Citation: Zhang Hong, Wang Mingyang, Wu Xinxin, Zhu Chen. Radical-Mediated Bromoalkylation of [1.1.1]propellane: Synthesis of Bromo-substituted Bicyclo[1.1.1]pentane Derivatives[J]. Chinese Journal of Organic Chemistry, ;2020, 40(10): 3431-3438. doi: 10.6023/cjoc202005001 shu

Radical-Mediated Bromoalkylation of [1.1.1]propellane: Synthesis of Bromo-substituted Bicyclo[1.1.1]pentane Derivatives

Zhang Hong ^a,† ,
Wang Mingyang ^a,† ,
Wu Xinxin ^a ,
Zhu Chen ^a,b,,

a.
College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123
b.
Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Shanghai 200032

Corresponding author: Zhu Chen, chzhu@suda.edu.cn
Received Date: 1 May 2020
Revised Date: 30 May 2020
Available Online: 8 June 2020
Fund Project: the National Natural Science Foundation of China 21722205Project supported by the National Natural Science Foundation of China (Nos. 21722205, 21971173)the National Natural Science Foundation of China 21971173

Figures(3)

As a bioisostere for phenyl rings, tert-butyl groups and internal alkynes, bicyclo[1.1.1]pentane (BCP) can improve the drug-like qualities of bioactive molecules. Therefore, the incorporation of high-value functional groups to BCP scaffold becomes an efficient synthetic strategy to design new bioisosteres in drug development. Herein a radical-mediated bromoalkylation of[1.1.1]propellane was disclosed, leading to brominated BCP derivatives. Bromoalkyl heteroarylsulfones were employed as dual-function reagents in the radical transformation, in which two functionalities, alkylheteroarylsulfone and bromine atom, were concurrently introduced into[1.1.1]propellane. These reactions proceeded rapidly, and were generally completed within 2 h at room temperature. A variety of new alkylheteroarylsulfone-substituted BCP derivatives were furnished with high product diversity. This protocol features excellent atom-economy, simple operation, and gram-scale preparation.
- radicals,
- difunctionalization,
- ring opening,
- [1.1.1]propellane,
- bicyclo[1.1.1]pentane (BCP)
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