手性磷酸催化的轴手性醌类化合物的合成

The Construction of Axially Chiral Naphthoquinones Derivatives by Chiral Phosphoric Acid Catalysis

张霄

11749249

硕士

化学

谭斌

2019-05-25

2019-07-10

哈尔滨工业大学

深圳

轴手性化合物广泛存在于生物活性的天然产物、配体和催化剂中，受到了有机化学家和药物学家的广泛关注。但这类化合物的合成一般需要多步反应，或者需要过渡金属的参与，大大限制了它们的应用范围。从简单的原料出发，通过不对称转化快速构建重要类型的手性分子骨架，不仅很好的满足国家环境保护“十二五”规划提出的“加快建设资源节约型、环境友好型社会”的要求，也是有机合成化学工作者不懈追求的目标之一。手性磷酸因其独特的催化模式以及手性环境的可调控性等特点被广泛地应用于多种类型的不对称催化反应中，近些年系统而深入的研究也使得手性磷酸的应用范围得到了极大的拓展。本论文的主要研究内容是以手性磷酸为催化剂，吲哚与醌为反应物，通过不对称迈克尔加成反应高对映选择性的合成轴手性醌类化合物。本论文首先筛选了反应物及其用量，确定了最优反应物投料比例，然后筛选了不同骨架的手性磷酸，确定了最优催化剂，接着又对氧化剂、反应溶剂、反应温度、反应浓度等变量进行了细致考察，最终确定了最优的反应条件。然后在此条件下考察了吲哚和醌类底物的普适性以及局限性，发现此方法对于取代基团兼容性较好。论文中共合成了 16 个含有不同取代基的轴手性醌类化合物，大部分底物都能以较高的收率和立体选择性给出目标产物，其中，最高收率为77%，最高对映选择性为93%。本论文合成的一系列轴手性吲哚醌类化合物有新颖的骨架，是对现有轴手性分子的重要补充。基于醌类化合物及其衍生物长期以来一直是构建高度官能团化分子的重要合成前体，它们在不对称有机催化中的应用一直在增加。因此，合成的一系列轴手性吲哚醌类化合物有着潜在的利用价值。

Axially chiral molecules have received extensive attention from organic chemists and pharmacologists because of their widespread appearance in biologically natural products, ligands and catalysts. The construction of privileged chiral molecular skeletons by readily asymmetric transformations with simple raw materials not only fulfills the requirements of “accelerating the construction of resource-saving and environment-benign societ”, but also one of the goals that organic synthetic chemists are constantly pursuing.Chiral phosphoric acid based organocatalysis has been studied most deeply and are widely used in various asymmetric catalytic reactions. The main research content of this thesis is the synthesis of axially chiral naphthoquinone derivatives with quinones and indoles as reactants in a high enantiocontrolled manner by chiral phosphoric acid catalytic asymmetric Michael-addition.In this thesis, the loading of reactants was firstly screened, and then the chiral phosphoric acids of different skeletons were evaluated. Subsequently, the external oxidant, reaction solvent, reaction temperature and reaction concentration were careful screened. After the determination of the optimal conditions, we next move to explore the universality and limitation of the quinone and indole substrates. The experimental results clearly indicated the good functional-group compatibility of this reaction. Up to 16 atropisomeric naphthoquinones with different substituents were synthesized in the thesis. Most of them gave the desired products in good yields with moderate to good enantioselectivities, with a maximum 77% yield and 93% enantioselectivity.The series of axially chiral compounds synthesized in this thesis contain novel skeletons and are important supplements to existing axially chiral molecules. Quinones and their derivatives have long been important synthetic precursors for the construction of highly functionalized molecules, and their use in asymmetric organic catalysis has been increasing. Therefore, a series of axially chiral quinones synthesized in this thesis have potential value.

不对称有机催化 手性磷酸 轴手性 萘醌 吲哚

asymmetric organocatalysis chiral phosphoric acid axial chirality naphthoquinone indole

中文

联合培养

南方科技大学

张霄. 手性磷酸催化的轴手性醌类化合物的合成[D]. 深圳. 哈尔滨工业大学,2019.