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串联的 5-Endo 卤代内酰胺化 C-H 键氧化官能团化合成 β - 卤代吡咯烷酮的新方法

串联的 5-Endo 卤代内酰胺化 C-H 键氧化官能团化合成 β - 卤代吡咯烷酮的新方法. 吕明灿 导师 : Richard P. Hsung 教授 唐宇 副教授 2013.05.23. 1. 背景介绍. 2. 课题设计. 3. 结果与讨论. 4. 结论. 5. 致谢. 5- 羟基吡咯 -2- 酮类化合物 A, 具有广泛的生物活性。 A1, 被证明具有良好的抗肿瘤活性， A2, 抗癌活性. 1. 背景介绍. 1.1 5- 羟基吡咯 -2- 酮类生物活性. 5-Hydroxypyrrol-2(5 H )-ones.

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串联的 5-Endo 卤代内酰胺化 C-H 键氧化官能团化合成 β - 卤代吡咯烷酮的新方法

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  1. 串联的5-Endo卤代内酰胺化C-H键氧化官能团化合成β-卤代吡咯烷酮的新方法串联的5-Endo卤代内酰胺化C-H键氧化官能团化合成β-卤代吡咯烷酮的新方法 吕明灿 导师: Richard P. Hsung 教授 唐宇 副教授 2013.05.23

  2. 1. 背景介绍 2. 课题设计 3. 结果与讨论 4. 结论 5. 致谢 Tianjin University

  3. 5-羟基吡咯-2-酮类化合物A, 具有广泛的生物活性。 A1, 被证明具有良好的抗肿瘤活性， A2, 抗癌活性. 1. 背景介绍 1.1 5-羟基吡咯-2-酮类生物活性 5-Hydroxypyrrol-2(5H)-ones Tianjin University

  4. 1.2 5-羟基吡咯-2-酮类化合物的有机应用 Tianjin University

  5. 1.3 吡咯烷酮类化合物的合成方法 • 1. 3.1 铜催化的2,3-连烯酰胺环合 --Ma, S. M.; Xie H. X. Org. Lett. 2000, 24, 3801 • 1.3.2 酰基氰类经金属催化的缩合环化 --Veronese, A. C.; Callegari, R. J. Chem. Soc., Perkin Trans. 1 1994, 1779 Tianjin University

  6. 1.3.3 镍催化的α-炔酮的氰化 --Arzoumanian, H.; Jean, M.; Nuel, D. Organometallics1997, 16, 2726. • 1.3.4 内酯的氨化 --Farina, F.; Victoria, M. M.; Carmen, P. M. et al. Heterocycles, 1984, 8, 1733. Tianjin University

  7. 1.3.5 5-Endo 电环化 --Igor, D. J.; Fabien G.; Zard, S. Z.Org. Lett. 2010, 12, 416 Tianjin University 7

  8. 2. 课题设计 • 2.1 选题依据 --Tang, Y.; Li,C. Z. Org. Lett. 2004, 6, 3229 Tianjin University

  9. --Tang, Y.; Li,C. Z. Tetrahedron Lett., 2006, 47, 3823 Tianjin University 9

  10. --Igor, D. J.; Fabien G.; Zard, S. Z.Org. Lett. 2010, 12, 416 Tianjin University 10

  11. 2.2 研究内容 A B Tianjin University 11

  12. 3. 结果与讨论 • 3.1 条件优化 Tianjin University

  13. aNo desired product was generated. bβ-Chloro product was obtained, yield was 34%. Tianjin University 13

  14. 3.2 目标化合物的合成 • 3.2 .1 β-碘代-吡咯烷酮的合成a aMethod A: Treating substrate 2 (1.0 equiv) with tBuOCl (3.0 equiv) and I2 (3.0 equiv) in acetonitrile at rt, stirring for 4 h. Method B: Treating substrate 2 (1.0 equiv) with NIS (4.0 equaiv）in acetonitrile-water (1:1) at rt, stirring for 20 h. b The datas in parenthesis were yield derived by using Method B. cThe reaction was stirred for 48 h. Tianjin University 14

  15. 3.2.2 方法的扩展 a The reaction was stirred for 10 h at 50 oC. b 20% of starting materials were recovered, the ratio of β-bromo-pyrrolidinones to β -iodo-pyrrolidinoneswas 1:6. c 18% of starting materials were recovered, the ratio of β-iodo-pyrrolidinones to β -chloro-pyrrolidinoneswas 1:3.5. Tianjin University 15

  16. 3.2.3 β-溴代-吡咯烷酮的合成a a Treating substrate 4 (1.0 equiv) with NBS (4.0 equiv) in acetonitrile-water (1:1) at 50 oC, stirring for 10 h. bpara-bromo-phenyl in product was derived. c 20% of starting materials were recovered Tianjin University 16

  17. 3.3 其他取代基底物的探索研究 • 3.3.1 --唐宇，[博士学位论文]，上海；中国科学院上海有机化学研究所，2005. Tianjin University 17

  18. 3.3.2 • 底物要求: β-位烯基碘代或溴代, Z-式结构 Tianjin University 18

  19. 3.4 反应机理探究 Tianjin University

  20. 3.5 方法的可应用性 Tianjin University 20

  21. 4 结论 • 1. 我们发展了一种以β-卤代-β,γ-不饱和酰胺为底物，在次氯酸叔丁酯与碘（或者NIS）的作用下，通过串联的5-endo环化，C-H键氧化官能团化来合成卤代吡咯烷酮类化合物的新方法，这一方法具有重要意义。 • 2. 用我们发现的方法成功构建了天然产物分 子Crispine A的母核结构，证明了我们发现的这一方法具有较高的可实用性。 • 3. 在温和的条件下完成了C-H键氧化官能团化。 Tianjin University

  22. 5 致谢 • 感谢Richard Hsung教授对我的支持 • 感谢唐宇副教授对我的悉心指导和教育 • 感谢杜云飞、黄剑辉副教授对本实验提出的宝贵意见 • 感谢冯鹤静、刘小凡、刘丽伟以及本课题组的所有成员 • 感谢各位答辩委员的莅临指导 • 感谢我的家人对我学业的支持 Tianjin University

  23. 谢谢 Tianjin University

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