A Decarboxylative Cross-Coupling Platform To Access 2-Heteroaryl Azetidines: Building Blocks with Application in Medicinal Chemistry
James T. Brewster, Samuel D. Randall, John P. Kowalski, Cole L. Cruz, Richard N. Shoemaker, Eugene Tarlton, Ronald J. Hinklin
Abstract
-rich chemical matter. Here, we report a nickel-catalyzed cross-coupling of commercially available or easily prepared redox-active NHP azetidine-2-carboxylates with commercially available heteroaryl iodides to yield 2-heteroaryl azetidines. This "off-the-shelf" approach yielded products amenable to diversification giving access to novel saturated heterocyclic scaffolds useful for medicinal chemistry programs. An alternative mechanism for Hantzsch ester within nickel-catalyzed cross-coupling of heteroaryl halides and α-amino radicals is also presented.
Topics & Concepts
ChemistryCatalysisCombinatorial chemistryHalideRadicalYield (engineering)NickelTransition metalOrganic chemistryMaterials scienceMetallurgyCatalytic C–H Functionalization MethodsRadical Photochemical ReactionsSynthesis and Catalytic Reactions