Aliphatic C–H Bond Halogenation by Iron(II)-α-Keto Acid Complexes and O₂: Functional Mimicking of Nonheme Iron Halogenases

Abstract

α-Ketoglutarate-dependent nonheme halogenases catalyze the halogenation of aliphatic C-H bonds in the biosynthesis pathway of many natural products. An iron(IV)-oxo-halo species has been established as the active oxidant in the halogenation reactions. With an objective to emulate the function of the nonheme halogenases, two iron(II)-α-keto acid complexes, [(phdpa)Fe(BF)Cl] (1) and [(1,4-tpbd)Fe(BF)Cl] (2) (where phdpa = N,N-bis(2-pyridylmethyl)aniline, 1,4-tpbd = N,N, N',N'-tetrakis(2-pyridylmethyl)benzene-1,4-diamine, and BF = benzoylformate), have been prepared. The iron complexes are capable of carrying out the oxidative halogenation of aliphatic C-H bonds using O as the terminal oxidant. Although the complexes are not selective toward C-H bond halogenation, they are the only examples of nonheme iron(II)-α-keto acid complexes mimicking the activity of nonheme halogenases. The dinuclear complex (2) exhibits enhanced reactivity toward C-H bond halogenation/hydroxylation.

Non‐Heme‐Iron‐Mediated Selective Halogenation of Unactivated Carbon−Hydrogen Bonds

“…[ 10 , 11 , 12 ] Various small‐molecule non‐heme‐iron complexes have been established as mechanistic models for non‐heme‐iron halogenases and/or have been shown to be able to halogenate alkanes in presence of oxidants such as H 2 O 2 or oxygen atom transfer agents [e. g., iodosylbenzene (PhIO) or meta‐chloroperoxobenzoic acid (mCPBA)]. [ 13 , 14 , 15 , 16 , 17 , 18 ] There are few examples, where the natural oxidant dioxygen is used to produce high‐valent oxido complexes,[ 19 , 20 , 21 ] and examples of halogenase mimics that operate by mechanisms different from that observed in the enzymes have also been described. [22] …”

Enhancing Chemo- and Stereoselectivity in C–H Bond Oxygenation with H2O2 by Nonheme High-Spin Iron Catalysts: The Role of Lewis Acid and Multimetal Centers

“…Taking lessons from these enzymes, multinuclear complexes gained attention because of their fascinating structural, magnetic, and electronic properties . Interactions between multiple metal centers in close proximity result in useful properties (e.g., cooperative electronic and steric effects), exhibiting enhanced catalytic processes compared to the mononuclear systems. − However, such an effect in bioinspired oxidation catalysis is less explored.…”

Recent Advances in First‐Row Transition‐Metal‐Mediated C−H Halogenation of (Hetero)arenes and Alkanes

“…[(phdpa)Fe(BF)Cl] ( 18) and [ (1,4-tpbd)Fe 2 (BF) 2 Cl 2 ] (19)(Figure 3) using phdpa (N,N,bis(2-pyridylmethyl)benzene-1,4-diamine), BF (benzoyl formate) and 1,4-tpbd (N,N,N',N'-tetrakis(2-pyridylmethyl)benzene-1,4-diamine]) as ligands for oxidative halogenation of aliphatic CÀ H bond by employing oxygen as terminal oxidant. [107] Formation of the corresponding halogenated product was observed along with generation of hydroxylated or oxidized product. This formation of the oxidized product can be explained on the basis of strong iron-chloro bond followed by slow chloride radical rebound towards the substrate derived alkyl radical.…”

“…Followed by that, the same group developed two non‐heme iron(II)‐α‐keto acid complex, eg. [(phdpa)Fe(BF)Cl] ( 18 ) and [ (1,4‐tpbd)Fe 2 (BF) 2 Cl 2 ] ( 19 )(Figure 3) using phdpa (N,N,‐bis(2‐pyridylmethyl)benzene‐1,4‐diamine), BF (benzoyl formate) and 1,4‐tpbd (N,N,N′,N’‐tetrakis(2‐pyridylmethyl)benzene‐1,4‐diamine]) as ligands for oxidative halogenation of aliphatic C−H bond by employing oxygen as terminal oxidant [107] . Formation of the corresponding halogenated product was observed along with generation of hydroxylated or oxidized product.…”