Bicyclo­[1.1.1]­pentanes (BCPs) are of great interest to the agrochemical, materials, and pharmaceutical industries. In particular, synthetic methods to access 1,3-dicarbosubsituted BCP-aryls have recently been developed, but most protocols rely on the stepwise C–C bond formation via the initial manipulation of BCP core to make the BCP electrophile or nucleophile followed by a second step (e.g., transition-metal-mediated cross-coupling step) to form the second key BCP-aryl bond. Moreover, despite the prevalence of C–F bonds in bioactive compounds, one-pot, multicomponent cross-coupling methods to directly functionalize [1.1.1]­propellane to the corresponding fluoroalkyl BCP-aryl scaffolds are lacking. In this work, we describe a conceptually different approach to access diverse (fluoro)­alkyl BCP-aryls at low temperatures and fast reaction times enabled by an iron-catalyzed multicomponent radical cross-coupling reaction from readily available (fluoro)­alkyl halides, [1.1.1]­propellane, and Grignard reagents. Further, experimental and computational mechanistic studies provide insights into the mechanism and ligand effects on the nature of C–C bond formation. Finally, these studies are used to develop a method to rapidly access synthetic versatile (difluoro)­alkyl BCP halides via bisphosphine-iron catalysis.

Bicyclo[1.1.1]pentanes (BCPs) are of great interest to the agrochemical, materials, and pharmaceutical industries. In particular, synthetic methods to access 1,3-dicarbosubsituted BCP-aryls have recently been developed but most protocols rely on stepwise C-C bond formation via initial manipulation of BCP core to make the BCP-electrophile or -nucleophile followed by a second step (e.g., transition-metal mediated cross-coupling step) to form the second key BCP-aryl bond. Moreover, despite prevalence of C-F bonds in bioactive compounds, one pot, multicomponent cross-coupling methods to directly functionalize BCP to the corresponding fluoroalkyl BCP-aryl scaffolds are lacking. In this work, we describe a conceptual different approach to access diverse (fluoro)alkyl BCP-aryls at low temperatures and fast reaction times enabled by an iron-catalyzed multicomponent radical cross-coupling reaction from readily available (fluoro)alkyl halides, bicyclo[1.1.1]pentane, and Grignard reagents. Further, experimental and computational mechanistic studies provide insights into mechanism and ligand effects on the nature of C-C bond formation. Finally, these studies are used to develop a new method to rapidly access synthetic versatile 1-(fluoro)alkyl,3-bromo and -iodo BCPs via bisphosphine iron catalysis.