SULFIDE SYNTHESIS ALKYL ARYL SULFIDES

Sodium toluene dispersion of, 55, 65 Sodium p-toluenesulfinate, 57, 103 Spiro[4 n] alkenones, 58, 62 Spiro[cyclopentane-l,l -indene] 55, 94 Squalene, 56, 116 Squalene, 2,3-epoxy, 56, 116 Stannic chloride, 56, 97 Steroids synthesis, 58, 85 E Stilbene, 55, 115,58, 73 z-Stilbene, 58, 133 Styrene, 56, 35,58, 43 Styrene glycol, 55, 116 Styrene glycol dimesylate, 55, 116 Succinic acid, 58, 85 Succinic anhydride, 58, 85 Sucunimide, 56, 50, 58, 126 Succimmide, Vbromo, 55, 28, 56, 49 SULFIDE CONTRACTION, 55, 127 Sulfide, dimethyl-, 56, 37 SULFIDE SYNTHESIS, 58, 143,58, 138 SULFIDE SYNTHESIS ALKYL ARYL SULFIDES, 58, 143 SULFIDE SYNTHFSIS DIALKYL SULFIDES, 58, 143 SULFIDE SYNTHESIS UNSYMMETRI-CAL DIALKYL DISULFIDES, 58, 147 SULFONYL CYANIDES, 57, 88 Sulfur tetrafluoride, 57, 51... 

Enantiomerically pure sulfoxides play an important role in asymmetric synthesis either as chiral building blocks or stereodirecting groups [156]. In the last years, metal- and enzyme-catalyzed asymmetric sulfoxidations have been developed for the preparation of optically active sulfoxides. Among the metal-catalyzed processes, the Kagan sulfoxidation [157] is the most efficient, in which the sulfide is enantioselectively oxidized by Ti(OzPr)4/tBuOOH in the presence of tartrate as chirality source. However, only alkyl aryl sulfides may be oxidized by this system in high enantiomeric excesses, and poor enantioselectivities were observed for dialkyl sulfides. 

Peroxidases have been used very frequently during the last ten years as biocatalysts in asymmetric synthesis. The transformation of a broad spectrum of substrates by these enzymes leads to valuable compounds for the asymmetric synthesis of natural products and biologically active molecules. Peroxidases catalyze regioselective hydroxylation of phenols and halogenation of olefins. Furthermore, they catalyze the epoxidation of olefins and the sulfoxidation of alkyl aryl sulfides in high enantioselectivities, as well as the asymmetric reduction of racemic hydroperoxides. The less selective oxidative coupHng of various phenols and aromatic amines by peroxidases provides a convenient access to dimeric, oligomeric and polymeric products for industrial applications. 

The typical S-oxidation with BVMOs allows the formation of chiral sulfoxides from organic sulfides. This oxidation has received much interest in organic chemistry due to its use in the synthesis of enantiomerically enriched materials as chiral auxiliaries or directly as biologically active ingredients. This reaction has been studied extensively with CHMO from Adnetohacter showing high enantioselectivi-ties in the sulfoxidation of alkyl aryl sulfides, disulfides, dialkyl sulfides, and cychc and acyclic 1,3-dithioacetals [90]. CHMO also catalyzes the enantioselective oxida-hon of organic cyclic sulfites to sulfates [91]. 

Synthesis of alkyl aryl sulfides. n-Butyl I -naphthyl sullide is prepared by charging a l-l. three-necked, round-bottomed flask equipped with a thermometer, a reflux... 

Another reaction of heteroatom oxidation is that of S-oxidation, which leads to the synthesis of sulfoxides, a reaction not very common in the plant cell biochemical factory. Enantiomerically pure sulfoxides are important chiral synthons in asymmetric synthesis, in particular in enantio-selective carbon-carbon bond formation [77]. The sulfoxide functional group is involved in different biological activities, and optically pure sulfoxides are of great pharmaceutical interest [82]. However, plant peroxidases, such as horseradish peroxidase, catalyze the enantio-selective sulfoxidation of alkyl aryl sulfides ... 

In an analogous approach, the effect of imidazole was also observed by Inoue et al. [114]. When alkyl aryl sulfides were oxidized with a novel iron porphyrin catalyst (52) (0.2 mol% equiv), the reaction proceeded enantioselectively under appropriate conditions. Iodosobenzene was used as oxidant in dichloromethane at -43°C. The turnover number increases to 142, and an ee of 73% was obtained in the presence of a 100 to 600 molar ratio of imidazole to catalyst for the synthesis of (5)-methoxymethyl phenyl sulfoxide. In the absence of imidazole, the enantioselectivity disappeared, giving the racemic sulfoxide. 

Mercaptoacetic acid stirred 4 hrs. at 60° with slightly more than 2 moles 0-benzyl-N,N -dicyclohexylisourea in abs. dioxane benzyl 2-(benzylthio)-acetate. Y 84%. F. e. s. E. Vowinkel and C. Wolff, B. 107, 496 (1974) alkyl aryl sulfides s. Synthesis 1974, 430. 

The synthesis of alkyl aryl sulfides has been achieved using sodium thiosulfate as the sulfur source (Scheme 5.1) [1]. This was a valuable approach since many of the classic methods for the synthesis of alkyl sulfides required the use of a thiol. Using this approach, an array of aryl halides and alkyl chlorides were converted into alkyl aryl sulfides. While aryl halides bearing electron-withdrawing groups as well as heteroaromatic halides were successfully transformed using this approach, electron-rich aryl halides were sluggish. Overall, this is an attractive approach to the synthesis of these compounds. 

The reaction of alkyl aryl sulfides with diaryliodonium salts generated unsymmetrical diaryl sulfides in moderate to excellent yields through cleavage of the sulfur-carbon(sp ) bond and formation of a new sulfur-carbon(sp ) bond (Scheme 5.38) [60]. The synthesis was transition metal free and tolerated a host of different electron-withdrawing and donating groups. Another noteworthy aspect of the chemistry was that it was successful in an acidic environment. This renders the work complementary to the transition metal-catalyzed routes that are typically carried out under basic conditions. In related work, the... 

The Aggarwal group has used chiral sulfide 7, derived from camphorsulfonyl chloride, in asymmetric epoxidation [4]. Firstly, they prefonned the salt 8 from either the bromide or the alcohol, and then formed the ylide in the presence of a range of carbonyl compounds. This process proved effective for the synthesis of aryl-aryl, aryl-heteroaryl, aryl-alkyl, and aryl-vinyl epoxides (Table 1.2, Entries 1-5). 

SULFIDE SYNTHESIS IN PREPARATION OF DIALKYL AND ALKYL ARYL SULFIDES NEOPENTYL PHENYL SULFIDE... 

HEXAHYDRO - 4a,5 - DIMETHYL - 2(3H) - NAPHTHALE-NONE and 2-TRIMETHYLSILYLOXY-1,3-BUTADIENE AS A REACTIVE DIENE DIETHYL trans -4-TRIMETHYL-SILYLOXY-4-CYCLOHEXENE-1,2-DICARBOXYLATE. Sulfur substitution also continues to be of high interest, and three preparations on sulfide synthesis are included BENZYL SULFIDE DIALKYL AND ALKYL ARYL SULFIDES NEOPENTYL PHENYL SULFIDE and UNSYMMETRICAL DIALKYL DISULFIDES sec-BUTYL ISOPROPYL DISULFIDE. 

Asymmetric synthesis of sulfoxides can be achieved by biocatalytic oxidation of sulfides and reduction of sulfoxides (Figure 33). i4-27s One example is the reduction of alkyl aryl sulfoxides by intact cells of Rhodobacter sphaeroides f.sp. denitrificans (Figure 33 (a)). 341 In the reduction of methyl -substituted phenyl sulfoxides, ( S )-cnanliomcrs were exclusively deoxygenated while enantiomerically pure (W)-isomcrs were recovered in good yield. For poor substrates such as ethyl phenyl sulfoxide, the repetition of the incubation after removing the toxic product was effective in enhancing the ee of recovered (f )-enantiomers to 100%. 

Sulfides, or thioethers, are sulfur analogues of ethers, and like ethers they can be either symmetrical (R2S) or unsymmetrical (RSR1, where R and R are different). Sulfides can be prepared from alkyl halides by a Williamson-type synthesis with sodium hydrogen sulfide, sodium thiolate or sodium sulfide from alkyl or aryl halides via the Grignard reagent (11) from alkenes by radical-catalysed addition of thiols or by reduction of sulfoxides (Scheme 9).2b... 

Potassium ert-butoxide, sodium hydride, butyllithium have all been used for this purpose. The alkyl(aryl)sulfanylcarbene (carbenoid) thus generated undergoes addition, often effectively, across the double bond of alkenes, enol ethers, ketene acetals and enamines. The use of chloromethyl phenyl sulfide, oxirane, tetraethylammonium bromide as a catalyst and an alkene gave phenylsulfanylcyclopropanes in rather low yield. For the synthesis of l,l-dimethyl-2-phenylsulfanylcyclopropane, see Houben-Weyl, Vol.4/3, p250 and of endoj exo-7-phenylsulfanylbicyclo[4.1.0]heptane, see Vol. E19b, pl691. 

Treatment of methyl phenyl sulfoxide with diethylaminosulfur trifluoride (DAST), in the presence of antimony trichloride provides 159 in quantitative yield (66). The reaction proceeds in good yield with dialkyl sulfoxides and alkyl aryl sulfoxides (163). Reoxidation of the a-fluorosulfide (165) to the corresponding sulfoxide (161), followed by pyrolysis, provides a direct synthesis of fluoroolefins (65). The reaction is believed to proceed by a Pummerer-type mechanism (l.e., a fluoro-Pummerer reaction, Scheme 48). Similarly, Umemoto (67) reported that N-fluorocollidine (167) converted sulfides to ot-fluorosulfides (170) presumably via an S-fluorosulfonium cation species 168 (Scheme 49). The synthetically challenging fluorovinyl ether nucleosides (175) and (176) were prepared using the fluoro-Pummerer reaction (Scheme 50) (60) the (E)-isomer (175) could be isomerized to 176 under photolytic conditions. Finch and co-workers (69) converted 160 to the sulfoximine 178 and demonstrated the utility of this compound as a mild fluoromethylene synthon (Scheme 51). Base-catalyzed condensation 178 with a carbonyl compound gave 179 which afforded... 

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