C–C Cross-Coupling Reactions of O6-Alkyl-2-Haloinosine Derivatives and a One-Pot Cross-Coupling/O6-Deprotection Procedure

摘要

Reaction conditions for the C–C cross-coupling of O⁶-alkyl-2-bromo- and 2-chloroinosine derivatives with aryl-, hetaryl-, and alkylboronic acids were studied. Optimization experiments with silyl-protected 2-bromo-O⁶-methylinosine led to the identification of [PdCl2(dcpf)]/K3PO4 in 1,4-dioxane as the best condition for these reactions (dcpf = 1,1’-bis(dicyclohexylphosphino)ferrocene). Attempted O⁶-demethylation, as well as the replacement of the C-6 methoxy group by amines, was unsuccessful, which led to the consideration of Pd-cleavable groups such that C–C cross-coupling and O⁶-deprotection could be accomplished in a single step. Thus, inosine 2-chloro-O⁶-allylinosine was chosen as the substrate and, after re-evaluation of the cross-coupling conditions with 2-chloro-O⁶-methylinosine as a model substrate, one-step C–C cross-coupling/deprotection reactions were performed with the O⁶-allyl analogue. These reactions are the first such examples of a one-pot procedure for the modification and deprotection of purine nucleosides under C–C cross-coupling conditions.