Osmium tetroxide-N-Methylmorpholine oxide

Osmium tetroxide/N-methylmorpholine oxide phenyl iodosoacetate... 

Osmium tetroxide N-methylmorpholine oxide peroxide a-Hydroxyketones from ethylene derivatives s. lA, 222 s. a. J. Org. Ghem. 2A, 1517 (1959) Platinum oxygen Carboxylic acids from alcohols s. 15, 261 C CH C(OH)CO Pt/0 CH2OH COOH... 

Osmium tetroxide-N-Methylmorpholine N-oxide, 0s04-NMM0, 7, 256-257 9, 334. 

Os04/N-methylmorpholine-N-oxide (NMO) (osmium tetroxide/ N-methylmorpholine-N-oxide) Acetone/water t-butanol RT alkene—> 1,2-diol... 

McCormick, J.P., Tomasik, W, and Johnson, M.W., a-Hydroxylation of ketones osmium tetroxide/ N-methylmorpholine-N-oxide oxidation of silyl enol ethers. Tetrahedron Lett., 22, 607,1981. 

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. 

Under stoichiometric and common catalytic osmylation conditions, alkene double bonds are hydroxylated by osmium tetroxide without affecting other functional groups such as hydroxyl groups, aldehyde and ketone carbonyl groups, acetals, triple bonds, and sulfides (see also Osmium Tetraxide-N-Methylmorpholine N-Oxide). 

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... 

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]. 

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 very sensitive ether peroxide test strips (Merckoquant, Art. No. 10011), available from E. Merck, Darmstadt, are used. If the test is still positive at this point, an additional 0.2 ml. of N-methyl morpholine is added. Stirring and heating at 75° are continued for another 5 hours. Remaining peroxide renders the work-up and drying of the product potentially hazardous. N-Methylmorpholine N-oxide (1) and hydrogen peroxide form a strong 1 1 complex. In the reaction with osmium tetroxide, this complex produces conditions similar to those of the Milas reaction,7 and some ketol formation may result. 

In this report we describe the conversion of cyclohexene to cis-diol 2 in 90% yield in a catalytic osmylation using 1 mole equivalent of N-methylmorpholine N-oxide (1) to regenerate the less than 1 mole % of osmium tetroxide catalyst. This procedure avoids the a-ketol by-products encountered with the presently available catalytic processes, and provides the high yields of the stoichiometric reaction without the expense and work-up problems. 

Other methods for a-hydroxy ketone synthesis are addition of O2 to an enolate followed by reduction of the a-hydroperoxy ketone using triethyl phosphite 9 the molybdenum peroxide-pyridine-HMPA oxidation of enolates 10 photooxygenation of enol ethers followed by triphenylphosphine reduction 11 the epoxidation of trimethyl silyl enol ethers by peracid 1 - the oxidation of trimethylsilyl enol ethers by osmium tetroxide in N-methylmorpholine N-... 

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 essential components of the catalyst for the asymmetric dihydroxylation process are osmium tetroxide (OSO4) and an ester of one or the other of the pseudoenantiomeiic cinchona alkaloids dihydro-quinidine (DH( D) and dihydroquinine (DHQ). An amine oxide, generally N-methylmorpholine N-oxide, serves as the oxidant for foe reaction. When an alkenic substrate is added very slowly to a... 

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. 

Osmium tetroxide is a reagent that transforms double bonds to 1,2-diols. For steric reasons, only the terminal double bond of 25 is attacked. OSO4 is an expensive and very toxic reagent therefore, it is used in catalytic amounts in the presence of 7V-methylmorpholine N-oxide (NMO, 62), which reoxidizes the Os(VI)-species 0s02(0H)2 to the Os(VIII)-species OSO4. When performing the reaction in this catalytic fashion, water must be present in the reaction mixture to quench the primarily formed osmate ester to afford the diol 61 and the Os(VI)-species. 

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