Enantioselective epoxidation alkenes

Development of chiral, nonracemic dioxiranes for the catalytic enantioselective epoxidation of alkenes 99SL847. 

E The writing has again been revised at the sentence level, streamlining the presentation, improving explanations, and updating a thousand small details. Several little-used reactions have been deleted (the alkali fusion of arene-sulfonic acids to give phenols, for instance), and a few new ones have been added (the Sharpless enantioselective epoxidation of alkene.s, for instance). 

Enantioselective epoxidation of unfunctionalized alkenes was until recently limited to certain ds-alkenes, but most types of alkenes can now be successfully epoxi-dized with sugar-derived dioxiranes (see Section 9.1.1.1) [2]. Selective monoepox-idation of dienes has thus become a fast route to vinylepoxides. Functionalized dienes, such as dienones, can be epoxidized with excellent enantioselectivities (see Section 9.1.2). 

Ordinary alkenes (without an allylic OH group) have been enantioselectively epoxidized with sodium hypochlorite (commercial bleach) and an optically active manganese-complex catalyst. Variations of this oxidation use a manganese-salen complex with various oxidizing agents, in what is called the Jacobsen-Katsuki... 

The first application of ionic hquids for salen complexes dealt with the epoxidation of alkenes [14]. Jacobsen s Mn complex was immobilized in [bmimjlPFe] and different alkenes were epoxidized with aqueous NaOCl solution at 0 °C. As the ionic solvent sohdified at this temperature, dichloromethane was used as a cosolvent. The recychng procedure consisted of washing with water, evaporation of dichloromethane, and product extraction with hexane. The results (Table 3) were excellent and only a slow decay in activity and enantioselectivity was detected after several cycles. 

Several catalysts that can effect enantioselective epoxidation of unfunctionalized alkenes have been developed, most notably manganese complexes of diimines derived from salicylaldehyde and chiral diamines (salens).62... 

A number of chiral ketones have been developed that are capable of enantiose-lective epoxidation via dioxirane intermediates.104 Scheme 12.13 shows the structures of some chiral ketones that have been used as catalysts for enantioselective epoxidation. The BINAP-derived ketone shown in Entry 1, as well as its halogenated derivatives, have shown good enantioselectivity toward di- and trisubstituted alkenes. 

The binaphthyl azepinium salt 59 (TT= tris(tetrachlorobenzenediolato)phosphate(V)) and corresponding azepine 60 were developed as effective catalysts for the enantioselective epoxidation of unfunctionalised alkenes, with enantiomeric excesses up to 87% <06TA2334>. 

Among many other methods for epoxidation of disubstituted E-alkenes, chiral dioxiranes generated in situ from potassium peroxomonosulfate and chiral ketones have appeared to be one of the most efficient. Recently, Wang et /. 2J reported a highly enantioselective epoxidation for disubstituted E-alkenes and trisubstituted alkenes using a d- or L-fructose derived ketone as catalyst and oxone as oxidant (Figure 6.3). 

Although the Sharpless catalyst was extremely useful and efficient for allylic alcohols, the results with ordinary alkenes were very poor. Therefore the search for catalysts that would be enantioselective for non-alcoholic substrates continued. In 1990, the groups of Jacobsen and Katsuki reported on the enantioselective epoxidation of simple alkenes both using catalysts based on chiral manganese salen complexes [8,9], Since then the use of chiral salen complexes has been explored in a large number of reactions, which all utilise the Lewis acid character or the capacity of oxene, nitrene, or carbene transfer of the salen complexes (for a review see [10]). 

Figure 11.3 Enantioselective epoxidation of alkenes by Mn salen complexes.

The tra x-[Ru (0)2(por)] complexes are active stoichiometric oxidants of alkenes and alkylaro-matics under ambient conditions. Unlike cationic macrocyclic dioxoruthenium I) complexes that give substantial C=C bond cleavage products, the oxidation of alkenes by [Ru (0)2(por)] affords epoxides in good yields.Stereoretentive epoxidation of trans- and cw-stilbenes by [Ru (0)2(L)1 (L = TPP and sterically bulky porphyrins) has been observed, whereas the reaction between [Ru (0)2(OEP)] and cix-stilbene gives a mixture of cis- and trani-stilbene oxides. Adamantane and methylcyclohexane are hydroxylated at the tertiary C—H positions. Using [Ru (0)2(i)4-por)], enantioselective epoxidation of alkenes can be achieved with ee up to 77%. In the oxidation of aromatic hydrocarbons such as ethylbenzenes, 2-ethylnaphthalene, indane, and tetrahydronaphthalene by [Ru (0)2(Z>4-por )], enantioselective hydroxylation of benzylic C—H bonds occurs resulting in enantioenriched alcohols with ee up to 76%. ... 

Although the chiral ketoiminatomanganese(lll) complexes were reported to catalyze the asymmetric aerobic alkene epoxidations, an aldehyde such as pivalaldehyde is required as a sacrihcial reducing agent. Groves reported that the dioxo(porphyrinato)ruthenium complexes 31, prepared with m-chloroperoxyben-zoic acid, catalyzed the aerobic epoxidation without any reductant. " On the basis of these reports, Che synthesized the optically active D4-porphyrin 35 and applied it to the truly aerobic enantioselective epoxidation of alkenes catalyzed by the chiral frani-dioxo (D4-porphyrinato)ruthenium(Vl) complex. The dioxoruthenium complex catalyzed the enantioselective aerobic epoxidation of alkenes with moderate to good enantiomeric excess without any reductant. In the toluene solvent, the turnovers for the epoxidation of T-(3-methylstyrene reached 20 and the ee of the epoxide was increased to 73% ee. 

Ru(0)(biqn)(tmtacn)](C10 )2 and [Ru(0)(diopy)(tmtacn)](C10 )2 (biqn=C2 symmetric 1,T-biisoquinoline, diopy=(R,R)-3,3 -(l,2-dimethylethylenedioxy)-2,2 -bipyridine) aremadefrom [RuCl(L)(tmtacn)] + (L=biqn, diopy) and(NH )2[Ce(N03)J with Li(ClO ). Electronic and IR spectra were measured (v(Ru=(0) bands lie at 760 and 795 cm" respectively). The (diopy) complex is paramagnetic with 2.88 B.M. As stoich. [Ru(0)(biqn)(tmtacn)] + and [Ru(0)(diopy)(tmtacn)] VCH3CN they oxidised alkenes (styrene, cis and fran.y-P-methylstyrenes, fran -stilbene, nor-bomene, cyclohexene) to mixtures of aldehydes and epoxides. Conttary to expectation the (diopy) complex did not effect enantioselective epoxidations except with fran -stilbene, for which a moderate e.e. of 33% was observed [623]. 

The enantioselective epoxidation of prochiral alkenes with an aldehyde dioxirane was achieved by Bez and Zhao . ... 

The haem peroxidases are a superfamily of enzymes which oxidise a broad range of structurally diverse substrates by using hydroperoxides as oxidants. For example, chloroperoxidase catalyses the regioselective and stereoselective haloge-nation of glycals, the enantioselective epoxidation of distributed alkenes and the stereoselective sulfoxidation of prochiral thioethers by racemic arylethyl hydroperoxides [62]. The latter reaction ends in (i )-sulfoxides, (S)-hydroperoxides and the corresponding (R)-alcohol, all In optically active forms. 

CATALYTIC ENANTIOSELECTIVE EPOXIDATION OF TRANS-DISUBSTITUTED AND TRISUBSTITUTED ALKENES WITH ARABINOSE-DERIVED ULOSE... 

Table 6.8 Enantioselective epoxidation of various alkenes over KG-60-FT. ...

The epoxidation procedure developed by Yian Shi of Colorado State University has become one of the workhorses of enantioselective synthesis. That work has been based around trans and trisubstituted alkenes. Professor Shi has now developed (Tetrahedron Lett. 2004,45, 8115) an efficient protocol for the enantioselective epoxidation of aryl-substituted cis alkenes such as 6. 

Highly enantioselective epoxidation of unfunctionalized alkenes was developed by using chiral metalloporphyrin catalysts.1214-1218 Remarkable anion axial ligand effects were observed with [Fe(TPFPP)X] complexes (X = triflate, perchlorate, nitrate).1219 Hexafluoroacetone was found to be an efficient cocatalyst with H202,1220 and alkenes could be epoxidized by ozone at ambient temperature.1221... 

Enantioselective epoxidation of simple alkenes is not easily achieved by reactions with alkylperoxy-Ti intermediates, however, cationic Pt(II)... 

Dexter AF, Lakner FJ, Campbell RA, Hager LP (1995) Highly Enantioselective Epoxidation of 1,1-Disubstituted Alkenes Catalyzed by Chloroperoxidase. J Am Chem Soc 117 6412... 

Lakner FJ, Cain KP, Hager LP (1997) Enantioselective Epoxidation of (o-Bromo-2-methyl-1-alkenes Catalyzed by Chloroperoxidase. Effect of Chain Length on Selectivity and Efficiency. J Am Chem Soc 119 443... 

Homologous biphenyl and binaphthyl tertiary azepines (4) and quaternary iminium salts, prepared from (+)-(5,5 )-L-acetonamine, behave as effective catalysts for the enantioselective epoxidation of unfunctionalized alkenes with Oxone (ee up to 83%).113... 

E. J. Allain, L. P. Hager, L. Deng, and E. N. Jacobsen, Highly enantioselective epoxidation of disubstituted alkenes with hydrogen peroxide catalyzed by chloro-peroxidase, J. Am. Chem. Soc. 1993, 115, 4415-4416. 

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. 

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