Dottorato in SCIENZE CHIMICHE

Titolo della tesi: Benzazetidines and Imidinium Ions as a versatile Building Blocks in Stereoselective Organic Synthesis

In this thesis work, three research projects are presented concerning the development of new synthetic strategies that identify benzazetidines and imidinium ions as key compounds for organocatalysis and asymmetric synthesis. In the first research project, benzazetidines have been synthetized by trapping an elusive cyclic, four-membered hemiaminal structure. The synthetic approach developed has no analogues in literature, being the first organocatalic approach completely metal free for the preparation of this substrates. We have demonstrated the flexibility of the reactions affording several benzazetidines in moderate to good yields (up to 81%). Furthermore, because a new stereocenter is generated from the intramolecular cyclization, preliminary experiments were carried out in order to develop an asymmetric version of this reaction. The second work presented the design of a novel class of chiral DMAP catalysts based on the PPY motif. We have designed a synthetic 3-step strategy that finds its strength in the use of a cheaper starting material (L-proline), in the use of mild reaction conditions and in a simple procedure, compared to the common strategies adopted in the literature. The catalytic activity of the catalyst was tested both in the kinetic resolution of secondary alcohols and in the enantioselective synthesis of benzazetidines. The first promising results, though modest, showing that the catalyst we have designed are able to perform enantioselective acyl transfer employed in catalytic amounts. The application of these new catalysts to asymmetric reactions could open new prospectives in synthetic organic chemistry, making this type of catalyst and its chemistry more accessible. Finally, a novel synthetic enantioselective strategy for the synthesis of enantioenriched γ-sulfonolactones and 1,4-dicarbonyl compounds has been investigated at the research laboratory of Prof. Nuno Maulide (University of Vienna, Austria) with the purpose of a future application of this synthetic approach for the preparation of useful natural molecules and drug. The approach developed involves the formation of a cyclic imidinium intermediate with three new stereocenters, generated by the nucleophilic addition of vinyl sulfoxides to activated amides. Satisfying results have been obtained leading to the products with a very good yield and high disteromeric ratio up to 11:9:83:6 (sulfonolactones) and 1:10 (1,4-dicarbonyls) in our best results.