Renaud Research Group
The total synthesis of natural products and analogues proved over the years to be a very reliable method for the discovery of new drugs. Due the structural complexity of many natural products, efficient synthetic methods are required to synthesize them in order to make them (as well as analogues) available to scientists involved in drug discovery. Our research program aims at finding methods and strategies that can be applied for efficient synthesis of different classes of products possessing an interesting biological profile. Development of processes involving radical chemistry, organometallic chemistry and enantioselective catalysis are investigated. Our research focus on increasing the efficiency of target molecule synthesis by minimizing the number of synthetic steps, by opening new synthetic pathways, and by developing environmentally friendly reagents.
Boron reagents for radical chemistry
Radical reactions have been intensively investigated during the last two decades. The new synthetic methods that aroused from this work are characterized by their mildness and their complement to ionic processes. The potential of these reactions is immense as demonstrated by their recent use in the synthesis of complex natural products. Our effort will be concentrated on the development of stable, non-toxic, and environmentally friendly reagents to perform efficient radical reactions. Organoboranes will be used to generate radicals that are functionalized close to the radical center and to control the absolute configuration of the products. The extremely rich chemistry of organoboron species will play a crucial role in developing these new reagents. The combination of organoborane chemistry with the chemistry of well-established antioxidants such as catechol and thiols will also be investigated in order to develop a simple an efficient procedure to reduce radicals and to run unique radical rearrangements.
The generation of congested tertiary and quaternary amino substituted carbon centers is a key process for the synthesis of complex alkaloids. Based on the chemistry of thioiminium ions, we will investigate processes allowing the substitution of the carbonyl group of amides/lactams by two geminal carbon residues. Polycyclic framework will be prepared by combining inter- and intramolecular carbon–carbon bond formation. Extension of this chemistry to the formation of up to three carbon–carbon bonds in a single step will be developed. Application to the synthesis of polycyclic Erythrinaalkaloids will be undertaken. Investigations of cationic rearrangements such as the 1,2-alkyl shift and the aza-Cope rearrangement are expected to provide new ways to synthesize the complex skeleton of Lycopodium alkaloids.
The formation of carbon-nitrogen bonds under very mild reaction conditions represents a very useful tool for the total synthesis of alkaloids. Reagents and procedures to prepare alkyl azides via radical pathways are explored. They will allow the development of highly efficient and practical syntheses of polycyclic alkaloids such as the hinckdentine A and Aspidosperma alkaloids. A unique rearrangement of alkyl azides, the intramolecular Schmidt reaction, has been for the first time run under non-acidic conditions. Further development of this process, in particular its asymmetric version, is expected to offer exceptional opportunities for the preparation of complex alkaloid skeletons in an excitingly concise manner. Starting from secondary hydroxylamines, the development of a rearrangement closely related to the Schmidt reaction will be developed in order to avoid the use of potentially hazardous azides.
Quantum dots for photoredox catalysis
Project in collaboration with Vincent Maurel, Jean-Marie Mouesca and Fabien Dubois at CEA-Grenoble.
In the last decade, the emergence of photoredox catalysis has revolutionized the field of synthetic organic chemistry. Catalyst design has been boosted by development of catalysts for solar energy conversion. Ruthenium and iridium coordination complexes are playing a major role in this development. Besides these homogeneous catalysts, the use of heterogenous semiconductor photoredox catalysts for synthesis is still in his infancy. We propose here a research program dedicated to the investigation of semiconductor colloidal quantum dots (QDs) as photoredox catalysts for synthetic organic chemistry. These nanocrystalline catalysts are highly attractive since they combine some of the advantages of the homogeneous catalysts, such as large extinction coefficient in the visible spectrum, and retain the ability to be removed by ultra-filtration or centrifugation. Moreover, QDs are very resistant to photobleaching and their redox properties may be fine-tuned by changing their composition (CdS, CdSe, ZnO, ZnSe), controlling their size and modifying the ligands used to stabilize them. Finally, finding substitutes to the costly ruthenium and particularly iridium catalysts, will open new perspective for industrial application of photoredox catalysis.