Trans-Sulfenylation

A monodentate palladium(II) complex trans-[Pd(py)2(H202)]2+ hydrolyzes Met-Aa amide bonds with a rate comparable with that promoted by [Pd(H20)3(0H)]+. Unlike Pd(H20)3(0H)]+, //chelated complex containing temed (A,A,AAA -tctramcthylcthylenediamine) hydrolyzes Met-Aa amide bonds with hydrolytic rate controlled by temed release. The action of the other two complexes, c -[Pd(ED-TA)C12] (EDTA = ethylene diaminetetraacetic acid) and cis-1,2-bis(2-formylglycinebenzene-sulfenyl)ethane Pd11 chloride differs from the action of similar complexes of U,v-[Pd(en)Cl2] and cw-[Pd(dtco-3-OH)Cl2] (dtco-3-OH = l,5-dithiacycooctan-3-ol).448... 

However, a few thiols (cysteine, N-acetylcysteine and thiosalicylic acid) also react with organic nitrates to release NO by another process that is difficult to discern. It could be that the nitrite reacts with a thiol to give an S-nitrosothiol, a ready source of NO, but nitrosation is unlikely to occur at biological pHs. Another possible route to NO involves formation of a thionitrate by trans-esterification [59] (Eq. (12)). This species could then decompose to give NO via an intermediate sulfenyl compound [60] (Eq. (13)). 

Addition of a sulfenyl chloride to an alkene in the presence of silver fluoride affords (3-fluoro sulfides, as shown in equation (2).18 The same trans adducts can also be prepared from the sulfenyl chloride adducts and silver fluoride. An alternative procedure for the formal addition of methanesulfenyl fluoride to alkenes involves the use of dimethyl(methylthio)sulfonium tetrafluoroborate and triethylamine tris(hy-drofluoride) as in equation (3).19... 

An example of addition of sulfenyl halides to an alkyne is shown in Scheme 1928 where the initial trans adduct of 1,4-dichlorobut-2-yne is further transformed by treatment with base or aluminum amalgam. Another example involves boron trifluoride-catalyzed addition of an arenesulfenamide to alkynes in the presence of acetonitrile, giving (3-acetamidinovinyl sulfides (Scheme 20),29 which can be hydrolyzed to (3-keto phenyl sulfides.30... 

Addition of sulfur chlorides and sulfenyl halides to hydrocarbon olefins is a classic example of electrophilic reaction which usually proceeds under mild conditions and results in stereospecific trans-addition via intermediate formation of cyclic episulfonium cation [134]. Ring-opening reactions of episul-fonium cation with nucleophile is responsible for formation of regioisomers when nonsymmetrical olefins are used as substrates. 

Similarly, enantiopure 3-substitutcd-/V-rnc thy I benzyl /3-sultams have been converted into A -methylbenzyl-a-amino acid thioesters via sulfenylation and Pummerer rearrangement with high or complete retention of configuration. Chiral sulfoxides were prepared by sulfenylation followed by oxidation of trans-isomers as two separable A and B stereoisomers. Treatment with TFAA gave chiral cr-amino acid thioesters in high yields with a de > 90%. Slight epimerization of the cr-chiral center of the cr-phenyl thioesters has been observed under the reaction conditions whereas no epimerization was observed in the case of -/-butyl thioesters (Scheme 28) <1998JOC8355>. 

Similarly, the /ra r-3-substituted-4-sulfenyl /3-sultams 126 can be synthesized as major products by treatment of 3-substituted /3-sultams with LDA followed by reaction with diphenyl disulfide. These are accompanied by the 3,4-air-isomers 127. It should be noted that these air-isomers can be converted to the trans-isomers by treatment with LDA in tetrahydrofuran (THF) at — 78 °C. Oxidation with /-chloroperbenzoic acid (MCPBA) provides /ra r-3-substituted-4-sulfinyl /3-sultams 128 as mixtures of stereoisomers at the sulfoxide moiety. This strategy was applied to obtain chiral 3-substituted-4-sulfinyl /3-sultams with a high diastereoselectivity (Scheme 38) <1998JOC8355>. 

Fully diastereoselective addition of sulfenyl chlorides is also observed with bridged alkenes such as norbornene19, norbornadiene19, and 9,10-dihydro-9,10-ethenoanthracene2°. In all cases the corresponding trans-addition products are formed. 

Thiocyanogen trichloride (from thiocyanogen and chlorine) behaves similarly to simple aliphatic or aromatic sulfenyl chlorides and reacts with cyclohexene to give the trans-adduct24. 

Owing to the urgent need of new drugs for the treatment of AIDS, many methods for converting the title lactones into antiviral dideoxynucleosides have been devised within the past few years. A viable synthesis of the potent anti-HIV agent 3 -deoxy-2, 3 -dehydrothymidine (d4T, 21) relies on trans selective sulfenylation of the lactone-derived silyl ketene acetal (20) with iV-(phenylthio)- -caprolactam (eq 11). In comparable fashion, (21) and related nucleosides have been prepared through seleneny-lation of (20). ... 

The intermediate a-sulfenyl carbonyl compounds may be alkylated prior to oxidative elimination. Phe-nylsulfenylation of the cw-fused butyrolactone (61), followed by methylation and oxidative elimination, gave the a-methylenebutyroiactone (62) because endocyclic elimination is stericaliy inhibited (Scheme 6). For the tran -fused butyrolactone (63), the alkylation was carried out first to ensure exocyclic elimination (Scheme 1). The intermediate a-sulfinylcarbonyl compounds may also be modified before elimination, the alkylation of keto sulfoxides (64) providing a useful synthesis of a,p-unsaturated -y-keto esters (65 Scheme In some cases the use of an excess of strong base provides a dimetaliated... 

Alkane-and arenesulfenyl chlorides add to alkenes and alkynes thus, the addition of 2,4-dinitrobezenesulfenyl chloride (61) may be used to prepare solid derivatives of alkenes, e.g. the adduct (62) (Scheme 37). The Markownikoff addition of a sulfenyl chloride to an alkene is stereospecifically trans the adduct may be sequentially treated with a Lewis acid and a nucleophilic reagent to achieve the introduction of a new carbon-carbon bond (64) via the episulfenium ion intermediate (63) (Scheme 38). The procedure can also be applied to the synthesis of unsaturated sulfides, e.g. (65) (Scheme 39). 

Halogeno-l,2,4-thiadiazol-5-yl sulfenyl chlorides (455) react rapidly with olefins at — 40°C to yield adducts (e.g., 456 from butene). The stereospecific mechanism of the exclusive trans addition probably involves epi-sulfonium ions as intermediates. Thus, erythro adducts arise from trans-2-buteneand threo adducts from ds-2-butene terminal olefins (e.g., isobutylene, 3,3-dimethylbut-l-ene) produce single products, the assigned structures of which (Markovnikov or otherwise) are consistent with their H NMR spectra.209... 

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