Phenols chemoselective protection

The parent 2(3/i/)-oxazolone moiety functions as a bifunctional leaving group when carboxyl groups are activated for acylations and condensations, similar to other five- and six-membered heterocycles such as imidazole, triazole, and 2-pyridinethiol. The excellent leaving ability of a 2(3//)-oxazolone moiety has led to the development of versatile reagents. Thus, 3-acyl- and 3-alkoxycarbonyl-2(3//)-oxazolones serve as ready-to-use -type agents for the regioselective and chemoselective N-protection of amino alcohols, amino phenols and polyamines. 

Selective solid-phase iodination of phenolic groups could be achieved using bis(pyridinium) iodotetrafluoroborate, which does not react with O-protected phenols under these mild conditions. Using this reagent, it was shown that in peptides containing multiple tyrosine residues (e.g. the analgesic peptide dermorphin) selective O-protection of the tyrosine residues could be used to chemoselectively iodinate the unprotected tyrosine residues (equation 88). 

Hydroxyl protection. Useful variations in chemoselectivity for the etherification of compounds containing different types of hydroxyl groups use TrCl and l-BuMe2SiCl. Thus, o-hydroxybenzyl alcohol is silylated at the aliphatic moiety but tritylated at the phenolic oxygen. 

The removal of methoxy and benzoxy protecting gronps in aryl alkyl ethers is the most widely used BX3 ether cleavage reaction. Overall, the reaction produces a phenol and an alkyl halide. The chemoselective deprotection of triphenylmethyl (trityl) ethers in the presence of differentially protected diols has been reported (Scheme 23.1). At -SO C, trityloxy ethers can be selectively unmasked by BCI3 while the C-O bond in silicon-based ethers as weU as benzyl ethers is unaffected. 

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