Tritiolyses of Benzylic N- and O-Functions

Palladium catalysts are well known to cleave N- and 0-benzyl moieties this can either be an opportunity or a serious side reaction in palladium-catalyzed tritiolyses of halo compounds. Again, the presence of an appropriate base may enhance the desired selectivity. In the case of 159 (X = Br), tritiodebromination over 5% Pd/C in ethanol in the absence of added base produced significant amounts of debenzylated bromo compound 160. whereas reduction in pyridine provided exclusively 159 (X = H) in excellent yield and at high specific activity °. Analogous results were obtained with the compound 134 above. In contrast, conditions giving satisfactory selectivity between tritiodebromination of 161 could not be found and the more reactive iodo analog 162 had to be resorted to (6kPa H2, Pd(OH)2, EtOH, 

Of commercial interest is the palladium-catalyzed tritiodeoxygenation of 5-formyluracil ( 165 ) to [methyl- H ]thymine (167). Aldehyde 165 could be reduced directly to 167 in the presence of acid, but the specific activity of the produce was only 29.7 Ci/mmol, about half of the theoretical level. The low pH of the protic medium probably contributed to this through relatively rapid tritium gas exchange with solvent. When the reaction sequence was carried out in two steps, by reduction of 165 to 166 in pH 7 buffer followed by tritideoxygenation in dioxane in the presence of PdCU to form the requisite acid in situ, [methyl- H ]thymine was obtained with a specific activity of 68.9 Ci/mmol, even higher than the 58 Ci/mmol expected for incorporation of two tritium atoms. In this case, H/H exchange of the formyl proton during the first step was proffered as the explanation for the increased tritium content of the product. 

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Figure 4.46 Selective deuteriodehalogenations catalyzed by Pd(PPhj)4 4.2.2 Tritiolyses of Benzylic N- and O-Functions...

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