Work

N-aryl/-alkenyl difluoroketenimines: Transient intermediates for the general synthesis of difluoroalkylated heterocycles

Year: 2025

Type: article

Abstract: Fluorinated ketenimines not only have unique reactivities but also can be used as fluorinated building blocks, however, the research on their synthesis and application remains in its infancy. We herein describe the first example of the generation and transformation of N -aryl/-alkenyl difluoroketenimines through the chemoselective coupling of functionalized isocyanides with difluorocarbene. Notably, no transition-metal catalysts or oxidants were required, which provides a green, pragmatic, and general method for the efficient de novo synthesis of eleven types of difluoromethylated/tetrafluoroethylated/difluoroalkylated heterocycles. The reactivity properties of these functionalized difluoroketenimines were revealed by a 6π electrocyclization in the mechanistic studies. Furthermore, the preliminary biological studies of the resulting products exhibited good antitumor potency. The first example of generation and transformation of N -aryl/-alkenyl difluoroketenimines was disclosed. These unprecedented functionalized transient intermediate enables the efficient de novo synthesis of eleven types of CF 2 R (R = H, CF 2 H, alkyl)-containing heterocycles through the cascade chemoselective coupling and 6π electrocyclization of functionalized isocyanides with difluorocarbene.

Source: Green Synthesis and Catalysis

DOI: 10.1016/j.gresc.2025.03.013