Benzyl alcohols protecting groups

The benzyl ether is prepared in a similar manner to the methoxymethyl ether, that is, by reaction of the conjugate base of the alcohol with benzyl bromide in an SN2 reaction. An example of a sequence that employs a benzyl ether protecting group is illustrated in the following sequence ... 

Under carefully worked out acidic conditions the lactone hemiacetal 34 rearranges into the dioxabicyclo[3.2.1]octane 35 (Scheme 6). By changing the alcohol protecting group and exchanging the methyl ester for a benzyl ester the diol 38a is obtained, whose C6-OH function is esterified with the... 

The benzyl group can serve as an alcohol-protecting group when acidic conditions for ether cleavage cannot be tolerated. The benzyl C-O bond is cleaved by catalytic hydrogenolysis," or with sodium in liquid ammonia. Allyl ethers are an alternative to benzyl ethers as a protecting group. Allyl ethers may be isomerized quantitatively by potassium r-butoxide in dimethyl sulfoxide to propenyl ethers, which are quite labile to dilute acid. ... 

Hydrogenolysis of benzyl ethers makes them useful as an alcohol protecting group. 

Last year in this Report (3,156) the oxidative removal of p-methoxybenzyl ethers, by homogeneous electron transfer from the stable cation radical of tris-(4-bromophenyl)amine, was featured. This procedure did not affect benzyl ethers, but a recent extension of these studies to cation radicals (61), of higher oxidation potential, has allowed development of methods to cleave benzyl protecting groups from alcohols [equation (10)]. The radicals may, as in the earlier report, be used either stoicheiometrically, or catalytically and regenerated electrochemically in situ. The potential selectivity between different benzyl type protecting groups now available by this method has been illustrated in a further publication. ... 

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... 

Six protective groups for alcohols, which may be removed successively and selectively, have been listed by E.J. Corey (1972B). A hypothetical hexahydroxy compound with hydroxy groups 1 to 6 protected as (1) acetate, (2) 2,2,2-trichloroethyl carbonate, (3) benzyl ether, (4) dimethyl-t-butylsilyl ether, (5) 2-tetrahydropyranyl ether, and (6) methyl ether may be unmasked in that order by the reagents (1) KjCO, or NH, in CHjOH, (2) Zn in CHjOH or AcOH, (3) over Pd, (4) F", (5) wet acetic acid, and (6) BBrj. The groups may also be exposed to the same reagents in the order A 5, 2, 1, 3, 6. The (4-methoxyphenyl)methyl group (=MPM = p-methoxybenzyl, PMB) can be oxidized to a benzaldehyde derivative and thereby be removed at room temperature under neutral conditions (Y- Oikawa, 1982 R. Johansson, 1984 T. Fukuyama, 1985). 

Certain functional groups may be protected from reduction by conversion to anions that resist reduction. Such anions include the alkoxides of allylic and benzylic alcohols, phenoxide ions, mercaptide ions, acetylide ions, ketone carbanions, and carboxylate ions. Except for the carboxylate, phenoxide, and mercaptide ions, these anions are sufficiently basic to be proton-ated by an alcohol, so they are useful for protective purposes only in the... 

Catalytic hydrogenolysis of an O-benzyl protective group is a mild, selective method introduced by Bergmann and Zervas to cleave a benzyl carbamate (>NC0-0CH2C6H5 —> >NH) prepared to protect an amino group during peptide syntheses. The method has also been used to cleave alkyl benzyl ethers, stable compounds prepared to protect alkyl alcohols benzyl esters are cleaved by catalytic hydrogenolysis under neutral conditions. 

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