A bis-Lewis basic 2-aminoDMAP/prolinamide organocatalyst for application to the enantioselective synthesis of Warfarin and derivatives

A new chiral sec-amine/amidine-base hybrid catalyst, 2-aminoDMAP/prolinamide, is reported, which is able to catalyze conjugate addition of 4-hydroxycoumarin and various benzylideneacetones, a reaction that directly gives anticoagulant Warfarin and its analogues, with good yields (70–87%) and enantioselectivities (58–72%).

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(S)-N-((1R,2R)-2-((4-(Dimethylamino)pyridin-2-yl)amino)cyclohexyl)pyrrolidine-2-carboxamideC18H29N5OSource of chirality: trans-(R,R)-1,2-diaminocyclohexane and (S)-Proline[α]D31 = −10.5 (c 0.25, CH2Cl2)Absolute configuration: (R,R) and (S)