高区域性、立体选择性氟化手性烯酰胺合成α-氟代酰亚胺的方法研究-药物化学专业论文.docxVIP

万方数据 万方数据 中文摘要 中文摘要 含氟化合物一般具有独特的化学和生物特性，已被发现存在于一些具有药理 活性的天然产物中，同时在有机反应中也有着重要的应用。近年来，化合物的非 对映选择性氟化反应成为构建手性氟碳中心的一个新的策略。该方法具有原料简 单易得以及绿色环保等优点，因此备受有机化学研究者的关注。现有的方法大多 数通过金属的参与，而且还存在一些区域和立体选择性不高等问题。 本文介绍了一种由手性烯酰胺控制的选择性氟化氧化反应制备 α-氟代酰胺 化合物的方法，该反应包括如下特点：1）Evans’辅基控制手性；2）手性四级含 氟碳中心的形成。 我们以手性烯酰胺化合物 183 为底物，以 NFSI（N-氟代双苯磺酰胺）为氟 化试剂，在含 2%水的乙腈溶液中 40 oC 反应，制备了 16 个具有手性氟碳中心的 酰胺类化合物。所有的产物都进行了氢谱、碳谱、红外、质谱及旋光表征，产物 184b 和 ent-184d 还通过单晶衍射的方法进行了结构确证。 同时我们还提出了该选择性氟化反应的可能机理，对中间体 173 的结构进行 鉴定，证明了反应机理的合理性。经过氧化反应，羟基被氧化为羰基，得到了非 对映选择性较高的氟化产物。除此之外，我们还对三取代的手性烯酰胺进行探索， 通过对产物的结构鉴定，我们得到了 α-氟代酮类化合物。 关键词：手性烯酰胺；氟化；立体选择性 I ABSTRACT ABSTRACT Generally organo-fluorine compounds have unique chemical and biological properties, and has been found in a number of natural products with pharmacological activity, while in organic reactions also has important applications. In recent years, the method of diastereoselective fluorination has became a new strategy to construct a chiral center of a fluorocarbon. Due to its simple and easy to get raw materials as well as simplicity of operation, it has drawn great attention by chemists. Most of the existing methods require the participation of a metal, limitations of the existing methods include low regio- and stereoselectivity. Herein, we disclosed a highly regio- and stereoselective synthesis of α-fluorinated imides via fluorination of chiral enamides. Features of this reaction include: 1) Evans chiral auxiliary group control the stereoselective; 2) construct fluorinated stereogenic carbon centers. We chose chiral enamide 183 as substrates, NFSI(N-fluoro-benzenesulfonimide) as the fluorinating agent, and 16 biaryls amide compound containing a chiral center fluorocarbon have been synthesized in acetonitrile containing 2% H2O at 40 oC. All the compounds have been well characterized by 1H NMR, 13C NMR, 19F NMR, IR, and HRMS. In addition, compounds 184b and ent-184d were also confirmed by its X-ray crystallography. A plausible mechanism of the reaction process has been prop