Site-selective synthesis of functionalized dibenzo[: F, h] quinolines and their derivatives involving cyclic diaryliodonium salts via a decarboxylative annulation strategy

Article abstract of DOI:10.1039/c8cc00300a

Here we report a site-selective synthesis of functionalized dibenzo[f,h]quinolines and their derivatives, which could be used as OLED materials. The key step is the double cross coupling reaction between the 2-chloropyridinyl acids and the cyclic diaryliodonium salts, where the carboxylic acid was unprecedentedly employed as both a traceless directing group and a functional handle in a one-pot atom- and step-economical process.

Full text of DOI:10.1039/c8cc00300a

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DOI: 10.1039/C8CC00300A
Journal Name
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Site-selective Synthesis of Functionalized Dibenzo[f,h]quinolines
and their derivatives involving cyclic diaryliodonium salts via
Decarboxylative Annulation Strategy
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Shuai Yang,a Wenkai Hua, a Yanqi Wu,b Tao Hu,a Feng Wang, a Xingxian Zhanga,* and Fengzhi
Zhanga,*
www.rsc.org/
Here we report
a
site-selective synthesis of functionalized growing areas of research.9 Previous work has shown that the
dibenzo[f,h]quinolines and their derivatives, which could be used carboxylic acid functionality could be used as either a functional
as OLED materials. The key step is the double cross coupling handle for decarboxylative cross coupling reactions10 or a
reaction between the
2-chloropyridinyl acids and cyclic removable/traceless directing group for direct arene
diaryliodonium salts, and the carboxylic acid was unprecedently functionalization.11 For example, Larrosa,12 Gooßen13 and
employed as both a traceless directing group and a functional Zhou14 reported the biaryl synthesis by coupling of 2-
handle in an one-pot atom- and step- economical process.
chlorobenzoic acids with iodobenzenes, arenediazonium salts
or diaryl iodonium salts respectively under transition-metal
catalysis (Scheme 1a-b). Larrosa also reported the direct
arylation of pyridine carboxylic acids with aromatic halides,15
which gave a mixture of pyridine O-arylated products in some
cases due to the challenge of regioselective C─H
activation/functionalization (Scheme 1c). In all those examples,
the carboxylic acid functionality was used only as a traceless
directing group for the ortho-arene arylation, which was then
removed via protodecarboxylation16 either in situ or by another
extra step. Also the chlorine substituent didn’t react with the
coupling partners and left intact.
Polycyclic aromatic hydrocarbons (PAHs) are regarded as segments
of infinite two-dimensional graphene, and have been extensively
exploited as potential electronic materials.1 Among these,
triphenylenes are the most often synthesized and investigated.2
Compared
with
their
all-hydrocarbon
analogues,
dibenzo[f,h]quinolines and their derivatives which exhibit
unprecedented chemical and physical properties have been far less
studied because of their limited accessibility.3 Previously, the
dibenzo[f,h]quinolines and dibenzo[a,c]acridines were mainly
prepared by thermal electrocyclization starting from the quinone
methides.4 They also could be prepared by the coupling of either
polyaryl carbonyl compounds with nitrogen donors5 or polyaryl
amines with carbonyl compounds.6 In addition, the fused helicenes
could be prepared either by intramolecular [2+2+2] co-
cycloisomerization of aromatic cyanodiynes7 or intramolecular
annulation of biphenyls with alkynes.8 However, there is no general
method for the synthesis of dibenzo[f,h]quinolines and current
available methods suffer from poor substrate scopes and long
synthetic sequence. Therefore, it’s desirable to develop general and
efficient synthetic strategies to access
functionalized
dibenzo[f,h]quinolines and their derivatives, which would bridge the
synthetic organic chemistry and material science.
The use of commercially available carboxylic acids for
transition-metal catalyzed reactions is one of the fastest
a.College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou,
310014, P. R. China. Email: zhangfengzhi@zjut.edu.cn
b.Institute of Information Resource, Zhejiang University of Technology, Hangzhou,
310014, P. R. China.
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
Scheme 1 Acid directed arylation
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In continuation of our research interest in decarboxylative First, we tested various commercially available pyridVinieew AcratircbleoOxnylilnice
cross-coupling reactions17 and cyclic diaryliodonium salt acid derivatives. The simple 2-chloronicotoDnOicI:a1c0i.d10d3e9r/iCv8aCtiCve0s03g0a0vAe
chemistry, 18 we would like to develop a site-selective synthesis the corresponding products in good yields (3a-b). The substrates with
of functionalized dibenzo[f,h]quinolines in an atom and step- either strong electron-donating or withdrawing substituents were
economical way.19 The key step is the unprecedented double effective (3c-d). Fluorine containing substituents such as F or CF3
cross-coupling reaction between the 2-chloropyridinyl acids and were compatible with the reaction conditions (3d-e). Interestingly, for
cyclic diaryliodonium salts, in which the carboxylic acids were the polychlorinated substrates only the chlorine next to the carboxylic
employed as both traceless directing groups and functional acid functionality was reacted (3f-h), which means our catalytic
handles, together with the cyclic diaryliodonium salts20-21 as the system can directly utilize carboxylic acids as directing groups for the
bis-electrophile for the cascade reaction (Scheme 1d).
ortho cross coupling reaction in preference to the strong coordination
of the pyridine nitrogen.15 The site selectivity makes the intact
We initiated the investigation by reacting the commercially
available 2-chloronicotinic acid 1a with cyclic diaryliodonium salt 2a
(Table 1). With Pd(OAc)2 as the catalyst, K2CO3 as the base and DMSO
as the solvent, no desired product 3a was detected (Table 1, entry 1).
By using DMF as the solvent, the product 3a was isolated in 20% yield
(Table 1, entry 2). The yield could be improved to 44% with NMP as
the solvent (Table 1, entry 3). However, by changing the reaction
temperature (Table 1, entries 4-5), the amounts of the cyclic
diaryliodonium salts 2a (Table 1, entries 6-7) and the base (Table 1,
entry 8) there was no any improvement at all. Finally, a catalyst
screening was carried out to optimize the yield (Table 1, entries 9-
12), and it was found that the desired dibenzo[f,h]quinoline 3a could
be obtained in 70% yield with PdCl2 (5 mol %) as the catalyst and
chlorine as
a potential functional handle for the further
transformations. For the substrate with a phenyl group next to the
nitrogen, surprisingly the pyridine directed arene C ─ H
functionalization didn’t happen. The reaction took place site-
selectively to give the dibenzo[f,h]quinoline 3i in 77% yield. The 2-
chloroquinoline-3-carboxylic acid gave the dibenzo[a,c]acridine 3j in
77% yield. The 3-chloroisonicotinic acids worked as well to give the
desired dibenzo[f,h]isoquinolines 3k and 3l in 86% and 64% yields
respectively. However, the yield of dibenzo[f,h]isoquinoxaline (3m)
is quite poor with 3-chloropyrazine-2-carboxylic acid as the substrate
probably because of the high Lewis basicity of the sp2-nitrogen, which
often results in side reactions due to the catalyst coordination and
poisoning.15
o
K2CO3 (2.2 equiv) as the base in NMP at 145 C for 12 h. There is no
1-chlorodibenzo[f,h]isoquinoline 4 detected, which means that this
reaction is highly site selective and no direct C4 pyridine arylation
happened as reported by Larrosa.15
Table 1 Reaction optimizationa
Entry
1
Variation from standard conditions
Pd(OAc)2, DMSO
Yield (%)c
-
2
Pd(OAc)2, DMF
20
44
10
46
30
28
29
-
3
Pd(OAc)2, NMP
4
Pd(OAc)2, 130 oC
5
Pd(OAc)2, 160 oC
6
2a (1.5 equiv), Pd(OAc)2
2a (0.7 equiv), Pd(OAc)2
Pd(OAc)2, Cs2CO3 as base
CuI as catalyst
7
8
9
10
11
12
Pd2(dba)3 as catalyst
PdCl2(dppf) as catalyst
standard
53
45
70
Scheme 2 Site-selective synthesis of dibenzo[f,h]quinolines and
With the optimum conditions in hand, we next examined the scopes
of this novel decarboxylative cyclization cascade sequence (Scheme 2).
derivatives
2 | J. Name., 2012, 00, 1-3
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Then a range of substituted cyclic diaryliodonium salts were
COMMUNICATION
In order to demonstrate that our cyclized dibenzo[f,h]quinoline
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prepared according to Olofsson’s method and subjected to the products could be converted into diversifiedDvOalIu: 1a0b.l1e03b9u/iCld8iCnCg0b0lo3c0k0sA,
optimized reaction protocol.22 For the symmetrical cyclic we managed to introduce other functional groups or handles to the
diaryliodonium salts the reactions gave the corresponding products framework by site selective direct C─H functionalization (Scheme 4).
in good yields (3n-q). However, the reaction of 2-chloronicotonic acid Treated dibenzo[f,h]quinoline 3a with the copper-catalyzed
with asymmetrical cyclic diaryliodonium salts afforded an condition with oxygen as the oxidant in tetrachloroethane at 130 oC
inseparable mixture of products (3r/3rʼ and 3s/3sʼ).
gave the chlorinated product 6 in 82% yield.26 With NBS as the
oxidant under Pd-catalyzed conditions, a C─Br bond can be
constructed in good yield to give product 7.27 Finally, by a
dehydrogenated cross coupling,28 the dibenzo[f,h]quinoline 3a
reacted with o-xylene under palladium catalysis affording the
arylated product 8 in moderate yield.
With the dibenzo[f,h]quinoline products in hand, we would like to
demonstrate that they can be further site selectively functionalized
by directed Pd-catalyzed C─H activation/functionalization methods
(Scheme 3),23 which would open a door for the rapid access to various
dibenzo[f,h]quinoline derivatives. Although there are some
examples for the direct C─H functionalization of PAHs,24 to our
knowledge the direct oxygenation of the dibenzo[f,h]quinolines has
never been reported. Firstly, we would like to introduce a hydroxyl
or acetate group to the framework inspired by Sanford’s method.25
With Pd(OAc)2 as the catalyst, PhI(OAc)2 as the oxidant, the simple
dibenzo[f,h]quinolines gave the hydroxylated products in moderate
to good yields (5a-d). For the other substrates, the acetoxylated
products were formed. The halogen groups such as F or Cl were
tolerated under the reaction conditions (5e-h). The reactions with
substrates bearing either strong electron- donating or withdrawing
substituents afforded the acetated products in moderate yields (5i-
j). By changing the solvent to MeOH or CF3CH2OH, a methoxy or
CF3CH2O group could be introduced to the skeleton in 89% and 90%
yield respectively (5k and 5l).
Scheme 4 Directed site-selective C─H halogenation and arylation of
dibenzoquinolines
In summary, with readily available pyridine carboxylic acids and
cyclic diaryliodonium salts as the starting materials we have
developed an unprecedented site-selective synthesis of
dibenzo[f,h]quinolines and their derivatives, which can be further
functionalized site-selectively to afford diversified building blocks for
material chemistry. The key for this novel method is the employment
of carboxylic acids as both directing groups and functional handles,
together with the cyclic diaryliodonium salts as the bis-electrophile
for this one-pot double cross-coupling reaction.
Acknowledgements
This research was supported by Zhejiang Provincial Natural Science
Foundation of China for Distinguished Young Scholars under grant No.
LR15H300001. We also thank the Zhejiang Provincial Thousand-
Talent Program and Zhejiang University of Technology for financial
support.
Scheme
dibenzo[f,h]quinolines
3
Directed
site-selective
oxygenation
of
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Conflicts of interest
There are no conflicts to declare.
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DOI: 10.1039/C8CC00300A
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DOI: 10.1039/C8CC00300A
Site-selective Synthesis of Functionalized Dibenzo[f,h]quinolines and their derivatives
involving cyclic diaryliodonium salts via Decarboxylative Annulation Strategy
Shuai Yang,a Wenkai Hua, a Yanqi Wu,b Tao Hu,a Feng Wang, a Xingxian Zhanga,* and Fengzhi
Zhanga,*
An unprecedented site-selective synthesis of dibenzo[f,h]quinolines and their derivatives was
reported via an acid directed decarboxylative annulation cascade