A Tandem Strategy: Wolff Rearrangement/Staudinger [2+2] Cycloaddition via Metal Carbenes for the Synthesis of Spiro[azetidine-3,3′-benzofuran]-2-ones
Abstract
The spiro[azetidine-3,3′-benzofuran]-2-one motif represents an important yet underexplored class of spirocyclic β-lactams, making the development of an efficient synthetic route to access this scaffold highly desirable. Herein, we report a concise tandem protocol for its synthesis from diazo compounds and imines. This tandem process proceeds through metal carbene formation, Wolff rearrangement, and Staudinger [2+2] cycloaddition to efficiently construct the target spirocyclic β-lactam with high diastereoselectivity. The practicality of this methodology was further demonstrated through a gram-scale synthesis and additional transformations. Notably, the synthesized compounds exhibited potent anti-influenza A virus activity, with an EC 50 value as low as 2.39 ± 0.21 μM.
Fields of Study & Subjects
Synthesis of β-Lactam Compounds
Cyclopropane Reaction Mechanisms
Synthesis and Catalytic Reactions
Publication details
- Journal / source
- The Journal of Organic Chemistry
- Publisher
- American Chemical Society (ACS)
- Volume
- 91
- Issue
- 2
- Pages
- 1086–1100
- Publication date
- 6 January 2026
- Language
- EN