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

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 NH4Cl 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 Et3N·3HF or TFA afforded a series of free C-ribonucleosides 3a–j or 6a–j in excellent yields (20 examples).