Alkenes, dihydroxylation, with osmium tetroxide

The first reaction, 8.30, is the classical alkene dihydroxylation with osmium tetroxide. In recent years the potential of this reaction has been vastly extended... 

Treatment of alkenes either with osmium tetroxide or with alkaline potassium permanganate results in 5yn-dihydroxylation of the double bond. 

The dihydroxylation reaction is very general, giving high yields of diol products from electron-rich or electron-poor alkenes. High levels of stereocontrol can often be obtained on dihydroxylation of alkenes bearing one or more chiral centre. The large steric requirements of the reagent normally dictates that dihydroxylation with osmium tetroxide takes place predominantly from the less-hindered side of the double bond. 

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. 

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). 

Figure 6 Enantiofacial selectivity in the dihydroxylation of alkenes with osmium tetroxide/alkaloid ester/NMO...

In an extension of the cis dihydroxylation of alkenes with osmium tetroxide. Sharpless has developed a series of reactions, reviewed by Case et al., in which an osmium imine species is added to an alkene. 

Bioxazolines have also been employed in the enantioselec-tive dihydroxylation of alkenes with Osmium Tetroxide The best results have been obtained in the dihydroxylation of 1-phenylcyclohexene with a complex, formed between OSO4 and the diisobutylbioxazoline (4) (R=CH2CHMe2>, as a stoichiometric reagent (70% ee). Styrene and trans -stilbene afford enantioselec-tivities below 20% ee under these conditions (for highly enantios-elective dihydroxylation catalysts, see Dihydmquinine Acetate and Osmium Tetroxide). 

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. ... 

Many different co-oxidants can be used in conjunction with osmium tetroxide for the catalytic dihydroxylation reaction. The most popular is A -methylmorpholine N-oxide (NMO) the use of NMO with less than one equivalent of osmium tetroxide is often referred to as the Upjohn conditions. Other oxidants, such as [K3Fe(CN)6], tert-hutyl hydroperoxide, hydrogen peroxide or bleach are effective. In these reactions, the intermediate osmate ester is oxidized to an osmium(VIII) species that is then hydrolysed with regeneration of osmium tetroxide to continue the cycle. For example, less than 1 mol% of osmium tetroxide is needed for the dihydroxylation of the alkene 74 (5.80). 

Related to the dihydroxylation of alkenes with osmium tetroxide is the direct conversion of alkenes into 1,2-amino alcohols. Treatment of an alkene with osmium tetroxide in the presence of A -chloramine-T (TsNClNa) provides the 1,2-hydroxy toluene-/ -sulfonamide (5.94). The sulfonylimido osmium compound 94 is believed to be the active reagent, and is continuously regenerated during the reaction. The sulfonamide products can be converted to their free amines by cleavage of the tosyl group with sodium in liquid ammonia. 

Alkenes are very susceptible to electrophilic addition reactions, which with osmium tetroxide gives the product of 1,2-dihydroxylation. 

The previous section described a method for anti dihydroxyladon of alkenes. In this section, we will explore two diflFerent sets of reagents that can accomplish syn dihydroxylation of alkenes. When an alkene is treated with osmium tetroxide (OSO4), a cyclic osmate ester is produced ... 

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... 

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]. 

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. 

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). 

The work by E.J. Corey [37], M. Hirama [38] and K. Tomioka [39], and their associates, on asymmetric dihydroxylation of alkenes with chiral diamine-osmium tetroxide complexes also deserves to be mentioned. 

Other functionalized supports that are able to serve in the asymmetric dihydroxylation of alkenes were reported by the groups of Sharpless (catalyst 25) [88], Sal-vadori (catalyst 26) [89-91] and Cmdden (catalyst 27) (Scheme 4.13) [92]. Commonly, the oxidations were carried out using K3Fe(CN)g as secondary oxidant in acetone/water or tert-butyl alcohol/water as solvents. For reasons of comparison, the dihydroxylation of trons-stilbene is depicted in Scheme 4.13. The polymeric catalysts could be reused but had to be regenerated after each experiment by treatment with small amounts of osmium tetroxide. A systematic study on the role of the polymeric support and the influence of the alkoxy or aryloxy group in the C-9 position of the immobilized cinchona alkaloids was conducted by Salvadori and coworkers [89-91]. Co-polymerization of a dihydroquinidine phthalazine derivative with hydroxyethylmethacrylate and ethylene glycol dimethacrylate afforded a functionalized polymer (26) with better swelling properties in polar solvents and hence improved performance in the dihydroxylation process [90]. 

In the synthesis of polyhydroxylated polyenes, osmium tetroxide induced dihydroxylation of an alkene adjacent to a coordinated iron atom has been used as the key synthetic step115. The reaction has been shown to be highly diastereoselective for E-alkenes and diastereospecific for Z-alkenes. With both types of alkene, the reaction occurs anti to the coordinated iron group (equation 18). 

Osmium tetroxide (0s04) is the reactive Os(VIII) species in the cw-vic-dihydroxylation of alkenes. This compound is a solid but is not easy to handle because it has a rather high vapor pressure. Therefore, it is often preferable to prepare the compound in situ. Such a preparation involves the oxidation of the potassium salt K,0s04 2H20 (K2OsO,(OH)4) of osmium(VI) acid with NMO as the oxidizing agent. This salt also is a solid but has a much... 

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