Nickel Catalysis: New Insights from Mechanistic Studies

镍催化交叉偶联化学是一种有吸引力的方法，用于合成一系列社会需要的分子，包括农用化学品，药品和材料。虽然它可能会取代一些钯催化过程，但它真正的优势在于它提供的更广泛的底物范围，以及它更有效地耦合sp3中心的能力。这一领域最近已成为许多研究小组关注的焦点，但我们对选择性和反应性的机制理解有些落后。本项目将结合有机化学和有机金属化学以及物理有机化学的方法，阐明关键的机理细节和结构/关系活动。这将用于优化，设计和开发交叉耦合反应的效用。项目目标：项目目标包括：*了解亲电试剂结构如何影响氧化加成速率。*了解Ni(I)配合物在催化过程中何时及为何产生。*了解配体结构对反应性和选择性的影响。*探索镍与烷基亲电试剂和有机金属交叉偶联伙伴的反应性，并探索任何观察到的杂芳基和芳基底物之间的差异。*了解杂芳基底物在镍催化反应中的行为，并探索任何观察到的杂芳基和芳基底物之间的差异。*利用这些信息，在温和和工业可接受的条件下（例如< 100℃，< 1 mol% Ni，没有大量过量的交叉偶联伙伴），允许亲电试剂-特别是醇衍生底物的交叉偶联，以便制备与先正达业务需求相关的分子。*培养一名使用多种技术进行催化研究的博士生，为英国知识经济做出贡献。*通过定期会议和讨论，并通过对博士生为期三个月的实习，将从该项目中学到的知识传授给先正达的研究人员。

Nickel catalysed cross-coupling chemistry is an attractive method for the synthesis of a range of molecules of societal need, including agrochemicals, pharmaceuticals, and materials. While it might replace some palladium-catalysed processes its real strengths are in the wider substrate scope that it offers, as well as its ability to couple sp3 centres more effectively. The area has been a focus for many research groups recently, but our mechanistic understanding regarding selectivity and reactivity lags somewhat behind. This project will combine approaches from organic and organometallic chemistry, as well as physical organic chemistry, to elucidate key mechanistic details and structure/relationship activities. This will be used to optimise, design, and develop cross-coupling reactions of utility.PROJECT OBJECTVES:The objectives of the project include:* To understand how electrophile structure influences oxidative addition rate.* To understand when and why Ni(I) complexes arise in catalysis.* To understand the effect of ligand structure on reactivity and selectivity.* To explore the reactivity of nickel with alkyl electrophiles and organometallic cross-coupling partners, and explore any observed differences between heteroaryl and aryl substrates.* To understand the behaviour of heteroaryl substrates in nickel-catalysed reactions, and explore any observed differences between heteroaryl and aryl substrates.* To use this information to allow the cross-coupling of electrophiles - especially alcohol-derived substrates - under mild and industrially-acceptable conditions (e.g. < 100 degreesC, < 1 mol% Ni, no large excesses of cross-coupling partners) so that molecules of relevance to Syngenta's business needs can be prepared.* To train a PhD student in the study of catalysis using a broad range of techniques, contributing to the UK knowledge economy.* To transfer learning from this project to researchers at Syngenta through regular meetings and discussions, and though a three-month placement for the PhD student.