Chemo-, regio-, and stereoselective tetrafunctionalization of fluoroalkynes enables divergent synthesis of 5-7-membered azacycles

被引:19
作者
Chen, Jia-Wei [1 ]
Ji, Wen-Jun [1 ]
Huang, Xue-Ying [1 ]
Ge, Danhua [1 ]
Shen, Zhi-Liang [1 ]
Guo, Kai [2 ]
Chu, Xue-Qiang [1 ]
机构
[1] Nanjing Tech Univ, Tech Inst Fluorochem, Sch Chem & Mol Engn, Nanjing 211816, Peoples R China
[2] Nanjing Tech Univ, Coll Biotechnol & Pharmaceut Engn, Nanjing 211816, Peoples R China
基金
中国国家自然科学基金;
关键词
F BOND FUNCTIONALIZATIONS; C-H; ACTIVATION; ALKYNES; HYDRODEFLUORINATION; DIAMINATION; CHEMISTRY; ANILINES;
D O I
10.1039/d4sc03230f
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Alkyne annulation has been widely used in organic synthesis for the construction of azacycles with unique structural and physicochemical properties. However, the analogous transformation of fluoroalkynes remains a challenge and has seen limited progress. Herein we report a 1,2,3,4-tetrafunctionalization of polyfluoroalkynes for the divergent construction of 5-7-membered (E)-1,2-difluorovinyl azacycles. The use of the fluorine atom as a detachable "activator" not only obviates the use of any transition metal catalysts and oxidizing reagents, but also ensures the [3-5 + 2]-annulation and defluorinative functionalization of fluoroalkynes with high chemo-, regio-, and stereoselectivities. This method exhibits a broad substrate scope, good functional group tolerance, and excellent scalability, providing a modular platform for accessing fluorinated skeletons of medicinal and biological interest. The late-stage modification of complex molecules, the multi-component 1,2-diamination of fluoroalkyne, and the synthesis of valuable organofluorides from the obtained products further highlight the real-world utility of this fluoroalkyne annulation technology. A 1,2,3,4-tetrafunctionalization of polyfluoroalkynes for the divergent construction of 5-7-membered (E)-1,2-difluorovinyl azacycles is developed.
引用
收藏
页码:12026 / 12035
页数:10
相关论文
共 50 条
[1]   Selective synthesis of fluorinated furan derivatives via AgNO3-catalyzed activation of an electronically deficient triple bond [J].
Arimitsu, Satoru ;
Hammond, Gerald B. .
JOURNAL OF ORGANIC CHEMISTRY, 2007, 72 (22) :8559-8561
[2]   Syntheses and Synthetic Applications of Functionalized Propargylic and Allylic Fluorides [J].
Arimitsu, Satoru .
CHEMICAL RECORD, 2023, 23 (09)
[3]   Metallomimetic C-F Activation Catalysis by Simple Phosphines [J].
Bonfante, Sara ;
Lorber, Christian ;
Lynam, Jason M. ;
Simonneau, Antoine ;
Slattery, John M. .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2024, 146 (03) :2005-2014
[4]   C-F bond activation enables synthesis of aryl difluoromethyl bicyclopentanes as benzophenone-type bioisosteres [J].
Chen, Mingshuo ;
Cui, Yuang ;
Chen, Xiaoping ;
Shang, Rui ;
Zhang, Xiaheng .
NATURE COMMUNICATIONS, 2024, 15 (01)
[5]   Chiral dipeptide mimics possessing fluoroolefin moiety: a relevant tool for conformational and medicinal studies [J].
Couve-Bonnaire, Samuel ;
Cahard, Dominique ;
Pannecoucke, Xavier .
ORGANIC & BIOMOLECULAR CHEMISTRY, 2007, 5 (08) :1151-1157
[6]   Nickel-Catalyzed Exhaustive Hydrodefluorination of Perfluoroalkyl Arenes [J].
Doi, Ryohei ;
Yasuda, Masashi ;
Kajita, Naoki ;
Koh, Kenta ;
Ogoshi, Sensuke .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2023, 145 (20) :11449-11456
[7]   Hydrodefluorination of perfluoroalkyl groups using silylium-carborane catalysts [J].
Douvris, Christos ;
Ozerov, Oleg V. .
SCIENCE, 2008, 321 (5893) :1188-1190
[8]   Synthesis of Fluorine-Containing Exoalkylidene β-Lactams [J].
El Dine, Assaad Nasr ;
Gree, Danielle ;
Roisnel, Thierry ;
Caytan, Elsa ;
Hachem, Ali ;
Gree, Rene .
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2016, 2016 (03) :556-561
[9]   Copper-catalyzed 1,2-double amination of 1-halo-1-alkynes. Concise synthesis of protected tetrahydropyrazines and related heterocyclic compounds [J].
Fukudome, Yasuhiro ;
Naito, Hiroyuki ;
Hata, Takeshi ;
Urabe, Hirokazu .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2008, 130 (06) :1820-+
[10]   gem-Difluoromethylene Alkyne-Enabled Diverse C-H Functionalization and Application to the on-DNA Synthesis of Difluorinated Isocoumarins [J].
Gao, Hui ;
Lin, Shuang ;
Zhang, Shuning ;
Chen, Weijie ;
Liu, Xiawen ;
Yang, Guang ;
Lerner, Richard A. ;
Xu, Hongtao ;
Zhou, Zhi ;
Yi, Wei .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2021, 60 (04) :1959-1966