Oxaziridine hydroxylation

The oxaziridine ring itself is stable towards alkali there is, for instance, no substitutive ring opening by hydroxyl ions as in oxiranes. 2-r-Butyl-3-phenyloxaziridine (56) is not attacked by methoxide ion in methanol during 12 h at room temperature 3-isopropyl-2-r-octyloxaziridine does not react at room temperature with either solid potassium hydroxide or potassium methoxide solution (57JA5739). 

TABLE 4-19. Diasteroselective Hydroxylation of Chiral Carboximide Sodium Enolates Using 2-(Phenylsulfonyl)-3-Phenyl-Oxaziridine (141) in THF at — 78°C... 

The hydroxyl group in alcohol 122 is then oxidized. Deprotonation of this ketone with KHMDS (1 eq.), followed by the addition of Davis oxaziridine (see Chapter 4 for a-hydroxylation of ketones)28 (2 eq.) allows the stereo-controlled introduction of the C-10 oxygen from the less hindered enolate face, providing only the (i )-hydroxyketone 123. Subsequent reduction of 123 with excess LAH provides the tetra-ol 124. Treatment of this compound with imidazole and TBSC1 followed by PPTS and 2-methoxypropene provides in one operation the acetonide 125 with 91% yield (Scheme 7-37). 

Fluorination of the sodium enolate of 2-methyl-1-tetralone by (-)-A-tluoro-2,10-(3,3-dichlorocamphorsultam) gives (5 )-(- -)-2-iluoro-2-methyl-1-tetralone in 70% ee, which corresponds to the opposite asymmetric induction to that achieved using non-racemic (camphorsulfonyl)oxaziridines as closely related hydroxylation reagents. ... 

Another very useful series of reagents for oxidation of enolates to a-hydroxy ketones are A -sill fonyl oxaziridines.185 The best results are frequently achieved by using KHMDS to form the enolate. The hydroxylation occurs preferentially from the less hindered face of the enolate. 

Photoexcited nitrobenzene may be used for benzylic hydroxylation (at C-9) of 17/3-acetoxy-3-methoxyoestra-l,3,5(10)-triene. The photochemistry of the 17/3-nitro-steroid (217) is markedly solvent dependent, the major products being in ether the 17-desnitro-compound (218), in propan-2-ol the hydroxylamine (219), and in EtOH-NaOEt the hydroxamic acid (220) and the cyclopropane (221). The hydroxamic acid (220) is probably formed through the oxaziridine (Scheme 7). Although there are analogies to this in the photochemistry of nitrones and oximes, the photoreduction of a nitroalkane in propan-2-ol to an alkyl-hydroxylamine appears to have no precedent. Further studies of photochemistry of conjugated... 

Hydroxylation of 4-oxo-substituted 1,2-thiazine 99 via the racemic Davis oxaziridine reagent 100 afforded alcohol 101 in good yields. Efforts to produce 101 as a single enantiomer with chiral oxaziridine reagents afforded products with only a modest 46% ee (Equation 9) <2002EJP221>. 

A typical example is alkylation of the steroid ester 11. Treatment of 1 with LDA in tetrahydrofuran at —78 °C for 1 hour followed by addition of 4-bromo-2-methyl-2-butene in the presence of HMPA at —78 °C to —20 °C furnished an 87 13 mixture of the monoalkylated esters 3a and 3b. The potassium enolate 2 (KHMDS, THF, —78 °C, 1 h) has been hydroxylated with an oxaziridine reagent in 70% yield to give a 3 1 mixture of a-hydroxy derivatives. 

Chiral Davis oxaziridines allow the oxidation of phosphonates to a-hydroxy-phosphonates in good ee with apparently wide generality and with a sense of induction that is well controlled by the chirality of the reagent used.109 mCPBA oxidation of a bi-cyclic e do-camphorylsulfonylimine surprisingly resulted in an exo-camphorylsulfonyl-oxaziridine, whereas all other camphorylsulfonylimines resulted only in endo-oxaziiidines.110 Asymmetric oxidation of sulfides to sulfoxides and the a-hydroxylation of enolates were predicted by models in which steric interactions are minimized. 

In the framework of these ideas, the phenol hydroxylation mechanism is implemented by oxygen transfer from the oxaziridine intermediate to phenol giving different intermediate compounds—benzene epoxide ... 

In all the following examples, the targeted double bonds were activated by suitable substituents to increase the efficacy of the desired cyclization mode. For the total synthesis of acutumine (26), an activated a,p-unsaturated ketone 27 was chosen as precursor (Scheme 10) [74, 75], Aryl radical additions to this type of alkenes are known to proceed about ten times faster than to comparable allylic alcohols. In a radical-polar crossover reaction, the spirocyclic product 28 was obtained in the presence of triethylaluminum as promoter and an oxaziridine as hydroxylating agent. The fact that even the efficient hydrogen donor tetrahydrofuran could be used as solvent nicely demonstrates the high efficacy of the cyclization step. 

Electrophilic amination with oxaziridines 91S327. A-Sulfonyloxaziridines as reagents in asymmetric hydroxylation of eno-lates 92CRV919. 

ASYMMETRIC HYDROXYLATION OF TETRALONE AND PROPIOPHENONE ENOLATES USING (CAMPHORYLSULFONYL)OXAZIRIDINES 1 AND 2... 

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). 

Extension of this procedure to provide a means of asymmetric hydroxylation has been the subject of more recent attention. Initially oxaziridines bearing a camphor-derived residue at nitrogen, for example... 

Enders and coworicers have shown that deprotonation of chiral SAMP/RAMP hydrazones (or their substituted analogs) derived from ketones or aldehydes, followed by reaction with Davis oxaziridine reagent provides the a-hydroxy hydrazones in moderate yield but with high diastereoselectivity. Direct unmasking or protection followed by unmasking provides the corresponding a-hydroxy ketones or aldehydes respectively (Scheme 24). Both antipodes of the hydroxylated compounds are available by appropriate choice of (5)- or (R)-proline-deiived auxiliaries. The direction of induction is predictable, if not wholly uniform (R substitution alters the a-stereochemistry for aldehyde hydrazones). The process clearly provides a valuable approach to both systems. 

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

Extension of this procedure to provide a means of asymmetric hydroxylation has been the subject of more recent attention. Initially oxaziridines bearing a camphor-derived residue at nitrogen, for example (45), were considered. Relatively low levels of chiral induction were achieved and a more rigid compressed system was sought. Camphorsulfonyloxaziridines (46a and b) were subsequently shown to... 

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