Stereoselective Nucleophilic Di‐ and Monofluoro(sulfoximidoyl)Methylation of C═C Bonds: Remote Neighboring Group Participation Enables Facile Access to Chiral γ‐Fluorinated Amines

There remains an ongoing challenge to develop facile methods for the preparation of chiral γ,γ-difluorinated amines, which are commonly considered a privileged motif in bioactive compounds. In this context, we report a straightforward protocol for the stereoselective nucleophilic difluoro(sulfoximidoyl)methylation of C═C bonds (considered to be more challenging than the reported C═O bonds), which exhibits high stereoselectivity and broad substrate scope. The key features of this chemistry include 1) stereoselective addition of the difluoro(sulfoximidoyl)methyl anion to C═C bonds, although it was considered to be highly unfavorable from the view of hard-soft acid-base (HSAB) theory; 2) intriguing neighboring group participation of the oxygen from the nitro group that was found to play a crucial role in controlling the stereoselectivity and efficiency of the transformation and was supported by mechanistic experiments and DFT calculations. This method has been applied to the late-stage modification of several complex molecules and the preparation of enantioenriched bioactive γ-fluorinated amines, such as a phytopathogenic fungi inhibitor, TRPC6 and CDK11 inhibitors, and even monofluorinated lorcaserin, which further demonstrated the significance and potential of this approach.