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: 10470374
• 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/10470374
• 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.

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.