Oxaziridine Davis reagents

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>. 

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. 

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. 

The synthesis of the 4 -spiroannulated ribonucleoside was aceomplished by elimination of the 2 -phenylthio group of compound 132 via a controlled oxidation with Davis oxaziridine reagent. 

Davis oxaziridine reagents such as 1 have exhibited ample synthetic utility as oxidizing agents for the hydroxylation of enolates to provide a-hydroxy carbonyl compounds, such as 2 with superb yield. When the oxaziridine is chiral and nonracemic, the hydroxylation has been shown to proceed with high stereoselectivity.1... 

Readers are directed to a thorough review on the chemistry of Davis oxaziridine reagents through 1992. While this work will occasionally be referenced, the primary focus of this section will be on the chemistry from 1992 to the present. 

Chiral auxiliaries have found abundant use in providing a template for efficient and highly diastereoselective enolate reactions. Concurrent with the development of chiral and nonracemic Davis oxaziridine reagents, the use of chiral auxiliaries to direct the stereoselectivity in these systems has been generalized. 

Several examples exist in the literature in which cyclic ketone enolates are enantioselectively hydroxylated by chiral, nonracemic Davis oxaziridine reagents. In contrast to their acyclic counterpart, the enolate geometry is fixed in cyclic systems. During the preparation of enantiomerically pure (-)-blebbistatin, the enolate of the quinolone 61 was reacted with the Davis reagent 5 to afford the optically enriched 62 with 82% yield and 86% ee.54 The related reagent 6 was used in the synthesis of (-t-)-o-trimethylbrazilin, which was... 

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