New Organometallic Catalysts for Multistep Coupling Reactions

在过去的6年里，我们的研究已经在过渡金属催化的几个不同领域取得了发现。这些包括：**** a)观察到金属催化芳基卤化物羰基化可以用于一个新的方向：组装高能亲电试剂（酸性氯化物）；**** b)利用金属催化在一步中将多种可用试剂转化为产品；**** c)制备共轭聚合物的替代方法，无需复杂的合成：金属催化的多组分聚合；**** d)用于环加成的新型和模类1,3偶极子；**** e)利用弱作用力如离子配对来设计活性和（对映）选择性金属催化剂。* ***总之，这些都表明，通过一次性将现有试剂简单组合在一起，可以形成多种多样的产品，如复杂的药物核心或高级聚合物，以及功能化碳氢化合物的新方法。我们发现钯催化芳基卤化物羰基化可以用来合成酸性氯化物，这表明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积累。在本提案中，我们将研究利用该平台作为合成酸性氯亲电试剂甚至超亲电试剂的一般方法的潜力，并将碳氢化合物功能化成酮，所有这些都由一氧化碳的反应性驱动。*******一步途径生物相关产品我们将基于我们最近的研究成果，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，并且可以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两类新的催化反应，以及通过催化直接构建重要药物结构的潜在应用。*******多组分聚合我们最近发现了一种高效组装复杂聚合物的新方法：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用的方式形成复杂聚合物的方法，并将用于生成新型共轭聚合物，获取聚酰胺的模块化方法，以及创建新的聚合物库以调整其性质

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.***