【作者】 刘伟；

【导师】 卢然；

【作者基本信息】 吉林大学 ， 有机化学， 2018， 博士

【摘要】 有机硫化合物在药物化学、材料化学、农业化学及化工等领域有着广泛的应用。作为有机硫化物的重要组成部分,环状有机硫化物(具有环状结构的有机硫化物)是很多药物和天然产物的核心结构,这类化合物往往具有较强的生物活性和优异的理化特性。同时,环状有机硫化物可以发生多种转化,是重要的有机合成中间体。因此,研究这类化合物的合成方法具有重要意义。硫-迈克尔加成反应(Sulfa-Michael Addition)是构建碳-硫键的经典方法,由其引发的串联环化反应不仅可以高效地制备环状有机硫化物,还可以构建产物分子中的手性中心,相应的不对称催化反应可以立体选择性地合成这类含有手性中心的环状有机硫化物。然而,这类反应通常需要化学计量的硫试剂参与,原子经济性较差,催化型硫-迈克尔加成/环化串联反应报道较少。本文发展了一个新颖的催化型硫-迈克尔加成/环化串联反应。该反应采用烯丙基取代的硫酯类化合物为底物,在催化量的引发剂作用下,通过sulfa-Michael-Aldol型串联环化反应构建了产物分子中的手性中心,立体选择性地合成了两类重要的氮杂环硫化物。主要研究内容如下:1.以催化型硫-迈克尔加成/环化串联反应非对映选择性地合成了吡咯[2,1-a]异喹啉类化合物。通过改变引发剂(苯硫酚钠、四丁基氰化铵)实现了反应的非对映选择性调控,分别合成了顺式和反式环化产物,并提出了可能的反应机理;2.发展了一个配体调控的不对称硫-迈克尔加成/环化串联反应,在催化量的手性氨基醚类配体(1S,2S)-L6和苯硫酚锂作用下,合成了3,3-二取代喹啉-2,4-二酮类化合物,构建了产物3位的季碳中心,对映选择性最高可以达到97/3 e.r.,并提出了可能的手性诱导机理。更多还原

【Abstract】 Organosulfur compounds are widely used in the fields of pharmaceutical chemistry,material chemistry,agricultural chemistry and chemical industry.As an important constituent of organosulfur compounds,cyclic organosulfur compounds(organosulfur compounds containing ring structure)are frequently present in nature and various biological systems and can also serve as useful synthetic scaffolds to a diverse array of building blocks.Therefore,it is of great significance for the construction of cyclic organosulfur compounds.Sulfa-Michael addition is one of the most classical methods for construction of carbon sulfur bond,which is widely applied in organic synthesis.The tandem cyclization reactions triggered by sulfa-Michael addition can prepare cyclic organosulfur compounds bearing stereocenters efficiently and stereoselectively.However,this kind of reaction always requires the involvement of stoichiometric organosulfur reagents,and the catalytic sulfa-Michael addition/cyclization tandem reaction is less reported.A novel catalytic sulfa-Michael addition/cyclization tandem reaction has been developed in this thesis.Starting from the allyl substituted thioesters as substrates,two important kinds of nitrogen heterocyclic organosulfur compounds were synthesised through a catalytic sulfa-Michael-Aldol tandem sequence.This thesis mainly includes the following aspects:1.We have developed a controllable stereoselective synthesis of pyrrolo[2,1-a]isoquinoline derivatives bearing a sulfur moiety with high diastereoselectivity in a catalytically atom-economic fashion.Both cis and trans-products can be readily prepared in moderate to high yields with excellent diastereoselectivities under the optimized reaction conditions.2.We have developed a ligand-mediated catalytic asymmetric sulfa-Michael addition/cyclization tandem reaction.A wide range of 3,3-disubstituted-quinoline-2,4-dione derivatives incorporating all-carbon quaternary stereocenters could be accessed efficiently in excellent yields and enantioselectivities(up to 97/3 e.r.)in a catalytically atom-economic fashion.更多还原