With RuO

Since 1980, mthenium tetroxide, RuO, has been used for staining a number of heterophase polymers for tern (221) it seems to be a more versatile staining agent than OsO. For instance, in SAN modified with acrylate mbber, where the mbber phase is fully saturated, an excellent contrast between the mbber and the matrix has been achieved (222). Crystalline polymers have been stained with RuO (223), and excellent cra2e stmctures have been revealed (221). The stain may be prepared by dissolving RuCl - 3H2O in aqueous sodium hypochlorite for immediate use (224). 

The two-electron oxidation of primary alcohols RCH OH to aldehydes RCHO is rarer with RuO than is the four-electron process to RCOOH (2.1, 2.4.1.1 Table 2.1). Examples include the reagents RuCyaq. Na(Br03)/( Bu N)Br/CH2Cl2... 

The absence of any acyclic products from the reaction of cyclobutanol with RuO suggests that clean two-electron steps are involved [276]. Kinetic data for the oxidation of 2-propanol to acetone by RuOyaq. HCIO indicated that at moderate acidities the rate-determining step involves hydride abstraction, while at very high acid concentrations carbonium ions may be formed [277]. 

Early work with RuO -assisted oxidations was much concerned with alcohol functions in carbohydrates, and there are early but illuminating reviews on such reactions [60, 263]. 

For secondary alcohol groups in carbohydrates, although the use of Na(10 ) as co-oxidant with RuO or RuClj is cotmnon for generating RuO in these reactions, use of the sparingly soluble K(10 ) as co-oxidant is said to reduce over-oxidation [91, 171, 247, 280],... 

The first observation of the c/x-dihydroxylation reaction with RuO was made by Sharpless et al. in 1976, who noted that E and Z-cyclododecene were oxidised by stoich. RuO /EtOAc/-78 C to the threo and erythro diols [299]. Later RuCyaq. Na(IO )/EtOAc-CH3CN/0 C was used and reaction conditions optimised for many alkenes [300] a useful paper with good practical examples discusses the scope and limitations of the procedure (Table 3.2) [301]. Later oxidations were done with stoich. RuOyaq. acetone/-70 C [302] the same reagent converted A, and A steroids to cw-diols, ketones or acids [303], while RuO /aq. Na(10 )/acetone gave diones and acids [304]. 

A few other oxidations involve no C=C bond cleavage. Cti-9-octadecene gave 9.10-diketo-octadecane with RuO /aq. Na(C10)/( Bu N)Br/CHjCl2 [324], while cyclo-octene was oxidised by RnCyaq. Na(10 )/DCE to 8-oxo-octanal [325]. Oxidation of A -, and A - steroids using RuO /aq. Na(10 )/acetone gave cis-diols, diones and acids [303] while RuO /aq. Na(10 )/CHjCyCH3CN oxidised 2,3-dichlorodecene to decane-2,3-dione [326]. 

Optically active A-ethyl and A-benzylpiperidine gave the 2,6-diones with RuO / aq. Na(IO )/CCl (Table 5.1) [404,405]. Regiospecific oxidations of 2-substimted -... 

In 1953 Djerassi and Engle showed that stoich. RuOyCCy oxidised several sulfides to the corresponding sulfones [236]. Sulfilimines (R R S=NR ) were oxidised to sulfoximes R R S(=0)=NR by RuO /aq. Na(IO )/CH2Cl2 [432] oxidation of thianthrene-5-oxide with RuO /aq. Na(IO )/CCyO°C gave thianthrene-5,5-dioxide. Comparisons were made between the behaviour of RuO, CrO Cl and [MnO ] for these reactions, and 0-atom transfer with a possible intermediacy of [RuO ] was postulated [433]. Oxidations of RSPh to the sulfoxides and sulfones by stoich. RuOyaq. CH CN were studied a concerted mechanism may be involved for these and for similar oxidations by [RuO ] and [RuO ] " (Fig. 1.12) [434]. 

K[RuO ] This dark green salt was first prepared by Deville and Debray by treatment of an aqueous solution of [RuO ] " with Cl [449], In later work a melt of RuClj, KNO3 and KOH was extracted by water and Cl at 0°C passed through the [RuO ] so formed to give the salt [450], Single crystals were made from RuO vapour with [RuO ] " in aqueous KOH [451],... 

The oxidation is first order with respect to catalyst and alcohol, while the order with respect to NMO is fractional. A rate expression was derived and formation of a catalyst snbstrate complex proposed [500]. Oxidation of 2-propanol to acetone (and other secondary alcohols) by stoich. TPAP/CH Cl may be anto-catalytic the initial redaction product (RuO ) may form an adduct [Ru0. nRu02] with [RuO ]. The initially slow rate of oxidation by TRAP accelerated sharply as the concentration of product built up and then decreased near the end of the reaction because of the lower concentration of reactants, giving a bell-shaped curve typical of autocatalytic reactions [501]. 

Benzyl-alkyl, dialkyl, cyclic and acyclic ethers were converted to esters or lactones by RuO or [RuO ] (RuClj/aq. Na(C10) or Ca(C10)j/CH2Cl2). It was not stated whether RuO or [RuO ] was the effective oxidant, but oxidation of jb-methoxy-benzyhnethyl ether apparently involved a one-electron transfer process, which might be more likely to occur with [RuO ] [426],... 

RUj(0)g(R-py) (R-py=4-fertbutyl pyridine (4- Bu-py), pyridine-3-carboxylate (nicotinate, nic), pyridine-4-carboxylate (isonicotinate, isonic) and pyridine-3,4-dicarboxylate (cinchonomeronate, cine) are made from (R-py) in CCl with RuO vapour the products are brown-green and of low solubility the 4-ferf-butylpyridine complex is dark red. The vibrational spectra of Ru2(0)g(4- Bu-py) show u"(Ru(0)3) at 822 cm" (Raman) and u "(Ru(0)3) at 815 cm" (Raman) [241]. 

Hydrated RuO is often used to generate RuO, [RuO ] or [RuO ] using cooxidants such as periodate or bromate. There are many examples in this and subsequent chapters of the use of RuOj.nH O as starting material with co-oxidants such as Na(IO ) for organic oxidations. Surprisingly, RuO was found to be inactive as an oxidation catalyst as RuOj.nHjO/NMO/acetone or DMF [647]. Oxidation of benzyl alcohol to benzaldehyde was effected with RuO or RuCljA Bu bOCl/aq. H O / CHjCy60°C [648]. 

Although this method is quite old it has stood the test of time, and is the basis of many modem oxidations with RuO. Sharpless used it for oxidations of alcohols, ethers, aromatic rings and for aUcene cleavage, so clearly it has a high range of applicability. 

Purine and pyrimidine nucleosides of AZT (Zidovudine, 3 -azido-3 -deoxythymidine) with [RuO ] (from RuClj/K S O/aq. M KOH) gave l-((3-azido-2,3-dideoxy-P-D-eryf/tro-pentafuranosyl-5-uronic acid)-thymine (Fig. 2.11) [335]. 

The reagent RuO /aq. Na(IO )/CCl oxidised a number of pyranoses and was the first catalytic Ru-based system for carbohydrates (Table 2.3) [2]. Although use of Na(10 ) as co-oxidant with RuO or RuClj is a common procedure for generating RuO in these reactions, it was noted that the use of the sparingly soluble K(IO ) in place of Na(10 ) as co-oxidant reduced over-oxidation [332] see also [330, 340, 341]. Conversion of pyranoses to lactones has been accomplished e.g. 2,4-di-O-benzyl-3-0-T)utyldiphenylsilyl-a,p-L-fucopyranose was oxidised by TPAP/NMO/ PMS/CHjCN to 2,4-di-0-benzyl-3-0- butyldiphenylsilyl-L-fuco-l,5-lactone (Fig. 2.17) [155]. 

Few epoxidations have been accomplished with RuO since the reagent is a prime alkene cleavage agent (but see Fig. 3.1 below). Because of the intrinsic interest in, and need for, epoxidations many Ru complexes have been studied for the purpose, but generally only those which are effective (i.e. give good yields and selectivities), are catalytic and do not require forcing conditions are included. Some of those omitted here are mentioned in Ch. 1 and listed in 3.1.1.4 below. 

Two ciT-dihydroxylation reactions of alkenes formed steps in the synthesis of the antiviral drug (-)-oseltamvir ( tamiflu ) were carried out with RuO /aq. Na(IO )/ EtOAc-CH3CN/4°C [169]. Terminal alkene groups in nucleosides were oxidised to alcohols by RuClj/aq. Na(lO )/EtOAc-CH3CN/0°C thus 3,5-di-0-benzyl-l,2-di-O-isopropylidene-3-C-vinyl-a-D-ribofuranose (1) gave the diol (2) which, on cleavage with Na(lO ) and reduction with NaBH yielded 3,5-di-0-benzyl-l,2-di-O-isopropylidene-3-C-hydroxy-methyl-a-D-ribofuranose (3) (Fig. 3.4) [170]. 

Oxidation of 1,5-dienes to c -tetiahydrofurandiols was accomplished with RuO /aq. Na(10 )/acetone-EtOAc thus 2,5-dimethyl-1,5-hexadiene gave tetrahydrofurandiol, geranyl acetate yielded cw-tetrahydrofurandiol, and trans, tra 5-2,6-dimethyl-2,6-octadiene-l,8-diol diacetate (1) gave tetrahydrofuran ketol diacetate (2) (Fig. 3.12 cf. mech. Ch. 1) [174],... 

The isoprenoid polyenes famesyl acetate, geranyl acetate and squalene underwent oxidative poly cyclisation to bis-, tris- and penta-tetrahydrofurans with RuO /aq. Na(IO )/CH3CN-EtOAc [185]-[188]. This oxidative polycyclisation of squalene with RuO was shown to lead to the cis-threo-cis-threo-trans-threo-trans-threo-trans penta-tetrahydrofuranyl diol product, this configuration being determined by 2D-NMR (Fig. 3.14) [185]-[188] cf mech. Fig. 1.8 [185]. 

In early work a>9-octadecane gave 9.10-diketo-octadecane with RuO /aq. Na(C10)/( Bu N)Br/CHjClj (Table 3.6) [190]. 

Djerassi and Engle showed that stoich. RuOyCCl oxidised phenanthrene to 9,10-phenanthrenequinone (Table 3.5) [239], The first catalytic reaction involving RuO was that of pyrene with RuO /aq. Na(IO )/acetone, giving a mixture of pyrene-4,5-quinone, pyrene-1,6-quinone, the lactol of 4-form-ylphenanthrene-5-carboxylic acid (OsOyH O /acetone was more specific, giving pyrene-4,5-quinone) [240],... 

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