Why
do you think your paper is highly cited?
Since around the turn of the millennium, the research
area of organocatalysis has grown with a breathtaking speed.
Among the various sub-domains, organocatalytic
multi-component domino reactions are at the forefront of
this new development in synthetic chemistry. These days one
can feel the great excitement among young chemists around
the world to enter the field and to make their own
contributions.
Does
it describe a new discovery, methodology, or synthesis of
knowledge?
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“Our research group has made contributions in
the field of asymmetric synthesis since the pioneering times of
the mid seventies, employing mainly stoichiometric methods.” |
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Catalytic asymmetric multi-component domino reactions
have recently been envisaged to construct complex molecules
from simple precursors in a single reaction cascade. Last
year the time was ripe to develop a first crossed
carbon-carbon bond forming organocatalytic triple cascade,
in which three consecutive C-C bonds are formed and four
stereogenic centres are created with virtually complete
asymmetric induction.
The protocol is simple; it leads to enantiopure
polyfunctional carbon frameworks based on a single, easily
available amine organocatalyst, and has the potential for
combinatorial approaches to produce large product libraries.
What will be possible in the future is indicated in
Figure 1,
where we combined the triple cascade with an intramolecular
Diels-Alder reaction creating five C-C bonds and eight
stereocentres in one pot.
Could
you summarize the significance of your paper in layman’s terms?
Organic synthesis of complex molecules is a difficult job
and one accompanied by many purification steps of
intermediates—the introduction and removal of protecting
groups, the change of oxidation states, as well as the
difficulty in producing a single mirror-image molecule of
the target.
By employing a single catalyst derived from the natural
amino acid proline complex, molecules can now be prepared in
a triple cascade reaction in one stroke and leading to pure
mirror-image molecules.
How
did you become involved in this research, and were there any
particular problems encountered along the way?
Our research group has made contributions in the field of
asymmetric synthesis since the pioneering times of the
mid-1970s, employing mainly stoichiometric methods. Later,
besides asymmetric transition metal catalysis, we became
involved in enantioselective reactions catalyzed by
N-heterocyclic nucleophilic carbenes (NHCs), another rapidly
developing area of what is now called organocatalysis. The
NHC-catalysis was already biomimetic, as Mother Nature uses
this principle in form of the so-called "active aldehyde" to
carry out nucleophilic acylations.
In the meantime, powerful organocatalytic protocols had
been developed, including those of our group, and we became
interested in mimicking Nature’s enzymatic cascades.
Standing on the shoulders of many others, the secret of
success for the triple cascade was to create a stimulating
innovative atmosphere in our research group and to be lucky
enough to cooperate with superb Ph.D. students of the
caliber of Christoph Grondal and Matthias Hüttl.
Are
there any social or political implications for your research?
Organocatalysis in general and especially multi-component
domino reactions are environ-mentally benign and "green"
techniques that will certainly be used in the near future
for the efficient and stereoselective synthesis of complex
biologically active compounds, even in industrial processes.
Dieter Enders
Professor of Organic Chemistry
Institute of Organic Chemistry
RWTH Aachen University
Aachen, Germany
