Intramolecular Oxidative Arylations in 7-Azaindoles and Pyrroles: Revamping the Synthesis of Fused N-Heterocycle Tethered Fluorenes

Article abstract of DOI:10.1002/chem.201604192

We revealed intramolecular oxidative arylations in 7-azaindoles and pyrroles that, for the first time, provided direct access to 7-azaindole- or pyrrole-fused isoindolines and tetrahydroisoquinolines. In addition, N-benzylation of 7-azaindoles or pyrroles with sterically hindered sec-benzyl alcohols by Mitsunobu reaction followed by intramolecular oxidative arylation allowed access to chiral congeners of fused isoindolines that have little precedence. A new opportunity in the design and synthesis of fluorene-based organic emitters is demonstrated in the preparation of novel fused N-heterocycle tethered fluorenes, including a chiral fluorene architecture.

Full text of DOI:10.1002/chem.201604192

A Journal of
Accepted Article
Title: Intramolecular Oxidative Arylations in 7-Azaindoles and Pyrroles:
Revamping the Synthesis of Fused N-Heterocycle Tethered
Fluorenes
Authors: Joydev K. Laha, Rohan Bhimpuria, and Mandeep Hunjan
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.201604192
Link to VoR: http://dx.doi.org/10.1002/chem.201604192
Supported by

10.1002/chem.201604192
Chemistry - A European Journal
FULL PAPER
Intramolecular Oxidative Arylations in 7-Azaindoles and Pyrroles:
Revamping the Synthesis of Fused N-Heterocycle Tethered
Fluorenes
Joydev K. Laha,* Rohan A. Bhimpuria, and Mandeep Kaur Hunjan
Abstract: The report unveils intramolecular oxidative arylations in 7-
benzylic oxidation, is also feasible. The designed targets could
be prepared by Suzuki reaction of the commercially available
9,9-dioctyl-9H-fluorene-2,7-diboronic acid bis(pinacol) ester and
fused isoindolines containing a preinstalled halogen.
azaindoles and pyrroles for the first time providing a direct access to
7-azaindoles
or
pyrroles
fused
isoindolines
and
tetrahydroisoquinolines. In addition, N-benzylation of 7-azaindoles or
pyrroles with sterically hindered sec-benzyl alcohols by Mitsunobu
reaction followed by intramolecular oxidative arylation allowed
access to chiral congeners of fused isoindolines that have rare
literature precedence. A new opportunity in the design and synthesis
of fluorene based organic emitters is demonstrated in the
preparation of novel fused N-heterocycle tethered fluorenes
including a chiral fluorene architecture.
However, the preparation of these newly designed organic
materials could present excessive challenge, as halo-substituted
7-azaindole or pyrrole fused isoindolines have rarely been
synthesized. As the retrosyntheic analysis reveals, the halo-
Introduction
The growing utilization of fused nitrogen heterocycles in the
synthesis of single fluorene based organic fluorescent materials
for potential use in organic light emitting devices (OLEDs) has
become a current trend of research in organic electronics.[1]
Many single fluorene molecule based organic emitters currently
available fall short of desirable properties, namely, a specific
emission, high charge-carrier mobility, good thermal and
electrochemical stability, high photoluminence quantum yield,
and facile chemical modification.[2] The attenuation of several
desirable properties is improved in many folds by tethering a
fused nitrogen heterocycle onto the fluorene backbone (Scheme
1). [3]
Scheme 1. Retrosynthetic Design of Fused N-Heterocycle Tethered Fluorenes.
Structurally related 7-azaindole, indole, and pyrrole fused
isoindolines possess electronic properties that significantly differ
from one to the other by virtue of the electronic properties of the
nitrogen heterocycle fused with isoindolines, with pyrrole being
the most electron-rich and 7-azaindole being the electron-
deficient. [4] While the synthesis of indole fused isoindolines and
their use in materials sciences are self-evident, [5] the related 7-
azaindole or pyrrole fused isoindolines appears to be captive for
similar applications.[6] Indeed, 7-azaindole or pyrrole fused
isoindolines incorporated into the fluorene backbone could lead
to extensive designing of new fluorescent organic materials
(Scheme 1). A blueprint of fluorene architecture that has a
substituent at the benzylic position, largely to stop adventitious
substituted fused isoindolines could, in principle, be obtained
either by regioselective halogenation of the corresponding fused
isoindolines, or intramolecular oxidative arylation in 7-azaindoles
or pyrroles containing a preinstalled halogen. 7-Azaindole or
pyrrole fused isoindolines have traditionally been synthesized
using transition metal-catalyzed intramolecular direct or cross
coupling reactions. [7] Although a few reports of intramolecular
oxidative couplings including a pioneering study by Greaney et
al., [8d] largely in 3-substituted indoles yielding medium ring fused
indoles, and subsequently by Bao, [8c] Guo, [8b] and DeBoef [8a] in
benzimidazoles and purines affording benzimidazole fused
isoindolines are available, they are limited to the nitrogen
heterocycles that have a substituent[8d] or nitrogen[8a-c] at the 3-
position, and perhaps more importantly, lacking demonstration
of the preparation of a halogen-installed fused isoindolines. The
underlying difficulties of implementing an intramolecular
oxidative arylation in 7-azaindoles and pyrroles could explain the
lack of literature precedence.
Dr. J. K. Laha, R. A. Bhimpuria and M. K. Hunjan
Department of Pharmaceutical Technology (Process Chemistry)
National Institute of Pharmaceutical Educational and Research (NIPER),
S.A. S. Nagar, Mohali- 160062
E-mail: jlaha@niper.ac.in
Based on this thematic background, we embarked on an
objective aimed at developing an intramolecular oxidative
arylation in 7-azaindoles and pyrroles that could meet the
Supporting information for this article is given via a link at the end of the
document.
This article is protected by copyright. All rights reserved.

10.1002/chem.201604192
Chemistry - A European Journal
FULL PAPER
preparative challenges of newly designed organic materials. The
underlying challenges in developing an intramolecular oxidative
coupling in 7-azaindoles and pyrroles would include: a) limited
literature precedence for regioselective halogenations in 7-
azaindoles,[9a] especially at the 3-position, b) untoward
intermolecular reaction,[8a] dehalogenation,[7d,9b] or potential
oxidation at the benzylic position[7d] that could occur during
intramolecular oxidative arylations in 7-azaindoles or pyrroles
containing a preinstalled halogen, and c) ability of pyridine
nitrogen in 7-azaindoles to co-ordinate with palladium.[10] To
resolve the cumulative challenge, the following measure were
taken into consideration: a) regioselective bromination of 7-
azaindoles under a mild condition, b) a judicious choice of
oxidant that could selectively effect intramolecular oxidative
arylation without affecting the benzylic position, c) a high acid
concentration could largely suppress the nucleophilicity of
pyridine nitrogen, and d) a careful choice of the acid to avoid any
potential reaction of the nucleophilic carboxylate anion.
Leveraging our previous experiences on oxidative C−C bond
formation in the synthesis of biaryl sultams,[11] heterobiaryl
sultams, [12] 4-azafluorenones, [13] carbazoles and α-carbolines, [14]
and C-2 arylated heterocycles,[15] we surmised that an
intramolecular oxidative arylation in 7-azaindoles and pyrroles
while an ambitious objective would be a distinct, straightforward
gateway to the synthesis of fused isoindolines. Herein, we
describe intramolecular oxidative arylations in 7-azaindoles and
pyrroles providing a direct access to 7-azaindoles or pyrroles
fused isoindolines including fused isoindolines containing a
stereocenter α to nitrogen and tetrahydroisoquinolines. The
pivotal to the success with oxidative arylations was a critical acid
concentration. The preparation of fused N-heterocycle tethered
fluorenes including a chiral fluorene is also demonstrated
warranting broad application of this protocol.
as enumerated are: a) debromination of 1 or 2 did not occur
under the optimized conditions, b) the nucleophilicity of pyridine
nitrogen is largely suppressed in the presence of high acid
concentrations avoiding catalyst poisoning, c) any product
corresponding to benzylic oxidation was not observed.
Next, we investigated the scope of substituted 7-azaindoles
and pyrroles that could participate in the intramolecular oxidative
arylation (Scheme 2). The preparation of starting substrates 3-
Table 1. Optimization Study[a]
Entry
1[c]
Catalyst
Oxidant
AgOAc
AgOAc
AgOAc
Acid
Solvent
-
%2[b]
37
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PivOH
PivOH
PivOH
2[c]
MeCN
00
3[c]
DMF/
00
DMSO
4[c] ,[d]
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(PPh3)4
AgOAc
AgOAc
AgOAc
K2S2O8
AgOAc
PivOH
PivOH
AcOH
PivOH
PivOH
DCE
00
69
21
00
57
5
6
7
8
[a]
-
-
-
-
Substrate (0.25 mmol), catalyst (10 mol%), oxidant (3 equiv),
solvent (4 mL), 130 oC, 12 h; [b] Isolated yield; [c] PivOH (2 mL), other
solvent, (if any, 2 mL) for entries 2-4; [d] Temp. 90 oC.
Results and Discussion
Our initial investigation was largely focused on identifying a
reaction condition that could effect intramolecular cyclization of
5-bromo-N-benzyl-7-azaindole (1) lacking a 3-substituent to
11 that participated in the intramolecular cyclization is detailed in
the Supporting Information. During the preparation of starting
materials, a regioselective bromination of 7-azaindole 3 and
pyrrole 9a was developed under mild conditions, which
furnish 7-azaindole fused isoindolines
2 under oxidative
conditions. Thus, when 1 was heated in the presence of
Pd(OAc)2 (10 mol%), AgOAc (3 equiv), and PivOH (125 mM) at
130 °C for 12 h, compound 2 was isolated, however, only in 37%
yield (Table 1, entry 1). The intramolecular cyclization when
performed in a mixture of PivOH and other solvent, e.g., MeCN,
DMF, DMSO, or DCE at higher dilution proved to have a
deleterious effect as no product formation was observed in any
case (entries 2-4). To our delight when PivOH was used as the
only solvent (625 mM), 2 was obtained in 69% isolated yield
(entry 5). The other acid such as acetic acid had adverse effect
in the reaction (entry 6). A stronger oxidant such as K2S2O8 did
not give any product (entry 7). A palladium (0) catalyst was less
effective (entry 8). Central to this investigation was the
observation that a high pivalic acid concentration in the reaction
medium was essential for successful intramolecular oxidative
arylation. The key features of intramolecular oxidative arylations
produced 3-bromo-7-azaindole
5 and 9b, respectively, in
excellent yields. 7-Azaindoles and C-2 substituted pyrroles
containing various electron-donating or -withdrawing groups
were viable substrates and reacted eventfully yielding diversely
substituted fused isoindolines 12-20. However, unsubstituted N-
benzylpyrrole (11a) or pyrrole containing an electron donating C-
2 substituent (for example, 11b) did not give the corresponding
intramolecular cyclization products 20a-20b under optimized
conditions. Notably, compatibility of the functional groups such
as aryl, halogen, -OMe, -CHO, CO2Me, CF3, etc. used in this
study is noteworthy. A mixture of regioisomers was obtained
when azaindole 8 was subjected to the optimized conditions.
The major regioisomer was formed in the intramolecular
cyclization occurred at the para-position of OMe group.
This article is protected by copyright. All rights reserved.

10.1002/chem.201604192
Chemistry - A European Journal
FULL PAPER
Bromination of compounds 12 and 18a using the mild conditions
described above gave compounds 14 and 18b demonstrating
the versatility of the brominating agent used in this study.
Notably, the regioselective bromination of fused isoindolines was
previously unknown. Although the compounds 14 and 18b were
preparaed from 12 and 18a, respectively, the brominated
heterocycles 5 and 9b could potentially serve as precursors to
them. It is important to note here that a bromo group in
compounds 14 and 18b could serve as synthetic handle for
further functionalizations. Taken together, only a few of these
fused isoindolines are available in literature, which have been
prepared using prefunctionalized substrates via direct arylation
or cross-coupling reactions. Distinct from the current literature,[8]
our protocol does not require any C-3 substituent in nitrogen
heterocycles.
Next, we investigated the synthesis of N-heterocycle fused
chiral isoindolines that have poor literature precedence.[7e]
Perhaps most importantly, their preparation using intramolecular
oxidative coupling has not hitherto been reported. This prompted
us to explore their synthesis under the optimized conditions. The
starting substrates for intramolecular cyclizations were prepared
from the corresponding nitrogen heterocycles via Mitsunobu
reaction, which readily installed a stereocenter α to nitrogen.
Reaction of 7-azaindoles or 2-trichloracetylpyrrole with an
optically pure sec-benzyl alcohol under Mitsunobu condition
gave the products either ready for intramolecular cyclization, or
further functionalization followed by cyclization. The optical
purity of the N-alkylated 7-azindole 24, obtained after Mitsunobu
reaction, was assessed by chiral HPLC. For this purpose,
Mitsunobu reaction of 7-azaindole 24 and racemic sec-alcohol
was performed. A method was developed to resolve the
enantiomers in the racemic maixture. It was found that the 7-
azindole 24 obtained in our study showed only one peak (see
ESI). Notably, such Mitsunobu reactions of 7-azaindoles are
currently unavailable in the literature. So, when 24-28 were
subjected to the optimized condition, all of them reacted
smoothly to deliver the cyclized products 29-32 in good to
excellent yields (Scheme 3). Pivotal to this study was unveiling
intramolecular oxidative arylations in 7-azaindoles and pyrroles
yielding chiral fused isoindolines with a defined stereocenter.
7-Azaindole or pyrrole fused tetrahydroisoqunolines are
important class of nitrogen heterocycles exhibiting diverse
biological profiles.[16] These compounds have invariably been
synthesized by direct arylations using prefunctionalized
substrates.[17]
R1
R1
Pd(OAc)2 (10 mol%)
AgOAc (3 equiv)
N
R2
N
R2
N
PivOH (625 mM)
130 oC, 12 h
N
3-11
12-20
R
R
N
N
N
N
R = H
R = Ph 4
3
R = H, 12 (73%)
13
R = Ph,
(66%)
R
R
N
N
N
N
R = H 12
oxone, NaBr,
CH3NO2, rt
R = H 3
R = Br 5
oxone, NaBr,
CH3NO2, rt
R = Br 14 (42%)
(S)-Phenylethanol (1.1 equiv)
PPh3 (1.3 equiv)
X
Pd(OAc)2 (10 mol%)
AgOAc (3 equiv)
X
X
R
R
D BAD (1.35 equiv)
t
N
N
N
PivOH (625 mM)
130 oC, 12 h
N
N
THF, rt, 12 h
N
N
N
N
H
N
21-23
24-28
29-32
R = Cl, 15 (76%)
R = CF3, 16 (47%)
R = Cl
R = CF3
6
7
Br
Br
N
N
N
N
OMe
N
29 (75%)
24 (75%)
N
N
N
OMe
X
Ph
2-OMe, 17a (52%)
17b
8
N
4-OMe,
(19%)
N
N
N
Suzuki
coupling
X = Br (24)
30 (79%)
N
N
X = Ph (25), 77%
R
R
R = CHO, 9a
R = CO2Me, 10
R = CHO, 18a (79%)
R = CO2Me, 19 (67%)
N
N
N
N
R
R
26 (29%)
31 (85%)
N
N
OHC
OHC
N
N
R
MeO2C
R = H 18a
R = H 9a
R = Br 9b
oxone, NaBr,
CH3NO2, rt
oxone, NaBr,
CH3NO2, rt
R = COCCl3, 27 (43%)
R = CO2Me, 28 (95%)
32 (55%)
K2CO3,
MeOH
R = Br 18b (88%)
Scheme 3. Fused Isoindolines with a Defined Stereocenter.
N
N
R
R
R = H, 11a
R = CH2OCH3, 11b
R = H, 20a (0%)
R = CH2OCH3, 20b (0%)
To demonstrate further generality of our protocol, N-alkyl 7-
azaindole 33 and pyrrole 34 were exposed to the optimized
conditions. The intramolecular oxidative arylations occurred
Scheme 2. Substrate Scope for Intramolecular Oxidative Cyclization.
This article is protected by copyright. All rights reserved.

10.1002/chem.201604192
Chemistry - A European Journal
FULL PAPER
smoothly
both
in
33
and
34
affording
fused
The photoluminescence spectra of these fluorenes are provided
in the Supporting Information. The detailed photophysical
properties of these organic materials will be reported elsewhere.
This preliminary study could open a new avenue for the
preparation of single fluorene based fluorescent organic
materials for potential use in OLEDs.
tetrahydroisoquinolines 35 and 36 in 88 and 81% yields,
respectively (Scheme 4).
Conclusions
In conclusion, we have developed a novel approach for the
intramolecular oxidative arylations in 7-azaindoles and pyrroles
providing a direct access to 7-azaindoles or pyrroles fused
isoindolines and tetrahydroisolquinolines. The high acid
concentration in the reaction medium was the key to the
successive development of the protocol. Reaction of 7-
azaindoles or pyrroles and sterically hindered optically pure sec-
benzyl alcohols under Mitsunobu condition followed by
intramolecular oxidative arylation of N-benzyl-7-azaindoles or
pyrroles allowed access to optically pure novel fused
isoindolines. A new opportunity in the design and synthesis of
single fluorene based organic emitters is demonstrated in the
preparation of fused N-heterocycle tethered fluorenes. The
detailed photophysical properties of these organic materials are
currently under investigation.
Scheme 4. Synthesis of Fused Tetrahydroisoquinolines.
Thus, our protocol is clearly distinct from the literature protocols
in terms of general applicability warranting preparation of both
fused isoindolines and tetrahydroisoquinolines.
To demonstrate a translational application of our newly
developed protocol, we prepared fluorene based organic
molecules 38-41 tethered with fused isoindolines 2, 14, 18b, and
29. Thus, reaction of 2, 14, 18b, or 29 and 9,9-dioctyl-9H-
fluorene-2,7-diboronic acid bis(pinacol) ester (37) under Suzuki
conditions gave novel fused N-heterocycle tethered fluorenes
38-41 (Scheme 5). The fluorene backbone is tethered with a
fused heterocycle either at 3- or 5-position of the heterocycle.
More importantly, the successful preparation of the designed
fluorenes including a chiral fluorene architecture not only
features their novelty, but also augurs a strong impetus towards
finding their applications in OLEDs.
Experimental Section
General procedure for palladium catalyzed intramolecular oxidative
coupling
To an oven-dried schlenk tube was charged with 7-azaindole/pyrrole
substrate (0.25 mmol), Pd(OAc)2 (10 mol%), AgOAc (3 equiv) and
Pivalic acid (4 mL). Reaction mixture was then heated at 130 oC for 12 h.
Following which it was cooled to room temperature and saturated
solution of sodium carbonate (20 mL) was added. It was then extracted
with EtOAc (2 x 20 mL), organic layer was concentrated under reduced
pressure followed by chromatography [silica, EtOAc-hexanes = 2:8 ~
2.5:8.5] to give cyclized product in good yields.
2, 14, 18b, or 29
Bpin
Bpin
Pd2(dba)3 (2 mol%)
X-Phos (3 mol%)
K3PO4 (6 equiv)
Dioxane/water
100 oC, 12 h
H3C(H2C)7H2C CH2 (CH2)7CH3
37
General procedure for Suzuki coupling for the synthesis of 38-41
N
N
37 (0.1 mmol), Substrate 2, 14, 18b or 29 (2.2 equiv), Pd2(dba)3 (2 mol%),
X-Phos (3 mol%) and K3PO4 (6 equiv) in 1,4-dioxane:water (4 mL, 3:1
mixture) was heated at 100 oC for 12 h. The reaction mixture was allowed
to cool to room temperature, diluted with EtOAc (5 mL) and was
concentrated under vacuum. The residue product was purified by silica
gel column chromatography (hexane/EtOAc, 96:4) to give 38-41 in good
yield.
N
N
N
N
N
N
H3C(H2C)7H2C CH2(CH2)7CH3
H3C(H2C)7H2C CH2(CH2)7CH3
38 (44%)
39 (53%)
CH3
H3C
General Procedure for N-benzylation of 7-azaindoles and pyrroles
N
N
N
N
N
N
CHO
OHC
Following a literature procedure[15], a dried round bottom flask equipped
with a magnetic stirrer bar was charged with 7-azaindole/pyrrole (2
º
mmol) and THF (5 mL). The reaction mixture was cooled down to 0 C
H3C(H2C)7H2C
CH2(CH2)7CH3
H3C(H2C)7H2C CH2(CH2)7CH3
and NaH (1.2 equiv) was added. After that alkyl halide (1.2 equiv) was
added and continued the stirring for 4-6 h. After completion of the
reaction it was quenched with water (10 mL) and was extracted with ethyl
acetate (3 x 20 mL). The combined organic layer was dried over Na2SO4
41 (79%)
40 (45%)
Scheme 5. Preparation of Novel Fused N-heterocycle Tethered Fluorenes.
This article is protected by copyright. All rights reserved.

10.1002/chem.201604192
Chemistry - A European Journal
FULL PAPER
and the solvent was removed under reduced pressure followed by
chromatography [silica, EtOAc-hexanes 0.1:9.9 0.5:9.5] gave
corresponding N-alkylated heterocycle in good yields.
4H), 7.75-7.73 (m, 4H), 7.62 (d, J = 7.3 Hz, 2H), 7.43-7.33 (m, 4H), 7.19-
7.16 (m, 2H), 5.36 (s, 4H), 2.17-2.13 (m, 4H), 1.15 (m, 12H), 0.78 (t, J =
6.5 Hz, 6H); 13C NMR (CDCl3): δ 151.4, 142.9, 142.4, 139.6, 132.7,
132.4, 128.5, 128.0, 127.7, 124.0, 123.3, 121.4, 120.0, 116.2, 108.6,
55.3, 47.7, 40.8, 31.8, 30.3, 29.4, 29.4, 24.2, 22.5, 14.0; HRMS (ESI) m/z
calcd for C59H63N4 [M+H]+ 827.5053, found 827.5055.
=
~
General procedure for Regioselective Bromination of 3, 12, 18a,
19[18]
To an oven dried round bottom flask equipped with magnetic stir bar was
charged with 3, 9a, 12, or 18a (1 mmol), NaBr (1.1 equiv) and oxone®
(1.2 equiv) and then nitromethane (2 mL) was added. Reaction mixture
was allowed to stir 20 min- 24 h depending on substrate to give
corresponding C-3 brominated products 5, 11, 14 and 18b in good to
moderate yields.
Acknowledgements
We greatly appreciate the Science & Engineering Research
Board (SERB) of DST, New Delhi for financial support. RAB
thanks the UGC, New Delhi for a research fellowship.
General procedure for MItsunobu reaction[7e]
Keywords: Intramolecular oxidative coupling • 7-Azaindoles •
Following a literature procedure2, an oven-dried round bottom flask
equipped with a magnetic stir bar was charged with 7-azaindole/pyrrole
substrate (1 mmol) and triphenylphosphine (1.3 equiv), following which
nitrogen was flushed three times and anhydrous THF (3 mL) was added.
Then, (S)-phenylethanol (1.1 equiv) dissolved in anhydrous THF (2 mL)
was added dropwise under nitrogen atmosphere. Then, Di-tert-
butylazodicarboxylate (DtBAD) (1.35 equiv) dissolved in anhydrous THF
(2 mL) was added under nitrogen atmosphere. Then, reaction was
allowed to continue overnight. After that, diethyl ether was added and
reaction mixture was stirred for 1 hr which was then filtered and filtrate
was concentrated under reduced pressure followed by chromatography
[silica, EtOAc-hexanes = 0.1:9.9 ~ 0.5:9.5] gave corresponding N-
alkylated heterocycle in good yields.
Fluorene based organic materials • pyrroles • Arylations
[1] a) A. C. Grimsdale, K. L. Chan, R. E. Martin, P. G. Jokisz, A. B.
Holmes, Chem. Rev. 2009, 109, 897-1091; b) C. G. Zhen, Z. H.
Chen, Q. D. Liu, Y. F. Dai, R. Y. C. Shin, S. Y. Chang, J. Kieffer,
Adv. Mater. 2009, 21, 2425-2429; c) J. Hongji, W. Junhua, H. Wei,
Sci. China Ser. B-Chem. 2008, 51, 497-520.
[2] S. Y. Cho, A. C. Grimsdale, D. J. Jones, S. E. Watkins, A. B.
Holmes, J. Am. Chem. Soc. 2007, 129, 11910-11911.
[3] a) I. Osken, A. S. Gundogan, E. Tekin, M. S. Eroglu, M. Ozturk,
Macromolecules 2013, 46, 9202-9210; b) P. Shih, C. L. Chiang, A.
K. Dixit, C. K. Chen, M. C. Yuan, R. Y. Lee, C. T. Chen, E. W. G.
Diau, C. F. Shu, Org. Lett. 2006, 8, 2799-2802; c) K. T. Wong, Y.
M. Chen, Y. T. Lin, H. C. Su, C. C. Wu, Org. Lett. 2005, 7, 5361-
5364.
Characterization Data for selected compounds
[4] a) J. A. Joule, K. Mills, in Heterocyclic Chemistry, Ed: 4 Wiley-
Blackwell, 2013, pp 233-309; b) J. Y. Merour, B. Joseph, Curr. Org.
Chem. 2001, 5, 471-506.
10H-Pyrido[3', 2':4,5]pyrrolo[2,1-a]isoindole (2)
[5] a) A. P. Kozikowski, D. Ma, Tetrahedron Lett. 1991, 32, 3317-
3320; b) R. Faust, P. J. Garratt, R. Jones, L. K. Yeh, A. Tsotinis, M.
Panoussopoulou, T. Calogeropoulou, M. T. Teh, D. Sugden, J.
Med. Chem. 2000, 43, 1050-1061; c) L. C. Campeau, P.
Thansandote, K. Fagnou, Org. Lett. 2005, 7, 1857-1860; d) T. S. A.
Heugebaert; B. I. Roman, C. V. Stevens, Chem. Soc. Rev. 2012,
41, 5626-5640.
º
Brownish solid, (48 mg, 69%). mp 177-178 C; IR (ATR, cm-1): 2930,
1
1591, 1331, 1100; H NMR (CDCl3): δ 8.28 (s, 1H), 8.03 (d, J = 1.9 Hz,
1H), 7.75 (d, J = 7.4 Hz, 1H), 7.53(d, J = 7.4 Hz, 1H), 7.47-7.38 (m, 2H),
6.52 (s, 1H), 5.19 (s, 2H); 13C NMR (CDCl3): δ 145.7, 143.8, 142.6, 141.9,
131.8, 131.1, 128.3, 128.3, 126.9, 123.9, 121.4, 111.6, 89.2, 48.0; HRMS
(ESI) m/z calcd for C14H10BrN2 [M+H]+ 285.0027, found 285.0022.
[6] a) F. Baert, C. Cabanetos, M. Allain, V. Silvestre, P. Leriche, P.
Blanchard, Org. Lett. 2016, 18, 1582-1585; b) S. M. Min Su
Park, D. H. Choi, B. S. Lee, J. Y. Jun Yeob Lee, J. Mater. Chem.
2012, 22, 3099-3104; c) Q. Li, J. Zou, J. Chen, Z. Liu, J. Qin, Z. Li,
Y. Cao, J. Phys. Chem. B 2009, 113, 5816-5822.
(R)-3-Bromo-10-methyl-10H-pyrido[3',2'4,5] pyrrolo[2,1-a]isoindole
(29): Colorless liquid, (56 mg, 75%); Specific rotation [α]589 = -56; IR
1
(ATR, cm-1): 2923, 1450, 878, 741; H NMR (CDCl3): δ 8.30 (d, J = 2.0
Hz, 1H), 8.05 (d, J = 2.1 Hz, 1H), 7.75 (d, J = 6.9 Hz, 1H), 7.49-7.39 (m,
3H), 6.51 (s, 1H), 5.52 (q, J = 6.7 Hz, 1H), 1.88 (d, J = 6.7 Hz, 3H); 13C
NMR (CDCl3): δ 149.5, 148.0, 144.6, 144.0, 142.6, 130.9, 130.9, 128.3,
127.2, 123.0, 121.3, 111.6, 89.0, 56.7, 19.8; HRMS (ESI) m/z calcd for
C15H12BrN2 [M+H]+ 299.0184, found 299.0179.
[7] For review, see: a) S. H. Cho, J. Y. Kim, J. Kwak, S. Chang, Chem.
Soc. Rev. 2011, 40, 5068-5083; b) I. V. Seregin, V. Gevorgyan,
Chem. Soc. Rev. 2007, 36, 1173-1193. Also see: c) S. E. Kazzouli,
J. Koubachi, N. E. Brahmi, G. Guillaumet, RSC Adv. 2015, 5,
15292-15327; d) J. K. Laha, N. Dayal, S. Singh, R. Bhimpuria, Eur.
J. Org. Chem. 2014, 5469-5475; e) J. K. Laha, G. D. Cuny, J. Org.
Chem. 2011, 76, 8477-8482; f) V. Auressi, M. Davoust, K. M.
Gericke, M. Lautens, Synlett 2009, 6, 1004-1008; g) L. C.
Campeau, M. Parisien, M. Leblanc, K. Fagnou, J. Am. Chem. Soc.
2004, 126, 9186-9187; h) A. P. Kozikowski, D. Ma, Tetrahedron
Lett. 1991, 32, 3317-3320.
5,6-dihydropyrido[3',2':4,5]pyrrolo[2,1-a]isoquinoline (35): Yellow
liquid, (44 mg, 88%); IR (ATR, cm-1): 2850, 2820, 1455; 1H NMR (CDCl3):
δ 8.32 (d, J = 4.6 Hz, 1H), 7.92 (d, J = 7.7 Hz, 1H), 7.80 (d, J = 7.5 Hz,
1H), 7.36-7.28 (m, 3H), 7.09-7.06 (m, 1H), 6.81 (s, 1H), 4.51 (t, J = 6.6
Hz, 2H), 3.23 (t, J = 6.5 Hz, 1H); 13C NMR (CDCl3): δ 147.8, 142.6, 135.9,
133.2, 128.5, 128.4, 128.3, 128.1, 127.2, 124.4, 121.6, 116.1, 94.2, 38.6,
28.9; HRMS (ESI) m/z calcd for C15H13N2 [M+H]+ 221.1079, found
221.1077.
[8] a) K. C. Pereira, A. L. Porter, B. Deboef, Tetrahedron Lett. 2014,
55, 1729-1732; b) G. Meng, H. Y. Niu, G. R. Qu, J. J. Fossey, J. P.
Li, H. M. Guo, Chem. Commun. 2012, 48, 9601-9603; c) M. Sun, H.
Wu, J. Zheng, W. Bao, Adv. Synth. Catal. 2012, 354, 835-838; d)
D. G. Pintori, M. F. Greaney, J. Am. Chem. Soc. 2011, 133, 1209-
1211.
5,5'-(9,9-dinonyl-9H-fluorene-3,6-diyl)bis(10H-pyrido[3',2':4,5]pyrrolo
º
[2,1-a]isoindole (38): Yellow solid; (36 mg, 44%); mp 177-178 C; IR
(KBr, cm-1): 2850, 1599, 1478, 1280, 1010, 994; 1H NMR (CDCl3): δ
(8.39 (d, J = 3.9 Hz, 2H), 8.19 (dd, J = 7.9, 1.3 Hz, 2H), 7.96-7.93 (m,
This article is protected by copyright. All rights reserved.

10.1002/chem.201604192
Chemistry - A European Journal
FULL PAPER
[9] a) M. M. Robinson, B. L. Robinson, J. Am. Chem. Soc. 1956, 78,
1247-1251; b) L. C. Campeau, K. Fagnou, Chem. Commun. 2006,
1253-1264.
[15] J. K. Laha, R. A. Bhimpuria, D. V. Prajapati, N. Dayal, S. Sharma,
Chem Commun. 2016, 52, 4329-4332.
[16] a) K. W. Bentley, Nat. Prod. Rep. 1992, 9, 365-391; b) T. Polssek,
R. Ambros, S. Von Angerer, G. Brand, F. Mannschreck, E. Von
Angerer, J. Med. Chem. 1992, 35, 3537-3547.
[10] E. Deserbre, J. Y. Mérour, Heterocycles 1995, 41, 1987-1988.
[11] J. K. Laha, K. P. Jethava, N. Dayal, J. Org. Chem. 2014, 79, 8010-
8019.
[17] a) C. Bressy, D. Alberico, M. Lautens, J. Am. Chem. Soc. 2005,
127, 13148-13149; b) C. Blaszykowski, E. Aktoudianakis, C.
Bressy, D. Alberico, M. Lautens, Org. Lett. 2006, 8, 2043-2045.
[18] R. K. Dieter, L. E. Nice, S. E. Velu, Tetrahedron Lett. 1996, 37,
2377-2380.
[12] J. K. Laha, N. Dayal, K. P. Jethava, D. V. Prajapati, Org. Lett. 2015,
17, 1296-1299.
[13] J. K. Laha, K. P. Jethava, S. Patel, Org. Lett. 2015, 17, 5890-5893.
[14] J. K. Laha, N. Dayal, Org. Lett. 2015, 17, 4742-4745.
This article is protected by copyright. All rights reserved.

10.1002/chem.201604192
Chemistry - A European Journal
FULL PAPER
FULL PAPER
Joydev K. Laha,* Rohan A. Bhimpuria,
and Mandeep Kaur Hunjan
R
R
N
Page No. – Page No.
N
N
N
Br
Br
H
Intramolecular
oxidative arylation
Title
Suzuki condition
N
N
N
N
37
Intramolecular Oxidative Arylations in
7-Azaindoles and Pyrroles:
R
H3C(H2 C)7H2C
CH2(CH2)7CH3
H
R
- Unveiled first time in 7-azaindoles and pyrroles
- Synthesis of fused isoindolines including chiral congeners
- Isoindolines with a preinstalled bromo group as synthetic handle
- Synthesis of tetrahydroisoquinolines demonstrating broad substrate scope
- Design and synthesis of novel fluorene architectures
Revamping the Synthesis of Fused N-
Heterocycle Tethered Fluorenes
This article is protected by copyright. All rights reserved.