cis-Dihydroxylation of Alkenes with Oxone Catalyzed by Iron Complexes of a Macrocyclic Tetraaza Ligand and Reaction Mechanism by ESI-MS Spectrometry and DFT Calculations

Abstract

[Fe(III)(L-N(4)Me(2))Cl(2)](+) (1, L-N(4)Me(2) = N,N'-dimethyl-2,11-diaza[3.3](2,6)pyridinophane) is an active catalyst for cis-dihydroxylation of various types of alkenes with oxone at room temperature using limiting amounts of alkene substrates. In the presence of 0.7 or 3.5 mol % of 1, reactions of electron-rich alkenes, including cyclooctene, styrenes, and linear alkenes, with oxone (2 equiv) for 5 min resulted in up to >99% substrate conversion and afforded cis-diol products in up to 67% yield, with cis-diol/epoxide molar ratio of up to 16.8:1. For electron-deficient alkenes including α,β-unsaturated esters and α,β-unsaturated ketones, their reactions with oxone (2 equiv) catalyzed by 1 (3.5 mol %) for 5 min afforded cis-diols in up to 99% yield with up to >99% substrate conversion. A large-scale cis-dihydroxylation of methyl cinnamate (9.7 g) with oxone (1 equiv) afforded the cis-diol product (8.4 g) in 84% yield with 85% substrate conversion. After catalysis, the L-N(4)Me(2) ligand released due to demetalation can be reused to react with newly added Fe(ClO(4))(2)·4H(2)O to generate an iron catalyst in situ, which could be used to restart the catalytic alkene cis-dihydroxylation. Mechanistic studies by ESI-MS, isotope labeling studies, and DFT calculations on the 1-catalyzed cis-dihydroxylation of dimethyl fumarate with oxone reveal possible involvement of cis-HO-Fe(V)═O and/or cis-O═Fe(V)═O species in the reaction; the cis-dihydroxylation reactions involving cis-HO-Fe(V)═O and cis-O═Fe(V)═O species both proceed by a concerted but highly asynchronous mechanism, with that involving cis-HO-Fe(V)═O being more favorable due to a smaller activation barrier.

One-electron oxidation of an oxoiron(IV) complex to form an [O═Fe V ═NR] + center

“…temperature spectroscopic analysis of catalytic reactions by EPR (30,31) and by mass spectrometry (10,12).…”

“…However, unlike the porphyrin ligand in cytochrome P450, none of the ligands in the nonheme iron active site appears likely to undergo one-electron oxidation to stabilize the high-valent state. Fe V ═O oxidants are also implicated in alkane hydroxylation (6,7), olefin epoxidation and cis-dihydroxylation (8)(9)(10), and water oxidation (11) by bioinspired nonheme iron catalysts supported by neutral tetradentate ligands, and direct evidence for the formation of oxoiron(V) oxidants has been obtained in two cases by mass spectrometry (10,12). Despite the wealth of synthetic oxoiron(IV) complexes identified during the last decade (13), to date there is only one spectroscopically well-characterized example of an oxoiron(V) complex, ½Fe V ðOÞðTAMLÞ − (where TAML is tetraamido macrocyclic ligand), which is stabilized by the tetraanionic nature of the TAML ligand (14).…”

Mechanism and Catalytic Diversity of Rieske Non-Heme Iron-Dependent Oxygenases

“…However, one of the problems with many current iron-based catalysts is that the substrate must be used in excess, creating issues with process scale-up. In an effort to overcome this, Che and co-workers have reported the use of a variety of iron complexes, previously reported as models for catechol dioxygenase by Krüger and co-workers (73, 74), in conjunction with oxone (peroxymonosulphate) rather than hydrogen peroxide as the oxidant. These complexes were used to oxidize a variety of alkenes with good selectivity for the cis -diol and with excellent conversion on a significant scale (~10g) (Figure 15) (74).…”

Formation of a Room Temperature Stable FeV(O) Complex: Reactivity Toward Unactivated C–H Bonds

“…9,14–16 Synthetic functional models of Rieske dioxygenase family of enzymes have been postulated to engage an Fe V (O) reactive species in C—H and C=C bond oxidations. 17,18 Several complexes having Fe V (O) have been reported, and they are thermally not stable above −40 °C. 19,20 Que et al has described the formation of an Fe V (O) complex from [Fe IV (O)(TMC)-(MeCN)] 2+ at −44 °C ( t 1/2 = 60 min).…”