Osmium tetroxide alkenes

There are many reagents that add two OH groups to a double bond. Osmium tetroxide (0s04) and alkaline KMn04 give syn addition from the less-hindered side of the double bond. Less substituted double bonds are oxidized more rapidly than more substimted alkenes. Osmium tetroxide adds rather slowly but almost quantitatively. The cyclic ester (78) is an intermediate and can be isolated, but usually decomposed... 

Enantioselective osmylotion of alkenes. Osmium tetroxide forms a 1 1 wine-red complex with the chiral diamine l2 that effects efficient enantioselective dihy-droxylation of monosubstituted, oww-disubstituted, and trisubstituted alkenes (83-99% ee) at -110° in THF. The enantioface differentiation in all cases corresponds to that observed with t/mr-3-hexene and the complex with (-)-l. Essentially complete asymmetric induction is observed with frans-l-phenylpropene (99% ee). 

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. 

Another method for the hydroxylation of the etliylenic linkage consists in treatment of the alkene with osmium tetroxide in an inert solvent (ether or dioxan) at room temperature for several days an osmic ester is formed which either precipitates from the reaction mixture or may be isolated by evaporation of the solvent. Hydrolysis of the osmic ester in a reducing medium (in the presence of alkaline formaldehyde or of aqueous-alcoholic sodium sulphite) gives the 1 2-glycol and osmium. The glycol has the cis structure it is probably derived from the cyclic osmic ester ... 

The reagent Is expensive and poisonous, consequently the hydroxylation procedure is employed only for the conversion of rare or expensive alkenes (e.g., in the steroid field) into the glycols. Another method for hydroxylation utilises catalytic amounts of osmium tetroxide rather than the stoichiometric quantity the reagent is hydrogen peroxide in tert.-butyl alcohol This reagent converts, for example, cyc/ohexene into cis 1 2- t/ohexanedlol. 

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 ... 

With this reaction, two new asymmetric centers can be generated in one step from an achiral precursor in moderate to good enantiomeric purity by using a chiral catalyst for oxidation. The Sharpless dihydroxylation has been developed from the earlier y -dihydroxylation of alkenes with osmium tetroxide, which usually led to a racemic mixture. 

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... 

Problems of acyl anion equivalents met above in the synthesis of similar TMs disappear if (25) is made from the alkene (26), A Wittig is the obvious method to make (26) and reaction between (27) and PhgCO will probably give (26), An alternative is the dehydration of (28), made by Grignard addition to ester (20), Osmium tetroxide was used for the hydroxylation. 

The most widely used reagent for oxidation of alkenes to glycols is osmium tetroxide. Osmium tetroxide is a highly selective oxidant that gives glycols by a stereospecific syn addition.39 The reaction occurs through a cyclic osmate ester that is formed by a [3 + 2] cycloaddition.40... 

Osmium tetroxide used in combination with sodium periodate can also effect alkene cleavage.191 Successful oxidative cleavage of double bonds using ruthenium tetroxide and sodium periodate has also been reported.192 In these procedures the osmium or ruthenium can be used in substoichiometric amounts because the periodate reoxidizes the metal to the tetroxide state. Entries 1 to 4 in Scheme 12.18 are examples of these procedures. Entries 5 and 6 show reactions carried out in the course of multistep syntheses. The reaction in Entry 5 followed a 5-exo radical cyclization and served to excise an extraneous carbon. The reaction in Entry 6 followed introduction of the allyl group by enolate alkylation. The aldehyde group in the product was used to introduce an amino group by reductive alkylation (see Section 5.3.1.2). 

Syn-Dihydroxylation. When the reaction was first discovered, the syn-dihydroxylation of alkenes was carried out by using a stoichiometric amount of osmium tetroxide in dry organic solvent.56 Hoffman made the observation that alkenes could react with chlorate salts as the primary oxidants together with a catalytic quantity of osmium tetroxide, yielding syn-vicinal diols (Eq. 3.11). This catalytic reaction is usually carried out in an aqueous and tetrahydrofuran solvent mixture, and silver or barium chlorate generally give better yields.57... 

Syn-hydroxylation of alkenes is also effected by a catalytic amount of osmium tetroxide in the presence of hydrogen peroxide. Originally developed by Milas, the reaction can be performed with aqueous hydrogen peroxide in solvents such as acetone or diethyl ether.58 Allyl alcohol is quantitatively hydroxylated in water (Eq. 3.12).59... 

A very effective way of carrying out syn-dihydroxylation of alkenes is by using an osmium tetroxide-tertiary amine N-oxide system. This dihydroxylation is usually carried out in aqueous acetone in either one-or two-phase systems, but other solvents may be required to overcome problems of substrate solubility.61... 

There are a number of reagents that, overall, add two OH groups to alkenes. Thus osmium tetroxide, 0s04, adds to yield cyclic osmic esters (46), which can be made to undergo ready hydrolytic cleavage of their Os—O bonds to yield the 1,2-diol (47) ... 

Potassium permanganate or osmium tetroxide oxidize alkenes to furnish 1,2-diols (glycols). 

The osmium-catalyzed dihydroxylation reaction, that is, the addition of osmium tetr-oxide to alkenes producing a vicinal diol, is one of the most selective and reliable of organic transformations. Work by Sharpless, Fokin, and coworkers has revealed that electron-deficient alkenes can be converted to the corresponding diols much more efficiently when the pH of the reaction medium is maintained on the acidic side [199]. One of the most useful additives in this context has proved to be citric acid (2 equivalents), which, in combination with 4-methylmorpholine N-oxide (NMO) as a reoxidant for osmium(VI) and potassium osmate [K20s02(0H)4] (0.2 mol%) as a stable, non-volatile substitute for osmium tetroxide, allows the conversion of many olefinic substrates to their corresponding diols at ambient temperatures. In specific cases, such as with extremely electron-deficient alkenes (Scheme 6.96), the reaction has to be carried out under microwave irradiation at 120 °C, to produce in the illustrated case an 81% isolated yield of the pure diol [199]. 

The history of asymmetric dihydroxylation51 dates back 1912 when Hoffmann showed, for the first time, that osmium tetroxide could be used catalytically in the presence of a secondary oxygen donor such as sodium or potassium chlorate for the cA-dihydroxylation of olefins.52 About 30 years later, Criegee et al.53 discovered a dramatic rate enhancement in the osmylation of alkene induced by tertiary amines, and this finding paved the way for asymmetric dihydroxylation of olefins. 

Since Sharpless discovery of asymmetric dihydroxylation reactions of al-kenes mediated by osmium tetroxide-cinchona alkaloid complexes, continuous efforts have been made to improve the reaction. It has been accepted that the tighter binding of the ligand with osmium tetroxide will result in better stability for the complex and improved ee in the products, and a number of chiral auxiliaries have been examined in this effort. Table 4 11 (below) lists the chiral auxiliaries thus far used in asymmetric dihydroxylation of alkenes. In most cases, diamine auxiliaries provide moderate to good results (up to 90% ee). 

In summary, the reaction of osmium tetroxide with alkenes is a reliable and selective transformation. Chiral diamines and cinchona alkakoid are most frequently used as chiral auxiliaries. Complexes derived from osmium tetroxide with diamines do not undergo catalytic turnover, whereas dihydroquinidine and dihydroquinine derivatives have been found to be very effective catalysts for the oxidation of a variety of alkenes. OsC>4 can be used catalytically in the presence of a secondary oxygen donor (e.g., H202, TBHP, A -methylmorpholine-/V-oxide, sodium periodate, 02, sodium hypochlorite, potassium ferricyanide). Furthermore, a remarkable rate enhancement occurs with the addition of a nucleophilic ligand such as pyridine or a tertiary amine. Table 4-11 lists the preferred chiral ligands for the dihydroxylation of a variety of olefins.61 Table 4-12 lists the recommended ligands for each class of olefins. 

Worked Example 8.17 The following kinetic data were obtained for the second-order reaction between osmium tetroxide and an alkene, to yield a 1,2-diol. Values of k are pseudo-order rate constants because the 0s04 was always in a tiny minority. Determine the second-order rate constant k2 from the data in the following table ... 

Figure 8.15 The rate constant of a pseudo-order reaction varies with the concentration of the reactant in excess graph of k (as V) against [alkene]0 (as V). The data refer to the formation of a 1,2-diol by the dihydrolysis of an alkene with osmium tetroxide. The gradient of the graph yields k2, with a value of 3.2 x 10 2 dm3 mol-1 s-1...

Another familiar example of the reaction proceeding in cis fashion is the hydroxylation of alkenes which occurs by osmium tetroxide or by the action of KMn04. 

Among oxo-metals, osmium tetroxide is a particularly intriguing oxidant since it is known to oxidize various types of alkenes rapidly, but it nonetheless eschews the electron-rich aromatic hydrocarbons like benzene and naphthalene (Criegee et al., 1942 Schroder, 1980). Such selectivities do not obviously derive from differences in the donor properties of the hydrocarbons since the oxidation (ionization) potentials of arenes are actually less than those of alkenes. The similarity in the electronic interactions of arenes and alkenes towards osmium tetroxide relates to the series of electron donor-acceptor (EDA) complexes formed with both types of hydrocarbons (26). Common to both arenes and alkenes is the immediate appearance of similar colours that are diagnostic of charge-transfer absorp-... 

Polymer-supported [e.g. 8, 9] and silica-supported [10] cinchona alkaloids have been used in the asymmetric dihydroxylation of alkenes using osmium tetroxide. Enantiomeric excesses >90% have been achieved for diols derived from styrene derivatives. 

Asymmetric hydroxylation of alkenes with osmium tetroxide... 

About a decade after the discovery of the asymmetric epoxidation described in Chapter 14.2, another exciting discovery was reported from the laboratories of Sharpless, namely the asymmetric dihydroxylation of alkenes using osmium tetroxide. Osmium tetroxide in water by itself will slowly convert alkenes into 1,2-diols, but as discovered by Criegee [15] and pointed out by Sharpless, an amine ligand accelerates the reaction (Ligand-Accelerated Catalysis [16]), and if the amine is chiral an enantioselectivity may be brought about. 

The stoichiometric enantioselective reaction of alkenes and osmium tetroxide was reported in 1980 by Hentges and Sharpless [17], As pyridine was known to accelerate the reaction, initial efforts concentrated on the use of pyridine substituted with chiral groups, such as /-2-(2-menthyl)pyridine but e.e. s were below 18%. Besides, it was found that complexation was weak between pyridine and osmium. Griffith and coworkers reported that tertiary bridgehead amines, such as quinuclidine, formed much more stable complexes and this led Sharpless and coworkers to test this ligand type for the reaction of 0s04 and prochiral alkenes. 

Further supporting evidence for this type of a mechanism comes from the consideration of an analogous reaction, the oxidation of alkenes by osmium tetroxide, which also produces cis-diols. In this reaction the... 

After the "asymmetric epoxidation" of allylic alcohols at the very beginning of the 80 s, at the end of the same decade (1988) Sharpless again surprised the chemical community with a new procedure for the "asymmetric dihydroxylation" of alkenes [30]. The procedure involves the dihydroxylation of simple alkenes with N-methylmorpholine A -oxide and catalytic amounts of osmium tetroxide in acetone-water as solvent at 0 to 4 °C, in the presence of either dihydroquinine or dihydroquinidine p-chlorobenzoate (DHQ-pClBz or DHQD-pClBz) as the chiral ligands (Scheme 10.3). 

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