Hydrogenolysis of benzyl groups

W. H. Hartung u. R. Simonoff, Hydrogenolysis of Benzyl Groups Attached to Oxygen, Nitrogen, or Sulfur, Organic Reactions, Vol.VII, S. 263—326, John Wiley Sons, London 1963. 

Hydrogenolysis of benzyl groups attached to oxygen, nitrogen, or sulfur. Hartung, W.H., Simonoff, R., Org. Reactions 7, 263 (1953). 

Debenzylation by reductive cleavage over palladium metal catalysts with molecular hydrogen has been widely utilized for many decades. A comprehensive review of the early literature on hydrogenolysis of benzyl groups emphasized the main applications and described a number of preparative procedures which are still frequently used, along with a wider range of newer chemical and catalytic methods. 

Many of the difficulties experienced with heterogeneous Pd-catalyzed hydrogenolysis of benzyl groups have been overcome by deploying such alternatives to molecular hydrogen as cyclohexene and formate anion. A recent review of catalytic transfer hydrogenation describes the application to hydrogenolysis of benzyl and allyl derivatives. ... 

Low pressure hydrogenation. A soln. of 3-indoleacetonitrile in ethanolic 10 %-NHg hydrogenated with Rh-on-alumina at 2.5 atm. until after less than 2 hrs. 2 moles of H2 have been absorbedtryptamine. Y 78.2%.—No hydrogenolysis of benzyl groups occurs with the above catalyst. F. e. s. M. Freifelder, Am. Soc. i2, 2386 (1960). 

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. 

Benzyl-oxygen bonds may be cleaved under conditions mild enough to leave an allylic hydroxy group (759) or an easily reduced N—OH bond intact (65,80). N-Hydroxyamino acids can be prepared in good yield by hydrogenolysis of benzyl hydroxamates as shown in the synthesis of N -hydroxylysine (6) from 5 (777). 

The structure of the substrate influences the rates of hydrogenolyses. Over Pd, the rates of hydrogenolysis of benzyl derivatives increase in the order OH < OR OAr < OCOR, according to their leaving group ability. Therefore, ben-... 

FIGURE 3.3 Deprotection of functional groups by reduction. Hydrogenolysis of benzyl-based protectors.1 Attack by electrons liberates the protector as the benzyl anion because the latter is stabilized by resonance. This is a simplified presentation of the reaction. 

Hydrogenolysis of benzyl alcohols 0-79 Reduction of benzylic ethers 0-86 Coupling of halides containing aryl groups... 

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