Hydrogenolysis transfer

Despite of the popularity of benzyl as a protective group there is a lack of fundamental studies on the mechanism of hydrogenolysis [9]. It is probable that hydrogenolysis occurs via two reaction routes. The first mechanism is characteristic of Pd and Pt and proceeds mainly with inversion of configuration at the carbon atom, whereas the second occurs with Ni and Cu and configuration is retained [11]. With unsymmetrically substituted oxiranes the two mechanisms have different regio-selectivity-the sterically less hindered bond is cleaved on Pt and Pd, whereas the more hindered bond is ruptured on Ni and Cu [11]. At the same time cis- 

It is thought that unreduced metal ions might play an important role in the insertion mechanism (electrophilic catalysis). The type of metal, the method of preparation, and additives present can influence the concentration and stability of these ions. Oxygen-containing compounds can oxidize metal surfaces and so produce electrophilic sites [53]. 

An SN2-like mechanism is likely on primary carbon atoms whereas the reaction probably has high SnI character for compounds containing tertiary or benzylic carbon atoms. For this S l mechanism, however, inversion of configuration is also expected, because rotation around the sigma bond is difficult because of steric interaction of the large groups with the catalyst surface. 

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In addition to standard catalytic hydrogenolysis, methods for transfer hydrogenolysis using hydrogen donors such as ammonium formate or formic acid with Pd-C catalyst are available.216 The Cbz group also can be removed by a combination of a Lewis acid and a nucleophile for example, boron trifluoride in conjunction with dimethyl sulfide or ethyl sulfide.217... 

Pd/CaC03 is also used for the hydrogenolysis of benzyl-oxygen bonds.152 Hydrogenation and hydrogenolysis of an unsaturated benzyl ether over 5% Pt/ C and Pd(OH)2 gave the saturated and deprotected product.153 In contrast, transfer hydrogenolysis with 1,4-cylohexadiene or ammonium formate failed to provide the product cleanly, rapidly, or dependably. 

Transfer hydrogenolysis of benzyl acetate was studied on Pd/C at room temperature using different formate salts.244 Hydrogen-donating abilities were found to depend on the counterion K+ > NH4 + > Na+ > Li+ > H+. Formate ion is the active species in this reaction. Adsorption of the formate ion on the Pd metal surface leads to dissociative chemisorption resulting in the formation of PdH- and C02. The kinetic isotope effect proves that the dissociative chemisorption of formate is the rate-limiting step. The adsorption and the surface reaction of benzyl acetate occurs very rapidly. 

Selective removal of the benzyl ether-protecting group in compound 9 (Fig. 4.1) was made through both transfer hydrogenolysis and the conventional catalytic hydrogenolysis. 

Carbamates Both O-Bn and N-Cbz protecting groups have been removed by transfer hydrogenolysis (Scheme 4.59). 

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... 

In spite of the successful application of catalytic transfer hydrogenolysis in the case of benzylic compounds, this method is not suitable for the cleavage of the allylic C-O bonds. 

During the asymmetric synthesis of a-aminophosphonates (14 in Fig. 4.4), numerous attempts to cleave the benzylic C—N bond, involving catalytic or transfer hydrogenolysis, resulted in epimerization at the a-carbon.319... 

N-Substituted pyrrolidines were subjected to catalytic transfer hydrogenolysis affording pyrrolidines, but the yields were low. However, when di-tert-butyl dicarbonate was added to the N-substituted pyrrolidines before catalytic hydrogenolysis, the N-Boc derivatives were all formed in good yield (Scheme... 

Transfer hydrogenolysis using Pd/C and cyclohexene has been used for de-N-benzylation in peptide synthesis. This process, however, is not suitable... 

N,N-Debenzylation was accomplished by Pd/C and HC02NH4.349 Debenzy-lation of an N,N-dibenzyltryptamine derivative was sluggish and incomplete using Pd/C as the catalyst. In contrast, transfer hydrogenolysis using ammonium formate-formic acid in the presence of Pd black efficiently afforded the free tryptamine (27) (Scheme 4.102).350... 

During the asymmetric synthesis of erythro and threo a-substituted 3-amino esters, the dimethylbinaphthyl moiety (28 in Fig. 4.5) was removed using transfer hydrogenolysis. 

Catalytic hydrogenation of azo compounds over Pt or Ra-Ni often leads to hydrogenolysis. 551 Catalytic transfer hydrogenolysis using cyclohexene and Pd is also used for the conversion of azobenzenes to anilines.552... 

Water-soluble transition-metal complexes have been used recently for transfer hydrogenolysis of halocarbons. Paetzold and Oehme [110] have realized the reductive dehaiogenation of allyl or benzyl halides in the presence of [(phosphine) 2PdCl2] complexes with sulfonated phosphines as ligands (e.g., Ph2P(CH2)3S03K) by... 

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