Chiral alcohols, preparation using catalytic

The reaction of alkenylcarbene complexes and imines in the presence of a Lewis acid generates pyrroline derivatives as a result of a [3C+2S] cyclisation process [76]. This reaction has been extended to an asymmetric version by the use of chiral alkenylcarbene complexes derived from several chiral alcohols. However, the best results are found when (-)-8-phenylmenthol-derived complexes are used and catalytic amounts of Sn(OTf)2 are added to the reaction. In these conditions high levels of trans/cis selectivity are achieved and the hydrolysis of the major tram diastereoisomers allows the preparation of optically pure 2,5-disubstituted-3-pyrrolidinone derivatives (Scheme 29). 

A typical example that illustrates the method concerns the lipase- or esterase-catalyzed hydrolytic kinetic resolution of rac-1-phenyl ethyl acetate, derived from rac-1-phenyl ethanol (20). However, the acetate of any chiral alcohol or the acetamide of any chiral amine can be used. A 1 1 mixture of labeled and non-labeled compounds (S)- C-19 and (f )-19 is prepared, which simulates a racemate. It is used in the actual catalytic hydrolytic kinetic resolution, which affords a mixture of true enantiomers (5)-20 and (J )-20 as well as labeled and non-labeled acetic acid C-21 and 21, respectively, together with non-reacted starting esters 19. At 50% conversion (or at any other point of the kinetic resolution), the ratio of (5)- C-19 to (1 )-19 correlates with the enantiomeric purity of the non-reacted ester, and the ratio of C-21 to 21 reveals the relative amounts of (5)-20 and (J )-20 (98). 

In the scale-up synthesis of linezolid21 (Pharmacia/Upjohn), the inexpensive (S)-epichlorohydrin was used as the chiral source and was used to prepare key intermediate 34, a crystalline material (Scheme 4). Treatment of carbamate 33 with BuOLi in alcohol-DMF, followed by addition of chloride 34, gave linezolid 14 in 73% isolated yield. In contrast, the Bayer team applied a much simpler method for the formation of oxazolidinone by directly heating the mixture of amino alcohol 35 with N.N1-carbonyldiimidazole (CDI) in refluxing THF, using catalytic amounts of DMAP, to provide oxazolidinone 36 (or 21) in 87% isolated yield. 

The oxazaborolidine-catalyzed borane reduction to prepare (R)-1 is an improvement over existing methods such as the p-chlorodiisopinocampheylborane reduction,6 and enzymatic resolution14 for several reasons. First, the reaction uses an easily obtained catalytic reducing agent that provides the chiral alcohol in 92% ee. Secondly, the reaction proceeds at a reasonable rate (6-8 hr) and affords the chiral alcohol (92% ee) In nearly quantitative yield (97%). Finally, the work-up, isolation and purification of the product is straightforward and requires no column chromatography, only bulb-to-bulb distillation and recrystallization, affording (R)-1 in 75% yield with 97% ee. In addition, the catalyst precursor, (S)-a,a-diphenylpyrrolidinemethanol. can be easily recovered in excellent yield. 

The serotonin antagonist LY426965 was synthesized using catalytic enantioselective allylation with a chiral biphosphoramide in the laboratory of S.E. Denmark. In order to prepare the necessary 3,3-disubstituted allyltrichlorosilane reagent, the ( -allylic alcohol was first converted by the Corey-Kim procedure to the corresponding chloride. 

Carboxylic acids. Primary alcohols are oxidized to acids (secondary alcohols to ketones) using catalytic amount of CrOj and excess HjIOg in wet MeCN. By this procedure there is very little racemization of the products bearing a chirality center adjacent to the emerging carbonyl group. Therefore this method is useful for the preparation of chiral a-amino acids. 

The aziridino alcohols that have been prepared and tested as chiral promoters for the catalytic asymmetric dialkylzinc alkylation of imines are shown in Fig. 4. The authors have investigated three different approaches to obtain the ligands in enantiomerically pure form (1) the use of the chiral pool, (2) the Sharpless asymmetric aminohydroxylation, and (3) the Sharpless asymmetric dihydroxylation. The starting materials for the preparation of the aziridino alcohols 30, 31a-h, 32a,b, and 33 were the readily available amino acids L-serine, L-threonine, and aZZo-L-threonine. 

During their studies on kinetic resolution (KR) of secondary alcohols, Connon et al. found that chiral pyridine catalyst 177 and its optimized analogue 178 promoted the synthetically useful KR of MBH adducts 179 derived from deactivated precursors (which were difficult to synthesize using catalytic asymmetric MBH reactions), allowing the convenient preparation of 179 in 62-90% ee and 82-97% ee, respectively (Scheme 2.87). This study also represents the first examples of effective non-enzymatic acylative KR of sec-sp -sp ... 

The majority of catalytic enantioselective allylation reactions involve the chiral Lewis-acid-catalysed additions of allylsilanes or allylstannanes to carbonyl compounds. Monothiobinaphthol has been used by Woodward et al. as a chiral promoter in the enantioselective catalytic allylation of aryl ketones with impure Sn(allyl)4, prepared from allyl chloride, air-oxidised magnesium and SnCl4. Therefore, the allylation of arylketones in these conditions was achieved very efficiently, since the corresponding allylic alcohols were formed in... 

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