Catalytic Stereoretentive-Enantioconvergent Cross-Coupling Reactions

该项目将在实验上建立不对称合成中的一个新概念：立体保留-对映体聚合催化。这将代表一种从外消旋底物开始获取对映体材料的全新方法，因此将影响合成化学的所有领域。手性分子不对映体的合成能力是至关重要的，这对制药工业来说是最明显的。这是因为生命的分子是手性的(例如D-糖和L-氨基酸)，而对映体与活体的相互作用通常非常不同。经典的利用外消旋底物进行不对称合成的最高产率仅为50%(例如，动力学拆分)。由于复杂的立体消旋或立体变异去外消旋过程，对映体聚合催化避免了这一限制，将起始材料的两个对映体转化为单一的富含对映体的产物。该项目将建立一种概念上的新的立体保留-二聚方法，导致起始材料的两个对映体都被合并到产品中，而不需要去外消旋。这一新概念将被证明对合成小的对映体构筑块具有很高的价值，这将在许多合成领域具有很高的价值，也将对复杂分子合成中更复杂的后期转化具有很高的价值。将采用几种方法来证明原理，并将在复杂的天然和非天然产物的合成中的应用来展示立体保留对映体聚合催化在目标定向合成中的潜力。

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.