Gem-difluorinative ring-expansion of alkenes

Abstract

Incorporating fluorine into aliphatic rings induces significant alterations in molecular conformation, acidity/basicity, and lipophilicity. Current methods for synthesizing fluorinated aliphatic rings, however, involve manipulating functional groups within pre-existing ring systems. Here, we have developed a novel chemical reaction - gem-difluorinative ring-expansion of methylenecycloalkanes. The reaction involves iodine(III) species, and allows the preparation of gem-difluorinated macrocyclic, fused, spiro, bridged, and natural product-derived structures. The protocol's practicality is demonstrated through several decagram-scale syntheses.