Prediction and control of reaction selectivity, a key requirement in late-stage C-H functionalization, is usually challenging as it requires to distinguish a specific C-H bond from many others with similar reactivity. Among available methodologies employed to overcome these challenges, those based on supramolecular catalysts, biomimetic models of natural enzymes, appear particularly promising. A strategy for predictable, remote C-H oxidation based on a nonheme Mn or Fe catalyst (1) functionalized with a benzo-18-crown-6 receptor, able to bind protonated primary amine substrates, has been recently developed by our research group. In this project we plan the synthesis of new supramolecular catalysts for recognition-driven remote C-H oxidation in which the crown ether recognition units are linked to both radical-like (nonheme-iron(IV)-oxo complex, (N4Py)FeIV=O) and radical (phthalimide-N-oxyl radical, PINO) hydrogen atom transfer (HAT) reagents. Catalyst 2, in which the stable iron-oxo complex (N4Py)FeIV=O is linked to the crown ether, will allow to measure and compare the rates of HAT from C-H bonds to the FeIV=O unit in the presence and absence of substrate binding. Effective molarities (EM), determined by the ratio of kinetic constants for the intramolecular and intermolecular processes, will provide us useful information on the effect of intramolecularity on the HAT reactivity and lay the foundation for the rational design of novel supramolecular catalysts. In supramolecular catalysts 3 and 4, the 18-crown-6 ether recognition unit will be linked to N-hydroxyphthalimide (NHPI), precursors of the HAT reagent PINO. The lack of metal ions in these supramolecular catalysts, will expand the substrate scope to other organic compounds, such as carboxylates, which can coordinate the metal ions in the catalytic center and inhibit metal-based supramolecular catalysts.
