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.

项目概要/摘要 拟议研究计划的总体目标是综合和机械地研究 用于活化和未活化 C-H 的选择性分子间胺化和烷基化的新型金属试剂 键，通过氮宾/氮烯类化合物和卡宾转移催化。所提出的工作依赖于系统。 催化剂设计，涉及配体开发和氧化还原活性第一行过渡元素（Mn、Fe、Co、 Cu)，与各种 N 和 C 供体源结合使用，以实现选择性、催化剂- 受控的 C-H 键功能化在天然和化学物质中大量存在。 合成产品，包括药品、农用化学品、催化和其他固态材料。 研究计划将针对三个具体目标：第一，不断壮大的三足动物家族的新成员。 将合成双足配体，以便沿轴向和新方向结合元素和残基 赤道配体场，用于调节亲电性和空间特征 推定的金属氮烯/氮烯类化合物和卡宾部分负责C-H胺化和烷基化， 一系列三足和双足金属试剂将与非贵金属元素（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（包括手性位点），以控制反应性并促进 C-H 的区分 其次，上一任务中获得的金属试剂将进行催化胺化反应。 与电子和空间多样化的氮烯（或类氮烯）和卡宾进行烷基化反应 供体来源，进一步影响催化 C-H 反应的反应性和选择性。 将大力发展胺化和烷基化，重点是区分苄基和烷基化 三级位点，同时也在追求具有挑战性的叔/秒/prim-C-H键的功能化，为 未来的研究希望将轻质烃原料纳入合成策略中。 以及与最有前途的胺化和烷基化催化剂相关的以底物为中心的事件 在第二项任务中，将通过机械和计算方法进行研究，以识别和光谱分析 表征活性实体，大概是金属氮烯或卡宾单元，负责执行 该活性剂相对于底物的作用模式将进一步探索。 立体化学探针和诊断技术库，以确定 C-H 键插入是否存在 以协调或逐步的方式发生，并表征中间体的性质和寿命。