New Catalytic Systems for Stereoselective C-H Amination

项目总结/摘要 立体选择性C-H胺化反应的新催化体系 含氮化合物在生物学和医学中具有核心重要性。的 开发合成方法，允许选择性转化无所不在的C-H键 有价值的胺官能团有望改变有机合成的艺术和实践 并将带来许多新的应用。在不同的方法中，催化C-H胺化通过 氮烯插入代表了最重要的一类化学转化。这种类型 催化氮烯转移过程的研究为氮烯的功能化提供了一条直接而通用的途径 通过立体选择性C-N键形成有机化合物中的C-H键。它作为一个有用的 设计和合成生物学和药学上重要的手性胺的工具 分子。虽然通过现有的催化剂用于C-H胺化已经取得了相当大的进展， 具有广泛使用的试剂PhI=NTs和相关的亚氨基碘烷衍生物作为氮烯的体系 尽管有各种来源，但实地仍然存在重大挑战，证明有必要确定更有效的 氮烯来源与C-H反应的新型金属催化剂的开发相结合 胺化。 在金属自由基催化（MRC）概念的指导下，本研究项目旨在 立体选择性C-H胺化反应新催化体系的开发。一样稳定 金属自由基，钴（II）配合物的卟啉[Co（Por）]已被证明是一个独特的功能， 通过逐步自由基机理的C-H胺化的一类催化剂。卟啉负载 带有酰胺官能团的配体，Co（II）基MRC已被证明是特别适合的。 有效地活化各种叠氮化物，使不同类型的C-H键自由基胺化， 在有效控制反应性和选择性的情况下形成胺衍生物。在这一新提案中， 我们将重点研究手性卟啉的钴（II）配合物[Co（II）（Por*）]作为手性卟啉的应用。 金属自由基催化剂，以促进立体选择性C-H胺化反应， 光学活性胺衍生物，包括氨基酸、二胺、氨基醇和 N-杂环 我们希望这些研究将最终导致开发基于Co（II）的新催化剂。 用于立体选择性C-H胺化反应的系统， 生物学上重要的含氮天然产物的合成和药物 有趣的化合物

PROJECT SUMMARY/ABSTRACT New Catalytic Systems for Stereoselective C–H Amination Nitrogen-containing compounds are of central importance in biology and medicine. The development of synthetic methodologies that allow for selective conversion of omnipresent C–H bonds into valuable amine functional groups promises to transform the art and practice of organic synthesis and should lead to many new applications. Among different approaches, catalytic C–H amination via nitrene insertion represents one of the most important classes of chemical transformations. This type of catalytic nitrene transfer process provides a direct and general approach for the functionalization of C–H bonds in organic compounds through stereoselective C–N bond formation. It serves as a useful tool for the design and synthesis of biologically and pharmaceutically important chiral amine molecules. While considerable progress has been made for C–H amination by existing catalytic systems with the widely-used reagent PhI=NTs and related iminoiodane derivatives as nitrene sources, important challenges remain in the field that validate the need to identify more effective nitrene sources in conjunction with the development of fundamentally new metal catalysts for C–H amination. Guided by the concept of metalloradical catalysis (MRC), this research project is directed toward the development of new catalytic systems for stereoselective C–H amination reactions. As stable metalloradicals, cobalt(II) complexes of porphyrins [Co(Por)] have been shown to function as a unique class of catalysts for C–H amination through stepwise radical mechanism. Supported by porphyrin ligands bearing amide functionalities, the Co(II)-based MRC has been shown to be particularly effective in activating various azides for radical amination of different types of C–H bonds, leading to formation of amine derivative with effective control of reactivity and selectivity. In this new proposal, we will focus on the utilization of cobalt(II) complexes of chiral porphyrins [Co(II)(Por*)] as chiral metalloradical catalysts to advance the enantioselective C–H amination reactions for stereoselective synthesis of optically active amine derivatives, including amino acids, diamines, amino alcohols and N-heterocycles. We hope these studies will ultimately lead to the development of Co(II)-based new catalytic systems for stereoselective C–H amination reactions that can be generally applied toward practical synthesis of biologically important nitrogen-containing natural products and pharmaceutically interesting compounds.