A new synthesis of benzo[b]thiophenes utilizing an interrupted Pummerer reaction

A convenient synthesis of 3-arylbenzo[b]thiophenes utilizing an interrupted Pummerer reaction of 2-(1-arylvinyl)phenyl ethyl sulfoxides is described. Thus, treatment of these sulfoxides, which were readily prepared from 2-sulfanylphenyl ketones or 2-fluoro-5-methoxybenzaldehyde, with acetic anhydride at 100 °C afforded 3-arylbenzo[b]thiophenes in reasonable yields.     

Hydrotelluration and carbotelluration of acetylenic sulfoxides: regio- and stereoselective preparation of α- and β-organotellurovinyl sulfoxides

(Z)-β-Organotellurovinyl sulfoxides were synthesized via a highly regio- and stereoselective anti-hydrotelluration of acetylenic sulfoxides. α-Organotellurovinyl sulfoxides were obtained from a three component syn-carbotelluration reaction of acetylenic sulfoxides, that is, syn-addition of monoorganocopper reagents to acetylenic sulfoxides followed by the electrophilic reaction of the vinyl copper intermediates with benzenetellurenyl iodide at low temperature. Synthetic applications of the organotellurovinyl sulfoxides have been investigated.     

The cleavage of meso-epoxides with homochiral thiols: synthesis of (+)- and (−)-trans-1-mercaptocyclohexan-2-ol

The synthesis of (+)- and (−)-trans-1-mercaptocyclohexan-2-ol is described. Ring opening of cyclohexene oxide with (−)-4-methoxybenzylnopan-3(R)-thiol 1a followed by oxidation gives two readily separable diastereomeric sulfoxides. These sulfoxides display very different thermal stability but both undergo regio-specific syn-elimination to give cyclohexan-1-ol-2-sulfenic acid that can be reacted in situ with 3,5-dimethylthiophenol to give a mixed disulfide. Reduction of these disulfides with lithium aluminium hydride gives the title compounds in enantiomerically pure form.     

Lewis acid-promoted electron transfer deoxygenation of epoxides, sulfoxides, and amine N-oxides: the role of low-valent niobium complexes from NbCl5 and Zn

A mild and operationally simple deoxygenation of epoxides, sulfoxides, and amine N-oxides is described using a sub-stoichiometric amount of low-valent niobium complexes generated in situ from commercially available NbCl₅ and zinc dust. The deoxygenation proceeds by a reductive cleavage of polarized O-C/O-N/O-S bonds through a single electron transfer from zinc metal to the niobium-substrate complex due to the high oxophilic nature of the niobium species. The presence of adjacent radical-stabilizing groups is beneficial to epoxide substrates; however the similar prerequisite does not apply to sulfoxides and amine N-oxides, where a broad range of substrates are efficiently deoxygenated in excellent yields.     

Preparation of symmetrical and unsymmetrical monomers towards bridge trifluoromethylated poly(p-phenylenevinylene)

The preparation and identification of a series of trifluoromethylated and bis(trifluoromethylated) precursors and monomers for bridge substituted trifluoromethylated poly(p-phenylenevinylene) (PPV) is reported. These monomers were prepared in several steps from terephthaldicarboxaldehyde and they contain symmetrical and unsymmetrical combinations of leaving groups and/or polarizers, including chlorides, sulfoxides, sulphones, tosylates and S-methyl (and also O-ethyl) xanthates. The electron withdrawing effect of the trifluoromethyl group dominated the regioselectivity of substitution, thus allowing the convenient and selective formation of unsymmetrically substituted products in high yield.     

Sulfoxide-controlled SN2′ displacements between cuprates and vinyl and alkynyl epoxy sulfoxides

The S_N2′ displacement of readily available vinyl epoxy sulfoxides with organocopper reagents takes place in good yields with high anti selectivity and a good degree of E/Z stereocontrol to produce enantiopure α-hydroxy vinyl sulfoxides. A second allylic displacement on the related mesyloxy vinyl sulfoxides allows for the asymmetric construction of two adjacent chiral centers. In addition, cuprate mediated S_N2′ addition to alkynyl epoxy sulfoxides affords α-hydroxy allenyl sulfoxides in good yields.     

Highly stereoselective additions of sulfur stabilized carbanions to [(S)R]-2-(p-tolylsulfinyl)cyclohexanones

We describe the addition reactions of α-thiocarbanions derived from sulfoxides, thioethers, and sulfones to 2-(p-tolylsulfinyl)cyclohexanones. The high stereoselectivity observed in the formation of the chiral hydroxylic carbon is controlled by the configuration of the sulfinyl group at the substrate, but it is modulated by the nature of the sulfur function at the reagent (SOTol>SO₂Ph>SPh). The highly stereoselective formation of the second stereogenic center generated in these reactions from prochiral anions is only achieved with sulfinylcarbanions, the configuration of which controls that of such a center.     

Wacker-type oxidative functionalization of β-substituted unsaturated sulfoxides

The Wacker-type oxidation is an important procedure catalyzed by palladium complexes. A mild and general method for the preparation of β-substituted-δ-oxosulfoxides from the corresponding β-substituted-γ,δ-unsaturated sulfoxides is described. The products are versatile synthetic intermediates for the preparation of syn- and anti-1,3-diol and 1,3-aminoalcohol derivatives.     

A practical synthesis of 4′-thioribonucleosides

A practical synthesis of 4′-thioribonucleosides starting from inexpensive l-arabinose is described. 1,4-Anhydro-2,3-O-isopropylidene-4-thioribitol, which was prepared by using a novel reductive ring-contraction reaction, was converted to the 5-O-silylated sulfoxides. The Pummerer-type thioglycosylation of the sulfoxides gave the 4′-thioribonucleosides stereoselectively.     

Biosensoric flow-through method for the determination of cysteine sulfoxides

Cysteine sulfoxides are known for their canceroprotective and antioxidant potential and have been detected in several plants, mainly those belonging to the leek family (Alliaceae). A number of these plants are used as herbal remedies, spices, or vegetables, including garlic (Allium sativum), onion (Allium cepa) and leek (Allium porrum). Determination of the quality and pharmacological activity of garlic-containing herbal remedies produced from garlic powder is by measurement of their content of the cysteine sulfoxide alliin. A convenient method allowing reliable routine estimation of the alliin levels present in the fresh plant material through to the final remedy is urgently required. The newly developed flow-through method described in this paper was designed in order to fulfill this demand. In contrast to conventional HPLC methods, neither a pre-column derivatization nor a chromatographic separation are required allowing a high throughput of samples. This technique is based on immobilized alliinase (EC 4.4.1.4), which was combined with an ammonia gas electrode mounted in a miniaturized flow-through cell. The lower detection limit obtained for alliin was 3.7×10⁻⁷ M alliin. High specificity for alliin was demonstrated for the electrode and a variety of garlic samples including garlic powders, dry extracts and garlic tablets were analyzed successfully. Results obtained with the new method showed a good correlation with those obtained with conventional HPLC methods. In conclusion, the flow-through method provides a valuable method for quality control of garlic preparations and screening plant materials for their cysteine sulfoxide-related health potential.     

α-Fluorination of β-keto sulfoxides

We have developed an efficient new procedure for α-fluorination of β-keto sulfoxide enolate anions which are generated $\text{in situ}$ via nucleophilic addition reactions to cyclopentenone sulfoxide 7. Perchloryl fluoride is used as the fluorinating agent. Characterization of the product α-fluoro β-keto sulfoxides includes ¹⁹F NMR spectroscopy.     

Sulfoxides derived from Cinchona alkaloids—chiral ligands in palladium-catalyzed asymmetric allylic alkylation

Phenyl sulfides derived from Cinchona alkaloids, 9-PhS-epi-CD, 9-PhS-epi-QN, 9-PhS-epi-QD, and 9-PhS-QN were oxidized into the corresponding sulfoxides. Regardless of the oxidation system used (NaIO₄, TEMPO/NaOCl, VO(acac)₂/chiral Schiff base/H₂O₂) a similar stereochemical outcome of the oxidation was observed. Four pure epimers of sulfoxides 9-PhSO-epi-CD and 9-PhSO-epi-QN were isolated and fully characterized (X-ray, CD, ¹H NMR-pattern). The chiral sulfoxides as well as the corresponding sulfides and sulfones were tested in the Pd-catalyzed allylic alkylation of dimethyl malonate with rac-1,3-diphenyl-2-propenyl acetate. The sulfoxides obtained from Cinchona alkaloids bearing the additional stereogenic center gave the main product of configuration dependent on the chirality of alkaloid framework only. Similar ees (up to 60%) but significantly higher yields (90%) were obtained as compared to the reaction with the corresponding thioethers. The results were in agreement with nucleophilic attack directed at the allylic carbon located trans to the sulfur atom in the M-shaped intermediate η³-allylpalladium complex.     

A novel method for the reduction of sulfoxides with the N,N,N’,N’-tetrabromobenzene-1,3-disulfonamide (TBBDA)/PPh3 system

A new method is described for the reduction of sulfoxides to sulfides using N,N,N’,N’-tetrabromobenzene-1,3-disulfonamide [TBBDA] in combination with triphenylphosphine. Good to excellent yields, short reaction times, high efficiency and facile isolation of the desired products are the advantages of this method.     

Catalytic Enantioselective Alkylation of Sulfenate Anions to Chiral Heterocyclic Sulfoxides Using Halogenated Pentanidium Salts

We report halogenated pentanidiums as phase‐transfer catalysts for the asymmetric alkylation of sulfenate anions to various sulfoxides with high enantioselectivities (up to 99 % ee) and yields (up to 99 %). This approach gives access to enantioenriched heterocyclic sulfoxides that might not be compatible with strong oxidants or organometallic reagents. Computational studies have revealed that the multiple noncovalent interactions such as halogen bonds and nonclassical hydrogen bonds are involved.     

Enantioselective synthesis of aryl sulfoxides via palladium-catalyzed arylation of sulfenate anions

Arylation of various sulfenate anions generated from beta-sulfinyl esters by retro-Michael reaction in the presence of palladium(0) and enantiopure ligands gave the corresponding aryl sulfoxides in enantio-enriched form. The Josiphos-type ligand (R)-(S)-PPF-t-Bu2 turned out to be the best ligand tested, allowing ee's up to 83% in a predictable sense.     

A novel route to fully substituted cyanoallenes from three components, ketones, chloromethyl p-tolyl sulfoxide, and nitriles, via α-bromocyclopropyl p-tolyl sulfoxides

Treatment of 1-chlorovinyl p-tolyl sulfoxides, which were derived from ketones and chloromethyl p-tolyl sulfoxide in high yields, with lithium α-carbanion of nitriles gave the adducts in quantitative yields. The adducts were converted to α-bromocyclopropyl p-tolyl sulfoxides in two steps in good yields. Finally, the sulfoxides were treated with excess lithium carbanion of isobutyronitrile to afford fully substituted cyanoallenes in high to quantitative yields via sulfoxide-lithium exchange reaction. This procedure offers a novel synthetic method for fully substituted cyanoallenes with coupling of three components (ketones, chloromethyl p-tolyl sulfoxide, and nitriles) in good overall yields.     

New synthesis of multi-substituted α-chlorocyclobutanones from 1-chloro-3-cyanoalkyl p-tolyl sulfoxides by 4-Exo-Dig nucleophilic ring closure of magnesium carbenoids to nitrile group as the key reaction

1-Chloro-3-cyanoalkyl p-tolyl sulfoxides were easily prepared from 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from carbonyl compounds and chloromethyl p-tolyl sulfoxide, with lithium α-cyano carbanion of acetonitrile derivatives in good yields. Treatment of these sulfoxides with i-PrMgCl resulted in the formation of multi-substituted α-chlorocyclobutanones in good to high yields via the 4-Exo-Dig nucleophilic ring closure of the generated magnesium carbenoid intermediates to the nitrile group. This procedure provides a new and good way for the synthesis of multi-substituted α-chlorocyclobutanones from carbonyl compounds and substituted acetonitriles with formation of three carbon–carbon bonds in relatively short steps.     

A new synthesis, including asymmetric synthesis, of alkylidenecyclopropanes by 1,2-CC insertion of cyclobutylmagnesium carbenoides as the key reaction

Treatment of 1-chlorovinyl p-tolyl sulfoxides, derived from ketones and chloromethyl p-tolyl sulfoxide, with lithium enolate of carboxylic acid tert-butyl esters gave adducts in high yields. The adducts were converted to 1-chlorocyclobutyl p-tolyl sulfoxides in four steps in high overall yields. Treatment of the 1-chlorocyclobutyl p-tolyl sulfoxides with cyclopentylmagnesium chloride in THF at −40 °C resulted in the formation of cyclobutylmagnesium carbenoids. The magnesium carbenoid 1,2-CC insertion reaction took place smoothly from the cyclobutylmagnesium carbenoids to afford alkylidenecyclopropanes in good to high yields. An asymmetric synthesis of optically active alkylidenecyclopropane was successfully achieved starting from optically active 1-chlorovinyl p-tolyl sulfoxide.     

Reactions of halometal alkoxides

Aryl thenyl and aryl aryl-α-thienylmethyl sulfides have been obtained by the action of oxalic acid esters on an equimolecular mixture of bromomagnesium thienyl or aryl α-thienyl carbinolates and bromomagnesium thiophenolates (or thionaphtholates). Derivatives of the sulfides, sulfoxides and sulfones, are also described.     

Highly regio- and stereoselective PdCl2(MeCN)2-catalyzed cross coupling of 1,2-allenylic sulfoxides with allyl bromide

2-Allyl-1(E),3(E)-dienyl sulfoxides were prepared highly stereoselectively via the PdCl₂(MeCN)₂-catalyzed coupling reaction of 1,2-allenylic sulfoxides and allyl bromide. A rationale was proposed for this transformation.