Biologically inspired non-heme iron-catalysts for asymmetric epoxidation; design principles and perspectives

Abstract

Iron coordination complexes with nitrogen and oxygen donor ligands have long since been known to react with peroxides producing powerful oxidizing species. These compounds can be regarded as simple structural and functional models of the active sites of non-heme iron dependent oxygenases. Research efforts during the last decade have uncovered basic principles and structural coordination chemistry motifs that permit us to control the chemistry that evolves when these iron complexes react with peroxides, in order to provide powerful metal-based, but at the same time selective, oxidising agents. Oxidation methodologies with synthetic value are currently emerging from this approach. The current review focuses on asymmetric epoxidation, a reaction which has large value in synthesis, and where iron/H2O2 based methodologies may represent not only a sustainable choice, but may also expand the scope of state-of-the-art oxidation methods. Basic principles that underlay catalyst design as well as H2O2 activation are discussed, whilst limitations and future perspectives are also reviewed.

Non‐Heme Imine‐Based Iron Complexes as Catalysts for Oxidative Processes

“…[11][12][13][14][15][16][17][18][19][20][21][22][23] These complexes proved to be also excellent catalysts for epoxidation [24][25][26][27][28][29][30][31] or cis-dihydroxylation [32][33][34][35][36][37][38] of olefins. Such catalysts offer several advantagesw hen compared to the currently used catalytic systems:( i) the abundant, cheap and environmentally friendly iron and H 2 O 2 are used as the metal centera nd the terminal oxidant, respectively,( ii)aselective, metal-based oxidation mechanism devoid of free diffusing radical formation is mostly operating, [13,[39][40][41][42] which ensures ag ood degree of selectivity by manipulation of the catalyst structure, [14,17,43] (iii)i nm any cases,s ynthesis of non-heme amine-based iron complexes is significantly less demanding than that of metalloporphyrin heme model complexes.…”

A bottom up approach towards artificial oxygenases by combining iron coordination complexes and peptides

“…2, 18 Highly enantioselective epoxidations, including those of notoriously difficult substrates have been recently described, but the current substrate scope remains narrow. 19–26 A current limitation of this approach is the high sensitivity of the H 2 O 2 activation reaction to the catalyst structure. Unproductive consumption of H 2 O 2 , often accompanied by generation of highly reactive radicals is very commonly observed when modest changes are made in the first coordination sphere of the effective catalysts.…”

“…Key to this approach are recent reports describing synergistic cooperation of carboxylic acids and chiral iron catalysts in activating H 2 O 2 to perform selective C-H and C=C oxidation reactions (Scheme 2d). 26 …”

Iron Catalyzed Highly Enantioselective Epoxidation of Cyclic Aliphatic Enones with Aqueous H2O2

“…[1][2][3][4] Catalytic epoxidation methodologies based on iron complexes and peroxides (especially H 2 O 2 ), which can be considered as biologically inspired, are interesting because of the availability and low environmental impact of these reagents. [5][6][7][8][9][10][11][12][13][14][15]16 Despite appealing, the approach is challenging because it requires the design of iron coordination complexes that can activate the O-O bond of peroxides to create selective metal based oxidants, and avoid the often facile production of hydroxyl radicals via the Fenton reaction. 10,11,17,18 Recent reports have disclosed successful examples where asymmetric epoxidation is accomplished, in some cases producing high levels of stereoselectivity ( Figure 1).…”

“…In this regard, an iron catalyzed H 2 O 2 -activation methodology was envisioned as a potential option because they commonly entail powerful, fast reacting oxidants. 12 On the other hand, the high reactivity of this kind of systems can be rapidly recognized as a challenging aspect for elaborating them into highly enantioselective catalysts. Herein we face some of these challenges by describing the first example of an iron catalyst that epoxidizes cyclic aliphatic enones in high yields and with good to excellent stereoselectivities, employing H 2 O 2 as oxidant.…”