A Metal-Free Cyclobutadiene Reagent for Intermolecular [4+2] Cycloadditions

Cyclobutadiene is a highly reactive antiaromatic hydrocarbon that has fascinated chemists for over sixty years. However, its preparation and uses in chemical synthesis are sparing, in part due to its lengthy synthesis that generates hazardous byproducts including excess heavy metals. Herein, we report a scalable, metal-free cyclobutadiene reagent, diethyldiazabicyclohexene dicarboxylate, and explore its intermolecular [4+2] cycloadditions with various electron-deficient alkenes. We also demonstrate its utility in a three-step total synthesis of dipiperamide G, and a diverse array of derivatizations including bromocyclobutadiene.