V- Methylmorpholine-N-oxide

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]. 

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. 

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. 

Scheme 10. i, allyltrimethylsilane-trimethylsilyltriflate ii, Hg(0Ac)2, acetone-water then 12, THF iii, PCC, CH2C12 iv, Ph3P, then NaHC03 v, MeCN vi, 0s04 cat, N-methylmorpholine-N-oxide, acetone-water vii, deprotection... 

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. 

Threshold volume fractions observed for cellulose acetate (CA and CTA), ethyl cellulose (EC) and hydroxypropyl cellulose (HPC), each in various solvents, are presented in Table 3. The results depend to some extent on the solventThe data included are not exhaustive. Other cellulose esters exhibit mesomorphic behavior Chanzy et al. observed mesomorphic behavior in solutions of cellulose itself when dissolved in N-methylmorpholine N-oxide containing water at concentrations of cellulose in the range 20-55 % w/v, depending on the temperature, the water content of the solvent and the degree of polymerization of the cellulose. Solutions of cellulose in mixtures of trifluoroacetic acid with 1,2-dichloroethane or with chloroform are hkewise lyotropic at concentrations of 20% (w/v) and above according to Patel and Gilbert... 

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. 

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]. 

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).

Scheme 6D.3. Catalytic cycle for asymmetric dihydroxylation using N-methylmorpholine-/V-oxide as cooxidant.

Griffith, Ley et al.n discovered that, in variance with the instability and complex behaviour of perruthenate and ruthenate ions in aqueous solution, TPAP in organic media is quite stable and behaves as a very good oxidant for alcohols. Normally, it is employed in catalytic quantities in dry CH2CI2 with addition of TV-methylmorpholine /V-oxide (NMO) as the secondary oxidant. Catalytic TPAP in the presence of NMO is able to oxidize alcohols to adehydes and ketones under very mild conditions in substrates adorned by complex functionalities, and it has become one of the routine oxidants for alcohols in most Synthetic Organic Chemistry laboratories. 

Fig. 17.15. Mechanism of the TPAP oxidation of an atcohot to an aldehyde (TPAP stands for tetrapropylammonium per-ruthenate). The effective oxidant is a Ru(VII) oxide, other than in Figure 17.12 where a Ru(VIII) oxide is employed. Here, the stoichiometrically used oxidizing agent is N-methylmorpholin-/V-oxide ("NMO"), whereas in Figure 17.12 NaI04 is used.

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. 

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