Intramolecular C–H Oxidation in Iron(V)-oxo-carboxylato Species Relevant in the γ-Lactonization of Alkyl Carboxylic Acids

Abstract

High-valent oxoiron species have been invoked as oxidizing agents in a variety of iron-dependent oxygenases. Taking inspiration from nature, selected nonheme iron complexes have been developed as catalysts to elicit C–H oxidation through the mediation of putative oxoiron(V) species, akin to those proposed for Rieske oxygenases. The addition of carboxylic acids in these iron-catalyzed C–H oxidations has proved highly beneficial in terms of product yields and selectivities, suggesting the direct involvement of iron(V)-oxo-carboxylato species. When the carboxylic acid functionality is present in the alkane substrate, it acts as a directing group, enabling the selective intramolecular γ-C–H hydroxylation that eventually affords γ-lactones. While this mechanistic frame is solidly supported by previous mechanistic studies, direct spectroscopic detection of the key iron(V)-oxo-carboxylato intermediate and its competence for engaging in the selective γ–C–H oxidation leading to lactonization have not been accomplished. In this work, we generate a series of well-defined iron(V)-oxo-carboxylato species (2c–2f) differing in the nature of the bound carboxylate ligand. Species 2c–2f are characterized by a set of spectroscopic techniques, including UV–vis spectroscopy, cold-spray ionization mass spectrometry (CSI-MS), and, in selected cases, EPR and Mössbauer spectroscopies. We demonstrate that 2c–2f undergo site-selective γ-lactonization of the carboxylate ligand in a stereoretentive manner, thus unequivocally identifying metal-oxo-carboxylato species as the powerful yet selective C–H cleaving species in catalytic γ-lactonization reactions of carboxylic acids. Reactivity experiments confirm that the intramolecular formation of γ-lactones is in competition with the intermolecular oxidation of external alkanes and olefins. Finally, mechanistic studies, together with DFT calculations, support a mechanism involving a site-selective C–H cleavage in the γ-position of the carboxylate ligand by the oxo moiety, followed by a fast carboxylate rebound, eventually leading to the selective formation of γ-lactones