Base-labile carboxylic esters

Our final example is a base-labile 4-(phenylsulfonyl)methyl-l,3-dioxolane protecting group for aldehydes and ketones.4 Protection is carried out by the reaction of diol 17,1 (obtained by dihydroxylation of ally phenyl sulfone) with a carbonyl compound in the presence of pyridinium p-toluene sulfonate [Scheme 2.17], Cleavage is accomplished by treatment with DBU. /erf-Butyldimethylsilyl ethers, p-toluenesulfonate esters, tetrahydropyranyl ethers, carboxylic esters and benzoates are well tolerated. A disadvantage to the use of 17.1 is the introduc-... 

In 1968 Miller and Stirling showed that the 2-tosylethyl ester function (abbreviated TSE) underwent easy base-catalysed elimination in the presence of 1 M sodium hydroxide or sodium carbonate (but not sodium hydrogen carbonate) in aqueous dioxane at room temperature to give p-toluenesulfinate anion, ethylene. and a carboxylate 215 Thus, this ester function complements the methylsul-fonylmethyl function (see section 6.4) derived from methylthiomethyl esters in its base-sensitivity. Electron withdrawing groups (e.g., p-nitro) on the aryl ring increase base lability — a feature that has been exploited for the protection of the 2f hydroxyl function in oligoribonucleotide synthesis.216... 

Esters can be prepared from alcohols and activated forms of carboxylic acids by a variety of meth-ods. Carboxylic acid esters are mainly base labile and, therefore, they complement the acid sensitive ether protecting groups. A variety of esters can be used for simpler and for more complex problems. Here, only the most practical groups will be treated. The application of esters as protected forms is frequently complicated by the possibility of acyl migration which may occur under basic, acidic and also neutral conditions. ... 

This ester was designed as a base-labile protecting group. Monoprotection of aspartic acid was achieved using the DCC/DMAP protocol. Cleavage is promoted with 0.1 M TEAR A comparison of other base-labile esters for the p-carboxyl group of aspartic acid to 0.1 M TEAR is provided in the table. ... 

Mild Hydrolysis. Acetates of primary and secondary alcohols such as cyclopropyl acetate [205] and methyl or ethyl carboxylates (such as the labile cyclopentadiene ester [206]) can be selectively hydrolyzed under mild conditions using PLE, avoiding decomposition reactions which would occur during a chemical hydrolysis under acid or base catalysis (Scheme 2.22). For example, this strategy has been used for the final deprotection of the carboxyl moiety of prostaglandin Ei avoiding the destruction of the delicate molecule [207, 208],... 

Acid-labile linkers are the oldest and still the most commonly used linkers for carboxylic acids. Most are based on the acidolysis of benzylic C-O bonds. Benzyl esters cleavable under acidic conditions were the first type of linker to be investigated in detail. The reason for this was probably the initial choice of polystyrene as an insoluble support for solid-phase synthesis [13]. Polystyrene-derived benzyl esters were initially prepared by the treatment of partially chloromethylated polystyrene with salts of carboxylic acids (Figure 3.3). 

Butyl benzyl phthalate is a mixed carboxylic acid ester formed by the condensation of phthalic acid with two different alcohols. No literature values could be found nor any directly applicable QSARs. Based on known reactivity of carboxylic acid esters, any acid hydrolysis should be very slow. Neutral hydrolysis, while reported in the literature for certain reactive esters, is not likely for the phthalate esters. The carboxylic acid esters are most labile to alkaline hydrolysis (Mabey and Mill, 1978). 

---