A Tandem Strategy: Wolff Rearrangement/Staudinger [2+2] Cycloaddition via Metal Carbenes for the Synthesis of Spiro[azetidine-3,3′-benzofuran]-2-ones

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 EC₅₀ value as low as 2.39 ± 0.21 μM.