Functionalised alkynes as starting materials to build up valuable organic scaffolds

The synthesis of organic compounds is of great interest nowadays, primarily because of their application in multiple fields, even in everyday life. A major concern, however, is the impact that organic synthetic methodologies may have on both environment and human health. Because of this, great effort has been devoted to the development of novel efficient synthetic strategies, with the concept of efficiency shifting from the only consideration of the overall yield to a much more complex definition, including also waste production, energy requirements, toxicity and hazard of chemicals used. Alkynes are emerging as interesting building blocks in organic synthesis, thanks to their versatility and the ability to act as both nucleophiles and electrophiles, upon activation by Brønsted and Lewis acids. Moreover, the presence of proximal functional groups, such as carbonyl, amino and hydroxy groups, allows alkynes to undergo cascade one-pot reaction to generate complex organic architectures. The present PhD work is centred on the use of alkynes, in particular nitrogen-containing alkynes, to access valuable organic scaffolds, using efficient synthetic strategies such as multi-bond forming reactions, microwave-assisted organic synthesis and transition-metal catalysis. Four different types of alkyne-containing substrates (2-alkynylanilines, β-(2-aminophenyl)-α,β-ynones, propargylamines and ynamides) have been successfully employed in the synthesis of valuable organic compounds that are expected to have potential applications in medicinal chemistry, material sciences or as intermediates in the synthesis of more complex organic compounds. Moreover, the synthesis of ten new potential TRPM8 antagonists has been carried out in collaboration with Dompé Farmaceutici S.p.A.; the project focused on the design of new phenyl thiazole derivatives and on the planning of the synthetic sequences to obtain them, with a particular attention on the improvement of already-planned strategies, especially in terms of reduction of wastes and sources of potential contamination of the final product. Moreover, the introduction of an alkyne moiety in the thiazole core enabled to access interesting new isocoumarin analogues.