Carboxylic Acid Protection

Oxazoles, prepared from carboxylic acids (benzoin, DCC NH4OAC, AcOH, BOSS % yield), have been used as carboxylic acid protective groups in a variety of synthetic applications. They are readily cleaved by singlet oxygen followed by hydrolysis (ROH, TsOH, benzene or K2CO3, MeOH ). 

In general, the methods for protection and deprotection of carboxylic acids and esters are not as convenient as for alcohols, aldehydes, and ketones. It is therefore common to carry potential carboxylic acids through synthetic schemes in the form of protected primary alcohols or aldehydes. The carboxylic acid can then be formed at a late stage in the synthesis by an appropriate oxidation. This strategy allows one to utilize the wider variety of alcohol and aldehyde protective groups indirectly for carboxylic acid protection. 

Finally, methyl ester 264 was elaborated into the zanamivir-related guanidine derivative 265 by guanidylation and selective removal of the hydroxyl and carboxylic acid protections. 

Carboxylic acids, protection of, 224-276 as amides and hydrazides, 270-276 as esters, 227-270 Reactivity Chart 6, 433-436 S-Carboxymethyl thioethers, to protect thiophenols, 294-295 Catechols, protection of, 170-174 as cyclic acetals and ketals, 170-172 as cyclic esters, 173-174 Reactivity Chart 4, 425-428 CBZ, see Benzyl carbamates Chloroacetamides, to protect amines, 352-353... 

If du Vigneaud and Bodanszky had wanted a carboxylic-acid-protecting group that was more stable towards attack by nucleophiles, they could have made a t-butyl ester with isobutene in sulfuric acid. 

The next step was to introduce the alkyl chain—this was best done by first oxidizing the sulfide to a sulfoxide, using sodium periodate. The sulfoxide was then deprotonated with -BuLi and alkylated with an alkyl iodide containing a carboxylic acid protected as its r-butyl ester. Reduction of the sulfoxide and hydrolysis back to the free acid gave biotin. 

A new carboxy protecting group that takes advantage of the facile solvolysis of cyclopropyl methyl substrates was proposed by Carpino et al.f The dicyclopropylmethyl (Dicyc-propme) ester can be used for carboxylic acid protection where selective removal is required in the presence of tBu or Trt side-chain protection. The ester is stable toward conditions of... 

We also applied these conditions of selective deprotection on amino acids it was possible to cleave the N-allyloxycarbamate of the L-proline derivative 16 without affecting the carboxylic acid protected by the dimethylallyl moiety (entry 3). 

Carboxylic Acid Protection. - Increasing the bulk of the substituents generally increases the stability of silyl protecting groups. This has been taken a step further with the introduction of the... 

Adapting the above-mentioned precedents in norbornene polymerization chemistry, the University of Texas research team was able to synthesize cycloaliphatic polymers with pendant-free carboxylic acid groups and carboxylic acids protected with acid-cleaveable groups, such as tert-hvAy esters tailored for 193-nm resist use. They polymerized norbornyl derivatives such as CBN and... 

---