Conventional methods for the construction of dehydroamino acids (ΔAAs), which are a unique class of nonproteinogenic amino acids, require the pre-installation of special amino acids. Herein, we report and demonstrate the practical utility of an N-chloropeptide strategy for the rapid construction of ΔAA-containing peptides. The electrophilic Nchlorination of peptide bonds is drastically accelerated by a catalytic amount of quinuclidine (ABCO), and the subsequent β-elimination of N-chloroamide efficiently provides ΔAAcontaining peptides in high yield. The strategy enables, for the first time, the construction of a wide variety of ΔAA residues in peptides without any pre-functionalized side chains and facilitates the late-stage installation of ΔAA motifs into already-constructed oligopeptides, including a medicinally important macrocyclic peptide.

A N‐chloropeptide strategy enables the rapid construction of ΔAA‐containing peptides. The quinuclidine (ABCO)‐catalyzed N‐chlorination of peptide bonds and the subsequent β‐elimination of N‐chloroamide efficiently provides ΔAA‐containing peptides in high yield. The strategy enables the late‐stage installation of ΔAA motifs into oligopeptides that have already been constructed, including into a macrocyclic peptide. More information can be found in the Research Article by T. Nanjo, Y. Takemoto, and co‐workers (DOI: 10.1002/chem.202201120).