Warfarin anticoagulants enantioselective Michael addition

CATALYTIC ENANTIOSELECTIVE MICHAEL ADDITION OF 1,3-DICARBONYL COMPOUNDS TO ACYCLIC ENONE FOR THE SYNTHESIS OF WARFARIN ANTICOAGULANTS IN ONE STEP... [Pg.261]

A highly enantioselective organocatalytic Michael addition of 4-hydroxycouma-rines and related compounds to a,p-unsaturated ketones has been also achieved using imidazolidine catalyst 137 [213]. The reaction, which gives high yields and enantioselectivities for a wide range of cyclic 1,3-dicarbonyl compounds and enones, has been successfully employed for the asymmetric synthesis of the anticoagulant warfarin (Scheme 2.78) and derivatives [213], With respect to the reaction mechanism, very recent studies have demonstrated that the truly active catalyst in the process was the chiral diamine 138, which is formed in catalytic amounts under the reaction conditions by reaction with the hydroxycoumarine (Schane 2.79)... [Pg.113]