Synthesis of Enantioenriched 1,2-cis Disubstituted Cycloalkanes by Convergent NiH Catalysis.

Enantioenriched multi-substituted cycloalkanes constitute an essential class of compounds in pharmaceuticals, natural products and agrochemicals. Here we report an NiH-catalyzed asymmetric migratory hydroalkylation process for the efficient and selective construction of such compounds. Through a dynamic kinetic asymmetric transformation (DYKAT), easily accessible racemic and isomeric mixtures of cycloalkenes could be directly utilized as starting materials, convergently producing thermo-dynamically disfavored chiral 1,2-cis disubstituted cycloalkanes bearing vicinal stereocenters with high levels of regio-, diastereo- and enantioselectivity. In addition, prochiral cyclic alkenes can be also employed, and deliver chiral 1,2-cis disubstituted cycloalkanes through desymmetrization process.

Enantioselective synthesis of α-aminoboronates by NiH-catalysed asymmetric hydroamidation of alkenyl boronates.

Chiral α-aminoboronic acids and their derivatives are generally useful as bioactive compounds and some have been approved as therapeutic agents. Here we report a NiH-catalysed asymmetric hydroamidation process that with a simple amino alcohol ligand can easily produce a wide range of highly enantioenriched α-aminoboronates from alkenyl boronates and dioxazolones under mild conditions. The reaction is proposed to proceed by an enantioselective hydrometallation followed by an inner-sphere nitrenoid transfer and C-N bond forming sequence. The synthetic utility of this transformation was demonstrated by the efficient synthesis of a current pharmaceutical agent, Vaborbactam.