Title: M2O2 Diamond Core: the Next Generation of Biomimetic Transition-metal Catalyst for Effective and Selective Aliphatic Hydrocarbon Functionalization. The selective installation of functional groups onto inert aliphatic carbon centers is a key step in many metabolic transformations, and finds many uses in the synthesis of pharmaceuticals, clinical reagents, materials and agrochemicals. For example, the halogenated biomolecules and drug candidates are expected to be more metabolically stable and have improved target-binding affinities. The introduction of the azide group, on the other hand, provides a convenient way to access a variety of functionalities through redox chemistry and the azide-alkyne cycloaddition reaction (?click chemistry?). In biological systems the functionalization of C?H bonds is catalyzed by metalloenzymes that utilize mono- or multi-nuclear active sites and employ earth-abundant transition metals. One representative example is the ?-ketoglutarate dependent nonheme halogenase SyrB2 that activates O2 as the natural oxidant and specifically converts a C?H bond to a C?Cl bond through a high-valent Cl?FeIV=O intermediate. A recent development has even shown that SyrB2 could carry out aliphatic C?N bond formation reactions, suggesting that this radical-based reaction pathway might be considered as a universal strategy for aliphatic C?H bond functionalization. While this enzymatic strategy appears highly attractive in designing biomimetic catalytic systems; great challenges exist for synthetic systems, which lack the enzymatic scaffold, in controlling the transfer of the functional group selectively onto the target carbon center. Competition between the functional group ?X and the ?OH group generated by the initial C?H bond cleavage from the substrate normally resulted in a reaction mixture composed of multiple products. In order to tackle these challenges, the proposed research is inspired by natural metalloenzymes that utilize dinuclear active sites possessing a specific M2(-O)2 ?diamond core? structure, and recent biomimetic studies showing that the M2(-O)2 ?diamond core? could be activated to release higher oxidizing ability upon interacting with Lewis bases. The proposed dinuclear synthetic catalysts would have a M2(-O)2 ?diamond core?, where the two metals function in a cooperative manner in the catalytic cycle. This project also integrates attractive features of high-valent metal-oxo chemistry for late-transition metals (Co, Ni) as active C?H bond cleaving oxidants. Specifically, the project contains three aims. The goal of the first aim is to design and evaluate the catalytic system, including synthesizing and characterizing ligands and catalysts, optimizing experimental conditions, expanding the substrate scope and the identity of the functional group, and investigating the reaction mechanism and the ligand effect on the catalytic activity. In the second aim, efforts will be devoted to the independent generation and characterization of high-valent late-transition metal-oxo intermediates involved in the catalytic cycle. The focus of the third aim is to investigate discriminating factors that affect functional group transfer and the selectivity, including the oxidation state of the metal and the configuration of the open core structure upon interacting with the functional group.
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