Morpholine-A-oxide

The reagent is toxic and expensive but these disadvantages are minimized by methods that use only a catalytic amount of osmium tetroxide. A very useful procedure involves an amine oxide such as morpholine-A-oxide as the stoichiometric oxidant.41... 

Since the reagent is quite expensive, different catalytic procedures have been developed. A very useful procedure involves an amine oxide, such as morpholine-A-oxide, as the stoichiometric secondary oxidant (Scheme 10.4) [29]. 

A more recent process for producing regenerated cellulose involves the use of V-methyl-morpholine-A-oxide, a highly polar solvent, at about 130°C to dissolve cellulose [Rosenau et al., 2001], About 5% of all regenerated cellulose is produced by this method. 

A milestone in the routine employment of perruthenate in the oxidation of alcohols was established with the publication by Griffith, Ley et al. in 1987 on the catalytic use of tetra- -propylammonium perruthenate (TPAP).11 The presence of the tetra- -propylammonium cation renders this compound soluble in apolar media and allows the existence of a high concentration of perruthenate ion in organic solvents. The tetra- -propylammonium perruthenate is easily prepared and can be employed catalytically in CH2CI2 solution in the oxidation of alcohols to ketones and aldehydes, using /V-methyl morpholine A-oxide (NMO) as the secondary oxidant. 

A one-sided binding of the complex to the support resulted in further improvements (92). This requires synthesis of nonsymmetric salen-type ligands, which is complicated by the tendency of such ligands to equilibrate to give mixtures containing symmetric Schiff bases. Excellent results were obtained with monomer 7d, diluted in a methacrylate polymer, by using a combination of meta-chloroperbenzoic acid (mCPBA) and A-methyl-morpholine-A-oxide (NMO) as the oxidants ... 

Although 0s04 is thought of as a specific oxidant for cis alkenes there are a few examples of hydroxylation of trans alkenes, e.g. cis- and frans-cyclodecene can be hydroxylated to the respective cis and irons diols.597 The Os04-alkene-pyridine reaction can be made catalytic by the use of suitable secondary oxidants such as H202, C103 , Bu OOH, A-morpholine A-oxide, I04 , 02 and CIO-. S54... 

A very broad class of primary oxidants act as oxygen atom transfer agents, the most widely nsed oxidants in oxidation catalysis. These inclnde peracids or their anion forms, snch as MCPBA or oxone (O-OSOs ) as well as A-oxides snch as A-methyl morpholine A-oxide or hypochlorite ion. They all have general structure XO, where X is a good leaving gronp. 

To a solution of 7 (458 mg, 1.7 mmol) and N-methyl morpholine A-oxide (244 mg) in t-butanol (1 mL), a few crystals of osmium tetraoxide dissolved in THF (1.5 mL) were added. After 3 days 40% aqueous solution of NaHSOj (3 mL) was added, the mixture was stirred for additional 30 min, and extracted with ethyl acetate (3 x 20 mL). The extracts were dried (MgS04) and concentrated to dryness. The residue was purified by chromatography on a silica gel column with light petroleum-ether-methanol (4 5 0.5) to yield 9 (371 mg, 72%) mp 89.5° (from a mixture of hexane and ethyl acetate), [a] + 52° (c 1.0, CHCI3). 

Another ruthenium-catalyzed oxidation uses tetrapropylammonium permthenate (TRAP) [24]. Being a ruthenium(VII) oxide, the permthenate ion is a less powerful oxidant than rutheni-um(VIII) oxide and more functional groups are stable to the oxidation conditions, including alkenes, alkynes, amines, amides, benzyl, trityl and silyl ethers [24]. However, alcohols and lactols still undergo oxidations in high yield with W-methyl-morpholine A-oxide (NMO) as the stoichiometric oxidant. The reactions are usually carried out in dichloromethane, acetonitrile, or mixtures of both in the presence of molecular sieves [24]. 

Discovered in 1987, the tetra-n-propylammonium perruthenate (TPAP) oxidation is straightforward to run. The reagent is expensive and thus it is used in catalytic amounts and becomes re-oxidized by A-methyl morpholine-A-oxide. For a review see Ley, S. V. Norman, J. Griffith, W. P Marsden, S. P. Synthesis 1994, 639-666. 

Tetrapropylammonium perruthenate (TPAP 63 mg) was added in 1 portion to a stirred mixture of A -Boc-4-fra .y-hydroxy-L-proline (1 g, 3.47 mmol), A-methyl-morpholine A-oxide (0.62 g, 15.6 mmol), and powdered molecular sieves (4 A, 1.78 g) in CH2CI2 (7 mL) at room temperature under argon. The mixture was stirred for 3 h, filtered, and evaporated in vacuo to give a black residue. The product was purified by... 

Some clear solutions of cellulose, however, are in fact micellar. Clear, apparently purely physical solutions of cellulose are formed in 7V-methyl-morpholine A -oxide (NMNO) and anhydrous dimethylacetamide-LiCl, but they can give rise to anomalously high DP values, because of association of the glucan chains in so-called fringe micelles , in which a group of chains associate chain-to-chain but the ends are largely random chain (Figure 4.34b and c). 

The product in this particular reaction (naproxen) is a high-value antiinflammatory drug. Even a simple microcapsulation of OSO4 into acrylonitrile-butadiene-styrene (ABS) polymer along with addition of a chiral ligand (N-methyl-morpholine A-oxide or l,4-bis(9-0-dihidroquinidinyl)phthalazine led to a considerable increase in the rate and in the chiral yield during the asymmetric dihydroxylation of olefins (Table 12-7) [64]. 

Catalytic amounts of camphor-10-sulfonic acid (CSA) in methanol and dichloro-methane smoothly cleave the orthoester function in 23, giving the intermediate y-lactone-l,3-diol. Subsequent protection of the primary alcohol function with di-methylphenylchlorosilane (TPSCl) in dimethylformamide with imidazole as the base and of the secondary alcohol function via alcoholate with benzylbromide (BnBr) following WiLLlAMSON s ether synthesis yields the y-lactone 24. Its reduction with lithiumaluminumhydride leads to two vicinal primary alcohol groups. Thereafter, camphor-10-sulfonic acid (CSA) in dichloromethane selectively cleaves the TBS ether and catalyzes the transketalization with acetone dimethyUcetal to the precursor 25 of the aldehyde 8. Smooth oxidation of the primary alcohol function in 25 is achieved with tetrapropylammoniumperruthenate (TPAP) and A-methyl-morpholine-A-oxide (NMO) in acetonitrile. 

This procedure has been modified to become an effective catalytic procedure in which A methyl-morpholine A(-oxide is used as the secondary oxidant. In this manner, (JE -sdlbene has been conver d into (+)-(/jreo-hydrobenzoin (55% yield after two recrystallizations, >99% ee) on a one molar scale, by treatment with osmium tetroxide (0.002 mol equiv.) and IV-methylmorpholine IV-oxide (1.2 mol equiv.) in aqueous acetone in the presence of dihydroquinidine p-chlorobenzoate (0.134 mol equiv.). The latter compound can be recovered in 91% yield. 

Commercially available enantiopure acetate 30 was aminated with sodium di-tert-butyloxy diimide by palladium catalyst to give bis-Boc amide 31, which was quantitatively dihydroxylated by using catalytic osmium tetraoxide and A -methyl morpholine A -oxide (NMO) in THF/water resulting in the cw-diol 32. The free base 33 was liberated from 32 by concentrated... 

Cy - cydohexyl pMB = p-methoxybenzyl pMPh = p-methoxyphenyl DDQ dichloro-dicyano-p-quinone NMO = /V-methyl-morpholine-A/oxide. 

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