Bpin-Enabled Nickel/Brønsted Acid Relay-Catalyzed Reductive [2+2+2] Cycloaddition: Facile Access to Unsymmetric Pentacyclic Pyridine Derivatives.

Herein, an unprecedented nickel/Brønsted acid relay-catalyzed reductive [2+2+2] cycloaddition that enables efficient construction of pentacyclic pyridine frameworks is reported. Mechanistic studies reveal that this transformation proceeds through a distinctive sequence involving azanickelacyclopentadiene intermediates, followed by unconventional protonation, dimerization, and cyclization steps. The proposed mechanism was systematically verified through controlled experiments and isotopic labeling mass spectrometry analysis. This work not only expands the structural diversity accessible through transition-metal-catalyzed [2+2+2] cycloadditions but also highlights the broad potential of relay catalysis strategies in mediating cycloaddition reactions of unsaturated substrates.