Exploitation of Fine Molecular Catalysts

(1)酮的不对称氢化：手性RuCl2(BINAP)(1，2-二胺)络合物允许各种简单的、无官能化的酮进行快速的对映选择性氢化，底物/催化剂摩尔比高达2400,000。随着这一过程的高度实用性得到认可，我们被鼓励开发一种坚固的(前)催化剂，在无碱条件下促进不对称反应。在这个程序的过程中，我们建立了RuH(η^1-BH_4)(BINAP)(1，2-二胺)络合物，允许单酮在异丙醇中不对称氢化，而不需要额外的强碱。各种碱敏感的酮可以转化为高对映体纯度的手性醇。最近，我们发现N-对甲苯磺酸乙二胺-Ru(II)络合物催化酮的不对称氢化反应，得到相应的手性甲醇，具有较高的对映体纯度。这些Ru(II)络合物是…不对称转移氢化的优良催化剂更多的离子，也可以用于不对称氢化。这一发现为单酮在非碱性和酸性条件下的对映选择性氢化提供了一种长远的方法。进一步的动力学研究、同位素标记实验、一系列不同的ID和2D核磁共振分析以及计算分析支持金属-配体通过六元周环过渡态的双功能机制。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建：与许多类型的原子经济的氧化和/或还原方法所实现的官能团转化相比，高效的催化形成碳-碳键仍然是一个相当大的挑战。特别是，在分子催化剂的存在下，开发温和而有效的涉及烯醇和烯酸酯类化合物的转化一直是有机合成中一直感兴趣的话题。催化剂负载量高、原子经济性低以及产生不良副产品的几个缺点需要改进。为了保持高的反应活性以实现最大的转化率，未来的催化剂应该是结构稳定的，其催化物种对空气和水是惰性的。这样的催化剂还应该能够区分和结合到复杂、多功能基团底物的单一官能团。最近，我们发现了一种通过分子识别事件表现出高催化活性的新型分子催化剂。这些催化剂具有由氨基有机硼和水组成的水团簇结构。这些催化剂的结构性质非常独特：只有一个水分子被两个氢键和一个配位键结合在一起。我们提出了水分子和催化剂中多个胺的特殊排列作为催化活性中心，从而通过与有机底物形成协同的酸碱相互作用来模拟酶的活性。(3)直接碳氢键芳基化：具有(杂)芳基-(杂)芳基键的有机分子是经常在天然产品或医药以及功能有机材料中发现的特权结构基元。因此，发展高效的联芳基合成方法在理论化学和应用化学的各个方面都具有无与伦比的重要性。尽管金属催化的有机金属化合物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芳基化反应具有巨大的合成潜力，因为它消除了偶联组分的预活化。作为我们旨在建立可编程合成(杂环)芳基星爆分子的计划的一部分，我们开发了一种新型的过渡金属催化剂，用于杂芳烃的直接C-H芳基化反应，表现出高活性和广泛的范围。我们的努力最终发现了简单芳烃的直接C-H芳基化反应，这一事实很好地说明了本催化剂进一步开发和应用的潜力。目前，反应机理的阐明，更多活性催化剂的开发，以及目前直接芳基化技术在材料和药物化学中的应用都在进行中。较少

(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