One-pot Cascade and Tandem Heterocycles Synthesis Catalysed by Multifunctional Solid Materials – CATHECLOSM

The main objective of the project is to develop novel efficient heterogeneously catalysed synthesis of complex organic molecules using environmentally friendly "one-pot" multi-steps reactions in order to reduce energy consumption and the production of wastes, with the long term application to the synthesis of biologically relevant fine chemicals. Among all catalytic metals used in the fine chemical synthesis, palladium is probably one of the most interesting due to its wide reaction spectrum. This is probably why this metal is often used as homogeneous catalyst for cascade synthesis of elaborated molecules. However, the one-pot synthesis approach combined to catalytic methods using innovative heterogeneous catalysts would provide a great number of possibilities to achieve environmentally friendly procedures in fine chemical synthesis, bringing also the advantage of easy separation, higher tolerance to reaction conditions and recycling. Since by nature, in one-pot synthesis several different reactions are conducted in the same reactor without intermediate separation, important parameters and questions of interest need to be addressed like the choice of the solvent, the catalysts, the additives… Based on our previous experiences, we choose to address these questions through the one-pot cascade and tandem synthesis of highly functional heterocycles which include substructures related to indoles, benzofurane/benzothiofuranes, flavones, coumarines… that are important substructures of various natural and synthetic bioactive compounds, and more particularly of anti-tumoral molecules. To achieve the goal it is necessary to develop new heterogeneous catalytic systems by combining palladium sites with other catalytically active transition metal (i.e. ruthenium, copper, rhodium…) or organic (i.e. amine) sites. Since, at least, two consecutive reactions (coupling reaction, annulation, oxidation…) implying different active sites should be performed in the same reactor without isolating the intermediates, the multi-functional catalysts should combine high performances, selectivity, stability and ease of recycling from heterogeneous catalysts. The key to the success of this project is an approach involving a wide variety of competencies. The group presenting the proposal federates both well known and emerging chemists from very different subfields (organic synthesis, organometallic synthesis, material preparation and characterisation, catalysis, kinetic…). The manager of this research team, Laurent DJAKOVITCH, was chosen based on his expertise with the palladium catalysed processes implying carbon-carbon coupling and cascade and tandem reactions. The financial support from ANR will give a new impulsion to these researches, by financing a PhD student and a post-doctoral researcher as well as analytical equipments as required by this project. All studies will be realised in close cooperation, with regular meeting (at least every 3-6 months) to discuss the results and decide of the orientation to give to the project. To lay the collaboration between all partners of the team, we like to incite the non-permanent researchers engaged within the project to perform their researches in all laboratories, that is encouraged by the geographical proximity of the partners.