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.

该项目的重点是开发一种半理性方法，用于发现/发明新的催化反应，主要基于ruthenium络合物的催化。以前未知或非常困难的转型不仅可能变得可行，而且会在高原子经济中进行。还将研究在彼此同时或连续存在的两种单独的过渡金属催化反应中的使用。因此，在一个锅中，将多达四个组件组合起来可以导致重要的合成构件。在以前存在的情况下，唯一的稳定氧化状态的稳定氧化状态非常广泛。在这些反应方案中，使用艾伦代替炔烃开放了烷烃/炔烃/醛3组分耦合循环的前景。将特别注意比较和对比[5+2]环加成的铑与ruthenium催化。唯一促进亲核试剂添加到碱中的添加提供了许多重要的结果，包括加水，提供新颖的氟烯烯醇合成。将检查一种涉及[3+2+1]多组分耦合以生成吡啶的新策略，这是许多在许多生物学上重要的靶标中发现的极为重要的异环菌。催化氧化还原异构化将被开发为调整氧化水平的原子经济方式。在此过程中拦截中间体为通过多组分耦合方案快速提高分子复杂性的机会提供了机会。在有机和大​​分子化学计划的支持下，斯坦福大学化学系的Barry Trost教授正在开发催化选择性和有效有机反应的新方法。从生物学到材料科学的无数应用中，需要日益复杂的有机分子，这增加了有机合成中成熟程度增加的需求。越来越多的问题不再是一个问题，即是否可以合成目标，而是如何合成目标。实际合成，无论是总还是部分，都来自基本合成反应集的存在。该基础设定的局限性削弱了我们广泛解决复杂综合问题的能力。该程序的目的是通过增加基本的合成有用反应集来提高合成复合分子的合成效率。迄今为止，选择性（化学，区域性，iastereo-和对映体）一直是流行的问题。原材料和环境问题的局限性需要注意一个同样重要但经常被忽视的问题 - 即原子经济，即，在很大程度上，在最大程度上发展了反应的发展，任何化学计量的副产品被最小化，而在理想的情况下，消除了止痛药的总和，即仅需要任何其他抗激型的抗激型。