铜催化的α-氨基丙二腈的脱氰氧代反应：一种合成叔酰胺的新方法

doi:10.6023/A20070296

化学学报 ›› 2020, Vol. 78 ›› Issue (10): 1064-1068.DOI: 10.6023/A20070296 上一篇下一篇

研究通讯

铜催化的α-氨基丙二腈的脱氰氧代反应：一种合成叔酰胺的新方法

梁欢^a, 苟阿龙^a, 高珠鹏^a, 雷林生^a, 王博文^a, 余兰^a, 徐学涛^b, 王少华^a

a 兰州大学药学院兰州 730000;
b 五邑大学生物科技与大健康学院江门 529020

投稿日期:2020-07-07 发布日期:2020-09-09
通讯作者: 余兰, 王少华 E-mail:yul@lzu.edu.cn;wangshh@lzu.edu.cn
基金资助:
国家自然科学基金（Nos.21472077，21772071）和广东省教育厅项目（Nos.2017KTSCX185，2017KSYS010，2016KCXTD005，2019KZDXM035）资助项目.中国发明专利申请号（No.202010648789.7）.

A New Strategy for the Synthesis of Tertiary Amides via a Copper-Catalyzed Decyanation Reaction of N,N-Disubstituted 2-Aminomalononitriles

Liang Huan^a, Gou Along^a, Gao Zhupeng^a, Lei Linsheng^a, Wang Bowen^a, Yu Lan^a, Xu Xuetao^b, Wang Shaohua^a

a School of Pharmacy, Lanzhou University, Lanzhou 730000, China;
b School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China

Received:2020-07-07 Published:2020-09-09
Supported by:
Project supported by the National Natural Science Foundation of China (Nos. 21472077, 21772071) and Department of Education of Guangdong Province (Nos. 2017KTSCX185, 2017KSYS010, 2016KCXTD005, 2019KZDXM035). Chinese patent pending (No. 202010648789.7).

文章分享

1. A20070296.pdf(9199KB)

摘要/Abstract

新反应、新试剂的发展是有机合成化学的重要研究内容，基于前期在α-氨基丙二腈合成方法学方面的工作基础，我们发展了一例铜催化的α-氨基丙二腈的脱氰氧代反应.通过将甲酰胺转化为α-氨基丙二腈后，借助其亲核属性来合成α-氨基丙二腈底物，而后将底物重新转化为酰胺，从而实现形式上的氨基甲酰负离子的亲核加成（取代）反应.该工作首次完成了形式上的甲酰胺碳原子的极性反转，实现了将α-氨基丙二腈作为氨基甲酰负离子替代物的反应新模式，为叔酰胺化合物的合成提供了新的思路和方法，且具有反应条件简单，底物适用性广及适合克级规模制备等特点.

关键词: α-氨基丙二腈, 甲酰胺, 氨基甲酰负离子, 铜催化

The development of new synthetic methodology and reagent is always a hot topic in organic synthesis community. Among the strategies used, chemical property investigation of synthetic intermediates with multifunctional groups represents a direct and efficient way. In this paper, as a systematic continuation of α-aminomalononitrile based synthetic application studies, α-aminomalononitrile has been developed for the first time as a surrogate for carbamoyl anions and applied to the synthesis of tertiary amides via a copper-catalyzed decyanation reaction. This strategy features simple reaction conditions, scalability, and wide substrate scope. This work not only further enriches the reaction model of aminonitrile compounds, but also provides an alternative synthetic strategy for the synthesis of substituted amides from simple formamides. In this process, the substrates could be readily synthesized through the nucleophilic addition or substitution reaction of α-aminomalononitriles, and they would be converted to corresponding tertiary amide in the presence of CuF₂ in DMSO. As an example, the formal hydrocarbamoylation reaction of unsaturated bonds could be achieved. A general procedure for the strategy is as follows:α-aminomalononitrile derived from formamide is used to undergo nucleophilic addition or substitution reaction with electrophilic reagents. Next, the two cyano groups of the synthesized substrates could be removed under the catalysis of CuF₂ to form a C=O double bond in situ, thereby achieving the synthesis of corresponding tertiary amide. During the reaction, the α-aminomalononitrile substrate (0.4 mmol), CuF₂ (5 mol%), DMSO (3 mL) were placed in a sealed reaction tube at 100℃ at an argon atmosphere for about 32 hours. Then, the reaction system was washed out with ethyl acetate, and the organic phase was washed with water to remove DMSO. Next, the aqueous phase was extracted with ethyl acetate. Finally all organic phases were combined, washed once with saturated brine. After drying the organic phase over anhydrous sodium sulfate, it was concentrated by a vacuum pump. Finally, the residue was purified by flash column chromatography to give amide product.

Key words: α-aminomalononitriles, formamides, carbamoyl anion, copper catalysis

引用此文

梁欢, 苟阿龙, 高珠鹏, 雷林生, 王博文, 余兰, 徐学涛, 王少华. 铜催化的α-氨基丙二腈的脱氰氧代反应：一种合成叔酰胺的新方法[J]. 化学学报, 2020, 78(10): 1064-1068.

Liang Huan, Gou Along, Gao Zhupeng, Lei Linsheng, Wang Bowen, Yu Lan, Xu Xuetao, Wang Shaohua. A New Strategy for the Synthesis of Tertiary Amides via a Copper-Catalyzed Decyanation Reaction of N,N-Disubstituted 2-Aminomalononitriles[J]. Acta Chimica Sinica, 2020, 78(10): 1064-1068.

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

分享此文

参考文献

[1] (a) Ahlbrecht, H.; Raab, W.; Vonderheid, C. Synthesis, 1979, 2, 127. (b) Husson, H.-P.; Royer, J. Chem. Soc. Rev. 1999, 28, 383. (c) Enders, D.; Shilvock, J. P. Chem. Soc. Rev. 2000, 29, 359. (d) Leclerc, E.; Vrancken, E.; Mangeney, P. J. Org. Chem. 2002, 67, 8928. (e) Couty, F.; Evano, G.; Prim, D.; Marrot, J. Eur. J. Org. Chem. 2004, 18, 3893. (f) Bernardi, L.; Bonini, B. F.; Capitò, E.; Comes-Franchini, M.; Dessole, G.; Fini, F.; Fochi, M.; Herrera, R. P.; Ricci, A. Eur. J. Org. Chem. 2006, 1, 207. (g) Chai, H.; Li, J.; Yang, L.; Liu, M.; Yang, D.; Zhang, Q.; Shi, D. Chin. J. Chem. 2014, 32, 865. (h) Yang, J.; Shi, D.; Liu, M.; Zhang, L.; Zhang, Q.; Li, J. Chin. J. Org. Chem. 2014, 34, 2424(in Chinese). (杨俊娟, 史大昕, 刘明星, 张立军, 张奇, 李加荣, 有机化学, 2014, 34, 2424). (i) Liu, Y.-L.; Yin, X.-P.; Zhou, J. Chin. J. Chem. 2018, 36, 321.
[2] (a) Ulbrich, K.; Holá, K.; Šubr, V.; Bakandritsos, A.; Tuček, J.; Zbořil, R. Chem. Rev. 2016, 116, 5338. (b) Zolnowska, B.; Slawinski, J.; Garbacz, K.; Jarosiewicz, M.; Kawiak, A. Int. J. Mol. Sci. 2019, 21, 210. (c) Wilhelm, E. A.; Torres, M.; Pereira, C. F.; Vogt, A. G.; Cervo, R.; Dos Santos, B. G. T.; Cargnelutti, R.; Luchese, C. Can. J. Physiol. Pharmacol. 2019, 98, 304. (d) Wilt, S. R.; Rodriguez, M.; Le, T. N.; Baltodano, E. V.; Salas, A.; Pecic, S. Chem. Biol. Drug Des. 2020, 95, 534. (e) Zheng, Q.; Peng, X.; Zhang, Y. BMC Anesthesiol. 2020, 20, 43. (f) Zhou, Y.; Gu, Z.; Liu, J.; Huang, K.; Liu, G.; Wu, J. Carbohydr. Polym. 2020, 230, 115640.
[3] (a) Guo, X.; Facchetti, A.; Marks, T.-J. Chem. Rev. 2014, 114, 8943. (b) Jiang, G.-L.; Wang, D.-Y.; Du, H.-P.; Wu, X.; Zhang, Y.; Tan, Y.-Y.; Wu, L.; Liu, J.-G.; Zhang, X. Polymers (Basel, Switz.), 2020, 12, 413. (c) Liu, J.; Chen, T.-W.; Yang, Y. L.; Bai, Z. C.; Xia, L.-R.; Wang, M.; Lv, X.-L.; Li, L. Carbohydr. Polym. 2020, 230, 115619. (d) Materna, K. L.; Lalaoui, N.; Laureanti, J. A.; Walsh, A. P.; Rimgard, B. P.; Lomoth, R.; Thapper, A.; Ott, S.; Shaw, W. J.; Tian, H.; Hammarstrom, L. ACS Appl. Mater. Interfaces 2020, 12, 4501.
[4] Wu, Z.; Du, Y.; Zhou, Q.; Chen, L. Pestic. Biochem. Physiol. 2020, 163, 51.
[5] (a) Zhou, L.; Lu, W. Acta Chim. Sinica 2015, 73, 1250. (in Chinese). (周励宏, 陆文军, 化学学报, 2015, 73, 1250). (b) Huang, P.-Q. Acta Chim. Sinica, 2018, 76, 357(in Chinese). (黄培强, 化学学报, 2018, 76, 357). (c) Li, C.; Wang, M.; Lu, X.; Yang, Y.; Zhang, L. Chin. J. Org. Chem. 2019, 39, 1109(in Chinese). (李春, 王梦娜, 陆逊花, 杨元勇, 张林, 有机化学, 2019, 39, 1109).
[6] (a) Trost, B. M. Acc. Chem. Res. 2002, 35, 695. (b) Yi, H.; Zhang, G.; Wang, H.; Huang, Z.; Wang, J.; Singh, A. K.; Lei, A. Chem. Rev. 2017, 117, 9016. (c) Newton, C.-G.; Wang, S.-G.; Oliveira, C.-C.; Cramer, N. Chem. Rev. 2017, 117, 8908. (d) Dong, Z.; Ren, Z.; Thompson, S. J.; Xu, Y.; Dong, G. Chem. Rev. 2017, 117, 9333. (e) Kalck, P.; Urrutigoïty, M. Chem. Rev. 2018, 118, 3833. (f) Gandeepan, P.; Müller, T.; Zell, D.; Cera, G.; Warratz, S.; Ackermann, L. Chem. Rev. 2019, 119, 2192.
[7] (a) Friedman, L.; Shechter, H. Tetrahedron Lett. 1961, 2, 238. (b) Angioni, S.; Ravelli, D.; Emma, D.; Dondi, D.; Fagnoni, M.; Albini, A. Adv. Synth. Catal. 2008, 350, 2209.
[8] Tsuji, Y.; Yoshii, S.; Ohsumi, T.; Kondo, T.; Watanabe, Y. J. Organomet. Chem. 1987, 331, 379.
[9] Kondo, T.; Okada, T.; Mitsudo, T.a. Organometallics 1999, 18, 4123.
[10] Nath, D. C. D.; Fellows, C. M.; Kobayashi, T.; Hayashi, T. Aust. J. Chem. 2006, 59, 218.
[11] Ko, S.; Han, H.; Chang, S. Org. Lett. 2003, 5, 2687.
[12] (a) Nakao, Y.; Idei, H.; Kanyiva, K.S.; Hiyama, T. J. Am. Chem. Soc. 2009, 131, 5070. (b) Miyazaki, Y.; Yamada, Y.; Nakao, Y.; Hiyama, T. Chem. Lett. 2012, 41, 298.
[13] Fujihara, T.; Katafuchi, Y.; Iwai, T.; Terao, J.; Tsuji, Y. J. Am. Chem. Soc. 2010, 132, 2094.
[14] (a) Kobayashi, Y.; Kamisaki, H.; Yanada, K.; Yanada, R.; Takemoto, Y. Tetrahedron Lett. 2005, 46, 7549. (b) Nakao, Y.; Morita, E.; Idei, H.; Hiyama, T. J. Am. Chem. Soc. 2011, 133, 3264. (c) Donets, P.A.; Cramer, N. J. Am. Chem. Soc. 2013, 135, 11772. (d) Armanino, N.; Carreira, E. M. J. Am. Chem. Soc. 2013, 135, 6814. (e) Correia, V. G.; Abreu, J. C.; Barata, C. A. E.; Andrade, L.H. Org. Lett. 2017, 19, 1060.
[15] Mou, X.-Q.; Xu, L.; Wang, S.-H.; Yang, C. Tetrahedron Lett. 2015, 56, 2820.
[16] Mou, X.-Q.; Xu, Z.-L.; Xu, L.; Wang, S.-H.; Zhang, B.-H.; Zhang, D.; Wang, J.; Liu, W.T.; Bao, W. Org. Lett. 2016, 18, 4032.
[17] Zhang, B.-H.; Lei, L.-S.; Liu, S.-Z.; Mou, X.-Q.; Liu, W.-T.; Wang, S.-H.; Wang, J.; Bao, W.; Zhang, K. Chem. Commun. 2017, 53, 8545.
[18] Bao, W.; Gao, Z.-P.; Jin, D.-P.; Xue, C.-G.; Liang, H.; Lei, L.-S.; Xu, X.-T.; Zhang, K.; Wang, S.-H. Chem. Commun. 2020, 56, 7641.
[19] Lei, L.-S.; Xue, C.-G.; Xu, X.-T.; Jin, D.-P.; Wang, S.-H.; Bao, W.; Liang, H.; Zhang, K.; Asiri, A. M. Org. Biomol. Chem. 2019, 17, 3723.
[20] Lei, L.-S.; Wang, B.-W.; Jin, D.-P.; Gao, Z.-P.; Liang, H.; Wang, S.-H.; Xu, X.-T.; Zhang, K.; Zhang, X.-Y. Adv. Synth. Catal. 2020, 362, 2870.

铜催化的α-氨基丙二腈的脱氰氧代反应：一种合成叔酰胺的新方法

A New Strategy for the Synthesis of Tertiary Amides via a Copper-Catalyzed Decyanation Reaction of N,N-Disubstituted 2-Aminomalononitriles

PDF

补充材料

可视化

摘要/Abstract

引用此文

分享此文

参考文献

相关文章 15

编辑推荐

相关统计

本文评价

[1]	鱼章龙, 李忠良, 杨昌江, 顾强帅, 刘心元. 铜催化的二醇类化合物对映选择性去对称化反应研究进展^★[J]. 化学学报, 2023, 81(8): 955-966.
[2]	孟庆端, 韩佳宏, 潘一骁, 郝伟, 范青华. C₁-对称手性氮杂环卡宾(NHC)配体的不对称合成及其催化性能研究^★[J]. 化学学报, 2023, 81(10): 1271-1279.
[3]	邱孔茜, 李杰, 马浩文, 周伟, 蔡倩. 捕捉环加成反应中的有机亚铜中间体构筑氮杂环化合物研究进展[J]. 化学学报, 2023, 81(1): 42-63.
[4]	徐清浩, 魏立谱, 张震, 肖斌. 铜促进的锗亲电试剂与烷基溴合成四烷基锗^※[J]. 化学学报, 2022, 80(4): 428-431.
[5]	满清敏, 付尊蕴, 刘甜甜, 郑明月, 蒋华良. Cu催化偶联反应合成烷基芳基醚的DFT机理研究[J]. 化学学报, 2021, 79(7): 948-952.
[6]	邓卓基, 欧阳溢凡, 敖运林, 蔡倩. 铜催化不对称去对称化分子内烯基C—N偶联反应[J]. 化学学报, 2021, 79(5): 649-652.
[7]	张荣华, 许冰, 张展鸣, 张俊良. Ming-Phos/铜催化的亚甲胺叶立德与硝基烯烃的不对称[3＋2]环加成反应[J]. 化学学报, 2020, 78(3): 245-249.
[8]	黄浩, 林华鑫, 王敏, 廖建. 1,2-苯基异噁唑为氮源的铜催化苯乙烯不对称硼胺化[J]. 化学学报, 2020, 78(11): 1229-1234.
[9]	成忠明, 陈品红, 刘国生. 光/铜共催化远程C—H键的不对称氰基化反应[J]. 化学学报, 2019, 77(9): 856-860.
[10]	张衡, 牟学清, 陈弓, 何刚. 铜催化苯甲酰亚胺高烯丙酯的分子内胺化全氟烷基化反应[J]. 化学学报, 2019, 77(9): 884-888.
[11]	林凤闺蓉, 梁宇杰, 郦鑫耀, 宋颂, 焦宁. 氧气氧化铜催化的苯胺邻位叠氮化反应[J]. 化学学报, 2019, 77(9): 906-910.
[12]	李雪飞, 林进顺, 王建, 李忠良, 顾强帅, 刘心元. 铜/手性磷酸催化烯烃不对称自由基胺芳基化[J]. 化学学报, 2018, 76(11): 878-882.
[13]	张涌灵, 王敏, 曹鹏, 廖建. 铜催化苯乙烯不对称硼胺化反应[J]. 化学学报, 2017, 75(8): 794-797.
[14]	李新玲, 王佳琪, 李龙, 尹应武, 叶龙武. 2H-吡咯的简易合成方法:金催化与路易斯酸催化的组合应用[J]. 化学学报, 2016, 74(1): 49-53.
[15]	詹益周, 王宝雷, 张丽媛, 张燕, 张晓, 李正名, 宋海斌. 基于Ugi反应的含芳氨基甲酰基1-氰基-1-环丙烷甲酰胺类新化合物的合成、结构和生物活性研究[J]. 化学学报, 2015, 73(11): 1173-1181.