以樟腦架構為基礎之掌性配位基進行醛基化合物之 Mukaiyama 類型醛醇加成反應之研究

Abstract

In recent years, our laboratories have been using camphor-based chiral ligands to catalyze asymmetric trimethylsilylcyanation of aldehydes and asymmetric reduction of prochiral ketones. In these two reactions, good isolated yields and ee values were achieved. In this study, this highly efficient and enantioselective chiral ligand was utilized to carry out the Mukaiyama-type aldol addition to aldehydes to afford β-hydroxy esters. The required amino alcohol was prepared from camphor in three steps, through the sequential formation of camphorquinone, camphorquinone oxime and amino alcohol. The amino alcohol was then reacted with salicylaldehyde to furnish the tridentate chiral ligand. The chiral ligand was reacted with Ti(OiPr)4 at 0 oC to afford the chiral catalyst which was used in the asymmetric aldol addition toward 14 different aldehydes under the same conditions. The best conditions were 20 mol% of the complex, the ratio of chiral ligand to Ti(OiPr)4 was 1.1:1, and hexane as the solvent in ice-bath. After 9 hours, the target product was obtained in 22-89% isolated yield and 5-64% of ee value, the ee value were determined by HPLC and rotation. Although the ee values are not very good, but for the synthesis of β- hydroxy esters, we provided a new method that is cheap and less of synthesis steps. We hope that we can use copper to replace titanium to catalyze the aldol addition enhance the enantiomeric excesses.