Asymmetric copper-catalyzed synthesis of alpha-amino boronate esters from N-tert-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.
Beenen
Melissa A
MA
Department of Chemistry, University of California, Berkeley, California 94720, USA.
An
Chihui
C
Ellman
Jonathan A
JA
D000447:Aldehydes / Q000737:chemistry*; D000588:Amines / Q000138:chemical synthesis*; D000970:Antineoplastic Agents / Q000138:chemical synthesis; D001897:Boronic Acids / Q000138:chemical synthesis*; D000069286:Bortezomib; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D007097:Imines / Q000737:chemistry*; D011480:Protease Inhibitors / Q000138:chemical synthesis; D011719:Pyrazines / Q000138:chemical synthesis*; D013441:Sulfinic Acids / Q000737:chemistry*
D000447:Aldehydes; D000588:Amines; D000970:Antineoplastic Agents; D001897:Boronic Acids; D007097:Imines; D011480:Protease Inhibitors; D011719:Pyrazines; D013441:Sulfinic Acids; D000069286:Bortezomib; D003300:Copper