Development of First-Row Transition-Metal Catalysts for Selective Nitrene/Carbene-Transfer Chemistry

项目摘要/摘要 所提议的研究计划的首要目标是综合和机械地调查 用于活化和未活化C-H分子间选择性胺化和烷基化反应的新型金属试剂 键，通过氮化/类硝化和卡宾转移催化。拟议的工作依赖于系统的 涉及配基开发和氧化还原活性的第一排过渡元素(Mn，Fe，Co， 铜)，与广泛的N和C给体来源一起工作，以实现选择性的催化剂- 受控的C-H键官能化。由此产生的功能在自然和 合成产品，包括药品、农用化学品、催化剂和其他固态材料。这个 研究计划将针对三个具体目标。首先，三脚架和三脚架家族的新成员 将合成两足配体，以便在轴向和轴向结合新的元素和残基 赤道配位场，用于调节一个化合物的亲电性和空间特性 C-H胺化和烷基化的推定金属-硝基/类硝基和卡宾部分， 分别进行了分析。一系列三脚架和双脚架金属试剂将与非贵重元素(MnII， FeII，CoII，Cui)，具有负电荷和正电荷，以及广泛的立体电子 和立体化学属性(包括手性位置)，以控制反应性和促进C-H的区分 债券。第二，前一项任务中获得的金属试剂将进行催化胺化和 与具有电子和空间多样性的硝烯(或类硝烯)和卡宾的烷基化反应 供体来源，以进一步影响催化反应的反应性和选择性。催化C-H 将大力推行胺化和烷基化，重点是区分苄基和烷基化。 第三级站点，但也在追求挑战Tert/sec/Prim-C-H键的功能化，为 希望将轻烃原料纳入合成战略的未来研究。第三，金属- 以及与已确定的最有希望的胺化和烷基化催化剂相关的底物中心事件 在第二个任务中，将从机械和计算方面进行研究，以进行鉴定和光谱分析 表征负责执行任务的活性实体，可能是金属-氮化物或-卡宾单元 C-H激活。该活化剂相对于底物的操作模式将进一步探讨 立体化学探针和诊断技术的武器库，以确定C-H键插入 以协调或逐步的方式发生，并表征中间体的性质和寿命。

Project Summary/Abstract The overarching goal of the proposed research program is to synthesize and mechanistically investigate new metal reagents for the selective intermolecular amination and alkylation of activated and unactivated C–H bonds, by means of nitrene/nitrenoid and carbene transfer catalysis. The proposed work relies on systematic catalyst design that involves ligand development and redox active first-row transition elements (Mn, Fe, Co, Cu), operating in conjunction with a wide range of N- and C-donor sources to achieve selective, catalyst- controlled C–H bond functionalization. The resulting functionalities are found in abundance in natural and synthetic products, including pharmaceuticals, agrochemicals, catalytic and other solid-state materials. The research program will be targeting three specific aims. First, new members of a growing family of tripodal and bipodal ligands will be synthesized, in order to incorporate novel elements and residues along the axial and equatorial ligand field for the purpose of modulating the electrophilicity and steric characteristics of a presumptive metal-nitrene/nitrenoid and carbene moiety responsible for C–H aminations and alkylations, respectively. A series of tripodal and bipodal metal reagents will be generated with nonprecious elements (MnII, FeII, CoII, CuI), featuring both negative and positive overall charges, along with a wide range of stereoelectronic and stereochemical attributes (including chiral sites), to control reactivity and facilitate discrimination of C–H bonds. Secondly, the metal reagents obtained in the previous task will be engaged in catalytic amination and alkylation reactions with an electronically and sterically diversified panel of nitrene (or nitrenoid) and carbene donor sources, to further influence the reactivity and selectivity of the catalytic reactions. Catalytic C–H aminations and alkylations will be vigorously pursued, with emphasis on differentiation between benzylic and tertiary sites, but also in pursuit of functionalization of challenging tert/sec/prim-C–H bonds, paving the way for future research that aspires to incorporate light hydrocarbon feedstock in synthetic strategies. Thirdly, metal- and substrate-centered events associated with the most promising amination and alkylation catalysts identified in the second task, will be investigated mechanistically and computationally to identify and spectroscopically characterize the active entity, presumably a metal-nitrene or -carbene unit, that is responsible for performing C–H activation. The mode of operation of this active agent vis-à-vis the substrate will be further explored with an arsenal of stereo-chemical probes and diagnostic techniques, to determine whether C–H bond insertion occurs in a concerted or stepwise fashion, and characterize the nature and lifetime of intermediates.