Transition Metal-Radical Hybrid Methods for Organic Synthesis

项目描述 该计划旨在开发一种新的可控选择性合成平台， 具有非反应性C（sp3）-H键的脂族分子的官能化。现有合成 制备复杂分子和药物的方法大多依赖于使用预官能化的 印刷受体.使用非官能化的饱和烃基更有吸引力，因为这些 部分更加丰富和便宜。此外，脂族C（sp3）-H键通常存在于 复杂的生物学重要分子和药物，因此它们的选择性功能化提供了 后期改造的有力工具。现有的几种用于脱饱和/官能化的方法 饱和基团不是通用的，因为官能化位点通常依赖于底物。而且这些 该方法在酸性条件下操作和/或使用限制底物范围的外部氧化剂。 因此，饱和基团的温和的区域和立体控制的去饱和/官能化仍然是一个圣杯 在现代合成化学中。我们提出了一种新的催化方法的发展， 饱和基团的区域控制的、温和的和外部无氧化剂的官能化。部位 功能化将通过设计的临时辅助工具包进行控制，这些工具包易于安装在 从产品中取出并取出。根据我们在实验室获得的大量初步结果， 实验室，该项目的成功开发是可行的。拟议项目包括三个主要部分： 1.脂肪族基团去饱和反应的高效催化体系研究进展。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端去饱和。3. 探索包括C（sp3）-H官能化的新型级联反应。

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.