Department of Organic and Nuclear Chemistry
Faculty of Science
Outline of the current research and future projects
Our group is currently engaged in several projects that encompass different areas of
organic chemistry involving transition metal compound catalysis such
(C-C bond activation, [2+2+2]cyclotrimerizations, cross-metathesis),
Lewis base organocatalysis, synthesis of natural compounds (estrone)
and biologically active substances (ligands for estrogenic receptors),
ferrocene and carborane chemistry.
(For the full account, see the list of papers section.)
1. Development of New Transition Metal-Catalyzed Reactions
Carbon-carbon bond forming and cleavage reactions are essential operations for organic synthesis.
In view of the aforementioned it is of a general interest to develop new procedures for catalytic
cleavage of the C-C bonds under mild reaction conditions by using inexpensive transition metal
compounds, e.g. Fe, Ni, and Co. In this regard we have developed an iron-complex catalyzed
alkylative cyclization of 2-chlorodienes to alkyl(methylidene)cycloalkanes in the presence
of trialkylaluminums. Outcome of these early studies was also the discovery of a new C-C bond
cleavage reaction: Ni-catalyzed deallylation of diallylmalonates and related compounds.
This reaction could also be carried with compounds where the allylic moiety is a part of a
cyclic system. In this instance cleavage of unstarined 5- and 6-membered rings could be
easily achieved. In addition we found that the course of the reaction the C-C cleavage or
formation can be controlled by Ni/organoaluminum ratio. We have recently also utilized the
C-C bond cleavage in biphenylene compounds catalyzed by a simple [RhCl(cod)]2/dppe catalytic
system followed by the subsequent reaction with alkynes yielding selectively substituted
phenanthrene and picene derivatives.
Eur. J. Org. Chem. 2004, 1280;
J. Am. Chem. Soc. 2004, 126, 10222;
Organometallics 2006, 25, 901;
New. J. Chem.2006, 30, 671;
Org. Lett. 2008, 10, 5261.
2. Synthesis of isoprenoid compounds
The aim of this project is to develop new methods for the construction of the steroid
framework by using transition-metal based methodologies. We have developed so far two
new diastereoselective approaches for the construction of estrone intermediate with core
tetracyclic steroid skeleton. The first is based on three-fold use of Cp2ZrBu2 (Negishi reagent)
and Ru-catalyzed ring closing metathesis. The second approach is based on two zirconium reactions
(oxidative addition, cycloisomerization), followed by cobalt-mediated cyclocarbonylation
(Pauson-Khand reaction). These early studies led to the development of a new enantioselective
approach to stroid skeleton based on asymmetric conjugated addition. This methodology was used
to synthesize (-)-estrone. The zirconocene–mediated cyclization was the cucial step in the
synthesis of sesquiterpenoid derivatives bearing protoilludane, illudane and marasmane skeletons.
J. Org. Chem. 2012, 29 (review);
Eur. J. Org. Chem. 2011, 3279;
Eur. J. Org. Chem. 2010, 646;
Synlett 2009, 2445;
J. Org. Chem. 2008, 73, 6202.
3. Synthesis and Application of Lewis Base Catalysts in Organic Synthesis
This project is focused on synthesis of axially chiral N,N’-dixodes with
bipyridine framework and their application in organic synthesis. The underlying synthetic
strategy is based on [2+2+2]-cyclotrimerization of suitably substituted diynes with nitriles
catalyzed by Co-complexes that gave rise to the desired bipyridines. Subsequent oxidation and
resolution furnished the corresponding chiral N,N’-dioxides. The prepared compound 1 was
in catalytic allylation of aromatic and alfa,beta-unsaturated aldehydes to homoallyl alcohols
high enantioselectivity (up to 99% ee). The reaction mechanism of the allylation reaction as
well as the asymmetric
induction was crucially influenced by solvent effects.
The prepared chiral homoallyl alcohols were used as building blocks for the synthesis
of simple natural compounds such as goniothalamin etc. Further applications of the
enantioselective allylation reaction are currently pursued. As potential targets have
been chosen compounds such as biologically active flavonoids (e.g. liquiritigenin),
pharmaceutically active substances (e.g. Ezetimibe and Duloxetine),
and other natural compounds (papulacandine D).
Chem. Eur. J. 2011, 17, 7162–7166;
Eur. J. Org. Chem. 2010, 7040;
Chem. Eur. J. 2010, 16, 9442;
J. Am. Chem. Soc. 2010, 132, 12660;
Pure Appl. Chem. 2010, 82, 1813;
Adv. Synth. Catal. 2009, 351, 1279;
J. Am.Chem. Soc. 2008, 130, 5341;
Chem. Commun. 2009, 2314.
4. Dewar benzenes
Dewar benzenes (DB) are fascinating compounds worth of study. The substituted DBs are often
remarkably stable compounds under ambient conditions and undergo rearrangement to benzenes only
at elevated temperatures. This makes them not only attractive targets for various experimental
and theoretical physical-organic studies but also interesting candidates for application in
organic synthesis such as intermediates for synthesis polyaryl compounds and others.
Synlett 2011, 396;
J. Org. Chem. 2010, 75, 576;
Dalton Trans. 2009, 3137;
Eur. J. Org. Chem. 2008, 47.
5. Ferrocene chemistry
The aims of this project are syntheses of various compounds that bear
the ferrocene moiety. The spectrum of compound encompasses a study of
cycloadditions with sterically hindered ferrocenylalkynes resulting in compounds
that could be otherwise difficult to access such as ferrocene-substituted polyaromatic
compounds (e.g. bis(ferrocenyl)phenanthrene), synthesis of ferrocenylcarboranes, synthesis
of ferrocenestrone as the first example of steroid analogue with
integrated metallocene unit in the steroid skeleton.
Selected papers: manuscripts are in preparation.
6. Synthesis of perfluoroalkylated compounds
The aim if his project is to use cross-metathesis reation between perfluoroalkylpropenes
with various terminal alkenes to synthesize perfluroalkylated compounds. Since the presence
of fluorinated side-chains in many biologically relevant substances can modify and improve
their properties, further synthesis of other of other analogues or derivatives represents
worthy goal. This methodlogy was used for synthesis of perfluroalkylted
carboranes, brassinosteroids or estradiol derivatives.
Eur. J. Org. Chem. 2010, 6256;
J. Med. Chem. 2010,53, 6947;
Synlett 2010, 885;
J. Med. Chem. 2009, 52,
Eur. J. Org. Chem. 2008, 4493.
7. Synthesis of new ligands for estrogenic receptors
The aim of this project is to synthsize new and selective ligands for estrogenic receptors alfa
and beta. The main startegz fo achieving this purpose is moification of esrradiol skeleton,
namely in positions 17 and 15. So far we have several types of modified estradiols have been
prepared possessing various level of selective binding to the aforementioned receptors.
The corresponding ligands have been prepared by using ransition metal catalyzed methodlogies
such as [2+2+2]-cyclotrimerization, alkene-alkene cross-metathesis, etc.
J. Med. Chem. 2010, 53, 4290;
J. Med. Chem. 2010, 53, 6947.
Our research is carried out also in collaboration with several groups:
Prof. P. Kočovský (University of Glasgow, UK)
Prof. M. Hocek (IOCB, Czech Republic)
Prof. I. Valterová (IOCB, Czech Republic), etc.