Non-benzenoid N -aryl oxalamide: synthesis of troponyl-oxalamide peptides by Pd(II)-catalyzed C(sp 3 )-H functionalization of glycinamides.

Aryl oxalamides are constituents of various promising drug-like molecules. Their aryl groups are derived from the benzenoid aromatic moiety. However, non-benzenoid aromatic molecules, troponoids, are found in various bioactive natural products. It would be thought-provoking to explore non-benzenoid aryl oxalamide derivatives. This report describes the synthesis of N -troponyl-oxalamide peptides by Pd(II)-catalyzed C(sp 3 )-H functionalization of N -troponyl glycinate peptides. This is the first instance of β-hydride elimination at the palladium complex of N -troponyl glycinates that generates imine in situ , rendering the synthesis of oxalamides. Importantly, the crystal structures of representative oxalamide derivatives form distinctive foldameric structures, such as β-sheet type structures, owing to the presence of additional troponyl carbonyl groups. Hence, these non-benzenoid oxalamides are potential scaffolds for tuning the structure and function of N -troponyl peptides, which could provide innovative avenues of research in the development of emerging structural and functional peptides.