Azetidine synthesis enabled by photo-induced copper catalysis via [3+1] radical cascade cyclization
Azetidines are an important type of saturated, highly strained, four-membered, nitrogen-containing heterocyclic compound. These compounds serve as important raw materials, intermediates, and catalysts in organic synthesis, as well as important active units in amino acids, alkaloids, and pharmaceutic...
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| Main Authors: | , , , , , , , , |
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Elsevier
2022-05-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666675822000406 |
| _version_ | 1851910553926107136 |
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| author | Jianye Li Lu Yu Yun Peng Bin Chen Rui Guo Xiaodong Ma Xiao-Song Xue Yunkui Liu Guozhu Zhang |
| author_facet | Jianye Li Lu Yu Yun Peng Bin Chen Rui Guo Xiaodong Ma Xiao-Song Xue Yunkui Liu Guozhu Zhang |
| author_sort | Jianye Li |
| collection | DOAJ |
| container_title | The Innovation |
| description | Azetidines are an important type of saturated, highly strained, four-membered, nitrogen-containing heterocyclic compound. These compounds serve as important raw materials, intermediates, and catalysts in organic synthesis, as well as important active units in amino acids, alkaloids, and pharmaceutically active compounds. Thus, the development of an efficient and concise method to construct azetidines is of great significance in multiple disciplines. In this work, we reported on the photo-induced copper-catalyzed radical annulation of aliphatic amines with alkynes to produce azetidines. This reaction occurred in a two- or three-component manner. The alkynes efficiently captured photogenerated α-aminoalkyl radicals, forming vinyl radicals, which initiated tandem 1,5-hydrogen atom transfer and 4-exo-trig cyclization. Density functional theory calculations indicated that the tertiary radical intermediate was critical for the success of cyclization. In addition, the resulting saturated azetidine scaffolds possessed vicinal tertiary-quaternary and even quaternary-quaternary centers. |
| format | Article |
| id | doaj-art-c8d1122d70824ea589f2ef220abcebde |
| institution | Directory of Open Access Journals |
| issn | 2666-6758 |
| language | English |
| publishDate | 2022-05-01 |
| publisher | Elsevier |
| record_format | Article |
| spelling | doaj-art-c8d1122d70824ea589f2ef220abcebde2025-08-19T22:02:08ZengElsevierThe Innovation2666-67582022-05-013310024410.1016/j.xinn.2022.100244Azetidine synthesis enabled by photo-induced copper catalysis via [3+1] radical cascade cyclizationJianye Li0Lu Yu1Yun Peng2Bin Chen3Rui Guo4Xiaodong Ma5Xiao-Song Xue6Yunkui Liu7Guozhu Zhang8CCNU-uOttawa Joint Research Centre, Key Laboratory of Pesticides & Chemical Biology Ministry of Education, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University (CCNU), 152 Luoyu Road, Wuhan, Hubei 430079, ChinaState Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, ChinaState Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, ChinaState Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Center for Excellence in Molecular Synthesis, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, ChinaState Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Center for Excellence in Molecular Synthesis, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, ChinaState Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Center for Excellence in Molecular Synthesis, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, ChinaState Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China; Corresponding authorState Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, China; Corresponding authorCCNU-uOttawa Joint Research Centre, Key Laboratory of Pesticides & Chemical Biology Ministry of Education, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University (CCNU), 152 Luoyu Road, Wuhan, Hubei 430079, China; State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Center for Excellence in Molecular Synthesis, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China; Corresponding authorAzetidines are an important type of saturated, highly strained, four-membered, nitrogen-containing heterocyclic compound. These compounds serve as important raw materials, intermediates, and catalysts in organic synthesis, as well as important active units in amino acids, alkaloids, and pharmaceutically active compounds. Thus, the development of an efficient and concise method to construct azetidines is of great significance in multiple disciplines. In this work, we reported on the photo-induced copper-catalyzed radical annulation of aliphatic amines with alkynes to produce azetidines. This reaction occurred in a two- or three-component manner. The alkynes efficiently captured photogenerated α-aminoalkyl radicals, forming vinyl radicals, which initiated tandem 1,5-hydrogen atom transfer and 4-exo-trig cyclization. Density functional theory calculations indicated that the tertiary radical intermediate was critical for the success of cyclization. In addition, the resulting saturated azetidine scaffolds possessed vicinal tertiary-quaternary and even quaternary-quaternary centers.http://www.sciencedirect.com/science/article/pii/S2666675822000406photoredoxazetidinecopper catalysisradicalalkyl aminealkyne |
| spellingShingle | Jianye Li Lu Yu Yun Peng Bin Chen Rui Guo Xiaodong Ma Xiao-Song Xue Yunkui Liu Guozhu Zhang Azetidine synthesis enabled by photo-induced copper catalysis via [3+1] radical cascade cyclization photoredox azetidine copper catalysis radical alkyl amine alkyne |
| title | Azetidine synthesis enabled by photo-induced copper catalysis via [3+1] radical cascade cyclization |
| title_full | Azetidine synthesis enabled by photo-induced copper catalysis via [3+1] radical cascade cyclization |
| title_fullStr | Azetidine synthesis enabled by photo-induced copper catalysis via [3+1] radical cascade cyclization |
| title_full_unstemmed | Azetidine synthesis enabled by photo-induced copper catalysis via [3+1] radical cascade cyclization |
| title_short | Azetidine synthesis enabled by photo-induced copper catalysis via [3+1] radical cascade cyclization |
| title_sort | azetidine synthesis enabled by photo induced copper catalysis via 3 1 radical cascade cyclization |
| topic | photoredox azetidine copper catalysis radical alkyl amine alkyne |
| url | http://www.sciencedirect.com/science/article/pii/S2666675822000406 |
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