Hydroxylation of enolates

E. Vedejs (1978) developed a general method for the sterically controlled electrophilic or-hydroxylation of enolates. This uses a bulky molybdenum(VI) peroxide complex, MoO(02)2(HMPTA)(Py), which is rather stable and can be stored below 0 °C. If this peroxide is added to the enolate in THF solution (base e.g. LDA) at low temperatures, oneO—O bond is broken, and a molybdyl ester is formed. Excess peroxide is quenched with sodium sulfite after the reaction has occurred, and the molybdyl ester is cleaved to give the a-hydroxy car-... 

Diastereoselective hydroxylation of enolates of chiral amides. Davis and coworkers1 have examined the asymmetric hydroxylation of the tetrasubstituted enolates of a chiral amide (2) with these chiral camphoryloxaziridines. Oxidation of the lithium enolate of 2 with (+ )-l proceeds with only moderate diastereoselectivity (48.4% de), which is somewhat less than that observed on hydroxylation with the achiral 2-(phenylsulfonyl)-3-phenyloxaziridine (4). Oxidation of the enolate of 2... 

HYDROXYLATION OF ENOLATES WITH OXODIPEROXYMOLYBDENUM(PYRIDINE)-(HEXAMETHYLPHOSPHORIC TRIAMIDE), MoOc-Py-HMPA (MoOPH) ... 

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. 

N-Sulfonyloxaziridines are an important class of selective, neutral, and aprotic oxidizing reagents.11 Enantiopure N-sulfonyloxaziridines have been used in the asymmetric hydroxylation of enolates to enantiomerically enriched a-hydroxy carbonyl compounds,9 11-13 the asymmetric oxidation of sulfides to sulfoxides,14 1S selenides to selenoxides,16 sulfenimines to sulfinimines,17 and the epoxidation of alkenes.18... 

Hydroxylation of enolate generated from 7-TES-13-oxobaccatin III 267 with various A -sulfonyloxaziridines, 33, (+)-146, and (+)-202, were studied by Baldelli et al. <2003JOC9773>. 7-TES-13-oxo-14/30H-baccatin III 268 was obtained in 83-88% yield. The yield and diastereoselectivity of the hydroxylation were not affected by the choice of oxaziridine, indicating that the stereoselectivity was substrate controlled. 

Asymmetric a-Hydroxylation of Enolates. a-Hydroxy lation of enolates represents one of the simplest and most direct methods for the synthesis of a-hydroxy carbonyl compounds, a key structural unit found in many natural products. Enolate oxidations using (+)- and (—)-(l) and their derivatives generally effect this transformation in good to excellent yields with a minimum of side reactions (e.g. over-oxidation). Furthermore, these reagents are the only aprotic oxidants developed to date for the direct asymmetric hydroxylation of prochiral enolates to optically active a-hydroxy carbonyl compounds. 

When chiral oxidants such as (+ )-2R,8aS and (-)-2S,8a/ camphor-ylsulfonyloxaziridines are used, the hydroxylation of enolates in the a positions with respect to the ester groups occurs enantioselectively, with enantiomeric excesses ranging from 12 to 85.5% and yields ranging from 35 to 88.5% (equation 467) [1032]. 

Zhou, P., Chen, B. C., Davis, F. A. Asymmetric hydroxylations of enolates and enol derivatives. Asyrrrrrrefr/c Oxidation Reactions 200, 128-145. 

Smith et al. described a study of the hydroxylation of enolates derived from 1,3-dioxin vinologous esters (127) with (63a) (88JOC4314). The regioselectivity depended on both the counterion and the ester substitution pattern, for example, the lithium enolate of (127 R = H) gave primarily the a-hydroxylated product (128) while the sodium enolate afforded mixtures of both (128) and (129). Particularly noteworthy is the fact that the sodium enolate of (127 R = Me) gave (129) while the lithium enolate gave (128) (Equation (28)). Moreover, imino-aldol products (18-26%) were isolated for the lithium enolates, but not with the sodium enolates. 

The enantioselective and diastereoselective hydroxylation of enolates with A-sulfonyloxaziridines has been critically reviewed in 1992 by Davis and Chen <92CRV919>. For this reason only illustrative examples and work reported since 1992 are recounted here. 

The popularity of MoOPH has waned with the discovery of the next type of reagents for hydroxylations. These /V-sull onyl oxaziridines should now probably be your first choice. In the 1986 volume of Organic Syntheses three recipes for hydroxylation of enolates stand side by side. Rubottom42 describes the formation of the kinetic lithium enolate of the enone 262 and the oxidation of the silyl enol ether 263 with mCPBA to give the a product 264 (see chapter 11 for the regioselectivity of such extended enolates). 

One strategy for tetracycline synthesis is to build a B/C precursor with suitable functionality for extension to ring A and with the tertiary a-hydroxy-carbonyl unit already in place. Two potential starting materials for different tetracyclines are 293 and 295 and both might be made by a-hydroxylation of enolates. 

The Li—F chelation is also useful for stereoselective reactions. In particular, chelation between lithium of enolates and a fluorine of a trifluoromethyl group results in conformational fixation of substrates, leading to markedly enhanced stereoselection. This concept has often been employed to achieve stereocontrol in fluorinated enolate chemistry. Morisawa reported Li—F chelation-controlled stereoselective a-hydroxylation of enolate of 40 [22]. The oxidant approaches from the less hindered side of the Li—F chelated enolate intermediate (41), affording anti-alcohol (42) exclusively (Scheme 3.11). The syn-alcohol (45) was prepared by NaBlrh reduction of ketoester (43) via a reaction course predicted by Felkin-Anh s model (44). 

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