Davis oxaziridine reagents hydroxylation

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. 

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... 

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... 

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. 

Despite high yield, the Rubottom oxidation is limited by the necessity for synthesis of the requisite silane ethers. The direct oxidation of enolates has thus emerged as the preferred method for the stereoselective formation of a-hydroxy carbonyl compounds because of the method s effectiveness for both acyclic and cyclic substrates. Davis s oxaziridine reagents have proved to be ideally suited for the one-step enolate hydroxylation process. The following chiral oxaziridine reagents have been utilized effectively in this protocol and will be showcased throughout the chapter. 

The utility of Davis chiral oxaziridine reagents has been more recently applied to the synthesis of optically active a-hydroxy phosphonates. Two groups have been largely responsible for developments in this area. Principally, Wiemer and co-workers have demonstrated the highly enantioselective hydroxylation of a series of benzyl phosphonates. As shown below for 69, hydroxylation makes use of oxaziridine 6, proceeding in moderate... 

Oxaziridines. Davis has developed the use of chiral 2-sulfonyloxaziridines derived from camphorsulfonic acid as chiral auxiliaries in the asymmetric oxidation reactions. Although other oxaziridines may be preferable, the camphor-derived oxaziridines can be used for the oxidation of sulfides and disulfides to sulfoxides and thiosulfinates as well as for the epoxidation of alkenes. On the other hand, the camphoryloxaziridines are the preferred reagents for hydroxylation of lithium enolates of esters, amides, and ketones, as utilized in the synthesis of kjellmanianone (eq 17). ... 

Asymmetric hydroxylation of etiolates. Davis and Chen1 have reviewed this reaction using in particular (R,R)- and (S,S)-2-phenylsulfonyl)-3-phcnyloxaziridene (1) and (camphorylsulfonyl)oxaziridine (2). Of these reagents, 1 and ( + )- and (—)-2, derived from (lR)-lO-camphorsulfonic acid, provide highest enantioselectivity and in addition are easy to prepare. They are effective for hydroxylatation of ketones, esters, /2-keto esters, amides, lactones, and lactams. 

---