Substituted benzyl esters

NBS, CCI4, BZ2O, reflux, 61-97% yield. Substituted benzyl esters are cleaved similarly. 

For the delicate transesterification of a p-Lactam intermediate (for carbacephalosphorin skeleton), where originally hydrolysis of methyl ester was done homogeneously and then formation of the benzyl (or substituted benzyl) ester was done separately, Doecke et al. (1991) have devised a mild and efficient methodology using PTC. A dual use of a PT catalyst, Bu4NBr, in one pot was made in a CH2CI2 - H2O system. In the first step 5N NaOH was used, then the pH was adjusted to 7.2 to 7.8 and subsequently benzyl (or substituted benzyl) bromide was added. 

We thus turned to a study of the effect of substituting a methyl group on the activity of a set of meta substituted benzyl esters that closely resembled the original data set. Most of our original work was done on monosubstituted benzyl esters of DVA while during later work we concentrated our efforts on the generally more active cis-3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2-dimethylcycopropanecarboxylic acid (TFP) esters. In order to include more compounds in com-... 

Kawahara [156] introduced pentafluorobenzyl esters, prepared by the following procedure. A mixture of four acids (0.8 mg of each) was dissolved in 100 ml of acetone, and 250 mg (25-fold excess) of a-bromo-2,3,4,5,6-pentafluorotoluene and 50 mg (10-fold excess of potassium carbonate were added (it can be replaced with an ethanolic solution of potassium hydroxide). After refluxing for 3 h, the mixture was diluted with 500 ml of diethyl ether and 20 ml of ethyl acetate, washed with 10 ml of water and dried with 8 g of anhydrous sodium sulphate. After filtration, the sulphate and the filter were washed with 50 ml of diethyl ether, the solvent was removed and the residue was dried at 40°C and 50 mmHg it was further dissolved in 100 ml of -hexane and, after an additional 100-fold dilution, 6 /il were injected. The ECD response to pentafluorobenzoate was almost the same as that to aldrin. A method for the preparation of p-substituted benzyl esters of lower monocarboxylic acids on the micro-scale [157] is based on the same reaction scheme. A 10-pl volume of an ethanolic solution of carboxylic acids (ca. 1 pg/pl)... 

The 2-phenylprop-2-yl (1-methyl-1-phenylethyl) ester, although closely resembling the tert-butyl group, is more sensitive toward acids due to its phenyl group.It can also be considered as a substituted benzyl ester. 2-Phenylprop-2-yl esters of Fmoc-, Z-, or Boc-protected anoino acids are prepared via the 2-phenylprop-2-yl trichloroacetinoidates in the absence of any catalyst.These esters are cleaved with 2-4% TFA in CH2CI2, leaving N-Boc and ferf-butyl esters and ethers intact. 

To avoid any loss of benzyl ester protection during acidolytic removal of the benzyloxy-carbonyl and ferf-butoxycarbonyl groups, electron-withdrawing substituents were used to destabilize the intermediate benzyl cation and thus to increase the acid stability. In addition to the very useful 4-nitrobenzyl esters (vide infra), the picolyl ester (see Section 2.2.1.2.2.3) as well as halo-P l or cyano-P°°l substituted benzyl esters have been reported, the latter being rarely used for a-carboxy protection. Conversely, an increase in sensitivity toward acids can be achieved by introduction of electron-releasing substituents, such as methoxy or methyl groups. Addition of scavengers to quench intermediate carbocations and to prevent electrophilic substitutions at sensitive amino acid side chains is beneficial in the deprotection of such esters. 

Of great importance in peptide chemistry are the f-butyl, benzyl and substituted benzyl es-ters. 226 They are more stable to acids than the corresponding urethanes. Benzyl and substituted benzyl esters can be prepared by azeotropic esterification with the respective benzyl alcohol, by activating the carboxy group, e.g. with dicyclohexylcarbodiimide (DCC) or by reacting a carboxylate with a benzyl halide (Scheme 65). The latter 5N2-type ester formation is particularly efficient if cesium carbox-ylates are employed. Under the conditions required for this reaction the racemization of a-chiral car-... 

Table 5 Substituted Benzyl Esters, RCO2R, as Carboxy-protecting Groups...

Benzyl esters and substituted benzyl esters are also easily prepared but possess the advantage that deprotection can be achieved without using alkali. Benzyl esters are... 

We have examined the [2 + 2] photodimerization of the fluorine-substituted benzyl esters of (Z,Z)- and (E,E)-muconic acids in the solid state (Scheme 24.3) [60]. The muconates undergo [2 + 2] cyclodimerization, EZ-isomerization, and... 

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