The non-heme iron halogenases CytC3 and SyrB2 catalyze C-H bond halogenation in the biosynthesis of some natural products via S = 2 oxoiron(IV)-halide intermediates. These oxidants abstract a hydrogen atom from a substrate C-H bond to generate an alkyl radical that reacts with the bound halide to form a C-X bond chemoselectively. The origin of this selectivity has been explored in biological systems but has not yet been investigated with synthetic models. Here we report the characterization of S = 2 [FeIV(O)(TQA)(Cl/Br)]+ (TQA = tris(quinolyl-2-methyl)amine) complexes that can preferentially halogenate cyclohexane. These are the first synthetic oxoiron(IV)-halide complexes that serve as spectroscopic and functional models for the halogenase intermediates. Interestingly, the nascent substrate radicals generated by these synthetic complexes are not as short-lived as those obtained from heme-based oxidants and can be intercepted by O2 to prevent halogenation, supporting an emerging notion that rapid rebound may not necessarily occur in non-heme oxoiron(IV) oxidations.
Bibliographical noteFunding Information:
We thank NSF for funding (CHE-1361773 to L.Q.), the University of Minnesota for a doctoral dissertation fellowship to M.P., the Indo?U.S. Science & Technology Forum for a postdoctoral fellowship to A.N.B., and Ms. Jale Ocal for results on cyclohexane oxidation by [FeIV(O)(TPA)(MeCN)]2+.