2025/10/03 by Bittu Chandra, Chupeng Li, Mursaleem Ansari +5 · 1 voice
Chemistry · Pharmacology, Toxicology and Pharmaceutics · #Metal-Catalyzed Oxygenation Mechanisms #Fluorine in Organic Chemistry #Synthesis and Catalytic Reactions
paper · doi:10.1021/acscatal.5c04331
openalex publication_date 2025/10/03 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/27
Fe IV ═O units found in the active sites of nonheme iron oxygenases and related synthetic analogs are intriguing intermediates capable of performing challenging oxygenation reactions. The first crystal structure of such a crucial species in a synthetic complex, [Fe IV (O anti )(TMC)(MeCN)] 2+ ( TMC- anti ), reported in 2003, utilizes a 14-TMC (tetramethylcyclam) N 4 -macrocyclic ligand. With a half-life of 10 h at 25 °C, TMC- anti is quite a sluggish oxidant, but axial ligand replacements enhance TMC- anti reactivity by as much as 50-fold. Herein we switch to an N 4 -equatorial modification approach by replacing the N -methyl groups in TMC- anti with N–CH 2 –aryl groups and fluorinated analogs in the secondary coordination sphere to generate even more reactive Fe IV (O)L complexes, namely [Fe IV (O anti )(TB F8 C)(MeCN)] 2+ ( 2- anti, t 1/2 = 6 min at 25 °C), [Fe IV (O syn )(TB F8 C)(MeCN)] 2+ ( 2- syn, t 1/2 = 2 min at 25 °C) and [Fe IV (O syn )(TB F8 C)(Cl)] + ( 3- syn, t 1/2 = 1.5 min at −20 °C). Surprisingly, despite the increased steric bulk introduced around the Fe IV ═O moiety, 2- syn and 3- syn exhibit reaction rates as much as a million-fold higher than TMC- anti in C–H bond cleavage as well as oxo-transfer reactions, including unprecedented catalytic epoxidation of olefins by 2- syn . Computations confirm the dramatic reactivity enhancement upon introduction of polyfluorinated arenes into the second coordination sphere of the nonheme Fe IV ═O complexes, which distort the Me 4 cyclam that decreases the energy gap between the ground S = 1 and the excited S = 2 spin states.