Pd-Catalyzed One-Pot Stepwise Synthesis of Benzo[b][1,6]naphthyridines from 2‑Chloroquinoline-3-carbonitriles Using Sulfur and Amines As Nucleophiles

A palladium-catalyzed one-pot stepwise coupling-annulation reaction of 2-chloroqunoline-3-carbonitriles enabled the direct synthesis of sulfur-substituted benzo­[b]­[1,6]­naphthyridines via multiple bond formation. The reaction provided an unusual mode for cyclization as sodium sulfide, a soft nucleophile, preferred to attack on the carbon of the nitrile group rather than on the C–C triple bond. The developed chemistry was extended with the secondary amines as nucleophiles to afford nitrogen-substituted benzo­[b]­[1,6]­naphythyridines while primary amines afforded hydroamination products . The hydromination products were transformed to benzo­[b]­[1,6]­naphthyridones via a base-mediated cyclization reaction. The developed protocol features inexpensive and easily synthesizable starting materials, easy operations, and a high efficiency and tolerance to a broad range of substrates.