Intercepting Methanimine for the Synthesis of Piperidine-Based N‑Heterocycles in an Aqueous Medium

We herein present an investigation into whether simple methodology could be used to intercept the highly reactive interstellar molecule methanimine. The use of an in situ aza-Diels–Alder reaction to trap out methanimine as simple piperidine-based N-heterocycles was explored. Subsequent investigations into alternative dienes revealed that the steric and electronic nature of the diene had a great effect on its effectiveness in trapping methanimine. While the yields of the resultant N-heterocycles are modest, the products formed are novel yet structurally simple and could be envisioned to be highly synthetically useful building blocks for further transformations. We also explored simple protecting groups that could be used to access a methanimine adduct as a discrete synthon, but density functional theory calculations indicated that cyclotrimerization, and thus deactivation, was likely.