Meso-1,2-diol

Enzymatic desymmetrization of prochiral or meso-alcohols to yield enantiopure building blocks is a powerful tool in the synthesis of natural products. For example, a synthesis ofconagenin, an immunomodulator isolated from a Streptomyces, involved two enzymatic desymmetrizations [149]. The syn-syn triad of the add moiety was prepared via a stereoselective acylation of a meso-diol, whereas the amine fragment was obtained by the PLE-catalyzed hydrolysis of a prochiral malonate (Figure 6.56). 

Various biocatalytic options have been presented for the desymmetrization of meso-diols to chiral hydroxyl-ketones. A particularly facile system is represented by... 

Several chiral Ru complexes have been applied successfully for the asymmetric hydrogenation of a-, (3-, and y-diketones. Hydrogenation of an a-diketone, 2,3-butandione, catalyzed by an (i )-BINAP-Ru complex gives optically pure (R,R)-2,3-butanediol and the meso-diol in a ratio of 26 74 (Equation (73)).12a... 

Compound 168 is a key intermediate for the synthesis of prostaglandin or prostacyclin compounds. Scheme 5-50 shows its preparation via a retro Diels-Alder reaction and subsequent treatment. Using enzyme-catalyzed acetylation, Liu et al.80 succeeded in the asymmetric synthesis of enantiomerically pure (+)/ (—)-156 and (—)-168 from the meso-Aio 164. When treated with vinyl acetate, meso-diol 164 can be selectively acetylated to give (+)-165 in the presence of Candida cyclindracea lipase (CCL). The yield for the reaction is 81%, and the enantiomeric excess of the product is 98.3%. 

Hydrogenation of diacetyl (5) catalyzed by (S)-l-Ru gives a 74 26 mixture of meso-6 and S,S-6. Evidently in this reduction catalyst control favoring formation of meso-diols dominates over substrate control favoring formation of / or d-diols. 

Selective protection of the primary alcohol gave 138 (P=TBDMS), which was then esterified with ( )-3-hexenoic acid to produce the key intermediate 139 for cyclization. Ireland ester-enolate Claisen rearrangement and hydrolysis produced a protected hydroxyacid, which, after reduction of the acid and deprotection of the alcohol, yielded meso diol 128 more quickly and efficiently than in the previous synthesis. The meso diol was then converted to the racemate of the lactol pheromone 130 as previously described. 

With a good route to the key meso diol 128 in hand, the authors turned their attention to desymmetrization, using the known asymmetric hydrolysis of meso diacetates by Lipase AK (Scheme 23). The meso diol 128 was first converted to diacetate 140, and then hydrolyzed with Lipase AK to cleave selectively one of the two acetates, producing chiral hydroxyester 141. Oxidation, cleavage of the acetate, and lactonization yielded the (3S,4.R) lactone 129. The corresponding lactol (3S,4 )-130 was found to be the enantiomer of the compound produced in the HLADH synthesis. 

The authors then used a modification of their Lipase-AK route to produce the natural enantiomer, as described in detail in the chapter by Kenji Mori in this volume. Instead of using the enzyme to execute a stereoselective monohydrolysis of meso diacetate 140, the enzyme was used to esterify selectively one of the hydroxy groups of meso diol 128, resulting in the antipodal hydroxyester. After oxidation of the free hydroxyl to the acid, and recrystallization of its salt with (JR)-l-naphthylethylamine, the purified acid was then carried through the remaining steps to furnish the chiral pheromone compound (see the chapter by Kenji Mori in this volume). 

Hiroi et al. also reported the asymmetric lactonization of meso-diols catalyzed by a Cp Ir complex bearing a chiral amido-aUcoxo ligand (Scheme 5.33) [72]. The reaction of meso-diol 34 in acetone/dichloromethane solvent at 30 °C for 45 h in the presence of a Cp lr catalyst bearing a chiral amido-alkoxo ligand 35 gave a corresponding lactone 36 in quantitative yield, with 80% ee. 

Monoacylation of achiral and meso diols has been a popular strategy for introducing asymmetry and, in addition to kinetic resolutions of secondary alcohols, a... 

Eu s planar chiral ferrocenyl 4-DMAP catalyst 16 was also shown to be effective for the ASD of mei o-diols as illustrated for the case of unusual meso-diol 22 (Scheme 9) [81]. 

Scheme 24 Oriyama s proline diamine catalyzed ASD of meso diols [180]...

Fig. 15. Connon/Song s and Fujimoto s catalysts for alcoholative ASD of cyclic meso-anhydrides and mono benzoylation of meso-diols respectively [220-225]...

The latter were transformed into (+)-64, (-)-65 and (+)-66, respectively, in good yields. Lactone (+)-66 was also prepared in 37 % yield by stereospecific Horse Liver Alcohol Dehydrogenase (HLADH) catalyzed oxidation of the meso-diol 67. Lactones (-)-64 and (+)-64 are potentially interesting starting materials for the... 

A chiral complex was used in Ru(N0)Cl(salen )/02/UV/CHCl3 for oxidative desymmetrisation of meso-diols to optically active lactols and lactones, e.g. of cis-1,2 -bis(hydroxyhnethyl)-cyclohexane to (1/ , 6S, 7/ 5)-7-hydroxy-8-oxabicyclo[4.3.0] nonane, cf mech. Ch. 1 [363],... 

Sharpless epoxidation of the meso-diol l,5-hexadiene-3.4-diol (3) could, in principle, yield four stereoisomers. In the event, 4 was the main product (see Section 43.3.2.3.3., p 420). Both relative and absolute configuration had to be determined. The relative configuration was established independently (not reported by the authors), and the absolute configuration could then be assigned by destroying all but one chiral unit, thus relating 4 with (S)-5 (vide supra)136. 

Hydrolase-catalyzed desymmetrizations of meso-diols have also been exploited (Scheme 4.16). Thus, the monoacetate 23 is produced in excellent yield and by acylation with vinyl acetate of the corresponding meso-diol catalyzed by CRL in hexane [62]. In a similar way the monoacetate 24 is produced from the meso-tetrol by acylation in vinyl acetate catalyzed by PPL [63]. The meso-piperidine derivative... 

Scheme 4.33 Some examples of products obtained by hydrolase-catalyzed desymmetrizations of meso-diols (products shown).

In contrast, hydrogenation of 1,2-diketones that proceeds via 2-hydroxy ketones exhibits marked syn or meso selectivity (Scheme 60), although the enantiomeric preference follows the general sense given in Scheme 47 (92). Thus, (i )-BINAP-Ru-aided hydrogenation of diacetyl gives a 26 74 mixture of enantiomerically pure (R,R)-2,3-butanediol and the meso diol. 

Several fluorinated diols 6 have been synthesized from highly fluorinated alkanols 5 via mercury-photosensitized dehydrodimerization in the vapor phase163 in a special reactor.164 In almost all cases, the corresponding dl- and meso-diols are obtained in a 50 50 ratio.163... 

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