Sulfides stereospecific

Electron-deficient alkenes add stereospecifically to 4-hydroxy-THISs with formation of endo-cycloadducts. Only with methylvinyl-ketone considerable amounts of the exo isomer are produced (Scheme 8) (16). The adducts (6) may extrude hydrogen sulfide on heating with methoxide producing 2-pyridones. The base is unnecessary with fumaronitrile adducts. The alternative elimination of isocyanate Or sulfur may be controlled using 7 as the dipolarenOphile. The cycloaddition produces two products, 8a (R = H, R = COOMe) and 8b (R = COOMe, R =H) (Scheme 9) (17). Pyrolysis of 8b leads to extrusion of furan and isocyanate to give a thiophene. The alternative S-elimi-nation can be effected by oxidation of the adduct and subsequent pyrolysis. 

Iron Sulfur Compounds. Many molecular compounds (18—20) are known in which iron is tetrahedraHy coordinated by a combination of thiolate and sulfide donors. Of the 10 or more stmcturaHy characterized classes of Fe—S compounds, the four shown in Figure 1 are known to occur in proteins. The mononuclear iron site REPLACE occurs in the one-iron bacterial electron-transfer protein mbredoxin. The [2Fe—2S] (10) and [4Fe—4S] (12) cubane stmctures are found in the 2-, 4-, and 8-iron ferredoxins, which are also electron-transfer proteins. The [3Fe—4S] voided cubane stmcture (11) has been found in some ferredoxins and in the inactive form of aconitase, the enzyme which catalyzes the stereospecific hydration—rehydration of citrate to isocitrate in the Krebs cycle. In addition, enzymes are known that contain either other types of iron sulfur clusters or iron sulfur clusters that include other metals. Examples include nitrogenase, which reduces N2 to NH at a MoFe Sg homocitrate cluster carbon monoxide dehydrogenase, which assembles acetyl-coenzyme A (acetyl-CoA) at a FeNiS site and hydrogenases, which catalyze the reversible reduction of protons to hydrogen gas. 

Oae and coworkers oxidized several diaryl, dialkyl and alkyl aryl sulfides to their corresponding sulfoxides using purified cytochrome P-450 obtained from rabbit liver microsomes138. In agreement with expectations, this enzyme did not exhibit much stereospecificity. Some examples including the observed e.e. values are shown by 121-125. A model was proposed to account for the absolute configurations of the sulfoxides produced (126). The sulfur atom is preferentially oxidized from the direction indicated. 

This enantiomeric specificity has been of interest in other contexts, and stereospecific biotransformation has been observed. Examples include the enantiomeric oxidation of sulfides to sulfoxides (Chapter 11, Part 2) and steroid and triterpene hydroxylation (Chapter 7, Part 2). 

The boron atom has tetrahedral coordination in pyridine complexes of 1,3,2,5-dioxaboraphosphorinane sulfides and selenides. These compounds exist as a mixture of conformers and stereoisomers [Eq. (86)]. In some cases it appeared possible to isolate three individual stereoisomers of one substance. The chemical shift in 31P NMR spectra was shown to be stereospecific. 

For the synthesis of the title compound, Oxone or 3-chloroperbenzoic acid2 can be used to oxidize the sulfide to the sulfone. The title compound is a key reagent for the preparation of fluoroalkenes from aromatic11 and aliphatic2 aldehydes. Recently, a stereospecific method to (E)- and (Z)-fluoroalkenes was reported using this reagant.12 13 14... 

An interesting example of a chemical method for determining the absolute configuration of diastereomeiic a-phenylethyl p-tolyl sulfoxides 195 based on the stereospecific sulfinate-sulfoxide conversion has been reported by Nishio and Nishihata (206). In this work optically active a-phenylethyl p-tolyl sulfoxides 195 and the corresponding sulfones 196 were prepared in two different ways and their specific rotations compared (see Scheme 18). Thus, oxidation of (-H5c) Phenylethyl p-tolyl sulfide 197 with hydrogen peroxide... 

The last synthesis to evolve which is due to Ito and his coworkers is interesting in that it relies on a stereospecific skeletal rearrangement of a bicyclo[2.2.2]octane system which in turn was prepared by Diels-Alder methodology (Scheme XLVIII) Heating of a toluene solution of cyclopentene 1,2-dicarboxylic anhydride and 4-methylcyclohexa-l,4-dienyl methyl ether in the presence of a catalytic quantity of p-toluenesulfonic acid afforded 589. Demethylation was followed by reduction and cyclization to sulfide 590. Desulfurization set the stage for peracid oxidation and arrival at 591. Chromatography of this intermediate on alumina induced isomerization to keto alcohol 592. Jones oxidation afforded diketone 593 which had earlier been transformed into gymnomitrol. 

In general, sulfoximines are accessible by various routes, and most of them involve sulfur oxidation/imination sequences. For example, enantiopure 9 is commonly prepared starting from sulfide 10, which is oxidized with hydrogen peroxide (under acidic conditions) giving sulfoxide 11 (Scheme 2.1.1.1). Subsequent imina-tion of 11 with a mixture of sodium azide and sulfuric acid affords sulfoximine 9 as a racemate. Enantiomer resolution can then be achieved with camphorsul-fonic acid, leading to both enantiomers of 9 with high efficiency [15]. Alternatively, many sulfoximine syntheses start from enantiopure sulfoxides [16, 17], which can be stereospecifically iminated with 0-mesitylenesulfonylhydroxyl-amine (MSH) [18], as shown for the synthesis of sulfoximine (1 )-13 in Scheme 2.I.I.2. 

It has been shown that this migration occurs stereospecifically with inversion in the absence of a solvent, bui nonstereospccifically in the presence of a solvent such as THF or dimethyl sulfide Midland Zolopa Halterman J. 

Where it is possible to distinguish the products, thiol additions show stereospecificity. The products of addition of hydrogen sulfide, thio-phenol, and thiolacetic acid to 1-chlorocyclohexene are to be 75%, 94%, and 66% cis-l, 2-disubstituted cyclohexane, respectively.88 The addition of thiolacetic acid is less stereopecific than the other thiols. The stereospecificity apparently depends upon the ratio of addendum to 1-chlorocyclohexene, Phenylthiyl radical addition to 1-methylcyclo-... 

Thiiranes react with benzyne in an efficient synthesis of phenyl vinyl sulfides. The reaction is stereospecific, thus producing ds-(phenylthio)stilbene from cis-2,3-diphenylthiirane and trans-(phenylthio)stilbene from fra .v-2,3-diphenylthiirane (Scheme 24) (84TL2679). 

Treatment of bis(trimethylsilyl)sulfide (8) with bromine in anhydrous dichloromethane at - 78°C followed by addition of 1,2-disubstituted alkenes (9) to the reaction mixture at the same temperature gave the thiiranes (10) in about 30% yields (Scheme 5) (88TL4177). This synthesis is (i) highly selective, since only 1,2-disubstituted alkenes undergo the transformation to thiiranes and (ii) stereospecific since the stereochemistry of the alkene is retained in the thiirane. The nature of the reagents suggests that the silyl subsituted sulfenyl bromide (11), formed by attack of bromine on (8), is an intermediate. 

Thiiranes can be formed directly and stereospecifically from 1,2-disubstituted alkenes by addition of trimethylsilylsulfenyl bromide, formed at -78 C from reaction of bromine with bis(trimethylsilyl) sulfide (Scheme 7).12 A two-step synthesis of thiiranes can be achieved by addition of succinimide-A/-sulfe-nyl chloride or phthalimide-A -sulfenyl chloride to alkenes followed by lithium aluminum hydride cleavage of the adducts (Scheme 8).13 Thiaheterocycles can also be formed by intramolecular electrophilic addition of sulfenyl chlorides to alkenes, e.g. as seen in Schemes 914 and 10.13 Related examples involving sulfur dichloride are shown in Schemes 1116 and 12.17 In the former case addition of sulfur dichloride to 1,5-cyclooctadiene affords a bicyclic dichloro sulfide via regio- and stereo-specific intramolecular addition of an intermediate sulfenyl chloride. Removal of chlorine by lithium aluminum hydride reduction affords 9-thiabicyclo[3.3.1]nonane, which can be further transformed into bicyclo[3.3.0]oct-1,5-ene.16... 

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