Oxaziridine-mediated hydroxylation

Oxaziridine-mediated hydroxylation of 0,0-dialkyl benzylphosphonates was also reported to be applied to the synthesis of enantiomerically pure l-hydroxy(phenyl) methylphosphonates, which is a stereoselective synthetic method with characteristics of simple operation and high efficiency [55, 56, 73]. 

The reactions were carried out at -78 °C under inert atmosphere with freshly distilled anhydrous solvents and avoided light. Two equivalents of oxaziridine were beneficial to yield of enantiomers of M2. Reaction time was a key factor affecting the stereoselective oxaziridine-mediated hydroxylation of (9,(9-dialkyl (substituted benzyl)phosphonates. Prolonging reaction time (>3 h) could result in the decrease of enantiomeric excess. Conversely, shortening reaction time (<3 h) might give a lower yield. 

L. Dorow, J. Am. Chem. Soc., 1985, 107, 4346, for oxaziridine-mediated asymmetric hydroxylation of chiral ester enolates. 

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. 

Modest to low ees are reported for the oxaziridine mediate asymmetric hydroxylation of 4,5-dihydroisoxazoles (177) to 4,5-dihydro-4-isoxazolols (178) (Equation (42)) <93JOC759i>. Dichloro oxaziridine (+)-(74) and the lithium enolate, generated in the presence of TMEDA, gave the best results. Transition state TS-2 predicts the absolute configuration of the product which was confirmed by chemical correlation. 

The asymmetric hydroxylation of A-non-substituted ethyl 2-carbamoyl-2-phenylacetate in THF was mediated by Davis oxaziridine, 2-(benzenesulfonyl)-3-phenyl-oxaziridine as oxidant in the presence of a combination of rare-earth metal alkoxide Pr(OPr )3 and the ligand A-((S)-l-(2-hydroxyphenylcarbamoyl)-2-methylpropyl)-2-hydroxybenzamide as catalyst afforded enantioenriched (68-92% ee) (R)-ethyl 2-carbamoyl-2-hydroxy-2-phenylacetate (yield 39-96%) with a densely... 

In the synthesis of a second-generation anticancer taxoid ortataxel, deprotonation of 13-oxobaccatinIIIby KHMDS (THF-HMPA, 83 17) followed by electrophilic oxidation with (IR)-(lO-camphorsulfonyl)oxaziridine afforded the C14-hydroxylated taxoid in 70% yield (eq 62). An analogous oxidation mediated by f-BuOK (THF-DMPU, 83 17) afforded the product in 83% yield (eq 62). The 14)8-OH epimer was formed exclusively, in accord with the approach of the oxidant from the less sterically hindered )8-face. The performance of several bases was compared, indicating the order of reactivity t-BuOK > LDEA (lithium diethylamide) > KHMDS > NaHMDS, in THF/HMPA or DMPU solvent mixtures. 

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