Catalytic Stereoretentive-Enantioconvergent Cross-Coupling Reactions

本项目将通过实验建立一个不对称合成的新概念：立体保留-对映聚合催化。这将代表一种从外消旋底物开始获取对映纯材料的全新方法，因此将影响合成化学的所有领域。以不纯形式合成手性分子的能力至关重要，这一点在制药行业最为明显。这是因为生命分子是手性的（例如，d -糖和l -氨基酸），对映体通常与生物体的相互作用非常不同。传统上，利用外消旋底物的不对称合成仅限于达到50%的最大产率（例如，动力学分辨率）。对映收敛催化避免了这一限制，由于复杂的立体蚀变或立体变去消旋过程，起始材料的两个对映体都转化为单一的对映体富集产物。该项目将建立一种概念性的新立体保留二聚化方法，使起始材料的两个对映体都被纳入产品中，而不需要去消旋。这一新概念将被证明对小对映体纯构建块的合成具有很高的价值，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。将采用几种方法来证明原理证明，并在合成复杂的天然和非天然产物中的应用，然后将用于证明定向合成中立体保留-对映收敛催化的潜力。

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.