手性助剂控制的不对称Michael加成立体选择性研究

Stereoselectivity of Asymmetric Michael Addition Reactions Controlled by Chiral Auxiliary

手性助剂控制的不对称反应是不对称合成的主要方法之一.采用不同空间位阻Evans手性助剂对呋喃基丙烯酸进行立体选择性控制,通过不同空间位阻的格氏试剂对Michael受体1进行不对称1,4-Michael加成反应研究,合成了一系列新的Michael加成产物2a～2h.研究结果表明手性助剂及格氏试剂的空间位阻是影响反应立体选择性的主要因素.当手性助剂及格氏试剂的取代基为芳基时,产物的de值都大于95%,而取代基为烷基、苄基及脂环基时,产物的de值则低于70%.

Chiral auxiliary controlled asymmetric reaction is one of the main methods in asymmetric synthesis. Under the control of the various chiral Evans auxiliaries, different Grignard reagents were added asymmetrically to the substrates I by the way of 1 A-Michael addition reaction and a series of Michael addition products 2a-2h have been synthesized. The results showed that the steric hindrance of the chiral auxiliaries and the Grignard reagents was the main factor to influence the stereoselectivity of Micheal addition. When the chiral auxiliaries and the Grignard reagents were aryl-substituted, good yield and high stereoselectivity could be achieved up to 95% de, while the de values were lower than 70% when the substituent groups were alkyl, benzyl or alcyl.