3,4-tetrahydroisoquin olin-3-yl)acrylate(3z):白色固体；24.1mg；56％yield；87.5:12.5e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝50/50,254nm UV检测器,1.0mL/min,t_R＝20.5min(major)and t_R＝29.8min(minor)]；mp＝168–169℃；[α]_D ²⁰＝+80.6(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.38–8.28(m,4H),7.96(dd,J＝7.9,1.3Hz,1H),7.53(td,J＝7.5,1.4Hz,1H),7.36(t,J＝7.7Hz,1H),7.21(d,J＝7.6Hz,1H),6.76(dd,J＝15.6,6.1Hz,1H),5.93(dd,J＝15.6,1.5Hz,1H),5.70–5.66(m,1H),4.19–4.06(m,2H),3.66(dd,J＝16.4,6.2Hz,1H),3.10(dd,J＝16.5,2.0Hz,1H),1.23(t,J＝7.1Hz,3H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ165.17,162.61,150.65,144.24,143.28,135.86,134.59,130.78,129.17,128.25,128.11,126.96,124.81,123.89,60.99,55.99,33.58,14.12；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₀H₁₈N₂O₇SNa)453.0732,测量值：453.0733.

(S,E)-2-((4-Nitrophenyl)sulfonyl)-3-(3-phenylprop-1-en-1-yl)-3,4-dihydroi soquinolin-1(2H)-one(3ba):淡黄色固体；28.7mg；64％yield；95:5e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝50/50,254nm UV检测器,1.0mL/min,t_R＝19.2min(major)and t_R＝49.8min(minor)]；mp＝176–177℃；[α]_D ²⁰＝+246.0(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.15–8.08(m,4H),7.95(d,J＝7.8Hz,1H),7.54(t,J＝7.5Hz,1H),7.36(t,J＝7.7Hz,1H),7.29–7.23(m,4H),6.97(d,J＝6.4Hz,2H),5.88–5.80(m,1H),5.56–5.53(m,1H),5.45(dd,J＝15.1,7.2Hz,1H),3.63(dd,J＝16.2,5.7Hz,1H),3.29(dd,J＝15.0,6.8Hz,1H),3.16(dd,J＝15.0,7.6Hz,1H),3.02(dd,J＝16.0,2.0Hz,1H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ163.02,150.34,144.50,138.96,136.95,134.27,134.12,130.69,129.01,128.70,128.38,128.31,127.71,127.68,127.34,126.55,123.61,57.20,38.51,34.79；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₄H₂₀N₂O₅SNa)471.0991,测量值：471.0996.

(S,E)-3-Styryl-2-tosyl-3,4-dihydroisoquinolin-1(2H)-one(3bb):白色固体；12.9mg；32％yield；90:10e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝70/30,254nm UV检测器,1.0mL/min,t_R＝20.7min(major)and t_R＝31.0min(minor)]；mp＝112–113℃；[α]_D ²⁰＝+72.6(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.01–8.98(m,3H),7.47(t,J＝7.5Hz,1H),7.31(t,J＝7.6Hz,1H),7.26–7.17(m,8H),6.63(d,J＝15.9Hz,1H),6.01(dd,J＝15.7,7.4Hz,1H),5.71–5.67(m,1H),3.66(dd,J＝16.2,5.9Hz,1H),3.05(dd,J＝16.3,1.9Hz,1H),2.38(s,3H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ162.87,144.71,136.81,136.23,135.67,133.82,133.75,129.39,129.18,128.98,128.57,128.20,128.15,127.89,127.55,126.61,126.21,57.38,34.85,21.66；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₄H₂₁NO₃SNa)426.1140,测量值：426.1140.

(S,E)-2-(Naphthalen-2-ylsulfonyl)-3-styryl-3,4-dihydroisoquinolin-1(2H)-one(3bc):黄色固体；28.5mg；65％yield；91.5:8.5e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝70/30,254nm UV检测器,1.0mL/min,t_R＝19.3min(major)and t_R＝28.9min(minor)]；mp＝160–161℃；[α]_D ²⁰＝+33.6(c＝1.0,CH₂Cl₂)；¹HNMR(400MHz,CDCl₃)δ8.67(s,1H),8.07(d,J＝8.8Hz,1H),7.97(d,J＝7.9Hz,1H),7.87(d,J＝9.3Hz,2H),7.74(d,J＝8.3Hz,1H),7.61(t,J＝7.6Hz,1H),7.53–7.47(m,2H),7.32–7.19(m,7H),6.74(d,J＝15.8Hz,1H),6.04(dd,J＝15.7,7.8Hz,1H),5.79–5.75(m,1H),3.73(dd,J＝16.2,5.8Hz,1H),3.09(d,J＝16.2Hz,1H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ162.82,136.79,136.03,135.57,135.28,134.09,133.88,131.77,131.54,129.67,129.22,129.02,128.62,128.46,128.32,128.16,127.78,127.74,127.59,127.28,126.68,126.08,124.07,57.70,34.90；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₇H₂₁NO₃SNa)462.1140,测量值：462.1141.

(S,E)-3-Styryl-2-((4-(trifluoromethyl)phenyl)sulfonyl)-3,4-dihydroisoquino lin-1(2H)-one(3bd):白色固体；35.2mg；77％yield；93:7e.r.；[DaicelCHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝70/30,254nm UV检测器,1.0mL/min,t_R＝7.8min(major)and t_R＝12.1min(minor)]；mp＝237–238℃；[α]_D ²⁰＝+48.0(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.23(d,J＝8.3Hz,2H),8.00(d,J＝8.0Hz,1H),7.70(d,J＝8.3Hz,2H),7.51(t,J＝7.5Hz,1H),7.35(t,J＝7.6Hz,1H),7.29–7.16(m,6H),6.64(d,J＝15.8Hz,1H),6.01(dd,J＝15.8,7.8Hz,1H),5.71–5.67(m,1H),3.71(dd,J＝16.3,5.9Hz,1H),3.09(dd,J＝16.3,2.0Hz,1H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ162.92,142.57,136.78,135.27,135.06(q,J＝32.9Hz),134.28,134.22,129.99,129.08,128.70,128.51,128.30,127.75,127.37,126.60,125.68(q,J＝3.7Hz),125.54,123.12(q,J＝268.5Hz),57.81,34.85；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₄H₁₈NO₃SF₃Na)480.0857,测量值：480.0859.

(S,E)-2-((2-Nitrophenyl)sulfonyl)-3-styryl-3,4-dihydroisoquinolin-1(2H)-o ne(3be):淡黄色固体；30.4mg；70％yield；90.5:9.5e.r.；[Daicel CHIRALPAK IC键合型手性色谱柱检测,n-hexane/i-PrOH＝80/20,254nm UV检测器,1.0mL/min,t_R＝14.7min(minor)and t_R＝16.0min(major),the absolute configuration of thestereogenic center was determined by the product of removing the N-protectinggroup,which was consistent with 4]；mp＝188–189℃；[α]_D ²⁰＝+5.6(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.67(d,J＝7.7Hz,1H),8.01(d,J＝7.8Hz,1H),7.85–7.75(m,3H),7.51(t,J＝7.5Hz,1H),7.35–7.18(m,7H),6.77(d,J＝15.8Hz,1H),6.22(dd,J＝15.8,6.6Hz,1H),5.53–5.49(m,1H),3.95(dd,J＝16.3,6.0Hz,1H),3.10(d,J＝16.1Hz,1H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ163.09,148.19,137.17,135.83,135.47,134.73,134.19,133.48,132.82,132.11,128.79,128.51,128.26,128.11,127.58,127.51,126.77,126.33,124.53,57.73,33.56；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₂₃H₁₈N₂O₅SNa)457.0834,测量值：457.0836.

(S,E)-3-styryl-2-((trifluoromethyl)sulfonyl)-3,4-dihydroisoquinolin-1(2H)-one(3bf):淡黄色固体；17.1mg；45％yield；88.5:11.5e.r.；[determined by HPLCanalysis Daicel Chirapak IB,n-hexane/i-PrOH＝90/10,254nm UV检测器,1.0mL/min,t_R＝8.1min(minor)and t_R＝8.5min(major)]；mp＝155–156℃；[α]_D ²⁰＝+33(c＝1.0,CH₂Cl₂)；¹H NMR(400MHz,CDCl₃)δ8.17(d,J＝7.9Hz,1H),7.60(t,J＝7.5Hz,1H),7.45(t,J＝7.6Hz,1H),7.30–7.21(m,6H),6.67(d,J＝15.8Hz,1H),6.07(dd,J＝15.7,7.9Hz,1H),5.54–5.37(m,1H),3.71(dd,J＝16.4,5.7Hz,1H),3.11(dd,J＝16.5,2.0Hz,1H)；¹³C{¹H}NMR(100MHz,CDCl₃)δ162.65,137.03,135.27,135.06,134.92,129.81,128.65,128.60,128.56,128.13,126.76,126.73,124.10,119.4(q,J＝322.8Hz),59.90,34.66；HRMS(ESI-TOF)m/z理论值：[M+Na]⁺(C₁₈H₁₄NO₃SF₃Na)404.0544,测量值：404.0546。

Claims

1.一种手性3,4-二氢异喹啉酮化合物的合成方法，其特征在于，包括：

所述的N-苯甲酰基磺酰胺类化合物的结构如式(II)所示：

所述的共轭二烯类化合物的结构如式(III)所示：

所述的手性3,4-二氢异喹啉酮化合物的结构如式(I)所示：

2.根据权利要求1所述的手性3,4-二氢异喹啉酮化合物的合成方法，其特征在于，R选自三氟甲基、萘基、取代或者未取代的苯基，该苯基上的取代基选自甲基、硝基或三氟甲基。

3.根据权利要求1所述的手性3,4-二氢异喹啉酮化合物的合成方法，其特征在于，R¹选自H、甲基、甲氧基、F、Cl、Br中的一个或者多个。

4.根据权利要求1所述的手性3,4-二氢异喹啉酮化合物的合成方法，其特征在于，R²选自H、乙氧羰基、取代或者未取代的苯基，所述苯基上的取代基选自H、甲基、甲氧基、F、Cl、Br中的一个或者多个。

5.根据权利要求1所述的手性3,4-二氢异喹啉酮化合物的合成方法，其特征在于，所述的手性配体为L1～L9中的一个：

6.根据权利要求1所述的手性3,4-二氢异喹啉酮化合物的合成方法，其特征在于，所述的有机溶剂为三氟甲苯。

7.根据权利要求1所述的手性3,4-二氢异喹啉酮化合物的合成方法，其特征在于，所述的氧化剂为2,6-二甲氧基-1,4-苯醌、2,5-二甲氧基-1,4-苯醌、苯醌或碳酸银，反应在空气氛围下进行。

8.根据权利要求1所述的手性3,4-二氢异喹啉酮化合物的合成方法，其特征在于，所述的碱为二异丙基乙胺。

9.根据权利要求1所述的手性3,4-二氢异喹啉酮化合物的合成方法，其特征在于，反应温度为80～90℃。

10.根据权利要求1所述的手性3,4-二氢异喹啉酮化合物的合成方法，其特征在于，所述的手性3,4-二氢异喹啉酮化合物为化合物3a～3bf中的一种；

化合物3a～3bf的结构如下：