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: 9311318
• 负责人: VLADIMIR GEVORGYAN
• 金额: $ 29.31万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 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 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9311318
• 关键词: Alcohols; Amides; Amination; Amines; Amino Acids; Biological; Complement 3d Receptors; Complex; Coupling; Cyclization; Development; Distal; Employment; Environment; Evaluation; Event; Health; Hybrids; Hydrocarbons; Hydrogen; Hydrogen Bonding; Light; Methodology; Methods; Modernization; Modification; Organic Synthesis; Oxidants; Pharmaceutical Chemistry; Pharmacologic Substance; Photosensitization; Photosensitizing Agents; Reaction; Research; Science; Site; Steroids; Synthesis Chemistry; System; Testing; Transition Elements; Work; abstracting; base; design; drug discovery; functional group; novel; programs; scaffold; sugar; 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-functionilized 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 desaturation/functionalization of saturated groups are not general, as the functionalization site is usually substrate-dependent. Also, these methods operate under acidic conditions and/or employ external oxidants, which limits the substrate scope. Thus, mild regio- and stereo-controlled desaturation/functionalization of saturated groups remains a holy grail in modern synthetic chemistry. We propose the development of a novel 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 are easily installed onto substrate and removed from the product. Based on a substantial amount of preliminary results obtained in our lab, a successful development of this project is feasible. The proposed project consists of three major Sections: 1. Development of efficient catalytic systems for desaturation of aliphatic groups. 2. Development of a tool-kit for general efficient and controlled proximal and remote desaturations of various organic molecules. 3. Exploration of novel cascade reactions including C(sp3)–H functionalizations.

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 用于后期修改的强大工具。现有的几种去饱和/功能化方法。 饱和基团并不通用，因为官能化位点通常依赖于底物。 方法在酸性条件下操作和/或使用外部氧化剂，这限制了底物范围。 因此，饱和基团的温和区域和立体控制去饱和/官能化仍然是一个圣杯 在现代合成化学中，我们建议开发一种新型催化方法。 饱和基团的区域控制、温和且无外部氧化剂的官能化。 功能化将由设计的临时辅助工具包控制，这些工具包可以轻松安装到 基于我们获得的大量初步结果。 实验室，该项目的成功开发是可行的。拟议的项目由三个主要部分组成： 1. 开发用于脂肪族去饱和的高效催化系统 2. 开发工具包。 用于各种有机分子的一般有效和受控的近端和远程去饱和。 探索新型级联反应，包括 C(sp3)–H 官能化。