The bicyclo[1.1.1]pentane (BCP) motif has been utilized as bioisosteres in drug candidates to replace phenyl, tert-butyl, and alkynyl fragments in order to improve physicochemical properties. However, bceause of the difficulty of synthesis, most BCP analogues prepared only bear 1,3-“para”-substituents. We report the first selective synthesis of 2,2-difluorobicyclo[1.1.1]pentanes via difluorocarbene insertion into bicyclo[1.1.0]butanes. Moreover, this methodology should inspire future studies on synthesis of other “ortho/meta-substituted” BCPs via similar mechanisms.

中文翻译：

---

2,2-二氟双环[1.1.1]戊烷类似物的选择性合成：“ BCP-F2”

双环[1.1.1]戊烷（BCP）基序已被用作候选药物中的生物等排体，以取代苯基，叔丁基和炔基片段，以改善其理化性质。然而，由于合成的困难，大多数制备的BCP类似物仅带有1,3-“对”取代基。我们报告通过二氟卡宾插入双环[1.1.0]丁烷中的第一个选择性合成2,2-二氟双环[1.1.1]戊烷。此外，这种方法应能激发通过类似机制合成其他“邻位/间位取代的” BCP的未来研究。