Protection-deprotection, functional

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 ... 

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]. 

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. 

There is a brief reference to electroreductive silicon polymer formation in COMC II (1995) (chapter Organopolysilanes, p 96), but the very limited extent of the field at that time precluded further comment. Since then, the field has seen considerable progress, and the mild conditions have permitted the synthesis of functionalized polymers of moderate molecular weight (104), an example of which is the co-polymer poly(rncthyM-rncthoxymethoxyphcnylsilylene)-r -poly(methylphenylsilylene), 26, with a protected phenolic function, which was prepared with a molecular weight Mw= 19,000.96 Deprotection afforded the phenolic polymer. Several reviews on the area have been published.113-115... 

Selective reaction at only one position in a molecule that contains two or more of the same functionality, or different functionalities that react in a similar manner, can be difficult to achieve chemically without lengthy protection/deprotection strategies. In contrast, such regio- and chemo-selective transformations can frequently be realized surprisingly easily with a biocatalyst, as demonstrated by the following examples. 

This enantioselective preparation of allylic alcohols has been applied to the synthesis of the side chain of prostaglandins . The addition to functionalized aldehydes, such as 483, allows the synthesis of C2-symmetrical 1,4-diols, such as 484, with excellent diastereoselectivity and enantioselectivity . An extension of this method allows the synthesis of C3-symmetrical dioF . Aldol-type products result from the catalytic enantioselective addition of functionalized dialkylzincs to 3-TIPSO-substituted aldehydes, such as 485, followed by a protection-deprotection and oxidation sequence affording 486 in 70% yield and 91% ee (Scheme 118) . The addition to a-alkoxyaldehydes provides a... 

The protection-deprotection procedure of the nitrogen atom of 2-azetidinones holds a prime position in synthetic methodologies leading to functionalized (3-lactam derivatives. 

Suitable chemistry must be chosen to allow the use of polyfunctional, unprotected reagents. In general, acylations and other reactions with electrophiles of a support-bound substrate will require the protection of functionalized side chains, both in the substrate and in the reagent. Protected, polyfunctional reagents are, however, rare and expensive, and protections/deprotections add further synthetic steps to the synthesis. Nucleophilic transformations, on the other hand, often enable the direct use of highly functionalized, unprotected reagents. Hence, nucleophilic transformations (e.g. 

Electroenzymatic reactions are not only important in the development of ampero-metric biosensors. They can also be very valuable for organic synthesis. The enantio- and diasteroselectivity of the redox enzymes can be used effectively for the synthesis of enantiomerically pure compounds, as, for example, in the enantioselective reduction of prochiral carbonyl compounds, or in the enantio-selective, distereoselective, or enantiomer differentiating oxidation of chiral, achiral, or mes< -polyols. The introduction of hydroxy groups into aliphatic and aromatic compounds can be just as interesting. In addition, the regioselectivity of the oxidation of a certain hydroxy function in a polyol by an enzymatic oxidation can be extremely valuable, thus avoiding a sometimes complicated protection-deprotection strategy. 

The three-component domino-Knoevenagel-hetero-Diels-Alder reaction is especially fruitful if one uses aldehydes containing a protected amino function. In such cases the formed dihydropyranyl ether moiety can be used as a source of an aldehyde moiety that can undergo a condensation with the amino group after deprotection. Thus, several alkaloids such as hirsutine 108, dihydrocorynantheine... 

The chiral bicyclic enones, levoglucosenone, isolevoglucosenone, and new functionalized L-arabinose enone possess excellent reactivity and functionality. Their properties mid application as convenient precursors in the synthesis of many attractive templates or intermediates of complex natural products are reviewed. These compounds are attracting increasing interest due to their structural rigidity and ability for stereoselective functionalization without protection, deprotection sequences necessary in many synthetic organic methodologies. 

Amino-277-thiopyrans are produced when protected 2-amino-4-dimethylaminothiabutadienes react with acrylic dienophiles. The initial adduct eliminates dimethylamine and subsequent deprotection generates the amine (Scheme 112). Using methyl vinyl ketone, the protected amino function is butanoylated <2004S1633, 2006T9226>. 

The vast array of similar functionality often turns out to be a major problem to the synthetic chemist who needs to differentiate between them. This can result in long, tedious, protection-deprotection sequences.1,6 7 Although enzymes can be of help, there is still a significant way to go. As carbohydrates are components of many pharmaceutical compounds, many methods have been developed for their synthesis.89 This includes methodology that is amenable to use at scale, including the Sharpless epoxidation.10-14... 

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