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.

环丁烷是一类重要的化合物，在化学工业中有多种用途。目前药物发现管道中有四十三个已批准或候选分子含有环丁烷功能。环丁烷还出现在许多天然产物和精细化学品中。然而，获取这类特殊化合物的方法尚未得到很好的开发，迫切需要开发新的合成策略，既可以获取新的环丁烷支架，又可以更有效地制造现有的支架。不对称金属催化转化是一种仅使用极少量的金属和配体，从简单组分构建复杂碳骨架的有效方法。这种转变的成功发展彻底改变了工业上可用于开发新药物、新香料、新材料和新催化剂的分子。在构建复杂的碳骨架时，我们经常会遇到控制 3D 排列的困难。对映体富集产品是仅选择一种高度特异性的 3D 形状的产品，这对化学家在药物治疗和其他复杂分子的生产中提出了重大挑战。该项目旨在开发新颖的转化方法，以有效获取多种对映体富集的环丁烷和其他类似化合物，重点是制造对于新药开发至关重要的富含 sp3 的分子类型。该项目的目标是开发技术以实现：i）合成手性环丁烷衍生物，其结构类似于许多生物活性分子和批准药物中发现的结构； ii) 更深入地了解这种转变发生的机制，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，展示这些新方法的实用性及其在医学上的适用性； iv) 其他对映体富集支架的合成，包括氮杂环和多个稠环系统，这将极大地扩展易于制备的含四元环结构的类别。这项工作开发了一种有效制备环丁烷和环丁烷的新策略然后我们将开展工作，以增进我们对化学运作方式的了解，从而优化反应并激励我们在未来解决更雄心勃勃的项目。通过以这种方式开发和扩大该技术的范围，我们显着增加了其对该技术的制药行业和其他最终用户的价值。最后，能够获得各种新型手性材料将使我们能够发现原本无法获得的新药物、香料、材料和催化剂。

项目成果

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

由芳基硼酸和吡啶催化对映选择性合成 3-哌啶。

• DOI: http://dx.10.1021/jacs.3c05044
• 发表时间: 2023
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Mishra S

Rhodium-Catalyzed Asymmetric Arylation of Cyclobutenone Ketals

铑催化环丁烯酮缩酮的不对称芳基化

• DOI: http://dx.10.1002/anie.202217381
• 发表时间: 2023
• 期刊: Angewandte Chemie International Edition
• 作者: Egea

Rhodium-Catalyzed Asymmetric Arylation of Cyclobutenone Ketals

铑催化环丁烯酮缩酮的不对称芳基化

• DOI: http://dx.10.1002/ange.202217381
• 发表时间: 2023
• 期刊: Angewandte Chemie
• 作者: Egea