Strained bicyclic substructures are increasingly relevant in medicinal chemistry discovery research because of their role as bioisosteres. Over the last decade, the successful use of bicyclo[1.1.1]pentane (BCP) as a para-disubstituted benzene replacement has made it a highly valuable pharmacophore. However, various challenges, including limited and lengthy access to useful BCP building blocks, are hampering early discovery research. Here we report a single-step transition-metal-free multi-component approach to synthetically versatile BCP boronates. Radicals derived from commonly available carboxylic acids and organohalides perform additions onto [1.1.1]propellane to afford BCP radicals, which then engage in polarity-matched borylation. A wide array of alkyl-, aryl- and alkenyl-functionalized BCP boronates were easily prepared. Late-stage functionalization performed on natural products and approved drugs proceeded with good efficiency to generate the corresponding BCP conjugates. Various photoredox transformations forging C–C and C–N bonds were demonstrated by taking advantage of BCP trifluoroborate salts derived from the BCP boronates.

由于它们作为生物等排物的作用，应变双环子结构在药物化学发现研究中越来越重要。在过去十年中，双环[1.1.1]戊烷 (BCP) 作为对位化合物的成功应用-双取代苯取代使其成为极具价值的药效团。然而，各种挑战，包括对有用的 BCP 构建块的有限和冗长的访问，正在阻碍早期发现研究。在这里，我们报告了一种单步无过渡金属的多组分方法来合成多功能 BCP 硼酸盐。衍生自常用羧酸和有机卤化物的自由基在 [1.1.1] 丙烷上进行加成以提供 BCP 自由基，然后进行极性匹配的硼化。各种烷基、芳基和烯基官能化的 BCP 硼酸盐很容易制备。对天然产物和批准的药物进行的后期功能化以良好的效率进行，以生成相应的 BCP 偶联物。