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

用于选择性氮烯/卡宾转移化学的第一行过渡金属催化剂的开发

• 批准号: 10045351
• 负责人: Pericles Stavropoulos
• 金额: $ 45.45万
• 依托单位: MISSOURI UNIVERSITY OF SCIENCE & TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10045351
• 关键词: Active Sites; Address; Agrochemicals; Alkylation; Amination; Apical; Catalysis; Characteristics; Charge; Chemicals; Chemistry; Collaborations; Computing Methodologies; Development; Diagnostic; Diagnostic Procedure; Discrimination; Electrons; Elements; Engineering; Environment; Evaluation; Event; Family; Goals; Hydrocarbons; Hydrogen Bonding; Intervention; Libraries; Ligands; Light; Literature; Mediating; Metals; Methodology; Nature; Outcome; Oxidation-Reduction; Pathway interactions; Pharmacologic Substance; Process; Reaction; Reagent; Research; Research Activity; Science; Series; Site; Source; Structure; Targeted Research; Techniques; Texas; Thermodynamics; Transition Elements; Universities; Work; c new; carbene; catalyst; cold temperature; computer studies; design; diagnostic panel; driving force; electronic structure; functional group; member; nitrene; novel; operation; preference; programs; scaffold; solid state

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.

项目摘要/摘要 拟议的研究计划的总体目标是合成和机械研究 用于选择性分子间分析和酗酒的新金属试剂激活和未激活的C – H 键，通过硝基/硝酸盐和卡宾转移催化剂。拟议的工作依赖于系统 涉及配体发育和氧化还原活性第一行跃迁元件的催化剂设计（Mn，Fe，Co， Cu），与广泛的N-和C-Donor来源一起运行，以实现选择性，催化剂 - 受控的C – H键功能化。在自然和 合成产品，包括药品，农业化学，催化和其他固态材料。 研究计划将针对三个具体目标。首先，越来越多的三座家族的新成员 将合成两种配体，以纳入新的元素并沿轴向保留，并保留 赤道配体场是为了调节A的亲电性和空间特征 负责C – H氨和烷基化的假定金属硝基/硝酸盐和卡宾部分 分别。一系列的三座和两种金属试剂将以非私致元素（MNII，，MNII， FEII，COII，CUI），具有负和正电荷，以及广泛的立体电子 和立体化学属性（包括手性位点），以控制反应性并促进C – H的歧视 债券。其次，在上一个任务中获得的金属试剂将参与催化分析和 烷基化反应与硝酸（或硝酸盐）和碳烯的电子和空间多样化面板 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 氨和烷基化将被大力追求，重点是苯并和烷基化 三级站点，但也要追求挑战者tert/sec/prim-c – h键的功能化，为 未来的研究渴望将光烃原料纳入合成策略。第三，金属 - 以及以底物为中心的事件，与确定的最有希望的胺化和酗酒催化剂有关 在第二个任务中，将通过机械和计算进行研究以识别和光谱 表征主动实体，大概是金属 - 硝基或 - 碳烯单元，负责执行 C – H激活。该活性代理相对于基板的操作方式将进一步探索 立体化学问题和诊断技术的武库，以确定C – H键是否插入 以一致或逐步的方式发生，并描述了中间体的性质和寿命。