Ni-Catalyzed Reductive Cross-Coupling of Cyclopropylamines and Other Strained Ring NHP Esters with (Hetero)Aryl Halides
Michael S. West, Alexis L. Gabbey, Malcolm P. Huestis, Sophie A. L. Rousseaux
Abstract
A nickel-catalyzed reductive cross-coupling of cyclopropylamine NHP esters with (hetero)aryl halides is reported. This efficient protocol provides direct access to 1-arylcyclopropylamines, a bioisosteric motif commonly used in small molecule drug discovery. The reaction proceeds rapidly (<2 h) with excellent functional group tolerance and without requiring heat- or air-sensitive reagents. The method can also be extended to the arylation of four-membered strained rings. The NHP esters are easily obtained from the corresponding commercially available carboxylic acids in one step with high yields and no column chromatography.
Topics & Concepts
ChemistryArylHalideReagentCatalysisCombinatorial chemistryFunctional groupNickelMoleculeCoupling reactionRing (chemistry)Organic chemistryPolymerAlkylCyclopropane Reaction MechanismsCatalytic C–H Functionalization MethodsCatalytic Cross-Coupling Reactions