Exploitation of Fine Molecular Catalysts

(1)酮类的不对称加氢：手性ruc12 (binap)（1,2 -二胺）配合物可以快速、对映选择性地加氢各种简单的、未官能化的酮类，其底物/催化剂的摩尔比高达240万。随着该方法的高度实用性得到认可，我们被鼓励开发一种强大的（预）催化剂，以促进无碱条件下的对映选择性反应。在这个程序的过程中，我们确定了RuH(η^1- bh_4)(binap)（1,2 -二胺）配合物允许简单酮在2-丙醇中不对称加氢，而不需要额外的强碱。各种碱敏感酮在高对映体纯度下可转化为手性醇。最近，我们发现n -甲二胺- ru （II）配合物催化酮的不对称氢化反应，得到相应的手性甲醇，其对映体纯度很高。这些Ru（II）配合物是不对称转移氢化反应的优良催化剂，也可用于不对称氢化反应。这一发现为在非碱性和酸性条件下对映选择性氢化简单酮提供了一种长期思考的方法。进一步的动力学研究、同位素标记实验、一组不同的ID和2D NMR分析以及计算分析支持金属-配体双功能机制通过六元周环过渡态。我们认为，目前的双功能分子催化剂为立体选择性分子转化开辟了新的基础。(2)涉及水功能的酸碱催化的创造：与许多类型的原子经济型氧化和/或还原方法获得的官能团转换相比，介导碳-碳键形成的高效催化仍然是一个相当大的挑战。特别是，在分子催化剂的存在下，涉及烯醇和烯酸酯等价物的温和而有效的转化的发展一直是有机合成领域持续关注的话题。高催化剂负载、低原子经济性和产生不良副产物的几个缺点需要改进。为了保持较高的反应活性以达到最大的转化率，未来的催化剂应该是结构稳定的，催化物质对空气和水是惰性的。这种催化剂还应该能够对复杂的、多官能团底物的单一功能进行区分和结合。最近我们发现了一种新的分子催化剂，通过分子识别事件显示出很高的催化活性。这些催化剂具有由氨基有机硼和水组成的水簇结构。这些催化剂的结构特性非常独特：只有一个水分子被两个氢键和一个配位键的结合所捕获。我们提出水分子和多种胺在催化剂内的特殊排列作为催化活性位点，从而通过与有机底物形成协同酸碱相互作用来模拟酶样活性。(3)直接碳氢键芳基化：具有（杂）芳基-（杂）芳基键的有机分子是天然产物或药物以及功能性有机材料中常见的特殊结构基序。因此，在纯化学和应用化学的各个方面，开发有效的联芳基方法一直是一个非常重要的课题。虽然金属催化的有机金属和有机卤化物的交叉偶联反应已经得到了广泛的应用，但杂芳烃和芳烃的直接C-H基化具有重要的合成潜力，因为它消除了偶联组分的预活化。作为我们建立可编程合成（杂）芳基核星爆分子计划的一部分，我们开发了一种新的过渡金属催化剂，用于杂芳烃的直接C-H甲基化，具有高活性和宽范围。我们的努力最终发现了简单芳烃的直接C-H芳基化，这一事实很好地说明了目前催化的进一步开发和应用潜力。反应机理的阐明、活性催化剂的开发以及现有的直接芳基化技术在材料化学和药物化学中的应用等方面正在进行中。少

(1) Asymmetric Hydrogenation of Ketones: Chiral RuC1_2(binap)(1, 2-diamine) complexes allow rapid, enantioselective hydrogenation of various simple, unfunctionalized ketones with a high substrate/catalyst molar ratio up to 2, 400, 000. As high practicality of this procedure became recognized, we have been encouraged to develop a robust (pre)catalyst that promotes the enantioselective reaction under base-free conditions. During the course of this program, we established that RuH(η^1-BH_4)(binap)(1, 2-diamine) complexes allow for asymmetric hydrogenation of simple ketones in 2-propanol without an additional strong base. Various base-sensitive ketones are convertible to chiral alcohols in a high enantiomeric purity. More recently, we discovered that N-tosylethylenediamine-Ru(II) complexes catalyze asymmetric hydrogenation of ketones giving the corresponding chiral carbinols in high enantiomeric purity. These Ru(II)-complexes, known as excellent catalysts for asymmetric transfer hydrogenat … More ion, can be used for asymmetric hydrogenation as well. This discovery provides a long-thought method for enantioselectively hydrogenating simple ketones under nonbasic and acidic conditions. Further kinetic studies, isotope labeling experiments, and a set of different ID and 2D NMR analyses as well as computational analysis supported a metal-ligand bifunctional mechanism passing through a six-membered pericyclic transition state. We believe the present bifunctional molecular catalyst offers a great opportunity to open up new fundamentals for stereoselective molecular transformation.(2) Creation of Acid-Base Catalysis Involving Water Functions: Compared with functional group conversions attained by many types of atom-economical oxidation and/or reduction methods, efficient catalysis that mediates carbon-carbon bond formation still remains a considerable challenge. In particular, the development of mild and efficient transformations involving enol and enolate equivalents in the presence of a molecular catalyst has been a topic of continuous interest in organic synthesis. Several drawbacks that come from a high catalyst loading, low atom economy and generation of undesirable by-products need improvement. In order to sustain high reactivity to achieve maximum conversion, future catalysts should be structurally stable with catalytic species that are inert to the air and water. Such catalysts should be also capable of discriminating and binding to a single functionality for complex, multi-functional group substrates. Recently we discovered a novel molecular catalyst that shows high catalytic activity through molecular recognition events. These catalysts have aqua-cluster structures composed of aminoorganoboron and water. The structural properties of these catalysts are very unique: only one water molecule is captured by the combination of two hydrogen bonds and one coordination bond. We proposed that a special arrangement of the water molecule and multiple amines within the catalyst serves as a catalytically active site, thereby mimicking enzyme-like activity by forming cooperative acid-base interactions with organic substrates.(3) Direct Carbon-hydrogen Bond Arylation: Organic molecures having (hetero)aryl-(hetero)aryl bonds represent privileged structural motifs frequently found in natural products or used in pharmaceuticals as well as functional organic materials. Therefore, the development of efficient methods for biaryl has been a topic of unparalleled importance in all aspects of pure and applied chemistry. Although metal-catalyzed cross-coupling reactions of organometallics and organic halides have enjoyed widespread applications, the direct C-H arylation of heteroarenes and arenes holds significant synthetic potential as it eliminates pre-activation of coupling components. As a part of our program aimed at establishing programmable synthesis of (hetero)aryl-core starburst molecules, we developed a new transition metal catalyst for direct C-H arylation of heteroarenes that manifested high activity paired with broad scope. The fact that our effort has culminated in the finding of direct C-H arylation of simple arenes speaks well for the potential of the present catalysis for further development and applications. Elucidation of reaction mechanism development of more active catalysts, and applications of present direct arylation technology for materials and pharmaceutical chemistry are currently ongoing. Less