New Organometallic Catalysts for Multistep Coupling Reactions

在过去的6年里，我们的研究在过渡金属催化的几个不同领域取得了新的发现。这些措施包括： A)观察到金属催化的卤代芳烃的羰基化反应可以用于一个新的方向：组装高能亲电试剂(酸性氯化物)； B)使用金属催化一步将多种可获得的试剂转化为产品； C)制备共轭聚合物而不需要复杂合成的另一种方法：金属催化多组分聚合； D)用于环加成反应的1，3-偶极的新的和模数类；以及 E)使用诸如离子配对之类的弱力来设计活性和(对映体)选择性金属催化剂。 总而言之，这些都表明，通过一次将现有试剂简单组合在一起，可以形成各种产品，如复杂的药芯或先进的聚合物，以及碳氢化合物功能化的新方法。这项提议将向三个方向发展这种化学反应，包括： 羰基电化学法我们发现钯催化的芳基卤代甲酰化反应可用于合成酸性氯化物，这表明使用简单的一氧化碳不仅可以作为试剂，而且可以作为一种化合物来驱动高能产物的形成。在这项建议中，我们将研究利用这一平台作为合成酸性氯化物亲电性甚至超级亲电性的一般方法的潜力，并将烃类官能化成酮，所有这些都是由一氧化碳的反应性驱动的。 一步通向生物相关产品我们将在我们最近的研究努力的基础上，利用金属催化开发简单的一步方法，直接从可用的构建块组装生物相关的核心结构。由于它们的效率，这些反应不仅可以直接进行，而且可以最大限度地减少浪费，并可以被证明是创造新的生物活性化合物变体的理想选择。这些努力将包括创造这些催化反应的新类别，以及这些反应的潜在应用，通过催化直接构建重要的药物结构。 多组分聚合我们最近发现了一种以有效的方式组装复杂聚合物的新方法：通过将几个简单的单体直接偶联成一种新的聚合物(金属催化的多组分聚合)。这可以提供一种以实际方式形成复杂聚合物的方法，并将针对产生新的共轭聚合物类别、访问聚酰胺的模块化方法以及创建新的聚合物库来调整其性能。

Our research during the last 6 years has led to discoveries in several different areas of transition metal catalysis. These include: a) the observation that metal catalyzed aryl halide carbonylations can be used in a new direction: the assembly of high energy electrophiles (acid chlorides); b) the use of metal catalysis to convert of multiple available reagents in one step into products; c) an alternative approach to prepare conjugated polymers without a complex synthesis: a metal catalyzed multicomponent polymerization; d) new and modular classes of 1,3-dipoles for application in cycloaddition; and e) the use of weak forces such as ion pairing to design active and (enantio)selective metal catalysts. Together, these suggest the potential to form products as diverse as complex pharmaceutical cores or advanced polymers from simple combinations of available reagents brought together at once, as well as new approaches to functionalize hydrocarbons. This proposal will develop this chemistry in three directions, including: Carbonylative Electrophile Synthesis Our discovery that palladium catalyzed aryl halide carbonylations can be used to synthesize acid chlorides shows that it is possible to use simple carbon monoxide not simply as a reagent, but as a compound that can drive the build-up of high energy products. In this proposal, we will examine the potential of exploiting this platform as a general method to synthesize acid chloride electrophiles or even super electrophiles, and to perform hydrocarbon functionalization into ketones, all driven by the reactivity of carbon monoxide. One Step Routes to Biologically Relevant Products We will build upon our recent research efforts to use metal catalysis to develop simple, one step methods to assemble biologically relevant core structures directly from available building blocks. Because of their efficiency, these reactions can be not only straightforward to perform, but also minimize waste, and can prove ideal for creating new variants of bio-active compounds. These efforts will include creating both new classes of these catalytic reactions, and the potential application of these to directly construct important pharmaceutical structures via catalysis. Multicomponent Polymerizations We have recently discovered a new method to assemble complex polymers in an efficient fashion: by coupling several simple monomers directly into a new polymer (a metal catalyzed multicomponent polymerization). This can provide an approach to form complex polymers in a practical manner, and will be directed towards generating new classes of conjugated polymers, modular methods to access polyamides, as well as the creation of novel polymer libraries to tune their properties.