Accessing Unsymmetrically Linked Heterocycles through Stereoselective Palladium-Catalyzed Domino-Cyclization.

A palladium-catalyzed strategy is presented to synthesize unsymmetrically-linked heterocycles within stereoselective tetrasubstituted olefins. This reaction is proposed to occur via a vinyl-Pd II intermediate capable of initiating the cyclization of various alkyne-tethered nucleophiles. Products are formed in up to 96% yield and excellent stereoselectivities are obtained using low catalyst loadings. The transformation was scalable up to 1 mmol and mechanistic studies suggest a syn - carbopalladation of the carbamoyl chloride followed by Pd II - catalyzed cyclization of alkyne-tethered nucleophiles.