COST Action on Organocatalysis CM0905 Aix

Transcription

COST Action on Organocatalysis
CM0905
Aix-Marseille Université
29-30 March 2012
Welcome to the second
ORCA summit
Marseilles, 29-30 march 2012
Dear Guest,
After the ORCA summit in Berlin last year, we have the pleasure to organize and to
welcome you in Marseille for this second meeting focused on the most recent
developments and advances in the exciting field of organic catalysis.
We are very honored to receive so many European specialists of organocatalysis and
we are certain that this meeting will inspire abundant fruitful discussions and be the
starting point of new collaborations.
We wish you all a nice meeting and hope that you will enjoy your stay in Marseilles.
The Organizing committee
Gaëlle Chouraqui, Cyril Bressy, Xavier Bugaut and Damien Bonne
The Scientific committee
Alexandre Alexakis, Petri Pihko, Albrecht Berkessel, Ben List and Pavel Kocovsky
ORCA Meeting, Marseilles, 29-30 march 2012
2
Page 4
Scientific program
Page 5
Lectures and oral communications
Page 32
Posters
Page 49
List of participants
3
SCIENTIFIC PROGRAM
Thursday 29. 3. 2012
Friday 30. 3. 2012
9.00 - 9.10
Rainer Mahrwald, Berlin
Opening remarks
Chair
Andre V. Malkov, Loughborough
Chair
Petri M. Pihko, Jyväskylä
9.10 - 9.40
Paolo Melchiorre, Tarragona
9.00-9.30
Benjamin List, Mülheim
9.40 - 10.10
Petri M. Pihko, Jyväskylä
9.30-10.00
Jan H. van Maarseveen, Amsterdam
10.10- 10.40
Christoforos G. Kokotos, Athens
10.00-10.30
Andre V. Malkov, Loughborough
Coffee
break
Coffee
break
11.00-11.15
Ismail Ibrahem, Sundsvall
11.00-11.30
Rainer Mahrwald, Berlin
11.15-11.30
Morgane Pigeaux, Caen
11.30-11.45
David Monge, Sevilla
11.30-11.45
Lionel Delaude, Liège
11.45-12.00
Sami Lakhdar, München
11.45-12.00
Gábor Speier, Veszprém
12.15-12.30
Biplab Maji, München
12.00-12.15
Andrea-Nekane Roig Alba,
Barcelona
Lunch
Lunch
Chair
Pavel Kocovsky, Glasgow
Chair
Benjamin List, Mülheim
14.00-14.15
Maurizio Benaglia, Milano
14.00-14.15
Michelangelo Gruttadauria, Palermo
14.15-14.30
Leonard J. Prins, Padova
14.15-14.30
Jörg Duschmalė, Zürich
14.30-14.45
Damien Mailhol, Marseilles
14.30-14.45
Ayhan S. Demir, Ankara
14.45-15.00
Yoann Coquerel, Marseilles
14.45-15.00
Simona M. Coman, Bucharest
15.00-15.15
Janez Cerkovnik, Ljubljana
15.00-15.15
Jean-François Brière, Rouen
15.15-15.30
Arnaud Voituriez, Gif-sur-Yvette
15.15-15.30
Efraim Reyes, Bilbao
15.30
Alexandre Alexakis, Geneva
Closing remarks
Poster session and coffee break
4
LECTURES AND ORAL COMMUNICATIONS
About the Asymmetric Functionalisation of Carbonyls after the
Advent of Cinchona-based Primary Amine Catalysis
Paolo Melchiorrea,b
a
ICIQ - Institute of Chemical Research of Catalonia, Tarragona (Spain)
b
ICREA - Institució Catalana de Recerca i Estudis Avançats, Barcelona (Spain)
Asymmetric aminocatalysis [1] has greatly expanded the chemist’s ability to stereoselectively
functionalise unmodified carbonyl compounds. Recent advances in cinchona-based primary
amine catalysis have provided new synthetic opportunities and conceptual perspectives for
successfully attacking major challenges in carbonyl compound chemistry, which traditional
approaches have not been able to address [2].
In particular, 9-amino(9-deoxy)epi cinchona alkaloids, primary amines easily derived from
natural sources, have enabled the stereoselective functionalisation of a variety of sterically
hindered carbonyl compounds, which cannot be functionalised using secondary amines and
which are often elusive substrates for metal-based approaches too. Their advent has greatly
expanded the synthetic potential of aminocatalysis (Figure 1).
Here, some recent contributions from our laboratories are presented [3].
Figure 1. The state-of-the-art of asymmetric aminocatalysis
References:
[1] (a) List, B.; Angew. Chem., Int. Ed. 2010, 49, 1730-1734. (b) Barbas, C. F. III; Angew. Chem., Int.
Ed. 2008, 47, 42-47.
[2] (a) Jiang, L.; Chen, Y.-C. Catal. Sci. Technol. 2011, 1, 354–365. (b) Bartoli, G.; Melchiorre, P.
Synlett 2008, 1759–1771.
[3] Recent examples: (a) Tian, X.; Cassani, C.; Liu, Y.; Moran, A.; Urakawa, A.; Galzerano, P.; Arceo,
E.; Melchiorre, P. J. Am. Chem. Soc. 2011, 133, 17934–17941. (b) Bencivenni, G.; Galzerano, P.;
Mazzanti, A.; Bartoli, G.; Melchiorre, P. Proc. Natl. Acad. Sci. U.S.A. 2010, 107, 20642–20647. (c)
Bergonzini, G.; Vera, S.; Melchiorre, P. Angew. Chem., Int. Ed. 2010, 49, 9685–9688.
5
From Co-catalysis to Dual Catalysis: Efficiency and Selectivity in
Organocatalysis
Petri M. Pihko
Departmenf of Chemistry, University of Jyväskylä, Finland . [email protected]
The use of catalysts bearing multiple hydrogen bond donor (MHBD) groups to increase the catalytic
activity via possible formation of several hydrogen bonds, or hydrogen bonds to two different sites,
[1-2]
represents an attractive option for enantioselective catalysis.
Although this approach has been
successfully used in multifunctional catalysts where all the necessary functionalities are incorporated
in the same catalyst molecule, the use of separate catalysts for electrophile and nucleophile activation
might allow more opportunities for catalyst and reaction screening since both catalysts could be
optimized separately. As an example, enantioselective enamine catalysts typically incorporate a
[3]
hydrogen bond donor site (Scheme 1, type A) or rely on steric control alone (type B).
Scheme 1.
Scheme 2.
[4]
In this presentation, we demonstrate that the use of a dual catalyst system can lead to significant
rate enhancements in enamine catalysis and describe the successful use of a dual MHBD/enamine
catalyst system for a highly enantioselective domino three-component reaction sequence (Scheme 2).
Both steps are catalyzed by the MHBD catalyst as well as the amine catalyst, and two different
aldehydes can also be used in a cross-domino sequence, providing the products in excellent
enantioselectivity, diastereoselectivity, and high yield.
[1] For reviews, see: a) M. Kotke, P. Schreiner, ‘(Thio)urea Organocatalysts.’ In: Hydrogen Bonding in Organic
Synthesis, P. M. Pihko, (Ed.), Wiley-VCH 2009, 141-352, b) Y. Takemoto, Chem. Pharm. Bull. 2010, 58,
593-601.
[2] Examples of catalysts bearing multiple hydrogen bond donors: a) C. K. De, E. G. Klauber, D. Seidel, J. Am.
Chem. Soc. 2009, 131, 17060-17061; b) C.-J. Wang, Z.-H. Zhang, X.-Q. Dong, X.-J. Wu, Chem. Commun. 2008,
1431-1433; c) R. P. Herrera, V. Sgarzani, L. Bernardi and A. Ricci, Angew. Chem. Int. Ed., 2005, 44, 6576; d) A.
Berkessel, K. Roland and J. M. Neudorfl, Org. Lett. 2006, 8, 4195; e) Z. R. Hou, J. Wang, Z. H. Liu, Z. M. Feng,
Chem. Eur. J. 2008, 14, 4484; f) for more examples, see ref 1a.
[3] For reviews of enamine catalysis, including a discussion of different activation modes, see: a) P. M. Pihko, I.
Majander, A. Erkkilä, Top. Curr. Chem. 2010, 291, 29-75; b) S. Mukherjee, J. W. Yang, S. Hoffman, B. List, Chem.
Rev. 2007, 107, 5471-5569; c) For the definition of Type A and Type B catalysts, see: C. Palomo, A. Mielgo,
Angew. Chem. Int. Ed. 2006, 45, 7876-7880; d) For a recent review of bulky silylated organocatalysts, see: L.-W.
Xu, L. Li, Z.-H. Shi, Adv. Synth. Catal. 2010, 352, 243-279.
[4] Rahaman, H.; Madarasz, Á, Pápai, I.; Pihko. P. M. Angew. Chem. Int. Ed., 2011, 50, 6123.
6
Providing Solutions for Challenging Asymmetric Transformations
via New Efficient Organocatalysts
Christoforos G. Kokotos*
Laboratory of Organic Chemistry, Department of Chemistry, University of Athens, Athens,
15771 Greece.
Since the dawn of Organocatalysis, a plethora of organocatalysts have appeared in the
literature able to promote a number of reactions and introduce novel modes of activation
providing new efficient protocols for until that time unknown transformations. However, even
among the most popular activation modes, there is a number of transformations that are not
yet amenable or a number of substrates that are considered problematic. One of our goals,
through the exploration of novel catalytic scaffolds, is the identification of appropriate catalytic
structures able to circumvent such problems and deliver the products of “difficult”
transformations in appreciable yields and selectivities.
This lecture will be focused on the identification and application of a new bifunctional primary
amine-thiourea able to promote “difficult” Michael reactions [1, 2]. Furthermore, the
successful identification of a catalyst able to promote the difficult aldol reaction between
methyl ketones and activated perfluoroalkyl ketones is going to be presented. Although a
number of benchmark catalysts fail to catalyze efficiently the reaction, our catalytic system
can provide high yields and selectivities even at low catalyst loadings (0.5-2 mol%) [3].
Moreover,
the
efficient
application
of
a
pyrrolidine-thioxotetrahydropyrimidinone
organocatalyst in the asymmetric α-alkylation of cyclic ketones will be disclosed [4].
References:
[1] Tsakos, M.; Kokotos, C. G.; Kokotos, G. Adv. Synth. Catal. 2012, early view, doi:
10.1002/adsc.201100636.
[2] Tsakos, M.; Kokotos, C. G. Eur. J. Org. Chem. 2012, 576-580.
[3] Kokotos, C. G. J. Org. Chem. 2012, 77, 1131–1135.
[4] Trifonidou, M.; Kokotos, C. G. Eur. J. Org. Chem. 2012, early view, doi: 10.1002/ejoc.201101509.
7
New frontiers in Aminocatalysis by Expansion with Transition Metal
Catalysis: Synergistic Catalysis
Ismail Ibrahem
Associate Professor. I. Ibrahem. Department of Natural Sciences, Engineering and
Mathematics, Mid Sweden University, SE-851 70 Sundsvall, Sweden.
E-mail: [email protected].
New trends in amino-catalysis. We show that it is possible to merge the catalytic cycles of
transition metal-catalyzed nucleophile activation with amine-catalyzed iminium activation of
-unsaturated aldehydes.[1-3] For example, the regiospecific and highly enantioselective βboration of α,β-unsaturated aldehydes by the combination of simple chiral amine and copper
catalysts is presented.[1] We will also disclose our latest results on highly enantioselective allylic alkylation of aldehydes by combination of transition metal and chiral amine catalysts
and its application in total synthesis.[4]
References:
[1] Ibrahem, I.*; Breistein, P.; Córdova. A.* Angew. Chem. Int. Ed. 2011, 50, 12036-12041.
[2] Afewerki, S.; Pirttilä, K.; Breistein, P.; Deiana, L.; Dziedzic, P.; Ibrahem, I.*; Córdova. A.* Chem. Eur.
J. 2011, 17, 8784-8788.
[3] Ibrahem, I.*; Santoro, S.; Himo, F.; Córdova. A.* . Adv. Synth. Catal. 2011.353, 245-252. For
highlight of this paper see SynFacts 2011, 5, 0532.
[4] Afewerki, S.; I. Ibrahem, I.*; Rydfjord, J.; Breistein, P.; Córdova. A.*.Chem. Eur. J. 2012, Early view.
8
A new type of catalyst for the enantioselective decarboxylative
protonation
Morgane Pigeaux, Jérôme Baudoux, Jacques Rouden
Laboratoire de Chimie Moléculaire et thioorganique, UMR CNRS 650, FR3038, ENSICAEN
Université de Caen Basse-Normandie, 6 Bd du Maréchal Juin, F 14050 Caen Cedex France
The enantioselective synthesis of amino acids is a research area of great interest due to the
ubiquity of these small molecules in biologically active products. Recently, our lab has
developed an efficient methodology to control the formation of carbon-hydrogen bond by an
asymmetric organocatalyzed protonation [1]. In this context, our project aims at developing a
versatile access to enantioenriched non-proteogenic phenylalanine derivatives, using
enantioselective decarboxylative protonation.
This methodology required first the preparation of racemic functionalized hemimalonic acids
using a minimum number of steps from readily availalble starting materials. Then, cinchona
alkaloids derivatives as chiral bases triggered the asymmetric decarboxylative protonation of
these substrates. Recently, the thioureas analogues of these alkaloids promoted the
-aminomalonates [2]. However, a stochiometric amount of base
and low temperature/long reaction time were necessary to achieve good enantioselectivivies.
This presentation summarizes our efforts to obtain high enantiomeric excess of
phenylalanine derivatives using a catalytic amount of a new catalyst family, the squaramides.
A comparative (squaramides vs thioureas) and comprehensive study of reaction parameters
including the nature of the N-protecting group (PG) is underway in the specific case of these
acyclic substrates.
References:
[1] Seitz, T.; Baudoux, J.; Bekolo, H.; Cahard, D.; Plaquevent, J.-C.; Lasne, M.-C.; Rouden, J.
Tetrahedron 2006, 62, 6155; Blanchet, J.; Baudoux, J.; Amere, M.; Lasne, M.-C.; Rouden, J.
Eur. J. Org. Chem. 2008, 5493.
[2] Amere, M.; Lasne, M.-C.; Rouden, J. Org. Lett. 2007, 9, 2621.
9
Stable Zwitterions of N-Heterocyclic Carbenes: Synthesis,
Properties and Organocatalytic Applications
Morgan Hans, Albert Demonceau, Lionel Delaude*
Laboratory of Organometallic Chemistry and Homogeneous Catalysis
Institut de Chimie (B6a), University of Liège, Sart-Tilman par 4000 Liège, Belgium
N-Heterocyclic carbenes (NHCs) form stable zwitterionic adducts with a range of allenes,
heteroallenes, and ketenes. Although the first representatives of this class of inner salts were
investigated as far back as the 1960s, they have only aroused a sustained interest from the
chemical community during the last decade. Depending on the nature of their anionic moiety,
NHC betaines display a very broad palette of reactivities and have found applications in
various fields of organic synthesis and catalysis [1].
Over the past few years, our laboratory has reported the synthesis of several representative
imidazol(in)ium carboxylates [2], thiocarboxylates [3], and dithiocarboxylates [4], which were
probed as ligands for ruthenium catalysts [5,6] and gold complexes [7,8]. The organocatalytic
potentials of NHC•COS zwitterions were also investigated in the acylation of benzyl alcohol
with vinyl acetate and in the benzoin condensation [3].
In this communication, we will present the latest results from our group concerning the
synthesis, properties, and organocatalytic applications of NHC betaines.
References:
[1] For a review, see: Delaude, L. Eur. J. Inorg. Chem. 2009, 1681–1699.
[2] Tudose, A.; Demonceau, A.; Delaude, L. J. Organomet. Chem. 2006, 691, 5356–5365.
[3] Hans, M.; Wouters, J.; Demonceau, A.; Delaude, L. Eur. J. Org. Chem. 2011, 7083–7091.
[4] Delaude, L.; Demonceau, A.; Wouters, J. Eur. J. Inorg. Chem. 2009, 1882–1891.
[5] Delaude, L.; Sauvage, X.; Demonceau, A.; Wouters, J. Organometallics 2009, 28, 4056–4064.
[6] Hans, M.; Willem, Q.; Wouters, J.; Demonceau, A.; Delaude, L. Organometallics 2011, 30, 6133–
6142.
[7] Naeem, S.; Delaude, L.; White, A. J. P.; Wilton-Ely, J. D. E. T. Inorg. Chem. 2010, 49, 1784–1793.
[8] Chia, E. Y.; Naeem, S.; Delaude, L.; White, A. J. P.; Wilton-Ely, J. D. E. T. Dalton Trans. 2011, 40,
6645–6658.
10
Organocatalytic Oxygenation with triplet Dioxygen
István BORS, Gábor SPEIER, József KAIZER and József S. PAP
Department of Chemistry, University of Pannonia, 8200 Veszprém, Hungary
The use of molecular oxygen in oxidative metabolic processes in biology is a common
feature. That means that triplet dioxygen can react with mostly singlet organic substrates.
Despite the violation of spin restriction these oxidation/oxygenation reactions proceed in
satisfactory speed. Biological processes use different methods to do so. One of them is the
use of organic co-factors such as FADH2 [1].
Attemps has been made to mimic these reactions using simple compounds of flavin cofactors in the oxygenation of amines, sulphides, etc. [2].
We found accidentally that certain heterocyclic compounds such as oxazaphospholes [3] are
able to react with triplet dioxygen at ambient condition. The so formed, probably
hydroperoxides are able to catalyze oxygenation/oxidation reactions. Now in this lecture we
present our results on studies of the peculier formation of the precursor oxazaphospholes,
their reaction with dioxygen, and the kinetic and spectroscopic results of the catalytic
Ph3P + 0.5 O2
oxygenation
of
triphenylphosphine.
oxazaphosphole
A plausible
O = PPh3
mechanism
for
the formation of
oxazaphospholes and the catalytic oxygenation of triphenylphosphines will be presented.
References:
[1] Ball, S.; Bruice, T. C. Journal of the American Chemical Society 1979, 101, 4017-4019.
[2] Modern Oxidation Methods, 2nd Edition ed.; Bäckwall, J.-E., Ed. Wiley-VCH: Weinheim, 2010.
[3] Speier, G.; Tyeklár, Z.; Fülöp, V.; Párkányi, L. Chemische Berichte 1988, 121, 1685-1688.
11
Organocatalytic Oxazolone Functionalization - Regioselectivity
Depending on the Chosen Electrophile
Andrea-Nekane R. Alba; Xavier Companyó; Guillem Valero; Ramon Rios, Albert Moyano
Universitat de Barcelona, Departament de Química Orgànica, Facultat de Química, C/Martí I
Franqués 1-11, 08028 Barcelona (Spain)
Oxazolones have a dual behaviour, presenting either nucleophilic or electrophilic nature.
There are three different nucleophilic sites and one electrophilic site. The acidic nature of the
proton at the C-4 position of the oxazolone scaffold allows for the easy formation of an
oxazolone enolate, which can react with a wide range of electrophiles from two endocyclic
positions (C-2 and C-4) or from the exocyclic oxygen. Attacks at the C-4 position are of
special interest, since they lead to precursors of quaternary- -alkyl-α-amino acid derivatives.
electrophilic
site
O
R1
N
H
O
R1
R2
Nuc
Nuc-
N
O
R2
O
H
O attack
O
R1
O
E
E
R1
N
O
R2
Amino acid derivatives
R1
N
C-4 attack
O
R2
E
C-2
attack
O
N
O
R2
E
Oxyaminals
In this communication, we discuss the regioselectivity trends observedin the organocatalytic
oxazolone addition to a set of electrophiles. C-2 Aryl substituted oxazolones react regio- (C2) and diastereoselectively with nitrostyrenes.[1] The addition to bis(phenylsulfonyl)ethylene
and cis-1,2-bis(phenylsulfonyl) takes place with complete regioselectivity (C4), leading to a
highly enantioselective entry to quaternary α-alkyl-α-amino acids.[2] The regiochemical
outcome of addition to maleimides depends on the substitution pattern of the oxazolone. C-2
Aryl-substitued oxazolones react with complete C-2 regioselectivity,[3] while C-2 alkylic ones
react with C-4 regioselectivity.[4] The alkylation with stabilized carbocations also gives rise to
C-4 disubstitued oxazolones.[5]
References:
[1] Balaguer, A.-N.; Companyó, X.; Calvet, T.; Font-Bardía, M.; Moyano, A.; Rios, R. Eur. J. Org. Chem.
2009, 199. [2] Alba, A.-N. R.; Companyó, X.; Valero, G.; Moyano, A.; Rios, R. Chem. Eur. J. 2010, 16,
5354; Bravo, N.; Alba, A.-N. R.; Valero, G.; Companyó, X.; Moyano, A.; Rios, R. New. J. Chem. 2010,
34, 1816. [3] Alba, A.-N. R.; Valero, G.; Calbet, T.; Font-Bardía, M.; Moyano, A.; Rios, R. Chem. Eur. J.
2010, 16, 9884. [4] Alba, A.-N. R.; Valero, G.; Calbet, T.; Font-Bardía, M.; Moyano, A. Rios, R. New J.
Chem. 2012, 36, 613. [5] Alba, A.-N. R.; Calbet, T.; Font-Bardía, M.; Moyano, A.; Rios, R. Eur. J. Org.
Chem. 2011, 2053.
12
Poly(methylhydrosiloxane)-supported chiral organic catalysts
Maurizio Benagliaa,* Stefania Guizzetti,a Alessandra Puglisi,a Jay S. Siegelb
a
Dipartimento di Chimica Organica e Industriale, Università di Milano, Via
Venezian 21, 20133, Milano, Italy. E-mail: [email protected]
b
Organisch-Chemisches Institut, Universität Zürich, Winterthurerstrasse 190,
CH-8057 Zürich, Switzerland.
Supporting catalysts and reagents on polymer backbones offers several engineering
advantages; in systems like grafted polyHDMS, where the final macromolecular properties
strongly reflect the nature of the grafts, one can anticipate control over solubility, isolability
and even stability through judicious tuning of graft composition and proportion.[1]
We have recently turned our attention to polymethylhydrosiloxane (PMHS) that presents
several positive features such as low cost, commercial availability, easy fuctionalization, and
very favorable solubility profile. Surprisingly its use as support for the immobilization of chiral
catalysts remained almost unexplored. Only a few years ago the use of PMHS-anchored
cinchona alkaloid derivatives has been reported.[2]
We have recently described for the first time the synthesis of PMHS-supported chiral organic
catalysts derived from MacMillan’s imidazolidin-4-ones and a study of their behaviour in the
stereoselective Diels-Alder cycloaddition. Recycling experiments showed that the supported
catalyst maintains its stereochemical efficiency for up to five reaction cycles. [3]
Me
Me
Me
TMSO
Si
TMSO
O
Me
Si
Si
O
O
TMS
TMS
Me
y
x
N
N H
O
O
OPh
NH
H
O
n
F3C
A
properly
modified
Takemoto’s
catalyst
was
N
H
also
N
H
N
succesfully
anchored
to
poly(methylhydrosiloxane) and employed in the stereoselective addition of activated carbon
nucleophiles to nitrostyrene. As a demonstration of the versatility of the methodology, a
related Jacobsen type catalyst was then supported and succesfully used in the acetylacetone
addition to nitroalkenes.
References:
[1] Benaglia, M. Ed. Recoverable and Recyclable Catalysts, 2009, John Wiley and Sons.
[2] DeClue, M. S., Siegel, J. S. Org. Biomol. Chem., 2004, 2, 2287-2298.
[3] Guizzetti, S., Benaglia, M., Siegel, J. S. Chem. Comm., 2012, in press.
13
Functionalized Au Nanoparticles for Catalysis
Leonard J. Prins
Department of Chemical Sciences, University of Padova, Via Marzolo 1, 35131 Padova, Italy.
E-mail: [email protected]
Monolayer protected Au colloids (Au MPCs) have emerged as important components of
innovative chemical systems for biomolecular recognition.[1] A current trend is the
development of Au MPCs equipped with different functionalities on the surface.[2]
Nonetheless, the synthesis, purification, and characterization of such Au MPCs is
challenging. Here, an alternative approach towards heterofunctionalized Au MPCs is
presented. This approach relies on the self-assembly of oligoanions on the surface of Au
MPCs
containing
a monolayer
terminating
with
a
triazacyclonanone
(TACN)•ZnII
complex.[3,4] Here we show that catalytically active peptide-nanoparticle complexes are
obtained by assembling small peptide sequences on the surface of cationic self-assembled
monolayers on gold nanoparticles. When bound to the surface, the peptides accelerate the
transesterification of N-Cbz phenylalanine by more than two orders of magnitude. The gold
nanoparticle serve as a multivalent scaffold for bringing catalysts and substrate in close
proximity, but also creates a local microenvironment that further facilitates catalysts. The
supramolecular nature of the system permits the catalytic activity of the system to be altered
in situ.
References:
1. D.A. Giljohann, D.S. Seferos, W.L. Daniel, M.D. Massich, P.C. Patel, and C.A. Mirkin,
Angew.Chem.Int.Ed., 2010, 49, 3280-3294.
2. C. Gentilini, L. Pasquato, J.Mater.Chem. 2010, 20, 1403-1412.
3. F. Manea, F.B. Houillon, L. Pasquato, P. Scrimin. Angew.Chem.Int.Ed. 2004, 43, 6165-6169.
4. Zaupa, G.; Mora, C.; Bonomi, R.; Prins, L.J.; Scrimin, P. Chem. Eur. J. 2011, 17, 4879-4889.
5. Bonomi, A. Cazzolaro, L. J. Prins, Chem. Commun. 2011, 47, 445 – 447.
6. Bonomi, R. ; Cazzolaro, A.; Sansone, A.; Scrimin, P.; Prins, L.J. Angew.Chem.In.Ed. 2011, 50,
2307-2312
Financial support from the European Research Council under the Seventh Framework Programme
(FP7/2007–2013)/ERC of the European Community (Starting Grant agreement no. 239898) is
acknowledged.
14
Enantioselective organocatalytic approach
to densely functionalized cyclobutanones
Damien Mailhol, María del Mar Sanchez Duque, Wilfried Raimondi,
Damien Bonne, Thierry Constantieux, Yoann Coquerel, Jean Rodriguez
Aix-Marseille Université - Institut des Sciences Moléculaires de Marseille – iSm2
UMR CNRS 7313 - Centre Saint Jérôme - 13397 Marseille Cedex 20 - France
The bending and ring strain found in small-ring molecules and particularly cyclobutanones
has for long attracted the interest of chemists, and synthetic applications of cyclobutanones
have so far concentrated on fragmentation and ring expansion reactions.[1]
Organocatalysis has emerged over the past decade as a thriving area of organic synthesis. [2]
Although cyclic ketones have been prominently studied in organocatalytic transformations,
examples involving cyclobutanones are rare and stereoselectivity remains an issue.[3]
In connection with our research program on applications of 1,3-dicarbonyl compounds,[4] we
have developed a highly stereoselective synthetic route to densely functionalised
cyclobutanones exhibiting an ‘all-carbon’ quaternary center via a Michael addition. These
very recent results will be discussed in this communication.
References:
[1] a) Namsylo, J. C.; Kaufmann, D. E. Chem. Rev. 2003, 103, 1485; b) Lee-Ruff, E.; Mladenova, G.
Chem. Rev. 2003, 103, 1449; c) Bellus, D.; Ernst, B. Angew. Chem. Int. Ed. 1988, 27, 797; d)
Seiser, T.; Saget, T.; Tran, D. N.; Cramer, N. Angew. Chem. Int. Ed. 2011, 50, 7740.
[2] a) MacMillan, D. W. C. Nature 2008, 455, 304; b) Melchiorre, P.; Marigo, M.; Carlone, A.; Bartoli, G.
Angew. Chem. Int. Ed. 2008, 47, 6138; c) Bertelsen, S.; Jørgensen, K. A. Chem. Soc. Rev. 2009,
38, 2178.
[3] a) Aitken, D. J.; Capitta, F.; Frongia, A.; Gori, D.; Guillot, R.; Ollivier, J.; Piras, P. P.; Secci, F.; Spiga,
M. Synlett 2011, 712; b) Kotrusz, P.; Toma, S.; Schmalz, Hans-Günther; Adler, A. Eur. J. Org. Chem.
2004, 1577.
[4] a) Sanchez Duque, M. M.; Baslé, O.; Isambert, N.; Gaudel-Siri, A.; Génisson, Y.; Plaquevent, J.-C.;
Rodriguez, J.; Constantieux, T. Org. Lett. 2011, 13, 3296; b) Bonne, D.; Coquerel, Y.; Constantieux,
T.; Rodriguez, J. Tetrahedron: Asymmetry 2010, 21, 1085.
15
N-Heterocyclic Carbene-Catalyzed Michael Additions and
Cyclopentannulations
Faisal Nawaz, Thomas Boddaert, Damien Bonne, Olivier Chuzel, Yoann Coquerel,
Jean Rodriguez
Aix-Marseille Université - Institut des Sciences Moléculaires de Marseille – iSm2
UMR CNRS 7313 - Centre Saint Jérôme - 13397 Marseille Cedex 20 - France
A few years ago, we reported the organocatalytic activity of 1,3-imidazol(in)-2-ylidenes (e.g.
SIMes and IPr) in the Michael addition of 1,3-dicarbonyl compounds to activated alkenes.[1]
Some aspects of this reaction will be discussed.
More recently, we have initiated a program on the organocatalytic properties of bifunctional
chiral 1,3-imidazolin-2-ylidenes containing a hydrogen-bond donor moiety. Some of these
NHCs
have
shown
excellent
cyclopentannulation reaction
[2]
organocatalytic
activity
in
Nair’s
enantioselective
with enals and chalcones. A glimpse of our current results will
be presented.
Ar N
O
N
O
chiral linker
H-bond
donor
+
MeO
up to 99% yield
up to 77% ee
MeO
References:
[1] a) Boddaert, T.; Coquerel, Y.; Rodriguez, J. Adv. Synth. Catal. 2009, 351, 1744 (erratum: Adv.
Synth. Catal. 2009, 351, 2541). b) Boddaert, T.; Coquerel, Y.; Rodriguez, J. Chem. Eur. J. 2011, 17,
2266.
[2] a) Nair, V.; Vellalath, S.; Poonoth, M.; Suresh, E. J. Am. Chem. Soc. 2006, 128, 8736. b) Chiang,
P.-C.; Kaeobamrung, J.; Bode, J. W. J. Am. Chem. Soc. 2007, 129, 3520.
16
Preparation of Substrates for the Synthesis of Dihydrogen Trioxide
(HOOOH)
Gregor Strle and Janez Cerkovnik
Faculty of Chemistry and Chemical Technology, University of Ljubljana,
P.O. Box 537, 1000 Ljubljana, Slovenia.
Dihydrogen trioxide (HOOOH), a higher homologue of hydrogen peroxide (HOOH) and
water, is believed to be key intermediate in low-temperature oxidations, atmospheric and
environmental chemistry, and in normal and pathological processes in the living organisms. 1,2
It was unambiguously identified only very recently by
17
O NMR,3a IR3b,c and microwave
spectroscopy.3d
Dihydrogen trioxide is commonly formed in the low-temperature ozonation of various
saturated organic substrates.1b Very recently we have found that HOOOH could be prepared
in an efficient direct catalytic transformation of some hydrotrioxides (ROOOH; see Scheme).4
To prepare concentrated solutions of pure HOOOH polymer-bound catalyst and some
polymer-bound substrates were prepared which will hopefully allow further studies on the
stability and reactivity of this polyoxide in more detail. In this contribution attempts to prepare
polymer-bound substrates for synthesis of HOOOH and his activation5 will be discussed.
References:
1 (a) Plesničar, B. Polyoxides. In Organic Peroxides; Ando, W., Ed.; Wiley: New York, 1992; pp 479533. (b) Plesničar, B. Acta. Chim. Slov. 2005, 52, 1.
2 (a) Eschenmoser, A.; Lerner, R. A.; et al. Science 2001, 293, 1806. (b) Xu, X.; Goddard, W. A., III.
Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 15308. (c) Wentworth, P., Jr.; Nieva, J.; Takeuchi, C.; et al.
Science 2003, 302, 1053. (d) Nyffeler, P. T.; Wentworth, P. Jr.; et al. Angew. Chem. Int. Ed. 2004, 43,
4656. (e) Wentworth, P. Jr.; et al. Chem. Commun. 2009, 3098.
3 (a) Plesničar, B.; Tuttle, T.; Cerkovnik, J.; Koller, J.; Cremer, D. J. Am. Chem. Soc. 2003, 125,
11553. (b) Cerkovnik, J.; Tuttle, T.; Kraka, E.; Lendero, N.; Plesničar, B.; Cremer, D. J. Am. Chem.
Soc. 2006, 128, 4090. (c) Engdahl, A.; Nelander, B. Science 2002, 295, 482. (d) Suma, K.; Sumiyoshi,
Y.; Endo Y. J. Am. Chem. Soc. 2005, 127, 14998.
4 Bergant, A.; Cerkovnik, J.; Plesničar, B.; Tuttle, T. J. Am. Chem. Soc. 2008, 130, 14086.
5 Tuttle, T.; Cerkovnik, J.; Koller, J.; Plesničar, B. J. Phys. Chem. A 2010, 114, 8003.
17
FerroPHANE as Chiral Organocatalyst for Enantioselective [3+2]
Cyclisations
Arnaud Voituriez and Angela Marinetti
ICSN, 1 av. de la Terrasse 91198 Gif-sur-Yvette, France
E-Mail : [email protected]
Phosphine organocatalysis is an emerging field in organic synthesis.1 In order to expand the
range of chiral phosphines for asymmetric organocatalysis, our group has developed recently
a synthetic approach to 2-phospha[3]ferrocenophanes with planar chirality, named
FerroPHANEs.2 Two recent studies will be presented here, which illustrate the usefulness of
this chiral phosphine.
Since desymmetrisation reactions represent one of the most powerful tools for the
preparation of chiral molecules, we have developed the first phosphine-promoted
enantioselective desymmetrisation of cyclic enones.
3
This process affords spirocyclic
compounds with good yields, high diastereoselectivity and enantiomeric excesses up to 94%:
In a second part of our work, chiral sulfides have been obtained by FerroPHANE-promoted
enantioselective cyclisations between allenoates and arylidene thiopyranones.4 Subsequent
totally diastereoselective oxidation of the sulfur centre furnished the corresponding spiranic
chiral sulfoxides:
1
a) Methot, J. L.; Roush, W. R. Adv. Synth. Catal. 2004, 346, 1035. b) Marinetti, A.; Voituriez, A.
Synlett 2010, 2, 174.
2
Voituriez, A.; Panossian, A.; Fleury-Brégeot, N.; Retailleau, P.; Marinetti, A. J. Am. Chem. Soc. 2008,
130, 14030.
3
Pinto, N.; Retailleau, P.; Voituriez, A.; Marinetti A. Chem. Commun. 2011, 45, 1015.
4
Duvvuru, D.; Pinto, N.; Gomez, C.; Betzer, J. –F.; Retailleau, P.; Voituriez, A.; Marinetti, A. Adv.
Synth. Catal. 2012, 354, 408.
18
Asymmetric Counteranion Directed Catalysis (ACDC):
A General Approach to Enantioselective Synthesis
Benjamin List
Max-Planck-Institut für Kohlenforschung, Mülheim an der Ruhr, Germany
[email protected]
Most chemical reactions proceed via charged intermediates or transition states. Such “polar
reactions” can be influenced by the counterion, especially if conducted in organic solvents,
where ion pairs are inefficiently separated by the solvent. Although asymmetric catalytic
transformations involving anionic intermediates with chiral, cationic catalysts have been
realized, analogous versions of inverted polarity with reasonable enantioselectivity, despite
attempts, only recently became a reality. In my lecture I will present the development of this
concept, which is termed asymmetric counteranion-directed catalysis (ACDC) and illustrate
its generality with examples from organocatalysis, transition metal catalysis, and Lewis acid
catalysis.
Since 2005, Benjamin List has been a director at the Max-Planck-Institut für
Kohlenforschung in Mülheim an der Ruhr (Germany). He obtained his Ph.D. in
1997 at the Johann-Wolfgang-Goethe-University in Frankfurt am Main. From
1997 until 1998 he conducted postdoctoral research at The Scripps Research
Institute in La Jolla (USA) and became an assistant professor there in January
1999. In 2003 he joined the Max-Planck-Institut für Kohlenforschung in
Mülheim. He has been an honorary professor at the University of Cologne
since 2004.
Professor List’s research focuses on organic synthesis and catalysis. He has contributed
fundamental concepts to chemical synthesis including aminocatalysis, enamine catalysis,
and asymmetric-counter-anion-directed catalysis (ACDC). His group has pioneered several
new amine- and amino acid-catalyzed asymmetric reactions originating from his discovery of
the proline-catalyzed direct asymmetric intermolecular aldol reaction in 2000. Shortly
thereafter, his group has developed the enamine catalysis concept and introduced the first
proline- catalyzed asymmetric Mannich reaction. Subsequently, his researchers pioneered
novel Michael reactions, α-aminations, enol-exo-aldolizations, and aldehyde α-alkylations.
Furthermore, his collaborative efforts have provided a clearer mechanistic understanding of
enamine catalysis and established the basis for the design of new reactions and catalysts.
His latest work deals with chiral anions in asymmetric catalysis. In 2006 he introduced the
concept of asymmetric counter-anion-directed catalysis (ACDC). This very general strategy
for asymmetric synthesis has recently found widespread use in organocatalysis, transition
metal catalysis, and Lewis acid catalysis.
The accomplishments of Ben List’s group have been recognized with the Synthesis-Synlett
Journal Award in 2000, the Carl-Duisberg-Memorial Award in 2003, the Degussa Prize for
Chiral Chemistry, the Lieseberg Prize of the University of Heidelberg, and the
“Dozentenstipendium” of the German Chemical Industry in 2004. He received the Novartis
Young Investigator Award in 2005, the JSPS-Fellowship Award in 2006, the Award of the
German Chemical Industry and the Astra Zeneca Research Award in Organic Chemistry in
2007, and was named a Thomson Reuters Citation Laureate in 2009. In 2011 his group has
been awarded an Advanced Grant (2.5M€) by the ERC. During the last years he has held
many appointments as visiting Professor and named lectureships.
19
An Enantioselective Organocatalytic Approach towards the
Mitragynine Series
Isabel P. Kerschgens, Martin J. Wanner, Henk Hiemstra, and Jan H. van Maarseveen
Van’t Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1098
XH Amsterdam, The Netherlands
Mitragynine, paynantheine and speciogynine belong to the group of corynanthe alkaloids, a
large class of biologically active indole alkaloids. They are present in the leaves of the Asian
plant Mitragyna speciosa Korth (Rubiaceae) and used by Thai and Malaysian natives as a
substitute for opium as well as for their stimulating activity and other medicinal applications
[1]. Interestingly, mitragynine has a stronger analgesic effect than morphine [2].
Paynantheine and speciogynine have slightly different activities.
Three syntheses of mitragynine have been developed, two starting from enantiopure starting
material [3,4] and a formal synthesis using organocatalysis [5]. Syntheses of paynantheine
and speciogynine have not been reported so far. Our successful approach to the three
alkaloids proceeds via an asymmetric Pictet-Spengler reaction relying on catalysis by
functionalized cinchona alkaloids instead of the usual binol-derived phosphorous acids [6].
Closure of the fourth ring was realized by a Tsuji-Trost allylic alkylation as developed earlier
by us [7].
References:
[1] Adkins, J. E.; Boyer, E. W.; McCurdy, R. Curr. Top. Med. Chem. 2011, 11, 1165-1175.
[2] Matsumoto, K.; Horie, S.; Ishikawa, H.; Takayama, H.; Aimi, N.; Ponglux, D.; Watanabe, K. Life Sci.
2004, 74, 2143-2155.
[3] Ma, J.; Yin, W.; Zhou, H.; Liao, X.; Cook, J. M. J. Org. Chem. 2009, 74, 264-273.
[4] Takayama, H.; Maeda, M.; Ohbayashi, S.; Kitajima, M.; Sakai, S.; Aimi, N. Tetrahedron Lett. 1995,
36, 9337-9340.
[5] Sun, X.; Ma, D. Chem. Asian J. 2011, 6, 2158-2165.
[6] Vakulya, B.; Varga, S.; Csámpai, A.; Soós, T. Org. Lett. 2005, 7, 1967-1969.
[7] Wanner, M. J.; Claveau, E.; Van Maarseveen, J. H.; Hiemstra, H Chem. Eur. J. 2011, 17, 1368013683.
20
Cross-Aldol Reactions of Ketones Catalyzed by Leucinol:
A Mechanistic Investigation and Application in the Enantioselective
Synthesis of Convolutamydine A and Speranskatine A
Andrei V. Malkov,*†,‡ Mikhail A. Kabeshov,†,‡ Ondřej Kysilka,‡ Marco Bella,*¶
Pavel Kočovský *‡
†
Department of Chemistry, Loughborough University, Leics LE11 3TU, UK, ‡School of
Chemistry, WestChem, Joseph Black Building, University of Glasgow, Glasgow G12 8QQ,
Scotland, UK, and ¶Department of Chemistry, University of Rome
“La Sapienza”, Piazzale Aldo Moro, 00185 Rome, Italy
Primary amino alcohols have been identified as efficient organocatalysts for an aldol
condensation of activated ketones, such as isatin, with acetone and other sterically
unhindered ketones. The acid-sensitive aldol products with a tertiary alcohol moiety, which
are prone to racemisation, were obtained in high enantiomeric purity. This reaction has
allowed an efficient enantioselective synthesis of natural convolutamydine A (93% ee with Dleucinol as catalyst)1 and (+)-speranskatine A (80% ee with L-leucinol). In the case of
convolutamydine A, the absolute configuration was confirmed by X-ray crystallography. The
proposed mechanism was used to tentatively assign the absolute configuration of natural
speranskatine A as (S)-(+).
.
O
(30 equiv)
MeO
O
MeO
OH
O
CH2Cl2, rt, 36 h
*
O
N
Me
O
O
(20 mol%)
H 2N
*
OH
N
Me
O
(+)-Speranskatine A
(80% ee)
The mechanistic investigation of the aldol reaction between isatins and acetone, catalysed by
primary amino alcohols, allowed identifying the intermediate oxazolidine as a resting state of
the catalyst. Experimental and computational studies unraveled the role of water in the
reaction mechanism. Further details will be discussed.
1.
Malkov, A. V.; Kabeshov, M. A.; Bella, M.; Kysilka, O.; Malyshev, D. A.; Pluháčková, K.;
Kočovský, P. Org. Lett. 2007, 9, 5473.
21
Amine-Catalyzed Direct Asymmetric Aldol additions
Ulf Scheffler, Kerstin Rohr, Morris Markert and Rainer Mahrwald
Department of Chemistry, Humboldt-University, Brook-Taylor Str. 2.,12 489 Berlin, Germany
Direct, enantioselective and catalytic aldol additions of hydroxylated ketones or aldehydes
provide an easy and direct access to defined configured polyhydroxylated aldol adducts,
which are in turn valuable intermediates in total syntheses of carbohydrates and polyketides.
We have developed a series of amine-catalyzed aldol-methodologies that yields defined
configured adjacent stereogenic centers. These methodologies include tertiary aminecatalyzed aldoladditions of hydroxylated ketones, amino acid-catalyzed aldol additions of
enolizable aldehydes, amine-catalyzed decarboxylative aldol additions, decarboxylative
Mannich-reactions and amine-catalyzed carbohydrate chain elongations.
Several examples showcase the new methodologies, which are characterized by
operationally simple and very mild conditions, but nonetheless high stereoselectivities and
high yields. Even predictions of configurative outcome are possible and will be discussed on
the base of the reaction mechanism. Matched and mismatched situations will be reviewed.
Using these new methodologies we were able to elaborate total syntheses of D-hamamelose,
boivinose and methyl-D-5-deoxyribose, which is the carbohydrate-moiety of trachycladines A
and B. Moreover a series of total syntheses of substituted pantolactones have been also
accomplished with these new methods.
22
Design and applications of new chiral bifunctional (H)-bonding-PTC
organocatalysts
David Monge,a) Rosario Fernándeza) and José M. Lassalettab)
a) Dpto. de Química Orgánica, Universidad de Sevilla.
b) Instituto de Investigaciones Químicas, Sevilla.
[email protected], [email protected]
The simultaneous activation of two reagents (or substrate and reagent) is a powerful tool that
has enabled to achieve extraordinary levels of activity and stereochemical control in many
contexts. In particular, the design of bifunctional catalysts in which one of the active sites of
the catalyst is a hydrogen bond donor (to activate electrophiles) has scored a major success
in the growing field of asymmetric organocatalysis [1]. Moreover, the inclusion of an anionic
nucleophile in an ion pair with chiral cations is a strategy widely used in asymmetric catalysis,
with activation by phase transfer catalysts as a particular case of the same [2]. Therefore, we
decided to study the combination of both strategies, i.e. the dual activation by bifunctional
catalysts having a quaternary ammonium group and a hydrogen bond donor function,
providing a new method of activation which had not been explored before. To this aim, we
have recently carried out the enantioselective catalytic cyanosilylation of nitroolefins using as
catalysts bifunctional derivatives of quinine containing tetraalkylammonium cyanide and
thiourea fragments [3]. The activation of the nitroolefin through hydrogen bonding with the
thiourea, combined with the presence of an "active" cyanide, afford -nitro nitriles with high
yields and good enantioselectivities.
The
mechanistic
considerations
that
led
to
the
design
of
first
generation
thiourea/tetraalkylammonium cyanide organocatalysts and the scope of this novel
methodology (synthesis of second generation catalysts and new applications) will be
discussed.
[1] Taylor, M. S.; Jacobsen, E. N. Angew. Chem. Int. Ed. 2006, 45, 1520.
[2] Maruoka, K. (Ed.) “Asymmetric Phase Transfer Catalysis”, Wiley-VCH, Weinheim, Alemania, 2008.
[3] Bernal, P.; Fernández, R.; Lassaletta, J. M. Chem. Eur. J. 2010, 16, 1691.
23
Structures and Reactivities of Reactive Intermediates in
Organocatalysis
Sami Lakhdar and Herbert Mayr
Department Chemie, Ludwig-Maximilians-Universität München
Butenandtstrasse 5-13 (Haus F), 81377 München
[email protected]
In previous work, we showed that the rate constants of the reactions of carbocations and
Michael acceptors with n-, - and -nucleophiles can be described by eq. 1, where
electrophiles are characterized by one parameter (E), while nucleophiles are characterized
by the solvent-dependent nucleophilicity parameter N and the sensitivity–parameter sN.1
lg k20°C = sN(N+E)
(1)
Electrophilenucleophile combinations are involved in many organocatalytic reaction cycles,
e.g., iminium– and enamine–activated processes.
In this communication we report on the structures and reactivities of various iminium ions and
enamines derived from chiral secondary amines. Scope and limitations of the use of various
organocatalysts in iminium– as well as enamine–activated reactions will be discussed.2
1) a) H. Mayr, M. Patz, Angew. Chem. Int. Ed. Engl. 1994, 33, 938-957; b) H. Mayr, B. Kempf, A. R.
Ofial, Acc. Chem. Res. 2003, 36, 66-77; c) H. Mayr, A. R. Ofial, J. Phys. Org. Chem. 2008, 21,
584-595. d) Database: www.cup.uni-muenchen.de/oc/mayr/reaktionsdatenbank/.
2) a) S. Lakhdar, H. Mayr, Chem. Commun. 2011, 47, 1866-1868. b) S. Lakhdar, R. Appel, H. Mayr,
Angew. Chem. Int. Ed. 2009, 48, 5034-5037. c) T. Kanzian, S. Lakhdar, H. Mayr, Angew. Chem.
Int. Ed. 2010, 49, 9526-9529. d) S. Lakhdar, T. Tokuyasu, H. Mayr, Angew. Chem. Int. Ed. 2008,
e
47, 8723-8726; ) Review: S. Lakhdar, A. R. Ofial, H. Mayr, J. Phys. Org. Chem. 2010, 23, 886892.
24
Reactivity Parameters of the Intermediates in NHC Catalyzed
Reactions
Biplab Maji and Herbert Mayr
Department Chemie der Ludwig-Maximilians-Universität München
Butenandtstraße 5-13 (Haus F), 81377 München, Germany
[email protected]
In previous investigations we have shown that the rates of the reactions of carbocations and
Michael acceptors with n, π, and σ-nucleophiles can be described by the linear free energy
relationship log k20 °C = sN(E + N), where E is an electrophilicity, N is a nucleophilicity, and sN
is a nucleophile-specific sensitivity parameter.[1] Use of this methodology for the
determination of the reactivity parameters of the intermediates in NHC catalyzed reactions
will be discussed in this communication.[2]
The nucleophilicities of NHCs are comparable to those of other nucleophilic organocatalysts
but they are much stronger Lewis bases which explains their special organocatalytic
activities.[3]
Figure 1. Comparison of relative rate constants and methyl cation affinities (MCAs) of NHCs
with other organocatalysts.[1c, 2]
References:
[1] a) Mayr, H.; Bug, T.; Gotta, M. F.; Hering, N.; Irrgang, B.; Janker, B.; Kempf, B.; Loos, R.; Ofial, A.
R.; Remennikov, G.; Schimmel, H.; J. Am. Chem. Soc. 2001, 123, 9500; b) Mayr, H.; Kempf, B.; Ofial,
A. R.; Acc. Chem. Res. 2003, 36, 66; c) For a comprehensive listing of nucleophilicity parameters N
and electrophilicity parameters E, see http://www.cup.uni-muenchen.de/oc/mayr/DBintro.html.
[2] Maji, B.; Breugst, M.; Mayr, H.; Angew. Chem. 2011, 50, 6915.
[3] a) Enders, D.; Niemeier, O.; Henseler, A.; Chem. Rev. 2007, 107, 5606; b) Marion, N.; DíezGonzález, S.; Nolan, S. P.; Angew. Chem. Int. Ed. 2007, 46, 2988.
25
Supported Organocatalysts, Multilayered Covalently Supported
Ionic Liquid Phase and Sequential Suzuki-Asymmetric Aldol
Reactions: New Approaches for Organocatalytic Reactions
Michelangelo Gruttadauria, Francesco Giacalone, Renato Noto
Università di Palermo, Dip. di Scienze e Tecnologie Molecolari e Biomolecolari (STEMBIO),
Viale delle Scienze, Palermo, Italy.
Here we describe our recent investigations regarding several aspects of the use of recyclable
supported organocatalysts and the combined use of a metal-based catalyst and an
organocatalyst for the sequential Suzuki-asymmetric aldol reactions.
Recyclable
polystyrene-supported
organocatalysts
were
tested
in
asymmetric
-
selenenylation of propanal, being this the first example of this reaction performed using a
supported catalyst and the Michael addition between nitrostyrene and aldehydes.[1]
More recently, we have developed a new kind of material called multilayer covalently
supported ionic liquid phase (mlc-SILP). This material can be used as organocatalyst,[2] or
as support for organocatalysts or for Pd nanoparticles. The latter material can be used in
combination with the 4-acyloxy-L-proline 2 for the sequential Suzuki-aldol reaction.[3]
References:
[1] F. Giacalone, M. Gruttadauria, P. Agrigento, V. Campisciano, R. Noto, Catal. Commun. 2011, 16, 75.
[2] C. Aprile, F. Giacalone, P. Agrigento, L. F. Liotta, J. A. Martens, P. P. Pescarmona, M. Gruttadauria,
ChemSusChem 2011, 4, 1830.
[3] M. Gruttadauria, L. A. Bivona, P. Lo Meo, S. Riela, R. Noto, Eur. J. Org. Chem. 2012, DOI:
10.1002/ejoc.201200092.
Peptide Catalyzed 1,4-Addition Reactions of Aldehydes to
26
α,β-Disubstituted Nitroolefins
Jörg Duschmalé and Helma Wennemers
Laboratorium für Organische Chemie, ETH Zürich,
Wolfgang-Pauli-Strasse 10, CH-8093 Zürich (Switzerland)
[email protected]
Whereas -mono-substituted nitroolefins are omnipresent as electrophiles in organocatalysis,
-disubstituted nitroolefins are widely underexamined due to their significantly lower
reactivity. These substrates are very interesting, because upon reaction with aldehydes, nitroaldehydes with three consecutive stereogenic centers are formed that can be readily
transformed into a variety of valuable chiral products including pyrrolidines as well as fully
substituted -amino acids and -butyrolactams. Here, we show that tripeptides of the type
Pro-Pro-Xaa (Xaa = acidic amino acid) [1,2] allow for reaction of aldehydes with these less
reactive nitroolefins while controlling the configuration at all three stereogenic centers.
The present work demonstrates that the large structural and functional diversity of small
peptides combined with their low molecular weight offers intrinsic advantages compared to
regular organocatalysts. While maintaining an original lead structure (Pro-Pro-Xaa), the
straightforward introduction of diversity offers the possibility to adapt to substrate
requirements. Thus, peptide catalysts are powerful tools for more demanding substrate
combinations.[3]
References:
[1] Wiesner, M.; Revell, J. D.; Wennemers, H. Angew. Chem. Int. Ed. 2008, 47, 1871-1874.
[2] Wiesner, M.; Upert, G.; Angelici, G.; Wennemers, H. J. Am. Chem. Soc. 2010, 132, 6-7.
[3] Duschmalé, J.; Wennemers, H. Chem. Eur. J. 2012, 18, 1111–1120.
Organocatalytic Michael addition reactions of α-azido ketones to
27
nitrostyrene
Demir, Ayhan S.; Gollu, M.; Khalily, M.A.; Okumuş, S. ; Canbolat, E.
Department of Chemistry, Middle East Technical University
06800 Ankara Turkey
Organocatalytic asymmetric Michael addition reactions have received widespread attention
for accessing a variety of optically active adducts which are synthetically useful building
blocks in versatile organic synthesis.1 Diaminoalcohols can be found in natural and
biologically active compounds and they are also used as ligands in organic transformations.2
Therefore, the synthesis of these compounds constitutes great importance.3
Since the azido group is a precursor of the amine group and α-azido ketones can be easily
obtained from α-bromo ketones and sodium azide, diaminoalcohols can be synthesized from
the Michael reaction of α-azido ketones to -nitrostyrene followed by selective reduction of all
functionalities. The organocatalytic Michael addition reaction of -azido ketones with nitro
alkenes catalyzed by various cinchona alkaloids afforded α-azido-γ-nitroketones in high anti
selectivity and > 95% enantiomeric excesses. The best conversion and selectivity was found
when the reaction carried out at -20oC in acetonitrile. Various azido ketones give comparable
results.
OH
R
O
R
N3 +
Ar
NO2
Ar
NH2
NH2
cat.
CH3CN
-20 oC
O
Ar
NO2
R
N3
Conv. >95%
ee= 90-96%
References:
1. Dalko, P. I.; Moisan, L. Angew. Chem., Int. Ed. Engl. 2004, 43, 5138
2. a) Wade, P. A.; Dailey, W. P.; Carroll, P. J. J. Am. Chem. Soc. 1987, 109, 5452. b)
Marchand, A. P.; Rajagopal, D.; Bott, S. G.; Archibold, T. G. J. Org. Chem. 1995, 60, 4943
3. Chowdari, N.S., Ahmad, M.; Albertshofer, K.; Tanaka, F.; Barbas III, C. F. Org. Lett. 2006, 8, 2839.
28
Organocatalysts versus chiral organometallic catalysts in the
asymmetric epoxidation of trans-methylcinnamate ester
Natalia Candu1, Loredana Protesescu1, Kristof Kranjc2, Marijan Kocevar2,
Simona M. Coman1
1
University of Bucharest, Faculty of Chemistry, Department of Organic Chemistry,
Biochemistry and Catalysis, Bdul. Regina Elisabeta, 4-12, Bucharest, Romania
2
University of Ljubljana, Faculty of Chemistry and Chemical Technology, Askerceva 5, SI1000 Ljubljana, Slovenia
One of the most important applications in asymmetric catalysis is the epoxidation of C=C
double bonds which provides access to enantiomerically enriched epoxides. They are of a
great practical value, in particular as intermediates for the production of enantiomerically
pure pharmaceuticals. In recent years dramatic development of methods for this purpose
was observed. In the field of metal-catalyzed epoxidations many applications were developed
[1]. For metal-free asymmetric epoxidation (e.g., organocatalysis) current methodology relies
mainly on the development of chiral ketones (e.g., so called Shi ketone prepared from cheap
renewable materials as D-fructose [2]). They are used for catalytic generation of dioxiranes
as epoxidizing agents. Such procedures seem to be the most advantageous in the
asymmetric epoxidation of a variety of non-functionalized olefins, dienes, enynes, and
hydroxyalkenes with >90% ee [3].
The difficulties in the preparation of cis-cinnamic esters are well known. These facts
prompted us to search for the methods toward the synthesis of (2R,3S)-phenyl glycidates via
the catalytic asymmetric epoxidation of commercially available and inexpensive trans-methyl
cinnamate. Moreover, such epoxidations should be environmentally friendly. To answer to
these requirements we compared from both economic and environmental point of view two
kinds of chiral catalysts: a chromium(III) dimmer salen complex [4] versus a Shi ketone for
the epoxidation of trans-methylcinnamate ester to (2R,3S)-phenyl glycidate. In the presence
of the Cr(III) based chiral catalyst S = 50-90% in phenyl glycidate with e.e. of 14-83% in
(2R,3S)-isomer for C=15-60% of trans-methylcinnamate were obtained while the Shi ketone
transformed the substrate in 21-77% proportion with S=40-56% and e.e. of up to 40%.
References:
[1] Comprehensive Asymmetric Catalysis, (E. N. Jacobsen, A. Pfaltz, H. Yamamoto, Eds.), Springer,
Berlin, 1999
[2] Y. Tu, Z.-X. Wang, Y. Shi, J. Am. Chem. Soc. 1996, 118, 9806
[3] (a) Z.-X. Wang, Y. Tu, M. Frohn, Y. Shi, J. Org. Chem. 1997, 62, 2328; (b) M. Frohn, Y. Shi,
Synthesis 2000, 1979
[4] L. Protesescu, M. Tudorache, S. Neatu, M. N. Grecu, E. Kemnitz, P. Filip, V.I. Parvulescu, S. M.
Coman, (2011): J. Phys. Chem. C 2011, 115 (4), 1112.
29
Organocatalyzed Synthesis of Heterocycles
Jean-François Brière and Vincent Levacher
Laboratory COBRA, IRCOF institute, University of Rouen - CNRS UMR 6014, INSA Rouen
1 rue Tesnière, 76821 Mont Saint Aignan cedex, France
[email protected]
Chiral 3,4 and 3,5-diarylpyrazolines (3, 4), bearing an electron-deficient functional group on
N1 (R1), belong to an important family of nitrogen heterocycles displaying a large array of
biological activities [1]. The presence of a polar electron-poor group on N1 markedly
contributes to both selectivities and affinities with bio-receptors. Nevertheless, the catalytic
and asymmetric synthesis of such pyrazoline derivatives has remained underdeveloped up to
recently [1], and only few enantioselective organocatalytic constructions of the 2-pyrazoline
ring have been published thus far [2]. Our group has been interesting in the development of
expeditious organocatalytic [1,3] synthesis of heterocyclic scaffolds and focused recently on
pyrazolines of type 3 or 4. In that context, we will discuss the scope and limitation of the
organo-catalytic formation of amide/ammonium ion-pairs from hydrazine derivatives 1
involved into domino sequences of aza-Michael-cyclocondensation reactions to provide
access to bio-relevant 1,4-dihydropyrazole compounds.
[1] Mahé, O.; Dez, I.; Levacher, V.; Brière, J. F. Angew. Chem. Int. Ed. 2010, 49, 7072 and references
cited therein.
[2] Müller S., List B. Angew. Chem. Int. Ed. 2009, 48, 9975–9978. (b) Campbell, N. R.; Sun, B.; Singh,
R. P.; Deng, L. Adv. Synth. Cat. 2011, 353, 3123. (c) Fernández, M.; Reyes, E.; Vicario, J. L.; Badía,
D.; Carrillo, L. Adv. Synth. Cat. 2012, 354, 371.
[3] (a) Mahé, O.; Frath, D.; Dez, I.; Marsais, F.; Levacher, V.; Brière, J. F. Org. Biomol. Chem. 2009, 7,
3648. (b) Gembus, V.; Bonnet, J.-J.; Janin, F.; Bohn, P.; Levacher, V.; Brière, J.-F. Org. Biomol. Chem.
2010, 8, 3287.
30
Cascade Reactions for the Asymmetric Construction of Complex
Molecules
Efraím Reyes, Maitane Fernández, Garazi Talavera, Jose L. Vicario and Luisa Carrillo
Departamento de Química Orgánica II, Facultad de Ciencia y Tecnología, Universidad del
País Vasco, UPV/EHU, Barrio Sarriena s/n, 48940, Leioa (Spain)
Domino or cascade reactions represent an advantageous approach for the straightforward
construction of biologically relevant compounds because they allow construction of complex
molecules in an efficient way, thereby minimizing the number of laboratory operations and
the generation of waste chemicals. In this sense, organocatalytic enantioselective domino
reactions represent a useful and competitive tool for the generation of molecular complexity
from readily available and cheap starting materials, as well as display exceptional
performance with regard to stereochemical control.[1]
Recently, we have reported several methodologies for the synthesis of carbo- and
heterocycles using cascade reactions using chiral secondary amines as catalysts In
particular we can access to pyridazines and pyrazolidines using the well known
iminium/enamine platform.[2] In addition, we have also developed a novel approach to highly
functionalized cyclobutanes by forma [2+2] cycloaddition between enals and nitroalkenes by
using for the first time the combination of dienamine and iminium activation.[3]
Fig 1. Some products synthesized in our group using aminocatalytic cascade reactions
References:
[1] For general reviews on organocatalytic cascade reactions, see: (a) Yu, X.; W. Wang, Org. Biomol.
Chem. 2008, 6, 2037; (b) Enders, D.; Grondal, C.; Huettl, M. R. M. Angew. Chem. Int. Ed. 2007, 46,
1570; (c) Guillena, G.; Ramon, D. J.; Yus, M. Tetrahedron: Asymmetry 2007, 18, 693
[2] (a) Fernández, M.; Vicario, J. L., Reyes, E.; Carrillo, L.; Badia, D. Chem. Commun. 2012, 48,
2092; (b) Fernández, M.; Reyes, E.; Vicario, J. L., Badia, D.; Carrillo, L. Adv. Synth. Catal. 2012,
354, 371.
[3] Talavera, G.; Reyes, E.; Vicario, J. L., Carrillo, L. Angew. Chem. Int. Ed. 2012, 51, in press.
31
POSTERS
One-Pot Asymmetric Cyclocarbohydroxylation for the
Enantioselective Synthesis of Functionalized Cyclopentanes
Wilfried Raimondi, Grégory Lettieri, Damien Bonne* and Jean Rodriguez*
Aix-Marseille Université, iSm2 UMR CNRS 7313, Centre Saint Jérôme, service 531, 13397
Marseille Cedex 20
The development of organocatalytic enantioselective methods to access enantiopure
molecules has received many attention for the last ten years due to the many advantages in
term of efficiency, selectivity and environmental benefits offer by organocatalysis.[1] When the
methodology involves simple starting materials and is associated with one-pot multiple bondforming transformations (MBFTs),[2] the resulting tools are particularly useful to reach high
level of structural complexity and functional diversity.
In this context, we present our results on the organocatalytic enantioselective Michael
addition between simple acyclic achiral 2-substitued malonates and nitroalkenes followed by
an in situ [3+2]-cycloaddition–fragmentation allowing the easy synthesis of densely
functionalized cyclopentanes bearing up to three stereogenic centers with very high
enantioselectivity and total diastereoselectivity.[3]
The high efficiency and the practical simplicity of the method make it an important way for the
stereoselective formation of highly substituted five-membered ring systems.
R3
NO2
R2
+
R1
MeO2C
Enantioselective
organocatalyzed
Michael addition
CO2Me
HO
HO
Intramolecular
carbohydroxylation
* R3
2
* R
N
R1
*
CO2Me
CO2Me
up to 99% yield
up to 98% ee
dr > 99:1
Fragmentation
ONE POT
References:
[1] (a) Special issue on asymmetric organocatalysis Chem. Rev. 2007, 107, 5413. (b) Enantioselective
Organocatalysis. Dalko, P. I., Ed; Wiley-VCH, Weinheim, 2007. (c) Asymmetric Organocatalysis: From
Biomimetic Concepts to Applications in Asymmetric Synthesis. Berkessel, A.; Groger, H.; MacMillan, D.
W. C., Eds; Wiley-VCH, Weinheim, 2005.
[2] Coquerel, Y.; Boddaert, T.; Presset, M.; Mailhol, D.; Rodriguez, J. in Ideas in Chemistry and
Molecular Sciences: Advances in Synthetic Chemistry; Pignataro, B., Ed.; Wiley-VCH: Weinheim,
2010 and references therein.
[3] Raimondi, W.; Lettieri, G.; Dulcère, J.-P.; Bonne, D.; Rodriguez, J. Chem. Commun. 2010, 46, 7247.
32
POSTERS
Organocatalysis with novel derivatives of Cinchona alkaloids
A. C. Breman, J. H. van Maarseveen, S. Ingemann, H. Hiemstra
Van ‘t Hoff Institute for Molecular Sciences, Faculty of Science,
University of Amsterdam, Science Park 904, 1098 XH Amsterdam,
The Netherlands
In this presentation the focus will be on the use of Cinchona alkaloids and their derivatives as
organocatalysts and the synthesis of new derivatives of these compounds. First, a new
procedure for the preparation of β-functionalized cysteines with the use of a thiourea
Cinchona alkaloid catalysts is described [1]. The procedure involves the conjugate addition of
thiols to α,β-unsaturated amino acids derivatives yielding the products given below in up to
95% ee and in a diastereomeric ratio of 5:1.
Another topic that will be presented is the influence of the structural environment of the
nitrogen atom of the quinuclidine ring on Cinchona alkaloid-catalyzed reactions. To this end,
we synthesized several new quinidine derivatives which lack a methylene group or have an
extra methylene group in the quinuclidine ring, so-called nor and homo-quinidine analogues.
With these analogues we studied three different types of conjugate additions to α,βunsaturated ketones and esters. The preliminary results obtained with the new derivatives of
quinidine indicate that the enantioselectivity of the examined reactions is significantly
different from the enantioselectivity obtained with unmodified quinidine. The differences in the
selectivity will be highlighted in the presentation.
References:
[1] Breman, A. C., van Maarseveen, J. H., Ingemann, S., Hiemstra, H. To be submitted
33
POSTERS
OrganoClick Reaction
A Metal-free Access to 1,2,3-Triazoles
Samia Belkheiraa, Douniazad El Abedb, Jean-Marc Ponsa, Cyril Bressya
a) UMR CNRS 7313 iSm2, Aix-Marseille Université, Centre Saint Jérôme, service 531,
13397 Marseille Cedex 20
b) Université d’Oran Es-Sénia, Laboratoire de Réactivité et Chimie Fine, Département de
Chimie, Faculté des Sciences, B.P.1524 El M’naour, 31100, Oran, Algérie.
Email : [email protected]
The synthesis of 1,2,3-triazoles became recently popular with the copper-catalyzed
version of azide-alkyne Huisgen cycloaddition developed independently by the groups of
Sharpless[1] and Meldal.[2] This powerful and highly regioselective reaction can be performed
in various media using several sources of copper catalyst but is usually restricted to terminal
alkynes.[3]
To circumvent this limitation, we developed another complementary access to this
kind of heterocycle starting from ketones and several sources of azides, and using proline as
organocatalyst. The approach is based on the enamine chemistry and the ability of these
molecules to perform cycloaddition with azides. The scope of the OrganoClick reaction will
be presented including a study of the regioselectivity and chemoselectivity.[4]
N
H
O
+
R1
CO2H
(cat.)
R3
R3 N3
MW irradiation
or
thermal heating
R2
R1
N N
N
R2
References:
[1] V. V. Rostovtsev, L. G. Green, V. V. Fokin, B. K. Sharpless Angew. Chem. Int. Ed. 2002, 41, 25962599.
[2] C. W. Tornoe, C. Christensen, M. Meldal, J. Org. Chem. 2002, 67, 3057-3064.
[3] a) M. Meldal, C. W. Tornoe Chem. Rev. 2008, 108, 2952-3015; b) J. E. Moses, A. D. Moorhouse
Chem. Soc. Rev. 2007, 36, 1249-1262.
[4] Belkheira, M.; El Abed, D.; Pons, J.-M.; Bressy, C. Chem. Eur. J. 2011, 17, 12917-12921.
34
POSTERS
N-Heterocyclic Carbene-Catalyzed
Enantioselective Hydroacylation of Cyclopropenes
Xavier Bugaut,1,2 Fan Liu,1 Michael Schedler,1 Roland Fröhlich,1 Frank Glorius1*
1
Westfälische Wilhelms-Universität Münster, Organisch-Chemisches Institut, Corrensstrasse
40, 48149 Münster, Germany. E-Mail: [email protected].
2
Present address: Aix-Marseille Université, iSm2, UMR CNRS 7313, Campus Scientifique St
Jérôme, service 541, 13397 Marseille Cedex 20, France. E-mail: [email protected].
The use of N-heterocyclic carbenes (NHCs) as organocatalysts[1] provides a unique activation
mode of aldehydes, inverting their innate reactivity by rendering the carbonyl position
nucleophilic. Recently, our group reported the use of this Umpolung strategy[2] to achieve the
NHC-catalyzed
hydroacylation
of
cyclopropenes
affording
structurally
valuable
acylcyclopropanes.[3-5] Mechanistic studies suggested that the product formation with these
electron-neutral olefins occurs via a concerted syn hydroacylation pathway.
We now describe the enantioselective variant of this reaction.[6] A new family of electron-rich,
2,6-dimethoxyphenyl-substituted NHCs induces excellent reactivity and enantioselectivity.
Preliminary kinetic studies unambiguously demonstrate the superiority of this family of
catalysts over known NHCs in this challenging transformation.
References:
[1] For excellent reviews, see: (a) Enders, D.; Niemeier, O.; Henseler, A. Chem. Rev. 2007,
107, 5606. (b) Moore, J. L.; Rovis, T. Top. Curr. Chem. 2010, 291, 77.
[2] For an up-to-date tutorial review on organocatalytic Umpolung, see: (a) Bugaut, X.;
Glorius, F. Chem. Soc. Rev. 2012, DOI: 10.1039/C2CS15333E.
[3] Bugaut, X.; Liu, F.; Glorius, F. J. Am. Chem. Soc. 2011, 133, 8130.
[4] For the related Rh-catalyzed hydroacylation of cyclopropenes using salicylaldehydes,
see: Phan, D. H. T.; Kou, K. G. M.; Dong, V. M. J. Am. Chem. Soc. 2010, 132, 16354.
[5] For a highlight on the NHC-catalyzed hydroacylation of unactivated olefins, see: DiRocco,
D. A.; Rovis, T. Angew. Chem. Int. Ed. 2011, 50, 7982.
[6] Liu, F.; Bugaut, X.; Schedler, M; Fröhlich, R.; Glorius, F. Angew. Chem. Int. Ed. 2011, 50,
12626.
35
POSTERS
Highly enantioselective organocatalytic construction of all-carbon
quaternary stereocenters by Michael addition with -ketoamides
Maria del Mar Sanchez Duque,(1) Olivier Baslé,(1) Nicolas Isambert,(1) Yves Génisson,(2) JeanChristophe Plaquevent,(2) Xavier Bugaut,(1) Jean Rodriguez,(1) Thierry Constantieux(1)
1) UMR CNRS 7313 iSm2, Aix-Marseille Université, Centre Saint Jérôme, service 531,
13397 Marseille Cedex 20
2) Université Paul Sabatier (Toulouse III), LSPCMIB-UMR-CNRS 5068, 118, route de
Narbonne, 31062 Toulouse cedex .9
The enantioselective construction of all-carbon quaternary stereocenters is one of the most
demanding key steps in the stereocontrolled synthesis of complex natural and/or
pharmaceuticals products.[1] In this context, the organocatalytic enantioselective conjugate
addition represents a powerful tool for the elaboration of these particular stereocenters.[3]
In this way, our research interest in ketoamides led us to develop the first organocatalytic
enantioselective conjugate addition of -substituted -ketoamides 1 to enones 2 using an
amino-thiourea bifunctional catalyst, involving an unprecedented cooperative effect of the
amide function in the activation process (cf scheme).[4],[5] The corresponding adducts 3
containing a highly functionalized all-carbon quaternary stereocenter are obtained in good
yields and high to excellent enantiomeric excesses. Moreover, the synthetic advantage of the
additional amide function is illustrated through an efficient enantioselective domino Michael/
spirocyclization sequence leading to chiral scaffolds 4 of high synthetic interest.
References:
[1] a) C. J. Douglas, L. E. Overman Proc. Natl. Acad. Sci. U.S.A., 2004, 101, 5363; b) B. M. Trost, C.
Jiang Synthesis, 2006, 3, 369.
[3] J. L. Vicario, D. Badía, L. Carrillo Synthesis, 2007, 14, 2065.
[4] M. M. Sanchez Duque, O. Baslé, N. Isambert, A. Gaudel-Siri, Y. Génisson, J.-C. Plaquevent, J.
Rodriguez, T. Constantieux, Org. Lett., 2011, 13, 3296.
[5] a) O. Baslé, W. Raimondi, M. M. Sanchez Duque, D. Bonne, T. Constantieux, J. Rodriguez Org.
Lett., 2010, 12, 5246-; b) M.M. Sanchez Duque, C. Allais, N. Isambert, T. Constantieux, J. Rodriguez
Top. Heterocycl. Chem., R. Orru Ed., Springer-Verlag (Berlin), 2010, 23, 227; c) F. Liéby-Muller, T.
Constantieux, J. Rodriguez J. Am. Chem. Soc., 2005, 127,17176.
36
POSTERS
Zwitterions of N-Heterocyclic Carbenes with Ketenes as Reactive
Intermediates in Organocatalysis: Synthesis and Characterization
Morgan Hans,a Johan Wouters,b Albert Demonceau,a Lionel Delaudea,*
a
Laboratory of Organometallic Chemistry and Homogeneous Catalysis,
Institut de Chimie (B6a), University of Liège, Sart-Tilman par 4000 Liège, Belgium
b
Departement of Chemistry, Facultés Universitaires Notre-Dame de la paix,
61 Rue de Bruxelles, 5000 Namur, Belgium
Over the past few years, N-heterocyclic carbenes (NHCs) have become increasingly popular
in organocatalysis. These divalent carbon species behave as powerful nucleophiles and were
successfully
employed
to
promote
Stetter
reactions,
transesterifications,
benzoin
condensations and many more [1]. Moreover, asymmetric induction could be achieved using
chiral carbenes, most often leading to good or excellent enantiomeric excesses [2].
Among others, NHCs were used as organocatalysts to promote the Staudinger cycloaddition
of a ketene and a N-protected imine into a -lactam. In 2007, the groups of Ye [3] and Smith
[4] simultaneously proposed the intermediacy of a NHC•ketene zwitterion in these reactions,
but they were not able to isolate it. Such a reactive intermediate was also postulated by Ye
and co-workers in the NHC-promoted synthesis of -alkylidenyl--lactones [5], 1,3,4-oxadiazin-6-ones [6], and dihydrocoumarins [7]. To the best of our knowledge, there is only one
example of a stable NHC•ketene betaine reported by Weber in 1970 [8]. In the present study,
we disclose the synthesis of five new NHC•ketene adducts. All the products were isolated in
high yields and fully characterized by 1H and 13C NMR, IR and XRD spectroscopy.
[1] Marion, N.; Díez-González, S.; Nolan, S. P. Angew. Chem. Int. Ed. 2007, 46, 2988.
[2] Moore, J.; Rovis, T. Top. Curr. Chem. 2009, 291, 77.
[3] Zhang, Y.-R.; He, L.; Wu, X.; Shao, P.-L.; Ye, S. Org. Lett. 2008, 10, 277.
[4] Duguet, N.; Campbell, C. D.; Slawin, A. M. Z.; Smith, A. D. Org. Biomol. Chem. 2008, 6, 1108.
[5] Lv, H.; Zhang, Y.-R.; Huang, X.-L.; Ye, S. Adv. Synth. Catal. 2008, 350, 2715.
[6] Huang, X.-L.; He, L.; Shao, P.-L.; Ye, S. Angew. Chem. Int. Ed. 2009, 48, 192.
[7] Lv, H.; You, L.; Ye, S. Adv. Synth. Catal. 2009, 351, 2822.
[8] Regitz, M.; Hocker, J.; Weber, B. Angew. Chem. Int. Ed. 1970, 9, 375.
37
POSTERS
Highly Enantioselective Direct Vinylogous Michael Addition of γButenolide to Enals
Alice Lefranc, Adrien Quintard, Alexandre Alexakis*
University of Geneva, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland.
In recent years, aminocatalysis and particularly iminium catalysis has become an essential
activation mode for the asymmetric β-functionalization of conjugated carbonyl compounds.
Our group recently developed Aminal- PYrrolidine (APY) catalysts as powerful tools for
aminocatalyzed reactions.[1] In this context, we disclosed the development of an
unprecedented and simple direct vinylogous addition of deconjugated butenolide to enals in
excellent stereoselectivities (>95% ee).[2] This methodology allows for the efficient
preparation of complex γ-butenolide from Angelica lactone derivatives, directly obtained
from readily available renewable resources. Fur- thermore, preliminary mechanistic
investigations allowed for a better understanding of the process.
Ph
N
PhO
N
H
O
O
+
R
O
R'
non-activated
N
Ph
O
APY 15 mol%
O
R'
toluene, rt
R
O
61-88% yield
2.3:1 to 7.3:1 dr
88-97% ee
References:
[1] a) A. Quintard, C. Bournaud, A. Alexakis, Chem. Eur. J., 2008, 14, 7504-7507 ; b) A. Quintard, S.
Belot, E. Marchal A. Alexakis, Eur. J. Org. Chem., 2010, 927-936.
[2] A. Quintard, A. Lefranc, A. Alexakis, Org. Lett., 2011, 13, 1540-1543.
38
POSTERS
Catalytic enantioselective protonation of enol trifluoroacetates
Aurélie Claraz, Jérôme Leroy, Sylvain Oudeyer, Vincent Levacher.
“Team Heterocycles”, UMR 6014 CNRS COBRA – IRCOF, Université et INSA de Rouen,
rue Tesnière, 76821 Mont Saint Aignan (France)
Tertiary carbon stereocenters are present in numerous biologically active compounds making
highly
desirable
efficient
catalytic
methodologies
to
control
this
stereoelement.
Enantioselective protonation of prochiral enol derivatives has emerged as a simple route for
the preparation of carbonyl compounds with an -stereogenic center. In this context, several
methodologies for the organocatalytic enantioselective protonations of silyl enol ethers have
been previously reported by our research group [1,2,3].
The use of stable substrates is the prerequisite to develop more general and efficient
processes of protonation. As such, enol esters have been widely used as substrates of
choice in enzymatic enantioselective protonation. Moreover, to date, their use in
enantioselective protonation by means of chemical processes remains rare [4]. Therefore, we
turned our attention to enol trifluoroacetates which, besides their improved stability compared
to silyl enolates, are known to provide a high degree of regioisomeric purity in favor of the
thermodynamic isomer [5]. Thus, the catalytic enantioselective protonation of several enol
trifluoroacetates was achieved by using potassium bicarbonate as protic nucleophile and
cinchona alkaloid derivatives as chiral proton shuttle. Good isolated yields in aromatic cyclic
ketone series along with high enantioselectivities up to 93 % have been obtained by applying
the conditions reported below. Mechanistic aspects of this first example of catalytic
enantioselective protonation of enols trifluoroacetates will be also discussed [6].
References:
[1] Poisson, T.; Dalla, V.; Marsais, F.; Dupas, G.; Oudeyer, S.; Levacher, V. Angew. Chem. Int. Ed.
2007, 46, 7090-7093.
[2] Poisson, T.; Oudeyer, S.; Dalla, V.; Marsais, F.; Levacher, V. Synlett 2008, 16, 2447-2450.
[3] Poisson, T.; Gembus, V.; Dalla, V.; Oudeyer, S.; Levacher, V. J. Org. Chem. 2010, 75, 7704-7716.
[4] For the only example, see: Yamamoto, E.; Nagai, A.; Hamasaki, A.; Tokunaga, M. Chem. Eur. J.
2011, 17, 7178-7182.
[5] Asensio, G.; Ana Cuenca, A.; Nuria Rodriguez N.; Medio-Simon, M. Tetrahedron:asymmetry, 2003,
14, 3851-3855.
[6] Claraz, A.; Leroy, J.; Oudeyer, S.; Levacher ,V. J. Org. Chem. 2011, 76, 6457-6463.
39
POSTERS
Towards lactamization organocatalysts
Stanimir Popovic, Henk Hiemstra, Jan van Maarseveen
Van ’t Hoff Institute for Molecular Science (HIMS), University of Amsterdam,
The Netherlands
Small cyclic peptides derived from two to five amino acid-residues are class of highly
bioactive natural compounds [1], but still not readily accessible via organic synthesis due to
their inherent ring strain. Few auxiliary mediated approaches partly overcome cyclization
step problems but still suffer from several disadvantages, such as ring-closure site
dependence [2] and the strong acidic conditions required for auxiliary removal [3]. These
difficulties could be overcome by a bifunctional catalyst as shown below displaying a thiol
and an electrophilic moiety for amine capture. A transthioesterification-intramolecular
hemiaminal formation sequence should form an intermediate suitable for S,N-acyl shift. In
order to explore these assumptions and limitations, several enantiopure peptide thioesters
were synthesized and cyclized towards 7-membered bislactams in moderate yields. A
delicate balance of the kinetics of direct lactamization, hydrolysis, racemization, and
oligomerization was found to be in the favor of the first one. Tuning the thioester still remains
the main challenge.
O
H2 N
SH
S
transthioesterification
PhSH
E
E
=
amine capture
O
RO
H2 N
SPh
O
SH
O
O
H
O
SH
SH
S
very slow
lactamization
SH
E
N E
H
unstable
compound
unstable
thioester
S! N shift
O
O
NH
N
7-15 membered lactams
E
HS
O
SH
?
disulfide
too stable
perfect
catalyst
thioester
too stable
References:
[1] Kawagishi, H.; Somoto, A.; Kuranari, J.; Kimura, A.; Chiba, S. Tetrahedron Letters 1993, 34, 3439.
[2] Chen, J.; Warren, J., D.; Wu, B.; Chen, G.; Wan, Q., Danishefsky, S., J. Tetrahedron Letters 2006,
47, 1969.
[3] Bieräugel, H.; Schoemaker, H., E.; Hiemstra, H.; Maarseveen, J.H. Organic & Biomolecular
Chemistry 2003, 1, 1830.
40
POSTERS
Regio- and diastereoselective anionic [3+2] cycloaddition
under phase transfer catalytic conditions
Vincent Gembus, Svetana Postikova, Vincent Levacher and Jean-François Brière
Laboratory COBRA, IRCOF institute, University of Rouen - CNRS UMR 6014, INSA Rouen
1 rue Tesnière, 76821 Mont Saint Aignan cedex, France
[email protected]
The regio- and stereoselective syntheses of chiral cyclopentenes have given rise to a great
deal of research activity due to their presence within biologically relevant architectures [1].
The organocatalytic phosphine promoted [3+2] cycloaddition from β-substituted electron-poor
alkenes afforded cyclopentenes 2 in diastereo- and enantioselective manner [2]. The nature
of phosphine catalysts achieved the regioselectivity control (α vs γ-addition pathway). The
synthesis of a second class of cyclopentene regioisomer 4 was developed via a formal
cycloaddition process involving Morita-Baylis-Hillman adducts 3 and a base through a γaddition pathway. Alternatively, we recently developed a highly trans and regioselective
anionic formal [3+2] cycloaddition on enones 6 under phase transfer organocatalytic
conditions [1], based on a modified Beak’s procedure [3]. Making use of allylic sulfones 5,
having an acrylamide backbone, the formation of unprecedented densely substituted
cyclopentenes 7 was thereby allowed.
[1] Gembus, V.; Postikova, S.; Levacher V.; Brière, J. F. J. Org. Chem. 2011, 76, 4194 and references
therein.
[2] For representative reviews: (a) Marinetti, A.; Voituriez, A. Synlett 2010, 174. (b) Cowen, B. J.; Miller,
S. J. Chem. Soc. Rev. 2009, 38, 3102–3116. (c) López, F.; Mascareñas, J. L. Chem. Eur. J. 2011, 17,
418-428.
[3] (a) Beak, P.; Burg, D. A. Tetrahedron Lett. 1986, 27, 5911. (b) Beak, P.; Burg, D. A. J. Org. Chem.
1989, 54, 1647-1654.
41
POSTERS
Evaluation of the Chiral DIANANE Backbone as Ligand for
Organolithium Reagents
Praz Jézabel Albrecht Berkessel* and Alexandre Alexakis*
University of Geneva, 30 Quai Ernest-Ansermet, CH-1211 Geneva
University of Köln, 4 Greinstrasse, D-50939 Köln, Germany
Chiral diamines are compounds of greatest interest in organic synthesis and particularly as
chiral ligands for various asymmetric reactions.
Our groups recently developed a new type of C2-symmetric tertiary diamines derived from
the DIANANE backbone.[1]
These news C2-symmetric diamines were then tested in various reactions using
organolithium reagents such as asymmetric deprotonation, asymmetric bromine-lithium
exchange and enantioselective additions of aryl and alkyllithium reagents to aromatic
imines.[2]
References:
[1] Chem., 2004, 69, 3050-3056.
[2] Jezabel Praz, Laure Guénée, Sarwar Aziz, Albrecht Berkessel and Alexandre Alexakis, Submitted,
2012.
42
POSTERS
1,2-dicarbonyl compounds as pro-nucleophiles in asymmetric
transformations
Wilfried Raimondi, Olivier Baslé, Maria del Mar Sanchez Duque, Thierry Constantieux*,
Damien Bonne* and Jean Rodriguez*
Aix-Marseille Université, UMR CNRS 7313 iSm2, Centre St Jérôme, Service 531, 13397
Marseille
Nowadays, the development of eco-compatible processes is becoming more and more
important given our planet’s environmental situation. To fulfill these ecological and
economical needs, the research towards organocatalytic enantioselective methods to access
enantiopure molecules has received much attention in the last ten years.[1] Such
methodologies have many advantages in terms of efficiency, selectivity and environmental
benefits. More particularly, the asymmetric organocatalysed Michael addition of various
nucleophiles to nitroolefins represents a very useful reaction as the reaction products can
easily be converted into highly functionalised cyclic or acyclic building blocks.
In this context, we became interested in the challenging reactivity of 1,2-dicarbonyl
compounds as pronucleophiles in organocatalysed transformations as only few examples
have been reported so far.[2] We successfully developed the first enantioselective
organocatalysed Michael additions of -ketoamides and -ketoesters onto nitroolefins with
excellent stereoselectivities and very good yields.[3,4] The Michael adducts can be used as
versatile synthetic platforms to make five-membered carbo- and heterocycles, as well as sixmembered carbocycles with the creation and control of additional stereocenters.
References:
[1] Enantioselective Organocatalysis : Reactions and Experimental procedures, Ed. P. I. Dalko, Wiley,
Weinheim, 2007.
[2] W. Raimondi, D. Bonne, J. Rodriguez, Angew. Chem. Int. Ed. 2012, 51, 40.
[3] O. Baslé, W. Raimondi, M. M. Sanchez Duque, D. Bonne, T. Constantieux, J. Rodriguez. Org. Lett.
2010, 12, 5246.
[4] W. Raimondi, O. Basle, D. Bonne, T. Constantieux , J. Rodriguez, Adv. Synth. Catal. 2012, DOI :
10.1002/adsc.201100739.
43
POSTERS
Organocatalyzed Desymmetrization of Meso Primary Diols
Christèle Rouxa, Mathieu Candya,b, Jean-Marc Ponsa, Olivier Chuzela and Cyril Bressya
a) Aix-Marseille Université – Institut des Sciences Moléculaires de Marseille iSm2 UMR
7313 – Equipe STeRéO – Campus de Saint Jérôme, service 532 - 13397 Marseille
cedex 20 – France
b) Current adress: Institut für Organische Chemie, RWTH Aachen University,
Landoltweg 1, D-52056, Aachen, Germany.
Email: [email protected] and [email protected]
The synthesis of complex targets with numerous stereogenic centers increases the number
of enantioselective steps. In order to reduce the number of these generally expensive steps,
a possible strategy is the single enantioselective step desymmetrization of meso precursors.
Aiming at this goal, our attention is focused on highly functionalized tetrahydropyran (THP)
rings since there are present in numerous biological active products[1] and also because we
recently proposed an efficient and versatile synthetic pathway for the elaboration of meso
primary diols derived from THP.[2] In order to circumvent the limitations of enzymatic
desymmetrization (poor tolerance towards structural variations of the substrates), the first
example of enantioselective desymmetrization of meso primary diols using chiral DMAP was
developed in our laboratory.
R3
R4 R5
R2
HO
R1
O
R3
R2
OH
R1
R3
R2
O
Organocatalyst
Acylating reagent
conditions
O
R4 R5
*
*
*
R1
O
*
*
R3
R2
OH
R1
meso diol
Encouraging results with high yields and high level of enantioselectivities will be presented.
References:
[1] (a) Ratjadone A : Schummer, D.; Gerth, K.; Reichenbach, H.; Höfle, G.; Liebigs Ann. Chem. 1995,
685-688; (b) Phorboxazole B : Searle, P. A.; Molinski, T. F. J. Am. Chem. Soc. 1995, 117, 8126-8127;
(c) Exiguolide : Ohta, S.; Uy, M.M.; Yanai, M.; Ohta, E.; Hirata, T.; Ikegami, S. Tetrahedron Lett. 2006,
47, 1957-1960.
[2] Candy, M.; Audran, G.; Bienaymé, H.; Bressy, C.; Pons, J.-M. Org. Lett. 2009, 11, 4950-4953. For
an application in total synthesis see : Candy, M.; Audran, G.; Bienaymé, H.; Bressy, C.; Pons, J.-M. J.
Org Chem. 2010, 75, 1354–1359.
44
POSTERS
Experimental Assessment and Theoretical Rationalization of the
Empirical Concept of Electrosteric Activation Using an ImidazoliumTagged Proline
Gian Pietro Miscione, Andrea Bottoni, Claudio Trombini, Marco Lombardo,
Elisa Montroni, Arianna Quintavalla
University of Bologna, Dep.of Chemistry “G. Ciamician”, via Selmi 2, Bologna, Italy
The empirical concept of electrosteric activation of organocatalytic reactions by
supplementary ionic groups properly installed on the catalyst framework [1] is validated in a
combined experimental-theoretical study using cis and trans L-hydroxyproline derivatives 1
tagged with an imidazolium cation, as catalysts of the benchmark cyclohexanone/
benzaldehyde aldol reaction. The activity of 1 is compared to that of trans-2 and cis-2, isoster
analogues of N-methylimidazolium tagged 1 (Fig.1).
Figure 1
The selected reaction conditions chosen for the comparison of reaction profiles was a
solvent-free protocol previously developed for cis-1 [2] and trans-1 [3], where a 5 molar
excess of cyclohexanone was used to ensure homogeneity, in the presence of a
stoichiometric amount of water. Transition states of the rate-determining addition of the
enamine to benzaldehyde have been modeled using DFT (M06-2X density functional, DVZP
basis set). Calculated free activation energies fit with the experimental data, and transition
state geometries provide physical evidence of the best approaches between charged centers
that optimize electrostatic interactions.
References:
[1] M. Lombardo, C. Trombini, ChemCatChem 2010, 2, 135.
[2] M. Lombardo, S. Easwar, F. Pasi, C. Trombini, Adv. Synth. Catal. 2009, 351, 276.
[3] M. Lombardo, F. Pasi, S. Easwar, C. Trombini, Synlett 2008, 16, 2471
45
POSTERS
A Two Stage Liquid-Liquid Biphasic Homogeneous Organocatalytic
Aldol Protocol Based on the Use of a Multilayered Ionic Liquid
Phase Covalently Bound to Silica Gel.
Marco Lombardo,a Elisa Montroni,a Arianna Quintavalla,a Claudio Trombini,a
Michelangelo Gruttadauria,b Francesco Giacaloneb
a
b
Università di Bologna, Dip. di Chimica “G. Ciamician”, via Selmi 2, Bologna, Italy
Università di Palermo, Dip. di Scienze e Tecnologie Molecolari e Biomolecolari (STEMBIO),
Viale delle Scienze, Palermo, Italy.
Multiphase homogeneous catalysis [1] offers solutions to the challenge of merging the
advantages of homogeneous catalysis, that generally displays higher reactivity and
selectivity under milder conditions, and those characteristic of heterogeneous processes,
where separation procedures require easier operations and catalyst recycle is possible.
We developed an innovative two liquid
phase reaction protocol based on the
use of the covalently bound multilayered
supported ionic liquid phase (mlc-SILP)
shown
in
the
Figure
[2].
The
imidazolium-tagged catalyst 1 [3] easily
dissolves into the multilayered supported
ionic
liquid
phase.
The
resulting
composite material is used to promote
the benchmark cyclohexanone 4-nitrobenzaldehyde aldol reaction in a two
stage protocol. In the reaction stage mlcSILP releases 1 to the cyclohexanone
phase, allowing a homogeneous reaction
to take place. In the second stage, when
diethylether is used to extract the product, mlc-SILP acts as a sponge for 1, restoring the
original solution of 1 in the ionic liquid film. Low catalyst loadings and extended recycling
ensured very high overall productivity levels.
References:
[1] M. Lombardo, A. Quintavalla, M. Chiarucci, C. Trombini, Synlett 2010, 1746.
[2] C. Aprile, F. Giacalone, P. Agrigento, L. F. Liotta, J. A. Martens, P. P. Pescarmona, M. Gruttadauria,
ChemSusChem 2011, 4, 1830.
[3] E. Montroni, S. P. Sanap, M. Lombardo, A. Quintavalla, C. Trombini, D. D. Dhavale, Adv. Synth.
Catal. 2011, 353, 3234.
46
POSTERS
Synthesis of novel organocatalysts derived from tartaric acid
Christopher D. Maycock,a,b M. Rita Venturaa
a
Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Apartado 127,
2780-901 Oeiras, Portugal. b Faculdade de Ciências da Universidade de Lisboa,
Departamento de Química e Bioquímica, 1749-016
Lisboa, Portugal
The synthesis of two new organocatalysts 2 and 3 (Figure 1), belonging to the families of
thiourea catalysts and chiral N,N’-dioxides, respectively, are described. Tartaric acid is an
abundant versatile chiral small building block and the 2,3-dimethoxybutane-2,3-dioxy acetal
dimethyl ester of tartaric acid 1 is readily available in isomerically pure form. It contains
additional stereocenters which could control the conformation of the molecule and influence
the stereochemical outcome of several reactions [1,2].
Preliminary results of the asymmetric cyanosilylation of aldehydes catalysed by 2 will also be
presented.
Figure 1
References:
[1] Barros, M. T.; Maycock, C. D.; Ventura, M. R. Org. Lett. 2003, 5, 4097.
[2] Burke, A. J.; Maycock, C. D.; Ventura, M. R. Org. Biomol. Chem. 2006, 4, 2361.
47
POSTERS
Novel Integrated Membrane Reactor Systems for Organocatalytic
Production of Olefins/Polyolefins
Zoe Ziaka2,1,* and Savvas Vasileiadis1
1.Hellenic Open University, Patras, Greece, 26335
2.International Hellenic University, Thermi-Thessaloniki, Greece, 57001
Novel integrated operations are presented for aliphatic (paraffin) hydrocarbon
dehydrogenation into olefins and subsequent polymerization into polyolefins (e.g., propane to
propylene to polypropylene, ethane to ethylene to polyethylene). Catalytic dehydrogenation
membrane reactors (permreactors) made by inorganic or metal membranes are utilized in
conjunction with fluid bed polymerization reactors using coordination catalysts. The catalytic
propane dehydrogenation is taken place as a first reaction in order to design an integrated
process of enhanced propylene polymerization. Moreover, accurate kinetic experimental data
of the propane dehydrogenation in a fixed bed type catalytic reactor is obtained which
indicates the molecular range of the produced C1-C3 hydrocarbons. Experimental membrane
reactor conversion and yield data have also studied.
Analytical models are discussed in terms of the operation of the reactors through
computational simulation, by varying key reactor and reaction parameters [2, 3]. The
obtained results show that it is effective for catalytic permreactors to provide streams of
olefins to successive polymerization reactors for end production of polyolefins (i.e.,
polypropylene, polyethylene) in homopolymer or copolymer form.
Optimized technical, economic and environmental benefits are analyzed from the
implementation of these processes [1,4,5,6]. The appropriate use of organo-catalysts for the
polymerization reaction is a subject of analysis for improved polymerization outcomes. A new
approach using organic catalysts could lead to well-defined, biodegradable molecules made
from renewable resources in an environmentally responsible method. Such an achievement
could lead to a new recycling process that has the potential to significantly increase the
ability to recycle and reuse common and plant-based plastics in the future. In addition, it can
contribute to the implications across a wide range of industries including biodegradable
plastics, plastics recycling, healthcare products and microelectronics. These processes, as
opposed to the more classical transition metal-based catalytic systems, have the advantage
of being more environmentally friendly and less toxic, as well as often being tolerant to a very
wide variety of different reaction conditions, including air and water. Such as systems do not
pollute products with traces of heavy metals, and these metal-free catalysts are also often of
a very convenient, robust and simplistic nature, making their large scale applications more
economical.
References:
[1] Potter, D.J.B., Polypropylene, third annual review. Chemical Week Associates, 4-10, 2000.
[2] Vasileiadis, S.; Ziaka, Z., Paper #361i, in Kinetics, Catalysis and Reaction Engineering, AIChE
annual symposium series, 2000.
[3] Vasileiadis, S.;Ziaka, Z., NASCRE 1st meeting, Houston, TX, 2001.
[4] Billmeyer, F.W., “Textbook of Polymer Science”, J.Wiley&Sons, 3rd Ed., 1984.
[5] Rodriguez, F., “Principles of Polymer Systems”, 3rd ed. Hemisphere Publ. Corp., 1989.
[6] Eldridge, R.B., Ind. Eng. Chem. Res., 1993, 32, 2208.
* corresponding author, Tel&Fax: +30-2310-275473, email: [email protected]
48
LIST OF PARTICIPANTS
First Name
Last Name
Email
Alexandre
Stephane
Jérôme
Maurizio
Damien
Arjen C.
Cyril
Jean-François
Xavier
Janez
Matthieu
Gaëlle
Olivier
Simona M.
Laurent
Xavier
Thierry
Yoann
Lionel
Ayhan S.
Haiying
Jörg
Charo
Lucia
Eric
Sébastien
Michelangelo
Morgan
Virginie
Kent
Ismail
Praz
Tõnis
Pavel
Christoforos G.
Sami
Alice
Grégory
José M.
Dimitrios
Benjamin
Marco
Annemieke
Alexakis
Anguille
Baudoux
Benaglia
Bonne
Breman
Bressy
Brière
Bugaut
Cerkovnik
Chellat
Chouraqui
Chuzel
Coman
Commeiras
Companyó
Constantieux
Coquerel
Delaude
Demir
Du
Duschmalé
Fernández
Forzi
Gayon
Goudedranche
Gruttadauria
Hans
Heran
Hung
Ibrahem
Jézabel
Kanger
Kocovsky
Kokotos
Lakhdar
Lefranc
Landelle
Lassaletta
Limnios
List
Lombardo
Madder
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
49
LIST OF PARTICIPANTS
First name
Last name
Email
Rainer
Damien
Biplab
Andrei V.
Renata
Angela
Paolo
David
Albert
Faisal
Ndiak
Sylvain
Jean-Luc
David
Morgane
Petri
Jean-Marc
Stanimir
Svetana
Vasile
Leonard J.
Wilfried
Efraím
Fabien
Andrea-Nekane
Fedor
Christèle
Maria del Mar
Gábor
Loic
Momar
Claudio
Guillem
Dmitry
Jan H.
Savvas P.
Rita M.
Jacques
José Luis
Arnaud
Martin J.
Zoe
Andris
Mahrwald
Mailhol
Maji
Malkov
Marcia de Figueiredo
Marinetti
Melchiorre
Monge
Moyano
Nawaz
Ndiaye
Oudeyer
Parrain
Pierrot
Pigeaux
Pihko
Pons
Popovic
Postikova
Parvulescu
Prins
Raimondi
Reyes
Rodier
Roig Alba
Romanov
Roux
Sanchez Duque
Speier
Tomas
Toure
Trombini
Valero
Valyaev
van Maarseveen
Vasileiadis
Ventura
Viala
Vicario
Voituriez
Wanner
Ziaka
Zicmanis
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
50
NOTES
51
NOTES
52
NOTES
53

COST Action on Organocatalysis CM0905 Aix

Transcription

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