Preparation of Lactams from Cyclic Anhydrides via N‐Carboxyanhydride Intermediates

Abstract

AbstractThe ring contraction‐lactamisation of anhydrides upon reaction with trimethylsilylazide in the presence of an amine catalyst has been studied. Under controlled conditions, 5,‐ 6‐ and 8‐membered ring lactams can be generated from cyclic anhydrides in an operationally simple procedure. In the case of γ‐lactams, the methodology allows for the synthesis of challenging systems incompatible with the usual disconnection involving an amine and an activated carbonyl group. The synthesis of simple larger ring lactams is hampered by inaccessible monomeric cyclic anhydride precursors ‐ a problem which can be circumvented through rigidification. Succinic anhydrides make N‐carboxyanhydrides of use in polymer chemistry and as β‐peptide precursors.