Ring Expansion Of Thiolactams Via Imide Intermediates: An Amino Acid Insertion Strategy

The Ag-I-promoted reaction of thiolactams with N-Boc amino acids yields an N-(alpha-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.