Enolate hydroxylation, Davis oxaziridine

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). 

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. 

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. 

During the highly stereoselective total synthesis of epothilone B by J.D. White and co-workers, the stereochemistry of the alcohol portion of the macrolactone was established by applying Davis oxaziridine oxidation of a sodium enolate. The sodium enolate was generated from the corresponding chiral oxazolidinone derivative, which upon oxidation gave 71% yield of a-hydroxylated compound. 

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... 

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. 

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... 

The hydroxylation of the unsaturated lactone (107) by the treatment of its potassium enolate with the Davis oxaziridine afforded the a-hydroxy lactone (108) as a single diastereoisomer (Scheme 6) <92TL67l>. Evans et al. have examined the diastereoselection of the azidation reaction of the potassium enolate derived from the unsaturated lactam (109). The product (110) was formed in only moderate yield, and as a 1 1.4 mixture of diastereoisomers (Scheme 6) <92TL6859>. 

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). ... 

An abbreviated synthesis of a substituted 1,7-dioxaspiro[5.5]undec-3-ene system constituting the C3-C14 portion of okadaic acid was developed in the laboratory of C.J. Forsyth. The C3-C8 fragment, a substituted valerolactone, was prepared in three steps. The diastereoselective a-hydroxylation of this lactone was accomplished by using Davis chirai camphorsuiphonyi oxaziridine on the corresponding lithium enolate at -78 °C. The isolated yield was 61% and the ratio of diastereomers was 10 1. 

Detailed studies by Davis et al. [63] demonstrated that enolate oxidation, using (camphorsulfonyl)oxaziridine (lS)-(+)-52 or (li<)-(-)-52 (Fig. 7) as a chiral oxidizing agent, was highly enantioselective. However, the yields and ees of the hydroxylated products are strongly dependent on the structure of the substrate and oxaziridine as well as the reaction conditions (enolate counter-ion, solvent, temperature) [64]. 

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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