C-C Cross-Coupling Reactions of O~(6)-Alkyl-2-Haloinosine Derivatives and a One-Pot Cross-Coupling/O~(6)-Deprotection Procedure

摘要

Reaction conditions for the C-C cross-coupling of O~(6)-alkyl-2bromo- and 2-chloroinosine derivatives with aryl-, hetaryl-, and alkylboronic acids were studied. Optimization experiments with silyl-protected 2bromo-O~(6)-methylinosine led to the identification of [PdCl_(2)(dcpf)]/K_(3)PO_(4) in 1,4-dioxane as the best conditions for these reactions (dcpf velence 1,1'-bis(dicyclohexylphosphino) ferrocene). Attempted O~(6)-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 O~(6)-deprotection could be accomplished in a single step. Thus, inosine 2chloro-O~(6)-allylinosine was chosen as the substrate and, after re-evaluation of the cross-coupling conditions with 2chloro-O~(6)-methylinosine as a model substrate, one-step C-C cross-coupling/ deprotection reactions were performed with the O~(6)-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.