Palladium-catalyzed aryl amination reactions of 6-bromo- and 6-chloropurine nucleosides

Article abstract of DOI:10.1002/adsc.200900728

Palladium-catalyzed C-N bond forming reactions of 6-bromo- as well as 6-chloropurine ribonucleosides and the 2′-deoxy analogues with arylamines are described. Efficient conversions were observed with palladium(II) acetate/Xantphos/cesium carbonate, in toluene at 100°C. Reactions of the bromonucleoside 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 [10mol% Pd(OAc)₂/ 15 mol% Xantphos] when the chloro analogue was employed. Among the examples evaluated, silyl protection for the hydroxy groups appears better as compared to acetyl. The methodology has been evaluated via reactions with a variety of arylamines 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.