Synthesis of benzamide- C-ribonucleosides by Pd-catalyzed aminocarbonylations

Abstract

A novel modular, efficient and practical methodology for preparation of p- and m-substituted benzamide- C-ribonucleosides was developed. Reaction of TBS-protected 3- and 4-bromophenyl- C-ribonucleosides 1 and 4 with various primary and secondary amines or NH 4Cl under atmospheric pressure of carbon monoxide and in the presence of Pd(OAc) 2 and Xantphos lead to the corresponding amides 2a– j and 5a– j in high yields. Subsequent deprotection of silylated nucleosides by Et 3N·3HF or TFA afforded a series of free C-ribonucleosides 3a– j or 6a– j in excellent yields (20 examples).