Aromatics alkenes, epoxidation

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]. 

As with several other functional groups considered earlier, epoxides are most commonly found in alkaloid metabolites rather than the original compound. These epoxides may arise via oxidation of alkenes or aromatic hydrocarbons. Epoxide hydrolase catalyzes hydrolysis of epoxides to the more hydrophilic diol. As seen in Scheme 6, this is usually a stereospecific reaction that always yields a... 

Table 6.3 Epoxidation of some aromatic alkenes by [RuVI(L1)02] (la).

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

S.3 Cytochrome P450 Model Compounds Functional. Ferric-peroxo species are part of the cytochrome P450 catalytic cycle as discussed previously in Section 7.4.4. For instance, these ferric-peroxo moieties are known to act as nucleophiles attacking aldehydic carbon atoms in oxidative deformylations to produce aromatic species.An example of this work, establishing the nucleophilic nature of [(porphyrin)Fe (02)] complexes, was achieved for alkene epoxidation reactions by J. S. Valentine and co-workers. The electron-deficient compound menadione (see Figure 7.18) yielded menadione epoxide when reacted with a [(porphyrin)Fe X02)] complex. 

For several alkene substrates, the yield of the epoxide product was lower when the reactions were carried out in pure CH2CI2 than in a mixed solvent system consisting of [BMIM]PFg/CH2Cl2 (3 1, v/v). The catalyst was also highly active for the epoxidation of aromatic alkenes. Although PhIO is an oxidant commonly used in organic solvents, it was found that the use of PhI(OAc)2 under the same conditions in the mixed solvent led to higher yields of the epoxides. 

As stoich. [Ru(0)(bpy)(tmtacn)]VCH3CN it functioned as a competent (sic) epoxidant for alkenes, though the products were often contaminated with by-products (e.g. fran -stilbene gave fran -stilbene oxide and benzaldehyde cw-stilbene gave cis- and trans- epoxides). Kinetics of the epoxidation of norbomene and styrene were reported, with activation parameters measured and discussed [682]. Kinetics of its non-stereospecific, stoicheiometric epoxidation of aromatic alkenes in CH3CN were studied, and the rates compared with those of oxidations effected by other Ru(IV) 0x0 complexes with N-donors, e. g. [Ru(0)(tmeda)(tpy)] ", trans-[Ru(0)(Cl3bpy)(tpy)] " and [Ru(0)Cl(bpy)(ppz )] + [676]. 

Figure 2.24 Reactions catalysed by mono-oxygenases, hydroxylation of carbon centres, aromatic hydroxylation, epoxidation of alkenes, heteroatom oxidation and Baeyer-Villiger oxidation of a ketone.

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... 

Another strategy for positioning a catalytic center across the entrance of a conical cavity is to employ a cavitand functionalized at one entrance by a pendent chelate arm (Scheme 13.16). Enantioselective epoxidations of aromatic alkenes was realized with catalysts 62, 63, and 64, 65, although the enantioselectivity remained modest [46]. (For experimental details see Chapter 14.13.11). The reaction requires the slow addition (over 1 h) of a solution of alkene 66 and Oxone to a solution of the catalyst. Both the size of the cavity and the structure of the bridged ketone influenced the reactivity. Hence, whilst the formation of the diol 68 was observed when 62 and 63 were used, the presence of 64 and 65 resulted only in the formation of epoxide 67. 

They include aromatic hydroxylation, hydrocarbon and alcohol oxidation, alkene epoxidation, nitro-aromatic reduction, dehydrogenation, carbonylation, cyclization, heterocycle functionalization, etc. 

Aromatic hydroxylation/alkene epoxidation Titanium silicate Styrene to phenylacetaldehyde, ethylene to ethylene oxide and other reactions... 

Whereas important progress has been made regarding the use of metalloporphyrins as catalysts for alkene epoxidations and alkane hydroxyla-tions, work concerning the mechanism of hydroxylation of aromatic hydrocarbons has received only limited attention. In fact, the main problem encountered with the design of systems capable of performing such oxidative reactions is in the preparation of superstructured porphyrins for the selective complexation of aromatic compounds. 

Synthesis of the chiroporphyrins (67) and (68) was achieved by reacting the chiral aldehydes (17 )-(-)-cw-caronaldehyde acid methyl ester and (1/ )-(-)-myrhenal with pyrrole [236]. Chloromanganese(III) derivatives of the Z)2-symmetric a a -atropisomers, which appear to be the most abundant, were applied to the epoxidation of some unfunctionalized aromatic alkenes with PhlO. A high ee value (70%) was obtained in the epoxidation of dihydronaphthalene with this type of catalyst whereas it was significantly lower when functionalized substrates were used (17% for p-chlorostyrene). 

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. 

Halomethyl sulfone reagents have been used as a-carbanion stabilizing substituents as well as precursors for alkenes, epoxides, and aziridines syntheses. It is worth mentioning that only aromatic substrates were used, typically phenyl sulfones, and no example has been reported with heterocyclic compounds such as phenyltetrazole. In this regard, we wUl focus on olefination reactions only. 

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. 

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. 

Ru(TDCPP)(CO)/M-41(m) also catalyzed selective alkene epoxidation using CljpyNO as an 0-donor in the presence of HC1 Aromatic and aliphatic alkenes gave epoxides in good yields (up to 98%, based on the amount of substrate consumed) with complete select vities, styrene, cis-stUbene, cA-P-methylstyrene, i -P-deuteriostyrene, norbomene and octene-1 giving only cA-products trani -stilbene was not oxidized. Of note, the formation of cA-oxides from cA-alkenes here is quite different from the preferred formation of trans-oxides from cis- or tran -stilbene catalyzed by... 

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. 

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