摘要/Abstract

双环[1.1.1]戊烷（BCP）常被用作苯基、叔丁基和炔基的生物等排体，以提高生物活性分子的类药性.因此，向BCP骨架引入实用性官能团为药物开发中设计新的生物等排体提供了有效策略.报道了自由基参与的[1.1.1]螺桨烷的溴烷基化反应，实现了溴代BCP衍生物的合成.该反应以溴代烷基杂芳基砜为原料，经自由基途径向螺桨烷同时引入烷基杂芳基砜和溴两种官能团.该反应快速高效，在室温下仅需2 h便能完成.产物多样性较好，能够获得一系列新颖的烷基杂芳基砜取代的BCP衍生物.此外，该反应还具备原子经济性高、操作简单和易于克级制备等优点.
关键词: 自由基, 双官能团化, 开环, [1.1.1]螺桨烷, 双环[1.1.1]戊烷(BCP)
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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