一种合成异喹啉酮类化合物或吡啶酮类化合物的方法转让专利
申请号 : CN202110267724.2
文献号 : CN113149895B
文献日 : 2022-07-05
发明人 : 孙嫚嫚 , 杨健国 , 吴海建 , 张晶
申请人 : 台州学院
摘要 :
本发明公开了一种合成异喹啉酮类化合物或吡啶酮类化合物的方法，包括：在钯催化剂和助催化剂的作用下，苯甲酰胺类化合物或丙烯酰胺类化合物与苯丙烯类化合物在有机溶剂中进行反应，反应结束后经过后处理得到所述的异喹啉酮类化合物或吡啶酮类化合物。该方法原料简单易得、条件温和、转化高效、区域选择性高、原子利用率高且操作简单。
权利要求 :
1.一种合成异喹啉酮类化合物的方法，其特征在于，包括：在钯催化剂和助催化剂的作用下，苯甲酰胺类化合物（1）与苯丙烯类化合物（2）在有机溶剂中进行反应，反应结束后经过后处理得到所述的异喹啉酮类化合物（3）；
反应式如下：
上式中，R为Ns‑、Ts‑或Ms‑；
1
R为H、C1~C4烷基、C1~C4烷氧基、三氟甲基或卤素中的一个或者多个；
2
R 为H、C1~C4烷基、苯基或卤素；
所述的钯催化剂为三氟乙酸钯；
所述的助催化剂为醋酸铜；
所述的有机溶剂为对二甲苯；
以摩尔量计，所述的苯甲酰胺类化合物：苯丙烯类化合物：钯催化剂：助催化剂=1：1.5~
2.5：0.1 0.2：0.2 0.3。
~ ~ 1
2.根据权利要求1所述的合成异喹啉酮类化合物的方法，其特征在于，R为H、甲基、乙基、甲氧基、三氟甲基、F或Cl中的一个或者多个；
2
R 为H、甲基、苯基或Cl。
3.根据权利要求1所述的合成异喹啉酮类化合物的方法，其特征在于，反应温度为100~
110℃，反应时间为12 24小时。
~
4.根据权利要求1所述的合成异喹啉酮类化合物的方法，其特征在于，所述的异喹啉酮类化合物为结构式如下所示的化合物中的一种：。
说明书 :
一种合成异喹啉酮类化合物或吡啶酮类化合物的方法
技术领域
[0001] 本发明属于有机合成领域，具体涉及一种合成异喹啉酮类化合物或吡啶酮类化合物的方法。
背景技术
[0002] 异喹啉酮和吡啶酮是两种活性天然产物和药物分子中重要的结构骨架。合成这两类化合物的传统方法包括6π‑电环化反应、Larock‑型杂环化反应、分子内胺羰环化反应、邻卤代苯甲酰胺与炔烃的环加成反应等，存在底物复杂和原子利用率低的缺点。过渡金属催化的导向C‑H活化环加成反应是从简单易得的底物经串联反应模式合成复杂环状化合物的重要方法。目前以苯甲酰胺和炔烃或联烯化合物已经实现了异喹啉酮化合物的合成，而以苯甲酰胺或丙烯酰胺和烯烃为原料，经一锅多步反应合成异喹啉酮或吡啶酮的方法还没有报道。烯烃结构广泛存在于天然产物中，烯烃化合物便宜、易得，因此发展以烯烃为底物，与苯甲酰胺或丙烯酰胺合成异喹啉酮或吡啶酮的方法具有重要意义。
[0003] 烯烃化合物性质活泼、反应位点多，因此在过渡金属催化的导向C‑H活化与烯烃的反应中存在区域选择性问题。如何高区域选择性地获得单一产物是化学研究中非常重要的课题。经化学家们研究发现，导向基团可以起到关键作用。例如，以CONHOPiv或CONHCl为导向基可在金属铑或钴催化下实现苯甲酰胺与苯丙烯的[4+2]环加成反应合成二氢异喹啉酮化合物，以NH‑pyrimidin为导向基可在金属铑催化下实现苯胺与苯丙烯的[3+2]环加成脱氢反应合成吲哚化合物。
发明内容
[0004] 本发明提供了一种合成异喹啉酮类化合物或吡啶酮类化合物的方法，该方法，该方法原料简单易得、条件温和、转化高效、区域选择性高、原子利用率高且操作简单。
[0005] 一种合成异喹啉酮类化合物或吡啶酮类化合物的方法，包括：在钯催化剂和助催化剂的作用下，苯甲酰胺类化合物(1)或丙烯酰胺类化合物(4)与苯丙烯类化合物(2)在有机溶剂中进行反应，反应结束后经过后处理得到所述的异喹啉酮类化合物(3)或吡啶酮类化合物(5)；
[0006] 反应式如下：
[0007]
[0008] 上式中，R为苯基或者烷基取代的磺酰基；
[0009] R1为H、C1～C4烷基、C1～C4烷氧基、三氟甲基或卤素中的一个或者多个；
[0010] R2为H、C1～C4烷基、苯基或卤素；
[0011] R3和R4为苯基、C1～C4烷基，或者R3、R4与连接R3、R4之间的C形成五元或者六元环。
[0012] 本发明中，所述R为Ns‑、Ts‑或Ms‑；
[0013] R1为H、甲基、乙基、甲氧基、三氟甲基、F或Cl中的一个或者多个；
[0014] R2为H、甲基、苯基或Cl；
[0015] R3和R4独立地为甲基、异丙基或苯基；
[0016] 或者R3和R4与连接R3、R4之间的C形成六元环。
[0017] 本发明中，所述的钯催化剂为三氟乙酸钯。
[0018] 本发明中，所述的助催化剂为醋酸铜。
[0019] 本发明中，所述的有机溶剂为对二甲苯。
[0020] 本发明中，以摩尔量计，所述的苯甲酰胺类化合物或丙烯酰胺类化合物：苯丙烯类化合物：钯催化剂：助催化剂＝1：1.5～2.5：0.1～0.2：0.2～0.3。
[0021] 本发明中，反应温度为100～110℃，反应时间为12～24小时。
[0022] 本发明中，所述的异喹啉酮类化合物为化合物3a～3q；
[0023] 所述的吡啶酮类化合物为化合物5a～5i。
[0024] 本发明中，所述的后处理包括柱层析。
[0025] 同现有技术相比，本发明的技术效果如下：
[0026] 本发明选择CONH‑sulfonyl为导向基，以Pd(TFA)2为催化剂、催化量Cu(OAc)2和空气为共同氧化剂，实现苯甲酰胺和丙烯酰胺与苯丙烯经C‑H烯丙基化/胺钯加成/β‑H消除/异构化过程的串联反应，合成一系列异喹啉酮和吡啶酮化合物。该方法原料简单易得、条件温和、转化高效、区域选择性高、原子利用率高且操作简单，是非常具有应用价值的合成异喹啉酮和吡啶酮的方法。
具体实施方式
[0027] 实施例1～13
[0028] 10ml史莱克管中加入苯甲酰胺1a(0.2mmol)，苯丙烯2a(0.4mmol)，催化剂(0.02mmol)，助催化剂(0.04mmol)，对二甲苯2mL，加热反应24小时。然后将反应体系冷却至室温，砂芯过滤，乙酸乙酯洗涤，浓缩溶剂，用石油醚/乙酸乙酯＝5/1过柱得到目标产品3a，具体反应条件和反应结果见表1。
[0029] 反应式如下：
[0030]
[0031] 表1实施例1～13的反应条件和反应结果
[0032]
[0033]
[0034] a反应条件:1a(0.2mmol),2a(0.4mmol),催化剂(0.02mmol),助催化剂b c d
(0.04mmol),对二甲苯(2ml),110℃空气氛围下反应24h；分离收率；加氧气气球；100℃.[0035] 实施例14～29
(0.04mmol),对二甲苯(2ml),110℃空气氛围下反应24h；分离收率；加氧气气球；100℃.[0035] 实施例14～29
[0036] 10ml史莱克管中加入苯甲酰胺1(0.2mmol)，苯丙烯2(0.4mmol)，三氟乙酸钯(6.6mg,0.02mmol)，醋酸铜(7.3mg,0.04mmol)，对二甲苯2mL，110度敞口搅拌反应24小时。然后将反应体系冷却至室温，砂芯过滤，乙酸乙酯洗涤，浓缩溶剂，用石油醚/乙酸乙酯＝5/
1或3/1过柱得到目标产品3b～3q，反应条件和结果如下：
1或3/1过柱得到目标产品3b～3q，反应条件和结果如下：
[0037]
[0038] 实施例30～38
[0039] 10ml史莱克管中加入丙烯酰胺4(0.2mmol)，苯丙烯2(0.4mmol)，三氟乙酸钯(6.6mg,0.02mmol)，醋酸铜(7.3mg,0.04mmol)，对二甲苯2mL，110度敞口搅拌反应24小时。然后将反应体系冷却至室温，砂芯过滤，乙酸乙酯洗涤，浓缩溶剂，用石油醚/乙酸乙酯＝5/
1或3/1过柱得到目标产品5a～5i。
1或3/1过柱得到目标产品5a～5i。
[0040]
[0041] 产物表征数据表征如下：
[0042] 异喹啉酮：
[0043] 3‑Benzyl‑2‑((4‑nitrophenyl)sulfonyl)isoquinolin‑1(2H)‑one(3a).Light yellow solid；73.9mg；88％yield；Rf＝0.44(hexane/EtOAc＝5/1as the eluent)；mp＝1
193–194℃；H NMR(400MHz,CDCl3)δ8.42–8.36(m,4H),7.97(dd,J＝7.8,1.4Hz,1H),7.48(td,J＝7.5,1.4Hz,1H),7.45–7.40(m,2H),7.37–7.32(m,4H),7.16(d,J＝7.6Hz,1H),6.82
13 1
(s,1H),4.01(s,2H)；C{ H}NMR(100MHz,CDCl3)δ163.1,150.6,145.3,137.9,134.3,
134.1,130.4,130.3,130.0,129.0,128.7,128.1,128.0,127.7,127.2,126.8,124.1,32.1；
+
HRMS(ESI‑TOF)m/z calcd for[M+Na](C22H16N2O5SNa)443.0678,found443.0676.[0044] 3‑Benzyl‑6‑methyl‑2‑((4‑nitrophenyl)sulfonyl)isoquinolin‑1(2H)‑one(3b).Light yellow solid；73.8mg；85％yield；Rf＝0.44(hexane/EtOAc＝5/1as the
1
eluent)；mp＝208–209℃；H NMR(400MHz,CDCl3)δ8.45–8.33(m,4H),7.85(d,J＝8.0Hz,
1H),7.42(t,J＝7.4Hz,2H),7.36–7.32(m,3H),7.13(d,J＝8.1Hz,1H),6.96(s,1H),6.80
13 1
(s,1H),3.96(s,2H),2.34(s,3H)；C{H}NMR(100MHz,CDCl3)δ163.2,150.5,145.6,145.4,
137.9,134.1,130.7,130.3,129.4,129.0,128.7,128.6,128.0,127.8,127.7,124.2,+
124.1,32.0,21.7；HRMS(ESI‑TOF)m/z calcd for[M+Na] (C23H18N2O5SNa)457.0834,found457.0837.
193–194℃；H NMR(400MHz,CDCl3)δ8.42–8.36(m,4H),7.97(dd,J＝7.8,1.4Hz,1H),7.48(td,J＝7.5,1.4Hz,1H),7.45–7.40(m,2H),7.37–7.32(m,4H),7.16(d,J＝7.6Hz,1H),6.82
13 1
(s,1H),4.01(s,2H)；C{ H}NMR(100MHz,CDCl3)δ163.1,150.6,145.3,137.9,134.3,
134.1,130.4,130.3,130.0,129.0,128.7,128.1,128.0,127.7,127.2,126.8,124.1,32.1；
+
HRMS(ESI‑TOF)m/z calcd for[M+Na](C22H16N2O5SNa)443.0678,found443.0676.[0044] 3‑Benzyl‑6‑methyl‑2‑((4‑nitrophenyl)sulfonyl)isoquinolin‑1(2H)‑one(3b).Light yellow solid；73.8mg；85％yield；Rf＝0.44(hexane/EtOAc＝5/1as the
1
eluent)；mp＝208–209℃；H NMR(400MHz,CDCl3)δ8.45–8.33(m,4H),7.85(d,J＝8.0Hz,
1H),7.42(t,J＝7.4Hz,2H),7.36–7.32(m,3H),7.13(d,J＝8.1Hz,1H),6.96(s,1H),6.80
13 1
(s,1H),3.96(s,2H),2.34(s,3H)；C{H}NMR(100MHz,CDCl3)δ163.2,150.5,145.6,145.4,
137.9,134.1,130.7,130.3,129.4,129.0,128.7,128.6,128.0,127.8,127.7,124.2,+
124.1,32.0,21.7；HRMS(ESI‑TOF)m/z calcd for[M+Na] (C23H18N2O5SNa)457.0834,found457.0837.
[0045] 3‑Benzyl‑7‑methyl‑2‑((4‑nitrophenyl)sulfonyl)isoquinolin‑1(2H)‑one(3c).Light yellow solid；44.3mg；51％yield；Rf＝0.46(hexane/EtOAc＝5/1as 1
theeluent)；mp＝172–173℃；H NMR(400MHz,CDCl3)δ8.41–8.35(m,4H),7.76(s,1H),7.42(t,J＝7.4Hz,2H),7.37–7.32(m,3H),7.29(d,J＝8.1Hz,1H),7.05(d,J＝7.8Hz,1H),6.81
13 1
(s,1H),3.96(s,2H),2.32(s,3H)；C{H}NMR(100MHz,CDCl3)δ163.3,150.5,145.3,137.7,
135.2,135.0,134.1,130.6,130.3,129.5,129.0,128.7,128.0,127.8,127.1,126.5,+
124.1,31.7,21.0；HRMS(ESI‑TOF)m/z calcd for[M+Na] (C23H18N2O5SNa)457.0834,found457.0839.
theeluent)；mp＝172–173℃；H NMR(400MHz,CDCl3)δ8.41–8.35(m,4H),7.76(s,1H),7.42(t,J＝7.4Hz,2H),7.37–7.32(m,3H),7.29(d,J＝8.1Hz,1H),7.05(d,J＝7.8Hz,1H),6.81
13 1
(s,1H),3.96(s,2H),2.32(s,3H)；C{H}NMR(100MHz,CDCl3)δ163.3,150.5,145.3,137.7,
135.2,135.0,134.1,130.6,130.3,129.5,129.0,128.7,128.0,127.8,127.1,126.5,+
124.1,31.7,21.0；HRMS(ESI‑TOF)m/z calcd for[M+Na] (C23H18N2O5SNa)457.0834,found457.0839.
[0046] 3‑Benzyl‑8‑methyl‑2‑((4‑nitrophenyl)sulfonyl)isoquinolin‑1(2H)‑one(3d).Light yellow solid；83.3mg；96％yield；Rf＝0.48(hexane/EtOAc＝5/1as 1
theeluent)；mp＝189–190℃；H NMR(400MHz,CDCl3)δ8.40–8.33(m,4H),7.41(t,J＝7.3Hz,
2H),7.35–7.29(m,4H),7.12(d,J＝7.6Hz,1H),6.98(d,J＝7.4Hz,1H),6.83(s,1H),3.92
13 1
(s,2H),2.58(s,3H)；C{ H}NMR(100MHz,CDCl3)δ163.5,150.5,145.6,143.0,138.7,
134.3,133.1,131.4,130.22,130.20,129.0,128.7,128.0,127.9,125.4,124.9,124.1,+
33.2,22.1；HRMS(ESI‑TOF)m/z calcd for[M+Na] (C23H18N2O5SNa)457.0834,found457.0832.
theeluent)；mp＝189–190℃；H NMR(400MHz,CDCl3)δ8.40–8.33(m,4H),7.41(t,J＝7.3Hz,
2H),7.35–7.29(m,4H),7.12(d,J＝7.6Hz,1H),6.98(d,J＝7.4Hz,1H),6.83(s,1H),3.92
13 1
(s,2H),2.58(s,3H)；C{ H}NMR(100MHz,CDCl3)δ163.5,150.5,145.6,143.0,138.7,
134.3,133.1,131.4,130.22,130.20,129.0,128.7,128.0,127.9,125.4,124.9,124.1,+
33.2,22.1；HRMS(ESI‑TOF)m/z calcd for[M+Na] (C23H18N2O5SNa)457.0834,found457.0832.
[0047] 3‑Benzyl‑6,8‑dimethyl‑2‑((4‑nitrophenyl)sulfonyl)isoquinolin‑1(2H)‑one(3e).Light yellow solid；85.1mg；95％yield；Rf＝0.49(hexane/EtOAc＝5/1asthe 1
eluent)；mp＝175–176℃；H NMR(400 MHz,CDCl3)δ8.39–8.32(m,4H),7.41(t,J＝7.4Hz,
2H),7.36–7.31(m,3H),6.93(s,1H),6.81(s,1H),6.79(s,1H),3.89(s,2H),2.53(s,3H),
13 1
2.27(s,3H)；C{H}NMR(100MHz,CDCl3)δ163.5,150.4,145.7,144.1,143.0,138.8,134.4,
132.2,130.4,130.1,129.0,128.7,127.9,127.7,125.6,124.0,122.6,33.1,22.0,21.4；
+
HRMS(ESI‑TOF)m/z calcd for[M+Na](C24H20N2O5SNa)471.0991,found471.0985.[0048] 3‑Benzyl‑6‑ethyl‑2‑((4‑nitrophenyl)sulfonyl)isoquinolin‑1(2H)‑one(3f).Light yellow solid；83.3mg；93％yield；Rf＝0.45(hexane/EtOAc＝5/1as
1
theeluent)；mp＝176–177℃；H NMR(400MHz,CDCl3)δ8.41–8.35(m,4H),7.87(d,J＝8.1Hz,
1H),7.43(t,J＝7.4Hz,2H),7.37–7.32(m,3H),7.15(d,J＝8.1Hz,1H),6.97(s,1H),6.80
13 1
(s,1H),3.98(s,2H),2.63(q,J＝7.6Hz,2H),1.19(t,J＝7.6Hz,3H)；C{H}NMR(100MHz,CDCl3)δ163.1,151.7,150.5,145.4,138.0,134.2,130.6,130.3,129.5,129.1,128.7,
128.0,127.8,127.5,126.6,124.3,124.1,32.1,29.0,15.0；HRMS(ESI‑TOF)m/z calcd for+
[M+Na](C24H20N2O5SNa)471.0991,found471.0986.
eluent)；mp＝175–176℃；H NMR(400 MHz,CDCl3)δ8.39–8.32(m,4H),7.41(t,J＝7.4Hz,
2H),7.36–7.31(m,3H),6.93(s,1H),6.81(s,1H),6.79(s,1H),3.89(s,2H),2.53(s,3H),
13 1
2.27(s,3H)；C{H}NMR(100MHz,CDCl3)δ163.5,150.4,145.7,144.1,143.0,138.8,134.4,
132.2,130.4,130.1,129.0,128.7,127.9,127.7,125.6,124.0,122.6,33.1,22.0,21.4；
+
HRMS(ESI‑TOF)m/z calcd for[M+Na](C24H20N2O5SNa)471.0991,found471.0985.[0048] 3‑Benzyl‑6‑ethyl‑2‑((4‑nitrophenyl)sulfonyl)isoquinolin‑1(2H)‑one(3f).Light yellow solid；83.3mg；93％yield；Rf＝0.45(hexane/EtOAc＝5/1as
1
theeluent)；mp＝176–177℃；H NMR(400MHz,CDCl3)δ8.41–8.35(m,4H),7.87(d,J＝8.1Hz,
1H),7.43(t,J＝7.4Hz,2H),7.37–7.32(m,3H),7.15(d,J＝8.1Hz,1H),6.97(s,1H),6.80
13 1
(s,1H),3.98(s,2H),2.63(q,J＝7.6Hz,2H),1.19(t,J＝7.6Hz,3H)；C{H}NMR(100MHz,CDCl3)δ163.1,151.7,150.5,145.4,138.0,134.2,130.6,130.3,129.5,129.1,128.7,
128.0,127.8,127.5,126.6,124.3,124.1,32.1,29.0,15.0；HRMS(ESI‑TOF)m/z calcd for+
[M+Na](C24H20N2O5SNa)471.0991,found471.0986.
[0049] 3‑Benzyl‑6‑methoxy‑2‑((4‑nitrophenyl)sulfonyl)isoquinolin‑1(2H)‑one(3g).Light yellow solid；74.7mg；83％yield；Rf＝0.47(hexane/EtOAc＝3/1as the 1
eluent)；mp＝190–191℃；H NMR(400MHz,CDCl3)δ8.40–8.35(m,4H),7.90(d,J＝8.8Hz,
1H),7.42(t,J＝7.4Hz,2H),7.36–7.32(m,3H),6.88–6.74(m,2H),6.61(s,1H),3.97(s,
13 1
2H),3.80(s,3H)；C{H}NMR(100MHz,CDCl3)δ164.3,162.8,150.5,145.6,140.3,134.2,
131.7,130.6,130.2,129.0,128.7,128.0,127.7,124.1,119.3,113.8,111.8,55.6,32.4；
+
HRMS(ESI‑TOF)m/z calcd for[M+Na](C23H18N2O6SNa)473.0783,found473.0774.[0050] 3‑Benzyl‑6‑chloro‑2‑((4‑nitrophenyl)sulfonyl)isoquinolin‑1(2H)‑one(3h).Light yellow solid；67.2mg；74％yield；Rf＝0.45(hexane/EtOAc＝5/1as the
1
eluent)；mp＝216–217℃；H NMR(400MHz,CDCl3)δ8.43–8.35(m,4H),7.90(d,J＝8.4Hz,
1H),7.43(t,J＝7.4Hz,2H),7.37(d,J＝7.1Hz,1H),7.34–7.28(m,3H),7.17(s,1H),6.83
13 1
(s,1H),3.97(s,2H)；C{ H}NMR(100MHz,CDCl3)δ162.3,150.6,145.1,140.8,139.6,
133.8,130.9,130.4,129.7,129.0,128.8,128.5,128.3,128.2,127.3,125.3,124.1,31.9；
+
HRMS(ESI‑TOF)m/z calcd for[M+Na](C22H15ClN2O5SNa)477.0288,found477.0281.[0051] 3‑Benzyl‑6‑fluoro‑2‑((4‑nitrophenyl)sulfonyl)isoquinolin‑1(2H)‑one(3i).Light yellow solid；65.7mg；75％yield；Rf＝0.42(hexane/EtOAc＝5/1as the
1
eluent)；mp＝193–194℃；H NMR(400MHz,CDCl3)δ8.44–8.33(m,4H),7.99(dd,J＝8.8,
5.6Hz,1H),7.43(t,J＝7.3Hz,2H),7.36(t,J＝7.5Hz,1H),7.32(d,J＝7.4Hz,2H),7.02
19
(td,J＝8.5,2.5Hz,1H),6.86(dd,J＝8.5,2.4Hz,1H),6.83(s,1H),3.99(s,2H)；F NMR
13 1 1
(376MHz,CDCl3)δ‑102.05–‑102.11(m,1F)；C{ H}NMR(100MHz,CDCl3)δ166.0(C–F,JC–F＝
3 3
258.0Hz),162.2,150.6,145.2,141.0(C–F,JC–F＝9.2Hz),133.8,132.4(C–F,JC–F＝
4
10.2Hz),130.3,129.8,129.0,128.9,128.4,128.3,124.1,123.2(C–F,JC–F＝2.8Hz),
2 2
115.4(C–F,JC–F＝22.3Hz),114.2(C–F,JC–F＝22.6Hz),32.1；HRMS(ESI‑TOF)m/z calcd +
for[M+Na](C22H15FN2O5SNa)461.0583,found461.0582.
eluent)；mp＝190–191℃；H NMR(400MHz,CDCl3)δ8.40–8.35(m,4H),7.90(d,J＝8.8Hz,
1H),7.42(t,J＝7.4Hz,2H),7.36–7.32(m,3H),6.88–6.74(m,2H),6.61(s,1H),3.97(s,
13 1
2H),3.80(s,3H)；C{H}NMR(100MHz,CDCl3)δ164.3,162.8,150.5,145.6,140.3,134.2,
131.7,130.6,130.2,129.0,128.7,128.0,127.7,124.1,119.3,113.8,111.8,55.6,32.4；
+
HRMS(ESI‑TOF)m/z calcd for[M+Na](C23H18N2O6SNa)473.0783,found473.0774.[0050] 3‑Benzyl‑6‑chloro‑2‑((4‑nitrophenyl)sulfonyl)isoquinolin‑1(2H)‑one(3h).Light yellow solid；67.2mg；74％yield；Rf＝0.45(hexane/EtOAc＝5/1as the
1
eluent)；mp＝216–217℃；H NMR(400MHz,CDCl3)δ8.43–8.35(m,4H),7.90(d,J＝8.4Hz,
1H),7.43(t,J＝7.4Hz,2H),7.37(d,J＝7.1Hz,1H),7.34–7.28(m,3H),7.17(s,1H),6.83
13 1
(s,1H),3.97(s,2H)；C{ H}NMR(100MHz,CDCl3)δ162.3,150.6,145.1,140.8,139.6,
133.8,130.9,130.4,129.7,129.0,128.8,128.5,128.3,128.2,127.3,125.3,124.1,31.9；
+
HRMS(ESI‑TOF)m/z calcd for[M+Na](C22H15ClN2O5SNa)477.0288,found477.0281.[0051] 3‑Benzyl‑6‑fluoro‑2‑((4‑nitrophenyl)sulfonyl)isoquinolin‑1(2H)‑one(3i).Light yellow solid；65.7mg；75％yield；Rf＝0.42(hexane/EtOAc＝5/1as the
1
eluent)；mp＝193–194℃；H NMR(400MHz,CDCl3)δ8.44–8.33(m,4H),7.99(dd,J＝8.8,
5.6Hz,1H),7.43(t,J＝7.3Hz,2H),7.36(t,J＝7.5Hz,1H),7.32(d,J＝7.4Hz,2H),7.02
19
(td,J＝8.5,2.5Hz,1H),6.86(dd,J＝8.5,2.4Hz,1H),6.83(s,1H),3.99(s,2H)；F NMR
13 1 1
(376MHz,CDCl3)δ‑102.05–‑102.11(m,1F)；C{ H}NMR(100MHz,CDCl3)δ166.0(C–F,JC–F＝
3 3
258.0Hz),162.2,150.6,145.2,141.0(C–F,JC–F＝9.2Hz),133.8,132.4(C–F,JC–F＝
4
10.2Hz),130.3,129.8,129.0,128.9,128.4,128.3,124.1,123.2(C–F,JC–F＝2.8Hz),
2 2
115.4(C–F,JC–F＝22.3Hz),114.2(C–F,JC–F＝22.6Hz),32.1；HRMS(ESI‑TOF)m/z calcd +
for[M+Na](C22H15FN2O5SNa)461.0583,found461.0582.
[0052] 3‑Benzyl‑2‑((4‑nitrophenyl)sulfonyl)‑6‑(trifluoromethyl)isoquinolin‑1(2H)‑one(3j).Light yellow solid；47.8mg；49％yield；Rf＝0.48(hexane/EtOAc＝5/1as 1
the eluent)；mp＝174–175℃；H NMR(400MHz,CDCl3)δ8.45–8.36(m,4H),8.10(d,J＝
8.2Hz,1H),7.59(d,J＝8.2Hz,1H),7.47–7.43(m,3H),7.37(t,J＝7.2Hz,1H),7.33(d,J＝
19 13 1
7.3Hz,2H),6.87(s,1H),4.07(s,2H)；F NMR(376MHz,CDCl3)δ‑63.34(s,3F)；C{H}NMR
2
(100MHz,CDCl3)δ161.9,150.7,144.9,138.7,135.5(C–F,JC–F＝33.0Hz),133.7,130.4,
3
130.1,129.9,129.3,129.0,128.9,128.9,128.4,124.6(C–F,JC–F＝3.6Hz),124.3(C–F,
3 1
JC–F＝3.7Hz),124.2,123.1(C–F,JC–F＝271.7Hz),31.9；HRMS(ESI‑TOF)m/z calcd for[M++
Na](C23H15F3N2O5SNa)511.0551,found511.0548.
the eluent)；mp＝174–175℃；H NMR(400MHz,CDCl3)δ8.45–8.36(m,4H),8.10(d,J＝
8.2Hz,1H),7.59(d,J＝8.2Hz,1H),7.47–7.43(m,3H),7.37(t,J＝7.2Hz,1H),7.33(d,J＝
19 13 1
7.3Hz,2H),6.87(s,1H),4.07(s,2H)；F NMR(376MHz,CDCl3)δ‑63.34(s,3F)；C{H}NMR
2
(100MHz,CDCl3)δ161.9,150.7,144.9,138.7,135.5(C–F,JC–F＝33.0Hz),133.7,130.4,
3
130.1,129.9,129.3,129.0,128.9,128.9,128.4,124.6(C–F,JC–F＝3.6Hz),124.3(C–F,
3 1
JC–F＝3.7Hz),124.2,123.1(C–F,JC–F＝271.7Hz),31.9；HRMS(ESI‑TOF)m/z calcd for[M++
Na](C23H15F3N2O5SNa)511.0551,found511.0548.
[0053] 3‑Benzyl‑2‑tosylisoquinolin‑1(2H)‑one(3k).Light yellow solid；56.0mg；1
72％yield；Rf＝0.56(hexane/EtOAc＝5/1as the eluent)；mp＝179–180℃；H NMR(400MHz,CDCl3)δ8.07(d,J＝8.4Hz,2H),8.00(d,J＝7.8Hz,1H),7.46–7.38(m,3H),7.36–
13 1
7.29(m,6H),7.13(d,J＝7.6Hz,1H),6.84(s,1H),3.96(s,2H),2.43(s,3H)；C{ H}NMR(100MHz,CDCl3)δ161.9,143.8,136.9,135.7,133.5,132.7,123.0,128.5,128.2,128.0,
127.9,127.5,126.7,126.4,126.3,125.9,31.0,20.6；HRMS(ESI‑TOF)m/z calcd for[M++
Na](C23H19NO3SNa)412.0983,found412.0981.
72％yield；Rf＝0.56(hexane/EtOAc＝5/1as the eluent)；mp＝179–180℃；H NMR(400MHz,CDCl3)δ8.07(d,J＝8.4Hz,2H),8.00(d,J＝7.8Hz,1H),7.46–7.38(m,3H),7.36–
13 1
7.29(m,6H),7.13(d,J＝7.6Hz,1H),6.84(s,1H),3.96(s,2H),2.43(s,3H)；C{ H}NMR(100MHz,CDCl3)δ161.9,143.8,136.9,135.7,133.5,132.7,123.0,128.5,128.2,128.0,
127.9,127.5,126.7,126.4,126.3,125.9,31.0,20.6；HRMS(ESI‑TOF)m/z calcd for[M++
Na](C23H19NO3SNa)412.0983,found412.0981.
[0054] 3‑Benzyl‑2‑(methylsulfonyl)isoquinolin‑1(2H)‑one(3l).White solid；1
57.6mg；92％yield；Rf＝0.48(hexane/EtOAc＝3/1as the eluent)；mp＝159–160℃；H NMR(400MHz,CDCl3)δ8.13(d,J＝7.8Hz,1H),7.51(t,J＝7.6Hz,1H),7.44–7.35(m,3H),7.34–
13 1
7.26(m,3H),7.17(d,J＝7.7 Hz,1H),6.67(s,1H),3.97(s,2H),3.63(s,3H)；C{H}NMR(100MHz,CDCl3)δ164.3,138.2,134.3,134.1,130.5,129.4,129.0,128.6,127.8,127.6,+
127.2,126.8,44.1,32.1；HRMS(ESI‑TOF)m/z calcd for[M+Na] (C17H15NO3SNa)336.0670,found336.0674.
57.6mg；92％yield；Rf＝0.48(hexane/EtOAc＝3/1as the eluent)；mp＝159–160℃；H NMR(400MHz,CDCl3)δ8.13(d,J＝7.8Hz,1H),7.51(t,J＝7.6Hz,1H),7.44–7.35(m,3H),7.34–
13 1
7.26(m,3H),7.17(d,J＝7.7 Hz,1H),6.67(s,1H),3.97(s,2H),3.63(s,3H)；C{H}NMR(100MHz,CDCl3)δ164.3,138.2,134.3,134.1,130.5,129.4,129.0,128.6,127.8,127.6,+
127.2,126.8,44.1,32.1；HRMS(ESI‑TOF)m/z calcd for[M+Na] (C17H15NO3SNa)336.0670,found336.0674.
[0055] 3‑(4‑Methylbenzyl)‑2‑((4‑nitrophenyl)sulfonyl)isoquinolin‑1(2H)‑one(3m).Light yellow solid；53.8mg；62％yield；Rf＝0.44(hexane/EtOAc＝5/1as the 1
eluent)；mp＝201–202℃；H NMR(400MHz,CDCl3)δ8.43–8.34(m,4H),7.96(dd,J＝7.9,
1.4Hz,1H),7.48(td,J＝7.5,1.5Hz,1H),7.33(t,J＝7.2Hz,1H),7.25–7.20(m,4H),7.15
13 1
(d,J＝7.5Hz,1H),6.78(s,1H),4.01(s,2H),2.39(s,3H)；C{ H}NMR(100MHz,CDCl3)δ
163.2,150.5,145.4,138.1,134.3,131.1,130.3,129.8,129.4,129.4,129.0,128.1,+
127.7,127.2,126.9,124.1,32.1,21.3；HRMS(ESI‑TOF)m/z calcd for[M+Na](C23H18N2O5SNa)457.0834,found457.0829.
eluent)；mp＝201–202℃；H NMR(400MHz,CDCl3)δ8.43–8.34(m,4H),7.96(dd,J＝7.9,
1.4Hz,1H),7.48(td,J＝7.5,1.5Hz,1H),7.33(t,J＝7.2Hz,1H),7.25–7.20(m,4H),7.15
13 1
(d,J＝7.5Hz,1H),6.78(s,1H),4.01(s,2H),2.39(s,3H)；C{ H}NMR(100MHz,CDCl3)δ
163.2,150.5,145.4,138.1,134.3,131.1,130.3,129.8,129.4,129.4,129.0,128.1,+
127.7,127.2,126.9,124.1,32.1,21.3；HRMS(ESI‑TOF)m/z calcd for[M+Na](C23H18N2O5SNa)457.0834,found457.0829.
[0056] 3‑(4‑Chlorobenzyl)‑2‑((4‑nitrophenyl)sulfonyl)isoquinolin‑1(2H)‑one(3n).Light yellow solid；48.1mg；53％yield；Rf＝0.45(hexane/EtOAc＝5/1as the 1
eluent)；mp＝205–206℃；H NMR(400MHz,CDCl3)δ8.44–8.34(m,4H),7.96(d,J＝7.8Hz,
1H),7.50(t,J＝7.1Hz,1H),7.40(d,J＝8.3Hz,2H),7.35(t,J＝7.6Hz,1H),7.27(d,J＝
13 1
6.9Hz,2H),7.16(d,J＝7.7Hz,1H),6.77(s,1H),3.97(s,2H)；C{H}NMR(100MHz,CDCl3)δ
163.0,150.6,145.1,137.6,134.5,134.1,132.5,130.9,130.4,130.3,129.4,129.0,+
127.9,127.2,126.74,126.71,124.1,32.0；HRMS(ESI‑TOF)m/z calcd for[M+Na](C22H15ClN2O5SNa)477.0288,found477.0288.
eluent)；mp＝205–206℃；H NMR(400MHz,CDCl3)δ8.44–8.34(m,4H),7.96(d,J＝7.8Hz,
1H),7.50(t,J＝7.1Hz,1H),7.40(d,J＝8.3Hz,2H),7.35(t,J＝7.6Hz,1H),7.27(d,J＝
13 1
6.9Hz,2H),7.16(d,J＝7.7Hz,1H),6.77(s,1H),3.97(s,2H)；C{H}NMR(100MHz,CDCl3)δ
163.0,150.6,145.1,137.6,134.5,134.1,132.5,130.9,130.4,130.3,129.4,129.0,+
127.9,127.2,126.74,126.71,124.1,32.0；HRMS(ESI‑TOF)m/z calcd for[M+Na](C22H15ClN2O5SNa)477.0288,found477.0288.
[0057] 吡啶酮：
[0058] 3‑Benzyl‑2‑((4‑nitrophenyl)sulfonyl)‑5,6,7,8‑tetrahydroisoquinolin‑1(2H)‑one(5a).Light yellow solid；44.9mg；53％yield；Rf＝0.43(hexane/EtOAc＝5/1as 1
the eluent)；mp＝177–178℃；H NMR(400MHz,CDCl3)δ8.39(d,J＝8.3Hz,2H),8.32(d,J＝
8.6Hz,2H),7.40(t,J＝7.5Hz,2H),7.34–7.28(m,3H),6.66(s,1H),3.34(s,2H),2.23–2.07
13 1
(m,4H),1.65–1.58(m,4H)；C{ H}NMR(100MHz,CDCl3)δ163.8,151.2,150.4,145.8,134.1,
130.1,129.8,129.1,128.6,127.9,126.4,126.0,124.1,34.0,30.4,22.7,21.6,21.5；HRMS+
(ESI‑TOF)m/z calcd for[M+Na](C22H20N2O5SNa)447.0991,found447.0999.[0059] 6‑Benzyl‑3,4‑dimethyl‑1‑((4‑nitrophenyl)sulfonyl)pyridin‑2(1H)‑one(5b).Light yellow solid；35.8mg；45％yield；Rf＝0.46(hexane/EtOAc＝5/1as the
1
eluent)；mp＝190–191℃；H NMR(400MHz,CDCl3)δ8.39(d,J＝9.0Hz,2H),8.31(d,J＝
8.9Hz,2H),7.41(t,J＝7.3Hz,2H),7.33(t,J＝7.3Hz,1H),7.29(d,J＝7.0Hz,2H),6.68(s,
13 1
1H),3.41(s,2H),1.86(s,3H),1.75(s,3H)；C{H}NMR(100MHz,CDCl3)δ164.0,150.4,
149.1,145.7,134.0,130.1,129.5,129.1,128.6,127.9,126.4,124.4,124.0,35.2,20.3,+
11.8；HRMS(ESI‑TOF)m/z calcd for[M+Na](C20H18N2O5SNa)421.0834,found421.0838.[0060] 6‑Benzyl‑3‑methyl‑1‑((4‑nitrophenyl)sulfonyl)‑4‑phenylpyridin‑2(1H)‑one(5c).Yellow solid；40.5mg；44％yield；Rf＝0.46(hexane/EtOAc＝5/1as the
1
eluent)；mp＝166–167℃；H NMR(400MHz,CDCl3)δ8.44–8.37(m,4H),7.41–7.29(m,8H),
13 1
7.11–7.06(m,2H),6.76(s,1H),3.72(s,2H),1.77(s,3H)；C{ H}NMR(100MHz,CDCl3)δ
164.6,150.5,150.3,145.6,138.0,133.9,130.2,129.6,129.0,128.9,128.7,128.7,+
129.0,127.4,126.8,125.7,124.1,35.3,13.6；HRMS(ESI‑TOF)m/z calcd for[M+Na](C25H20N2O5SNa)483.0991,found483.0991。
the eluent)；mp＝177–178℃；H NMR(400MHz,CDCl3)δ8.39(d,J＝8.3Hz,2H),8.32(d,J＝
8.6Hz,2H),7.40(t,J＝7.5Hz,2H),7.34–7.28(m,3H),6.66(s,1H),3.34(s,2H),2.23–2.07
13 1
(m,4H),1.65–1.58(m,4H)；C{ H}NMR(100MHz,CDCl3)δ163.8,151.2,150.4,145.8,134.1,
130.1,129.8,129.1,128.6,127.9,126.4,126.0,124.1,34.0,30.4,22.7,21.6,21.5；HRMS+
(ESI‑TOF)m/z calcd for[M+Na](C22H20N2O5SNa)447.0991,found447.0999.[0059] 6‑Benzyl‑3,4‑dimethyl‑1‑((4‑nitrophenyl)sulfonyl)pyridin‑2(1H)‑one(5b).Light yellow solid；35.8mg；45％yield；Rf＝0.46(hexane/EtOAc＝5/1as the
1
eluent)；mp＝190–191℃；H NMR(400MHz,CDCl3)δ8.39(d,J＝9.0Hz,2H),8.31(d,J＝
8.9Hz,2H),7.41(t,J＝7.3Hz,2H),7.33(t,J＝7.3Hz,1H),7.29(d,J＝7.0Hz,2H),6.68(s,
13 1
1H),3.41(s,2H),1.86(s,3H),1.75(s,3H)；C{H}NMR(100MHz,CDCl3)δ164.0,150.4,
149.1,145.7,134.0,130.1,129.5,129.1,128.6,127.9,126.4,124.4,124.0,35.2,20.3,+
11.8；HRMS(ESI‑TOF)m/z calcd for[M+Na](C20H18N2O5SNa)421.0834,found421.0838.[0060] 6‑Benzyl‑3‑methyl‑1‑((4‑nitrophenyl)sulfonyl)‑4‑phenylpyridin‑2(1H)‑one(5c).Yellow solid；40.5mg；44％yield；Rf＝0.46(hexane/EtOAc＝5/1as the
1
eluent)；mp＝166–167℃；H NMR(400MHz,CDCl3)δ8.44–8.37(m,4H),7.41–7.29(m,8H),
13 1
7.11–7.06(m,2H),6.76(s,1H),3.72(s,2H),1.77(s,3H)；C{ H}NMR(100MHz,CDCl3)δ
164.6,150.5,150.3,145.6,138.0,133.9,130.2,129.6,129.0,128.9,128.7,128.7,+
129.0,127.4,126.8,125.7,124.1,35.3,13.6；HRMS(ESI‑TOF)m/z calcd for[M+Na](C25H20N2O5SNa)483.0991,found483.0991。