Ethers, trityl alcohol protection

Triphenylmethyl ethers (trityl ethers) have been used to protect primary alcohols selectively [see (14)] , and unhindered secondary alcohols. 

The introduction and cleavage of the trityl ether proceeds through a very well-stabilised triphenylmethyl carbocation. In the case of trityl ether bond formation, the reaction is performed under anhydrous conditions and the carbocation, which is formed by an SN1 mechanism, reacts with an alcohol. In the case of cleavage, the triphenylmethyl carbocation ion is formed by treatment with acid, which is then trapped by water or a nucleophilic solvent to give trityl alcohol or other derivatives, respectively. Trityl ethers have also been used to protect thiols. 

Benzyl trichloracetimidate (48) is a new reagent for acid-catalysed benzylation of alcohols in the presence of trifluoromethanesulphonic acid, and benzyl p-toluenesulphonate-potassium carbonate has been recommended as abenzylat-ing system for phenols, especially in cases where benzyl chloride-potassium carbonate gives C-alkylated impurities.Facile removal of benzyl ether protecting groups has been achieved by catalytic transfer hydrogenation with Pd(OH)2 on carbon and cyclohexene as hydrogen-donor. A new procedure for O-tritylation by treatment of an alcohol trimethylsilyl ether with trityl trimethylsilyl ether is shown in equation (6). The synthesis and characterization has been completed of 4-dimethylamino-N-triphenylmethylpyridinium chloride (49)," a postulated intermediate in the formation of trityl ethers from alcohols... 

Ethers are among the most used protective groups in organic synthesis. They vary from the simplest, most robust, methyl ether to the more elaborate, substituted, trityl ethers developed for use in nucleotide synthesis. They are formed and removed under a wide variety of conditions. Some of the ethers that have been used to protect alcohols are included in Reactivity Chart 1. ... 

As previously discussed, ethyl chlorocarbonate reacts rapidly and selectively with an equatorial 3-hydroxyl group to give the corresponding cathylate. Trityl ethers, usually employed as a selective protecting group for primary hydroxyls, can be prepared from A -3j3-ols by heating with triphenylmethyl chloride in pyridine, and from 5a-3 -alcohols by more prolonged heat-... 

Clean removal of trityl ether groups from O-isopropylidenated furanoses by using NaHS04-Si02 was previously described by Das et al.116 and afforded the corresponding alcohols at room temperature. The chemoselective deprotection was accomplished in yields above 91% within 2-2.5 h, leaving other protective-groups intact (Scheme 27). 

A concise synthesis of tetra-O-ethyl aldonolactam 83 starting from 1 has been reported [102]. After protection of its primary alcoholic moiety as a trityl ether, saponification and treatment with EtBr generated 80. Acidic hydrolysis liberated 81 that was esterified (tosylate). The latter was displaced with NaNs to give azide 82. Reduction of 82 resulted in lactam 83 (Scheme 24). 

The employment of trityl trifluoroborate is particularly interesting. This reagent is able to introduce trityl groups on both primary and secondary alcohols54 and to selectively oxidize secondary trityl ethers to ketones in the presence of primary trityl ethers.55 Thus, treatment of diols with trityl trifluoroborate leads to tritylation of both alcohols followed by oxidation of the secondary trityl ether, resulting in the formation of a ketone possessing a trityl-protected primary alcohol. A work-up by mild acidic hydrolysis provides the deprotection of the primary trityl ether and formation of a hydroxy ketone.54... 

Cleavage of acid-labile protective groups.1 The reaction of H202 (70%, FMC) and CI3CCOOH in CH2C12/(-butyl alcohol converts a dimethyl acetal (1) into a hydroperoxy methyl acetal (a), which can be isolated but which for convenience (and safety) is reduced to the aldehyde 2 in 80% overall yield. The same conditions can effect oxidative cleavage of tetrahydropyranyl and trityl ethers. 

One widely used method of formation of protected compounds involves polymer-supported reagents,21-27 with the advantage of simple workup by filtration and automated syntheses, especially of polypeptides. Polymer-supported reagents are used to protect a terminal —COOH group as a polymer-bound ester (RCOOR — ) during peptide syntheses,21 to protect primary alcohols as — trityl ethers,28 and to protect 1,2- and 1,3-diols as —phenyl boronates.29 Monoprotection of symmetrical dialdehydes and diacid chlorides has been reported 23 some diprotection occurs with diols and diamines.23... 

Next, one of the acetals is hydrolysed under very mild conditions, and the primary alcohol is protected as a trityl ether. This is an SN1 reaction with an enormous electrophile—so big that it goes on primary alcohols only. 

Protection of primary alcohols. This trityl bromide in the presence of AgNO, m DMF reacts selectively with the primary hydroxyl group of carbohydrates and nucleosides. The CPTr ether group is stable to aqueous pyridine and 80% acetic acid, but is selectively cleaved by hydrazine in pyridine-acetic acid. This protecting group is useful in the synthesis of oligoribonucleotides. 

The aziridine 12i has been derived from the trans amino alcohol 12h by the two-step, one-pot process i) selective protection of the amino functionality with trityl chloride and ii) mesylation of the hydroxyl in the presence of triethylamine. Under these conditions, the mesylate intermediate has been converted to aziridine 12i. Treatment of 12i with /-pentyl alcohol in the presence of 1.5 equiv of BF3-Et20 followed by acetylation of the crude product provides the ether 121. Finally, reduction of the azide functionality and saponification of the ester group in 121 give GS4071,12. 

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