Memorandum of Understanding
For the implementation of a European Concerted Research Action
Designated as COST Action D24
"Sustainable Chemical Processes:
Stereoselective Transition Metal-Catalysed Reactions”
The Signatories to this Memorandum of Understanding, declaring their common
intention to participate in the Concerted Action referred to above and described in the
Technical Annex to the Memorandum, have reached the following understanding:
1.
The Action will be carried out in accordance with the provisions of document
COST 400/94 "Rules and Procedures for Implementing COST Actions", the
contents of which are fully known to the Signatories.
2.
The main objective of the Action is to develop new transition metal-catalyzed
reactions with special emphasis on stereoselectivity to strengthen their
application in chemical, biotechnological, pharmacological and environmental
sciences.
3.
The overall cost of the activities carried out under the Action has been estimated,
on the basis of information available during the planning of the Action, at Euro
100 million at 1999 prices.
4.
The Memorandum of Understanding will take effect on being signed by at least
five Signatories.
5.
The Memorandum of Understanding will remain in force for a period of 5 years,
unless the duration of the Action is modified according to the provisions of
Chapter 6 of the document referred to in Point 1 above.
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TECHNICAL ANNEX - ACTION D24
“Sustainable Chemical Processes:
Stereoselective Transition Metal-Catalysed Reactions.”
A. GENERAL BACKGROUND
A1: Why a COST Action on this topic
The subject of stereoselective transition metal catalysis constitutes a broad
interdisciplinary research field, representing an intellectually attractive and
experimentally demanding frontier in modern chemical synthesis. Its scope is
enormous, ranging from chemical synthesis and catalysis to environmental sciences.
As far as sustainable processes are concerned there will certainly be a general trend to
develop catalytic reactions in all fields of organic synthesis and it should be
emphasized that these reactions will be of particularly high value from the ecological
point of view, because they generate a smaller amount of toxic waste products.
Catalytic processes also offer considerable economical benefits, since they often rely
on cheap starting materials, e.g. hydrogen or isopropanol for reductions, oxygen for
oxidations.
Transition metals compares very favorably as catalysts due to their non-toxicity,
stability to various reaction conditions and ease of preparation and handling.
Furthermore, the reactivity and selectivity of the metal catalyst can easily be tuned
and refined by complexation to a organic ligand which makes it possible to design
catalysts for a specific purpose.
Central to these investigations is the need to synthesize with atom economy and in an
elegant manner complex molecules via selective and efficient methods. The high
efficiency is required in view of the quest for organic transformations that make
economic use of feedstocks, energy and produce less waste.
The key importance of the interdisciplinary field centred on the development of
stereoselective reactions has been previously recognised within COST Action D2
(Selective Synthesis 1992-1997), and subsequently within COST Action D12
(Organic Transformations: selective processes and Asymmetric Catalysis), with
participation of many working groups. There are presently about 100 laboratories
from 21 countries organised in 20 working groups within the COST D12 programme
which carry out research on various aspects of stereoselective synthesis. In light of the
fact that this very successful action will be terminated in 2002, this justifies the
launch of a new COST action on “Stereoselective transition metal catalysed
reactions”, with the objective to co-ordinate future efforts by the participating groups
and, possibly, new research teams working in this area on topics of timely and
relevant interest.
Finally, there is a large interest from the pharmaceutical and fine-chemical industry to
collaborate with academia on the development of new catalytic processes. This is
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evident from the COST D12 program where several working groups have established
fruitful collaborations with companys such as; CIBA, Novartis, AstraZeneca,
Pharmacia Inc., and Degussa. A new COST action in the field of selective catalytic
reactions would certainly further strengthen and expand the scope of these
collaborations.
A2: Status of the research in the field
The field of stereoselective catalysis is at a favourable stage of development. An
increasing number of the basic types of metal catalysts have been developed, together
with an overall better understanding of the reaction mechanisms. Several key
intermediates for essential processes of metal catalysts have been structurally
characterised. These are often complex molecules, and the increased knowledge of
structural details brings an obvious advancement in the assessment of mechanistic
details of catalyst function, since these can be approached at the molecular level.
Thus, research can now focus more intensely on learning how function relates to
structure.
The significance of the stereoselective reactions performed by transitions metals is
very broad and not limited to the field of organic chemistry. It has a strong impact on
the medical sciences (e.g. development and production of new medicines),
pharmacological sciences (e.g. enzyme inhibition, protein receptors, metal toxicity),
and environmental sciences (development of new sustainable processes).
A3: Relationship with other European Programmes
Several conference series, both on a world wide international scale, with visible
European participation, and on a European level have been set up since the early 80's
to encourage scientific exchange in the field of metastereoselective reactions and
specifically on metal catalysis and asymmetric catalysis. These are:
(i) Biannual "International Symposium on Homogeneous Catalysis (ISHC)"
(ii) Biannual "International Conference on Organometallic Chemistry (ICOMC)",
(iii) Biannual "IUPAC International Symposium on Organo-Metallic Chemistry
directed towards Organic Synthesis (OMCOS)"
(iv) "European Research Conferences (EURESCO)", held in different places, among
others in Albufeira, Portugal (1994), San Miniato, Italy (1995), Tomar,
Portugal (1997 and 1999);
(v) Various other national or bi- and trilateral conferences on this theme.
We also expect collaborations with industry via organisations such as NICE
(Network for Industrial Catalysis in Europe) and CEFIC (the European Chemical
Industry Council).
B. OBJECTIVES OF THE ACTION AND SCIENTIFIC CONTENT
B1: Main objective
The main objective of the Action is to develop new transition metal-catalyzed
reactions with special emphasis on stereoselectivity to strengthen their application in
chemical, biotechnological, pharmacological and environmental sciences. This
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objective will be pursued by discovering new catalysts providing high activity and
enantioselectivity for a number of organic transformations, paying special attention to
the recovery of the catalyst.
This COST Action will co-ordinate new joint research efforts and strengthen existing
ones in the interdisciplinary field dealing with stereoselective transition metal
catalysed reactions. Promotion of more intensive scientific exchange between
individual groups, particularly those with complementary expertise, will be beneficial
for European research and lead to a stronger impact of this research in a rapidly
growing field. It is expected that the proposed Action will be attractive also for
industrial research groups interested in asymmetric catalysis.
While the detailed scientific programme will depend on the projects submitted, there
is a will to encourage participation in certain priority areas, which appear to be of
particular importance for the progress of the field. These priority areas are outlined in
the following sub-topics, which report proposed research activities, by a number of
potential participants to this Action (listed in the Annex).
As a consequence of this action we expect a substantial improvement of the
understanding of stereoselective catalysis as well as the discovery of new catalytic
processes.
B2: Sub-Topics
(a) Development of new efficient catalytic systems
Efficient catalysts for asymmetric synthesis must combine high activity with high
selectivity. This is particularly important in industrial applications where a high
catalyst to substrate ratio is crucial. One aim of this action will be to enhance the
available methods for production of organic molecules on a large scale and
development of methods that are amenable to scale up for industrial processes. Here,
special attention will be focussed on development of stable catalysts possessing high
turn over frequencies (TOF) and turn over number (TON). Example of reactions to be
studied involves aerobic oxidation processes and transfer-hydrogenation reactions,
both of which would be particularly advantageous from an ecological/economical
point of view.
(b) Asymmetric catalysis
Asymmetric catalysis is a key area to be explored due to its remarkable potential for
the production of compounds as single enantiomers. This is particularly important in
the case of bioactive compounds for pharmaceutical application since often only one
of the two enantiomers is the active component. Many compounds are also required in
enantiomerically pure form to function as catalysts, chiral reagents, or templates.
While there has been considerable progress in these areas in recent years there
remains much to be achieved and further development is therefore imperative.
(c) Structural, mechanistic and computational studies of transition metal
catalysts
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To achieve the above-mentioned goals, a detailed knowledge of the factors which
control the reactivity of transition metal-catalyzed organic transformations is of great
importance. A key feature is to develop an understanding of the factors, both steric
and electronic, which control the interaction between the catalyst, ligand and
substrate. Combination of experimental observation with computer modeling is a
powerful method and can provide the synthetic chemists with a more detailed insight
into factors that influence stereocontrol in asymmetric catalysts. This detailed
comprehension will allow design of catalytic systems that provide a better control of
reactivity, in this case specifically the stereoselectivity of the catalytic system.
Similarly, the search for catalytic systems of wide scope and general utility and
design of readily available ligands which allows for easy structural modifications are
other important challenges to be tackled.
(d) Development and application of new chiral ligands
A catalyst is normally made up by two components, a transition metal and a organic
ligand. Development of new systems requires considerable knowledge about the role
of both these components and this goal is best accomplished by joining the expertise
of different groups in a synergistic way. In addition, chiral ligands are often difficult
to prepare and the action would allow several groups to benefit from exchanging
ligands and then evaluate them in various metal-catalyzed reactions.
(e) Implementations of new technology
Furthermore, this action would also involve the implementation of new techniques in
the search and screening of candidate catalysts. Parallell synthesis and high
throughput screening should be used on a routine basis.
C. ORGANISATION, MANAGEMENT AND RESPONSIBILITIES
C1: Organisation and Management
Research projects fitting topics mentioned above will be submitted to the
Management committee for approval. Approval will be subject to the evaluation of
their relevance for the establishment of Sustainable Chemical Processes of interest for
the European member countries. The organisational structure is shown below
Technical Committee for Chemistry
↑↓
Management Committee
↔
Secretariat
↑↓
Project 1
Project 2
Project 3
Project 4
C2: Responsibilities
The management committee has responsibilities for:
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Project 5
etc.
1. Drawing up the inventory during the first year, organisation of workshops and start
of the activity; existing contacts will be used which should greatly facilitate this task.
2. Co-ordination of the joint activities with other COST Actions, CEFIC Sustech
Clusters; joint meetings are likely to result from this activity;
3. Explore the possibilities for wider participation and exchange of information with
EU-specific programmes, ESF, EUREKA, etc;
4. Planning the intermediate report, the final report and the concluding symposium.
Progress reports will also be provided by each respective participant in the projects in
their own countries within the framework of existing programmes.
C3: Evaluation of Progress
The progress of the programme will be monitored by means of brief annual reports
from each of the participating scientists. These will describe the results of research
obtained through concerted action. The Management Committee will prepare a
milestone report after 2 years of joint activities. The report will be presented to the
COST Technical Committee for Chemistry for their review and to the COST Senior
Officials Committee for information. A final report will be published to inform nonparticipating scientists and research workers interested in the results about the
scientific achievements of the Action. It is expected that some review by participants,
which describe the progress, made and state of the field, will be published in
International Journals. To conclude the COST Action, a symposium will be held after
5 years. It will be accessible to other scientists and potential users of industry.
D. TIME-TABLE
The programme will cover five years and consist of the following stages:
Stage 1:
Stage 2:
Stage 3:
Stage 4:
After the first meeting of the Management Committee a detailed inventory
of on-going research and existing plans of the participating groups to
begin joint projects will be made. This will result in a discussion
document to allow further planning.
It will be evident which projects are closely related and would benefit
from joint activities. Researchers (and co-workers) will set-up (and
continue) joint collaborative projects and exchange their recent research
results. It may be appropriate to explore wider collaboration with other
European countries during this stage.
An intermediate progress report will be prepared after two years for
review by the COST Technical Committee for Chemistry and for
information to the COST Senior Officials Committee.
This final phase will begin after four years and will involve the evaluation
of the results obtained. It may include the organisation of a symposium for
all the participants and co-workers. The final report will be submitted to
the COST Technical Committee for Chemistry for scientific assessment
and after to the COST Senior Officials Committee.
In summary the total timetable can be represented as follows:
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- Start 1st year
- Formation of projects 1st and 2nd year
- Workshop of group leaders end of 1st year and each year later on
- Overview available; start meetings; continue meetings on subtopics end of 2nd year
- Start exploration of wider participation 3rd and 4th year
- Intermediate Progress Report available for Technical Committee and CSO end 2nd year
- Start evaluation of results continuously each year after 1st year at the yearly workshop
- Concluding Symposium end of 5th year
Five years are required because of the complexity of the research focus. Especially, the design
of new catalysts and the fine-tuning of the ligands to be studied is a complicated and time
consuming process. In addition, for each problem an analytical set-up is needed to study the
stereochemical outcome (enantiomeric excess) of such processes. Therefore, different chiral
columns (GC, HPLC) have to be evaluated and conditioned for every catalysis problem.
E. DURATION OF THE ACTION
The Action will last for five years
F. ECONOMIC DIMENSION OF THE ACTION
It is to be expected that several teams of the presently running COST D12 Action as
well as some of the groups active in catalysis in other actions will apply for admission
to the new COST Action. It is estimated that a total of at least of 20 countries and 40
laboratories will eventually be involved in the Action. Based on experience in the
COST D12 programme, it is estimated that the economic dimension of the Action
(initial estimate of total costs = personnel + operational + running + Commission
costs) will be 100 M €.
The total human effort in the Action "Sustainable Chemical Processes: Stereoselective
Transition Metal-Catalysed Reactions " described above, amounts to 800 man-years
(160 researchers during 5 years), being equivalent to 80 M €.
F1. Personnel costs (research and administration) will be approximately 80 M €
(covered by participant groups).
F2. Operational and running costs
The estimate of the total operational and running costs including costs of instruments
and materials is 20 M € (covered by participant groups).
The estimate of the total economic dimension of the action is therefore 100 M €.
G. DISSEMINATION OF SCIENTIFIC RESULTS
All publications arising from research carried out under COST Action D24 will credit
COST support and the Management Committee will encourage and promote all coauthored papers. Results of research carried out by the working groups under COST
Action D24 will be submitted to international scientific journals and reviewers.
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Joint meetings among different working groups in COST Action D24 and with
working groups from other COST Actions, will be organised so as to best promote
interdisciplinary communication.
The Management Committee (MC), in conjunction with the working groups (WG) of
the Action will meet every year with the main aim of presenting results to the MC as a
whole and, where possible, the MC will invite potential users and interested parties to
this meeting.
The Management Committee will, during the first year of the Action, also set up a
work-plan for interdisciplinary events for the dissemination of results of the Action
COST D24.
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ANNEX
The current list of potential participants to the D24 Action is given below by country.
Austria
Prof. Widham Michael
Inst. of Organic Chemistry
Univ. Vienna
Währingerstrasse 38
A-1090 Vienna
Belgium
Prof. Istwan E. Markó
Department de Chimie
Université Catholique de Louvain
Place Louis Pasteur 1
B-1348 Louvain-La Neuve
Denmark
Prof. Jorgensen Karl Anker
Chemistry Department
Aarhus University
DK-8000 Aarhus C
France
Prof. Bruono Gérad
Université d'Aix-Marseille 3
Faculté des Sciences et Techniques de Saint-Jérôme
Avenue Escadrille Normandie-Niemen
F-13397 MARSEILLE Cedex 20
Germany
Prof. Schinzer Dieter
Chemical Institute
University of Magdeburg
Universitaetsplatz 2
D-39106 Magdeburg
Prof. Carsten Bolm
RWTH Aachen
Professor-Pirlet-Str. 1
D-52056 Aachen
Prof. Alois Fürstner
MPI Mülheim/Ruhr
Kaiser-Wilhelm-Platz 1
D-45470 Mülheim/Ruhr
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Prof. Hans-Joachim Knölker
Inst. of Organic Chemistry
TU Karlsruhe
Richard-Willstätter-Allee 2
D-76128 Karlsruhe
Hungary
Prof. Tungler Antal
Inst. Organi. Chem. Technology TU
Univ. Budapest
Budafoki ut 8
H-1521 Budapest
Ireland
Prof. Maguire Anita
Dept. Chemistry
University College Cork
Irl – Cork
Italy
Prof. Cainelli Gianfranco
Dip. di Chimica
Universita di Bologna
Via Selmi 2
I-40126 Bologna
Prof. Cinquini Mauro
Dipartimento di Chimica
Organica e industriale
Universita degli studi di Milano
Via Golgi 19
I-20133 Milano
Norway
Prof. Sydnes Leiv K.
Dept. of Chemistry
University of Bergen
Allégt. 41
N-5007 Bergen
Romania
Prof. Parvulescu Vasile
Faculty of Chemistry
Dept. of Chemical Technology
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and Catalysis
B-dul Republicii 13
RO-70346 Bucharest
Slovenia
Prof. Kocevar Marijan
Dept. Chemistry and chem..
Technol. Univ. Ljubljana
Askerceva 5
SLO-61000 Ljubljana
The Netherlands
Prof. Liskamp Rob
Utrecht University
Dept. Medicinal Chemistry
Sorbonnelaan 16
NL-3584 CA Utrecht
Prof. van Koten Gerard
University of Utrecht
Debye Research Institute
Padualaan 8
NL-3584 CH Utrecht
Spain
Prof. Cativiela Carlos
Depto Quimica y Quimica Fisica
Univ. Zaragoza / Fac de Cencias
Pedro Carbuna 12
E-50009 Zaragoza
Prof. Plumet Ortega Joaquim
Universidad Complutense
Dept. de Quimica organica I
Ciudad Universitaria
E-28071 Madrid
Sweden
Prof. Bäckvall Jan-Erling
Department of Organic Chemistry
Arrhenius Laboratory
Stockholm University
S-106 91 Stockholm
Prof. Andersson Pher G.
Uppsala University
Department of Organic Chemistry
Box 531
S-751 21 Uppsala
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Switzerland
Prof. Renaud Philippe
Université de Fribourg
Institut de Chimie Organique
Pérolles
Ch-1700 Fribourg
United Kingdom
Prof. Jackson Richard F. W.
Department of Chemistry
Bedson Building
The University of Newcastle upon Tyne
UK-Newcastle upon Tyne NE1 7RU
Prof. Thomas E. J.
Dept. of Chemistry
Univesity of Manchester
Oxford Road
UK-Manchester M 13 9PL
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