Trityl cleavage

The cleavage proceeds by initial reduction of the nitro groups followed by acid-catalyzed cleavage. The DNB group can be cleaved in the presence of allyl, benzyl, tetrahydropyranyl, methoxy ethoxy methyl, methoxymethyl, silyl, trityl, and ketal protective groups. 

CF3COOH, r-BuOH, 20°, 2-30 min, then Bio-Rad 1x2 (OH ) resin.These conditions were used to cleave the trityl group from the 5 -hydroxyl of a nucleoside. Bio-Rad resin neutralizes the hydrolysis and minimizes cleavage of,glycosyl bonds. 

Me3SiI, CH2CI2, 25°, 15 min, 85-95% yield.Under these cleavage conditions i,3-dithiolanes, alkyl and trimethylsilyl enol ethers, and enol acetates are stable. 1,3-Dioxolanes give complex mixtures. Alcohols, epoxides, trityl, r-butyl, and benzyl ethers and esters are reactive. Most other ethers and esters, amines, amides, ketones, olefins, acetylenes, and halides are expected to be stable. 

The bulky triphenylmethyl group has been used to protect a variety of amines such as amino acids, penicillins, and cephalosporins. Esters of N-trityl a-amino acids are shielded from hydrolysis and require forcing conditions for cleavage. The a-proton s also shielded from deprotonation, which means that esters elsewhere in the molecule can be selectively deprotonated. 

Ph3C BF4, CH2CI2, 5-30 min, 80-95% yield. " The mechanism of this cleavage has been determined to involve complex formation by the trityl cation with the sulfur, followed by hydrolysis, rather than by hydride abstraction. ... 

The trityl group was introduced on a primary amide, RCONH2, in the presence of a secondary amide with TrOH, AC2O, H2SO4, AcOH, 60°, 75% yield. It is stable to BOC removal with 1 N HCl in 50% isopropyl alcohol, 30 min, 50°, but can be cleaved with TFA. The following table gives the cleavage rates with TFA for a number of protected primary amides. 

Eda and Kurth applied a similar solid-phase combinatorial strategy for synthesis of pyridinium, tetrahydropyridine, and piperidine frameworks as potential inhibitors of vesicular acetylcholine transporter. One member of the small library produced was prepared from amino-functionalized trityl resin reacting with a 4-phenyl Zincke salt to give resin-bound product 62 (Scheme 8.4.21). After ion exchange and cleavage from the resin, pyridinium 63 was isolated. Alternatively, borohydride reduction of 62 led to the 1,2,3,6-tetrahydropyridine 64, which could be hydrogenated to the corresponding piperidine 65. 

The use of iodotrimethylsilane for this purpose provides an effective alternative to known methods. Thus the reaction of primary and secondary methyl ethers with iodotrimethylsilane in chloroform or acetonitrile at 25—60° for 2—64 hours affords the corresponding trimethylsilyl ethers in high yield. The alcohols may be liberated from the trimethylsilyl ethers by methanolysis. The mechanism of the ether cleavage is presumed to involve initial formation of a trimethylsilyl oxonium ion which is converted to the silyl ether by nucleophilic attack of iodide at the methyl group. tert-Butyl, trityl, and benzyl ethers of primary and secondary alcohols are rapidly converted to trimethylsilyl ethers by the action of iodotrimethylsilane, probably via heterolysis of silyl oxonium ion intermediates. The cleavage of aryl methyl ethers to aryl trimethylsilyl ethers may also be effected more slowly by reaction with iodotrimethylsilane at 25—50° in chloroform or sulfolane for 12-125 hours, with iodotrimethylsilane at 100—110° in the absence of solvent, " and with iodotrimethylsilane generated in situ from iodine and trimcthylphenylsilane at 100°. ... 

Hydroxamic acids are an important class of compounds targeted as potential therapeutic agents. A-Fmoc-aminooxy-2-chlorotrityl polystyrene resin 61 allowed the synthesis and subsequent cleavage under mild conditions of both peptidyl and small molecule hydroxamic acids (Fig. 14) [70]. An alternative hydroxylamine linkage 62 was prepared from trityl chloride resin and tV-hydroxyphthalimide followed by treatment with hydrazine at room temperature (Scheme 30) [71]. A series of hydroxamic acids were prepared by the addition of substituted succinic anhydrides to the resin followed by coupling with a variety of amines, and cleavage with HCOOH-THF(l 3). 

An imidazolide-supported polymer was used for transacylation of phosphatidylcholine. The polymer was obtained from a chloromethylated polystyrene with two mol-% divinylbenzene. The imidazolide group was anchored by reaction with 3-hydroxymethyl-1-tritylimidazole, cleavage of the trityl group, and condensation with palmitic acid 122]... 

Furthermore, several functionalities remained unaffected, namely the acid-labile TBDMS or PMB groups.118 Deprotection yields were in the range of 85-95% when methanol was used at room temperature as the solvent, whereas acetonitrile or dichloromethane led to very sluggish or nonexistent reactions, respectively. Cleavage of primary trityl ethers was also accomplished using the same conditions in a very rapid and effective fashion. The trityl pyranosides and furanosides assayed were selectively deprotected in 2-3 h and yields higher than 85% were achieved. This reaction was also more efficient when conducted in methanol, which acts as a nucleophile to trap the generated trityl cation. 

Because of the high stability of the triphenylmethyl carbocation, the reductive ether cleavage of trityl ethers with EtySiH/trimethylsilyl triflate (TMSOTf) is highly successful. This reaction even occurs in the presence of highly reactive sugar ketals, leaving the ketals intact (Eq. 126).269... 

For these reasons, an alternative route and more acid labile linkers compared to p-carboxy trityl linker 24a initially used were sought, to avoid high concentrations of TFA for the final cleavage. The synthesis of the alkoxysubstitued linkers 24b (Meisenbach and Voelter 1997) and 24c, which can be synthesised directly on the solid support in five steps, offer the possibility of linkers with tailor-made stability. 

FIGURE 6.21 (A) Removal of trityl and acetamidomethyl from sulfhydryl by oxidative cleavage by iodine. (B) Cleavage of terf-butylsulfanyl by mercury(II) acetate,88 followed by displacement of the metal ion by hydrogen sulfide. 

The next landmark was the synthesis of the germylium, 22, and the stannylium ion, 23, by one-electron oxidations from the corresponding stable radicals with trityl TPFPB by Sekiguchi and co-workers. As in the case of the allyl cleavage to generate the mesityl-substituted cations, the reaction, in this case the oxidation, occurs at the periphery of the molecule and gives the possibility for efficient steric protection of the incipient cation. Both trivalent cations were obtained as their TPFBP salts and the crystal structure show well separated anions and cations. 

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