Asymmetric oxidation sulfoxides from

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. 

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... 

In combination with H2O2 (salen)Mn(III) complexes 173a, b, i-n have also been employed by Jacobsen and coworkers as catalysts for the asymmetric oxidation of sulfides to sulfoxides, without a need for additives. From the structurally and electronically different Mn-salen catalysts screened, 173i turned out to be the most active and selective one (equation 58) . While dialkyl sulfides underwenf uncafalyzed oxidation with H2O2, aryl alkyl sulfides were oxidized only slowly compared wifh fhe cafalyzed pathway. Using... 

A further catalytic method for asymmetric sulfoxidation of aryl alkyl sulfides was reported by Adam s group, who utilized secondary hydroperoxides 16a, 161 and 191b as oxidants and asymmetric inductors (Scheme 114) . This titanium-catalyzed oxidation reaction by (S)-l-phenylethyl hydroperoxide 16a at —20°C in CCI4 afforded good to high enantiomeric excesses for methyl phenyl and p-tolyl alkyl sulfides ee up to 80%). Detailed mechanistic studies showed that the enantioselectivity of the sulfide oxidation results from a combination of a rather low asymmetric induction in the sulfoxidation ee <20%) followed by a kinetic resolution of the sulfoxide by further oxidation to the sulfone... 

Optically active Schiff-base oxovana-dium(IV) complexes catalyze the asymmetric oxidation of sulfides to sulfoxides by peroxides [86]. The catalytically active species is VO(V) rather than VO(IV) and is formed in situ under the reaction conditions. A series of related complexes based on the optically active ligand shown in Eig. 15 shows linear dependence of their oxidation Ef values on the Hammett parameters of functional group X. These values ranged from 0.18 V versus Cp2Ee/DMSO for X = NO2 to —0.18 V for X = OCH3 [87]. A few complexes of planar tetradentate non-Schiff base ligands have also been investigated [88]. 

Oxometalloporphyrins were taken as models of intermediates in the catalytic cycle of cytochrome P-450 and peroxidases. The oxygen transfer from iodosyl aromatics to sulfides with metalloporphyrins Fe(III) or Mn(III) as catalysts is very clean, giving sulfoxides, The first examples of asymmetric oxidation of sulfides to sulfoxides with significant enantioselectivity were published in 1990 by Naruta et al, who used chiral twin coronet iron porphyrin 27 as the catalyst (Figure 6C.2) [79], This C2 symmetric complex efficiently catalyzed the oxidation... 

Similar to the evolution of omeprazole (Prilosec) to esomeprazole (Nexium), the switch from racemic modafinil to enantioenriched armodafinil utilized asymmetric oxidation of sulfide.35 Although several asymmetric oxidation methods to provide enantiopure sulfoxides have been developed, the modified Kagan system [(Ti(Oi-Pr)4/(5,5)-DET] was selected due to superior yields and optical purities (% ee).36b The Kagan method is very useful, but it is substrate dependant (Table 3). Several sulfide derivatives of modafinil were screened to determine a direction for optimization. It was found the sulfide amide 11 provided excellent optical purity and further optimization. 

Biocatalytic asymmetric oxidation of 2,3-dihydrobenzo[. ]thiophene to (—)-(lJ)-sulfoxide in excellent yield has been reported. The enzyme used is a chloroperoxidase from the marine fungus Caldariomycesfumago. This enzyme is relatively stable and does not require any cofactor. Hydrogen peroxide was the oxygen source. Using this system, 2,3-dihydro-benzo[. ]thiophene was converted to the (—)-(i )-sulfoxide in 99.5% yield, with an ee of 99%. Similarly, 1,3-dihydro-benzo[f]thiophene could be oxidized to the corresponding sulfoxide in 80% yield <1998CH246>. 

Enantiomeric purities ranging from 20 to 80% have been reported for the acid-promoted asymmetric oxidation of sulfides to sulfoxides by binaphthyl-derived oxaziridines has been described <2007T6232>. A novel amino hydroxylation of olefins has been developed using /ra t-2-phenylsulfonyl-3-phenyloxaziridine 33 <2007JA1866>. The reaction, which is catalyzed by copper(ll) salts, affords good yields of the product. Oxidation of aldimines to oxaziridines using alumina-supported M0O3 catalyst and anhydrous /-butyl hydroperoxide (TBHP) has been described. Yields are excellent. 

Oxaziridines. Davis has developed the use of chiral 2-sulfonyloxaziridines derived from camphorsulfonic acid as chiral auxiliaries in the asymmetric oxidation reactions. Although other oxaziridines may be preferable, the camphor-derived oxaziridines can be used for the oxidation of sulfides and disulfides to sulfoxides and thiosulfinates as well as for the epoxidation of alkenes. On the other hand, the camphoryloxaziridines are the preferred reagents for hydroxylation of lithium enolates of esters, amides, and ketones, as utilized in the synthesis of kjellmanianone (eq 17). ... 

Major interest has been expressed in the synthesis of chiral sulfoxides since the early 1980s, when it was discovered that chiral sulfoxides are efficient chiral auxiliaries that are able to bring about important asymmetric transformations [22]. Sulfoxides are also constituents of important drugs (e.g., omeprazole (Losec , Priso-lec )) [23]. There is a plethora of routes of access to enantioenriched sulfoxides, and many involve metal-catalyzed asymmetric oxidations [24]. Examples of ruthenium metal-based syntheses of sulfoxides are scarce, presumably due to the tendency of sulfur atoms to bind irreversibly to a ruthenium center. Schenk et al. reported a dia-stereoselective oxidation of Lewis acidic Ru-coordinated thioethers with dimethyl-dioxirane (DMD) (Scheme 10.16) [25[. Coordination of the prochiral thioether to the metal is followed by diastereoselective oxygen transfer from DMD in high yield. The... 

Bohe, L., Lusinchi, M., Lusinchi, X. Oxygen atom transfer from a chiral N-alkyloxaziridine promoted by acid. The asymmetric oxidation of sulfides to sulfoxides. Tetrahedron 1999, 55,155-166. 

Related reagents 2.83, obtained from camphor imine, are usefid for asymmetric oxidation of sulfides and selenides to chiral sulfoxides and selenoxides [S06, 749]. To obtain high enantioselectivities, the substituents on the sulfur or selenium must be of a sufficiently different size. 

A great deal of effort has been expended in the development of ways to carry out the asymmetric oxidation of sultides to sulfoxides progress in this field has been exhaustively reviewed [114], This is interesting from th a theoretical viewpoint and from the utility of certain chiral sulfoxides as reagents in asymmetric synthesis [115]. Some natural products also contain sulfoxide stereogenic centers. 

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