Cation-controlled chemoselective synthesis of N-aroylureas and imides via amidation of N-Boc arylamides

In this study, the first highly chemoselective amidation of Boc and amide groups of N-R-N-Boc arylamides is advanced. This practical and operationally-simple method enables the preparation of either N-aroylureas or imides in good to excellent yields without addition of transition metals. The choice of base plays a significant role in controlling the reactivity of the inequivalent carbonyl groups. The amidation of the Boc group was observed with arylamides, ArCONH2, when subjected to (KOBu)-Bu-t while imides were produced with LiOH. DFT studies are employed to explore the divergent mechanisms. It is anticipated that these chemoselective methods will be of interest to the synthetic and medicinal chemistry communities.

Automated summary

This study presents a highly chemoselective amidation method for the Boc and amide groups of N-R-N-Boc arylamides. The method is practical and easy to carry out, allowing for the preparation of N-aroylureas or imides in high yields without the use of transition metals. The choice of base determines the reactivity of the different carbonyl groups, with arylamides undergoing amidation with (KOBu)-Bu-t and imides being produced with LiOH. DFT studies are employed to investigate the mechanisms involved. These chemoselective methods are expected to be valuable in synthetic and medicinal chemistry.