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

Photoredox-transition metal dual catalysis provides a unique platform for constructing sp 3-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...

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Bibliographic Details
Published in:Organic letters 2022-12, Vol.24 (49), p.9123-9129
Main Authors: Randall, Samuel D., Kowalski, John, Cruz, Cole, Shoemaker, Richard, Tarlton, Eugene, Hinklin, Ronald J.
Format: Article
Language:English
Subjects:
Azetidines
Catalysis
Chemistry, Pharmaceutical
Nickel
Oxidation-Reduction
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Summary:Photoredox-transition metal dual catalysis provides a unique platform for constructing sp 3-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.
ISSN:1523-7060
1523-7052
DOI:10.1021/acs.orglett.2c03852