Electrophilic Amination of Hydrocarbons via Novel Transition-Metal Nitrenes, Amidos and Nitrenoids

项目摘要 建议研究的主要目标是发展和探讨 用于非官能化碳氢化合物胺化反应的新型第一排过渡金属试剂。这个 建议的试剂将氮基(硝基、氨基、硝基)输送到脂肪族碳氢化合物(C-H 键)和烯烃(C=C键)，用于构建C-N键。胺化部位过多。 天然和合成产品，包括药品、农用化学品、催化剂和固态 材料，以便赋予活动所需的主干特征和特定功能。这个 主要目标将通过三个具体目标来实现，这些目标是并行和相互实现的 消息灵通的时尚。首先，将合成一种新型的立体-电子多样化的配体支架文库，并 用作固定金属位置的坚固框架，产生二价铁、锰、钴和 一价铜试剂，用作胺化反应的催化剂。第二，金属试剂 将探索作为催化剂将氮基(硝基、氨基、类硝基)从合适的 多用途碳质底物受体(烷烃、烯烃)的前体，导致形成 重要的功能单元(胺、二胺、未保护的氮杂环丙烷)。化学计量反应涉及 将进行金属试剂和氮源(在没有底物的情况下)以确定 以金属为中心的关键中间体，负责将氮基输送到基材。第三， 最有希望的试剂将被机械地调查，以报告转移的方式和随后的 将氮基单元插入/添加到底物，并进一步引导催化剂开发以实现高效 和选择性的性行为。拟议的工作取决于是否有自制的新型金属图书馆可用 试剂，其特点是成员在C-N键结构方面具有公认的记录，但需要扩展到 在更广泛的胺化产品的合成中实现适当水平的选择性。此外， 拟议的研究探索了在催化和反应中可能具有共同特征的反应模式 酶学，间接解决由涉及到的新兴酶类引起的机制问题 胺化反应。拟议活动的最终结果是在 合成化学家的军火库，源于丰富的第一排过渡元素，并渴望 在范围、选择性和安全性方面超过或补充当前的C-N键构建方法 机械的洞察力。

Project Summary The overarching objective of the proposed research is to develop and explore the mode of operation of a novel family of first-row transition-metal reagents for the amination of unfunctionalized hydrocarbons. The proposed reagents deliver nitrogen groups (nitrenes, amidos, nitrenoids) to aliphatic hydrocarbons (C–H bonds) and olefins (C=C bonds) for the construction of C–N bonds. Sites of amination are present in a plethora of natural and synthetic products, including pharmaceuticals, agrochemicals, catalytic agents and solid-state materials, in order to confer backbone characteristics and specific functionalities necessary for activity. The principal objective will be accomplished via three specific aims, accomplished in a parallel and mutually informed fashion. First, a novel library of stereo-electronically diverse ligand scaffolds will be synthesized and used as a robust framework to anchor metal sites, producing divalent iron, manganese, cobalt, and monovalent copper reagents, functioning as catalysts for amination reactions. Secondly, the metal reagents will be explored as catalysts for the transfer of nitrogen groups (nitrenes, amidos, nitrenoids) from suitable precursors to versatile carbonaceous substrate acceptors (alkanes, alkenes), leading to the formation of important functional units (amines, diamines, unprotected aziridines). Stoichiometric reactions involving the metal reagents and the nitrogen-group sources (in the absence of substrates) will be conducted to identify critical metal-centered intermediates responsible for delivering the nitrogen group to the substrate. Thirdly, the most promising reagents will be mechanistically investigated, to report on the mode of transfer and subsequent insertion/addition of the nitrogen group unit to the substrate, and further guide catalyst development for efficient and selective aminations. The proposed work relies on the availability of a library of house-made novel metal reagents, featuring members with a proven record in C–N bond construction, but requiring expansion to achieve appropriate levels of selectivity in the synthesis of a wider range of amination products. Moreover, the proposed research explores reactivity patterns that may share common characteristics in catalysis and enzymology, to indirectly address mechanistic questions arising from emerging classes of enzymes involved in amination reactions. The eventual outcome of the proposed activities is to introduce novel reagents in the arsenal of the synthetic chemist, deriving from the abundant first-row transition elements, and aspiring to surpass or complement current C–N bond construction methodologies in terms of scope, selectivity, and mechanistic insight.