Diastereoselectivity hydroxylation

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... 

Diastereoselective hydroxylation of ester etiolates The (E)-enolate of the chiral ester 1, derived from ( + )-camphor, generated with lithium N-isopropyl-cyclohexylamide (LICA) and HMPT (7, 209-210), undergoes hydroxylation with this reagent (11, 382) from the less hindered side with excellent diastereoselection. The (Z)-enolate as expected shows opposite, but modest, diastereoselectivity. 

Diastereoselective hydroxylation has also been observed at an alkenic center in an acyclic system that is guided by a sulfoxide group that is more remote than the homoallylic position. Alkenes (18 equation... 

Diastereoselective hydroxylations are more common, for example Streptomyces rimosus (NRRL 2234) will hydroxylate zearalenone (25) to give the (S)-8 -hydroxy derivative (26 equation 7). Other microorganisms gave reduction of the 6 -ketone group in (25). 

There are many examples of the asymmetric and diastereoselective hydroxylation of metal enolates using the enantiomerically pure camphor-derived A -sulfonyloxaziridines (- -)-146 and (+)-202, commercially available in both enantiomerically pure forms <20030R1>. The enantiomeric purity of the a-hydroxy products is good to excellent and can be obtained in both enantiomeric forms, as the absolute configuration of the oxaziridine controls the stereoinduction. Examples are given in Table 21. 

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. 

Table 17 Diastereoselective hydroxylation of carboximide enolates with oxaziridine (63a) at —78°C.

While more plentiful, alcohol-based chiral auxiliaries have been limited in their ability to direct the diastereoselective hydroxylation for the preparation of tertiary a-hydroxy acids. Among these, the best results in this series were obtained when oxidation of the enolate of chiral ester substrate 24 with (+)-5 yielded (5)-25.ub The use of (-)-S as the hydroxylating agent, provided a reversal in stereoselectivity, providing (i )-25. Interestingly, when substoichiometric amounts (0.5 equiv) of (+)-5 were used, stereoselectivity improves (94% de), a fact attributed to the matching of the enolate geometry to the oxidant. This speculation is credible, as evidenced by the fact that oxidation with 0.50 equivalent of (-)-5 produces (5)-25 in only 37% de in a stereochemically mismatched case. 

The syntheses of a-hydroxy P-amino acids has also been accomplished using a perhydropyrimidin-4-one template to direct the stereoselectivity of the hydroxylation,39 For example, the enolate of perhydropyrimidin-4-one 52 was diastereoselectively hydroxylated to obtain S3.40 Examination of several oxidizing agents and bases revealed LiHMDS and the... 

Hydroxylations. Titanium enolates undergo diastereoselective hydroxylation to furnish a-ketols (60-97%) on exposure to dimethyldioxirane. The reaction is very rapid (-78°C, 1 min). 

Natural polyketide macrolides cpothiloncs A and B were synthesized via a diastereoselective hydroxyl directed nitrile oxide cycloaddition and a new chemoselective protocol for isoxazoline reduction <01JOC6410, 01JA3611>. In particular, Mg(ll) directed 1,3-DC of nitrile oxides with chiral allylic alcohols 56 could be used to generate isoxazolines 57 in a high selective fashion <01AG(E)2082>, and conjugate A -isoxazolines, such as 58,... 

This methodology, in association with a highly diastereoselective hydroxylation procedure, was exploited to great effeet by Solladi6 in the asymmetric synthesis of protected L-arabinitol (17), (Scheme 4.14) [21]. 

Electrochemical Asymmetric Synthesis, Scheme 5 Diastereoselective hydroxylation... 

Diastereoselective Hydroxylation Direct electrochemical oxidation of 6-acetoxymethyl-2,3-didehydropiperidine derivative afforded 3,6-trans isomer, while indirect one gave 3,6-cis isomer in high diastereos-electivity (Scheme 5) [7], Indirect method using r as a mediator proceeded via inversion of... 

Scheme 12.12 Regio- and diastereoselective hydroxylation of a-ionone (35) and p-ionone (38).

The diastereoselective hydroxyl-directed cyclopropanation shown in Scheme 22 was one of a number studied which proceed with high stereoselectivity. The chiral auxiliary could be removed as indicated, and use of the equivalent derivative of 6-deoxy-L-glucose gave the enantiomeric cyclopropylmethanols.l 13... 

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