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Diversity-oriented functionalization of 2-pyridones and uracils.

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/DCO₂Na, boronic acid/ester, terminal alkene and alkyne are compatible with this protocol. Thus, a large number of valuable 2-pyridone derivatives, including deuterium/CD₃-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.

SUBMITTER: Shang Y

PROVIDER: S-EPMC8137914 | biostudies-literature |

REPOSITORIES: biostudies-literature

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