Protection and deprotection

Protection and Deprotection.- A convenient procedure for preparing t-butyl chloromethyl ether, used for protecting alcohols as their 

Trimethylsilyl azide is a reactive silylating agent for primary and 121 

K-10 montmorilIonite, an acidic clay, has been found useful for the con ethers, 

Rapid and selective detritylation of primary alcohols has been achieved with formic acid in various solvents (ether, acetonitrile, ethyl acetate) and the conditions are mild enough to ensure the 

4- dimethoxybenzyl ethers ( f. 9, 252). The mild hydrolytic conditions necessary for the conversion of alkoxymethyl aryl ethers 

Protection and Deprotection.- A review of the use of organosilicon reagents for the protection of alcohols and of 1,2- and 1,3-diols 

8-diazabicyclo[5.4.O]undec-7-ene (DBU) to be a milder and more general base for TBDMS ether formation than the imidazole-DMF 

Boron trifluoride etherate-sodium (or potassium) iodide is a 

Quaternary ammonium iodides have been found to improve the yield of aluminium iodide promoted aromatic ether cleavages to 

Hydroquinone dimethyl ethers have been shown to be oxidatively 

Protection and Deprotection.—The 5-dibenzosuberyl group (27) has been shown to be useful in the masking of both carboxylic acid and amino groups in amino acids. Specific removal of one protecting group in the presence of the other is possible. 

One role that a metal reagent plays is simply to act as a protecting group. Conventional protection works test for heteroatom functionalities, but alkene 

AlkyM Cobalt Carbonyl Alkynes are protected as the tetrahedrane-like clusters 14.7. In this case, deprotection is carried out oxidatively with a reagent such as FeCIa, or Et3NO as we saw in Section 4.3, oxidation often 

Nicholas has shown how carbonium ions alpha to the alkyne carbon are stabilized in the Co complex and can react with a variety of nucleophiles, such as the allylsilane in Eq. 14.56. The positive charge is probably stabilized by delocalization into the cluster by some such resonance form as 14.8. 

Diene Iron Carbonyl Dienes are most commonly protected with the Fe(CO)3 group. Once again, an oxidative deprotection step with FeCls is often used. One important application is the protection of a diene in the B ring of certain steroids (e.g., 14.9). Under these circumstances, the side chain 

C=C groups can be successfully converted into a number of useful derivatives by osmylation, hydroboration, or hydrogenation, without affecting the diene.  

A further report has appeared on the use of trimethylsilyl iodide for ester cleavage/ Although lengthy reaction times are often required, yields of carboxylic acids are excellent. This reagent also offers the possibility of selectivity, as t-butyl and benzyl esters react rapidly at room temperature whereas other alkyl esters (Me, Et, Pr ) require temperatures at 50 °C for reaction to occur. A disadvantage of the reagent is that it will also attack ethers, ketals, and alcohols. An improvement of this method is the use of mixtures of phenyltrimethylsilane and iodine. Benzyl esters can be deprotected by oxidative cleavage with nitrosonium hexafluorophosphate. This method could be valuable as almost all non-hydrolytic methods for the removal of benzyl esters are reductive. 

Arenes are generally protected with the Cr(CO)3 group, but as this complexation leads to a number of other important changes in the chenoical properties of the arene, in particular making it much more susceptible to nucleqrhilic attack.  

Complexation has also been used to trap highly reactive species that might otherwise decompose. An early example was cyclobutadiene, not isolable except in the complexed form, such as the Fe(CO 3 complex. Ce(IV) oxidation releases the free diene. In the case of 14.10, trapping as the Pt(PHi3)2 complex allowed this unusually strained and reactive alkene to be purified and stored. The alkene itself, which is stable for short periods under ambient conditions, is released by treatment of the complex with 

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In addition to the preparation of l-alkenes, the hydrogenolysis of allylic compounds with formate is used for the protection and deprotection of carboxylic acids, alcohols, and amines as allyl derivatives (see Section 2.9). 

Another method for deallylation of ally esters is the transfer of the allyl group to reactive nucleophiles. Amines such as morpholine are used[415-417], Potassium salts of higher carboxylic acids are used as an accepter of the allyl group[418]. The method is applied to the protection and deprotection of the acid function in rather unstable /f-lactam 664[419,420]. 

Sections 27 15 through 27 17 describe the chemistry associated with the protection and deprotection of ammo and carboxyl functions along with methods for peptide bond formation The focus m those sections is on solution phase peptide synthesis Section 27 18 shows how these methods are adapted to solid phase synthesis... 

A series of substituted benzimidazoles and pyrroles was protected and deprotected using this methodology. 

Two new sections on the protection for indoles, imidazoles, and pyrroles, and protection for the amide — NH are included. They are separated from the regular amines because their chemical properties are sufficienth different to affect the chemistry of protection and deprotection. The Reactivity Charts in Chapter 8 are identical to those in the first edition. The chart number appears beside the name of each protective group when it is first discussed. 

The steps involved in automated oligonucleotide synthesis illustrate the current use of protective groups in phosphate chemistry (Scheme 1). Oligonucleotide synthesis involves the protection and deprotection of the 5 -OH, the amino groups on adenine, guanine, and cytosine, and -OH groups on phosphorus. 

All the approaches for deblocking protective groups described earlier in this book have found application in the removal of protective groups from phosphorus derivatives. Because phosphate protection and deprotection are commonly associated with compounds that contain acid-sensitive sites (e.g., glycosidic linkages and DMTr-O- groups of nucleotides), the most widely used protective groups on phosphorus are those that are deblocked by base. 

Two new sections on the protection of phosphates and the alkyne-CH are included. All other sections of the book have been expanded, some more than others. The section on the protection of alcohols has increased substantially, reflecting the trend of the nineties to synthesize acetate- and propionate-derived natural products. An effort was made to include many more enzymatic methods of protection and deprotection. Most of these are associated with the protection of alcohols as esters and the protection of carboxylic acids. Here we have not attempted to be exhaustive, but hopefully, a sufficient number of cases are provided that illustrate the true power of this technology, so that the reader will examine some of the excellent monographs and review articles cited in the references. The Reactivity Charts in Chapter 10 are identical to those in the first edition. The chart number appears beside the name of each protective group when it is first introduced. No attempt was made to update these Charts, not only because of the sheer magnitude of the task, but because it is nearly impossible in... 

In the course of the investigation of methodologies for the protection of iodopy-razoles during acetylenic cross-coupling, different authors have been seeking protecting groups that satisfy the criterion that both protection and deprotection occur efficiently under mild conditions. 

Advantages of the Stille reaction include neutral conditions under which the reaction takes place, often with full retention of stereochemistry, and compatibility with nearly all functional groups thus eliminating additional steps required for protection and deprotection. Conversely, a highly undesirable drawback is the use of toxic tin compounds and the ensuing difficult removal of these from the reaction mixture. 

Despite impressive advances in the design of highly selective reagents, protection and deprotection of functional groups is still very... 

This modular methology involves the repetition of directed protection/cyclo-addition/deprotection steps, and allows for the synthesis of monodisperse dendritic oligophenylenes of the first (46a, 22 benzene rings) and second (46b, 62 benzene rings) generation [60]. Within the synthetic sequence, the authors made use of the different reactivities of protected and deprotected ethynylene functions within the key cycloadditon step. 

The reason why synthesis of natural urushiols involves multistep, tedious procedures is that the reactive unsaturated group cannot be directly introduced on the catechol moiety protection and deprotection of the catechol moiety are... 

Enzymes are the catalyst per excellence for reactions in water, which is their natural habitat. Moreover, the use of enzymes often circumvents the need for functional group protection and deprotection steps. For example, enzymatic hydrolysis of penicillin G to 6-APA (Fig. 2.30) proceeds in one step at ambient temperature while chemical deacylation requires three steps, a temperature of - 40 C and various stoichiometric reagents, leading to a high E factor. 

Functional Group Interconversion by Substitution, Including Protection and Deprotection... 

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