基于非对称性三唑萘啶吡啶铜催化合成吡嗪与酮衍生物

doi:10.6023/cjoc202107018

摘要/Abstract

发展了一种基于非对称性配体的催化剂TNP-Cu@rGO, 并将该催化剂用于催化合成吡嗪和酮衍生物的新方法. 对该反应中碱的种类、溶剂、反应温度和时间等条件进行了优化, 确定了最优的反应条件. 接着对该反应的底物普适性进行了研究, 实验表明该催化体系显示了良好的官能团耐受性, 并对该催化体系和反应进行了机理研究和探索. 催化剂的回收循环再利用实验表明, 该催化剂循环使用五次仍能保持较高的催化活性.

关键词: 借氢, 非对称性, 吡嗪, 铜

A novel method for the synthesis of pyrazine and ketone derivatives was developed by using asymmetric ligand-based catalyst TNP-Cu@rGO. The screening of reaction bases, solvents, reaction temperatures and time was conducted to determine optimal reaction conditions. The reaction scope and generality of this methodology for the synthesis of pyrazines were tested and the results showed that this catalytic system had good functional tolerance. More than twenty substrates experiments were successfully set up, and pyrazines with moderate to high yields were isolated. Additionally, this catalytic system could also be used to the systhesis of ketones in good yields. Furthermore, the mechanism investigations were conducted for the synthesis of pyrazine derivatives to better understand the synthesis of pyrazines. The recycling test of TNP-Cu@rGO for the synthesis of pyrazines was investigated and the experiments showed that the catalyst could still maintain high catalytic activity for five times.

Key words: borrowing hydrogen, unsymmetrical, pyrazine, copper

引用此文

李家豪, 杨义科, 胡文康, 夏晓峰, 王大伟. 基于非对称性三唑萘啶吡啶铜催化合成吡嗪与酮衍生物[J]. 有机化学, 2022, 42(1): 190-199.

Jiahao Li, Yike Yang, Wenkang Hu, Xiaofeng Xia, Dawei Wang. Catalytic Synthesis of Pyrazine and Ketone Derivatives by Unsymmetrical Triazolyl-Naphthyridinyl-Pyridine Copper[J]. Chinese Journal of Organic Chemistry, 2022, 42(1): 190-199.

导出引用 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

分享此文

图/表 9

图式1. 吡嗪类活性药物

Scheme 1. Pyrazine active drugs

Entry	Base	Solvent	Temp./℃	Yield^b/%
1	K₂CO₃	Xylene	140	24
2	Na₂CO₃	Xylene	140	Trace
3	K₃PO₄	Xylene	140	33
4	Cs₂CO₃	Xylene	140	97
5	KO^tBu	Xylene	140	95
6	NaO^tBu	Xylene	140	91
7	KOH	Xylene	140	89
8	NaOH	Xylene	140	86
9	CsOH•H₂O	Xylene	140	75
10	Cs₂CO₃	Toluene	140	79
11	Cs₂CO₃	1,4-Dioxane	140	30
12	Cs₂CO₃	DMF	140	61
13	Cs₂CO₃	DMA	140	Trace
14	Cs₂CO₃	1,2-Ethanediol	140	Trace
15	Cs₂CO₃	Xylene	120	76
16	Cs₂CO₃	Xylene	150	97
17	Cs₂CO₃	Xylene	140	85 ^c
18	Cs₂CO₃	Xylene	140	97 ^d
19	Cs₂CO₃	Xylene	140	Trace^e

表1. 反应条件的优化a

Table 1. Optimization of reaction conditions

表2. 底物的普适性考察a,b

Table 2. Substrate scope of the reaction

表3. 苄醇与酮反应的底物普适性考察a,b

Table 3. Substrate expansion for the reaction of alcohols with ke-tones

图式2. 控制实验

Scheme 2. Control experiments

图1. 化合物3a合成过程中中间体的研究

Figure 1. Intermediate research for the synthesis of 3a

图式3. 中间体捕获实验

Scheme 3. Intermediate capture experiments

图式4. 合成3a的反应机理

Scheme 4. Reaction mechanism of the synthesis of 3a

图式5. 催化剂TNP-Cu@rGO的回收实验

Scheme 5. Recycled experiments of TNP-Cu@rGO catalyst

参考文献 14

[1]	(a) Cai, L.; Zhang, K.; Chen, S.; Lepage, R. J.; Houk, K. N.; Krenske, E. H.; Kwon, O. J. Am. Chem. Soc. 2019, 141, 9537. doi: 10.1021/jacs.9b04803
	(b) Ding, B.; Jiang, Y.; Zhang, Y.; Ye, R.; Sun, J.; Yan, C. Chin. J. Org. Chem. 2020, 40, 1003. (in Chinese) doi: 10.6023/cjoc201910016
	(丁邦东, 姜业朝, 张瑜, 叶蓉, 孙晶, 颜朝国, 有机化学, 2020, 40, 1003.) doi: 10.6023/cjoc201910016
	(c) Wen, D.; Zheng, Q.; Wang, C.; Tu, T. Org. Lett. 2021, 23, 3718. doi: 10.1021/acs.orglett.1c01106
	(d) Zhou, Y.; Zhao, Z.; Zeng, L.; Li, M.; He, Y.; Gu, L. Chin. J. Org. Chem. 2021, 41, 1072. (in Chinese) doi: 10.6023/cjoc202007049
	(周娅琴, 赵志恒, 曾亮, 李鸣, 何永辉, 谷利军, 有机化学, 2021, 41, 1072.) doi: 10.6023/cjoc202007049
	(e) Xie, R.; Lu, G.-P.; Jiang, H.-F.; Zhang, M. J. Catal. 2020, 383, 239. doi: 10.1016/j.jcat.2020.01.034
	(d) Liu, Y.; Meng, J.; Li, C.; Lin, L.; Xu, Y. Chin. J. Org. Chem. 2020, 40, 2742. (in Chinese) doi: 10.6023/cjoc202003056
	(刘颖杰, 孟建萍, 李晨, 林立青, 许颖, 有机化学, 2021, 40, 2742.)
[2]	(a) Yu, H.; Zhang, R.; Yang, F.; Xie, Y.; Guo, Y.; Yao, W.; Zhou, W. Trends Food Sci. Technol. 2021, 112, 795. doi: 10.1016/j.tifs.2021.04.028
	(b) Chen, J.; Wang, Y.; Yu, J.; Cheng, J.; Zheng, H. Chin. J. Org. Chem. 2020, 40, 78. (in Chinese)
	(陈晶晶, 王莹淑, 余珺, 成佳佳, 郑辉东, 有机化学, 2020, 40, 78.) doi: 10.6023/cjoc201908001
	(c) Wang, F.; Wei, M.; Duan, X.; Liu, X.; Yao, S.; Wang, J.; Zhu, H.; Chen, C.; Gu, L.; Zhang, Y. Org. Chem. Front. 2020, 7, 3616. doi: 10.1039/D0QO01030H
	(d) Zhang, H. J.; Yang, Z. P.; Gu, Q.; You, S. L. Org. Lett. 2019, 21, 3314. doi: 10.1021/acs.orglett.9b01060
[3]	(a) Hassan, N. W.; Saudi, M. N.; Abdel-Ghany, Y. S.; Ismail, A.; Elzahhar, P. A.; Sriram, D.; Nassra, R.; Abdel-Aziz, M. M. Bioorg. Chem. 2020, 96, 103610. doi: 10.1016/j.bioorg.2020.103610
	(b) Kučerová-Chlupáčová, M.; Opletalová, V.; Jampílek, J.; Doležel, J.; Dohnal, J.; Pour, M.; Kuneš, J.; Voříšek, V. Collect. Czech. Chem. C 2008, 73, 1. doi: 10.1135/cccc20080001
	(c) Wang, N.; Mani, A.; Chen, X.; Wang, B.; Chen, S.; Yao, C.; Wang, Z. Chin. J. Org. Chem. 2019, 39, 2771. (in Chinese) doi: 10.6023/cjoc201904061
	(王能, Arulkumar, Mani, 陈孝云, 王柏文, 陈思鸿, 姚辰, 汪朝阳, 有机化学, 2019, 39, 2771.) doi: 10.6023/cjoc201904061
	(d) Liu, J.; Xie, Y.; Yang, Q.; Huang, N.; Wang, L. Chin. J. Org. Chem. 2021, 41, 2374. (in Chinese) doi: 10.6023/cjoc202012040
	(刘金妮, 谢益碧, 阳青青, 黄年玉, 王龙, 有机化学, 2021, 41, 2374.) doi: 10.6023/cjoc202012040
	(e) Tian, A.-Q.; Luo, X.-H.; Ren, Z.-L.; Zhao, J.; Wang, L. New J. Chem. 2021, 45, 9614. doi: 10.1039/D1NJ00861G
	(f) Yu, S.-Q.; Liu, N.; Liu, M.-G.; Wang, L. J. Chem. Res. 2021, 45, 237. doi: 10.1177/1747519820966985
[4]	(a) Wei, R.; Bao, H. Chin. J. Org. Chem. 2020, 40, 1797. (in Chinese) doi: 10.6023/cjoc202000034
	(韦榕标, 鲍红丽, 有机化学, 2020, 40, 1797.) doi: 10.6023/cjoc202000034
	(b) Navarro, O.; Marion, N.; Mei, J.; Nolan, S. P. Chem. Eur. J. 2006, 12, 5142. doi: 10.1002/(ISSN)1521-3765
	(c) Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119, 6054. doi: 10.1021/ja964391m
	(d) Mizuta, T.; Sakaguchi, S.; Ishii, Y. J. Org. Chem. 2005, 70, 2195. doi: 10.1021/jo0481708
	(4e) Vernin, G.; Hornwood, M. P.-E. Chichester 1982, 305, 70.
[5]	(a) Hao, S.; Yang, J.; Liu, P.; Xu, J.; Yang, C.; Li, F. Org. Lett. 2021, 23. 2553. doi: 10.1021/acs.orglett.1c00475
	(b) Liu, P.; Yang, J.; Ai, Y.; Hao, S.; Chen, X.; Li, F. J. Catal. 2021, 396, 281. doi: 10.1016/j.jcat.2021.02.030
	(c) Wei, D.; Yang, P.; Yu, C.; Zhao, F.; Wang, Y.; Peng, Z. J. Org. Chem. 2021, 86, 2254. doi: 10.1021/acs.joc.0c02407
	(d) Meng, C.; Liu, P.; Tung, N. T.; Han, X.; Li, F. J. Org. Chem. 2020, 85, 5815. doi: 10.1021/acs.joc.9b03411
	(e) Zhu, Z.-H.; Li, Y.; Wang, Y.-B.; Lan, Z.-G.; Zhu, X.; Hao, X.-Q. Organometallics 2019, 38, 2156. doi: 10.1021/acs.organomet.9b00146
[6]	(a) Li, F.; Xie, J.; Shan, H.; Sun, C.; Chen, L. RSC Adv. 2012, 2, 8645. doi: 10.1039/c2ra21487c pmid: 29039671
	(b) Liang, R.; Li, S.; Wang, R.; Lu, L.; Li, F. Org. Lett. 2017, 19, 5790. doi: 10.1021/acs.orglett.7b02723 pmid: 29039671
	(c) Fujita, K.-I.; Toyooka, G.; Tuji, A. Synthesis 2018, 50, 4617. doi: 10.1055/s-0037-1610252 pmid: 29039671
	(d) Nallagangula, M.; Sujatha, C.; Bhat, V. T.; Namitharan, K. Chem. Commun. 2019, 55, 8490. doi: 10.1039/C9CC04120F pmid: 29039671
	(e) Sankar, V.; Kathiresan, M.; Sivakumar, B.; Mannathan, S. Adv. Synth. Catal. 2020, 362, 4409. doi: 10.1002/adsc.v362.20 pmid: 29039671
[7]	(a) Cao, L.; Zhao, H.; Tan, Z.; Guan, R.; Jiang, H.; Zhang, M. Org. Lett. 2020, 22, 4781. doi: 10.1021/acs.orglett.0c01580
	(b) Tan, Z.; Ci, C.; Yang, J.; Wu, Y.; Cao, L.; Jiang, H.; Zhang, M. ACS Catal. 2020, 10, 5243. doi: 10.1021/acscatal.0c00394
	(c) Xie, F.; Li, Y.; Chen, X.; Chen, L.; Zhu, Z.; Li, B.; Huang, Y.; Zhang, K.; Zhang, M. Chem. Commun. 2020, 56, 5997. doi: 10.1039/C9CC09649C
	(d) Wu, D.; Cheng, X.; Liu, Y.; Cheng, G.; Guan, X.; Deng, Q. Chin. J. Org. Chem. 2020, 40, 3362. (in Chinese) doi: 10.6023/cjoc202005090
	(吴敦奇, 成轩, 刘炎开, 成果, 管笑宇, 邓清海, 有机化学, 2020, 40, 3362.) doi: 10.6023/cjoc202005090
	(e) Zhang, G.; Jiang, Y.; Ding, C.; Hou, X. Chin. J. Org. Chem. 2020, 40, 3399. (in Chinese) doi: 10.6023/cjoc202006007
	(张高鹏, 江阳杰, 丁昌华, 侯雪龙, 有机化学, 2020, 40, 3399.) doi: 10.6023/cjoc202006007
	(f) Cao, Z.; Qiao, H.; Zeng, F. Organometallics 2019, 38, 797. doi: 10.1021/acs.organomet.8b00791
	(g) Li, S.; Li, X.; Li, Q.; Yuan, Q.; Shi, X.; Xu, Q. Green Chem. 2015, 17, 3260. doi: 10.1039/C4GC02542C
[8]	(a) Balamurugan, G.; Ramesh, R.; Malecki, J. G. J. Org. Chem. 2020, 85, 7125. doi: 10.1021/acs.joc.0c00530
	(b) Liu, Z.; Zhang, X.; Zhang, H.; Jiang, H.; Zhao, X.; Shi, L.; Zhu, X.; Hao, X.; Song, M. Chin. J. Org. Chem. 2020, 40, 2755. (in Chinese) doi: 10.6023/cjoc202003068
	(刘子琳, 张小洁, 张恒, 姜辉, 赵雪梅, 石林林, 朱新举, 郝新奇, 宋毛平, 有机化学, 2020, 40, 2755.) doi: 10.6023/cjoc202003068
	(c) Xie, F.; Li, Y.; Chen, X.; Chen, L.; Zhu, Z.; Li, B.; Huang, Y.; Zhang, K.; Zhang, M. Chem. Commun. 2020, 56, 5997. doi: 10.1039/C9CC09649C
[9]	(a) Yao, W.; Zhang, Y.; Zhu, H.; Ge, C.; Wang, D. Chin. Chem. Lett. 2020, 31, 701. doi: 10.1016/j.cclet.2019.08.049
	(b) Cao, F.; Duan, Z.-C.; Zhu, H.; Wang, D. Mol. Catal. 2021, 503, 111391.
	(c) Xu, Z.; Yu, X.; Sang, X.; Wang, D. Green Chem. 2018, 20, 2571. doi: 10.1039/C8GC00557E
	(d) Yang, Q.; Zhang, Y.; Zeng, W.; Duan, Z.-C.; Sang, X.; Wang, D. Green Chem. 2019, 21, 5683. doi: 10.1039/C9GC02409C
[10]	(a) Tao, R.; Yang, Y.; Zhu, H.; Hu, X.; Wang, D. Green Chem. 2020, 22, 8452. doi: 10.1039/D0GC02341H
	(b) Zhu, G.; Duan, Z.-C.; Zhu, H.; Qi, M.; Wang, D. Mol. Catal. 2021, 505, 111516.
	(c) Zhu, G.; Duan, Z.-C.; Zhu, H.; Ye, D.; Wang, D. Chin. Chem. Lett. 2021, 32, 10.1016/j.cclet.2021.06.060.
	(d) Hu, X.; Yang, B.; Yao, W.; Wang, D. Chin. J. Org. Chem. 2018, 38, 3296. (in Chinese) doi: 10.6023/cjoc201805019
	(胡昕宇, 杨伯斌, 姚玮, 王大伟, 有机化学, 2018, 38, 3296.) doi: 10.6023/cjoc201805019
[11]	Hu, W.; Zhang, Y.; Zhu, H.; Ye, D.; Wang, D. Green. Chem. 2019, 21, 5345. doi: 10.1039/C9GC02086A
[12]	Yang, F.-L.; Wang, Y.-H.; Ni, Y.-F.; Gao, X.; Song, B.; Zhu, X.; Hao, X.-Q. Eur. J. Org. Chem. 2017, 2017, 3481.
[13]	(a) Donthiri, R. R.; Pappula, V.; Mohan, D. C.; Gaywala, H. H.; Adimurthy, S. J. Org. Chem. 2013, 78, 6775. doi: 10.1021/jo400834h
	(b) Li, S.; Li, X.; Li, Q.; Yuan, Q.; Shi, X.; Xu, Q. Green Chem. 2015, 17, 3260. doi: 10.1039/C4GC02542C
	(c) Walsh, K.; Sneddon, H. F.; Moody, C. J. ChemSusChem 2013, 6, 1455. doi: 10.1002/cssc.201300239
	(e) Duron, S. G.; Lindstrom, A.; Bonnefous, C.; Zhang, H.; Chen, X.; Symons, K. T.; Sablad, M.; Rozenkrants, N.; Zhang, Y.; Wang, L.; Yazdani, N.; Shiau, A. K.; Noble, S. A.; Rix, P.; Rao, T. S.; Hassig, C. A.; Smith, N. D. Bioorg. Med. Chem. Lett. 2012, 22, 1237. doi: 10.1016/j.bmcl.2011.11.073
[14]	(a) Cao, X. N.; Wan, X. M.; Yang, F. L.; Li, K.; Hao, X. Q.; Shao, T.; Zhu, X.; Song, M. P. J. Org. Chem. 2018, 83, 3657. doi: 10.1021/acs.joc.8b00013
	(b) Liu, P.; Liang, R.; Lu, L.; Yu, Z.; Li, F. J. Org. Chem. 2017, 82, 1943. doi: 10.1021/acs.joc.6b02758

[1]	宋晓, 卿晶, 黎君, 贾雪雷, 吴福松, 黄均荣, 金剑, 游恒志. 铜催化格氏试剂的不对称烯丙基烷基化连续流反应[J]. 有机化学, 2023, 43(9): 3174-3179.
[2]	陆晓雨, 孙晓梅, 钮亚琴, 王俊超, 殷文婧, 高梦婷, 刘孜, 韦正桓, 陶庭骅. 铜催化氟代丙烯酸与氧杂吖丙啶的脱羧交叉偶联反应[J]. 有机化学, 2023, 43(6): 2110-2119.
[3]	鲍志成, 李慕尧, 王剑波. 铜催化芳基重氮乙酸酯与双[(频哪醇)硼基]甲烷的偶联反应[J]. 有机化学, 2023, 43(5): 1808-1814.
[4]	李春生, 连晓琪, 陈莲芬. 铜催化亚砜叶立德与邻苯二胺[4＋2]环加成反应[J]. 有机化学, 2023, 43(4): 1492-1498.
[5]	刘洋, 黄翔, 王敏, 廖建. 铜催化环酮亚胺与β,γ-不饱和N-酰基吡唑不对称Mannich-Type反应[J]. 有机化学, 2023, 43(4): 1499-1509.
[6]	刘春阳, 李燕, 张前. 铜催化环状烯烃烯丙位C(sp³)—H磺酰化反应研究[J]. 有机化学, 2023, 43(3): 1091-1101.
[7]	韩彪, 李维双, 陈舒晗, 张泽浪, 赵雪, 张瑶瑶, 朱磊. 铜催化不饱和化合物硅加成反应的研究进展[J]. 有机化学, 2023, 43(2): 555-572.
[8]	许力, 吕兰兰, 王香善. 铜催化烯醇硅醚与芳基亚磺酸钠合成β-酮砜的研究[J]. 有机化学, 2023, 43(10): 3644-3651.
[9]	陈志远, 杨梦维, 徐建林, 徐允河. 铜催化双炔膦氧化物硅质子化反应合成β-硅基取代的乙烯基膦氧化物[J]. 有机化学, 2023, 43(10): 3598-3607.
[10]	贾雪锋, 仝向娟. 铜(II)配合物催化Chan-Lam偶联反应研究进展[J]. 有机化学, 2022, 42(9): 2640-2658.
[11]	陈飞, 陶晟, 刘宁, 代斌. CNN型双核Cu(I)配合物室温催化固定CO₂的直接羧基化反应[J]. 有机化学, 2022, 42(8): 2471-2480.
[12]	马丽文, 魏晓叶, 赵紫琳, 赵昂, 邓祥文, 霍丙南, 马刚, 张春芳. 端炔偶联反应中铜变价催化机制的理论研究[J]. 有机化学, 2022, 42(6): 1811-1819.
[13]	黄志友, 李哲陟, 何波, 李文胜, 杨平, 陈立军. 超声促进CuSO₄/NaAsc水相中高效催化合成N-苯磺酰基苯乙酰胺及其抑制种子萌发的研究[J]. 有机化学, 2022, 42(6): 1667-1676.
[14]	李晖, 殷亮. 铜催化的直接型插烯反应研究进展[J]. 有机化学, 2022, 42(6): 1573-1585.
[15]	孙天义, 张依凡, 孟远倢, 王怡, 朱琦峰, 姜玉新, 刘石惠. 可见光-铜共催化的糖类区域选择性氧烷基化反应[J]. 有机化学, 2022, 42(5): 1414-1422.