Pd-Catalysed Migratory 1,1-Cycloannulation Reaction of Alkenes

One of the central goals of synthetic chemistry is to develop efficient methods for constructing heterocyclic architectures, given their broad distribution in a wide range of natural compounds, pharmaceuticals, agrochemicals, and materials. As a result, methods that allow for the modular and diverse synthesis of heterocyclic compounds via one single approach are in high demand. Here, we report a novel strategy for the preparation of diverse heterocycles via a Pd-catalysed migratory 1,1-cycloannulation reaction (MCAR) of alkenes. Starting from readily available alkenyl amines and alkenyl alcohols, this approach allows the formation of a wide range of heterocycles, including five to seven-membered azaheterocycles and oxaheterocycles with high efficiency and good functional group tolerance. The key to the realisation of this reaction is the use of 4-iodophenol or 2-iodophenol derivatives, where the phenolic hydroxyl group plays a critical role in controlling the direction of migration and the ring-size of the heterocycles through the formation of a quinone methide intermediate. The utility of this strategy in synthetic chemistry and medicinal chemistry were preliminarily demonstrated by the late-stage introduction of heterocycle scaffolds into complex drug molecules, and the efficient preparation of serval bioactive compounds.