Methyl -2-hydroxy-3-phenylpropionate

The asymmetric hydroxylation of ester enolates with N-sulfonyloxaziridines has been less fully studied. Stereoselectivities are generally modest and less is known about the factors influencing the molecular recognition. For example, (/J)-methyl 2-hydroxy-3-phenylpropionate (10) is prepared in 85.5% ee by oxidizing the lithium enolate of methyl 3-phenylpropionate with (+)-( ) in the presence of HMPA (eq 13). Like esters, the hydroxylation of prochiral amide enolates with N-sulfonyloxaziridines affords the corresponding enantiomerically enriched a-hydroxy amides. Thus treatment of amide (11) with LDA followed by addition of (+)-( ) produces a-hydroxy amide (12) in 60% ee (eq 14). Improved stereoselectivities were achieved using double stereodifferentiation, e.g., the asymmetric oxidation of a chiral enolate. For example, oxidation of the lithium enolate of (13) with (—)-(1) (the matched pair) affords the a-hydroxy amide in 88-91% de (eq 15). (+)-(Camphorsulfonyl)oxaziridine (1) mediated hydroxylation of the enolate dianion of (/J)-(14) at —100 to —78 °C in the presence of 1.6 equiv of LiCl gave an 86 14 mixture of syn/anti-(15) (eq 16). The syn product is an intermediate for the C-13 side chain of taxol. 

Methyl-2-hydroxy-3-phenylpropionamide (179 mg, 1 mmol) was refluxed in hydrochloric acid (6 N, 29 ml) for 3 h to give, after extraction witli EtOAc and column chromatography using a silica gel column with a mixture of petroleum ether and EtOAc (1 2) as an eluent, 2 -(+)-2-methyl-2-hydroxy-3-phenylpropionic acid as a white solid (166 mg, 92%). 

In contrast, reaction of diethyl propionylphosphonate with lithium bis-(trimethylsilyl)amide (LiHMDS) at -78 °C gave the expected enolate as evidenced by its highly diastereoselective condensation with benzaldehyde, leading to the formation of 3-hydroxy-2-methyl-3-phenylpropionic acid (equation 91) " . An attempt was made to develop this concept to enantioselective aldol condensation. However, condensation of a cyclic chiral propionylphosphonamidate (31), synthesized from ( S)-A-isopropyl-4-aminobutan-2-ol, with benzaldehyde yielded 3-hydroxy-2-methyl-3-phenylpropionic acid in disappointingly low 47% e.e. (equation 92)... 

Hydroxy 2-methyl 1-phenyl 1-propanone 4-(p-Hydroxyphenyl)-2-butanone Isoeugenol Isopropyl benzoate 1 -(p-Methoxyphenyl)-2-propanone 4-Methyl benzyl acetate a-Methylbenzyl acetate -a-Methylbenzyl acetate Methylbenzyl acetate, mixed o-, m-, p-Methyl 3-phenylpropionate... 

Hydroxy-3-phenylbutyric acid, A51.il 2-(p-Methoxyphenyl)propionic acid, Y5.7 2-Hydroxy-2-methyl-3-phenylpropionic acid,... 

P-Hydroxycarboxylic acids. Propionyldimethyl-/ r -butylsilane added dropwise at — 78° to a soln. of /-Pr2NLi in THF/hexane under N2, after stirring for 25 min benzaldehyde added in one portion, quenched after 2 min with aq. NH4CI, extracted, the crude adduct dissolved in methanol/30% H2O2/3 N NaOH, and the slurry stirred at room temp, for 20 min (2SR,3RS)-3-hydroxy-2-methyl-3-phenylpropionic acid. 

To a 2 L, 3-neck Morton flask fitted with a thermometer, a mechanical stirrer, and an addition funnel was added the methyl 3-hydroxy-2-methylene-3-phenylpropionate (305.9 g, 1.585 mol) followed by addition of 48% HBr (505 ml, 4.46 mol) in one portion. The flask was immersed in an ice-water bath, at which time concentrated sulfuric acid (460 ml, 8.62 mol) was added dropwise over 90 min and the internal temperature of the reaction mixture was maintained at 23°-27°C throughout the addition process. After removal of the ice-water bath, the mixture was allowed to stir at room temperature overnight. The solution was then transferred to a separatory funnel and the organic layer was allowed to separate from the acid layer. The acids were drained and the organic layer was diluted with 2 L of a 1 1 ethyl acetate/hexane solution, washed with saturated aqueous sodium bicarbonate solution (1 L), dried over sodium sulfate, and concentrated to yield 400.0 g (99%) of the desired (Z)-l-bromo-2-carbomethoxy-3-phenyl-2-propene as a light yellow oil, which was used without any additional purification, boiling point 180°C (12 mm). 

Chiral sulphoxides, chiral phosphine, oxazolidinones, rerr.-butyl 2-methyl-.l-hydroxy-3-phenylpropionic acid thiocster... 

Hydroxy-7a,l 7-dimethyl-4-androsten-3-one 17 /3-Hydroxyestr-4-en-3-one /3-phenylpropionate 17 /3-Hydroxy-l 7-ethyl-estr-4-en-3-one 17 /3-Hydroxy-l 7-methyl-2-oxa-5[Pg.214]

Phenylpentanoic acid, A49.9, A"46 Pyrethrolone, T17.4 Isopyrethrolone, T17.2 2-Hydroxy-2-phenylpentan-3-one, A51.5 9-Methyl-A -octalin-l,6-dione, A 38.10 2-Ethyl-3-phenylpropionic acid, A"48.17 Homoadamantane-2,7-dione, X"10.8... 

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