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Asymmetric Transfer Hydrogenation of <i>gem</i>‐Difluorocyclopropenyl Esters: Access to Enantioenriched <i>gem</i>‐Difluorocyclopropanes

Khalil Yamani, Hugo Pierre, Alexis Archambeau, Christophe Meyer, Janine Cossy

2020Angewandte Chemie International Edition51 citationsDOI

Abstract

Abstract Catalytic 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.

Topics & Concepts

Enantioselective synthesisTransfer hydrogenationRutheniumCatalysisChemistryCombinatorial chemistryAsymmetric hydrogenationLigand (biochemistry)TosylSurface modificationOrganic chemistryMedicinal chemistryReceptorBiochemistryPhysical chemistryFluorine in Organic ChemistryCyclopropane Reaction MechanismsAsymmetric Hydrogenation and Catalysis
Asymmetric Transfer Hydrogenation of <i>gem</i>‐Difluorocyclopropenyl Esters: Access to Enantioenriched <i>gem</i>‐Difluorocyclopropanes | Litcius