A General and Efficient Solution to Monofluoroalkylation: Divergent Synthesis of Aliphatic Monofluorides with Modular Synthetic Scaffolds

Abstract

Monofluoroalkane has seen its prevalence in many pharmaceuticals, agrochemicals and functional materials. However, the lack of easily available and transformable monofluoroalkylating reagents that facilitate broad array of transformations has hampered the application of monofluoroalkylation. Herein, we report a general and efficient method of preparing diverse aliphatic monofluorides with modular synthetic scaffold-monofluoroalkyl triflate. Leveraged by both nickel-catalyzed hydromonofluoroalkylation of unactivated alkenes and copper-catalyzed C-C bond formation, the general diversification of the monofluoroalkylating scaffold has been exhibited. Aside from new methodologies, we have further demonstrated broad utilities of this monofluoroalkylating reagent by concise conversion to various conventional fluoroalkylating reagents and construction of monofluoro-alkoxy, -alkylamino motifs with commercially available heteroatom-based coupling partners.