Ruthenium chloride ether oxidation

The diols (97) from asymmetric dil droxylation are easily converted to cyclic sii e esters (98) and thence to cyclic sulfate esters (99).This two-step process, reaction of the diol (97) with thionyl chloride followed by ruthenium tetroxide catalyzed oxidation, can be done in one pot if desired and transforms the relatively unreactive diol into an epoxide mimic, ue. the 1,2-cyclic sulfate (99), which is an excellent electrophile. A survey of reactions shows that cyclic sulfates can be opened by hydride, azide, fluoride, thiocyanide, carboxylate and nitrate ions. Benzylmagnesium chloride and thie anion of dimethyl malonate can also be used to open the cyclic sulfates. Opening by a nucleophile leads to formation of an intermediate 3-sidfate aiuon (100) which is easily hydrolyzed to a -hydroxy compound (101). Conditions for cat ytic acid hydrolysis have been developed that allow for selective removal of the sulfate ester in the presence of other acid sensitive groups such as acetals, ketals and silyl ethers. 

The remaining three steps are accomplished without purification of the intermediate products. The secondary hydroxy group is protected by acetylation and the benzyl ether is removed by hydrogenolysis to provide a primary alcohol. The alcohol is oxidized to a carboxylic acid by ruthenium(III) chloride or pyridinium dichromate. This method has been applied to the synthesis of various enzyme inhibitors containing the 1-hydroxyethylene isostere. 

Pure homoallylic alcohols are converted into y-amino-p-hydroxy acids by protection as the TBDMS ether or A(0-acetonide followed by degradative oxidation of the terminal alkene using a catalytic amount of ruthenium(III) chloride and sodium periodate (Scheme... 

A powerful oxidizer and very reactive material. It has been the cause of many industrial explosions. May explode on heating. Explosive reactions with ammonium chloride, aqua regia + ruthenium, sulfur dioxide solutions in ether or ethanol. Reacts with fluorine to form the explosive gas fluorine perchlorate. 

In view of the purification and waste disposal problems with the chromium oxidations catalytic methods with ruthenium catalysts are more attractive. Ruthenium(Vlll) oxide is a strong oxidant that will also oxidize alkenes, alkynes, sulfides, and in some cases benzyl ethers. The method is compatible with glycosidic linkages, esters and acetals, and is usually carried out in a biphasic solvent system consisting of water and a chlorinated solvent. Acetonitrile or a phase-transfer catalyst has been shown to further promote the oxidation [29,30]. Normally, a periodate or a hypochlorite salt serve as the stoichiometric oxidant generating rutheni-um(VIII) oxide from either ruthenium(IV) oxide or ruthenium(III) chloride [30]. 

Butyrolactones.—A simple method for the direct conversion of protected buty-rolactols into the corresponding butyrolactones is by oxidation with m-chloro-peroxybenzoic acid in the presence of a catalytic amount of boron trifluoride etherate. Yields are usually high but, disappointingly, the method fails with 5-lactols. Unsaturated amide (50) can be converted into the substituted buty-rolactone (51) by treatment with phenyl selenenyl chloride. The generality of this reaction remains to be established. 2-Chloro-4-alkylbutyrolactones (52 X = H or Cl) can be formed from di- or tri-chloroacetic acid respectively and alk-l-enes in the presence of dichlorotris(triphenylphosphine)ruthenium(ii). ... 

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