Palladium-Catalyzed Annulation of Internal Alkynes: Direct Access to π-Conjugated Ullazines

Article abstract of DOI:10.1021/acs.orglett.6b01182

A palladium-catalyzed cyclization reaction of 1-(2,6-dibromophenyl)-1H-pyrroles with alkynes has been developed to construct various π-conjugated indolizino[6,5,4,3-ija]quinolones (ullazines) with a reactive functional group tolerance. As illustrative examples, three new ullazine-based sensitizers are synthesized, and the performance of these dyes is examined in DSSC devices, which demonstrates the potential of direct C-H functionalization in the construction of organic optoelectronic materials.

Full text of DOI:10.1021/acs.orglett.6b01182

Letter
pubs.acs.org/OrgLett
Palladium-Catalyzed Annulation of Internal Alkynes: Direct Access to
π‑Conjugated Ullazines
Danyang Wan,† Xiaoyu Li,† Ruyong Jiang,† Boya Feng,† Jingbo Lan,† Ruilin Wang,‡ and Jingsong You*,†
†Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, and State Key Laboratory of
Biotherapy, West China Medical School, Sichuan University, 29 Wangjiang Road, Chengdu 610064, P. R. China
‡College of Materials Science and Engineering, Sichuan University, 29 Wangjiang Road, Chengdu 610064, P. R. China
S
* Supporting Information
ABSTRACT: A palladium-catalyzed cyclization reaction of 1-
(2,6-dibromophenyl)-1H-pyrroles with alkynes has been
developed to construct various π-conjugated indolizino-
[6,5,4,3-ija]quinolones (ullazines) with a reactive functional
group tolerance. As illustrative examples, three new ullazine-
based sensitizers are synthesized, and the performance of these
dyes is examined in DSSC devices, which demonstrates the
potential of direct C−H functionalization in the construction of organic optoelectronic materials.
itrogen-containing polyaromatic hydrocarbons (PAHs)
have been attracting considerable interest owing to their
describing the skeleton synthesis have appeared. The initial
route developed by Balli needs a lengthy series of functional
group transformations.5 Later, Takahashi reported the
chromium-mediated annulation reaction to construct this
polycyclic system from 1-phenylpyrrole and alkynes to shorten
N
potential applications in high-performance electronic devices
such as organic field-effect transistors (OFETs),1 organic
photovoltaics (OPVs),2 and organic light-emitting diodes
(OLEDs).3 Among these various N-doped π-systems,
indolizino[6,5,4,3-ija]quinoline (with the trivial name ullazine)
(Scheme 1), an isoelectronic compound of pyrene, has received
the synthesis steps.6 Recently, Gratzel developed an efficient
̈
synthesis of ullazine core from easily available starting materials
in four steps by utilizing the Furstner cyclization as the key
̈
procedure.4a Almost at the same time, Ren applied the metal-
free Friedel−Crafts intramolecular arylation strategy to access
the ullazine derivative at room temperature.7 Unlike the above-
mentioned methods starting from pyrroles, Nozaki8 and
Scheme 1. Synthesis of Ullazines
Mullen9 independently employed azomethine ylides and
̈
various alkenes or alkynes to synthesize these nitrogen-
containing PAHs though 1,3-dipolar cycloaddition reactions.
Though these methods are efficient and useful, they might
suffer from disadvantages such as tedious synthetic procedures,
uneasily available starting materials, and narrow substrate scope,
which to a certain extent limit the rapid diversification of
ullazines. Thus, the development of more efficient, convenient,
and practical methods to construct this skeleton would open a
window for screening of ullazine-based electronic materials.
Transition-metal-catalyzed direct C−H functionalization
reactions have been significantly developed in recent years,
and various types of cyclic compounds have been obtained
through catalytic C−H annulations with alkynes.10 This
attractive and powerful strategy has been extensively used in
the construction of various PAHs.11 Herein, we describe a
novel palladium-catalyzed C−H cyclization of 1-(2,6-dibromo-
phenyl)-1H-pyrroles with alkynes to construct diverse π-
conjugated ullazines and elucidate the usefulness of this
protocol by applying it in ullazine-based DSSCs.
extensive interest in the photovoltaic field for its excellent
performance as a strong donating group.4 The ullazine core has
a planar 16π-system that can facilitate a strong intramolecular
charge transfer (ICT) and modification of multiple substitution
sites, which indicate a good potential for more optoelectronic
applications. However, facile and versatile methods to ullazines
are extremely rare in the literature, and only a few reports
Received: April 23, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b01182
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
We initiated our investigation by utilizing 1-(2,6-dibromo-
phenyl)-1H-pyrrole (1a) and 1,2-diphenylacetylene (2a) as
model substrates to produce 3,4,8,9-tetraphenylindolizino-
[6,5,4,3-ija]quinoline 3aa (Table 1). Pleasingly, the expected
Scheme 2. Scope of Alkynes
a
Table 1. Optimization of Reaction Conditions
b
entry
catalyst
additive
base
yield (%)
c
c
c
c
c
c
,
,
,
d
1
2
3
4
5
6
7
8
9
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
Pd(OAc)2, L1
Pd(OAc)2, L2
Pd(OAc)2, L3
Pd(OAc)2, L4
Pd(OAc)2, L5
Pd(OAc)2, L6
Pd(OAc)2, L7
Pd(OAc)2, L8
Pd(TFA)2, L5
Pd(TFA)2, L9
Pd(TFA)2, L9
Pd(TFA)2, L9
LiCl
NaOAc
NaOAc
Et3N
7
trace
trace
10
e
LiCl
d
LiCl
LiCl
NaOAc
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
LiCl
10
Y(OTf)3
Y(OTf)3
Y(OTf)3
Y(OTf)3
Y(OTf)3
Y(OTf)3
Y(OTf)3
Y(OTf)3
Y(OTf)3
Y(OTf)3
Y(OTf)3
Y(OTf)3
LiCl
15
27
trace
33
10
11
12
13
14
15
16
17
18
19
trace
24
55
29
13
a
Reaction conditions: 1a (0.25 mmol), 2 (0.75 mmol, 3.0 equiv),
Pd(TFA)2 (0.05 mmol), tBu3P·HBF4 (0.10 mmol), Y(OTf)3 (0.50
mmol), and K2CO3 (0.75 mmol) were stirred in MeCN (2.0 mL) at
120 °C for 24 h under a N2 atmosphere.
trace
70
72
20
f
Y(OTf)3
51
moderate to good yields. tert-Butyl, one of the most commonly
used groups to improve the solubility of PAHs,14 could be
tolerated in this reaction to afford 3ac in a 67% yield. In
particular, the tolerance of the hexyloxy group will be of great
importance to reduce the π−π interaction of ullazines and
facilitate the applications in organic semiconductors (Scheme 2,
3ai).15 Moreover, some reactive functional groups such as
nitrile, ester, and ketone were tolerated in our catalytic system
(Scheme 2, 3ah, 3aj, and 3ak). Unfortunately, heteroaryl-
containing alkynes such as pyridine and thiophene compounds
are not tolerated, and this method is not suitable for
synthesizing asymmetrical compounds.
Subsequently, the scope of this annulation reaction was
extended to various substituted dibromophenylpyrroles
(Scheme 3). It was observed that a variety of functional groups
such as alkyl, alkyloxy, trifluoromethyl, chloro, ester, and nitrile
were tolerated under the optimized conditions (Scheme 3,
3ca,fa−ja). However, the substituent that was installed in the
meta-position on the arene had a negative effect on this
cyclization reaction and slightly reduced the yield (Scheme 3,
3da). An extended π-conjugated ullazine 3ea was obtained in a
good yield when 1-(3,5-dibromo[1,1′-biphenyl]-4-yl)-1H-pyr-
role 1e was utilized as a substrate.
a
The reaction was performed with 1a (0.25 mmol), 2a (0.75 mmol,
3.0 equiv), catalyst (0.05 mmol), ligand (0.10 mmol), additive (0.50
mmol), and base (0.75 mmol) in 2.0 mL of MeCN under a N2
atmosphere. Isolated yield. L1 = 2-(di-tert-butylphosphino)biphenyl,
L2 = tris(2-methoxyphenyl)phosphine, L3 = butyldi-1-adamantyl-
phosphine, L4 = X-phos, L5 = tricyclohexylphosphine, L6 = 2-
(dicyclohexylphosphino)biphenyl, L7 = 1,3-bis(diphenylphosphino)-
propane, L8 = 1,10-phenanthroline, L9 = tri-tert-butylphosphine
tetrafluoroborate. PdCl2(PPh3)2 (10 mol %) was used. N,N-
Dimethylacetamide was used instead of MeCN. Toluene was used
b
c
d
e
f
instead of MeCN. The reaction temperature was 100 °C.
annulation reaction occurred when 10 mol % of PdCl2(PPh3)2
was used as a catalyst and 3.0 equiv of NaOAc as a base (Table
1, entry 1). The solvent and base parameters were next
explored, and the use of MeCN and K2CO3 slightly improved
the yield (Table 1, entries 2−5). Taking consideration of the
vital function of Lewis acid additives in some alkyne-involved
annulations,12 Y(OTf)3 was added to improve the yield of 3aa
to 15% (Table 1, entry 6). It is well-known that catalyst
precursor plays the decisive role in transition-metal-catalyzed
coupling reactions of sp2/sp3 C−H bonds with aryl halides.13
Thus, a variety of catalysts and ligands were screened, and the
best results were obtained when Pd(TFA)2/L9 was used
(Table 1, entries 8−17). In addition, several Lewis acid
additives were screened under the optimized conditions, and
the results were not superior to Y(OTf)3 (Table S1).
Based on the palladium-catalyzed annulation reaction
reported by Larock,16 a plausible mechanism for this trans-
formation is described in Scheme 4. The reaction starts with an
oxidative addition of 1a with Pd(0) to give the intermediate A,
which subsequently reacts with alkyne to afford the palladium-
(II) complex B. This vinylic palladium intermediate then
undergoes a ring-closing reaction via an electrophilic attack on
the C−2 position of pyrrole, forming the monoannulated
product D after reductive elimination. The further annulation
With the optimized conditions now in hand, we next
investigated the substrate scope of this method. As summarized
in Scheme 2, various alkynes with both electron-donating and
electron-withdrawing groups smoothly underwent the cycliza-
tion reaction with 1a, delivering a series of ullazines in
B
DOI: 10.1021/acs.orglett.6b01182
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Scheme 3. Scope of 2,6-Dibromophenylpyrroles
Scheme 5. Synthesis of Ullazine-Based Sensitizers
a
Reaction conditions: 1a (0.25 mmol), 2 (0.75 mmol, 3.0 equiv),
Pd(TFA)2 (0.05 mmol), tBu3P·HBF4 (0.10 mmol), Y(OTf)3 (0.50
mmol), and K2CO3 (0.75 mmol) were stirred in MeCN (2.0 mL) at
120 °C for 24 h under a N2 atmosphere.
Scheme 4. Proposed Catalytic Pathway
Figure 1. Absorption spectra of 5a−c (a) in CH2Cl2 solution (1.0 ×
10−5 M) and (b) on TiO2 film; (c) photocurrent−voltage (J−V) plots
obtained with 5a−c and N719 under simulated AM 1.5G irradiation
(100 mW/cm2); (d) incident photon-to-current efficiency (IPCE)
curves of the DSSCs based on 5a−c and N719.
transmission of an electron from the excited dye to the TiO2
conduction band.17
of D with alkyne through a similar catalytic cycle gives the
desired product 3aa.
The performance of these ullazine-based dyes was then
examined in DSSC devices under simulated AM 1.5G
irradiation (Figure 1). As shown in Table S3, the cell based
on 5a exhibits the lowest conversion efficiency (η) of 2.6% (Jsc
= 6.45 mA cm−2, Voc = 0.635 V, and FF = 0.633), perhaps due
to a low solubility. Thus, we added four alkoxy chains to 5a,
and the η value of 5b-based DSSC was increased to 3.9% (Jsc =
9.06 mA cm−2, Voc = 0.649 V, and FF = 0.663). When the
anchoring group was changed to give 5c as a sensitizer, the
highest power conversion efficiency (η = 6.1%, Jsc = 9.06 mA
cm−2, Voc = 0.649 V, and FF = 0.663) was obtained, and the
incident photon-to-electron conversion efficiency (IPCE) of
5c-based DSSC device shows a broad band in the region of
300−600 nm with a maximum of 70% at 471 nm (Figure 1).
In conclusion, we have developed a facile and efficient
method to construct various π-conjugated ullazines via the
palladium-catalyzed direct C−H cyclization of dibromophenyl-
pyrroles with alkynes. This method is compatible with various
electron-donating groups and electron-withdrawing groups
such as alkyloxy, chloro, ester and nitrile, which could be
Finally, we elucidated the usefulness of the current method
by using it for the synthesis of new ullazine-based sensitizers.
The concise synthesis of 5a, 5b, and 5c could be performed by
the sequential palladium-catalyzed cyclization of dibromophe-
nylpyrrole with alkyne, Vilsmeier−Haak reaction, and Knoeve-
nagel condensation with cyanoacetic acid or rhodanine-3-acetic
acid (Scheme 5).
The absorption spectra of ullazine-based dyes 5a−c in
CH2Cl2 solution and on TiO2 film are displayed in Figure 1.
Both 5a and 5b have a strong absorbance in the range of 400−
550 nm, while the absorption band of 5c is distinctly red-shifted
by >50 nm, indicating an enhanced capacity of light-harvesting.
Subsequently, the ground-state oxidation potential (Eo1/x2) and
HOMO−LUMO transition energy value (E0−0) of each dye
were estimated from cyclic voltammetry (CV) and absorption/
ox
1/2
emission spectra (Table S2 and Figure S1). The E values
range from 0.86−0.96 V vs NHE, which are more positive than
ox
1/2
that of the iodide/triiodide redox shuttle, and the E * values
were calculated to be −1.17 to −1.48 V vs NHE, ensuring the
C
DOI: 10.1021/acs.orglett.6b01182
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
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ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.6b01182.
Detailed experimental procedures, characterization data,
and copies of 1H and 13C NMR spectra of key
intermediates and final products (PDF)
(12) (a) Mamane, V.; Hannen, P.; Furstner, A. Chem. - Eur. J. 2004,
̈
10, 4556. (b) Komeyama, K.; Igawa, R.; Takaki, K. Chem. Commun.
2010, 46, 1748. (c) Shukla, S. P.; Tiwari, R. K.; Verma, A. K. J. Org.
Chem. 2012, 77, 10382.
AUTHOR INFORMATION
Corresponding Author
■
(13) (a) Ackermann, L.; Vicente, R.; Kapdi, A. R. Angew. Chem., Int.
Ed. 2009, 48, 9792. (b) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010,
110, 1147.
*E-mail: jsyou@scu.edu.cn.
Notes
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̈
̈
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2099. (b) Draper, S. M.; Gregg, D. J.; Madathil, R. J. Am. Chem. Soc.
2002, 124, 3486. (c) Wu, J.; Watson, M. D.; Tchebotareva, N.; Wang,
The authors declare no competing financial interest.
Z.; Mullen, K. J. Org. Chem. 2004, 69, 8194. (d) Wang, Z.; Tomovic,
́
̈
̌
Z.; Kastler, M.; Pretsch, R.; Negri, F.; Enkelmann, V.; Mullen, K. J. Am.
̈
ACKNOWLEDGMENTS
■
Chem. Soc. 2004, 126, 7794. (e) Chen, T.-A.; Liu, R.-S. Chem. - Eur. J.
This work was supported by grants from 863 Program
(2013AA031901), the National NSF of China (Nos.
21432005 and 21321061), and the Comprehensive Training
Platform of Specialized Laboratory, College of Chemistry,
Sichuan University.
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DOI: 10.1021/acs.orglett.6b01182
Org. Lett. XXXX, XXX, XXX−XXX