Reduction of sulfoxides

Preparation of chiral sulfoxides can be achieved by the biocatalytic reduction of sulfoxides. One example is the reduction of alkyl aryl sulfoxides by intact cells of Rhodobacter sphaeroides f sp. denitrificans (Fig. 10.15). ° In the reduction of methyl para-substituted phenyl sulfoxides, S-enantiomers were exclusively deoxygenated while enantiomerically pure R-isomers were recovered in good yield. For poor substrates such as ethyl phenyl sulfoxide, the repetition 

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Biologically, the reduction of methionine sulfoxide to methionine with NADPH is catalyzed by an enzyme79. Recently, the mechanism of reduction of sulfoxides by treatment with an NADPH model has been studied80. 

It was shown that dibenzothiophene oxide 17 is inert to 1-benzyl-l,4-dihydro nicotinamide (BNAH) but that, in the presence of catalytic amounts of metalloporphyrin, 17 is reduced quantitatively by BNAH. From experimental results with different catalysts [meso-tetraphenylporphinato iron(III) chloride (TPPFeCl) being the best] and a series of substituted sulfoxides, Oae and coworkers80 suggest an initial SET from BNAH to Fe1 followed by a second SET from the catalyst to the sulfoxide. The results are also consistent with an initial coordination of the substrate to Fem, thus weakening the sulfur-oxygen bond in a way reminiscent of the reduction of sulfoxides with sodium borohydride in the presence of catalytic amounts of cobalt chloride81. 

On the other hand, borane reduction of sulfoxide 46 gave a mixture of 47 and 48 in equal amounts and, more interestingly, no reaction of 47 occurred with borane under the same conditions. These results indicated that borane reduction of the olefin in 46 required the activation and potential direction by the sulfoxide oxygen. 

Reduction of sulfoxide (S)-40 was carried out in toluene using 1.05 equiv of 1M BH3-THF at 10°C, producing the cis-diaryl dihydrobenzoxathiin 12 with complete stereoselectivity. Upon work-up and crystallization from toluene and heptane, the desired product 12 was isolated in 88% yield and over 99% ee (Scheme 5.13). Borane dimethylsulfide led to a slower reaction. To the best of our knowledge, this synthetically useful reaction is unprecedented in the literature [13].1 Investigation... 

Reduction of sulfoxide 210 with the corresponding arylsulfanyl derivative 212 can be done using diphosphorus tetraiodide (Scheme 26) <1990CL1547>. 

Musker and Doi84 reported convincing kinetic evidence for the intervention of a disulfonium dication during reduction of sulfoxide 13 with iodide in... 

Titanium(III) chloride has been used both as a reagent for the quantitative determination of sulfoxides (49,247) and preparatively in the reduction of sulfoxides, RjSO (R = nBu, Ph, benzyl) to the corresponding thioethers. The attraction of using low-valent early transition metals as reductants is the high selectivity of the reaction as shown in Eq. (17). 

RA Houghten, CH Li. Reduction of sulfoxides in peptides and proteins. (/V-methyl-sulfamylacetamide) Anal Biochem 98, 36, 1979. 

Solid-state reductions of sulfoxides such as 449 have been performed with potassium iodide andp-toluenesulfonic acid monohydrate [144]. Dibenzothi-ophene (450) or similarly bis-4-tolylsulfide (451) are obtained with 100% yield. 

In the rings containing sulfur, reduction of sulfoxides of phenoxathiin and thianthrene can be performed in excellent yield with the aluminium chloride/sodium iodide or zinc dust/l,4-dibromobutane systems <1996CHEC-II(6)447>. 

The proposed mechanism of the oxidative cleavage of S-protecting groups by the chlorosilane/sulfoxide procedure is outlined in Scheme 8. 95 The first reaction is considered to be formation of the sulfonium cation 9 from diphenyl sulfoxide (7) and the oxygenophilic silyl compound 8. The formation of a sulfonium ion of this type is known and has been utilized for the reduction of sulfoxides. 97 Subsequent electrophilic attack of 9 on the sulfur atom of the S-protected cysteine residue leads to the formation of intermediate 10, whereby the nature of the silyl chloride employed should be the main factor that influences the electrophilicity of 9. The postulated intermediate 10 may then act as the electrophile and react with another S-protected cysteine residue to generate the disulfide 11 and the inert byproduct diphenyl sulfide (12). This final step is analogous to the reaction of a sulfenyl iodide as discussed in Section 6.1.1.2.1. 

Deoxygenation of sulfoxides, selenoxides, oximes, and nitroalkanes.2 The reduction of sulfoxides and selenoxides is possible with PI3 or P2I4 in CH2C.l2 even at temperatures of —78°. Yields are 70-95%. 

Sulfoxide Reduction. The reduction of sulfoxides has been reported to occur in mammalian tissues. Soluble thioredoxin-dependent enzymes in the liver are responsible in some cases. It has been suggested that oxidation in the endoplasmic reticulum followed by reduction in the cytoplasm may be a form of recycling that could extend the in vivo half-life of certain toxicants. 

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