Catalytic Enantioselective Synthesis of Geminally-Bismetallated Organic Compounds

项目摘要/摘要 手性分子的新型催化对映选择性合成是一个至关重要的研究方向。 合成有机化学中的重要学科。这项拟议研究的目标是发明 光学活性两性双官能团有机化合物的有效合成方法 分子。考虑到大多数治疗剂和药物是单一的对映体 这些手性分子的手性实体、易获得性和实用性被认为是非常重要的。 PI研究计划的长期目标是开发对映体选择性的一般策略 在重要治疗药物中发现的具有挑战性的多官能化分子骨架的合成。 为此，拟议的研究试图发明新型的金属催化和有机催化 双金属双金属手性分子的合成。这种对映体选择性的一般方法 双金属有机化合物的合成尚不清楚。我们的假设是过渡- 金属催化剂和有机催化剂可以有效地激活硅-硼(Si-B)键生成 以富对映体的形式存在的女性化双金属物种。我们开发催化剂的基本原理 双金属双金属有机物种的合成是从易得的原料中制备的 起始材料。此外，由此产生的有机宝石-双金属物种可以参与 随后的合成转变，以快速建立分子复杂性。为了实现这一目标， PI提出了以下具体目标。(1)PI‘s小组将开发过渡金属催化硅- B(Si-B)键被激活。将发明一种新的硅-硼键激活模式 过渡金属催化剂。(2)我们将发明催化对映体选择性合成-- 双官能化有机化合物。合适的手性催化剂将加快反应速度，并将 在产品中诱导对映体过量。手性宝石双金属有机分子的制备 将会被证明。(3)我们的小组将开发有机催化方法，以实现对映体的女性化- 双金属手性分子。将开发一种新的催化对映体选择方法 有机催化剂。该方法将揭示一种新的不对称催化模式，其机理是 将进行研究，以阐明新的催化循环。改善人类健康与此密切相关 涉及到高效和选择性地制备富对映体手性分子的能力。这个 拟议的研究将通过开发对映体选择性催化来解决这一需求 医药中间体和生物活性分子。

Project Summary/Abstract The development of new catalytic enantioselective synthesis of chiral molecules is a vitally important subject in synthetic organic chemistry. The objective of the proposed research is to invent efficient synthetic methods for the construction of optically active geminally-bisfunctionalized organic molecules. Considering that the majority of therapeutic agents and drugs are single enantiomers of chiral entities, easy accessibility and utility of such chiral molecules are regarded significantly important. The long-term goal of the PI's research program is to develop general strategies for enantioselective synthesis of challenging poly-functionalized molecular frameworks found in important therapeutic agents. Toward this end, the proposed research seeks to invent novel metal-catalyzed and organocatalytic synthesis of geminally-bismetallated chiral molecules. This general approach toward enantioselective synthesis of geminally-bismetallated organic compounds is unknown. Our hypothesis is that transition- metal catalysts and organocatalysts can effectively activate silicon-boron (Si-B) bonds to generate geminally bismetallated species in enantioenriched form. Our rationale for the development of catalytic synthesis of geminally-bismetallated organic species is that they are prepared from readily available starting materials. Furthermore, the resulting organo gem-bismetallic species can participate in subsequent synthetic transformations to rapidly build up molecular complexity. To achieve this goal, the PI proposes the following specific aims. (1) The PI's group will develop transition-metal catalyzed silicon- boron (Si-B) bond activation. A new activation mode of silicon-boron bond will be invented using transition-metal catalysts. (2) We will invent catalytic enantioselective synthesis of geminally- bisfunctionalized organic compounds. Suitable chiral catalysts will accelerate the reaction rate and will induce enantiomeric excess in the product. The preparation of chiral gem-bismetallic organic molecules will be demonstrated. (3) Our group will develop organocatalytic method to enantioenriched geminally- bismetallated chiral molecules. A novel catalytic enantioselective method will be developed using organocatalysts. The method will disclose a new mode of asymmetric catalysis, and the mechanistic studies will be performed to elucidate the new catalytic cycle. Improving human health is deeply related to the ability to prepare enantioenriched chiral molecules with high efficiency and selectivity. The proposed research will address this need by developing enantioselective catalysis to prepare pharmaceutical intermediates and biologically active molecules.