Research & Initiatives

Biomimetic Oxidation of Unactivated Alkyl C-H bonds

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Chemoselective oxidation of alkyl C–H bonds in complex natural products under mild conditions have the power to reorient biomimetic natural product synthesis. Non-heme iron complexes bearing tetradentate N-donor ligands with cis labile sites, mimicking the active site of Rieske Dioxygenase enzymes, show great promise for chemoselective aliphatic C−H hydroxylation. However formidable hurdle that limits their widespread application include obtaining high levels of positional selectivity and expanding the substrate scope to include complex structures. Our laboratory works on the development of a peroxidase mimicking Fe-complex based on the bTAML macrocyclic ligand framework (Fe-bTAML), that perform selective oxidation of unactivated 3° bonds with unprecedented regioselectivity (3°:2° of 110:1 for adamantane oxidation), high stereoretention (99%), and high turnover numbers (TONs up to 300) using mCPBA/NaOCl/O2 as the oxidant.

 

 

 

 

 

 

 

 

 

 

Understanding reactivity of high-valent metal-oxo intermediates

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High valent iron-oxo intermediates play key roles in enzymatic oxidations. For example, in the cytochrome P450 enzymes, the high valent FeIV(O)(porphyrin radical-cation), isoelectronic with FeV(O), has been shown to be the reactive intermediate in the selective hydroxylation of camphor.  In the Rieske dioxygenase enzyme family an FeV(O) active intermediate has been proposed. FeV(O) has also been proposed as the reactive intermediate for several oxidation reactions catalysed by Fe-based non-heme complexes. We have successfully synthesized an FeV(O) complex of a biuret-containing Fe-TAML complex at room temperature. This complex displays remarkably higher stability at room temperature. This higher stability has allowed us to study oxidation reactions with unactivated aliphatic C-H bonds, O-H bonds and olefins and at room temperature.