Crown Catalyzed Esterification

Crown Catalyzed Esterification of BOC-Amino Acids to Chloromethylated Resins... 

Especially for large-scale work, esters, may be more safely and efficiently prepared by reaction of carboxylate salts with alkyl halides or tosylates. Carboxylate anions are not very reactive nucleophiles so the best results are obtained in polar aprotic solvents54 or with crown ether catalysts.55 The reactivity for the salts is Na+ < K+ < Rb+ < Cs+. Cesium carboxylates are especially useful in polar aprotic solvents. The enhanced reactivity of the cesium salts is due both to high solubility and to the absence of ion pairing with the anion.56 Acetone has been found to be a good solvent for reaction of carboxylate anions with alkyl iodides.57 Cesium fluoride in DMF is another useful combination.58 Carboxylate alkylation procedures have been particularly advantageous for preparation of hindered esters that can be relatively difficult to prepare by the acid-catalyzed esterification method (Fischer esterification) which will be discussed in Section... 

Padwa and Dehm62 have prepared furanones (36) by reaction of carbox-ylates with bromo aldehydes, catalyzed by 18-crown-6. The first step of the reaction is also an esterification of the potassium phenylacetate the next step is equivalent to an intermolecular addition of a carbanion to an aldehyde, followed by elimination. 

Wong,K. H., and A. P. W. Wai, Solid-Liquid Phase Transfer Kinetics of / -Nitrobenzoate Esterification Catalyzed by Crown Ethers ... 

Not only will crown ethers, quaternary ions, and amines catalyze the esterification reaction, but cryptates are also effective in this application. Potassium carboxylates react in good yield with a variety of alkyl halides in the presence of a catalytic amount of [2.2.2]-cryptafe to yield the corresponding esters [28]. The results are summarized in Table 6.9. 

Another methodology used to increase the reaction rate and/or the enantioselectivity is to add some compounds not involved in the reaction, such as crown ethers. In this way we have reported (see Table 7A [107]) the effect of several external compounds on the esterification of (i ,S)-ibuprofen with n-propanol, catalyzed by Novozym 435 (C. antarctica lipase B immobilized on an anionic resin). As can be observed, the presence of additives does not change the enantiopreference of the lipase B of C. antarctica, which again acts preferably on the R enantiomer. Therefore, interpretation of data based on a possible interaction of the additives with the active site—which would control the stereoselectivity—should be avoided. 

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