一类线性β, γ-不饱和α-酮酸色醇酯类化合物的合成

引用本文: 余接强, 贾俊, 王兴旺. 一类线性β, γ-不饱和α-酮酸色醇酯类化合物的合成[J]. 有机化学, 2020, 40(9): 2778-2787. doi: 10.6023/cjoc202005051 shu

Citation: Yu Jieqiang, Jia Jun, Wang Xingwang. Synthesis of a Type of Linear β, γ-Unsaturated α-Keto Tryptophol Ester Compounds[J]. Chinese Journal of Organic Chemistry, 2020, 40(9): 2778-2787. doi: 10.6023/cjoc202005051 shu

一类线性β, γ-不饱和α-酮酸色醇酯类化合物的合成

余接强 ^a, ,
贾俊 ^{b,
,} ,
王兴旺 ^{a,
,}

a.
苏州大学材料与化学化工学部江苏苏州 215123
b.
苏州大学分析测试中心江苏苏州 215123

通讯作者: 贾俊, jiajun@suda.edu.cn; 王兴旺, wangxw@suda.edu.cn

基金项目:

国家自然科学基金(No.21971176)资助项目

摘要: 色醇类衍生物是一类十分重要的化合物，具有广谱的药理和生理活性.报道了以1-（3-二甲氨基丙基）-3-乙基碳二亚胺盐酸盐（EDCI）和1-羟基苯并三唑（HOBt）作为缩合试剂，在温和的条件下对各种取代的色醇与β，γ-不饱和α-酮酸进行的缩合酯化反应，制备了一系列β，γ-不饱和-α-酮酸色醇酯类化合物.该方法底物适应性广，原料易得且操作简便.

关键词:

English

Synthesis of a Type of Linear β, γ-Unsaturated α-Keto Tryptophol Ester Compounds

Yu Jieqiang ^a, ,
Jia Jun ^{b,
,} ,
Wang Xingwang ^{a,
,}

a.
College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, Jiangsu 215123
b.
Analysis and Testing Center, Soochow University, Suzhou, Jiangsu 215123

Corresponding author: Jia, Jun, E-mail: jiajun@suda.edu.cn; Wang, Xingwang, E-mail: wangxw@suda.edu.cn

Received Date: 19 May 2020
Revised Date: 22 June 2020
Available Online: 25 September 2020
Fund Project:

Project supported by the National Natural Science Foundation of China (No. 21971176)

Abstract: Tryptophol derivatives are very important compounds with wide spectrum of pharmaceutical and physiological activity. Herein, the esterification reaction of trypthol and its derivatives with β, γ-unsaturated α-keto acids was reported by the use of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) and 1-hydroxybenzotriazole (HOBt) as conden-sation reagents. A series of β, γ-unsaturated α-keto trypanol ester derivatives were prepared in moderate to high yields. This method has advantages of riched functional group tolerance, readily available starting materials and easy operation.

Key words:

condensation reagent
/ tryptophol
/ esterification
/ β, γ-unsaturated α-keto acid
/ β, γ-unsaturated α-keto trypanol ester

天然产物分子和生物活性分子中常常含有氮杂环的结构, 其中吲哚结构的化合物在动植物的生命活动中发挥着重要作用, 如具有神经活性的物种5-羟基色胺^[1]以及一部分植物生长调节剂^[2].由于吲哚及其衍生物有多个亲核性位点, 其通过C(3)、C(2)、C(1)或者N(1)等位点可发生Friedel-Crafts烷基化反应、Pictet-Spengler环化反应和N-烷基化反应等类型的反应^[3], 从而被广大化学工作者关注.

在自然界中, 色醇存在于一些生命体如植物、细菌、真菌的代谢产物中, 其衍生物表现出抗生素、抗胆碱能、聚合酶抑制剂等生理活性^[4], 由于色醇及其衍生物广谱的生理和药理活性^[5], 对其结构的修饰和衍生, 在药理研究方面具有重要意义.另外, 色醇作为一种非常重要的合成原料, 其氧原子具有较高的可塑性, 即可用于合成相应的色胺, 进而转化成咔啉类化合物^[6]以及其它具有生物活性的化合物.也可通过其它亲核类反应连接不同的取代基用作反应底物, 在有机小分子或金属络合物催化下构建一些环状合物, 如吲哚并六元环、螺环吲哚类化合物等^[7-10].

酮酸色醇酯类化合物具有潜在的抗菌能力^[11].但目前为止, 这类化合物的合成研究相对较少.在之前的文献报道中, 色醇与3-甲基-2-氧戊酸可在二环己基碳二亚胺(DCC)的作用下转化成相应的酮酸色醇酯类化合物^[11](Scheme 1).另外, 3-吲哚醇和丙酮酸可以在DCC和吡啶的作用下发生缩合酯化反应得到酮酸3-吲哚酯^[12](Scheme 1).在此工作中, 我们使用1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDCI)和1-羟基苯并三唑(HOBt)^[13]作为缩合试剂, 实现了取代的色醇与芳基不饱和酮酸的缩合酯化反应, 构建了一类线性的β, γ-不饱和α-酮酸色醇酯类化合物(Scheme 1).

Scheme 1

Scheme 1. 酮酸色醇酯类化合物的合成

Scheme 1. Synthesis of α-keto tryptophol ester compounds

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1. 结果与讨论

以色醇1a和苯基不饱和酮酸2a作为模板底物, 对两对组合缩合试剂DCC/4-二甲氨基吡啶(DMAP)和EDCI/HOBt以及其它的反应条件进行优化, 反应结果见表 1.当选用DCC/DMAP作为组合缩合试剂时, 二氯甲烷为溶剂, 在25 ℃条件下, 反应无法顺利进行(表 1, Entry 1).即使提高反应温度至回流条件, 也没有检测到目标产物(表 1, Entry 2).然后将组合缩合试剂换成EDCI/HOBt, 以四氢呋喃(THF)为溶剂, 在25 ℃下进行反应, 发现反应能以45%的产率得到化合物3a(表 1, Entry 3), 如果进一步增大色醇的用量, 反应的产率进一步得到提高(表 1, Entry 4).但是提高反应温度至回流时, 反应收率无明显变化(表 1, Entry 5).经过以上实验, 获得了反应的最佳条件为: THF为溶剂, 试剂用量为色醇(1.6 equiv.), 苯基不饱和酮酸(1.0 equiv.), EDCI (2.0 equiv.)和HOBt (2.0 equiv.), 在25 ℃下反应6 h.

表 1

表 1 优化反应条件^a

Table 1. Optimization of reaction conditions

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Entry	Condensation reagents	Solvent	Yield^b/%
1	DCC/DMAP	DCM	nr
2^c	DCC/DMAP	DCM	nr
3	EDCI/HOBt	THF	45
4^d	EDCI/HOBt	THF	65
5^e	EDCI/HOBt	THF	63
^a Unless otherwise indicated, all reactions were carried out with tryptol 1a (3 mmol), phenyl unsaturated keto acid 2a (3 mmol) and DCC (6 mmol)/DMAP (10 mol%) or EDCI (6 mmol)/HOBt (6 mmol) in corresponding solvent (25 mL) at 25 ℃ for 6 h. ^b Isolated product after column chromatography. ^c Reflux at 50 ℃. ^d 1a (4.8 mmol) was used. ^e 1a (4.8 mmol) was used, reflux at 80 ℃.

为了研究反应底物的普适性, 首先对色醇底物中不同取代基R¹、R²和R³进行了考察, 结果列于表 2, 该反应对各种取代的色醇适应性良好.我们发现苯环上取代基为卤素原子和供电基团时, 反应能以16%~80%的产率得到化合物3b~3o(表 2, Entries 1~14), 其中4-甲基色醇作为底物时, 能以80%的产率合成酮酸色醇酯类化合物3b.但是以6-氯色醇为底物, 产率有明显的降低, 反应仅能以16%收率得到化合物3l.然后又研究了色醇的吲哚2位以及N原子上的取代基效应, 发现2-位带有甲基或苯基(3p, 3q)以及氮原子上连有甲基或苄基(3r, 3s), 反应产率为42%~64%(表 2, Entries 15~18).由此可见, 该反应有较好的官能团兼容性.

表 2

表 2 反应底物1普适性的考察^a

Table 2. Investigation on the universality of reaction substrate 1

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Entry	3	R¹	R²	R³	Yield^b/%
1	3b	4-CH₃	H	H	80
2	3c	4-Cl	H	H	44
3	3d	4-Br	H	H	67
4	3e	5-CH₃	H	H	43
5	3f	5-OCH₃	H	H	42
6	3g	5-F	H	H	43
7	3h	5-Cl	H	H	45
8	3i	5-Br	H	H	50
9	3j	6-CH₃	H	H	74
10	3k	6-F	H	H	37
11	3l	6-Cl	H	H	16
12	3m	6-Br	H	H	52
13	3n	7-CH₃	H	H	68
14	3o	4, 7-Cl₂	H	H	26
15	3p	H	2-CH₃	H	42
16	3q	H	2-Ph	H	59
17	3r	H	H	N-CH₃	53
18	3s	H	H	N-Bn	64
^a Unless otherwise indicated, all reactions were carried out with 1 (4.8 mmol), 2a (3 mmol), EDCI (6 mmol), HOBt (6 mmol) in THF (25 mL) at 25 ℃ for 6 h. ^b Isolated product after column chromatography.

随后又考察了带有不同取代基的底物2对该反应的普适性情况, 结果列于表 3.如表 3所示, 苯环2-位上有吸电子取代基团2-F和2-NO₂时, 反应能以54%和52%的产率顺利得到相应的β, γ-不饱和α-酮酸色醇酯化合物3t和3u(表 3, Entries 1, 2).如果在苯环的3位引入供电子基团Me和OMe或弱吸电子基团如F和Cl, 相应的反应能以30%~77%的产率得到对应的产物3v~3y(表 3, Entries 3~6).另外, 在苯环的3位引入强吸电子基团NO₂和CF₃, 反应仍然可以顺利进行, 分别能以60%和52%的产率得到产物3aa和3bb(表 3, Entries 8, 9).但是将溴原子引入苯环的3-位, 可能由于空间位阻较大导致反应活性较差, 反应仅以12%的收率得到化合物3z(表 3, Entry 7).随后, 无论是吸电子取代基还是供电子取代基(F, Cl, Br, NO₂, CF₃, Ph, ⁱPr, CN)被引入到苯环的4-位, 官能团都能较好地兼容, 反应分别能以30%~77%的产率得到化合物3ac~3aj(表 3, Entries 10~17).当在苯环上引入两个卤原子(2, 4-Cl₂, 3-Br-4-Cl, 3, 5-F₂)或者两个甲基(3, 4-Me₂)时, 反应也都能以38%~65%的产率得到β, γ-不饱和α-酮酸色醇酯化合物3ak~3ao(表 3, Entries 18~22).当Ar为2-噻吩基或2-呋喃基这样的杂环时, 反应产率均以68%的产率得到化合物3ap和3aq(表 3, Entries 23, 24).当芳基被2-萘基这样的稠环以及苯乙烯基取代时, 反应也能顺利得到化合物3ar和3as(表 3, Entries 25, 26).

表 3

表 3 反应底物2普适性的考察^a

Table 3. Investigation on the universality of reaction substrate 2

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Entry	3	Ar	Yield^b/%
1	3t	2-FC₆H₄	54
2	3u	2-NO₂C₆H₄	52
3	3v	3-MeC₆H₄	39
4	3w	3-OMeC₆H₄	77
5	3x	3-FC₆H₄	58
6	3y	3-ClC₆H₄	30
7	3z	3-BrC₆H₄	12
8	3aa	3-NO₂C₆H₄	60
9	3ab	3-CF₃C₆H₄	52
10	3ac	4-FC₆H₄	77
11	3ad	4-ClC₆H₄	47
12	3ae	4-BrC₆H₄	51
13	3af	4-NO₂C₆H₄	41
14	3ag	4-CF₃C₆H₄	40
15	3ah	4-PhC₆H₄	30
16	3ai	4-ⁱPrC₆H₄	45
17	3aj	4-CNC₆H₄	48
18	3ak	2, 4-Cl₂C₆H₃	38
19	3al	2, 6-Cl₂C₆H₃	62
20	3am	3-Br-4-ClC₆H₃	65
21	3an	3, 4-Me₂C₆H₃	41
22	3ao	3, 5-F₂C₆H₃	41
23	3ap	2-Furyl	68
24	3aq	2-Furyl	68
25	3ar	2-Naphthyl	33
26	3as	Cinnamyl	60
^a Unless otherwise indicated, all reactions were carried out with 1a (4.8 mmol), 2 (3 mmol), EDCI (6 mmol), HOBt (6 mmol) in THF (25 mL) at 25 ℃ for 6 h. ^b Isolated product after column chromatography.

2. 结论

研究了以EDCI和HOBt作为缩合试剂, 对色醇及其衍生物和β, γ-不饱和α-酮酸进行缩合酯化反应.在温和的反应条件下, 反应均能以中等至良好的收率得到一类线性的β, γ-不饱和α-酮酸色醇酯类化合物.该反应具有底物适应性广、反应条件温和及原料易获得等特点, 为β, γ-不饱和α-酮酸色醇酯类化合物的合成提供了一种可行的路径.

3. 实验部分

3.1 仪器与试剂

¹H NMR、¹³C NMR和¹⁹F NMR由Varian UNITY INOVA 400 MHz型核磁共振仪测定(溶剂用CDCl₃以TMS为内标, 用DMSO-d₆为溶剂时以溶剂峰为内标); 高分辨质谱由仪器Micromass TOF-MS测定.本实验所用柱层析硅胶由烟台维启化工有限公司生产(300~400目).实验所用溶剂和试剂均为分析纯.无水溶剂在使用前按溶剂常规干燥方法处理.

3.2 底物1和2的合成

底物1和2的合成方法参考文献[14~18].

3.3 化合物3的合成

参考文献[19], 在氮气保护下, 向100 mL三口烧瓶中加入化合物1 (4.8 mmol), 化合物2 (3 mmol), EDCI (6 mmol)和HOBt (6 mmol), 并加入干燥处理的THF (25 mL).上述混合物在室温条件下搅拌6 h.薄层色谱(TLC)检测反应结束, 减压旋干溶剂.粗产物经硅胶柱层析分离提纯(乙酸乙酯/石油醚, V:V＝1:6)得到目标化合物3.

(E)-2-氧代-4-苯基丁-3-烯酸-2-(1H-吲哚-3-基)乙酯(3a):黄色固体, 收率65%. m.p. 119.7~120.6 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.93 (s, 1H), 7.74~7.70 (m, 3H), 7.62 (d, J＝3.6 Hz, 1H), 7.50~7.45 (m, 3H), 7.38 (d, J＝2.4 Hz, 1H), 7.27 (dd, J＝11.2, 5.2 Hz, 2H), 7.09 (t, J＝7.2 Hz, 1H), 7.00 (t, J＝7.2 Hz, 1H), 4.56 (t, J＝7.2 Hz, 2H), 3.17 (t, J＝6.8 Hz, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 184.4, 162.8, 148.5, 136.7, 134.2, 132.1, 129.6, 129.5, 127.6, 123.8, 121.9, 121.5, 118.9, 118.8, 111.9, 110.2, 66.4, 24.6; IR (KBr) ν: 3407, 2921, 1724, 1686, 1593, 1257, 1080, 734 cm^－1; ESI-HRMS calcd for C₂₀H₁₇NO₃Na [M+Na]⁺ 342.1101, found 342.1093.

(E)-2-氧代-4-苯基丁-3-烯酸-2-(4-甲基-1H-吲哚-3-基)乙酯(3b):橙黄色固体, 收率80%. m.p. 72.8~73.6 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.94 (s, 1H), 7.77~7.70 (m, 1H), 7.50~7.42 (m, 1H), 7.31 (d, J＝7.2 Hz, 1H), 7.23 (d, J＝2.4 Hz, 1H), 6.97 (t, J＝7.6 Hz, 1H), 6.74 (d, J＝2.8 Hz, 1H), 4.57 (t, J＝7.2 Hz, 1H), 3.34 (t, J＝7.2 Hz, 1H), 2.67 (s, 1H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.9, 162.3, 148.0, 136.7, 133.8, 131.7, 129.5, 129.20, 129.1, 125.6, 123.5, 121.3, 121.1, 120.3, 110.3, 109.6, 66.8, 25.9, 20.1; IR (KBr) ν: 3329, 1736, 1598, 1257, 1112, 976, 733, 682 cm^－1; ESI-HRMS calcd for C₂₁H₁₉NO₃Na [M+Na]⁺ 356.1257, found 356.1257.

(E)-2-氧代-4-苯基丁-3-烯酸-2-(4-氯-1H-吲哚-3-基)乙酯(3c):黄色固体, 收率44%. m.p. 76.4~77.1 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 11.32 (s, 1H), 7.73~7.69 (m, 3H), 7.51~7.43 (m, 3H), 7.36~7.35 (m, 2H), 7.28 (d, J＝8.4 Hz, 1H), 7.07~7.00 (m, 2H), 4.58 (t, J＝7.2 Hz, 2H), 3.37 (t, J＝6.8 Hz, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.84, 162.21, 147.98, 137.96, 133.73, 131.71, 129.16, 125.79, 124.52, 123.45, 121.88, 121.37, 119.44, 110.96, 109.54, 66.68, 25.21; IR (KBr) ν: 3309, 2920, 1734, 1597, 1259, 974, 823, 768 cm^－1; ESI-HRMS calcd for C₂₀H₁₆ClNO₃Na [M+Na]⁺ 376.0711, found 376.0709.

(E)-2-氧代-4-苯基丁-3-烯酸-2-(4-溴-1H-吲哚-3-基)乙酯(3d):黄色固体, 收率67%. m.p. 74.7~75.7 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 9.41 (s, 1H), 7.59 (s, 1H), 7.37 (d, J＝7.9 Hz, 1H), 6.76 (d, J＝8.1 Hz, 1H), 5.52 (d, J＝14.2 Hz, 1H), 4.36~4.08 (m, 4H), 1.36 (t, J＝6.7 Hz, 6H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.8, 162.2, 148.0, 137.8, 133.7, 131.6, 129.1, 126.0, 124.7, 122.9, 122.2, 121.4, 112.8, 111.5, 110.0, 66.6, 25.0; IR (KBr) ν: 3300, 1732, 1594, 1573, 1336, 1257, 973, 735 cm^－1; ESI- HRMS calcd for C₂₀H₁₆BrNO₃Na [M+Na]⁺ 420.0206, found 420.0206.

(E)-2-氧代-4-苯基丁-3-烯酸-2-(5-甲基-1H-吲哚-3-基)乙酯(3e):黄色固体, 收率43%. m.p. 128.3~129.2 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.80 (s, 1H), 7.71 (t, J＝16.8 Hz, 3H), 7.46 (td, J＝14.0, 7.2 Hz, 3H), 7.39 (s, 1H), 7.29~7.25 (m, 2H), 7.21 (s, 1H), 6.92 (d, J＝2.8 Hz, 1H), 4.55 (t, J＝6.8 Hz, 2H), 3.14 (t, J＝6.8 Hz, 2H), 2.36 (s, 3H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 184.0, 162.4, 148.1, 134.7, 133.8, 131.7, 129.2, 129.1, 127.5, 126.9, 123.5, 122.7, 121.3, 118.0, 111.2, 109.3, 66.1, 24.2, 21.3; IR (KBr) ν: 3428, 1731, 1609, 1261, 1090, 993, 792, 690 cm^－1; ESI-HRMS calcd for C₂₁H₁₉N- O₃Na [M+Na]⁺ 356.1257, found 356.1258.

(E)-2-氧代-4-苯基丁-3-烯酸-2-(5-甲氧基-1H-吲哚- 3-基)乙酯(3f):黄色固体, 收率42%. m.p. 120.1~121.1 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.77 (s, 1H), 7.34~7.69 (m, 3H), 7.49~7.44 (m, 3H), 7.26 (dd, J＝11.6, 7.6 Hz, 3H), 7.12 (s, 1H), 6.75 (d, J＝8.4 Hz, 1H), 4.55 (t, J＝6.4 Hz, 2H), 3.76 (s, 3H), 3.14 (t, J＝6.4 Hz, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 184.0, 162.4, 153.2, 148.1, 133.8, 131.7, 131.4, 129.2, 129.1, 127.5, 124.0, 121.4, 112.1, 111.3, 109.6, 100.2, 66.1, 55.3, 24.2; IR (KBr) ν: 3431, 2989, 1730, 1573, 1262, 959, 830, 743 cm^－1; ESI-HRMS calcd for C₂₁H₁₉NO₄Na [M+Na]⁺372.1206, found 372.1208.

(E)-2-氧代-4-苯基丁-3-烯酸-2-(5-氟-1H-吲哚-3-基)乙酯(3g):黄色固体, 收率43%. m.p. 118.0~119.0 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 11.03 (s, 1H), 7.82~7.64 (m, 3H), 7.57~7.31 (m, 6H), 7.27 (d, J＝6.8 Hz, 1H), 6.92 (td, J＝9.2, 2.4 Hz, 1H), 4.53 (t, J＝6.8 Hz, 2H), 3.13 (t, J＝6.8 Hz, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.9, 162.3, 158.0 (d, J＝231.1 Hz), 155.7, 148.1, 133.7, 132.9, 131.7, 129.2, 129.1, 127.5 (d, J＝9.9 Hz), 127.4, 125.6, 121.3, 112.5, 112.4 (d, J＝9.8 Hz), 110.3, 110.2 (d, J＝4.8 Hz), 109.4, 109.1 (d, J＝26.1 Hz), 103.3, 103.1 (d, J＝23.2 Hz), 66.0, 24.1; ¹⁹F NMR (376 MHz, DMSO-d₆) δ: －125.3; IR (KBr) ν: 3423, 1732, 1610, 1265, 1177, 956, 852, 784 cm^－1; ESI-HRMS calcd for C₂₀H₁₆FNO₃ [M+Na]⁺ 360.1006, found 360.0999.

(E)-2-氧代-4-苯基丁-3-烯酸-2-(5-氯-1H-吲哚-3-基)乙酯(3h):黄色固体, 收率45%. m.p. 119.1~119.9 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 11.14 (s, 1H), 7.71~7.67 (m, 4H), 7.47~7.34 (m, 5H), 7.25 (d, J＝10.0 Hz, 1H), 7.07 (d, J＝4.4 Hz, 1H), 4.53 (s, 2H), 3.14 (s, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.9, 162.3, 148.1, 134.7, 133.8, 131.7, 129.2, 128.4, 125.3, 123.4, 121.3, 121.1, 117.8, 113.0, 110.0, 66.1, 24.0; IR (KBr) ν: 3422, 1728, 1609, 1258, 957, 864, 790, 689 cm^－1; ESI-HRMS calcd for C₂₀H₁₆ClNO₃Na [M+Na]⁺ 376.0711, found 376.0716.

(E)-2-氧代-4-苯基丁-3-烯酸-2-(5-溴-1H-吲哚-3-基)乙酯(3i):黄色固体, 收率50%. m.p. 114.6~115.5 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.30 (s, 1H), 7.80~7.74 (m, 2H), 7.54~7.51 (m, 2H), 7.41~7.38 (m, 3H), 7.26~7.22 (m, 3H), 7.07 (s, 1H), 4.54 (s, 2H), 3.15 (s, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.8, 162.2, 148.0, 134.9, 133.7, 131.6, 129.1, 129.0, 125.1, 123.5, 121.3, 120.7, 113.4, 111.2, 109.8, 65.9, 40.1, 39.9, 39.7, 39.5, 39.3, 39.1, 39.0, 23.9; IR (KBr) ν: 3420, 1731, 1690, 1264, 989, 865, 791, 690 cm^－1; ESI-HRMS calcd for C₂₀H₁₆BrNO₃Na [M+Na]⁺ 420.0206, found 420.0208.

(E)-2-氧代-4-苯基丁-3-烯酸-2-(6-甲基-1H-吲哚-3-基)乙酯(3j):橙黄色固体, 收率74%. m.p. 98.3~99.2 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.77 (s, 1H), 7.70 (d, J＝2.8 Hz, 3H), 7.48~7.44 (m, 4H), 7.26 (d, J＝8.8 Hz, 1H), 7.17 (s, 2H), 6.83 (d, J＝2.8 Hz, 1H), 4.55 (s, 2H), 3.14 (s, 2H), 2.38 (s, 3H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 184.0, 162.4, 148.1, 136.8, 133.7, 131.6, 130.1, 129.2, 129.1, 125.2, 122.6, 121.4, 120.3, 118.0, 111.3, 109.6, 66.0, 24.3, 21.4; IR (KBr) ν: 3335, 1735, 1681, 1257, 970, 864, 740, 687 cm^－1; ESI-HRMS calcd for C₂₁H₁₉NO₃Na [M+Na]⁺ 356.1257, found 356.1259.

(E)-2-氧代-4-苯基丁-3-烯酸-2-(6-氟-1H-吲哚-3-基)乙酯(3k):黄色固体, 收率37%. m.p. 92.9~93.9 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 11.02 (s, 1H), 7.75~7.67 (m, 3H), 7.60 (dd, J＝7.2, 1.6 Hz, 1H), 7.52~7.39 (m, 3H), 7.27 (dd, J＝6.0, 0.4 Hz, 2H), 7.16 (dd, J＝5.2, 3.2 Hz, 1H), 6.85 (ddd, J＝8.8, 6.4, 0.8 Hz, 1H), 4.55 (t, J＝6.9 Hz, 2H), 3.15 (t, J＝6.8 Hz, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.9, 162.3, 160.2 (d, J＝234.0 Hz), 157.8, 148.1, 136.2, 136.0 (d, J＝12.7 Hz), 133.8, 131.7, 129.2, 129.1, 124.2, 124.0 (d, J＝3.4 Hz), 123.9, 121.3, 119.4 (d, J＝10.3 Hz), 119.3, 110.2, 107.1 (d, J＝24.4 Hz), 106.9, 97.6 (d, J＝24.4 Hz), 97.3, 66.0, 24.1; ¹⁹F NMR (376 MHz, DMSO-d₆) δ: －122.2; IR (KBr) ν: 3360, 2923, 1732, 1594, 1253, 974, 837, 736 cm^－1; ESI-HRMS calcd for C₂₀H₁₆FNO₃Na [M+Na]⁺ 360.1006, found 360.0996.

(E)-2-氧代-4-苯基丁-3-烯酸-2-(6-氯-1H-吲哚-3-基)乙酯(3l):黄色固体, 收率16%. m.p. 113.9~114.8 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 11.07(s, 1H), 7.69 (dd, J＝7.2, 1.2 Hz, 3H), 7.61 (d, J＝6.0 Hz, 1H), 7.54~7.42 (m, 3H), 7.40 (d, J＝1.0 Hz, 1H), 7.31 (d, J＝1.0 Hz, 1H), 7.24 (d, J＝8.2 Hz 1H), 6.99 (dd, J＝4.8, 2.8 Hz, 1H), 4.53 (t, J＝6.8 Hz, 2H), 3.14 (t, J＝6.8 Hz, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.9, 162.3, 148.1, 136.5, 133.6, 131.7, 129.1, 126.0, 125.9, 124.6, 121.4, 119.7, 118.8, 111.1, 110.3, 66.0, 23.9; IR (KBr) ν: 3318, 1732, 1593, 1255, 970, 804, 739, 685 cm^－1; ESI-HRMS calcd for C₂₀H₁₆ClNO₃Na [M+Na]⁺ 376.0711, found 376.0711.

(E)-2-氧代-4-苯基丁-3-烯酸-2-(6-溴-1H-吲哚-3-基)乙酯(3m):黄色固体, 收率52%. m.p. 119.0~120.0 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 11.09 (s, 1H), 7.69 (dd, J＝7.6, 3.6 Hz, 3H), 7.57 (d, J＝3.6 Hz, 2H), 7.52~7.41 (m, 3H), 7.30 (s, 1H), 7.28~7.21 (m, 1H), 7.10 (d, J＝8.4 Hz, 1H), 4.54 (t, J＝6.8 Hz, 2H), 3.14 (d, J＝6.8 Hz, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.9, 162.3, 148.0, 137.1, 133.7, 131.6, 129.1, 126.3, 124.5, 121.3, 120.2, 114.1, 113.9, 110.3, 65.9, 24.0; IR (KBr) ν: 3312, 2921, 1710, 1592, 1258, 962, 807, 741 cm^－1; ESI-HRMS calcd for C₂₀H₁₆BrNO₃Na [M+Na]⁺ 420.0206, found 420.0204.

(E)-2-氧代-4-苯基丁-3-烯酸-2-(7-甲基-1H-吲哚-3-基)乙酯(3n):黄色固体, 收率68%. m.p. 103.1~104.1 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.90 (s, 1H), 7.69 (dd, J＝7.2, 3.2 Hz, 3H), 7.53~7.39 (m, 4H), 7.30~7.20 (m, 2H), 6.91 (q, J＝9.6 Hz, 2H), 4.56 (t, J＝6.8 Hz, 2H), 3.16 (t, J＝6.8 Hz, 2H), 2.46 (s, 3H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 184.1, 162.4, 148.1, 136.0, 133.8, 131.7, 129.2, 129.1, 126.9, 123.1, 121.6, 121.4, 120.6, 118.7, 115.9, 110.2, 66.0, 24.3, 16.8; IR (KBr) ν: 3361, 2962, 1727, 1693, 1261, 994, 847, 738 cm^－1; ESI-MS calcd for C₂₁H₁₉NO₃Na [M+Na]⁺ 356.1257; found 356.1254.

(E)-2-氧代-4-苯基丁-3-烯酸-2-(4, 7-二氯-1H-吲哚- 3-基)乙酯(3o):黄色固体, 收率26%. m.p. 109.1~110.1 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 11.69(s, 1H), 7.70 (t, J＝6.8 Hz, 3H), 7.51~7.42 (m, 4H), 7.27 (d, J＝10.0 Hz, 1H), 7.15 (d, J＝4.4 Hz, 1H), 7.03 (d, J＝5.2 Hz, 1H), 4.58 (t, J＝6.8 Hz, 2H), 3.37 (t, J＝6.8 Hz, 3H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 184.2, 162.6, 148.4, 134.7, 134.2, 132.1, 129.6, 127.5, 125.4, 124.0, 121.8, 121.7, 120.8, 116.0, 111.7, 66.8, 25.4; IR (KBr) ν: 3407, 2921, 1722, 1685, 1592, 1078, 734, 678 cm^－1; ESI-HRMS calcd for C₂₀H₁₅C_l2NO₃Na [M+Na]⁺ 410.0324, found 410.0324.

(E)-2-氧代-4-苯基丁-3-烯酸-2-(2-甲基-1H-吲哚-3-基)乙酯(3p):黄色固体, 收率42%. m.p. 70.3~71.2 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.83 (s, 1H), 7.80~7.66 (m, 3H), 7.57~7.40 (m, 4H), 7.34~7.21 (m, 2H), 7.01 (t, J＝6.8 Hz, 1H), 6.95 (t, J＝6.8 Hz, 1H), 4.45 (t, J＝6.8 Hz, 2H), 3.11 (t, J＝7.2 Hz, 2H), 2.37 (s, 3H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.7, 162.2, 147.9, 135.2, 133.7, 132.9, 131.6, 129.1, 129.0, 128.3, 121.2, 120.1, 118.3, 117.2, 110.5, 105.4, 65.9, 23.1, 11.2; IR (KBr) ν: 3340, 2920, 1731, 1306, 1205, 1076, 737, 684 cm^－1; ESI- HRMS calcd for C₂₁H₁₉NO₃Na [M+Na]⁺ 356.1257, found 356.1260.

(E)-2-氧代-4-苯基丁-3-烯酸-2-(2-苯基-1H-吲哚-3-基)乙酯(3q):橙黄色固体, 收率59%. m.p. 114.7~115.6 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 11.33 (s, 1H), 7.77~7.65 (m, 6H), 7.56~7.32 (m, 7H), 7.26 (d, J＝10.0 Hz, 1H), 7.14 (t, J＝7.2 Hz, 1H), 7.05 (t, J＝7.2 Hz, 1H), 4.59 (t, J＝7.2 Hz, 2H), 3.33 (t, J＝6.8 Hz, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.4, 162.1, 147.8, 136.1, 135.5, 133.8, 132.6, 131.7, 129.2, 129.1, 128.8, 128.7, 128.0, 127.6, 121.8, 121.2, 119.1, 118.6, 111.4, 106.6, 65.7, 23.8; IR (KBr) ν: 3388, 2939, 1745, 1591, 1573, 1232, 737, 682 cm^－1; ESI-MS calcd for C₂₆H₂₁NO₃Na [M+Na]⁺ 418.1414; found 418.1411.

(E)-2-氧代-4-苯基丁-3-烯酸-2-(1-甲基-1H-吲哚-3-基)乙酯(3r):黄色固体, 收率53%. m.p. 80.4~81.3 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 7.77~7.68 (m, 3H), 7.63 (d, J＝3.2 Hz, 1H), 7.53~7.41 (m, 3H), 7.38 (d, J＝3.2 Hz, 1H), 7.28 (d, J＝7.2 Hz, 1H), 7.21 (s, 1H), 7.15 (t, J＝7.2 Hz, 1H), 7.03 (t, J＝6.8 Hz, 1H), 4.54 (t, J＝7.2 Hz, 2H), 3.70 (s, 3H), 3.15 (t, J＝6.8 Hz, 2H); ¹³C NMR (101 MHz, CDCl₃) δ: 183.9, 162.3, 148.0, 136.6, 133.8, 131.7, 129.2, 129.1, 127.7, 127.5, 121.4, 121.2, 118.5, 109.6, 109.1, 66.0, 32.2, 24.0; IR (KBr) ν: 3057, 2952, 1721, 1690, 1605, 1088, 733, 689 cm^－1; ESI-HRMS calcd for C₂₁H₁₉NO₃Na [M+Na]⁺ 356.1257, found 356.1262.

(E)-2-氧代-4-苯基丁-3-烯酸-2-(1-苄基-1H-吲哚-3-基)乙酯(3s):黄色固体, 收率64%. m.p. 94.1~95.1 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 7.79~7.60 (m, 4H), 7.56~7.35 (m, 5H), 7.21 (m, 6H), 7.10 (t, J＝7.6 Hz, 1H), 7.02 (t, J＝7.2 Hz, 1H), 5.34 (s, 2H), 4.56 (t, J＝6.4 Hz, 2H), 3.18 (t, J＝6.4 Hz, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.9, 162.3, 148.1, 138.3, 136.0, 133.8, 131.7, 129.2, 129.1, 128.5, 127.8, 127.3, 126.9, 121.4, 121.3, 118.9, 118.7, 110.2, 109.8, 65.9, 49.0, 24.1; IR (KBr) ν: 3070, 2961, 1692, 1605, 1284, 1073, 734, 686 cm^－1; ESI-HRMS calcd for C₂₇H₂₃NO₃Na [M+Na]⁺ 432.1570, found 432.1567.

(E)-2-氧代-4-(2-氟苯基)丁-3-烯酸-2-(1H-吲哚-3-基)乙酯(3t):黄色固体, 收率54%. m.p. 66.5~67.5 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.92 (s, 1H), 7.85~7.74 (m, 2H), 7.60 (d, J＝5.2 Hz, 1H), 7.52 (td, J＝7.2, 1.6 Hz, 1H), 7.38 (dd, J＝9.2, 2.4 Hz, 2H), 7.33~7.23 (m, 3H), 7.08 (t, J＝6.8 Hz, 1H), 6.99 (t, J＝7.6 Hz, 1H), 4.53 (t, J＝6.8 Hz, 2H), 3.16 (t, J＝6.8 Hz, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.1, 162.5, 161.8 (d, J＝253.4 Hz), 159.9, 139.2 (d, J＝2.7 Hz), 136.3, 133.7 (d, J＝9.1 Hz), 133.6, 130.1 (d, J＝2.0 Hz), 130.0, 127.2, 125.3, 125.2 (d, J＝3.4 Hz), 124.0, 123.5 (d, J＝6.3 Hz), 123.4, 121.6 (d, J＝11.0 Hz), 121.5, 121.1, 118.5, 118.3, 116.4, 116.2 (d, J＝21.6 Hz), 111.5, 109.8, 66.1, 24.2; ¹⁹F NMR (376 MHz, DMSO-d₆) δ: －114.3; IR (KBr) ν: 3404, 1736, 1607, 1485, 1291, 986, 791, 736 cm^－1; ESI-HRMS calcd for C₂₀H₁₆FNO₃Na [M+Na]⁺ 360.1006, found 360.1007.

(E)-2-氧代-4-(2-硝基苯基)丁-3-烯酸-2-(1H-吲哚-3-基)乙酯(3u):黄色固体, 收率52%. m.p. 86.1~87.1 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.93 (s, 1H), 8.08 (dd, J＝11.6, 3.2 Hz, 2H), 7.87 (d, J＝3.2 Hz, 1H), 7.78 (t, J＝7.2 Hz, 1H), 7.69 (t, J＝7.6 Hz, 1H), 7.61 (d, J＝2.8 Hz, 1H), 7.37 (d, J＝4.0 Hz, 1H), 7.32~7.22 (m, 2H), 7.08 (t, J＝7.2 Hz, 1H), 6.99 (t, J＝7.6 Hz, 1H), 4.54 (t, J＝6.8 Hz, 2H), 3.17 (t, J＝6.8 Hz, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.0, 161.6, 148.5, 142.4, 136.2, 134.1, 131.7, 129.3, 129.2, 127.1, 125.2, 124.9, 123.4, 121.1, 118.5, 118.3, 111.5, 109.7, 66.2, 24.1; IR (KBr) ν: 3394, 2960, 1734, 1518, 1282, 971, 822, 728 cm^－1; ESI-HRMS calcd for C₂₀H₁₆N₂O₅Na [M+Na]⁺ 387.0951, found 387.0946.

(E)-2-氧代-4-(3-甲基苯基)丁-3-烯酸-2-(1H-吲哚-3-基)乙酯(3v):棕色固体, 收率29%. m.p. 83.3~84.2 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.92 (s, 1H), 7.70~7.60 (m, 2H), 7.57~7.48 (m, 2H), 7.39~7.29 (m, 3H), 7.28~7.20 (m, 2H), 7.09 (t, J＝7.2 Hz, 1H), 6.99 (t, J＝7.6 Hz, 1H), 4.55 (t, J＝7.2 Hz, 2H), 3.16 (t, J＝6.8 Hz, 2H), 2.34 (s, 3H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 184.0, 162.4, 148.2, 138.4, 136.2, 133.6, 132.4, 129.5, 129.0, 127.1, 126.4, 123.3, 121.2, 121.0, 118.4, 118.2, 111.4, 109.7, 65.9, 24.1, 20.7; IR (KBr) ν: 3399, 2961, 1726, 1601, 1260, 995, 796, 737 cm^－1; ESI-HRMS calcd for C₂₁H₁₉NO₃Na [M+Na]⁺ 356.1257, found 356.1262.

(E)-2-氧代-4-(3-甲氧基苯基)丁-3-烯酸-2-(1H-吲哚- 3-基)乙酯(3w):橙黄色固体, 收率77%. m.p. 63.1~64.0 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.94 (s, 1H), 7.73 (d, J＝7.6 Hz, 1H), 7.63(d, J＝2.4 Hz, 1H), 7.42~7.27 (m, 6H), 7.11 (t, J＝7.2 Hz, 1H), 7.03 (dd, J＝11.2, 1.6 Hz, 2H), 4.57 (t, J＝6.4 Hz, 2H), 3.79 (s, 3H), 3.18 (t, J＝6.8 Hz, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 184.0, 162.5, 159.8, 148.1, 136.3, 135.0, 130.2, 127.3, 123.4, 121.8, 121.7, 121.2, 118.6, 118.4, 117.9, 113.8, 111.6, 109.9, 66.1, 55.3, 24.2; IR (KBr) ν: 3399, 1726, 1605, 1280, 992, 833, 738, 684 cm^－1; ESI-HRMS calcd for C₂₁H₁₉NO₄Na [M+Na]⁺ 372.1206, found 372.1208.

(E)-2-氧代-4-(3-氟苯基)丁-3-烯酸-2-(1H-吲哚-3-基)乙酯(3x):橙黄色固体, 收率58%. m.p. 124.5~125.3 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.94 (s, 1H), 7.81~7.20 (m, 9H), 7.09 (s, 1H), 7.00 (s, 1H), 4.56 (s, 2H), 3.17 (s, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.8, 163.7, 162.1 (d, J＝244.4 Hz), 161.2, 146.4, 136.3, 136.2 (d, J＝6.5 Hz), 131.1, 131.0 (d, J＝8.3 Hz), 127.2, 125.5, 123.4, 122.7, 121.1, 118.5, 118.4, 118.3 (d, J＝21.2 Hz), 118.2, 115.3, 115.1 (d, J＝22.1 Hz), 111.5, 109.8, 66.1, 24.2; ¹⁹F NMR (376 MHz, DMSO-d₆) δ: －112.3; IR (KBr) ν: 3340, 1725, 1607, 1272, 993, 832, 736, 675 cm^－1; ESI-HRMS calcd for C₂₀H₁₆FNO₃Na [M+Na]⁺ 360.1006, found 360.1002.

(E)-2-氧代-4-(3-氯苯基)丁-3-烯酸-2-(1H-吲哚-3-基)乙酯(3y):橙黄色固体, 收率30%. m.p. 138.1~139.0 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.92 (s, 1H), 7.87 (s, 1H), 7.75~7.64 (m, 2H), 7.61 (d, J＝2.8 Hz, 1H), 7.54 (d, J＝4.0 Hz, 1H), 7.51~7.40 (m, 1H), 7.38~7.32 (m, 2H), 7.25 (d, J＝2.4 Hz, 1H), 7.08 (t, J＝7.2 Hz, 1H), 6.98 (t, J＝7.2 Hz, 1H), 4.54 (t, J＝7.2 Hz, 2H), 3.16 (t, J＝6.8 Hz, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.9, 162.0, 146.1, 136.2, 136.0, 133.9, 131.1, 130.9, 128.7, 127.6, 127.1, 123.38, 122.8, 121.1, 118.4, 118.3, 111.5, 109.7, 66.0, 24.1; IR (KBr) ν: 3398, 2915, 1723, 1561, 1276, 993, 814, 736 cm^－1; ESI-HRMS calcd for C₂₀H₁₆ClNO₃Na [M+Na]⁺ 376.0711, found 376.0713.

(E)-2-氧代-4-(3-溴苯基)丁-3-烯酸-2-(1H-吲哚-3-基)乙酯(3z):橙黄色固体, 收率12%. m.p. 144.8~145.6 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.92 (s, 1H), 7.74 (d, J＝3.2 Hz, 1H), 7.67 (dd, J＝10.4, 6.0 Hz, 2H), 7.61 (d, J＝2.4 Hz, 1H), 7.41 (t, J＝7.6 Hz, 1H), 7.38~7.31 (m, 2H), 7.25 (d, J＝2.0 Hz, 1H), 7.08 (t, J＝7.2 Hz, 1H), 6.98 (t, J＝7.2 Hz, 1H), 4.54 (t, J＝7.2 Hz, 2H), 3.16 (t, J＝7.2 Hz, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.9, 162.1, 146.0, 136.2, 134.0, 131.6, 131.1, 127.9, 127.1, 123.4, 122.8, 122.4, 121.1, 118.4, 118.3, 111.5, 109.7, 66.0, 24.1; IR (KBr) ν: 3340, 2918, 1724, 1609, 1277, 993, 814, 737 cm^－1; ESI-HRMS calcd for C₂₀H₁₆BrNO₃Na [M+Na]⁺ 420.0206, found 420.0206.

(E)-2-氧代-4-(3-硝基苯基)丁-3-烯酸-2-(1H-吲哚-3-基)乙酯(3aa):橙黄色固体, 收率60%. m.p. 99.1~100.0 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.91 (s, 1H), 8.55 (s, 1H), 8.27 (d, J＝3.6 Hz, 1H), 8.14 (d, J＝5.6 Hz, 1H), 7.82 (d, J＝7.6 Hz, 1H), 7.70 (t, J＝8.0 Hz, 1H), 7.60 (d, J＝4.8 Hz, 1H), 7.43 (d, J＝10.0 Hz, 1H), 7.36 (d, J＝4.4 Hz, 1H), 7.26 (s, 1H), 7.07 (t, J＝7.2 Hz, 1H), 6.98 (t, J＝7.2 Hz, 1H), 4.56 (t, J＝6.8 Hz, 2H), 3.17 (t, J＝6.8 Hz, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.7, 161.9, 148.3, 145.1, 136.2, 135.5, 134.6, 130.5, 127.1, 125.5, 123.8, 123.7, 123.4, 121.1, 118.5, 118.3, 111.5, 109.7, 66.1, 24.2; IR (KBr) ν: 3396, 3085, 1724, 1536, 1207, 996, 815, 729 cm^－1; ESI-HRMS calcd for C₂₀H₁₆N₂O₅Na [M+Na]⁺ 387.0951, found 387.0935.

(E)-2-氧代-4-(3-三氟甲基苯基)丁-3-烯酸-2-(1H-吲哚-3-基)乙酯(3ab):橙黄色固体, 收率52%. m.p. 82.2~83.0 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.92 (s, 1H), 8.15 (s, 1H), 8.03 (d, J＝4.8 Hz, 1H), 7.88~7.76 (m, 2H), 7.67 (t, J＝8.0 Hz, 1H), 7.61 (d, J＝3.6 Hz, 1H), 7.44 (d, J＝6.8 Hz, 1H), 7.37 (d, J＝2.0 Hz, 1H), 7.26 (d, J＝0.8 Hz, 1H), 7.08 (t, J＝7.2 Hz, 1H), 6.98 (t, J＝7.2 Hz, 1H), 4.56 (t, J＝7.2 Hz, 2H), 3.17 (t, J＝7.2 Hz, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 184.4, 162.6, 146.4, 136.7, 135.3, 132.9, 130.6, 130.3, 128.1, 127.6, 126.4 (q, J＝6.1 Hz), 126.3, 125.7, 123.8, 123.7, 123.0, 121.5, 118.9, 118.7, 111.9, 110.1, 66.5, 24.6; ¹⁹F NMR (376 MHz, DMSO-d₆) δ: －61.3; IR (KBr) ν: 3408, 1726, 1604, 1260, 937, 812, 738, 693 cm^－1; ESI-HRMS calcd for C₂₁H₁₆F₃NO₃Na [M+Na]⁺ 410.0974, found 410.0978.

(E)-2-氧代-4-(4-氟苯基)丁-3-烯酸-2-(1H-吲哚-3-基)乙酯(3ac):橙黄色固体, 收率77%. m.p. 121.1~122.0 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.93 (s, 1H), 7.80 (s, 2H), 7.71 (d, J＝8.4 Hz, 1H), 7.61 (d, J＝4.8 Hz, 1H), 7.37 (d, J＝5.6 Hz, 1H), 7.31~7.20(m, 4H), 7.09 (t, J＝6.8 Hz, 1H), 6.99 (t, J＝6.8 Hz, 1H), 4.55 (t, J＝6.0 Hz, 2H), 3.16 (t, J＝6.0 Hz, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.9, 165.3 (d, J＝250.9 Hz), 162.8, 162.3, 146.8, 136.2, 131.7 (d, J＝8.8 Hz), 131.6, 130.4 (d, J＝3.0 Hz), 127.2, 123.4, 121.2, 121.1, 118.5, 118.3, 116.4, 116.1 (d, J＝22.0 Hz), 111.5, 109.7, 66.0, 24.2; ¹⁹F NMR (376 MHz, DMSO-d₆) δ: －107.8; IR (KBr) ν: 3399, 1722, 1693, 1598, 1241, 940, 858, 736 cm^－1; ESI-MS calcd for C₂₀H₁₆FNO₃Na [M+Na]⁺ 360.1006; found 360.1002.

(E)-2-氧代-4-(4-氯苯基)丁-3-烯酸-2-(1H-吲哚-3-基)乙酯(3ad):橙黄色固体, 收率47%. m.p. 134.5~135.5 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.92 (s, 1H), 8.05~7.17 (m, 9H), 7.08 (s, 1H), 6.99 (s, 1H), 4.54 (s, 2H), 3.16 (s, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.8, 162.1, 146.4, 136.2, 132.6, 130.8, 129.2, 127.1, 123.3, 122.0, 121.1, 118.4, 118.3, 111.5, 109.7, 66.0, 24.1; IR (KBr) ν: 3410, 3394, 1725, 1608, 1491, 998, 820, 737 cm^－1; ESI-HRMS calcd for C₂₀H₁₆ClNO₃Na [M+Na]⁺ 376.0711, found 376.0709.

(E)-2-氧代-4-(4-溴苯基)丁-3-烯酸-2-(1H-吲哚-3-基)乙酯(3ae):黄色固体, 收率51%. m.p. 148.3~149.2 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.93 (s, 1H), 7.64 (s, 6H), 7.48~7.20 (m, 3H), 7.09 (s, 1H), 7.00 (s, 1H), 4.55 (s, 2H), 3.16 (s, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.7, 162.1, 146.5, 136.2, 133.0, 132.1, 130.9, 127.1, 125.2, 123.3, 122.0, 121.1, 118.4, 118.3, 111.5, 109.7, 66.0, 24.1; IR (KBr) ν: 3441, 3407, 1729, 1605, 1486, 991, 828, 739 cm^－1; ESI-HRMS calcd for C₂₀H₁₆BrNO₃Na [M+Na]⁺ 420.0206, found 420.0205.

(E)-2-氧代-4-(4-硝基苯基)丁-3-烯酸-2-(1H-吲哚-3-基)乙酯(3af):黄色固体, 收率41%. m.p. 161.3~162.2 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.92 (s, 1H), 8.26 (d, J＝2.4 Hz, 2H), 7.98 (d, J＝4.4 Hz, 2H), 7.78 (d, J＝9.6 Hz, 1H), 7.61 (d, J＝2.4 Hz, 1H), 7.40 (dd, J＝26.0, 9.6 Hz, 2H), 7.27 (s, 1H), 7.08 (t, J＝6.8 Hz, 1H), 6.98 (t, J＝7.2 Hz, 1H), 4.55 (t, J＝6.4 Hz, 2H), 3.16 (t, J＝6.8 Hz, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.4, 161.7, 148.6, 144.4, 140.0, 136.2, 130.1, 127.2, 124.9, 124.0, 123.4, 121.1, 118.5, 118.3, 111.5, 109.7, 66.2, 24.1; IR (KBr) ν: 3436, 3401, 1729, 1510, 1256, 989, 852, 738 cm^－1; ESI-HRMS calcd for C₂₀H₁₇N₂O₅ [M+H]⁺365.1137, found 365.1133.

(E)-2-氧代-4-(4-三氟甲基苯基)丁-3-烯酸-2-(1H-吲哚-3-基)乙酯(3ag):黄色固体, 收率40%. m.p. 149.8~150.8 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.92 (s, 1H), 7.94 (d, J＝2.8 Hz, 2H), 7.78 (t, J＝8.4 Hz, 3H), 7.61 (d, J＝3.2 Hz, 1H), 7.38 (dd, J＝17.2, 0.8 Hz, 2H), 7.26 (d, J＝2.4 Hz, 1H), 7.08 (t, J＝7.2 Hz, 1H), 6.99 (t, J＝7.2 Hz, 1H), 4.55 (t, J＝7.2 Hz, 2H), 3.16 (t, J＝6.8 Hz, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.6, 161.9, 145.5, 137.7, 136.2, 131.0, 129.7, 127.1, 126.0, 125.9 (q, J＝5.5 Hz), 123.8, 123.4, 121.1, 118.5, 118.3, 111.5, 109.7, 66.1, 24.2; ¹⁹F NMR (376 MHz, DMSO-d₆) δ: －61.4; IR (KBr) ν: 3398, 2359, 1732, 1614, 1259, 992, 839, 744 cm^－1; ESI-HRMS calcd for C₂₁H₁₆F₃NO₃Na [M+Na]⁺ 410.0974, found 410.0971.

(E)-2-氧代-4-([1, 1'-联苯基]-4-基)丁-3-烯酸-2-(1H-吲哚-3-基)乙酯(3ah):黄色固体, 收率30%. m.p. 161.8~162.7 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.94(s, 1H), 7.77 (dt, J＝24.2, 8.4 Hz, 7H), 7.63 (d, J＝2.8 Hz, 1H), 7.49 (t, J＝7.2 Hz, 2H), 7.45~7.36 (m, 2H), 7.29 (dd, J＝17.6, 1.2 Hz, 2H), 7.10 (t, J＝6.8 Hz, 1H), 7.00 (t, J＝7.2 Hz, 1H), 4.56 (t, J＝7.2 Hz, 2H), 3.18 (t, J＝6.8 Hz, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.9, 162.4, 147.6, 143.1, 139.0, 136.3, 132.9, 130.0, 129.1, 128.3, 127.2, 127.1, 126.8, 123.4, 121.2, 121.1, 118.0, 118.3, 111.5, 109.8, 66.0, 24.2; IR (KBr) ν: 3422, 2918, 1729, 1553, 1082, 990, 801, 737 cm^－1; ESI-HRMS calcd for C₂₆H₂₂NO₃ [M+H]⁺ 396.1599, found 396.1586.

(E)-2-氧代-4-(4-异丙基苯基)丁-3-烯酸-2-(1H-吲哚- 3-基)乙酯(3ai):黄色固体, 收率24%. m.p. 85.4~86.2 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.93 (s, 1H), 7.77~7.54 (m, 4H), 7.47~7.16 (m, 5H), 7.09 (t, J＝7.2 Hz, 1H), 6.99 (t, J＝7.6 Hz, 1H), 4.55 (t, J＝6.8 Hz, 2H), 3.16 (t, J＝6.8 Hz, 2H), 2.95~2.87 (m, 1H), 1.20 (d, J＝6.8 Hz, 6H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 184.0, 162.5, 152.8, 148.2, 136.3, 131.5, 129.4, 127.2, 123.4, 121.1, 120.5, 118.4, 118.3, 111.5, 109.8, 66.0, 33.5, 24.2, 23.5; IR (KBr) ν: 3327, 2956, 1733, 1597, 1255, 973, 830, 740 cm^－1; ESI-HRMS calcd for C₂₃H₂₃NO₃Na [M+Na]⁺ 384.1570, found 384.1569.

(E)-2-氧代-4-(4-氰基苯基)丁-3-烯酸-2-(1H-吲哚-3-基)乙酯(3aj):橙黄色固体, 收率48%. m.p. 126.5~127.4 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.90 (s, 1H), 7.87 (s, 4H), 7.72 (d, J＝8.4 Hz, 1H), 7.60 (d, J＝4.8 Hz, 1H), 7.46~7.33 (m, 2H), 7.26 (s, 1H), 7.08 (t, J＝7.2 Hz, 1H), 6.99 (t, J＝7.6 Hz, 1H), 4.55 (t, J＝6.8 Hz, 2H), 3.16 (t, J＝6.4 Hz, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.5, 161.8, 145.2, 138.1, 136.2, 132.8, 129.6, 127.2, 124.3, 123.4, 121.1, 118.5, 118.3, 113.2, 111.5, 109.7, 66.2, 24.1; IR (KBr) ν: 3385, 2957, 1728, 1615, 1068, 980, 829, 745 cm^－1; ESI-HRMS calcd for C₂₁H₁₉N₂O₃Na [M+Na]⁺ 367.1053, found 367.1037.

(E)-2-氧代-4-(2, 4-二氯苯基)丁-3-烯酸-2-(1H-吲哚- 3-基)乙酯(3ak):橙黄色固体, 收率28%. m.p. 57.8~58.8 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.02 (s, 1H), 7.97 (d, J＝8.0 Hz, 1H), 7.47 (d, J＝4.0 Hz, 1H), 7.35 (d, J＝2.4 Hz, 1H), 7.26 (s, 1H), 7.17 (d, J＝3.6 Hz, 1H), 7.10~6.98 (m, 3H), 6.95 (t, J＝7.2 Hz, 1H), 6.89 (s, 1H), 4.42 (t, J＝6.8 Hz, 2H), 3.06 (t, J＝6.8 Hz, 2H); ¹³C NMR (101 MHz, CDCl₃) δ: 182.5, 161.9, 142.5, 137.7, 136.8, 136.3, 130.8, 130.3, 128.7, 127.8, 127.4, 123.0, 122.6, 122.2, 119.6, 118.7, 111.4, 111.1, 66.7, 24.6; IR (KBr) ν: 3417, 1738, 1581, 1228, 1091, 970, 801, 739 cm^－1; ESI-HRMS calcd for C₂₀H₁₅Cl₂NO₃Na [M+Na]⁺ 410.0321, found 410.0321.

(E)-2-氧代-4-(2, 6-二氯苯基)丁-3-烯酸-2-(1H-吲哚- 3-基)乙酯(3al):橙黄色固体, 收率62%. m.p. 83.4~84.4 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.90 (s, 1H), 7.74 (d, J＝8.4 Hz, 1H), 7.57 (d, J＝5.2 Hz, 3H), 7.50~7.30 (m, 3H), 7.24 (d, J＝2.8 Hz, 1H), 7.05 (t, J＝8.0 Hz, 1H), 6.96 (t, J＝7.6 Hz, 1H), 4.52 (t, J＝7.2 Hz, 2H), 3.14 (t, J＝6.8 Hz, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 182.7, 161.2, 139.7, 136.2, 134.4, 131.7, 130.8, 129.4, 129.0, 127.1, 123.4, 121.0, 118.4, 118.2, 111.4, 109.7, 66.2, 24.1; IR (KBr) ν: 3355, 2918, 1744, 1609, 1303, 1092, 957, 739 cm^－1; ESI-HRMS calcd for C₂₀H₁₅Cl₂NO₃- Na [M+Na]⁺ 410.0321, found 410.0322.

(E)-2-氧代-4-(3-溴-4-氯苯基)丁-3-烯酸-2-(1H-吲哚-3-基)乙酯(3am):黄色固体, 收率65%. m.p. 129.7~130.7 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.10 (s, 1H), 7.77 (d, J＝1.2 Hz, 1H), 7.64 (d, J＝5.6 Hz, 1H), 7.60 (d, J＝8.0 Hz, 1H), 7.46 (d, J＝4.8 Hz, 1H), 7.41~7.33 (m, 2H), 7.23~7.07 (m, 4H), 4.60 (t, J＝7.2 Hz, 2H), 3.24 (t, J＝6.8 Hz, 2H); ¹³C NMR (101 MHz, CDCl₃) δ: 182.6, 162.0, 145.4, 137.6, 136.3, 134.2, 133.8, 131.0, 128.5, 127.4, 123.5, 122.6, 122.4, 122.2, 119.9, 118.8, 111.4, 24.7; IR (KBr) ν: 3408, 1714, 1689, 1605, 1090, 997, 806, 779 cm^－1; ESI-HRMS calcd for C₂₀H₁₅BrClNO₃Na [M+Na]⁺ 453.9816, found 453.9819.

(E)-2-氧代-4-(3, 4-二甲基苯基)丁-3-烯酸-2-(1H-吲哚-3-基)乙酯(3an):黄色固体, 收率41%. m.p. 129.5~129.4 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.92 (s, 1H), 7.63 (d, J＝9.6 Hz, 2H), 7.51 (s, 1H), 7.44 (d, J＝4.0 Hz, 1H), 7.37 (d, J＝2.0 Hz, 1H), 7.22 (dd, J＝12.4 3.6 Hz, 3H), 7.08 (s, 1H), 6.99 (s, 1H), 4.54 (s, 2H), 3.16 (s, 2H), 2.25 (s, 6H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.9, 162.4, 147.6, 143.1, 139.0, 136.3, 132.9, 130.0, 129.1, 128.3, 127.2, 127.1, 126.8, 123.4, 121.2, 121.1, 118.0, 118.3, 111.5, 109.8, 66.0, 24.2; IR (KBr) ν: 3419, 2920, 1729, 1595, 1266, 1084, 877, 734 cm^－1; ESI-HRMS calcd for C₂₂H₂₁NO₃Na [M+Na]⁺ 370.1414, found 370.1427.

(E)-2-氧代-4-(3, 5-二氟苯基)丁-3-烯酸-2-(1H-吲哚-3-基)乙酯(3ao):橙黄色固体, 收率41%. m.p. 146.5~146.4 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.92 (s, 1H), 7.82~7.47 (m, 4H), 7.39 (d, J＝10.0 Hz, 3H), 7.25 (s, 1H), 7.07 (s, 1H), 6.98 (s, 1H), 4.54 (s, 2H), 3.16 (s, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.8, 163.7 (d, J＝259.9 Hz), 161.9 (d, J＝246.7 Hz), 161.3, 145.0, 137.4 (t, J＝9.7 Hz), 136.2, 127.1, 124.0, 123.4, 121.1, 118.4 (d, J＝15.9 Hz), 118.3, 112.2, 112.0 (d, J＝25.9 Hz), 111.5, 109.7, 106.8, 106.6 (t, J＝26.6 Hz), 106.3, 66.0, 24.1; ¹⁹F NMR (376 MHz, CDCl₃) δ: －108.5; IR (KBr) ν: 3398, 3119, 1722, 1589, 1260, 855, 737, 626 cm^－1; ESI-HRMS calcd for C₂₀H₁₅F₂NO₃Na [M+Na]⁺ 378.0912, found 378.0897.

(E)-2-氧代-4-(噻吩-2-基)丁-3-烯酸-2-(1H-吲哚-3-基)乙酯(3ap):棕色固体, 收率68%. m.p. 102.1~103.0 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.94 (s, 1H), 7.94 (d, J＝7.6 Hz, 1H), 7.84 (d, J＝0.8 Hz, 1H), 7.63 (dd, J＝5.2, 1.6 Hz, 2H), 7.39 (d, J＝5.2 Hz, 1H), 7.26 (d, J＝1.2 Hz, 1H), 7.23~7.16 (m, 1H), 7.10 (t, J＝7.2 Hz, 1H), 7.00 (dd, J＝10.8, 4.0 Hz, 2H), 4.54 (t, J＝6.8 Hz, 2H), 3.16 (t, J＝7.2 Hz, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 182.8, 162.1, 140.4, 139.1, 136.3, 134.7, 132.3, 129.1, 127.2, 123.4, 121.1, 119.4, 118.5, 118.3, 111.5, 109.8, 66.0, 24.2; IR (KBr) ν: 3411, 3398, 1596, 1322, 1096, 984, 736, 695 cm^－1; ESI-HRMS calcd for C₁₈H₁₅NO₃S [M+Na]⁺ 348.0665, found 348.0667.

(E)-2-氧代-4-(呋喃-2-基)丁-3-烯酸-2-(1H-吲哚-3-基)乙酯(3aq):黄色固体, 收率68%. m.p. 64.9~65.8 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.93 (s, 1H), 7.92 (s, 1H), 7.59 (dd, J＝12.4, 4.4 Hz, 2H), 7.40 (d, J＝3.2 Hz, 1H), 7.26 (s, 1H), 7.10 (t, J＝7.6 Hz, 2H), 7.02 (dd, J＝6.8, 3.6 Hz, 2H), 6.68 (s, 1H), 4.53 (t, J＝6.8 Hz, 2H), 3.16 (t, J＝6.8 Hz, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 182.7, 162.1, 150.5, 147.6, 136.3, 133.5, 127.2, 123.4, 121.2, 119.7, 118.6, 118.4, 117.8, 113.7, 111.6, 109.9, 66.1, 24.2; IR (KBr) ν: 3397, 1728, 1606, 1261, 1095, 986, 738, 686 cm^－1; ESI-HRMS calcd for C₁₈H₁₅NO₄Na [M+Na]⁺ 332.0893, found 332.0895.

(E)-2-氧代-4-(萘-2-基)丁-3-烯酸-2-(1H-吲哚-3-基)乙酯(3ar):黄色固体, 收率18%. m.p. 175.9~176.8 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.96 (s, 1H), 8.19 (s, 1H), 8.01~7.90 (m, 3H), 7.86 (dd, J＝6.8, 0.8 Hz, 2H), 7.64 (d, J＝3.6 Hz, 1H), 7.62~7.53 (m, 2H), 7.40 (dd, J＝6.0, 2.8 Hz, 2H), 7.29 (d, J＝2.0 Hz, 1H), 7.11 (t, J＝7.6 Hz, 1H), 7.01 (t, J＝7.6 Hz, 1H), 4.59 (t, J＝7.2 Hz, 2H), 3.20 (t, J＝6.8 Hz, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 182.8, 162.1, 140.4, 139.1, 136.3, 134.7, 132.3, 129.1, 127.2, 123.4, 121.1, 119.4, 118.5, 118.3, 111.5, 109.8, 66.0, 24.2; IR (KBr) ν: 3427, 2922, 1730, 1685, 1604, 1080, 827, 736 cm^－1; ESI-HRMS calcd for C₂₄H₁₉NO₃Na [M+Na]⁺ 392.1257, found 392.1257.

2-(1H-吲哚-3-基)乙基(3E, 5E)-2-氧代-6-苯基六-3, 5-二烯酸酯(3as):黄色固体, 收率60%. m.p. 131.6~132.5 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 10.93 (s, 1H), 7.74~6.94 (m, 13H), 6.76 (d, J＝9.2 Hz, 1H), 4.52 (s, 2H), 3.14 (s, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ: 183.7, 162.4, 148.6, 144.3, 136.2, 135.6, 129.8, 129.0, 127.7, 127.1, 127.0, 124.5, 123.3, 121.0, 118.4, 118.3, 111.4, 109.7, 65.8, 24.1; IR (KBr) ν: 3406, 1727, 1581, 1260, 1077, 1016, 896, 741 cm^－1; ESI-HRMS calcd for C₂₂H₁₉NO₃Na [M+Na]⁺ 368.1257, found 368.1248.

辅助材料(Supporting Information)化合物3a~3as的¹H NMR, ¹³C NMR以及¹⁹F NMR原始谱图.这些材料可以免费从本刊网站(http://sioc-journal.cn/)上下载.

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Scheme 1 酮酸色醇酯类化合物的合成

Scheme 1 Synthesis of α-keto tryptophol ester compounds

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表 1 优化反应条件^a

Table 1. Optimization of reaction conditions


Entry	Condensation reagents	Solvent	Yield^b/%
1	DCC/DMAP	DCM	nr
2^c	DCC/DMAP	DCM	nr
3	EDCI/HOBt	THF	45
4^d	EDCI/HOBt	THF	65
5^e	EDCI/HOBt	THF	63
^a Unless otherwise indicated, all reactions were carried out with tryptol 1a (3 mmol), phenyl unsaturated keto acid 2a (3 mmol) and DCC (6 mmol)/DMAP (10 mol%) or EDCI (6 mmol)/HOBt (6 mmol) in corresponding solvent (25 mL) at 25 ℃ for 6 h. ^b Isolated product after column chromatography. ^c Reflux at 50 ℃. ^d 1a (4.8 mmol) was used. ^e 1a (4.8 mmol) was used, reflux at 80 ℃.

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表 2 反应底物1普适性的考察^a

Table 2. Investigation on the universality of reaction substrate 1


Entry	3	R¹	R²	R³	Yield^b/%
1	3b	4-CH₃	H	H	80
2	3c	4-Cl	H	H	44
3	3d	4-Br	H	H	67
4	3e	5-CH₃	H	H	43
5	3f	5-OCH₃	H	H	42
6	3g	5-F	H	H	43
7	3h	5-Cl	H	H	45
8	3i	5-Br	H	H	50
9	3j	6-CH₃	H	H	74
10	3k	6-F	H	H	37
11	3l	6-Cl	H	H	16
12	3m	6-Br	H	H	52
13	3n	7-CH₃	H	H	68
14	3o	4, 7-Cl₂	H	H	26
15	3p	H	2-CH₃	H	42
16	3q	H	2-Ph	H	59
17	3r	H	H	N-CH₃	53
18	3s	H	H	N-Bn	64
^a Unless otherwise indicated, all reactions were carried out with 1 (4.8 mmol), 2a (3 mmol), EDCI (6 mmol), HOBt (6 mmol) in THF (25 mL) at 25 ℃ for 6 h. ^b Isolated product after column chromatography.

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表 3 反应底物2普适性的考察^a

Table 3. Investigation on the universality of reaction substrate 2


Entry	3	Ar	Yield^b/%
1	3t	2-FC₆H₄	54
2	3u	2-NO₂C₆H₄	52
3	3v	3-MeC₆H₄	39
4	3w	3-OMeC₆H₄	77
5	3x	3-FC₆H₄	58
6	3y	3-ClC₆H₄	30
7	3z	3-BrC₆H₄	12
8	3aa	3-NO₂C₆H₄	60
9	3ab	3-CF₃C₆H₄	52
10	3ac	4-FC₆H₄	77
11	3ad	4-ClC₆H₄	47
12	3ae	4-BrC₆H₄	51
13	3af	4-NO₂C₆H₄	41
14	3ag	4-CF₃C₆H₄	40
15	3ah	4-PhC₆H₄	30
16	3ai	4-ⁱPrC₆H₄	45
17	3aj	4-CNC₆H₄	48
18	3ak	2, 4-Cl₂C₆H₃	38
19	3al	2, 6-Cl₂C₆H₃	62
20	3am	3-Br-4-ClC₆H₃	65
21	3an	3, 4-Me₂C₆H₃	41
22	3ao	3, 5-F₂C₆H₃	41
23	3ap	2-Furyl	68
24	3aq	2-Furyl	68
25	3ar	2-Naphthyl	33
26	3as	Cinnamyl	60
^a Unless otherwise indicated, all reactions were carried out with 1a (4.8 mmol), 2 (3 mmol), EDCI (6 mmol), HOBt (6 mmol) in THF (25 mL) at 25 ℃ for 6 h. ^b Isolated product after column chromatography.

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