Halland Nis, Velgaard Thomas, Jørgensen Karl Anker
Danish National Research Foundation: Center for Catalysis, Department of Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark.
J Org Chem. 2003 Jun 27;68(13):5067-74. doi: 10.1021/jo0343026.
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.
本文介绍了环状1,3 - 二羰基化合物与烯胺对不饱和2 - 酮酯的催化直接迈克尔加成反应。一系列不同的4 - 羟基香豆素、4 - 羟基 - 6 - 甲基 - 2 - 吡喃酮、3 - 羟基 - 1H - 菲 - 1 - 酮、2 - 羟基 - 1,4 - 萘醌、5,5 - 二甲基 - 1,3 - 环己二酮以及环状1,3 - 二酮的各种烯胺均以对映选择性方式加成到不饱和4 - 取代2 - 酮酯上。该反应由手性双恶唑啉 - 铜（II）配合物催化，在无碱条件下进行，以良好至高产率得到迈克尔加成产物，对映体过量值高达98%。所形成的产物是重要生物和药物分子骨架中的子结构。本文还讨论了该新反应的适用范围和潜力以及催化对映选择性反应的机理。
