From Bonding and Structure to Mechanism and Catalytic Reactivity of Late Transition Metal Complexes

化学领域的重大挑战之一涉及发现温和的、经济上可行的工艺，将容易获得的原材料转化为更高价值的产品。这些增值产品的进一步功能化可以允许制造能够改善日常生活的救命药品和材料。随着减少废物产生的压力越来越大，有必要开发新的、更绿色的反应方法。催化反应特别可取，因为根据定义，它们使用少量的催化剂，这些催化剂在反应结束时再生，原则上可以重复使用。过渡金属催化剂越来越多地用于医药、材料和精细化学品的工业合成，但控制催化剂活性的因素和催化反应的各个步骤往往知之甚少。这种缺乏催化洞察力极大地阻碍了设计(而不是偶然)反应发现的能力。我的研究计划的目标是发现过渡金属催化剂的基本反应性，并利用这一知识开发有用和高效的反应，在合成具有有趣的生物或材料特性的化学品方面具有广泛的实用价值。这项建议描述了三个研究领域，重点是将金属-配体成键的基础知识转化为合成有用的催化反应。在这项提议的五年窗口期间，我们将合成、分离和表征大量的配体和金属络合物。我们将探索电子结构和反应性之间的关系。我们将利用这些研究的见解来指导我们设计新的反应，包括催化反应和化学计量反应。我们将探索这些反应的机理，作为改善反应条件和配体设计的一种方式，以及一种发现新的反应性的手段。最终，我们将展示这些反应在生物活性靶标合成中的应用。总体而言，拟议的研究将为我们实现有机金属化学中的几个长期目标提供基础。这一独特的研究计划为各级HQP提供了出色的培训。我们的研究结果将引起广泛的化学工业的兴趣，特别是精细化学品、制药和农用化学品。

One of the grand challenges in chemistry involves the discovery of mild, economically-viable processes for the conversion of readily-available raw materials into higher value products. Further functionalization of these value-added products can allows the manufacturing of life-saving pharmaceuticals and materials that enhance everyday life. As pressures grow to minimize waste production, there is a significant need to develop new, “greener” reaction methods. Catalytic reactions are particularly desirable, since by definition they use a small amount of catalyst that is regenerated at the conclusion of the reaction, and in principle can be reused. Transition metal catalysts are increasingly used in the industrial synthesis of pharmaceuticals, materials and fine chemicals, yet the factors that control catalyst activity and the individual steps of a catalytic reaction are often poorly understood. This lack of catalytic insight greatly impedes the ability for designed (as opposed to serendipitous) reaction discovery. The goal of my research program is to discover fundamental reactivity of transition metal catalysts and to use this knowledge to develop useful and efficient reactions of broad utility in the synthesis of chemicals with interesting biological or materials properties. This proposal describes three areas of research focused on translating fundamental knowledge of metal-ligand bonding into synthetically useful catalytic reactions. During the five year window for this proposal, we will synthesize, isolate and characterize numerous ligands and metal complexes. We will explore the relationship between electron structure and reactivity. We will use the insight from these studies to guide our design of new reactions, both catalytic and stoichiometric. We will explore the mechanisms of these reactions as a way to improve reaction conditions and ligand design, as well as a means to uncover new reactivity. Ultimately, we will demonstrate the utility of these reactions in the synthesis of bioactive targets. Overall, the proposed studies will provide the basis for us to achieve several long-standing goals in organometallic chemistry. This unique research program provides excellent training for HQP at all levels. Our results will be of interest to a broad range of chemical industries, particularly fine chemicals, pharmaceuticals and agrochemicals.