Hydrogenolysis, of benzyl esters

Benzyl esters of carboxylic acids are frequently used in organic synthesis for the protection of carboxyl groups. The C-O bond in benzyl esters can be cleaved more easily than the corresponding benzyl ether bond. The hydrogenolysis of an ester leads to carboxylic acid and toluene. Examples of debenzylation of benzyl esters of carboxylic acids on Pd/C catalysts are summarized in Table 4.4. 

For certain hindered benzyl esters, tertiary amines are used as promoters. Such hydrogenolyses have been performed over 10% Pd/C in the presence of triethylamine in acetone at room temperature and 30 psi for 18 hours,201 or in t-BuOH at atmospheric pressure for 1.5 hours.202 

Both the benzyl ester and benzyl ether groups are hydrogenolyzed on Pd(OH)2/C,203 over Pd black in THF-H20-AcOH (16 4 1) under 1 atm H2 at 25°C for 8 hours,204 on Pd/C in THF-HC104,205 or over 10% Pd/C in MeOH.206 

Concomitant hydrogenolysis of a benzyl ester and hydrogenation of a diene were performed in one step over Pt02 in AcOEt.207 In contrast, 10% Pd(OH)2/C in AcOEt or EtOH at room temperature for 1 hour under hydrogen was used for the hydrogenolysis of a benzyl group without the saturation of a cyclic carbon-carbon double bond.208 

Removal of the 4-chlorobenzyl protecting group of a protected cryptand was performed under buffered condtions 210 in the presence of sodium ace- 

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The hydrogenolysis of benzyl esters provides a means for the selective eonversion of the ester to the acid under mild conditions. Substituted dibenzyl malonates are easily converted to the substituted malonic acids by hydrogenolysis in neutral medium thus avoiding the acyl cleavage or decarboxylation which can result from base or acid catalyzed ester hydrolysis (Eqns. 20.26-27).5 . 58 Monobenzylmalonates are selectively debenzylated and decarboxylated to give the substituted acetic esters. 

Hydrogenolysis of benzyl ester 202 furnished N-1 unsubstituted carboxylic acid 201 (R = H, = Me, X = O), which on decarboxylation yielded C-5 unsubstituted derivatives (76M587). While N-1 unsubstituted 22 (R = H, X = O) are inert toward acid or base hydrolysis, N-1 methyl 22 (R = Me, X = O) was saponified using 5% alcoholic KOH to carboxylic acid 201 (R = Me) (Scheme 76). The unreactivity of the ester may be attributed to strong conjugation with the adjacent vinylic alkene, supported by the fact that the hexahydropyrimidine carboxylic ester is readily hydrolyzed (33JA3781). 

The catalytic hydrogenolysis of benzyl esters — a well known and clean procedure in conventional peptide chemistry — recently was applied successfully to peptide cleavage from polystyrene supports [216]. The hydrogenation of the polymeric benzyl ester anchor bonds was performed in the presence of palladium II acetate with hydrogen at 60 psi,... 

A related fluorodenitration was shown to proceed efficiently allowing for transformation of benzyl 5-nitrofuran-2-carboxylate 35 into 5-fluoro derivative 36 in 59 % yield. The reaction did not proceed with methyl or tcrt-butyl esters as well as in the case of free acid or nitrile. Hydrogenolysis of benzyl ester allowed to obtain... 

The most useful property of benzyl esters is that they are readily cleaved by hydrogenolysis. 

The a-carbonyl function of a lactam was removed by transfer hydrogenolysis. Its benzyl ester was dissolved in MeOH under argon ammonium formate and 5% Pd/C were added and the reaction mixture was stirred for 1.5 hours.271,272... 

The platinum catalysts are universally used for hydrogenation of almost any type of compound at room temperature and atmospheric or slightly elevated pressures (1-4 atm). They are usually not used for hydrogenolysis of benzyl-type residues, and are completely ineffective in reductions of acids or esters to alcohols. At elevated pressures (70-210atm) platinum oxide converts aromatics to perhydroaromatics at room temperature very rapidly [5]. 

In contrast to phenolic hydroxyl, benzylic hydroxyl is replaced by hydrogen very easily. In catalytic hydrogenation of aromatic aldehydes, ketones, acids and esters it is sometimes difficult to prevent the easy hydrogenolysis of the benzylic alcohols which result from the reduction of the above functions. A catalyst suitable for preventing hydrogenolysis of benzylic hydroxyl is platinized charcoal [28], Other catalysts, especially palladium on charcoal [619], palladium hydride [619], nickel [43], Raney nickel [619] and copper chromite [620], promote hydrogenolysis. In the case of chiral alcohols such as 2-phenyl-2-butanol hydrogenolysis took place with inversion over platinum and palladium, and with retention over Raney nickel (optical purities 59-66%) [619]. 

Cleavage of a bond by the addition of hydrogen. For example, catalytic hydrogenolysis cleaves benzyl esters, (p. 1171)... 

Both catalytic and chemical methods are effective for the hydrogenolysis of benzyl ethers. Catalytic methods have found much wider use than the chemical methods, presumably because of the milder conditions that prevail. A general survey of the hydrogenolysis of benzyl compounds (benzyl amines, sulfides, and esters are also subject to hydrogenolysis to varying degrees) has recently been made, and the reader is referred to this discussion for a complete treatment of the scope of the reaction. 

Benzyl esters are versatile protecting groups for carboxylic acids. They are usually prepared from acid chlorides and benzyl alcohol in the presence of pyridine or from carboxylic acids and benzyl chloroformate in the presence of EtjN and a catalytic amount of DMAP. A very useful feature of benzyl esters is that they are readily depro-tected by hydrogenolysis. ... 

The most useful property of benzyl esters is that they are readily cleaved by hydrogenolysis. It is possible to hydrogenate an olefin and retain the benzyl ester. ... 

Catalytic hydrogenolysis of C—O bonds of benzyl esters and similar compounds by deuterium has rarely been used for preparation of labeled compounds, whereas predeuterated Pd in D20 is recommended for formation of deuterated alcohols from epoxides.63... 

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