0-Hydroxy esters, chiral building blocks

Hydroxy-L-prolin is converted into a 2-methoxypyrrolidine. This can be used as a valuable chiral building block to prepare optically active 2-substituted pyrrolidines (2-allyl, 2-cyano, 2-phosphono) with different nucleophiles and employing TiQ as Lewis acid (Eq. 21) [286]. Using these latent A -acylimmonium cations (Eq. 22) [287] (Table 9, No. 31), 2-(pyrimidin-l-yl)-2-amino acids [288], and 5-fluorouracil derivatives [289] have been prepared. For the synthesis of p-lactams a 4-acetoxyazetidinone, prepared by non-Kolbe electrolysis of the corresponding 4-carboxy derivative (Eq. 23) [290], proved to be a valuable intermediate. 0-Benzoylated a-hydroxyacetic acids are decarboxylated in methanol to mixed acylals [291]. By reaction of the intermediate cation, with the carboxylic acid used as precursor, esters are obtained in acetonitrile (Eq. 24) [292] and surprisingly also in methanol as solvent (Table 9, No. 32). Hydroxy compounds are formed by decarboxylation in water or in dimethyl sulfoxide (Table 9, Nos. 34, 35). 

The enantioselective hydrogenation of /(-keto esters is important, because the resulting optically active /(-hydroxy esters are converted to useful chiral building blocks [1-4]. The development of BINAP-Ru(II) catalysts allowed the highly enantioselective hydrogenation of /(-keto esters. As shown in Figure 32.6, methyl-... 

Given the importance of [l-hydroxy esters as versatile chiral building blocks in organic synthesis and medicinal chemistry, further development of this p-keto ester hydrogenation process continues. 

Roche ester, (R)-3-hydroxy-2-methylpropionic acid methyl ester (16b), is a chiral building block for the synthesis of vitamins (a-tocopherol), natural products (spiculoic acid A), antibiotics (calcimycin), and fragrance components (muscone) and therefore of high interest for industry. Faber and coworkers employed ERs for the asymmetric synthesis of methyl 2-hydroxymethylacrylate derivatives... 

In this chapter, we review the production methods for optically active -hydroxy-carboxylic acids (esters), and chiral building blocks derived from optically active 3-hydroxy acids and their use in the synthesis of optically active bioactive compounds. 

Chiral 4-chloro-3-hydroxybutanoate esters are important chiral C4-building blocks [43-53]. For example, (i )- and (S)-isomers can be converted to L-car-nitine and the hydroxymethyl glutaryl-CoA reductase inhibitor. Since these compounds are used as pharmaceuticals, a high optical purity is required. A practical enzymatic method for the production of chiral 4-chloro-3-hydroxy-butanoate esters from prochiral carbonyl compounds, i.e.,4-chloroacetoacetate esters, or racemic 4-chloro-3-hydroxybutanoate esters is described. 

Microbial reduction of prochiral cyclopentane- and cyclohexane-1,3-diones was extensively studied during the 1960 s in connection with steroid total synthesis. Kieslich, Djerassi, and their coworkers reported the reduction of 2,2-dimethylcyclohexane-l,3-dione with Kloeokera magna ATCC 20109, and obtained (S)-3-hydroxy-2,2-dimethylcyclohexanone. We found that the reduction of the 1,3-diketone can also be effected with conventional baker s yeast, and secured the hydroxy ketone of 98-99% ee as determined by an HPLC analysis of the corresponding (S)-a-methoxy-a-trifluoromethylphenylacetate (MTPA ester).(S)-3-Hydroxy-2,2-dimethy1cyc1ohexanone has been proved to be a versatile chiral non-racemic building block in terpene synthesis as shown in Figure 1. 

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