Benzyl ethers cleaved

Debenzylation. Benzyl ethers, cleaved by catalysis of Sc(CTf i, Friedel-Crafts acylation. - Scan tipurpose catalyst. Besides prontotu Diels-Alder reaction and Meerweii -... 

The benzyl group has been widely used for the protection of hydroxyl functions in carbohydrate and nucleotide chemistry (C.M. McCloskey, 1957 C.B. Reese, 1965 B.E. Griffin, 1966). A common benzylation procedure involves heating with neat benzyl chloride and strong bases. A milder procedure is the reaction in DMF solution at room temperatiue with the aid of silver oxide (E. Reinefeld, 1971). Benzyl ethers are not affected by hydroxides and are stable towards oxidants (e.g. periodate, lead tetraacetate), LiAIH, amd weak acids. They are, however, readily cleaved in neutral solution at room temperature by palladium-catalyzed bydrogenolysis (S. Tejima, 1963) or by sodium in liquid ammonia or alcohols (E.J. Rcist, 1964). 

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. 

NBS, CH3CN, H2O, 62-90% yield.The POM group has been selectively removed in the presence of an ethoxy ethyl ether, TBDMS ether, benzyl ether, p-methoxybenzyl ether, an acetate, and an allyl ether. Because the hydrolysis of a pentenyl 2-acetoxyglycoside was so much slower than a pentenyl 2-benzyloxyglycoside, the 2-benzyl derivative could be cleaved selectively in the presence of the 2-acetoxy derivative. The POM group is stable to 75% AcOH, but is cleaved by 5% HCl. 

Lithium aluminum hydride will also cleave benzyl ethers, but this is seldom practical because of its high reactivity to other functional groups. ... 

C1O3/ACOH, 25°, 50% yield, [- ROCOPh (- ROH + PhC02H)]. This method was used to remove benzyl ethers from carbohydrates that contain functional groups sensitive to catalytic hydiogenation or dissolving metals. Esters are stable, but glycosides or acetals are cleaved. 

Several methoxy-substituted benzyl ethers have been prepared and used as protective groups. Their utility lies in the fact that they are more readily cleaved oxidatively than the unsubStituted benzyl ethers. The table below gives the relative rates of cleavage with dichlorodicyanoquinone (DDQ). ... 

Dichlorodicyanoquinone (DDQ), CH2CI2, H2O, 40 min, it, 84-93% yield.This method does not cleave simple benzyl ethers. This method was found effective in the presence of a boronate. The following groups are stable to these conditions ketones, epoxides, alkenes, acetonides, to-sylates, MOM ethers, THP ethers, acetates, benzyloxymethyl (BOM) ethers, and TBDMS ethers. 

The o-nitrobenzyl and p-nitrobenzyl ethers can b prepared and cleaved by many of the methods described for benzyl ethers. The p-nitrobenzyl ether is also prepared from an alcohol and p-nitrobenzyl alcohol (trifluoroacetic anhydride, 2,6-lutidine, CH2CI2, 67% yield). In addition, the o-nitrobenzyl ether can be cleaved by irradiation (320 nm, 10 min, quant, yield of carbohydrate " 280 nm, 95% yield of nucleotide ). The p-nitrobenzyl ether has been cleaved by electrolytic reduction (—1.1 V, DMF, R4N X, 60% yield) and by reduction with Na2S204 (pH 8-9, 80-95% yield). These ethers can also be cleaved oxidatively (DDQ or electrolysis) after reduction to the aniline derivative. ... 

FeCl3, CH2CI2, 2-3 min, 68% yield. Benzyl ethers are cleaved in 15-20 min under these conditions. Methyl glycosides, acetates and benzoates were not affected by this reagent. 

Historically, simple Vz-alkyl ethers formed from a phenol and a halide or sulfate were cleaved under rather drastic conditions (e.g., refluxing HBr). New ether protective groups have been developed that are removed under much milder conditions (e.g., via nucleophilic displacement, hydrogenolysis of benzyl ethers, and mild acid hydrolysis of acetal-type ethers) that seldom affect other functional groups in a molecule. 

Lithium diphenyphosphide (THF, 25°, 2 h HCl, H2O, 87% yield) selectively cleaves an aryl methyl ether in the presence of an ethyl ether.It also cleaves a phenyl benzyl ether and a phenyl allyl ether to phenol in 88% and 78% yield, respectively. ... 

Bromo-l,3,2-benzodioxaborole, CH2CI2 (cat. BF3 Et20), 25°, 0.5-36 h, 95-98% yield. Aryl benzyl ethers, methyl esters, and aromatic benzoates are also cleaved. ... 

NaAlH2(0CH2CH20CH3)2, PhCH3, reflux, 10 h, 62% yield/ An aryl allyl ether is selectively cleaved by this reagent (which also cleaves aryl benzyl ethers) in the presence of an A-allylamide. 

Pd-C, 1,4-cyclohexadiene, 25°, 1.5 h, 95-100% yield.Palladium black, a more reactive catalyst than Pd-C, must be used to cleave the more stable aliphatic benzyl ethers. 

Na, /-BuOH, 70-80°, 2 h, 78%. In this example sodium in /-butyl alcohol cleaves two aiyl benzyl ethers and reduces a double bond that is conjugated with an aromatic ring nonconjugated double bonds are stable. 

Me3SiI, CH3CN, 25-50°, 100% yield. Selective removal of protective groups is possible with this reagent since a carbamate, =NCOOCMe3, is cleaved in 6 min at 25° an aryl benzyl ether is cleaved in 100% yield, with no formation of 3-benzyltyrosine, in 1 h at 50°, at which time a methyl ester begins to be cleaved. 

CF3CO2H, PhSCH3, 25°, 3 h. ° The use of dimethyl sulfide or anisole as a cation scavenger was not as effective because of side reactions. Benzyl ethers of serine and threonine were slowly cleaved (30% in 3 h complete cleavage in 30 h). The use of pentamethylbenzene had been shown to increase the rate of deprotection of 0-Bn-tyrosine. ... 

An 6>-nitrobenzyl ether.can be cleaved by photolysis. In tyrosine this avoids the use of acid-catalyzed cleavage and the attendant conversion to S-beirayltyrosine. (Note that this unwanted conversion can also be suppressed by the addition of thioanisole see section on benzyl ether cleavage.)... 

The 4-(dimethylaminocarbonyl)benzyl ether has been used to protect the phenolic hydroxyl of tyrosine. It is stable to CF3CO2H (120 h), but not to HBr/AcOH (complete cleavage in 16 h). It can also be cleaved by hydrogenolysis (H2/Pd-C). ... 

BuMc2SiH, Pd(OAc)2, CH2CI2, Et3N, 100% yield. Cbz groups and Alloc groups are also cleaved, but benzyl ethers are stable. 

Electrolysis —2.9 V, DMF, R4N X , 70-80% yield or Pd/graphite cathode, MeOH, AcOH, 2.5% NaCl04 (0.5 mol/L), 99% yield.Benzyl ethers and tosylates are stable to these conditions, but benzyl esters are cleaved. 

Esters and amides are quite resistant to hydrogenation under almost all conditions so their presence is not expected to cause difficulties. Alkyl ethers and ketals are generally resistant to hydrogenolysis but benzyl ethers are readily cleaved, particularly over palladium or Raney nickel catalysts. ... 

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. 

AlCl3-PhNMe2, CH2CI2, 73-100% yield." Benzyl ethers are also cleaved. 

C0CI2, AcCl, CH3CN, rt, 8-12 h, 71-84% yield. Benzyl ethers are among those that are also cleaved." ... 

Propargyl ethers are cleaved with TiCl3-Mg in THF, 54-92% yield. Allyl and benzyl ethers were not cleaved phenolic propargyl ethers are also cleaved. ... 

Raney Nickel W2 or W4, EtOH, 85-100% yield. Mono- and dimethoxy-substituted benzyl ethers and benzaldehyde acetals are not cleaved under these conditions, and trisubstituted alkenes are not reduced. 

EtSH, BF3 Et20, 63% yield." Benzylamines are stable to these conditions, but BF3 Et20/Me2S has been used to cleave an allylic benzyl ether." ... 

I2, MeOH, reflux, 12-16 h, 75-91% yield. Benzyl ethers are stable to these conditions, but isopropylidenes are cleaved. ... 

SnBr2, AcBr, CH2CI2, rt, 81-92% yield. These conditions, which also cleave alkyl and aryl benzyl ethers, produce an acetate that must then be hydrolyzed with base to release the alcohol. When SnCl2/PhOCH2COCl is used, only MPM ethers are cleaved, leaving benzyl ethers unaffected. 

The o nitrobenzyl and /7 nitrobenzyl ethers can be prepared and cleaved by many of the methods described for benzyl ethers. The p-nitrobenzyl ether is also... 

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