FeCl3 mediated dimerization of dihydropyrrolo[2,1-: A] isoquinolines and chlorination of tetrasubstituted pyrroles

Article abstract of DOI:10.1039/c9ob02607j

We have developed a mild and direct dimerization of dihydropyrrolo[2,1-a]isoquinolines through FeCl₃-mediated oxidative homocoupling. A series of dimeric dihydropyrroloisoquinoline derivatives were obtained in acceptable to excellent yields (up to >99%). Attempts to expand this dimerization system to the synthesis of dimeric pyrroles failed and chlorination products were obtained in most cases instead of dimeric pyrroles.

Full text of DOI:10.1039/c9ob02607j

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FeCl3 mediated dimerization of dihydropyrrolo
[2,1-a]isoquinolines and chlorination of tetra-
substituted pyrroles†
Cite this: DOI: 10.1039/c9ob02607j
Xue-Fei Jiang, Hao Tan and Hai-Lei Cui
*
We have developed a mild and direct dimerization of dihydropyrrolo[2,1-a]isoquinolines through FeCl3-
mediated oxidative homocoupling. A series of dimeric dihydropyrroloisoquinoline derivatives were
obtained in acceptable to excellent yields (up to >99%). Attempts to expand this dimerization system to
the synthesis of dimeric pyrroles failed and chlorination products were obtained in most cases instead of
dimeric pyrroles.
Received 7th December 2019,
Accepted 16th December 2019
DOI: 10.1039/c9ob02607j
rsc.li/obc
this transformation.6–10 Although fruitful achievements have
been made through the methods mentioned above, the
Introduction
Dimeric heterocyclic compounds, especially dimers of privi- efficiency, variation of heterocycles and choice of reagents
leged heterocycles, are important core structures present in a have been far from satisfactory. Harsh reaction conditions,
large number of natural products, biologically active molecules directing groups and additives are the requirements for many
and functional materials (Fig. 1).1,2 For instance, biindole is known approaches.
found to be a core unit in many biologically active natural pro-
On the other hand, although a large number of bihetero-
ducts, while bithiophene is a key structure present in many cycles have been prepared by means of the reaction systems
organic semiconducting oligomers that have been widely used mentioned above, direct dimerization reaction systems of aza-
in thin film transistors. Besides, dimerized heterocyles are also cycles are mainly limited to indoles and pyridines
valuable building blocks for the synthesis of natural products (Scheme 1).6,7 A few examples have been reported so far for the
and bioactive compounds.3 In this regard, efficient construction dimerizations of other kinds of nitrogen-containing hetero-
of dimeric heterocycles with easily accessible materials under cycles. Kita and co-wokers reported the first efficient and
mild reaction conditions is much desirable.4–10
straightforward hypervalent iodine(III) mediated synthesis of
Traditional methodologies for the synthesis of dimeric het- bipyrroles in the presence of bromotrimethylsilane.10 The You
erocycles always require the preactivation of heteroaromatic group has developed an elegant regioselective dimerization of
compounds and multi-step synthetic operation involving the indolizines through Pd-catalyzed C–H functionalization,
preparation of halogenated or/and metalated aromatics.4 affording various biindolizines.11 Qian and Bao have disclosed
Thus, direct dimerization of heterocyclic compounds through an efficient and convenient Cu(OAc)2/air mediated dimeriza-
oxidative coupling reaction has become an increasingly power- tion of azoles through oxidative homocoupling.12 Cao and co-
ful tool for the construction of dimerized heterocyclic com-
pounds and thus has attracted much attention in the field of
synthetic chemistry.5 Consequently, a series of elegant proto-
cols for the direct dimerization of heterocycles have been
developed. Cu, Pd, Fe, RANEY® Ni, Tl, carbon catalyst, DDQ,
nitrosonium tetrafluoroborate and hypervalent iodine(III)
reagents have been used as effective catalysts or reagents for
Laboratory of Asymmetric Synthesis, Chongqing University of Arts and Sciences, 319
Honghe Ave., Yongchuan, Chongqing, 402160, PR China.
E-mail: cuihailei616@163.com
†Electronic supplementary information (ESI) available: General experimental
procedures and NMR spectra of all new compounds. CCDC 1957349. For ESI
and crystallographic data in CIF or other electronic format see DOI: 10.1039/
c9ob02607j
Fig. 1 Representative examples.
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Table 1 Optimization of reaction conditionsa,b
Entry MLn
Eq. Additive Solvent
T (h) Yield (%)
1
2
3
4
5
6
7
8
FeCl3
FeCl3
FeCl3
FeBr3
3
2
1
2
2
2
2
2
2
2
2
2
2
2
2
0
6
6
6
6
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
HFIP
TFE
7
7
72
>99
86
63
94
0
0
0
0
0
0
0
0
0
0
0
79
60
76
42
34
27
0
78
28
3
46
46
3
Fe(OTf)3
Fe2(SO4)3
Fe(acac)3
FePO4
FeCl2
Fe(OTf)2
Fe(C2O4)2H2O
CuCl2
Cu(OAc)2
Pd(OAc)2
AgOAc
None
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
9
15
3
10
11
12
13
14
15
16
17
18
19
20
21c,d
22c,d
23c,d
24c,d
25c,e
28
15
15
15
15
15
5
3
3
3
H2O
0.2 TBHP
0.2 DTBP
0.2 DDQ
0.2 mCPBA
0.2 O2
DCM
DCM
DCM
DCM
47
47
5
5
0
23
Scheme 1 Direct dimerization of azacycles.
FeCl3
mXylene 22
a Reaction conditions: 1 and MLn in DCM (0.1 M) at rt. b Isolated yield.
c The yield was determined by 1H NMR using CH2Br2 as an internal
standard. d With 3.0 equiv. of oxidant. e At 50 °C. TBHP: t-butylhydro-
peroxide; DTBP: di-t-butyl peroxide; DDQ: 2,3-dichloro-5,6-dicyano-1,4-
benzoquinone; mCPBA: m-cholorperoxybenzoic acid; TFE: trifluor-
oethanol; HFIP: hexafluoroisopropanol.
workers have achieved an impressive CuI-catalyzed direct C–H
homocoupling of imidazo[1,2-a]pyridines with excellent regio-
selectivity.13 Apparently, dimerizations of azacycles other than
indoles, pyridines, pyrroles and indolizines have been less
explored. Exploration of a novel direct dimerization system
and extension to more heterocycles of great importance are
urgent and challenging tasks.
We have been focusing on the development of the efficient
construction of important heterocyclic compounds with easily
accessible materials. As a result, several kinds of pyrroloisoqui-
noline derivatives14 have been prepared.15,16 To further expand
the molecular complexity and realize the modifications of pri-
vileged frameworks, we have found that the dimerization of
dihydropyrroloisoquinolines can be achieved by iron salt
mediated oxidative coupling reaction.17,18 Since iron salts are
cheap, abundant and nontoxic reagents, the development of
chemical transformations involving iron salts is much attrac-
tive. Here, we report our findings on the FeCl3-mediated
dimerization of dihydropyrroloisoquinolines.
loisoquinoline 2a was isolated in 72% yield. The structure of
compound 2a was confirmed by single crystal X-ray analysis
(Fig. 2).19 When reducing the amount of iron chloride to
2 equivalents, 99% yield was obtained (entry 2). However,
further reduction of FeCl3 to 1 equivalent led to decreased
yield (86%) and prolonged reaction time (78 h, entry 3). FeBr3
and Fe(OTf)3 can also serve as effective oxidants for the homo-
coupling reaction, giving the desired product 2a in 63% and
94% yields, respectively (entries 4 and 5). Other iron salts
(Fe2(SO4)3, Fe(acac)3, FePO4, FeCl2, Fe(OTf)2, and Fe(C2O4)
2H2O) as well as other metal salts (CuCl2, Cu(OAc)2, Pd(OAc)2,
and AgOAc) shown in Table 1 were ineffective as oxidants for
this homocoupling dimerization (entries 6–15). As a control
experiment, the reaction in the absence of FeCl3 and open to
air was tested and no product could be detected (entry 16). It
indicates that dioxygen in air alone is ineffective for this trans-
formation too. A brief screening of solvents identified DCM to
Results and discussion
Initially, we began this study by treating dihydropyrroloisoqui- be the best choice as solvent (entries 17–20).
noline 1a with 3 equivalents of FeCl3 in DCM at room tempera-
As a catalytic oxidative dimerization system is much more
ture (Table 1, entry 1). Pleasingly, the desired dimerized pyrro- attractive, we then tested the synthesis of dimeric dihydropyr-
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Fig. 2 X-ray crystallographic structure of 2a.
roloisoquinoline using a catalytic amount of iron chloride
(20 mol%) in the presence of oxidants (TBHP, DTBP, DDQ and
mCPBA). Poor reaction yields were observed in the cases
employing TBHP and DTBP as oxidants (34% and 27% yields,
respectively, entries 21 and 22), while the use of DDQ and
mCPBA as oxidants resulted in the decomposition and/or side
reactions of the starting material 1a (entries 23 and 24). A cata-
lytic reaction under an O2 atmosphere has also been carried
out (entry 25). 23% yield could be obtained by stirring the reac-
tion mixture at 50 °C for 22 h in the presence of 20 mol% of
FeCl3 under an oxygen atmosphere. It indicates that the re-
cycling of catalyst could be realized by exposing the reaction
mixture to dioxygen.
Scheme 2 Examination of substrate scope. Reaction conditions: 1 and
FeCl3 (2 equiv.) in DCM (0.1 M) at rt. Isolated yield. a Using 3 equiv. of
FeCl3. b TFE was used as solvent. c HFIP was used as solvent.
Next, we investigated the substrate scope and limitations
under the identified reaction conditions. As shown in
Scheme 2, various polysubstituted dihydropyrroloisoquino-
lines can be employed in this reaction system. Functional synthesis of dimeric polysubstituted pyrroles. Therefore, a
groups on the C1 phenyl ring are well tolerated, regardless of reaction for constructing dimeric tetrasubstituted pyrroles has
the electronic nature of the substituents (compounds 2a–2i, been developed. To test this hypothesis, tetrasubstituted pyr-
78–>99% yields). Unfortunately, the exclusion of dimethoxy roles 3 were prepared following a reported procedure devel-
groups on the quinoline moiety led to the formation of com- oped by Jana and co-workers.21 As shown in Table 2, a range of
pounds 2j and 2k in dramatically decreased yields (35% and iron salts were screened. Unfortunately, stoichiometric
45%, respectively). Pleasingly, the inclusion of an amide group amounts of iron salts were found to be ineffective in the
into the dimeric dihydropyrroloisoquinoline was successful, dimerization reaction of 3a (Table 2, entries 1–7). The corres-
affording compound 2l in 81% yield.
ponding dimeric tetrasubstituted pyrrole 4a could not be
Unfortunately, the dimerization reactions for the synthesis detected in all the tested reaction systems, while only chlori-
of compound 2m employing DCM as the solvent were dis- nation product 5a was isolated when iron chloride was used as
ordered. As the use of fluorinated solvents has been found to the oxidant. Furthermore, attempts for the synthesis of
play a critical role in the synthesis of biheterocycles through dimeric pyrrole through a catalytic system using additive
the cation-radical pathway, we wondered whether the dimeriza- oxidant (DTBP, THBP, DDQ and mCPBA) or switching to other
tion of compound 2m can be realized by using these kinds of solvents failed (entries 8–14).
solvents.20 We were pleased to find that the dimerization reac-
As shown in Scheme 3, a series of tetrasubstituted pyrroles
tion of dihydropyrroloisoquinoline possessing the cyano group have been further examined using iron chloride as the oxidant,
proceeded smoothly delivering the desired dimer 2m using since we suspected that the substituents may have a critical
TFE or HFIP as the solvent (58% and 88% yields, respectively). influence on the chemoselectivity in this reaction. However,
We reasoned that TFE and HFIP as solvents may be more suit- the corresponding dimeric tetrasubstituted pyrroles 4 could
able for the formation of the cation radical intermediate and not be obtained in these reactions. Chlorination products 5
thus beneficial for the dimerization reaction.20 Notably, exclu- were isolated in low to good yields instead. The differences in
sion of air or moisture is not required for this process.
the chemoselectivity between tetrasubstituted pyrroles and
As dihydropyrroloisoquinoline is actually a tetrasubstituted dihydropyrroloisoquinolines under the current dimerization
pyrrole, this dimerization system may be also applicable to the system are not clear at present. The dimethoxyphenyl moiety
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Table 2 Attempts for the dimerization of tetrasubstituted pyrrolesa,b
Entry
Iron salts
Eq.
Additive
Solvent
T (h)
Yield of 4ac (%)
Yield of 5ac (%)
1
2
3
4
5
6
7
FeCl3
FeCl3·6H2O
FePO4
3
3
3
5
3
3
3
0.1
0.1
0.1
0.1
0.1
2
—
—
—
—
—
—
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
HFIP
HFIP
HFIP
EtOH
72
60
60
72
60
60
60
67
92
92
39
39
39
44
0
0
0
0
0
0
0
0
0
0
0
0
0
0
27
0
0
55
0
0
0
0
0
0
0
0
30
0
FeCl3
Fe(OTf)3
Fe2(SO4)3
Fe(C2O4)·2H2O
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
8c
9c
10d
11c
12c
13
14
DTBP
THBP
DDQ
THBP
mCPBA
—
3
—
a Reaction conditions: 3a and iron salts in solvent (0.1 M) at rt. b The yield was determined by 1H NMR using CH2Br2 as an internal standard.
c With 3.0 equiv. of oxidant. d With 2.0 equiv. of oxidant.
Scheme 4 Proposed mechanism.
could be generated by the nucleophilic attack of dihydropyrro-
loisoquinoline 1 to cation radical A. Further oxidation to dicatio-
nic intermediate C through single-electron-transfer and a final
aromatization lead to dimeric dihydropyrroloisoquinoline 2.
Scheme 3 Examination of substituent effect. Reaction conditions: 3
Conclusions
and FeCl3 (3 equiv.) in DCM (0.1 M) at rt. Isolated yield.a HFIP was used
as solvent.
In conclusion, we have established a mild and straightforward
dimerization of dihydropyrroloisoquinolines through an iron
chloride mediated oxidative homocoupling reaction. A series
in dihydropyrroloisoquinolines might play an important role of dimeric dihydropyrroloisoquinoline derivatives were pre-
in the dimerization process. The relatively low yields observed pared in acceptable to excellent yields (up to >99%). Notably,
in the cases of 2j and 2k could partly support this explanation. dihydropyrroloisoquinolines possessing amide groups and
A possible mechanism was proposed based on our results cyano groups can be compatible in this process. Attempts to
and previous reports (Scheme 4).22 Cation radical A would be prepare dimeric polysubstituted pyrroles failed under the
formed firstly in the presence of iron chloride as the oxidant current reaction conditions. Chlorination products were
through single-electron-transfer (SET). Next, intermediate B obtained in most cases instead of the desired dimeric pyrroles.
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The difference in the chemoselectivity between dihydropyrro-
loisoquinolines and polysubstituted pyrroles under the current
dimerization system has not been determined yet.
2 (a) C. Wang, H. Dong, W. Hu, Y. Liu and D. Zhu, Chem.
Rev., 2012, 112, 2208–2267; (b) A. R. Murphy and
J. M. J. Fréchet, Chem. Rev., 2007, 107, 1066–1096;
(c) M. Funahashi and J.-I. Hanna, Adv. Mater., 2005, 17,
594–598.
3 (a) S. Liu and X.-J. Hao, Tetrahedron Lett., 2011, 52, 5640–
5642; (b) B. Witulski and T. Schweikert, Synthesis, 2005,
1959–1966; (c) S. Han, K. C. Morrison, P. J. Hergenrother
and M. Movassaghi, J. Org. Chem., 2014, 79, 473–486;
(d) X. Qi, H. Bao and U. K. Tambar, J. Am. Chem. Soc., 2011,
133, 10050–10053.
4 (a) M. Bandini and A. Eichholzer, Angew. Chem., Int. Ed.,
2009, 48, 9533–9537; (b) I. Hussain and T. Singh, Adv.
Synth. Catal., 2014, 356, 1661–1696.
Experimental
General methods
1H NMR and 13C NMR spectra were recorded using a Bruker
Avance 400. Chemical shifts are reported in ppm downfield
from CDCl3 (δ = 7.26 ppm) for 1H NMR and relative to the
central CDCl3 resonance (δ = 77.0 ppm) for 13C NMR spec-
troscopy. Coupling constants are given in Hz. ESI-MS analysis
was performed using an Agilent 6210 ESI/TOF mass spectro-
meter. All reagents and solvents were obtained from commer-
cial sources and used without further purification unless
otherwise noted. DCM and other solvents tested in Table 1
and 2 were dried with 4 Å molecular sieves. All the reactions in
this study were performed without the exclusion of air. FeCl3
(AR) was purchased from Shanghai Titan Scientific Co., Ltd.
Dihydropyrrolo[2,1-a]isoquinolines 1 were prepared according
to the reported procedure.18
5 For reviews on oxidative coupling reaction, see: (a) Y. Yang,
J. Lan and J. You, Chem. Rev., 2017, 117, 8787–8863;
(b) M. C. Kozlowski, Acc. Chem. Res., 2017, 50, 638–643;
(c) M. Grzybowski, K. Skonieczny, H. Butenschcön and
D. T. Gryko, Angew. Chem., Int. Ed., 2013, 52, 9900–9930.
6 For selected examples on dimerization of indoles through
direct homocoupling, see: (a) T. Wirtanen, M. K. Mäkelä,
J. Sarfraz, P. Ihalainen, S. Hietala, M. Melchionna and
J. Helaja, Adv. Synth. Catal., 2015, 357, 3718–3726;
(b) Z. Liang, J. Zhao and Y. Zhang, J. Org. Chem., 2010, 75,
170–177; (c) J. Bergman, E. Koch and B. Pelcman,
Tetrahedron Lett., 1995, 36, 3945–3946; (d) J. Le, Y. Gao,
Y. Ding and C. Jiang, Tetrahedron Lett., 2016, 57, 1728–
1731; (e) L. Bering, F. M. Paulussen and A. P. Antonchick,
Org. Lett., 2018, 20, 1978–1981; (f) L. Peng, X. Zhang and
C. Yang, Molecules, 2019, 24, 960–972; (g) E. Kianmehr,
M. Ghanbari, N. Faghih and F. Rominger, Tetrahedron Lett.,
2012, 53, 1900–1904; (h) Y. Li, W.-H. Wang, S.-D. Yang,
B.-J. Li, C. Feng and Z.-J. Shi, Chem. Commun., 2010, 46,
4553–4555; (i) A. García-Rubia, B. Urones, R. G. Arrayμs and
J. C. Carretero, Chem. – Eur. J., 2010, 16, 9676–9686;
( j) R. Odani, M. Nishino, K. Hirano, T. Satoh and
M. Miura, Heterocycles, 2014, 88, 595–602; (k) P. A. Keller,
N. R. Yepuri, M. J. Kelso, M. Mariani, B. W. Skelton and
A. H. White, Tetrahedron, 2008, 64, 7787–7795; (l) T. Niu
and Y. Zhang, Tetrahedron Lett., 2010, 51, 6847–6851;
(m) T. Wirtanen, S. Aikonen, M. Muuronen,
M. Melchionna, M. Kemell, F. Davodi, T. Kallio, T. Hu and
J. Helaja, Chem. – Eur. J., 2019, 25, 12288–12293.
General procedure for the synthesis of compound 2
A mixture of dihydropyrrolo[2,1-a]isoquinoline 1 (1.0 equiv.)
and FeCl3 (2.0 equiv.) in DCM (0.1 M) was stirred at rt without
exclusion of air (monitored by TLC). Upon the consumption of
dihydropyrrolo[2,1-a]isoquinolines 1, the mixture was then
purified directly by silica gel flash chromatography (hexane/
EtOAc) to afford compound 2.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
We are grateful for the support provided for this study by the
National Natural Science Foundation of China (21502013,
21871035). We sincerely thank Xiao-Hui Tang, Hui-Lin Tan,
Xiao-Li Ju and Xin-Xin Zhu (University of Arts and Sciences)
for experimental contributions. We also thank Han-Zhao Liu
and Jia Xu (International Academy of Targeted Therapeutics
and Innovation, Chongqing University of Arts and Sciences)
for NMR and HRMS data acquisition.
7 For selected examples on dimerization of pyridines and qui-
nolines through direct homocoupling, see: (a) H. Hagelin,
B. Hedman, I. Orabona, T. Åkermark, B. Åkermark and
C. A. Klug, J. Mol. Catal. A: Chem., 2000, 164, 137–146;
(b) H. Rapoport, R. Iwamoto and J. R. Tretter, J. Org. Chem.,
1960, 25, 372–373; (c) G. M. Badger and W. H. F. Sasse,
J. Chem. Soc., 1956, 616–620; (d) X. Guo, G. Deng and
C.-J. Li, Adv. Synth. Catal., 2009, 351, 2071–2074; (e) Y. Xie,
D. Xu, W.-W. Sun, S.-J. Zhang, X.-P. Dong, B. Liu, Y. Zhou
and B. Wu, Asian J. Org. Chem., 2016, 5, 961–965.
Notes and references
1 (a) P. C. Jimenez, D. V. Wilke, E. G. Ferreira, R. Takeara,
M. O. de Moraes, E. R. Silveira, T. M. C. Lotufo, N. P. Lopes
and L. V. Costa-Lotufo, Mar. Drugs, 2012, 10, 1092–1102;
(b) J. Legros and B. Figadère, Nat. Prod. Rep., 2015, 32,
1541–1555; (c) I. S. Young, P. D. Thorntonb and
A. Thompson, Nat. Prod. Rep., 2010, 27, 1801–1839.
8 For selected examples on dimerization of O- and
S-heterocycles through direct homocoupling, see:
(a) L. Grigorjeva and O. Daugulis, Org. Lett., 2015, 17,
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Org. Biomol. Chem.

View Article Online
Paper
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1204–1207; (b) M. Takahashi, K. Masui, H. Sekiguchi, 13 S. Lei, H. Cao, L. Chen, J. Liu, H. Cai and J. Tan, Adv.
N. Kobayashi, A. Mori, M. Funahashi and N. Tamaoki, Synth. Catal., 2015, 357, 3109–3114.
J. Am. Chem. Soc., 2006, 128, 10930–10933; (c) K. Masui, 14 For reviews on natural products and bioactive compounds
H. Ikegami and A. Mori, J. Am. Chem. Soc., 2004, 126, 5074–
5075; (d) Q. Zhang, X. Wan, Y. Lu, Y. Li, Y. Li, C. Li, H. Wua
and Y. Chen, Chem. Commun., 2014, 50, 12497–12499;
(e) K. Fukuzumi, Y. Nishii and M. Miura, Angew. Chem., Int.
Ed., 2017, 56, 12746–12750; (f) I. V. Kozhevnikov, React.
Kinet. Catal. Lett., 1977, 6, 401–408; (g) T. Dohi,
containing pyrroloisoquinoline as the core structure, see:
(a) H. Fan, J. Peng, M. T. Hamann and J.-F. Hu, Chem. Rev.,
2008, 108, 264–287; (b) D. Baunbæk, N. Trinkler,
Y. Ferandin, O. Lozach, P. Ploypradith, S. Rucirawat,
F. Ishibashi, M. Iwao and L. Meijer, Mar. Drugs, 2008, 6,
514–527.
K. Morimoto, Y. Kiyono, A. Maruyama, H. Tohma and 15 (a) H.-L. Cui, Y. Shi, H.-Q. Deng, J.-J. Lei, X.-J. Xu, X. Tian,
Y.
Kita,
Chem.
Commun.,
2005,
2930–2932;
J. Qiao and L. Zhou, Synlett, 2019, 30, 167–172;
(b) S.-W. Liu, Y.-J. Gao, Y. Shi, L. Zhou, X. Tang and
H.-L. Cui, J. Org. Chem., 2018, 83, 13754–13764; (c) X. Tang,
M.-C. Yang, C. Ye, L. Liu, H.-L. Zhou, X.-J. Jiang, X.-L. You,
B. Han and H.-L. Cui, Org. Chem. Front., 2017, 4, 2128–
2133; (d) X. Tang, Y.-J. Gao, H.-Q. Deng, J.-J. Lei, S.-W. Liu,
L. Zhou, Y. Shi, H. Liang, J. Qiao, L. Guo, B. Han and
H.-L. Cui, Org. Biomol. Chem., 2018, 16, 3362–3366;
(e) S.-W. Liu, C. Yuan, X.-F. Jiang, X.-X. Wng and H.-L. Cui,
Asian J. Org. Chem., 2019, DOI: 10.1002/ajoc.201900630.
(h) M. Takahashi, K. Masui, H. Sekiguchi, N. Kobayashi,
A. Mori, M. Funahashi and N. Tamaoki, J. Am. Chem. Soc.,
2006, 128, 10930–10933; (i) N.-N. Li, Y.-L. Zhang, S. Mao,
Y.-R. Gao, D.-D. Guo and Y.-Q. Wang, Org. Lett., 2014, 16,
2732–2735; ( j) K. Morimoto, T. Nakae, N. Yamaoka, T. Dohi
and Y. Kita, Eur. J. Org. Chem., 2011, 6326–6334.
9 For selected examples on the synthesis of biheterocycles
through other routes, see: (a) X.-H. Xu, G.-K. Liu, A. Azuma,
E. Tokunaga and N. Shibata, Org. Lett., 2011, 13, 4854–
4857; (b) X. Qin, B. Feng, J. Dong, X. Li, Y. Xue, J. Lan and 16 For our efforts on other polycyclic azacycles, see:
J. You, J. Org. Chem., 2012, 77, 7677–7683; (c) T. Li, Y. Yang,
B. Li and P. Yang, Chem. Commun., 2019, 55, 353–356;
(d) S. P. H. Mee, V. Lee, J. E. Baldwin and A. Cowley,
Tetrahedron, 2004, 60, 3695–3712.
(a) H.-L. Cui, J.-F. Wang, H.-L. Zhou, X.-L. You and
X.-J. Jiang, Org. Biomol. Chem., 2017, 15, 3860–3862;
(b) H.-L. Cui, S. Liu and L. Jiang, Eur. J. Org. Chem., 2019,
4941–4950; (c) H.-L. Cui, L.-J. Peng, H.-L. Zhou, X.-L. You
and X.-J. Jiang, Org. Biomol. Chem., 2017, 15, 5121–5125.
10 For selected examples on dimerization of pyrroles through
direct homocoupling, see: (a) T. Itahara, J. Chem. Soc., 17 For reviews on iron catalysis, see: (a) A. A. O. Sarhan and
Chem. Commun., 1980, 49b–50; (b) K. Morimoto, T. Dohi
and Y. Kita, Synlett, 2017, 28, 1680–1694; (c) T. Dohi,
K. Morimoto, A. Maruyama and Y. Kita, Org. Lett., 2006, 8,
2007–2010; (d) T. Itahara, M. Hashimoto and
H. Yumisashi, Synthesis, 1984, 255–256; (e) H. Falk and
H. Flödl, Monatsh. Chem., 1988, 119, 247–252.
C. Bolm, Chem. Soc. Rev., 2009, 38, 2730–2744; (b) C. Bolm,
J. Legros, L. L. Paih and L. Zani, Chem. Rev., 2004, 104,
6217–6254; (c) I. Bauer and H.-J. Knölker, Chem. Rev., 2015,
115, 3170–3387; (d) K. Gopalaiah, Chem. Rev., 2013, 113,
3248–3296.
18 H.-L. Cui, L. Jiang, H. Tan and S. Liu, Adv. Synth. Catal.,
2019, 361, 4772–4780.
11 (a) J.-B. Xia, X.-Q. Wang and S.-L. You, J. Org. Chem., 2009,
74, 456–458; (b) A. Kakehi, S. Ito, A. Hamaguchi and 19 CCDC 1957349 (2a)† contains the supplementary crystallo-
T. Okano, Bull. Chem. Soc. Jpn., 1981, 54, 2833–2834; graphic data for this paper.
(c) T. Kreher, H. Sonennschein, L. Schmid and S. Hünig, 20 (a) L. Eberson, M. P. Hartshorn, O. Persson and F. Radner,
Liebigs Ann. Chem., 1994, 1173–1176; (d) L. Cardellini,
P. Carloni, L. Greci, G. Tosi, R. Andruzzi, G. Marrosu and
A. Trazza, J. Chem. Soc., Perkin Trans. 2, 1990, 2117–2121;
(e) R. Andruzzi, L. Cardellini, L. Greci, P. Stipa, M. Poloni
and A. Trazza, J. Chem. Soc., Perkin Trans. 1, 1988, 3067–
Chem. Commun., 1996, 2105–2112; (b) A. Kirste, M. Nieger,
I. M. Malkowsky, F. Stecker, A. Fischer and S. R. Waldvogel,
Chem. – Eur. J., 2009, 15, 2273–2277; (c) H. Hamamoto,
G. Anilkumar, H. Tohma and Y. Kita, Chem. – Eur. J., 2002,
8, 5377–5383.
3070; (f) H. Sonnenschein, H. Kosslick and F. Tittelbach, 21 S. Maiti, S. Biswas and U. Jana, J. Org. Chem., 2010, 75,
Synthesis, 1998, 1596–1598. 1674–1683.
12 Y. Li, J. Jin, W. Qian and W. Bao, Org. Biomol. Chem., 2010, 22 M. Grzybowski, K. Skonieczny, H. Butenschçn and
8, 326–330.
D. T. Gryko, Angew. Chem., Int. Ed., 2013, 52, 9900–9930.
Org. Biomol. Chem.
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