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

Abstract

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.

Enantioenriched α-aminoboronic acid, a structural unit in many bioactive molecules, is also a valuable synthon in organic synthesis. Here, the authors disclose a NiH-catalysed asymmetric hydroamidation process for their direct synthesis.