Styrene Aziridination with [Co^III(TAML^red)]– in Water; Understanding and Preventing Epoxidation via Nitrene Hydrolysis

Enabling (radical-type) nitrene transfer reactions in water can open up a wide range of (novel) applications, such as the in vivo synthesis of medicines. However, these reactions typically suffer from oxygen-containing side-product formation, of which the origin is not fully understood. Therefore, we investigated aqueous styrene aziridination using a water-soluble [CoIII(TAMLred)]– catalyst known to be active in radical-type nitrene transfer in organic solvents. The cobalt-catalyzed aziridination of styrene in water (pH = 7) yielded styrene oxide as the major product, next to minor amounts of aziridine product. Based on 18O-labeling studies, catalysis and mass spectrometry experiments, we demonstrated that styrene oxide formation proceeds via hydrolysis of the formed nitrene radical complexes. Computational studies support that this process is facile and yields oxyl radical complexes active in oxygen atom transfer to styrene. Based on these mechanistic insights, the pH was adjusted to afford selective aziridination in water.