A Selective Synthesis of 2,2-Difluorobicyclo[1.1.1]pentane Analogues: “BCP-F2”

• DOI: 10.1021/acs.orglett.9b02026
• Publication Date: 2019-07-11T15:08:42Z
• Authors: Xiaoshen Ma; David L. Sloman; Yongxin Han; David J. Bennett
• Keywords: Pentane; Difluorocarbene

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