Asymmetric oxidations

Various heterogeneous asymmetric oxidation reactions using inorganic supports are listed in Table 2.2. A few selected examples will be described herein on the basis of reachon type. 

Owing to the instability of many (chiral) ligands under oxidative reaction conditions, asymmetric oxidation is not an easy reaction to perform. However, much progress has been achieved over the last decades. Because of the relatively low volumes and high added value of the products asymmetric oxidation allows the use of more expensive and environmentally less attractive oxidants such as hypochlorite and N-methylmorpholine-N-oxide (NMO). 

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Sulfonyloxazindines as aprollc neutral oxidizing reagents oxidainn of amines, sulfides, selenides and asymmetric oxidation. 

Bartoli recently discovered that by switching from azide to p-anisidine as nucleophile, the ARO of racemic trans- 3-substituted styrene oxides could be catalyzed by the (salen)Cr-Cl complex 2 with complete regioselectivity and moderate selectivity factors (Scheme 7.36) [14]. The ability to access anti-P-amino alcohols nicely complements the existing methods for the preparation of syn-aryl isoserines and related compounds [67] by asymmetric oxidation of trans-cinnamate derivatives [68]. 

Cyclodextrins, toroidal molecules composed of 6, 7 and 8 D-glucose units, are now commercially available at reasonable cost. They form inclusion compounds with a variety of molecules and often differentially include sulfoxide enantiomers29,30. This property has been used to partially resolve some benzyl alkyl, phenyl alkyl and p-tolyl alkyl sulfoxides. The enantiomeric purities after one inclusion process ranged from 1.1 % for t-butyl p-tolyl sulfoxide to 14.5% for benzyl r-butyl sulfoxide. Repeating the process on methyl p-tolyl sulfoxide (10) increased its enantiomeric purity from 8.1% to 11.4% four recrystallizations raised the value to 71.5%. The use of cyclodextrins in asymmetric oxidations is discussed in Section II.C.l and in the resolution of sulfmate esters in Section II.B.l. 

Significant improvements in asymmetric oxidations were made by Modena and, especially, by Kagan, and their coworkers. Both groups used chiral peroxotitanium complexes patterned after the Sharpless reagent as the oxidants. 

The use of optically active peracids for asymmetric oxidation of sulphides will be discussed in Section III dealing with the synthesis of optically active sulphoxides. 

A convenient and simple route to chiral sulphoxides is an asymmetric oxidation of prochiral sulphides by optically active oxidizing reagents. 

TABLE 15. Asymmetric oxidation of sulphides, RXSR2, to optically active sulphoxides, R R2S—O... 

Based on detailed kinetic investigations, a tentative mechanism for this asymmetric oxidation was proposed (Scheme 2) according to which optically active sulphoxides may be formed by two pathways external attack on the sulphur atom by the chiral titanium hydroperoxide (path A) or coordination of sulphur to titanium prior to the oxidation step (path B). Although paths A and B could not be distinguished experimentally, the temperature effect was tentatively ascribed to a change of the mechanism, path A being predominant above — 20 °C and path B becoming competitive at lower temperatures (or vice versa). 

The modified Sharpless reagent was also successfully applied288 for the asymmetric oxidation of a series of 1,3-dithiolanes 248 to their S-monooxides 249 (equation 134). It was observed that the optical induction on sulphur (e.e. from 68 to 83%) is not significantly affected by the substituents R1 and R2. Asymmetric oxidation of a few aryl methyl sulphides by organic hydroperoxides in the presence of a catalytic amount of the optically active Schiff base-oxovanadium(IV) complexes gave the corresponding sulphoxides with e.e. lower than 40%289. 

Asymmetric oxidation of this sulphide was also catalyzed by two isocytochromes P 450 purified from phenobarbital induced rat liver309. Both P 450 isocytochromes, termed PB-1 and PB-4, when reconstituted with purified rat liver NADPH-cytochrome P 450 reductase and cytochrome b5 afforded ethyl p-tolyl sulphoxide with S-configuration at the sulphur atom. In the case of PB-1 optical purity of this sulphoxide was 58% whereas with PB-4 it was 78%. 

Davis and coworkers40 have developed use of diastereomerically pure 2-sulfonyl and 2-sulfamyloxaziridines for asymmetric oxidation of sulfides into sulfoxides (equation 7). The best results (using the sulfamyloxaziridines) range from 38 to 68% enantiomeric purity of the resultant sulfoxides. The structural diversity of such substituted oxaziridines, their... 

Aryl vinyl sulphones, reactions of 646 Aryl vinyl sulphoxides 620 optical resolution of 287 reactions of 354, 355, 360, 361, 621 Asscher-Vofsi reaction 189 Asymmetric induction 625 Asymmetric oxidation 72-78 Asymmetric reduction 78, 79 Asymmetric synthesis 824-846 Atomic orbitals 2, 3 Azetidinones 790, 791 ot-Azidoaldehydes, synthesis of 811 Azidosulphones, photolysis of 883, 884 Azosulphones, photolysis of 879 Azoxysulphones, photolysis of 879 1-Azulyl sulphoxides, synthesis of 265... 

Dithiolane oxides, synthesis of 241 Dithiolanes, asymmetric oxidation of 291 Divinyl sulphones, reactions of 642, 1021 Divinyl sulphoxides reactions of 349, 352, 353, 359 synthesis of 240 Donor-acceptor capacities 387... 

Azerad, R. (2006) Asymmetric Oxidation Reactions, Oxford University Press,... 

Colonna, S., Gaggero, N., Carrea, G. and Pasta, P. (2001) Asymmetric Oxidation Reactions (ed. T. Katsuki), Oxford University Press, Oxford, pp. 227-235. 

The application of this biphasic system to the asymmetric oxidation of arylmethylsulfides [9] did not lead to such successful results. Conversions (78-100%) and selectivities to sulfoxide (88-99%) were excellent, much better in general than in homogeneous phase, but enantioselectivities were always very low (up to 17% ee). 

Optically stable racemic phosphines have been oxidized with one half equivalents of optically active peracid. The remaining phosphine, oxidized with perbenzoic acid, showed low optical activity, but the phosphine oxides obtained in the asymmetric oxidation were optically inactive. ... 

Kiefer, C. et al.. Identification and characterization of a mammalian enzyme catalyzing the asymmetric oxidative cleavage of provitamin A, J. Biol. Chem., 276, 14110, 2001. 

Okrasa and co-workers reported an interesting combination reaction of glucose oxidase and peroxidase in a mixed solvent of [bmimJpFg] with water (Fig. 18). Asymmetric oxidation of sulfide was accomplished successfully in the reaction system. ... 

Figure 18 Glucose oxidase-mediated asymmetric oxidation of sulfide in IL...

Table 7.2 Chiral NHC-Pd(II) complexes in asymmetric oxidative Heck reaction...

Mikolajczyk and coworkers have summarized other methods which lead to the desired sulfmate esters These are asymmetric oxidation of sulfenamides, kinetic resolution of racemic sulfmates in transesterification with chiral alcohols, kinetic resolution of racemic sulfinates upon treatment with chiral Grignard reagents, optical resolution via cyclodextrin complexes, and esterification of sulfinyl chlorides with chiral alcohols in the presence of optically active amines. None of these methods is very satisfactory since the esters produced are of low enantiomeric purity. However, the reaction of dialkyl sulfites (33) with t-butylmagnesium chloride in the presence of quinine gave the corresponding methyl, ethyl, n-propyl, isopropyl and n-butyl 2,2-dimethylpropane-l-yl sulfinates (34) of 43 to 73% enantiomeric purity in 50 to 84% yield. This made available sulfinate esters for the synthesis of t-butyl sulfoxides (35). 

In 1960, Montanari and Balenovic and their coworkers described independently the first asymmetric oxidation of sulfides with optically active peracids. However, the sulphoxides were formed in this asymmetric reaction (equation 130) with low optical purities, generally not higher than 10%. The extensive studies of Montanari and his group on peracid oxidation indicated that the chirality of the predominantly formed sulphoxide enantiomer depends on the absolute configuration of the peracid used. According to Montanari the stereoselectivity of the sulphide oxidation is determined by the balance between one transition state (a) and a more hindered transition state (b) in which the groups and at sulphur face the moderately and least hindered regions of the peracid,... 

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