Raney Ni desulfurization

Further elaboration of the sulfur cycloadducts could be achieved by the use of a Pummerer rearrangement in the syntheses of 5-(hydroxymethyl)prolines. Oxidation of adduct 298 to sulfoxide 299, followed by treatment with TEA in DCM and quenching with either methanol or benzyl alcohol, delivered the Pummerer products 300 in 57% yield for R = Me and 38% for R = Bn as single diastereoisomers. Raney Ni desulfurization and Pearlman s catalyst mediated hydrogenolysis, for R = Bn furnished the final enantiopure proline derivative (Scheme 3.99). 

Characterization of Organically Bound Sulfur in High-Molecular-Weight, Sedimentary Organic Matter Using Flash Pyrolysis and Raney Ni Desulfurization... 

From comparative studies, it appears that a number of G=C double bonds are tolerated only when Raney Ni has been deactivated.It has been claimed" that desulfurization of thiophenes could lead to acceptable yields of unsaturated products, but this result seems to be due to steric hindrance in the unsaturation formed. Curiously it has been found that Raney Ni desulfurization of unsaturated lithium thio-lates resulting from Li-EtNH2 desulfurization (vide infra) takes place easily, while direct reduction of the starting heterocycles is unsatisfactory (Scheme 1). ... 

An enantioselective synthesis of chiral QUINAP 234 was reported by Knochel et al. (07SL2655). The organolithium species obtained from l-(2-bromo-l-naphthyl)isoquinoline by treatment with f-BuLi reacted with (—)-menthyl (S)-p-toluene-sulfinate at-78 °C. The resulting diastereomers were separated via column chromatography. One pot sulfoxide lithium exchange at low temperature, Ph2PCl reaction, sulfur protection with Ss and a Raney-Ni desulfurization step afforded optically pure QUINAP (99% ee) in 60% yield. The s)mthetic route avoided the use of Pd complexes for the resolution. The ees were determined after resulfurization on Chiralcel OD-H. 

Diels-Alder reactions of 6 and 8 with butadiene and 2,3-dimethylbutadiene under thermal conditions led to the expected mixtures of diastereomers 11a,b-14a,b. Reaction of 6 and 8 with 2-trimethylsilyloxybutadiene proceeded, however with full regioselectivity and afforded mixtures of 15a,b and 16a,b after desilylation. (Figure 5.) Due to the presence of the chiral carrier a moderate diastereoselection could be observed in some cases. The diastereomeric mixtures could be separated only in the case of 16a,b. The configurations of C-2 in the thiopyran part of lla,b-16a,b could not be deduced from the NMR spectra. In order to prove the structures of 15a,b and 16a,b we have used Raney-Ni desulfurization to get the expected 5-ketohexanoate esters (Figure 6.). 

Three different methods have been discussed previously (sections III-C,III-D and IV-A) for the replacement of a carbonyl oxygen by two deuteriums. However, in the conversion of a 3-keto steroid into the corresponding 3,3-d2 labeled analog, two of the three methods, electrochemical reduction (section ni-C) and Raney nickel desulfurization of mercaptal derivatives (section IV-A), lead to extensive deuterium scrambling and the third method, Clemmensen reduction (section III-D), yields a 2,2,3,3,4,4-dg derivative. 

Catalytic desulfurization Raney Ni/DMF, column, few hours, satisfactory yields." ... 

The o-nitrobenzenesulfenamide has been used for the protection of amino acids. o-Nitrobenzenesulfenamides, B, are also cleaved by acidic hydrolysis (HCl/Et20 or EtOH, 0°, 1 h, 95% yield)" by nucleophiles (13 reagents, 5 min-12 h, 90% cleaved) by PhSH or HSCH2CO2H, 22°, 1 h by 2-mercaptopyri-dine/CH2Cl2, 1 min, 100% yield) by NH4SCN, 2-methyl-1-indolylacetic acid and by catalytic desulfurization (Raney Ni/DMF, column, a few hours, satisfactory yield). 

Surprisingly, Kashima et al. (83TL209) reported the formation of individual 1,4-dihydro- and 1,6-dihydropyrimidines on desulfurization of the corresponding pyrimidine-2-thiones with Raney Ni and claimed that no tautomerization occurs under the reaction conditions (heating under reflux in MeOH). 

As previously reported in CHEC-II(1996) <1996CHEC-II(8)249>, this ring system is fairly resistant to reduction, and, under more forcing conditions, the six-membered ring is reduced preferably. Desulfurization with Raney-Ni of 7-SMe derivatives was reported <1999T7645> to occur efficiently, as shown in Scheme 2. 

The reaction protocol also accommodated the use of sulfur containing aldehyde 3-thia-5-hexenal, furnishing the expected product 298 in 75% purified yield (66,67). Desulfurization with Raney Ni, followed by hydrogenolysis, resulted in formation of (IS, 4R, 5R)-4,5-dimethylproline (Scheme 3.98). 

The synthesis of thiiranes with subsequent elimination of sulfur is an important procedure for the creation of C=C bonds, especially for sterically crowded systems (47,48), in analogy to the Eschenmoser-sulfide-contraction reaction (116). The spontaneous elimination of sulfur was observed in the rhodium-catalyzed reaction of diazo compound 62, which gave rise to the formation of cyclopentenone derivative 63 (117) (Scheme 5.24). A synthesis of indolizomycin was published by Danishefsky and co-workers (118) and involved a similar annulation step. In this case, however, the desulfurization reaction was achieved by treatment with Raney Ni. 

The enantiomeric synthesis of rranj-3,4-disubstituted tetrahydrothiophenes using a sulfur ylide cycloaddition has been reported <990L1667>. The sulfur ylide derived from the action of cesium fluoride on sulfide 111 underwent an asymmetric cycloaddition with chiral a,p-unsaturated camphorsultam amide 112 giving tetrahydrothiophene 113 (80% de). The configuration was confirmed by cleavage of the chiral auxiliary followed by reductive desulfurization with Raney-Ni which gave known carboxylic acid 114. 

Catalytic dehalogenation (mostly by H2/Pd) and desulfurization (by Raney-Ni) are important tools for structural analysis. This way chlorine can be removed from positions 2, 5, and 7 [64CPB204 66JCS(C)2031]. Zinc was used for dechlorination at C-7 (59YZ903). The 5,7-dichloro-TPs (61CPB801) and 6,7-dichloro-TPs (59CPB903) in the presence of H2/Pd first lose the more reactive chlorine from C-7 the remaining 6-chloro compound can be dechlorinated only by Raney-Ni. 

Sulfur removal still remains a useful synthetic tool for the preparation of important molecules. A benzothiophene derivative was the staiting point for the prepaition of 1,11-epithio steriod 52 that was converted to estradiol by the stereoselective removal of sulfur (W-7 Raney Ni) to provide the necessary 9a-H configuration <95TL4467>. Desulfurization of the thienothiophene derivative 53... 

Treatment of l,2-dihydro[l,4]thiazino[4,3-a]quinolin-l-ones with NaBH4 in EtOH afforded 2-[(2-hydroxyethy)thiomethyl]quinolines (73IJC1051). Desulfurization of 8-formyloxy-8-methylperhydropyrido[2,l-c][l,4]thiazin-4-one with Raney Ni in boiling EtOH gave l-acetyl-2,4-dimethyl-4-piperidinol (82TL3811 85T2861). 

The thiophene can be considered a four-carbon synthon via reductive desulfurization with Raney nickel. A strategy using the thiophene as a lynch-pin for the construction of complex building blocks was utilized in a total synthesis of the cytotoxic sponge metabolite haliclamine A <02JOC6474>. Thienyl cyclopropyl ketone (108) was elaborated into 109. Reduction of 109 with Raney Ni gave 110 which was taken on to haliclamine A. 

The sulfur compounds contained as impurities in a substrate or solvent may have a profound effect on hydrogenation, particularly over platinum metals where the amounts of catalyst used are usually much smaller than in the case of base metals. An excellent way to remove such impurities is to treat the sample with Raney Ni at slightly elevated temperatures22 (usually 50-80°C). The impurities in benzene or cyclohexane can thus be removed simply by refluxing with Raney Ni for 0.5 h (see Section 13.3). Granatelli applied this desulfurization with Raney Ni to determine quantitatively as little as 0.1 ppm of sulfur contained in 50 g of nonolefinic hydrocarbons.23... 

Hydrogenolysis of carbon-sulfur bonds is a widely utilized reaction for removing sulfur from sulfur-containing organic compounds, and is known as desulfurization or hydrodesulfurization. Bougault et al. used Raney Ni for the first time for the desulfurization of aliphatic thioalcohols and disulfides in neutral and alkaline solution.126 Since then the reaction has been widely applied, for example, for organic syntheses, purification of solvents and substrates, structural studies, and determination of sulfur contents.127... 

Hauptmann et al. found that aromatic disulfides, thioesters, and thiols were transformed into thioethers when refluxed in xylene (140°C) in the presence of Raney Ni degassed at 200°C.130,134,135 However, when these compounds were heated at 220°C with degassed Raney Ni or reduced Ni, biphenyls were obtained in good yields. The yields of the products with Raney Ni degassed at 500°C were never lower and were sometimes higher than those obtained with Raney Ni degassed at 200°C, as seen from an example shown in eq. 13.64. On the basis of these results, it was concluded that the presence of hydrogen was not essential for these desulfurizations.136... 

The desulfurization of organic sulfur compounds with Raney Ni using far greater amounts than a catalytic is not a catalytic hydrogenolysis in the strict sense but involves a stoichiometric chemical reaction, since the catalyst itself is converted into nickel sulfide. However, since it has found many useful applications with Raney Ni (a hydrogenation catalyst), this reaction has been treated in this section. 

Thiols are more readily hydrogenolyzed than thioethers by treatment with Raney Ni to give the corresponding desulfurized products. For example, 3-mercaptotetrahy-drothiophene was selectively desulfurized to tetrahydrothiophene when the reaction was interrupted at an appropriate time that was indicated by estimation of thiol values (eq. 13.65).141... 

Thiol derivatives of carbohydrates were desulfurized with Raney Ni without complication. For example, 1,6-dithiodulcitol was desulfurized to 1,6-dideoxydulcitol in aqueous solution with Raney Ni, and acetylation of the product gave tetraacetyl-1,6-dideoxydulcitol (eq. 13.66).142... 

Phenylimidazole was synthesized by treatment with Raney Ni of the corresponding thiohydantoin derivative. This desulfurization was considered to take place via the tautomeric dimercaptoimidazole, as shown in eq. 13.67.143... 

On the other hand, the reaction of mercarptothiazoles with Raney Ni usually gives the thiazoles only in small amounts, and the predominant products are those desulfurized not only at the mercapto group but also at the thiazole ring, as seen from the examples shown in eqs. 13.70 and 13.71.146 The Raney Ni used in these equations was prepared by a procedure similar to that for W-4 but developed at a lower temperature, and appeared to have a much greater amount of adsorbed hydrogen than did W-2 or W-4.147... 

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