Ni-Catalyzed Reductive Cross-Coupling of Cyclopropylamines and Other Strained Ring NHP Esters with (Hetero)Aryl Halides



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 other 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.


Thumbnail image of Arylcyclopropylamine_RCC_Manuscript_ChemRxiv.pdf

Supplementary material

Thumbnail image of Arylcyclopropylamine_RCC_SupportingInfo_Combined_ChemRxiv.pdf
Supporting Information
Reaction optimization tables, synthetic procedures, characterization data, proposed mechanism, PXRD traces, and NMR spectra (PDF)