Development of New Stereoselective Metal-Catalyzed Organic Reactions

 描述(由申请人提供)：我们合成碳-碳键的能力是获取无数有机分子的重要生物活性所不可或缺的。许多有价值的治疗药物以非外消旋形式存在，由多种立体生成元素组成。这些特点突出表明，迫切需要新的化学反应，使化学家能够有效地制备具有高选择性的有机化合物。这一研究计划的重点是通过将1，1-双金属亲核试剂加到一些类别的亲电试剂上，开发新的立体选择性金属催化的碳-碳键形成方法。这些研究将导致战略性地替代C-C键断开，从而以对映体纯的形式提供重要的功能分子。这里描述的许多反应没有现有的催化方案。(1)我们将开发实用和强大的铜催化的对映体和非对映选择性的烷基化反应，这些反应将导致一系列非环羟基和氨基硼酸酯的合成，这是其他方法不容易获得的。这些方法的价值是通过安装高度通用的立体生成C-B键来增加的。(2)我们将开发一系列的烷基、烯基、芳基、烯丙基取代的1，1-异双金属亲核试剂与缺电子的烯烃加成的铜催化的一般对映体聚合方法。这一反应技术将导致更有效地合成生物活性分子中常见的高烯丙基醇和胺的化学结构。(3)反应发展还将证明，1，1-双金属试剂为底物导向的立体选择性催化反应提供了独特的途径。该计划中开发的新催化剂和催化方法为对映体选择性合成适应性分子提供了独特的和选择性的途径。通过对药理活性物质的简明合成的应用，我们将展示我们的方法的实用性，以及确定它们的局限性。

 DESCRIPTION (provided by applicant): Our ability to synthesize carbon-carbon bonds is integral to accessing the important biological activity of myriad organic molecules. Many valuable therapeutic agents exist in non-racemic form comprised of multiple stereogenic elements. Such characteristics highlight the critical need for new chemical reactions that allow chemists to efficiently prepare organic compounds with high levels of selectivity. The focus of this research program involves the development of new stereoselective metal-catalyzed processes for carbon-carbon bond formation via the addition of 1,1-bimetallic nucleophiles to a number of classes of electrophiles. These studies will lead to strategically alternative C-C bond disconnections that deliver important functional molecules in enantiomerically pure form. Many of the reactions described herein do not have existing catalytic protocols. (1) We will develop practical and robust Cu-catalyzed enantio-and diastereoselective alkylations of carbonyls and their derivatives with alkyl boron-containing reagents; these reactions will lead to the synthesis of a range of acyclic hydroxy- and amino-boronates that cannot be easily accessed by others methods. The value of these methods is increased by the installation of a highly versatile stereogenic C-B bond. (2) We will develop general enantioconvergent Cu-catalyzed processes for the addition of a range of alkyl-, alkenyl-, aryl-, allyl- substituted 1,1-heterobimetallic nucleophiles to electron-deficient alkenes. This reaction technology will lead to more efficient ways to synthesize homoallyl alcohols and amines common chemical structures found in bioactive molecules. (3) Reaction development will also demonstrate that 1,1-bimetallic reagents offer unique approaches to substrate-directed stereoselective catalytic reactions. The new catalysts and catalytic methods developed in this program offer unique and selective routes to the enantioselective synthesis of adaptable molecules. Through applications to concise synthesis of pharmacologically active agents, we will demonstrate the utility of our methods, in addition to identifying their limitations.