SIOC English
有机化学
高级检索

有机化学 >

2020 , Vol. 40 >Issue 10: 3431 - 3438

DOI: https://doi.org/10.6023/cjoc202005001

研究论文

自由基参与的[1.1.1]螺桨烷溴烷基化反应:溴代双环[1.1.1]戊烷衍生物的合成

  • 张红 ,
  • 王明扬 ,
  • 吴新鑫 ,
  • 朱晨
展开
  • a 苏州大学材料与化学化工学部 苏州 215123;
    b 中国科学院上海有机化学研究所 天然产物有机合成重点实验室 上海 200032

收稿日期: 2020-05-01

  修回日期: 2020-05-30

  网络出版日期: 2020-06-10

基金资助

国家自然科学基金（Nos.21722205，21971173）资助项目.

收起

Radical-Mediated Bromoalkylation of [1.1.1]propellane: Synthesis of Bromo-substituted Bicyclo[1.1.1]pentane Derivatives

  • Zhang Hong ,
  • Wang Mingyang ,
  • Wu Xinxin ,
  • Zhu Chen
Expand
  • a College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123;
    b Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Shanghai 200032

Received date: 2020-05-01

  Revised date: 2020-05-30

  Online published: 2020-06-10

Supported by

Project supported by the National Natural Science Foundation of China (Nos. 21722205, 21971173).

Fold

摘要

双环[1.1.1]戊烷（BCP）常被用作苯基、叔丁基和炔基的生物等排体，以提高生物活性分子的类药性.因此，向BCP骨架引入实用性官能团为药物开发中设计新的生物等排体提供了有效策略.报道了自由基参与的[1.1.1]螺桨烷的溴烷基化反应，实现了溴代BCP衍生物的合成.该反应以溴代烷基杂芳基砜为原料，经自由基途径向螺桨烷同时引入烷基杂芳基砜和溴两种官能团.该反应快速高效，在室温下仅需2 h便能完成.产物多样性较好，能够获得一系列新颖的烷基杂芳基砜取代的BCP衍生物.此外，该反应还具备原子经济性高、操作简单和易于克级制备等优点.

关键词： 自由基; 双官能团化; 开环; [1.1.1]螺桨烷; 双环[1.1.1]戊烷(BCP)

本文引用格式

张红 , 王明扬 , 吴新鑫 , 朱晨 . 自由基参与的[1.1.1]螺桨烷溴烷基化反应:溴代双环[1.1.1]戊烷衍生物的合成[J]. 有机化学, 2020 , 40(10) : 3431 -3438 . DOI: 10.6023/cjoc202005001

Abstract

As a bioisostere for phenyl rings, tert-butyl groups and internal alkynes, bicyclo[1.1.1]pentane (BCP) can improve the drug-like qualities of bioactive molecules. Therefore, the incorporation of high-value functional groups to BCP scaffold becomes an efficient synthetic strategy to design new bioisosteres in drug development. Herein a radical-mediated bromoalkylation of[1.1.1]propellane was disclosed, leading to brominated BCP derivatives. Bromoalkyl heteroarylsulfones were employed as dual-function reagents in the radical transformation, in which two functionalities, alkylheteroarylsulfone and bromine atom, were concurrently introduced into[1.1.1]propellane. These reactions proceeded rapidly, and were generally completed within 2 h at room temperature. A variety of new alkylheteroarylsulfone-substituted BCP derivatives were furnished with high product diversity. This protocol features excellent atom-economy, simple operation, and gram-scale preparation.

Key words： radicals; difunctionalization; ring opening; [1.1.1]propellane; bicyclo[1.1.1]pentane (BCP)

参考文献

[1] (a) Pellicciari, R.; Raimondo, M.; Marinozzi, M.; Natalini, B.; Costantino, G.; Thomsen, C. J. Med. Chem. 1996, 39, 2874.
(b) Auberson, Y. P.; Brocklehurst, C.; Furegati, M.; Fessard, T. C.; Koch, G.; Decker, A.; Vecchia, L. L.; Briard, E. ChemMedChem 2017, 12, 590.
(c) Goh, Y. L.; Cui, Y. T.; Pendharkar, V.; Adsool, V. A. ACS Med. Chem. Lett. 2017, 8, 516.
(d) Westphal, M. V.; Wolfstädter, B. T.; Plancher, J.-M.; Gatfield, J.; Carreira, E. M. ChemMedChem 2015, 10, 461.
(e) Barbachyn, M. R.; Hutchinson, D. K.; Toops, D. S.; Reid, R. J.; Zurenko, G. E.; Yagi, B. H.; Schaadt, R. D.; Allison, J. W. Bioorg. Med. Chem. Lett. 1993, 3, 671.
(f) Makarov, I. S.; Brocklehurst, C. E.; Karaghiosoff, K.; Koch, G.; Knochel, P. Angew. Chem., Int. Ed. 2017, 56, 12774.
[2] (a) Meanwell, N. A. Chem. Res. Toxicol. 2016, 29, 564.
(b) Dockery, K. P.; Bentrude, W. G. J. Am. Chem. Soc. 1997, 119, 1388.
(c) Marinozzi, M.; Fulco, M. C.; Rizzo, R.; Pellicciari, R. Synlett 2004, 1027.
(d) Bunker, K. D.; Sach, N. W.; Huang, Q. H.; Richardson, P. F. Org. Lett. 2011, 13, 4746.
[3] Pellicciari, R.; Raimondo, M.; Marinozzi, M.; Natalini, B.; Costantino, G.; Thomsen, C. J. Med. Chem. 1996, 39, 2874.
[4] Stepan, A. F.; Subramanyam, C.; Efremov, I. V.; Dutra, J. K.; O'Sullivan, T. J.; DiRico, K. J.; McDonald, W. S.; Won, A.; Dorff, P. H.; Nolan, C. E.; Becker, S. L.; Pustilnik, L. R.; Riddell, D. R.; Kauffman, G. W.; Kormos, B. L.; Zhang, L.; Lu, Y.; Capetta, S. H.; Green, M. E.; Karki, K.; Sibley, E.; Atchison, K. P.; Hallgren, A. J.; Oborski, C. E.; Robshaw, A. E.; Sneed, B.; O'Donnell, C. J. J. Med. Chem. 2012, 55, 3414.
[5] (a) Nicolaou, K. C.; Vourloumis, D.; Totokotsopoulos, S.; Papakyriakou, A.; Karsunky, H.; Fernando, H.; Gavrilyuk, J.; Webb, D.; Stepan, A. F. ChemMedChem 2016, 11, 31.
(b) Auberson, Y. P.; Brocklehurst, C.; Furegati, M.; Fessard, T. C.; Koch, G.; Decker, A.; Vecchia, L. L.; Briard, E. ChemMedChem 2017, 12, 590.
(c) Goh, Y. L.; Cui, Y. T.; Pendharkar, V.; Adsool, V. A. ACS Med. Chem. Lett. 2017, 8, 516.
(d) Measom, N. D.; Down, K. D.; Hirst, D. J.; Jamieson, C.; Manas, E. S.; Patel, V. K.; Somers, D. O. ACS Med. Chem. Lett. 2017, 8, 43.
[6] (a) Kanazawa, J.; Uchiyama, M. Synlett. 2018, 30, 1.
(b) Dockery, K. P.; Bentrude, W. G. J. Am. Chem. Soc. 1994, 116, 10332.
(c) Gianatassio, R.; Lopchuk, J. M.; Wang, J.; Pan, C.-M.; Malins, L. R.; Prieto, L.; Brandt, T. A.; Collins, M. R.; Gallego, G. M.; Sach, N. W.; Spangler, J. E.; Zhu, H. C.; Zhu, J. J.; Baran, P. S. Science 2016, 351, 241.
(d) Kokhan, S. O.; Valter, Y. B.; Tymtsunik, A. V.; Komarov, I. V.; Grygorenko, O. O. Eur. J. Org. Chem. 2017, 82, 6450.
(e) Trongsiriwat, N.; Pu, Y.; Nieves-Quinones, Y.; Shelp, R. A.; Kozlowski, M. C.; Walsh, P. J. Angew. Chem., Int. Ed. 2019, 58, 13416.
(f) Kanazawa, J.; Maeda, K.; Uchiyama, M. J. Am. Chem. Soc. 2017, 139, 17791.
(g) Shelp, R. A.; Walsh, P. J. Angew. Chem., Int. Ed. 2018, 57, 15857.
(h) Hughes, J. M. E.; Scarlata, D. A.; Chen, A. C.-Y.; Burch, J. D.; Gleason, J. L. Org. Lett. 2019, 21, 6800.
[7] Wu, Z.; Xu, Y.; Liu, J.; Wu, X.; Zhu, C. Sci. China Chem. 2020, 63, 1025.
[8] Ding, K. L.; Xiao, W. J.; Wu, L.-Z. Acta Chim. Sinica 2017, 75, 5(in Chinese). (丁奎岭, 肖文精, 吴骊珠, 化学学报, 2017, 75, 5.)
[9] (a) Liu, J.; Wu, S.; Yu, J.; Lu, C.; Wu, Z.; Wu, X.; Xue, X.-S.; Zhu, C. Angew. Chem., Int. Ed. 2020, 59, 8195.
(b) Niu, T.; Liu, J.; Wu, X.; Zhu, C. Chin. J. Chem. 2020, 38, 803.
Options
文章导航

/

〈 〉