Natural model: The synthesis of a close structural analogue of the active site of [Fe]‐hydrogenase is described (see structure; C gray, H dark blue, Fe green, N light blue, O red, S yellow). Nature most probably constructs the five membered ferracyclic ring to poise the 2‐hydroxy pyridine substituent in a position to assist the heterolytic cleavage of dihydrogen, and the accessibility of the analogue should now provide opportunities for probing this.

The [Fe]-hydrogenase, also known as “H2-forming methylenetetrahydromethanopterin dehydrogenase” (Hmd) or “iron-sulfur cluster-free hydrogenase”, is the third distinct class of hydrogenase enzyme to be discovered. In the presence of its carbocation substrate, it catalyzes the reversible cleavage of dihydrogen into H+ and H-, placing the later concomitantly onto the substrate molecule. This review describes the emerging chemistry behind this fascinating enzyme

The active site of the [Fe]-hydrogenase features an iron(II) centre bearing cis carbonyl groups and a chelating pyridine-acyl ligand. Reproducing these unusual features in synthetic models is an intriguing challenge, which will allow both better understanding of the enzymatic system and more fundamental insight into the coordination modes of iron. By using the carbamoyl group as a surrogate for acyl, we have been able to synthesize a range of ferracyclic complexes. Initial reaction of Fe(CO)4Br2 with 2-aminopyridine yields a complex bearing a labile solvent molecule, which can be replaced by stronger donors bearing phosphorus atoms to produce a number of derivatives. Introduction of a hydroxy group using this method is unsuccessful both with a free OH group and when this is silyl-protected. In contrast, the analogous reactions starting from 2,6-diaminopyridine does allow synthesis of complexes bearing a pendant basic group.

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