Indole as Neutral Leaving Group in Silver Nitrate Induced Cyclization Reactions of N-{2-[Alkynyl(hetero)aryl]methylene}indolin-1-amines for the Synthesis of Annulated Pyridine Derivatives

N-{2-[Alkynyl(hetero)aryl]methylene}indolin-1-amines 3 undergo, upon treatment with silver nitrate in chloroform at 60 degrees C, electrophilic cyclization reactions to afford annulated pyridine derivatives 4. Mechanistically, the silver(I)-assisted 6-endo-dig ring-closure process of compounds 3 leads to the formation of an intermediate pyridinium cation, which releases - besides the products 4 - indole as unusual but efficient neutral leaving group after N-N bond cleavage. It is shown that among the hydrazones studied, only the 1-amino-indoline-derived substrates N-{2-[alkynyl(hetero)aryl]methylene}indolin-1-amines 3 are suitable to produce annulated pyridine derivatives 4 in high yield. The reaction can be performed in air and even in the presence of water in the reaction medium. Since during the course of the reaction indole is oxidized by the silver(I) ions, stoichiometric amounts of silver salt are required. Quantum chemical calculations have been applied in order to gain additional information on the reaction mechanism and the key reactive intermediates.