Selective Deprotonated Amide Activation of Dehydroalanine for Peptide Modification.

Herein, we have discovered a unique deprotonated amide activation of dehydroalanine and developed a remote functionalization reaction of the double bond under mild conditions. The reaction exhibits good chemoselectivity and site-selectivity and is compatible with different kinds of peptides. Mechanistic studies first disclose in situ generated electron-rich enamine after deprotonation of amide hydrogen in Dha, followed by an intermolecular charge transfer process between the enamine and diaryliodonium salt.