Enolate hydroxylation, Davis oxaziridine reagents

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. 

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

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