Synthesis of Masked 2-Pyridones from 1,3-Enynyl Esters via Tandem Gold-Catalyzed Cycloisomerization and Oxidative Nitrogen Insertion

An efficient synthetic method to regioselectively assemble masked 2-pyridones that relies on sequential gold-catalyzed cycloisomerization and phenyliodonium diacetate (PIDA)-mediated oxidative nitrogen insertion from 1,3-enynyl esters in a one-pot, two-step manner is described. The synthetic utility of the cascade protocol was further demonstrated by the 2 mmol scale synthesis of one example and its elaboration to other potentially useful building blocks as well as the late-stage modification of a diverse array of structurally complex bioactive molecules.