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 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.

Automated summary

A nickel-catalyzed reductive cross-coupling reaction has been developed for the synthesis of 1-arylcyclopropylamines. The method is efficient, fast, and tolerant of different functional groups.