Selective C-H Bond Oxidation Catalyzed by the Fe-bTAML Complex: Mechanistic Implications.

Nonheme iron complexes bearing tetradentate N-atom-donor ligands with cis labile sites show great promise for chemoselective aliphatic C-H hydroxylation. However, several challenges still limit their widespread application. We report a mechanism-guided development of a peroxidase mimicking iron complex based on the bTAML macrocyclic ligand framework (Fe-bTAML: biuret-modified tetraamido macrocyclic ligand) as a catalyst to perform selective oxidation of unactivated 3° bonds with unprecedented regioselectivity (3°:2° of 110:1 for adamantane oxidation), high stereoretention (99%), and turnover numbers (TONs) up to 300 using mCPBA as the oxidant. Ligand decomposition pathways involving acid-induced demetalation were identified, and this led to the development of more robust and efficient Fe-bTAML complexes that catalyzed chemoselective C-H oxidation. Mechanistic studies, which include correlation of the product formed with the Fe(O) reactive intermediates generated during the reaction, indicate that the major pathway involves the cleavage of C-H bonds by Fe(O). When these oxidations were performed in the presence of air, the yield of the oxidized product doubled, but the stereoretention remained unchanged. On the basis of O labeling and other mechanistic studies, we propose a mechanism that involves the dual activation of mCPBA and O by Fe-bTAML, leading to formation of the Fe(O) intermediate. This high-valent iron oxo remains the active intermediate for most of the reaction, resulting in high regio- and stereoselectivity during product formation.