Bidirectional skeletal remodelling of SF 5 -nitrobenzenes into azepine, bicyclic, and benzimidazole frameworks

Abstract

The development of PFAS-free fluorinated scaffolds that preserve the desirable physicochemical attributes of perfluoroalkyl groups remains a central challenge in contemporary fluorine chemistry. Herein, we report a rapid and bidirectional skeletal-remodelling platform that enables controlled interconversion between aromatic, medium-sized, and bicyclic SF5-containing heterocycles from readily accessible SF5-nitrobenzenes. Phosphorus-catalyzed iterative deoxygenation of SF5-nitrobenzenes generates arylnitrene intermediates that undergo remarkably accelerated dearomative ring expansion, furnishing seven-membered SF5-azepines within dramatically shortened reaction times compared to non-SF5 analogues. These azepines function as versatile skeletal nodes, enabling divergent downstream transformations: photoinduced 4π-electrocyclization provides access to previously unexplored SF5-azabicyclo[3.2.0]hepta-2,6-diene frameworks, while selective fluoroacylative activation promotes reverse skeletal reconstruction to restore aromaticity and deliver SF5-substituted benzimidazoles. Collectively, this work demonstrates that strategic incorporation of the SF5 group not only expands accessible heterocyclic architectures but also fundamentally alters skeletal rearrangement kinetics, enabling rapid and controllable skeletal editing from a common, practical precursor. Given the OECD classification of SF5-containing molecules as non-PFAS, this unified skeletal-remodelling approach substantially broadens the design space of fluorinated scaffolds for applications in pharmaceuticals, agrochemicals, and functional materials, advancing the principles of sustainable fluorine chemistry.