A Catalytic Asymmetric Cross-Coupling Approach to the Synthesis of Cyclobutanes

环丁烷合成的催化不对称交叉偶联方法

• 批准号: EP/W007363/1
• 负责人: Stephen Fletcher
• 金额: $ 52.31万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FW007363%2F1
• 关键词: Catalytic; Asymmetric; Cross; Coupling; Approach

Cyclobutanes are an important class of compounds, which have a number of uses in the chemical industry. There are currently forty-three approved or candidate molecules in the drug discovery pipeline which contain the cyclobutane functionality. Cyclobutanes also appears in a number of natural products and fine chemicals. Methods to access this privileged class of compounds are however not very well developed and there is a pressing need to develop novel synthetic strategies, both to access novel cyclobutane scaffolds and to allow existing ones to be made more efficiently.An asymmetric metal-catalysed transformation is an efficient method to build a complex carbon skeleton from simple components, using only a very small quantity of metal and ligand. The successful development of such transformations revolutionises the molecules available to industry for the development of new medicines, new fragrances, new materials, and new catalysts. In building a complex carbon skeleton, we often come across difficulties in controlling the 3D arrangement. An enantioenriched product is a product in which only one, highly specific, 3D shape is selected for, and this represents a significant challenge to chemists in the production of pharmaceutical treatments and other complex molecules. This project aims to develop novel transformations which provide efficient access to a diverse array of enantioenriched cyclobutanes and other similar compounds, with focus on making the type of sp3-rich molecules that are essential for the development of new medicines.The objectives of this project are to develop technology to enable: i) the synthesis of chiral cyclobutane derivatives, similar to the structures found in a number of biologically active molecules and approved drugs; ii) a greater understanding of the mechanism by which this transformation is occurring, allowing us to further optimise and expand the reaction; iii) the synthesis of biologically active compounds, showcasing the utility of these novel methods and their applicability to medicine; iv) the synthesis of other enantioenriched scaffolds, including nitrogen heterocycles and multiple fused-ring systems, which would greatly expand the classes of 4 membered ring containing structures that can be easily prepared.The work develop a new strategy for the efficient preparation of cyclobutanes and then work will be conducted to increase our understanding of how the chemistry operates so that the reactions can be optimized and inspire us to tackle even more ambitious projects in the future. By developing and expanding the scope of this technology in this way, we significantly increase its value to the pharmaceutical industry and other end users of the technology. Finally, being able to access a diverse range of novel chiral materials will enable the discovery of new medicines, fragrances, materials and catalysts that would otherwise be inaccessible.

循环型是一类重要的化合物，它们在化学工业中具有多种用途。目前，有四十三个批准或候选分子，其中包含环丁烷功能。循环植物也出现在许多天然产品和精细化学物质中。然而，访问这种特权化合物类别类别的方法不是很好，并且需要开发新型的合成策略，既要访问新型的环丁烷脚手架，又可以使现有的脚手架更有效地使现有的型号更有效。一种有效的方法是一种有效的方法，是一种有效的方法，是一种从简单的构造中建立一个复杂的碳骨架，仅使用一个简单的碳骨骼，仅使用一个非常小的金属。这种转变的成功发展改变了工业可用于开发新药物，新香水，新材料和新催化剂的分子。在建造复杂的碳骨架时，我们经常遇到控制3D布置方面的困难。富含映体的产品是一种产品，其中只选择一种高度特异性的3D形状，这对化学家在药物处理和其他复杂分子的生产中构成了重大挑战。该项目旨在开发新的转变，从而有效地访问各种源代元素的环形植物和其他类似的化合物，重点是使SP3的富含SP3的分子类型，这些分子对于开发新药物至关重要。并批准药物； ii）对这种转化发生的机制有更深入的了解，使我们能够进一步优化和扩展反应； iii）生物活性化合物的合成，展示了这些新方法的实用性及其对医学的适用性； iv）综合其他富含对的脚手架，包括氮杂环和多个融合环系统，这些系统将大大扩展包含4个成员环的类别，这些结构可以易于准备。雄心勃勃的项目将来。通过以这种方式开发和扩展该技术的范围，我们大大提高了其对制药行业和该技术其他最终用户的价值。最后，能够获取各种新型的手性材料将使新药物，香水，材料和催化剂否则无法获得。

项目成果

Catalytic Enantioselective Synthesis of 3-Piperidines from Arylboronic Acids and Pyridine.

• DOI: 10.1021/jacs.3c05044
• 发表时间: 2023-07-05
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Mishra, Sourabh;Karabiyikoglu, Sedef;Fletcher, Stephen P.
• 通讯作者: Fletcher, Stephen P.

Rhodium-Catalyzed Asymmetric Arylation of Cyclobutenone Ketals

• DOI: 10.1002/anie.202217381
• 发表时间: 2023-02-17
• 期刊: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
• 影响因子: 16.6
• 作者: Egea-Arrebola, David;Goetzke, F. Wieland;Fletcher, Stephen P.
• 通讯作者: Fletcher, Stephen P.