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A non‐catalytic, mild, and easy‐to‐handle protecting group switched 1,3‐dipolar cycloaddition (1,3‐DC) between bi‐ or mono‐N‐protected Dha and C,N‐cyclic azomethine imines, which afford various quaternary amino acids with diverse scaffolds, is disclosed. Specifically, normal‐electron‐demand 1,3‐DC reaction occurs between bi‐N‐protected Dha and C,N‐cyclic azomethine imines, while inverse‐electron‐demand 1,3‐DC reaction occurs between mono‐N‐protected Dha and C,N‐cyclic azomethine imines. Above all, the reactions can be carried out between peptides with Dha residues at the position of interest and C,N‐cyclic azomethine imines, both in homogeneous phase and on resins in SPPS. It provides a new toolkit for late‐stage peptide modification, labeling, and peptide–drug conjugation. To shed light on the high regioselectivity of the reaction, DFT calculations were carried out, which were qualitatively consistent with the experimental observations. [ABSTRACT FROM AUTHOR]

Enantioselective synthesis of imidazolidin-5-ones through a phosphoric acid catalyzed reaction between azlactones and N-substituted β-carbolines is reported. The reaction takes place via an initial formal [2+2] cycloaddition to generate an a-amino-β-lactam, which subsequently undergoes an acid-catalyzed asymmetric penicillin–penillonic acid (PPA) rearrangement with high diastereo- and enantioselectivity. To the best of our knowledge, this represents the first [2+2] cyclization of azlactones with imines and the first asymmetric PPA rearrangement, which are linked together by the phosphoric acid catalyst. [ABSTRACT FROM AUTHOR]