These projects are now developed in
collaboration with Pr. Gwilherm Evano, head of the
Laboratory of Organic
Chemistry at the Université Libre de Bruxelles
Natural products and total synthesis have long been a source of inspiration and motivation as well as considerable innovation and are at the centre of our research. They represent a unique opportunity for the fine-tuning of original techniques which have allowed us to gain access to the target molecules shown below.
We are equally involved in another research direction:
copper catalysis and development of new copper-mediated transformations
for organic synthesis. In this area, we have developed for example a
new pathway to pyrrolindoles, a structural motif which is found in numerous
natural or biologically active products, and designed various efficient
processes for the synthesis of heterosubstituted alkenes and alkynes.
More recently, we also have started to study the reactivity of stable
organocopper reagents such as copper acetylides under oxidative conditions,
which led to the development of efficient alkynylation procedures under
especially mild and neutral conditions. These reactions we have developed
are now commonly used in the group for the development of the chemistry
of ynamides and for natural product synthesis as well.
We have started in 2009 a research program aimed at the development of the chemistry of ynamides, most useful building blocks in organic synthesis whose chemistry is under intense exploration. In order to bring significant developments in this area, we have studied the chemistry of ynamides using a global approach involving the development of new and general ynamide syntheses, the design of new transformations with these building blocks and a combined theoretical/experimental approach to better apprehend their reactivity. In this context, we have reported three generations of ynamides syntheses based on copper-mediated transformations with dibromoalkenes, potassium alkynyltrifluoroborates and copper acetylides. These complementary routes allow the preparation of most classes of ynamides and are routinely used on a multigram scale in the lab. We have also developed new classes of ynamides such as ynimines, compound that display promising reactivities, and we have recentlydeveloped new processes with ynamides such as, for examples, new syntheses of dihydropyridines, pyridines, aminovinylphosphonates or fluoroenamides.
Total Synthesis of Paliurine F. Toumi, M.; Couty, F.; Evano, G. Angew. Chem. Int. Ed. 2007, 46, 572-575 (article en couverture de numéro, repris dans Synfacts 2007, 571).
Copper-Mediated Coupling Reactions and Their Applications in Natural Products and Designed Biomolecules Synthesis. Evano, G.; Blanchard, N.; Toumi, M. Chem. Rev. 2008, 108, 3054-3131.
Total Synthesis of Chaetominine, Toumi, Couty, F.; Marrot, J.; Evano, G. Org. Lett. 2008, 10, 5027-5030.
Copper-Mediated Coupling of 1,1-Dibromo-1-alkenes with Nitrogen Nucleophiles: A General Method for the Synthesis of Ynamides, Coste, A.; Karthikeyan, G.; Couty, F.; Evano, G. Angew. Chem. Int. Ed. 2009, 48, 4381-4385 (repris dans Synfacts 2009, 907).
Copper-Catalyzed Cyclization Reactions for the Synthesis of Alkaloids, Evano, G.; Toumi, M. Coste, A. Chem. Commun. 2009, 4166-4175.
Synthesis of Ketene N,N-Acetals by Copper-Catalyzed Double-Amidation of 1,1-Dibromo-1-alkenes, Coste, A.; Couty, F.; Evano, G. Org. Lett. 2009, 11, 4454-4457.
Ynamides: Versatile Tools in Organic Synthesis, Evano, G.; Coste, A.; Jouvin, K. Angew. Chem. Int. Ed. 2010, 49, 2840-2859.
Copper-Catalyzed Alkynylation of Amides with Potassium Alkynyltrifluoroborates: A Room-Temperature, Base-Free Synthesis of Ynamides, Jouvin, K.; Couty, F.; Evano, G. Org. Lett. 2010, 12, 3272-3275.
Copper-Catalyzed Oxidative Alkynylation of Diaryl Imines with Terminal Alkynes: A Facile Synthesis of Ynimines, Laouiti, A.; Rammah, M. M.; Rammah, M. B.; Marrot, J.; Couty, F.; Evano, G. Org. Lett. 2012, 14, 6-9.
Click-Alkynylation of N- and P-Nucleophiles by Oxidative Cross-Coupling with Alkynylcopper Reagents: a General Synthesis of Ynamides and Alkynylphosphonates, Jouvin, K.; Heimburger, J.; Evano, G. Chem. Sci. 2012, 3, 756-760.
Copper-Catalyzed Coupling of 1,1-Dibromo-1-alkenes with Phenols: A General, Modular, and Efficient Synthesis of Ynol Ethers, Bromo Enol Ethers, and Ketene Acetals , Jouvin, K.; Bayle, A.; Legrand, F.; Evano, G. Org. Lett. 2012, 14, 1652-1655.
De Novo Synthesis of 1,4-Dihydropyridines and Pyridines, Gati, W.; Rammah, M. M.; Rammah, M. B.; Couty, F.; Evano, G. J. Am. Chem. Soc. 2012, 134, 9078-9081 (repris dans Synfacts 2012, 900).