NEW SYNTHETIC STRATEGIES FOR THE PREPARATION OF HETEROCYCLIC AND HETEROPOLYCYCLIC COMPOUNDS

The aim of the project of this doctoral thesis is the development of new synthetic strategies for the preparation of heterocyclic and heteropolycyclic compounds of potential interest in biological and pharmacological fields. In particular, we studied new general, flexible and regioselective synthetic approaches to oxygen and nitrogen heterocycles. We showed the versatility of nucleophilic addition/annulation domino reactions of alkyne compounds bearing a proximate nucleophile in the synthesis of heterocyclic systems, such as dihydroisobenzofurans, isoquinolines and naphthyridines. These approaches have been successfully transformed in Pd-catalysed multicomponent processes involving a one-pot coupling/addition/cyclisation sequence starting from the simple building blocks, such as ortho-bromoarylaldehydes, terminal alkynes and methanol or ammonia. In some cases, the reactivity of less reactive alkyne substrates has been enhanced by the catalysis of alkynophilic transition metals, such as gold and silver. In particular, we reported a new silver-catalysed approach to 2-methylisoquinolines and 5-methyl-1,6-naphtyridines by tandem addition/cyclisation of γ-ketoalkynes with ammonia. The domino approach has been also extended to 2-acetyl-N-propargylpyrroles for the synthesis of pyrrolo[1,2-a]pyrazine. In this case TiCl4 revealed to be the best promoter. Microwave heating demonstrated to be able to improve the efficiency of both domino and multicomponent processes. Finally, the project developed at the Institut für Organische und Biomolekulare Chemie in the Georg-August-Universität Göttingen (Germany), under the supervision of Prof. L. Ackermann, concerned with the direct arylations of indoles and pyrroles with differently substituted diaryliodonium salts in the absence of metal catalysts. The protocol proved broadly applicable, thereby enabling C-H bond functionalisations of free (NH)- as well as N-substituted indoles and pyrroles.