.
Angewandte
Communications
DOI: 10.1002/anie.201108105
Asymmetric C–F Activation
Synthesis of the Smallest Axially Chiral Molecule by Asymmetric
Carbon–Fluorine Bond Activation**
Moritz F. Kuehnel, Tobias Schlçder, Sebastian Riedel, Belꢀn Nieto-Ortega, Francisco J. Ramꢁrez,
Juan T. Lꢂpez Navarrete, Juan Casado, and Dieter Lentz*
The homochirality of lifeꢀs building blocks has been intriguing
generations of chemists and its origin is still under consid-
fluorinated allenes and cumulenes involving mid-to-late
[
9]
transition-metal complexes. When tetrafluoroallene (1) is
added to a toluene suspension of the metallocene hydride
complex [Cp ZrHCl] (2; Cp = C H ), allenylic carbon–fluo-
[
1]
erable debate. Today, asymmetric reactions represent an
integral part of synthetic chemistry that has been honored
2
5
5
[
2]
with the Nobel Prize in 2001. Despite substantial success,
small unfunctionalized molecules generally elude enantiose-
lective preparations. Thermodynamically stable small chiral
molecules are highly sought-after targets for the experimental
rine bond cleavage under formation of [Cp ZrClF] (4) affords
2
the hydrodefluorination products trifluoroallene (3) and
difluoroallene (5a,b, Scheme 1). Although 3 and 5a have
[
10]
been known for almost 40 years,
their chemistry has
[
3]
detection of molecular parity violation (PV). Herein, one of
the smallest possible C -symmetric molecules was synthesized
2
by an unprecedented asymmetric carbon–fluorine bond
activation.
The long atmospheric persistence of halofluorocarbons
and its consequences in terms of ozone depletion and global
[
4]
warming are contrasted by the benefits of organofluorine
chemistry in controlling the lipophilicity and metabolic
[5]
stability of pharmaceuticals and agrochemicals.
As
a result, both the selective construction and deconstruction
of carbon–fluorine bonds are of great interest to medicinal
Scheme 1. Hydrodefluorination of tetrafluoroallene (1). Top: Synthesis
of trifluoroallene (3); bottom: synthesis of 1,3-difluoroallene (5a) and
[6]
and environmental chemistry. Fluorine forms the strongest
known s-bond to carbon; its cleavage under mild conditions is
challenging but has been achieved by designing suitable
1,1-difluoroallene (5b).
[7]
reagents and catalysts.
It has been established, that Group 4 hydride complexes
remained largely unexplored because of the limited synthetic
access based on low-yield multi-step preparations starting
from the now banned halofluorocarbons CF Br and CHFBr ,
[8]
are highly reactive towards vinylic carbon–fluorine bonds.
We have previously studied the organometallic chemistry of
2
2
2
respectively. Depending on the stoichiometry, our new
approach allowed for the isolation and characterization of 3
and 5a in reasonable yield. In 5a, the chemically equivalent
yet magnetically inequivalent fluorine and hydrogen nuclei
[
*] Dr. M. F. Kuehnel, Prof. Dr. D. Lentz
Freie Universitꢀt Berlin, Institut fꢁr Chemie und Biochemie
Fabeckstrasse 34–36, 14195 Berlin (Germany)
E-mail: dieter.lentz@fu-berlin.de
1
9
give rise to an AA’XX’ spin system (Figure 1). The F NMR
spectrum was analyzed by a simulation and subsequent least-
squares refinement; the resulting coupling constants agree
T. Schlçder, Dr. S. Riedel
Institut fꢁr Anorganische und Analytische Chemie
Albert-Ludwigs Universitꢀt Freiburg
[11]
with calculated literature values.
Albertstrasse 21, 79104 Freiburg i. Br. (Germany)
Single-crystalline samples of 3 and 5a suitable for X-ray
structure determination were obtained in situ by maintaining
sealed glass capillaries slightly below the melting points of the
B. Nieto-Ortega, Prof. Dr. F. J. Ramꢂrez,
Prof. Dr. J. T. Lꢃpez Navarrete, Prof. Dr. J. Casado
Department of Physical Chemistry, University of Mꢄlaga
Campus de Teatinos s/n, 29071 Mꢄlaga (Spain)
[
12]
compounds (125 and 166 K, respectively). Surprisingly, the
carbon backbones of 3 and 5a deviate by 4.4(3)8 and 4.6(2)8
from the linearity that would be expected based on their sp-
hybridized central carbon atoms (Figure 2). Furthermore, the
two terminal F-C-H planes in 5a have a torsion angle of
[
**] D.L. and M.F.K. thank the Deutsche Forschungsgemeinschaft
(
DFG) for financial support within the graduate school program
GRK 1582/1 “Fluor als Schlꢁsselelement”. M.F.K. in grateful to the
AG Fluorchemie at GDCh for a conference scholarship. S.R. thanks
the Fonds der Chemischen Industrie and the DFG for financial
support. S.R. and T.S. thank the BWGrid for providing computa-
tional resources. This work was supported by the Ministerio de
Ciencia e Innovaciꢃn (MICINN) of Spain (project CTQ2009-10098)
and by the Junta de Andalucꢂa (project PO9-4708). B.N.-O. thanks
MICINN for a personal doctoral grant (FPU-AP2009-2797).
9
1.9(2)8. The previously reported structures derived from
microwave spectroscopy do not show the same distortions
Supporting Information, Table S2), because erroneously, the
(
[13]
refinement was based on a constrained linear geometry. To
exclude the influence of packing effects on the observed
distortions, we performed theoretical calculations at the
coupled-cluster level of theory. The optimized structures of
2
218
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 2218 –2220