Enantioselective Assembly of Cycloenones with a Nitrile-Containing All-Carbon Quaternary Center from Malononitriles Enabled by Ni-Catalysis.

Chiral nitriles are valuable molecules in modern organic synthesis and drug discovery. Selectively differentiating the two nitrile groups of widely available malononitrile derivatives is a straightforward yet underdeveloped route to construct enantioenriched nitriles. Here we report an enantioselective nickel-catalyzed desymmetrization of malononitriles for the generation of nitrile-containing all-carbon quaternary stereocenters. This protocol involves a nickel-catalyzed addition of aryl boronic acids to alkynes followed by a selective nitrile insertion, providing unprecedented access to enantioenriched 5-7-membered alpha-cyano cycloenones with a fully substituted olefin from a broad range of substrates. The synthetic utility of these nitrile products is demonstrated by gram-scale synthesis and conversion to several useful functional groups.