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

James T Brewster, Samuel D Randall, John Kowalski, Cole Cruz, Richard Shoemaker, Eugene Tarlton, Ronald J Hinklin

Organic letters 2022 Dec 16

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Photoredox-transition metal dual catalysis provides a unique platform for constructing sp3-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.

Citation

James T Brewster, Samuel D Randall, John Kowalski, Cole Cruz, Richard Shoemaker, Eugene Tarlton, Ronald J Hinklin. A Decarboxylative Cross-Coupling Platform To Access 2-Heteroaryl Azetidines: Building Blocks with Application in Medicinal Chemistry. Organic letters. 2022 Dec 16;24(49):9123-9129