Stereoselective a-hydroxylation

Stereoselective a-hydroxylation of p-trifluoromethyl esters Hydroxylation of the ester 1 with the Vedejs reagent results in predominate formation of the (2S,3S)-isomer. NaBH4 reduction of the ketone 3 shows opposite stereoselectivity. Since the steric bulk of CF3 is similar to that of CH3, electronic factors may be important. 

Synthetic application includes Paquette s recent s lication in work directed toward the total synthesis of sterpuric acid. Exposure of enol ether (55) to peracid provided a single diastereomer of the silyloxy compound (56) in good yield. It was from this substrate (55) that the first stable trimethylsilyloxy epoxide was obtained (57) and examined by X-ray crystallography. Similarly stereoselective oxygenation of p-keto ester (49) via the corresponding silyl enol ether provided (50), also in 76% yield. Lastly efficient and highly stereoselective a-hydroxylation by this method was employed during studies towards the synthesis of helenanolides (58 to 59). ... 

In addition to uvidins A (3.14) and B (3.36) (10), more recently several new fatty acid esters of drimenol (3.2-3.6) and uvidin A (3.16-3.20) (11), and three new sesquiterpenes (12) with the bicyclofarnesane skeleton have been isolated from L. uvidus (Table 3). The stereostructures of the three uvidins C (3.29), D (3.34), and E (3.22) have been established by speetroscopic data and chemical reactions (12). In the interesting synthesis of uvidin E (3.22) from uvidin A (3.14), the Rubottom s procedure was employed for the regiospecific and stereoselective a-hydroxylation at C-5 of the enone 3.10 (12) (Scheme 2). 

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). 

The key step in this synthesis was the stereoselective a-hydroxylation of the /-lactone moiety that consisted of trapping the lactone enolate, generated by LDA at -70 °C, with O2 at 0 °C. However, direct hydroxylation of santonin (Scheme 12) by Ais procedure did not give the desired product 93. Instead, compound 92 was obtained in low yield along with a complex mixture of by-products. The formation of compound 92 is rationalized as depicted in Scheme 12. 

Another example, in which the piperidine cycle is generated de novo, exploits a hetero Diels-Alder cycloaddition of 1 -/r-tolylsulfinyl-1,3-penta-diene 91 with benzylnitrosoformate, that generates an oxazine 92 with complete regioselectivity and 7i-facial diastereoselectivity.69 Osmilation of the double bond inserts stereoselectively two hydroxyl groups on the oxazine skeleton, protection and catalytic hydrogenation finally afforded the enantiomerically pure imino sugars 94 (Fig. 38). 

The preceding discussions have clearly shown that type II photosensitized oxygenation of olefins is a powerful tool for the preparation of allyl hydroperoxides and allyl alcohols. The introduction of a hydroxyl group into an olefin occurs under mild conditions and can even be achieved at very low temperatures if the instability of the starting material or the expected allyl hydroperoxides requires such conditions. In many cases a stereoselective introduction of a hydroperoxy group occurs which makes this method even more valuable, especially since hydroperoxides can easily be reduced with retention of configuration. 

Selective epoxidation of allylic alcohols. This reagent is particularly useful for completely selective epoxidation of a double bond allylic to a hydroxyl group in the presence of another double bond. In this respect it is superior to t-BuOOH in combination with VO(acac)2, Al(0-f-Bu)3, or Ti(0-/-Pr)4. The stereoselectivity with 1 is fairly similar to that of f-BuOOH-VO(acac)2. 

Reduction of isoxazolines, i-amino alcohols. Lithium aluminum hydride reduction of the ready available isoxazolines 1 is effected with unusually high 1,3-asymmetric induction (equation I). The stereoselectivity is not affected drastically by the presence of a hydroxyl group in the side chains at C3 or C5, but isoxazolines bearing a 4a-hydroxyl group are reduced almost entirely to the erythro ( fi)-diastereomer.1... 

However, various attempts to introduce stereospecifically the a-hydroxyl group at the desired position of the double bond by hydroboration were unsuccessful. Eventually hydration of the double bond was accomplished by mercuration-reduction protocol, which although occurring both with high regio and stereoselectivity furnished only the p hydroxy compound 339. The conversion of the latter with formaldehyde into ( )-epielwesine (335) constituted in a formal sense, the synthesis of ( )-elwesine (320) as well, since Sanchez et al 88 had shown that the inversion of the hydroxyl group in 335 could be accomplished with diethylazodicarboxylate, triphenylphosphine and formic acid. 

Kiipfer A, Branch RA. Stereoselective mephobarbital hydroxylation cosegregates with mephenytoin hydroxylation. Clin Pharmacol Ther 1985 38 414-418. 

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