Asymmetric Epoxidation of Aromatic Alkenes

The direct epoxidation of terminal aromatic alkenes using classic chemocatalysts, such as Jacobsen s salen transition metal catalysts, suffer from poor stereoselectivity ( -36%ee) [95] and/or imprachcal reaction temperatures of -78 °C (86% ee) [96]. To achieve opfically pure sfyrene oxide, a more universal approach is to use hydrolytic kinetic resolution following unselective epoxidation reactions, which leads to a product with high optical purity but only 50% yield [11]. 

The reactions are routinely carried out in a two-liquid phase system that alleviates the product/substrate inhibition by in situ product extraction and substrate supply [103, 104]. In the pilot-scale preparation of enantiopure (S)-styrene oxide using fhe SMO from Pseudomonas sp. VLB120 expressed in recombinant E. coli, a bis(2-ethyl-hexyl) phthalate (BEHP)/aqueous biphasic system was applied with the product concentration reaching up to 36.3 gl and volumetric productivities of 4.19 gl h h The bioprocess performed best in terms of production costs compared with three chemocatalysis processes [103,105]. 

SMO-catalyzed asymmetric epoxidation of styrene derivatives and analogues. 

Enantiomeric dihydroxyiation of aryi oiefins cataiyzed with SMO and epoxide hydrolase in (a) a tandem system or (b) using recombinant Escherichia coii coexpressing SMO and epoxide hydroiase. 

Besides SMOs, recombinant E. coli expressing the xylene monooxygenase from P. putida mt-2, which typically oxidizes toluene and xylenes to the corresponding benzyl alcohol derivatives, can as well catalyze the epoxidation of styrene into (S)-styrene oxide [49, 108]. However, the substrate spectrum for the enzyme was extremely narrow. Only styrene, 3-chlorostyrene, and 4-chlorostyrene were oxidized without side reactions, yielding epoxides with 92%, 96%, and 37% ee, respectively, while 3-methylstyrene and 4-methylstyrene were primarily oxidized at the methyl moiety rather than the vinyl group [49]. 

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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]. 

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. 

Table 6.3 depicts the results of the asymmetric epoxidation of some aromatic alkenes. 

A very simple yet elegant method for efficient epoxidation of aromatic and aliphatic alkenes was presented by Beller and coworkers [63, 64], FeCl3 hexahydrate in combination with 2,6-pyridinedicarboxylic add and various organic amines gave a highly reactive and selective catalyst system. An asymmetric variant (for epoxidations of trans-stilbene and related aromatic alkenes) was published recently [65] using N-monosulfonylated diamines as chiral ligands (Scheme 3.7). 

V-Alkoxycarbonyl- and /V-carboxamido-oxaziridines (35) have been developed as reagents capable of converting aromatic alkenes into epoxide, aziridine, or hydrooxidation products, in ratios depending on the oxaziridine structure. Chiral oxaziridines can effect epoxidation and hydrooxidation with promising levels of asymmetric induction.48... 

Jacobsen epoxidation turned out to be the best large-scale method for preparing the cis-amino-indanol for the synthesis of Crixivan, This process is very much the cornerstone of the whole synthesis. During the development of the first laboratory route into a route usable on a very large scale, many methods were tried and the final choice fell on this relatively new type of asymmetric epoxidation. The Sharpless asymmetric epoxidation works only for allylic alcohols (Chapter 45) and so is no good here. The Sharpless asymmetric dihydroxylation works less well on ris-alkenes than on trans-alkenes, The Jacobsen epoxidation works best on cis-alkenes. The catalyst is the Mn(III) complex easily made from a chiral diamine and an aromatic salicylaldehyde (a 2-hydroxybenzaldehyde). 

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