Carboxylic acids masked anions

Acylation is one of the most fundamental and useful reactions in organic synthesis and is normally achieved by the reaction either with carboxylic acid derivatives and organometallic compounds or with masked acyl anions and aUcyl halides. 

Polyphenylsilane, (PhSiH) , can be derivatized by free-radical hydrosilylation in the presence of a radical initiator. Alkenes, ketones and aldehydes react readily, to replace up to 93% of the Si-H bonds. This route can be employed to make polysilanes with hydrophilic groups, such as hydroxy, amino and carboxylic acid functions.43 Dialkylamino substituted polysilanes, made by the anionic polymerization of masked disilenes (see equation (17)), when treated with acetyl chloride give chloro-substituted poly silanes. The chlorine can then be displaced by other nucleophiles.27... 

Asymmetric Synthesis via Alkylations cf Anions of Masked Carboxylic Acid Derivatives... 

Schdllkopf and cowoikers have pioneered the development of anions of another type of masked carboxylic acid derivative, i.e. bislactim ethers such as (159), derived from (5)-valine and glycine or alanine, for the asymmetric synthesis of amino acids. As shown in Scheme 78, compounds such as... 

Synthesis of trifluoromethylated compounds 152 has been achieved via ester-enolate [2,3]-Wittig and [3,3]-lreland-Claisen rearrangements. Perfluorocyclo-butane phosphonium ylides, e.g. 153, have been used as a masked fluoride anion source in their reactions with alcohols and carboxylic acids which lead to alkyl-and acyl-fluorides. Ylides 153 are also reported to cleave Si-C and Si-O bonds, cause dimerisation of fluoro-olefins, and also react with acid chlorides or other activated aromatic compounds under halogen exchange. ... 

Masking the chelating carboxylic acid groups with acetoxymethyl (AM) esters, BAPTA and its fluorescent derivatives can be converted to nonpolar compounds that passively cross the plasma membrane. Once in the cell, non-specific esterases cleave the AM ester back to the free indicator and the resulting tetra or penta anion accumulates in the cytosol. Cells incubated in a very dilute dye solution (1-S /aM) still reach a useful concentration of indicator (>2S fiM). This is an extremely valuable technique, especially vfhen used with Ca indicators that exhibit a shift in excitation or emission on ion binding. By these means, researchers can estimate intracellular Ca changes in single cells or populations of cells (8). 

If a substituent has the same electronic effect in solution as in the gas phase, then the apparent acid-weakening effect of alkyl substituents in solution must arise because of a solvent effect that masks the charge-dispersing properties of the substituent. In solution methoxide anion is stabilized by 9.5 kcal/mol more than is the f-butoxide anion. Therefore, solvation of the anion overcomes the electronic effect, and methanol is the most acidic member of the series. Solvent effects also influence the relative acidity of carboxylic acids. In the gas phase the order of acidity is acetic acid < propionic acid < butanoic acid, but the opposite order is found in aqueous solution. Interestingly, formic acid might be predicted by this explanation to... 

Preparation and Protection.—An ingenious, high-yield method has been published for the chain-lengthening of carboxylic acids by three carbon atoms, via the alkylation of oxazol-5-one anions. The method owes its success to the electrophilic C-2 atom in the oxazolone (8), in effect a masked carboxyl carbon, becoming nucleophilic on transition to the anion (9). Acids are readily converted into oxazol-5-ones by treatment of the corresponding acid chloride with d/-valine, followed by cyclization with acetic anhydride, as shown in Scheme 7. Reaction of the oxazolone with acrylonitrile in the presence of triethylamine gives the alkylated product (10), which can be readily cleaved to a y-ketonitrile or a y-ketoacid. 

Similarly, Ohveira et al. have reported the synthesis of all four possible dia-stereomers of a component of the pheromone blend of the carpenter bee Xylocopa hirutissima via alkylation of 4,4-dimethyl-2-oxazoline derivatives [61] (Scheme 23). In this case, the carboxylic acid, allowing the formation of the 5-lactone, is masked as an oxazoline. The reaction of the anion of 2-ethyl-4,4-dimethyl-2-oxazoline 120 with iodide 121 gave compound 122 in 92 % yield, which was hydrolyzed and cyclized in one-pot under acidic conditions to provide a mixture of stereoisomers 123 and 124. 

A variety of reagents could be used to carry out such a conversion (18,19). We chose to react the alkoxide ion with succinic anhydride (SA), because the alkoxide ion could be converted quantitatively to the carboxylate ion when excess of SA is used, and also because no side reactions are reported (19). The carboxylate anion, 3, thus formed was used to polymerize PVL giving the masked poly(oxyethylene)-b-po y(pivalolactone) co-polymeric salt, 4. The salt, 4, was converted to the teiechelomer, 5, by acid hydrolysis.. ... 

Ureas and thioureas possess two parallel NH hydrogen bond donor groups and have been shown in a wide variety of receptors to function as highly efficient binding sites for Y-shaped anions such as carboxylates. Thioureas are more acidic than analogous ureas and on this basis might be expected to form stronger complexes with anions. However, other effects can often mask or reverse this expected trend. 

---