Rhodium-Catalyzed Desymmetric Addition of Boronic Acids to Malononitriles

Malononitrile is a privileged chemical feedstock for building complex nitrogen-containing molecules of interest. However, achieving high enantiocontrol in transformations of its derivatives is often challenging, as the spatial arrangement of the two linear nitriles impedes the chelative assistance commonly exploited in related multifunctionalized reactants. Here, we demonstrate a customized phosphoramidite ligand for a rhodium-catalyzed desymmetric addition of carbon nucleophiles to malononitriles. The chiral pocket, enclosed by a vaulted, chlorinated binaphthol skeleton and an iminostilbene motif, is proposed to restrict the C(ipso)-C(α) bond rotation of complexed nitrile and thus enforces precise substrate orientation. Consequently, β-ketonitriles bearing a quaternary stereocenter are obtained in good enantiopurity with versatile reactivity arising from the remaining nitrile, the newly generated ketone, and diverse substituents retained from the malononitrile reactant.