可见光促进的酰胺氮自由基参与的分子内氢胺化反应
收稿日期: 2016-07-28
修回日期: 2016-09-20
网络出版日期: 2016-09-27
基金资助
项目受国家自然科学基金（Nos.21272087，21472058，21472057，and 21232003）和武汉市青年科技晨光计划项目（No.2015070404010180）资助.
Visible Light Photocatalytic N-Radicalbased Intramolecular Hydroamination of Benzamides
Received date: 2016-07-28
Revised date: 2016-09-20
Online published: 2016-09-27
Supported by
Project supported by the National Natural Science Foundation of China (Nos. 21272087, 21472058, 21472057, and 21232003), and the Youth Chen-Guang Project of Wuhan (No. 2015070404010180).
报道了可见光促进的邻烯基取代苯甲酰胺的分子内自由基氢胺化反应.在该反应中，通过脱质子光致电子转移策略实现了氮-氢键的直接催化活化来产生氮自由基，随后通过氮自由基与烯烃的加成来实现氢胺化反应.该反应以优异的收率合成了一系列具有潜在生理活性的3，4-二氢异喹啉酮衍生物.该反应体系利用有机染料催化剂EosinY Na作为光氧化还原催化剂、廉价易得的NaOH作为碱试剂、反应条件温和、操作简单、且官能团兼容性好.另外，该反应在放大量到克级规模、或者利用太阳光作为光源，均能以优异的收率得到相应目标化合物.因此，这类反应为3，4-二氢异喹啉酮的合成提供了一个简便有效的方法.
关键词： 可见光催化; 氮自由基; 氢胺化反应; 氮杂环; 3,4-二氢异喹啉酮
余晓叶 , 周帆 , 陈加荣 , 肖文精 . 可见光促进的酰胺氮自由基参与的分子内氢胺化反应[J]. 化学学报, 2017 , 75(1) : 86 -91 . DOI: 10.6023/A16070367
The 3,4-dihydroisoquinolinones are a privileged class of heterocyclic motifs and widely found in numerous biologically active compounds. Thus, the development of more efficient and practical methods for their synthesis is highly desirable. Traditional methods are typically focused on transition-metal catalyzed C-H functionalization. Inspired by the recent process of the visible light photocatalytic generation and exploration of N-radicals in organic synthesis, our group in 2014 developed a visible light-induced photocatalytic strategy for direct conversion of the N-H bonds of β,γ-unsaturated hydrazones into N-centred radicals for the first time, and used them in intramolecular radical hydroamination, enabling efficient synthesis of 4,5-dihydropyrazole derivatives. By employing suitable additives or changing reaction parameters, we also successfully achieved highly regioselective 6-endo N-radical cyclization and oxyamination reactions based on N-centred radicals, providing the valuable 1,6-dihydropyradazines, pyrazolines, and pyridazines in good yields. In the hope of extending such N-radical-mediated heterocycle synthesis further, we reported a transition-metal free and visible light photocatalytic N-radical-based intramolecular hydroamination of benzamides. The reaction provides a practical and efficient approach to various biologically important 3,4-dihydroisoquinolinones with generally high yields. Importantly, the continuous flow reaction could significantly shorten the reaction time and still give rise to satisfactory yield. The sunlight irradiation reaction and gram-scale reaction also highlighted the potential synthetic utility of this method. A general procedure for the reaction is as follows:EosinY Na (6.21 mg, 0.009 mmol), NaOH (14.4 mg, 0.36 mmol), amide 1 (0.3 mmol) were dissolved in MeOH (6.0 mL), then, the resulting mixture was degassed via a ‘freeze-pump-thaw’ procedure (3 times). After that, the resulting mixture was stirred at a distance of ca. 5 cm from 3 W blue LEDs (450~460 nm) at room temperature until the starting amides were consumed as monitored by TLC analysis. After concentration in vacuo, the reaction residue was purified by flash chromatography on silica gel[V(petroleum ether)/V(ethyl acetate)=5:1~2:1] directly to give the desired product.
[1] (a) Goldberg, D. US 2006276496, 2006[Chem. Abstr. 2006, 146, 1286266].
(b) Goldberg, D. US 2010190773, 2010[Chem. Abstr. 2006, 146, 1286266].
(c) Freeze, B. S. WO 20120051410, 2014[Chem. Abstr. 2012, 156, 573694].
(d) Freeze, B. S. US 2015148334, 2015[Chem. Abstr. 2012, 156, 573694].
(e) Zhang, L.; Wang, C.; Han, J.; Huang, Z. B.; Zhao, Y. J. Org. Chem. 2016, 81, 5256.
(f) Welsch, M. E.; Snyder, S. A.; Stockwell, B. R. Curr. Opin. Chem. Biol. 2010, 14, 347.
[2] For selected reviews, see:(a) Zhao, J.; Zhang, Q. Acta Chim. Sinica 2015, 73, 1235. (赵金钵, 张前, 化学学报, 2015, 73, 1235.)
(b) Yuan, J.-W.; Liu, C.; Lei, A.-W. Chem. Commun. 2015, 51, 1394. For selected examples, see:
(c) Guimond, N.; Gorelsky, S. I.; Fagnou, K. J. Am. Chem. Soc. 2011, 133, 6449.
(d) Rakshit, S.; Grohmann, C.; Besset, T.; Glorius, F. J. Am. Chem. Soc. 2011, 133, 2350.
(e) Tang, Q.; Xia, D.; Jin, X.; Zhang, Q.; Sun, X. Q.; Wang, C. J. Am. Chem. Soc. 2013, 135, 4628.
(f) Wodrich, M. D.; Ye, B.; Gonthier, J. F.; Corminboeuf, C.; Cramer, N. Chem. Eur. J. 2014, 20, 15409.
(g) Sivakumar, G.; Vijeta, A.; Jeganmohan, M. Chem. Eur. J. 2016, 22, 5899.
(h) Hao, X.-Q.; Du, C.; Zhu, X.; Li, P.-X.; Zhang, J.-H.; Niu, J.-L.; Song, M.-P. Org. Lett. 2016, 18, 3610.
[3] For selected reviews on the N-radical chemistry, see:(a) Zard, S. Z.; Chem. Soc. Rev. 2008, 37, 1603.
(b) Quiclet-Sire, B.; Zard, S. Z. Beilstein J. Org. Chem. 2013, 9, 557.
(c) Hioe, J.; Šaki?, D.; Vr?ek, V.; Zipse, H. Org. Biomol. Chem. 2015, 13, 157.
[4] For selected examples, see:(a) Sherman, E. S.; Chemler, S. R.; Tan, T. B.; Gerlits, O. Org. Lett. 2004, 6, 1573.
(b) Sherman, E. S.; Fuller, P. H.; Kasi, D.; Chemler, S. R. J. Org. Chem. 2007, 72, 3896.
(c) Zeng, W.; Chemler, S. R. J. Am. Chem. Soc. 2007, 129, 12948.
(d) Zhu, X.; Wang, Y.-F.; Ren, W.; Zhang, F.-L.; Chiba, S. Org. Lett. 2013, 15, 3214.
(e) Zhu, M.-K.; Chen, Y.-C.; Loh, T. P. Chem. Eur. J. 2013, 19, 5250.
(f) Duan, X.-Y.; Zhou, N.-N.; Fang, R.; Yang, X.-L.; Yu, W.; Han, B. Angew. Chem. Int. Ed. 2014, 53, 3158.
(g) Duan, X. Y.; Yang, X. L.; Jia, P. P.; Zhang, M.; Han, B. Org. Lett. 2015, 17, 6022.
[5] For selected reviews on the visible light photocatalysis, see:(a) Xuan, J.; Xiao, W.-J. Angew. Chem. Int. Ed. 2012, 51, 6828.
(b) Shi, L.; Xia, W.-J. Chem. Soc. Rev. 2012, 41, 7687.
(c) Prier, C. K.; Rankic, D. A.; Macmillan, D. W. Chem. Rev. 2013, 113, 5322.
(d) Xi, Y.-M.; Yi, H.; Lei, A.-W. Org. Biomol. Chem. 2013, 11, 2387.
(e) Dai, X.; Xu, X.; Li, X. Chin. J. Org. Chem. 2013, 33, 2046. (戴小军, 许孝良, 李小年, 有机化学, 2013, 33, 2046.)
(f) Schultz, D. M.; Yoon, T. P. Science 2014, 343, 985.
(g) Xuan, J.; Zhang, Z.-G.; Xiao, W.-J. Angew. Chem. Int. Ed. 2015, 54, 15632.
(h) Tan, F.; Xiao, W.-J. Acta Chim. Sinica 2015, 73, 85. (谭芬, 肖文精, 化学学报, 2015, 73, 85.)
(i) Karkas, M. D.; Porco Jr., J. A.; Stephenson, C. R. Chem. Rev. 2016, 116, 9683.
(j) Romero, N. A.; Nicewicz, D. A. Chem. Rev. 2016, 116, 10075.
(k) Chen, J.-R.; Hu, X.-Q.; Lu, L.-Q.; Xiao, W.-J. Acc. Chem. Res. 2016, doi:10. 1021/acs. accounts. 6b00254.
[6] For recent reviews, see:(a) Chen, J.-R.; Hu, X. Q.; Lu, L.-Q.; Xiao, W.-J. Chem. Soc. Rev. 2016, 45, 2044.
(b) Xiong, T.; Zhang, Q. Chem. Soc. Rev. 2016, 45, 3069.
[7] For recent examples on the visible light-induced N-radical reactions, see:(a) Cecere, G.; Konig, C. M.; Alleva, J. L.; MacMillan, D. W. J. Am. Chem. Soc. 2013, 135, 11521.
(b) Allen, L. J.; Cabrera, P. J.; Lee, M.; Sanford, M. S. J. Am. Chem. Soc. 2014, 136, 5607.
(c) Musacchio, A. J.; Nguyen, L. Q.; Beard, G. H.; Knowles, R. R. J. Am. Chem. Soc. 2014, 136, 12217.
(d) Song, L.; Zhang, L.; Luo, S.; Cheng, J.-P. Chem. Eur. J. 2014, 20, 14231.
(e) Kim, H.; Kim, T.; Lee, D. G.; Roh, S. W.; Lee, C. Chem. Commun. 2014, 50, 9273.
(f) Qin, Q.; Yu, S. Org. Lett. 2015, 17, 1894.
(g) Jiang, H.; An, X.; Tong, K.; Zheng, T.; Zhang, Y.; Yu, S. Angew. Chem. Int. Ed. 2015, 54, 4055.
(h) Miller, D. C.; Choi, G. J.; Orbe, H. S.; Knowles, R. R. J. Am. Chem. Soc. 2015, 137, 13492.
(i) Davies, J.; Booth, S. G.; Essafi, S.; Dryfe, R. A. W.; Leonori, D. Angew. Chem. Int. Ed. 2015, 54, 14017.
(j) Davies, J.; Svejstrup, T. D.; Fernandez Reina, D.; Sheikh, N. S.; Leonori, D. J. Am. Chem. Soc. 2016, 138, 8092.
(k) Zhu, L.; Xiong, P.; Mao, Z.-Y.; Wang, Y.-H.; Yan, X.-M.; Lu, X.; Xu, H.-C. Angew. Chem. Int. Ed. 2016, 55, 2226.
(l) Zhao, Y.; Huang, B.; Yang, C.; Xia, W. Org. Lett. 2016, 18, 3326.
(m) Brachet, E.; Marzo, L.; Selkti, M.; König, B.; Belmont, P. Chem. Sci. 2016, 7, 5002.
[8] Hu, X.-Q.; Chen, J.-R.; Wei, Q.; Liu, F.-L.; Deng, Q.-H.; Beauchemin, A. M.; Xiao, W.-J. Angew. Chem. Int. Ed. 2014, 53, 12163.
[9] (a) Hu, X.-Q.; Qi, X.; Chen, J.-R.; Zhao, Q.-Q.; Wei, Q.; Lan, Y.; Xiao, W.-J. Nat. Commun. 2016, 7, 11188.
(b) Hu, X.-Q.; Chen, J.; Chen, J.-R.; Yan, D.-M.; Xiao, W.-J. Chem. Eur. J. 2016, doi:10. 1002/chem. 201602597.
[10] Please see the Supporting Information for more details.
[11] For selected reviews, see:(a) Knowles, J. P.; Elliott, L. D.; Booker-Milburn, K. I. Beilstein J. Org. Chem. 2012, 8, 2025.
(b) Su, Y.; Straathof, N. J. W.; Hessel, V.; Noël, T. Chem. Eur. J. 2014, 20, 10562.
(c) Garlets, Z. J.; Nguyen, J. D.; Stephenson, C. R. Isr. J. Chem. 2014, 54, 351.
[12] Yang, G.-Q.; Shen, C.-R.; Zhang, W.-B. Angew. Chem. Int. Ed. 2012, 51, 9141.
[13] (a) Nicewicz, D. A.; Nguyen, T. M. ACS Catal. 2014, 4, 355.
(b) Hari, D. P.; Konig, B. Chem. Commun. 2014, 50, 6688.
/
| 〈 |
|
〉 |
