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Ecole Doctorale de Chimie Moléculaire de Paris Centre - ED 406 - Director: Prof. Anna Proust !

Program of the 16th Conference of the Doctoral School

Amphitheatre Herpin

Monday, May 23, 2016 morning sessions

Moderator

8h45 – 9h00 Opening of the 16th conference by Prof. A. Proust

9h00 – 10h00

Prof. Michel Etienne Distorsions CC agostiques et le ligand cyclopropyle : expérience, théorie, réactivité

10h00 – 10h15 Laura Ferrand Cationic niobium as a new catalytic system for hydro-functionalization of C‒C multiple bonds

Prof. Anna Proust

10h15 – 10h30 Maxime Laugeois Synergistic Pd(0)/amine catalysis: a powerful tool for the asymmetric formal [3+2] cycloaddition of vinyl cyclopropanes with enals

10h30 – 11h00 Coffee break

11h00 – 11h15 Morgan Languet Rhodium(III) catalyzed C−H activation of heterocycles under mild conditions

11h15 – 11h30 Fabrizio Medici New silicon derived frustrated Lewis pairs

11h30 – 11h45 Christophe Lévêque Development of a versatile approach for the generation of alkyl radicals by photooxidation of alkylsilicates

Dr. Maxime Vitale

11h45 – 12h00 Fei Ye Solvent-free ruthenium trichloride-mediated [2 + 2 + 2] Cycloaddition: an efficient access toward fluorenone derivatives

12h00 – 14h00 Lunch

Monday, May 23, 2016 afternoon sessions

Moderator

14h00 – 14h15 Radhouan Maazaoui Domino methylenation–hydrogenation of aldehydes and ketones by combining Matsubara reagents and Wilkinson’s catalyst

14h15 – 14h30 Liang Chang Methyl coumalate involved Morita-Baylis-Hillman reaction

14h30 – 14h45 Alexandra Feraldi Ring contraction: synthesis of functionalized α-(trifluoromethyl)-pyrrolidines and piperidines

Dr. Marion Barbazanges

14h45 – 15h00 Thomas Aubineau Formation of N-containing heterocycles

15h00 – 15h30 Coffee break

15h30– 15h45 Ludovic Leleu Kojic acid : a natural compound for organic synthesis and access to biologically active molecules

15h45 – 16h00 Benjamin Flamme Rational design of 5V organic electrolytes

16h00 – 16h15 François-Xavier Guillon Electrochemical microRNA biosensors: an ergonomic miniaturized two-electrode setup

Dr. Cyril Ollivier

16h15 – 16h30 Xia Wang Photocatalytic CO2 reduction by multinuclear metal complexes

16h30 – 17h30 Prof. Marc Robert Molecular catalysis of the reduction of CO2 with iron porphyrins. From mechanistic studies to optimization of catalysts and to efficient electrolizers for CO2 splitting into CO and O2

Tuesday, May 24, 2016 morning sessions

Moderator

8h45 – 9h45 Prof. William B. Motherwell The measurement of noncovalent functional group interactions with π clouds using designed molecular balances.

9h45 – 10h00

Pascal Matton Glycolipid functionalized microdroplets for cells vectorization

10h00 – 10h15 Thomas Denèfle TSP-1 mimetic peptides inducing selective apoptosis of cancer cell lines: design, synthesis and structure-activity relationship studies

Prof. Matthieu Sollogoub

10h15 – 10h30 Sébastien Cardon Quantification of the internalization efficacy of homeoproteins and derived-cell penetrating domains

10h30 – 11h00 Coffee break

11h00 – 11h15 Thomas Driant On the influence of the protonation states of active site residues on AChE reactivation: a QM/MM approach

11h15 – 11h30 Mathilde Belnou Modulation of the calmodulin binding domain of the protein FKBP52

11h30 – 11h45 Caroline Thebault Ultra-magnetic liposomes and their in vivo guidance monitoring by MRI for cancer therapy

Dr. Sébastien Blanchard

11h45 – 12h00 Frédéric Thiebaut Identification of rare DNA base protein partner using photolabeling and mass spectrometry

12h00 – 14h00 Lunch

Tuesday, May 24, 2016 afternoon sessions

Moderator

14h00 – 14h15 Ourania Makrygenni Hybrid polyoxometalates for homogeneous supported catalysis

14h15 – 14h30 Juan Ramón Jiménez-Gallego Switchable redox active Fe/Co cyanide molecular cube encapsulating K+ or Cs+

14h30 – 14h45 Emilie Mathieu Antioxidant manganese complexes: Investigation of their activity and sub-cellular location.

Dr. Guillaume Vives

14h45 – 15h00 Emmanuel Puig Novel class of Pt(II) metallocages : design and self-assembly

15h00 – 15h30 Coffee break

15h30 – 15h45 Florence Hiault Synthesis of α-amino β-hydroxy acids Biocatalytic aldolization and kinetic resolution of 1,2-diols

15h45 – 16h00 Laurine Gonnard Metal-catalyzed arylation of piperidines

16h00 – 16h15 Caleb Medena Helicenes: synthesis and application in catalysis

Prof. Giovanni Poli

16h15 – 17h15 Prof. Maurizio Prato Novel Functional Materials from Nanocarbons to Perylene Bisimides

Journées)de)Chimie)Moléculaire)2016! Michel!ETIENNE!

Distorsions!CC!agostiques!et!le!ligand!cyclopropyle!:!expérience,!théorie,!réactivité!!

michel.etienne@lcc,toulouse.fr!!

Laboratoire)de)Chimie)de)Coordination)du)CNRS)et)Université)Toulouse)III)–)Paul)Sabatier,)205)route)de)Narbonne,)

BP)99044,)31077)Toulouse)Cedex)4.)

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Alors! que! les! nombreuses! observations,! la! nature,! les! causes! et! les! conséquences! des! distorsions! CH!agostiques!–!formellement!interactions!à!3!centres!et!2!électrons!(3c,2e)!entre!une!liaison!CH!d’un!ligand!et!un!métal!M!–!sont!connues!toujours!plus!en!détail,!de!telles!manifestations!pour!d’autres!liaisons!saturées!CX,! en! particulier! CC,! sont! beaucoup! plus! rares.1! Ceci! est! au! moins! vrai! pour! des! raisons! stériques! et!statistiques!mais!revêt!une!importance!certaine!dans!le!cadre!très!actuel!d’études!sur!l’activation!de!liaisons!fortes!et!inertes.!! Il! y! a!quelques!années,!on!a!découvert!dans! l’équipe!une! famille!de! complexes!de!niobium!dans!lesquels!un!ligand!cyclopropyle!c,C3H5!présentait!de!telles!distorsions!CC!agostiques.!Les!complexes!iso,!et!n,propyle!présentent!plus!classiquement!des!distorsions!CH!agostiques.!A!la!recherche!d’autres!exemples!de!ces!manifestations,!je!présenterai!une!excursion!dans!la!chimie!des!métaux!des!groupes!5!à!1!avec!le!ligand!cyclopropyle! aussi! bien! du! point! de! vue! structural! que! de! la! réactivité! (activation! de! liaisons! CH!d’hydrocarbures,!méthane! en! particulier).! A! la! lumière! de! certains! outils! de! la! chimie! computationnelle,!j’ajouterai! une! réflexion! sur! la!description!et! la!nature!de! ces!distorsions!qui! varient! selon! la!nature!des!métaux!et!des!complexes.!

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1 “Intramolecular C–C Agostic Complexes: C–C Sigma Interactions by Another Name”. M. Etienne, A. S. Weller, Chem. Soc. Rev. 2014, 43, 242-259.

Journées)de)Chimie)Moléculaire)2016! Marc!Robert!

Molecular!catalysis!of!the!reduction!of!CO2!with!iron!porphyrins.!!From!mechanistic!studies!to!optimization!of!catalysts!!

and!to!efficient!electrolizers!for!CO2!splitting!into!CO!and!O2!

robert@univ,paris,diderot.fr!

Université)Paris)Diderot,)Sorbonne)Paris)Cité,)Laboratoire)Electrochimie)Moléculaire,)UMR)CNRS)7591,))

15)rue)Jean)de)Baïf,)75013)Paris,)France)

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Recent!attention!aroused!by!the!reduction!of!carbon!dioxide!has!as!main!objective!the!production!of!useful!products!−!the!“solar!fuels”!−!in!which!solar!energy!would!be!stored.!One!route!to!this!goal!consists!in!first!converting!sunlight!energy!into!electricity!than!could!be!further!used!to!reduce!CO2!electrochemically.!Conversion!of!carbon!dioxide!into!carbon!monoxide!is!a!key,step!through!the!classical!dihydrogen,reductive!Fischer,Tropsch!chemistry.!We!will!describe!our!work!in!this!field!using!various! iron!tetraphenylporphyrin!derivatives,!that!prove!to!be!remarkable!catalysts!of!the!reduction!of!CO2!to!CO!when!reduced!at!the!Fe(0)!oxidation! state,! both! in! terms! of! selectivity,! durability,! overpotential! and! turnover! frequency.! 1,2,3,4,5,6!Understanding!the!molecular!mechanisms!for!catalysis!allows!identifying!the!main!factors!that!control!the!process!and!optimizing!the!catalyst!structure.!7!

!Extending! these! studies,! we! recently! discovered! that! it! was! possible,! with! a! water,soluble! Fe!

porphyrin,!to!catalyze!the!electrochemical!conversion!of!carbon!dioxide!into!carbon!monoxide!in!pure!water!8!as!well!as!to!transfer!catalytic!activity!to!solid!surfaces!by!grafting!of!the!molecular!catalysts.9!Finally,!and!based!on!these!advances,!we!very!recently!designed!an!efficient!electrolyzer!for!CO2!splitting!in!neutral!water!using!only!earth!abundant!materials.10!!

Acknowledgments:!ANR,!SATT!IDF!Innov!as!well!as!Labex!MiChem!are!gratefully!acknowledged!for!funding.!! !

1 S. Drouet, C. Costentin, M. Robert, J-M. Savéant, Science, 2012, 338, 90. 2 C. Costentin, M. Robert, J-M. Savéant, Chem. Soc. Rev., 2013, 42, 2423. 3 C. Costentin, G. Passard, M. Robert, J-M. Savéant, (a) J. Am. Chem. Soc., 2013, 135, 9023.(b) J. Am. Chem. Soc., 2014,

136, 11821. 4 C. Costentin, M. Robert, J-M. Savéant, Acc. Chem. Res., 2015, 48, 2996. 5 C. Costentin, G. Passard, M. Robert, J-M. Savéant, PNAS, 2014, 111, 14990. 6 J. Bonin, M. Robert, M. Routier, J. Am. Chem. Soc., 2014, 136, 16768. 7 M. Robert et al., submitted. 8 C. Costentin, M. Robert, J-M. Savéant, A. Tatin, PNAS, 2015, 112, 6882. 9 A. Maurin, M. Robert, J. Am. Chem. Soc., 2016, 138, 2492. 10 M. Robert et al., PNAS, 2016, in press.

Journées)de)Chimie)Moléculaire)2016! William!Motherwell,!FRS,!FRSE.!!

The!Measurement!of!Noncovalent!Functional!Group!Interactions!with!π!Clouds!using!designed!Molecular!Balances.!

!w.b.motherwell@ucl.ac.uk!

!Christopher)Ingold)Laboratory,)Department)of)Chemistry,)University)College)London,)20,)Gordon)St.,)London,)

WC1HOAJ.))UK.)

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Noncovalent! interactions!are!now!firmly!established!as!vital! control!elements! for!chemical!and!biological!recognition,! and!detailed!quantitative! knowledge!of! these! very!weak! forces! is! now! therefore! considered!essential! for! the! rational!design!of!organocatalysts,!new!drugs!and! supramolecular!materials.!Our! recent!progress!in!this!area!using!a!unique!top!pan!molecular!balance!based!on!the!dibenzobicyclo[3.2.2]nonane!molecular!framework!and!related!congeners!will!be!discussed.!!!!

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For a leading reference see: I. Pavlakos, T. Arif, A.E. Aliev, W.B. Motherwell, G.J. Tizzard, and S. J. Coles, Angew. Chem. Int. Ed. 2015, 54, 8169. ! !

Journées)de)Chimie)Moléculaire)2016! Maurizio!Prato!!

Novel!Functional!Materials!from!Nanocarbons!to!Perylene!Bisimides!

!prato@units.it!

!Dipartimento)di)Scienze)Chimiche)e)Farmaceutiche,)Università)degli)Studi)di)Trieste,)Piazzale)Europa)1,)34127)Trieste,)

Italy)and)CIC)BiomaGUNE,)San)Sebastian,)Spain)

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We! will! show! how! nanocarbons! are! particularly! suited! for! a! variety! of! applications,! ranging! from!neurosciences!to!energy.! In!particular,!we!will!discuss!how!with!carbon!nanotubes!are! ideal!materials! for!integration!with!neuronal!tissues.!Nanotubes!are!compatible!with!neurons,!but!especially!they!play!a!very!interesting! role! in! interneuron! communication,! opening! possibilities! towards! applications! in! spinal! cord!repair!therapy.!In!addition,!in!combination!with!catalysts!of!different!nature,!carbon!nanotube!modified!surfaces!can!serve!for!many! scopes.! Experiments! aiming! at! the! splitting! of!water! to! give! oxygen,! and! therefore,!molecular!hydrogen,!ideal!for!clean!energy!generation,!will!be!described.!Finally,!moving! from!electrochemical! devices! to! light,driven! processes,!we!will! discuss! the! synthesis! and!applications!of!perylene!bisimides,!which,!in!combination!with!polyoxometalates,!are!ideal!partners!in!the!photosplitting!of!water.!!! !

!Journées)de)Chimie)Moléculaire)2016! Laura!FERRAND!!

Cationic!niobium!as!a!new!catalytic!system!for!hydroRfunctionalization!of!C‒C!

multiple!bonds!laura.ferrand@upmc.fr!

PhD!advisors:!Dr!Muriel!Amatore,!Dr!Corinne!Aubert!Institut)Parisien)de)Chimie)Moléculaire))

Université)Pierre)&)Marie)Curie)

)4,)place)Jussieu)75252)PARIS)Cedex)05)

!Located!between!vanadium!and!tantalum!in!the!periodic!table,!niobium!is!known!for!its!large!applications!notably! in! the! fields!of! steel! and!aeronautical! industries!and! in!medicine!as!well.!Niobium!has!also!been!widely!studied!in!the!field!of!inorganic!chemistry,!with!the!synthesis!of!a!large!number!of!niobium!complexes.!However,!this!element!is!definitely!much!less!known!in!organic!chemistry.!1!!The!most!common!niobium!complex!is!the!commercially!available!NbCl5!and!it!has!been!used,!either! in!a!stoichiometric!or!in!a!catalytic!amount,!as!a!Lewis!acid!in!different!organic!reactions!such!as!Aldol!reactions!and!Diels,Alder!reactions.!!As!for!many!other!chlorinated!metals,! it!has!been!demonstrated!that! it!was!possible!to!generate!cationic!niobium(V)!from!NbCl5,!and!thus!to!change!the!properties!of!the!complex.!However,!this!methodology!has!only!been!applied!once!for!Friedel,Crafts!acylation!and!Sakurai,Hosomi!reaction!of!acetals.!2!!In!this!context!and!with!the!aim!to!get!more!insight!into!the!reactivity!of!cationic!niobium(V),!we!envisaged!!to!explore!the!behavior!of!this!catalytic!system!for! intramolecular!hydro,functionalization!of!C‒C!multiple!bonds.!Indeed!this!reaction!is!well!known!to!be!a!powerful!strategy!for!the!construction!of!important!building!blocks!in!organic!synthesis,!and!it!has!been!widely!studied!over!the!past!ten!years.!3!!It! was! found! that!mixtures! of! NbCl5! and! AgX! salts! displayed! an! efficient! catalytic! activity! for! the! hydro,functionalization!of! alkenes,! leading! to! the! straightforward! formation!of! a!wide! range!of!heterocycles.!A!survey!of!the!preliminary!substrate!scope!will!be!presented.!!

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Access)to)tetrahydrofuran,)tetrahydropyran,)pyrrolidine,)lactam,)lactone…)

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Aknowledgment:!We!wish!to!acknowledge!the!Ministère!de!l’Enseignement!Supérieur!et!de!la!Recherche.!!! !

1 Jr. V. Lacerda, D. A. dos Santos, L. Carlos da Silva-Filho, S. J. Greco, R. B. dos Santos, Aldrichim. Acta 2012, 45,

19‒26 ; Y. Obora, Eur. J. Org. Chem. 2015, 5041‒5054. 2 S. Arai, Y. Sudo, A. Nishida, Tetrahedron 2005, 61, 4639‒4642. 3 N. T. Patil, R. D. Kavthe, V. S. Shinde, Tetrahedron 2012, 68, 8079‒8146.

Journées)de)Chimie)Moléculaire)2016! Maxime!LAUGEOIS!!

Synergistic!Pd(0)/amine!catalysis!:!a!powerful!tool!for!the!asymmetric!formal![3+2]!

cycloaddition!of!vinyl!cyclopropanes!with!enals!maxime.laugeois@chimie,paristech.fr!

PhD!advisors!:!Dr.!Virginie!Ratovelomanana,Vidal,!Dr.!Véronique!Michelet!and!Dr.!Maxime!Vitale!PSL)Research)University,)Chimie)ParisTech)–)CNRS,)Institut)de)Recherche)de)Chimie)Paris,)Paris,)75005)

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The! stereoselective! construction! of! the! carbocyclic! core! of! cyclopentane! derivatives! through! an!asymmetric![3+2]!cycloaddition!process!is!undeniably!one!of!the!most!efficient!and!straightforward!synthetic!method!available.1!

In!1985,!Tsuji!et)al.!established!that,!under!palladium(0)!catalysis,!vinylcyclopropanes!(VCPs)!bearing!electron!withdrawing!groups!could!undergo![3+2]!cycloaddition!reactions!with!electron,poor!olefins!via)the!formation! of! transient! zwitterionic! π,allyl! palladium! intermediates.2! Since! then,!much! efforts! have! been!dedicated!to!the!development!of!enantioselective!versions!of!this!cyclopentannulation!process,!essentially!based!on!the!use!of!highly!activated!acceptors!and!a!Pd(0)/chiral!ligand!strategy.3!

!Aware!of!these!limitations,!we!envisioned!an!alternative!catalytic!strategy!in!which!iminium/enamine!

organocatalysis!and!palladium(0)!catalysis!would!be!merged.4!As!direct!benefit!of!this!original!approach,!the!synergy!operating!between! the! chiral! secondary! amine! and! the!palladium! complex!permitted! to! employ!simple!enals!and!to!control!the!stereoselectivity!with!a!readily!available!source!of!chirality.!

This!new!synthetic!method!provided!access!to!a!wide!range!of!optically!active!cyclopentane!scaffolds!in!good!yields!and!diastereoselectivities!and!excellent!enantiomeric!excesses.51!

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Aknowledgment:!MESR!! !

1 N. Iwasawa, in Comprehensive Organic Synthesis II, ed. P. Knochel and G. A. Molander, Elsevier, 2014, vol. 5, pp.

273-350. 2 I. Shimizu, Y. Ohashi and J. Tsuji, Tetrahedron Lett., 1985, 26, 3825-3828. 3 (a) B. M. Trost and P. J. Morris, Angew. Chem. Int. Ed., 2011, 50, 6167-6170; (b) L. Mei, Y. Wei, Q. Xu and M. Shi,

Organometallics, 2012, 31, 7591-7599; (c) F. Wei, C.-L. Ren, D. Wang and L. Liu, Chem. Eur. J., 2015, 21, 2335-2338; (d) M.-S. Xie, Y. Wang, J.-P. Li, C. Du, Y.-Y. Zhang, E.-J. Hao, Y.-M. Zhang, G.-R. Qu and H.-M. Guo, Chem. Commun., 2015, 51, 12451-12454; (e) Z.-S. Liu, W. Li, T. Kang, L. He and Q. Liu, Org. Lett., 2015, 17, 150-153.

4 For a recent review, see: S. M. Inamdar, V. S. Shinde and N. T. Patil, Org. Biomol. Chem., 2015, 13, 8116-8162. 5 M. Laugeois, S. Ponra, V. Ratovelomanana-Vidal, V. Michelet and M. R. Vitale, Chem. Commun., 2016, 52, 5332-

5335.

Journées)de)Chimie)Moléculaire)2016! Morgan!LANGUET!!

Rhodium(III)!catalyzed!C−H!activation!of!heterocycles!under!mild!conditions!

morgan.languet@espci.fr!PhD!advisors:!Pr.!Janine!Cossy!&!Dr.!Stellios!Arseniyadis!

Laboratoire)de)Chimie)Organique,)ESPCI)Paris)Tech,)10)rue)Vauquelin)75231)PARIS)CEDEX)5)

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Five!membered!heterocycles! represent! an! important! class!of!molecules!which! are! found! in! a!number!of!natural!products!as!well! as! various!pharmaceuticals!and!agrochemicals.1!As! such,! the! synthesis!of!highly!functionalized!heterocycles!remains!still!today!a!great!challenge!still!today!in!organic!chemistry.!!During!the!past!two!decades,!C−H!activation!has!appeared!as!a!robust!and!highly!straightforward!method!to!access!diversely!substituted!heterocycles,2!particularly!with!Rhodium!catalysts.3!However,!to!the!best!of!our!knowledge,!there!are!only!a!few!examples!of!C−H!activation!processes!involving!cyclic! dienol! carbamates! reported! in! the! literature.4! Based! on! this! observation,! a! cationic! Rhodium(III),catalyzed!C−H!olefination!has!been!developed!offering!high!levels!of!regioselectivity!with!a!wide!range!of!substituted!heterocycles,!thus!enabling!the!efficient!introduction!of!an!acrylate!moiety!under!mild!conditions!and!with!a!low!catalyst!loading!(Scheme!1).!!

Scheme!1.!

!We! will! present! and! discuss! the! scope! and! limitations! of! this! method! as! well! as! various! post,functionalizations.! !

1 (a) B. A. Keay, J. M. Hopkins, P. W. Dibble in Comprehensive Heterocyclic Chemistry III, Vol. 3 (Eds.: G. Jones, C. A.

Ramsden), Elsevier, Amsterdam, 2008, 571-623. (b) Lipshutz, B. H. Chem. Rev. 1986, 86, 795. 2 For recent reviews on C−H activation, see: (a) Engle, K. M.; Mei, T.-S.; Wasa, M.; Yu, J.-Q. Acc. Chem. Res. 2012, 45,

788. (b) Leow, D.; Li, G.; Mei, T.-S.; Yu, J.-Q. Nature 2012, 486, 518. (c) Ackermann, L. Chem. Rev. 2011, 111, 1315. (d) Song, G.; Wang, F.; Li, X. Chem. Soc. Rev. 2012, 41, 3651. (e) Patureau, F. W.; Wencel-Delord, J. Glorius, F. Aldrichimica Acta 2012, 45, 31.

3 (a) Boultadakis-Arapinis, M.; N. Hopkins, M.; Glorius, F. Org. Lett. 2014, 16, 1630. (b) Gong, T.-J.; Xiao, B.; Liu, Z.-J.; Wan, J.; Xu, J.; Luo, D.-F.; Fu, Y.; Liu, L. Org. Lett. 2011, 13, 3235. (c). D. Otley, K.; A. Ellman, J. Org. Lett. 2015, 17, 1332. (d) Lu, Y.; Wang, H.-W.; E. Spangler, J.; Chen, K.; Cui, P.-P.; Zhao, Y.; Sun, W.-Y.; Yu, J.-Q. Chem. Sci. 2015, 6, 1923. (e) Feng, C.; Loh, T.-P. Chem. Commun. 2011, 47, 10458.

4 Schröder, N.; Lied, F.; Glorius, F. J. Am. Chem. Soc. 2015, 137, 1448.

X

O DGRh

R

H X

O DG

Radditive, solvent, T

25 examplesup to 93% yieldGram-ScaleMild conditions

X

O

R

X

H

R

X

Ar

R

(X = O, N, S)

C−O bondcleavage

Removal

Directing Group

Cross-coupling

Journées)de)Chimie)Moléculaire)2016! Fabrizio!MEDICI!!

New!Silicon!Derived!Frustrated!Lewis!Pairs!

Fabrizio.medici@upmc.fr!!PhD!advisor:!Pr.!Louis!Fensterbank

Laboratory!Institut)Parisien)de)Chimie)Moleculaire,)UMR)CNRS)8232)Sorbonne Universités UPMC-Paris06, 4 Place Jussieu, 75252 Paris

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A!Frustrated!Lewis!Pair!(FLP)!is!a!partially!formed!Lewis!Acid,Base!adduct!in!which!the!properties!of!the!two!centres!are!unquenched1.!This!means!that!the!adduct!still!features!an!electrophilic!centre!and!a!nucleophilic!centre!active! in!close!proximity.!As!now!well! illustrated! in!the! literature! it! is!possible!to!use!FLPs’! for!the!activation!of!small!molecules,!like!H2

2!and!CO23.!

My!thesis!work!focuses!on!the!study!of!the!possible!application!of!the!Martin!spirosilane4!as!a!Lewis!acid!in!the!formation!of!new!FLPs.!This!particular!spirosilane!was!chosen!because!of!its!high!Lewis!acidity!and!of!the!ability!of!silicon!to!become!hypervalent5.!The!chosen!Lewis!bases!as!partners!of!the!Martin!spirosilane!are!NHC!carbenes6!due!to!their!high!nucleophilicity!and!steric!hindrance.!Our!findings!along!these!lines!will!be!presented.!!!!!

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1 Jenny S. J. McCahill, Gregory C. Welch, and Douglas W. Stephan, Angew. Chem. Int. Ed., 2007, 46, 4968-4971 2 Douglas W. Stephan, Org. Biomol. Chem., 2012, 10, 5740-5746 3 X. Zhao, Douglas W. Stephan, Chem. Commun., 2011, 47, 1833-1835 4 Edmund F. Perozzi, J. C. Martin, J. Am. Chem. Soc, 1979, 101, 1591-1953 5 Robert J. P. Corriu, Journal of Organometallic Chemistry, 1990, 400, 81-106!6 Anthony J. Arduengo III, Michael Kline, Joseph C. Calabrese, F. Davidson, J. Am. Chem. Soc., 1991, 113, 9704-9705!

Journées)de)Chimie)Moléculaire)2016! Christophe!Lévêque!!

Development!of!a!versatile!approach!for!the!generation!of!alkyl!radicals!by!

photooxidation!of!alkylsilicates!

e,mail!address:!cleveque@ens,cachan.fr!PhD!advisor(s):!Louis!FENSTERBANK!and!Cyril!OLLIVIER.!

Laboratory:)Institut)Parisien)de)Chimie)Moléculaire,)Equipe)MACO)

)Université)Pierre)et)Marie)Curie)Sorbonne)Universités)

4)Place)Jussieu,)Bât)F)2eme)ét.)case)229,)75252)Paris)cedex)5)

!Visible,light!photoredox!catalysis!has!emerged!as!a!very!powerful!strategy!to!generate!radical!species!

swiping! all! the! tin,mediated! or! some! stoichiometric! redox!methodologies1.!Many! opportunities! are! now!available! to! access! a! large! range! of! C,centered! radicals,! based! either! on! photooxidative! or! reductive!processes.2!However,!generation!of!unstabilized!alkyl!radicals!is!still!a!challenge.!Methodologies!have!been!developed! to! generate! stabilized! alkyl! radicals! by! photooxidation! of! organotrifluoroborates3! or! α,aminocarboxylates.4!Recently,!our!group!first!reported!the!generation!of!unstabilized!alkyl!primary!radicals!by!photooxidation!of!bis(catecholato),alkylsilicates.5!These!radicals!can!be!trapped!by!radical!acceptors!or!engaged!with!(hetero)aryl!halides!or!alkenyl!halides!as!electrophiles!in!dual!photoredox/nickel!catalysis!for!the!formation!of!C(sp3),C(sp2)!bonds.6!Usually,!metal!complexes!based!on!ruthenium!or!iridium!are!used!as!photocatalysts! but! increasing! efforts! have! been! realized! to! develop! processes! involving! organic!photocatalysts.7!

Scheme 2 Photooxidation of bis(catecholato)-akylsilicates: toward C-C bond formation.

Acknowledgment:!Ministère!de!l’Enseignement!Supérieure!et!de!la!Recheche,!ENS!Cachan.!! !

1 (a) P. Renaud, M. P. Sibi in Radicals in Organic Synthesis, 2001, vol 1& 2, Wiley-VCH, Weinheim. (b) D. P. Curran, N. A. Porter, B. Giese in Stereochemistry of Radical Reactions, 1996, Wiley-VCH, Weinheim. 2 C. K. Prier, D. A. Rankic, D. W. C. MacMillan Chem. Rev. 2013, 113, 5322−5363. 3 Y. Yasu, T. Koike, M. Akita Adv. Synth. Catal. 2012, 354, 3414–3420. 4 Z. Zuo, D. W. C. MacMillan J.Am.Chem.Soc. 2014, 136, 5257−5260. 5 V. Corcé, L.-M. Chamoreau, E. Derat, J.-P. Goddard, C. Ollivier, L. Fensterbank Angew.Chem. Int.Ed. 2015, 54, 11414 –11418. 6 C. Lévêque, L. Chenneberg, V. Corcé, J.-P. Goddard, C. Ollivier, L. Fensterbank Org. Chem. Front. 2016, 3, 462-465. 7 D. A. Nicewicz, T. M. Nguyen ACSCatal, 2014, 4, 355−360.

Journées)de)Chimie)Moléculaire)2016! Fei!YE!!

SolventRFree!Ruthenium!TrichlorideRMediated![2!+!2!+!2]!Cycloaddition:!!

An!Efficient!Access!Toward!Fluorenone!Derivatives!!

fei.ye@chimie,paristech.fr!!PhD!advisors:!Mansour!Haddad,!Véronique!Michelet!and!Virginie!Vidal!!

Laboratory:)Institut)de)Recherche)de)Chimie)Paris)(UMR)8247),)équipe)Catalyse,)Synthèse)de)Biomolécules)et)

Développement)Durable)(CSB2D)fChimie)ParisTech,)11)rue)Pierre)et)Marie)Curie,)75005)Paris,)France))

!Fluorenones!derivatives1!are!found!in!many!natural!and!pharmaceutical!products.2!These!compounds!have!also!been!used!as!intermediates!in!material!science.3!Transition,metal,catalyzed![2+2+2]!cycloadditions!have!been! recognized!as!one!of! the!most!powerful! atom,economical!method! to! access! carbo,!or!heterocyclic!aromatic! compounds.4! To! the! best! of! our! knowledge,! only! a! single! report! describes! the! use! of! [2+2+2]!cycloaddition!reactions!to!access!such!scaffolds.5!As!a!continuation!of!our!research!program!to!explore!the!metal,catalyzed![2+2+2]!cycloadditions!under!solvent,free!conditions,6!we!present!here!a!novel!and!general!route!for!the!preparation!of!highly!substituted!fluorenones!via!RuCl3rnH2O,promoted![2+2+2]!cycloaddition!of!substituted!carbonyl!bridged!diynes!with!substituted!internal!alkynes.7!

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!

Acknowledgment:!F.!Y.!thanks!the!China!Scholarship!Council!(CSC).! ! !

1. For recent publications, see: H. Li, R. Zhu, W. Shi, K. He, Z. Shi, Org. Lett., 2012, 14, 4850; Z. Shi and F. Glorius, Chem. Sci.,

2013, 4, 829; J. K. Laha, K. P. Jethava and S. Patel, Org. Lett., 2015, 17, 5890; D. R. Kumar and G. Satyanarayana, Org. Lett., 2015, 17, 5894; J. Song, F. Wei, Wei Sun, Ke Li, Y. Tian, C. Liu, Y.Li, and L.Xie, Org. Lett. 2015, 17, 2106 and references cited therein.

2. M. L. Greenlee, J. B. Laub, G. P. Rouen, F. Dininno, M. L. Hammond, J. L. Huber, J. G. Sundelof and G. G. Hammond, Bioorg. Med. Chem. Lett. 1999, 9, 3225; P. J. Perry, M. A. Read, R. T. Davies, S. M. Gowan, A. P. Reszka, A. A. Wood, L. R. Kelland and S. Neidle, J. Med. Chem., 1999, 42, 2679; M. T. Tierney and M. W. Grinstaff, J. Org. Chem., 2000, 65, 5355.

3. Q. Liu, W. Yao, Y. Shi and J. Tang, Heterocycles 2012, 85, 1077. A. Leliege, C. L. Regent, M. Allain, P. Blanchard and J. Roncali, Chem. Commun. 2012, 48, 8907.

4. S. Saito, Y. Yamamoto, Chem. Rev. 2000, 100, 2901; V. Gandon, C. Aubert, M. Malacria, Chem. Commun. 2006, 21, 2209; D. M. D’Souza, T. J. J. Muller, Chem. Soc. Rev. 2007, 36, 1095; N. Weding, M. Hapke, Chem. Soc. Rev. 2011, 40, 4525; G. Domingez, J. Pérez-Castells, Chem. Soc. Rev. 2011, 40, 3430; Y. Shibata, K. Tanaka, Synthesis 2012, 44, 323; Y. Yamamoto, Heterocycles 2013, 87, 2459; F. R. Truscott, G. Maestri, R. Rodriguez, M. Malacria, in: Modern Alkyne Chemistry, (Eds.: B. M. Trost, C.-J. Li), Wiley-VCH, Weinheim, 2014, 143; G. Domingez, J. Pérez-Castells, in: Comprehensive Organic Synthesis, 2nd edn., (Eds.: P. Knochel,G. A, Molander), Elsevier, Amsterdam, 2014, 5, 1537; M. Amatore, C. Aubert, Eur. J. Org. Chem. 2015, 265.

5. R. P. Kaiser, F. Hessler, J. Mosinger, I. Císařová and M. Kotora, Chem. Eur. J., 2015, 21, 13577. 6. J. Jacquet, A.-L. Auvinet, A. K. Mandadapu, M. Haddad, V. Ratovelomanana-Vidal and V. Michelet, Adv. Synth. Catal. 2015, 357,

1387. 7. Manuscript in preparation.!

! AtomReconomical!process!! CostReffective!ruthenium!catalyst!! Nontoxic!solventRfree!conditions!! Ligand!and!additive!free!system!!! Access!to!aromatic!and!heterocyclic!fluorenones!! Wide!range!of!functional!groups!tolerated!! Gram!scale!synthesis!

O

R1

R2

R3

R3R2

R1O

R3

R3

RuCl3 · nH2O 5 mol%no solvent

50 to 80 °C, 2-18 h(2 eq.) 18 examples

up to 81% yield

Journées)de)Chimie)Moléculaire)2016! Radhouan!MAAZAOUI!!

Domino!Methylenation–Hydrogenation!of!Aldehydes!and!ketones!by!Combining!

Matsubara!Reagents!and!Wilkinson’s!Catalyst!!

radhouanmaazaoui@hotmail.fr!!PhD!advisor(s):!Pr.!Fabrice!Chemla,!Dr.!Olivier!JACKOWSKI!!

!Development!of!new!synthetic!processes!that!meet!both!economic!and!environmental!needs!is!one!of!the!major!challenges!in!organic!chemistry!and!its!main!source!of!innovation.!Finding!new!strategies!that!reduce!the!number!of!elementary!operations!required!to!achieve!a!given!transformation!participates!to!this!effort!since! it!allows!significant!waste!diminution.1!Thus,! in! this! context,!one,pot!multiple! transformations!have!attracted! an! ever,increasing! interest.2,3! Carbonyl! methylenation! is! an! important! method! for! C–C! bond!formation!because!the!resulting!alkene!offers!a!valuable!handle!for!further!elaboration.!However,!processes!wherein! the! generated! alkene! undergoes! a! subsequent! transformation! in! the! same! reaction!media! are!scarce.4!!A!case!to!the!point! is! the!combination!of!aldehyde!methylenation!and!hydrogenation.!This!sequence! is!a!common!strategy!to!introduce!an!ethyl!group!from!aldehydes!in!multi,step!synthesis!of!natural!products,5!bioactive! analogues6! or! key! intermediates.7! In! this! context,! the! combination! of! Matsubara’s! reagents![CH2(ZnI)2]! and! Wilkinson’s! complex! allows! the! domino! methylenation–hydrogenation! of! aromatic! and!aliphatic!aldehydes!and!ketones!in!good!yields.!The!scope!and!limitation!of!this!process!will!be!discussed.!!

H"or"R'R

OR="Alkyl"or"Aryl

IZn ZnI , ClRh(PPh3)3

H2"atmosphere

Domino&Process

H"or"R'R

up"to"86% !!

!1! "(a)"Sheldon,"R."A."Green%Chem.,"2007,"9,"1273."(b)"Constable,"D."J."C.;"Dunn,"P."J.;"Hayler,"J."D.;"Humphrey,"G."R.;"Leazer,"J."L."Jr.;"Linderman,"R."J.;"

Lorenz,"K.;"Manley,"J.;"Pearlman,"B."A.;"Wells,"A.;"Zaks,"A.;"Zhang,"T."Y.""Green%Chem.2007,"9,"411."2! (a) Anastas, P. T.; Kirchhoff, M. M. Acc. Chem. Res. 2002, 35, 686. (b) Anastas, P. T.; Warner, J. C. Green chemistry

theory and practice, Oxford, Oxford University press, 1998, pp135. 3! For a seminal review on domino reactions, see: (a) Tietze, L. F. Chem. Rev., 1996, 96, 115; (b) Tietze, L. F.; G.

Brasche, G.; Gericke, K. M. in Domino Reactions in Organic Synthesis, Wiley-VCH,Weinheim, 2006. (c) Borukhova, S.; Tietze, L. F. Green Processing and Synthesis 2014, 3, 501.

4! (a) Kawasaki, T.; Ogawa, A.; Terashima,R. Saheki, T.; Ban, N.; Sekiguchi,H; . Sakaguchi, K; Sakamoto,M. J. Org. Chem.2005, 70, 2957; (b) Kawasaki, T.;Shinada, M.;Kamimura, D.; Ohzono, M.; Ogawa, A. Chem. Commun.2006, 4, 420; (c) Breit, B.; Zahn, S; K. Angew. Chem. Int Ed. 1999, 38, 969; (d) Breit, B.; Zahn, S. K. Tetrahedron2005, 61, 6171; (e) Farwick, A.; Helmchen, G. Adv. Synth. Catal. 2010, 352, 1023; (f) Prasad Mishra, G.; Venkata Ramana, G.; Venkateswara Rao, B. Chem. Commun. 2008, 3423.

5! Mizoguchi, H.; Oikawa, H.; Oguri, H. Nature Chem.2014, 6, 57. 6! Rhoden, J. B.; Bouvet, M.; Izenwasser, S.; Wade, D.; Lomenzo, S. A.; Trudell, M. L. Biorg. Med. Chem.2005, 13,

5623. 7! Yamane, T.; Izhizaki, M.; Suzuki, M.; Takahashi, M.; Hiroya, K.; Takano, S.; Ogasawara, K. Heterocycles1996, 42,

65. ! !

Sorbonne!Universités,!UPMC!Univ!Paris!06,!CNRS!UMR!8232,!Institut!Parisien!de!Chimie!Moléculaire!(IPCM),!CC!229,!4!place!Jussieu,!F,75252!Paris!Cedex!05,!France.!

Journées)de)Chimie)Moléculaire)2016! Liang!CHANG!!

Methyl!Coumalate!Involved!MoritaRBaylisRHillman!Reaction!

liang.chang@upmc.fr!PhD!advisors:!Dr.!Luc!Dechoux,!Pr.!Serge!Thorimbert!

Laboratory:)IPCM)Chembio)group)

!!The!Morita,Baylis,Hillman!(MBH)!reaction!is!an!atom,economic!carbon,carbon!bond,forming!reaction.!!!In!general!it!could!be!described!as!a!coupling!between!activated!electron!deficient!alkenes!(alkynes)!and!electrophiles!catalyzed!by!Lewis!base!providing!a!classes!of!functionalized!molecules.1!!Different! types! of! activated! alkenes! such! as! cyclic! and! acyclic! derivatives! have! been! used! in! the!MBH!reaction.! In! spite! of! the! advances! reached,! MBH! reactions! with! aromatic! heterocycles! have! not! been!reported!to!date.!!!Prepared!from!malic!acid,!methyl!coumalate! is!a!biorenewable!heterocyclic!compound,!which!provide!an!environmentally,benign!approach!for!organic!synthesis.2!!We!now!report!a!study!of!the!behavior!of!methyl!coumalate!under!Morita,Baylis,Hillman!conditions!upon!reaction!with!imines!and!aldehydes.!!!

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Acknowledgment:!Omar!KHALED!for!HRMS,!Lise!Marie CHAMOREAU!for!XRD,!CSC!for!scholarship.!UPMC!&!CNRS!for!financial!support.!!

1 D. Basavaiah, B. S. Reddy, S. Badsara, Chem. Rev. 2010, 110, 5447. 2 a) J. Lee, G. Kraus. Green Chem. 2014, 16, 2111. b) G. Kraus, S. Riley, T. Cordes. Green Chem. 2011, 13, 2734. c) S.

Zheng, X. Lu. Org. Lett. 2009, 11, 3978. d) J. Agarwal, O. Bayounes, S. Thorimbert, L. Dechoux. RSC Advances. 2014, 4, 2272.

Journées)de)Chimie)Moléculaire)2016! Alexandra!FERALDI!!

Ring!Contraction:!Synthesis!of!functionalized!αR(trifluoromethyl)Rpyrrolidines!and!

piperidines!

alexandra.feraldi@espci.fr!PhD!advisor:!Prof.!Janine!Cossy,!Dr.!Domingo!Gomez!Pardo!

Laboratoire)de)Chimie)Organique,)Institute)of)Chemistry,)Biology)and)Innovation)(CBI),)UMR)8231)

ESPCI)Paris/CNRS)/PSL*)Research)University,))

10)rue)Vauquelin,)75231)Paris)Cedex)05)

!Introduction!of!a!fluorine!atom!on!molecules!often!improves!their!biological!properties!by!increasing!their!hydrophobicity,! their! thermal! and! metabolic! stability.! Therefore,! it! became! obvious! that! fluorinated!compounds!have!a!remarkable!record!in!medicinal!chemistry!and!will!play!a!continuous!role!in!providing!lead!compounds! for! therapeutic! applications.1! Amongst! these! compounds,! amines! possessing! an! α,trifluoromethyl! substituent!are!of! great! importance!as! they!are!present! in!a! variety!of!biologically!active!compounds.2!!In!this!context,!a!series!of!2,substituted!2,(trifluoromethyl)pyrrolidines!containing!a!quaternary!center!at!the!C2!position!were!synthesized!from!3,hydroxy,3,(trifluoromethyl)piperidine.!The!reaction!proceeds!via!a!ring!contraction!to!form!an!aziridinium!intermediate!which,!after!the!attack!of!a!nucleophile,!gives!the!desired!substituted! pyrrolidines! (eq! 1).3! In! addition,! this! ring! contraction! affords! 2,substituted!2,(trifluoromethyl)piperidines!from!3,hydroxy,3,(trifluoromethyl)azepane!(eq!2).!It!is!worth!mentioning!that!a!chirality!transfer!takes!place!during!this!ring!contraction!

!

!

!

!

!

!!! !

1 For fluorine in medicinal chemistry see: [a] H.-J. Bohm, D. Banner, S. Bendels, M. Kansy, B. Kuhn, K. Muller, U.

Obst-Sander, M. Stahl, ChemBioChem 2004, 5, 637–643, [b] K. L. Kirk, Org. Process Res. Dev. 2008, 12, 305–321, [c] S. Purser, P. R. Moore, S. Swallow, V. Gouverneur, Chem. Soc. Rev. 2008, 37, 320–330.

2 [a] Fluorine- Containing Amino Acids : Synthesis and Properties (Eds.: V. P. Kukhar, V. A. Soloshonok), Wiley, New York, 1995, [b] G. Chaume, N. lensen, N. Caupene, T. Brigaud, Eur. J. Org. Chem. 2009, 2009, 5717–5724.

3 A. Feraldi-Xypolia, D. Gomez Pardo, J. Cossy, Chem. Eur. J. 2015, 21, 12876–12880.

NBn

OHCF3

NBn

CF3 NBn

CF3Nu (eq-2)

Nu

22'

NBn

CF3

NuNBn

CF3

NBn

CF3OH

2

2'

Nu

(eq1)

Journées)de)Chimie)Moléculaire)2016! Thomas!AUBINEAU!!

Formation!of!NRcontaining!heterocycles!

thomas.aubineau@espci.fr!PhD!advisor:!Pr.!Janine!Cossy!

Laboratoire)de)Chimie)Organique)–)Institute)of)Chemistry,)Biology)and)Innovation)(CBI))–)UMR8231)f)ESPCI)Paris,)CNRS,)

PSL)Research)University)

10)rue)Vauquelin)–)75231)Paris)Cedex)05)

!Nitrogen,containing!six,membered!heterocycles!are!widely!encountered!in!the!structure!of!pharmaceutical!and!agrochemical!products.1!As!such,!new!methods!to!access!these!compounds!are!desirable.!We!focused!our! attention! on! the! formation! of! heterocycles! possessing! two! heteroatoms! such! as! piperazines! and!morpholines.!!The! formation! of! piperazines! derivatives!was! envisioned! by! using! the! powerful! alkynylating! hypervalent!iodine,based! reagent! trimethylsilylethynylbenziodoxolone! (TMS,EBX).! After! having! shown! the!chemoselectivity!of!this!reagent!towards!sulfonylated!amines!in!comparison!with!carbamates!or!amides,!a!one,pot!cyclization!leading!to!tetrahydropyrazines!from!orthogonally!protected!ethylene,diamines!has!been!developed!(Scheme 3).2!!

Scheme 3

!In!addition,!2,6,morpholines!were!synthesized!by!taking!advantage!of!the!metal,catalyzed!activation!of!allylic!alcohols.3! A! thermodynamic! equilibrium! leading! to! the! formation! of! cisfmorpholines! with! good!diastereoselectivities!has!been!highlightened!(Scheme 4).!!

Scheme 4!

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1 E. Vitaku, D. T. Smith, J. T. Njardarson, J. Med. Chem. 2014, 57, 10257-10274. 2 T. Aubineau, J. Cossy, Chem. Commun. 2013, 49, 3303-3305. 3 J. Cornil, L. Gonnard, C. Bensoussan, A. Serra-Muns, C. Gnamm, C. Commandeur, M. Commandeur, S. Reymond,

A. Guérinot, J. Cossy, Acc. Chem. Res. 2015, 48, 761-773.

NH

HN

N

N

N

HN

R

TMS-EBX

NaH

NaH

(1 equiv)

(2 equiv)

NaH(1 equiv)

R

R

Ts

Ts

RTs

DMF

IO TMS

TMS-EBX

O

-NR = amides, carbamates

1,2

1,2

1,2

N

Ts

R

OH

OH O

N

R

Ts

FeCl3.6H2O (5 mol %)

CH2Cl2, 50 °C, 2 h

cis/trans = 90/10 to 99/1

H H

Journées)de)Chimie)Moléculaire)2016! Ludovic!LELEU!!

Kojic!acid!:!a!natural!compound!for!organic!synthesis!and!access!to!

biologically!active!molecules!!!

ludovic.leleu@chimie,paristech.fr!PhD!advisor:!Christian!Girard!

UTCBS,)U)1022)INSERM,)UMR)8258)CNRS,)Chimie)Paristech,)11)rue)Pierre)et)Marie)Curie,)75005)Paris)

!Kojic!acid! is!a!by,product!of!alcoholic! fermentation! industries.! It! comes! from!hexose!and!glucose!

transformations,!especially!during!rice!fermentation.1!This!substituted!pyranone!was!considerably!studied!in!literature!for!its!various!properties,!and!is!often!used!for!its!actions!on!pigmentation!in!food!and!cosmetic!industries.2!(Food!preservation!/!skin!whitening)!

Structure!and!reactivity!of!kojic!acid!allow!further!transformations!and!the!synthesis!of!structurally!diversified!polycyclic!compounds!will!be!presented.!These!heterocycles!can!be!obtained!in!several!steps!using!typical! reactions! like! [5+2]! cycloadditions,! Diels,Alder,! [5+2]/[4+2]! tandem! cycloadditions.3,4! All! the!compounds!were!produce!in!a!classical!organic!chemistry!manner!and!the!use!of!specific!equipments!like!microwave!reactor! !and!continuous,flow!chemistry!equipments!were!also!developing!to!obtain!syntheses!more!efficient!and!more!specific.!

!!

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!!

! !

1 R. Bentley, Nat. Prod. Rep., 2006, 23, 1046–1062. 2 M. Rosfarizan, M. Mohd Shamzi, S. Nurashikin, M. Madihah Mohd Salleh, A. B. Arbakariya, Biotech. Mol. Biol.

Rev., 2010, 5, 24-37.!3 A. Rumbo, L. Castedo, A. Mourino, J. L. Mascarenas, J. Org. Chem., 1993, 58, 5585-5586. 4 J. R. Rodriguez, A. Rumbo, L. Castedo, J. L. Mascarenas, J. Org Chem., 1999, 64, 966-970.

Journées)de)Chimie)Moléculaire)2016! Benjamin!FLAMME!!

Rational!design!of!5V!organic!electrolytes!Benjamin.flamme@chimie,paristech.fr!

Mansour!HADDAD1,!Phannarath!PHANSAVATH1,!Virginie!VIDAL1,!Alexandre!CHAGNES1,2!1Chimie)ParisTech,)PSL)Research)University,)CNRS,)Institut)de)Recherche)de)Chimie)Paris)(IRCP),)Ff75005)Paris,)France.)

2Réseau)sur)le)Stockage)Electrochimique)de)l’Energie)(RS2E),)FR)CNRS)3459,)France.)

!The! development! of! new! technologies! for! electrochemical! energy! storage! is! one! of! the! main!

challenges!of!the!next!decades.!Many!hopes!now!rely!on!lithium,ion!batteries!(LiBs)!that!have!invaded!the!market!of!laptops!and!which!appear!to!be!the!best!choice!in!a!short!term!for!electric!vehicles,!and!perhaps!for! network! applications! (electricity! storage! from!wind! turbines! or! solar! cells! for! example).!Many!works!concern!the!search!for!cathodes!with!high,energy!density!but!only!few!studies!focus!on!the!synthesis!of!new!dipolar! aprotic! organic! solvents! for! LiBs! electrolytes.! Thus,! there! is! a! need! to! deviate! from! traditional!approaches! for! identifying! new! electrolytes! stable! to! high! voltage! that! are! based! on! "Trial! and! Errors"!approaches.!Research!groups!from!organic!chemistry,!electrochemistry,!solution!chemistry,!thermodynamics!and! theoretical! chemistry! were! included! in! this! multidisciplinary! project.! The! present! poster! aims! at!presenting!recent!advances!on!the!design!of!new!organic!electrolytes!for!high,voltage!batteries.!!

First,! a! critical! review! of! the! physicochemical! and! electrochemical! properties! of! the! organic!electrolytes!was!conducted!(boiling!and!melting!points,!viscosity,!ionic!conductivity!in!the!presence!of!lithium!salts,!oxidation!potential,!etc.).!This!critical!review!highlights!the!lack!of!homogeneity!in!the!literature!data!for! performing! rational! design! of! electrolytes! by! means! of! quantitative! structure,property! relationship!calculations! (QSPR).! Therefore,! these! data! were! completed! and! homogenized! by! performing! new!experiments.!In!particular,!more!than!20!new!dipolar!aprotic!organic!solvents!based!on!sulfone!moiety!were!synthesized!and!characterized.!!

!

!!

Second,! the! physicochemical! properties! of! these! new! dipolar! aprotic! organic! solvents! including!viscosity,! ionic! conductivity! and! their! electrochemical! behaviors! on! graphite,! ! Nickel! Manganese! Cobalt!(NMC)!and!Lithium!Rich!electrodes!as!well!as!platinum!and!glassy!carbon!electrodes!will!be!presented!and!discussed.!!

Finally,!we!will!highlight!the!main!drawbacks!and!the!next!challenges!in!the!design!of!new!organic!electrolytes!for!5V!lithium,ion!batteries.!!!

!

K. Xu, Chem. Rev., 2004, 104, 4303−4417, Y. Sasaki, Electrochemistry, 2008, 76, 2-15 A. Abouimrane, I. Belharouak, K. Amine, Electrochem. Commun., 2009, 11, 1073–1076, C.-C. Su, M. He, P. Redfern, L. A. Curtiss, C. Liao, L. Zhang, A. K. Burrell, Z. Zhang, ChemElectroChem., 2016, DOI: 10.1002/celc.201500550.! !

Journées)de)Chimie)Moléculaire)2016! FrançoisRXavier!GUILLON!!

Electrochemical!microRNA!biosensors:!

an!ergonomic!miniaturized!twoRelectrode!setup!

fx.guillon@chimie,paristech.fr!PhD!advisor(s):!Mathieu!LAZERGES!(MCF!Paris!Descartes),!Fethi!BEDIOUI!(DR!CNRS)!

Laboratory:)UTCBS)–)UMR)8258)–)INSERM)U1022)

École)Nationale)Supérieure)de)Chimie)de)Paris)

)11)rue)Pierre)et)Marie)Curie,)75231)Paris)Cedex)05)

)

MicroRNAs!are!RNAs!from!18!to!23!bases!involved!in!many!biological!processes.!They!particularly!regulate!gene!expression!by!partial!matching!with!messenger!RNAs1.!They!were!recently!discovered!and!they!are!the!last!biological!class!of!molecules!making!up!the!genetic!code.!They!can!be!found!in!different!biological!liquids,!they!enable!the!diagnosis!of!several!pathologies2!and!can!be!considered!as!excellent!biomarkers3.!

However! quantification! of!microRNAs,! from!10,12! to! 10,18!M! in!complex! matrixes! is! a! real! challenge! since! it! requires! the!development! of! a! specific! and! very! sensitive!measurement! tool.!Electrochemical!biosensors!and!particularly!the!long,range!electron!transfer!DNA,sensors!offer!an!efficient!way!to!do!so4.!In!this!study!we!develop!an!ergonomic!DNA,biosensor!based!on!a!two,electrode!electrochemical!setup!and!using!a!microelectrode!as!working!electrode,!well!adapted!for!detection!in!microliter!samples!and! miniaturization.! A! 23,base! DNA,probe! self,assembled!monolayer!was! first! formed!onto!a!50!µm,diameter!gold!surface.!The!microelectrode!extremity!was!then!immersed!in!a!50!µL!DNA,target! solution! drop! itself! deposited! onto! a! 5!mm,diameter! gold!counter! electrode.! Transduction! occurs! via! long,range! electron!

transfer,!which! is!enhanced!subsequently! to!hybridization,!due!to!DNA,base!π,stacking5.!Single!mismatch!detection!of! this! first!prototype!was!matched!at! room! temperature! in! the!nanomolar! range!without!any!optimization.!!!!!!!!!!!!Aknowledgment: FXG!acknowledges!support!from!the!program!«Investissements!d’Avenir!»!launched!by!the!French!Government!and!implemented!by!ANR!with!the!references!ANR,10,LABX,XXX!and!ANR,10,IDEX,0001,02!PSL!for!PhD!fellowship! !

1 H. Vaucheret, C. Béclin, M. Fagard, Journal of Cell Science 2001, 114, 3083-3091 2 J. Lu, G. Getz, E. Miska, Nature 2005, 435, 834-838 3 Q. Shi, X. Yang, D. Mendrick, Biomarkers in Medicine 2013, 7, 307-315 4 S. Kelley, E. Boon, J. Barton, Nucleic Acids Research 1999, 27, 4830-4837 5 K. Hashimoto, K. Ito, Y. Ishimori, Analytical Chemistry 1994, 66, 3830-3833

Figure 1: Scheme of a long-range electron transfer RNA biosensor with redox intercalator

Journées)de)Chimie)Moléculaire)2016! Xia!WANG!!

Photocatalytic!CO2!reduction!by!multinuclear!metal!complexes!

Xia.wang@college,de,france.fr!PhD!advisor:!Marc!FONCTECAVE!

Laboratory)of)Chemistry)of)Biological)Processes)

11)Place)Marcelin)Berthelot)75005)Paris)

!The!general!field!of!energy!storage!is!crucial!to!the!successful!development!and!implementation!of!renewable!energy!technologies.!Storing!energy!in!the!form!of!chemical!bonds!allows!for!the!production!of!energetically!dense!fuels.!Carbon!dioxide,!through!its!reduction,!is!an!ideal!candidate!as!a!carbon!source!for!such!fuels.!The!metal,based!molecular!approach!to!the!development!of!catalysts!has!long!been!favored!for!fundamental!studies!due!to!the!facile!modification!of!the!catalytic!active!sites,!which!is!ideal!for!investigating!fundamental!questions!such!as!selectivity!and!mechanism.1!

Since! 2005,! Ishitani! and! co,workers! have! been! focusing! on! Re,Ru! bimetallic! complexes! for!photocatalytic! CO2! reduction,! where! the! Re! center! serves! as! a! catalyst! and! the! Ru! center! serves! as! a!photosensitizer.2! Inspired! by! their! study,! a! series! of! Co,Ru,! Ru,Ru! and! Ru,Co,Ru! complexes! have! been!synthesized,! and! the! photocatalytic! activities! for! CO2! reduction! are! being! studied.! Having! surveyed! and!identified!a!set!of!optimal!conditions,!photokinetic!studies!on!each!complex!were!investigated.!After!16!hours!irradiation!up!to!332!turnover!numbers!(TONs)!for!formate!was!observed!for!a!Ru,Co,Ru!complex,!and!60!TONs!for!CO!for!a!Co,Ru!complex.!No!products!were!formed!in!the!absence!of!either!the!complexes!or!light.!Also!the!addition!of!mercury!into!our!photocatalytic!system!did!not!affect!the!amount!of!products!formed.!Taken! together,! it! suggested! that! the! catalysts! involved! in! CO2! photoreduction! were! the! molecular!complexes.!Studies!on!effects!of!the!peripheral!ligands!and!the!central!bridge!between!the!metals!indicated!that!the!ligands!influenced!the!selectivity!between!carbon,based!products!and!H2!production.!!!!!!!

!!

!

!

!

!

!

!

!

!

!

Aknowledgment:!

I!acknowledge!D.!Meyer!(DR,!ICSM)!for!providing!complexes,!and!Paris!Sciences!et!Lettres!(PSL)!Research!University!for!financial!support.! !

1!X.!Wang,!M.!Fontecave,!et!al.,!Chem.)Soc.)Rev.!(submitted)!2!O.!Ishitani,!et!al.,!!Inorg.)Chem.,!2005,!44,!2326,2336!!

N

N

NH

N

N

N

N

HN

R1

R2

A B

A:!Ru(bpy)2,!Ru(4,4’,Mebpy)

2!

B:!Co(phen)2,!Co(tpy)Cl,!Ru(bpy)

2,!Ru(4,4’,Mebpy)

2!

R1:!H,!tBu!

R2:!H,!OH!

Journées)de)Chimie)Moléculaire)2016! Pascal!MATTON!!

Glycolipid!functionalized!microdroplets!for!cells!vectorization!

pascal.matton@ens.fr!PhD!advisor(s):!Jean!Maurice!MALLET1,!Jacques!FATTACCIOLI2!

1Laboratoires)des)biomolecules,)CNRS)UMR)7203,)Department)of)Chemistry,)ENS,)24)rue)Lhomond,)Paris)75005)2Laboratoire)P.A.S.T.E.U.R,)CNRS)UMR)8640,)UPMC,)Department)of)Chemistry,)ENS,)24)rue)Lhomond,)Paris)75005)

)

! Some!pathogens!or!tumor!cells!escape!the!immune!system!because!the!immune!cells!misrecognize!them.!Therapeutic!approaches,!promoting!the!recognition!of!these!poorly!immunogenic!peptides!or!proteins!are!thus!very!attractive.11!The!strategy!is!then!to!process!directly!peptides!or!proteins!through!the!immune!system.!To!this!end,!some!systems!have!been!described,!based!on!lipopolyplexe2!or!nanoparticle3.!We!propose!to!use!an!oil!droplet!based!system.!! Among!the!microparticles,!vegetal!oil!microdroplets!have!numerous!advantages!over!solid!microparticles.!Made!of!natural!triglycerides,!they!are!biocompatible!and!biodegradable;!their!liquid!nature!gives!them!a!greatly!stealth!(no!adsorption!of!proteins!on!their!surface,!low!recognition!by!immune!cells).!A!previous!work,!with!IgG,functionalized!oil,in,water!emulsion!droplets!for!phagocytosis!studies!with!macrophage,!has!shown!that!during!the!recognition!by!macrophages,!IgGs!are!driven!and!concentrate!in!the!contact!zone!by!interaction!and!thus!increase!the!sensitivity.!They!are!ideal!platforms!to!build!multifunctional!assemblies!for!vectorization4.!! The!goal!of!this!project!is!to!build!and!use!for!vectorisation!a!lipidic!shuttle:!Oil!microdroplets!(diameter!:!5,7!µm),!functionalized!with!the!required!immunogenic!molecules!and!with!molecules!determining!their!behavior!in!front!of!immune!cells,!in!particular!different!concentration!of!glycolipid!which!is!a!cell!lectins!ligand!(Fig!1).!!

!!

Figure!1!:!(left)!lectins!interaction!with!fluorescence,labeled!glycolipid!in!oil!droplet.!(right)!:!Micro!droplet!functionalized!with!a!fluorescent!mannolipide!viewed!in!fluorescent!microscopy.! ! In!the!preliminary!work!reported!here,!we'll!present!the!synthesis!and!physical!properties!(CMC,!surface!tension,!...)!of!mannose!and!galactose!glycolipids.!The!glycolipids!were!functionalized!by!a!robust!and!hydrophobic!fluorophore!in!order!to!verify!their!correct!functionalization!at!the!surface!of!the!droplet!(figure!1,!right).!The!galacto!and!manno!labeled!droplets!were!then!brought!into!contact!with!fluorescent!soluble!lectins:!PNA!(for!galactose)!and!ConA!(for!mannose),!and!specific!recognitions!were!observed.!Based!on!this!encouraging!observation,!we!are!now!studying!interactions!of!the!droplet!with!cells.!! !

1 Tagliamonte, M.; Petrizzo, A.; Tornesello, M. L.; Buonaguro, F. M.; Buonaguro, L. Hum. Vaccines Immunother.

2014, 10 (11), 3332. 2 Midoux, P.; Pichon, C. Expert Rev. Vaccines 2015, 14 (2), 221. 3 Zhao, L.; Seth, A.; Wibowo, N.; Zhao, C.-X.; Mitter, N.; Yu, C.; Middelberg, A. P. J. Vaccine 2014, 32 (3), 327. 4 Ben M’Barek, K.; Molino, D.; Quignard, S.; Plamont, M.-A.; Chen, Y.; Chavrier, P.; Fattaccioli, J. Biomaterials 2015,

51, 270.

Fluorescent+lec,n+

Droplet++

Fluorescent+glycolipid++

Journées)de)Chimie)Moléculaire)2016! Thomas!DENEFLE!!

TSPR1!mimetic!peptides!inducing!selective!apoptosis!of!cancer!cell!lines:!design,!

synthesis!and!structureRactivity!relationship!studies!!

thomas.denefle@upmc.fr!PhD!advisor:!Pr.!Philippe!Karoyan!

!LBM)–)site)GSK,)25f27)avenue)du)Québec,)91140)VillebonfSurfYvette,)France.)

Sorbonne)Universites,)UPMC)Univ)Paris)06,)Ecole)Normale)Superieure,)CNRS,)Laboratoire)des)Biomolécules)(LBM),)4)

place)Jussieu,)75005)Paris,)France))

Departement)de)Chimie,)Ecole)Normale)Superieure,)PSL)Research)University,)UPMC)Univ)Paris)06,)CNRS,)Laboratoire)

des)Biomolecules)(LBM),)Paris,)France))

)

)

!!!!!!!!!!!

!!

Figure:!TSP,1!derived!peptide!inducing!selective!apoptosis!of!tumor!cells!in)vitro.!!

Thrombospondin!1!(TSP,1),!a!multidomain!glycoprotein!from!the!extracellular!matrix,!is!able!to!bind!to!many!cell! surface! receptors! such! as! CD47.! The! TSP,1/CD47! interaction! triggers! programmed! cell! death.! We!demonstrated!that!4N1K,!a!short!peptide!derived!from!C,terminal!binding!domain!of!TSP,1,!induced!selective!apoptosis! of! numerous! cancer! cell! lines! sparing! normal! cells.1! In! order! to! improve! the! pharmacological!properties!of!this!compound,!we!initiated!a!complete!structure,activity!relationship!study!through!rational!design.!As!part!of!my!PhD,!this!work!leads!to!the!discovery!of!active!and!serum,stable!new!peptides!derived!from!this!protein,protein!interaction!epitope!that!will!be!presented!herein.2!

!

Acknowledgments:!!

INCa,!ANR,!Labex!Michem!and!SATT!Lutech!(Michael!Machicoane)!are!gratefully!acknowledged!for!financial!support!and!Pr.!Philippe!Karoyan!deeply!thanks!GSK!for!hosting!and!partnership.!! !

1 a) Susin, S-A. ; Merle-Beral, H. ; Launay, P. ; Karoyan, P. PCT Int. Appl. 2013, WO 2013182650 A1 20131212. b) Martinez-Torres, A-C. ; Quiney, C. et al. PLoS Med. 2015, 12(3): e1001796. 2 Denèfle, T. et al. 2016. Submitted manuscript.

Journées)de)Chimie)Moléculaire)2016! Sébastien!CARDON!!QUANTIFICATION!OF!THE!INTERNALIZATION!EFFICACY!OF!HOMEOPROTEINS!AND!

DERIVEDRCELL!PENETRATING!DOMAINS!

Sebastien.cardon@ens.fr!

Sandrine!Sagan!

Laboratoire)des)Biomolécules,)Sorbonne)UniversitésfUPMC,)ENS)Department)of)Chemistry)PSLfResearch)University,)

CNRS)UMR7203,)Paris,)France)

Homeoprotein! (HP)! transcription! factors! and! HP,derived! homeodomains! (HD)! have! the! characteristic! of!

being!secreted!and!internalized!by!eukaryotic!cells![1].!The!internalization!mechanism!of!these!proteins!and!

peptides!is!not!yet!fully!understood.!!

At!the!molecular!level,!it!was!found!that!the!16!amino!acid!long!third!helix!of!HD!provides!the!driving!force!

for! internalization! [2].! Interaction!with! cell,surface,!which! is! the! first! step! in! the! internalization! process,!

predominantly!relies!on!carbohydrates!and!was!reported!to!be!predominant!for!HD![3],!Penetratin,!and!HPs!

binding!to!distinct!cell!types.!!

!

The! aim! of! the! work! is! to! delineate! the!mechanisms! of! entry! of! HPs,! HDs! and! derived,cell,penetrating!

peptides! at! the! molecular! level.! We! chose! Engrailed! 2! as! a! representative! HP.! Quantification! of! the!

internalization!efficacy!of! these!proteins,!analysis!of! their! secondary! structure,!when! free! in!buffer,!or! in!

interaction!with!model!membranes,! together!with!thermodynamic!analyses!of! their! interactions!with!cell!

surface!sugars!are!the!first!steps!of!this!study.!!

!

Aknowledgment:!Laura!Molina,!Alain!Joliot,!Fabienne!Burlina,!Gérard!Bolbach,!Astrid!Walrant,!Olivier!Lequin,!

Ludovic!Carlier,!Sandrine!Sagan!!

!

! !

Journées de Chimie Moléculaire 2016 Thomas DRIANT

On the influence of the protonation states of active site residues on AChE

reactivation: a QM/MM approach

thomas.driant@upmc.fr

PhD advisor(s): Etienne Derat

Laboratory: Institut Parisien de Chimie Moléculaire UMR8232 Université Pierre et Marie Curie, 4 Place Jussieu

Structure optimisée du réactif de la réactivation par la 2-PAM de l’AChE inhibée par le VX.

Acetylcholinesterase (AChE) is an enzyme of the serine hydrolase superfamily and a mediator of the signal

transmission at cholinergic synapses.1 This enzyme is vulnerable to inhibition by organophosphate (OP)

compounds, especially combat gasses such as Sarin, VX, Tabun and Soman. The inhibition of AChE results in

the over activation of the synapses which leads to death by respiratory arrest.2 The covalent inhibition of

AChE does not revert spontaneously and known reactivator compounds have limited effects.3 We used an

hybrid QM/MM (B3LYP-D3:CHARMM) method to perform reactivation simulations of VX inhibited AChE by

2-PAM. During those simulation we studied the protonation state of a glutamate in close proximity with the

active site, Glu202. This work uncovers for the first time the key role of this residue in AChE reactivation.

The deprotonation of 2-PAM, an important step towards reactivation, was also explored in both

protonation states of Glu202. Those simulations allowed for a broader view of the effect of protonation

states in the active site. They allow us to conclude on the protonation states that make reactivation

possible.

Aknowledgment: DGA, Florian Nachon, Pierre-Yves Renard, MACO team

1 Quinn, D. M. Chem. Rev. 1987, 87 (5), 955–979. 2 Marrs, T. C.; Maynard, R. L. Cell Biol Toxicol 2013, 29 (6), 381–396. 3 Mercey, G.; Verdelet, T.; Renou, J.; Kliachyna, M.; Baati, R.; Nachon, F.; Jean, L.; Renard, P.-Y. Acc. Chem. Res. 2012, 45 (5), 756–766.

Journées)de)Chimie)Moléculaire)2016! Mathilde!BELNOU!!

Modulation!of!the!Calmodulin!Binding!Domain!of!the!protein!FKBP52!

mathilde.belnou@upmc.fr!Yves!Jacquot!

Laboratoire)des)biomolécules,)4)Place)Jussieu,)Tour)23f33)5ème)étage)

!

! FKBP52!(FK506+Binding!Protein)!is!an!immunophilin!protein!of!52!kDa!that!binds!immunosuppressant!

macrolide!drugs!such!as!rapamycin.!FKBP52!is!composed!of!four!distinct!domains:!(i)!an!FK1!domain,!which!

shares! peptidylprolyl! isomerase! (PPIase! or! rotamase)! enzymatic! activity! and! that! recognizes! macrolide!

immunomodulators!and!other!proteins!such!as!steroid!hormone!receptors,!(ii)!an!FK2!domain!that!binds!ATP!

and!GTP,!(iii)!a!tetratricopeptide!repeat!domain!(TPR)!that!recruits!the!heat+shock!protein!Hsp90!and!(iv)!a!

putative!Ca2++calmodulin+binding!domain1,2.!!

Calmodulin!is!a!small!calcium!sensing!protein,!which!participates!in!various!signalling!processes.!We!

are! interested! in! the! interaction! of! FKBP52! with! Calmodulin3.! In! the! present! research! project,! we! have!

synthesised! a! small! library! of! FKBP52+derived!peptides! and! tested! their! interaction!with! Calmodulin! using!

different! biophysical! approaches! such! as! Fluorescence! spectroscopy,! NMR! spectroscopy! and! Isothermal!

Titration!Calorimetry.!We!have!identified!FKBP52!TPR!domain+derived!peptides!that!bind!calmodulin!with!a!Kd!

∼!150!nM!and!a!stoechiometry!of!1:1.!This!process!is!calcium!dependent!and!the!mode!of!interaction!of!the!

peptide!with!Ca2++calmodulin!seems!canonical.!!

!!!!

!

!

!

!

!

!

!

!

!

!

!

!

!

!

Aknowledgments:!LBM!team!1:!Yves!Jacquot,!Cillian!Byrne,!Caroline!Bushdid,!LBM!team!3:!!Ludovic!Carlier,!Institut!Professeur!Baulieu:!E.E.!Baulieu,!Béatrice!Chambraud,! IBPS:!Gérard!Bolbach,!Emmanuelle!Sachon,!Gilles!Clodic,!Lucrèce!Matheron,!IBBMC:!Michel!Desmadril,!Magalie!Nicaise,!INSA:!Guy!Lippens!! !

1 A.Kamah et al, J. Mol. Biol., 2016 2 J. Giustiniani et al., The FASEB Journal, 2015,29 3 O’Day, Journal of Alzheimer’s disease, 2015, 46, 553-569

�(15

N) [

ppm

]

�(1H) [ppm]

Residue number

A

C

amid

e C

SP

[ppm

]

�(1H) [ppm]

�(13

C) [

ppm

]

B

D

Ca4CaM:FKBP52{278-300} 1:0 Ca4CaM:FKBP52{278-300} 1:1

N-ter

C-ter

hydrophobic pockets A57

G113 Ca4CaM:FKBP52{278-300} 1:0 Ca4CaM:FKBP52{278-300} 1:1

F19

V55

M71

M109

M145

A147

0,0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

0 10 20 30 40 50 60 70 80 90 100 110 120 130 140

Methionine methyl groups of Ca4CaM

Synthetic!FKBP52+derived!Calmodulin!binding!peptide!!

Journées)de)Chimie)Moléculaire)2016! Caroline!THEBAULT!!

UltraRMagnetic!Liposomes!and!their!in)vivo!Guidance!Monitoring!by!MRI!for!

Cancer!Therapy!

caroline.thebault@chimie,paristech.fr!!PhD!advisors:!Bich,Thuy!DOAN!and!Christine!MÉNAGER!!

))Chimie)ParisTech,)PSL)Research)University,)Unité)de)Technologies)Chimiques)et)Biologiques)pour)la)Santé)(UTCBS),)Ff

75005)Paris,)France)Sorbonne)Universités,)UPMC)Univ)Paris)06,)CNRS,))Laboratoire)PHENIX,)Case)51,)4)place)Jussieu,)Ff75005)Paris,)France))

)))

Theranostic!systems!are!developed!to!monitor!a!treatment!in)vivo!according!to!their!abilities!for!both!imaging!and! therapy1.! We! propose! an! innovative! strategy! to! treat! colon! cancer! with! the! design! of! magnetic!thermosensitive!liposomes2!that!enable!to!target!a!superficial!tumor!under!a!magnetic!field!gradient!and,!after!accumulation,!to!deliver!an!antitumoral!drug!by!High!Intensity!Focused!Ultrasounds!(HIFU)!application.!These! objects! can! be! track! in) vivo! due! to! their! imaging! properties.! In! this! study,! we! demonstrate! the!significant!increase!of!accumulation!of!Ultra,Magnetic!Liposomes!(UML)!in!CT26!murine!colon!tumor!using!Magnetic!Targeting!(MT)!compared!with!passive!Enhanced!Permeability!Retention!(EPR)!effect.!UMLs!are!highly!loaded!with!magnetic!nanoparticles!of!iron!oxide!(γ,Fe2O3)!enabling!both!magnetic!targeting!and!in)vivo!monitoring!by!MRI.!Liver!up,take!of!UMLs!after!I.V.!injection!was!followed!with!dynamic!susceptibility!contrast! imaging! in!MRI.!UMLs!accumulation! in! tumors!was!visualized!by!breath,triggered!multislice!T2*,weighted!MRI!with!adapted!dynamic!follow!up!in!time!at!7T.!The!figure!below!shows!an!MRI!slice!of!mouse!(A)!before!injection!(Reference!Tumors)!and!(B)!30min!after!the!injection!of!UML!with!a!Magnetic!Targeting!on!the!right!tumor!and!passive!accumulation!on!the!left!one.!!!

!!

MRI! image! by! low! percentile! processing! on! in) vivo! images! enabled! us! to! evaluate! the! difference! of!accumulation!between!Magnetic!Targeting!and!EPR!effect.!The!addition!of!a!fluorescent!NIR!Cy5.5!probe!on!the!liposome!membrane!allowed!the!visualization!of!UMLs!by!fluorescent!confocal!microscopy!to!confirm!the! guidance! of! the!whole! liposome.!Ex) vivo! iron! dosage! by! ICP,AES,! Cy5,5! quantification! and! histology!confirmed! the! increase! of! accumulation! with! Magnetic! Targeting.! Co,encapsulation! of! magnetic!nanoparticles! with! an! antitumoral! drug! gave! theranostic! properties! to! our! thermosensitive! liposomes.!Application!of!HIFU!can,!then,!be!used!in!the!tumor!for!an!active!release!of!the!drug!in!the!region!of!interest!for!the!development!of!an!innovative!therapy.!Functional!MRI!methods!will!enable!to!study!the!impact!of!antitumoral!drugs!on!the!tumor.!!

Aknowledgment:!

This!work!was!financially!supported!by!the!labex!MICHEM,!UPMC.!We!thank!our!collaborators!N.!Mignet,!G.!Ramniceanu,!J.!Seguin,!C.!Beauvineau,!C.!Girard,!B.!Larrat.!! !

1 B. Sumer, J. Gao, Nanomedicine, 2008, 3, 137-140 2 G. Béalle, R. Di Corato, J. Kolosnjaj-Tabi, V. Dupuis, O. Clément, F. Gazeau, C. Wihelm, C. Ménager, Langmuir,

2012, 28, 11834-11842.

Journées)de)Chimie)Moléculaire)2016! Frédéric!THIEBAUT!!

Identification!of!rare!DNA!base!protein!partner!using!photolabeling!and!mass!

spectrometry!

Frederic.thiebaut@upmc.fr!PhD!advisor(s):!Dominique!Guianvarc’h,!Carole!Saintomé!

Laboratory:)Laboratoire)des)BioMolécules,)UMR7203,)Université)Pierre)et)Marie)CuriefParis)6fENSfCNRS,)4,)place)

Jussieu,)75252)Paris)Cedex)05)

!Over!the!past!few!decades,!DNA!methylation!at!the!5,position!of!cytosine!(5,methylcytosine,!5mC)!

has!emerged!as!an!important!epigenetic!modification!that!plays!essential!roles!in!development,!aging!and!disease.!However,! the!mechanisms!controlling!5mC!dynamics! remain!elusive.!Recent!studies!have!shown!that! ten,eleven! translocation! (Tet)! proteins! can! catalyze! 5mC! oxidation! and! generate! 5mC! derivatives,!including!5,hydroxymethylcytosine!(5hmC)!.!!

5hmC! was! until! recently! believed! to! be! a! minor! modification,! resulting! of! oxidative! damage.!However,! results!published! in!2009!have!challenged!this!understanding! (1,!2).! In! fact,!5hmC! is!abundant! in!some!cell!types!and!its!formations!results!from!an!active!process.!These!recent!discoveries!raise!the!question!of!the!biological!role!of!5hmC.!Indeed,!If!the!role!of!5mC!in!gene!expression!regulation!is!well!established,!the!biological!role!of!5hmC!is!still!a!hot!topic.!Its!implication!in!the!DNA!demethylation!process!seems!a!major!reported!activity.!In!the!study!context!of!this!base!and!its!oxydative!derivatives,!it!is!needed!to!characterize!the!proteins!which!interact!with!this!pattern.!

!!!

!!

!The!identification!and!the!characterisation!of!these!proteins!should!give!us!a!better!insight!regarding!

this! epigenetic! mecanisms! and! therefore! could! reveal! new! therapeutic! targets.! Recent! studies! have! be!realised!in!the!field(3)!and,!subsequently!we!propose!here!a!photolabeling!strategy!to!seek!to!spot!new!protein!partners.!!

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Aknowledgment:!Programme!Interface!pour!le!vivant,!UPMC!! !

Journées)de)Chimie)Moléculaire)2016! Ourania!MAKRYGENNI!!

Hybrid!Polyoxometalates!for!homogeneous!supported!catalysis!

ourania.makrygenni@upmc.fr!!PhD!advisor:!Richard!Villanneau!

Laboratory:)EfPOM,)4)Place)Jussieu)75252)

!Polyoxometalates! (POMs)! are! nanoscopic! clusters! consisting! of! metal! ions! in! their! highest! oxidation!

number! (WVI, MoVI, VV) assembled by O2- ligands.! Due! to! their! strong! acidity! (in! their! acidic! form)! and!favorable!redox!properties,!POMs!and!their!derivatives!have!been!used!in!homogeneous!organic!synthesis!and!catalytic!reactions!as!acid!and!oxidation!catalysts.!Meanwhile,!their!applications!as!catalyst!supports!for!transition!metal! active! species! have! also!been!explored! and! good! reusability! could!be! realized!by! taking!advantage!of!their!large!framework.!

However,!these!homogeneous!systems!have!major!limitations!related!to!separation!issues:!loss!of!active!centers,!pollution!of!products!and!incompatibility!with!processes!in!pharmacology.!Therefore,!it!is!possible!to!prepare!heterogeneous!analogues!of! the!most!commonly!used!soluble!and!homogeneous!catalysts!by!their! immobilization!on! various! insoluble! supports. The!heterogenization!of! soluble! catalysts! can! lead! to!improved!robustness!and!therefore! increased!efficiency,!as! long!as!the!dispersion!and!accessibility!of!the!active!sites!on!the!support!are!optimized.!

Thus,!two!strategies!were!chosen!for!the!heterogenization!of!POMs:!•! The!use!of!platforms!with!large!specific!area!for!the!anchorage!and!with!porosity!ranging!from!5!to!

20nm,!such!as!structured!mesoporous!materials!(Silica!type!SBA15)!•! The!use!of!core!shell!nanoparticles,!consisting!of!a!magnetic!core!(maghemite)!and!a!silica!shell.1!The!

recovery!of!the!catalyst!can!be!easily!performed!magnetically!with!a!simple!magnet.!!These! two! supports! can! be! easily! functionalized! with! reactive! organic! functions! (carboxylic! acids,!

amines)!allowing!them!to!covalently!graft!the!catalysts.2!The!synthesized!materials!were!tested!in!targeted!model!catalytic!reactions,!such!as!the!epoxidation!of!

cyclic!alkenes!from!environmentally!friendly!oxidant!(air,!O2!or!failing!H2O2).3!

!!!!!!

!

!

Image!1:!POMs!grafted!on!mesoporous!silica!(left)!and!magnetic!nanoparticles!(right).!!

Acknowledgment:!Work!supported!by!“Ministère!de!l’éducation!nationale,!de!l’enseignement!supérieur!et!de!la!recherche”!! !

1 T. Georgelin, V. Maurice, B. Malezieux, J-M. Siaugue, V. Cabuil, J Nanopart Res. 2010, 12, 675-680 2 R. Villanneau, A. Marzouk, Y. Wang, A. Ben Djamaa, G. Laugel, A. Proust, F. Launay, Inorg. Chem. 2013, 52, 2958-

2965. 3 F. Bentaleb, O. Makrygenni, D. Brouri, C-C. Diogo, A. Mehdi, A. Proust, F. Launay, R. Villanneau, Inorg. Chem.

2015, 54 (15), 7607–7616.

Journées)de)Chimie)Moléculaire)2016! Juan!Ramón!JIMÉNEZRGALLEGO !

Switchable!redox!active!Fe/Co!cyanide!molecular!cube!encapsulating!K+!or!Cs+!

e,mail:juanjg30490@hotmail.com!PhD!advisor(s):!Pr.!Rodrigue!Lescouëzec!and!Dr.!Laurent!Lisnard!

Adresse:))Institut)Parisien)de)Chimie)Moléculaire)–)CNRS)UMR)8232,)UPMCfParis)6,)Sorbonne)Universités,)Ff75252,)Paris)cedex)05,)France.)Equipe)de)Recherche)en)Magnétisme)Moléculaire)et)Spectroscopie)

(ERMMES)))

In! 1996! Sato!et! al.1! described! the! first! photoinduced!magnetic!material,! K0.2Co1.4[Fe(CN)6]r6.9H2O,! in!which!an!Electron!Transfer!Coupled!to!a!Spin!Transition!(ETCST)!converts!the!diamagnetic!{FeIILSRCNRCoIII

LS}!pairs!into!paramagnetic!{FeIIILSRCNRCoII

HS}!ones!(LS:!low!spin,!HS:!high!spin)!under!light!irradiation.!The!physical!properties! of! this! 3D! inorganic! polymer,! known! as! Fe/Co! Prussian! Blue! analogues! (PBAs),! are! highly!dependent!on!their!chemical!composition!and!especially!on!the!amount!and!the!nature!of!the!inserted!alkali!ions2.!!

!

In!recent!years,!intense!research!efforts!have!been!devoted!to!the!synthesis!of!low!dimensional!models!(2D,!1D!or!0D)!of!the!Fe/Co!PBAs!in!order!to!develop!new!discrete!switchable!materials!that!can!be!easily!manipulated! and! studied3.! In! particular,! the! synthesis! of! elementary! units! of! the! PBA!network! has! been!attracting! much! interest! due! to! their! potential! magnetic! and! encapsulation! properties! and! multiredox!behaviour4.!!!

In!the!present!work,!we!will!describe!the!synthesis!and!structure!of!a!novel!octametallic!A⊂{Fe4Co4}!(A=!K+!or!Cs+)!cyanide!molecular!cube.!We!have!investigated!these!compounds!both!in!solution!and!in!the!solid!state.!Electrochemical!and!paramagnetic!NMR!reveal!the!stability!of!the!cube!in!solution!as!well!as!its!multi,redox! behaviour.!Magnetic! studies! have! shown! that! the! cubes! behave! as! switchable! units! and! as! field,induced!molecular!magnets.!!!

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1 Sato, O.; Iyoda, T.; Fujishima, A.; Hashimoto, K. Science 1996, 272, 704-705. 2 Cafun, G. Champion, M.-A. Arrio, C. C. dit Moulin and A. Bleuzen, J.Am.Chem.Soc. 2010, 132, 11552-11559.!3 R. Lescouëzec, L. M. Toma, J. Vaissermann, M. Verdaguer, F. S. Delgado, C. Ruiz-Pérez, F. Lloret and M. Julve,

Coord. Chem. Rev 2005, 249, 2691.!4 Boyer, J-L. Kuhlman, M-L. Rauchfuss, T-B. Accounts of Chemical Research 2007, 40, 233-242. D.-F. Li, R. Clérac,

O. Roubeau, E. Harté,C. Mathonière, R. Le Bris and S. M. Holmes, J. Am. Chem. Soc., 2008, 130, 252

Journées)de)Chimie)Moléculaire)2016! Emilie!MATHIEU!!

Antioxidant!manganese!complexes:!!

Investigation!of!their!activity!and!subRcellular!location.!emilie.mathieu@ens.fr!

PhD!advisor(s):!Clotilde!Policar,!Nicolas!Delsuc!Laboratory:)Laboratoire)des)Biomolécules,)24)rue)Lhomond,)75005)Paris)

!

Oxidative!stress!has!been!identified!as!an!important!event!implicated!in!several!diseases!ranging!from!inflammatory! diseases! to! neurodegeneration! or! cancer.! SuperOxide! Dismutases! (SOD)! are! a! family! of!metallo,enzymes! implicated! in! the! reduction! of! oxidative! stress! and! inflammation! process! by! tightly!controlling! the! concentration! of! superoxide! in! cells.! In! patients!with! Inflammatory!Bowel!Diseases! (IBD),!these!enzymes!are!either!overproduced!in!an!inactive!form!or!overwhelmed.1!Thus,!the!therapeutic!use!of!purified!SOD!has!been!envisioned!but!is!limited!by!a!poor!cell!penetration!of!the!enzyme,!and!immunogenicity!problems.!To!overcome!these!drawbacks!small!complexes!mimicking!the!activity!of!SODs!have!been!designed!and!their!activity!have!been!studied!on!models!ranging!from!prokaryotic!cells!to!mices.2,3!The!challenge!is!now!to!understand!at!the!molecular!scale!their!mechanism!of!action!in!cells,!and!thus!to!answer!the!question!of!the!bioavailability!of!such!complexes.!

!!!!!!

!! In!our!group,!MnII,complex!mimicking! the!activity!of!SODs!are!designed!and!studied!on!a!cellular!model!of!IBD.!The!complex!1!have!demonstrated!a!good!SOD!activity!in)vitro)(Figure!1).4!In!this!work,!1!has!been!studied!in!a!cellular!environment.!Its!speciation,!its!location!and!its!activity!have!been!investigated!in!details.!1!exerts!an!intracellular!anti,inflammatory!activity,!as!demonstrated!by!looking!at!different!markers!of!inflammation!(IL8!and!COX2)!using!biochemistry!techniques.!Its!quantification!by!EPR!in!cell!lysates,!and!the!determination!of!its!location!using!spatially!resolved!X,ray!fluorescence,!are!correlated!with!its!activity.!These!results!led!to!the!design!of!new!derivatives!bearing!either!cell!penetrating!peptides!(CPP)!to!enhance!cellular! internalization! or! mitochondria! penetrating! peptides! (MPP),! to! accumulate! the! complex! in!mitochondria!where!the!superoxide!is!mostly!generated.5!!

!

Aknowledgment:!ENS,!CNRS!(UMR7203),!UPMC,!ANR,!PSL,!are!acknowledged!for!financial!support.!ENS,Cachan!is!gratefully!acknowledged!for!E.M.’s!fellowship.!We!thank!TGE!RENARD!(FR!3443,!CNRS)!and!UMR8601!for!access!to!the!EPR!spectrometer!for!the!EPR!experiments!and!Dr.!Boucher!for!useful!discussions,!Institut!Curie!(Orsay)!for!free!access!to!cryofixation!and!freeze,drying!facility!and!Dr.!Guerquin,Kern!and!Dr.!Marco!for!useful!discussions!and!help!in!sample!preparation,!and!APS!committee!for!beamtime.!! !

1 D. Salvemini, C. Muscoli, D. P. Miley, S. Cuzzocrea, Pulmonary Pharmacology and Therapeutics, 2002, 15, 439-447. 2 O. Iranzo, Bioinorganic Chemistry, 2011, 39, 73-8 3 I. Batinic-Haberle, A. Tovmasyan, E.R.H. Roberts, Z. Vujaskovic, K.W. Leong, I. Spasojevic, Antiox. Redox. Sign.,

2014, 20, 2372-2415 4 A.-S. Bernard, C. Giroud, H. Y. V. Ching, A. Meunier, V. Ambike, C. Amatore, M. Guille Collignon, F. Lemaître, C.

Policar, Dalton Trans., 2012, 41, 6399-6403 5 H.Y.V. Ching, I. Kenkel, N. Delsuc, E. Mathieu, I. Ivanović-Burmazović, C. Policar, J. Inorg. Biochem, 2016,

10.1016/j.jinorgbio.2016.01.025

Figure*1.*Parent"complex"1,"and"cell"penetrating"peptides"(CPP)"or"mitochondria"penetrating"peptides"(MPP)"derivatives"

"

N NN

N

NNO

MnII

+

CPP or MPP

N NHN

N

NNO

MnII

+

1

Journées)de)Chimie)Moléculaire)2016! Emmanuel!PUIG!!

Novel!class!of!Pt(II)!metallocages!:!Design!and!selfRassembly!

emmanuel.puig@upmc.fr!PhD!advisors:!Christophe!Desmarets!and!Hani!Amouri!!

Laboratory:)Institut)Parisien)de)Chimie)Moléculaire,)Equipe)ARChitecture)moléculaire))

!The!design!and!construction!of!discrete!metal,organic!architectures!such!as!metal,organic!polyhedra,!

cages,!bowls!or!capsules!continue!to!attract!attention![1]!because!of!their!potential!applications!as!containers!for!storage,!recognition,!delivery!and!catalysis.![2]!The!combination!of!Pd(II)!metal!centers!associated!by!self,assembly!with!highly!directional!bridging!pyridyl!ligands!have!proved!successful!and!reliable!approach!for!the!construction!of!these!tridimensional!cages!structures.!However,!the!formation!of!platinum!nanocages!and!especially!of!type!Pt2L4!remains!relatively!scarce.![3]!

In!this!context,!our!group!have!recently!described!the!use!of!rigid!bis(ethynylpyridine)!based!ligands!which!lead!to!Pd2L4!luminescent!nanocapsules.[4]!This!nanocages!displayed!two!complementary!effects!that!operate!in!synergy!for!the!encapsulation!of!a!kinetically!labile!metal!complex![Pt(NO2)4]2,.!Our!approach!relies!on!the!use!in!a!cooperative!manner:!unsaturated!metal!center!and!assembling!ligands!displaying!endohedral!functionality!for!guest!encapsulation.!

In!this!work,!functionalized!bis(ethynylpyridine)aniline!based!bidentate!ligands,!have!been!prepared!and!fully!characterized.!They!allow!the!construction!of!a!novel!family!of!platinum!metallocages.!(Figure!1)!

Figure 1: Platinum-based metallocages!

! !

1 a) J. W. Steed and J. L. Atwood, Supramolecular Chemistry, Wiley, Chichester, 2000, b) J.-M. Lehn, Supramolecular

Chemistry, Concept and Perspectives, VCH, Weinheim, 1995. 2 a) J. J. Henkelis, M. J. Hardie Chem. Commun. 2015, 11929. b) L. Li, D. J. Fanna, N. D. Shepherd, L. F. Lindoy, F. Li

J. Inc. Phe. Mac. Chem. 2015, 82, 3. c) S. Goeb, D. Canevet, M. Salle Org. Synth. Mol. Engineering 2014, 213. d) L. Adrienssens, P. Ballester Chem. Soc. Rev. 2013, 42, 3261. e) M. M. J. Smulders, I. A. Riddell, C. Browne, J. R. Nitschke Chem. Soc. Rev. 2013, 42, 1728. f) H. Amouri, C. Desmarets, J. Moussa Chem. Rev. 2012, 112, 2015. g) D. Ajami, J. Rebek Top. Curr. Chem. 2012, 319, 57. h) T. Murase, Y. Nishijima, M. Fujita J. Am. Chem. Soc. 2012, 134, 162. i) Z. Laughera, B. C. Gibbs Chem Soc. Rev. 2011, 40, 363.

3 a) Ahmedova, A.; Momekova, D.; Yamashina, M.; Shestakova, P.; Momekov, G.; Akita, M.; Yoshizawa, M. Chem. - An Asian J. 2016, 11 (4), 474–477, b) Clever, G. H.; Kawamura, W.; Tashiro, S.; Shiro, M.; Shionoya, M. Angew. Chemie Int. Ed. 2012, 51 (11), 2606–2609, c) Clever, G. H.; Shionoya, M. Chem. - A Eur. J. 2010, 16 (39), 11792–11796, d) Liao, P.; Langloss, B. W.; Johnson, A. M.; Knudsen, E. R.; Tham, F. S.; Julian, R. R.; Hooley, R. J. Chem. Commun. 2010, 46 (27), 4932.

4 a) C. Desmarets, G. Gontard, A. L. Cooksy, M;-N. Rager, H. Amouri, Inorg. Chem. 2014, 53, 4587. b) C. Desmarets, T. Ducarre; M;-N. Rager, G. Gontard, H. Amouri, Materials 2014, 7, 287.

Journées)de)Chimie)Moléculaire)2016! Florence!HIAULT!!

Synthesis!of!αRamino!βRhydroxy!acids!!Biocatalytic!aldolization!and!kinetic!resolution!of!1,2Rdiols!

!florence.hiault@espci.fr!

PhD!advisors:!Pr.!Janine!COSSY,!Dr.!Christophe!MEYER!Laboratoire)de)Chimie)Organique,)Institute)of)Chemistry,)Biology)and)Innovation)(CBI),)

ESPCI)Paris,)CNRS)(UMR8231),)PSL*)Research)University,))10)rue)Vauquelin,)75231)Paris)Cedex)05,)France)

!Optically!active!α,amino!β,hydroxy!acids!are!encountered!in!several!natural!or!synthetic!compounds!

exhibiting! interesting!bioactivities.1,2!Among! the!different!possible!strategies! for! their! synthesis,! the!aldol!condensation!between!glycine!derivatives!and!aldehydes!represents!one!of!the!most!direct!entry!towards!α,amino!β,hydroxy!acids.2!However,!use!of!protecting!groups! is!often! required.!On! the!contrary,! threonine!aldolases!are!able!to!catalyze!such!aldol!condensations!using!unprotected!glycine,!with!an!excellent!control!of!the!amino,substituted!stereocenter!(α!position)!but!with!moderate!diastereoselectivity!with!respect!to!the! hydroxy,substituted! β! position.3! We! have! examined! the! substrate! scope! of! this! biocatalyst! for! the!synthesis!of!various!α,amino!β,hydroxy!acids.!

!

!!In!addition,!α,β,dihydroxy!esters!can!be!used!as!precursors!of!α,amino!β,hydroxy!acids!possessing!a!

quaternary!stereocenter!at!the!α!position.4!The!synthesis!of!these!latter!dihydroxyesters!was!achieved!with!very!high!enantiomeric!purities!by!a!lipase,mediated!kinetic!resolution!of!the!racemic!by!monoacetylation.!

!

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!

Acknowledgment:!Financial!support!from!Protéus/PCAS!(CIFRE!grant)!is!acknowledged.! !

1 (a) K. Li, G. Tan, J. Huang, F. Song, J. You, Angew. Chem. Int. Ed. 2013, 52, 12942. (b) W. Lee, J.-H. Youn, S. H.

Kang, Chem. Commun. 2013, 49, 5231. 2 Y. Zhang, H. Farrants, X. Li, Chem Asian J. 2014, 9, 1753-1764. 3 N. Dückers, K. Baer, S. Simon, H. Gröger, W. Hummel, Appl. Microbiol. Biotechnol. 2010, 88, 409-424. 4 H. Shao, Q. Zhu, M. Goodman, J. Org. Chem. 1998, 63, 5240-5244.

Journées)de)Chimie)Moléculaire)2016! Laurine!Gonnard!!

MetalRcatalyzed!arylation!of!piperidines!!

laurine.gonnard@espci.fr!PhD!advisor(s):!Dr.!Amandine!Guérinot!and!Pr.!Janine!Cossy!

Laboratoire)de)Chimie)Organique,)Institute)of)Chemistry,)Biology)and)Innovation)(CBI)fUMR)8231)

ESPCI)Paris,)CNRS,)PSL*)Research)University,)10)Rue)Vauquelin)75231)Paris)Cedex)05,)France,!!

N,Heterocycles! such! as! piperidines! are! important! moieties! present! in! natural! and! synthetic!compounds!and!are!known!for!their! interesting!biological!properties.1!Since!piperidine!is!one!of!the!most!commonly!used!heterocycle!in!medicinal!chemistry,!2!the!development!of!new!and!efficient!methods!for!its!functionalization! is! of! great! interest.! In! particular,! the!direct! arylation!of! 4,! and!3,halogenopiperidine!by!cross,coupling!reaction,!using!cheap!and!non,toxic!complexes,!appears!to!be!a!powerful!strategy.!Moreover,!very!few!examples!of!metal,catalyzed!cross,couplings!applied!to!3,halogenopiperidines!have!been!reported!in!the!literature.3!!

For! our! part,! we! have! developed! a! cobalt,based! catalytic! system! allowing! the! efficient! and!convenient!cross,coupling!between!4,!and!3,iodo,piperidine!and!aryl!or!(hetero)aryl!Grignard!reagents.4!

!

!!

For! the! C2! functionalization! of! piperidines,! a! different! strategy! implying! directed! ruthenium,catalyzed!sp3!C,H!activation!has!then!been!considered!to!access!2,arylpiperidines.!According!to!pioneering!work! developed! by!Maes!et) al.5! and! Schnürch) et) al.6,! the! real! challenge! relies! on! the! development! of! a!selective!mono,arylation!procedure.!Taking!up!this!challenge,!investigations!are!currently!under!way!to!study!the!effect!of!substituted!pyridines!as!directing!groups.!!!

1 D. O’Hagan,!Nat. Prod. Rep. 2000, 17, 435–446!2 R. D. Taylor, M. MacCoss, A. D. G. Lawson, J. Med. Chem. 2014, 57, 5845-5859 3 G. A. Molander, K. M. Traister, B. T. O’Neill, J. Org. Chem., 2014, 79, 5771–5780 4 a) B. Barré, L. Gonnard, R. Campagne, S. Reymond, J. Marin, P. Ciapetti, M. Brellier, A. Guérinot, J. Cossy, Org. Lett.

2014, 16, 6160-6163 b) L. Gonnard, A. Guérinot, J. Cossy, Chem. Eur. J. 2015, 21, 12797-12803 5 A. Peschiulli, V. Smout, T. E. Storr, E. A. Mitchell, Z. Elias, W. Herrebout, D. Berthelot, L. Meerpoel, B. U. W. Maes,

Chem. Eur. J. 2013, 19, 10378-10387 6 M. C. Schwarz, N. Dastbaravardeh, K. Kirchner, M. Schnürch, M. D. Mihovilovic, Monastch. Chem. 2013, 144, 539-

552

Journées)de)Chimie)Moléculaire)2016! Caleb!Medena!!

Helicenes:!Synthesis!and!application!in!catalysis!

Caleb.medena@upmc.fr!PhD!advisors:!Pr.!Corinne!Aubert,!Dr.!Marion!Barbazanges!

Laboratory:)Institut)Parisien)de)Chimie)Moléculaire,)UMR)8232)

IPCM,)4)place)Jussieu)75252,)CC229,)Paris)cedex)05)

)Helicenes!are!polycyclic!aromatic!compounds!comprised!of!ortho,fused!benzene!rings,!which!adopt!

a!helical!configuration.!They!possess!a!series!of!interesting!chiral,!physical,!electronic!and!optical!properties.!!Helicenes!are!used!in!several!fields,!for!examples!as!chiral!ligands!or!auxiliaries!in!the!asymmetric!synthesis.1!!! We! will! present! the! synthesis! of! [6],carbohelicene! 1! by! intramolecular! [2+2+2]! cycloaddition!reaction2!of!triyne!2!and!photocyclisation!reaction3!of!distilbene!3.!!!!

!!

The!use!of!helical!gold!complex!4!in!enynes!cycloisomerization!reaction!will!also!be!disclosed.!!

!

!

!!!

Aknowledgment:!ANR!HELICATS!(ANR,13,JS07,0013).

1 (a) Y. Shen, C.-F.Chen, Chem. Soc. Rev. 2012, 112, 1463; (b) M. Gingras, Chem. Soc. Rev. 2013, 42, 958; (c) M.

Gingras, G. Félix, R. Peresutti, chem. Soc. Rev. 2013, 42, 1007; (d) M. Gingras, Chem. Soc. Rev. 2013, 42, 1051. (e) M. Gingras, Chem Soc Rev.!2013. 42, 968; (f) Y. Shen, C. F. Chen, Chem. Rev. 2012, 112, 1463; (g) M. Gingras, G. Félix, R. Peresutti, Chem. Soc. Rev. 2013, 42, 1007; (i) P. Aillard, A. Voituriez, A. Marinetti. Dalton Trans 2014, 43, 15263-78; (j) J. Maurice, N. Takenaka, Eur. J. Org. Chem. 2014, 21.

2 F. Teplý, I. G. Stará, I. Starý, A. Kollárovic, Daniel Lustinec,, Z. Krausová, D. Saman, P. Fiedler, Eur. J. Org. Chem. 2007, 4244.

3 C. Wachsmann, E. Weber, M Czugler, W. Seichter, Eur. J. Org. Chem. 2003, 2863

MeO

MeO

MeO

MeO

OMe OMe1) [2+2+2] Cycloaddition2) Aromatization

Photocyclisation

(±)1 32

reaction

XR1

R2

R3R4

X

R2R4

R1R3

4 (2 %mol)AgSbF6 (5 %mol)

CH2Cl2

O

O

(±)

P

PAuPh Ph

Ph Ph

AuCl

Cl

4