Tailoring Diindenochrysene through Intramolecular Multi-Assemblies by C?F Bond Activation on Aluminum Oxide

Article abstract of DOI:10.1002/chem.201901450

The unique nature of the alumina-mediated cyclodehydrofluorination gives the opportunity to execute the preprogrammed algorithm of the C?C couplings rationally built into a precursor. Such multi-assemblies facilitate the construction of the carbon-skeleton, superseding the conventional step-by-step by the one-pot intramolecular assembly. In this work, the feasibility of the alumina-mediated C?F bond activation approach for multi-assembly is demonstrated on the example of a fundamental bowl-shaped polycyclic aromatic hydrocarbon (diindenochrysene) through the formation of all “missing” C?C bonds at the last step. Beside valuable insights into the reaction mechanism and the design of the precursors, a facile pathway enabling the two-step synthesis of diindenochrysene was elaborated, in which five C?C bonds form in a single synthetic step. It is shown that the relative positions of fluorine atoms play a crucial role in the outcome of the assembly and that governing the substituent positions enables the design of effective precursor molecules “programmed” for the consecutive C?C bond formations. In general, these findings push the state of the field towards the facile synthesis of sophisticated bowl-shaped carbon-based nanostructures through multi-assembly of fluoroarenes.

Full text of DOI:10.1002/chem.201901450

A Journal of
Accepted Article
Title: Tailoring Diindenochrysene through Intramolecular Multi-
Assemblies via C-F Bond Activation on Aluminum Oxide
Authors: Vladimir Akhmetov, Mikhail Feofanov, Sergey Troyanov, and
Konstantin Y Amsharov
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To be cited as: Chem. Eur. J. 10.1002/chem.201901450
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Tailoring Diindenochrysene through Intramolecular Multi-
Assemblies via C-F Bond Activation on Aluminum Oxide
Vladimir Akhmetov[a], Mikhail Feofanov[a], Sergey Troyanov[b] and Konstantin Amsharov*[a]
Abstract: The unique nature of the alumina-mediated
cyclodehydrofluorination gives an opportunity to execute the
preprogrammed algorithm of the C-C couplings rationally built into a
precursor. Such multi-assemblies facilitates the construction of the
carbon-skeleton superseding the conventional step-by-step by the
one-pot intramolecular assembly. In this work, we demonstrate the
feasibility of the alumina mediated C-F bond activation approach for
multi-assembly on the example of fundamental bowl-shaped PAH
(diindenochrysene) through the formation of all “missing” C-C bonds
at the last step. Beside valuable insights into the reaction mechanism
and the design of the precursors we have elaborated a facile pathway
enabling two-step synthesis of diindenochrysene where five C-C
bonds are created in one synthetic step. We show that the relative
positions of fluorine atoms play a crucial role in the outcome of the
assembly and that governing the substituents’ positions enables
design of effective precursor molecules “programmed” for the
consecutive C-C bond formations. In general, our findings push the
state of the field towards facile synthesis of sophisticated bowl-shaped
carbon-based nanostructures via multi-assembly of fluoroarenes.
electrophiles via periphery as a conventional PAHs to give a
product of SEAr, on the other hand it also reacts in fullerene-like
(olefin) fashion with both nucleophiles and electrophiles via
addition to the central double bond.[1,17] Even though 1 appears
as an easy target molecule, there are only two currently published
approaches allowing its synthesis (Figure 1).[18–22] The first one
was published by Scott et. all, where flash vacuum pyrolysis
approach was employed. Another known pathway is based on
intramolecular Pd-catalyzed aryl-aryl coupling. Both of the
methods have some severe limitations including low overall yields
and moderate yields at the last step. In this regard, alumina
mediated HF elimination appears to be attractive alternative
allowing both effective and selective aryl-aryl coupling. Here we
report facile synthesis of 1 and its derivatives via C-F bond
activation on alumina exploiting various multiple bond assemblies.
Geodesic polyarenes constitute the unique group of polycyclic
aromatic hydrocarbons (PAHs) which contain pentagons and
possess a concave surface, [1–3] which formally can be considered
as fragments of the fullerene cages. Although the synthesis of the
smallest representative, corannulene, is known for more than fifty
years,[4,5] organic chemistry still faces the lack of approaches that
allow facile synthesis of this class of molecules. Among the main
reasons for this are the substantial strain energies, which need to
be overcome in order to create bowl-shaped geometry. The
following existing approaches such as flash-vacuum pyrolysis
(FVP),[6] Pd-catalyzed arylation,[7–9] and coupling via C-F bond
activation[10–14] must be mentioned. While the first two methods
face both low group tolerance and moderate yields, the last one
often possess high selectivity and frequently leads to nearly
quantitative yields showing tolerance to various functional
groups.[15,16] Diindeno[1,2,3,4-defg:1',2',3',4'-mnop]chrysene (1)
is one of the simplest representative of geodesic polyarenes
containing two pentagons. It possesses intriguing both physical
and chemical properties. For example, 1 may react with
Figure 1. Known and implemented in this work approaches to the synthesis of
diindenochrysene.
In accordance with our experience in the field, cove-region serves
as a very attractive fragment to create five-membered rings via
intramolecular aryl-aryl coupling (cove-region-closure),[10,12]
hence our first approach included simultaneous closure of two
cove-regions (Figure 2). The required dibenzochrysene core can
be obtained via several known procedures,[23–27] however, not all
of them are suitable for the synthesis of derivatives with fluorine
atoms in cove-regions. We have proposed a simple synthetic
route to 4 and 5 with two substituents on the periphery. However,
during the synthesis of 4 formation of traces of several
regioisomers (see SI) makes it barely possible to isolate the
desired precursor in pure form. Nevertheless, using the mixture of
the regioisomers of 4 for next step allows obtaining the desired
diindenochrysene’s derivative 6 in substantial yields of 60%.
[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
Institut für Chemie Humboldt-Universität zu Berlin,
Brook-Taylor-Str. 2, 12489 Berlin-Adlershof,
Germany.
Supporting information for this article is given via a link at the end of
the document.
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Figure 2. a) The synthesis of 6 and 7 via cove-region closures. b) ORTEP
plot of 6 and 7 in the crystal. Thermal ellipsoids are drawn at the 50%
probability level (only one orientation of 7 in the crystal is shown for clarity).
c) HPLC profile of the reactionary mixture of 7 as obtained after reaction.
Minor side products and the respective peaks on HPLC are coded by the
same color.
Figure 3. Implemented approaches to 1 via consecutive triple aryl-aryl
coupling. “active” and “inactive” fluorine atoms coded by green and red
respectively.
This observation indicates that the presence of fluorine in 8
within the phenanthrene core exacerbates the first electrophilic
attack, redirecting the pathway of the reaction to the hydrolysis
of C-F bond forming 11. This viewpoint accounts for the
absence of such a by-product in case of 9, where the reaction
breaks off as soon as 12 is formed. According to our current
knowledge on the mechanism of the alumina mediated HF
elimination the reaction takes place via cation intermediates
formed after SEAr-like attack.[28] The relative positions of the
fluorine atoms can be rationally altered in order to
exclude/minimize undesired electron withdrawing effect on the
attacked π-system and thus to facilitate the reaction. Our
current efforts show that it is important not only to take into a
consideration the electron-withdrawing effects of the fluorine
but also their mutual effect. Both 9 and 10 after HF elimination
gave 12 as a major product, showing that such an ortho-
position of the fluorine atoms does not allow further coupling.
Precursor 10 combines advantages of both 8 and 9 having all
electron-withdrawing groups out of the attacked π-system and
no adjacent fluorine atoms in the bay-region which could lead
to the by-product analogous to 11. Moreover, 10 has flexibility
in terms of the choice which cycle to form first. It might be either
five-membered ring to give 12 or the six-membered ring to give
the corresponding dibenzochrysene derivative 13. We found
that, pentagon formation dominates that leads to the abruption
of the further reactivity whereas 1 is formed as a minor product.
Note, that no other products were observed according to HPLC
analysis showing only two distinct peaks corresponding to 1
and 12. These findings also reveal that transformation of 10 to
13 is considerably hindered supposedly due to appearance of
two cove regions leading to the substantial strain energy
connected with the -system twisting.
In order to avoid the formation of the mixture of isomers along
with 4 we have modified our approach by the replacement of
methyl groups with fluorine atoms. As a result of this
modification we were able to synthesize 5 as a single product
and to confirm its structure by means of X-Ray crystallography
(see SI). The synthesis of 7 was implemented in 5 steps with
the overall yield of 26% which is comparable or even exceeds
the yields of the last stages implemented in the previously
known approaches. Furthermore, the HPLC monitoring of the
last step demonstrates the essential absence of the side
products and gradual full conversion of the initial
dibenzochrysene to give the desired 7 in 80% yield (Figure 2c).
Thus, the final product requires virtually no further purification.
The obtained derivatives 6 and 7 were fully characterized via
analytical methods including X-Ray crystallography (Figure
2b). These findings make this approach superior over all
existing alternative methods and allow estimating the alumina
mediated HF-elimination as a selective and efficient tool to
obtain various geodesic polyarenes and their derivatives. Even
though the schemes described above allow the synthesis of
highly interesting derivatives in high yields exploiting
conventional reactions it still possesses some complications
during the implementation and requires multi-step synthesis of
the precursors. One of the possibilities to improve the
procedure is to postpone the maximal number of C-C bonds
formation to the last step. Following this logic, we synthesized
and investigated precursors 8, 9 and 10, which could be
directly, converted to 1 via consecutive triple domino-like aryl-
aryl couplings (Figure 3). Indeed, the cyclization of 8 allowed
us to obtain 1 via triple HF-zipping with quite moderate yields
which was connected to the unexpected side product 11
containing dibenzofuran fragment.
In the course of our attempts to obtain 1 via 8, 9 and 10 we
have observed valuable results that shed a light on some
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idiosyncrasies of the alumina mediated HF-elimination. First of
all, we found out that beside the necessity to facilitate the SEAr-
like step, there are some other factors affecting the eventual
product formation. It remains unclear why 12 does not undergo
the second HF-elimination while 14 readily reacts, since the
latter is supposed to be less prone to undergo the electrophilic
attacks. We have tested several precursors that might lead to
1 via three consequent C-C bond formations and found that 8
indeed gives 1 on activated alumina, which makes the reaction
attractive since only few steps exploiting conventional methods
are required in order to obtain 8. Moreover, the experimental
data provide us with some valuable insights into the design of
the precursors for other related buckybowls.
Our further endeavors were aimed to manage the formation of
the maximum number of C-C bonds at the last stage.
According to this strategy, we have attempted to implement the
synthetic scheme (Figure 4a) where 1 was supposed to be
formed from 16 after the sequence of four aryl-aryl couplings.
Unfortunately, our efforts led neither to the desired product nor
to any of the expected intermediate products, nevertheless the
initial reagent was not observed in the extract after the
reaction. The observed experimental data evidence that the
attack of the formed cation-like species does not occur and
some other side reactions proceed leading to the irreversible
adsorption of the by-products on the solid phase. We assume
that the reaction can be hindered by two possible factors. The
unfavorable rigid geometry and thus the lack of the
conformational flexibility, which plays the crucial role in the
intramolecular interactions, serve as the first factor. Secondly,
the reactive double C-C bond of 16 might be polarized on
frustrated Lewis pairs formed on the surface of activated
alumina, thus leading to undesired side reactions.
In order to avoid the undesired reactions of the double bond
and to increase the number of possible conformers, we
modified our approach as shown in Figure 4b. The
incorporation of sp3-hybridized carbon atoms in 17 introduces
additional flexibility into a system circumventing substantial
strain energy arising during aryl-aryl coupling otherwise. The
required precursor 18 can be obtained by standard McMurry
coupling of the respective fluorinated benzophenone.[28] Thus
we have suggested a possible pathway enabling facile three-
step synthesis of 1 from 19. After subjecting 19 to the
conditions of the alumina mediated HF-elimination we
observed rather complicated mixture, nevertheless we
managed to isolate three major fractions exploiting HPLC.
Surprisingly, instead of the expected intermediate 17 we have
observed the formation of the target molecule 1 along with
several interesting side products such as 20, 21 and 22. At this
point, multiple fundamental questions arise, first of all the major
question is how the formation of the middle double bond
occurs. Therefore, we have investigated whether
dehydrogenation may occur under the conditions of HF-
elimination. For this purpose, we subjected 9H,9'H-9,9'-
bifluorene to activated alumina under vacuum and observed a
significant conversion to 9,9'-bifluorenylidene which was
detected via HPLC analysis. This transformation shows that
alumina can initiate the dehydrogenation. Moreover, in
accordance with the previous experiment (Figure 4a) the
dehydrogenation step must occur no sooner as at least one of
C(aryl)-C(aryl) bond is formed. Otherwise, it leads to 16 and
the abruption of the further reaction. One of the possible
explanations for the presence of 20 is supported by the
formation of the cation-like species, which can hardly undergo
intramolecular SEAr due to the presence of the electron-
withdrawing groups. The system may undergo several
alternative reactions e.g. such as a double bond formation via
loss of HF (see SI), thus three out of four fluorine atoms are
responsible for aryl-aryl coupling while the elimination of the
fourth HF leads to the double bond formation. The described
above processes may serve as an account for the formation of
both 1 and 20, however the mechanism leading to the
formation of 21 and 22 remains obscure. The ipso-substitution
appears to be the only reasonable explanation of the
observations, which accounts for the positions of the fluorine
atoms in 21 and 22 (see SI). Since we consider the SEAr to be
the direction-determining step, all three processes described
above as side reactions might be suppressed upon the
facilitation of SEAr. It comes naturally to promote the
electrophilic attack via disposal of fluorine atoms from the π-
system. For this reason, we have obtained 23, which is
supposed to undergo SEAr easily, and could also shed a light
on the sequence of couplings. The following experiment
(Figure 4d) revealed two main products 24 and 25, which
correspond to double HF and H2 elimination. In addition, by
means of HPLC we have found some phenanthrene
derivatives that were not isolated or characterized though,
however the collected data allows us to conclude that at first
the
six-membered
ring
is
formed
leading
to
Figure 4. Multi-assemblies of fluorinated tetraphenyl ethanes.
diphenylphenanthrene derivatives, after which multiple
pathways are possible. Having these observations in hand we
tried to carry out the synthesis of 1 in the most efficient way.
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The precursor 27 possesses both flexibility of sp3-hybridized
atoms and non-substituted phenyl rings that may be readily
attacked by electrophiles. As expected 27 gave 1 after creation
of five C-C bonds in quite reasonable yield along with the
intermediate (28). Moreover, the attempt to obtain 1 from 28
revealed that 28 does not undergo Aryl-Aryl coupling on
alumina, which allowed us claiming that 1 is formed via another
intermediate.
not yield 1, both experimental and DFT data testify that the
formation of 1 occurs via IM10 and the following closures of the
cove-regions. Both 23 and 27 are obtained as mixtures of
diastereomers
from
the
corresponding
fluorinated
benzophenones, thus beside the variability in terms of the
competition between formation of five- and six-membered ring
at the first stage there is also a competition between two
diastereomers leading to either syn- or anti- dislocation of
hydrogens adjacent to sp3-carbon atoms. The calculations
show that anti-position generally prevails over syn-, not
significantly though. Moreover, aromatization appears to occur
after the first aryl-aryl coupling thus eliminating the issue in the
following up closures.
Summing up, we contribute to the fundamental question of C-
C bond creation in PAHs and show comprehensive sets of C-
C coupling demonstrating the viability of the algorithm
execution concept. We show that the multiple C-C coupling can
be performed in a truly domino-like fashion and the whole
process can be rationally governed via managing the electronic
effects. To our surprise and pleasure, we also discovered that
alumina
allows
effective
one-pot
multi
C-C
coupling/aromatization. In general, we demonstrate the
unprecedentedly high flexibility in the design of precursors
showing five new synthetic approaches to diindenochrysene
core. Additionally, structurally related PAHs such as chrysene
derivatives 20, 24 and 25 that are hardly available and require
meticulous synthesis, might be easily obtained exploiting our
approach. Moreover, the multi-assembly of 27 appears to be a
very attractive approach for the preparative synthesis of 1
since it can be obtained just in one step. We also suppose that
the multi-assembly approach via C-F bond activation on
alumina will provide facile access to other interesting related
bowl-shaped PAH systems.
Figure 5. Graphical representation of the DFT-based thermochemistry
analysis. ΔH (kcal/mol) fluorinated precursors and corresponding σ-
complexes are referenced to the lowest value in each separate step.
In order to establish the pathway that takes place during the
transformation of 27 to 1 we applied Bell-Evans-Polanyi
principle in order to estimate relative rates of the competing
reactions. For this purpose, we have calculated the differences
between the enthalpies of formation of the precursors before
HF elimination and corresponding σ-complexes formed during
SEAr–like process. The calculations were carried on B3LYP/6-
31G(d) level. Having in hand experimental results such as the
formation of 24 and 25 from 23 and the absence of 26 one may
reasonably infer the sequence that at first the six-membered
ring is formed, while the both options for the second aryl-aryl
coupling occur in equal shares since the eventual yields of 24
and 25 are comparable. These experimental observations go
in line with the calculated data (Figure 5a) which predict the
prevalence of IM2 leading to the phenanthrene’s derivative
during the first step and the equality between IM4 and IM5
leading to 24 and 25, respectively. In the case of 27 the DFT
data reveal the similar preference toward IM7 formation over
the IM6, this leads to the formation of IM8, which has three
further pathways. Leaving aside IM9 as an obviously
unfavorable direction we found out that the formation of IM11
should prevail over IM10 in contrast to the analogous situation
with IM4 and IM5 where 24 and 25 are formed with almost the
same yield. Taking into a consideration the fact that 28 does
Acknowledgements
Authors are thankful to Dr. Harald Maid for NMR measurements and
spectra interpretations.
Funded by the Deutsche Forschungsgemeinschaft (DFG)
–
Projektnummer 182849149 – SFB 953, AM407
Keywords: C-F activation • Buckybowls • Multi-Assembly • C-C
coupling • Aromatization
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Vladimir Akhmetov, Mikhail Feofanov,
Sergey Troyanov and Konstantin
Amsharov*
Page No. – Page No.
Tailoring Diindenochrysene through
Intramolecular Multi-Assemblies via
C-F Bond Activation on Aluminum
Oxide
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