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

项目摘要 拟议研究的总体目标是发展和探索一个 用于未官能化烃的胺化的第一行过渡金属试剂的新族。的 所提出的试剂将氮基团（氮烯、酰胺、类氮烯）传递到脂族烃（C-H 键）和烯烃（C = C键）用于构建C-N键。胺化位点存在于过多的 天然和合成产品，包括药物、农用化学品、催化剂和固态 材料，以赋予活性所需的骨架特征和特定功能。的 主要目标将通过三个具体目标来实现，这些目标将平行地、相互地实现。 知情的时尚。首先，将合成立体电子多样性配体支架的新文库， 用作稳固的骨架以锚金属位点，产生二价铁、锰、钴， 一价铜试剂，用作胺化反应的催化剂。第二，金属试剂 将被探索作为催化剂，用于从合适的氮基团（氮烯，酰胺，类氮烯）转移 多功能碳质底物受体（烷烃，烯烃）的前体，导致形成 重要的功能单元（胺、二胺、未保护的氮丙啶）。化学计量反应涉及 将进行金属试剂和氮基源（在不存在底物的情况下）以鉴定 关键的金属中心的中间体负责提供氮基团的基板。三是 最有前途的试剂将进行机械研究，报告转移模式和随后的 这有助于将氮基团单元插入/添加到基底上，并进一步引导催化剂开发，以实现高效的 和选择性胺化。这项拟议中的工作依赖于一个自制的新型金属图书馆的可用性 试剂，具有在C-N键结构方面具有证明记录的成员，但需要扩展到 在合成更宽范围的胺化产物中实现适当水平的选择性。而且 拟议的研究探索了可能在催化中具有共同特征的反应模式， 酶学，间接解决机制问题所产生的新兴类别的酶参与 胺化反应拟议活动的最终结果是在生物技术中引入新试剂。 合成化学家的武器库，从丰富的第一行过渡元素中衍生出来，并渴望 在范围、选择性和 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.