Osmium tetroxide, reaction with toxicity

Osmium tetroxide, reaction with alkenes, 235-236 toxicity of, 235 Oxalic add, structure of, 753 Oxaloacetic acid, structure of, 753 Oxetane, reaction with Grignard reagents, 680 Oxidation, 233, 348 alcohols, 623-626 aldehydes, 700-701 aldoses, 992-994 alkenes, 233-236 biological, 625-626 phenols, 631 sulfides, 670 thiols, 668... 

Unfortunately, a serious problem with the osmium tetroxide reaction is that Os04 is both very expensive and very toxic. As a result, the reaction is usually carried out using only a small, catalytic amount of OsO, in the presence of a stoichiometric amount of a safe and inexpensive co-oxidant such as A -methylmorpholine N-oxide, abbreviated NMO. The initially formed osmate intermediate reacts rapidly with NMO to yield the product diol plus... 

From the mechanism shown in Scheme 7.23, we would expect the dihydroxylation with syn-selectivity. The cyclic intermediate may be isolated in the osmium reaction, which is formed by the cycloaddition of OSO4 to the alkene. Since osmium tetroxide is highly toxic and very expensive, the reaction is performed using a catalytic amount of osmium tetroxide and an oxidizing agent such as TBHP, sodium chlorate, potassium ferricyanide or NMO, which regenerates osmium tetroxide. For example, Upjohn dihydroxylation allows the syn-selective preparation of 1,2-diols from alkenes by the use of catalytic amount of OSO4 and a stoichiometric amount of an oxidant such as NMO. 

Osmium tetroxide is highly toxic, volatile, and very expensive. For these reasons, methods have been developed that permit OSO4 to be used catalytically in conjunction with a co-oxi-dant. A very small molar percentage of OSO4 is placed in the reaction mixture to do the dihydroxylation step, while a stoichiometric amount of co-oxidant reoxidizes the OSO4 as it... 

Because osmium tetroxide is expensive, and its vapors are toxic, alternate methods have been explored for effecting vic-glycol formation. In the aliphatic series, olefins can be hydroxylated with hydrogen peroxide with the use of only a catalytic amount of osmium tetroxide. Anhydrous conditions are not necessary 30% hydrogen peroxide in acetone or acetone-ether is satisfactory. The intermediate osmate ester is presumably cleaved by peroxide to the glycol with regeneration of osmium tetroxide. When this reaction was tried on a A -steroid, the product isolated was the 20-ketone ... 

This new process has one unexpected benefit the rates and turnover numbers are increased substantially with the result that the amount of the toxic and expensive 0s04 is considerably reduced (usually 0.002 mole %). The rate acceleration is attributed to formation of an Os04-alkaloid complex, which is more reactive than free osmium tetroxide. Increasing the concentration of 1 or 2 beyond that of 0s04 produces only negligible increase in the enantiomeric excess of the diol. In contrast quinuclidine itself substantially retards the catalytic reaction, probably because it binds too strongly to osmium tetroxide and inhibits the initial osmylation. Other chelating tertiary amines as well as pyridine also inhibit the catalytic process. 

Fig. syn-Hydroxylation with KMn04 The reaction works better with osmium tetroxide. However, this is a highly toxic and expensive reagent and has to be handled with care. 

The reaction was originally performed using a stoichiometric amount of the oxidant OSO4, with attendant problems of toxicity and cost.P2] The appeal of the method was greatly enhanced by the discovery that the asymmetric oxidation worked just as well under the more modem catalytic conditions, with only a trace of osmium tetroxide and(V-methylmorpholine(V-oxide (68) as the reoxidant. P3] The method is tolerant of a wide variety of functional groups (esters, allylic halides) and, unlike the Sharpless oxidation, has no need of an allylic hydroxyl group as an internal ligand. [ 4]... 

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