Benzylation catalyst poisoning

In a penicillin synthesis, the carboxyl group was protected as a / -bromophenacyl ester that was cleaved by nucleophilic displacement (PhSK, DMF, 20°, 30 min, 64% yield). Hydrogenolysis of a benzyl ester was difficult (perhaps because of catalyst poisoning by sulfur) basic hydrolysis of methyl or ethyl esters led to attack at the /3-lactam ring. ... 

Pd-C(en), H2, Dabco or DMAP, MeOH. Benzyl esters are cleaved in the presence of N-Cbz groups unless the Cbz is attached to an aromatic amine which gives competitive hydrogenolysis. These conditions also reduce olefins in the presence of benzyl ethers. 2,2 -Dipyridyl also serves as a catalyst poison that will allow the selective hydrogenolysis of a benzyl ester in the presence of a benzyl phenyl ether. 

The adduct resulting from this Ugi-Smiles coupling contains an N-aryl unit that offers great synthetic potential for further functionalization. Scheme 5.26 shows just one such an example. The reaction of 2-iodo-4-nitrophenol (90) with allylamine, 3-methylbutanal, and benzyl isocyanide in the presence of ammonium chloride afford the Ugi-Smiles adduct 91, which, without purification, underwent palladium-catalyzed Heck cydization to afford indole 92 in 72% yield. Trifluoroacetic add (O.lequiv.) was introduced before addition of the palladium catalyst in order to destroy any remaining isocyanide, which was harmful to the subsequent cydization due to catalyst poisoning [51]. 

Treatment of benzyl 2-acetamido-4,6-0-benzylidene-2 deoxy-D-glucopy-ranoside and related muramyl-peptide derivatives with sodium in liquid ammonia removed both the benzyl and benzylidene groups simultaneously, providing a useful alternative to catalytic hydrogenation for glyco-peptides which are catalyst poisons. " Benzyl 2-acetamido-2-deoxy- -D-glucopyrano-side has been converted to the muramic acid derivative (20) which was used to... 

Minute amounts of halide have a powerful poisoning effect upon the catalyst it is advisable to distil the benzyl cyanide from Raney nickel. 

Catalytic transfer hydrogenation (entries 2 and 3 below) can be used to cleave benzyl esters in some compounds that contain sulfur, a poison for hydrogenolysis catalysts. 

It was found in the case of O-benzyl systems that palladium oxide is much more effective than palladium metal. No such effect was observed with the N-benzyl system.8 It is possible that the N-compounds can poison the electrophile metal ions, and the hydrogenolysis of the N-benzyl bond can take place only by the hydrogenolytic cleavage instead of the insertion mechanism. This is supported by the experimental finding that the product amine can inhibit the catalyst, and this can be minimized by buffering at a pH less than 4. 

Benzyl cyanide, prepared according to Org. Syn. Coll. Vol. 1, 1941, 107, should be distilled from Raney nickel. Minute traces of halide ha - a strong poisoning effect on the catalyst. If the reduction does not occur within an hour, the contents of the bomb should be removed and filtered. New catalyst is then added and the process is repeated. 

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