N-Heterocycle-Fused Pentalenes by a Gold-Catalyzed Annulation of Diethynyl-Quinoxalines and -Phenazines

Article abstract of DOI:10.1002/chem.201803096

The gold-catalyzed annulation of diethynyl N-heterocycles for the synthesis of quinoxaline-/phenazine-based pentalenes and the study of their optoelectronic properties are described. The inhibition of the gold catalyst by the nitrogen centers in the subst

Full text of DOI:10.1002/chem.201803096

A Journal of
Accepted Article
Title: N-Heterocycle-Fused Pentalenes by a Gold-Catalyzed Annulation
of Diethynyl-Quinoxalines and -Phenazines
Authors: Kohei Sekine, Fabian Stuck, Jürgen Schulmeister, Thomas
Wurm, Dominik Zetschok, Frank Rominger, Matthias Rudolph,
and A. Stephen K. Hashmi
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10.1002/chem.201803096
Chemistry - A European Journal
N-Heterocycle-Fused Pentalenes by a Gold-Catalyzed Annulation of
Diethynyl-Quinoxalines and -Phenazines
Kohei Sekine,a Fabian Stuck,a Jürgen Schulmeister,a Thomas Wurm,a Dominik
Zetschok,a Frank Rominger,a Matthias Rudolph,a A. Stephen K. Hashmia,b,*
a Dr. K. Sekine, Bc. F. Stuck, B. Mc. J. Schulmeister, Dr. T. Wurm, Mc. D.
Zetschok, Dr. F. Rominger, Dr. M. Rudolph, Prof. Dr. A. S. K. Hashmi
Organisch-Chemisches Institut, Heidelberg University, Im Neuenheimer Feld
270, 69120 Heidelberg, Germany
b Prof. Dr. A. S. K. Hashmi
Chemistry Department, Faculty of Science
King Abdulaziz University, Jeddah 21589, Saudi Arabia
Keywords; gold catalysis, annulation, pentalenes, N-heterocycles, diynes
Abstract
The gold-catalyzed annulation of diethynyl N-heterocycles for the synthesis of
quinoxaline-/phenazine-based pentalenes, and the study of their optoelectronic
properties is described. The inhibition of the gold catalyst by the nitrogen centers
in the substrate and the product could be overcome by increasing the reaction
temperature to 130 °C, which in gold catalysis usually leads to catalyst
decomposition. At 130 °C 6,7-di(arylethynyl)quinoxalines in chlorobenzene at
afford
the
corresponding
pentalenes.
The
annulation
of
2,3-
di(arylethynyl)quinoxalines requires an even higher temperature under
microwave irradiation. The quinoxaline-based pentalenes showed lower LUMO
levels compared to the corresponding naphthalene-based pentalenes.
Introduction
Homogeneous gold catalysis underwent a dramatic development during the last
two decades.[1] Gold catalysts show a mild carbophilic  Lewis acidity and
promote intra-/intermolecular nucleophilic addition reactions onto carbon-carbon
multiple bonds. The alkyne itself can not only act as an electrophile but also as a
nucleophile. For example gold acetylides can react as nucleophiles with -
activated alkynes, giving rise to vinylidene intermediates; non-terminal alkynes
can be reacted with another -activated alkyne to generate vinyl cation
intermediates. Gold-catalyzed domino cyclizations of diynes provide an excellent
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10.1002/chem.201803096
Chemistry - A European Journal
entry towards polycyclic compounds including complicated and/or highly -
conjugated compounds.[2]
Pentalenes attract much interest due to their antiaromatic property. For the
construction of dibenzo[a,e]pentalene structures, various synthetic routes were
developed. For instance, a palladium-/rhodium-catalyzed intermolecular
annulation of alkynes, a B(C6F5)3-mediated cyclization of 1,2-diethynylbenzenes
and anionic or radical anionic trans-annulations.[3] The development of synthetic
methods towards dibenzo[a,e]pentalenes have been accompanied by studies
focusing on their properties and potential application.[4] The optical and
electrochemical properties of dibenzo[a,e]pentalenes are typically tuned by
functional groups on the 5- and 10-position and on the benzene rings. In addition,
heteroaromatic rings fused to the pentalene core have an effect on the properties.
A thiophene moiety was shown to push up the HOMO level while an electron
deficient pyridine moiety decreases the HOMO and LUMO levels.[5]
Dibenzo[a,e]pentalenes show transistor properties especially -extended
derivatives were used as p-type semiconductors;[6] on the other hand, thiophene-
substitued dibenzo[a,e]pentalenes, diacenopentalene dicarboximides and 5,10-
bis(arylalkynyl)-substituted dibenzo[a,e]pentalenes exhibit lower-lying LUMO
levels suitable for n-type semiconductor.[7] From the viewpoint of the lower LUMO
energy, the introduction of quinoxaline/phenazine moieties is attractive because
they typically push down the LUMO level. However, pyrazine
dibenzo[a,e]pentalene derivatives are unknown, the development of a synthesis
of the pentalene motif fused to quinoxaline/phenazine ring is highly desirable. Our
group recently reported the (IPr)Au(NCMe)SbF6-catalyzed annulation of 1,2-
di(arylethynyl)benzenes to produce dibenzo[a,e]pentalene derivatives via a vinyl
cation as key intermediate.[8] Based on that work, we envisioned a gold-catalyzed
convenient synthetic route for quinoxaline-/phenazine-fused pentalenes from
di(arylethynyl)quinoxlines and di(aryl)ethynylphenazines as easily available
precursors. With regard to N-heterocycles such as pyridine and pyrazine in gold
catalysis, the problem is that the coordination of N-heterocycles to the active
cationic gold species typically deactivates the catalysts. Our studies on a gold-
catalyzed annulation to afford quinoxaline-/phenazine-based pentalene
derivatives in high yields are reported in this contribution, accompanied by optical
and electronic property measurements of these new products.
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Scheme 1. Design of a synthesis of quinoxaline-/phenazine-based pentalenes.
2,3-Di(p-methylphenylethyny)quinoxaline 1aa, which was synthesized from
commercially available chemicals in two steps, was used as a model substrate
(Table 1). First, we tested the previous reaction conditions,[8] but the reaction did
not proceed at all with (IPr)AuCl/AgSbF6 in benzene at room temperature (Entry
1). Considering a possible deactivation of the gold catalyst by the coordination of
a pyrazine moiety, the reaction temperature was examined. At 110 °C in
chlorobenzene, the desired pentalene 2aa was produced in 50% yield while 29%
of starting material 1aa still remained (Entry 2). At 130 °C, diyne 1aa was
completely consumed within 16 h and pentalene 2aa was obtained in 82% yield
(Entry 3). The reaction was accelerated under microwave irradiation but the yield
was not significantly improved (Entry 4). In contrast, neither (IPr)AuCl nor AgSbF6
alone promoted the desired reaction, showing that a cationic gold species is
necessary for the annulation (Entries 5 and 6).
Next, the synthesis of a pentalene directly fused to a pyrazine moiety was
investigated. Under the optimized conditions for 1aa, the 6,7-di(p-
methylphenylethyny)quinoxaline 1ba was completely consumed, but only a trace
amount of the desired pentalene 2ba was detected. Fortunately, pentalene 2ba
was produced in 47% yield at 130 °C for 1 h under microwave irradiation. The
rapid and efficient heating by using microwave seems to assist the annulation of
the vinyl cation and the aromatic ring. In the case of (IPr*)AuCl, the yield of the
pentalene reached 89% (Entry 9).
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Table 1. Optimization of the reaction conditions.
Next we explored the substrate scope (Scheme 2). The substituents at
the aromatic moieties of the 2,3-di(arylethynyl)quinoxaline starting materials 1aa-
1af were examined first. The reactions of tBu (1ab) and H (1ac) completed within
16 h at 130 °C giving rise to pentalenes 2ab and 2ac in 85% and 81% yields,
respectively. A brownish single crystal of 2ac was obtained and the connectivity
was unambiguously confirmed by X-ray structural analysis (Figure 1). For
electron donating groups, a MeO-substituted pentalene 2ad produced in 26%
yield, while a Me2N-substituted diyne only gave a complex mixture. A fluoro-
substituted substrate also transferred into the corresponding pentalene 2ae in
moderate yield. The introduction of a benzothiophen ring to the quinoxaline-fused
pentalene is attractive because it is expected that the HOMO level of pentalene
is pushed up and the HOMO-LUMO energy gap becomes smaller.[9] Therefore
the reaction with 2-ethynylbenzothiophene-substituted quinoxaline 1af was
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Chemistry - A European Journal
carried out and the corresponding donor-acceptor-substituted pentalene 2af was
successfully obtained in 24% yield. With regard to the 6,7-
di(arylethynl)quinoxalines, the annulation of the diynes 1bb and 1bc also
proceeded at 130 °C under microwave irradiation delivering pentalenes 2ba and
2bc directly fused to the pyrazine moiety in high yields. For -extened pentalenes,
the annulation of phenazine-substrates 1ca and 1cb were conducted and the
corresponding pentalenes 2ca and 2cb were produced in 95% and 56% yields,
respectively.
Scheme 2. The gold-catalyzed annulation of di(arylethynl)quinoxalines and
phenazines.
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Figure 2. Solid state molecular structure of 2ac. Hydrogen atoms are omitted for
clarity.
We also attempted the reaction of 6-ethynylquinoxaline-substituted
benzene 3a (Scheme 3a). In this case besides the blocking of the catalyst, we
wanted to know if the relatively electron-deficient quinoxaline was also able to
insert into the intermediate vinyl cation. Indeed, under the optimized reaction
conditions the annulation proceeded selectively at the 5-position of the
quinoxaline to afford the corresponding pentalene 4a in 30% yield. Based on
the result with 2-ethynylnaphthalene-substituted benzene 3b to selectively give
the pentalene 4b in high yield (Scheme S1), the selectivity is probably caused
by the steric repulsion of the gold catalyst and the quinoxaline moiety. Inspired
by the above result, we applied the optimized conditions to 6-
ethynylquinoxaline-substituted quinoxaline 1ag (Scheme 3b). The
diquinoxaline-fused pentalene 2ag was obtained in 26% yield.
Et
N
N
N
Et
Et
N
N
Et
Et
N
(IPr)AuCl/AgSbF6
(10 mol %)
Et
N
(a)
PhCl, 16 h, 130 °C
N
N
N
Et
Et
N
N
[Au]
3
4
30% yield
Et
N
N
Et
Et
N
Et
Et
N
N
N
(IPr)AuCl/AgSbF6 (10 mol %)
PhCl, 24 h, 130 °C
Et
(b)
N
N
N
N
Et
Et
N
N
1ag
2ag 26% yield
Scheme 3. The reaction of 6-ethynylquinoxaline-substituted benzene 3 (a) and 6-
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ethynylquinoxaline-substituted quinoxaline 1ag (b).
3000
2500
2000
1500
1000
500
50000
40000
30000
20000
10000
0
2aa (Me)
2ad (MeO)
2ae (F)
2af
0
450
500
550
600
650
700
 (nm)
2ag
300
325
350
375
400
425
450
 (nm)
475
500
525
550
575
600
Figure 2. UV absorption of 2aa, 2ba, 2ad, 2ae, 2af and 2ag.
The optical properties of the pentalenes 2aa, 2ba, 2ca, 2ad, 2ae, 2af, 2ag,
4 were measured by UV/Vis absorption spectroscopy (Figure 2 and S1). The
absorptions at 428 nm and 456 nm of 2aa can mainly be attributed to the
symmetry-allowed HOMO → LUMO+1 and HOMO-1 → LUMO transitions (Table
S2) based on TD-DFT calculations in CH2Cl2. The pentalene 2ba exhibits the
corresponding two peaks at similar wavelengths ( = 424 and 450 nm) than 2aa.
In contrast, the benzothiophene-fused pentalene 2af and diquinoxaline-fused
pentalene 2ag shows a significant bathochromic shift of the wavelengths (2af; 
= 455 and 487 nm, 2ag;  = 440 and 469 nm). Moreover, in the case of pentalen
2af, the absorption of the symmetry-forbidden HOMO → LUMO transitions is
observed at around 567 nm, which is also suggested by TD-DFT calculations.
The HOMO and LUMO levels of 2aa, 2ba, 2ca, 2af, 2ag, 4 were estimated by
cyclic voltammetry in CH2Cl2 and TD-DFT calculations in the gas phase (Table
S1). According to cyclic voltammetry, LUMO levels (2aa; -3.19 eV, 2ba; -3.33 eV,
2ca; -3.26 eV, 2af; -3.33 eV, 2ag; -3.26 eV, 4; -3.15 eV) are lower than in the
corresponding 12-phenylbenzo[4,5]pentaleno[1,2-b]naphthalene 2d (LUMO = -
3.01 eV) (Supporting Information),[10] as expected due to the introduction of a
pyrazine moiety. The benzothiophene moiety contributed strongly to a smaller
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HOMO-LUMO energy gap (Eg) of the pentalene 2af (2aa; Eg = 2.61 eV, 2ba; Eg
= 2.51 eV, 2ca; Eg = 2.61 eV, 2af; Eg = 2.21 eV, 2ag; 2.64 eV, 4; Eg = 2.41 eV).
In conclusion, we developed the synthesis of quinoxaline-/phenazine-based
dibenzo[a,e]pentalenes from the corresponding diynes by gold catalysts. The
reactivity of 6,7-di(arylethynyl)quinoxalines and 2,3-di(arylethynyl)quinoxalines
are significantly different; the annulation of 6,7-di(arylethynyl)quinoxalines
proceeded at high temperature to afford the corresponding pentalenes in good to
high yields, but the reaction of 2,3-di(arylethynyl)quinoxalines requires high
temperature under microwave irradiation. The quinoxaline-based pentalenes
showed lower LUMO levels compared to the corresponding naphthalene-based
pentalene. As the poisoning of gold catalysts by such N-heterocyclic substrates
is a general problem in gold catalysis, the protocol developed here, which is
based on the increased thermal stability of the gold catalysts in the presence of
these catalyst poisons, will certainly be very useful for many researchers in the
field beyond the synthesis of -extended N-heterocycle-fused pentalenes for
material science reported here.
Acknowledgement
The authors are grateful to funding by the DFG (SFB 1249-NHeteropolyzyklen
als Funktionsmaterialien).
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TOC
130 °C
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