Iron-Catalyzed Asymmetric Epoxidations

Using 2mol% of complex [Fe20(24)Cl4] as the catalyst for the epoxidation of a series of aromatic alkenes resulted in the formation of the corresponding epoxides in good yields and in moderate enantioselectivity. 

Even though only moderate enantiomeric excesses were obtained using the chiral iron-containing catalysts described above, these examples are of particular interest, since further elaboration along these lines could produce more selective catalysts. 

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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...

F. G. Gelalcha, B. Bitterlich, A. Anilkumar, M. K. Tse, M. Beller, Iron-catalyzed asymmetric epoxidation of aromatic alkenes using hydrogen peroxide, Angew. Chem. Int. Ed. 46 (2007) 7293. 

Gadissa Gelalcha, R, Bitterlich, B., AnUkumar, G., et al. (2007). Iron-Catalyzed Asymmetric Epoxidation of Aromatic Alkenes Using Hydrogen Peroxide, Angew. Chem. Int. Ed., 46, pp. 7293-7296. 

Gadissa Gelalcha, F., AniUcumar, G., Tse, M., et al. (2008). Biomimetic Iron-Catalyzed Asymmetric Epoxidation of Aromatic Alkenes by Using Hydrogen Peroxide, Chem. Eur. J., 14, pp. 7687-7698. 

These reports sparked off an extensive study of metalloporphyrin-catalyzed asymmetric epoxidation, and various optically active porphyrin ligands have been synthesized. Although porphyrin ligands can make complexes with many metal ions, mainly iron, manganese, and ruthenium complexes have been examined as the epoxidation catalysts. These chiral metallopor-phyrins are classified into four groups, on the basis of the shape and the location of the chiral auxiliary. Class 1 are C2-symmetric metalloporphyrins bearing the chiral auxiliary at the... 

Better results for the porphyrin complex-catalyzed asymmetric epoxidation of prochiral olefins were achieved by Naruta et al.98 using iron complexes of chiral binaphthalene or bitetralin-linked porphyrin 128 as chiral catalysts. As shown in Scheme 4-45, asymmetric epoxidation of styrene or its analogs provided the product with good ee. Even better results were obtained with substrates bearing electron-withdrawing substituents. 

The discovery of iron complexes that can catalyze olefin czs-dihydroxylation led Que and coworkers to explore the possibility of developing asymmetric dihydroxylation catalysts. Toward this end, the optically active variants of complexes 11 [(1R,2R)-BPMCN] and 14 [(1S,2S)- and (lP-2P)-6-Me2BPMCN] were synthesized [35]. In the oxidation of frans-2-heptene under conditions of limiting oxidant, 1R,2R-11 was foimd to catalyze the formation of only a minimal amount of diol with a slight enantiomeric excess (ee) of 29%. However, 1P-2P-14 and 1S,2S-14 favored the formation of diol (epoxide/diol = 1 3.5) with ees of 80%. These first examples of iron-catalyzed asymmetric ds-dihydroxylation demonstrate the possibility of developing iron-based asymmetric catalysts that may be used as alternatives to currently used osmium-based chemistry [45]. 

Not only the porphyrins having binaphthyl groups, strapped type metalloporphyrins are also able to catalyze asymmetric epoxidation. For example, Mansuy et al. synthesized a "Basket-Handle" iron porphyrin bearing L-phenylalanine residues (Fig. 11(d)) [297]. Collman et al. employed threitol-strapped Mn porphyrins (Fig. 11(e)) [298]. Metalloporphyrin complexes conjugated with glycosylated groups [299], p-cyclodextrin [300], and camphanoyl groups [301] were also prepared. These chiral metalloporphyrin complexes were shown to catalyze asymmetric oxidations. 

Collman et al.99 reported the asymmetric epoxidation of terminal olefins catalyzed by iron porphyrin complex 129. The catalyst was synthesized by connecting binaphthyl moieties to a readily available aa/ / -tetrakis(aminophenyl)-porphyrin (TAPP). Epoxidation of unfunctinalized olefins was carried out using iodosylbenzene as the oxidant. As shown in Scheme 4-46, excellent results were... 

Chiral porphyrins are also effective in the asymmetric epoxidation of alkenes. For example, a Cj-symmetiic iron porphyrin (29) <99JA460> catalyzes the efficient epoxidation of terminal alkenes, such as 30, with very good ee s and up to 550io turnovers. Similarly, trons-disubstituted... 

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. ... 

The oxidation of saturated hydrocarbons in the presence of iron- or manganese-containing catalysts can be achieved by using a variety of oxidants including alkyl hydroperoxides, peroxycarboxylic acids, iodosyl-benzene, dihydrogen peroxide, and dioxygen (9-11). It has been shown that chiral iron- and manganese-porphyrin complexes catalyze the asymmetric epoxidation of unfunctionalized alkenes (75). Except for a number of experiments in which up to 96 % enantiomeric excess (ee) has been reported (16,17), in most epoxidation reactions with chiral porphyrins only a low to moderate enantiomeric excess of the product is obtained (18,19). In association with these catalysts, alkyl hydroperoxides and iodosylbenzene are often used as primary oxidants (18,19). 

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