Iron-catalyzed Epoxidations

The use of iron salts and complexes for alkene epoxidation is in many respects similar to that of manganese catalysts. Thus, iron porphyrins can be used as epoxidation catalysts, but often conversion and selectivity is inferior to that obtained with its 

An additional contribution to the field ofbiomimetic non-heme iron complexes for alkene oxidation was recently reported by Klein Gebbink and coworkers [109]. They found that iron(II) complexes formed with the neutral ligand propyl 3,3-bis(l-methylimidazol-l-yl)propionate (20) were active as catalysts for the oxidation of various simple alkenes. When complex 21 was employed as the catalyst for the oxidation of cyclooctene in the presence of 10 equivalents of hydrogen peroxide, a mixture of epoxide and diol in a ratio of 2.5 1 was obtained. However, the conversion was rather poor (39%). 

In further optimizations, Beller and coworkers examined various benzyl amines as replacement for pyrrolidine in the FeCl3-H2pydic catalyst system. They found thatthe use of different benzyl amines resulted in higher yields and better selectivity for the formation of epoxides, predominantly from aliphatic alkenes [111]. As seen in Table 2.8, the epoxidation of trans-l,2-disubstituted alkenes such as frans-2-octene and fruns-5-decene resulted in high yields, whereas aliphatic terminal alkenes appear to be problematic substrates. The epoxidation of aromatic alkenes using this catalytic system gave similar results to those obtained using pyrrolidine as base. 

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 

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

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

Scheme 9.15 Iron-catalyzed epoxidation and ring-opening reaction.

M. Fujita, L. Que Jr., In situ formation of peracetic acid in iron-catalyzed epoxidations by hydrogen peroxide in the presence of acetic acid, Adv. Synth. Catal. 346 (2004) 190. 

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. 

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]. 

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

Dioxo-ruthenium porphyrin (19) undergoes epoxidation.69 Alternatively, the complex (19) serves as the catalyst for epoxidation in the presence of pyridine A-oxide derivatives.61 It has been proposed that, under these conditions, a nms-A-oxide-coordinated (TMP)Ru(O) intermediate (20) is generated, and it rapidly epoxidizes olefins prior to its conversion to (19) (Scheme 8).61 In accordance with this proposal, the enantioselectivity of chiral dioxo ruthenium-catalyzed epoxidation is dependent on the oxidant used.55,61 In the iron porphyrin-catalyzed oxidation, an iron porphyrin-iodosylbenzene adduct has also been suggested as the active species.70... 

Salicylaldimine complexes of iron(III) catalyze epoxidation of stilbene by hypochlorite. ... 

The iron-catalyzed addition of Grignard reagents to propargylic epoxides developed by Furstner and Mendez allows one to prepare a yw-allenol, which is an important intermediate for the synthesis of a precursor of the amphidinolide X (Scheme 67). 

In the wake of this report, many chiral iron(III)- and Mn(III)-porphyrin complexes have been synthesized and applied to the epoxidation of styrene derivatives [20]. Because these asymmetric epoxidations are discussed in the first edition of this book [21], the discussion on metalloporphyrin-catalyzed epoxidation here is limited to some recent examples. Most chiral metallopor-phyrins bear chiral auxi Maries such as the one derived from a-amino acid or binapthol. Differing from these complexes is complex 6, which has no chiral auxiliary but is endowed with facial chirality by introducing a strap and has been reported by Inoue et al. [20f]. Epoxidation of styrene by using only 6 as the catalyst shows low enantioselectivity, but the selectivity is remarkably enhanced when the reaction is performed in the presence of imidazole (Scheme 6B.11). This result can be explained by assuming that imidazole coordinates to the unhindered face of the complex and the reaction occur on the strapped face [20f. ... 

Although the iron-catalyzed synthesis of allenes from propargylic halides was reported by Pasto and coworkers in 1978 [67], little progress was achieved in this field until recently [68]. In 2003, Fiirstner and coworkers discovered propargylic epoxides as valuable substrates for the reaction with Grignard reagents in presence of catalytic amounts of Fe(acac)3 to generate 2,3-allenol derivatives (Scheme 5.24) [69]. 

CpFe(CO)2(thf)]+, is generated by protonation of the respective iron-methyl complex with HBF4 in THF solution. Iron-catalyzed reactions of phenyldiazomethane with aldehydes resulted in mixtures of ketones and epoxides [29]. 

Scheme 9.45 Carbonylative iron-catalyzed ring expansion of epoxides.

The iron-catalyzed ring expansion reaction is a complementary alternative to Ti(III) chemistry for the ring expansion of epoxides [110]. However, so far the reaction is limited to styrene oxide derivatives, while the alkene can be broadly varied. 

Progress in decoding the mechanism of cytochrome P-450, which catalyzes epoxidation and hydroxylation of various hydrocarbons, has stimulated the search for comparatively simple and effective iron porphyrin systems [20-24], The reaction mechanism of monooxygenation can be illustrated by the following diagram ... 

An intermolecular iron-catalyzed ring expansion reaction involving epoxides and alkenes provided tetrahydrofurans via radical processes <07CEJ4312>. Cp2TiCl is able to promote cyclization of 2,3-epoxy alcohols containing a p-(alkoxy)acrylate moiety to form tetrahydrofurans <07TL6389>. As shown in the following example, an intramolecular addition of carbon radicals to aldehydes was reported to afford tetrahydrofuran-3-ols... 

The observation that iron porphyrins can catalyze, under mild conditions, epoxidations of alkenes when iodosylbenzene is used as the oxidant has been followed up by a number of studies on metallopor-phyrins as models for cytochrome P-4S0 enzymes. Cytochrome P-4S0 enzymes catalyze epoxidation of alkenes by molecular oxygen in the presence of a hydrogen donor, NAOPH cofactor. This has led to the study of a number of systems based on a metalloporphyrin/02/reducing agent, to bring about epoxidation of alkenes. 

Iron-mediated oxygen transfer is also at play in the chloroperoxidase (CPO) catalyzed epoxidation of simple alkenes, which has the added advantage of providing high enantiomeric excesses. For example, c/s-2-heptene 35 is converted to the chiral epoxide 36 in 78% yield. However, the protocol is generally limited to fairly accessible disubstituted alkenes the more imbedded olefin of cis-3-heptene only undergoes 12% conversion, while the epoxides derived from terminal olefins tend to alkylate the enzyme and serve as suicide inhibitors <0374701>. 

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