A -Methylmorpholine IV-oxide

The original procedure has been modified by the use of a slow addition of the alkene to afford the diol in higher optical purity, and ironically this modification results in a faster reaction. This behavior can be rationalized by consideration of two catalytic cycles operating for the alkene (Scheme 9.20) the use of low alkene concentrations effectively removes the second, low enantio-selective cycle.145151 The use of potassium ferricyanide in place of A-methylmorpholine-iV-oxide (NMMO) as oxidant also improves the level of asymmetric induction.152153... 

A number of reoxidants for selenium dioxide have been examined. For example, while hydrogen peroxide is sometimes successful, oxidation of cholecalciferol (27) or derivatives widi selenium dioxide alone gave poor results not improved by addition of hydrogen peroxide. In this case, use of sodium periodate or tetra-R-butylammonium periodate gave increased yields. The reaction was much improved when carried out under reflux in methanol or solvent mixtures containing methanol, and indeed selenous acid and dialkyl selenites, suggested as intermediates in die reaction, both accomplished a similar oxidation in nonalcoholic solvents in die presence of a reoxidant, A -methylmorpholine iV-oxide proving superior. 

AIBN = 2,2 -azobisisobutyronitrile 9-BBN = 9-borabicyclo [3.3.1]nonane Bn = benzyl BOC = f-butoxycarbonyl Bz = benzoyl CAN = ceric anunoninm nitrate Cp = cyclopenta-dienyl Cy = cyclohexyl DAST = diethylaminosnllur trifln-oride DBA = l,3-dibromo-5,5-dttnethylhydantoin DDQ = 2,3-dichloro-5,6-dicyano-l,4-benzoquinone DET = diethyl tartrate DIAD = diisopropyl acetylene dicarboxylate DIBAL-H = diisobutylalummum hydride DIPEA = diisopropyl ethyl amine DMDO = dimethyldioxirane HMPA = hexamethylphosphortriamide EDA = lithium diisopropy-lamide Ms = methylsulfonyl MOM = methoxymethyl NBS = iV-bromosuccmimide NMO = A-methylmorpholine iV-oxide PDC = pyridinium dichromate PMP = p-methoxyphenyl THP = tetrahydropyranyl TIPS = trisiso-propylsilyl TMANO = trimethylamine A-oxide TBDMS = t-butyldimethylsilyl Tf = trifluoromethanesulfonyl TMP = 2,2,6,6-tetramethylpiperidyl TMS = trimethylsilyl Ts = p-toluenesulfonyl. 

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. 

Cellulose has been dissolved in A-methylmorpholine iV-oxide at high temperature and the recrystallization of the polysaccharide upon cooling investigated." The crystallization system is analogous to the solidification of binary mixtures of polymer and diluent, which present unusual thermodynamic and morphological properties. The system provides a new method of texturing cellulose. 

GOL Golova, L.K., Makarov, I.S., Matukhina, E.V., and Kulichikhin, V.G., Solutions of cellulose and its blends with synthetic polymers in A/-methylmorpholine-iV-oxide Preparation, phase state, structure, and properties, Polym. Sci., Ser. A, 52, 1209, 2010. 

To a solution of compound 166 (306 mg, 1 mmol) [Eq. (30)] in 12 mL of CH2CI2 was added in one portion cobalt carbonyl (343 mg, 1.1 mmol) at room temperature. The mixture was stirred for 3 h, and then anhydrous 4-methylmorpholine IV-oxide monohydrate (850 mg, 6.3 mmol) was slowly added and stirring was continued for 5 h more. Part of the solvent was evaporated, and the suspension was purified by flash chromatography (hexane-EtOAc) to provide compound 168 (194 mg, 66%) [a]D —17° (c 2.3, CHC13). 

A recent method for the highly chemoselective oxidation of sulfides to sulfones using Af-methylmorpholine IV-oxide (NMP) and a catalytic perruthenatc was found to be also applicable in the presence of isolated or allylic double bonds [115]. 

Tetrapropylammonium perruthenate (0.027 mmol) was added to a mixture of (15,4/ )-4-(f-butyldimethylsilanyloxy)cyclopent-2-enol (0.54 mmol), 4-methylmorpholine IV-oxide (0.81 mmol), and 270 mg crushed 4 A molecular sieves dissolved in 10 ml CH2C12. The mixture was stirred 30 minutes at ambient temperature, then filtered through a plug of silica gel with CH2C12, concentrated, and the product isolated in 86% yield. 

TPAP (Pr4N"Ru04 ) is an air-stable oxidant for primary and secondary alcohols. It is commercially available and environmentally friendly since it is used in catalytic amounts in the presence of a co-oxidant such as AT-methylmorpholine-iV-oxide (NMO). 

Alternatively, Liskamp s group [175] initially reported the use of j8-substituted sulfinyl chlorides 119 (Fig. 19) as activated monomers. NMM-mediated coupling to the polymer-bound amine led to the corresponding sulfinamide, which was further oxidized (Os04/A-methylmorpholine-iV-ox-ide) to sulfonamide on the solid support [66]. However, the yield of the oxidation step is highly dependent on the sequence of the peptidosulfon-amide. Hence the former method utilizing /3-sulfonyl chloride derivatives 117 is preferred [174]. 

BASF chemists oxidized a variety of chloromethyl heterocycles to the corresponding aldehydes under mild conditions, using a trialkylainine iV-oxide. For example, treatment of 4-(chloromethyl)-2-(4-fluorophenyl)oxazole 619 with 7V-methylmorpholine iV-oxide monohydrate gave 2-(4-fluorophenyl)-4-oxazolecar-boxaldehyde 620 in 48% yield (Scheme 1.169). This reaction was reported to be quite general for live- and six-membered ring heterocycles. 

The avoidance of a-ketol by-products is an important feature of a new catalytic osmylation procedure for the preparation of cis-1,2-diols. Reaction involves treatment of the olefin with N-methylmorpholine iV-oxide dihydrate in aqueous acetone, and osmium tetroxide in t-butyl alcohol at 25 °C, overnight. Reduction (NaHS03), adsorption on to magnesium silicate, filtration, neutralization, and ethyl acetate extraction afforded the diols in moderate to excellent yield. An example is the synthesis of (397 55 %) from (396). 

In 1990, a major breakthrough for the utility of the PKR occurred when Schreiber reported the use of iV-methylmorpholine-iV-oxide (NMO) as a promoter. As shown, the addition of NMO allowed the reaction to be run at ambient temperature and produced enhanced diastereoselectivity. 

A remarkable multicatalytic relay system consisting of tetra-propylammonium perruthenate/N-methylmorpholine iV-oxide (TPAP/NMO) as oxidant, and chiral diarylprolinol trimethylsilyl ethers as organocatalysts, has recently been developed by Rueping et al. and applied in the efficient construction of various valuable chiral molecules through domino reactions. The latter were all based on the in situ generation of ot,p-unsaturated... 

The most impressive use of a tandem strategy involving the Nicholas reaction in a total synthesis project is Schreiber s preparation of (+)-epoxydict5miene (61). Cobalt complexation of 58 followed by an endocyclic intramolecular Nicholas reaction with an allylsilane nucleophile yields Pauson-Khand precursor 59. Treatment of 59 with iV-methylmorpholine-iV-oxide (NMO) promotes the Pauson-Khand reaction to furnish tetracycle 60 which was ultimately converted to the target natural product 61. ... 

Al-Methylmorpholine iV-oxide, preferably as monohydrate, as well as MesNO not only induces cyclopentenone formation under very mild conditions (0-20 °C) and in frequently excellent yields, but also removes some earlier limitations. The reductive processes (eqs 58 and 59) do not occur when these promoters or DMSO are used under oxygen. Hence two efficient syntheses of (—)-kainic acid have employed cyclizations of allylpropar-gylamine derivatives as the key step in one of these (eq 62), as well as in a synthesis of the dendrobine skeleton, use of a chiral precursor was shown to result in enantiospecific bicyclization. ... 

From the study of a microbially mediated oxidation of arteether 28b, sufficient quantities of 7a-hydroxy 180 and 15-hydroxy derivatives 182 were obtained to employ them as intermediates for the preparation of fluorinated compounds. The hydroxyl groups were oxidized to the corresponding aldehyde 187, or ketone 188, with catalytic quantities of tetra- -propylammonium perruthenate (TPAP) in the presence of excess iV-methylmorpholine A -oxide. On reaction with DAST, 187 and 188 were converted into the corresponding geminal difluoro derivatives, 189 (63%) and 190 (42%). In addition to 190, a monofluoro olefin 191 was obtained in 25% yield from 188 on reaction with DAST <1995JME4120>. 

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. 

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