Transition Metal-Radical Hybrid Methods for Organic Synthesis

有机合成的过渡金属-自由基杂化方法

• 批准号: 10297697
• 负责人: VLADIMIR GEVORGYAN
• 金额: $ 31.98万
• 依托单位: UNIVERSITY OF TEXAS DALLAS
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10297697
• 关键词: Alkenes; Amines; Biological; Chemistry; Complex; Coupling; Cyclization; Development; Employment; Esters; Felis catus; Generations; Health; Hybrids; Hydrocarbons; Hydrogen; Hydrogen Bonding; Ketones; Methodology; Methods; Modernization; Modification; Organic Synthesis; Oxidants; Pharmaceutical Preparations; Pharmacologic Substance; Property; Reaction; Research; Science; Site; Synthesis Chemistry; System; Techniques; Transition Elements; Visible Radiation; Work; abstracting; base; catalyst; design; drug discovery; improved; migration; novel; programs; tool

Project Description The proposed program aims at the development of a new synthetic platform for controlled selective functionalizations of aliphatic molecules possessing unreactive C(sp3)–H bonds. The existing synthetic methods toward complex molecules and pharmaceuticals mostly rely on employment of pre-functionalized substrates. Employment of non-functionalized saturated hydrocarbon groups is much more appealing as these moieties are much more abundant and cheap. Moreover, the aliphatic C(sp3)–H bonds are often present in complex biologically important molecules and pharmaceuticals, and thus their selective functionalization offers a powerful tool for late stage modifications. The few existing methods for functionalization of saturated groups are not general, as the functionalization site is usually substrate-controlled. Also, these methods operate under acidic conditions and/or employ external oxidants, which limits the substrate scope. Thus, mild regio- and stereo-controlled functionalization of saturated groups remains a holy grail in modern synthetic chemistry. We propose the development of a novel visible light-induced transition metal-radical hybrid catalytic methodology for regiocontrolled, mild, and external oxidant-free functionalizations of saturated groups. The site of functionalization will be controlled by a designed tool-kit of temporary auxiliaries, which potentially in one-pot fashion will be routinely installed onto substrate and removed from the product. The feasibility of a successful development of this project is supported by a vast amount of preliminary results obtained in our lab. The proposed project consists of three major Sections: 1. Development of efficient catalytic systems for functionalization of aliphatic groups. 2. Development of a tool-kit for general efficient and site-controlled proximal and remote functionalizations of various organic molecules. 3. Implementation of novel reactivity of transition metal-radical hybrid complexes under development toward new transformations including C(sp3)–H functionalizations and cascade reactions.

项目描述 拟议的计划旨在开发一种新的控制选择性合成平台 具有非反应性 C(sp3)–H 键的脂肪族分子的官能化 现有的合成。 复杂分子和药物的方法主要依赖于预功能化的使用 使用非官能化饱和烃基团更具吸引力。 此外，脂肪族 C(sp3)-H 键通常存在于。 复杂的具有重要生物学意义的分子和药物，因此它们的选择性功能化提供了 用于后期修饰的强大工具。现有的少数饱和基团功能化方法。 这些方法并不通用，因为功能化位点通常是受底物控制的。 酸性条件和/或使用外部氧化剂，这限制了底物范围，因此，温和的区域和。 饱和基团的立体控制官能化仍然是现代合成化学的圣杯。 提出开发一种新型可见光诱导的过渡金属-自由基混合催化方法 用于饱和基团的区域控制、温和且无外部氧化剂的官能化。 功能化将由一个设计的临时辅助工具包控制，该工具包可能在一锅中 将时装定期安装到基材上并从产品上移除的可行性。 该项目的开发得到了我们实验室获得的大量初步结果的支持。 拟议项目由三个主要部分组成： 1. 开发高效催化系统 2. 开发通用高效和位点控制的工具包。 3. 各种有机分子的近端和远端功能化。 正在开发的过渡金属-自由基杂化配合物，以实现包括 C(sp3)–H 在内的新转变 功能化和级联反应。