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2025 , Vol. 45 >Issue 7: 2552 - 2565

DOI: https://doi.org/10.6023/cjoc202410010

研究论文

Brønsted碱促进的o-羟基席夫碱与乙烯基磺酰氟通过Michael-Mannich-SuFEx串联反应构建磺基色烯并[4,3‑b]吡咯烷化合物

  • 张放 a ,
  • 谢佩 a ,
  • 张启超 a ,
  • 武磊芳 , b, * ,
  • 何林 a ,
  • 杜广芬 , a, *
展开
  • a 石河子大学化学化工学院 化工绿色过程省部共建国家重点实验室培育基地 新疆石河子 832000
  • b 石河子大学分析测试中心 新疆石河子 832000

收稿日期: 2024-11-27

  修回日期: 2024-12-11

  网络出版日期: 2025-01-20

基金资助

新疆天山英才计划(2023TSYCCX0122)

石河子大学国际合作(GJHZ202204)

石河子大学引导(2022ZD021)

石河子大学引导(2022ZD067)

收起

Brønsted Base-Catalyzed Assembly of Sulfochromeno[4,3-b]-pyrrolidines via Michael-Mannich-SuFEx Tandem Reaction of o-Hydroxy Schiff Bases and Vinylsulfonyl Fluorides

  • Fang Zhang a ,
  • Pei Xie a ,
  • Qichao Zhang a ,
  • Leifang Wu , b, * ,
  • Lin He a ,
  • Guangfen Du , a, *
Expand
  • a School of Chemistry and Chemical Engineering, Shihezi University/State Key Laboratory Incubation Base for Green Processing of Chemical Engineering, Shihezi, Xinjiang 832000
  • b Analysis and Testing Center of Shihezi University, Shihezi, Xinjiang 832000
*E-mail: ;

Received date: 2024-11-27

  Revised date: 2024-12-11

  Online published: 2025-01-20

Supported by

Tianshan Talent Research Project of Xinjiang(2023TSYCCX0122)

International Cooperation Project of Shihezi University(GJHZ202204)

Guidance Project of Shihezi University(2022ZD021)

Guidance Project of Shihezi University(2022ZD067)

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摘要

介绍了一种在温和条件下通过Michael-Mannich-SuFEx串联反应高效合成磺基色烯并[4,3-b]吡咯化合物的方法. 使用o-羟基席夫碱与2-取代乙烯基磺酰氟作为底物, 产率高达99%, 非对映选择性超过95∶5, 共合成了37种目标化合物. 19F NMR监测和密度泛函理论(DFT)研究显示, 该反应经历了Michael-Mannich-SuFEx三个阶段. 抑菌测试表明, 部分化合物对金黄壳囊孢菌有一定抑制作用.

关键词： 点击反应; 乙烯基磺酰氟; o-羟基席夫碱; 磺基色烯并[4,3‑b]吡咯烷

本文引用格式

张放 , 谢佩 , 张启超 , 武磊芳 , 何林 , 杜广芬 . Brønsted碱促进的o-羟基席夫碱与乙烯基磺酰氟通过Michael-Mannich-SuFEx串联反应构建磺基色烯并[4,3‑b]吡咯烷化合物[J]. 有机化学, 2025 , 45(7) : 2552 -2565 . DOI: 10.6023/cjoc202410010

Abstract

A method for the efficient synthesis of sulfochromeno[4,3-b]pyrrole compounds through the Michael-Mannich- SuFEx tandem reaction under mild conditions is introduced. Using o-hydroxy Schiff base and 2-substituted vinylsulfonyl fluoride as substrates, the yield was as high as 99%, the diastereoselectivity exceeded 95:5, and a total of 37 target compounds were synthesized. 19F NMR monitoring and density functional theory (DFT) studies showed that the reaction went through three stages of Michael-Mannich-SuFEx. Antibacterial tests show that some compounds have inhibitory effects on Cytospora chrysosperma.

Key words： SuFEx chemsitry; vinylsulfonyl fluoride; o-hydroxy Schiff base; sulfochromeno[4,3-b]pyrrolidines

多取代吡咯烷类化合物是一类重要的氮杂环化合物, 广泛存在于天然产物和生物活性分子中, 尤其是α-芳基吡咯烷类化合物, 因其普遍存在于天然产物[1]和药物化合物[2]中, 在药物合成领域备受青睐. 例如, BIRZ227[3]被确定为白三烯生物合成抑制剂, 是治疗哮喘、关节炎、炎症性肠病和牛皮癣等炎症性疾病的潜在治疗剂(图1, a). 拉罗替尼[4]是一种高度选择性的神经营养蛋白受体激酶抑制剂, 被批准用于治疗含有神经营养蛋白受体(NTRK)基因融合的肿瘤(图1, b). 阿提卡普兰[2b]是一种高效的κ-阿片受体拮抗剂, 可有效治疗抑郁症和焦虑症(图1, c). 磺基色烯衍生物d[5]则是人类碳酸酐酶抑制剂(图1, d). 在过去十几年中, 色烯并[4,3-b]吡咯烷类药物分子在有机合成[6]和药物化学[7]领域受到广泛关注, 然而作为生物电子等排体的磺基色烯并[4,3-b]吡咯烷[8]尚未得到深入研究. 考虑到α-芳基吡咯烷和磺基色烯的重要性, 开发合成吡咯烷稠合磺基色烯的有效方法对药物发现至关重要.
图1 具有生物活性的α-芳基吡咯烷和磺基香豆素衍生物

Figure 1 Biologically active α-arylpyrrolidine and sulfocoumarin derivatives

经过多年的发展, 硫氟交换(SuFEx)点击化学[9]已成为模块化合成磺酸酯和磺酰胺类化合物的强大工具, 其中2-取代乙烯基磺酰氟[10]作为SuFEx反应的重要反应链接子, 为磺酸内酯的合成提供了一条简单高效的途径. 基于对SuFEx点击化学和有机硫化物合成[11]的深入研究, 我们发现氨基丙二酸酯衍生的o-羟基席夫碱[6,12]在Brønsted碱催化下与乙烯基磺酰氟反应, 可高效合成磺基色烯并[4,3-b]吡咯烷类化合物(Scheme 1a)[11b]. 基于此研究, 设想通过苄胺衍生的o-羟基席夫碱与乙烯基磺酰氟反应生成α-芳基取代的磺基色烯并[4,3-b]吡咯烷衍生物. 在前期研究中发现苄基胺衍生的o-羟基席夫碱与乙烯基磺酰氟不反应, 推测可能是苄位氢原子酸性不够导致的. 因此, 通过调节苄胺苯环取代基电性, 使其通过串联反应与乙烯基磺酰氟生成α-芳基取代的磺基色烯并[4,3-b]吡咯烷(Scheme 1b). 在此, 将详细介绍这一研究工作的结果.
图式1 o-羟基席夫碱与乙烯基磺酰氟参与的反应

Scheme 1 Reaction involving o-hydroxy Schiff base and vinylsulfonyl fluoride

1 结果与讨论

首先基于Hirshfeld电荷分析[13]对o-羟基席夫碱的苄基碳(C8)氢原子的酸性进行了系统筛选(表1). 结果显示, 未取代的苄基碳与乙烯基磺酰氟反应时, 未监测到目标产物的生成(表1, Entry 1), 而带有供电子基团4-甲氧基的苄基碳由于酸性不足, 也未能进行反应(表1, Entry 2). 接着, 在苄基的对位引入三氟甲基、氰基和硝基三种拉电子官能团, 随着拉电子能力的增强, 反应效果逐渐改善(表1, Entries 3~5). 2,4,6-三氟和2,3,4,5,6-五氟取代的苄基碳未能顺利进行(表1, Entries 6, 7). 此外, 使用3,5-(CF3)2取代的苄基碳与乙烯基磺酰氟进行串联反应时反应较为复杂, 未能分离出目标产物(表1, Entry 8).
表1 o-羟基席夫碱的筛选a

Table 1 Screening of o-hydroxy Schiff bases

Entry Ar1 Hirshfeld
charge		 Yieldb/% drc
1 Ph 0.0737 N.D.d —
2 4-MeOC6H4 0.0733 N.D.d —
3 4-CF3C6H4 0.0755 <10% —
4 4-CNC6H4 0.0763 <10% —
5 4-NO2C6H4 0.0767 56 83∶17
6 2,4,6-F3C6H2 0.0698 N.D.d —
7 2,3,4,5,6-F5C6 0.0738 N.D.d —
8 3,5-(CF3)2C6H3 0.0774 Complex —

a Reaction conditions: 1 (0.20 mmol), 2h (0.20 mmol), Et3N (20 mol%), 4 Å MS (200 mg), MeCN (2.0 mL), r.t., 48 h, atmosphere. b Determined by 1H NMR using CH2Br2 as the internal standard. c Diastereomeric ratio determined by 1H NMR spectroscopy. d N.D.=Not detected.

选取p-NO2苄胺衍生的o-羟基席夫碱(1a)和p-甲基苯乙烯基磺酰氟(2h)作为模板反应底物, 用20 mol% Et3N作为催化剂, 4 Å分子筛作为添加剂, 在室温下反应48 h, 成功获得目标产物3h, 产率为56%, dr 83∶17. 在此基础上对反应条件进行优化, 首先筛选不同种类的碱(表2, Entries 1~5). 当用N,N-二异丙基乙胺(DIPEA)时, 可以中等收率和中等非对映选择性获得目标产物(表2, Entry 2); 当用碱性较强的1,8-二氮杂二环[5.4.0]十一碳-7-烯(DBU)或1,5-二氮杂二环[4.3.0]壬-5-烯(DBN)时, 分别以92%, 89%的收率和94∶6, 91∶9的非对映选择性得到目标产物(表2, Entries 3, 4); 但用无机碱Cs2CO3时, 仅得到31%的产率(表2, Entry 5). 接下来, 选择DBU作为最优催化剂, 对反应溶剂进行了筛选(表2, Entries 6-12), 结果显示, 当使用极性溶剂二甲基亚砜(DMSO)和N,N-二甲基甲酰胺(DMF)时, 产率都能达到90%以上, dr>95∶5(表2, Entries 6, 7); 当使用二氯甲烷(DCM)和四氢呋喃(THF)作为溶剂时, 仅能以中等收率获得目标产物(表2, Entries 8, 9); 当使用醇类溶剂甲醇或乙醇时, 产率仅为21%~34%, 且非对映选择性较差(表2, Entries 10, 11); 当使用水作溶剂时, 反应无法进行(表2, Entry 12). 接下来对DBU和分子筛的用量进行了研究, 减少DBU的用量至10 mol%时, 产率下降到66%(表2, Entry 13). 在没有DBU的情况下, 反应无法进行, 表明碱作为催化剂是必不可少的(表2, Entry 14). 当不使用分子筛时, 反应能进行但产率仅为40%, dr>95∶5, 且存在大量副反应(表2, Entry 15), 表明反应过程中生成的HF未能被及时吸收, 导致反应终止; 使用100 mg分子筛时, 目标产物的产率提高至92%(表2, Entry 16). 进一步空白实验表明, 若不使用DBU和分子筛, 反应无法进行(表2, Entry 17). 最终确定表2中的Entry 6为最优反应条件.
表2 反应条件优化a

Table 2 Optimization of reaction conditions

Entry Base Solvent Yieldb/% drc
1 Et3N MeCN 56 83∶17
2 DIPEA MeCN 42 92∶8
3 DBU MeCN 92 94∶6
4 DBN MeCN 89 91∶9
5 Cs2CO3 MeCN 31 90∶10
6 DBU DMSO 99 (99)d >95∶5
7 DBU DMF 94 >95∶5
8 DBU DCM 41 85∶15
9 DBU THF 57 93∶7
10 DBU MeOH 21 51∶49
11 DBU EtOH 34 56∶44
12 DBU H2O Trace —
13e DBU DMSO 66 >95∶5
14f — DMSO N.D.j —
15g DBU DMSO 40 >95∶5
16h DBU DMSO 92 >95∶5
17i — DMSO N.D.j —

a Reaction conditions: 1a (0.20 mmol), 2h (0.20 mmol), base (20 mol%), 4 Å MS (200 mg), solvent (2.0 mL), r.t., 48 h, atmosphere, PNP=p-nitrophenyl. b Determined by 1H NMR using CH2Br2 as the internal standard. c Diastereomeric ratio determined by 1H NMR spectroscopy. d Isolated yield. e DBU (10 mol%) was used. f Without DBU. g Without 4 Å MS. h 4 Å MS (100 mg) was used. i Without DBU and 4 Å MS. j N.D.=Not detected.

在确定了最优反应条件后, 对反应底物的普适性进行了研究, 如表3所示. 首先, 考察了2-取代乙烯基磺酰氟苯环上的取代基对反应的影响(3a~3t). 结果表明, 无论苯环上含有拉电子基团还是给电子基团, 都能以高产率(90%~99%)和高非对映选择性(dr>95∶5)获得目标产物(3a~3q). 二取代的苯乙烯基磺酰氟与o-羟基席夫碱1a反应时, 也能以92%的收率获得目标产物(3r). 同样, 当使用大位阻1-萘基取代的乙烯基磺酰氟与1a反应时, 产物3s同样具有优异的分离产率和非对映选择性. 2-噻吩取代的乙烯基磺酰氟与1a进行串联反应时, 也能够以90%的产率获得产物3t. 在DMSO中培养了3j的单晶, 并进行了X射线衍射实验以确定其结构和相对构型[14].
表3 2-取代乙烯基磺酰氟普适性研究a

Table 3 Scope of 2-substituted vinylsulfonyl fluorides

a Reaction conditions: 1a (0.20 mmol), 2 (0.20 mmol), DBU (20 mol%), 4 Å MS (200 mg), DMSO (2.0 mL), r.t., 48 h, atmosphere. Diastereomeric ratio determined by 1H NMR spectroscopy, all of the case dr>95∶5. Isolated yield.

此外, 对o-羟基席夫碱的底物范围进行了研究(表4). 结果表明, 无论在o-羟基席夫碱的苯环3、4、5、6位引入拉电子基团还是供电子基团, 均能很好地与苯乙烯基磺酰氟2a发生串联反应, 以91%~99%的产率, dr>95∶5非对映选择性生成目标产物(3u~3ag). 二取代的o-羟基席夫碱同样能与2a顺利反应(3ah~3aj), 然而使用乙烯基磺酰氟(ESF)进行该串联反应时, 由于ESF的活性太高, 反应比较复杂, 并不能很好地分离出目标产物(3ak). 另外, o-氨基席夫碱1al与2a的反应复杂, 也未能成功得到目标产物(3al). 有趣的是, o-羟基苯乙酮衍生的席夫碱1am与2a反应, 能够以97%的产率和dr>95∶5的非对映选择性顺利生成目标产物3am. 在DMSO中培养了3am的单晶, 并进行了X射线衍射实验以确定其结构和相对构型[14].
表4 o-羟基席夫碱普适性研究a

Table 4 Scope of o-hydroxy Schiff bases

a Reaction conditions: 1 (0.20 mmol), 2a (0.20 mmol), DBU (20 mol%), 4 Å MS (200 mg), DMSO (2.0 mL), r.t., 48 h, atmosphere; diastereomeric ratio determined by 1H NMR spectroscopy, all of the case dr>95∶5. Isolated yield.

为了探讨这种串联反应的实用性, 开展了3a的克级合成实验. 如Scheme 2所示, 以o-羟基席夫碱1a (4.0 mmol)和2a (4.0 mmol)为反应底物, 在最优条件下成功获得1.176 g产物3a. 该产物作为高效有机小分子催化剂, 能够催化丙酮与靛红之间的aldol反应[12h]. 为验证磺基色烯并[4,3-b]吡咯烷在抑菌方面的应用, 采用菌丝生长速率法对3a~3v进行了抑菌活性测试(表5). 结果显示, 3a, 3e~3g和3o对金黄壳囊孢菌(Cytospora chrysosperma)的生长具有一定的抑制作用, 进一步证明磺基色烯并[4,3-b]吡咯烷具有一定的抗菌活性.
图式2 克级反应及应用

Scheme 2 Gram-level reactions and applications

表5 抑金黄壳囊孢菌活性测试a

Table 5 Antifungal activity test of C. chrysosporium

Compd. Inhibitory
rate±SD/%		 Compd. Inhibitory
rate±SD/%
3a 65.1±2.3 3l 43.1±7.1
3b 60.9±6.4 3m 45.3±3.2
3c 48.3±2.3 3n 61.4±4.1
3d 58.9±2.3 3o 77.0±2.6
3e 64.5±1.8 3p 45.2±2.3
3f 76.8±4.7 3q 40.4±7.7
3g 63.5±7.7 3r 23.3±3.2
3h 58.4±3.8 3s 53.3±3.8
3i 59.1±4.0 3t 31.4±3.5
3j 48.2±3.2 3u 51.8±0.8
3k 53.8±1.5 3v 50.2±4.0

a 50 mg/L drug-containing culture medium was used; each test was performed in triplicate.

为了进一步探讨反应过程, 进行了氘代实验(Scheme 3). 在以MeCN-d6作为溶剂的条件下, 未能获得氘代产品, 表明3a中吡咯烷NH是通过羟基质子转移形成的. 为了深入理解反应机理, 通过19F NMR实验研究了反应过程. 如图2所示, 反应开始时在δ 62.3处只监测到底物2h的氟NMR信号, 反应进行30 min后δ 59.6处出现了新的氟NMR信号, 这可能形成了Michael加成中间体3h-I. 有趣的是, 直到反应结束未观察到新的氟NMR信号, 表明在该串联反应中, SuFEx反应的能垒足够低, Mannich反应生成的中间体迅速转化为产物3h. 48 h后所有氟信号消失, 表明中间体已完全转化为最终产品, 并且成功分离出了中间体3h-I. 在最优反应条件下, 该中间体转化为最终产物3h, 收率达到80%(Scheme 4), 但是未能分离出中间体3h-II.
图式3 氘代实验

Scheme 3 Deuterium experiment

图2 19F NMR实验

Figure 2 19F NMR experiment

图式4 中间体转化实验

Scheme 4 Conversions of intermediates

为进一步阐明高非对映选择性的产生机制, 在M062X-D3/ma-def2-TZVPP//def2-SVP水平下对Michael加成反应和Mannich反应进行了密度泛函理论(DFT)计算(图3). 随着o-羟基席夫碱负离子1a－逐渐接近苯乙烯基磺酰氟2a, C—C键逐渐形成, 至0.362 nm时形成中间体INT1. 随着C—C键进一步缩短, 席夫碱负离子1a－通过过渡态TS1 (47.77 kJ/mol)与2a发生Michael加成反应, 生成中间体INT2. 紧接着, INT2经历分子内Mannich反应, 通过过渡态TS2 (50.16 kJ/mol)形成中间体INT3. Mannich反应过程中伴随质子转移(O—H…N转变为N—H…O), 这一现象与氘代实验的结果高度一致. 新形成的酚氧负离子为后续分子内SuFEx反应提供了反应基础.
图3 DFT计算

Figure 3 DFT calculations

此外, 分别对水杨醛衍生的席夫碱1a和o-羟基苯乙酮衍生的席夫碱1am与苯乙烯基磺酰氟2a进行Michael-Mannich反应进行了DFT计算, 并深入分析了高非对应选择性产生的机理, 计算结果表明, Michael加成反应中不同构型的能量差异是导致高非对映选择性的关键因素.
基于我们先前的研究、相关文献[12]及DFT计算结果, 对可能的反应机理进行了合理推测(Scheme 5). 首先, DBU从o-羟基席夫碱1a中夺取质子, 生成负离子I. 继而该负离子对苯乙烯基磺酰氟2a进行亲核进攻, 生成中间体II. 之后通过Mannich反应生成多取代吡咯烷III. 接下来发生分子内SuFEx反应, 脱去氟离子, 最终得到目标产物3a. 在这一过程中, 分子筛作为高效HF吸收剂, 使DBU得以再生并持续催化反应循环.
图式5 可能的反应机理

Scheme 5 Possible reaction mechanism

2 结论

发展了一种在温和条件下, 通过Michael-Mannich- SuFEx串联反应高效合成α-芳基取代的磺基色烯并[4,3-b]吡咯化合物的方法, 以高达99%的产率和大于95∶5的非对映选择性成功地合成了37种产物. 19F NMR监测和DFT研究表明该反应经历了Michael- Mannich-SuFEx三个阶段. 抑菌测试显示, 部分产物对金黄壳囊孢菌具有一定的抑制作用. 此合成方法的显著优势在于反应条件温和, 高效, 原料易得, 高产率和高非对映选择性.

3 实验部分

3.1 仪器与试剂

熔点使用WRS-1B型熔点仪测定; 所有化合物的1H NMR、13C NMR、19F NMR谱使用Bruker Avance III 400 HD型核磁共振仪测定, 以TMS为内标; 产物3j和3am的X射线衍射在Bruker D8 VENTURE photon II衍射仪上测定, 使用APEX III程序获得; 红外吸收光谱(IR)在Bruker vertex 70 V上测定, 溴化钾(KBr)压片; 高分辨质谱在配备有来自Thermo Scientific的APCI源的Q Exactive质谱仪和LTQ Orbitrap XL质谱仪上获得. 柱色谱使用的硅胶(200~300目)购买于烟台新诺新材料技术有限公司, 石油醚和乙酸乙酯购买于上海泰坦科技股份有限公司(General-reagent), 其他试剂购买于上海泰坦科技股份有限公司(Adamas-beta). 所有试剂均为分析纯, 反应中使用的溶剂通过标准方法干燥处理后使用.

3.2 实验方法

3.2.1 原料的合成

乙烯基磺酰氟[10e]根据文献方法制备, o-羟基席夫 碱[12h,12i]根据文献制备.

3.2.2 化合物3的合成

向装有磁子的10 mL反应管中依次加入o-羟基席夫碱1 (0. 20 mmol)、乙烯基磺酰氟2 (0. 20 mmol)、4 Å MS (200 mg)、DMSO (2.0 mL)和DBU (0. 04 mmol), 室温下搅拌48 h. 待反应结束后(通过TLC监测), 用乙酸乙酯稀释反应液, 水(20 mL×3)萃取, 合并有机相, 用无水硫酸钠干燥. 粗产物经硅胶柱层析(石油醚/二氯甲烷, V/V=1/2)纯化, 得到目标产物3.
2-(4-硝基苯基)-3-苯基-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯4,4-二氧化物(3a): 白色固体, 83.7 mg, 99%产率. m.p. 274.0~274.5 ℃; 1H NMR (400 MHz, Acetone-d6) δ: 7.98~7.83 (m, 2H), 7.72~7.66 (m, 1H), 7.52~7.37 (m, 4H), 7.25~7.19 (m, 1H), 7.12~6.99 (m, 5H), 5.42 (d, J=10.0 Hz, 1H), 5.00 (d, J=11.2 Hz, 1H), 4.57 (dd, J=12.0, 10.4 Hz, 1H), 4.26 (t, J=11.6 Hz, 1H), 4.20 (s, 1H); 13C NMR (100 MHz, Acetone-d6) δ: 151.6, 150.2, 147.5, 136.6, 130.2, 130.1, 129.7, 128.8, 128.3, 128.0, 126.8, 126.4, 123.1, 118.3, 65.5, 63.5, 60.4, 50.8; IR (KBr) ν: 3501, 2600, 1715, 1672, 1518, 1190, 1106, 1014, 952, 887 cm－1. HRMS (ESI) calcd for C22H19N2O5S [M＋H]＋ 423.1009, found 423.1013.
3-(4-氟苯基)-2-(4-硝基苯基)-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯4,4-二氧化物(3b): 白色固体, 81.1 mg, 92%产率. m.p. 241.5~241.9 ℃; 1H NMR (400 MHz, Chloroform-d) δ: 7.94 (d, J=8.4 Hz, 2H), 7.51 (d, J=6.8 Hz, 1H), 7.48~7.33 (m, 2H), 7.20 (d, J=8.0 Hz, 3H), 6.88~6.71 (m, 4H), 5.20 (d, J=9.6 Hz, 1H), 4.99 (d, J=11.2 Hz, 1H), 4.45 (t, J=10.8 Hz, 1H), 3.76 (t, J=11.2 Hz, 1H), 2.99 (s, 1H); 13C NMR (100 MHz, Chloroform-d) δ: 162.3 (d, J=246.0 Hz), 150.7, 147.7, 130.2 (d, J=3.0 Hz), 130.1 (d, J=9.0 Hz), 129.8, 128.7, 127.1, 126.1, 124.9, 123.1, 118.4, 115.8 (d, J=22.0 Hz), 64.7, 63.7, 59.2, 49.5; IR (KBr) ν: 3621, 2953, 1700, 1606, 1515, 1346, 1230, 1160, 855, 756 cm－1. HRMS (ESI) calcd for C22H18FN2O5S [M＋H]＋ 441.0915, found 441.0917.
3-(4-氯苯基)-2-(4-硝基苯基)-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯4,4-二氧化物(3c): 白色固体, 87.7 mg, 96%产率. m.p. 205.7~206.1 ℃; 1H NMR (400 MHz, Acetone-d6) δ: 8.00~7.90 (m, 2H), 7.72~7.65 (m, 1H), 7.52~7.45 (m, 3H), 7.43~7.37 (m, 1H), 7.24~7.20 (m, 1H), 7.16~7.07 (m, 4H), 5.44 (d, J=10.0 Hz, 1H), 4.99 (d, J=11.2 Hz, 1H), 4.59 (dd, J=12.0, 10.4 Hz, 1H), 4.28 (t, J=11.6 Hz, 1H), 4.23 (s, 1H); 13C NMR (100 MHz, Acetone-d6) δ: 151.6, 150.0, 147.7, 135.8, 133.5, 131.5, 130.3, 130.2, 128.9, 128.1, 126.9, 126.5, 123.3, 118.4, 65.4, 63.6, 60.4, 50.1; IR (KBr) ν: 3503, 3007, 1717, 1653, 1541, 1346, 1190, 1155, 854, 722 cm－1. HRMS (ESI) calcd for C22H18ClN2O5S [M＋H]＋ 457.0619, found 457.0622.
3-(4-溴苯基)-2-(4-硝基苯基)-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯4,4-二氧化物(3d): 白色固体, 95.2 mg, 95%产率. m.p. 231.5~231.8 ℃; 1H NMR (400 MHz, Chloroform-d) δ: 7.99~7.87 (m, 2H), 7.54~7.48 (m, 1H), 7.46~7.39 (m, 1H), 7.38~7.32 (m, 1H), 7.25~7.13 (m, 5H), 6.76~6.66 (m, 2H), 5.19 (d, J=10.0 Hz, 1H), 4.97 (d, J=11.6 Hz, 1H), 4.40 (dd, J=12.0, 10.0 Hz, 1H), 3.75 (t, J=11.6 Hz, 1H), 3.00 (s, 1H); 13C NMR (100 MHz, Chloroform-d) δ: 150.7, 147.5, 147.2, 133.5, 131.8, 130.1, 129.8, 128.7, 127.0, 126.1, 125.0, 123.1, 122.2, 118.3, 64.6, 63.5, 59.2, 49.6; IR (KBr) ν: 3600, 3012, 1717, 1653, 1541, 1396, 1157, 1085, 857, 783 cm－1. HRMS (ESI) calcd for C22H18BrN2O5S [M＋H]＋ 501.0114, found 501.0116.
2-(4-硝基苯基)-3-(4-(三氟甲基)苯基)-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯4,4-二氧化物(3e): 白色固体, 93.2 mg, 95%产率. m.p. 225.7~226.3 ℃; 1H NMR (400 MHz, Chloroform-d) δ: 7.92 (d, J=8.8 Hz, 2H), 7.55~7.48 (m, 1H), 7.48~7.40 (m, 1H), 7.40~7.30 (m, 3H), 7.24~7.14 (m, 3H), 6.98 (d, J=8.0 Hz, 2H), 5.26 (d, J=9.6 Hz, 1H), 5.01 (d, J=11.2 Hz, 1H), 4.51 (dd, J=11.6, 10.0 Hz, 1H), 3.83 (t, J=11.6 Hz, 1H), 3.03 (s, 1H); 13C NMR (100 MHz, Chloroform-d) δ: 150.7, 147.2, 138.6, 130.3 (d, J=12.8 Hz), 129.9, 129.0, 128.7, 126.9, 126.2, 125.6 (d, J=4.0 Hz), 125.0, 123.7 (d, J=271.0 Hz), 123.2, 118.4, 64.7, 63.3, 59.4, 49.9; 19F NMR (376 MHz, Chloroform-d) δ: －62.87; IR (KBr) ν: 3682, 2948, 1734, 1700, 1637, 1521, 1455, 1347, 1160, 856 cm－1. HRMS (ESI) calcd for C23H18F3N2O5S [M＋ H]＋ 491.0883, found 491.0887.
4-(2-(4-硝基苯基)-4,4-二氧化-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-3-基)苯甲腈(3f): 白色固体, 87.7 mg, 98%产率. m.p. 263.5~264.2 ℃; 1H NMR (400 MHz, Acetone-d6) δ: 7.99~7.89 (m, 2H), 7.72~7.66 (m, 1H), 7.53~7.46 (m, 5H), 7.44~7.35 (m, 3H), 7.23 (dd, J=8.0, 1.2 Hz, 1H), 5.52 (dd, J=10.0, 6.4 Hz, 1H), 5.02 (dd, J=11.2, 6.0 Hz, 1H), 4.70 (dd, J=11.8, 10.2 Hz, 1H), 4.40 (t, J=11.2 Hz, 1H), 4.28 (t, J=6.4 Hz, 1H); 13C NMR (100 MHz, Acetone-d6) δ: 151.6, 149.5, 147.8, 142.5, 132.7, 130.9, 130.3, 127.9, 127.0, 126.6, 123.4, 119.0, 118.4, 111.9, 65.5, 63.1, 60.6, 50.5; IR (KBr) ν: 3620, 2985, 1716, 1699, 1653, 1558, 1456, 1346, 1156, 856 cm－1. HRMS (ESI) calcd for C23H18N3O5S [M＋H]＋ 448.0962, found 448.0973.
4-(2-(4-硝基苯基)-4,4-二氧化-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-3-基)苯基硫氟酸盐(3g): 白色固体, 93.7 mg, 90%产率. m.p. 259.3~259.7 ℃; 1H NMR (400 MHz, Acetone-d6) δ: 8.01~7.83 (m, 2H), 7.73~7.66 (m, 1H), 7.53~7.44 (m, 3H), 7.44~7.39 (m, 1H), 7.39~7.31 (m, 2H), 7.30~7.16 (m, 3H), 5.48 (d, J=10.0 Hz, 1H), 5.02 (d, J=11.2 Hz, 1H), 4.70 (dd, J=11.6, 10.4 Hz, 1H), 4.38 (t, J=11.2 Hz, 1H), 4.26 (s, 1H); 13C NMR (100 MHz, Acetone-d6) δ: 151.6, 150.0, 149.7, 147.8, 138.2, 132.0, 130.2, 128.0, 127.0, 126.5, 123.3, 121.5, 118.4, 65.6, 63.1, 60.6, 49.9; IR (KBr) ν: 3621, 2972, 1734, 1700, 1559, 1521, 1451, 1347, 1231, 1151 cm－1. HRMS (ESI) calcd for C22H18FN2O8S2 [M＋ H]＋ 521.0483, found 521.0486.
2-(4-硝基苯基)-3-(对甲苯基)-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3h): 白色固体, 86.5 mg, 99%产率. m.p. 213.5~213.9 ℃; 1H NMR (400 MHz, Chloroform-d) δ: 7.96~7.84 (m, 2H), 7.55~7.47 (m, 1H), 7.46~7.38 (m, 1H), 7.37~7.30 (m, 1H), 7.21~7.12 (m, 3H), 6.85 (d, J=8.0 Hz, 2H), 6.69 (d, J=8.0 Hz, 2H), 5.17 (d, J=10.0 Hz, 1H), 4.97 (d, J=11.6 Hz, 1H), 4.41 (dd, J=11.6, 10.0 Hz, 1H), 3.79 (t, J=11.6 Hz, 1H), 2.97 (s, 1H), 2.17 (s, 3H); 13C NMR (100 MHz, Chloroform-d) δ: 150.7, 148.1, 147.0, 137.7, 131.1, 129.7, 129.3, 128.8, 128.3, 127.3, 125.9, 125.0, 122.9, 118.3, 64.8, 63.5, 59.2, 50.0, 21.1; IR (KBr) ν: 3662, 2954, 1733, 1653, 1606, 1455, 1189, 1159, 854, 765 cm－1. HRMS (ESI) calcd for C23H21N2O5S [M＋H]＋ 437.1166, found 437.1172.
3-([1'-联苯]-4-基)-2-(4-硝基苯基)-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3i): 白色固体, 98.7 mg, 99%产率. m.p. 254.6~254.9 ℃; 1H NMR (400 MHz, Chloroform-d) δ: 7.90~7.83 (m, 2H), 7.53~7.47 (m, 1H), 7.44~7.38 (m, 3H), 7.38~7.32 (m, 3H), 7.31~7.26 (m, 3H), 7.22~7.14 (m, 3H), 6.87 (d, J=8.4 Hz, 2H), 5.18 (d, J=9.6 Hz, 1H), 4.98 (d, J=11.2 Hz, 1H), 4.47 (dd, J=12.0, 10.0 Hz, 1H), 3.83 (t, J=11.6 Hz, 1H), 2.98 (s, 1H); 13C NMR (100 MHz, Chloroform-d) δ: 150.6, 147.9, 146.9, 140.6, 140.0, 133.3, 129.6, 128.9, 128.8, 128.8, 127.6, 127.2, 127.1, 126.9, 126.0, 125.0, 122.9, 118.2, 64.7, 63.3, 59.2, 49.9; IR (KBr) ν: 3614, 2954, 1717, 1684, 1541, 1488, 1456, 1346, 1155, 855 cm－1. HRMS (ESI) calcd for C28H23N2O5S [M＋H]＋ 499.1322, found 499.1328.
3-(4-甲氧基苯基)-2-(4-硝基苯基)-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3j): 白色固体, 81.5 mg, 90%产率. m.p. 235.2~235.8 ℃; 1H NMR (400 MHz, Chloroform-d) δ: 7.95~7.87 (m, 2H), 7.54~7.49 (m, 1H), 7.46~7.39 (m, 1H), 7.39~7.31 (m, 1H), 7.19 (d, J=8.8 Hz, 3H), 6.73 (d, J=8.4 Hz, 2H), 6.58 (d, J=8.8 Hz, 2H), 5.16 (d, J=9.6 Hz, 1H), 4.97 (d, J=11.2 Hz, 1H), 4.41 (dd, J=11.6, 10.0 Hz, 1H), 3.75 (t, J=11.6 Hz, 1H), 3.67 (s, 3H), 2.96 (s, 1H); 13C NMR (100 MHz, Chloroform-d) δ: 159.2, 150.7, 148.1, 147.0, 129.7, 129.6, 128.8, 127.3, 126.1, 126.0, 124.9, 122.9, 118.3, 114.0, 64.7, 63.6, 59.1, 55.2, 49.7; IR (KBr) ν: 3612, 2820, 1734, 1653, 1541, 1344, 1254, 1156, 1031, 756 cm－1. HRMS (ESI) calcd for C23H21N2O6S [M＋H]＋ 453.1115, found 453.1112.
3-(3-氟苯基)-2-(4-硝基苯基)-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3k): 白色固体, 86.3 mg, 98%产率. m.p. 286.9~287.5 ℃; 1H NMR (400 MHz, Acetone-d6) δ: 8.02~7.88 (m, 2H), 7.72~7.65 (m, 1H), 7.53~7.45 (m, 3H), 7.44~7.36 (m, 1H), 7.25~7.19 (m, 1H), 7.16~7.07 (m, 1H), 6.99 (d, J=7.6 Hz, 1H), 6.96~6.90 (m, 1H), 6.86~6.76 (m, 1H), 5.46 (dd, J=10.0, 5.2 Hz, 1H), 5.00 (dd, J=11.2, 4.8 Hz, 1H), 4.61 (dd, J=12.0, 10.0 Hz, 1H), 4.34 (t, J=11.6 Hz, 1H), 4.23 (s, 1H); 13C NMR (100 MHz, Acetone-d6) δ: 163.3 (d, J=243.0 Hz), 151.7, 150.0, 147.8, 139.7 (d, J=7.0 Hz), 130.8, 130.7, 130.3, 130.2, 128.1, 127.0, 126.5, 125.9 (d, J=3.0 Hz), 123.3, 118.4, 116.6 (d, J=22.0 Hz), 114.9, 114.7, 65.5, 63.4, 60.5, 50.3; IR (KBr) ν: 3594, 2815, 1717, 1653, 1541, 1474, 1396, 1363, 1151, 833 cm－1. HRMS (ESI) calcd for C22H18FN2O5S [M＋H]＋ 441.0915, found 441.0917.
3-(3-氯苯基)-2-(4-硝基苯基)-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3l): 白色固体, 86.8 mg, 95%产率. m.p. 272.3~272.9 ℃; 1H NMR (400 MHz, DMSO-d6) δ: 7.96~7.89 (m, 2H), 7.64~7.59 (m, 1H), 7.50~7.45 (m, 1H), 7.42~7.37 (m, 3H), 7.29~7.25 (m, 1H), 7.22~7.18 (m, 1H), 7.06 (d, J=1.2 Hz, 3H), 5.24 (dd, J=10.0, 7.2 Hz, 1H), 4.76 (dd, J=11.8, 6.4 Hz, 1H), 4.68~4.58 (m, 2H), 4.53~4.44 (m, 1H); 13C NMR (100 MHz, DMSO-d6) δ: 150.2, 149.0, 146.1, 138.5, 132.6, 129.5, 129.5, 129.3, 128.7, 127.5, 126.9, 126.5, 126.1, 125.5, 122.3, 117.2, 63.9, 61.6, 59.4, 48.4; IR (KBr) ν: 3627, 2980 1717, 1699, 1541, 1474, 1346, 1157, 1042, 854 cm－1. HRMS (ESI) calcd for C22H18ClN2O5S [M＋H]＋ 457.0619, found 457.0622.
2-(4-硝基苯基)-3-(间甲苯基)-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3m): 白色固体, 83.8 mg, 96%产率. m.p. 261.8~262.4 ℃; 1H NMR (400 MHz, DMSO-d6) δ: 7.91~7.85 (m, 2H), 7.64~7.59 (m, 1H), 7.50~7.43 (m, 1H), 7.42~7.37 (m, 1H), 7.37~7.32 (m, 2H), 7.26 (dd, J=8.0, 1.2 Hz, 1H), 6.92~6.86 (m, 2H), 6.84~6.78 (m, 2H), 5.20 (dd, J=9.0, 7.2 Hz, 1H), 4.76 (dd, J=9.6, 7.2 Hz, 1H), 4.60 (t, J=6.8 Hz, 1H), 4.47~4.36 (m, 2H), 2.07 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 150.2, 149.4, 146.0, 136.7, 135.7, 129.5, 129.4, 129.3, 127.6, 127.5, 126.4, 126.4, 125.7, 125.5, 122.1, 117.2, 64.0, 62.2, 59.3, 49.0, 20.7; IR (KBr) ν: 3667, 2972, 1716, 1699, 1653, 1507, 1456, 1340, 1148, 850 cm－1. HRMS (ESI) calcd for C23H21N2O5S [M＋H]＋ 437.1166, found 437.1180.
3-(3-甲氧基苯基)-2-(4-硝基苯基)-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3n): 白色固体, 87.8 mg, 97%产率. m.p. 248.3~248.7 ℃; 1H NMR (400 MHz, Chloroform-d) δ: 7.94~7.82 (m, 2H), 7.53~7.46 (m, 1H), 7.43~7.37 (m, 1H), 7.36~7.30 (m, 1H), 7.23~7.12 (m, 3H), 6.94 (t, J=7.6 Hz, 1H), 6.61~6.54 (m, 1H), 6.42~6.34 (m, 2H), 5.15 (d, J=9.6 Hz, 1H), 4.94 (d, J=11.2 Hz, 1H), 4.39 (dd, J=11.6, 10.0 Hz, 1H), 3.78 (t, J=11.6 Hz, 1H), 3.57 (s, 3H), 2.99 (s, 1H); 13C NMR (100 MHz, Chloroform-d) δ: 159.5, 150.7, 147.9, 147.0, 135.8, 129.7, 129.6, 128.7, 127.2, 126.0, 125.0, 122.9, 120.8, 118.3, 114.6, 113.2, 64.8, 63.4, 59.3, 55.2, 50.2; IR (KBr) ν: 3605, 2852, 1734, 1653, 1559, 1541, 1473, 1362, 1155, 835 cm－1. HRMS (ESI) calcd for C23H21N2O6S [M＋H]＋ 453.1115, found 453.1112.
3-(2-氟苯基)-2-(4-硝基苯基)-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3o): 白色固体, 82.8 mg, 94%产率. m.p. 251.6~252.1 ℃; 1H NMR (400 MHz, Acetone-d6) δ: 7.98~7.86 (m, 2H), 7.72~7.65 (m, 1H), 7.52~7.45 (m, 3H), 7.44~7.37 (m, 1H), 7.26~7.21 (m, 1H), 7.19~7.03 (m, 2H), 7.02~6.90 (m, 1H), 6.90~6.77 (m, 1H), 5.46 (d, J=10.0 Hz, 1H), 5.04 (d, J=11.2 Hz, 1H), 4.76 (t, J=10.8 Hz, 1H), 4.42 (t, J=11.6 Hz, 1H); 13C NMR (100 MHz, Acetone-d6) δ: 161.4 (d, J=243.0 Hz), 151.6, 149.9, 147.8, 130.2, 130.1, 128.1, 126.9, 126.6, 124.8 (d, J=3.0 Hz), 123.9, 123.8, 123.3, 118.4, 115.7 (d, J=20.0 Hz), 64.5, 62.0, 60.5; IR (KBr) ν: 3650, 2462, 1635, 1541, 1521, 1473, 1457, 1362, 1154, 752 cm－1. HRMS (ESI) calcd for C22H18FN2O5S [M＋H]＋ 441.0915, found 441.0917.
2-(4-硝基苯基)-3-(邻甲苯基)-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3p): 白色固体, 84.7 mg, 97%产率. m.p. 248.2~248.8 ℃; 1H NMR (400 MHz, Acetone-d6) δ: 7.94~7.83 (m, 2H), 7.72~7.66 (m, 1H), 7.51~7.45 (m, 1H), 7.45~7.38 (m, 3H), 7.26~7.20 (m, 1H), 7.08 (d, J=7.6 Hz, 1H), 6.95~6.89 (m, 1H), 6.81 (d, J=7.2 Hz, 1H), 6.73 (t, J=7.2 Hz, 1H), 5.51 (d, J=9.6 Hz, 1H), 5.04 (d, J=11.2 Hz, 1H), 4.76 (dd, J=11.6, 10.0 Hz, 1H), 4.31 (t, J=11.6 Hz, 1H), 4.18 (s, 1H), 2.54 (s, 3H); 13C NMR (100 MHz, Acetone-d6) δ: 151.6, 150.5, 147.7, 137.1, 134.7, 131.0, 130.1, 130.0, 128.8, 128.7, 127.9, 126.8, 126.6, 126.3, 123.2, 118.4, 63.8, 63.3, 60.3, 47.3, 20.1; IR (KBr) ν: 3602, 2907, 1749, 1733, 1653, 1520, 1455, 1345, 1157, 885 cm－1. HRMS (ESI) calcd for C23H21N2O5S [M＋H]＋ 437.1166, found 437.1170.
3-(2-甲氧基苯基)-2-(4-硝基苯基)-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3q): 白色固体, 86.9 mg, 96%产率. m.p. 258.1~258.6 ℃; 1H NMR (400 MHz, DMSO-d6) δ: 7.85 (d, J=8.4 Hz, 2H), 7.59 (d, J=6.8 Hz, 1H), 7.50~7.44 (m, 1H), 7.41~7.36 (m, 1H), 7.35~7.31 (m, 2H), 7.28 (d, J=8.0 Hz, 1H), 7.09~6.95 (m, 2H), 6.74 (d, J=7.6 Hz, 1H), 6.59 (t, J=7.6 Hz, 1H), 5.22 (dd, J=9.6, 6.4 Hz, 1H), 4.85~4.76 (m, 1H), 4.74~4.64 (m, 1H), 4.63~4.54 (m, 1H), 4.47 (t, J=6.8 Hz, 1H), 3.82 (s, 3H), 3.12 (s, 1H); 13C NMR (100 MHz, DMSO-d6) δ: 156.1, 150.2, 149.5, 146.0, 129.5, 129.3, 128.3, 127.7, 126.4, 126.4, 125.5, 123.6, 122.0, 119.6, 117.3, 109.9, 63.0, 59.8, 59.4, 55.2, 54.9; IR (KBr) ν: 3633, 2906, 1717, 1699, 1653, 1520, 1457, 1345, 1158, 855 cm－1. HRMS (ESI) calcd for C23H21N2O6S [M＋H]＋ 453.1115, found 453.1112.
3-(4-溴-3-甲基苯基)-2-(4-硝基苯基)-2,3,3a,9b-四 氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3r): 白色固体, 94.8 mg, 92%产率. m.p. 286.5~287.3 ℃; 1H NMR (400 MHz, Chloroform-d) δ: 7.99~7.86 (m, 2H), 7.54~7.47 (m, 1H), 7.46~7.39 (m, 1H), 7.38~7.32 (m, 1H), 7.25~7.10 (m, 4H), 6.72 (d, J=2.0 Hz, 1H), 6.46 (dd, J=8.0, 2.0 Hz, 1H), 5.18 (d, J=10.0 Hz, 1H), 4.96 (d, J=11.2 Hz, 1H), 4.36 (dd, J=11.6, 10.0 Hz, 1H), 3.75 (t, J=11.2 Hz, 1H), 2.99 (s, 1H), 2.17 (s, 3H); 13C NMR (100 MHz, Chloroform-d) δ: 150.7, 147.6, 147.1, 138.2, 133.7, 132.5, 131.0, 129.8, 128.8, 127.2, 127.0, 126.1, 124.9, 124.6, 123.0, 118.3, 64.6, 63.6, 59.2, 49.6, 22.8; IR (KBr) ν: 3611, 2924, 1749, 1670, 1569, 1541, 1375, 1156, 1028, 854 cm－1. HRMS (ESI) calcd for C23H20BrN2O5S [M＋H]＋ 515.0271, found 515.0266.
3-(萘-1-基)-2-(4-硝基苯基)-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3s): 白色固体, 90.7 mg, 96%产率. m.p. 270.9~271.4 ℃; 1H NMR (400 MHz, DMSO-d6) δ: 8.45 (d, J=8.8 Hz, 1H), 7.83~7.80 (m, 1H), 7.72~7.67 (m, 1H), 7.65~7.62 (m, 3H), 7.60 (d, J=8.4 Hz, 1H), 7.55~7.51 (m, 1H), 7.50~7.45 (m, 1H), 7.43~7.41 (m, 1H), 7.34~7.29 (m, 2H), 7.17~7.11 (m, 3H), 5.55 (dd, J=10.0, 7.2 Hz, 1H), 5.22 (t, J=11.2 Hz, 1H), 5.02~4.91 (m, 2H), 4.66~4.62 (m, 1H); 13C NMR (100 MHz, DMSO-d6) δ: 150.2, 149.4, 145.9, 132.8, 131.4, 131.4, 129.4, 129.3, 128.6, 127.4, 126.7, 126.5, 126.4, 125.7, 125.6, 125.5, 124.7, 123.8, 121.8, 117.3, 63.2, 60.5, 59.2, 45.5; IR (KBr) ν: 3632, 2986, 1716, 1699, 1652, 1558, 1507, 1341, 1142, 872 cm－1. HRMS (ESI) calcd for C26H21N2O5S [M＋H]＋ 473.1166, found 473.1169.
2-(4-硝基苯基)-3-(噻吩-2-基)-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3t): 白色固体, 77.1 mg, 90%产率. m.p. 246.2~246.6 ℃; 1H NMR (400 MHz, Acetone-d6) δ: 8.00~7.88 (m, 2H), 7.71~7.63 (m, 1H), 7.53~7.44 (m, 3H), 7.42~7.35 (m, 1H), 7.27~7.15 (m, 2H), 7.14~7.07 (m, 1H), 6.79~6.70 (m, 1H), 5.37 (d, J=10.0 Hz, 1H), 4.95 (d, J=11.6 Hz, 1H), 4.68 (dd, J=11.6, 10.4 Hz, 1H), 4.21 (t, J=11.6 Hz, 1H), 2.84 (s, 1H); 13C NMR (100 MHz, Acetone-d6) δ: 151.6, 150.4, 147.7, 137.6, 130.2, 130.1, 128.6, 128.3, 126.9, 126.5, 126.4, 124.1, 123.1, 118.3, 65.2, 64.2, 60.4, 46.3; IR (KBr) ν: 3652, 2905, 1733, 1716, 1653, 1520, 1456, 1344, 1154, 886 cm－1. HRMS (ESI) calcd for C20H17N2O5S2 [M＋H]＋ 429.0573, found 429.0574.
9-氯-2-(4-硝基苯基)-3-苯基-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3u): 白色固体, 89.6 mg, 98%产率. m.p. 238.7~239.2 ℃; 1H NMR (400 MHz, DMSO-d6) δ: 7.90~7.85 (m, 2H), 7.53~7.45 (m, 2H), 7.40~7.35 (m, 2H), 7.32~7.28 (m, 1H), 7.11~7.07 (m, 2H), 7.07~6.99 (m, 3H), 5.20 (dd, J=10.4, 4.0 Hz, 1H), 4.99~4.88 (m, 2H), 4.61~4.49 (m, 1H), 4.40 (t, J=11.2 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ: 151.3, 149.5, 145.9, 135.5, 132.7, 130.4, 129.6, 128.8, 127.7, 127.6, 126.9, 123.5, 122.1, 117.5, 63.3, 60.8, 60.4, 47.2; IR (KBr) ν: 3602, 2958 1717, 1699, 1541, 1437, 1346, 1187, 1141, 854 cm－1. HRMS (ESI) calcd for C22H18ClN2O5S [M＋H]＋ 457.0619, found 457.0622.
9-甲氧基-2-(4-硝基苯基)-3-苯基-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3v): 白色固体, 87.8 mg, 97%产率. m.p. 236.2~236.9 ℃; 1H NMR (400 MHz, DMSO-d6) δ: 7.96~7.87 (m, 2H), 7.51~7.41 (m, 3H), 7.18~7.12 (m, 2H), 7.10~7.02 (m, 4H), 6.93~6.86 (m, 1H), 5.20 (dd, J=10.8, 6.0 Hz, 1H), 4.82 (dd, J=10.8, 4.0 Hz, 1H), 4.75 (t, J=11.6 Hz, 1H), 4.50~4.44 (m, 1H), 4.41 (t, J=11.2 Hz, 1H), 3.92 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 158.3, 150.9, 149.9, 145.9, 136.0, 130.0, 129.8, 128.9, 127.6, 126.8, 122.1, 112.8, 110.1, 108.3, 62.9, 60.8, 59.3, 56.1, 47.0; IR (KBr) ν: 3627, 2975 1717, 1699, 1541, 1439, 1351, 1176, 1067, 823 cm－1. HRMS (ESI) calcd for C23- H21N2O6S [M＋H]＋ 453.1115, found 453.1112.
8-氟-2-(4-硝基苯基)-3-苯基-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3w): 白色固体, 81.0 mg, 92%产率. m.p. 240.3~240.8 ℃; 1H NMR (400 MHz, Acetone-d6) δ: 7.97~7.84 (m, 2H), 7.51~7.40 (m, 3H), 7.31~7.21 (m, 2H), 7.11~7.02 (m, 5H), 5.43 (d, J=10.0 Hz, 1H), 5.02 (d, J=11.2 Hz, 1H), 4.58 (dd, J=12.0, 10.0 Hz, 1H), 4.30 (t, J=11.6 Hz, 1H), 4.21 (s, 0H); 13C NMR (100 MHz, Acetone-d6) δ: 160.7 (d, J=241.0 Hz), 150.1, 147.6, 147.5 (d, J=3.0 Hz), 136.4, 131.1 (d, J=8.0 Hz), 130.2, 129.7, 128.9, 128.1, 123.1, 120.3, 120.2, 116.4 (d, J=24.0 Hz), 113.7, 113.5, 65.4, 63.1, 60.3, 50.9; IR (KBr) ν: 3593, 2947, 1699, 1637, 1520, 1475, 1347, 1191, 1149, 852 cm－1. HRMS (ESI) calcd for C22H18FN2O5S [M＋H]＋ 441.0915, found 441.0917.
8-氯-2-(4-硝基苯基)-3-苯基-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3x): 白色固体, 89.6 mg, 98%产率. m.p. 227.6~228.2 ℃; 1H NMR (400 MHz, Acetone-d6) δ: 7.97~7.84 (m, 2H), 7.73~7.66 (m, 1H), 7.53~7.47 (m, 1H), 7.47~7.39 (m, 2H), 7.25 (d, J=8.4 Hz, 1H), 7.13~7.02 (m, 5H), 5.43 (d, J=10.0 Hz, 1H), 5.02 (d, J=11.2 Hz, 1H), 4.59 (dd, J=12.0, 11.6 Hz, 1H), 4.36 (t, J=11.6 Hz, 1H), 4.20 (s, 1H); 13C NMR (100 MHz, Acetone-d6) δ: 150.2, 150.1, 147.6, 136.3, 131.2, 130.5, 130.2, 129.9, 129.7, 128.9, 128.1, 126.8, 123.1, 120.1, 65.4, 63.0, 60.1, 50.8; IR (KBr) ν: 3625, 2972, 1749, 1699, 1521, 1473, 1374, 1318, 1159, 837 cm－1. HRMS (ESI) calcd for C22H18ClN2O5S [M＋ H]＋ 457.0619, found 457.0625.
8-溴-2-(4-硝基苯基)-3-苯基-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3y): 白色固体, 99.3 mg, 99%产率. m.p. 231.5~231.9 ℃; 1H NMR (400 MHz, Acetone-d6) δ: 7.94~7.86 (m, 2H), 7.86~7.81 (m, 1H), 7.68~7.61 (m, 1H), 7.48~7.40 (m, 2H), 7.19 (d, J=8.4 Hz, 1H), 7.12~7.02 (m, 5H), 5.43 (d, J=10.0 Hz, 1H), 5.03 (d, J=11.2 Hz, 1H), 4.59 (dd, J=12.0, 10.0 Hz, 1H), 4.36 (t, J=11.6 Hz, 1H), 4.24 (s, 1H); 13C NMR (100 MHz, Acetone-d6) δ: 150.8, 150.1, 147.6, 136.4, 132.9, 130.8, 130.3, 129.8, 129.7, 128.9, 128.1, 123.1, 120.5, 118.7, 65.5, 63.0, 60.2, 50.8; IR (KBr) ν: 3684, 2965, 1734, 1699, 1519, 1473, 1364, 1191, 1159, 835 cm－1. HRMS (ESI) calcd for C22H18BrN2O5S [M＋ H]＋ 501.0114, found 501.0117.
8-甲基-2-(4-硝基苯基)-3-苯基-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物 (3z): 白色固体, 86.4 mg, 99%产率. m.p. 234.5~235.0 ℃; 1H NMR (400 MHz, Acetone-d6) δ: 7.94~7.85 (m, 2H), 7.51~7.46 (m, 1H), 7.47~7.41 (m, 2H), 7.30~7.24 (m, 1H), 7.12~7.00 (m, 6H), 5.40 (d, J=10.4 Hz, 1H), 4.95 (d, J=11.2 Hz, 1H), 4.55 (dd, J=11.6, 10.0 Hz, 1H), 4.20 (t, J=11.6 Hz, 1H), 4.12 (s, 1H); 13C NMR (100 MHz, Acetone-d6) δ: 150.2, 149.6, 147.6, 136.7, 136.2, 130.5, 130.3, 129.7, 128.9, 128.0, 128.0, 127.2, 123.1, 118.2, 65.6, 63.8, 60.5, 50.8, 20.9; IR (KBr) ν: 3665, 2960 1733, 1699, 1519, 1457, 1363, 1166, 1107, 852 cm－1. HRMS (ESI) calcd for C23H21N2O5S [M＋H]＋ 437.1166, found 437.1188.
8-甲氧基-2-(4-硝基苯基)-3-苯基-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3aa): 白色固体, 86.0 mg, 95%产率. m.p. 235.7~236.2 ℃; 1H NMR (400 MHz, Acetone-d6) δ: 8.00~7.83 (m, 2H), 7.51~7.40 (m, 2H), 7.27~7.22 (m, 1H), 7.21~7.14 (m, 1H), 7.12~6.97 (m, 6H), 5.42 (dd, J=10.4, 6.8 Hz, 1H), 4.97 (dd, J=11.2, 5.6 Hz, 1H), 4.56 (t, J=10.0 Hz, 1H), 4.23~4.10 (m, 2H), 3.88 (s, 3H); 13C NMR (100 MHz, Acetone-d6) δ: 158.4, 150.4, 147.7, 145.2, 136.7, 130.4, 130.1, 129.8, 128.9, 128.1, 123.2, 119.6, 114.7, 112.1, 65.6, 63.8, 60.7, 56.3, 51.1; IR (KBr) ν: 3637, 2980 1734, 1699, 1541, 1457, 1346, 1158, 1031, 852 cm－1. HRMS (ESI) calcd for C23H21N2O6S [M＋H]＋ 453.1115, found 453.1112.
8-硝基-2-(4-硝基苯基)-3-苯基-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3ab): 白色固体, 85.1 mg, 91%产率. m.p. 268.8~269.5 ℃; 1H NMR (400 MHz, Acetone-d6) δ: 8.63~8.52 (m, 1H), 8.43~8.34 (m, 1H), 7.97~7.83 (m, 2H), 7.53~7.39 (m, 3H), 7.17~7.00 (m, 5H), 5.51 (dd, J=9.6, 6.4 Hz, 1H), 5.15 (dd, J=11.2, 6.4 Hz, 1H), 4.67 (dd, J=12.0, 9.6 Hz, 1H), 4.62~4.55 (m, 1H), 4.53 (t, J=6.8 Hz, 1H); 13C NMR (100 MHz, Acetone-d6) δ: 155.8, 150.0, 147.7, 145.9, 136.2, 130.3, 129.8, 129.7, 129.0, 128.3, 125.9, 123.2, 123.0, 119.5, 65.5, 62.5, 60.1, 50.8; IR (KBr) ν: 3624, 2972 1733, 1699, 1521, 1473, 1347, 1167, 1107, 852 cm－1. HRMS (ESI) calcd for C22H18N3O7S [M＋H]＋ 468.0860, found 468.0862.
7-氯-2-(4-硝基苯基)-3-苯基-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3ac): 白色固体, 87.7 mg, 96%产率. m.p. 257.9~258.6 ℃; 1H NMR (400 MHz, DMSO-d6) δ: 7.91~7.84 (m, 2H), 7.64~7.59 (m, 1H), 7.52~7.47 (m, 2H), 7.37~7.31 (m, 2H), 7.09~6.99 (m, 5H), 5.23 (dd, J=10.0, 7.2 Hz, 1H), 4.76 (dd, J=10.8, 6.4 Hz, 1H), 4.69~4.58 (m, 2H), 4.51~4.43 (m, 1H); 13C NMR (100 MHz, DMSO-d6) δ: 150.5, 149.3, 146.0, 135.6, 133.0, 129.5, 128.7, 127.9, 127.8, 127.0, 125.5, 125.4, 122.2, 117.4, 63.8, 61.3, 58.9, 48.9; IR (KBr) ν: 3627, 2960 1717, 1699, 1541, 1457, 1348, 1164, 1107, 887 cm－1. HRMS (ESI) calcd for C22- H18ClN2O5S [M＋H]＋ 457.0619, found 457.0622.
7-溴-2-(4-硝基苯基)-3-苯基-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3ad): 白色固体, 96.3 mg, 96%产率. m.p. 263.4~263.7 ℃; 1H NMR (400 MHz, DMSO-d6) δ: 7.90~7.85 (m, 2H), 7.64~7.59 (m, 2H), 7.57~7.52 (m, 1H), 7.36~7.31 (m, 2H), 7.08~7.00 (m, 5H), 5.22 (dd, J=10.0, 6.4 Hz, 1H), 4.74 (dd, J=11.2, 5.6 Hz, 1H), 4.68~4.58 (m, 2H), 4.50~4.43 (m, 1H); 13C NMR (100 MHz, DMSO-d6) δ: 150.6, 149.3, 146.0, 135.6, 129.5, 128.7, 128.4, 128.1, 127.8, 127.0, 125.9, 122.2, 121.0, 120.1, 63.8, 61.3, 59.0, 48.9; IR (KBr) ν: 3625, 2980 1717, 1699, 1541, 1457, 1346, 1164, 1107, 903 cm－1. HRMS (ESI) calcd for C22- H18BrN2O5S [M＋H]＋ 501.0114, found 501.0116.
7-甲基-2-(4-硝基苯基)-3-苯基-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3ae): 白色固体, 79.4 mg, 91%产率. m.p. 257.4~257.9 ℃; 1H NMR (400 MHz, DMSO-d6) δ: 7.90~7.85 (m, 2H), 7.49 (d, J=8.0 Hz, 1H), 7.38~7.33 (m, 2H), 7.21 (d, J=7.6 Hz, 1H), 7.10 (s, 1H), 7.08~6.99 (m, 5H), 5.25~5.18 (m, 1H), 4.73 (dd, J=10.4, 6.8 Hz, 1H), 4.58 (t, J=7.2 Hz, 1H), 4.48~4.39 (m, 2H), 2.38 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 150.1, 149.4, 145.9, 139.3, 135.9, 129.5, 128.7, 127.7, 126.9, 126.1, 126.1, 123.3, 122.2, 117.5, 64.0, 62.1, 59.2, 49.0; IR (KBr) ν: 3627, 2975 1717, 1699, 1541, 1436, 1363, 1172, 1106, 888 cm－1. HRMS (ESI) calcd for C23H21N2O5S [M＋H]＋ 437.1166, found 437.1172.
6-氟-2-(4-硝基苯基)-3-苯基-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3af): 白色固体, 83.7 mg, 95%产率. m.p. 242.4~242.7 ℃; 1H NMR (400 MHz, DMSO-d6) δ: 7.92~7.84 (m, 2H), 7.49~7.38 (m, 3H), 7.38~7.32 (m, 2H), 7.12~7.00 (m, 5H), 5.24 (dd, J=10.0, 7.2 Hz, 1H), 4.85 (dd, J=11.2, 6.0 Hz, 1H), 4.75 (t, J=11.6 Hz, 1H), 4.69 (t, J=6.8 Hz, 1H), 4.54~4.46 (m, 1H); 13C NMR (100 MHz, DMSO-d6) δ: 149.8 (d, J=246.0 Hz), 149.3, 146.0, 137.8, 137.6, 135.5, 129.5, 128.9, 128.7, 127.8, 127.0, 126.0 (d, J=7.0 Hz), 122.2, 121.8 (d, J=3.0 Hz), 116.1 (d, J=17.0 Hz), 63.8, 61.4, 59.3, 49.0; IR (KBr) ν: 3665, 2972 1717, 1684, 1541, 1437, 1346, 1156, 1061, 854 cm－1. HRMS (ESI) calcd for C22H18FN2O5S [M＋H]＋ 441.0915, found 441.0917.
6-乙氧基-2-(4-硝基苯基)-3-苯基-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3ag): 白色固体, 90.5 mg, 97%产率. m.p. 230.7~231.4 ℃; 1H NMR (400 MHz, DMSO-d6) δ: 7.94~7.88 (m, 2H), 7.41~7.33 (m, 3H), 7.24~7.19 (m, 2H), 7.12~7.03 (m, 5H), 5.29~5.23 (m, 1H), 4.82 (dd, J=10.0, 6.4 Hz, 1H), 4.61 (t, J=6.8 Hz, 1H), 4.55~4.46 (m, 2H), 4.22~4.14 (m, 2H), 1.41 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 149.5, 147.1, 146.0, 139.0, 135.8, 129.5, 128.7, 127.9, 127.8, 126.9, 125.7, 122.2, 117.2, 113.4, 64.4, 64.0, 61.9, 59.5, 49.2; IR (KBr) ν: 3625, 2980 1700, 1684, 1541, 1474, 1346, 1153, 1061, 854 cm－1. HRMS (ESI) calcd for C24H23N2O6S [M＋H]＋ 467.1271, found 467.1275.
6,8-二氯-2-(4-硝基苯基)-3-苯基-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3ah): 白色固体, 93.3 mg, 95%产率. m.p. 242.5~243.1 ℃; 1H NMR (400 MHz, DMSO-d6) δ: 7.91~7.86 (m, 2H), 7.84 (d, J=2.4 Hz, 1H), 7.65~7.61 (m, 1H), 7.38~7.31 (m, 2H), 7.10~6.99 (m, 5H), 5.25 (dd, J=10.0, 6.8 Hz, 1H), 4.92~4.79 (m, 2H), 4.68 (t, J=6.0 Hz, 1H), 4.50 (t, J=10.8 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ: 149.3, 146.0, 144.8, 135.3, 130.5, 129.6, 129.5, 128.9, 128.7, 127.8, 127.1, 125.1, 122.3, 122.2, 63.8, 60.9, 59.1, 49.0; IR (KBr) ν: 3625, 2997 1717, 1684, 1541, 1419, 1346, 1161, 1109, 854 cm－1. HRMS (ESI) calcd for C22H17Cl2N2O5S [M＋H]＋ 491.0230, found 491.0236.
6-溴-8-氯-2-(4-硝基苯基)-3-苯基-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3ai): 白色固体, 101.8 mg, 95%产率. m.p. 237.1~237.6 ℃; 1H NMR (400 MHz, Acetone-d6) δ: 7.95~7.86 (m, 2H), 7.85~7.76 (m, 1H), 7.75~7.67 (m, 1H), 7.48~7.40 (m, 2H), 7.11~7.03 (m, 5H), 5.47 (d, J=10.0 Hz, 1H), 5.10 (d, J=11.2 Hz, 1H), 4.62 (dd, J=12.0, 10.0 Hz, 1H), 4.55~4.45 (m, 1H), 4.36 (s, 1H); 13C NMR (100 MHz, Acetone-d6) δ: 150.1, 147.6, 147.4, 136.0, 132.7, 132.6, 131.6, 130.2, 129.7, 128.9, 128.2, 126.1, 123.1, 112.5, 65.6, 63.0, 60.3, 50.9; IR (KBr) ν: 3668, 2975 1717, 1699, 1541, 1437, 1346, 1157, 1121, 854 cm－1. HRMS (ESI) calcd for C22H17BrClN2O5S [M＋H]＋ 534.9725, found 534.9726.
6,8-二溴-2-(4-硝基苯基)-3-苯基-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3aj): 白色固体, 111.4 mg, 96%产率. m.p. 229.5~230.1 ℃; 1H NMR (400 MHz, Acetone-d6) δ: 7.95~7.87 (m, 3H), 7.87~7.83 (m, 1H), 7.47~7.41 (m, 2H), 7.12~7.03 (m, 5H), 5.47 (dd, J=10.0, 6.8 Hz, 1H), 5.10 (dd, J=10.8, 6.4 Hz, 1H), 4.62 (dd, J=12.0, 9.6 Hz, 1H), 4.55~4.46 (m, 1H), 4.28 (t, J=6.4 Hz, 1H); 13C NMR (100 MHz, Acetone-d6) δ: 150.0, 147.9, 147.6, 136.0, 135.5, 132.9, 130.2, 129.6, 129.1, 128.9, 128.2, 123.1, 118.9, 112.7, 65.6, 63.0, 60.3, 50.9; IR (KBr) ν: 3652, 2972 1734, 1699, 1541, 1457, 1374, 1155, 1118, 853 cm－1. HRMS (ESI) calcd for C22H17Br2N2O5S [M＋H]＋ 578.9219, found 578.9215.
9b-甲基-2-(4-硝基苯基)-3-苯基-2,3,3a,9b-四氢-1H-苯并[5,6][1,2]氧硫杂环己烷[4,3-b]吡咯-4,4-二氧化物(3am): 白色固体, 84.7 mg, 97%产率. m.p. 247.6~248.3 ℃; 1H NMR (400 MHz, DMSO-d6) δ: 8.03 (d, J=8.8 Hz, 2H), 7.81 (dd, J=7.4, 2.0 Hz, 1H), 7.47~7.38 (m, 2H), 7.34~7.20 (m, 8H), 4.76~4.64 (m, 2H), 4.31 (d, J=6.8 Hz, 1H), 1.85 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ:149.5, 146.9, 146.8, 136.6, 133.1, 129.2, 128.7, 128.6, 128.4, 128.0, 127.7, 126.9, 123.2, 118.8, 70.8, 66.4, 64.5, 57.0, 30.2; IR (KBr) ν: 3650, 2970 1735, 1696, 1538, 1458, 1372, 1150, 1120, 855 cm－1. HRMS (ESI) calcd for C23H21N2O5S [M＋H]＋ 437.1166, found 437.1168.
2-(2-羟基苯基)-5-(4-硝基苯基)-4-(对甲苯基)吡咯烷-3-磺酰氟(3h-I): 白色固体, 56.6 mg, 62%产率. m.p. 202.5~202.8 ℃; 1H NMR (400 MHz, Chloroform-d) δ: 12.56 (s, 1H), 8.44 (s, 1H), 8.18~8.06 (m, 2H), 7.45~7.34 (m, 1H), 7.30~7.25 (m, 1H), 7.24~7.18 (m, 2H), 7.08 (d, J=8.0 Hz, 2H), 7.04~6.99 (m, 1H), 6.96~6.89 (m, 1H), 6.84~6.76 (m, 2H), 5.06~4.96 (m, 1H), 3.89~3.68 (m, 3H), 2.31 (s, 3H); 13C NMR (100 MHz, Chloroform-d) δ: 168.6, 160.9, 147.6, 147.3, 138.6, 133.9, 132.5, 131.8, 129.5, 128.7, 128.3, 123.9, 119.5, 118.3, 117.3, 75.1, 53.4, 53.2, 47.5, 21.2; 19F NMR (376 MHz, Chloroform-d) δ: 59.60. HRMS (ESI) calcd for C23H22FN2O5S[M＋H]＋ 457.1228, found 457.1227.

3.2.3 化合物6a的合成

向装有磁子的10 mL反应管中依次加入靛红(0.20 mmol)、3a (0.02 mmol)、乙酸/乙醇(V∶V=1∶7, 2.0 mL)和丙酮(0.5 mL), 室温下搅拌48 h, 待反应结束后(通过TLC监测), 在减压条件下浓缩混合物, 得到的粗产物通过硅胶柱层析(石油醚/乙酸乙酯, V∶V=5∶1~1∶1)纯化得到3-羟基-3-(2-氧丙基)吲哚-2-酮(6a)[13h]. 1H NMR (400 MHz, DMSO-d6) δ: 10.21 (s, 1H), 7.27~7.21 (m, 1H), 7.21~7.12 (m, 1H), 6.94~6.86 (m, 1H), 6.81~6.73 (m, 1H), 5.97 (s, 1H), 3.27 (d, J=16.4 Hz, 1H), 3.00 (d, J=16.8 Hz, 1H), 2.00 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 205.1, 178.1, 142.5, 131.5, 129.0, 123.7, 121.2, 109.4, 72.6, 50.3, 30.6.
辅助材料(Supporting Information) 所有目标化合物的1H NMR和13C NMR谱图, 单晶数据和DFT计算数据. 这些材料可以免费从本刊网站(http://sioc-journalcn/.)上下载.
(Lu, Y.)
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CCDC 2353272 (3j) and 2380699 (3am) contain the supplementary crystallographic data for this paper.

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