Cyclopropyl-1,1-Dinitrile as a Five-Atom Synthon: Regioselective Ring-Opening and a Keteneimine–Enamine-Based Nitrile-to-Nitrile Condensation Affording an Entry to Pyridines

Key Points

• The research aims to explore a novel reaction pathway involving cyclopropyl-1,1-dinitriles for synthesizing polyfunctionalized pyridines.
• Donor-acceptor cyclopropane (DAC) ring-opening was conducted under regioselective conditions.
• Control experiments, DFT calculations, and synthesis of N-heterocycles were performed to validate the process.
• Utilized a metal-DAC-nitrile complex and BTMG for efficient reaction progression.
• Achieved regioselective ring-opening of DAC yielding aryl-cyclopropyl-1,1-dinitriles.
• Synthesis of polyfunctionalized pyridines demonstrated effective utilization of the ketene-amine-enamine-guided condensation.
• New versatile N-heterocyclic skeletons and drug motifs were successfully synthesized.