Methyl-/?-tolyl sulfoxide, oxidation

The oxidation of methyl tolyl sulfoxide, a representative substrate, was monitored by the buildup of the sulfoxide as a function of time under many sets of conditions (42). A representative concentration time plot is presented in Pig. 1. In this case, and in all the others, the buildup curves showed similar features, the most noticeable of which is a distinct induction period. Its length depends on the concentrations, decreasing with increasing [Bu OOH] and [1], At the same time the rate itself was... 

Enantioselective Oxidation of Sulfides Synthesis of (-)-(S)-Methyl -Tolyl Sulfoxide... 

The efficiency of the enantioselective oxidation was significantly improved by replacing t-BuOOH by cumene hydroperoxide (CHP), eg using CHP, methyl tolyl sulfoxide and methyl n-octyl sulfoxide were formed in 90% ee and 80% ee (instead of... 

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. 

The enantiomeric purity of the crude (S)-methyl p-tolyl sulfoxide produced from the oxidation is close to 90% (measurement made on a sample of 200 mg of material purified by flash chromatography on silica gel, eluent ethyl acetate - ethanol = 96 4). However, when oxidation is performed on a... 

S. H. Zhao, 0. Samuel, and H. B. Kagan 49 ENANTIOSELECTIVE OXIDATION OF A SULFIDE (S)-(-)-METHYL p-TOLYL SULFOXIDE... 

Little work has been done in this area with Ru catalysts. CM-A-[Ru(0)(py)(bpy)3] V water-CH3CN was used for the stoicheiometric oxidation of methyl-p-tolyl sulfide to (R)-methyl-p-tolyl sulfoxide with an e.e. of ca 15% [121],... 

Oxidation of thioethers derived from the natural chirality pool , the readily available lactic acid and 3-hydroxybutyric acid, has been used in molar-scale preparation of enantiomerically pure sulfoxides methyl ( )-2-(phenylsulfinyl)acrylate and (K)-isopropenyl p-tolyl sulfoxide [107]. 

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... 

Uemura et al. [49] found that (R)-1,1 -binaphthol could replace (7 ,7 )-diethyl tartrate in the water-modified catalyst, giving good results (up to 73% ee) in the oxidation of methyl p-tolyl sulfoxide with f-BuOOH (at -20°C in toluene). The chemical yield was close to 90% with the use of a catalytic amount (10 mol %) of the titanium complex (Ti(0-i-Pr)4/(/ )-binaphthol/H20 = 1 2 20). They studied the effect of added water and found that high enantioselectivity was obtained when using 0.5-3.0 equivalents of water with respect to the sulfide. In the absence of water, enantioselectivity was very low. The beneficial effect of water is clearly established here, but the amount of water needed is much higher than that in the case of the catalyst with diethyl tartrate. They assumed that a mononuclear titanium complex with two binaphthol ligands was involved, in which water affects the structure of the titanium complex and its rate of formation. 

Microbiological oxidation is the easiest procedure because it uses the intact cells. Scheme 6C. 11 shows results obtained by using Aspergillus Niger [101], Enantioselectivity can be very high but experiments are performed on a small scale, which results in a low yield of sulfoxides. Both enantiomers of methyl p-tolyl sulfoxide were prepared by Sih et al. with Mortierella isabellina NRRL 1757, giving (/ )-sulfoxide with 100% ee in 60% yield or with Helminthosporium sp NRRL 4671, giving (S)-sulfoxide with 100% ee in 50% yield [104], A similar result was obtained for ethyl p-tolyl sulfide. A predictive model for sulfoxidation by Helminthosporium sp NRRL 4671 was proposed by Holland et al. [105], which was based on the analysis of more than 90 biotransformations of sulfides. 

Chiral sulfoxides. The Sharpless reagent lor asymmetric epoxidation also effects asymmetric oxidation of prochiral sulfides to sulfoxides. The most satisfactory results are obtained for the stoichiometry Ti(0-(-Pr)4/L DET/H20/(CH,),C00H = 1 2 1 2 for I equiv. of sulfide. In the series of alkyl p-tolyl sulfides, the (R)-sulfoxide is obtained in 41-90% ee the enantioselectivity is highest when the alkyl group is methyl. Methyl phenyl sulfide is oxidized to the (R)-sulfoxide in 81% ee. Even optically active dialkyl sulfoxides can be prepared in 50-71% ee the enantioselectivity is highest for methyl octyl sulfoxide. 

Preparative Methods conveniently prepared - by reaction of the magnesium enolate of r-butyl acetate (readily made with Bromomagnesium Diisopropylamide) with (-)-(lR,2S,5R)-Menthyl (S)-p-Toluenesulfinate (eq 1). It was also made in 91% yield by reacting a solution of Lithium Diisopropylamide with (R)-(+)-methyl p-tolyl sulfoxide and 7-butyl carbonate (eq 2). It should be noted that asymmetric oxidation of 7-butyl 2- p-tolylsulfinyl)acetate with a modified Sharpless reagent gave a... 

The most important example of stoichiometric asymmetric oxidation is probably the titanium-catalysed conversion of sulfides into sulfoxides by cumene hydroperoxide in the presence of stoichiometric diethyl tartrate. A simple example is the efficient asymmetric synthesis of methyl p-tolyl sulfoxide 162, an important starting material for much sulfoxide-controlled asymmetric synthesis.30... 

Figure 16.8-1. Oxidation of methyl p-tolyl sulfide to methyl p-tolyl sulfoxide by a monooxygenase. The product can either be of the R- or 5-configuration depending on the monooxygenase used.

A graphite electrode modified chemically with L-phenylalanine gave an ee of 9.7% in the reduction of phenylglyoxalic acid into mandelic acid and an ee of 2.5% in the oxidation of methyl / -tolyl sulfide into its sulfoxide Later this oxidation reaction was improved... 

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