Fluoroiodocarbene Addition to Bicyclobutanes: A Radical Handle for Quaternary Fluorinated Bicyclo[1.1.1]pentanes

Abstract Fluorinated bicyclo[1.1.1]pentanes (F-BCPs) are valuable three-dimensional bioisosteres in drug discovery, yet methods for the direct construction of bridge-monofluorinated and quaternary F-BCPs remain scarce. Here, we report a fluoroiodocarbene addition to bicyclobutanes under mild conditions, providing 2-fluoro-2-iodobicyclo[1.1.1]pentanes. The C–I bond serves as a versatile radical handle, enabling synthesis of quaternary bridge-fluorinated BCPs, including Giese-type additions to activated alkenes and desulfonylative couplings. This strategy offers a practical, modular entry to bridge-fluorinated BCP architectures of potential interest for medicinal chemistry.