Diastereoselective Construction of Bridged Azabicyclo[3.2.1]octane via Copper-Catalyzed Formal [4 + 3] Cycloaddition
Xu Yan1, Fang Wang2, Tonghui Peng1
1Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei 430030, People's Republic of China.
Abstract:
A novel copper-catalyzed formal diastereoselective [4 + 3] cycloaddition of 2-arylaziridines and 2-substituted cyclopentadiene was developed. This transformation provided an efficient protocol for the assembly of a highly strained bridged azabicyclo[3.2.1]octane scaffold, which is widespread in bioactive natural products. A likely mechanism showed that the reaction proceeds through [3 + 2] cycloaddition, ring opening, and aza-Michael addition cascade reaction. This protocol features high efficiency and diastereoselectivity, wide functional group compatibility, and a cheap catalyst.
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