Studies on hydrozirconation of 1-alkynyl sulfoxides or sulfones and the application for the synthesis of stereodefined vinyl sulfoxides or sulfones

The hydrozirconation reaction of 1-alkynyl sulfoxides or sulfones with Cp2Zr(H)Cl in THF at room temperature predominantly gave Z-beta-zirconated vinyl sulfoxides or sulfones with excellent regioselectivity. Compared with 1-alkynyl sulfoxides, the hydrozirconation reaction of 1-alkynyl sulfones exhibits great synthetic potential, leading to the efficient preparation of Z-beta-halovinyl sulfones, Z-beta-sulfonyl alpha,beta-unsaturated ketones, and Z-beta-alkynyl vinyl sulfones. Although the reaction mechanisms are still not clear, the neighboring group participation of the sulfinyl or sulfonyl group may be playing an important role in this unique hydrozirconation reaction.     

Synthesis of fluorinated allylic amines: Reaction of 2-(trimethylsilyl)ethyl sulfones and sulfoxides with fluorinated imines

A new synthesis of fluorinated allylamines through the reaction of 2-(trimethylsilyl)ethyl sulfones and sulfoxides (as vinyl anion equivalents) with imines and imino esters has been described. The process includes a TBAF-mediated fragmentation of 2-(trimethylsilyl)ethyl sulfones to afford the desired allylic amines. When the reaction is performed with the corresponding sulfoxides, the fragmentation takes place under the addition conditions, affording the final products in a single step.     

The mass spectra of thiochromanone and related compounds

The mass spectra of thiochromanone (I), isothiochromanone (II)-2-, 3- and 8-methylthiochromanone and the sulfoxides and sulfones derived from these cyclic sulfides have been determined and the major fragmentation routes established. For the iso series loss of SO or SO₂ competes effectively with the retro-Diels-Alder reaction; however, for the thiochromanone derivatives the retro-Diels-Alder reaction is the major fragmentation route. There is no evidence for rearrangement of the sulfoxides or sulfones to sulfenates or sulfinates, respectively, prior to fragmentation.     

Sulfenylation of heterocyclic 1,3‐dicarbonyl systems: 4‐Hydroxy‐2‐pyrones, 6‐hydroxy‐4‐pyrimidones, 4‐hydroxy‐2‐pyridones, 4‐hydroxy‐6‐pyridazinones,and 5‐hydroxy‐3‐pyrazolones

Anions of enolized heteroaromatic 1,3‐dicarbonyl systems, such as the title compounds 1, 9,14 , and 19 , react in dimethylformamide in the presence of potassium carbonate with diaryl disulfides 2 to yield arylsulfenyl derivatives ( 3, 10, 15, 20 ). The arylthiolate anions 4 formed in this reaction can be oxidized by air to yield the starting disulfides 2 again. Tetraalkylthiuram disulfides 7 react in the same manner to yield dialkylaminothiocarbonylthio derivatives ( 8, 13, 18 ) of the title compounds. Oxidation of the arylsulfenyl derivatives with hydrogen peroxide in sodium hydroxide solution usually leads to sulfoxides ( 5, 11, 16 ), whereas oxidation with peracetic acid affords sulfones ( 6, 12, 17 ).     

Chiral sulfoxides from (R)-α- dimethylaminoethylferrocene

Chiral sulfoxides and sulfones of potential interest in organic synthesis are prepared by the reaction of 2-lithio-1-(dimethylaminoethyl)-ferrocene with disulfides, followed by oxidation of the sulfides thus obtained with sodium metaperiodate on alumina or with 3-chloropcrbenzoic acid. Most of the reactions, in particular oxidations of the sulfides to form the sulfoxides, proceed with high diastereoselectivity. The sulfoxides and sulfones can be isolated as pure enantiomers. Assignment of absolute configurations is based on independent synthesis together with ¹H- and ¹³C-NMR data and ORD measurements.     

Efficient synthesis of racemic and chiral alkenyl sulfoxides by palladium-catalyzed Suzuki coupling

Alkenyl sulfoxide derivatives are obtained in high yields through a palladium-catalyzed Suzuki/Miyaura cross-coupling reaction of racemic and chiral 1-halo sulfoxides with aryl and alkenyl boronic acids. Chiral substrates react with no loss of optical purity and high optical yields. The reaction takes place with different palladium catalysts, such as Pd(PPh₃)₄ or Pd(OAc)₂/DABCO. Although nitrogen ligands like DABCO lead to an active palladium catalyst, they are less effective than the phosphine ones.     

5-Schwefelsubstituierte 1,2-Dithiol-3-one

1, 2-Dithioles with sulfur substitutents in position 5 are prepared by reaction of 4-chloro-1, 2-dithiol-3-ones with thiols, sulfinates, dithiocarbamates, or potassium ethylxanthate. Bis-(4-chloro-1, 2-dithiol-3-on-5-yl) sulfide is produced from 4, 5-dichloro-1, 2-dithiol-3-one with sodium thiosulfate and other thiol forming reagents. The 5-alkylthio- and 5-arylthio-1, 2-dithiol-3-ones can be oxidized with peracids to sulfoxides and, partly, to sulfones; the sulfones can also be obtained from sulfinates. 4-Chloro-5-(α-methyl-benzylthio)-1, 2-dithiol-3-one reacts differently with peracetic acid, giving bis-(4-chloro-1, 2-dithiol-3-on-5-yl) disulfide besides 4-chloro-1, 2-dithiol-3-one. With oxalyl chloride, 4-chloro-5-alkylthio-1, 2-dithiol-3-ones form 3, 4-dichloro-dithioliumchlorides, which react with anilines to give 3-phenylimino-4-chloro-5-alkylthio-1, 2-dithioles.     

Fe(NO3)3·9H2O-catalyzed aerobic oxidation of sulfi des to sulfoxides under mild conditions with the aid of trifl uoroethanol

Selective oxidation of sulfides to sulfoxides was successfully performed by employing readily available Fe(NO3)3·9H2O as the active catalyst with oxygen as the oxidant in 2,2,2-trifluoroethanol (TFE) without the formation of sulfones. Nitrate anion could play a crucial role in promoting the reaction due to the oxidation capacity under acidic media. High yields of sulfoxides were exclusively obtained from the corresponding sulfides. Furthermore, both aromatic and aliphatic sulfides gave moderate to high yields of sulfoxides with this protocol.     

Tandem mass spectra of divalent metal ion adducts of glycosyl sulfides, sulfoxides and sulfones; distinction among stereoisomers

The tandem mass spectra of the divalent metal ion (Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Ni2+, Co2+ and Zn2+) adducts of acetylated 1,2-trans-glycosyl sulfides, sulfoxides and sulfones were examined using low energy collision-induced dissociation on a Quattro II quadrupole tandem mass spectrometer. Abundant doubly charged ions, such as [3M + Met]2+ and [2M + Met]2+, were observed with alkaline earth metal chlorides. The other ions observed were [M + MetCl]+, [M + MetOAc]+, [M + MetO2SPh]+ and [2M + MetCl]+. The deprotonated metal adducts [M + Met-H]+ were seen only in the sulfones. The divalent metal ion adducts showed characteristic fragmentation pathways for the glycosyl sulfides, sulfoxides and sulfones, depending on the site of metal attachment. The doubly charged metal ion adducts dissociate to two singly charged ions, [M + MetOAc]+ and [M - OAc]+, in the sulfides and sulfoxides. In the sulfones, the adducts dissociate to [M + MetO2SPh]+ and [M - O2SPh]+. In contrast to the alkaline earth metals, which attach to the acetoxy functions, the transition metals attach to the sulfide and sulfoxide functions. The metal chloride adducts display characteristic fragmentation for the sulfides, sulfoxides and sulfones. The glucosyl, mannosyl and galactosyl sulfides, sulfoxides and sulfones could be differentiated on the basis of the stereochemically controlled MS/MS fragmentations of the metal chloride adducts.     

Evidence of Two Key Intermediates Contributing to the Selectivity of P450‐Biomimetic Oxidation of Sulfides to Sulfoxides and Sulfones

A mild process for the selective oxidation of sulfides is in great demand. Therefore, probing the mechanism underlying the biological oxidation of sulfides under ambient conditions may provide valuable insights for the development of such a reaction. Based on porphyrin models of P450 enzymes, evidence of two key intermediates, Int0 and Int1 , in this reaction is provided. Spectroscopic studies indicated the formation of a hydroperoxide‐iron(III) species ( Int0 ) upon addition of H₂O₂. This intermediate proved to be highly selective for sulfoxide production. By contrast, a defined porphyrin oxoiron(IV) cation radical ( Int1 ) directly reacted with sulfoxides, leading selectively to the corresponding sulfones. Interestingly, the available sulfoxides reversibly act as a new axial ligand for Int0 forming a more active species Int0 _SO. The amount of Int0 increased in the presence of alkyl, aryl, or aromatic sulfides, while Int1 formed in the absence of these sulfides. Thus, sulfoxides and sulfones would selectively form under conditions that favor the corresponding intermediates, which elucidate the biological oxidation pathway.     

Sulfur-containing spirocyclic compounds based on 3-methyl-(amino)-1-phenylpyrazol-5-ones

3-Methyl(amino)-1-phenylpyrazol-5-ones react with N-chlorosulfenylphthalimide to give 4-phthalimidothiopyrazoles which decompose to form 3-methyl(amino)-1-phenylpyrazol-5-one-4-thiones. They were identified as their spirocyclic adducts with dienes. Oxidation of the latter with m-chloroperbenzoic acid gives spirocyclic sulfoxides and sulfones.Institute of Organic Chemistry, Ukraine Academy of Sciences, Kiev 253660. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 187–192, February, 2000.     

Products of Reaction of Tricyclo[4.1.0.02,7]heptane and 1-Bromotricyclo[4.1.0.02,7]heptane with Hydrogen Sulfide,and Syntheses Based Thereon

By reactions of 1-R-tricyclo[4.1.0.02,7]heptanes (R = H, Br) with hydrogen sulfide initiated by UV irradiation endo-6-bicyclo[3.1.1]heptanethiols and bis(endo-6-bicyclo[3.1.1]heptyl) sulfides were synthesized. The sulfides were oxidized to the corresponding sulfoxides and sulfones. The results of HBr elimination from the bromine-substituted sulfoxides and sulfones effected by potassium tert-butylate are discussed. The latter reaction results in the recovery of the system of 1-substituted tricyclo[4.1.0.02,7]heptane.     

Synthesis and oxidation of sulfides based on caryophyllene oxide and phenylmethanethiol

Lewis acid-catalyzed reaction of (–)-caryophyllene oxide with phenylmethanethiol gave sulfides with clovane and caryophyllane structure which were oxidized to the corresponding sulfoxides and sulfones in 74 and 84% yield, respectively.     

A Convenient Procedure for the Reduction of Sulfones to Sulfoxides

Although there have been a relatively large number of publications recently dealing with the reduction of sulfoxides fo sulfides^1,2 there are still very few general procedures for the reduction of sulfones to sulfides and none at all, as far as we are aware, for the reduction of sulfones to sulfoxides. In his paper dealing with the use of diisobutylaluminum hydride (DIBAL-H) for the reduction of sulfones to sulfides, for example, Gardner³ points out the inadequacies of the more readily available lithium aluminum hydride for this reduction. We have developed a two part procedure for reducing sulfones 1 to sulfoxides 2 which fills an important gap in the functional group interconversion of organosulfur compounds, the results of which we now describe.     

Use of sulfur derivatives as an ortho directing group for the metalation of diazines. Metalation of diazines. XVIII

The metalation of thioethers, methyl and phenyl sulfoxides and sulfones of pyrazine and pyridazine has been performed. Methyl sulfoxides and sulfones were first metalated on the methyl group. The ortho directing effect of thioethers, sulfoxides and sulfones have been compared with the methoxy group. The sulfoxides were shown to be very good ortho directing groups.     

Selective Oxidation of Sulfides to Sulfoxides/Sulfones by 30% Hydrogen Peroxide

Abstract

A selective and efficient procedure for the oxidation of various sulfides with sodium tungstate dihydrate with 30% hydrogen peroxide in the presence of trioctylmethylammonium dihydrogen phosphate, respectively, to the corresponding sulfoxides and sulfones is reported. The oxidation reaction is carried out at –5 to 0 °C in the presence of hydroxypropyl-β-cyclodextrins for sulfoxides or at 50–60 °C for sulfones. The mild reaction conditions, easy workup, and good yields of the products are the major advantages of this method.     

New synthesis of allylidenecyclobutanes by the reaction of cyclobutylmagnesium carbenoids with vinyl sulfones

The reaction of cyclobutylmagnesium carbenoids, which were generated from 1-chlorocyclobutyl p-tolyl sulfoxides with EtMgCl via the sulfoxide-magnesium exchange reaction at low temperature, with carbanions derived from vinyl sulfones with n-BuLi or LDA resulted in the formation of allylidenecyclobutanes in moderate to good yields. The actual reactive species of the sulfones in this reaction were proved to be the lithium α-sulfonyl carbanion of allyl sulfones derived from the vinyl sulfones by double bond migration with the bases used. Mono- and di-substituted allylidenecyclobutanes can be obtained by using a variety of vinyl sulfones.     

1-(2′-烷硫基乙氧基)甲基尿嘧啶及其氧化物的合成

采用30％H202／DEAD的试剂组合,用于将硫醚及亚砜的衍生物氧化成砜类物质的反应,合成了1-(2-烷硫基乙氧基)甲基尿嘧啶及其氧化物,产物结构经元素分析、1H NMR和IR进行表征,并研究了其抗癌活性.     

Synthesis of novel 1-phenyl-1H-indole-2-carboxylic acids. II. Preparation of 3-dialkylamino, 3-alkylthio, 3-alkylsulfinyl,and 3-alkylsulfonyl derivatives

The synthesis of novel indole-2-carboxylic acids with amino- and sulfur-containing substituents in the indole 3-position is described. An Ullmann reaction with bromobenzene converted 1H-indoles with 3-(acetylamino)- and 3-(diethylamino)-substituents into 1-phenyl-1H-indoles. Reaction of 3-unsubstituted indoles with thionyl chloride provided indole 3-sulfinyl chlorides, which reacted with alkyl and aryl Grignard reagents to form the corresponding sulfoxides. The indole sulfoxides thus obtained were reduced to sulfides or oxidized to sulfones.     

Cross-metathesis reaction of vinyl sulfones and sulfoxides

Cross-metathesis reactions of α,β-unsaturated sulfones and sulfoxides in the presence of molybdenum and ruthenium pre-catalysts were tested. A selective metahesis reaction was achieved between functionalized terminal olefins and vinyl sulfones by using the ‘second generation’ ruthenium catalysts 1c-h while the highly active Schrock catalyst 1b was found to be functional group incompatible with vinyl sulfones. The cross-metathesis products were isolated in good yields with an excellent (E)-selectivity. Both the molybdenum and ruthenium-based complexes were, however, incompatible with α,β- and β,γ-unsaturated sulfoxides.