Highly diastereoselective oxidations of a thioether appended with a neighboring hydroxyl group (original) (raw)
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Diastereoselective oxidation of substituted 1,2-dithiolan-3-ones
Tetrahedron Letters, 1994
Stereochemical control in the oxidation of thioethers to sulfoxides has been much studied recently. Enantiosekctive oxidations, both uuymatic' and chemical,* have betn m. Dia&reoscktive oxidations are also well-known. However, mective oxidation of sulfoxidcs to sulfones is almost unknown. Recently Nakayama and coworker9 qorted some examples. In this papez diastaeoselective oxidations of sulfoxides which are more ma%ive than those of the corresponding thioethers and which have a diffirent me&anSc basis-for selectivity than those pleviously reported, are presulted. Oxidation of substitutfd Metanes lad with m-chloroperoxybenxok acids (MCPBA) gave the w
Asymmetric oxidation of thioethers
Tetrahedron Letters, 1989
p-hydroqsulfoxides. of fairly high optical purity (up to 80%) may be prepared by direct asymmetric oxidation [EutO~H. Ti(OPr')d, (+)-DET] of acetylated or silylated S-methyl p-hydronysuljides and subsequent deprotection. The upgrading of the optical purity from 78% up to ~98% by simple crystallization has been obtained. Access to optically pure a-hydroxysulfoxides by direct asymmetric oxidation of the parent a-hydroxysulfides would be a significant synthetic achievement in view of their vast utilization in asymmetric transformations2. Unfortunately, the titanium-catalyzed procedure developed in our laboratory for the asymmetric oxidation of thioethers3, while rather effective for some classes of substrates e.g. methylaryl sulfides3 and 2-substituted-dithiolanes4~5 (e.e. 70-98%), gives poor results in the oxidation of a-hydroxysulfides6. Unsatisfactory results have also been obtained when the Sharpless reagent7 or the Kagan's procedure* were employed. We have recently reported6 that the enantioselection in the oxidation of a series of I+hydroxysulfides (Ph-CH(OH)-CHa-S-R; R=t-Butyl, o-Tolyl, Naphtyl; e.e. 20-47%) is lower than that attainable in the oxidation of structurally similar unfunctionalyzed sulfides. Therefore our data indicate that, at variance with the asymmetric epoxidation of allylic alcohols by the Sharpless reagent7, in p-hydroxysulfide oxidations the hydroxy group plays a negative role as far as the enantioselection is concerned. At the same time we have critically examined all the data on sulfide asymmetric oxidations9 reaching the conclusion that the simple steric differentiation of the two groups attached to the sulfur atom plays a dominant role in determining high enantioselections9.
Oxidation of thioethers to sulfoxides by iodine. II. Catalytic role of some carboxylic acid anions
Journal of the American Chemical Society, 1968
2096 product on the basis of recovered starting material, together with some unidentified by-products. 111-OH and V-OH were treated similarly, except that the product from 111-OH was collected directly from the reaction flask in a cold trap. The results of the pmr analyses of the products are summarized in Table IV. Pmr Studies. Both Varian Models A-60 and A-60A were used in the present study. The spectra of IV-ODNB, V-ODNB, and their nondeutrated analogs, were taken in chloroform-dl and all of the other spectra in carbon tetrachloride. The peak positions of the protons which were used in the analyses are collected in Table IX. The amount of scrambling in each of the reaction products was, in most cases, determined by integrations which were made several times in order to minimize the error. But, in those cases where the peak separations are not great enough, the spectra were taken with slower sweep time and the peak heights were used for analyses. An internal standard technique was also employed for the determination of the per cent scrambling in each of the olefinic products IV-01 and V-01. For this purpose, desoxybenzoin was chosen and the methylene group absorption peak (6 4.05) of the standard was compared with the vinyl proton peaks of the sample.
The Journal of Organic Chemistry, 1987
The energy difference between equatorial and axial sulfur functions at C(3) in oxane has been determined in various solvents by low-temperature 13C NMR spectroscopy. The values in CDBClz are as follows: MeS,-1.21 f 0.11 kcal/mol; SOMe, more polar isomer, 4. 1 0 f 0.05 kcal/mol, less polar isomer, 4-4 3 f 0.13 kcal/mol; SOZMe, ca.-1.45 kcal/mol; Me2S+, 0.55 kcal/mol; HS,-1.1 f 0.1 kcal/mol (negative values meaning preference for the equatorial conformer). The configurations of the two sulfoxides were determined by a combination of X-ray crystallography and proton and 13C NMR spectroscopy. In the case of MeS,-AGO is close to the average of the corresponding conformational free energy differences in cyclohexane and dioxane (at C-5). For MeSO the same is true for the mean-AGO of the two sulfoxides but not for the individual values. In the case of MeS02, the experimental value of-AGO is much larger than the above average, supporting an earlier hypothesis that in 1,3-dioxan-5-yl methyl sulfone the methyl group is turned into the ring. In the methyl 3-tetrahydropyranyl sulfone, this would produce serious steric compression with the axial hydrogen a t C(5). In previous publications we have discussed conformational equilibria of oxanes substituted with nonpolar (methyl) group^,^ of thianes and their sulfoxides, and sulfones substituted with hydroxy, alkoxy, and acetoxy groups,la as well as conformational properties of acyclic compounds with vicinal oxygen and sulfur function^.^ The present work deals with oxanes substituted in position 3 with sulfide, sulfoxide, sulfone, and sulfonium functions and serves as a check for the magnitudes of pertinent sulfur/oxygen gauche interactions; it also points to some characteristic differences in conformational equilibria of sulfur-substituted cyclohexanes and corresponding 1,3dioxanes (substituent in 5) on one hand and 3-substituted oxanes on the other. In contrast to the conformational energies of nonpolar substituents in ~x a n e s ,~ the AGO values for polar substituents are not necessarily midway between those in cyclohexanes and those in 1,3-dioxanes. Synthesis and Configurational Assignment. Compounds in the 3-substituted oxane series were synthesized as shown in Scheme 1, R = H. Free radical catalyzed addition of thiolacetic acid to dihydropyran followed by saponification to mercaptide and methylation gave the methylthio ether 1, which was oxidized with 1 equiv of sodium periodate to a diastereomer mixture of sulfoxides 2 and 3, which were separated by chromatography. Oxidation of 1 with excess periodate gave the sulfone 4; sulfonium salt 5 was prepared from 1 and methyl ptoluenesulfonate. Acidification of the solution of mercaptide (vide supra) gave thiol 6. We also prepared the corresponding cis-and trans-6methyl compounds (Scheme I, R = CH3) by starting from 6-methyldihydr~pyran~ in place of dihydropyran. The diastereomeric 2-methyl-5-(methylthio)oxanes (7) were separated by chromatography and the cis isomer was (1) (a) Part 4 6
Tetrahedron Letters, 2000
Treatment of p-tert-butylthiacalix[4]arene (1) with benzyl bromide in THF–DMF using NaH as the base catalyst afforded the tetrabenzyl ether of cone conformation (4C) as the major product, oxidation of which, with NaBO3 in CHCl3–acetic acid, proceeded readily to give the corresponding sulfinyl compound (5) with the four SO groups disposed on the same side of the plane defined by the macrocyclic ring probably to avoid the steric hindrance imposed by the benzyllic moieties. Cleavage of the ether bonds gave a new stereoisomer of p-tert-butylsulfinylcalix[4]arene (2(ccc)) with the four SO groups arranged in a cis–cis–cis configuration.
Highly Enantioselective Oxidations of Ketene Dithioacetals Leading to Trans Bis-sulfoxides
The Journal of Organic Chemistry, 2003
Solvents and reagents: Commercial grade solvents were dried and purified by standard procedures, as specified in Purification of Laboratory Chemicals, 3 rd ed. (Perrin, D. D.; Armarego, W. L. F. Pergamon Press: New York, 1988). Chromatography: Flash chromatography was performed on silica gel (400-630 mesh). TLC was performed on S-2 aluminium-backed silica plates precoated with silica (0.2 mm), which were developed using standard visualising agents: UV fluorescence (254 & 366 nm), ∆ , molybdic acid / ∆ , anisaldehyde. Optical rotations: These were recorded at 589 nm (Na D-line) with a path length of 1 dm. Concentrations (c) are quoted in g / 100 mL. Infra red spectra: Only selected absorbances (υ max) are reported. 1 H NMR spectra: These were recorded at either 250, 270 or 400 MHz. Chemical shifts (δ H) are quoted in parts per million (ppm), referenced to the appropriate solvent peak. 13 C NMR spectra: These were recorded at either 68, 75.7 or 100 MHz. Chemical shifts (δ) are quoted in ppm referenced to the appropriate solvent peak. Mass spectra: Only the molecular ions (M +) and major peaks are reported with intensities quoted as percentages of the base peak. Enantiomeric excesses were determined by HPLC using a chiracel chiral OD or OJ column. General Procedure for the Synthesis of Ketene Dithioacetals 3a-3e. 2-Cyclohexylidene-1,3-dithiane 3c. 2-Trimethylsilyl-1,3-dithiane (3.00 g, 15.63 mmol) was dissolved in THF (30 mL) under nitrogen with stirring. The solution was cooled to-78 C and n-BuLi (1.6 M solution in hexanes: 11.70 mL, 18.73 mmol) was added. The solution was allowed to warm to 0 C over 5 hours. The solution was re-cooled to-78 C and cyclohexanone (2.06 mL, 19.88 mmol) was added. The solution was allowed to warm to room temperature over 47 hours. The reaction solution was poured onto H 2 O (50 mL) and extracted with CH 2 Cl 2 (5 x 50 mL), dried (MgSO 4) and the solvent removed under reduced pressure. Purification by column chromatography, on SiO 2 , (hexane / Et 2 O, 1:0-0.9:0.1) afforded 3c as a
The Journal of Organic Chemistry, 1987
Reaction of (trimethylsily1)methanesulfonyl chloride (6a) or-sulfonic anhydride (6b) with cesium fluoride in the presence of cyclopentadiene affords 2-thiabicyclo[ 2.2.lIhept-5-ene 2,a-dioxide (4) by way of sulfene CH2=S02. Similar reaction of (trimethylsily1)methanesulfinyl chloride (7) gave the unstable 2-thiabicyclo[2.2.1] hept-5-ene endo-2-oxide (3) via the intermediacy of sulfine CH2=S0. Compound 3 can be oxidized to 4 and reduced to 2-thiabicyclo[2.2.1]hept-5-ene (1) and the latter oxidized to the stable 2-thiabicyclo[2.2.1]hept-5-ene exo-2-oxide (2). Fluorodesilylation of 1-(trimethylsily1)propanesulfonic anhydride (8) in the presence of cyclopentadiene gave a 77/23 ratio of endo/exo-3-ethyl-2-thiabicyclo[2.2.l]hept-5-ene 2,2-dioxide (9a/b) by way of propanethial S,S-dioxide. The structure of the major isomer 9a was established by an X-ray structure of the corresponding exo-epoxide lla, formed from 9a by oxidation. Reaction of 4 with n-butyllithium followed by ethyl iodide gave a compound identical with minor isomer 9b. Reaction of propanethial S-oxide with cyclopentadiene gave unstable endo-3-ethyl-2-thiabicyclo[2.2.l]hept-5-ene endo-5-oxide (loa). The structure of loa was established by oxidation to sulfone 9a, by reduction and reoxidation to a stable exo-5-oxide lob, by its facile [2,3] sigmatropic rearrangement to exo-4-ethyl-2-oxa-3-thiabicyclo[3.3.0]oct-7-ene (14c), and by NMR spectroscopic methods. Compound 14c was characterized by NMR spectroscopy and by ita reactions. Oxidation of 14c gave the endolexo-3-oxides 15c/15c' and the 3,3-dioxide 16c. Reaction of 14c with phenyllithium gave alcohol 17c, which was desulfurized and oxidized to 5-propyl-2-cyclopentenone or was oxidized at both carbon and sulfur to give (E)-5-propylidene-2-cyclopentenone 21c on gentle warming. Reaction of 14c with tert-butyl alcohol gave exo-6-tert-butoxy-exo-3-ethyl-syn-7hydroxy-2-thiabicyclo[2.2.l]heptane (24), characterized by further oxidation to crystalline hydroxy sulfone 25 and keto sulfone 26. Mechanisms are proposed for the above series of reactions. (1) (a) The Chemistry of Sulfines. 13. (b) Part 12 Block, E.; Ahmad, S.