Chiral Calcium-BINOL Phosphate Catalyzed Diastereo- and Enantioselective Synthesis of syn-1,2-Disubstituted 1,2-Diamines: Scope and Mechanistic Studies

A highly enantioselective, chiral, Lewis acid calcium- bis(phosphate) complex, Ca[3a](n), which catalyzes the electrophilic amination of enamides with azodicarboxylate derivatives 2 to provide versatile chiral 1,2-hydrazinoimines 4 is disclosed. The reaction gives an easy entry to optically active syn-1,2-disubstituted 1,2-diamines 6 in high yields with excellent enantioselectivities, after a one-pot reduction of the intermediate 1,2-hydrazinoimines 4. The geometry and nature of the N-substituent of the enamide affect dramatically both the reactivity and the enantioselectivity. Al-though the calcium-bis(phosphate) complex was a uniquely effective catalyst, the exact nature of the active catalytic species remains unclear. NMR spectroscopy and MS analysis of the various calcium complexes Ca[3](n) reveals that the catalysts exist in various oligomer forms. The present mechanistic study, which includes nonlinear effects and kinetic measurements, constitutes a first step in understanding these calcium- bis(phosphate) complex catalysts. DFT calculations were carried out to explore the mechanism and the origin of the enantioselectivity with the Ca[3](n) catalysts.