Lewis Acid catalysis in the Synthesis of Small Molecules: Carbon-Nitrogen bond formation

Nitrogen containing compounds are of great importance due to their interesting and different biological activities. The construction of C-N bond is for this of significant importance because it allows the introduction of the nitrogen atoms in organic molecules. Despite the numerous advancements, the construction of the C-N bond is still a major challenge especially the development of alternative, milder and cheaper methodologies. The project during my doctorate in the group of prof. Cristina Cimarelli and prof. Enrico Marcantoni has been mainly focused on the application of Lewis acid catalysis for the formation of C – N bonds in the synthesis of small molecules, in particular to the formation of secondary propargylamines. A brief introduction to importance of propargylamines both from biological point of view and as versatile buildings block for the synthesis of nitrogen containing heterocycles will be given. Then the A coupling reaction will be presented, the most common synthetic strategies to afford these class molecules. Finally the key-role of copper acetylides in various reactions and the applications of two different Lewis acids, iodine and cerium trichloride hephtahydrate in the formation of the C – N bond. Since their first synthesis by Charles J. Pedersen in the 1960’s, crown ether or cyclic polyethers have received a particular attention. The unique structure of the crown ethers has attracted the attention of many scientists both in organic synthesis and in drugdelivery process with also the formulation of nano-drugs. Recently, the group of Prof. Jérôme Lacour reported the straightforwards synthesis of chiral crown ethers (cyclic polyethers) obtained from simple cyclic ether building blocks (5,6,7-membered rings), α-diazo- β-ketoesters and aromatic amines. This particular family of molecule were applied in field as various as asymmetric catalysts, ion and salt receptors, (chiro)optical switches and pH-indipendent nanosensors. The project during my internship in the group was to study through various spectroscopic techniques the possibility to use the chiral macrocycles as chiral ligand for metal ions and in particular lanthanides. The interaction between terbium(III)salt and various macrocycles (ligand) bearing different aromatic moieties (antenna) was studied. Depending on the nature of the cyclic ring and the antenna, the affinity of terbium for the ligand could be measured by absorbance, fluorescence, circular dichroism (ECD) and circularly polarized luminescence (CPL). A brief introduction on the importance and general synthesis of macrocycles and later on crown ethers with their applications will be presented first. Then the macrocyclization strategies from diazo precursor, a versatile building blocks for various reaction. A particular focus on the synthetic approach developed by the group of prof. Jérôme Lacour in Geneva for the chiral crown ether synthesis will be given. Finally the formation of the complex with lanthanide and the CPL will be described.