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Acid-Mediated Ring Expansion of 2,2-Disubstituted Azetidine Carbamates to 6,6-Disubstituted 1,3-Oxazinan-2-ones
- Boddy, Alexander J., Cordier, Christopher J., Goldberg, Kristin, Madin, Andrew, Spivey, Alan C., Bull, James A.
- Organic letters 2019 v.21 no.6 pp. 1818-1822
- Bronsted acids, ambient temperature, carbamates, chemical reactions, chemical structure, drugs
- The ring expansion of 2-ester-2-arylazetidine carbamates can be achieved using Brønsted acids to form 6,6-disubstituted 1,3-oxazinan-2-ones. The reaction is rapid at room temperature with Boc or Cbz derivatives and proceeds with excellent yield (up to 96%) and broad substrate scope. Derivatives of drug compounds and natural products are incorporated. The combination of this ring expansion in a three-step N–H insertion/cyclization/expansion sequence is applied to directly access medicinally relevant scaffolds from acyclic precursors.