Protection Deprotection

Titanium tetrakis(diethylamide) selectively adds to aldehydes in the presence of ketones and to the least hindered ketone in compounds containing more than one ketone. The protection is in situ, which thus avoids the usual protection/deprotection sequence. Selective aldol and Grignard additions are readily performed employing this protection methodology. ... 

Acylation of the monosubstituted piperazine, 99 (obtainable by the protection-deprotection scheme outlined above), with cinnamoyl chloride gives the corresponding amide (100). Reduction of the carbonyl by means of lithium aluminum hydride affords cinnarizine (101). ... 

Thus, heterobifunctional cyclohexadienes are accessible from benzene by temporary complexation to Fe2+ which reverses the reactivity of the aromatic. Double nucleophilic attack is possible but only using protection-deprotection by hydride. 

The 20e complex Fe(C6Me6)2, easily synthesized in high yield by Na/Hg reduction of the dry di-cationic precursor in THF at 20 °C [28], is also very useful for functionalization. Its reaction with electrophiles RX directly gives functional cyclohexadienyl iron cations, which saves one step with respect to the route using hydride protection/deprotection [47] Scheme V ... 

Another advantage of the synthesis by mixed Kolbe electrolysis is that polar groups in the carboxylic acid are tolerated in radical coupling. This makes additional protection-deprotection steps unneccessary, which are often needed in polar CC-bond forming reactions and can make these approaches less attractive in such cases. 

A recent development has been the synthesis of bioerodible poly-phosphazenes that bear glyceryl side groups (35). The synthesis of these polymers requires a protection-deprotection sequence to reduce the functionality of the glycerol and prevent crosslinking. 

This route has been widely exploited because of the availability of a-amino azomethine compoimds from natural (S)-a-amino acids, through the corresponding a-amino aldehydes, which are configurationally stable provided that the amino function is suitably protected. Moreover, some a-amino acids are available with the R configuration and a number of enzymatic and chemical transformations have been described for the preparation of optically active unnatural a-amino acids. Overall, the route suffers from the additional steps required for protection/deprotection of the amino function and, in the case of hydrazones and nitrones, cleavage of the N - N or N - O bond. 

In line with a second novel synthetic principle, the authors further developed the repetitive Diels-Alder procedure, in which monomers containing cyclopentadienone (dienophile) units were reacted with protected/deprotected ethynylene functions (see [31]). In this way, they generated a novel class of highly arylated phenylene dendrimers 46, starting from a 3,3, 5,5 -tetraethynyl-substituted biphenyl core [60]. 

Multiple protection-deprotections that were highly inefficient for scale-up. 

Reduce Derivatives Unnecessary derivatization - use of blocking groups, protection/ deprotection, and temporary modification of physical/chemical processes - should be minimized or avoided if possible, because such steps require additional reagents and can generate waste. 

The presence in carbohydrates of multiple hydroxyl groups of similar reactivity makes the chemo- and regio-selective manipulation frequently required quite difficult. For this reason, multistep protection-deprotection approaches are regularly employed in carbohydrate chemistry, and versatile techniques for these transformations are particularly helpful. The following section addresses this aspect, concentrating on the catalytic procedures that have been developed employing zeolites and related siliceous materials. 

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. 

Scheme 13.16. Protection-deprotection strategy in microwave-enhanced fluoro-debromination reaction.

Unnecessary derivatization (blocking group, protection/deprotection, temporary modification of physical/chemical processes) should be avoided whenever possible. 

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