Catalytic Enantioselective Synthesis of Difluoromethylated Tetrasubstituted Stereocenters in Isoindolones Enabled by a Multiple-Fluorine System
Meng‐Yu Rong, Jinshan Li, Yin Zhou, Fa‐Guang Zhang, Jun‐An Ma
Abstract
A poly trifluoromethylated chiral spirocyclic phosphoric acid was developed and employed with hexafluoroisoproyl alcohol (HFIP) to render the catalytic asymmetric Mukaiyama-Mannich reaction of difluoroenoxysilanes with in situ formed ketimines. This unique multiple-fluorine system provides rapid access to difluoromethylated tetrasubstituted stereocenters in isoindolones with wide substrate scope under mild conditions. Further synthetic transformations to enantioenriched CF2H-isoindolones and CF2-decorated fused isoindolones were also implemented with good efficiency.
Topics & Concepts
StereocenterEnantioselective synthesisChemistryCatalysisPhosphoric acidFluorineSubstrate (aquarium)Combinatorial chemistryOrganocatalysisAlcoholOrganic chemistryGeologyOceanographyFluorine in Organic ChemistryAsymmetric Synthesis and CatalysisCarbohydrate Chemistry and Synthesis