Carboxylic acids with ruthenium tetroxide

Internal alkynes are oxidized to acytoins by thalliuin(III) in acidic solution (A. McKil-lop, 1973 G.W. Rotermund, 1975) or to 1,2-diketones by permanganate or by in situ generated ruthenium tetroxide (D.G. Lee, 1969, 1973 H. Gopal, 1971). Terminal alkynes undergo oxidative degradation to carboxylic acids with loss of the terminal carbon atom with these oxidants. 

Hydroxy-5-oxo-3,5-seco-4-norandrostane-3-carboxylic acid has been prepared by ozonolysis of testosterone2-4 or of testosterone acetate, followed by alkaline hydrolysis,5 and by the oxidation of testosterone acetate with ruthenium tetroxide.9... 

Ethers in which at least one group is primary alkyl can be oxidized to the corresponding carboxylic esters in high yields with ruthenium tetroxide.297 Cyclic ethers give lactones. The reaction, a special case of 9-16, has also been accomplished with CrO, in sulfuric acid.39" with benzyltriethylammonium permanganate,299 and with trichloroisocyanuric acid in the presence of an excess of water.300 In a similar reaction, cyclic tertiary amines (e.g., 28) can... 

Sodium hypochlorite is used for the epoxidation of double bonds [659, 691] for the oxidation of primary alcohols to aldehydes [692], of secondary alcohols to ketones [693], and of primary amines to carbonyl compounds [692] for the conversion of benzylic halides into acids or ketones [690] for the oxidation of aromatic rings to quinones [694] and of sulfides to sulfones [695] and, especially, for the degradation of methyl ketones to carboxylic acids with one less carbon atom [655, 696, 697, 695, 699] and of a-amino acids to aldehydes with one less carbon [700]. Sodium hypochlorite is also used for the reoxidation of low-valence ruthenium compounds to ruthenium tetroxide in oxidations by ruthenium trichloride [701]. 

Sodium periodate (sodium metaperiodate), NaI04 (mp 300 °C dec), which is commercially available, is applied mainly in aqueous or aqueous-alcoholic solutions. Like the free periodic acid, sodium periodate cleaves vicinal diols to carbonyl compounds [762], This reaction is especially useful in connection with potassium permanganate [763, 764] or osmium tetroxide [765], Such mixed oxidants oxidize alkenes to carbonyl compounds or carboxylic acids, evidently by way of vicinal diols as intermediates. Sulfides are transformed by sodium periodate into sulfoxides [322, 323, 766, 767, 768, 769, 770, 771, 772], and selenides are converted into selenoxides [773]. Sodium periodate is also a reoxidant of lower valency ruthenium in oxidations with ruthenium tetroxide [567, 774],... 

The oxidative cleavage of alkenes resulting in the formation of carboxylic acids is also accomplished with chromium trioxide in sulfuric acid or acetic acid [567, 569] with potassium dichromate in sulfuric acid [1111] and with ruthenium tetroxide, generated in situ from ruthenium trichloride... 

The oxidation of alcohols with ruthenium tetroxide prepared by oxidation of ruthenium trichloride hydrate with sodium bromate takes place at room temperature. However, aldehydes may undergo further oxidation to carboxylic acids [940]. 

Hydroxy carboxylic acids and their esters are oxidized to keto acids and their esters, respectively. o-Nitromandelic acid is oxidized to o-nitro-phenylglyoxylic acid with a dilute solution of potassium permanganate at room temperature in 54% yield [886], The oxidation-of ethyl 3-hydroxy-cyclobutanecarboxylate with ruthenium tetroxide and sodium periodate in... 

Amino acids. Oxidation of aliphatic primary amines with ruthenium tetroxide leads to complex products. However, oxidation of aralkylamines at pH 3.0 with periodate (12 eq.) and RuCls 3H2O (0.02 eq.) converts the aromatic ring into a carboxyl group to give amino acids. Cleavage is facilitated by a 4-methoxy or hydroxy substituent in the ring. ... 

The conversion of primary alcohols and aldehydes into carboxylic acids is generally possible with all strong oxidants. Silver(II) oxide in THF/water is particularly useful as a neutral oxidant (E.J. Corey, 1968 A). The direct conversion of primary alcohols into carboxylic esters is achieved with MnOj in the presence of hydrogen cyanide and alcohols (E.J. Corey, 1968 A,D). The remarkably smooth oxidation of ethers to esters by ruthenium tetroxide has been employed quite often (D.G. Lee, 1973). Dibutyl ether affords butyl butanoate, and tetra-hydrofuran yields butyrolactone almost quantitatively. More complex educts also give acceptable yields (M.E. Wolff, 1963). 

Ruthenium tetroxide is a four-electron oxidant which directly transforms alkenic compounds into oxidative cleavage products, i.e. carbonyl compounds and carboxylic acids.288 The reaction can be visualized as proceeding according to a [4 + 2] cycloaddition of the cis-dioxo moiety with the alkene, resulting in the formation of a RuVI cyclic diester which decomposes to ruthenium(IV) dioxide and oxidative cleavage products (equation 114).288 This reaction can be made catalytic... 

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 physical properties, preparation and reactions of ruthenium tetroxide have been reviewed by Lee and van den Engh, Rylander," Haines and Hetuy and Lange. A more vigorous oxidant than osmium tetroxide, its reaction with double bonds produces only cleavage products. " Under neutral conditions aldehydes are formed from unsaturated secondary carbons while carboxylic acids are obtained under alkaline or acidic conditions. For example, Shalon and Elliott" found that ruthenium tetroxide reacted with compound (11) to give the corresponding aldehyde under neutral conditions, but that a carboxylic acid was formed in acidic or alkaline solvents (equation 23). 

Sodium periodate, used ong with catalytic amounts of osmium tetroxide, ruthenium dioxide or potassium permanganate, can also be employed to cleave carbon-double bonds. When used with osmium tetroxide, carbonyls are produced however, the presence of permanganate results in the formation of more highly oxidized products (carboxylic acids) from secondary carbons. 

Sodium ruthenate, Na2Ru04, is prepared in situ from ruthenium tetroxide (in solution in carbon tetrachloride) and 1 M sodium hydroxide by shaking for 2 h at room temperature. The reagent remains in the aqueous layer, which acquires bright-orange color [937]. It oxidizes primary alcohols to carboxylic acids and secondary alcohols to ketones and is comparable with but stronger than potassium ferrate [937]. 

The reagent of choice for the oxidation of phenyl groups to carboxyls seems to be ruthenium tetroxide with sodium periodate [231, 941] or sodium hypochlorite [701] as reoxidants. Phenylcyclohexane is oxidized to cyclohexanecarboxylic acid (equation 156) [774, 941], and -phenylpro-pionic acid is transformed mainly into succinic acid (equation 157) [701]. 

The unusual oxidant nickel peroxide converts aromatic aldehydes into carboxylic acids at 30-60 °C after 1.5-3 h in 58-100% yields [934. The oxidation of aldehydes to acids by pure ruthenium tetroxide results in very low yields [940. On the contrary, potassium ruthenate, prepared in situ from ruthenium trichloride and potassium persulfate in water and used in catalytic amounts, leads to a 99% yield of m-nitrobenzoic acid at room temperature after 2 h. Another oxidant, iodosobenzene in the presence of tris(triphenylphosphine)ruthenium dichloride, converts benzaldehyde into benzoic acid in 96% yield at room temperature [785]. The same reaction with a 91% yield is accomplished by treatment of benzaldehyde with osmium tetroxide as a catalyst and cumene hydroperoxide as a reoxidant [1163]. 

Besides ruthenium tetroxide, other ruthenium salts, such as ruthenium trichloride hydrate, may be used for oxidation of carbon-carbon double bonds. Addition of acetonitrile as a cosolvent to the carbon tetrachloride-water biphase system markedly improves the effectiveness and reliability of ruthenium-catalyzed oxidations. For example, RuCl3 H20 in conjunction with NaI04 in acetonitrile-CCl4-H20 oxidizes (Ej-S-decene to pentanoic acid in 88% yield. Ruthenium salts may also be employed for oxidations of primary alcohols to carboxylic acids, secondary alcohols to ketones, and 1,2-diols to carboxylic acids under mild conditions at room temperature, as exemplified below. However, in the absence of such readily oxidized functional groups, even aromatic rings are oxidized. 

Oxidation of the products by ruthenium(VIII) oxide with the TIPS group still in place gives a mixture of carboxylic acid and an a-keto acyl silane (silyl a-diketone (eq 13), an otherwise rare class of compounds compare the oxidation of disubstituted alkynes to 1,2-diketones by Ru04 9 and the osmium tetroxide-f-butyl hydroperoxide oxidation of TMS-aUcynes. ... 

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