The Development and Study of Practical C-H Functionalization Reactions Using Mechanistic Tools

Abstract

The unactivated C-H bonds of hydrocarbons are some of the most common chemical functionalities in organic molecules. Despite their ubiquity, they are some of the most difficult functional groups to manipulate because of their kinetic inertness, stemming from the strong non-polar C-H bond. The focus of this work is the development and mechanistic study of processes that break strong C-H bonds in a selective manner.

Sulfonated oxoFeIV porphyrins (models of the compound II state of CYP) are shown to be basic with measureable pKa values. This measured pKa represents a novel two-proton electromeric equilibrium between oxoFeIV porphyrin and the corresponding (OH2)2FeIII porphyrin cation radicals. The nature of this equilibrium, in combination with the empirical observation of both substrate and solvent-derived deuterium kinetic isotope effects, indicates a new mode of C-H bond scission. The solvent-proton-assisted, proton-coupled electron transfer proposed leads to a net increase in the thermodynamic driving force of C-H cleavage when compared to a single proton model. An extension of this work shows that sulfonated iron porphyrins were shown to have oxidation behavior, which was highly dependant upon both the electronics of the porphyrin ring and the novel two-proton pKa.

The mechanism of a reaction system that utilizes combinations of high-valent iodine oxides and catalytic amounts of chloride to selectively oxidize methane was determined to function via a radical pathway. Mechanistic studies suggest a catalytic cycle where alkyl radicals generated by hydrogen atom abstraction from chlorine atoms are able to react with iodine generated in situ. The transiently formed alkyl iodide then undergoes solvolysis to yield the product ester. This process of radical based C-H ester formation is extended to substrates containing benzylic C-H bonds by replacing the catalyst with the well-studied N-oxyl catalyst N-hydroxyphthalimide (NHPI). This NHPI-iodate system was shown to be effective in the functionalization of primary and secondary benzylic C-H bonds in moderate to good yield.