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，主要基于钌配合物的催化作用。以前未知或相当困难的转变不仅可能变得可行，而且将以高原子经济性进行。还将研究同时或连续发生的两个单独的过渡金属催化反应的使用。因此，在一锅中，组合多达四种成分可以产生重要的合成构件。钌极其广泛的稳定氧化态可能会赋予其先前存在的反应性。在这些反应方案中使用丙二烯代替炔烃开启了烯烃/炔烃/醛三组分偶联环化的前景。将特别关注[5+2]环加成的铑与钌催化的比较和对比。钌促进亲核试剂向炔的加成提供了许多重要的结果，包括加水，提供了烯醇钌的新型合成。将研究一种涉及 [3+2+1] 多组分偶联生成吡啶的新策略，吡啶是在许多生物学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发展为一种调节氧化水平的原子经济方法。在此过程中拦截中间体为通过多组分偶联方案快速增加分子复杂性提供了机会。在有机和高分子化学计划这一奖项的支持下，斯坦福大学化学系的 Barry Trost 教授正在开发新的催化选择性和高效有机反应的方法。从生物学到材料科学等众多应用对日益复杂的有机分子的需求，提高了对有机合成复杂性的需求。越来越多的问题不再是能否合成目标，而是如何合成。实际合成，无论是全部合成还是部分合成，都源于基本合成反应集的存在。该基础集的局限性削弱了我们广泛解决复杂合成问题的能力。该计划的目标是通过增加基本的合成有用反应集来提高复杂分子合成的合成效率。选择性（化学-、区域-、非对映-和对映-）是迄今为止普遍存在的问题。原材料的限制和环境问题需要关注一个同样重要但经常被忽视的问题 - 原子经济性，即反应的发展，其中尽可能最大程度地减少任何化学计量副产物，并且在理想情况下，消除，使得产物是反应物与仅需要催化作用的任何附加试剂的总和。