Transition Metal-Radical Hybrid Methods for Organic Synthesis

项目说明 提出的方案旨在开发一种新的受控选择综合平台 具有非反应性C(SP3)-H键的脂肪族分子的官能化。现有的合成材料 针对复杂分子和药物的方法大多依赖于预官能化的使用 底物。使用非官能化饱和烃基团更具吸引力，因为 部分产品更丰富，价格也更便宜。此外，脂肪族C(SP3)-H键通常存在于 复杂的生物重要分子和药物，因此它们的选择性官能化提供了 后期修改的强大工具。已有的几种饱和群的泛化方法 不是一般的，因为功能化部位通常是底物控制的。此外，这些方法在 酸性条件和/或使用外部氧化剂，这限制了底物的范围。因此，温和的地区-和 饱和基团的立体可控官能化仍然是现代合成化学中的圣杯。我们 提出了一种新的可见光诱导过渡金属-自由基复合催化方法的开发 用于饱和基团的区域控制、温和和外部无氧化剂官能化。地点： 功能化将由一个设计的临时辅助工具包控制，该工具包可能在一个锅中 时尚将被例行地安装在基材上，并从产品中移除。成功的可行性 这一项目的开展得到了我们实验室取得的大量初步成果的支持。这个 拟议的项目包括三个主要部分：1.开发高效的催化系统 脂肪基团的官能化。2.开发通用、高效、现场控制的工具包 各种有机分子的近端和远端官能化。3.实现新的反应性 过渡金属-自由基杂化配合物正在向包括C(SP3)-H在内的新转变方向发展 官能化和级联反应。

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.