Diversity-oriented functionalization of 2-pyridones and uracils.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34016986.
- Also identified by DOI 10.1038/s41467-021-23058-3 and PMC identifier 8137914.
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Abstract
Heterocycles 2-pyridone and uracil are privileged pharmacophores. Diversity-oriented synthesis of their derivatives is in urgent need in medicinal chemistry. Herein, we report a palladium/norbornene cooperative catalysis enabled dual-functionalization of iodinated 2-pyridones and uracils. The success of this research depends on the use of two unique norbornene derivatives as the mediator. Readily available alkyl halides/tosylates and aryl bromides are utilized as ortho-alkylating and -arylating reagents, respectively. Widely accessible ipso-terminating reagents, including H/DCO<sub>2</sub>Na, boronic acid/ester, terminal alkene and alkyne are compatible with this protocol. Thus, a large number of valuable 2-pyridone derivatives, including deuterium/CD<sub>3</sub>-labeled 2-pyridones, bicyclic 2-pyridones, 2-pyridone-fenofibrate conjugate, axially chiral 2-pyridone (97% ee), as well as uracil and thymine derivatives, can be quickly prepared in a predictable manner (79 examples reported), which will be very useful in new drug discovery.
Medical subject headings
- Chemistry, Pharmaceutical
- Drug Discovery
- Pharmaceutical Preparations