【作者】 王杰；

【导师】 杨雄里；

【作者基本信息】 兰州大学 ， 生物化学与分子生物学， 2018， 硕士

【摘要】 近年来,随着医药领域的迅猛发展,手性药物越来越受到人们的重视。为了得到具有高度立体选择性的立体化学中心,需要开发出高效的立体化学控制方法,这在有机化学合成中占有着非常重要的地位。随着人们的重视,不对称合成方法也因此发展迅速。而能够同时合成多个具有高度立体选择性的手性中心的有效方法则更为重要。不对称烯丙基烷基化反应,自1970年代早期发现以来,已经成为了有机化学中重要的工具。通过不对称烯丙基烷基化,能够很容易的获得多种类型的手性烯丙基中间体。在酸性助催化剂的帮助下,通过双重活化策略,丙烯醇可以在温和条件下进行不对称烯丙基烷基化反应。但是硝基烯丙基乙酸酯在不对称烯丙基烷基化反应中的应用尚未完全开发,可以通过硝基烯丙基乙酸酯构建不同的手性烯丙基中间体。在前人的基础上,我们开发了:经过镍介导,硝基乙酯与经过修饰的咪唑酮可以在温和的条件下进行不对称烯丙基烷基化反应。通过使用简单的手性二胺-镍催化剂催化,产生一系列新的硝基烯丙基手性化合物。反应具有中等至良好产率和优异的对映选择性。此外,烯丙基加成产物可以高效的生成具有三个连续立体中心的手性γ-硝基酯。更多还原

【Abstract】 In recent years,with the rapid development of the medical field,chiral drugs have attracted more and more attention.In order to obtain a stereochemical center with a high degree of stereoselectivity,it is necessary to develop an efficient stereochemical control method,which occupies a very important position in the organic synthesis chemistry.These years,asymmetric synthesis methods have developed rapidly.However,simultaneously synthesizing chiral drugs with multiple chiral centers still composes huge challenge.Asymmetric allylic alkylation(AAA)reaction represents a well-established and important tool for organic chemistry since its discovery in the early 70 s,which allows easy access to diverse types of chiral allylic intermediates.And utlizing dual acitivation strategy,often with the assistance of acid co-catalyst,allylic alcohols are also able to undergo the asymmetric allylic alkylation reactions under mild conditions.However,the application of nitroallylic acetates in asymmetric allylic alkylation reactions has not been successfully developed,which can efficiently construct chiral nitroalkenes.Here,a nickel catalyzed asymmetric allylic alkylation reaction between imidazole-modified ketones and nitroallylic acetates is presented.This reaction is catalyzed by a simple chiral diamine-Ni(II)catalyst under mild conditions,leding to moderate to good yields of a series of enantioenriched α-allylic adducts with excellent enantioselectivities.Furthermore,transformation of the reactant allylic adducts can smoothly lead to chiral γ-nitro-esters which contain three continuous stereocenters.更多还原