Palladium-Catalyzed Asymmetric Acetoxylative Cyclization/Acyl Transfer Cascade of Alkyne-Tethered Malononitriles with Carboxylic Acids

Palladium-catalyzed asymmetric intermolecular trans-acetoxypalladation/desymmetric cyclization/acyl transfer cascades of alkyne-tethered malononitriles with carboxylic acids have been demonstrated. Such a sequence enables the formation of multifunctionalized nitriles bearing α-all-carbon quaternary stereocenters with a high degree of enantiocontrol with a broad substrate scope. Moreover, synthetic elaborations present these multifunctionalized molecules as promising chiral building blocks. Mechanistic studies illustrate that the cascade process proceeds via a key imine intermediate, and the desymmetric cyclization is the enantio-determining step.