Direct Asymmetric Michael Reactions of Cyclic 1,3-Dicarbonyl Compounds and Enamines Catalyzed by Chiral Bisoxazoline−Copper(II) Complexes

The catalytic direct Michael addition of cyclic 1,3-dicarbonyl compounds and enamines to
unsaturated 2-ketoesters is presented. A series of different 4-hydroxycoumarins, 4-hydroxy-6-methyl-2-pyrone, 3-hydroxy-1H-phenalene-1-one, 2-hydroxy-1,4-naphthoquinone, 5,5-dimethyl-1,3-cyclohexanedione, and various enamines of cyclic 1,3-diketones all add to unsaturated 4-substituted
2-ketoesters in an enantioselective manner. The reaction is catalyzed by chiral bisoxazoline−copper(II) complexes and proceeds in the absence of base to afford Michael adducts in good to high yields
and with up to 98% ee. The products formed are substructures found in skeletons of important
biological and pharmaceutical molecules. The scope and potential of the new reaction are discussed
as well as the mechanism for the catalytic enantioselective reaction.