Palladium‐Catalyzed Aryl Amination Reactions of 6‐Bromo‐ and 6‐Chloropurine Nucleosides

Palladium-catalyzed C-N bond forming reactions of 6-bromo- as well as 6-chloropurine ribonucleosides and the 2'-deoxy analogues with aryl amines are described. Efficient conversions were observed with Pd(OAc)(2)/Xantphos/Cs(2)CO(3), in PhMe at 100 °C. Reactions of the bromo nucleoside derivatives could be conducted at a lowered catalytic loading (5 mol % Pd(OAc)(2)/7.5 mol % Xantphos), whereas good product yields were obtained with a higher catalyst load (10 mol % Pd(OAc)(2)/15 mol % Xantphos) when the chloro analogue was employed. Among the examples evaluated, silyl protection for the hydroxyls appears better as compared to acetyl. The methodology has been evaluated via reactions with a variety of aryl amines and by synthesis of biologically relevant deoxyadenosine and adenosine dimers. This is the first detailed analysis of aryl amination reactions of 6-chloropurine nucleosides, and comparison of the two halogenated nucleoside substrates.