Osmium tetroxide, application

A catalytic enantio- and diastereoselective dihydroxylation procedure without the assistance of a directing functional group (like the allylic alcohol group in the Sharpless epox-idation) has also been developed by K.B. Sharpless (E.N. Jacobsen, 1988 H.-L. Kwong, 1990 B.M. Kim, 1990 H. Waldmann, 1992). It uses osmium tetroxide as a catalytic oxidant (as little as 20 ppm to date) and two readily available cinchona alkaloid diastereomeis, namely the 4-chlorobenzoate esters or bulky aryl ethers of dihydroquinine and dihydroquinidine (cf. p. 290% as stereosteering reagents (structures of the Os complexes see R.M. Pearlstein, 1990). The transformation lacks the high asymmetric inductions of the Sharpless epoxidation, but it is broadly applicable and insensitive to air and water. Further improvements are to be expected. 

CARBON - CARBON AND ARTIFICIALGRAPHITE - APPLICATIONS OF BAKED AND GRAPHITIZED CARBON] (Vol 4) -With osmium tetroxide catalyst [PLATINUM-GROUP METALS, COMPOUNDS] (Vol 19)... 

Another important reaction associated with the name of Sharpless is the so-called Sharpless dihydroxylation i.e. the asymmetric dihydroxylation of alkenes upon treatment with osmium tetroxide in the presence of a cinchona alkaloid, such as dihydroquinine, dihydroquinidine or derivatives thereof, as the chiral ligand. This reaction is of wide applicability for the enantioselective dihydroxylation of alkenes, since it does not require additional functional groups in the substrate molecule ... 

Martin R, Barlow J, Miralto A. Application of the zinc-iodide-osmium tetroxide impregnation of synaptic vesicles in cephalopod nerves. Brain Res 1969 15 1-16. 

Grafting a modified cinchona alkaloid to hexagonal mesoporous molecular sieve SBA-15 afforded catalyst (27) with excellent activity. 1-Phenyl-1-propene was converted to the corresponding diol in 98% yield (98% ee), while trans-stilbene yielded the desired product in 97% yield (99% ee) [92]. Other examples in this field are the utilization of microencapsulated osmium tetroxide by Kobayashi [93] and the application of continuous dihydroxylation mns in chemzyme membrane reactors described by Woltinger [94]. 

Application of a drop of 1% solution of osmium tetroxide to a rabbit eye caused severe corneal damage, permanent opacity, and superficial vascularization." Osmium compounds have a caustic action on the skin, resulting in eczema and dermatitis. ... 

Miscellaneous. Aside from the oxidation chemistry described, only a few catalytic applications are reported, including hydrogenation of olefins (114,115), a, [3-unsaturated carbonyl compounds (116), and carbon monoxide (117) and the water gas shift reaction (118). This is so owing to the kinetic inertness of osmium complexes. A 1% by weight osmium tetroxide solution is used as a biological stain, particulady for preparation of samples for electron microscopy. In the presence of pyridine or other heterocyclic amines it is used as a selective reagent for single-stranded or open-form B-DNA (119) (see Nucleic acids). Osmium tetroxide has also been used as an indicator for unsaturated fats in animal tissue. Osmium tetroxide has seen limited if controversial use in the treatment of arthritis (120,121). 

Inclusion in the reaction of a cooxidant serves to return the osmium to the osmium tetroxide level of oxidation and allows for the use of osmium in catalytic amounts. Various cooxidants have been used for this purpose historically, the application of sodium or potassium chlorate in this regard was first reported by Hofmann [7]. Milas and co-workers [8,9] introduced the use of hydrogen peroxide in f-butyl alcohol as an alternative to the metal chlorates. Although catalytic cis dihydroxylation by using perchlorates or hydrogen peroxide usually gives good yields of diols, it is difficult to avoid overoxidation, which with some types of olefins becomes a serious limitation to the method. Superior cooxidants that minimize overoxidation are alkaline t-butylhydroperoxide, introduced by Sharpless and Akashi [10], and tertiary amine oxides such as A - rn e t h y I rn o r p h o I i n e - A - o x i d e (NMO), introduced by VanRheenen, Kelly, and Cha (the Upjohn process) [11], A new, important addition to this list of cooxidants is potassium ferricyanide, introduced by Minato, Yamamoto, and Tsuji in 1990 [12]. 

The focus of this chapter is to acquaint the reader with details of catalytic asymmetric dihydroxylation with osmium tetroxide and the scope of results that one can expect to achieve with current optimum conditions. The literature through mid-1992 has been reviewed in compiling this chapter. Osmium tetroxide catalyzed hydroxy]ations of olefins and acetylenes are the subject of an extensive review by Schroder published in 1980 [2a]. A comprehensive review of research and industrial applications of asymmetric dihydroxylations is in preparation [2b]. 

Osmium tetroxide is the traditional osmium species used in the dihydroxylation of olefins. For large-scale reactions, osmium tetroxide may be weighed and transferred as the solid. For many catalytic applications on a laboratory scale, the amount of osmium tetroxide required is too small to be weighed conveniently. In these cases, advantage can be taken of the solubility of osmium tetroxide in organic solvents by the preparation of a stock solution of known concentration and the use of an aliquot for the small-scale reaction. 

Cotton R, Rodrigues NR, Campbell RD. Reactivity of cytosine and thymine in single-base-pair mismatches with hydroxylamine and osmium tetroxide and its application to the study of mutations. Proc Natl Acad Sci USA 1988 85 4397-4401. 

As a consequence of the development of the N-methylmorpholine N-oxide (NMO) and later the potassium ferricyanide cooxidant systems the amounts of osmium tetroxide and chiral ligand used in the reaction could be considerably reduced. However, the method remains problematic for large-scale applications. The cooxidants for Os(VI) are expensive and large amounts of waste are produced (Table 5). Lately, several groups have addressed this problem and new reoxidation processes for osmium(VI) species have been developed. 

The first heterogeneous osmium catalyst applicable for asymmetric dihydroxylation reactions was described by Kobayashi and coworkers (Table 9, entry 1) [38, 39]. Osmium tetroxide was enveloped in a polymer capsule by microencapsulation techniques [40,41]. The asymmetric dihydroxylation of transmethylstyrene with poly(acrylonitrile-co-butadiene-co-styrene) microencapsulated (ABS-MC) osmium tetroxide as catalyst, NMO as the cooxidant, and (DHQD)2PHAL as the chiral ligand completed in 88% yield with 94% ee [38]. The catalyst and the chiral ligand were reused in five consecutive runs without loss of activity. However, the use of NMO as cooxidant required the slow... 

Permanganate oxidation of 1,5-dienes to prepare f r-2,5-disubstituted tetrahydrofurans is a well-known procedure (Equation 80). The introduction of asymmetric oxidation methodology has revived interest in this area. Sharpless-Katsuki epoxidation has found widespread application in the catalytic enantioselective synthesis of optically active tetrahydrofurans and the desymmetrization of w ro-tetrahydrofurans <2001COR663>. A general stereoselective route for the synthesis of f-tetrahydrofurans from 1,5-dienes has been developed which uses catalytic amounts of osmium tetroxide and trimethyl amine oxide as a stoichiometric oxidant in the presence of camphorsulfonic acid <2003AGE948>. 

Osmium tetroxide-mediated cis hydroxylation of a silyl enol ether has been demonstrated to produce the corresponding a-hydroxy ketone in moderate yield after exposure to an acidic work-up, e.g. (64) to (65). The success of the catalytic procedure bodes well for future application and furthermore bears some possibilities for asymmetric hydroxylation. ... 

For the oxidation of alkenes, osmium tetroxide is used either stoichiometrically, when the alkene is precious or only small scale operation is required, or catalytically with a range of secondary oxidants which include metal chlorates, hydrogen peroxide, f-butyl hydroperoxide and N-methylmorpholine A -oxide. The osmium tetroxide//V-methylmorpholine A -oxide combination is probably the most general and effective procedure which is currently available for the syn hydroxylation of alkenes, although tetrasubstituted alkenes may be resistant to oxidation. For hindered alkenes, use of the related oxidant trimethylamine A -oxide in the presence of pyridine appears advantageous. When r-butyl hydroperoxide is used as a cooxidant, problems of overoxidation are avoided which occasionally occur with the catalytic procedures using metal chlorates or hydrogen peroxide. Further, in the presence of tetraethylam-monium hydroxide hydroxylation of tetrasubstituted alkenes is possible, but the alkaline conditions clearly limit the application. 

On adding water to the acetonium ion (26), however, the bridge is attacked rapidly to give the two monoacetates of the 2/9,3j -diol [ioy,xo8]. This reaction sequence effects m-hy-droxylation from the more hindered side of the olefinic bond, and so gives the as-glycol of configuration opposite to that obtained with osmium tetroxide. Unfortunately, the process does not seem to be applicable to more highly substituted olefins. 

Other Applications. Other (/ ,/ )-stilbenediamine derivatives have been used to direct the stereochemical course of alkene dihydroxylation (with stoichiometric quantities of Osmium Tetroxide and epoxidation of simple alkenes with Sodium Hypochlorite and manganese(III) complexes. ... 

Burton and Elad" in an investigation of a natural product introduced a new method of osmate cleavage. A solution of the olefinic product and osmium tetroxide in dioxane was let stand for 48 hrs. and hydrogen sulfide was passed in to precipitate hlack osmium dioxide this was removed by filtration and the diol recovered from the filtrate. An application of this procedure impressive for the scale on which costly chemicals were expended is reported by Hirschmann et al. of Merck in the synthesis from prednisone (I) of A-norcortisol (9), which proved to be devoid of physiological activity. A solution of 100 g. of prednisone BMD (2) in 720 ml. of pyridine was cooled to 5° and treated with a solution of 69.9 g. of osmium tetroxide (l.l X theoryI) in 40H ml. of pyridine. Black material began to separate in 5 min. After. 5 days at room temperature the reuclion mixture was stirred into 13.4 I. of petroleum ether and the precipitate was collected, washed, and dissolved in 8 I. of dioxane. The solution was cooled In an ice bath and saturated with hydrogen sulfide. The precipitated osmium dioxide was removed, and the bulk of the solvent removed... 

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