Sulfides, 3-hydroxy

P-Hydroxy sulfides. Phenylthioacetic acid can be converted into the dianion (1) by treatment with 2 eq. of hthium diisopropylamide in THF at 0°. The dianion can be alkylated in high yield. The monoalkylated product can be converted into the fuUy substituted acid (3) by repetition of the process-conversion to the dianion followed by alkylation. Reduction of (3) with lithium aluminum hydride then gives a 0-hydroxy sulfide (4) in overall yields of 50-90%. 

Hydroxy sulfides (4) can be converted into olefins of the type C=CH, by... 

ORGANOSULFUR COMPOUNDS 2.1. C-chiral hydroxy sulfides and derivatives... 

C-chiral racemic y-hydroxy sulfides were also resolved using PEL under kinetic resolution conditions. The products were transformed into optically active 3-(alkanesulfonyloxy)thiolane salts (Scheme 1). Similarly, 1,2-cyclic sulfite glycerol derivatives cis and trans) were resolved into enantiomers via a Pseudomonas cepacia-catalysed acylation with vinyl butyrate. The E values depended on the solvent used and varied from 2 to 26. ... 

An attempt at the enzymatic hydrolysis of racemic a-acetoxymethyl sulfoxides rac-25 gave the recovered esters in yields up to 40% and with ees up to 95%. The hydrolysis products, a-hydroxymethyl sulfoxides 26, underwent decomposition like in the case of analogous hydroxy sulfides (Equation 1) and hydroxy... 

Isoborneol-derived P-hydroxy-sulfide ligand for addition of ZnEt2 to benzaldehyde. 

On the other hand, several S/O ligands have been successfully applied to the enantioselective addition of ZnEt2 to aldehydes. As an example, Aral et al. have developed isoborneol-derived p-hydroxy-sulfide ligands and employed them in the enantioselective addition of ZnEt2 to benzaldehyde, providing enantio-selectivities of up to 88% ee (Scheme 3.54). These authors showed that the enantioselectivity of the reaction did not depend on the substituent of the sulfur atom. 

Procedure 2 Oxidation of jS-Hydroxy Sulfides to yS-Hydroxy Sulfoxides Catalyzed by CHMO... 

Table 11.2 Oxidation of racemic (3-hydroxy sulfides catalyzed by CHMO...

The kinetic resolution of /3-hydroxy sulfides mediated by CHMO provides an excellent result in the case of sulfide ( )-2 and moderate results with ( )-l and ( )-3. Indeed, the enzyme-catalysed oxidation to sulfoxide 2a showed remarkable enantio- and diastereo-selectivity with an enantiomeric ratio E of 299 and with an ee > 98 % (C = 47 %). 

However, formation of this bond through the conjugate addition of a soft sulfur nucleophile to a,P-unsaturated aldehydes is efficiently catalysed using iminium ion catalysis [116], Using diarylprolinol silyl ether 55 the addition of a series of sulfur based nucleophiles to a variety of a,P-unsaturated aldehydes was shown to be effective (73-87% yield 89-97% ee). The products were isolated as their p-hydroxy sulfide derivatives 73 after in situ reduction of the products (Scheme 33). 

R) and (S)-3-octanol, (i )-2-dodecanol, (i )-2-methyl-4-heptanol and (i )-2-methyl-4-octanol, the pheromones of Myrmica scabrinodis, Crematogaster castanea, C. liengmei, C. auberti and Metamasius hemipterus were synthesized starting from nonracemic P-hydroxy sulfides. 

Analogs ofl-lithiocyclopropyl phenyl sulfide bearing a methylsulfanyl instead of a phenyl-sulfanyl group were obtained from dibromocyclopropanes by sequential treatment with butyl-lithium, dimethyl sulfide and butyllithium. Addition to aldehydes occurred readily and rearrangement of the resulting /7-hydroxy sulfides 10 with trifluoroacetic acid yielded cyclobutanones II.172... 

Selenides and tellurides can be prepared similarly.774 When epoxides are substrates, p-hydroxy sulfides are obtained in a manner analogous to that mentioned in 0-35. Epoxides can also be directly converted to episulfides,775 by treatment with a phosphine sulfide such as PI13PS776 or with thiourea and titanium tetraisopropoxide.777... 

Interestingly, when a fi-substituted alcohol is used in the Barton-McCombie reaction and if a [3-elimination process occurs faster than the hydrogen transfer step, then the formation of a double bond is observed. We have just seen such an example with a dixanthate (see Section 3.1.3). Many others are known as in [3-hydroxy sulfides [231] and [3-hydroxysulfones [232,233] in a modified Julia synthesis of olefins. 

Sulfenate ester (RO-SAr) (7) has a weak S-O bond, so the corresponding alkoxyl radical is formed under photolytic conditions with a mercury lamp, followed by 1,5-H shift where the formed carbon-centered radical reacts with the starting sulfenate ester to give 8-hydroxy sulfide (8) via a chain pathway, as shown in eq. 6.5 [9, 10]. 

Hydroxysulphenylation. The reaction of these two reagents in CH2Cl2/tri-fluoroacetic acid with allylic esters gives vic-trifluoroacetoxy sulfides, which are hydrolyzed to vic-hydroxy sulfides. The reaction with allyl acetate (equation I)... 

Dimethyl-2-hydroxy- -sulfid-Imidazolium-Salz aus 4,5-Dimethyl-1,3,2-dioxaphospholan-2-oxid und Imidazol E2, 663... 

The oxidation system VO(acac)2/TBHP has been used for a series of / - and y-hydroxy sulfides to sulfoxides with moderate to good diastereoselectivity (Figure 3.100).407... 

The ring opening of epoxides with thiols provides an efficient route for the formation of (3-hydroxy sulfides. A one-pot method for the direct synthesis of (3-hydroxy sulfoxides has been developed <07JOC4524>. Treatment of an epoxide with PhSH, Ga(O IT)3, and H202 directly provides the sulfoxide with little to no over oxidation. 

Many of these a-hydroxy sulfides can be cleaved by a reagent composed of lead tetraacetate, pyridine, and acetic acid in a molar ratio of about 2 4 3 per mole of substrate. A tran -diaxial arrangement is required and highly hindered a-hydro"Xy sulfides are not cleaved. 

Alkene synthesis," Diphosphorus tetraiodide [or phosphorusflll) iodide] converts di- and trisubstituted /3-hydroxy sulfides into alkenes. The reaction is conducted for 2-6 hours in refluxing methylene chloride. The reaction is regiospecific, and involves anfi-elimination of the OH and RS groups. Yields are 80-90%. Thionyl chloride is the preferred reagent for a similar reaction with tetrasubstituted )S-hydroxy sulfides. 

Chiral epoxides. A new method for resolution of racemic epoxides involves cleavage with sodium thiophenoxide to give racemic -hydroxy sulfides (2a and 2b) these are converted by reaction with 1 into diastereomeric carbamates, which can be resolved by chromatography. Cleavage of either carbamate with trichlorosilane affords optically pure j3-hydroxy sulfides (2) in yields of 80-90%. These are converted into optically active epoxides (3) by trimethyloxonium tetrafluoroborate followed by treatment with base. The epoxides are obtained in optical purities of 85-100%. ... 

Treatment of 2,3 Cpoxy-l-amines with Lewis acid induces a rearrangement to aziridinium ions that react efficiently with a nucleophiles to give functionalized hydroxy sulfides or hydroxy amines (Equation 23) <1997SL11>. Under the influence of ethylaluminium chloride, an epoxide tethered to an azide undergoes Lewis acid-assisted cyclization followed by an intramolecular Schmidt reaction and subsequent in situ reduction of the intermediate iminium species upon addition of sodium borohydride (Scheme 8). This protocol was used as a key step in a novel synthesis of indolizidine alkaloids of pharmaceutical interest <20030L583, 2004JOC3093>. 

THFs and tetrahydropyrans are formed stereoselectively, via intermediate thiiranium ions formed from hydroxy sulfides 224, upon treatment with acid <2001JHC765>. d-OTrfo-Cyclizations produced the kinetic product 225 (THE) whereas 6-( vo-cyclization produced the thermodynamically more stable tetrahydropyran 227. The four-membered ring 226, which would be formed by 4- o-cyclization, was not observed but it could be an intermediate rapidly equilibrated with the thiiranium ion, as shown in Scheme 47. More concentrated perchloric acid converted 227 slowly to THF 225 in low yield (Scheme 59). 

The additives (MeaSiCl or BF3 Et20) may activate the carbonyl compound or stabilize the intermediate. BF3 Et20 has been used as an activator in the reaction of aldehydes with lithiated phenylsulfones [111] although its fimc-tion remains vague. It may be noted that acyclic products were formed on silylation of the hydroxy sulfides obtained in the reaction of oxazol-2-yl sulfides with aldehydes [80]. 

The formation of alkenes from TB or MDC derivatives of (3-hydroxy sulfides and sulfones is also a useful procedure. When the 1,4-bis-MDC derivative (88) was reacted with BusSnH, the tetrahydrothio-phene (89) was produced, presumably by the process shown in Scheme 8. The first intramolecular step is related to the attack on C=S by a carbon radical in the reactions of 1,2-bis-TB derivatives with BusSnH (equation 16). ... 

Finally, mention may be made of those articles in which this method is utilized in the synthesis of optically active oxiranes for example, the simple synthesis of monosubstituted (S)-oxiranes and the asymmetric cyclization of some chlorohydrins catalyzed by optically active cobalt (salen)-type complexes, or in the enantiomeric selection of racemic oxiranes via halohydrins and /3-hydroxy sulfides. A useful three-step synthesis has been worked out from (S)-amino acids to (R)-alkyloxiranes as well as enantiomer resolution for chiral oxiranes by complexation gas chromatography. ... 

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