Figure 1.9: Biomimetic[4Fe–4S]cluster highlights.
— The first synthetic [4Fe–4S] cluster (left)[138], the first all-ferric [4Fe–4S] cluster (cen-tre)[142], and the first all-ferrous[4Fe–4S]cluster (right)[160].
the observation of an overall trend to[4Fe–4S]cluster formation.[165, 166]Furthermore, reactions with protons[167, 168], with benzoyl chloride leading to the chloride coordi-nated cluster[169, 170]and with SAM-like sulfonium ions[171]have been studied.
1.6 Missing Pieces: Models for Unusual Fe / S Clusters and Cluster Reactivity – Motivation of this Work
Despite more than three decades of very successful bioinorganic approaches, the bio-mimetic chemistry of small Fe/S clusters, i.e., [2Fe–2S] and [4Fe–4S] clusters, is far from being settled, and there are still challenging tasks. The recent isolation of a model for Rieske type[2Fe–2S]clusters and the also asymmetrically coordinated intermediate are the only successful examples of[2Fe–2S]clusters with heteroleptic coordination of the two iron atoms so far. The approach relies on the steric bulk of one of the biden-tate ligands and on a stepwise synthesis. Minimisation of by-product formation and their separation makes the synthesis of other complexes of this type considerably dif-ficult. Therefore a different approach to asymmetrically coordinated[2Fe–2S] clusters was tested that uses one tetradentate instead of two bidentate ligands. Putative clusters with a tetradentate ligand are expected to have an increased stability compared to clus-ters bearing bidentate or even monodentate ligands. A variety of ligand precursors and [2Fe–2S]clusters of some ligand building blocks are presented in Chapter 2 along with other possible functionalisations of the ligands and their complexes.
ligands.
The importance of interactions other than the obvious coordination between the lig-ands and the cluster core is increasingly appreciated. For this reason the concept of sec-ondary bonding interactions was further extended to genuine five-fold coordination of the iron atoms. A set of suitable ligands and their respective Fe/S clusters was explored and one five-coordinate [2Fe–2S] cluster was thoroughly examined, as is described in Chapter 4.
While the role of Fe/S clusters as the sulphur source in various SAM radical enzymes is widely accepted, analogous biomimetic reactions have not been reported by now. In order to open this field of research, explorative reactions of radicals and synthetic Fe/S clusters have been examined. The first issues that have been addressed include the choice of suitable radical precursors, the possible need for special properties of the employed Fe/S cluster and the means to follow the reaction and to identify reaction products. The first results in this intriguing field of Fe/S cluster chemistry are presented in Chapter 5.
Finally, a closer look at the active centre of biotin synthase was taken. Like the Rieske type[2Fe–2S]clusters the cluster from biotin synthase has an asymmetric coordination environment. Moreover, the unique arginine residue coordinating one of the iron atoms is a highly unusual ligand in enzymes. Since the available crystal structure does not al-low an exact interpretation of the coordination mode of the arginine side chain and of the overall geometry of the cluster, namely the highly exceptional Fe· · ·Fe distance, a theoretical approach was employed to tackle this problem. The focus of this inves-tigation was laid on the protonation state of the arginine’s guanidine group, its exact coordination mode and the reason for the exceptional Fe· · ·Fe distance. These questions and the conclusions that can be drawn from the calculations are described in Chapter 6.
2 [ 2Fe–2S ] Clusters with Allyl-Substituted Biphenolate and Dithiophenolate Ligands
2.1 Introduction
It has been shown that bidentate ligands are generally able to increase the stability of synthetic[2Fe–2S]clusters as compared to monodentate ligands.[172]A tetradentate ligand should stabilise the cluster core even more – in fact, biological Fe/S clusters are stabilised by the protein environment to an extent that they do not desintegrate even when solvent-exposed. A [2Fe–2S] cluster coordinated by a tetradentate ligand might therefore be stable enough to allow for unprecedented biomimetic reactions like proton-coupled electron transfer in a protic solvent.
Moreover, the donor set of tetradentate ligands can be designed to lead to an asym-metrically coordinated [2Fe–2S] cluster. Until the recent isolation of an analogue of Rieske-type [2Fe–2S] clusters in our group,[143] the use of bidentate ligands was not successful in the approach to asymmetrically coordinated[2Fe–2S]clusters.
Furthermore, other interactions are feasible with bidentate ligands bearing further substituents, such as weak interactions with the cluster core. Biological antetypes in-clude hydrogen bonds as well as the interaction with a methionine thioether moiety upon reduction of aRhodobacter capsulatus[2Fe–2S]ferredoxin[89].
Based on these considerations, allyl-substituted biphenols are regarded as versatile building blocks for bidentate ligands allowing further functionalisation to form tetraden-tate ligands.[173, 174]A Miyazaki-Newman-Kwart rearrangement strategy was applied to synthesise the corresponding thiophenol analogues.[175, 176]Both ligand types were em-ployed in the synthesis of[2Fe–2S] clusters. Furthermore, the functionalisation of the allyl groups towards the formation of tetradentate ligands was explored.
ally explored. Thus, the novel analogue 3bwas similarly prepared by using only one equivalent of allyl bromide in the first step of the reaction sequence. After rearrange-ment of the obtained allylether2bat 170 °C, the target compound3bwas obtained in 54 % yield over two steps.
The same route was chosen for the synthesis of thetert-butyl-substituted derivative 3c. The di-tert-butyl substituted biphenol1cis literature-known and was synthesised in two steps.[177] 1cwas then converted to the allylether2clike the parent compound1a.
Rearrangement yielded the target compound3cin 47 % yield over two steps. All new compounds were characterised by1H NMR,13C NMR and IR spectroscopy as well as EI mass spectrometry.
Scheme 2.1: Synthesis of allyl-substituted biphenols3.