Prochiral diol asymmetrization

By performing the desymmetrization on a prochiral diol, a far more efficient asymmetric biocatalytic route was subsequently developed. Enzyme screening found that... 

Asymmetrization of Prochiral Diol Double-Step Process... 

Asymmetrization of prochiral diols by esterification also shows anomalous behavior. More experiments have to be carried out before final conclusions can be drawn. 

Prochiral Compounds. The enantiodifferentiation of prochi-ral compounds by lipase-catalyzed hydrolysis and transesterification reactions is fairly common, with prochiral 1,3-diols most frequently employed as substrates. Recent reports of asymmetric hydrolysis include diesters of 2-substituted 1,3-propanediols and 2-0-protected glycerol derivatives. The asymmetric transesterification of prochiral diols such as 2-0-benzylglycerol and various other 2-substituted 1,3-propanediol derivatives is also fairly common, most frequently with Vinyl Acetate as an irreversible acyl transfer agent. 

Asymmetric lactonization of prochiral diols has been performed vsdth chiral phosphine complex catalysts (Ru2Cl4((-)-DIOP)3 and [RuCl((S)-BINAP)(QH6)]Cl [17, 18]. Kinetic resolution of racemic secondary alcohol was also carried out with chiral ruthenium complexes 7 and 8 in the presence of a hydrogen acceptor, and optically active secondary alcohols were obtained with >99% e.e. (Eqs. 3.7 and 3.8) [19, 20]. 

Oxidation of Meso Diols. Asymmetric induction of meso and prochiral diols by lipases is very successful in the field of organic synthesis. Also it is well known that selective oxidation of prochiral or meso diols by HLADH provides oxidized products with a significant degree of enantioselectivity. However, it has not been reported that alcohol oxidases were applied to such types of oxidation. The microbial oxidation of meso diols by Candida boidinii SA051 was carried out and gave optically active hydroxy ketones (Figure 8). 

Continuous-flow mode asymmetric acetylation of the prochiral diol 16b with isopropenyl acetate was performed in a small stainless steel PBR filled with sol-gel/Celite entrapped Pseudomonas Jluorescens lipase (PfL) (Lipase AK) [107]. Optimization of the process resulted in (R)-17b with up to 91% ee. 

Chiral N-sulfonyldiamine ligands are used to create effective chiral bifunctional amidoiridium catalysts for the asymmetric aerobic oxidation of meso- and prochiral diols to give up to >99% ee of hydroxyl ketones and 50%ee oflactones. " These catalysts can be also applied for an efficient oxidative kinetic resolution of racemic secondary alcohols affording R enantiomers with >99% ee and with 46—50% yields. 

Hydrolases and mainly lipases have appeared as valuable biocatalysts for the development of asymmetric transformations. Several strategies have been carried out involving the classical KR and DKR of racemic alcohols and the desymmetrization of meso- and prochiral diols. Taking into account the reversibility of this type of process in complementary hydrolysis pathway and adequate conditions must be established to favor synthetic acylation reactions. 

Another method for the asymmetric version of the Baeyer-Villiger reaction was presented by Lopp and coworkers in 1996516. By employing overstoichiometric quantities of Ti(OPr-z)4/DET/TBHP (1.5 eq./1.8 eq./1.5 eq.), racemic and prochiral cyclobutanones were converted to enantiomerically enriched lactones with ee values up to 75% and moderate conversions up to 40% (Scheme 171). Bolm and Beckmann used a combination of axially chiral C2-symmetric diols of the BINOL type as ligands in the zirconium-mediated Baeyer-Villiger reaction of cyclobutanone derivatives in the presence of TBHP (or CHP) as oxidant (Scheme 172)497. With the in situ formed catalysts 233a-d the regioisomeric lactones were produced with moderate asymmetric inductions (6-84%). The main drawback of this method is the need of stoichiometric amounts of zirconium catalyst. 

A variation within the osmium-catalysed asymmetric dihydroxylation (AD) of alkenes has been described that yields cyclic boronic esters from alkenes in a straightforward manner. A protocol based on the Sharpless AD conditions (for enantiose-lective oxidation of prochiral olefins) has been developed that gives cyclic boronic esters, rather than free diols, with excellent enantiomeric excesses. Some of the... 

The proper stereochemistry was achieved by enzyme catalyzed desymmetrization of the prochiral 1,3-diol 30. Candida antarctica lipase (CAL)-catalyzed transesterification yielded the monoacetate 31, which gave rise to the methyl with the proper stereochemistry 32. The generation of the desired chiral epoxide 35 was achieved by asymmetric dihydroxylation employing AD-mix-a,42 followed by epoxide formation. Base-catalyzed etherification yielded the mixture of the enantiopure (+)-heliannuol A and (-)-heliannuol D. Unfortunately these compounds correspond to the opposite d/l series and correspond to the enantiomers of the natural products (-)-heliannuol A and (+)-heliannuol D (Fig. 5.6.A). 

Irwin, A.J. and Jones, J.B. (1977) Asymmetric syntheses via enantiotopicaUy selective horse liver alcohol dehydrogenase catalyzed oxidations of diols containning a prochiral center. Journal of the American Chemical Society, 99, 555-551. 

Efficient synthetic approaches to the optically active spiro-sulfuranes and their oxides have been reported by Martin and Drabowicz [65]. The preparation of optically active spirosulfuranes 45 and 46 was performed by asymmetric dehydration of the corresponding prochiral sulfoxide diols 47, as shown in Scheme 29. The optically active oxides 48 and 49 were prepared by oxidation of 45 and 46 with m-chloroperbenzoic acid (mCPBA). The synthesis of the optically active oxides was conducted by the stereoselective conversion of the chiral sulfuranes using Ru04, according to the procedure reported earlier [66]. 

The prochiral sulfoxide diols were dehydrated under asymmetric conditions to yield spirosulfuranes with a rather low enantiomeric excess (below 5%), as described above. Further, Szabd et al. have reported the first stereospecific synthesis of optically active spirosulfuranes as shown in Scheme 31 [69]. Optical active spirosulfuranes 54-57 were prepared by dehydration of the optically active diaryl sulfoxides 58-61, carrying reactive CH2OH and COOH substituents in very high yields. The molecular structures, including the absolute configurations, were determined by X-ray crystallography. 

Because of the results with numerous prochiral diesters and diols, which have been subjected successfully to hydrolase-catalyzed enantioselective hydrolysis and acylation, respectively, and because of the desire to predict the sense of the asymmetric induction in the conversion of a new substrate, active-site or substrate models have been developed for the hydrolases pig liver esterase171 731, pig pancreas... 

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