Group Transfer to an Aliphatic Bond: A Biomimetic Study Inspired by Nonheme Iron Halogenases

Abstract

In this work, we predict a group-transfer reaction to an aliphatic substrate on a biomimetic nonheme iron center based on the structural and functional properties of nonheme iron halogenases. Transferring groups other than halogens to C-H bonds on the same catalytic center would improve the versatility and applicability of nonheme iron halogenases and enhance their use in biotechnology; however, few studies have been reported on this matter. Furthermore, very few biomimetic models are known that are able to transfer halogens or other groups to aliphatic C-H bonds. To gain insight into group transfer to an aliphatic C-H bond, we performed a detailed computational study on a biomimetic nonheme iron complex and studied the reactivity patterns with a model substrate (ethylbenzene). In particular, we investigated the reaction mechanisms of [FeIV(O)(TPA)X]+, TPA = tris(2-pyridylmethy1)amine, and X = Cl, NO2, N3 with ethylbenzene leading to 1-phenylethanol and 1-phenyl-1-X-ethane products. Interestingly, we find that the product distributions vary with the nature of the equatorial X-substituent on the metal center. Thus, [FeIV(O)(TPA)NO2]+ reacts with ethylbenzene by dominant hydroxylation of the substrate, whereas with halide/azide in the cis-position a group transfer is more likely. As such, we predict a catalytic mechanism of azidation of aliphatic groups using a biomimetic nonheme iron oxidant. The results have been analyzed with thermochemical cycles, valence bond schemes and electronic assignments of reactants and products, which put our results in a broad perspective and predict the effect of other substituents. Finally, predictions are given on how these systems could be utilized in vivo.