Design and Synthesis of Dinucleating Nitrogen Ligands

描述（由申请人提供）：非血红素二铁活性位点在整个自然界的金属酶中普遍存在。这些活性位点的合成类似物进一步加深了我们对控制这些酶反应性的基本原理的理解。拟议的研究概述了一个一般性的战略，用于在创建这些二铁活性位点的合成类似物，在这种情况下的甲烷氧化酶甲烷单加氧酶（MMO）的活性位点的合成新的，空间位阻双核氮配体的合成。这项工作的影响范围从获得有关这些双金属中心的知识到开发用于烃氧化的小分子催化剂，这些催化剂可能会影响有关精细化学品和药品生产的健康领域。 提出的研究涉及设计的一般策略，用于合成一组结构多样的双核氮配体。这些双螯合配体的结构将基于两个杂环胺官能团，二氢吲哚和异二氢吲哚。钯催化的碳-碳键形成过程的能力将用于以短顺序组装这些配体，并将这些螯合部分安装在空间要求苛刻的环境中。连接两个单齿胺官能团的碳框架将容易变化，从而产生不同的配体组。合成策略将通过从相同中间体产生多个配体集合来增强多样性。分子模拟的结论是，控制手性C2对称和meso二胺的相对立体化学将控制这种新的配体集的空间环境和配位几何形状。

DESCRIPTION (provided by applicant): Non-heme diiron active sites are prevalent in metalloenyzmes throughout Nature. Synthetic analogues of these active sites have furthered our understanding of the fundamental principles that control the reactivity of these enzymes. The proposed study outlines a general strategy for the synthesis of novel, sterically encumbered dinucleating nitrogen ligands for use in the creation of synthetic analogues of these diiron active sites, in this case the active site of the methane-oxidizing enzyme methane monooxygenase (MMO). The implications of this work span from knowledge gained about these dimetallic centers to the development of small molecule catalysts for hydrocarbon oxidation that could impact the health field concerning the production of fine chemicals and pharmaceuticals. The research proposed involves the design of a general strategy for the synthesis of a structurally diverse set of dinucleating nitrogen ligands. The structure of these bischelating ligands will be based upon two heterocyclic amine functionalities, the indoline and isoindoline. The power of palladium catalyzed carbon-carbon bond forming processes will be employed to assemble these ligands in short order and install these chelating moieties inside sterically demanding environments, The carbon framework that links the two monodentate amine functionalities will be readily varied, resulting in the production of a diverse set of ligands. The synthetic strategy will enhance diversity by generating multiple ligand sets from the same intermediate. Molecular modeling concludes that controlling the relative stereochemistry of the chiral C2 symmetric and meso diamines produced will control the steric environment and coordination geometry of this novel ligand set.