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 α-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.