Diversity-oriented functionalization of 2-pyridones and uracils

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 2 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 3 -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. Diversity-oriented synthesis of 2-pyridone and uracil derivatives is in urgent need in medicinal chemistry as they are useful pharmacophores. Here the authors show that palladium/norbornene cooperative catalysis enabled dual-functionalization of iodinated 2- pyridones and uracils.