Unusual Fusion of α-Fluorinated Benzophenones under McMurry Reaction Conditions

Article abstract of DOI:10.1002/chem.201805290

By exposure of α-fluorinated benzophenones to McMurry reaction conditions, we have observed the remarkable formation of 9,10-diphenylanthracene derivatives. This unexpected transformation necessitates the cleavage of the exceptionally stable aromatic C?F bond under mild McMurry conditions. In this work, the condensation of several related fluorinated benzo- and acetophenones has been investigated, which allow us to propose a domino-like fusion mechanism for this unusual transformation. The scope and limitations of the fluorine-promoted benzophenone fusion are subsequently discussed.

Full text of DOI:10.1002/chem.201805290

A Journal of
Accepted Article
Title: The unusual fusion of α–fluorinated benzophenones under
McMurry reaction conditions
Authors: Vladimir Akhmetov, Mikhail Feofanov, Vitaliy Ioutsi, Frank
Hampel, and Konstantin Y Amsharov
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The unusual fusion of α–fluorinated benzophenones under
McMurry reaction conditions
Vladimir Akhmetov[a], Mikhail Feofanov[a], Vitaliy Ioutsi[b], Frank Hampel[a] and Konstantin Amsharov*[a]
Abstract: By exposing of -fluorinated benzophenones to McMurry
reaction conditions, we have observed remarkable formation of 9,10-
diphenylanthracene’s derivatives. This unexpected transformation
necessitates the cleavage of the exceptionally stable aromatic C-F
bond under mild McMurry conditions. In this work we have
investigated the condensation of several related fluorinated benzo-
and acetophenones, which allow us to propose the domino-like fusion
mechanism for this unusual transformation. The scope and limitation
of the fluorine-promoted benzophenone fusion is discussed.
the respective fluorinated benzophenone (1). McMurry reaction is
well known for its high functional group tolerance and appears as
a well-established synthetic approach to various alkenes using
carbonyl compounds as reactants.[8] The reaction is also suitable
for the preparation of highly substituted phenylethanes.[9]
Surprisingly, beside the expected product we observed the
formation
of
non-symmetrical
fluorinated
9,10-
diphenylanthracene (5). Due to the idiosyncrasy of the structure it
is virtually impossible to synthesize such a derivative via known
conventional methods.[10] Even though the obtained molecule is
interesting itself as a precursor to non-IPR fullerenes’ fragment[11]
,
it is even more important to consider this side product as a
harbinger of a great potential of the C-F bond and its exploitation
under various conditions.
Introduction
Fluoroorganic chemistry remains to be poorly investigated field
due to often misleading assumption of the bond stability and thus
its inertness. Nevertheless, there are some pioneering works in
the field showing applicability of the C-F bond for organic
synthesis[1] e.g. for Aryl-Aryl coupling.[2] Moreover, some methods
allow the synthesis of highly interesting strained polycyclic
aromatic hydrocarbons (PAHs) with a curved surface, known as
geodesic polyarenes,[3-5] which remain to be hardly available
since there are only a few synthetic approaches enabling their
preparative synthesis. [6]
Results and Discussion
The 2,6-difluoro-benzophenone (1) was chosen for the synthesis
of target diindenochrysene (4) in accordance with Scheme 1. As
a first step fluorinated benzophenone was subjected to standard
McMurry conditions. Analysis of the reactionary mixture revealed
the formation of the two diastereomers of the desired product (2)
with 50% yield and the presence of an unexpected side product,
which turned out to have a UV-vis spectrum corresponding to
anthracene’s core. The product was isolated and investigated by
means of NMR and X-ray diffraction analysis, which revealed that
the molecular structure of the isolated substance corresponds to
10-(2,6-difluorophenyl)-1-fluoro-9-phenylanthracene (5).
Scheme 1. Three step synthetic approach to (4) from commercially available
2,6-difluoro-benzophenone.
Addressing the issue we have suggested a possible pathway
enabling facile three-step synthesis of diindeno[1,2,3,4-
defg:1',2',3',4'-mnop]chrysene (4) which may serve as an
example of the important representative of geodesic
polyarenes.[7] Leaving aside the final outcome of our efforts to
synthesize (4) here we describe rather unexpected reaction
observed during the implementation of the first step
corresponding to the transformation of (1) to (2). The required
precursor (2) can be obtained by standard McMurry coupling of
Figure 1. The implementation of the first step of the synthesis. The
benzophenone molecules participating in the fusion are highlighted by different
colors. (inset) ORTEP plot of (5) in the crystal. Thermal ellipsoids are drawn at
the 50% probability level (only one orientation of 5 in the crystal is shown for
clarity).
The yield of anthracene (5) was found to be 35%. Among
major (2) and (5) only trace amounts of several unidentified
byproducts were detected according HPLC analysis. In order to
investigate whether this reaction is applicable for different related
substrates a set of reactions with various α-fluorinated aceto- and
benzophenone derivatives were carried out (Scheme 2). As a
matter of fact, only in case of -fluorinated benzophenone the
[a]
[b]
Friedrich-Alexander University Erlangen-Nuernberg,
Department of Chemistry and Pharmacy, Organic Chemistry II
Nikolaus-Fiebiger Str. 10, 91058 Erlangen, Germany
E-mail: konstantin.amsharov@fau.de
Endocrinology Research Centre, 117036 Moscow, Dmitriya
Ul’yanova str. 11
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10.1002/chem.201805290
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formation of 9,10-diphenylanthracene core (7) was observed
along the formation of the expected tetraphenylethane (6).
However, exposing 2,2’-difluorobenzophenone to the reactionary
conditions has led to the isolation of (8) as a single major product
with the moderate yields.
attack activated π-system of the fluoroarene leading to the
aromatic nucleophilic substitution of fluoride. The substitution is
facilitated by the presence of the electron withdrawing groups.
The next step according to our experimental observation most
probably includes electrophilic aromatic substitution, since the
presence of the electron-withdrawing groups in the attacked
phenyl ring tends to prevent the further formation of the
anthracene’s cores as it was observed in cases of (9), (11) and
(13). This step can be induced by polarization of carbonyl group
by Lewis acids such as Ti3+ and Zn2+ containing species. Another
strong evidence for the cationic nature of the last step is the
formation of (7) without the second possible isomer containing
fluorine atom within anthracene fragment, which was confirmed
by means of X-Ray diffraction analysis (see SI).
Scheme 2. Transformations of various -fluorinated phenylcarbonyl
compounds under McMurry reaction conditions.
Scheme 3. Suggested mechanism of the transformation of 2,6-difluoro-
benzophenone under McMurry reaction conditions.
In the case of 2-fluoroacetophenone and 2-fluorobezaldehyde no
anthracene formation was detected and only expected McMurry
products were isolated. Two isomers of (10) and only E-isomer
(12) respectively. Additionally, we attempted to investigate
whether perfluoro aromatic compounds show the formation of the
corresponding anthracene derivatives. For this purpose we
Considering the proposed mechanism it is reasonable to
assume that the yields and selectivity of the reaction might be
increased via introduction of additional electron-withdrawing
groups to the fluorinated rings of benzophenone and electron
donating groups to opposite one, thus facilitating both steps, initial
nucleophilic attack of C-F bond and consequent electrophilic
substitution.
In order to estimate and compare kinetic barriers of the
nucleophilic attacks by carbonyl anion leading to either McMurry
products or anthracene based compounds we carried out model
DFT calculations on PBE/TZ2p level. In the model the titanium
particle was replaced with a hydrogen atom for simplicity
reason.[12]
subjected
2,3,4,5,6-tetrafluorobezophenone
to
McMurry
conditions and obtained a complicated mixture which did not
contain any major product that could be isolated. Moreover, we
did not observe any products that would have UV-vis spectrum
corresponding to an anthracene derivative. This evidence shows
that the activation of C-F bonds in such case is not selective and
leads to a huge number of possible reaction pathways.
Due to heterogeneous nature of the McMurry reaction the
investigation of the reaction mechanism appears to be difficult.
However, on the basis of the common knowledge the following
mechanism can be proposed (Scheme 3). As a first step a set of
single-electron transfers from reduced titanium particles to the
carbonyl group of the reactant takes place. Generated anion then
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Acknowledgments
The authors thank the Deutsche Forschungsgemeinschaft (DFG-
SFB 953 “Synthetic Carbon Allotropes” - Projects A6, AM-407).
We also thank Olga Mazaleva for the help wih carrying out DFT
calculations.
Keywords: McMurry reaction • Anthracene • C-F chemistry
[1] a) S. Duttwyler, C. Douvris, N.L.P. Fackler, F.S. Tham, C. Reed, K.K.
Baldridge, J.S. Siegel, Angew. Chem. Int. Ed., 2010, 49, 7519 –7522; b)
T. Fujita, M. Takazawa, K. Sugiyama, N. Suzuki, J. Ichikawa, Org. Lett.,
2017, 19(3), 588–591; c) T. Fujita, K. Fuchibe, J. Ichikawa, Angew. Chem.
Int. Ed., 10.1002/anie.201805292.
[2] a) A.-K. Steiner, K.Y. Amsharov, Angew. Chem. Int. Ed., 2017, 56, 14732
–14736; b) A.K. Dutta, A. Linden, L. Zoppi, K.K. Baldridge, J.S. Siegel,
Angew. Chem. Int. Ed., 2015, 54, 10792–10796; c) O. Allemann, S.
Duttwyler, P. Romanato, K. K. Baldridge, J. S. Siegel, Science, 2011,
332, 574–577.
Figure 2. Schematic representation of the DFT data on the competition between
two nucleophilic attacks.
[3] a) K. Yu. Amsharov, M. A. Kabdulov, M. Jansen Angew. Chem. Int. Ed.,
2012, 51, 4594–4597; b) O. Papaianina, V.A. Akhmetov, A.A. Goryunkov,
F. Hampel, F.W. Heinemann, K.Y. Amsharov, Angew. Chem. Int. Ed.,
2017, 56, 4834–4838.
The obtained energies (Figure 2) are going in line with the
observed experimental data showing lower barriers for
nucleophilic attack of carbonyl group and 2-3 times higher,
although still reasonable values for the attack of fluorinated
carbon.
[4] M.A Petrukhina in Fragments of fullerenes and carbon nanotubes. (Ed.:
L.T. Scott), A John Wiley&Sons, inc., 2012.
[5] a) L. T. Scott, Pure Appl. Chem., 1996, 68, 291; b) P. W. Rabideau, A.
Sygula, Acc. Chem. Res., 1996, 29, 235; c) L. T. Scott, Angew. Chem.
Int. Ed., 2004, 43, 4994; d) L.T. Scott, Jackson E.A., Zhang Q., Steinberg
B.D., Bancu M., Li B, J. Am. Chem. Soc., 2012, 134, 107-110.
[6] a) A.M. Butterfield, B. Gilomen, J.S. Siegel, Org. Process Res. Dev.,
2012, 16(4), 664–676; b) V. M. Tsefrikas, L. T. Scott, Chem. Rev., 2006,
106, 4868-4884; c) D. Alberico, M.E. Scott, M. Lautens, Chem. Rev.,
2007, 107, 174-238; d) N. Suzuki, T. Fujita, K.Y. Amsharov, J. Ichikawa,
Chem. Commun., 2016, 52, 12948-12951.
Experimental Section
Supporting Information (see footnote on the first page of this article):
Experimental procedures, and compound characterization data (1H NMR;
13C NMR; UV-vis; X-Ray diffraction data). This material is available free of
charge in the Supporting Information.
[7] a) L.T. Scott, H.E. Bronstein, D.V. Preda, R.B.M. Ansems, M.S. Bratcher,
S Hagen, Pure&Appl. Chem., 1999, 71(2), 209-219; b) H.I. Chang, H.T.
Huang, C.H. Huang, M.Y. Kuo, Y.T. Wu, Chem. Commun., 2010, 46,
7241-7243; c) L.T. Scott, H.E. Bronstein, N. Choi, J. Am. Chem. Soc.,
2002, 124, 8870-8875.
Conclusions
Since C-F bond is considered to be one of the most stable bonds
in organic chemistry, it is commonly assumed that it difficult to be
exploited in organic synthesis due to being inert. However, there
are quite a few evidences revealed during recent years, which
refute this fallacy. Discovered reaction proves that fluoroorganic
chemistry still remains to be undeveloped and extremely
promising field. Moreover, the transformation seems to be quite
attractive tool enabling synthesis of fluorinated 9,10-
diphenylanthracenes not available otherwise.
[8] X. Duan, J. Zeng, J. Lu¨, Z. Zhang, J. Org. Chem., 2006, 71, 9873-9876.
[9] a) R. Willem, H. Pepermans, K. Hallenga, M. Gielen, R. Dams, H. J.
Giese, J. Org. Chem., 1983, 48, 1890-1898; b) F.A. Bottine, P.
Finocchiaro, E. Libertini, A. Reale, A. Recca, J. Chem. Soc. Perkin
Trans., 2. 1982, 77-81; c) F.-A. von Itter,; F. Vꢀgtle, Chem. Ber., 1985,
118, 2300-2313.
[10] a)W. Fudikar, T. Linker, Chem. Commun., 2008, 0, 1771-1773; b) W. Cui,
Y. Wu, H. Tian, Y. Geng, F. Wang, Chem. Commun., 2008, 0, 1017-
1019; c) C. Shu, C.-B. Chen, W.-X. Chen, L.-W. Ye, Org. Lett., 2013,
15(21), 5542-5545.
[11] K. Amsharov, Phys. Status Solidi B, 2017, 1700170.
Conflicts of Interest
[12] a) D. N. Laikov, Chem. Phys. Lett. 1997, 281, 151−156; b) J. P.
Perdew; K. Burke, M. Ernzerhof, Phys. Rev. Lett.1996, 77, 3865−3868.
The authors declare no conflict of interest.
CCDC-1867159-1867160
contains
the
supplementary
crystallographic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif.
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It was found that -fluorinated
benzophenones undergo unusual
fusion under standard McMurry
conditions (see figure) leading to the
Vladimir Akhmetov, Mikhail Feofanov,
Vitaliy Ioutsi, Frank Hampel, Konstantin
Amsharov*
formation
anthracene
derivatives
Page No. – Page No.
which necessitates the cleavage of the
exceptionally stable aromatic C-F
bond. Discovered reaction proves that
fluoroorganic chemistry still remains to
be undeveloped and extremely
promising field.
The unusual fusion of α–fluorinated
benzophenones under McMurry
reaction conditions
This article is protected by copyright. All rights reserved.