Hydroarylation of Alkenes Using Anilines in Hexafluoroisopropanol
Ignacio Colomer
Abstract
Providing new methods for the selective functionalization of small molecules is highly desirable, because installing molecular diversity in a desired position, for example, allows one to modulate bioactive molecules. This work reports a method for the selective functionalization of anilines using hexafluoroisopropanol (HFIP) as a solvent to promote an acid-catalyzed hydroarylation of olefins. Mechanistic experiments revealed that HFIP both protonates the alkene and selectively enables anilines toward the electrophilic aromatic substitution. This powerful strategy has been applied to the functionalization of the anti-inflammatory mefenamic acid with chemocontrol and regiocontrol.
Topics & Concepts
Surface modificationAlkeneCombinatorial chemistryChemistryMoleculeCatalysisElectrophileOrganic chemistrySolventMefenamic acidPhysical chemistryChromatographyCatalytic C–H Functionalization MethodsSynthesis and Catalytic ReactionsAsymmetric Hydrogenation and Catalysis