New Synthetic Methodology Enabled by Base-Promoted Halogen and Electron Transfer Processes

碱促进卤素和电子转移过程实现的新合成方法

• 批准号: 10390432
• 负责人: Jeffrey S Bandar
• 金额: $ 36.78万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10390432
• 关键词: Address; Chemical Structure; Chemicals; Coupling; Drug Industry; Electron Transport; Goals; Halogens; Improve Access; Medicine; Methodology; Methods; Organic Synthesis; Pharmaceutical Preparations; Process; Production; Reaction; Research; Route; Series; Structure; Work; aryl halide; base; catalyst; drug candidate; functional group; improved; novel; novel therapeutics; operation; programs; promoter

Project Summary There remains a critical need to develop synthetic methodology that increases the efficiency and diversity of access to chemicals desired in medicinal research. In particular, fundamentally new transformations that employ abundantly available starting materials can greatly facilitate the discovery and manufacture of new drugs. The long-term goal of this research program is to use strong bases as catalysts and promoters for new reactions that address major limitations in organic synthesis. The overall objective for this application is to use inexpensive Brønsted and Lewis bases to achieve new functionalization methods of aryl halides, heteroarenes and trifluoromethylarenes. This proposal is built on the hypothesis that strong bases can unlock previously unknown or underutilized mechanistic processes of common organic functional groups. Specifically, the research plan will exploit base-catalyzed aryl halide isomerizations and intermolecular halogen transfers, as well as single electron transfer processes from base-activated organosilicates. Based on extensive preliminary results, a series of novel arene functionalization reactions are described that are primarily targeted at improving heteroarene derivatization. The monoselective coupling of organosilanes to trifluoromethylarenes is also presented as a practical and broadly useful approach to difluorobenzylic compounds. The impact of these methods is demonstrated through single-step access to compounds that were either previously inaccessible or required tedious multistep operations, their use for late stage diversification of drug-like structures and dramatically improved routes to specific drug candidates. Upon completion of the proposed work, chemists will have at their disposal a set of powerful reactions that increase the efficiency, practicality and scope of access to molecules widely desired in the pharmaceutical industry.

项目摘要 开发综合方法论以提高效率和多样性仍然存在迫切的需求 在医学研究中获得所需的化学物质的机会。特别是，从根本上讲是新的转变 员工绝对可用的起始材料可以极大地支持新药的发现和制造。 该研究计划的长期目标是将强碱用作新反应的催化剂和促进者 该解决有机合成的主要局限性。该应用程序的总体目标是使用便宜的 Brønsted和Lewis基座，以实现芳基卤化物，杂种和 三氟甲基烯烯。该提议建立在以下假设的基础上，即强碱可以解锁以前未知的 或普通有机官能团的原理机械过程。具体而言，研究计划将 利用碱催化的芳基卤化物异构化和分子间卤素转移以及单个电子 从碱基激活有机硅的转移过程。基于广泛的初步结果，一系列新颖 描述了主要旨在改善异质动物的芳烃官能化反应 衍生化。有机硅与三氟甲基烯烯的单取道耦合也作为一个 实用且广泛有用的方法，用于差异化合物。这些方法的影响是 通过单步访问以前无法访问或必需的化合物证明 乏味的多步操作，它们用于类似药物的结构的晚期多样化，并急剧 改进了特定候选药物的路线。拟议的工作完成后，化学家将在他们的 处置一组强大的反应，以提高获得分子的效率，实用性和范围 制药行业广泛期望。