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.
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
L. Chabaud, Y. Landais, P. Renaud Org. Lett.,
2005, 7, 2587-2590.
Y. Landais, Compt. Rendu Acad. Sc., 2005,
L. Chabaud, Y. Landais, P. Renaud, F. Robert, F. Castet, M.
Lucarini, and K. Schenk Chem. Eur. J. 2008,
14, 2744 – 2756.
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,
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
G. Rouquet, F. Robert, R. Méreau, F. Castet,
P. Renaud Y. Landais Chem. Eur. J. 2012,
Acylsilanes : precursors of
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,
J. Labarre-Lainé, I. Periñan, V. Desvergnes, Y.
Landais Chem. Eur. J. 2014, 20,
II. Novel Free-radical
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,
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
E. Godineau, Y. Landais, J. Am. Chem. Soc. 2007,
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.
- A carbo-alkynylation reaction
V. Liautard, F. Robert, Y. Landais Org. Lett. 2011,
- A carbo-alkenylation reaction
C. Poittevin, V. Liautard, R. Beniazza, F. Robert, Y. Landais
Org. Lett. 2013, 15, 2814-2817.
M. R. Heinrich, H. Jasch, Y. Landais, Chem. Eur. J. 2013,
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 α-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
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,
J. Alsarraf, F. Robert, H. Cramail, Y. Landais Polymer
Chem. 2013, 4, 904-907.