Protection-Deprotection Cleavage Reactions

Although inherently wasteful, protection-deprotection reaction sequences constitute an integral part of organic syntheses such as the preparation of monomers, fine chemicals, and precursors for pharmaceuticals. These reactions often involve 

2-25) [85]. By changing the surface characteristics of the solid support from neutral to acidic, the cleavage of the 9-fluorenylmethoxycarbonyl (Fmoc) group and related protected amines can be achieved in a similar manner. The hydrolytic deprotection of carboxylic acids from their corresponding allyl esters, under dry conditions , has also been reported on montmorillonite KIO clay [86]. 

and this general reaction does not yield any byproducts except in the case of substrates bearing free phenohc groups, where ring nitrahon is observed. A report on the cleavage of thioacetals with clayan (80-89%) has also appeared subsequently [92] 

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The protection-deprotection reaction sequences constitute an integral part of organic syntheses such as the preparation of monomers, fine chemicals, and reaction intermediates or precursors for pharmaceuticals. These reactions often involve the use of acidic, basic or hazardous reagents and toxic metal salts [30], The solvent-free MW-accelerated protection/deprotection of functional groups, developed during the last decade, provides an attractive alternative to the conventional cleavage reactions. 

The methodology was successfully extended to a one-pot total synthesis of complex heterocyclic systems such as pyrazino [2,1-b] quinazolines 79, encountered in nature as alkaloids 80-82 (Scheme 50) [125]. To assemble the pyrazino[2,l-fo]quinazoline core, N-Boc protected amino acid 76 was employed instead of carboxylic acid 72 (Scheme 49) in the synthesis of the corresponding intermediate benzoxazinones 77. The subsequent reaction with an amine moiety of another amino acid ester 78 was accompanied by concomitant cleavage of the N-Boc protecting group and diketopiperazine-like cyclization (for the one-pot deprotection-cyclization reaction of N-Boc dipeptide esters to afford 2,5-piperazinedione under microwave dielectric heating, see [128]) to afford the target heterocycle 79. Hence, the total... 

Then another N-protected amino acid is coupled to the free amino group of the polymer-bound substrate using the dicyclohexylcarbodiimide activation or the active ester method. The N-deblocking and coupling steps are repeated until the desired sequence is formed. Finally the resin-peptide bond is split by a suitable acid cleavage reaction with HBr—AcOH, trifluoroacetic acid or HF. This results in a simultaneous N-deblocking and deprotection of most of the side-chain functionalities. 

In Banwell s de novo synthesis of Neu5Ac [136] cis-1,2-dihydrocatechol 228, a product of microbial oxidation of chlorobenzene, has been converted into a protected form of Neu5Ac via a fifteen steps reaction sequence (Scheme 50). Synthesis started from azido alcohol 229, obtained from catechol 228 by an established procedure [137]. This was subjected to ozonolytic cleavage and a reductive work-up to afford diol 230. Protection-deprotection reaction sequence led to alcohol 232 which was then oxidized to D-mannosamine derivative 233 using the Swem protocol. Condensation with the organozinc reagent derived from... 

Alcohol 225 on protection and cleavage of olefin afforded aldehyde 228, which on Wittig olefination and deprotection gave ester 229. Acryloylation of 229 and reaction with DBN furnished acid 230. Yamaguchi esterification of 230 with 227 afforded ester 231, which on macrocyclization and treatment with TiCl4 in CH2CI2 furnished 191 (Scheme 6.42). 

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. 

In addition, the phenoi group, as a part of the protection group, is virtualfy a masked promoter. After the cleavage reaction, the deprotected compound, phenol fi om the phenoi group, acts as a dissolution promoter since it is very soluble in aqueous base solutions. As the result, the sensitivity of the tystem should be improved. 

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