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Abstract
Carboxylate-ligated, non-haem iron enzymes demonstrate the capacity for catalysing such remarkable processes as hydroxylations, chlorinations and desaturations of inert, aliphatic C–H bonds. A key to functional diversity is the enzymes' ability to divert fleeting radicals towards different types of functionalization using active site and/or substrate modifications. We report that a non-haem iron hydroxylase catalyst [Fe(PDP)] can also be diverted to catalytic, mixed hydroxylase/desaturase activity with aliphatic C–H bonds. Using a taxane-based radical trap that rearranges under Fe(PDP) oxidation to furnish a nortaxane skeleton, we provide the first direct evidence for a substrate radical using this class of stereoretentive hydroxylation catalysts. Hydroxylation and desaturation proceed by means of a short-lived radical that diverges in a substrate-dependent manner in the presence of carboxylic acids. The novel biomimetic reactivity displayed by this small molecule catalyst is harnessed to diversify natural product derivatives as well as interrogate their biosynthetic pathways. Non-haem iron catalyst [Fe(PDP)] promotes mixed oxygenase/desaturase activity from unactivated, aliphatic C–H bonds. This novel reactivity is substrate dependent, relying on the presence of a carboxylic acid, and proceeds via a short-lived carbon-centred radical. Direct evidence for this intermediate is provided through rearrangement of a novel taxane-based radical probe. Cite this article
Bigi, M., Reed, S. & White, M. Diverting non-haem iron catalysed aliphatic C–H hydroxylations towards desaturations. Nature Chem 3, 216–222 (2011). https://doi.org/10.1038/nchem.967 