Racemic carboxylic acid esters

Table 11.1-5. Pig liver esterase-catalyzed enantiomer-differentiating hydrolysis of racemic carboxylic acid esters and lactones in aqueous solution (HLE horse liver esterase).

Table 11.1-13. Lipase-catalyzed enantiomer-differentiating hydrolysis of racemic carboxylic acid esters and lactones in aqueous solution (PPL pig pancreas lipase, PSL Pseudomonas sp lipase, PFL Pseudomonasfluorescens lipase, CCL Candida cylindracea lipase, ANL Aspergillus niger lipase, PCL Pseudomonas cepacia lipase, CAL-A Candida antarctica A lipase, CRL Candida rugosa lipase, CAL Candida antarctica lipase, not specified).

Miyazawa, T. Kurita, S. Shimaoka, M. Ueji, S. Yamada, T. Resolution of racemic carboxylic acids via the lipase-catalyzed irreversible transesterification of vinyl esters. Chirality 1999, 11 554-560. 

Imagine the reaction between a chiral, but racemic alcohol and a chiral, but racemic carboxylic acid, to give an ester in an ordinary acid-catalysed esterification (Chapter 12). 

To our knowledge, one alternative route to simple enantiopure quinuclidine-2-carboxylic acid has recently been described by Corey who assembled target molecule 68 whereas racemic 68 was first synthesized several decades ago by Prelog and [44]. Parent quinuclidine-2-carboxylic acid ester 68 that is structurally related to proline and pipecolinic acid was obtained from commercial 4-(2-hydroxyethyl)-piperidine in six chemical steps including one tartaric acid-mediated resolution (Scheme 12.17) [45]. A cyanoactivated intramolecular SN2 reaction delivered the strained [2.2.2]bicyclic system. The cyano group serves as a handle of further functionality and elaboration. 

As well as the above-described intermolecular alcoholysis of esters, the intramolecular version has been successfully utilized for the synthesis of lactones from racemic hydroxy carboxylic acid esters (25-41, 64—66) (Table 11.1-22). High selectivity in the pig pancreas lipase-catalyzed enantiomer-differentiating lactonization of y-hydroxy carboxylic acid esters with formation of butyrolactones substituted in... 

A new route to racemic a-amino-acids in general consists of an overall a-amination of simple carboxylic acid esters in a relative of the Japp-Klingermann reaction, a method which is usually only successful with active methylene compounds such.as malonates. Thus, 0-silyl-enolates of esters (464) condense with benzenediazonium tetrafluoroborate to give, after isomerization,... 

Carboxylic acids from carboxylic acid esters Enzymatic resolution of racemates... 

The cleavage of the chiral auxiliary requires an oxidative decomplexation with bromine, chlorine, iodine, or cerium(IV) salts and others in the presence of water, alcohols, and amines yielding carboxylic acids, esters, and amides, respectively. In all cases, the stereochemical integrity of the newly created stereocenter is maintained, whereas the iron-based chirality is "sacrificed upon the decomplexation. For example, the decomplexation with bromine leads to a substitution of the acyl group by bromide under retention at the iron atom. However, the complex [(PPh3)(CO)(Cp)FeBr] is susceptible to racemization in solution [61]. 

Subsequently, Shiina et al. developed a practical method for the KR of racemic carboxylic acids involving an achiral alcohol, PMBA or pivalic anhydride, and a tetramisole-based catalyst [56]. After an exhaustive parameter screen, it was shown that a combination of bis(a-naphthyl)methanol, pivahc anhydride, and (S)-P-Np-BTM (53) induced the best levels of selectivity at room temperature, affording the corresponding esters with high s factors ranging from s = 20 to 484 (Scheme 41.9). 

The reaction proceeds via the formation of a first chiral zwitterionic intermediate from pivaUc anhydride and the amidine-based catalyst A mixed anhydride is then generated in the presence of the racemic carboxylic acid and activated by the chiral acyl-transfer catalyst to form the second zwitterionic intermediate. The latter species selectively reacts with a nucleophilic alcohol to afford the desired enantioenriched carboxyUc ester (Scheme 41.10). 

Selective ester hydrolysis of racemic A-protected a-[ C]amino acid and [ C]carboxylic acid esters by proteolytic enzymes (method B) ... 

R = H, R =Br, R" =Et) was prepared by cyclization of aroylacetate 314 (R = H, R =Br, r2 = H, X = F) (OOMIPIO). 9,10-Difluoro-3(5)-methyl-7-oxo-7//-pyrido[l,2,3- /e]-l,4-benzoxazine-6-carboxylic acid and its racemic form were prepared in the reaction of ethyl 2-(2,3,4,5-tetrafluorobenzoyl)-2-ethoxymethyleneacetate and (R)- or (i ,5)-2-aminopropanol and subsequent hydrolysis of the ring closed tricyclic esters (98MI45). Cyclization of ethyl 2-(2,3-difluoro-5-iodobenzoyl)-2-[A-(2-hydroxyethyl)aminomethylene]acetate 315 in the presence of K2CO3 in DMF at 95 °C for 3.5 h yielded 9-iodo-7-oxo-2,3-dihydro-7//-pyrido[l,2,3- /e]-l,4-benzoxazine-6-carboxylate (01MIP2). 

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