Cascade intramolecular imidoylation and C-H activation/annulation of benzimidoyl chlorides with alkynes: One-pot synthesis of 7: H -dibenzo [de, h] quinoline analogues

Article abstract of DOI:10.1039/c9cc03400e

Reported herein is a cascade Lewis acid-promoted intramolecular Friedel-Crafts-type imidoylation and Rh(iii)-catalyzed C-H activation/annulation of benzimidoyl chlorides and alkynes, providing a general and concise one-pot approach to 7H-dibenzo[de,h]quinoline analogues. This divergent approach is based on a convergent retrosynthetic disconnection strategy.

Full text of DOI:10.1039/c9cc03400e

View Article Online
View Journal
ChemComm
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: J. Liu, H. Fang, R.
Cheng, Z. Wang, Y. Yang and J. You, Chem. Commun., 2019, DOI: 10.1039/C9CC03400E.
This is an Accepted Manuscript, which has been through the
Volume 52 Number
1 4 January 2016 Pages 1–216
Royal Society of Chemistry peer review process and has been
accepted for publication.
ChemComm
Accepted Manuscripts are published online shortly after
Chemical Communications
www.rsc.org/chemcomm
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1359-7345
COMMUNICATION
Marilyn M. Olmstead, Alan L. Balch, Josep M. Poblet, Luis Echegoyenet al.
Reactivity differences of Sc3N@C2n (2n 68 and 80). Synthesis of the
first methanofullerene derivatives of Sc N@D5h-C80
=
3
rsc.li/chemcomm

Please do not adjust margins
Page 1 of 4
ChemComm
View Article Online
DOI: 10.1039/C9CC03400E
Journal Name
COMMUNICATION
Cascade intramolecular imidoylation and C−H activation/annulat-
ion of benzimidoyl chlorides with alkynes: one-pot synthesis of 7H-
dibenzo[de,h]quinoline analogues
Received 00th January 20xx,
Accepted 00th January 20xx
Jiao Liu, Hao Fang, Rui Cheng, Zhishuo Wang, Yudong Yang,* and Jingsong You*
DOI: 10.1039/x0xx00000x
www.rsc.org/
Reported herein is a cascade Lewis acid-promoted intramolecular mainly depend on sequential Suzuki cross-coupling/nucleophilic
Friedel–Crafts-type imidoylation and Rh(III)-catalyzed C–H aromatic substitution/anionic cascade ring-closing reaction (for C7-
activation/annulation of benzimidoyl chlorides and alkynes, heteroanalogues of 7H-dibenzo[de,h]quinolines, Scheme 2a),2 and
providing
a general and concise one-pot approach to 7H- successive thermal cyclization of phthalimide derivatives at an
dibenzo[de,h]quinoline analogues. This divergent approach is extremely high temperature (for 7H-dibenzo[de,h]quinolin-7-ones,
based on a convergent retrosynthetic disconnection strategy.
Scheme 2b).1g,1j,3 Despite the significance of these methods, they
typically suffer from tedious synthetic routes, low atom-/step-
economy, poor functional group tolerance and harsh reaction
The
chromeno[2,3,4-ij]isoquinolines,
kl]acridines and
7H-dibenzo[de,h]quinoline
analogues,
7-methyl-7H-pyrido[4,3,2-
such
as
a) traditional approach to C7-heteroanalogues of 7H-dibenzo[de,h]quinoline derivatives
7H-dibenzo[de,h]quinolin-7-ones
Br
(oxoisoaporphines), widely exist in natural products and
pharmaceuticals. Molecules containing these motifs often exhibit a
broad spectrum of biological activities such as antiplasmodial,
antifungal, antitumor and DNA binding activities (Scheme 1).1
Conventional approaches to 7H-dibenzo[de,h]quinoline analogues
CN
CN
Suzuki
coupling
XH
O
F
Cl
B
F
+
O
F
SNAr
F
N
Br
CN
tBuLi
X
-78 C to r.t.
THF
OH
F
F
X
MeOSO3
X = O, S, N(H)Me
Me
Me
N
N
b) traditional appraoch to 7H-dibenzo[de,h]quinolin-7-one
N
OH
N
O
HO
O
F
O
(CH2)2NH2
EtOH
AlCl3, NaCl
220-230 o
N
+
O
OH
N
Me
C
Reflux
O
Me
Me
O
OH
O
O
cassiarin F
antiplasmodial activity
RHPS 4
necatorone
DNA binding activity
telomerase inhibitor
N
N
COOH
conc. H2SO4
230-240 o
N
O
C
N
Cl
O
c) this work: cascade intramolecular imidoylation and annulation of benzimidoyl chlorides and alkynes
OMe
N
H
aromatic C-H activation/
annulation with alkynes
R1
topoisomerase II inhibitor
antiplasmodial activity
R2
R
N
R1
R2
N
Scheme 1. Selected examples of 7H-dibenzo[de,h]quinoline
derivatives and their heteroanalogues
Triple roles of directing group:
(1) chelation-assistance
(2) internal oxidant
A
B
X
(3) incorporated moiety
X
R = OH or OMe
X = O, NR3, CO
Friedel-Crafts-type
ring closure
Key Laboratory of Green Chemistry and Technology of Ministry of Education, College
of Chemistry, Sichuan University, 29 Wangjiang Road, Chengdu 610064, P. R. China.
Email: yangyudong@scu.edu.cn; E-mail: jsyou@scu.edu.cn.
Electronic Supplementary Information (ESI) available: Detailed experimental
procedures, characterization data, X-ray crystallographic data (CCDC 1899576 (3b),
1913390 (3d), 1899575 (3e), 1899578 (3f), 1899572 (5g), 1899579 (5h) and 1899574
This cascade reaction:
R1
R2
Cl
N
 broad substrate scope
 excellent functional group tolerance
 good regioselectivity
R
[Rh]/Lewis acid
X
One-pot stragey
cascade reaction
 high step-economy
Scheme 2. Synthesis of 7H-dibenzo[de,h]quinoline derivatives
and their heteroanalogues
(7d)).
For
ESI
and
crystallographic
data
in
CIF
or
other electronic format see DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 2 of 4
COMMUNICATION
Journal Name
conditions. Therefore, the development of a more general, concise phenyl ring gave higher yields than their analogues with the electron-
View Article Online
DOI: 10.1039/C9CC03400E
and efficient method for the synthesis of 7H-dibenzo[de,h]quinoline withdrawing group (3b and 3c vs 3d and 3e). Notably, the electronic
analogues is still in high demand.
nature of substituents on phenyl ring had a significant influence on
In the past decade, transition metal-catalyzed annulation of the regioselectivity of C−H activation. The relatively more electronic-
aromatic compounds with alkynes through chelation-assisted C–H rich aryl ring typically preferred to undergo the annulation with an
activation has emerged as one of the most straightforward and alkyne, implying that an electrophilic aromatic substitution (SEAr)
efficient methods to construct polycyclic (hetero)aromatic process might be involved in the C−H rhodation step (3b, 3c and 3e).7
compounds.4,5
In
particular,
the
redox-neutral
C–H However, an exception was found in the case of product 3d, probably
activation/annulation reaction is highly attractive owing to the owing to the large steric effect of -Me. The Aryl alkyl, dialkyl and
obviation of external metal oxidants.6 Moreover, this strategy may diaryl acetylenes with various electronically different substituents
provide a completely different retrosynthetic opportunity for the were also suitable substrates (3f-3o). When aryl alkyl alkynes were
synthesis of complex molecules. Indeed, the retrosynthetic analysis subjected to the reaction, the C−N bond formation tended to take
of 7H-dibenzo[de,h]quinoline derivatives and their C7-aza/-oxa place at the acetylene carbon neighboring to the aryl substituent (3f
analogues suggests that the pyridyl ring (ring A) could be constructed and 3g). In addition, the X-ray single crystal diffraction of 3b, 3d, 3e
by the annulation of an oxime with an alkyne component. The ring B and 3f further confirmed the product structures. It is worth noting
could be accessed via an intramolecular Friedel–Crafts-type that only H2O and HCl were produced as the by-products in this
imidoylation (Scheme 2c). Based on this convergent retrosynthetic reaction. Notably, N-acetoxy-2-phenoxybenzimidoyl chloride 1f was
logic, herein we disclose
a cascade Lewis acid-promoted also proved to be an effective substrate, giving the desired product
intramolecular Friedel–Crafts-type imidoylation and Rh(III)-catalyzed 3a in 49% yield. However, the attempt with a N-methoxy-analogue
C–H activation/annulation using benzimidoyl chlorides and alkynes (1g) was failed. Additionally, the reaction of 1a and phenylacetylene
as the starting materials, providing a divergent synthetic short-cut to failed to deliver the desired product.
7H-dibenzo[de,h]quinoline deriv-atives and their C7-aza/-oxa Table 1. Scope of N-hydroxy-2-phenoxybenzimidoyl chlorides
analogues. This reaction features a broad substrate scope, excellent and alkynesa
functional group tolerance, good regioselectivity and high step-
economy. Notably, the directing group in this reaction plays triple
R2
R1
roles as a chelation-assisted group, internal oxidant and incorporated
moiety in the final product.
N
O
R1
Cl
N
R2
[Rh]/AgSbF6
Zn(OAc)2
OH
O
R1
R
+
N
O
DCE, 120 oC, N2
With the retroanalysis in mind, N-hydroxy-2-phenoxybenzimidoyl
chloride 1a was initially synthesized and selected as the model
substrate (Table S1). Reaction of 1a (0.10 mmol) with
diphenylacetylene 2a (0.15 mmol) gave rise to chromeno[2,3,4-
ij]isoquinoline 3a in 35% yield in the presence of [Cp*RhCl2]2 (5
mol %), AgSbF6(20 mol %), PivOH (2.0 equiv) and Zn(OAc)2·2H2O (1.0
equiv) in DCE at 140 °C under nitrogen atmosphere for 24 h (Table
S1, entry 1). Other Lewis acids such as Zn(OTf)2, Mn(OAc)2,
Ni(OAc)2·4H2O, Mg(OAc)2·2H2O and bases such as LiOAc and CsOAc
were proven to be less efficient in this transformation (Table S1,
entries 2-7). Lowering the reaction temperature to 120 °C could
slightly improve the yield to 40% (Table S1, entry 8). Further lowering
the temperature led to a diminished yield (Table S1, entries 9 and 10).
An improved yield of 67% was observed in the absence of PivOH,
indicating the detrimental effect of PivOH to this reaction (Table S1,
entry 11). Adjusting the stoichiometric ratio of 1a:2a to 1.5:1 led to
87% yield (Table S1, entry 13). In addition, no desired product was
detected in the absence of either [Cp*RhCl2]2 or AgSbF6, suggesting
the essential role of these two additives (Table S1, entries 14 and 15).
Only trace amounts of the desired product was detected when
[Cp*Co(CO)I2]2 was employed as the catalyst (Table S1, entry 17).
Finally, the optimal reaction conditions were assigned as follow:
[Cp*RhCl2]2 (5 mol %), AgSbF6 (20 mol %), and Zn(OAc)2 (1.0 equiv) in
DCE at 120 °C under N2 for 24 h.
R
R2
or
R
1
2
3
Ph
Ph
Ph
Ph
N
N
MeOOC
O
O
3a
3b
, 59%
, 87%
Ph
Ph
Ph
Ph
N
N
Br
Me
O
O
3c
3d
, 84%
, 54%
Ph
Ph
Ph
Et
N
O
N
O
Me
O
3f
, 74%
3e
, 78%
R2
, R1 = Me, R2 = Ph, 68%
3g
3h
3i
, R1 = R2 = 4-BrC6H4, 68%
3l
R1
, R1 = R2 = 4-MeC6H4, 70%
, R1 = R2 = 3-MeC6H4, 80%
, R1 = R2 = 3-OMeC6H4, 79%
, R1 = R2 = Et, 63%
N
O
3m
, R1 = R2 = 4-OMeC6H4, 47%
3n
3o
, R1 = R2 = 4-t-BuC6H4, 76%
3j
3k
, R1 = R2 = 4-ClC6H4, 69%
Cl
N
Cl
N
OAc
O
OMe
O
With the optimized reaction conditions in hand, we investigated
the scope of substrates (Table 1). A variety of N-hydroxy-2-
aryloxybenzimidoyl chlorides 1 could smoothly react with diphenyl
alkyne 2a under the standard condition (3a-3e). Common functional
groups including -COOMe, -Br, -Me and -OMe were tolerated (3b-3e).
Typically, the substrates with the electron-donating group on the
1f
, 49%
1g
, trace
a Reaction condition A: 1 (0.15 mmol), 2 (0.10 mmol), [Cp*RhCl2]2 (5
mol %), AgSbF6 (20 mol %), Zn(OAc)2 (1.0 equiv) and DCE (2 mL) at
120 °C under N2 for 24 h. Isolated yield. DCE = 1,2-dichloroethane.
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 3 of 4
ChemComm
Please do not adjust margins
Journal Name
COMMUNICATION
Table 2. Scope of N-methoxy-2-(methyl(phenyl)amino)benzimidoyl
The reaction of 2-benzoyl-N-methoxybenzimidoylVicewhlAorrtiicdleeOnalninde
diphenyl acetylene under the reaction coDnOdiIt:i1o0n.1s03A9/aCn9dCCB03w40e0rEe
conducted for the synthesis of oxoisoaporphine derivative. However,
no desired product was detected perhaps because the strong
electron-withdrawing effect of the carbonyl group inhibits the
intramolecular Friedel–Crafts-type ring closure. To our delight, the
cascade annulation of 2-benzyl-N-methoxybenzimidoyl chloride 6
and alkynes 2 could furnish the oxoisoaporphine derivatives 7 in
good to excellent yields in the presence of a Cu(OAc)2/O2 oxidative
system (Table 3).
chlorides and alkynesa
R
R
Cl
Me
N
F
N
R
[Rh]/AgSbF6
Zn(OAc)2• 2H2O, PivOH
OMe
F
R1
R2
R2
R1
N
+
DCE, 140 oC, N2
N
R
Me
4
2
5
Ph
Ph
, R1 = R2 = H, 89%, (87%)b
, R1 = Cl, R2 = H, 40%
, R1 = H, R2 = Cl, 35%
, R1 = Br, R2 = H, 38%
, R1 = H, R2 = Me, 44%
5a
Ph
Ph
5b
5c
5d
5e
5f
F
N
F
N
R1
R2
a)
Ph
OMe
Cl
Me
N
N
Ph
F
N
OMe
F
N
[Rh]/Zn(OAc)2•2H2
O
[Rh]/Zn(OAc)2•2H2
O
F
B
condition
N
N
, R1 = R2 = OMe, 73%
Me
Et
B
condition
Ph
Ph
N
N
5g
, 95%
Me
8,
Me
5a
5i
5j
5k
5l
5m
5n
5o
5p
, R = naphthalene-2-yl, 85%
, R = 4-MeC6H4, 97%
, R = 3-MeC6H4, 99%
4a
, 92%
51%
R
Ph
N
b)
c)
OMe
R
Ph
condition
yield
61%
Cl
N
F
N
N
F
N
N
F
Me
N
OMe
F
Zn(OAc)2•2H2O/PivOH
or [RhCp*Cl2]2/AgSbF6
, R = 4-OMeC6H4, 80%
Zn(OAc)2•2H2O (2 equiv)
PivOH (2 equiv)
, R = 3-OMeC6H4, 99%
, R = 4-FC6H4,94%
, R = CH2OEt, 66%
, R = Et, 97%
DCE, 12 h, 140 o
C
[RhCp*Cl2]2 (5 mol%)
AgSbF6 (20 mol%)
N
Me
trace
4a
8
Me
Ph
5h
, 56%
MeO
Ph
N
N
O
Ph
[Rh]/Cu(OAc)2
C
condition
a Reaction condition B: 4 (0.15 mmol), 2 (0.1 mmol), [Cp*RhCl2]2 (5
+
TFE, O2, 24 h, 120 o
C
Ph
mol %), AgSbF6 (20 mol %), Zn(OAc)2·2H2O (0.1 mmol), PivOH (0.2
O
mmol) and DCE (2 mL) at 140 °C under N2 for 12 h. Isolated yield. b
1
9
7a, 77%
2a
mmol
scale.
DCE
=
1,2-dichloroethane.
Cp*
d)
[RhCp*Cl2]2 (50 mol %)
PivOH (2 equiv)
Zn(OAc)2•2H2O (1 equiv)
Cl
Me
N
N
MeO
F
OMe
F
Rh
N
detected by ESI-HRMS
M +
[
] calcd. 493.1157,
Encouraged by these results, the cascade reaction for the
synthesis of pyrido[4,3,2-kl]acridine derivatives was carried out
(Table 2). Under a slightly modified reaction condition, N-
methoxy benzimidoyl chlorines 4 could smoothly react with
acetylenes 2, giving the desired products 5 in moderate to
excellent yields. This reaction exhibited a broad substrate scope
for both N-methoxy benzimidoyl chlorines and acetylenes (5a-
5p). Similarly, the electron-donating substituents on the phenyl
ring of 4 showed a positive effect on the yield (5f vs 5b-5e).
However, terminal alkynes did not work in this reaction, as
exemplified by the reaction of 4a with phenylacetylene.
Table 3. Scope of 2-benzyl-N-methoxybenzimidoyl chloride and
alkynesa
DCE, 12 h, 120 o
C
found 493.1157
4a
N
Me
Scheme 3. Mechanistic investigation
To gain some insights into the reaction mechanism, several control
experiments were conducted. First, the reaction of benzimidoyl
chloride 4a in the absence of acetylene under the standard condition
B gave 8 in 51% yield. Further reaction of 8 and diphenyl acetylene
1a could deliver 5a in 92% yield (Scheme 3a). These results suggested
an
intramolecular
Friedel–Crafts
imidoylation/C–H
activation/annulatuion sequence for this cascade reaction. In
addition, the imidoylation could proceed well in the absence of
[Cp*RhCl2]2 and AgSbF6 (Scheme 3b). However, only trace amounts
R
of the desired product
8 was detected in the absence of
OMe
N
R
N
Cl
R
Zn(OAc)2·2H2O (Scheme 3b). These results indicated that the
Friedel–Crafts imidoylation was mainly mediated by Zn(OAc)2 rather
than rhodium or silver species. Additionally, treatment of oxime 9
with diphenyl alkyne 2a under the condition C provided the
corresponding annulated product 7a in 77% yield (Scheme 3c). This
observation implied that oxime 9 might be an intermediate in the
cascade annulation of 6 and alkynes 2. Considering that 2-benzoyl-N-
methoxybenzimidoyl chloride is not an effective substrate in this
cascade reaction, the oxidation of the methylene group might take
place after the intramolecular imidoylation but before the
annulation with alkynes. Finally, in the reaction mixture of 4a with
stoichiometric amounts of [Cp*RhCl2]2 (condition B, 120 °C), a
cationic rhodacycle complex was detected by ESI-HRMS ([M]+ calcd.
493.1157, found 493.1157), suggesting a C−H activation process was
involved (Scheme 3d).
[Rh]/AgSbF6
Cu(OAc)2, PivOH
TFE, 120 oC, O2
+
R
O
6
2
7
R
N
R
R
R
N
O
7a
7b
7c
, R = Ph, 83%
, R = 4-t-BuC6H4, 75%
, R = 3-MeC6H4, 76%
O
7d
, R = 4-BrC6H4, 95%
a
Reaction condition C: 2 (0.1 mmol), 6 (0.15 mmol), [Cp*RhCl2]2 (5
mol %), AgSbF6 (20 mol %), Cu(OAc)2 (0.3 mmol), PivOH (0.2 mmol)
and TFE (2 mL) at 120 °C under O2 for 24 h. Isolated yield. TFE = 2,2,2-
trifluoroethanol.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 4 of 4
COMMUNICATION
Journal Name
Based on the above observations and previous reports8, a
tentative reaction mechanism is proposed (Scheme 4). First, a
cationic rhodium species is produced by chloride abstraction with
AgSbF6. Then, an oxime-directed ortho C−H rhodation of 8, which is
generated by Zn(OAc)2-mediated intramolecular Friedel–Crafts-type
imidoylation of N-methoxy benzimidoyl chlorines 4a, delivers a five-
membered rhodacycle species IM1. Following migratory insertion of
the alkyne 2a delivers rhodacycle IM3, which then undergoes a
redox-neutral process to furnish the desired product 5a with the re-
lease of rhodium catalyst for the next catalytic cycle.
1
(a) K. M. Marshall and L. R. Barrows, Nat. Prod. Rep., 2004, 21,
View Article Online
731; (b) J. Kaur and P. Singh, Expert Opin. Ther. Patents, 2011,
DOI: 10.1039/C9CC03400E
21, 437; (c) J. Stanslas, D. J. Hagan, M. J. Ellis, C. Turner, J.
Carmichael, W. Ward, T. R. Hammonds and M. F. G. Stevens,
J. Med. Chem., 2000, 43, 1563; (d) L. Bouffier, R. Dinica, J.
Debray, P. Dumy and M. Demeunynck, Bioorg. Med. Chem.
Lett., 2009, 19, 4836; (e) J. R. De la Fuente, C. Aliaga, C.
Poblete, G. Zapata, C. Jullian, C. Saitz, A. Cañete, G. Kciuk, E.
Sobarzo-Sanchez and K. J. Bobrowski, Phys. Chem. A, 2009,
113, 7737; (f) J. Deguchi, T. Hirahara, S. Oshimi, Y. Hirasawa,
W. Ekasari, O. Shirota, T. Honda, and H. Morita, Org. Lett.,
2011, 13, 4344; (g) V. Castro-Castillo, C. Suárez-Rozas, A.
Pabón, E. G. Pérez, B. K. Cassels and S. Blair, Bioorg. Med.
Chem. Lett., 2013, 23, 327; (h) A. R. O. Cousins, D. Ritson, P.
Sharma, M. F. G. Stevens, J. E. Moses and M. S Searle, Chem.
Commun., 2014, 50, 15202; (i) A. Rizzo, S. Iachettini, P. Zizza,
C. Cingolani, M. Porru, S. Artuso, M. Stevens, M.
Hummersone, A. Biroccio, E. Salvati and C. Leonetti, J. Exp.
Clin. Cancer Res., 2014, 33, 81; (j) Z.-F. Chen, Q.-P. Qin, J.-L.
Qin, Y.-C. Liu, K.-B. Huang, Y.-L. Li, T. Meng, G.-H. Zhang, Y.
Peng, X.-J. Luo and H. Liang, J. Med. Chem., 2015, 58, 2159.
J. L. Kristensen, P. Vedsø and M. Begtrup, J. Org. Chem., 2003,
68, 4091.
[Cp*RhCl2]2
4a
intramolecular
Friedel-Crafts
imidoylation
AgSbF6
AgCl
5a + MeOH
Zn(OAc)2•2H2O
Cp*Rh(SbF6)2
OMe
H
H
Cp*
Rh
F
N
N
Ph
SbF6
MeO
F
Ph
N
2
3
H
Me
8
N
Y.-P. Li, F.-X. Ning, M.-B. Yang, Y.-C. Li, M.-H. Nie, T.-M. Ou, J.-
H. Tan, S.-L. Huang, D. Li, L.-Q. Gu and Z.-S. Huang, Eur. J. Med.
Chem., 2011, 46, 1572.
IM3 Me
Cp*
SbF6
MeO
F
Rh
4
(a) T. Satoh and M. Miura, Chem. —Eur. J. 2010, 16, 11212; (b)
P. B. Arockiam, C. Bruneau and P. H. Dixneuf, Chem. Rev.,
2012, 112, 5879; (c) Y. Yang, K. Li, Y. Cheng, D. Wan, M. Li and
J. You, Chem. Commun., 2016, 52, 2872; (d) M. Gulías and J. L.
Mascareñas, Angew. Chem., Int. Ed., 2016, 55, 11000; (e) S.
Prakash, R. Kuppusamy and C.-H. Cheng, ChemCatChem.,
2018, 10, 683; (f) G. Duarah, P. P. Kaishap, T. Begum and S.
Gogoi, Adv. Synth. Catal., 2019, 361, 654.
N
Ph
migratory
insertion
SbF6
Cp*
MeO
F
Ph
Rh
N
N
IM1
Me
N
Ph
Ph
IM2 Me
5
(a) G. Zhang, L. Yang, Y. Wang, Y. Xie and H. Huang, J. Am.
Chem. Soc., 2013, 135, 8850; (b) S. Warratz, C. Kornhaaβ, A.
Cajaraville, B. Niepötter, D. Stalke and L. Ackermann, Angew.
Chem., Int. Ed., 2015, 54, 5513; (c) S. Prakash, K. Muralirajan
and C.-H. Cheng, Angew. Chem., Int. Ed., 2016, 55, 1844; (d) X.
Xu, H. Zhao, J. Xu, C. Chen, Y. Pan, Z. Luo, Z. Zhang, H. Li and L.
Xu, Org. Lett., 2018, 20, 3843; (e) J. Yin and J. You, Angew.
Chem., Int. Ed., 2019, 58, 302; (f) A. Obata, A. Sasagawa, K.
Yamazaki, Y. Ano and N. Chatani, Chem. Sci., 2019, 10, 3242.
(a) J. Mo, L. Wang, Y. Liu and X. Cui, Synthesis, 2015, 47, 439;
(b) L. Zheng and R. Hua, Chem. Rec., 2018, 18, 556; (c) B. Sun,
T. Yoshino, M. Kanai and S. Matsunaga, Angew. Chem., Int.
Ed., 2015 ,54, 12968; (d) Z. Zhou, G. Liu, Y. Chen and X. Lu, Adv.
Synth. Catal., 2015, 357, 2944; (e) K.-H. He, W.-D. Zhang, M.-
Y. Yang, K.-L. Tang, M. Qu, Y.-S. Ding and Y. Li, Org. Lett., 2016,
18, 2840; (f) A. Lerchen, S. Vásquez-Céspedes and F. Glorius,
Angew. Chem., Int. Ed., 2016, 55, 3208; (g) Q. Lu, S. Greßies,
S. Cembellín, F. J. R. Klauck, C. G. Daniliuc and F. Glorius,
Angew. Chem., Int. Ed., 2017, 56, 12778; (h) Y.-F. Liang, R.
Steinbock, A. Münch, D. Stalke and L. Ackermann, Angew.
Chem., Int. Ed., 2018, 57, 5384.
(a) W. Ma, R. Mei, G. Tenti and L. Ackermann, Chem. —Eur. J.,
2014, 20, 15248; (b) E. Tan, O. Quinonero, M. E. Orbe and A.
M. Echavarren, ACS Catal., 2018, 8, 2166; (c) Y. Shi, L. Zhang,
J. Lan, M. Zhang, F. Zhou, W. Wei and J. You, Angew. Chem.,
Int. Ed., 2018, 57, 9108.
(a) G. Song and X. Li, Acc. Chem. Res., 2015, 48, 1007; (b) N.
Guimond, S. I. Gorelsky and K. Fagnou, J. Am. Chem. Soc.,
2011, 133, 6449; (c) M. Sen, D. Kalsi and B. Sundararaju, Chem.
—Eur. J., 2015, 21, 15529; (d) J. Tang, S. Li, Z. Liu, Y. Zhao, Z.
She, V. D. Kadam, G. Gao, J. Lan and J. You, Org. Lett., 2017,
19, 604.
Scheme 4. Plausible mechanistic pathway.
In summary, we have developed a general, concise and efficient
protocol for the synthesis of 7H-dibenzo[de,h]quinoline analogues
via a cascade Lewis acid-promoted intramolecular Friedel–Crafts-
type imidoylation and Rh(III)-catalyzed C–H activation/annulation of
benzimidoyl chlorides with alkynes. This reaction features a broad
substrate scope, good functional group tolerance and excellent
regioselectivity, and could enable rapid scaffold diversification. A
variety of chromeno[2,3,4-ij]isoquinoline, 7-methyl-7H-pyrido[4,3,2-
kl]acridine and 7H-dibenzo[de,h]quinolin-7-one could be obtained in
this cascade reaction. Studies on the application of this reaction to
the exploitation of bioactive molecules are ongoing in our laboratory.
We thank the National Natural Science Foundation of China (Nos.
21432005 and 21502123) for financial support. We also thank the
Open Fund of the Key Laboratory of Functional Molecular
Engineering of Guangdong Province (2016kf05, South China
University of Technology) and the Comprehensive Training Platform
Specialized Laboratory, College of Chemistry, Sichuan University.
6
7
8
Conflicts of interest
There are no conflicts to declare.
Notes and references
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins