Ethers benzyl, hydrogenolysis

Bamford-Stevens decomposition of tosylhy-drazones, 351 p-Benzoquinone, 308 Benzyl ether hydrogenolysis, 139 Benzyl thioenol ethers, 87 Birch reduction, 11, 49, 50 Birch reduction of estrone methyl ether diethyl ketal, 51... 

Catalytic hydrogenolysis offers the mildest method for deprotecting benzyl ethers. Hydrogenolysis of 2°- and 3°-benzyl ethers may be sluggish. Protection of alcohols using (benzyloxy)methyl chloride produces the corresponding (benzyloxy)methyl ethers (RO-BOM), which are cleaved more readily than the corresponding ROBn ethers. ... 

The following table shows how substituents can affect the relative rate of benzyl ether hydrogenolysis ... 

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. 

The 2,6-dimethylbenzyl ether is considerably more stable to hydrogenolysis than is the benzyl ether. It has a half-life of 15 h at 1 atm of hydrogen in the presence of Pd-C whereas the benzyl ether has a half-life of —45 min. This added stability allows hydrogenation of azides, nitro groups, and olefins in the presence of a di-methylbenzyl group. ... 

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). ... 

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. 

Pd/C, H2, EtOAc, >52% yield. The p-phenylbenzyl ether is more easily cleaved by hydrogenolysis than are normal benzyl ethers. This property was used to great advantage in the deprotection of the following vineo-mycinone intermediate ... 

Catalytic hydrogenation in acetic anhydride-benzene removes the aromatic benzyl ether and forms a monoacetate hydrogenation in ethyl acetate removes the aliphatic benzyl ether to give, after acetylation, the diacetate. Trisubstituted aDcenes can be retained during the hydrogenolysis of a phenolic benzyl ether. ... 

Platinum may be more useful than palladium in reduction of nitro compounds containing functions easily reduced by palladium. Hydrogenation of I over 5% Pd-on-C was nonselective with hydrogenolysis of the benzyl ethers competing with nitro hydrog ation, but over PtO in ethanol 2 was obtained in 96% yield (4). 

Hydrogenolysis (Section 26.7) Cleavage of a bond by reaction with hydrogen. Benzylic ethers and esters, for instance, are cleaved by hydrogenolysis. 

From intermediate 28, the construction of aldehyde 8 only requires a few straightforward steps. Thus, alkylation of the newly introduced C-3 secondary hydroxyl with methyl iodide, followed by hydrogenolysis of the C-5 benzyl ether, furnishes primary alcohol ( )-29. With a free primary hydroxyl group, compound ( )-29 provides a convenient opportunity for optical resolution at this stage. Indeed, separation of the equimolar mixture of diastereo-meric urethanes (carbamates) resulting from the action of (S)-(-)-a-methylbenzylisocyanate on ( )-29, followed by lithium aluminum hydride reduction of the separated urethanes, provides both enantiomers of 29 in optically active form. Oxidation of the levorotatory alcohol (-)-29 with PCC furnishes enantiomerically pure aldehyde 8 (88 % yield). 

The C2-symmetric epoxide 23 (Scheme 7) reacts smoothly with carbon nucleophiles. For example, treatment of 23 with lithium dimethylcuprate proceeds with inversion of configuration, resulting in the formation of alcohol 28. An important consequence of the C2 symmetry of 23 is that the attack of the organometallic reagent upon either one of the two epoxide carbons produces the same product. After simultaneous hydrogenolysis of the two benzyl ethers in 28, protection of the 1,2-diol as an acetonide ring can be easily achieved by the use of 2,2-dimethoxypropane and camphor-sulfonic acid (CSA). It is necessary to briefly expose the crude product from the latter reaction to methanol and CSA so that the mixed acyclic ketal can be cleaved (see 29—>30). Oxidation of alcohol 30 with pyridinium chlorochromate (PCC) provides alde-... 

The oxirane ring in 175 is a valuable function because it provides a means for the introduction of the -disposed C-39 methoxy group of rapamycin. Indeed, addition of CSA (0.2 equivalents) to a solution of epoxy benzyl ether 175 in methanol brings about a completely regioselective and stereospecific solvolysis of the oxirane ring, furnishing the desired hydroxy methyl ether 200 in 90 % yield. After protection of the newly formed C-40 hydroxyl in the form of a tert-butyldimethylsilyl (TBS) ether, hydrogenolysis of the benzyl ether provides alcohol 201 in 89 % overall yield. 

The completion of the synthesis of 1 only requires two deprotection steps. Hydrogenolysis of the four benzyl ethers, followed by cleavage of the triisopropylsilyl ether with hydrofluoric acid in acetonitrile, provides paeoniflorin (1) in an overall yield of 92 %. 

Hydrogenolysis of the C-7 benzyl ether, followed sequentially by selective triethylsilylation of the newly liberated C-7 hydroxyl and mesylation of the C-5 secondary hydroxyl, provides compound 34 in 60% overall yield (see 33—>34, Scheme 6). On the basis of Potier s studies,35 it was hoped that the C 20 hydroxyl group,... 

Palladium-catalyzed aminations of aryl halides is now a well-documented process [86-88], Heo et al. showed that amino-substituted 2-pyridones 54 and 55 can be prepared in a two-step procedure via a microwave-assisted Buchwald-Hartwig amination reaction of 5- or 6-bromo-2-benzyloxypyri-dines 50 and 51 followed by a hydrogenolysis of the benzyl ether 52 and 53, as outlined in Fig. 9 [89]. The actual microwave-assisted Buchwald-Hartwig coupling was not performed directly at the 2-pyridone scaffold, but instead at the intermediate pyridine. Initially, the reaction was performed at 150 °C for 10 min with Pd2(dba)3 as the palladium source, which provided both the desired amino-pyridines (65% yield) as well as the debrominated pyridine. After improving the conditions, the best temperature and time to use proved... 

The last reaction perhaps involves an intermediate such as 33a which expells a proton and dimethyl sulfide. Formation of the Schiff s base with t-butylamine, reduction with sodium borohydride and hydrogenolysis of the benzyl ether produces sulfonterol (28). Despite the fact that the methylene hydrogen of sulfonterol must be much less acidic than of the corresponding urea proton on carbuterol or the sulfonamide proton on soterenol, good bioactivity is retained. 

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