Citation: Ye Shengqing, Wu Jie. 4-Substituted Hantzsch Esters as Alkylation Reagents in Organic Synthesis[J]. Acta Chimica Sinica, ;2019, 77(9): 814-831. doi: 10.6023/A19050170 shu

4-Substituted Hantzsch Esters as Alkylation Reagents in Organic Synthesis

Ye Shengqing ^a ,
Wu Jie ^a,b,c,,

a.
School of Pharmaceutical and Materials Engineering, Taizhou University, Taizhou 318000, China
b.
Department of Chemistry, Fudan University, Shanghai 200438, China
c.
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China

Corresponding author: Wu Jie, Jie_wu@fudan.edu.cn
Received Date: 12 May 2019
Available Online: 12 September 2019
Fund Project: the National Natural Science Foundation of China 21532001the National Natural Science Foundation of China 21672037Project supported by the National Natural Science Foundation of China (Nos. 21672037, 21532001)

Figures(31)

Hantzsch Esters were first synthesized by Arthur Rudolf Hantzsch in 1881, and widely used in pharmaceutical chemistry. The application of Hantsch Esters in organic synthesis in the early time was mainly focused on the dehydrogenation of 1, 4-dihydrogen pyridines (DHPs) in the synthesis of functional pyridines. In 1955, Mauzerall and Westheimer found that Malachite Green could be reduced by Hantzsch Esters to generate the hydrogenated product. Then these DHPs were extensively used as a reductant for decades due to their electron and hydrogen donating properties. In recent years, scientist found that C-C bond cleavage at 4-position of 4-substituted Hantzsch Esters would lead alkyl transfer, and the alkylation process was a radical process. With the rapid development of free radical chemistry, various alkylation reactions using 4-substituted Hantzsch Esters as alkylation reagent have been developed, such as addition reactions of imines and alkenes; cross-coupling reactions with aryl halides; substitution reactions with functional aromatics; Tsuji-Trost reaction; radical insertion with sulfur dioxide; and asymmetric alkylation etc. The advantages in alkylation transfer by using 4-substituted Hantzsch Esters as alkyl source in the past five years were witnessed dramatically:(1) Highly toxic alkyl metal reagents could be avoided in the alkylation reactions; (2) Compared with the moisture sensitivity of alkyl metal reagents Hantzsch Esters are easily handling; (3) 1, 4-Dihydrogen pyridines (DHPs) are biologically-inspired model molecular of reduced nicotinamide adenine dinucleotide (NADH), which would expand the application in biosynthesis. A brief summary in this field is presented in this review, and the advances are classified according to different reaction types. Although these creativity works were developed, there are still some challenges:(1) Could aromatic groups at 4-position of 4-substituted Hantzsch Esters serve as arylation reagents? (2) How to recover the rest pyridine part of Hantzsch Esters after alkylation; (3) New type reactions need to be developed for the asymmetric synthesis.
- 4-substituted Hantzsch Ester,
- 1, 4-dihydropyridine,
- free radical,
- alkylation
1. [1]
  Hantzsch, A. Ber. Dtsch. Chem. Ges. 1881, 14, 1637. doi: 10.1002/cber.18810140214
2. [2]
  (a) Janis, R. A.; Triggle, D. J. J. Med. Chem. 1983, 25, 775. (b) Bocker, R. H.; Guengerich, F. P. J. Med. Chem. 1986, 29, 1596. (c) Xie, W.; Wu, Y.; Zhang, J.; Mei, Q.; Zhang, Y.; Zhu, N.; Liu, R.; Zhang, H. Eur. J. Med. Chem. 2018, 145, 35. (d) Xie, W.; Zhang, H.; He, J.; Zhang, J.; Yu, Q.; Luo, C.; Li, S. Bioorg. Med. Chem. Lett. 2017, 27, 530.
3. [3]
  Bergstrom, F. W. Chem. Rev. 1944, 35, 77. doi: 10.1021/cr60111a001
4. [4]
  Mauzerall, D.; Westheimer, F. H. J. Am. Chem. Soc. 1955, 77, 2261. doi: 10.1021/ja01613a070
5. [5]
  For selected reviews see: (a) Ouellet, S. G.; Walji, A. M.; Macmillan, D. W. C. Acc. Chem. Res. 2007, 40, 1327. (b) de Vries, J. G.; Mrsic, N. Catal. Sci. Technol. 2011, 1, 727. (c) Zheng, C.; You, S.-L. Chem. Soc. Rev. 2012, 41, 2498. (d) Huang, W.; Cheng, X. Synlett 2017, 28, 148. (e) Li, X.; Meng, Y.; Yi, P.; Stepień, M.; Chmielewski, P. J. Angew. Chem., Int. Ed. 2017, 56, 10810.
6. [6]
  Loev, B.; Snader, K. M. J. Org. Chem. 1965, 30, 1914. doi: 10.1021/jo01017a048
7. [7]
  Wei, Z.; Li, J.; Wang, Z.; Li, P.; Wang, Y. Chin. J. Org. Chem. 2017, 37, 1835(in Chinese).
8. [8]
  For selected examples see: (a) Zou, Y.-Q.; Hörmann, F. M.; Bach, T. Chem. Soc. Rev. 2018, 47, 278. (b) Wang, F.; Chen, P.; Liu, G. Acc. Chem. Res. 2018, 51, 2036. (c) Wang, K.; Kong, W. Chin. J. Chem. 2018, 36, 247. (d) Qiu, S.; Wang, C.; Xie, S.; Huang, X.; Chen, L.; Zhao, Y.; Zeng, Z. Chem. Commun. 2018, 54, 11383. (e) Xie, L.-Y.; Peng, S.; Liu, F.; Chen, G.-R.; Xia, W.; Yu, X.; Li, W.-F.; Cao, Z.; He, W.-M. Org. Chem. Front. 2018, 5, 2604. (f) Lu, L.-H.; Zhou, S.-J.; He, W.-B.; Xia, W.; Chen, P.; Yu, X.; Xu, X.; He, W.-M. Org. Biomol. Chem. 2018, 16, 9064. (g) Zheng, Y.; Liu, M.; Qiu, G.; Xie, W.; Wu, J. Tetrahedron 2019, 75, 1663. (h) Liu, K.-J.; Jiang, S.; Lu, L.-H.; Tang, L.-L.; Tang, S.-S.; Tang, H.-S.; Tang, Z.; He, W.-M.; Xu, X. Green Chem. 2018, 20, 3038. (i) Xie, L.-Y.; Peng, S.; Liu, F.; Yi, J.-Y.; Wang, M.; Tang, Z.; Xu, X.; He, W.-M. Adv. Synth. Catal. 2018, 360, 4259. (j) Xie, L.-Y.; Peng, S.; Liu, F.; Chen, G.-R.; Xia, W.; Yu, X.; Li, W.-F.; Cao, Z.; He, W.-M. Org. Chem. Front. 2018, 5, 2604. (k) Guo, T.; Wei, X.-N.; Liu, Y.; Zhang, P.-K.; Zhao, Y.-H. Org. Chem. Front. 2019, 6, 1414.
9. [9]
10. [10]
  Li, G.; Chen, R.; Wu, L.; Fu, Q.; Zhang, X.; Tang, Z. Angew. Chem., Int. Ed. 2013, 52, 8432. doi: 10.1002/anie.201303696
11. [11]
  Zhang, H.-H.; Yu, S. J. Org. Chem. 2017, 82, 9995. doi: 10.1021/acs.joc.7b01425
12. [12]
  Gu, F.; Huang, W.; Liu, X.; Chen, W.; Cheng, X. Adv. Synth. Catal. 2017, 360, 925.
13. [13]
  Wu, Q.-Y.; Min, Q.-Q.; Ao, G.-Z.; Liu, F. Org. Biomol. Chem. 2018, 16, 6391. doi: 10.1039/C8OB01641K
14. [14]
  Mcdonald, B. R.; Scheidt, K. A. Org. Lett. 2018, 20, 6881.
15. [15]
  Van Leeuwen, T.; Buzzetti, L.; Perego, L. A.; Melchiorre, P. Angew. Chem., Int. Ed. 2019, 58, 4953. doi: 10.1002/anie.201814497
16. [16]
  Milligan, J. A.; Phelan, J. P.; Polites, V. C.; Kelly, C. B.; Molander, G. A. Org. Lett. 2018, 20, 6840. doi: 10.1021/acs.orglett.8b02968
17. [17]
  Chen, H.; Anand, D.; Zhou, L. Asian J. Org. Chem. 2019, 8, 661. doi: 10.1002/ajoc.201900026
18. [18]
  Chen, W.; Liu, Z.; Tian, J.; Li, J.; Ma, J.; Cheng, X.; Li, G. J. Am. Chem. Soc. 2016, 138, 12312. doi: 10.1021/jacs.6b06379
19. [19]
  Nakajima, K.; Nojima, S.; Nishibayashi, Y. Angew. Chem., Int. Ed. 2016, 55, 14106. doi: 10.1002/anie.201606513
20. [20]
  Gutiérrez-Bonet, Á.; Tellis, J. C.; Matsui, J. K.; Vara, B. A.; Molander, G. A. ACS Catal. 2016, 6, 8004. doi: 10.1021/acscatal.6b02786
21. [21]
  Dumoulin, A.; Matsui, J. K.; Gutiérrez-Bonet, Á.; Molander, G. A. Angew. Chem., Int. Ed. 2018, 57, 6614. doi: 10.1002/anie.201802282
22. [22]
  Badir, S. O.; Dumoulin, A.; Matsui, J. K.; Molander, G. A. Angew. Chem., Int. Ed. 2018, 57, 6610. doi: 10.1002/anie.201800701
23. [23]
  Nakajima, K.; Guo, X.; Nishibayashi, Y. Chem. Asian J. 2018, 13, 3653. doi: 10.1002/asia.201801542
24. [24]
  Buzzetti, L.; Prieto, A.; Roy, S. R.; Melchiorre, P. Angew. Chem., Int. Ed. 2017, 56, 15039. doi: 10.1002/anie.201709571
25. [25]
26. [26]
  Liu, X.; Liu, R.; Dai, J.; Cheng, X.; Li, G. Org. Lett. 2018, 20, 6906. doi: 10.1021/acs.orglett.8b03050
27. [27]
  Song, Z.-Y.; Zhang, C.-L.; Ye, S. Org. Biomol. Chem. 2019, 17, 181. doi: 10.1039/C8OB02912A
28. [28]
  Li, G.; Wu, L.; Lv, G.; Liu, H.; Fu, Q.; Zhang, X.; Tang, Z. Chem. Commun. 2014, 50, 6246. doi: 10.1039/C4CC01119H
29. [29]
  Nakajima, K.; Nojima, S.; Sakata, K.; Nishibayashi, Y. ChemCatChem 2016, 8, 1028. doi: 10.1002/cctc.201600037
30. [30]
  Wang, Z.-J.; Zheng, S.; Matsui, J. K.; Liu, Z.; Molander, G. A. Chem. Sci. 2019, 10, 4389. doi: 10.1039/C9SC00776H
31. [31]
  Cao, L.; Zheng, L.; Huang, Q. J. Organomet. Chem. 2014, 768, 56. doi: 10.1016/j.jorganchem.2014.06.021
32. [32]
  For selected examples see: (a) Xie, L.-Y.; Peng, S.; Tan, J.-X.; Sun, R.-X.; Yu, X.; Dai, N.-N.; Tang, Z.-L.; Xu, X.; He, W.-M. ACS Sustainable Chem. Eng. 2018, 6, 16976. (b) Xie, L.-Y.; Peng, S.; Lu, L.-H.; Hu, J.; Bao, W.-H.; Zeng, F.; Tang, Z.; Xu, X.; He, W.-M. ACS Sustainable Chem. Eng. 2018, 6, 7989. (c) Xie, L.-Y.; Peng, S.; Jiang, L.-L.; Peng, X.; Xia, W.; Yu, X.; Wang, X.-X.; Cao, Z.; He, W.-M. Org. Chem. Front. 2019, 6, 167.
33. [33]
  Gutiérrez-Bonet, Á.; Remeur, C.; Matsui, J. K.; Molander, G. A. J. Am. Chem. Soc. 2017, 139, 12251. doi: 10.1021/jacs.7b05899
34. [34]
  Matsui, J. K.; Gutiérrez-Bonet, Á.; Rotella, M.; Alam, R.; Gutierrez, O.; Molander, G. A. Angew. Chem., Int. Ed. 2018, 57, 15847. doi: 10.1002/anie.201809919
35. [35]
  For selected examples see: (a) Gong, X.; Wang, M.; Ye, S.; Wu, J. Org. Lett. 2019, 21, 1156. (b) Ye, S.; Qiu, G.; Wu, J. Chem. Commun. 2019, 55, 1013. (c) Ye, S.; Zheng, D.; Wu, J.; Qiu, G. Chem. Commun. 2019, 55, 2214. (d) Ye, S.; Li, Y.; Wu, J.; Li, Z. Chem. Commun. 2019, 55, 2489. (e) Gong, X.; Li, X.; Xie, W.; Wu, J.; Ye, S. Org. Chem. Front. 2019, 6, 1863. (f) Zhang, J.; Xie, W.; Ye, S.; Wu, J. Org. Chem. Front. 2019, 6, 2254. (g) Ye, S.; Xiang, T.; Li, X.; Wu, J. Org. Chem. Front. 2019, 6, 2183. (h) Ye, S.; Li, X.; Xie, W.; Wu, J. Asian J. Org. Chem. 2019, 8, 893. (i) Ye, S.; Li, X.; Xie, W.; Wu, J. Eur. J. Org. Chem. 2019, 10.1002/ejoc.201900396. (j) Zhang, J.; Li, X.; Xie, W.; Ye, S.; Wu, J. Org. Lett. 2019, 21, DOI: 10.1021/acs.orglett.9b01323.(k)Zong,Y.;Lang,Y.;Yang,M.;Li,X.;Fan,X.;Wu,J.Org.Lett.2019,21,1935.
36. [36]
  Wang, X.; Li, H.; Qiu, G.; Wu, J. Chem. Commun. 2019, 55, 2062. doi: 10.1039/C8CC10246E
37. [37]
  Wang, X.; Yang, M.; Xie, W.; Fan, X.; Wu, J. Chem. Commun. 2019, 55, 6010. doi: 10.1039/C9CC03004B
38. [38]
  Verrier, C.; Alandini, N.; Pezzetta, C.; Moliterno, M.; Buzzetti, L.; Hepburn, H. B.; Vega-Penaloza, A.; Silvi, M.; Melchiorre, P. ACS Catal. 2018, 8, 1062. doi: 10.1021/acscatal.7b03788
39. [39]
  Goti, G.; Bieszczad, B.; Vega-Penaloza, A.; Melchiorre, P. Angew. Chem., Int. Ed. 2019, 58, 1213. doi: 10.1002/anie.201810798
40. [40]
  de Assis, F. F.; Huang, X.; Akiyama, M.; Pilli, R. A.; Meggers, E. J. Org. Chem. 2018, 83, 10922. doi: 10.1021/acs.joc.8b01588
41. [41]
  Zhang, H.-H.; Zhao, J.-J.; Yu, S. J. Am. Chem. Soc. 2018, 140, 16914. doi: 10.1021/jacs.8b10766
42. [42]
  Li, F.; Tian, D.; Fan, Y.; Lee, R.; Lu, G.; Yin, Y.; Qiao, B.; Zhao, X.; Xiao, Z.; Jiang, Z. Nat. Commun. 2019, DOI:10.1038/s41467-019-09857-9. doi: 10.1038/s41467-019-09857-9
1. [1]
  Lei Shi . Nucleophilicity and Electrophilicity of Radicals. University Chemistry, 2024, 39(11): 131-135. doi: 10.3866/PKU.DXHX202402018
2. [2]
  Zhilian Liu , Wengui Wang , Hongxiao Yang , Yu Cui , Shoufeng Wang . Ideological and Political Education Design for the Synthesis of Irinotecan Drug Intermediate 7-Ethyl Camptothecin. University Chemistry, 2024, 39(2): 89-93. doi: 10.3866/PKU.DXHX202306012
3. [3]
  Danqing Wu , Jiajun Liu , Tianyu Li , Dazhen Xu , Zhiwei Miao . Research Progress on the Simultaneous Construction of C—O and C—X Bonds via 1,2-Difunctionalization of Olefins through Radical Pathways. University Chemistry, 2024, 39(11): 146-157. doi: 10.12461/PKU.DXHX202403087
4. [4]
  Shiyan Cheng , Yonghong Ruan , Lei Gong , Yumei Lin . Research Advances in Friedel-Crafts Alkylation Reaction. University Chemistry, 2024, 39(10): 408-415. doi: 10.12461/PKU.DXHX202403024
5. [5]
  Gaofeng WANG , Shuwen SUN , Yanfei ZHAO , Lixin MENG , Bohui WEI . Structural diversity and luminescence properties of three zinc coordination polymers based on bis(4-(1H-imidazol-1-yl)phenyl)methanone. Chinese Journal of Inorganic Chemistry, 2024, 40(5): 849-856. doi: 10.11862/CJIC.20230479
6. [6]
  Jingzhao Cheng , Shiyu Gao , Bei Cheng , Kai Yang , Wang Wang , Shaowen Cao . 4-氨基-1H-咪唑-5-甲腈修饰供体-受体型氮化碳光催化剂的构建及其高效光催化产氢研究. Acta Physico-Chimica Sinica, 2024, 40(11): 2406026-. doi: 10.3866/PKU.WHXB202406026
7. [7]
  Jiajia Li , Xiangyu Zhang , Zhihan Yuan , Zhengyang Qian , Jian Zhu . 3D Printing Based on Photo-Induced Reversible Addition-Fragmentation Chain Transfer Polymerization. University Chemistry, 2024, 39(5): 11-19. doi: 10.3866/PKU.DXHX202309073
8. [8]
  Zijian Zhao , Yanxin Shi , Shicheng Li , Wenhong Ruan , Fang Zhu , Jijun Jiang . A New Exploration of the Preparation of Polyacrylic Acid by Free Radical Polymerization Based on the Concept of Green Chemistry. University Chemistry, 2024, 39(5): 315-324. doi: 10.3866/PKU.DXHX202311094
9. [9]
  Zhaoyang WANG , Chun YANG , Yaoyao Song , Na HAN , Xiaomeng LIU , Qinglun WANG . Lanthanide(Ⅲ) complexes derived from 4′-(2-pyridyl)-2, 2′∶6′, 2″-terpyridine: Crystal structures, fluorescent and magnetic properties. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1442-1451. doi: 10.11862/CJIC.20240114
10. [10]
  Yongqing Kuang , Jie Liu , Jianjun Feng , Wen Yang , Shuanglian Cai , Ling Shi . Experimental Design for the Two-Step Synthesis of Paracetamol from 4-Hydroxyacetophenone. University Chemistry, 2024, 39(8): 331-337. doi: 10.12461/PKU.DXHX202403012
11. [11]
  Tianlong Zhang , Rongling Zhang , Hongsheng Tang , Yan Li , Hua Li . Online Monitoring and Mechanistic Analysis of 3,5-diamino-1,2,4-triazole (DAT) Synthesis via Raman Spectroscopy: A Recommendation for a Comprehensive Instrumental Analysis Experiment. University Chemistry, 2024, 39(6): 303-311. doi: 10.3866/PKU.DXHX202312006
12. [12]
  Chengqian Mao , Yanghan Chen , Haotong Bai , Junru Huang , Junpeng Zhuang . Photodimerization of Styrylpyridinium Salt and Its Application in Silk Screen Printing. University Chemistry, 2024, 39(5): 354-362. doi: 10.3866/PKU.DXHX202312014
13. [13]
  Fan JIA , Wenbao XU , Fangbin LIU , Haihua ZHANG , Hongbing FU . Synthesis and electroluminescence properties of Mn²⁺ doped quasi-two-dimensional perovskites (PEA)₂Pb_yMn_1-yBr₄. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1114-1122. doi: 10.11862/CJIC.20230473
14. [14]
  Liyang ZHANG , Dongdong YANG , Ning LI , Yuanyu YANG , Qi MA . Crystal structures, luminescent properties and Hirshfeld surface analyses of three cadmium(Ⅱ) complexes based on 2-(3-(pyridin-2-yl)-1H-pyrazol-1-yl)benzoate. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1943-1952. doi: 10.11862/CJIC.20240079
15. [15]
  Guangming YIN , Huaiyao WANG , Jianhua ZHENG , Xinyue DONG , Jian LI , Yi'nan SUN , Yiming GAO , Bingbing WANG . Preparation and photocatalytic degradation performance of Ag/protonated g-C₃N₄ nanorod materials. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1491-1500. doi: 10.11862/CJIC.20240086
16. [16]
  Jinyao Du , Xingchao Zang , Ningning Xu , Yongjun Liu , Weisi Guo . Electrochemical Thiocyanation of 4-Bromoethylbenzene. University Chemistry, 2024, 39(6): 312-317. doi: 10.3866/PKU.DXHX202310039
17. [17]
  Jianyin He , Liuyun Chen , Xinling Xie , Zuzeng Qin , Hongbing Ji , Tongming Su . ZnCoP/CdLa₂S₄肖特基异质结的构建促进光催化产氢. Acta Physico-Chimica Sinica, 2024, 40(11): 2404030-. doi: 10.3866/PKU.WHXB202404030
18. [18]
  Keke Han , Wenjun Rao , Xiuli You , Haina Zhang , Xing Ye , Zhenhong Wei , Hu Cai . Two new high-temperature molecular ferroelectrics [1,5-3.2.2-Hdabcni]X (X = ClO₄⁻, ReO₄⁻). Chinese Chemical Letters, 2024, 35(6): 108809-. doi: 10.1016/j.cclet.2023.108809
19. [19]
  Guang Huang , Lei Li , Dingyi Zhang , Xingze Wang , Yugai Huang , Wenhui Liang , Zhifen Guo , Wenmei Jiao . Cobalt’s Valor, Nickel’s Foe: A Comprehensive Chemical Experiment Utilizing a Cobalt-based Imidazolate Framework for Nickel Ion Removal. University Chemistry, 2024, 39(8): 174-183. doi: 10.3866/PKU.DXHX202311051
20. [20]
  Zhuoming Liang , Ming Chen , Zhiwen Zheng , Kai Chen . Multidimensional Studies on Ketone-Enol Tautomerism of 1,3-Diketones By ¹H NMR. University Chemistry, 2024, 39(7): 361-367. doi: 10.3866/PKU.DXHX202311029

Get Citation

PDF

XML

Metrics

PDF Downloads(392)
Abstract views(13860)
HTML views(7058)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142