The research in the Department of Organometallic Chemistry is focused on the development and understanding of organometallic reagents and catalysts, as well as on their application to the synthesis of structurally complex targets of biological significance. Particular attention is paid to the development and validation of catalytic methods for C-C-bond formation. Long term projects of current interest concern alkene and alkyne metathesis, the development and use of pi-acids (platinum, gold etc.), iron catalysis and cross coupling in general.
Moreover, the group is engaged in the development of novel donor ligands, including carbenes and compounds containing formally "zerovalent" carbon atoms. All methods are scrutinized by applications to the total synthesis and "diverted total synthesis" of natural products and pharmaceutically active compounds.
since 2013 Member of the Editorial Board "Comptes Rendus Chimie"
since 2012 Member of the International Advisory Board of "ChemPlusChem"
since 2010 Member of the Editorial Board „Angewandte Chemie" and of the Advisory Board
"Israel Journal of Chemistry"
since 2009 Member of the Advisory Board "ChemCatChem"
2009-2013 Member of the Advisory Board "Synthesis" and "Synlett"
since 2007 Member of the Advisory Board "Nachrichten aus der Chemie"
since 2006 Member of the Advisory Boards "ChemMedChem"
since 2005 Member of the Editorial Advisory Board "Progress in Heterocylic Chemistry"
2002-2004 Member of the Editorial Advisory Board "Journal of Organic Chemistry“
since 2000 Member of the Advisory Board "Advanced Synthesis & Catalysis"
since 1997 Member of the Editorial Board "Topics in Organometallic Chemistry"
2014 Siegfried-Hünig Lecture (Germany)
2013 Elhuyar-Goldschmidt Lecture (Spain)
2012 First Novartis Eastern Europe Lectureship (Russia, Poland)
2012 Durham University Musgrave Lecture (United Kingdom)
2011 Lilly European Distinguished Lectureship (Greece)
2009 Astellas Lecture (Japan)
2008 Sir Robert Robinson Distinguished Lecture (United Kingdom)
2008 Westschweizer Graduierten Kolleg (3ème Cycle) (Switzerland)
2008 Andrew Derome Lecture (United Kingdom)
2007 Eli Lilly Lecture (USA)
2007 Roessler Lecture Series (USA)
2007 Pfizer Michigan Tour (USA)
2005 Abbott Process Chemistry Lecture (USA)
2005 Bristol-Myers Squibb Lecture (USA)
2004 Merck Frosst Lecture (Canada)
2004 Wyeth Lecture (USA)
2004 Merck Lecture (United Kingdom)
2004 Centenary Lecture der Royal Society of Chemistry (United Kingdom)
2003 Bristol-Myers Squibb Lecture (USA)
2002 Novartis Central Europe Lectureship (Czech Republik, Slovakia, Hungary)
2001 Victor Grignard - Georg Wittig Lecture (France)
2000 Holm Lecture (Denmark)
1999 Bürgenstock (Schweiz)
1999 Organic Reactions Lectureship (USA)
1999 Merck-Frosst Lecture (Canada)
1999 16th H. C. Brown Lecturer (Canada)
1999 Smith-Kline Lecture (USA)
1997 Novartis Lectureship (Switzerland)
1997 Nozaki Lecture (Japan)
Whereas alkene metathesis is a striking success in the catalytic arena and was rapidly embraced by the synthetic community, the related metathesis of alkynes is much less commonly used. However, the reaction has several assets: it benefits from a surprisingly strong driving force and is mechanistically well understood; alkyne metathesis is unambiguous in its stereochemical consequences when combined with controlled semi-reduction; alkynes are amenable to a large variety of post-metathesis transformations, most notably by activation with carbophilic Lewis acid catalysts.
Our group is committed to demonstrate the remarkable performance of this transformation in synthesis. To this end, we are engaged in the development of new alkyne metathesis catalysts and in understanding their mode of action. The latest generation of catalysts described by our group is molybdenum-nitrides and molybdenum-alkylidynes endowed with silanolate ligands. These complexes combine a previously unknown level of reactivity with an exquisite functional group tolerance. At the same time, they can easily be rendered air stable, which makes them highly practical and user-friendly.
In parallel work, our group is constantly probing and expanding the preparative scope of alkyne metathesis by applications to structurally complex and biologically relevant target molecules. The projects encompass prostaglandins, peptides, alkaloids, macrolide antibiotics and various anti-cancer agents. Prominent examples in the past were epothilone, the latrunculins, cruentaren A, amphidinolide V, the ecklonialactones, and lactimidomycin.
The keen interest in alkene metathesis dates back to the outset of Prof. Fürstner's independent career in the early 1990s. Our initial work showed the outstanding performance of the then brand new molybdenum and ruthenium alkylidene complexes developed by Schrock and Grubbs, respectively, for the preparation of medium-sized and macrocyclic rings. Rules were spelled out how to implement ring closing metathesis into retrosynthetic planning and examples were given, which demonstrated the complementary logic of this transformation.
Subsequent work aimed at the development of readily accessible and even more efficient catalysts (ruthenium allenylidenes and -indenylidenes, “second generation” ruthenium carbenes endowed with NHC ligands etc.), some of which are now commercially available. A rapid parallel assay was established to test the performance of new catalysts by IR thermography. Moreover, the first examples of metathesis reactions in supercritical carbon dioxide were reported, which showed the advantages of this particular medium in the formation of macrocyclic fragrance ingredients as well as in ROMP polymerizations.
Significant efforts are made to demonstrate the strategic advantages of alkene metathesis for advanced organic synthesis. Starting from early work on macrocyclic musk, the group has gone on to the total synthesis of highly complex polyketides, alkaloids, terpenes, and glycolipids.
Catalysis based on the activation of p-systems with the aid of carbophilic Lewis acids such as Pt(2+) and Au(1+) has gained considerable momentum. Except for a few pioneering studies, this field was virtually inexistent until the late 1990’s but is currently one of the most rapidly growing areas of homogeneous catalysis.
As early as 1998, the Fürstner group proposed a unifying mechanism, which guided our investigations during the following years. This hypothesis-driven approach led to the discovery of several new reactions, which were successfully scrutinized by several natural product total syntheses. Moreover, we are dedicated to the characterization of pertinent reactive intermediates to refine the mechanistic understanding for gold and platinum catalysis. Likewise, the development of practical asymmetric variants is actively pursued.
We are interested in the development of catalysts based on cheap, non-toxic, benign and readily available transition metals as substitutes for traditional noble metal complexes. Although not limited to, iron catalysis is prominently featured in this context.
Particular attention is paid to the development of iron catalysts for cross coupling, cycloisomerization reactions, cycloadditions of unactivated substrates, and carbometalations of π-bonds. Considerable efforts are made to identify, isolate and characterize short-lived and, in part, highly reactive organoiron intermediates to gain a better understanding for the largely unknown mechanisms of such iron-catalyzed C-C bond-forming reactions. Applications of the new methods to the preparation of relevant target molecules complement our portfolio.
Various lines of research are pursued by which we intend to establish new principles for catalysis and to develop conceptually novel ligand architectures.
We are striving to replace notoriously stoichiometric reactions of proven versatility by catalytic processes. Successful examples are the first Nozaki-Hiyama-Kishi (NHK) reactions catalytic in chromium as well as carbonyl coupling reactions catalytic in titanium. The latter opened a new entry into indoles and various other types of aromatic heterocycles.
Our group has introduced the “9-methoxy-9-BBN variant” of the Suzuki reaction as a highly versatile and base-free procedure for cross coupling. Moreover, an improved method for Stille-Migita reactions was recently described, which is applicable to polyfunctionalized and sensitive substrates.
Download Diverse Methods
Whereas the σ-donor qualities of N-heterocyclic carbenes (NHC's) are undisputed and extensively used in homogeneous catalysis, the π-acceptor properties of such ligands are often considered negligible. However, recent studies from this laboratory showed that the acceptor properties of NHCs can be up-regulated to the extent that they start dictating the observed reactivity. Therefore the general perception of this important class of ligands may need to be revised. Moreover, we proposed several alternative design principles for stable singlet carbenes, including amino-ylide carbenes (AYC’s), carbenes stabilized by lateral enamines, and push-pull carbene structures.
Coordination Chemistry at Carbon:
Organic molecules are commonly understood as substances based on carbon atoms which involve all four valence electrons in bonding. If two electrons form a lone-pair, one crosses the traditional borders to coordination chemistry and/or enters the realm of reactive intermediates. Compounds, wherein a carbon atom configures all four valence electrons in form of two lone-pairs may seem elusive at first sight. Following insightful early reports and recent computational studies, however, our group is investigating the preparation and reactivity of compounds, in which carbon serves as the central atom of a complex. The description of certain carbogenic materials as coordination compounds differs fundamentally from the common understanding of organic chemistry.
A significant part of our work is dedicated to the application of organometallic catalysis to the total synthesis of structurally complex natural products of biological significance; where indicated, we are also committed to prepare analogues by “diverted total synthesis” for further evaluation.
From the chemical viewpoint, all projects intend to scrutinize the synthetic methods of interest to our group. We wish to develop syntheses that are concise, convergent, productive and scalable; ideally, they should be largely catalysis-based and require a minimum of protecting group manipulations. With regard to the targets, our choice is based on considerations of structural complexity, biological activity, and non-availability of meaningful amounts from the natural sources. Biological assessments of the compounds prepared in the laboratory are carried out in close collaboration with external partners.
Dec 09 – Apr 13 PhD Student
Arto Suárez, Tamara
Sep 2013 – Dec 2013 Visiting PhD Student
Feb 08 – May 11 PhD Student
May 11 – June 14 PhD Student
Dr. Casitas Montero, Alicia
Dr. Chaładaj, Wojciech
Mar 11 – Mar 12 Post-doc
Dr. Corbet, Matthieu
Dec 09 – Apr 11 Post-doc
Dao, Quang Minh
Dr. de Haro García, Teresa
Jun 12 – Nov 13 Post-doc
Dr. Flasz, Jakub
Dr. Fuchs, Michael
Dr. Fukuda, Tsutomu
Jul 12 – Jul 13 Visiting Scientific Co-worker
Prof. Dr. Fürstner, Alois
Jan 09 – Dec 11 PhD Student
Jul 12 – Sep 12 Visiting PhD Student
Dr. Handa, Shinya
Apr 10 – Oct 11 Post-doc
Aug 09 – Nov 12 PhD Student
Dr. Jouvin, Kévin
Sep 12 – Feb 14 Post-doc
Dr. Kausch-Busies, Nina
Jan 11 – Jan 12 Scientific Co-worker
Dr. Kondoh, Azusa
Apr 10 – Mar 12 Post-doc
Dr. Lackner, Aaron
Sep 99 – Sep 14 Permanent Staff
Oct 10 – Dec 13 PhD Student
Dr. Lhermet, Rudy
Jun 12 – May 14 Post-doc
Dr. Llaveria Cros, Josep
Oct 11 – Feb 14 Post-doc
Dr. Müller, Marc-André
Dr. Mailhol, Damien
Dr. Mantilli, Luca
Nov 11 – Apr 13 Post-doc
Martín Lasanta, Ana
Sep 11 – Dec 11; Dec 12 – Feb 13 Visiting PhD Student
Dr. Miao, Xiaowei
Dec 10 – Nov 11 Post-doc
Dr. Micoine, Kevin
Nov 09 – Sep 11 Post-doc
Aug 12 – Oct 12 Visiting PhD Student
Oct 10 – Dec 13 PhD Student
Jun 13 – Nov 13 Visiting PhD Student
Dr. Regens, Christopher S.
May 09 – Jul 11 Post-doc
Dr. Roşca, Dragoş-Adrian
Nov 12 – Feb 13 PhD Student
Jan 09 – Aug 11 Permanent Staff
Apr 65 – Feb 69; Oct 72 – Feb 14 Permanent Staff
Sep 08 – Aug 11 PhD Student
Dr. Sun, Chang-Liang
Oct 11 – Oct 14 Post-doc
Dr. Sundararaju, Basker
Oct 11 – Sep 13 Post-doc
Jun 13 – Sep 13 Visiting PhD Student
Dr. Takagi, Akira
Apr 13 – Jul 14 Post-doc
Nov 08 – Dec 11 PhD Student
Oct 11 – Dec 11 Visiting PhD Student
Dr. Valot, Gaëlle
Oct 11 – Mar 14 Post-doc
Dr. Weber, Dieter
Jul 12 – Jun 14 Scientific Co-worker
Dr. Webster, Matthew
Jan 10 – May 11 Post-doc
Dr. Werlé, Christophe
Dr. Yada, Akira
Apr 10 – Jun 11 Post-doc