Benzyl derivatives hydrogenolysis

Attempted synthesis of 3-methylinosine by treatment of JV,iV-dimethyI-adenosine with excess methyl iodide failed because glycosyl cleavage occurred. Although the synthesis was successful with the 2, 3, 5 -tri-0-benzyl derivative, hydrogenolysis to deblock the product resulted in reduction of the purine ring. The problem was overcome by use of the 2, 3, 5 -tribenzoate. The ribosyl bond in 3-methylinosine was found to be unusually susceptible to acid... 

Benzyl carbamates substituted with one or more halogens are much more stable to acidic hydrolysis than are the unsubstituted benzyl carbamates.For example, the 2,4-dichlorobenzyl carbamate is 80 times more stable to acid than is the simple benzyl derivative. Halobenzyl carbamates can also be cleaved by hydrogenolysis with Pd-C. The following halobeni yl carbamates have been found to be useful when increased acid stability is required. 

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-... 

M. C. Cruzado and M. Martin-Lomas, The heterogeneous, catalytic, transfer hydrogenolysis of tri-O-benzyl derivatives of 1,6-anhydro-p-rvhexopyraiioses, Carbohydr. Res. 770 249 (1987). 

O-Deacetylation of J58 and successive O-benzylation gave the tri-O-benzyl derivative (159), [a]p +36.7° (chloroform). When 159 was hydrolyzed with aqueous acetic acid and subsequently hydrogenated with sodium borohydride, the compound (160), [a] + 4.4° (chloroform), was obtained. Periodic acid oxidation of 160 and reduction with sodium borohydride afforded 4,6-di-0-acetyl-l,2,3-tri-0-benzyl-pseudo-(3-L-allopyr-anose (161), [a] —40.2° (chloroform), after acetylation. Catalytic hydrogenolysis of 161 and successive acetylation gave pseudo-P-L-allopyranose pentaacetate (162), m.p. 135-136 °C, [a] f +3.7° (chloroform) [36]. (Scheme 25). 

Hydrogenation of 38b under mild conditions yields the dimeric yttrium hydrides 44b (Eq. 17). The benzyl derivatives 39b can also be used as starting materials, but the rate of hydrogenolysis is considerably slower due to the presence of coordinated THF. The dimeric hydrides are extremely sensitive towards oxygen and moisture but thermally quite stable [27, 55, 65, 66]. 

Because 1-methyl vincoside and its dihydro derivative were spontaneously lactamized, for studies of the subsequent cyclization their aglucones (3i -93a)=(3/ -4-debenzyl-96a) and (3i -93b)=(3i -4-debenzyl-96b) were prepared in situ by catalytic hydrogenolysis of their benzyl derivatives (3i -96a) and (3i -96b). 

Hydrogenolysis can occur using dissolving metal conditions, and is particularly useful for the cleavage of O-benzyl and N-benzyl derivatives. It is widely used as a useful alternative to catalytic hydrogenation. Treatment with sodium in ammonia cleaves the O-benzyl group, as in the conversion of 491 to 492 (in 90% yield), in Mulzer s synthesis of hastanecine. l Note that the byproduct is toluene. It is also possible to cleave other reactive C—O (or C—N) bonds. Allylic acetates, for example, are cleaved to the hydrocarbon, as shown by the reaction of 493 with lithium and ammonia to give an 81% yield of 494. ... 

Nitrogen on heterocycles has frequently been protected as the Af-benzyl derivative. Thus, 2-benzylimidazole 399 was successfully debenzylated to 400 in excellent yield (Scheme 118).[i i It should be noted that the benzylic ketone in 399 was not hydrogenated. Transfer hydrogenolysis with ammonium formate was also effective for the removal of the benzyl group in A -benzyl-2-methylimidazole. 

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