A cooperative approach to iron-catalyzed C-H functionalization

利用定义明确的催化剂体系开发可预测的铁催化，为探索标准贵金属未观察到的令人兴奋的独特化学反应性提供了前景。这种反应性对于合成化学的进步是必不可少的，并且可以归因于铁的独特性质。使设计合理的、定义明确的催化剂具有挑战性的一个性质是铁在反应条件下形成不明确结构的倾向。该研究项目将通过合成以定制硼基z型配体为中心的定义明确的铁配合物，为克服不明确的催化剂结构提供必要的工具。这种方法将通过开发催化C-H功能化的新策略来证明，这是一种从低成本和广泛可用的起始材料到高价值产品的无废物途径。尽管有很高的兴趣，但在C-H功能化化学中仍然存在许多挑战，特别是3d金属催化剂的应用。由于这一挑战，尽管铁催化碳氢化合物功能化具有潜力，但只有一个铁催化碳氢化合物功能化的例子，使用定义明确的配合物，突出表明这是一个潜在的富有成果和未开发的高影响化学领域。我们将使用的铁配合物包含从金属到硼的弱西格玛型相互作用，当暴露于小分子时，会在M-B键上产生氧化加成。这导致硼烷通过接受氢化物而变成硼氢化物，从而促进了铁上可预测的正式双电子过程。初步研究将确定这些铁配合物在一系列具有不同导向基团的底物中对C-H键激活的可行性，这在贵金属催化的C-H功能化化学中是常见的。然后探索将转向探索底物偶联伙伴和后续催化的范围。化学的对映体选择性变体的发展也将是研究的关键考虑因素。这将通过以高度模块化的方法从商业手性池起始材料合成硼烷配体来实现。这项工作与EPSRC的几个优先领域（如催化和新型高效化学合成）保持一致，并映射到EPSRC的“Dial-a-Molecule”大挑战以及与“制造未来”相关的其他优先领域，如化学反应动力学和机制、化学生物学和医疗保健技术：诊断。此外，拟议的研究解决了EPSRC可持续化学挑战，这是未来制造过程的一个关键方面。

The development of predictable iron catalysis using well-defined catalysts systems offer the prospect to explore exciting and unique chemical reactivity not observed with canonical precious metals. This reactivity is essential for the advancement of synthetic chemistry and can be attributed to the unique properties of iron. One property which renders designing rational, well-defined catalysts challenging is the propensity of iron to form ill-defined structures under reaction conditions. This research program will deliver the tools necessary to overcome the ill-defined catalyst structures, through the synthesis of well-defined iron complexes centred on tailored boron-based Z-type ligands.This approach will be exemplified by the development of novel strategies for catalytic C-H functionalization, a waste-free route to high value products from low-cost and widely available starting materials. Despite the high interest, many challenges still remain in C-H functionalization chemistry, in particular, the application of 3d-metal catalysts. As a result of this challenge and despite the potential of iron-catalyzed C-H functionalizations, there is only a single example of iron-catalyzed C-H functionalization using well-defined complexes, highlighting this as a potentially fruitful and unexplored high impact areas of chemistry. The iron complexes we will utilize contain a weak sigma-type interaction from the metal to the boron and upon exposure to small molecules results in an oxidative addition across the M-B bond. This results in the borane becoming a borohydride by accepting the hydride and thereby facilitating a predictable, formal two electron process at iron. Initial investigations will establish the viability of these iron complexes towards the activation of C-H bonds in a range of substrates bearing different directing groups which are commonplace in precious-metal catalyzed C-H functionalization chemistry. Exploration will then turn to explore the scope of substrate coupling partners and subsequent catalysis. The development of enantioselective variants of the chemistry will also be a key consideration of the research. This will be achieved by synthesizing borane ligands from commercial chiral pool starting materials in a highly modular approach.This work is firmly in line with several EPSRC Priority Areas such as Catalysis and Novel and Efficient Chemical Synthesis and maps onto EPSRC "Dial-a-Molecule" Grand Challenge and onto other Priority Areas associated with "Manufacturing the Future" such as Chemical Reactions Dynamics and Mechanism, Chemical Biology and Healthcare Technologies: Diagnostics. Furthermore, the proposed research addresses the EPSRC Sustainable Chemistry Challenge, a key aspect for tomorrow's manufacturing processes.