Trityl benzyl ether

In a typical experiment, trityl benzyl ether (5.0 mmole) is added to a stirred solution of the trityl salt (0.50 mmole) in acetonitrile. After4 hr., water is added and the products isolated, fienzaldehyde and triphenylmethane are obtained in quantitative yields. The reaction thus provides a method for oxidation of alcohols to aldehydes or ketones. 

The reaction probably involves a cationic chain reaction involving hydride transfer, and indeed the rate-limiting step in the oxidation of trityl benzyl ether was shown to be a chain-propagating step (equation I). 

Me3SiBr, CH2CI2, 0°, 8-9 h, 80-97% yield.This reagent also cleaves the acetonide, THP, trityl, and r-BuMe2Si groups. Esters, methyl and benzyl ethers, r-butyldiphenylsilyl ethers, and amides are reported to be stable. 

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 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°. ... 

Benzyl ethers bearing electron-donating groups can be cleaved by treatment with acids or oxidants. The rate of solvolysis increases with the number of electron-donating groups, and in the series benzyl < benzhydryl < trityl. For the solid-phase synthesis of oligonucleotides, the 5 -hydroxyl group is usually protected as 4,4/-dimethoxytrityl... 

The disilyl derivative of all-cix-1,2-epoxycyclopentane-3,5-diol 5 7 was treated with diethyloctynylalane to afford after cleavage of the silylether function the triol 58. This triol was convered via the acetonide to the benzyl ether 59. Hydrolysis with aqueous trifluoroacetic acid yielded the diol benzylether 60 which could be prepared by an alternative route as well. This route proceeds via the monotrityl epoxide 61 and benzylation to the trityl benzylether 62 and then reaction with diethyl octynyl alane to the diolbenzylether 60 and the isomeric 1,3-diol. 

Benzyl 2,2,2-trichloroacetimidate (bp 106-114 °C/0.07 kPa) alkylates alcohols in the presence of trifluoromethanesulfomc acid.311 Esters, imides, isopropylidene and benzylidene acetals are unaffected. This method allows the formation of benzyl ethers in molecules that are base-sensitive. In the example [Scheme 4,167],312 benzylation of the P-hydroxy ester 167.1.1 under the usual basic conditions would lead to retro-aldol reactions and/or elimination. A synthesis of the cellular messenger L-a-phosphatidyl-D-myo-inositol 3,4-bisphosphate exemplifies the use of trityl cation-promoted benzylation of two adjacent hydroxyls [Scheme 4.168].313314... 

In the dosing stages of a synthesis of Mitomycin derivative FR-900482, a densely functionalised intermediate had to be shorn of its robust MOM protector [Scheme 4.250].46S The task was accomplished with trityl tetrafluoroborate under conditions devised some years ago by Kishi and co-workers.466 Lithium tetrafluoroborate in refluxing aqueous acetonitrile has been successfully deployed in the deprotection of a MOM ether in the presence of a benzyl ether [Scheme 4 2511 467... 

In the early 1970s, Barton et al. published the results of their woik on the oxidation of acetals and ethers by hy de transfer. o They observed that substituted benzyl ethers and benzyloxy carbonates, on brief exposure to trityl tetrafluoroborate in dichloromethane at 0 C followed by aqueous work-up, afforded go( yields of the parent alcohols together with the corresponding bennldehydes. Undw the same conditions, the tetrahydropyranyl ether of cholesterol was also efficiently deprotected. A mechanism was proposed which involved an initial hydrogen abstraction, followed by quenching of the resulting stabilized cation by water (Scheme 6). 

Ten years later, a Japanese group led by Oikawa developed a mechanistically related method for the selective debenzylation of substituted benzyl ethers based on the reagent 2,3-dichloro-S,6-dicyanobenzo-quinone (DDQ). In contrast to the trityl tetrafluoroborate reaction, the oxidation proceeds at room temperature in the presence of water. Furthermore, under these convenient and essentially neutral conditions, many functional groups, including other common protecting groups, such as isopropylidine, methoxy-methyl, benzyloxymethyl, tetrahydropyranyl, acetyl, r-butyldimethylsilyl, benzyl, benzoyl and tosyl, are unaffected. As a result of the hig levels of selectivity which can be achieved, this method for the depro-... 

Lactonization Reaction of 1 with trityl tetrafluoroborate not only effects oxidative debenzylation as expected (4, 567), but also cyclization to 2, d/-aplysis-tatin, a brominated sesquiterpene. Attempted hydrogenolysis of the benzyl ether resulted only in hydrogenation of the double bond. 

Oxidation of benzyl ethers with trityl fluoroborate can be used either to prepare aromatic aldehydes or to cleave benzyl ethers of alcohols. 

A new cortisone derivative, 3,20-dioxo-lljS,17a,21-trihydroxypregna-l,4,7-triene (298), has been prepared from the intermediate (297) by a classical combination of chemical and microbiological reactions.The chemistry of 17,20-and 20,21-acetonides, epimeric at C(20), has been described. A deprotection of masked steroidal alcohols by hydride transfer has been reported.Several benzyl ethers and bismethylenedioxy-steroids have been prepared and treated with trityl fluoroborate. The results demonstrated that the benzyl hydrogen atoms are sufficiently basic to give a benzyloxonium ion, as shown in the conversion of the 17,20 20,21-bismethylenedioxy-corticoid (299) into its free analogue (302) (see Part II, Chapter 1, refs. 120 and 323). 

Cleavage of the MOM group with dilute acids or with PPTS in r-BuOH regenerates the alcohol. A mild and selective reagent for removing the MOM group in the presence of methyl or benzyl ethers, -SiPh2 -Bu ethers, or esters is bromotrimethyl-silane. However, TMSBr will also cleave acetals and trityl ethers. ... 

TPAP tolerates a wide variety of functional groups, including double bonds, enones, halides, epoxides, esters, and lactones. Protecting groups, such as MEM, trityl, silyl and benzyl ethers, THP, and acetals, are not affected. 

Allyl, p-anisylmethyl, and especially, benzyl ethers undergo elimination to give alkenes on exposure to BuLi On the other hand, ethers of the THP, MOM, and trityl types are stable under such conditions. 

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