4- Hydroxy carboxylic esters

The biotechnological synthesis of lactones has reached a high standard. Besides microbial production, lactones can also be enzymatically produced. For instance, a lipase-catalysed intramolecular transesterification of 4-hydroxy-carboxylic esters leads enantioselectively (ee>80%) to (S)-y-lactones the chain length may vary from C5 to Cl 1 [13]. y-Butyrolactone can be produced in that way with lipase from Mucor miehei [30]. 

Corey s auxiliary reagent 10 is also applied in order to obtain a f/-2-bromo-3-hydroxy-carboxylic esters in enantiomeric purities of 91-98%. The a-bromo esters thus obtained are useful intermediates for the preparation of a-unsubstituted /Miydroxy esters as well as for 2-amino-3-hydroxy- and 3-amino-2-hydroxycarboxylates64a b. 

The cyanohydrins were hydrolyzed with concentrated HC1 at ambient temperature in very high yield without any racemization to give 2-hydroxy carboxylic acids [71], Likewise, cyanohydrins were solvolyzed in solution of 2 m HC1 and 2 m alcohol to afford corresponding 2-hydroxy carboxylic ester [72],... 

Ojima (43) used the same DIOPRh catalyst earlier to add Et2SiH2, PhMeSiH2, Ph2SiH2 and a-naph-PhSiH2 to a-ketoesters to synthesize optically active a-hydroxy carboxylate esters. With diethyl- or phenyl-methylsilane and propyl pyuvate, a double hydrosilation occurred to chiefly make a cyclic product with double asymmetry. 

In these synthesis, the optically active (R)-cyanohydrin is transformed into the corresponding a-hydroxy carboxylic ester and the hydroxyl funchon is achvated by sulfonylahon. The treatment of the corresponding intermediate with tetra-hydrothieno[3,2-c]pyridine stereoselectively yields the (S)-configured clopidogrel (Scheme 10.23). In the second case, a mutant of the recombinant almond (Pmnus amigdalus) (R)-oxynitrilase isoenzyme 5 catalyzes the formation of enantiopure (R)-2-hydroxy-4-phenylbutyronitrile [54]. Reaction of the sulfonylated hydroxyester derivative with the corresponding dipeptide leads to the formation of enalapril or lisinopril (Scheme 10.24). 

Asymmetric synthesis of fi-hydroxy carboxylic estersEsters of 1 in the presence of f-butylmagnesium bromide as base react with aldehydes and ketones to form optically active a-sulfinyl-jS-hydroxy carboxylic esters, which are desulfurized by aluminum amalgam in aqueous THF (equation I). Chemical yields are 75% of... 

Aldol condensation of a-amino silyl ketene acetals (l).10 2-Dibenzylami-noketene trimethylsilyl acetals (1) react with aldehydes premixed with TiCl4 to give a-amino-p-hydroxy carboxylic esters (2) with moderate to high syn-selectivity. Surprisingly, TiCl4-catalyzed reaction of 1 with a chiral a-alkoxy aldehyde proceeds with low asymmetric induction. 

Aldol condensation.2 Theenolateofl reacts with aldehydes to form preferentially cn7hm-f/-methyl-a,/f-di hydroxy carboxylic esters (equation I). The O-MEM ether of methyl lactate shows similar erythro-selectivity (ca. 6 1). In contrast, the anion of... 

The products are converted into P-hydroxy carboxylic esters by oxidation with NBS in CHjCh/CjHjOH at 0°. 

Enantiomerically enriched a- and P-hydroxy carboxylic esters are valuable reagents for optical resolution and are important intermediates in the preparation of pharmaceuticals and agrochemicals [18,19], Esters of mandelic acid are used as precursors... 

Stereoselective addition of a dithiane anion to chiral 2-metiiyl-3-trimethylsUyl-3-butenal combined with the stereoselective addition of a Grignard reagent to the chiral a-alkoxy ketone affords a practical method for the construction of a, y-dimethyl-a,p-dihydroxy compounds, useful intermediates for the synthesis of erythronolides (Scheme 33). -Hydroxy carboxylic esters were synthesized by the addition of ethyl 1,3-dithiolanyl-2-carboxylate enolate to a chiral aldehyde, followed by desulfurization. ... 

Acylation of chiral alcohols The pyridinium triflates and tetrafluoroborates are useful reagents for delivery of acyl groups to chiral secondary alcohols such as a-hydroxy carboxylic esters. 

Alkylation of fahydroxy carboxylic esters (8, 258). Dianions of / -hydroxy carboxylic esters (LDA, —50° to —20°) are alkylated stereoselectively to give mainly f/irao-compounds (equation I). The alkylation of dianions of a-mono-... 

Binder, J., and Zbiral, E., A new procedure for homologation of carbonyl compounds to a-hydroxy-carboxylic esters by means of diethyl (trimethylsilylethoxymethyl)phosphonate. Tetrahedron Lett., 27, 5829, 1986. 

To the secondary aliphatic alcohols, which have been resolved into their enantiomers, belong a variety of hydroxy carboxylic esters and acids (35,100-102,125,126, 131-140, 150, 151, 166, 168-172, 174, 182, 183), some hydroxy ketones (128-130, 141) and a crown ether derivative (203) (Table 11.1-20). Even the tetraphenylpor-phyrin derivatives 204 and 205 were substrates for different lipases. 

In some cases secondary alcohols can be converted into keto compounds by lead tetraacetate, e.g., -hydroxy carboxylic esters into <%-keto carboxylic esters 449 this reaction with lead tetraacetate is advantageously effected in... 

Alcoholysis of lactones occurs with ring fission analogously to the cleavage of esters to hydroxy carboxylic esters.868-870... 

The action of peroxyacids, such as Caro s acid, on cyclic ketones affords co-hydroxy carboxylic acids or their lactones, the latter being convertible into co-hydroxy carboxylic esters by the action of an alcohol and an acid cyclohexanone, for instance, gives a 6-hydroxyhexanoic ester in this way 126,127... 

Lucente, G., A. Romeo, and G. Zanotti A New Route to 2-Acylamido-2-hydroxy-carboxylic Esters. Chem. and Ind. 1968, 1602. 

---