New Catalytic Reactions for Enhanced Synthetic Efficiency

提高合成效率的新催化反应

• 批准号: 0647358
• 负责人: Barry Trost
• 金额: $ 46.9万
• 依托单位: Stanford University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0647358&HistoricalAwards=false
• 关键词: New; Catalytic; Reactions; Enhanced; Synthetic

This project focuses on the development of a semi-rational approach for discovery/invention of new catalytic reactions largely based upon catalysis by complexes of ruthenium. Transformations that previously were unknown or quite difficult not only may become feasible but will be performed with high atom economy. The use of two separate transition metal catalyzed reactions occurring in the presence of each other either concurrently or consecutively will also be examined. Thus, in one pot, combining up to four components can lead to important synthetic building blocks. The extraordinarily broad range of stable oxidation states of ruthenium may impart reactivity where it did previously exist. Use of allenes in place of alkynes in these reaction schemes opens the prospect of alkene/alkyne/aldehyde 3-component coupling cyclizations. Special attention will be paid to comparing and contrasting rhodium vs. ruthenium catalysis of [5+2] cycloadditions. Ruthenium promoted additions of nucleophiles to alkyne offer a number of significant outcomes, including the addition of water, offering a novel synthesis of ruthenium enolates. A new strategy involving a [3+2+1] multicomponent coupling to generate pyridines, an extremely important class of heterocycles found in many biologically important targets, will be examined. Catalytic redox isomerization will be developed as an atom economic way to adjust oxidation levels. Intercepting the intermediates in the process provides opportunities for rapid increase of molecular complexity by multicomponent coupling protocols.With the support of this award from the Organic and Macromolecular Chemistry Program, Professor Barry Trost, of the Department of Chemistry at the Stanford University, is developing new methods to catalyze selective and efficient organic reactions. The need of increasingly complex organic molecules for a myriad of applications ranging from biology to material science heightens the need for increased sophistication in organic synthesis. Increasingly, it is no longer a question of whether a target can be synthesized, but rather how. Practical syntheses, whether total or partial, derive from the existence of the basic set of synthetic reactions. The limitations of that base set cripples our ability to broadly solve the problems of complex synthesis. The goal of this program is to enhance synthetic efficiency for the synthesis of complex molecules by increasing the basic set of synthetically useful reactions. Selectivity (chemo-, regio-, diastereo-, and enantio-) has been the prevailing issue to date. Limitations of raw materials and environmental concerns require attention to an equally important but frequently overlooked issue - atom economy, i.e., the development of reactions in which, to the greatest extent possible, any stoichiometric by-products are minimized and, in the ideal case, eliminated so that the product is the sum of the reactants with any additional reagent being required only catalytically.

这个项目的重点是开发一种半理性的方法来发现/发明主要基于Ru络合物催化的新催化反应。以前未知或相当困难的转变不仅可能变得可行，而且将以很高的原子经济性进行。还将考察在彼此同时或连续存在的情况下使用两种不同的过渡金属催化反应。因此，在一个锅中，将多达四个组分组合在一起可以产生重要的合成构件。Ru的非常广泛的稳定氧化态可能会赋予它以前存在的反应性。在这些反应方案中，用烯取代炔烃，开辟了烯/炔/醛三组分偶联环合反应的前景。将特别注意比较和对比Rh和Ru催化的[5+2]环加成反应。Ru促进的亲核加成反应提供了许多重要的结果，包括水的添加，提供了一种新的Ru烯醇酸酯的合成方法。将研究一种利用[3+2+1]多组分偶联来生成吡啶的新策略，吡啶是许多生物重要靶标中发现的一类极其重要的杂环化合物。催化氧化还原异构化将作为一种原子经济的方法来调节氧化水平。在此过程中，中间体的截留为多组分偶联协议提供了快速增加分子复杂性的机会。在有机化学和高分子化学项目的支持下，斯坦福大学化学系的Barry Trost教授正在开发新的方法来催化选择性和高效的有机反应。从生物学到材料科学的各种应用对日益复杂的有机分子的需求增加了对有机合成的复杂性的需求。越来越多的问题不再是能否合成一个目标，而是如何合成。实际的合成，无论是完全的还是部分的，都源于合成反应的基本集合的存在。这个基组的局限性削弱了我们广泛解决复杂综合问题的能力。该计划的目标是通过增加合成有用的反应的基本集合来提高合成复杂分子的合成效率。选择性(化学-、区域-、非对映-和对映体-)是迄今为止普遍存在的问题。原材料的局限性和环境问题需要注意一个同样重要但经常被忽视的问题--原子经济，即发展反应，在这种反应中，最大限度地减少任何化学计量副产物，在理想情况下，消除这些副产物，使产物是反应物的总和，任何额外的试剂只需要催化作用。