简单烯烃作为廉价易得的原料和重要的合成砌块, 其高效官能团化一直是有机化学的研究热点[1]. 新兴的自由基介导的官能团迁移(FGM)策略为烯烃的双官能化提供了更为新颖、高效的途径. 该过程通过自由基对烯烃的加成, 引发后续的分子内官能团迁移, 一步实现烯烃的双官能团化. 在过去的近十年间, 尤为突出的是可见光驱动的自由基介导官能团迁移策略, 展现出了广阔的研究空间, 可实现复杂分子的模块化构建及高效后期修饰[2-3]. 基于分子内的官能团迁移策略, 我们课题 组[4-5]利用精心设计的双官能团试剂, 发展了分子间的“对接-迁移”反应(Scheme 1a), 进一步推动了该领域的进展.
图式1 (a)自由基对接-迁移策略; (b)利用砜基杂环化试剂构建含氮稠杂芳烃; (c)本文工作: 可见光促进的亚砜杂环化试剂参与的含氮稠杂芳烃的构建Scheme 1 (a) Radical-mediated docking-migration strategy; (b) Sulfone-based heterocyclizing agents for construction of N-fused heteroarenes; (c) This work: visible-light promoted construction of N-fused heteroarenes using sulfoxide-based heterocyclizing agents |
杂环化合物, 凭借其独特的结构与性质, 在有机化学、制药及材料科学等领域展现出广阔的应用前景[6]. 特别是含氮杂环, 作为大量生物活性分子的基本骨架, 在制药工业中发挥着不可或缺的作用. 2024年, Njar- darson等[7]发表了美国食品药品监督管理局(FDA)批准含氮杂环化合物的综述, 指出含氮杂环药物数量显著增长: 先前调查显示59%的药物含有氮杂环, 现已增至82%. 此外, 研究发现已报道的药物骨架中, 大多数含氮杂环由六元或五元芳香环或非芳香环构成. 这些化合物已知具有广泛的生物活性(抗菌、抗癌、抗病毒等关键药理活性)[8]. 尽管其应用价值驱动了海量合成研究, 但现有方法(如缩合反应、点击化学以及新型多组分多米诺反应等)往往依赖于强酸/碱、高温或昂贵原料, 在效率和选择性方面存在一些局限[9]. 因此, 发展条件温和、步骤经济的高效合成方法, 实现结构新颖的含氮杂环的构建, 一直是现代有机合成的研究热点.
受自由基介导的对接-迁移反应实现烯烃双官能化研究的启发, 我们设想了将烯烃双官能化与后续环化反应组合的串联策略, 并将其应用于含氮稠杂芳烃的合成. 我们[4d]设计了一系列基于砜的杂环化试剂, 其结构特点为杂芳基与带有两个离去基团的烷基分处两端. 该策略的独特之处在于: 在完成初始的烯烃双官能化后, 杂芳基的氮原子进一步与烷基之间发生分子内亲核取代关环, 促使一个离去基团脱除; 随后发生环异构化反应, 并伴随第二个离去基团的消除, 最终生成含氮稠杂芳烃(Scheme 1b). 该反应体系适用于活化与非活化烯烃, 能够高效构建结构多样、官能团兼容性好的氮杂环化合物, 并成功构建了七类重要的氮杂环骨架, 为复杂天然产物及药物分子的后期修饰提供了有力工具. 然而, 该反应条件较为苛刻, 需在高温和较长时间下进行. 因此, 发展一种改进的反应条件及更温和的合成方法具有重要意义. 我们尝试对试剂进行合理修改, 以期待在温和的可见光反应条件下实现类似的迁移-环化过程. 我们将连接单元作为首要考虑因素, 考虑到砜与亚砜在性质上可能存在差异, 因此以亚砜作为连接单元, 合成了双官能化试剂. 值得关注的是, 亚砜试剂相较于砜基试剂确实展现出显著不同的反应特性. 在本文中, 我们以亚砜官能化试剂为核心, 在温和的光催化条件下, 通过自由基介导的官能团迁移-环化反应, 成功实现了含氮稠杂芳烃的高效合成(Scheme 1c).
1 结果与讨论
室温下, 选择双官能化试剂(1a)和苯乙烯(2a)作为反应底物, 系统地考察了反应溶剂、光催化剂、碱以及光源对该反应的影响(Table 1).
表1 反应条件优化aTable 1 Optimization of reaction conditions |
| Entry | Photocatalyst | Base | Solvent | Yieldb/% |
|---|---|---|---|---|
| 1 | Ir[dF(CF3)ppy]2(dtbbpy)PF6 | K2HPO4 | DMF | 47 |
| 2 | Ir[dF(CF3)ppy]2(dtbbpy)PF6 | K2HPO4 | CH3COCH3 | 36 |
| 3 | Ir[dF(CF3)ppy]2(dtbbpy)PF6 | K2HPO4 | CH3CN | 20 |
| 4 | Ir[dF(CF3)ppy]2(dtbbpy)PF6 | K2HPO4 | DCM | 45 |
| 5 | Ir[dF(CF3)ppy]2(dtbbpy)PF6 | K2HPO4 | EtOAc | 49 |
| 6 | Ir[dF(CF3)ppy]2(dtbbpy)PF6 | K2HPO4 | THF | 52 |
| 7 | Ir[dF(CF3)ppy]2(dtbbpy)PF6 | K2HPO4 | DMAc | 56 |
| 8 | Ir[dF(CF3)ppy]2(dtbbpy)PF6 | K2HPO4 | 1,4-Dioxane | 0 |
| 9 | Eosin Y | K2HPO4 | DMAc | 0 |
| 10 | fac-Ir(ppy)₃ | K2HPO4 | DMAc | 47 |
| 11 | Ru(bpy)3Cl2•6H2O | K2HPO4 | DMAc | 64 |
| 12 | Ru(bpy)3Cl2•6H2O | K3PO4 | DMAc | 30 |
| 13 | Ru(bpy)3Cl2•6H2O | Na2HPO4 | DMAc | 52 |
| 14c | Ru(bpy)3Cl2•6H2O | K2HPO4 | DMAc | 73 |
| 15c | None | K2HPO4 | DMAc | 0 |
| 16d | Ru(bpy)3Cl2•6H2O | K2HPO4 | DMAc | 0 |
a Reaction conditions: 1a (0.2 mmol, 1.0 equiv.), 2a (0.3 mmol, 1.5 equiv.), base (0.3 mmol, 1.5 equiv.), and photocatalyst (3 mol%) in organic solvent (2 mL), irradiated with 12 W blue LEDs for 7 h at room temperature under N2. b Yields of isolated products are given. c 10 W 520 nm green LEDs. d In dark. |
首先, 以Ir[dF(CF3)ppy]2(dtbbpy)PF6作为光催化剂, 磷酸氢二钾作为碱, N,N-二甲基甲酰胺为反应溶剂, 在室温、氮气氛围以及12W蓝光照射条件下对反应可行性进行了探究, 反应7 h以47%的分离收率得到目标产物3a (Table 1, Entry 1). 为了提高反应收率, 随后对反应溶剂进行了筛选(Entries 2~8). 实验结果表明, 丙酮和乙腈作为溶剂时, 反应也能顺利进行, 但产率均有不同程度的下降(Entries 2~3). 以二氯甲烷和乙酸乙酯作反应溶剂时, 反应效果与N,N-二甲基甲酰胺相当(Entries 4~5). 将反应溶剂替换为四氢呋喃或者N,N-二甲基乙酰胺时, 反应收率均有小幅度提升(Entries 6~7). 1,4-二氧六环作反应溶剂时(Entry 8), 未检测到目标化合物的生成. 接着, 以N,N-二甲基乙酰胺作为最优反应溶剂, 考察了不同类型的光催化剂对反应的影响(Entries 9~11). 以Ru(bpy)3Cl2•6H2O为催化剂时, 反应效果最佳, 表现出更高的催化效率; 而染料型光敏剂Eosin Y并不能顺利驱动反应. 考虑到碱在中和副产物HBr时关键作用, 对不同的碱进行了筛选(Entries 12~13). 磷酸钾和磷酸氢二钠作为碱时, 反应效果均有不同程度地降低. 最后, 为了进一步提高反应收率, 以520 nm的绿光作为光源并开展反应, 能以73%收率获得目标产物(Entry 14). 对照实验结果表明, 在没有光催化剂或可见光照射的情况下, 反应不能发生(Entries 15~16). 至此, 确定了最优反应条件.
在确定最佳反应条件后, 对底物的适用范围进行了探究(Table 2). 首先对一系列取代的芳基烯烃进行了适用性考察. 从实验结果来看, 苯环对位、间位或者邻位带有各种不同取代基时, 反应均能顺利发生, 能以中等至良好收率得到相应产物(3a~3q). 环化产物结构由化合物3q的单晶X射线衍射分析确认(CCDC号为 2480115). 该反应对一系列不同的具有给电子基(甲基、甲氧基、叔丁基、叔丁氧基、苯基; 3b~3f)以及吸电子基(卤素、三氟甲基、氰基、酰氧基、酯基、醛基, 3g~3n)取代的苯乙烯均具有良好的兼容性, 但缺电子的烯烃比富电子烯烃反应效果稍好. 此外, 芳环间位或者邻位取代基的电性和位阻效应(3p~3q)对反应的影响较小. 值得注意的是, 当反应底物上存在内炔基时, 该反应仅专一性地在烯基部分发生, 内炔基不受影响(3o). 将苯基替换为萘基时, 同样可以得到相应的苯并噻唑并吡咯产物(3r~3s). 除了苯乙烯类芳香族烯烃, 杂芳基烯烃同样也适用于该反应. 一系列苯并五元杂环烯烃(1,2-亚甲基二氧苯、苯并噻唑、苯并噻吩、苯并呋喃、吲哚; 3t~3x)也能与该反应兼容, 得到相应的目标产物. 此外, 其它杂芳基(如吡啶)也表现出良好的反应效果, 可以中等收率获得目标化合物(3y). 乙烯基苯硫醚在标准条件也能顺利发生转化(3z). 为了进一步探究这种策略的合成实用性, 将底物的范围扩展到了一系列复杂的天然产物和药物分子衍生的烯烃. 具有不同结构特征的几个复杂骨架能以中等的产率生成相应的高度官能化的含氮稠杂芳烃(3aa~3ae). 在探究了烯烃的适用范围之后, 将注意力转向通过引入其它具有迁移性能的含氮杂芳基来修饰杂环化试剂, 并通过迁移-环化反应构建不同的稠杂环核. 当苯并噻唑取代的杂环化试剂上连有官能团时, 其电子和空间效应并不影响与烯烃的反应(3ah~3ai). 将溴代烷基一侧的甲基换成氢原子或者酯基时, 底物也能在该条件下顺利转化为目标产物(3af~3ag). 除了苯并噻唑外, 噻唑取代的亚砜试剂也能在标准条件下反应(3aj).
表2 底物拓展aTable 2 Substrate scope |
 |
a Reaction conditions: 1 (0.2 mmol, 1.0 equiv.), 2 (0.3 mmol, 1.5 equiv.), K2HPO4 (0.3 mmol, 1.5 equiv.), and Ru(bpy)3Cl2•6H2O (3 mol%) in DMAc (2 mL), irradiated with 10 W 520 nm green LEDs for 7 h at room temperature under N2. Yields of isolated products are given. |
为了深入了解反应机理, 开展了开/关灯实验. 在反应引发后, 即使在无光照条件下, 反应产率仍然有一定的增长, 这一现象表明反应存在着自由基链式反应过程(Scheme 2a). 基于已有的实验结果以及之前相关文献报道, 提出以下可能的反应机理(Scheme 2b): 产率首先, 激发态的RuII光催化剂被化合物1氧化淬灭, 产生RuIII络合物以及自由基中间体a. 随后, 该烷基中间体加成至烯烃底物2的双键末端上, 得到苄基自由基中间体b. 后者经过五元环状过渡态以及环状碳硫键的断裂发生Smiles型重排, 从而实现杂芳基的迁移, 得到自由基中间体c. 该亚砜自由基中间体进一步实现“SO”的脱除, 进而得到自由基中间体d, 而该自由基中间体会快速从底物1上攫取溴原子(XAT过程), 得到烯烃双官能化产物e, 并且重新再生初始自由基a, 实现自由基的链式循环反应. 由于中间产物e上苯并噻唑的氮原子具有一定的亲核性, 且化合物另一端有溴原子作为良好的离去基团, 因此该中间体e可以进行分子内的亲核反应发生环化, 从而生成离子中间体f. 而该中间体经历环异构化并伴随着溴化氢的消除, 最终得到目标产物3.
2 结论
综上所述, 我们成功开发了一类以亚砜为连接单元的新型杂环化试剂, 实现了芳基烯烃的自由基杂环化反应. 该试剂能在可见光条件下与烯烃反应, 经由杂芳基迁移实现烯烃双官能化后, 继续发生分子内环化与环异构化, 完成一锅法串联过程, 从而高效构建多类含氮稠杂芳烃骨架. 该反应条件温和、官能团兼容性好、操作简便、烯烃原料易得. 利用此合成策略, 可便捷、高效地获取结构多样性的含氮稠杂芳烃, 适用于具有复杂骨架的烯烃分子的后期转化.
3 实验部分
3.1 仪器与试剂
Bruker公司400或500 MHz AVANCE III HD核磁共振仪, 溶剂CDCl3, 内标TMS; BRUKER公司VERTEX 70傅里叶变换红外光谱仪; Waters Micromass 公司GCT Premier高分辨质谱仪; INESA WRR显微熔点仪测定. 实验用的所有试剂均为市售试剂(均购于乐研、毕得、阿达玛斯, 纯度均为98%以上), 没有经过进一步纯化.
3.2 实验方法
在5 mL的反应瓶中, 依次加入0.2 mmol化合物1, 0.3 mmol磷酸二氢钾和3 mol% Ru(bpy)3Cl2•6H2O, 真空抽换氮气三次. 然后, 向反应瓶中加入烯烃2的N,N-二甲基乙酰胺(2 mL)溶液, 再置于10 W 520 nm绿光下室温反应7 h. 反应结束后, 用乙酸乙酯(10 mL×3)和水进行萃取, 用饱和氯化钠溶液洗涤有机相. 合并有机层, 用无水硫酸钠干燥, 减压旋干溶剂, 经柱层析分离得到目标产物3.
1-甲基-3-苯基苯并[d]吡咯[2,1-b]噻唑(3a): 产率73%, 黄色固体, m.p. 97~98 ℃; 1H NMR (500 MHz, CDCl3) δ: 7.78 (d, J=8.0 Hz, 1H), 7.66 (d, J=8.0 Hz, 1H), 7.57~7.53 (m, 2H), 7.45~7.41 (m, 2H), 7.38~7.34 (m, 1H), 7.26~7.22 (m, 1H), 7.21~7.17 (m, 1H), 6.63 (s, 1H), 2.76 (s, 3H); 13C NMR (125 MHz, CDCl3) δ: 135.7, 134.7, 131.6, 128.8, 125.5, 124.8, 124.6, 124.6, 123.8, 123.2, 122.9, 113.1, 112.6, 111.5, 14.5; FT-IR ν: 2920, 1556, 1469, 1371, 1315, 1095, 1066, 1041 cm－1; HRMS [ESI] calcd for C17H14NS [M＋H]＋ 264.0841, found 264.0835.
1-甲基-3-(对甲苯基)苯并[d]吡咯[2,1-b]噻唑(3b): 产率54%, 棕色固体, m.p. 122~123 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.78 (d, J=8.0 Hz, 1H), 7.66 (d, J=8.0 Hz, 1H), 7.50~7.46 (m, 2H), 7.40~7.34 (m, 1H), 7.29~7.22 (m, 3H), 6.63 (s, 1H), 2.77 (s, 3H), 2.42 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 135.7, 134.4, 131.9, 131.7, 129.5, 125.4, 124.6, 124.4, 123.8, 123.1, 122.4, 113.2, 112.6, 111.4, 21.2, 14.5; FT-IR ν: 2920, 1587, 1531, 1471, 1392, 1301, 1246, 972 cm－1; HRMS [ESI] calcd for C18H15NNaS [M＋Na]＋ 300.0817, found 300.0822.
3-(4-甲氧基苯基)-1-甲基苯并[d]吡咯[2,1-b]噻唑(3c): 产率47%, 棕色固体, m.p. 101~102 ℃; 1H NMR (500 MHz, CDCl3) δ: 7.76 (d, J=8.5 Hz, 1H), 7.64 (d, J=8.0 Hz, 1H), 7.49~7.45 (m, 2H), 7.37~7.32 (m, 1H), 7.24~7.20 (m, 1H), 7.00~6.96 (m, 2H), 6.55 (s, 1H), 3.85 (s, 3H), 2.75 (s, 3H); 13C NMR (125 MHz, CDCl3) δ: 157.2, 135.8, 131.6, 127.6, 125.8, 125.4, 124.4, 123.8, 123.1, 121.7, 114.3, 112.9, 112.5, 111.3, 55.4, 14.5; FT-IR ν: 2920, 1585, 1529, 1462, 1394, 1249, 1178, 1033 cm－1; HRMS [ESI] calcd for C18H15NNaOS [M＋Na]＋ 316.0767, found 316.0761.
3-(4-(叔丁基)苯基)-1-甲基苯并[d]吡咯[2,1-b]噻唑(3d): 产率46%, 棕色油. 1H NMR (500 MHz, CDCl3) δ: 7.77 (d, J=8.5 Hz, 1H), 7.65 (d, J=8.0 Hz, 1H), 7.51~7.45 (m, 4H), 7.37~7.33 (m, 1H), 7.25~7.21 (m, 1H), 6.61 (s, 1H), 2.76 (s, 3H), 1.38 (s, 9H); 13C NMR (125 MHz, CDCl3) δ: 147.7, 135.8, 131.9, 131.7, 125.7, 125.4, 124.4, 124.4, 123.8, 123.1, 122.5, 113.1, 112.6, 111.5, 34.5, 31.4, 14.5; FT-IR ν: 2960, 1531, 1471, 1392, 1303, 1246, 1193, 1028 cm－1; HRMS [ESI] calcd for C21H22NS [M＋H]＋ 320.1467, found 320.1477.
3-(4-(叔丁氧基)苯基)-1-甲基苯并[d]吡咯[2,1-b]噻唑(3e): 产率44%, 黄色固体, m.p. 114~115 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.78~7.73 (m, 1H), 7.66~7.62 (m, 1H), 7.46~7.41 (m, 2H), 7.37~7.32 (m, 1H), 7.25~7.19 (m, 1H), 7.08~7.04 (m, 2H), 6.57 (s, 1H), 2.74 (s, 3H), 1.39 (s, 9H); 13C NMR (125 MHz, CDCl3) δ: 152.6, 135.7, 131.6, 130.1, 125.5, 125.0, 124.7, 124.5, 123.8, 123.1, 122.1, 112.9, 112.6, 111.4, 78.5, 28.9, 14.5; FT-IR ν: 2974, 1587, 1527, 1471, 1363, 1244, 1161, 895 cm－1; HRMS [ESI] calcd for C21H22NOS [M＋H]＋336.1417, found 336.1425.
3-([1'-联苯]-4-基)-1-甲基苯并[d]吡咯并[2,1-b]噻唑(3f): 产率65%, 黄色固体, m.p. 143~144 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.79 (d, J=8.0 Hz, 1H), 7.69~7.64 (m, 5H), 7.63~7.59 (m, 2H), 7.48~7.43 (m, 2H), 7.40~7.32 (m, 2H), 7.28~7.22 (m, 1H), 6.66 (s, 1H), 2.78 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 141.0, 137.4, 135.7, 133.8, 131.6, 128.8, 127.5, 127.0, 126.8, 125.6, 124.9, 124.8, 123.9, 123.2, 123.1, 112.8, 112.7, 111.5, 14.5; FT-IR ν: 2920, 1585, 1535, 1469, 1392, 1303, 1259, 1193 cm－1; HRMS [ESI] calcd for C23H18NS [M＋H]＋ 340.1154, found 340.1156.
3-(4-氯苯基)-1-甲基苯并[d]吡咯[2,1-b]噻唑(3g): 产率50%, 黄色固体, m.p. 146~147 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.77 (d, J=7.6 Hz, 1H), 7.66~7.62 (m, 1H), 7.45~7.41 (m, 2H), 7.38~7.35 (m, 2H), 7.35~7.30 (m, 1H), 7.26~7.22 (m, 1H), 6.56 (s, 1H), 2.74 (s, 3H); 13C NMR (125 MHz, CDCl3) δ: 135.6, 133.3, 131.4, 130.0, 128.9, 128.7, 125.7, 125.6, 124.8, 123.9, 123.3, 112.7, 112.1, 111.3, 14.5; FT-IR ν: 2920, 1568, 1526, 1483, 1396, 1246, 1093, 1008 cm－1; HRMS [ESI] calcd for C17H13Cl- NS [M＋H]＋ 298.0452, found 298.0459.
3-(4-溴苯基)-1-甲基苯并[d]吡咯[2,1-b]噻唑(3h): 产率67%, 白色固体, m.p. 169~170 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.76 (d, J=8.4 Hz, 1H), 7.64 (d, J=8.0 Hz, 1H), 7.53~7.48 (m, 2H), 7.39~7.33 (m, 3H), 7.27~7.21 (m, 1H), 6.55 (s, 1H), 2.73 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 135.5, 133.7, 131.8, 131.4, 126.1, 125.6, 124.9, 123.8, 123.3, 123.3, 117.9, 112.7, 112.1, 111.3, 14.4; FT-IR ν: 2920, 1556, 1465, 1392, 1247, 1182, 1074, 1030 cm－1; HRMS [ESI] calcd for C17H13BrNS [M＋H]＋341.9947, found 341.9951.
3-(4-氟苯基)-1-甲基苯并[d]吡咯[2,1-b]噻唑(3i): 产率68%, 黄色固体, m.p. 115~116 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.77 (d, J=8.0 Hz, 1H), 7.65 (d, J=8.0 Hz, 1H), 7.49~7.44 (m, 2H), 7.39~7.33 (m, 1H), 7.26~7.21 (m, 1H), 7.14~7.08 (m, 2H), 6.55 (s, 1H), 2.75 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 160.5 (d, JF-C=242.5 Hz), 135.7, 131.4, 131.0 (d, JF-C=3.1 Hz), 126.0, 125.8 (d, JF-C=35.2 Hz), 124.7, 123.9, 123.2, 122.5, 115.6 (d, JF-C=21.3 Hz), 112.7, 112.3, 111.4, 14.4; 19F NMR (376 MHz, CDCl3) δ: －118.1 (s); FT-IR ν: 2920, 1556, 1495, 1398, 1274, 1220, 1159, 1060 cm－1; HRMS [ESI] calcd for C17H13FNS [M＋H]＋ 282.0747, found 282.0752.
1-甲基-3-(4-(三氟甲基)苯基)苯并[d]吡咯[2,1-b]噻唑(3j): 产率64%, 黄色固体, m.p. 163~164 ℃; 1H NMR (500 MHz, CDCl3) δ: 7.81~7.76 (m, 1H), 7.68~7.62 (m, 3H), 7.59~7.54 (m, 2H), 7.41~7.35 (m, 1H), 7.29~7.23 (m, 1H), 6.61 (s, 1H), 2.74 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 138.3 (q, JF-C=1.2 Hz), 135.4, 131.3, 126.2 (q, JF-C=32.2 Hz), 124.6 (q, JF-C=269.8 Hz), 125.7 (q, JF-C=11.3 Hz), 125.7, 125.2, 124.5, 124.3, 123.9, 123.5, 112.8, 111.9, 111.4, 14.4; 19F NMR (470 MHz, CDCl3) δ: －62.0 (s); FT-IR ν: 2920, 1537, 1462, 1359, 1274, 1163, 1093, 1066 cm－1; HRMS [ESI] calcd for C18H13F3NS [M＋H]＋ 332.0715, found 332.0712.
4-(1-甲基苯并[d]吡咯[2,1-b]噻唑-3-基)苯腈(3k): 产率64%, 黄色固体, m.p. 190~191 ℃; 1H NMR (500 MHz, CDCl3) δ: 7.81 (d, J=8.0 Hz, 1H), 7.68 (d, J=8.0 Hz, 1H), 7.65~7.62 (m, 2H), 7.54~7.50 (m, 2H), 7.42~7.38 (m, 1H), 7.31~7.27 (m, 1H), 6.61 (s, 1H), 2.76 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 139.3, 135.3, 132.6, 131.2, 126.0, 125.6, 125.5, 124.5, 123.9, 123.7, 119.6, 113.0, 111.7, 111.4, 107.0, 14.4; FT-IR ν: 2920, 2355, 1614, 1556, 1454, 1371, 1095, 1066 cm－1; HRMS [ESI] calcd for C18H12N2NaS [M＋Na]＋ 311.0613, found 311.0604.
4-(1-甲基苯并[d]吡咯[2,1-b]噻唑-3-基)苯基乙酸酯(3l): 产率70%, 黄色固体, m.p. 124~125 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.76~7.72 (m, 1H), 7.64~7.61 (m, 1H), 7.54~7.49 (m, 2H), 7.37~7.31 (m, 1H), 7.25~7.19 (m, 1H), 7.16~7.12 (m, 2H), 6.57~6.54 (m, 1H), 2.73 (s, 3H), 2.33 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 169.8, 147.8, 135.6, 132.7, 131.4, 125.5, 125.5, 124.7, 123.8, 123.2, 122.9, 121.9, 112.7, 112.4, 111.5, 21.2, 14.4; FT-IR ν: 2920, 1753, 1529, 1450, 1367, 1246, 1199, 1167 cm－1; HRMS [ESI] calcd for C19H16NO2S [M＋H]＋ 322.0896, found 322.0905.
4-(1-甲基苯并[d]吡咯[2,1-b]噻唑-3-基)苯基乙酸酯(3m): 产率75%, 黄色固体, m.p. 162~163 ℃; 1H NMR (400 MHz, CDCl3) δ: 8.08~8.03 (m, 2H), 7.77 (d, J=8.4 Hz, 1H), 7.66 (d, J=7.6 Hz, 1H), 7.55~7.50 (m, 2H), 7.40~7.33 (m, 1H), 7.28~7.22 (m, 1H), 6.64 (s, 1H), 3.92 (s, 3H), 2.74 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 167.2, 139.3, 135.4, 131.4, 130.3, 125.8, 125.7, 125.2, 124.9, 124.0, 123.9, 123.5, 112.8, 112.3, 111.6, 51.9, 14.4; FT-IR ν: 2920, 1720, 1587, 1469, 1392, 1280, 1197, 1114 cm－1; HRMS [ESI] calcd for C19H16NO2S [M＋H]＋322.0896, found 322.0905.
4-(1-甲基苯并[d]吡咯[2,1-b]噻唑-3-基)苯甲醛(3n): 产率73%, 黄色固体, m.p. 185~186 ℃; 1H NMR (500 MHz, CDCl3) δ: 9.93 (s, 1H), 7.89~7.85 (m, 2H), 7.78 (d, J=8.0 Hz, 1H), 7.67 (d, J=8.0 Hz, 1H), 7.60~7.56 (m, 2H), 7.41~7.36 (m, 1H), 7.30~7.26 (m, 1H), 6.65 (s, 1H), 2.74 (s, 3H); 13C NMR (125 MHz, CDCl3) δ: 191.5, 141.0, 135.3, 132.6, 131.3, 130.6, 125.9, 125.7, 125.6, 124.4, 123.9, 123.7, 112.9, 112.2, 111.6, 14.5; FT-IR ν: 2920, 1693, 1556, 1487, 1392, 1274, 1198, 1170 cm－1; HRMS [ESI] calcd for C18H14NOS [M＋H]＋ 292.0791, found 292.0799.
3-(4-(丁-2-炔-1-氧基)苯基)-1-甲基苯并[d]吡咯[2,1- b]噻唑(3o): 产率54%, 黄色固体, m.p. 119~120 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.75 (d, J=8.4 Hz, 1H), 7.63 (d, J=7.6 Hz, 1H), 7.50~7.43 (m, 2H), 7.38~7.31 (m, 1H), 7.25~7.19 (m, 1H), 7.07~7.01 (m, 2H), 6.55 (s, 1H), 4.68 (s, 2H), 2.74 (s, 3H), 1.89 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 155.4, 135.7, 131.6, 128.2, 125.7, 125.4, 124.4, 123.8, 123.1, 121.8, 115.3, 112.8, 112.5, 111.4, 83.7, 74.3, 56.6, 14.4, 3.8; FT-IR ν: 2918, 1529, 1471, 1394, 1303, 1222, 1180, 1004 cm－1; HRMS [ESI] calcd for C21H18NOS [M＋H]＋ 332.1104, found 332.1097.
3-(3-溴苯基)-1-甲基苯并[d]吡咯[2,1-b]噻唑(3p): 产率64%, 黄色固体, m.p. 116~117 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.72~7.68 (m, 1H), 7.62~7.56 (m, 2H), 7.39~7.35 (m, 1H), 7.34~7.28 (m, 1H), 7.25~7.17 (m, 3H), 6.51 (s, 1H), 2.68 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 136.9, 135.4, 131.3, 130.3, 127.4, 127.4, 125.6, 124.9, 123.8, 123.7, 123.3, 123.1, 123.0, 112.7, 111.7, 111.3, 14.4; FT-IR ν: 2920, 1614, 1591, 1523, 1477, 1392, 1247, 1070 cm－1; HRMS [ESI] calcd for C17H13BrNS [M＋H]＋ 341.9947, found 341.9941.
3-(2-氟苯基)-1-甲基苯并[d]吡咯[2,1-b]噻唑(3q): 产率60%, 黄色固体, m.p. 84~85 ℃; 1H NMR (500 MHz, CDCl3) δ: 7.88 (d, J=8.0 Hz, 1H), 7.73 (d, J=7.5 Hz, 1H), 7.67~7.61 (m, 1H), 7.47~7.42 (m, 1H), 7.37~7.27 (m, 3H), 7.26~7.21 (m, 1H), 6.79 (s, 1H), 2.86 (s, 3H); 13C NMR (125 MHz, CDCl3) δ: 159.2 (d, JF-C=245.5 Hz), 135.7, 131.7 (d, JF-C=3.3 Hz), 127.6 (d, JF-C=4.8 Hz), 126.3 (d, JF-C=8.1 Hz), 125.4, 124.9, 124.3 (d, JF-C=3.5 Hz), 124.3, 123.4 (d, JF-C=49.9 Hz), 123.8 (d, JF-C=13.5 Hz), 121.6, 116.1 (d, JF-C=22.3 Hz), 113.8 (d, JF-C=6.5 Hz), 112.7, 107.9, 14.4; 19F NMR (470 MHz, CDCl3) δ: －114.3 (s); FT-IR ν: 2920, 1556, 1524, 1479, 1392, 1303, 1211, 1074 cm－1; HRMS [ESI] calcd for C17H13FNS [M＋H]＋ 282.0747, found 282.0737.
1-甲基-3-(萘-2-基)苯并[d]吡咯[2,1-b]噻唑(3r): 产率66%, 黄色固体, m.p. 123~124 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.93~7.86 (m, 3H), 7.85~7.81 (m, 1H), 7.78~7.72 (m, 2H), 7.68~7.65 (m, 1H), 7.52~7.47 (m, 1H), 7.45~7.40 (m, 1H), 7.38~7.33 (m, 1H), 7.26~7.22 (m, 1H), 6.75~6.72 (m, 1H), 2.76 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 135.6, 134.1, 132.3, 131.6, 131.4, 128.4, 127.7, 127.6, 126.2, 125.6, 124.9, 124.8, 124.0, 123.8, 123.4, 123.2, 122.2, 113.2, 112.7, 111.7, 14.5; FT-IR ν: 2918, 1573, 1521, 1435, 1302, 1246, 1159, 1072 cm－1; HRMS [ESI] calcd for C21H16NS [M＋H]＋ 314.0998, found 314.1002.
1-甲基-3-(萘-1-基)苯并[d]吡咯[2,1-b]噻唑(3s): 产率61%, 棕色固体, m.p. 124~125 ℃; 1H NMR (400 MHz, CDCl3) δ: 8.31~8.26 (m, 1H), 7.95~7.90 (m, 1H), 7.85~7.79 (m, 2H), 7.66~7.59 (m, 2H), 7.57~7.51 (m, 3H), 7.40~7.35 (m, 1H), 7.26~7.21 (m, 1H), 6.61 (s, 1H), 2.84 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 136.1, 134.2, 133.6, 131.5, 131.2, 128.5, 126.7, 126.4, 125.8, 125.8, 125.8, 125.7, 125.4, 125.0, 124.0, 123.9, 123.2, 115.3, 112.7, 112.5, 14.5; FT-IR ν: 2920, 1556, 1494, 1392, 1247, 1163, 1089, 1037 cm－1; HRMS [ESI] calcd for C21H16NS [M＋H]＋ 314.0998, found 314.0989.
3-(苯并[d][1,3]二噁烷-5-基)-1-甲基苯并[d]吡咯[2,1-b]噻唑(3t): 产率38%, 黄色固体, m.p. 148~149 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.77~7.73 (m, 1H), 7.65~7.62 (m, 1H), 7.37~7.32 (m, 1H), 7.25~7.20 (m, 1H), 7.05~7.03 (m, 1H), 7.00~6.97 (m, 1H), 6.90~6.86 (m, 1H), 6.51~6.49 (m, 1H), 5.98 (s, 2H), 2.74 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 148.1, 145.0, 135.7, 131.4, 129.3, 125.5, 124.4, 123.8, 123.1, 122.1, 117.9, 113.1, 112.6, 111.4, 108.7, 105.5, 100.9, 14.4; FT-IR ν: 2920, 1523, 1485, 1471, 1394, 1253, 1226, 1039 cm－1; HRMS [ESI] calcd for C18H14NO2S [M＋H]＋ 308.0740, found 308.0735.
3-(苯并[d]噻唑-2-基)-1-甲基苯并[d]吡咯[2,1-b]噻唑(3u): 产率54%, 黄色固体, m.p. 166~167 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.98 (d, J=8.4 Hz, 1H), 7.80 (d, J=7.6 Hz, 1H), 7.74 (d, J=8.4 Hz, 1H), 7.68 (d, J=8.0 Hz, 1H), 7.44~7.38 (m, 1H), 7.36~7.30 (m, 1H), 7.27~7.21 (m, 2H), 6.69 (s, 1H), 2.70 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 162.2, 154.4, 135.3, 134.1, 132.3, 129.4, 125.9, 125.8, 125.6, 124.1, 123.8, 123.6, 121.9, 121.3, 113.1, 112.0, 108.6, 14.3; FT-IR ν: 2920, 1537, 1485, 1435, 1323, 1257, 1180, 941 cm－1; HRMS [ESI] calcd for C18H13N2S2 [M＋H]＋ 321.0515, found 321.0513.
3-(苯并[b]噻吩-2-基)-1-甲基苯并[d]吡咯[2,1-b]噻唑(3v): 产率55%, 黄色固体, m.p. 98~99 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.81 (d, J=7.6 Hz, 1H), 7.77~7.71 (m, 2H), 7.68~7.64 (m, 1H), 7.38~7.31 (m, 2H), 7.27~7.22 (m, 2H), 7.19 (s, 1H), 6.57 (s, 1H), 2.73 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 141.1, 138.4, 138.2, 135.6, 131.7, 125.7, 125.0, 124.4, 124.4, 124.0, 123.4, 123.0, 122.5, 122.1, 115.9, 112.8, 112.0, 108.2, 14.3; FT-IR ν: 2920, 1568, 1492, 1390, 1301, 1249, 1128, 1068 cm－1; HRMS [ESI] calcd for C19H14NS2 [M＋H]＋ 320.0562, found 320.0572.
3-(苯并呋喃-2-基)-1-甲基苯并[d]吡咯[2,1-b]噻唑(3w): 产率43%, 黄色固体, m.p. 103~104 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.81~7.78 (m, 1H), 7.70~7.66 (m, 1H), 7.55~7.48 (m, 2H), 7.40~7.35 (m, 1H), 7.29~7.24 (m, 1H), 7.23~7.18 (m, 2H), 6.64~6.62 (m, 1H), 6.59~6.57 (m, 1H), 2.77~2.75 (m, 3H); 13C NMR (100 MHz, CDCl3) δ: 154.2, 152.7, 135.7, 132.1, 129.9, 125.6, 125.2, 125.0, 124.0, 123.5, 122.7, 122.7, 119.8, 112.8, 110.8, 110.7, 104.8, 97.6, 14.3; FT-IR ν: 2920, 1614, 1556, 1450, 1392, 1253, 1186, 1006 cm－1; HRMS [ESI] calcd for C19H14NOS [M＋H]＋ 304.0791, found 304.0798.
1-甲基-3-(1-甲苯磺酰基-1H-吲哚-3-基)苯并[d]吡咯[2,1-b]噻唑(3x): 产率45%, 黄色固体, m.p. 133~134 ℃; 1H NMR (500 MHz, CDCl3) δ: 8.08 (d, J=8.5 Hz, 1H), 7.86 (d, J=8.0 Hz, 1H), 7.81 (d, J=8.0 Hz, 2H), 7.78 (d, J=8.5 Hz, 1H), 7.64 (d, J=7.5 Hz, 1H), 7.62 (s, 1H), 7.39~7.34 (m, 2H), 7.32~7.27 (m, 1H), 7.25~7.22 (m, 1H), 7.20 (d, J=8.0 Hz, 2H), 6.62 (s, 1H), 2.77 (s, 3H), 2.30 (s, 3H); 13C NMR (125 MHz, CDCl3) δ: 144.8, 135.8, 135.5, 135.1, 131.5, 129.9, 129.9, 126.8, 125.6, 124.8, 124.4, 124.0, 123.7, 123.4, 123.3, 121.1, 121.1, 118.1, 113.9, 112.8, 112.8, 105.1, 21.6, 14.4; FT-IR ν: 2922, 1593, 1504, 1462, 1394, 1265, 1174, 1132 cm－1; HRMS [ESI] calcd for C26H21N2O2S2 [M＋H]＋ 457.1039, found 457.1044.
1-甲基-3-(2-吡啶基)苯并[d]吡咯[2,1-b]噻唑(3y): 产率60%, 黄色固体, m.p. 144~145 ℃; 1H NMR (400 MHz, CDCl3) δ: 8.55~8.51 (m, 1H), 8.00~7.96 (m, 1H), 7.85~7.81 (m, 1H), 7.76~7.73 (m, 1H), 7.45~7.40 (m, 1H), 7.29~7.24 (m, 1H), 7.07 (s, 1H), 7.06~7.01 (m, 1H), 6.77~6.72 (m, 1H), 2.48 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 163.7, 154.5, 133.6, 131.9, 125.9, 123.5, 122.6, 121.7, 121.6, 121.1, 120.5, 120.1, 113.5, 112.3, 106.8, 11.5; FT-IR ν: 2920, 1563, 1514, 1436, 1365, 1251, 1114, 1058 cm－1; HRMS [ESI] calcd for C16H13N2S [M＋H]＋ 265.0794, found 265.0785.
1-甲基-3-(苯硫基)苯并[d]吡咯[2,1-b]噻唑(3z): 产率47%, 棕色油. 1H NMR (400 MHz, CDCl3) δ: 7.78 (d, J=8.0 Hz, 1H), 7.62 (d, J=8.0 Hz, 1H), 7.39~7.34 (m, 1H), 7.28~7.24 (m, 1H), 7.24~7.17 (m, 2H), 7.16~7.12 (m, 2H), 7.10~7.05 (m, 1H), 6.34 (s, 1H), 2.74 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 139.0, 136.4, 133.8, 131.7, 128.8, 125.9, 125.5, 125.1, 124.9, 124.1, 123.6, 118.7, 112.9, 97.1, 14.4; FT-IR ν: 2918, 1581, 1514, 1495, 1390, 1294, 1080, 1024 cm－1; HRMS [ESI] calcd for C17H14NS2 [M＋H]＋ 296.0562, found 296.0568.
(8R,9R,13S,14S)-13-甲基-3-(1-甲基苯并[d]吡咯并[2,1-b]噻唑-3-基)-6,7,8,9,11,12,13,14,15,16-十氢-17H-环戊[a]菲烷-17-酮(3aa): 产率75%, 黄色固体, m.p. 184~185 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.76 (d, J=8.4 Hz, 1H), 7.64 (d, J=7.6 Hz, 1H), 7.37~7.32 (m, 3H), 7.26~7.20 (m, 2H), 6.59 (s, 1H), 3.02~2.96 (m, 2H), 2.75 (s, 3H), 2.56~2.42 (m, 2H), 2.35~2.27 (m, 1H), 2.20~2.11 (m, 1H), 2.10~2.02 (m, 2H), 2.01~1.95 (m, 1H), 1.70~1.58 (m, 3H), 1.55~1.49 (m, 2H), 1.48~1.43 (m, 1H), 0.93 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 221.1, 136.8, 136.4, 135.7, 132.3, 131.6, 125.8, 125.5, 125.1, 124.5, 123.8, 123.1, 122.5, 122.3, 112.9, 112.6, 111.5, 50.5, 48.1, 44.4, 38.3, 35.9, 31.6, 29.6, 26.6, 25.8, 21.6, 14.5, 13.9; FT-IR ν: 2926, 1737, 1504, 1462, 1394, 1303, 1246, 1082 cm－1; HRMS [ESI] calcd for C29H30NOS [M＋H]＋ 440.2043, found 440.2037.
甲基(4-(1-甲基苯并[d]吡咯[2,1-b]噻唑-3-基)苯基甲基)邻苯二甲酸酯(3ab): 产率77%, 黄色固体, m.p. 80~81 ℃; 1H NMR (400 MHz, CDCl3) δ: 8.10 (dd, J=7.6 Hz, 1.6 Hz, 1H), 7.75 (d, J=8.0 Hz, 1H), 7.64 (dd, J=8.0 Hz, 0.8 Hz, 1H), 7.57~7.52 (m, 3H), 7.49~7.45 (m, 2H), 7.37~7.33 (m, 1H), 7.33~7.29 (m, 1H), 7.26~7.20 (m, 1H), 7.10 (dd, J=8.0 Hz, 0.8 Hz, 1H), 6.63~6.60 (m, 1H), 5.32 (s, 2H), 2.74 (s, 3H), 2.16 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 169.8, 164.6, 150.7, 135.6, 135.1, 133.9, 132.1, 131.6, 131.5, 129.4, 126.1, 125.6, 124.8, 124.7, 123.9, 123.8, 123.4, 123.4, 123.3, 112.7, 112.6, 111.4, 67.2, 20.8, 14.5; FT-IR ν: 2922, 1768, 1720, 1533, 1450, 1367, 1251, 1074 cm－1; HRMS [ESI] calcd for C27H22NO4S [M＋H]＋ 456.1264, found 456.1259.
乙基 2-(4-异丁氧基-3-(1-甲基苯并[d]吡咯并[2,1-b]噻唑-3-基)苯基)-4-甲基噻唑-5-羧酸酯(3ac): 产率34%, 黄色固体, m.p. 123~124 ℃; 1H NMR (400 MHz, CDCl3) δ: 8.06 (d, J=2.0 Hz, 1H), 7.82 (dd, J=8.4 Hz, 2.0 Hz, 1H), 7.78 (d, J=8.0 Hz, 1H), 7.63 (d, J=8.0 Hz, 1H), 7.36~7.31 (m, 1H), 7.25~7.19 (m, 1H), 6.99 (d, J=8.8 Hz, 1H), 6.76 (s, 1H), 4.36 (q, J=7.2 Hz, 2H), 3.39 (d, J=6.8 Hz, 2H), 2.80 (s, 3H), 2.77 (s, 3H), 2.37~2.29 (m, 1H), 1.40 (t, J=7.2 Hz, 3H), 1.05 (d, J=6.8 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ: 170.3, 162.5, 161.0, 157.8, 135.9, 132.2, 126.7, 125.7, 125.6, 125.2, 125.0, 125.0, 123.7, 123.5, 123.0, 120.8, 114.5, 112.6, 112.4, 109.6, 75.5, 61.1, 28.0, 19.6, 17.6, 14.5, 14.4; FT-IR ν: 2924, 1710, 1519, 1469, 1371, 1259, 1093, 1020 cm－1; HRMS [ESI] calcd for C28H29N2O3S2 [M＋H]＋ 505.1614, found 505.1618.
异丙基 2-甲基-2-(4-(4-(1-甲基苯并[d]吡咯[2,1-b]噻唑-3-基)苯甲酰)苯氧基)丙酸酯(3ad): 产率65%, 黄色固体, m.p. 147~148 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.86~7.82 (m, 2H), 7.81~7.75 (m, 3H), 7.67~7.63 (m, 1H), 7.58~7.54 (m, 2H), 7.39~7.33 (m, 1H), 7.26~7.22 (m, 1H), 6.92~6.87 (m, 2H), 6.65 (s, 1H), 5.15~5.07 (m, 1H), 2.74 (s, 3H), 1.68 (s, 6H), 1.22 (d, J=6.4 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ: 194.9, 173.3, 159.2, 138.8, 135.4, 133.7, 131.9, 131.3, 131.3, 130.9, 125.8, 125.3, 124.9, 123.9, 123.8, 123.5, 117.3, 112.8, 112.3, 111.6, 79.4, 69.3, 25.4, 21.6, 14.5; FT-IR ν: 2926, 1730, 1598, 1531, 1487, 1246, 1174, 1101 cm－1; HRMS [ESI] calcd for C31H30NO4S [M＋H]＋ 512.1890, found 512.1895.
甲基2-(5-甲氧基-1-(4-(1-甲基苯并[d]吡咯并[2,1-b]噻唑-3-基)苯甲酰)-1H-吲哚-3-基)乙酸酯(3ae): 产率41%, 黄色固体, m.p. 160~161 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.82~7.76 (m, 3H), 7.69~7.66 (m, 1H), 7.59~7.55 (m, 2H), 7.42~7.36 (m, 1H), 7.30~7.25 (m, 1H), 7.01~6.97 (m, 2H), 6.69~6.65 (m, 2H), 3.84 (s, 3H), 3.72 (s, 3H), 3.70 (s, 2H), 2.77 (s, 3H), 2.45 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 171.6, 169.2, 155.8, 139.6, 136.2, 135.4, 131.3, 131.2, 131.0, 130.7, 130.4, 125.9, 125.5, 125.3, 124.1, 123.9, 123.6, 115.0, 112.9, 112.1, 111.6, 111.6, 111.4, 101.1, 55.8, 52.1, 30.3, 14.5, 13.2; FT-IR ν: 2924, 1737, 1600, 1531, 1454, 1317, 1246, 1166 cm－1; HRMS [ESI] calcd for C31H27N2O4S [M＋H]＋ 523.1686, found 523.1684.
3-苯基苯并[d]吡咯[2,1-b]噻唑(3af): 产率38%, 黄色固体, m.p. 115~116 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.68~7.64 (m, 1H), 7.60~7.55 (m, 3H), 7.53~7.51 (m, 1H), 7.46~7.40 (m, 2H), 7.40~7.36 (m, 1H), 7.29~7.24 (m, 1H), 7.22~7.17 (m, 1H), 6.97~6.94 (m, 1H); 13C NMR (100 MHz, CDCl3) δ: 134.6, 131.1, 128.9, 125.8, 125.1, 124.7, 124.4, 123.9, 123.8, 114.6, 112.6, 111.5, 111.4, 104.3; FT-IR ν: 2920, 1537, 1469, 1392, 1274, 1182, 1089, 1040 cm－1; HRMS [ESI] calcd for C16H12NS [M＋H]＋ 250.0685, found 250.0676.
乙基3-苯基苯并[d]吡咯[2,1-b]噻唑-1-羧酸酯(3ag): 产率57%, 灰色固体, m.p. 107~108 ℃; 1H NMR (500 MHz, CDCl3) δ: 9.22 (d, J=8.5 Hz, 1H), 7.70 (s, 1H), 7.65~7.61 (m, 1H), 7.61~7.57 (m, 2H), 7.46~7.40 (m, 3H), 7.33~7.28 (m, 1H), 7.27~7.22 (m, 1H), 4.39 (q, J=7.0 Hz, 2H), 1.44 (t, J=7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 160.5, 135.7, 133.3, 130.6, 129.0, 126.1, 126.0, 125.7, 125.1, 124.6, 123.1, 122.2, 120.1, 118.0, 115.2, 60.5, 14.6; FT-IR ν: 2922, 1755, 1723, 1541, 1465, 1392, 1257, 1063 cm－1; HRMS [ESI] calcd for C19H16NO2S [M＋H]＋ 322.0896, found 322.0899.
6-溴-1-甲基-3-苯基苯并[d]吡咯[2,1-b]噻唑(3ah): 产率62%, 黄色固体, m.p. 103~104 ℃; 1H NMR (500 MHz, CDCl3) δ: 7.71~7.69 (m, 1H), 7.54~7.51 (m, 1H), 7.50~7.47 (m, 2H), 7.44~7.38 (m, 3H), 7.22~7.17 (m, 1H), 6.59 (s, 1H), 2.66 (s, 3H); 13C NMR (125 MHz, CDCl3) δ: 134.6, 134.3, 133.5, 128.9, 128.5, 126.2, 125.0, 124.7, 124.6, 122.4, 115.7, 113.5, 113.5, 111.8, 14.3; FT-IR ν: 2922, 1598, 1523, 1469, 1392, 1284, 1062, 1004 cm－1; HRMS [ESI] calcd for C17H13BrNS [M＋H]＋ 341.9947, found 341.9949.
1-甲基-3-苯基苯并[d]吡咯[2,1-b]噻唑-7-腈(3ai): 产率66%, 黄色固体. m.p. 125~126 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.94 (s, 1H), 7.71 (d, J=8.0 Hz, 1H), 7.51~7.47 (m, 3H), 7.45~7.39 (m, 2H), 7.24~7.18 (m, 1H), 6.66 (s, 1H), 2.74 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 137.7, 135.7, 133.9, 128.9, 126.5, 125.5, 125.2, 124.8, 124.4, 122.2, 118.8, 115.4, 114.4, 112.7, 108.9, 14.4; FT-IR ν: 2920, 2356, 1556, 1465, 1392, 1259, 1158, 1080 cm－1; HRMS [ESI] calcd for C18H13N2S [M＋H]＋ 289.0794, found 289.0803.
2-溴-3,5-二甲基-7-苯基吡咯并[2,1-b]噻唑(3aj): 产率47%, 无色油. 1H NMR (400 MHz, CDCl3) δ: 7.43~7.35 (m, 4H), 7.16~7.11 (m, 1H), 6.58~6.56 (m, 1H), 2.61 (s, 3H), 2.56 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 134.4, 129.7, 128.8, 124.6, 124.4, 123.7, 123.6, 112.3, 111.0, 96.2, 13.8, 13.4; FT-IR ν: 2920, 1598, 1519, 1444, 1392, 1201, 1082, 1028 cm－1; HRMS [ESI] calcd for C14H13BrNS [M＋H]＋ 305.9947, found 305.9951.
辅助材料(Supporting Information) 化合物1a、1af~1aj、3a~3aj的1H NMR、13C NMR以及3i、3j和3q的19F NMR谱图. 这些材料可以免费从本刊网站(http://sioc-journal.cn/)上下载.
(Cheng, F.)