SILVER CATALYSED INTRAMOLECULAR CYCLISATION OF 2-ALKYNYL-ACETOPHENONES AND 3-ACETYL-2-ALKYNYLPYRIDINES IN THE PRESENCE OF AMMONIA

The development of new domino approaches for the synthesis of nitrogen containing heterocycles is a research field in continuous evolution. In particular, for many years we have been interested in the synthesis of nitrogen containing rings starting from alkyne derivatives in the presence of ammonia. Recently we reported a valuable approaches to the synthesis isoquinolines starting from 2-alkynyl-benzaldehydes,2 and the approach was also successfully transformed in a multicomponent process.3 Unexpectedly, when we tried to react 2-alkynylacetophenone derivatives under optimized conditions the reaction failed. This result prompt us to investigate the reaction of alkynyl ketones more in depth. We started our study looking for the best conditions to trigger the domino reaction on a model compound. We tried some metal catalysts potentially able to promote both the imine formation as Lewis acid, and the intermolecular hydroamination step as alkynophilic catalysts.4 We were delighted to find that the metal catalysed reaction gave the desired isoquinoline, beside variable amounts of the isomeric naphthalen-1-amine. The best results were obtained with AgOTf in terms of conversion, selectivity and reaction times. Scope and limitation of the approach have been extensively studied. We found that the silver-catalyzed/microwave-promoted domino imination/annulation of alkynes bearing a proximate carbonyl group in the presence of ammonia is an interesting alternative for the synthesis of aromatic heterocycles and carbocycles. A plausible mechanism is also suggested.