Direct electrophilic and radical isoperfluoropropylation with i-C3F7-Iodine(III) reagent (PFPI reagent)

The isoperfluoropropyl group (i-C3F7) is an emerging motif in pharmaceuticals, agrichemicals and functional materials. However, isoperfluoropropylated compounds remain largely underexplored, presumably due to the lack of efficient access to these compounds. Herein, we disclose the practical and efficient isoperfluoropropylation of aromatic C-H bonds through the invention of a hypervalent-iodine-based reagent-PFPI reagent, that proceeds via a Ag-X coupling process. The activation of the PFPI reagent without any catalysts or additives was demonstrated in the synthesis of isoperfluoropropylated electron-rich heterocycles, while its activity under photoredox catalysis was shown in the synthesis of isoperfluoropropylated non-activated arenes. Detailed mechanistic experiments and DFT calculations revealed a SET-induced concerted mechanistic pathway in the photoredox reactions. In addition, the unique conformation of i-C3F7 in products, that involved intramolecular hydrogen bond was investigated by X-ray single-crystal diffraction and variable-temperature NMR experiments.

Automated summary

This article introduces the emerging application of the isoperfluoropropyl group (i-C3F7) in pharmaceuticals, agrichemicals, and functional materials. By inventing a hypervalent-iodine-based reagent-PFPI reagent, the efficient isoperfluoropropylation of aromatic C-H bonds is achieved through an Ag-X coupling process. The PFPI reagent is demonstrated to activate without catalysts or additives in the synthesis of isoperfluoropropylated electron-rich heterocycles, and its activity under photoredox catalysis is shown in the synthesis of isoperfluoropropylated non-activated arenes. The mechanistic pathway in the photoredox reactions is revealed through detailed experiments and DFT calculations, and the unique conformation of i-C3F7 involving intramolecular hydrogen bond in products is investigated.