thiols; chiral catalysts; asymmetric synthesis; natural products; organoboron chemistry; environmentally-friendly processes; organic synthesis; organometallic reagents; catechols; organocopper chemistry; non-toxic reagents; radical reactions; alkaloids
Suravarapu Sankar Rao, Peter Bettina, Renaud Philippe (2019), Radical-mediated hydroalkylation of 2-vinylpyrrolidine derivatives: a versatile entry into indolizidine alkaloids, in Science China Chemistry
, 62(11), 1504-1506.
Millius, Lapointe, Renaud (2019), Two-Step Azidoalkenylation of Terminal Alkenes Using Iodomethyl Sulfones, in Molecules
, 24(22), 4184-4184.
Tappin Nicholas D. C., Michalska Weronika, Rohrbach Simon, Renaud Philippe (2019), Cyclopropanation of Terminal Alkenes through Sequential Atom‐Transfer Radical Addition/1,3‐Elimination, in Angewandte Chemie International Edition
, 58(40), 14240-14244.
Gnägi Lars, Martz Severin Vital, Meyer Daniel, Schärer Robin Marc, Renaud Philippe (2019), A Short Synthesis of (+)‐Brefeldin C through Enantioselective Radical Hydroalkynylation, in Chemistry – A European Journal
, 25(50), 11646-11649.
Meyer Daniel, Jangra Harish, Walther Fabian, Zipse Hendrik, Renaud Philippe (2018), A third generation of radical fluorinating agents based on N-fluoro-N-arylsulfonamides, in Nature Communications
, 9(1), 4888-4888.
Tappin Nicholas D. C., Gnägi-Lux Manuel, Renaud Philippe (2018), Radical-Triggered Three-Component Coupling Reaction of Alkenylboronates, α-Halocarbonyl Compounds, and Organolithium Reagents: The Inverse Ylid Mechanism, in Chemistry - A European Journal
, 24(44), 11498-11502.
Povie Guillaume, Suravarapu Sankar Rao, Bircher Martin Peter, Mojzes Melinda Meyer, Rieder Samuel, Renaud Philippe (2018), Radical chain repair: The hydroalkylation of polysubstituted unactivated alkenes, in Science Advances
, 4(7), eaat6031-eaat6031.
JimenoCiril, RenaudPhilippe (2018), Trichloromethanesulfonyl Chloride, Wiley, Chichester, 1-4.
Soulard Valentin, Villa Giorgio, Vollmar Denis Patrick, Renaud Philippe (2017), Radical Deuteration with D 2 O: Catalysis and Mechanistic Insights, in Journal of the American Chemical Society
, 140(1), 155-158.
Mateo Pierre, Cinqualbre Joséphine E., Meyer Mojzes Melinda, Schenk Kurt, Renaud Philippe (2017), Reductive Alkylation of Tertiary Lactams via Addition of Organocopper (RCu) Reagents to Thioiminium Ions, in The Journal of Organic Chemistry
, 82(23), 12318-12327.
Gloor Christian Simon, Dénès Fabrice, Renaud Philippe (2017), Hydrosulfonylation Reaction with Arenesulfonyl Chlorides and Tetrahydrofuran: Conversion of Terminal Alkynes into Cyclopentylmethyl Sulfones, in Angewandte Chemie International Edition
, 56(43), 13329-13332.
Meyer Daniel, Renaud Philippe (2017), Enantioselective Hydroazidation of Trisubstituted Non-Activated Alkenes, in Angewandte Chemie International Edition
, 56(36), 10858-10861.
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 will be 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. The project is subdivided in three sub-chapters according to synthetic methods: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.Azide chemistry. 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.Geminal disubstitution of amides and lactams. 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 Erythrina alkaloids 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 skeletons of Lycopodium alkaloids.