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

doi:10.6023/cjoc202005001

Chinese Journal of Organic Chemistry ›› 2020, Vol. 40 ›› Issue (10): 3431-3438.DOI: 10.6023/cjoc202005001 Previous Articles Next Articles

Special Issue: 黄乃正院士七十华诞专辑

自由基参与的[1.1.1]螺桨烷溴烷基化反应:溴代双环[1.1.1]戊烷衍生物的合成

张红^a, 王明扬^a, 吴新鑫^a, 朱晨^a,b

a 苏州大学材料与化学化工学部苏州 215123;
b 中国科学院上海有机化学研究所天然产物有机合成重点实验室上海 200032

收稿日期:2020-05-01 修回日期:2020-05-30 发布日期:2020-06-10
通讯作者: 朱晨 E-mail:chzhu@suda.edu.cn
基金资助:
国家自然科学基金（Nos.21722205，21971173）资助项目.

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

Received:2020-05-01 Revised:2020-05-30 Published:2020-06-10
Supported by:
Project supported by the National Natural Science Foundation of China (Nos. 21722205, 21971173).

1. 203431S.pdf(2253KB)

Abstract

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.

Key words: radicals, difunctionalization, ring opening, [1.1.1]propellane, bicyclo[1.1.1]pentane (BCP)

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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.

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自由基参与的[1.1.1]螺桨烷溴烷基化反应:溴代双环[1.1.1]戊烷衍生物的合成

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

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