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

环丁烷是一类重要的化合物，在化学工业中有许多用途。目前，在药物发现流水线中有43个已批准或候选的分子包含环丁烷官能团。环丁烷也出现在许多天然产品和精细化学品中。然而，获得这类特权化合物的方法还不是很成熟，迫切需要开发新的合成策略，既可以获得新型的环丁烷支架，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从简单组分构建复杂碳骨架的有效方法，只使用非常少量的金属和配体。这种转化的成功开发使工业上可用于开发新药、新香料、新材料和新催化剂的分子发生了革命性的变化。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。富含对映体的产品是一种只选择一种高度特定的3D形状的产品，这对化学家在药物处理和其他复杂分子的生产中提出了重大挑战。这个项目的目标是开发新的转化方法，使人们能够有效地获得各种不同的富含对映体的环丁烷和其他类似的化合物，重点是制造对新药开发至关重要的富含SP3的分子。这个项目的目标是开发技术，以使：i)合成手性环丁烷衍生物，类似于在一些生物活性分子和批准的药物中发现的结构；ii)更好地了解这种转化发生的机理，使我们能够进一步优化和扩大反应；iii)合成具有生物活性的化合物，展示这些新方法的实用性和它们在医学上的适用性；Iv)合成其他富含对映体的支架，包括含氮杂环和多稠环体系，这将极大地扩展包含容易制备的结构的四元环的类别。工作开发了一种新的有效制备环丁烷的策略，然后将开展工作以增加我们对化学操作的理解，以便对反应进行优化，并激励我们在未来进行更雄心勃勃的计划。通过以这种方式开发和扩大这项技术的范围，我们显著增加了它对制药行业和该技术的其他终端用户的价值。最后，能够获得各种新手性材料将使发现原本无法获得的新药、香料、材料和催化剂成为可能。

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.