Enolates MoOPH hydroxylation

The MoOPH reagent also hydroxylates branched or unbranched ester, amide, and nitrile anions. 7 For unknown reasons, MoOPH hydroxylations often do not give complete conversion of enolates into products, and recovery of 5-15% of the starting carbonyl substrate is to be expected. 

Methyl ketone enolates are hydroxylated by MoOPH, but the products tend to undergo condensation with the starting enolate, resulting in poor yields. Methyl ketone hydroxylation has been described by Moriarty, using c6H5I=0/CH30H-°He.a... 

The method described for MoOPH hydroxylation of the camphor enolate Is representative for ketone enolate hydroxylations, but optimization in each Individual case to determine the best temperature and concentration is recommended. Large scale oxidations may benefit from addition of reagent in several portions over time, and enolates which are sensitive to selfcondensation may give higher yields if enolate is added slowly to excess MoOPH. 

HYDROXYLATION OF ENOLATES WITH OXODIPEROXYMOLYBDENUM(PYRIDINE)-(HEXAMETHYLPHOSPHORIC TRIAMIDE), MoOc-Py-HMPA (MoOPH) ... 

Asymmetric hydroxylation of chiral imides The (Z)-spdium enolates of the chiral imides 2 and 3 undergo asymmetric hydroxylation on reaction with 2-(phen-ylsulfonyl)-3-phenyloxaziridine (1). The products [(R)-4 and (S)-6] are solvo-lyzed to (R)- and (S)-a-hydroxy esters. This hydroxylation can also be effected with MoOPh, which is much less reactive than 1 but slightly more stereoselective. In general 1 is preferred to MoOPh because of the higher yields. 

Enolate hydroxylation cf. 11, 108).- Enolates of ketones or esters are oxidized by this oxaziridine to a-hydroxy carbonyl compounds. Yields are highly dependent on the base they are highest with potassium hexamcihyldisilazide. Yields are generally higher than those obtained with the Vedejs reagent (MoOPH, 8, 207). 

Reagents which effect epoxidation of the enol ether unsaturation effect a-hydroxylation comparable to the peracid approach. Thus a combination of molybdenum hexacarbonyl and r-butyl hydroperoxide converts the substrates to a-silyloxy derivatives. The peroxide generate in situ from benzonitrile, potassium carbonate and hydrogen peroxide can also perform the oxidation. Molybdenum-peroxy complexes, including MoOPH, could presumably also effect this transformation. Lastly, dimethyldioxirane has been used to epoxidize alkenes and it is likely that application of this useful, debris free, organic peroxide to these reactions will soon emerge. 

MoOPH (Section 2.3.2.1.2.ii) may be a suitable reagent for lactam enolate hydroxylation. This is suggested by the oxidation of lactam (148). Cleariy the label enolate is not strictly applicable to the bridgehead carbanion and it is likely that more forcing conditions would be necessary for genuine enolate hydroxylations. It is not clear whether V-oxidation would then emerge as a source of problems. 

MoOPH may be used to a -hydroxylate lithium enolates of a,3-unsaturated ketones (c/. Section 2.3.2.1.2.ii), although the conversion is less efficient than the equivalent process with saturated sub-... 

Enolate Hydroxylation. Treatment of the sodium enolates with the Davis oxaziridine reagent affords the hydroxylated products with the same sense of induction as the alkylation products (eq 23). Although high diastereoselectivity may be achieved with Oxodiperoxymolybdenum(pyridine)(hexamethylphosphoric triamide) (MoOPH), such reactions proceed in lower yields. 

Stereoselective trans a-hydroxylation of (5)-dihydro-5-(t-butyldiphenylsiloxymethyl)-2(3/f)-furanone can be realized in good yield by enolization and reaction with the Oxodiperox-ymolybdenum(pyridine)(hexamethylphosphoric triamide) complex (MoOPH) (eq 10). Appropriate manipulation of the resulting trans-hydroxylactone provides 1,3-polyols typified by (18), as well as tetrahydropyran (19) which is a key intermediate in mevinic acid syntheses. ... 

Oxodiperoxymolybdenum-pyridine-hexamethylphosphoric triamide, MoOj CjHsN-HMPA (MoOPH), which is prepared from molybdenum trioxide, M0O3 [531,532], hydroxylates the enolates of ketones and esters in the a position with respect to the carbonyl groups [537, 532, 533] and, in the presence of mercuric acetate, converts acetylenes into a-dicarbonyl compounds [534]. 

Oxidations - 3,5-Dinitroperbenzoic acid is a stable storable peracid equivalent in activity to trlfluoroperacetic acid. A full paper has appeared which gives the experimental details for the a-hydroxylation of carbonyl compounds by treatment of the anions of enol silanes with Mo05 HMPA (MOOPH). Anions from carboxylic esters (LiN(iPr)2>LDA -78°C) can be efficiently, regiospecifically chlorinated or brominated by treatment with respectively CCl or CBr. Treatment of enol silanes from conjugated ketones with m-chloroperbenzolc acid (MCPBA) followed by removal of silicon affords the a-hydroxyketones. ... 

MoOPH [pronounced moof and more correctly oxidoperoxymolybdenum(aqua)-(hexa-methylphosphoric triamide)] is a molybdenum peroxide complex 245 that hydroxylates lithium enolates.39... 

In a typical reaction, the lithium enolate of the carbonyl compound 247 is prepared in the usual way and reacted with yellow MoOPH to give the hydroxylated product 248 and blue molybdenum compounds so that the reaction is self-indicating. The best feature of the method is that it uses lithium enolates since the regioselective preparation of these intermediates is much easier to control than that of other metal enolates. Hence 2-phenylcyclohexanone 249 gives a single regioisomer of the hydroxyketone 250 from kinetic enolisation with good stereoselectivity. 

There is stereoselectivity here, as in the last example, and both are determined by the substrate, that is the molecule being hydroxylated. The reagent MoOPH is large and it attacks the less hindered side of the substrate under kinetic control. Some control can be achieved in the interesting hydroxylation of aspartic acid enolates.41 The lithium enolate of the dimethyl ester of N-protected aspartic acid 259 gives high svn selectivity in hydroxylation next to only one of the two ester groups 260. 

If 259 is first treated with BuLi and then turned into the lithium enolate and reacted with MoOPH, a good yield of the other diastereoisomer, anti-261 is formed. The first result is probably hydroxylation opposite the very large NHR group in a Houk conformation of the enolate (chapter 21) while anti-selective hydroxylation probably results from chelation control. 

The popularity of MoOPH has waned with the discovery of the next type of reagents for hydroxylations. These /V-sull onyl oxaziridines should now probably be your first choice. In the 1986 volume of Organic Syntheses three recipes for hydroxylation of enolates stand side by side. Rubottom42 describes the formation of the kinetic lithium enolate of the enone 262 and the oxidation of the silyl enol ether 263 with mCPBA to give the a product 264 (see chapter 11 for the regioselectivity of such extended enolates). 

Vedejs and Larsen43 describe the preparation of MoOPH and the hydroxylation of the lithium enolate of camphor 265 to give a good yield of a 5 1 ratio of endotexo alcohols 266 while Mori-arty44 gives an example of a method we have not discussed, the hydroxylation of potassium enolates with o-iodosobenzoic acid. 

Prolonged exposure to light, or failure to control exothermic reactions in prior steps, results in a sticky product which smells of pyridine. No method for purifying partly decomposed MoOPH has been found, and "sticky" product should not be used for enolate hydroxyl ation. Suspect material can be decomposed by stirring with aqueous sodium sulfite (Na2S03) solution. 

Enolate hydroxylation is a problem of long standing. Direct oxygenation succeeds with the fully substituted enolates of certain o,a-disubstituted ketones and a variety of carboxylic acid derivatives (ester anions, acid dianions, amide anions), but the reaction of enolates, RCH = C(0")R or CH2 = C(0")R, with oxygen results in complex products of overoxidation. The stable molybdenum peroxide reagent MoOj Py-HMPA (MoOPH), first prepared by Mimoun, allows the conversion of RCH = C(0Li)R into RCH(0H)C0R in generally good yields (Table I). In some cases, the a-diketone is formed as a byproduct. 

R) or (3S)-3-Hydroxyaspartutes. These amino acids can be prepared in high diastereoselectivity by hydroxylation of the enolate of N-(9-phenylfluorenyl)aspartates. Thus this derivative 1 of L-aspartic acid on treatment with a base followed by reaction with MoOPH provides the 3-hydroxy derivative, syn- and anti-2. The stereoselectivity of this hydroxylation is highly dependent on the base and the solvent. The highest sy/i-selectivity is obtained with LHMDS, LiN[Si(CH3)3]2, as base in THF-DMPU or THF-HMPA. The highest a/iri-selectivity is obtained by treatment first with BuLi and then with LHMDS in THF. 

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