The Application Of Chiral Semi-Aza-Crown Ether Ligand In The Catalytic Asymmetric Michael Reaction Of 4-hydroxycoumarin

The asymmetry Michael addition reaction is one of the most important method for chiral carbon-carbon bond formation in mondern organic chemistry, and it is widely used in the synthesis of biologically active or pharmaceutical active compounds and natural products. Coumarins, whose common structure is 4-hydroxycoumarin, is a kind of oral anticoagulant drugs.This paper mainly discusses the design and synthesis of a series of chiral semi-azacrown ligands. These ligands were employed to catalyze asymmetric Michael addition reaction of 4-hydroxycoumarin to β,γ-unsaturated-α-ketoesters. got good result(up to 93% ee, up to 86% yield) after 18 h. For another, the scope of reaction was explored with a range of β,γ-unsaturated-α-ketoester derivatives. According to the experimental data and related literatures, a possible mechanism was proposed.We report the use of bis-Pro Phenol dinuclear zinc complex as an efficient catalyst to promote asymmetric Michael reaction of 4-hydroxylcoumarin with β,γ-unsaturated-α-ketoesters. For one thing we optimized the experimental conditions such as solvent, additive, temperature and so on. At optimized conditions, toluene as solvent, 20 mol% of chiral ligand L* and 40 mol% of Et2 Zn as catalyst, at 10 °C, we...