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。使用非官能化的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。现有的几种去饱和化/功能化方法 饱和基团不是一般的，因为官能化位置通常是底物依赖的。还有，这些 方法在酸性条件下工作和/或使用外部氧化剂，这限制了底物的范围。 因此，轻度区域和立体控制的饱和群体的去饱和化/功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的催化方法学 饱和基团的区域控制、温和和外部无氧化剂官能化。地点： 功能化将由设计的临时辅助工具包控制，这些工具包很容易安装到 基材并从产品中移除。基于在我们的研究中获得的大量初步结果 实验室方面，本项目的成功开发是可行的。拟议的项目包括三个主要部分： 1.脂肪基脱饱和高效催化体系的开发。2.开发工具包 用于各种有机分子的一般、高效和可控的近端和远程脱饱和度。3. 探索包括C(SP3)-H官能化在内的新型级联反应。

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-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.