C-H Functionalization of Peptides via Cyclic Aminal Intermediates

Protected dipeptides can be converted into cyclic ketoaminals, which can be subjected to palladium-catalyzed regioselective C-H functionalization. The best results are obtained using the 2-(methylthio)aniline (MTA) directing group, which is superior to the commonly used 8-aminoquinoline (AQ) group. No epimerization of stereogenic centers is observed. Subsequent cleavage of the directing and protecting groups allows the incorporation of a modified dipeptide into larger peptide chains.

Automated summary

Protected dipeptides can be converted into cyclic ketoaminals, which can undergo palladium-catalyzed regioselective C-H functionalization. The use of the MTA directing group was found to be superior to the commonly used AQ group. Incorporation of modified dipeptides into larger peptide chains is possible after cleavage of the directing and protecting groups.