苯并异噻唑衍生物与亚甲胺叶立德不对称偶极环加成反应研究

发布时间：2018-05-03 21:14

本文选题：苯并异噻唑衍生物 + 亚甲胺叶立德　；参考：《青岛科技大学》2017年硕士论文

【摘要】：1,3-偶极环加成反应因具有立体选择性好和反应条件温和的特点,成为合成五元杂环化合物的常用方法。自二十世纪六十年代Huisgen提出1,3-偶极环加成反应概念,环加成反应的机理及应用研究一直是化学领域研究的热点。近年来以非手性的1,3-偶极体和烯烃为底物,利用手性金属络合物催化剂获得具有光学活性化合物的合成方法,受到有机合成化学家的广泛关注。受天然吲哚啉类螺环化合物合成方法及生物活性的启发,提出以亚甲胺叶立德为偶极体,与苯并异噻唑衍生物进行1,3-偶极环加成反应合成新型吡咯螺苯并异噻唑类化合物。同时对以苯并异噻唑衍生物为骨架的1,3-偶极环加成反应进行深入研究,探索手性催化条件下反应的非对映选择性和对映选择性,建立进行此类反应的一般方法。为构建具有类似结构的化合物提供方法学依据,并为进一步研究此类化合物的不对称1,3-偶极环加成反应打下重要基础。本论文主要完成的工作有:(1)以邻溴苯胺为原料,经分子内N-烷基化、N-甲基化以及环化反应合成1,3-二氢-2,1-苯并异噻唑-2,2-二氧化物。通过脂肪醛和芳香醛与1,3-二氢-2,1-苯并异噻唑-2,2-二氧化物的Knoevenagel缩合反应合成含有双键结构的3-取代亚甲基-2,1-苯并异噻唑-2,2-二氧化物亲偶极体。(2)以甘氨酸甲酯盐酸盐及甘氨酸叔丁酯为底物,通过与脂肪醛、含有不同取代基的芳香醛及具有杂环结构的醛类物质进行缩合反应,制备不同种类的亚胺。(3)以3-取代亚甲基-2,1-苯并异噻唑-2,2-二氧化物为亲偶极体,与亚甲胺叶立德进行非手性条件下的1,3-偶极环加成反应以及在三氟甲磺酸铜/DM-Segphos催化体系作用下的不对称1,3-偶极环加成反应,合成新型吡咯螺苯并异噻唑类化合物,获得通过一步反应构建具有四个手性中心、三个叔碳原子和一个螺碳原子的吡咯螺苯并异噻唑类化合物的新方法。探讨不同种类路易斯酸、配体、碱、溶剂、温度和反应时间对反应的影响,确定较佳反应条件。该方法具有高度对映选择性,ee值最高可达99%。通过X-射线单晶衍射确定了产物的绝对构型,提出了三氟甲磺酸铜/DM-Segphos催化体系参与不对称反应的催化作用机理。
[Abstract]:Due to its good stereoselectivity and mild reaction conditions, 1H _ 3-dipolar cycloaddition reaction has become a common method for the synthesis of five-member heterocyclic compounds. Since Huisgen put forward the concept of 1 ~ (3) -dipolar cycloaddition reaction in 1960s, the mechanism and application of cycloaddition reaction have been a hot topic in the field of chemistry. In recent years, the synthesis of optically active compounds by using chiral metal complex catalysts using non-chiral 1 / 3 dipolar and olefin as substrates has attracted extensive attention of organic synthesis chemists. Inspired by the synthetic method and biological activity of natural indolines, a new type of pyrrolidine benzoisothiazole compounds was synthesized by using methylamine ylide as dipole and benzoisothiazole derivatives as dipole cycloaddition reaction. At the same time, the dipolar cycloaddition reaction with benzoisothiazole derivatives as the skeleton was studied in depth. The enantioselectivity and enantioselectivity of the reaction under chiral catalysis were explored, and a general method for such reactions was established. It provides a methodological basis for the construction of compounds with similar structures and lays an important foundation for the further study of asymmetric 1 ~ (3) -dipolar cycloaddition reactions of these compounds. The main work of this thesis is: (1) using o-bromoaniline as the raw material, the intramolecular N-alkylation, N-methylation and cyclization reaction are used to synthesize 1o _ 3-dihydro-2o _ 1-benzoisothiazole-2o _ 2-dioxo _ 2. Knoevenagel condensation of aliphatic aldehydes and aromatic aldehydes with 1o 3-dihydro-2o 1-benzoisothiazole-2o 2-dioxide to synthesize 3- substituted methylene methylene-1-benzoisothiazole-2-dioxide-dipolar hydrophilic dipolar compound with double bond structure.) Methyl glycine hydrochloride And tert-butyl glycine as substrate, By condensation reaction with aliphatic aldehydes, aromatic aldehydes with different substituents and aldehydes with heterocyclic structures, different kinds of imines were prepared. A new type of pyrrolidine benzoisothiazole compounds was synthesized by the non-chiral 1o 3- dipolar cycloaddition reaction with methylamine ylide and the asymmetric 1 + 3 dipolar cycloaddition reaction with copper trifluoromeresulfonate / DM-Segphos catalyst system. A new method for the construction of pyrrole spirobenzoisothiazole compounds with four chiral centers, three tertiary carbon atoms and one snail carbon atom was obtained by one step reaction. The effects of different kinds of Lewis acid, ligand, alkali, solvent, temperature and reaction time on the reaction were discussed, and the optimum reaction conditions were determined. The method has a high enantioselectivity of ee value up to 99. The absolute configuration of the product was determined by X-ray single crystal diffraction, and the catalytic mechanism of copper trifluorosulfonate / DM-Segphos catalyst system for asymmetric reaction was proposed.
【学位授予单位】：青岛科技大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O621.251

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