New Catalytic Stereoselective Strategies for Hydrocarbon Functionalization Via Ionic Intermediates

通过离子中间体进行烃官能化的新催化立体选择性策略

• 批准号: 10711833
• 负责人: Liela Romero
• 金额: $ 32.28万
• 依托单位: BAYLOR UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10711833
• 关键词: Acceleration; Address; Area; Biological; Catalysis; Chemicals; Development; Generations; Goals; Hydrocarbons; Imaging Techniques; Improve Access; Isomerism; Methodology; Pharmaceutical Preparations; Preparation; Process; Reagent; Research; Source; Technology; Work; base; catalyst; chemical addition; chemical synthesis; chiral molecule; drug development; drug discovery; drug-like compound; halogenation; innovation; novel strategies; programs; small molecule therapeutics; tool

Project Summary Chemical methodologies for the predictable transformation of hydrocarbons to functional synthetic intermediates have revolutionized the preparation of small-molecule therapeutics. Nonetheless, the continued development of new chemical tools that compliment current existing technologies and address gaps in synthetic strategy offer the potential to further accelerate drug innovation and imaging techniques. The goal of this proposed research program is to develop new areas of asymmetric catalysis by means of chiral ionic intermediates. More specifically, the two research areas proposed here are centered on the study of catalysts that promote the stereoselective trapping of cationic intermediates to address longstanding challenges in synthesis. The first research area will focus on the development of novel strategies for catalytic enantioselective halogenation via chiral Lewis base catalysis. This work draws upon our initial findings in this area regarding the Lewis base activation of latent halide sources for the catalytic generation of chiral halogenating reagents. The second research area details a conceptually novel approach for the generation of chiral molecules via hydride abstraction processes. Specifically, we aim to exploit the reactivity and selectivity of superacid catalysts to enable the regio- and stereoselective functionalization of saturated hydrocarbons. This strategy represents the starting point for a broader research program aimed at developing a new mode of asymmetric Csp3–H functionalization. Taken together, these research programs will expand the available chemical space and streamline chemical synthesis for drug discovery and development.

项目概要 碳氢化合物可预测转化为功能性合成中间体的化学方法 尽管如此，小分子治疗药物的制备却发生了革命性的变化。 新的化学工具可以补充当前的现有技术并解决合成策略提供的差距 进一步加速药物创新和成像技术的潜力是这项研究的目标。 该计划是通过手性离子中间体开发不对称催化的新领域。 具体来说，这里提出的两个研究领域集中于促进催化剂的研究 立体选择性捕获阳离子中间体以解决合成中长期存在的挑战。 研究领域将重点开发催化对映选择性卤化的新策略 这项工作借鉴了我们在该领域关于路易斯碱的初步发现。 活化潜在卤化物源以催化生成手性卤化试剂。 研究领域详细介绍了一种通过氢化物提取生成手性分子的概念新颖方法 具体来说，我们的目标是利用超强酸催化剂的反应性和选择性来实现区域- 该策略代表了饱和烃的立体选择性官能化的起点。 旨在开发一种新的不对称 Csp3-H 功能化模式的更广泛的研究计划。 这些研究项目将共同扩大可用的化学空间并简化化学合成 用于药物发现和开发。