Oxidation of methyl aryls

An interesting behavior of the Padua reagent (Ti(0-i-Pr)4/(/ ,i )-DET = 1 4) was described by Scretti et al. [42,43], who used racemic furylhydroperoxides 1 instead of cumyl hydroperoxide as oxidant. The enantioselectivities in the oxidation of methyl aryl sulfides are very good. For example, methyl p-tolyl sulfoxide was obtained in 75% yield and >95% ee together with about 15% of sulfone by using hydroperoxide 1(R =OEt,R = /-PrandR3 = Me) Simultaneously there is a kinetic resolution of the racemic hydroperoxide takes place is used in excess (2 mol equiv. with respect to sulfide). Thus in the example mentioned above, the enantiopurity of the residual hydroperoxide was 81% ee. It has also been established that some kinetic resolution of... 

This reagent can also be used for the oxidation of methylated aryl derivatives to the corresponding aryl aldehyde, in what has become known as the Etard reaction. Tillotson and Houston found that the Etard reaction is catalyzed by small amounts of alkene, added to or present in the reaction medium. The reaction involves addition of chromyl chloride to a carbon disulfide or carbon tetrachloride solution of the arene. A dark brown, insoluble, and explosive intermediate usually precipitates. Dilute sulfurous acid is added to decompose the precipitate to the aldehyde. Toluene is converted to benzaldehyde and ethylbenzene was oxidized to phenylacetaldehyde with this reagent. 

Table 1.4 Influence of substituent on the vanadium catalyst upon the asymmetric oxidation of methyl aryl sulfide...

Aryl-substituted 6-methyl-4//-pyrazolo[3,4-c]-l,2,5-oxadiazoles 275 are easily obtained in 88-97% yields by the oxidation of 2-aryl-5-methyl-4-nitroso-2//-pyrazol-3-amines 274 with Pb(OAc)4 (Equation 52) <2000S72>. 

Ozone oxidation of 6-aryl-2-methylthiopyrido[2,3-methyl sulfone with /ra j-4-aminocyclohexanol afforded the amino pyridopyrimidinone derivative 176 <2002W02002018380>. Amination of 6-dimethoxyphenyl-8-ethyl-2-methylthiopyrido[2,3-t7 pyrimidin-7-one with 4-aminopyridine and LiNH2 in THF at 50°C produced the 2-[(4-pyridyl)amino] derivative 177 <2003W02003027110>. 

Electrochemical oxidation of alkyl aryl ethers results in oxidative dealkylation and coupling of the intermediate radicals. Electro-oxidation of alkyl (4-fluorophenyl) ethers in the presence of a hydrogen fluoride double salt leads to 4,4-difluorocyclohexa-2,5-dienone in 50% yield (Table 10).182 In the electrochemical oxidation of methyl tetrafluorophenyl ethers with a hydrogen atom at the para position, coupled products 6 arc obtained.183 If the para position in the substrate is occupied by a fluorine substituent, then no reaction occurs. 

The oxidation of an aryl methyl ketone, with selenium dioxide [Method (a)] in a suitable solvent, to an aryl 1,2-ketoaldehyde is illustrated by the preparation... 

In the same year, Fujita s group63 reported the asymmetric oxidation of aryl methyl sulfide by hydroperoxides (TBHP, CHP) and an optically active catalyst formed by a Schiff base-oxovanadium(IV) complex 32, giving (S)-sulfoxides in low ee (up to 40%) (Fig. 4). Later, they developed64 a more promising approach using 33, a binuclear Schiff base-titanium(IV) complex (4 mol% equiv) to catalyze the asymmetric oxidation of methyl phenyl sulfide by trityl hydroperoxide in methanol at 0 °C. The (ft)-methyl phenyl sulfoxide was obtained with 60% ee. 

The main methodologies developed until now for enantioselective oxidation of sulfides are effective only in the oxidation of alkyl aryl sulfoxides. Dialkyl sulfoxides on the other hand are generally oxidized with only poor selectivity. In an attempt to solve this problem, Schenk s group69 recently reported a stereoselective oxidation of metal-coordinated thioethers with DMD. The prochiral thioether is first coordinated to a chiral ruthenium complex by reaction with the chloride complexes [CpRu[(S,S)-chiraphos]Cl], 36. Diastereoselective oxygen transfer from DMD produces the corresponding sulfoxides in high yield and selectivity. The chiral sulfoxides 37 are liberated from the complexes by treatment with sodium iodide. Several o.p. aryl methyl sulfoxides have been obtained by this method in moderate to high ee (Scheme 12). 

This I04 -5i02 reagent is not very elective in the oxidation of sulfides into sulfoxides. However, sulfuryl chloride adsorbed wet silica gel is an excellent reagent for this transformatim (equation 5). High yields of methyl aryl, diaryl, allylic. benzylic and dialkyl sulfoxides are thus obtainable. The procedure commends itself by its simplicity and its extension to thioacetals provides a good, quantitative re-... 

In the former case, almost complete stereoselective oxidation to the chiral selenoxides has been accomplished quite recently. The Davis oxidant, 3,3-di-chloro-l,7,7-trimethyl-2 -(phenylsulfonyl)spirobicyclol2.2.11heptane-2,3 -oxa-ziridine, was found to be the most efficient reagent for the enantioselective oxidation of a variety of prochiral alkyl aryl selenides [81. Asymmetric oxidation was accomplished by the treatment of the selenides with 1 molar equivalent of the Davis oxidant at 0°C to afford the corresponding chiral alkyl aryl selenoxides in quantitative yields with 91-95% ee (Scheme 1). The oxidation of methyl phenyl selenide was complete within 1 min, whereas that of triiso-propyl(a bulkier alkyl) phenyl selenide required a few hours. Typical results are... 

Oxidation of 7V-aryl-7V-methyl-substituted jff-aminoalcohols using pyridinium dichromate (PDC) has recently been reported to give moderate to excellent yields of oxazolidines (Scheme 28) [230]. 

The products of the electrochemical oxidation of alkyl aryl sulfides, ArSR, are remarkably dependent upon the structure of R, the water content of the solvent, and the supporting electrolyte. If R can yield stabilized carbocations like benzyl or triphenyl-methyl cations, extensive cleavage of the S-C bond occurs during the oxidation [84, 85] ... 

Neighbouring sulfur atom participation in the electrochemical oxidation of alkyl aryl sulfides was also shown to be occurring, such as in naphtho[l,8-, c]-l,5-dithiocin (XXI) [101] and 2,6-bis[(methylthio)methyl]phenyl phenyl sulfide (XXII) [101]. 

Uemura described use of a Ti(OiPr)4/(i )-BINOL complex for the oxidation of alkyl aryl sulfides with aqueous ferf-butyl hydroperoxide as stoichiometric oxidant [22]. At room temperature p-tolyl methyl sulfide was converted into the corresponding sulfoxide with 96% ee in 44% yield with as little as 5 mol % of the chiral ligand. The reaction is insensitive to air, while the presence of water seems to be essential for the formation of the catalytically active species, long catalyst lifetime, and high asymmetric induction. The authors observed a large positive non-linear effect which indicates that the actual catalyst consists of a titanium species with more than one (K)-BINOL ligand (11) coordinated to the metal. 

The first example of FB oxidation of sulfides dates back to 1995 dibenzothiophene and diphenyl stdfide gave the corresponding sulfones in low yields (1.4% and 10%, respectively) upon treatment with O2 at 100 °C in the presence of a not fully characterized perfluorocarbon-soluble iron—phthalocyanine [19]. Following this earlier report, Co(ll)—tetraarylporphyrin Co-5 and Co(I I [—phthalocyanine Co-12 (cf Stmcture) were tested as catalysts for the FB oxidation of methyl phenyl sulfide and para-substituted aryl methyl sulfides with O2 and a sacrificial aldehyde (Table 3) [20]. 

A similar methodology was applied by Colonna et al. [101] to the oxidation of aryl alkyl sulfides with Bu OOH as oxidizing agent and a catalytic amount of a titanium A-salicylidene-L-amino acid complex (47) (0.1 mol equiv) in benzene at room temperature. This catalyst is not very enantioselective, and often yields mixtures of sulfoxides and sulfones. The highest enantioselectivity was achieved in the oxidation of f-butyl (p-nitrophenylthio)acetate, which gave sulfoxide in 21% ee and 25% yield. Like the Kagan reagent, but to a lesser measure, the use of a stoichiometric amount of titanium complex substantially influences the enantioselectivity, which increases from 12% (catalytic) to 21% (stoichiometric) for the oxidation of methyl p-tolyl sulfide. 

More recently, Katsuki et al. [109] prepared the Salen manganese complex (50) (Figure 1.6), which is efficient in the oxidation of alkyl aryl sulfide with iodosobenzene as oxidant. With 1 mol% of catalyst, they obtained the 2-nitrophenyl methyl sulfoxide in 1 h at -20°C in acetonitrile solution with 90% ee and 88% yield. This is currently one of the best results for catalytic asymmetric sulfoxidation. 

The use of (S,S)-l,2-bis- butyl-l,2-ethanediol (S,S)-30) in the titanium-catalyzed oxidation of various aryl methyl sulfides by cumene hydroperoxide afforded sulfoxides in ees up to 95% (Scheme 8.5) [68[. Interestingly, the authors observed that the ee of the sulfoxide increased with the reaction time, indicating a kinetic resolution of the sulfoxide product. A control experiment with racemic p-tolyl sulfoxide showed that the (i )-enantiomer is oxidized to sulfone three times faster than the (S)-enantiomer by the catalytic system employed. For this reason, the yields of the chiral sulfoxides are moderate and in the range of 40-50%. 

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