Four-Step Domino Reaction Enables Fully Controlled Non-Statistical Synthesis of Hexaarylbenzene with Six Different Aryl Groups**

Article abstract of DOI:10.1002/anie.202104437

Hexaarylbenzene (HAB) derivatives are versatile aromatic systems playing a significant role as chromophores, liquid crystalline materials, molecular receptors, molecular-scale devices, organic light-emitting diodes and candidates for organic electronics. Statistical synthesis of simple symmetrical HABs is known via cyclotrimerization or Diels–Alder reactions. By contrast, the synthesis of more complex, asymmetrical systems, and without involvement of statistical steps, remains an unsolved problem. Here we present a generally applicable synthetic strategy to access asymmetrical HAB via an atom-economical and high-yielding metal-free four-step domino reaction using nitrostyrenes and α,α-dicyanoolefins as easily available starting materials. Resulting domino product—functionalized triarylbenzene (TAB)—can be used as a key starting compound to furnish asymmetrically substituted hexaarylbenzenes in high overall yield and without involvement of statistical steps. This straightforward domino process represents a distinct approach to create diverse and still unexplored HAB scaffolds, containing six different aromatic rings around central benzene core.

Full text of DOI:10.1002/anie.202104437

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Four-step domino reaction enables fully controlled non-statistical
synthesis of hexaarylbenzene with six different aryl groups
Authors: Benedikt W. Grau, Maximilian Dill, Frank Hampel, Axel Kahnt,
Norbert Jux, and Svetlana B. Tsogoeva
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.202104437
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10.1002/anie.202104437
Angewandte Chemie International Edition
RESEARCH ARTICLE
Four-Step
Domino
Reaction
Enables
Fully
Controlled
Non-statistical Synthesis of Hexaarylbenzene with Six Different
Aryl Groups
[a]
Benedikt W. Grau,[a] Maximilian Dill,[b] Frank Hampel,[a] Axel Kahnt,[c] Norbert Jux,[b] Svetlana B. Tsogoeva
*
Dedication ((optional))
[a]
B. Grau, Dr. F. Hampel, Prof. Dr. S.B. Tsogoeva
Organic Chemistry Chair I and Interdisciplinary Center for Molecular Materials (ICMM)
Friedrich-Alexander University of Erlangen-Nürnberg
Nikolaus Fiebiger-Straße 10, 91058 Erlangen, Germany
E-mail: svetlana.tsogoeva@fau.de
[b]
[c]
M. Dill, Prof. Dr. N. Jux
Organic Chemistry Chair I and Interdisciplinary Center for Molecular Materials (ICMM)
Friedrich-Alexander University of Erlangen-Nürnberg
Nikolaus Fiebiger-Straße 10, 91058 Erlangen, Germany
PD Dr. A. Kahnt
Leibniz Institute of Surface Engineering (IOM)
Permoserstr. 15, 04318 Leipzig, Germany
Abstract: Hexaarylbenzene (HAB) derivatives are versatile aromatic systems playing a significant role as
chromophores, liquid crystalline materials, molecular receptors, molecular-scale devices, organic light-emitting
diodes and candidates for organic electronics. Statistical synthesis of simple symmetrical HABs is known via low-
yielding cyclotrimerization or Diels-Alder reactions. By contrast, the synthesis of more complex, asymmetrical
systems, and without involvement of statistical steps, remains an unsolved problem. Here we present a generally
applicable synthetic strategy to access asymmetrical HAB via an atom-economical and high-yielding metal-free
four-step domino reaction using nitrostyrenes and α,α-dicyanoolefins as easily available starting materials.
Resulting domino product – functionalized triarylbenzene (TAB) - can be used as a key starting compound to furnish
asymmetrically substituted hexaarylbenzenes in high overall yield and without involvement of statistical steps. This
straightforward domino process represents a distinct approach to creating diverse and still unexplored HAB
scaffolds, containing six different aromatic rings around central benzene core.
Introduction
Benzene, a six-membered hydrocarbon aromatic ring system, is one of the most abundant structural
features in chemistry, ranging e.g., from natural products,[1] ligand systems for metal complexes[2] to
pharmaceutics.[3] The benzene ring possesses manifold interesting electronic properties which makes it
indispensable as building block in extended conjugated systems used as organic semiconductors.[4]
Expansion of polycyclic aromatic hydrocarbons leads to a smaller gap between HOMO and LUMO of the
molecule – which means they can be more easily transferred into their excited state: as a result, these
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10.1002/anie.202104437
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RESEARCH ARTICLE
molecules absorb in the UV or visible light range, are often colored and find use as photosensitizers,
dyes or chromophores.[5]
If every hydrogen atom in benzene is replaced by further benzene rings, the system is expanded to
hexaphenylbenzene (HPB, Fig. 1a), which exhibits propeller chirality and toroidal delocalization.[6] By
substitution of the outer phenyl rings with the same or different functional groups, these derivatives can
be described in general as hexaarylbenzenes (HAB, Fig. 1a). These systems are of high interest,[7] as
they have been already established in multiple applications like molecular chromophores,[8]
mesomorphic materials[9] or molecular capsules.[10] By Scholl-oxidation HAB can be converted to
hexabenzocoronene (HBC), which is used in electronics,[11] spintronics,[12] catalysis[13] and as model for
graphene[14] or its synthesis.[15] As a result, construction of novel asymmetrical HABs, their investigation
and fine tuning of their properties, is of high demand. However, existing synthetic methods, like Diels-
Alder reactions,[16] cyclotrimerization[17] or Suzuki-coupling of multi-halogenated derivatives,[18] do not
offer full control of the final HAB constitution, i.e., access to all 36 combinatorically possible constitution
isomers or substitution patterns for arbitrary substituents.[19] Moreover, for a given six different aryl groups
around benzene core, there are 6!/6 = 120 distinguishable isomers possible (because each of the six
substituents can be assigned to any of the six core benzene carbons), comprising of 60 position isomers
that exist each as a pair of - rapidly racemizing - enantiomers, due to propeller chirality of the HAB.[20] As
a result, conventional synthesis gives complex mixtures of very similar molecules, bearing similar
physical properties. Separation and isolation of a desired single target HAB is hardly possible and only
in low yield (Fig. 1b). Moreover, examples of controlled post-modification of HAB scaffolds are still very
rare.[17b] Hence, these standard methodologies are not feasible to obtain more complex, asymmetrically
substituted systems. Under these circumstances it is not surprising that to date there is only one single
example for a HAB, bearing six differently substituted phenyl rings.[21] Although the approach, which
functionalizes 2-methoxy thiophene, marks a great milestone, it suffers from low overall yields, small
scales and harsh reaction conditions. Additionally, final [4+2] cycloaddition is a statistical reaction, which
results in two different products when employing an asymmetric tolan (Fig. 1c). The mixture of
stereoisomers was inseparable without post-modification of the final product, therefore critically limiting
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10.1002/anie.202104437
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RESEARCH ARTICLE
the applicability of this method. The challenge of designing a general, reliable and non-statistical route
for synthesis of HABs is, therefore, not yet met, which makes development of new synthetic approaches
highly desirable.
In addition to conventional “stop-and-go” synthetic methodologies, domino reactions have attracted high
attention since recently. These processes include a cascade of multiple reactions which proceed
sequentially and where previous step triggers its successor, yielding complex molecules with a single
workup and purification process. Thereby domino processes are time saving, waste reducing, atom
efficient and can be considered a green method superior to step-wise synthesis approaches.[22] Even
more cost efficient are metal-free multi-step domino reactions, as these are much less expensive than
those using metal catalysts.[23]
Having this in mind, we developed a novel 4-step domino-process yielding hexa-substituted
triarylbenzene (TAB) derivatives to fill the existing gap in non-statistical synthetic methods towards HAB
(Fig. 1d). The domino sequence, employing easily available precursors, gives full control of the
substitution pattern on the central benzene core. The three additional and different functional groups on
the core-ring of TAB domino product allow stepwise introduction of three further aromatic rings via further
synthetic steps. This approach offers the first scalable synthetic method towards HAB without any
statistical steps, which allows access to complete theoretically possible chemical space for HABs in a
pre-designed way.
Results and Discussion
A novel domino reaction as a key unlocking the non-statistical synthesis of hexaarylbenzene:
Reaction development
We set out by investigating three-component domino reaction of 4-methylnitrostyrene (1a), 1-(4-
fluorophenyl)-2-phenylethan-1-one and malononitrile using DABCO as catalyst and acetonitrile as
solvent (Fig. 2a). However, no conversion towards desired product 6a was observed, since Knoevenagel
condensation step was not feasible under the chosen conditions (see Fig. S1). Instead, Michael product
of nitrostyrene and malononitrile (see Fig. S2) preferably forms, and reacts further to a complex mixture
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10.1002/anie.202104437
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RESEARCH ARTICLE
of undesired products (see Fig. S3 and Fig. S4). Hence, we decided to use preformed Knoevenagel
product 2a in the domino reaction towards TAB 6a (Fig. 2b).
.
a
H
H
H
H
H
H
Benzene
Hexaphenylbenzene (HPB)
Hexaarylbenzene (HAB)
b
c
d
product mixture
I
statistical
Sonogashira
Co2(CO)8
isolation impossible
only symmetrical HAB
Cyclotrimerisation
elaborate precursor synth.
direct separation impossible
<1 % overall yield
+
O
S
6-step synthesis
S
statistical
O
[4+2] Cycloaddition
NO2
NO2
domino reaction - key step
NH2
CN

4-step
linear
domino
non-statistical
+
no statistical step


CN
CN
12.4 % overall yield
Triarylbenzene (TAB)
Fig. 1. Outline of known and proposed synthesis of HABs. a, Benzene and hexaarylbenzene. b, Shortcomings
of established synthetic methods like cyclotrimerization or c, Diels-Alder reaction. d, This work: novel approach to
the synthesis of hexaarylbenzene with complete control over aryl-installing steps.
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RESEARCH ARTICLE
a
NO2
N
N
NH2
CN
O
CN
CN
NO2
no conversion
+
+
CH3CN, 50 °C, 18 h
1a
F
6a
F
b
NO2
CN
NH2
CN
NO2
catalyst
additive
CN
up to >99% yield
+
solvent, 50 °C, time
1a
2a
F
6a
F
c
Entry
Base
Solvent
Time
(h)
Yield
Entry
Base / Additive
Solvent
Time
(h)
Yield
(equiv.)
(equiv./equiv.)
1#
2
DABCO (1)
DABCO (1)
DABCO (1)
CH3CN
CH3CN
THF
18
18
72
n.c.
76%
78%
9
DMAP (1 / 0)
Pyridine (1 / 0)
TEA (1 / 0)
CH3CN
CH3CN
CH3CN
CH3CN
18
18
22
96
46%
n.c.
10
11
12
3
55%
58%
DABCO/CuBr2
(1 / 0.25)
4
5
6
7
8
DABCO (1)
DABCO (1)
DABCO (1)
DBU (1)
Toluene
H2O
72
18
72
18
18
70%
n.c.
13
14
15
16*
DABCO/Thiourea CH3CN
(1 / 0.25)
96
96
72
18
94%
63%
DABCO/Urea
(1 / 0.25)
CH3CN
CH2Cl2
CH3CN
CH3CN
41%
14%
22%
DABCO/Thiourea CH3CN
(1 / 0.5)
>99%
>99%
DABCO/Thiourea CH3CN
(1 / 0.5)
DIPEA (1)
#conditions shown in Fig. 2a were used
* Reaction temperature: 70 oC
Fig. 2. Development of novel domino reaction. a, Initial attempt of synthesizing TAB compound 6a via three-
component domino reaction (see entry 1). b, Developed two-component four-step domino reaction towards TAB
6a (entries 2-16), additional entries can be found in Table S1. c, Screening of reaction conditions.
To our delight, this second attempt of the two-component domino reaction using DABCO in acetonitrile
already resulted in good yield of 76% after 18 h (Fig. 2c, entry 2). As we were able to identify the
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10.1002/anie.202104437
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cyclohexadiene intermediate 5a (Fig. 3d), we prolonged the reaction time till the corresponding spots of
reactants on TLC disappeared completely. Extensive screening of solvents (Fig. 2c, entries 3-6) and
catalysts (Fig. 2c, entries 7-11) did not result in any improvements, so we focused on using different
additives (Fig. 2c, entries 12-16). While copper(II)bromide (Fig. 2c, entry 12) and urea (Fig. 2c, entry 14)
were decreasing the yield, addition of thiourea improved the yield significantly to 94% (Fig. 2c, entry 13).
After optimizing the amounts of additive (Fig. 2c, entry 15) and the temperature (Fig. 2c, entry 16), we
were able to isolate the desired product in quantitative yield. The role of thiourea additive in the presented
domino reaction is not trivial. In the first glance, thiourea can be expected to interact, via hydrogen-
bonding, with a nitro group of the nitroolefins and to enhance their electrophilicity, and, therefore, to
accelerate the Michael addition step.[24] However, since urea additive did not have a similarly beneficial
effect on the reaction yield as its thio analogue (Fig. 2c, entries 12-14), a hydrogen bonding mechanism
can be clearly ruled out. Notably, recently reported theoretical investigations demonstrate that e.g.,
superoxide radical anion and hydroxyl radical can be scavenged efficiently by thiourea but not by urea.[25]
In line with this, we propose, that thiourea might trap some radicals, suppressing undesired side reactions
during the aromatization step, resulting in high product yields.
Having the optimized reaction conditions in hand, we next explored the scope of reaction to investigate
effect of different types of substituents at aromatic rings of TAB (Fig. 3a). To show the power of the
reaction and demonstrate its versatility, we first synthesized derivatives 6b-6m (Fig. 3b). By simply
varying the corresponding starting materials, we were able to construct TABs with electron donating or
electron withdrawing groups selectively on each of the three rings in up to 88% yield (i.e. average of 97%
per step). Since no clear trends of substituents’ influence on reaction outcome was observable, we
additionally synthesized derivative 6n with unsubstituted phenyl rings. The moderate yield of 40%
confirmed that substituents in general seem to have a beneficial influence on the overall yield. In addition,
we also synthesized derivatives 6o and 6p, which might be interesting candidates for post-modifications
e.g., for synthesis of CF3-containing bioactive quinazoline-scaffolds (starting from 6o) or Suzuki-coupling
reactions (using 6p). Finally, we employed sterically hindered nitrostyrenes leading to 6q, 6r, 6s and 6t
in moderate to good yields (up to 51% over four steps). Even though a 34% yield for dicarbazole based
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TAB 6t seems only moderate at first sight, one has to note that this corresponds to an average yield of
76% per step over four steps, which is still remarkable. In general, all substituents were well tolerated by
the reaction, allowing for moderate to excellent yields, confirming the novel domino reaction as a new
powerful approach to highly functionalized aromatic systems.
As reaction mechanism we proposed a linear four-step domino process as depicted in (Fig 3d): the first
step consists of a vinylogous Michael addition, resulting in dicyanoolefin 3. As 3 possesses two
stereocenters, it consequently yields a mixture of two diastereomers, which we isolated and
characterized during our investigations for 3a. Compound 3 can then again be deprotonated on the
nitroalkane unit to allow intramolecular cyclization by attacking one cyano-group to give six-membered
ring containing structure 4. The resulting imine can now undergo an imine-enamine tautomerization to
yield cyclohexadiene derivative 5, which we isolated and characterized for 5a. In the final step, the six-
ring in 5a is aromatized towards the desired product 6.
Synthesis of hexaarylbenzene
After having developed the synthetic route towards key precursor 6a, we next aimed at the synthesis of
the HAB derivative bearing six different aryl rings. To achieve this goal, we carried out big scale synthesis
of starting materials: Nitrostyrene 1a and α,α-dicyanoolefin 2a were synthesized according to literature
known procedures[23a, 26] in multi-gram scale (Fig. 4a). To ensure our four-step domino reaction was
applicable in gram scale, we performed an upscaling, resulting in 1.64 g of product in 78% yield (94%
per step). This result again verifies the novel reaction as key stepping stone for HAB synthesis, albeit
the reaction time had to be prolonged to 24 hours.
Starting with more than 1g of 6a, we chose a set of conventional transformations to carry out a
straightforward synthesis of selected HAB 15 (Fig. 4c). To keep the whole procedure facile and general,
we decided to introduce the fourth aromatic ring as late as possible. Therefore, we choose first to
transform 6a with copper(II)bromide and iso-amyl nitrite in a Sandmeyer-type reaction to the
corresponding bromine derivative 7, which could be obtained in 98% yield.
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.
NO2
CF3
a
NO2
NO2
NH2
CN
c
NH2
CN
NH2
CN
4-step
linear
domino
CN
NO2
+
CN
DABCO, Thiourea
CH3CN, 18 h, 70 °C
1
2
6
6n 40%
6o
61%
b
O
F
O
NO2
NO2
NO2
NO2
NO2
Br
NO2
O
NO2
NH2
CN
NH2
CN
NH2
CN
NH2
CN
NH2
CN
NH2
CN
6q
51%
6b
50%
NO2
6c
6d
6e
72%
78%
88%
6p
92%
NO2
NO2
NO2
NH2
CN
NH2
CN
NH2
CN
N
NH2
CN
NO2
NO2
NH2
CN
NH2
CN
O
O
F
O
6f
6g
6h
6i
66%
86%
NO2
72%
NO2
34%
6s
42%
6r
21%
NO2
NO2
NH2
CN
NH2
CN
N
NH2
CN
NH2
NO2
CN
NH2
CN
N
O
6m
F
O
O
6t
34%
6k
6l
54%
49%
71%
6j
74%
d
NO2
CN
isolated + characterized
CN
reaction progress
4h 6h
i
n
t
r
a
c
m
n
3
s
y
5min
10min
12h
13h
NO2
o
o
u
i
c
t
o
l
e
c
i
l
i
z
g
d
a
1
o
d
u
l
a
r
n
l
t
a
y
i
-
o
l
n
i
v
e
+
a
h
c
CN
i
M
N
CN
NO2
NH
CN
N
S
2
H2N
NH2
NO2
4
e
NH2
n
i
a
n
o
i
r
m
o
t
a
m
a
n
z
a
i
e
r
e
t
-
i
CN
z
e
a
n
m
i
t
i
o
NO2
o
t
m
i
n
u
a
t
NH2
CN
5
6
isolated + characterized
6a
Fig. 3. Scope of the novel four-step linear domino reaction. a, General reaction equation. b, Systematic
evaluation of functional group influence on isolated product yield. c, Scope expansion. d, Reaction mechanism,
color change of the reaction mixture over time and crystal structure of 6a.
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RESEARCH ARTICLE
a
CN
CN
OH
O
O
Br
NO2
O
a
b
c
d
+
1a
2a
F
F
F
F
b
NO2
NO2
NO2
Br
e
CN
NH2
CN
Br
CN
NO2
4-step
linear
domino
NH2
O
CN
g
f
+
1a
2a
6a
7
Key step
F
8
F
F
F
h
NO2
NO2
NO2
NO2
Br
Br
O
NH2
j
i
N
O
h'
Br
NH2
H
without
isolation
8'
9
11
10
F
F
F
F
k
O
NO2
NH2
Br
l
n
m
CN
CN
CN
CN
13
14
12
F
F
F
15
F
c
d
6a
7
11
15
l
e
e
F
N
H
C
n
n
H
3
C
O
a
e
T
3
H
e
x
u
l
H
e
C
M
o
C
h
T
o
s
I
14
13
12
Fig. 4. Total synthesis of hexaarylbenzene with domino reaction as key step. a, Synthesis of starting
materials: a) CH3NO2, NH4OAc, reflux, 95 % yield; b) 1. Mg, Et2O, benzylbromide, r.t. → 40°C, 2. 4-
fluorobenzaldehyde, -78°C → 40°C >99 % yield; c) Pyridinium chlorochromate, CH2Cl2, r.t., 89 % yield; d)
malononitrile, NH4OAc/HOAc, Toluene, 120°C, 92 % yield. b, e) Large scale synthesis of 6a (78% yield); f) CuBr2,
iso-amyl nitrite, CH3CN, 50°C, 98 % yield; g) H2O2/DMSO, r.t.; 91 % yield; h) 1. bis(methoxycarbonyl)phenyliodine,
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KOH, MeOH, 0°C → r.t., 2. KOH/MeOH (aq. 30%), reflux, 89 % yield; i) Pd(dppf)Cl2ꞏDCM, Cs2CO3, corresponding
boronic acid, toluene/H2O, 100°C, 88% yield; j) CuBr2, iso-amyl nitrite, CH3CN, 50°C, 94 % yield; k)
Pd(dppf)Cl2ꞏDCM, Cs2CO3, corresponding boronic acid, toluene/H2O, 100°C, 80% yield; l) Zn, FeCl3, DMF/H2O
(5:1), ultrasonic bath, 66% yield; m) isoamyl nitrite, bromoform, 100°C, 59% yield; n) Pd(dppf)Cl2ꞏDCM, Cs2CO3,
corresponding boronic acid, toluene/H2O, 100°C, 57% yield. Overall yield: 7.5% (12.4% starting from domino
product 6a). c, Crystal structures of 6a, 7, 11, 12 and 14. d, Crystal structure and solvatochromic effect of 15.
Subsequently, we chose the hydrolysis and the Hoffman rearrangement as follow-up steps, in order to
convert the nitrile group into the corresponding amine 9. Unfortunately, literature reported procedures
were not feasible for bromine 7 as the derivative is quite insoluble in polar or aqueous media.[27] For this
reason, we chose to modify the procedure by changing the ratio of DMSO to H2O2 from 2:1 to 5:1, which
resulted in reduced reaction time of 30 minutes with 91% isolated yield of 8. Since reaction conditions of
both steps of following Hoffmann-rearrangement are quite similar, we combined these two steps in an
unprecedented one-pot procedure to give amine 9 in overall yield of 89%. Next, we chose modified
Suzuki conditions,[28] employing Pd(dppf)Cl2 DCM as catalyst, which gave the desired four-ring system
●
10 in 88% yield, starting from compound 9. The obtained 4-tbutylaryl derivative 10 subsequently
underwent Sandmeyer type transformation, towards the corresponding bromine 11 in 94% yield.
Attempts to reduce the nitro group in 11 before Suzuki-coupling, were not successful, because all
reactions employed did either not show any conversion or resulted in dehalogenation. We therefore
decided to change the order of steps and introduced the fifth ring through Suzuki-coupling, before
reduction of the nitro group, in 80 % yield of 12. Reduction of nitro-group in 4-cyanoaryl derivative 12
turned out to be quite challenging, since different established methodologies did not result in conversion
to the desired amine 13. To our delight, after thorough screening (see Table S2), we found that using
combination of Zn and FeCl3 in DMF/H2O led to success. After converting amine 13 to bromine derivative
14 via modified Sandmeyer type reaction using bromoform/isoamyl nitrite, we performed the final
palladium catalyzed reaction towards target HAB system 15, with six different aromatic rings around
central benzene core.
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We succeeded to obtain a single crystal of topologically achiral (due to practically free internal rotation
in solution around C-C bonds connecting the aryls to benzene core) but propeller chiral C1 non-
symmetrical 15 and determined its structure (see Fig. S5-S9). The unit cell contains dimers of two
enantiomers each of 15, stacked face-to-face in an antiparallel manner (see Fig. S5 and Fig. S6). Within
the monoclinic I2/a achiral space group, four of these dimers inhabit the unit cell. The packing motif
consists of dimers, which are slightly tilted with respect to each other. Dispersion interactions dominate
the packing; for example, the aliphatic methyl and tertiary butyl groups of 15 are clustered together (Fig.
S7). Also, nitrile and methoxy substituents pair up in the structure(Fig. S8), whereas the fluorine
substituents form quite rare C-H…F-C hydrogen bonds[29] to various aromatic protons of neighboring
molecules (Fig. S9).
Photophysical study
With a substantial amount of 15 in hand, we decided to conduct a basic photochemical study of the
compound, taking the solvatochromic effect in observed blue fluorescence (see Fig. 4d) into account. It
is important to mention, that HPB itself does not possess fluorescent properties, which gives evidence
that the new route of synthesis opens the door for tailormade optical properties of future compounds. To
shed light on the optical properties of the electronic ground state of 15, absorption spectra were
measured in cyclohexane exhibiting absorptions in the UV region below 330 nm with a shoulder-like
peak around 285 nm (see Fig. S10). First insights into excited states properties of 15 came from steady
state and time resolved fluorescence measurements. HAB 15 exhibits in cyclohexane, THF and
acetonitrile strong fluorescence in the UV and blue range of the optical spectrum, with fluorescence
maxima and fluorescence quantum yields depending on solvent polarity: 353 nm (ΦFlu = 0.15) in
cyclohexane, 380 nm (ΦFlu = 0.16) in THF and 415 nm (ΦFlu = 0.19) in acetonitrile (see Fig. S11). The
trend of increasing fluorescence quantum yield with increasing solvent polarity is also reflected in the
fluorescence lifetimes, which are prolonged from 2.2 ns in cyclohexane to 3.0 ns in THF and 4.8 ns in
acetonitrile (see Fig. S12). Transient absorption spectroscopy based on nanosecond laser flash
photolysis exciting 15 at 266 nm in cyclohexane helped to investigate the S1-SN and T1-TN transitions.
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The transient absorption of the first singlet excited state was obtained from taking the transient absorption
spectrum within the nanosecond laser pulse and exhibited a spectrum dominated by a negative transient
absorption signal in the UV and blue region of the optical spectrum which is best explained by the strong
fluorescence of 15 in this spectral region and a featureless transient absorption band in the visible and
NIR region with a maximum around 640 nm. Well in line with the obtained fluorescence lifetimes -
reflecting the singlet first excited state lifetime - this transient absorption feature decays within the
instrument response function of our nanosecond transient absorption setup, and gives rise to a new set
of transient absorptions with a dominating maximum around 360 nm and a smaller shoulder-like
maximum around 600 nm (see Fig. S13 and Fig. S14). This transient absorption decays on the
microsecond time scale. The monoexponential fit of the time profile at 360 nm, measured in cyclohexane,
gives a lifetime of 2.9 µs. The most plausible rationale for this transient absorption is the triplet first
excited state of 15, which is further corroborated by the observed – for a triplet excited state expected –
oxygen sensitivity of this transient absorption (see Fig. S14). These optical properties might be further
fine-tuned by deliberately designing certain asymmetrically substituted HABs with explicit push-pull
substituents (electron donating and withdrawing groups) in order to allow specific “delayed fluorescence”
applications, e.g., in blue OLEDs.[30]
Conclusion
The results presented here demonstrate that the developed versatile high-yielding metal-free four-step
domino reaction can be used as a key step to access specific asymmetrically substituted HABs in high
overall yield and without involvement of statistical steps. We believe that this efficient domino reaction,
featured by functional group tolerance, modularity, simplicity and scalability, will likely be of great utility
for creating diverse and hitherto inaccessible HAB scaffolds for a wide range of applications. Hence, this
generally applicable synthetic procedure should give access to all possible 60 position isomers for HABs
with six different substituents, as well as to symmetric configurations, when three or more substituents
are equal - including the last six constitution isomers, which are not yet reported to the best of our
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knowledge. Chiral separation of appropriately substituted HABs could also allow to exploit chirality of the
chromophore, e.g. to achieve circularly polarized luminescence.[31]
Data and materials availability
All data supporting the findings of this study are available within the paper or Supplementary Information.
Crystallographic data for compounds 6a, 7, 11, 12, 13, 14 and 15 are available free of charge from the
Cambridge Crystallographic Data Centre under CCDC identifiers 2055879, 2055878, 2055881, 2055884,
2055883, 2055882 and 2055880, respectively (www.ccdc.cam.ac.uk/structures/).
Acknowledgments
S.B.T. thanks Deutsche Forschungsgemeinschaft (DFG) for funding by grants TS87/17-1; TS87/23-1,
and the Solar Technologies go Hybrid (Research Network SolTech) initiative of the Bavarian State
Ministry for Science, Research and Art for research funding. N.J. thanks the Deutsche
Forschungsgemeinschaft (DFG, SFB953) for research grant Nr. 182849149. We acknowledge H. Maid,
C. Placht (FAU) for assistance with NMR-measurements and M. Dzialach, W. Donaubauer (FAU) for
assistance with high-resolution mass spectrometry measurements.
Conflict of interest
The authors declare no conflict of interest.
Keywords: domino reaction, functionalized triarylbenzene, non-statistical synthesis, hexaarylbenzene, aromatic
system
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Entry for the Table of Contents
RESEARCH ARTICLE
B. W. Grau, M. Dill, F. Hampel,
A. Kahnt, N. Jux, S. B. Tsogoeva*
Page No. – Page No.
Four-step domino reaction enables
fully controlled non-statistical
synthesis of hexaarylbenzene with
six different aryl groups
A high yielding and scalable metal-free four-step linear domino reaction results in
functionalized triarylbenzene (TAB) and opens the door for making a broad variety of
synthetically challenging hexaarylbenzene (HAB) molecules with six different aryl
groups.
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