Silver-Catalyzed Tandem Synthesis of Naphthyridines and Thienopyridines via Three-Component Reaction

An
efficient approach for the silver-catalyzed regioselective tandem
synthesis of highly functionalized 1,2-dihydrobenzo­[1,6]­naphthyridines 6a–z and 7a–e by the reaction of ortho-alkynylaldehydes 3a–n with amines 4a–d and ketones 5a–c/active
methylene compounds 5d–g, under mild
reaction conditions, is described. The scope of the developed chemistry
was successfully extended for the direct synthesis of 1,2-dihydrobenzo­[4,5]­thieno­[2,3-c]­pyridines 8a–e, which
is known as the sulfur analogue of β-carbolines. Naphthyridines 6a–z and thienopyridines 8a–e were obtained via dual activation concept
using l-proline as organocatalyst; however, naphthyridines 7a–e were synthesized without using organocatalyst.
The reaction shows selective N–C bond formation on the more
electrophilic alkynyl carbon, resulting in the regioselective 6-endo-dig-cyclized products. Reactivity
behavior of electron-deficient and electron-rich ortho-alkynylaldehydes in the synthesis of naphthyridines and thienopyridine
by three-component reaction is supported by the control experiment.