Catalytic Stereoretentive-Enantioconvergent Cross-Coupling Reactions

催化立体保留-对映会聚交叉偶联反应

• 批准号: 2493511
• 金额: --
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2493511
• 关键词: Catalytic; Stereoretentive; Enantioconvergent; Cross; Coupling

This project will experimentally establish a new concept in asymmetric synthesis: stereoretentive-enantioconvergentcatalysis. This will represent a completely new method for accessing enantiopure materials starting from racemicsubstrates and will therefore impact all areas of synthetic chemistry. The ability to synthesise chiral molecules inenantiopure form is vitally important, most recognisably for the pharmaceutical industry. This is because the molecules oflife are chiral (e.g., D-sugars and L-amino acids) and enantiomers often interact very differently with living organisms.Classically, asymmetric synthesis utilising racemic substrates is limited to achieving a maximum yield of 50% (e.g., kineticresolutions). Enantioconvergent catalysis avoids this limitation with both enantiomers of the starting material beingconverted into a single enantioenriched product, thanks to complex stereoablative or stereomutative de-racemisationprocesses. This project will establish a conceptually new stereoretentive-dimerisation approach that results in bothenantiomers of the starting material being incorporated into the product with no de-racemisation required. This new conceptwill prove highly valuable for the synthesis of small enantiopure building blocks, which will be of high value in many areas ofsynthesis, and also for more complex late-stage transformations in complex molecule synthesis. Several approaches willbe pursued to demonstrate proof-of-principle, and applications in the synthesis of complex natural and unnatural productswill then be used to demonstrate the potential of stereoretentive-enantioconvergent catalysis in target-orientated synthesis.

本项目将在实验上建立一个不对称合成的新概念：立体保留-对映体会聚催化。这将代表一种从外消旋底物开始获得对映体纯材料的全新方法，因此将影响合成化学的所有领域。合成对映体纯形式的手性分子的能力是至关重要的，这在制药工业中最为明显。这是因为生命的分子是手性的（例如，典型地，利用外消旋底物的不对称合成限于实现50%的最大产率（例如，动力学分辨率）。对映会聚催化避免了这种限制，由于复杂的立体烧蚀或立体突变去外消旋过程，起始材料的两种对映异构体被转化为单一的对映体富集产物。该项目将建立一种概念上新的立体保留二聚化方法，该方法可使起始材料的两种对映体均掺入产品中，而无需进行消旋化。这一新概念对于合成小的对映体纯的结构单元具有很高的价值，这将在许多合成领域具有很高的价值，并且对于复杂分子合成中更复杂的后期转化也具有很高的价值。几种方法将被追求，以证明的原则，并在复杂的天然和非天然产品的合成中的应用，然后将被用来证明立体保留-对映收敛催化在靶向合成的潜力。