V-methylmorpholine-A -oxide

Unambigous structural confirmation was obtained by converting 53a to diol carbonate 56, which was independently synthesised from baccatin III. Selective deprotection of 53a with TBAF gave alcohol 54, which was oxidised with tetra-n-propylammonium perruthenate/)V-methylmorpholine A -oxide (CH2CI2, molecular sieves, 25 °C, 1.5 h) to ketone 55 in 86% overall yield from 53a. Deprotection (HF, pyridine, CH3CN, 96%) of gave diol carbonate 56, identical to the compound prepared from baccatin III. 

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. 

In the stoichiometric ADH of ( )-3-hexene the highest ee was achieved using the ligand 4b (88% ee). On the other hand, the catalytic process (Table 10.4, entries 1-3) was carried out by slow addition of ( )-3-hexene (1 equiv.) to a mixture of 4a (0.25 equiv.), A-methylmorpholine A-oxide (NMO, 1.5 equiv.) and OSO4 (0.004 equiv.) in acetone-water (10/1, v/v) at 0 °C, followed by working-up with Na2S205. Although the catalytic reaction was slow and required a slower addition... 

Similarly to oxidative olefin cleavage with periodate, the first intermediate formed is ester 35, here a perruthenate at the oxidation level +VI1 A -elimination releases ketone 6 and the mthenium(V) acid 36 /V-Methylmorpholine-N-oxide (NMO) serves in this case to regenerate the perruthenate(VII) speck s, and must therefore be introduced in stoichiometric quantity. 

The intramolecular version presents a very useful synthetic route to various polycyclic compounds. Even terminal alkenes give cyclopentenones in good yields, assisted by the addition of /V-methylmorpholine N-oxide (NMO) [85], The addition of trimethylamine A -oxidc also dramatically accelerates the reaction in the presence of oxygen, and both inter- and intramolecular reactions proceed at 0°C to room temperature [86]. The reaction was found to proceed rapidly at 25 °C by the addition of aqueous NH4OH [87]. Numerous applications to natural product syntheses have been reported. The tri- and tetracyclic skeletons 214 for crinipellin B, from 213 [88], and the triquinacene derivative 216, from 215, have been constructed [89,90], These results show that internal alkynes and terminal alkenes react smoothly in the intramolecular reactions. Domino reaction of the endiyne 217 produced the strained molecule of oxa[5.5.5.5]fenestrenedione (219) via 218 [91]. 

If no iV-methylmorpholine-iV-oxidc were added the ruthenium(V) acid would be converted into RuOz. In that case, Ru(VII) would be a three-electron oxidizing agent just like Cr(VI) (Figure 14.10). Such a conversion of Ru(V) into Ru(IV) could in principle occur, since Ru(V) also oxidizes alcohols. This oxidation presumably would proceed via an a-hydroxylated radical as discussed for the Cr(IV) oxidation of alcohols (Fig 14.10, center). Yet, there is no indication for such a radical pathway to occur when the reaction is carried out in the presence of A-methylmorpholine-A-oxide. Hence, it appears that A-methylmorpholine-A-oxide reoxidizes the ruthenium(V) acid to per-ruthenate faster than the ruthenium(V) acid could attack an alcohol molecule. 

Reagents i, LiNEt2-THF ii, Ac20-pyridine iii, A-methylmorpholine A-oxide-Os04-Bu 0H-THF-H20 iv, NaI04 v, K2C03... 

Cellulose is primarily a structural polymer in plants (especially in cotton, ramie and hemp) and trees. In the latter, cellulose is the principal structural material and constitutes about 50 weight percent of wood. Cellulose is also produced by bacteria in the form of exocellular microfibrils. In all forms, cellulose is a very highly crystalline, high molecular weight polymer, which is infusible and insoluble in all but the most aggressive, hydrogen-bond breaking solvents such as /V-methylmorpholine N-oxide. Because of its infusibility and insolubility, cellulose is usually converted into derivatives to make it processable. 

Scheme 8.8. A representation of the oxidation of cnck>-bicyclo[2.2.1]heptan-2-ol to the corresponding ketone (bicyclo[2.2.1]heptan-2-one) with tetra-n-propylammoniumperruthenate (TPAP) in the presence of A-methylmorpholine A-oxide. Despite what is shown, all four ruthenium-oxygen (Ru-O) bonds in TPAP are equivalent and the process may actually involve a series of one-electron rather than two-electron redox steps. Curved arrows representing two-electron processes are used for convenience. The actual path is not yet known in detail (see Ley, S. V. Griffith, W. P. J. Chem.Soc. Chem. Commun., 1978,1625).

BASF AG CRBPII dba DBN DBU DIBAL-H DMAP DMF DMF-DMA DMPU HMDS HMPA HMPT H-LR LDA LDE LRAT MCPBA MOM NMO NMP PCC PhH = Badische Anilin- Soda Fabrik AG = cellular retinol-binding protein type II r dibenzylideneacetone = 1,5-diazabicyclo[4.3.0]non-5-ene = l,8-diazabicyclo[5.4.0]undec-7-ene = diisobutylaluminium hydride = 4-dimethylaminopyridine = A V-dimethylformamide = A,V-dimethylformamide, dimethylacetal = 1,3 -dimethyl-3,4,5,6-tetrahydro-2( 1H)-pyrimidone = hexamethyldisilazane = hexamethylphosphoramide = hexamethylphosphorous triamide = Hoffmann-La Roche = lithium diisopropylamide = lithium diethylamide = lecithin retinol acyltransferase = m-chloroperbenzoic acid = methoxymethyl = iV-methylmorpholine oxide = l-methyl-2-pyrrolidinone = pyridinium chlorochromate = benzene... 

Osmium tetroxide is commonly used to add two OH groups to a double bond.15 The mechanism gives syn addition from the less hindered side of the alkene. Since 0s04 is expensive and highly toxic it is therefore mostly used in a catalytic fashion using stoichiometric cooxidants, like H202 or /V-methylmorpholine-/V-oxide (NMO). 

This procedure has been modified to become an effective catalytic procedure in which (V-methyl-moipholine A/-oxide is used as the secondary oxidant. In this manner, (iE -stilbene has been converted into (+)-rhreo-hydrobenzoin (55% yield after two recrystallizations, >99% ee) on a one molar scale, by treatment with osmium tetroxide (0.002 mol equiv.) and A(-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. 

Tony, K. J., Mahadevan, V., Rajaram, J., Swamy, C. S. Oxidation of secondary alcohols by N-methylmorpholine-N-oxide (NMO) catalyzed by a trans-dioxo ruthenium(VI) complex or perruthenate complex a kinetic study. React. Kinet. Catal. Lett. 1997, 62,105-116. 

Osmium tetroxide is very expensive and very toxic which made using it quite unattractive. For a long time, many people who used osmium tetroxide to convert olefins to diols—and this was long before enantioselective dihydroxylations came on the scene—used the Upjohn procedure.20 This process used catalytic amounts of osmium tetroxide, NMO (/V-methylmorpholine /V-oxidc) 87 as the stoichiometric oxidant, and one solvent phase. The solvent was water, acetone and tert-butyl alcohol. The osmate ester 86 was hydrolysed under these conditions and the osmium (VI) species was reoxidised to 0s04 by NMO. 

Chitosan, derived from crab shell chitin, is —80% deacetylated. It is dissolved in 1 M HO Ac (5 g/L) and freeze dried to yield a white, soft material. The chitosan is washed with 0.9 M A-methylmorpholine (NMM) in DMF followed by DMF. The Rink linker (0.4 mmol) is dissolved in 6 mL of DMF containing N-[(17/-benzotriazol-1 -yl)(dimethylamino)methylene]-A-methyl-methanaminium tetrafluoroborate A-oxide (TBTU) (0.3 M), HOBt (0.3 M), and NMM (0.4 M) and added to 150 mg (dry weight) of chitosan. The mixture is incubated at 45°C for 1 h, washed with DMF, and the chitosan capped with acetic anhydride-dry pyridine (1 1, v/v) for 1 h at 45°C. This procedure yields Fmoc-linker substituted chitin (Fig. 16). After drying in vacuo, the degree of substitution is determined by measuring the Fmoc released after treatment of a sample with piperidine-DMF (3 7) for 30 min at room temperature. Typically, chitosan substitution levels are 0.08-0.35 mmol/g. 

Pyridine N-oxide derivatives were found to produce a remarkable rate enhancement. It is not believed that they function as an axial ligand on the active catalyst species, since product ee s and cis/trans epoxide ratios are insensitive to the presence of these additives. Current theory suggests that the active Mn(V) oxo complex exists in equilibrium with an inactive dimer with the Mn(III) complex (see below). By binding to the latter, pyridine N-oxide derivatives shift the equilibrium toward the free active catalyst and thus enhance the reaction rates. It has also been observed that in dichloromethane, N-methylmorpholine N-oxide (NMO) and m-chloroperbenzoic acid (MCPB A) produce a 1 1 salt which is unreactive toward olefins yet which is very efficient in oxidizing the (salen)Mn catalyst. This is significant in preserving the enantioselectivity of the process, as it prevents uncatalyzed racemic side-oxidation of the substrate [94JA9333]. 

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