Michael addition warfarin anticoagulants

The best known and most widely used anticoagulant rodenticide is 3-(l-phenyl-2-acetylethyl)-4-hydroxycoumarin, (warfarin, 21). It is synthesised from 4-hydroxycoumarin (22) by Michael addition with 1 -phenyl-3-oxobutene-1 as the reagent (23) (Ikawa et al, 1944). 

Dicumarol 18 and warfarin 19 are anticoagulants used in the treatment of thrombosis. Warfarin is synthesized by a Michael addition of benzylidene acetone to 4-hydroxycoumarin [29],... 

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)... 

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

Dicarbonyl compounds are versatile stabilized enolate-type nucleophiles in asymmetric Michael addition reactions. In particular, the reaction of 4-hydroxy-2H-chromen-2-one and a,p-enones provided a direct and efficient synthesis of warfarin, a widely prescribed anticoagulant. Recently, Chin reported a simply vicinal... 

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