Ring Expansion of Thiolactams via Imide Intermediates: An Amino Acid Insertion Strategy

The AgI‐promoted reaction of thiolactams with N‐Boc amino acids yields an N‐(α‐aminoacyl) lactam that can rearrange through an acyl transfer process. Boc‐deprotection results in convergence to the ring‐expanded adduct, thereby facilitating an overall insertion of an amino acid into the thioamide bond to generate medium‐sized heterocycles. Application to the site‐specific insertion of amino acids into cyclic peptides is demonstrated. Put a ring on it: AgI‐promoted reaction of thiolactams and amino acids enables an insertion‐ring expansion process of an amino acid into the thioamide bond to generate medium‐sized heterocycles. Application to the site‐specific insertion of amino acids into cyclic peptides is demonstrated.