钯催化三组分烯丙基串联反应: 化学专一性合成N-酰亚甲基-2-吡啶酮

doi:10.6023/A19060210

化学学报 ›› 2019, Vol. 77 ›› Issue (10): 993-998.DOI: 10.6023/A19060210 上一篇下一篇

研究通讯

钯催化三组分烯丙基串联反应: 化学专一性合成N-酰亚甲基-2-吡啶酮

姚坤^a, 刘浩^a, 袁乾家^a, 刘燕刚^a, 刘德龙^a^*(), 张万斌^a^b^*()

^a 上海市手性药物分子工程重点实验室上海交通大学药学院上海 200240
^b 上海交通大学化学化工学院上海 200240

投稿日期:2019-06-13 发布日期:2019-08-15
通讯作者: 刘德龙,张万斌 E-mail:dlliu@sjtu.edu.cn;wanbin@sjtu.edu.cn
基金资助:
项目受国家自然科学基金(21971162);项目受国家自然科学基金(21672142);项目受国家自然科学基金(21620102003);项目受国家自然科学基金(21831005);上海市教委(201701070002E00030)

Pd-Catalyzed Three-Component Chemospecific Allylic Substitution Cascade for the Synthesis of N-Carbonylmethylene-2-Pyridones

Yao, Kun^a, Liu, Hao^a, Yuan, Qianjia^a, Liu, Yangang^a, Liu, Delong^a^*(), Zhang, Wanbin^a^b^*()

^a Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Pharmacy, Shanghai Jiaotong University, Shanghai 200240
^b School of Chemistry and Chemical Engineering, Shanghai Jiaotong University, Shanghai 200240

Received:2019-06-13 Published:2019-08-15
Contact: Liu, Delong,Zhang, Wanbin E-mail:dlliu@sjtu.edu.cn;wanbin@sjtu.edu.cn
Supported by:
Project supported by the National Natural Science Foundation of China(21971162);Project supported by the National Natural Science Foundation of China(21672142);Project supported by the National Natural Science Foundation of China(21620102003);Project supported by the National Natural Science Foundation of China(21831005);Shanghai Municipal Education Commission(201701070002E00030)

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1. 钯催化三组分烯丙基串联反应: 化学专一性合成N-酰亚甲基-2-吡啶酮.pdf(5369KB)

摘要/Abstract

N-酰亚甲基-2-吡啶酮是一类非常重要的结构单元, 广泛存在于天然产物和其它具有生物活性的化合物中. 其合成通常是通过2-羟基吡啶与相应的亲电试剂发生分子间亲核取代反应. 然而, 由于2-羟基吡啶的双亲核特性, 这一方法往往面临着N/O化学选择性难以控制的问题. 报道了一例钯催化三组分烯丙基取代反应, 化学专一性地合成难以构建的大位阻N-酰亚甲基-2-吡啶酮衍生物, 收率最高可达98%, 未见有O-烷基化副产物的生成. 该反应可以在克级规模下进行, 依然取得98%的收率. 本方法所得到的N-酰亚甲基-2-吡啶酮产物经过简单转化, 可方便地制得含吡啶酮结构的非天然氨基酸类化合物. 实验结果显示, 该三组分反应是经过一个串联的亲核取代和烯丙基取代反应而专一性地合成N-酰亚甲基-2-吡啶酮衍生物.

关键词: 烯丙基串联反应, 三组分, 化学专一性, N-酰亚甲基-2-吡啶酮

Functionalized N-carbonylmethylene-2-pyridones are some of the most important structural motifs and exist in many natural products and bioactive compounds. Thus, the efficient construction of such skeletons has attracted much attention. Generally, the synthesis of N-carbonylmethylene-2-pyridones is realized via an intermolecular nucleophilic substitution of 2-hydroxypyridines and appropriate electrophiles. However, the above reactions often suffer from low yields caused by poor O/N chemoselectivities due to the dual nucleophilicity of the 2-hydroxypyridines. As far as the structure is concerned, N-carbonylmethylene-2-pyridones can be divided into three sections: a pyridone, a carbonylmethyl group and a side chain. When the side chain is a H atom, the N-substituted pyridones can be constructed conveniently via a reaction of 2-hydroxypyridines and primary α-bromocarbonyl compounds in high yields with excellent chemoselectivities. However, when the side chain is not a H atom, for example an alkyl group, only limited examples have been reported and only moderate yields of the desired N-substituted pyridine products are obtained by a combination of 2-hydroxypyridines and bulky secondary α-bromocarbonyl compounds, mainly due to the poor O/N chemoselectivities. To achieve a general synthetic pathway for the latter, the following practical strategy was designed. 2-Hydroxypyridines were first treated with primary α-bromocarbonyl compounds to generate the unique N-substituted intermediates in situ, which then reacted with the side chain electrophiles to give only the N-alkylated final products. Thus, a Pd-catalyzed three-component chemospecific allylic substitution cascade has been developed for the synthesis of N-carbonylmethylene-2-pyridone derivatives, with the desired products being obtained in up to 98% yield. No O-alkylated by-product was observed. The results suggested that the N-carbonylmethylene-2-pyridones are constructed via a cascade reaction consisting of a nucleophilic substitution followed by an allylic alkylation. The reaction was performed on a gram scale and the corresponding alkylated product was conveniently converted to a pyridone-containing unnatural amino acid. This methodology allows for the highly chemoselective synthesis of biologically important N-carbonylmethylene-2-pyridone derivatives.

Key words: allylic substitution cascade, three-component, chemospecificity, N-carbonylmethylene-2-pyridone

引用此文

姚坤, 刘浩, 袁乾家, 刘燕刚, 刘德龙, 张万斌. 钯催化三组分烯丙基串联反应: 化学专一性合成N-酰亚甲基-2-吡啶酮[J]. 化学学报, 2019, 77(10): 993-998.

Yao, Kun, Liu, Hao, Yuan, Qianjia, Liu, Yangang, Liu, Delong, Zhang, Wanbin. Pd-Catalyzed Three-Component Chemospecific Allylic Substitution Cascade for the Synthesis of N-Carbonylmethylene-2-Pyridones[J]. Acta Chimica Sinica, 2019, 77(10): 993-998.

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图/表 7

图1. N-酰亚甲基-2-吡啶酮衍生物

Figure 1. N-Carbonylmethylene-2-pyridones

图式1. N-取代-2-吡啶酮的构建

Scheme 1. Construction of functionalized N-substituted-2-pyridones

表1. 烯丙基底物拓展a,b

Table 1. Exploration of the allylic substrates

表2. 溴代酮与烯丙基底物的拓展a,b

Table 2. Exploration of the allylic substrates and α-bromoketones

图式2. 分步反应试验

Scheme 2. Study on step by step reaction

图式3. 推测的反应路径

Scheme 3. Proposed reaction pathway

图式4. 5a的克级制备和4a的转化

Scheme 4. Gram-scale synthesis of 5a and transformation of 4a

参考文献 10

[1]	For selected reviews, see: (a) Lenglet, A.; Liabeuf, S.; Bodeau, S.; Louvet, L.; Mary, A.; Boullier, A.; Lemaire-Hurte, A. S.; Jonet, A.; Sonnet, P.; Kamel, S.; Massy, Z. A. Toxins 2016, 8, 339. doi: 10.3390/toxins8110339
	(b) Stazi, G.; Zwergel, C.; Mai, A.; Valente, S . Expert Opin. Ther. Pat. 2017, 27, 797. doi: 10.3390/toxins8110339
	(c) Fioravanti, R.; Stazi, G.; Zwergel, C.; Valente, S.; Mai, A . Chem. Rec. 2018, 18, 1818. doi: 10.3390/toxins8110339
	(d) Shao, T.; Jiang, Z . Acta Chim. Sinica 2017, 75, 70. doi: 10.3390/toxins8110339
	( 邵天举, 江智勇, . 化学学报, 2017, 75, 70.) doi: 10.3390/toxins8110339
	(e) Ye, M.; Qiu, S.; Yin, G . Chin. J. Org. Chem. 2017, 37, 667. doi: 10.3390/toxins8110339
	( 叶明琰, 邱少中, 殷国栋, . 有机化学, 2017, 37, 667.) doi: 10.3390/toxins8110339
	(c) Bai, F.; Hu, D.; Liu, Y.; Wei, L . Chin. J. Org. Chem. 2018, 38, 2054. doi: 10.3390/toxins8110339
	( 白飞成, 胡德庆, 刘云云, 韦丽, . 有机化学, 2018, 38, 2054.) doi: 10.3390/toxins8110339
[2]	For selected reviews, see: (a) Torres, M.; Gil, S.; Parra, M. Curr. Org. Chem. 2005, 9, 1757. doi: 10.2174/138527205774610886
	(b) Hill, M. D.; Movassaghi, M. Chem.-Eur. J. 2008, 14, 6836. doi: 10.2174/138527205774610886
	For selected examples, see: (c) Fang, Y.-Q.; Bio, M. M.; Hansen, K. B.; Potter, M. S.; Clausen, A . J. Am. Chem. Soc. 2010, 132, 15525. doi: 10.2174/138527205774610886
	(d) Li, B.; Wang, G.; Yang, M.; Xu, Z.; Zeng, B.; Wang, H.; Shen, J.; Chen, K.; Zhu, W . Eur. J. Med. Chem. 2013, 70, 677. doi: 10.2174/138527205774610886
	(e) Li, C.; Kähny, M.; Breit, B . Angew. Chem., Int. Ed. 2014, 53, 13780. doi: 10.2174/138527205774610886
	(f) Zhang, X.; Yang, Z.-P.; Huang, L.; You, S.-L . Angew. Chem., Int. Ed. 2015, 54, 1873. doi: 10.2174/138527205774610886
	(g) Feng, B.; Li, Y.; Li, H.; Zhang, X.; Xie, H.; Cao, H.; Yu, L.; Xu, Q . J. Org. Chem. 2018, 83, 6769. doi: 10.2174/138527205774610886
[3]	(a) Sato, T.; Yoshimatsu, K.; Otera, J . Synlett 1995,845. doi: 10.1016/0040-4039(95)01917-7
	(b) Liu, H.; Ko, S.-B.; Josien, H.; Curran, D. P. Tetrahedron Lett. 1995, 36, 8917. doi: 10.1016/0040-4039(95)01917-7
[4]	For selected, examples see: (a) Itami, K.; Yamazaki, D.; Yoshida, J.-I . Org. Lett. 2003, 5, 2161. doi: 10.1021/ol0346234
	(b) Rodrigues, A.; Lee, E. E.; Batey, R. A . Org. Lett. 2010, 12, 260. doi: 10.1021/ol0346234
	(c) Yeung, C. S.; Hsieh, T. H. H.; Dong, V. M . Chem. Sci. 2011, 2, 544. doi: 10.1021/ol0346234
	(d) Tasker, S. Z.; Bosscher, M. A.; Shandro, C. A.; Lanni, E. L.; Ryu, K. A.; Snapper, G. S.; Utter, J. M.; Ellsworth, B. A.; Anderson, C. E . J. Org. Chem. 2012, 77, 8220. doi: 10.1021/ol0346234
	(e) Pan, S.; Ryu, N.; Shibata, T . Org. Lett. 2013, 15, 1902. doi: 10.1021/ol0346234
	(f) Cheng, L.-J.; Brown, A. P. N.; Cordier, C. J . Chem. Sci. 2017, 8, 4299. doi: 10.1021/ol0346234
[5]	(a) Ogata, M.; Matsumoto, H.; Kida, S.; Shimizu, S.; Tawara, K.; Kawamura, Y . J. Med. Chem. 1987, 30, 1497. doi: 10.1021/jm00391a037
	(b) Straub, C. S.; Padwa, A . Org. Lett. 1999, 1, 83. doi: 10.1021/jm00391a037
	(c) Reichelt, A.; Bur, S. K.; Martin, S. F . Tetrahedron 2002, 58, 6323. doi: 10.1021/jm00391a037
	(d) Abreo, M. A.; Meng, J. J.; Agree, C. S . WO 2002016365 2002. doi: 10.1021/jm00391a037
	(e) McArdle, B. M.; Quinn, R. J . ChemBioChem 2007, 8, 788. doi: 10.1021/jm00391a037
	(f) Jiang, M. X.; Zhou, Y. J . J. Asian Nat. Prod. Res. 2008, 10, 1009. doi: 10.1021/jm00391a037
	(g) Payne, R. J.; Bulloch, E. M. M.; Kerbarh, O.; Abell, C . Org. Biomol. Chem. 2010, 8, 3534. doi: 10.1021/jm00391a037
	(h) Micale, N.; Ettari, R.; Lavecchia, A.; Di Giovanni, C.; Scarbaci, K.; Troiano, V.; Grasso, S.; Novellino, E.; Schirmeister, T.; Zappalà, M . Eur. J. Med. Chem. 2013, 64, 23. doi: 10.1021/jm00391a037
	(i) Scarbaci, K.; Troiano, V.; Micale, N.; Ettari, R.; Tamborini, L.; Di Giovanni, C.; Cerchia, C.; Grasso, S.; Novellino, E.; Schirmeister, T.; Lavecchia, A.; Zappalà, M . Eur. J. Med. Chem. 2014, 76, 1. doi: 10.1021/jm00391a037
[6]	For selected examples, see: (a) Bannwarth, L.; Kessler, A.; Pèthe, S.; Collinet, B.; Merabet, N.; Boggetto, N.; Sicsic, S.; Reboud-Ravaux, M.; Ongeri, S . J. Med. Chem. 2006, 49, 4657. doi: 10.1021/jm060576k
	(b) Gibson, S.; Fernando, R.; Jacobs, H. K.; Gopalan, A. S . Tetrahedron 2015, 71, 9271. doi: 10.1021/jm060576k
	(c) Loughlin, W. A.; Jenkins, I. D.; Karis, N. D.; Healy, P. C . Eur. J. Med. Chem. 2017, 127, 341. doi: 10.1021/jm060576k
	(d) Dawson, T. K.; Dziedzic, P.; Robertson, M. J.; Cisneros, J. A.; Krimmer, S. G.; Newton, A. S.; Tirado-Rives, J.; Jorgensen, W. L . ACS Med. Chem. Lett. 2017, 8, 1287. doi: 10.1021/jm060576k
[7]	For selected examples, see: (a) DeRuiter, J.; Brubaker, A. N.; Whitmer, W. L.; Stein, J. L . J. Med. Chem 1986, 29, 2024. doi: 10.1021/jm00160a038
	(b) New, J. S.; Christopher, W. L.; Jass, P. A . J. Org. Chem 1989, 54, 990. doi: 10.1021/jm00160a038
	(c) , . Eur. J. Org. Chem. 2006, 2715. doi: 10.1021/jm00160a038
	(d) Litchfield, J.; Sharma, R.; Atkinson, K.; Filipski, K. J.; Wright, S. W.; Pfefferkorn, J. A.; Tan, B.; Kosa, R. E.; Stevens, B.; Tu, M.; Kalgutkar, A. S . Bioorg. Med. Chem. Lett. 2010, 20, 6262. doi: 10.1021/jm00160a038
	(e) Torhan, M. C.; Peet, N. P.; Williams, J. D . Tetrahedron Lett. 2013, 54, 3926. doi: 10.1021/jm00160a038
	(f) Xin, B.-T.; de Bruin, G.; Plomp, J.-W.; Florea, B. I.; van der Marel, G. A.; Overkleeft, H. S . Eur. J. Org. Chem. 2016, 1132. doi: 10.1021/jm00160a038
[8]	Selected reviews of Pd-catalyzed allylic substitutions: (a) Trost, B. M.; Van Vranken, D. L. Chem. Rev. 1996, 96, 395. doi: 10.1021/cr9409804
	(b) Helmchen, G.; Pfaltz, A. Acc. Chem. Res. 2000, 33, 336. doi: 10.1021/cr9409804
	(c) Trost, B. M.; Crawley, M. L. Chem. Rev. 2003, 103, 2921. doi: 10.1021/cr9409804
	(d) Lu, Z.; Ma, S. Angew. Chem., Int. Ed. 2008, 47, 258. doi: 10.1021/cr9409804
	(e) Trost, B. M.; Zhang, T.; Sieber, J. D . Chem. Sci. 2010, 1, 427. doi: 10.1021/cr9409804
	(f) Tosatti, P.; Nelson, A.; Marsden, S. P . Org. Biomol. Chem. 2012, 10, 3147. doi: 10.1021/cr9409804
	(g) Trost, B. M . Org. Process Res. Dev. 2012, 16, 185. doi: 10.1021/cr9409804
	(h) Lumbroso, A.; Cooke, M. L.; Breit, B . Angew. Chem., Int. Ed. 2013, 52, 1890. doi: 10.1021/cr9409804
	(i) Butt, N. A.; Liu, D.; Zhang, W . Synlett 2014, 25, 615. doi: 10.1021/cr9409804
	(j) Zhuo, C.-X.; Zheng, C.; You, S.-L . Acc. Chem. Res. 2014, 47, 2558. doi: 10.1021/cr9409804
	(k) Butt, N. A.; Zhang, W . Chem. Soc. Rev. 2015, 44, 7929. doi: 10.1021/cr9409804
	(l) Butt, N.; Yang, G.; Zhang, W . Chem. Rec. 2016, 16, 2687. doi: 10.1021/cr9409804
	(m) Fu, J.; Huo, X.; Li, B.; Zhang, W . Org. Biomol. Chem. 2017, 15, 9747. doi: 10.1021/cr9409804
[9]	Selected recent, papers: (a) Zhao, X.; Liu, D.; Guo, H.; Liu, Y.; Zhang, W. J. Am. Chem. Soc. 2011, 133, 19354. doi: 10.1021/ja209373k
	(b) Zhao, X.; Liu, D.; Xie, F.; Liu, Y.; Zhang, W Org. Biomol. Chem 2011, 9, 1871. doi: 10.1021/ja209373k
	(c) Huo, X.; Quan, M.; Yang, G.; Zhao, X.; Liu, D.; Liu, Y.; Zhang, W . Org. Lett 2014, 16, 1570. doi: 10.1021/ja209373k
	(d) Huo, X.; Yang, G.; Liu, D.; Liu, Y.; Gridnev, I. D.; Zhang, W . Angew. Chem., Int. Ed 2014, 53, 6776. doi: 10.1021/ja209373k
	(e) Wei, X.; Liu, D.; An, Q.; Zhang, W . Org. Lett 2015, 17, 5768. doi: 10.1021/ja209373k
	(f) Yao, K.; Liu, D.; Yuan, Q.; Imamoto, T.; Liu, Y.; Zhang, W . Org. Lett 2016, 18, 6296. doi: 10.1021/ja209373k
	(g) An, Q.; Liu, D.; Shen, J.; Liu, Y.; Zhang, W . Org. Lett 2017, 19, 238. doi: 10.1021/ja209373k
	(h) Xia, C.; Shen, J.; Liu, D.; Zhang, W . Org. Lett 2017, 19, 4251. doi: 10.1021/ja209373k
	(i) Huo, X.; He, R.; Fu, J.; Zhang, J.; Yang, G.; Zhang, W . J. Am. Chem. Soc 2017, 139, 9819. doi: 10.1021/ja209373k
	(j) Huo, X.; Fu, J.; He, X.; Chen, J.; Xie, F.; Zhang, W . Chem. Commun 2018, 54, 599. doi: 10.1021/ja209373k
	(k) Yao, K.; Yuan, Q.; Qu, X.; Liu, Y.; Liu, D.; Zhang, W . Chem. Sci 2019, 10, 1767. doi: 10.1021/ja209373k
	We also developed several Ir-catalyzed asymmetric allylic substitution reactions, see: (l) Huo, X.;He, R.;Zhang, X.;Zhang, W . J. Am. Chem. Soc. , 2016, 138, 11093. doi: 10.1021/ja209373k
	(m) He, R.; Liu, P.; Huo, X.; Zhang, W . Org. Lett 2017, 19, 5513. doi: 10.1021/ja209373k
	(n) Huo, X.; Zhang, J.; Fu, J.; He, R.; Zhang, W . J. Am. Chem. Soc. 2018, 140, 2080. doi: 10.1021/ja209373k
[10]	For selected reviews, see: (a) de Graaff, C.; Ruijter, E.; Orru, R. V. A . Chem. Soc. Rev. , 2012, 41, 3969. doi: 10.1039/c2cs15361k
	(b) , . Med. Chem. Commun. , 2012, 3, 1189. doi: 10.1039/c2cs15361k
	(c) Eppe, G.;Didier, D.;Marek, I . Chem. Rev. , 2015, 115, 9175. doi: 10.1039/c2cs15361k
	(d) Vetica, F.;de Figueiredo, R. M.;Orsini, M.;Tofani, D.;Gasperi, T . Synthesis , 2015, 47, 2139. doi: 10.1039/c2cs15361k

钯催化三组分烯丙基串联反应: 化学专一性合成N-酰亚甲基-2-吡啶酮

Pd-Catalyzed Three-Component Chemospecific Allylic Substitution Cascade for the Synthesis of N-Carbonylmethylene-2-Pyridones

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