Asymmetric Transfer Hydrogenation of gem‐Difluorocyclopropenyl Esters: Access to Enantioenriched gem‐Difluorocyclopropanes

Abstract

AbstractCatalytic enantioselective access to disubstituted functionalized gem‐difluorocyclopropanes, which are emerging fluorinated motifs of interest in medicinal chemistry, was achieved through asymmetric transfer hydrogenation of gem‐difluorocyclopropenyl esters, catalyzed by a Noyori–Ikariya (p‐cymene)‐ruthenium(II) complex, with (N‐tosyl‐1,2‐diphenylethylenediamine) as the chiral ligand and isopropanol as the hydrogen donor. The resulting cis‐gem‐difluorocyclopropyl esters were obtained with moderate to high enantioselectivity (ee=66–99 %), and post‐functionalization reactions enable access to valuable building blocks incorporating a cis‐ or trans‐gem‐difluorocyclopropyl motif.