Research

Our research activity has concentrated on the development of new methodologies, based on the use of radical and organometallic processes, with a main goal, their application to the total synthesis of targets of biological interest (natural or not).
We are currently dealing with three main topics :

  1. The organosilicon chemistry and particularly the sterecocontrol induced by organosilicon substituents located on a carbon framework. We are also dealing with the chemistry of silyl radicals.
  2.  The discovery of new reactions based on radical processes and their application to organic synthesis.
  3. And finally, organocatalysis and especially the development of new catalysts for a « metal-free » polymerization.

 Targets

As mentioned above, methodologies developed in our team are in certain cases applied to the synthesis of natural compounds of biological interest. Are summarized below some natural and non- natural targets, the synthesis of which was completed in the past and some new targets, which synthesis is currently under investigation.

Present

Past

 

Research – Theme 1 : Organosilicon Chemistry

Allylsilanes

Organosilicon chemistry constitutes the laboratory founding research axis, with basic research on the reactivity of organosilanes, the role of silicon in the stereocontrol in free-radical processes or the elaboration of new organosilicon-based reagents and catalysts. Recently, we studied the enhanced reactivity of allylsilanes towards electrophilic radical species, for instance in free-radical carboazidation processes (work in collaboration with Prof. P. Renaud, Bern University, Switzerland). The stereogenic center bearing the silicon group controls the stereochemistry of the newly created stereocenter, during the formation of the C-N bond. This reaction was used as a key-step during the total enantioselective synthesis of Hyacinthacine A1, isolated from Muscari Armeniacum.

L. Chabaud, Y. Landais, P. Renaud Org. Lett., 2005, 7, 2587-2590.
Y. Landais, Compt. Rendu Acad. Sc., 2005, 8, 823-832
L. Chabaud, Y. Landais, P. Renaud, F. Robert, F. Castet, M. Lucarini, and K. Schenk Chem. Eur. J. 2008, 14, 2744 – 2756

 

Silyl Radicals

We are also interested by the use in free-radical chemistry of organosilicon compounds as tin reagent surrogates, as the latter are considered as toxic and very often difficult to remove from reaction products. The use of allylsilanes and allylthioethers allowed to carry out oximation, alkenylation and allylation of alkyl halides using sulfonyl reagents. The process is based on the reactivity of these allylic substrates toward the electrophilic PhSO2 radical, which allows the generation of the silyl radical, itself able to abstract an halogen in primary, secondary or tertiary alkyl halides.

P. d’Antuono, R. Méreau, F. Castet, G. Rouquet, F. Robert, Y. Landais Organometallics 2010, 29, 2406-2412
G. Rouquet, F. Robert, R. Méreau, F. Castet, Y. Landais Chem. Eur. J. 2011, 17, 13904-13911

 

The silyl radical may also be generated through an intramolecular homolytic substitution process (SHi), using silyl-boranes formed through hydroboration of olefins bearing a silyl substituent. The addition of a radical initiator (DTBHN) or oxygen on the alkylborane triggers the formation of a C-centered radical, which attacks the silicon center and generates a Me3Si radical, which can then be trapped by acceptors, including allylsulfones.

G. Rouquet, F. Robert, R. Méreau, F. Castet, P. Renaud Y. Landais Chem. Eur. J. 2012, 18, 940-950
 

Acylsilanes : precursors of spiroketals

The silicon version of the Stetter reaction (sila-Stetter) has been used for the synthesis of spiro- and bis-spiroketals, motifs present in several macrocyclic marine natural products (spirolides, pinnatoxines,….). A “one-pot” process allowed the formation of the 1,4-diketone through a carbene-catalyzed Stetter reaction, followed by the deprotection of the silyl ethers and ketalization under acidic conditions.

J. Labarre-Lainé, R. Beniazza, V. Desvergnes, Y. Landais, Org. Lett., 2013, 15, 4706–4709
J. Labarre-Lainé, I. Periñan, V. Desvergnes, Y. Landais Chem. Eur. J. 2014, 20, 9336-9341

 

Research – Theme 2: Novel Free-radical Reactions 

Our group developed recently new methods to functionalize olefins, through free-radical multicomponent processes. Olefins are abundant, commercially available and relatively cheap, offering an access to a broad range of useful synthons for organic synthesis. These multicomponent processes allow the formation of new C-C and C-X bonds (C-N for instance) through the coupling between an alkyl halide (or a xanthate), an olefin and a suitable sulfone.

E. Godineau, and Y. Landais Chem. Eur. J. 2009, 15, 3044-3055
Y. Landais, G. Rouquet, L. Huet, Techniques de l’Ingénieur, 2011, CHV 2 – 224, 1-19
V. Liautard, Y. Landais, in Multicomponent Reactions, Eds. Zhu, J., Wang, Q., Wang, M. X., Wiley, 2nd Edition. 2014.

 

Several processes have thus been developed:

Carbo-oximation and carbo-aminomethylation reactions

E. Godineau, Y. Landais, J. Am. Chem. Soc. 2007, 129, 12662-12663
E. Godineau, Y. Landais, J. Org. Chem. 2008, 73, 6983 – 6993. (Featured Article and Highlighted in Synfact 2008, 12, 1306)
Y. Landais, F. Robert, E. Godineau, L. Huet, N. Likhite, Tetrahedron, 2013, 69, 10073-10080

Carbo-alkynylation reaction

V. Liautard, F. Robert, Y. Landais Org. Lett. 2011, 10, 2658-2661

 

Carbo-alkenylation reactionC. Poittevin, V. Liautard, R. Beniazza, F. Robert, Y. Landais Org. Lett. 2013, 15, 2814-2817
M. Heinrich, H. Jasch, Y. Landais, Chem. Eur. J. 2013, 19, 8411

 

Research – Theme 3 : Organocatalysis

BIP, an efficient organocatalyst

Organocatalysis expands rapidly and constitutes currently one of the hottest topics in synthetic chemistry. The use of small organic molecules, natural or synthetic, to replace pollutants and non-renewable organometallic catalysts, constitutes an important challenge that arouse enormous interest in many countries (USA, United-Kingdom, Germany,…). We have recently discovered a simple catalyst, derived from L-proline (benzoimidazole pyrrolidine: BIP) which catalyzes aldolisation and a-amination of ketones as well as Robinson annelation. This organocatalyst works in the presence of a Brönsted acid and is efficient in only 5% amount, the aldol reaction being performed with a single equivalent of ketone, which is not the case with most organocatalysts (as a comparison, L-proline requires 20 equiv of ketone).

J.-M. Vincent, C. Margottin, D. Cavagnat, T. Buffeteau, Y. Landais, Chem. Commun. 2007, 4782-4784
V. Liautard, D. Jardel, C. Davies, M. Berlande, T. Buffeteau, D. Cavagnat, F. Robert, J. M. Vincent, Y. Landais Chem. Eur. J. 2013, 19, 14532-14539
 

New organocatalysts for polymerization

Polymerization processes catalyzed through the help of small organic compounds has recently attracted a wide interest, especially for the synthesis of commodity polymers (polyurethanes (PU), polyesters, polyethers,….). In this context, we initiated in collaboration with the team of Prof. H. Cramail and Prof. D. Taton (LCPO, University of Bordeaux) a program on the development of new catalysts, based on the guanidine functional group, which are able to accelerate the formation of polyurethanes through addition of diols onto diisocyanates. In the course of this research, we isolated new heterocycles, formed through the reaction of guanidines with isocyanates, which revealed to be excellent latent catalysts (T° > 50°C) for polyurethanization.

J. Alsarraf, Y. Ait Ammar, F. Robert, E. Cloutet, H. Cramail, Y. Landais Macromolecules 2012, 45, 2249-2256
J. Alsarraf, F. Robert, H. Cramail, Y. Landais Polymer Chem. 2013, 4, 904-907