Modular Synthesis of Cyclopropane‐Fused N‐Heterocycles Enabled by Underexplored Diazo Reagents

Cyclopropane-fused N-heterocycles are featured in various biologically active compounds and represent attractive scaffolds in medicinal chemistry. However, synthesis routes to access structurally and functionally diverse cyclopropane-fused N-heterocycles remain underexplored. Leveraging novel α-diazo acylating agents, we report a general approach for the direct and modular synthesis of cyclopropane-fused lactams from unsaturated amines. The operationally simple transformation, which proceeds through successive acylation, (3+2) cycloaddition and fragmentation, tolerates a broad range of functional groups and yields a wide spectrum of complex molecular scaffolds, including fused, bridged and spiro ring systems. We demonstrate the utility of this transformation in the concise syntheses of therapeutic agents milnaciprane and amitifadine.