Of methyl-p-tolyl sulfoxide

An optically active sulfoxide may often be transformed into another optically active sulfoxide without racemization. This is often accomplished by formation of a new bond to the a-carbon atom, e.g. to the methyl carbon of methyl p-tolyl sulfoxide. To accomplish this, an a-metallated carbanion is first formed at low temperature after which this species may be treated with a large variety of electrophiles to give a structurally modified sulfoxide. Alternatively, nucleophilic reagents may be added to a homochiral vinylic sulfoxide. Structurally more complex compounds formed in these ways may be further modified in subsequent steps. Such transformations are the basis of many asymmetric syntheses and are discussed in the chapter by Posner and in earlier reviews7-11. 

AS -8 to +4 e.u. Even though the racemization rate constants differ slightly, their distinct dependence on the steric and to a lesser extent on the electronic effects of the substituents bonded to the sulfinyl sulfur atom was noted. It deserves adding that the activation volume for racemization of methyl p-tolyl sulfoxide 41, A F 0 ml/mol, is also consistent with the pyramidal inversion mechanism (249). 

Both enantiomers of methyl p-tolyl sulfoxide are available from the above procedure by selection of the appropriate diethyl tartrate. This procedure describes the preparation of (S)-(-)-methyl p-tolyl sulfoxide which is not easy to prepare by the Andersen method " using (+)-raenthol. 

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. 

It was also reported that using methyJJithium instead of the methyl Grignard could give some racemization of methyl p-tolyl sulfoxide as a result of methyl group exchange via a methylene sulfine intermediate. ... 

Both enantiomers of methyl p-tolyl sulfoxide are also prepared from diacetyl D-glucose giving, with mesyl chloride, and according to the base used, the (S)-methyl sulfinate with diisopropylethy-lamine or the (J )-methyl sulfinate with pyridine, which are then transformed with p-tolyhnagnesium bromide into the corresponding (5)- or (f )-methyl p-tolyl sulfoxide (eq 3). ... 

It was also shown in the enantioselective synthesis of the macrolide patulolide that the anion of methyl p-tolyl sulfoxide was more reactive towards the imidazolide, prepared from the hemi ethyl sebacate, than the ester group (eq 7). 

It was known that photoracemization of optically active sulfoxides can be induced upon sensitization with naphthalene [13]. Hence, by using (/ )-A -acetyl-1-naphthylethylamine 26 as a chiral sensitizer, the first photoderacemization of methyl p-tolyl sulfoxide 25a was performed to give an ee of 2.25% at the apparent photostationary state (pss) after prolonged irradiation [14]. However, more detailed examination, starting with 25a of 3.2% ee and 5.1% led to the conclusion that the ultimate value at the pss is 4.1% ee. With more a bulky substrate 25b, a higher ee of 12% was obtained upon photosensitization with (-f-)-W(trifluoro-methyl)-l-naphthylethylamine 27 [15]. 

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... 

A quite general method of access to optically pure sulfoxides is due to Andersen [96-98] a menthyl sulfinate ester is reacted with a Grignard reagent. Both enantiomers of menthyl p-toluenesulfinate are commercially available. A large-scale preparation of (-)-menthyl (S)-p-toluenesulfinate as well as that of (/ )-(+)-methyl p-tolyl sulfoxide is described [99] by Solladie et at. Other related approaches are presented and discussed in [86]. 

Montanari s procedure allows access to both enantiomers of methyl p-tolyl sulfoxide. The sulfinamides (14) were, however, observed to racemize on exposure to light, but were reported to be optically stable in the dark. 

A stirred mixture of methyl p-tolyl sulfoxide, molecular sieve 3 A as water scavenger, and methylene chloride treated dropwise with satd. ethereal HCl, and stirring continued 2 hrs. at room temp. -> diloromethyl p-tolyl sulfide. Y 77%. F. e. s. R. H. Rynbrandt, Tetrah. Let. 1971, 3553. 

A selection of biocatalytic deoxygenation reactions is shovm in Figure 1.8. The reducing power of baker s yeast in an ethanol-water mixture and sodium hydroxide at 60° C has been found effective for the rapid and selective reduction of a series of N-oxides like aromatic and heteroaromatic N-oxide compounds [118]. DMSO reductase from Rhodobacter sphaeroides f sp. denitrificans catalyzed the (S)-enantioselective reduction of various sulfoxides and enabled the resolution of racemic sulfoxides for the synthesis of (R)-sulfoxides with >97% ee [119,120]. Purified dimethyl sulfoxide reductase from Rhodobacter capsulatus resolved a racemic mixture of methyl p-tolyl sulfoxide by catalyzing the reduction of (S)-methyl p-tolyl sulfoxide and gave enantio-merically pure (J )-methyl p-tolyl sulfoxide in 88% yield, while whole cells of E. coli,... 

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