Asymmetric Copper-Catalyzed Synthesis of α-Amino Boronate Esters from <i>N</i>-<i>tert</i>-Butanesulfinyl Aldimines

A general and efficient new method for the asymmetric synthesis of alpha-amino boronate esters has been developed. The key step is the Cu(I)-catalyzed addition of bis(pinacolato)diboron to N-tert-butanesulfinyl aldimines, which proceeds in good yields (52-88%) and with very high diastereoselectivities (>96:2) for a variety of aldimine substrates. This method was applied to an efficient synthesis of bortezomib, a potent alpha-amino boronic acid inhibitor of the proteasome that is in clinical use for the treatment of multiple myeloma and mantle cell lymphoma.