Catalytic Enantioselective Synthesis of Geminally-Bismetallated Organic Compounds

双金属化有机化合物的催化对映选择性合成

• 批准号: 9232843
• 负责人: Hee Yeon Cho
• 金额: $ 42.9万
• 依托单位: LOYOLA UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2020-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9232843
• 关键词: Address; Boron; Catalysis; Chemicals; Communities; Development; Goals; Health; Human; Investigation; Manuscripts; Metals; Methodology; Methods; Molecular; Organic Chemistry; Osteogenesis; Outcome; Paper; Pharmaceutical Preparations; Pharmacologic Substance; Preparation; Process; Publications; Publishing; Reaction; Research; Silicon; Therapeutic Agents; Transition Elements; abstracting; catalyst; chemical synthesis; chiral molecule; enantiomer; improved; innovation; manufacturing process; novel; programs; reaction rate; undergraduate student

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.

项目总结/摘要 发展新型的催化不对称合成手性分子的方法是一个重要的研究方向 合成有机化学中重要课题。这项研究的目的是发明 用于构建光学活性偕双官能化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化合物的单一对映体， 手性实体、这种手性分子的容易获得性和实用性被认为非常重要。 PI研究计划的长期目标是开发对映选择性的一般策略， 合成在重要治疗剂中发现的具有挑战性的多官能化分子框架。 为此，拟议的研究旨在发明新的金属催化和有机催化 偕双金属化手性分子的合成。这种对映选择性的一般方法 双生双金属化有机化合物的合成尚不清楚。我们的假设是- 金属催化剂和有机催化剂可以有效地活化硅-硼（Si-B）键， 对映体富集形式的成对双金属化物质。我们开发催化剂的基本原理 偕双金属化有机物质的合成的一个重要特征是它们由容易获得的 起始材料此外，所得的有机宝石-双金属物种可以参与 随后的合成转化，以迅速建立分子的复杂性。为了实现这一目标， PI提出了以下具体目标。(1)PI的团队将开发过渡金属催化硅- 硼（Si-B）键活化。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选择性合成偕- 双官能化有机化合物。合适的手性催化剂将加速反应速率， 诱导产物中的对映体过量。手性偕双金属有机分子的制备 将被证明。(3)本课题组将发展有机催化法合成对映体富集的偕- 双金属手性分子。本文将发展一种新的催化对映选择性方法， 有机催化剂该方法将揭示一种新的不对称催化模式， 并会进行研究，以阐明新的催化循环。改善人类健康与 涉及以高效率和高选择性制备对映体富集的手性分子的能力。的 拟议的研究将通过开发对映选择性催化来解决这一需求，以制备 药物中间体和生物活性分子。