Divergent synthesis of chiral amines via Ni-catalyzed chemo- and enantioselective hydrogenation of alkynone imines

Ligand-mediated nickel-catalyzed asymmetric hydrogenation of alkynone imines has been achieved. By using Ni(OAc)2·4H2O/(S, S)-Ph-BPE complex as a catalyst, the chemo- and enantioselective hydrogenation of alkynone imines occurred efficiently to afford chiral propargyl amines with high yields and excellent enantioselectivities (up to 99% yield, >99% ee), leaving the readily reducible alkynyl group intact. Both the C=N and C≡C bonds of alkynone imines were hydrogenated efficiently in the presence of Ni(OAc)2·4H2O and Josiphos SL-J011-1, furnishing unfunctionalized chiral imines efficiently (up to 99% yield, >99% ee). The (Z)-allylamines and (E)-allylamines were also efficiently prepared from alkynone imines by the combination of the different catalytic systems. The preliminary mechanism study revealed that the reduction of alkynone imines was a stepwise process and the C=N bonds were preferably hydrogenated in the complete reduction of alkynone imines. The synthetic utility of this method was demonstrated by its application in the late-stage modification of the antiviral drug Zidovudine and the concise synthesis of chiral dibenzoazepine.[graphic not available: see fulltext]