Osmium tetroxide, hydroxylation double bonds

Organic sulfides, MA distillation additives, 22 Osmium tetroxide, ozonization catalyst, 69, 70 Osmium tetroxide/ferricyanide, double bond hydroxylation catalyst, 71, 72 Osmometry, CTC detection, 209 Oxalic acid... 

The action of three oxidizing agents on the velbanamine component in vinblastine and related compounds has also been studied.1676 Osmium tetroxide hydroxylates the double bond between positions 15 and 20, if present, but also... 

A THC and other active constituents are believed to be metabolically converted to substances oxidized at C(7), and this oxidation has been carried out by osmium tetroxide hydroxylation of A THC (333) and subsequent removal of the tertiary hydroxy-group (Scheme 20). The isomerization of the double bond to A THC is most conveniently carried out by photo-isomerization in propan-2-ol and xylene for 14 days, " although a second method is available that depends on an El elimination reaction of the hydrogen chloride adduct of A THC, using a sterically hindered base (after blocking the phenolic hydroxy-group). ... 

Reactions with unsaturated compounds. /-Butyl hydroperoxide decomposes smoothly at 95-105° and hydroxylates double bonds, and even a,)3-unsaturated ketones the reactions are catalyzed by small amounts of osmium tetroxide and afford cir-glycols. In benzene solution in the presence of Triton B as catalyst it converts a ,/3-unsaturated ketones into the corresponding epoxides in yields of 50-90%. The steric requirement of the base-catalyzed reaction are indicated by the failure to react with isophorone or A -3-ketosteroids. Payne effected smooth preparation of /3-phenylglycidaldehyde by allowing cinnamaldehyde and /-butyl... 

A classical method for the vicinal hydroxylation of a double bond involves treatment with osmium tetroxide to give a cyclic ester, followed by reductive cleavage to the glycol ... 

Hydroxylation of the double bond of methyltestosterone by means of osmium tetroxide and hydrogen peroxide affords the 4,5 diol. This undergoes beta elimination on treatment with base to yield oxymestrone (83). ... 

Osmium tetroxide and permanganate are the textbook examples for the direct addition of the hydroxyl function to double bonds as shown in Scheme 3. They have been rationalized to be feasible because of their large thermodynamic exothermi-cities,30 and the existence of a low-energy pathway discussed in Section 2.1 for the transfer of two oxygen atoms from the metal to the adjacent alkene carbons. 

The oxidation of alkenes by permanganate is one of the frequently used examples in freshman chemistry. It is also well known as the Baeyer test for unsaturation. There are many reagents that add two hydroxyl groups to a double bond,44 but osmium tetroxide and permanganate are the most prominent ones. The mechanism of the permanganate oxidation is believed to be similar to the oxidation of alkenes by 0s0445 46... 

Syn hydroxylation is most commonly performed using osmium tetroxide or potassium permanganate, and addition usually occurs from the less hindered side of the double bond in the absence of other directing effects. With Aese reagents, the stereospecificity of syn addition results from formation of cyclic ester intermediates. Support for these arises from isolation of solid addition complexes (1) on reaction of... 

With careful choice of reagent and reaction conditions, alkenes containing other functionalities can be selectively hydroxylated without complicating side reactions. For example, the oxidation may be carried out in the presence of ester, ether, sulfide, carboxylic acid, acetal, carbonyl, halo, alcohol and aryl groups. Regioselective hydroxylation is also possible in dienes in which one center is electron poor, and some selectivity is also found between isolated double bonds. For example, syn hydroxylation of diene (5) with a catalytic amount of osmium tetroxide and N-methylmorpholine N-oxide as the secondary oxidant gives diol (6) in 46% yield, and phase transfer catalyzed permanganate oxidation of diene (7) affords diol (8) in 83% yield. 

Hydroxylation by hydrogen peroxide in t-butyl alcohol solution is catalyzed by osmium tetroxide. The catalyst is volatile and dangerous to handle but is conveniently used in a solution of the tertiary alcohol. The yields of diols are usually low (30-60%), and the process has not been adapted to large-scale preparations. In contrast to hydroxylation by performic acid, this procedure leads to cis addition of the two hydroxyl groups to the double bond. An extensive study of other catalysts has been made. Some catalysts, e.g., selenium dioxide and pertungstic acid, catalyze addition in the trans direction. Hydroxylation of cyclopentadiene takes place in the 1,4-positions to give 2-cyclopenten-l,4-diol. ... 

Osmium tetroxide is also a catalyst in the oxidation of the double bond by chlorates. Cis addition of hydroxyl groups takes place as is shown by the preparation of cis-l,2-cyclohexanediol from cyclohexene and the formation of the proper diastereoisomeric dihydroxy derivatives of maleic, fumaric, and 4-halocrotonic acids. Silver chlorate is preferred to potassium chlorate in the hydroxylation of crotonic acid. ... 

The next step involved the selective reduction of one of the double bonds in 12, specifically the double bond in ring C. No reliable method existed to secure the required hydrogenation selectivity. Therefore, the double bond in ring D was hydroxylated with osmium tetroxide and the resulting diol converted into the corresponding acetal 13. In addition to simplifying the selectivity problem... 

Tittle is known about the detailed mechanism of the addition of osmium tetroxide to a double bond, although the immediate product is a cyclic osmate (i) which may be decomposed to give a cw-glycol [6 ]. The addition normally follows the rule of a-attack , with the exceptions noted previously (p. 70 due to abnormal steric effects, cis-Hydroxylations with permanganate probably involve similar cyclic intermediates, although these have not been isolated... 

Dienes may be hydroxylated at one or at both double bonds, depending on the amount of oxidants used. Cyclopentadiene, on treatment with an excess of hydrogen peroxide and osmium tetroxide as a catalyst in tert-butyl alcohol, gives a mixture of 21% of 3,5-cyclopentenediol and 61% of 1,2,3,4-cyclopentanetetrol [152. ... 

The addition of two hydroxylic groups to the double bonds of unsaturated ketones is carried out by the same methods used for hydroxylations of alkenes (equations 71-83). As an example, hydroxylation of the double bond in 3p-hydroxyandrost-5-en-17-one is accomplished by treatment with one equivalent of osmium tetroxide in pyridine and subsequent reductive cleavage of the osmate ester with sodium bisulfite in aqueous pyridine (equation 442) [950. ... 

Hydroxylation at double bonds of unsaturated carboxylic acids is accomplished stereoselectively by the same reagents as those used to hy-droxylate alkenes. syn Hydroxylation is carried out with potassium permanganate [101] or osmium tetroxide with hydrogen peroxide [130], sodium chlorate [310, 715], potassium chlorate [715], or silver chlorate [310] as reoxidant, anti Hydroxylation is achieved with peroxyacids, such as peroxybenzoic acid [310] or peroxyformic acid, prepared in situ from hydrogen peroxide and formic acid [101] (equation 472). 

Sodium permanganate and, especially, osmium tetroxide oxidize sulfoxides to sulfones but do not oxidize sulfides [837]. When a mixture of equimolar amounts of diphenyl sulfide, diphenyl sulfoxide, and osmium tetroxide is refluxed in ether for 48 h, the sulfoxide is oxidized in 96% yield to the sulfone, whereas the sulfide is completely recovered [837], Certain unsaturated sulfoxides treated with a catalytic amount of osmium tetroxide and trimethylamine oxide as a reoxidant are not only oxidized to sulfones but also hydroxylated at the double bond. The sulfoxide group exerts a steric influence in the hydroxylation two stereoisomers of a sulfoxide yield, by syn hydroxylation, two different stereoisomeric diols (equation 580) [1102]. 

Allylic and propargylic 3-keto sulfoxides could be reduced as well as saturated compounds. Optically active allylic 3-hydroxy sulfoxides present some specific interest because of the possible hydroxylation of the double bond leading to vicinal triols. The osmium tetroxide catalyzed hydroxylation reaction of the double bond in the presence of trimethylamine N-oxide is highly stereoselective the (/ ,/ )-3-hydroxy sulfoxide gave only one diastereoisomeric triol as a result of a cis hydroxylation of the double bond and a symbiotic effect of the two chiral centers in the asymmetric induction (the (S,/ )-isomer gave a lower de). 

Hydroxylation of the 15, 20 double bond in (266) by means of osmium tetroxide could not be accomplished satisfactorily however, osmylation of the iVb -oxide of (266) followed by reductive (HaS) work-up afforded a hydroxyvinblastine formulated as the /8-diol, i.e. the C-15 epimer of (262). Since the stereochemical assignments are at present tentative, it is unfortunate that an authentic specimen of vincadioline was not available for direct comparison. ... 

---