Synthesis of Diverse N‑Acryloyl Azetidines and Evaluation of Their Enhanced Thiol Reactivities

Acyl azetidines exhibit nonplanar hybridization, leading to lower amide-like character of the corresponding (O)­C–N bonds. This impacts N-acryloyl azetidines by producing enhanced electrophilicy at appended Michael acceptors. Herein, reactivity data are reported in the presence of glutathione (GSH) in phosphate buffer (pH 7.4) at 37 °C. Wide reactivity ranges are observed by varying substitution at the Michael acceptor or by modulating the electron-withdrawing character of substituents at the C3 position of the azetidine.