Iron epoxidation

In fact, the chemists working on these compounds wanted only one enantiomer of the irons epoxide—the top left stereoisomer. They were able to separate the trans epoxide from the cis epoxide by chromatography, because they are diastereoisomers. However, because they had made both diastereoisomers in the laboratory from achiral starting materials, both diastereoisomers were racemic mixtures of the two enantiomers. Separating the top enantiomer of the trans epoxide from the bottom one was much harder because enantiomers have identical physical and chemical properties. To get just the enantiomer they wanted the chemists had to develop some completely different chemistry, using enantiomerically pure compounds derived from nature. 

N—Fe(IV)Por complexes. Oxo iron(IV) porphyrin cation radical complexes, [O—Fe(IV)Por ], are important intermediates in oxygen atom transfer reactions. Compound I of the enzymes catalase and peroxidase have this formulation, as does the active intermediate in the catalytic cycle of cytochrome P Q. Similar intermediates are invoked in the extensively investigated hydroxylations and epoxidations of hydrocarbon substrates cataly2ed by iron porphyrins in the presence of such oxidizing agents as iodosylbenzene, NaOCl, peroxides, and air. 

Methylene chloride is one of the more stable of the chlorinated hydrocarbon solvents. Its initial thermal degradation temperature is 120°C in dry air (1). This temperature decreases as the moisture content increases. The reaction produces mainly HCl with trace amounts of phosgene. Decomposition under these conditions can be inhibited by the addition of small quantities (0.0001—1.0%) of phenoHc compounds, eg, phenol, hydroquinone, -cresol, resorcinol, thymol, and 1-naphthol (2). Stabilization may also be effected by the addition of small amounts of amines (3) or a mixture of nitromethane and 1,4-dioxane. The latter diminishes attack on aluminum and inhibits kon-catalyzed reactions of methylene chloride (4). The addition of small amounts of epoxides can also inhibit aluminum reactions catalyzed by iron (5). On prolonged contact with water, methylene chloride hydrolyzes very slowly, forming HCl as the primary product. On prolonged heating with water in a sealed vessel at 140—170°C, methylene chloride yields formaldehyde and hydrochloric acid as shown by the following equation (6). 

In conformationally fixed irons- and cts-4-f-buiylcyclohexene epoxides, ihe direction of ring opening is such as to give the axial alcohol, regardless of solvent (/). 

Que and coworkers reported on a similar monomeric iron complex, formed with the BPMEN ligand but without acetic acid [128]. This complex was able to epoxidize cyclooctene in reasonably good yield (75%), but at the same time a small amount of the ris-diol (9 %) was formed. This feature observed with this class of complexes has been further studied and more selective catalysts have been prepared. Even though poor levels of conversion are often obtained with the current... 

Scheme 10.5 Tentative mechanism for cytochrome P450-cata-lyzed epoxidation of a double bond. The reactive iron-oxo species VII (see Scheme 10.4) reacts with the olefin to give a charge transfer (CT) complex. This complex then resolves into the epoxide either through a radical or through a cationic intermediate.

Scheme 10.27 Catalytic cycle of HppE. Dashed arrows indicate electron transport. In this scheme HPP binds to iron1". After a one-electron reduction, dioxygen binds and reoxidizes the iron center. The peroxide radical is capable of stereospecifically abstracting the (pro-R) hydrogen. Another one-electron reduction is required to reduce one peroxide oxygen to water. Epoxide formation is mediated by the resulting ironlv-oxo species.

Abstract In this review, recent developments of iron-catalyzed oxidations of olefins (epoxidation), alkanes, arenes, and alcohols are summarized. Special focus is given on the ligand systems and the catalytic performance of the iron complexes. In addition, the mechanistic involvement of high-valent iron-oxo species is discussed. 

Scheme 1 BPMEN and TPA ligands for the iron-catalyzed epoxidation of olefins...

In addition, also nonheme iron catalysts containing BPMEN 1 and TPA 2 as ligands are known to activate hydrogen peroxide for the epoxidation of olefins (Scheme 1) [20-26]. More recently, especially Que and coworkers were able to improve the catalyst productivity to nearly quantitative conversion of the alkene by using an acetonitrile/acetic acid solution [27-29]. The carboxylic acid is required to increase the efficiency of the reaction and the epoxide/diol product ratio. The competitive dihydroxylation reaction suggested the participation of different active species in these oxidations (Scheme 2). 

Scheme 4 Selected ligands for iron-catalyzed epoxidation of alkenes...

To mimic the square-pyramidal coordination of iron bleomycin, a series of iron (Il)complexes with pyridine-containing macrocycles 4 was synthesized and used for the epoxidation of alkenes with H2O2 (Scheme 4) [35]. These macrocycles bear an aminopropyl pendant arm and in presence of poorly coordinating acids like triflic acid a reversible dissociation of the arm is possible and the catalytic active species is formed. These complexes perform well in alkene epoxidations (66-89% yield with 90-98% selectivity in 5 min at room temperature). Furthermore, recyclable terpyridines 5 lead to highly active Fe -complexes, which show good to excellent results (up to 96% yield) for the epoxidation with oxone at room temperature (Scheme 4) [36]. 

Until recently only few examples on asymmetric epoxidation using iron-based catalysts were reported in the literature (Scheme 6) [42-44]. With [Fe(BPMCN) (CF3S03)2] 10, 58% of the epoxide with 12% ee was obtained in the oxidation of frans-2-heptene [42]. 

A breakthrough in iron-catalyzed asymmetric epoxidation of aromatic alkenes using hydrogen peroxide has been reported by our group in 2008. Good to excellent isolated yields of aromatic epoxides are obtained with ee-values up to 97% for stilbene derivatives using diphenylethylenediamines 9 as ligands (Scheme 5) [45, 46]. 

Table 1 Selected result of the epoxidation using iron trichloride hexahydrate, pyridine-2,6-dicarboxylic acid, and an organic amine...

Scheme 7 Recently reported ligands for iron-catalyzed asymmetric epoxidations...

Asymmetric epoxidation systems using iron porphyrin heme-mimics are also known, however the labor-intensive and expensive syntheses is hmiting their applications [49]. 

T able 2 Epoxidation of cyclooctene with iron catalysts and H2O2... 

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