Rational Design of Bioinspired Catalysts for Selective Oxidations

Abstract

Recognizing Nature’s unique ability to perform challenging oxygenation reactions with exquisite selectivity parameters at iron-dependent oxygenases, chemists have long sought to understand and mimic these enzymatic processes with artificial systems. In the last two decades, replication of the reactivity of non-heme iron oxygenases has become feasible even with simple coordination complexes of iron and manganese. A bona fide minimalistic functional model was the tetradentate-N4 ligand based iron complex [Fe­(tpa)­(CH3CN)2]2+(Fe­(tpa), tpa = tris­(2-methylpyridyl)­amine), which activates H2O2 via a mechanism that mirrors key steps of enzymatic O2 activation processes at mononuclear iron centers: controlled O–O bond cleavage, generation of a high-valent FeO oxidant, and promotion of almost the full spectrum of its oxidative reactivity (C–H hydroxylation, olefin epoxidation, syn-dihydroxylation, and desaturation). These landmark discoveries set the mechanistic framework to use iron coordination complexes with nitrogen-rich ligands as catalysts for oxidizing organic substrates under synthetically relevant conditions. Due to proof-of-concept demonstrations of the potential of these catalysts in organic synthesis, this chemistry has flourished over the past decade. In parallel to the realization of the potential of this class of catalysts in diverse organic transformations, effort has been spent to manipulate the catalyst structure with the aim of tuning both the reactivity and selectivity of the oxidation reactions. This perspective provides an overview of the progress of this research. Some key features of the archetypical Fe­(tpa) catalyst have stayed surprisingly true throughout this evolution, but a series of alterations that modulate its electronic, steric, or binding properties allowed a rational elicitation of a specific reactivity or selectivity. In some cases, the replacement of iron by manganese has also proven beneficial. Overall, the rational optimization of the catalyst structure has enabled the development of highly asymmetric olefin epoxidation, syn-dihydroxylation, and site-selective and even enantioselective C–H oxidation reactions.

A bioinspired oxoiron(iv) motif supported on a N2S2 macrocyclic ligand

“…For over 40 years, small-molecule complexes synthesized as active-site models of the high-valent intermediates in heme and non-heme oxygenases have advanced our understanding of the catalytic cycles. 3,[11][12][13][14][15][16][17][18][19][20] Despite these efforts, the synthesis of an oxoiron(IV) porphyrin complex with a thiolate ligand has not yet been achieved. Furthermore, [(TMCS)Fe IV (O)] + (TMCS = 1-mercaptoethyl-4,8,11-trimethyl-1,4,8,11-tetraazacyclotetra-decane; (Scheme 1)), represents the only synthetic complex 21 thus far to model the RS-Fe IV QO unit associated with the active oxidants of cytochrome P450 2,6 and chloroperoxidase.…”

Recent Trends and Prospects in Homogeneous Manganese‐Catalysed Epoxidation

“…More recently, Costas and coworkers extensively analyzed the structural evolution of Mn and Fe catalysts bearing N 4 -tetradentate ligands enclosing all the recent developments that emerged in tuning the catalytic reactivity and selectivity. [31] Scheme 9. Olefin epoxidation with Mn-SR-mesoPYBP(ClO 4 ) 2 .…”

Recent Advances on Catalytic Osmium‐Free Olefin syn‐Dihydroxylation

“…Therefore, bio‐inspired nonheme iron catalysis has been studied and developed intensively particularly over the past 10 years, showing great potential for such transformations (racemic and asymmetric). [ 57 ] Finally, combined with their selectivity and to the fact that iron is one of the most abundant metals on earth, it makes the development of such complexes very attractive for future sustainable economic growth. Several excellent reviews covering non‐heme iron oxidation reactions have been recently published, [ 7b,53,58 ] therefore we will only focus on the most remarkable results of the last decade.…”