A Decarboxylative Cross-Coupling Platform To Access 2-Heteroaryl Azetidines: Building Blocks with Application in Medicinal Chemistry

• DOI: 10.1021/acs.orglett.2c03852
• Publication Date: 2022-12-07T14:48:54Z
• Authors: James T. Brewster; Samuel D. Randall; John Kowalski; Cole Cruz; Richard Shoemaker; Eugene Tarlton; Ronald J. Hinklin
• Keywords: Nickel; Chemistry, Pharmaceutical; Azetidines; Oxidation-Reduction; 01 natural sciences; Catalysis; 0104 chemical sciences

Photoredox-transition metal dual catalysis provides a unique platform for constructing sp3-rich chemical matter. Here, we report nickel-catalyzed cross-coupling of commercially available or easily prepared redox-active NHP azetidine-2-carboxylates with heteroaryl iodides to yield 2-heteroaryl azetidines. This "off-the-shelf" approach yielded products amenable diversification giving access novel saturated heterocyclic scaffolds useful medicinal chemistry programs. An alternative mechanism Hantzsch ester within halides and α-amino radicals is also presented.