Enantioselective Synthesis of Nelfinavir via Asymmetric Bromocyclization of Bisallylic Amide

We describe a concise enantioselective synthesis of the HIV-protease inhibitor nelfinavir (1) via a new route in which the key step is construction of the central optically active 1,2-amino alcohol framework via asymmetric bromocyclization of bisallylic amide with N-bromosuccinimide in the presence of a catalytic amount of (S)-BINAP or (S)-BINAP monoxide. The remaining alkene and bromo functionalities were used to install the requisite thioether and chiral perhydroisoquinoline units, respectively.