烯烃自由基双氧化及胺氧化立体选择性的理论研究  

A DFT Study on the Stereoselectivity of Radical Dioxygenation/Oxyamination of Alkenes

作　　者：匡鸣 王永恒[2] 巫瑞波[2] 王来友[1] 

机构地区：[1]广东药科大学中医药研究院,广东省代谢病中西医结合研究中心,广州510006 [2]中山大学药学院,广州510006

出　　处：《河南大学学报（自然科学版）》2016年第3期341-350,共10页Journal of Henan University:Natural Science

基　　金：国家自然科学基金面上项目(21272289);教育部第46批留学回国人员科研启动基金项目

摘　　要：烯烃自由基双氧化或胺氧化避免了使用过渡金属作为催化剂,具有良好的应用前景.在这里,我们运用密度泛函理论对以异羟肟酸为底物的烯烃自由基双氧化及胺氧化的立体选择性进行了研究.对于分子内反应,立体选择性很大程度上取决于六元环或五元环的骨架结构.由于异羟肟酸结构的特殊性,六元环自由基中间体采取人们通常所认为极不稳定的船式构象,两个大位阻的取代基所在的碳采取重叠式构象,使得顺式产物的形成极为不利,大大提高了反式选择性;而在五元环中位阻作用不是很明显,化学选择性较低.对于分子间的反应,立体选择依赖于反应前体的构象分布.在最稳定的构象中,底物取代基与碳中心自由基存在轨道相互作用,不利于氧气的顺式进攻.可见,底物结构的特殊性不仅提高了六元环反应的反式选择性,还有利于分子间的反式加成.Radical dioxygenation or oxyamination of alkenes avoided using transition metals as catalysts and thus attracted much synthetic application. To understand the stereoselectivity of metal-free radical dioxygenation/ oxyamination of alkenes with hydroxamic acids as substrates recently developed by Alexanian et al., we selected three reactions from the experiments, two intramolecular and one intermolecular reactions, and performed density functional theory （DFT） calculations on the rate-determining steps of those reactions at the UB3LYP/6-31G（d） level. The stereoselectivity of intramolecular reactions is mainly derived from six-membered or five-membered ring skeleton structure. Because of the amide oxo structure in hydroxamic acids, the six-membered ring radical intermediate adopts a boat-like conformation, which is usually unstable for most six-membered rings, and the two carbons with bulky substituents adopt eclipsed conformation, which disfavors the formation of cis product and enhances the trans-selectivity of six-membered ring radical cyclization largely~ while the steric effect in five- membered ring radical intermediate is unconspicuous, leading to a lower trans-selectivity of five-membered ring radical cyclization. The stereoselectivity of intermolecular reactions depends on the conformation distribution of the carbon-centered radical intermediate, which will react with oxygen. In the most stable conformation, there are orbital interactions between the n-electron substituent of substrate and the carbon-centered radical, which hinders the cis-addition of oxygen. Hence, it is the specific structure of substrates that enhances the trans-selectivity of six- membered ring radical cyclization and favors transddition of oxygen in the intermolecular reaction.

关 键 词：烯烃 自由基 双氧化 胺氧化 密度泛函 异羟肟酸 立体选择性 

分 类 号：O641[理学—物理化学]