Tandem cyclization of o-alkynylanilines with isocyanides triggered by intramolecular nucleopalladation: Access to heterocyclic fused 2-aminoquinolines

Article abstract of DOI:10.1039/c8cc02028k

Herein, a novel strategy for the synthesis of various heterocyclic fused 2-aminoquinolines via palladium-catalyzed tandem cyclization of o-alkynylanilines with isocyanides has been developed. This process includes trans-oxy/aminopalladation, isocyanide in

Full text of DOI:10.1039/c8cc02028k

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Tandem Cyclization of o-Alkynylanilines with Isocyanides
Triggered by Intramolecular Nucleopalladation: Access to
Heterocyclic Fused 2-Aminoquinolines
Received 00th January 20xx,
Accepted 00th January 20xx
Wanqing Wu,*a,b Meng Li,b Jia Zheng,b Weigao Hu,b Chunsheng Lib and Huanfeng Jiangb
DOI: 10.1039/x0xx00000x
www.rsc.org/
Herein, a novel strategy for the synthesis of various heterocyclic alkynes, as a powerful tool to construct multiple new carbon-
fused 2-aminoquinolines via palladium-catalyzed tandem carbon or/and carbon-heteroatom bonds, has been widely
cyclization of o-alkynylanilines with isocyanides has been investigated over the past decades.10 In addition, this strategy
developed. This process includes trans-oxy/aminopalladation, shows great functional group compatibility and step economy.
isocyanide insertion, elimination and 1,3-hydrogen migration. However, challenges are still remained, such as the control of
Besides high atom and step economy, this method shows good regio-, chemo- or stereoselectivities. Therefore, developing
functional group compatibility with excellent chemo- and new and efficient methods to solve these problems is of great
regioselectivities under mild reaction conditions.
significance. Typically, o-alkenyl/alkynylanilines are useful
synthons widely used in transition metal-catalyzed or Lewis
acid-catalyzed tandem cyclization reactions to construct highly
functionalized N-heterocycles.11 And in most cases, the
indolylpalladium complexes will be formed firstly through a
quick intramolecular trans-aminopalladation and then react
with another substrate to afford various cyclization products.
However, when two or more nucleophilic groups coexist in one
system, the sequence of reaction pathways is usually
unpredictable and it is challenging to enhance the selectivity
for nucleopalladation of the weaker one to develop diverse
reaction processes. To the best of our knowledge, few
examples have been established in the literature up to now.12
Based on our continuing interest in heteropalladation13 and
isocyanide insertion reactions,9a,14 herein, we disclose a novel
palladium-catalyzed tandem cyclization reaction of o-
alkynylanilines with isocyanides under mild conditions
(Scheme 1). This chemistry provides an efficient approach for
the construction of diverse heterocyclic fused 2-
aminoquinolines with excellent chemo- and regioselectivities
as well as high atom economy in one-pot manner via an
intramolecular trans-oxy/aminopalladation followed by the
2-Aminoquinolines and their derivatives are one of the most
important members in the family of quinolines, which exhibit
particular biological and pharmacological activities, such as
anthelmintic,1
antidepressant,2
anti-cancer3
and
antihypertensive4 activities etc.5 Generally, the 2-
aminoquinoline skeletons could be synthesized by the
following strategies: (i) the reductive cyclization of
nitrophenylacrylonitriles,6 (ii) direct amination of aryl halides7
and quinolone-N-oxides,8 (iii) intermolecular cyclization of
alkynes or alkenes under transition metal catalysis.9 These
achievements, however, still suffer from some limitations such
as the requirement of acidic or alkaline conditions, multistep
operation, expensive starting materials or narrow substrate
scope. Moreover, though these established examples provide
2-aminoquinolines with single or double substitutions at C-3 or
C-4 position successfully, few reports have been demonstrated
the building of heterocyclic fused 2-aminoquinolines which are
valuable precursors of many pharmaceutical intermediates for
the treatment of unusual chronic diseases.1a,5b Hence, it is still
highly desirable and meaningful to develop innovative
protocols for the construction of such unconventional
molecular skeleton.
insertion of isocyanides.
R2
R2
XH
X
On the other hand, the heteropalladation of alkenes and
X
R2
[Pd]
R1
N
R3
R1
+
C
R3
NH2
R1
N
N
[Pd]
H
NH2
X = O or NTs
R2 = H or alkyl
a
State Key Laboratory of Luminescent Materials and Devices, South China
University of Technology, Guangzhou 510640, China. Fax: +86 20-87112906; Tel:
+86 20-87112906; E-mail: cewuwq@scut.edu.cn
Available materials
Excellent chemo- and regioselectivities
C-X, C-C, C=N Bond formations
High Atom and step economy
b
Key Laboratory of Functional Molecular Engineering of Guangdong Province,
School of Chemistry and Chemical Engineering, South China University of
Technology, Guangzhou 510640, China.
† Electronic supplementary information (ESI) available. CCDC 1578030. For ESI
Scheme 1. Palladium(II)-catalyzed tandem cyclization of o-
alkynylanilines with isocyanides
and crystallographic data in CIF or other electronic format see DOI:
10.1039/b000000x
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Table 1. Optimization of reaction conditionsa
(Me, OMe) and electron-withdrawing (F, Cl, Br, COOMe)
groups at the C-4 position of the aryl ring could proceed
smoothly to afford the corresponding products in moderate to
good yields (3a-g). The structure of 3a was undoubtedly
yield
(%)b
confirmed by X-ray diffraction (see the Supporting Information
for details).15 Further observations indicated that similar
results were obtained when the substituents were shifted to
entry
catalyst
oxidant
ligand
solvent
1
2
3
4
5
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
BQ
-
-
-
-
-
toluene
toluene
toluene
toluene
DMSO
trace
15
AgOAc
TBHP
Table 2. Synthesis of 2-amino-furanoquinolines initiated by
intramolecular trans-oxypalladationa
trace
25
Cu(OAc)2
Cu(OAc)2
trace
toluene/MeCN =
6
7
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
-
-
35
1:1
1,10-
phen
toluene/MeCN =
trace
60
1:1
toluene/MeCN =
1:1
toluene/MeCN =
1:1
toluene/MeCN =
1:1
toluene/MeCN =
8
PPh3
dppe
dppp
dppp
dppp
dppp
dppp
dppp
dppp
9
58
10
11
12c
13
14d
15
16
65
28
1:1
toluene/MeCN =
1:1
toluene/MeCN = 72
1:1
toluene/MeCN =
1:1
toluene/MeCN =
1:1
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
-
52
(68)
62
n.r.
toluene/MeCN =
1:1
Pd(PPh3)4
trace
a Reaction conditions: 1a (0.1 mmol), 2a (0.15 mmol), catalyst (10 mol %),
b
Cu(OAc)2 (2 equiv), ligand (20 mol %), solvent (1 mL), 100 °C, 9 h.
Determined by GC using dodecane as internal standard. Number in
parentheses is isolated yield. n.d. = not detected. n.r. = no reaction. c 90 oC. d
aReaction conditions: 1 (0.1 mmol), 2 (0.15 mmol), Pd(PPh3)4 (10 mol %),
dppp (20 mol %), Cu(OAc)2 (2.0 equiv), solvent (1mL) at 100 oC for 9 h. Yield
is isolated yield. dppp = 1,3-bis(diphenyphosphino)propane.
110 oC. 1,10-phen
=
1,10- phenanthroline; dppp
=
1,3-
bis(diphenyphosphino)propane; PPh3 = triphenylphosphine.
Table 3. Synthesis of 2-aminopyrroloquinolines initiated by
intramolecular trans-aminopalladationa
Initially, 4-(2-aminophenyl)but-3-yn-1-ol (1a) and tert-butyl
isocyanide (2a) were chosen as model substrates for condition
optimization (Table 1). To our delight, 25% yield of product 3a
was obtained in the presence of 2.0 equiv of Cu(OAc)2, while
other oxidants such as BQ, AgOAc or TBHP was not effective in
this reaction system (entries 1-4). Switching toluene to other
solvents did not promote this process. The product yield
increased to 35% when the mixed solvent of toluene/MeCN
(1:1) was used (entries 4-6). Subsequently, different ligands
were investigated, and dppp was found to be the most
effective phosphine ligand for this transformation (entries 7-
10). Compared with other palladium catalysts, a slightly
increased yield was observed with the employment of
Pd(PPh3)4 (entries 11, 13). Additionally, lowering or raising the
temperature could not improve the product yield (entries 12,
14). Finally, control experiments demonstrated that this
reaction did not occur in the absence of palladium catalyst or
oxidant (entries 15-16).
aReaction conditions: 4 (0.1 mmol), 2 (0.15 mmol), Pd(PPh3)4 (10 mol %),
Cu(OAc)2 (2.0 equiv), dppp (20 mol %), solvent (1mL), at 100 oC for 9 h. Yield
is isolated yield. dppp = 1,3-bis(diphenyphosphino)propane.
With the optimized reaction conditions in hand, we began to
investigate the generality of this tandem cyclization (Table 2).
Pleasingly, all the tested substrates with electron-donating
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the C-5 or C-6 position of the aryl ring. Moreover, the experiment was implemented to study the origin of the free
corresponding products 3o 3p and 3q could be also isolated in hydrogen atom in the final product (Scheme 3, Eq. 3).
,
satisfied yields when di-substituted substrates were employed. Eventually, 3a was isolated in 38% yield without being labeled
It was worth noting that the substrate bearing an ethyl on the by deuterium. Thus, it could be concluded that this annulation
homopropargyl moiety could convert into 3r in 65% yield. As process might not be initiated by the reaction of the amino
for the scope of isocyanides, alkyl isocyanides were suitable for group with isocyanides.
this transformation (3s
hindered 1-admantyl isocyanide and 1,1,3,3-tetramethylbutyl
isocyanide gave better results than those of
-v). Interestingly, the more sterically
cyclopentylisocyanide and cyclohexylisocyanide. However, aryl
isocyanides could not be transformed to the corresponding
products in this reaction for the low reactivity.
To testify the universality of this method, another important
class of substrates containing the nucleophilic unit of NHTs
were conducted under the optimal conditions (Table 3).
Fortunately, various functional groups such as methyl, fluorine
and trifluoromethyl were all founded to be well tolerated, and
the desired products could be obtained in acceptable yields
Scheme 3. Control experiments
(5a-e). Furthermore, 3,5-dichloro- and 3,5-dimethyl-
substituted o-alkynylanilines also exhibited good compatibility
for this transformation, which were transformed to the target
products in 58% and 63% yields, respectively. Additionally,
Based on these control experiments above and previous
reports,12-14 a plausible mechanism for this tandem cyclization
of o-alkynylanilines with isocyanides is proposed in Scheme 4.
First, the oxidation of Pd(0) species gives the active Pd(II)
species, which would coordinate with the amino group and
cyclopentylisocyanide
(
2h
)
and 1,1,3,3-tetramethylbutyl
isocyanide (2i) were screened as well, and the corresponding
product 5i was provided in a higher yield.
carbon-carbon triple bond of
nucleopalladation generates the vinylpalladium intermediate
Followed by the migration insertion of , the intermediate
1 to afford A. Subsequent trans-
In order to demonstrate the utility of this method in the
synthesis of highly functionalized molecules, alkenylation16 and
alkynylation17 of 3f were attempted and the coupling products
6a and 7a could be achieved in excellent yields, which
improved the complexity of the quinolone molecules (Scheme
2, Eqs. 1-2). In addition, these newly formed products such as
B
.
2
C
is
formed and soon converts into the seven-membered
azapalladacyclic intermediate . Then reductive elimination
affords the Pd(0) species, which is reoxidized to Pd(II) for the
next cycle. Finally, the isomerization of intermediate
D
E
3a, 3b and 3f could be smoothly transformed into the
provides the desired products 3 via 1,3-hydrogen migration.
corresponding 2-aminoquinoline derivatives,18 which are
useful synthons and versatile skeletons in organic synthetic
chemistry (Scheme 2, Eq. 3).19
Scheme 2. Synthetic transformations of 3
Scheme 4. Proposed mechanism
Subsequently, several control experiments were carried out
to explore the mechanism of this reaction. Intriguingly, no
desired product was detected when N-benzyl and N-tosyl
protecting o-alkynylanilines were subjected to the standard
conditions, suggesting that the primary amine moiety was
necessary for this transformation (Scheme 3, Eq. 1). Further
investigation of substrates with a shorter or longer carbon
tether did not afford the expected products, which might be
resulted from the strain of rings or the flexible long carbon
In conclusion, an expedient access to a series of heterocyclic
fused 2-aminoquinolines via palladium-catalyzed tandem
cyclization of o-alkynylanilines with isocyanides has been
developed. Both aniline-tethered homopropargylic alcohols
and amines could be well tolerated in this transformation.
Furthermore, this reaction features readily available materials,
good functional group tolerance, high atom and step economy,
mild reaction conditions and excellent chemo- and
regioselectivities. Further studies on the application of this
chain (Scheme 3, Eq. 2). Finally,
a deuterium labeling
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Wang, W. Chen and Y. Peng, Tetrahedron Lett., 2016, 72, 952. (f)
P. Xu, T. Zhu, T. Wei, Y. Wang and S. Ji, RSC Adv., 2016, 6, 32467.
10. (a) S. Cacchi and G. Fabrizi, Chem. Rev., 2011, 111, PR215. (b) J.
Li, S. Yang, W Wu and H. Jiang, Eur. J. Org. Chem., 2018, 1284-
1306. (c) S. Kumar Alamsetti, A. K. Å. Persson and J.-E. Backväll,
Org. Lett., 2014, 16, 1434. (d) M. Li, Y. Wei, H. Chen, L. Lu and W.
Xiao, J. Am. Chem. Soc., 2017, 139, 14707. (e) M. Yang, D. Yan, Q.
Zhao, J. Chen and W. Xiao, Org. Lett., 2017, 19, 5208. (f) M. Zheng,
P. Chen, L. Huang, W. Wu and H. Jiang, Org. Lett., 2017, 19, 5756.
(g) C. M. R. Volla and J.-E. Backväll, ACS Catal., 2016, 6, 6398.
11. (a) Q. Wang, L. Huang, X. Wu and Jiang, H. Org. Lett., 2013, 15,
5940. (b) J. Chen, X. Han and X. Lu, J. Org. Chem., 2017, 82, 1977.
(c) J. Chen, X. Han and X. Lu, Angew. Chem., Int. Ed., 2017, 56, 1.
(d) D. Li and F. Zeng, Org. Lett., 2017, 19, 6498. (e) R. Yu, D. Li and
F. Zeng, J. Org. Chem., 2018, 83, 323. (f) B. Miao, S. Li, G. Li and S.
Ma, Org. Lett., 2016, 18, 2556. (g) B. V. Subba Reddy, M. Swain, S.
M. Reddy, J. S. Yadav and B. Sridhar, J. Org. Chem., 2012, 77,
11355. (h) K. S. Ock and W. S. Youn, Bull. Korean Chem. Soc., 2010,
31, 704. (i) C. Zhu and S. Ma, Angew. Chem. Int. Ed., 2014, 53,
13532.
strategy for the construction of other N-heterocycles are in
progress in our group.
The authors thank the National Key Research and
Development Program of China (2016YFA0602900), the
National Natural Science Foundation of China (21472051 and
21672072), and Pearl River S&T Nova Program of Guangzhou
(201610010160) for financial support.
Conflicts of interest
There are no conflicts to declare.
Notes and references
1. (a) C. A. Leach, T. H. Brown, R. J. Ife, D. J. Keeling, S. M. Laing, M.
E. Parsons, C. A. Price and K. J. Wiggall, J. Med. Chem., 1992, 35,
1845. (b) J. J. Pfister, Nat. Prod., 1988, 5, 969.
2. A. A. Alhaider, A. M. Abdelkader and E. J. Lien, J. Med. Chem.,
1985, 28, 1394.
3. O. Afzal, S. Kumar, M. R. Haider, M. R. Ali, R. Kumar, M. Jaggi and
S. Bawa, Eur. J. Med. Chem., 2015, 97, 871.
4. S. F. Campbell, J. D. Hardstone and M. J. Palmer, J. Med. Chem.,
1988, 31, 1031.
12. (a) B. C. J. van Esseveldt, F. L. van Delft, R. Gelder and F. P. J. T.
Rutjes, Org. Lett., 2003, 5, 1717. (b) K. Muñiz, J. Am. Chem. Soc.,
2007, 129, 14542. (c) B. Yao, Q. Wang and J. Zhu, Angew. Chem.,
Int. Ed., 2012, 51, 5170. (d) M. V. Karkhelikar, R. R. Jha, B. Sridhar,
P. R. Likhar and A. K. Verma, Chem. Commun., 2014, 50, 8526. (e)
T. M. Ha, B. Yao, Q. Wang and J. Zhu, Org. Lett., 2015, 17, 5256. (f)
J. Zheng, Z. Li, W. Wu and H. Jiang, Org. Lett., 2016, 18, 6236.
13. (a) Y. Yu, L. Huang, W. Wu and H. Jiang, Org. Lett., 2014, 16,
2146. (b) J. Li, S. Yang, W. Wu and H. Jiang, Chem. Commun., 2014,
50, 1381. (c) J. Li, W. Yang, S. Yang, L. Huang, W. Wu, Y. Sun and H.
Jiang, Angew. Chem., Int. Ed., 2014, 53, 7219. (d) Z. Zhang, L. Wu,
J. Liao, W. Wu, H. Jiang, J. Li and J. Li, J. Org. Chem., 2015, 80,
7594. (e) J. Li, C. Li, S. Yang, Y. An, W. Wu and H. Jiang, J. Org.
Chem., 2016, 81, 2875.
14. (a) H. Jiang, H. Gao, B. Liu and W. Wu, Chem. Commun., 2014,
50, 15348. (b) H. Jiang, H. Gao, B. Liu and W. Wu, RSC Adv., 2014,
4, 17222. (c) H. Jiang, M. Yin, Y. Li, B. Liu, J. Zhao and W. Wu,
Chem. Commun., 2014, 50, 2037. (d) J. Peng, Y. Gao, W. Hu, Y.
Gao, M. Hu, W. Wu and H. Jiang, Org. Lett., 2016, 18, 5924. (e) W.
Hu, J. Zheng, J. Li, B. Liu, W. Wu and H. Jiang, J. Org. Chem., 2016,
81, 12451. (f) W. Hu, J. Li, Y. Xu, W. Wu, H. Liu and H. Jiang, Org.
Lett., 2017, 19, 678. (g) J. Peng, Y. Gao, C. Zhu, B. Liu, Y. Gao, M.
Hu, W. Wu and H. Jiang, J. Org. Chem., 2017, 82, 3581.
5. (a) Y.Cheng, T. C. Judd, M. D. Bartberger, J. Brown, K. Chen, R. T.
Fremeau, D. Hickman, S. A. Hitchcock, B. Jordan, V. Li, P. Lopez, S.
L. Louie, Y. Luo, K. Michelsen, T. Nixey, T. S. Powers, C. Rattan, E.
A. Sickmier, D. J. S. Jean, R. C. Wahl, P. H. Wen and S. Wood, J.
Med. Chem., 2011, 54, 5836. (b) K. Grychowska, G. Satała, T. Kos,
A. Partyka, E. Colacino, S. Chaumont-Dubel, X. Bantreil, A.
Wesołowska, M. Pawłowski, J. Martinez, P. Marin, G. Subra, A. J.
Bojarski, F. Lamaty, P. Popik and P. Zajdel, ACS Chem. Neurosci.,
2016, 7, 972. (c) M. A. Cinelli, H. Li, G. Chreifi, P. Martasek, L. J.
Roman, T. L. Poulos and R. B. Silverman, J. Med. Chem., 2014, 57,
1513.
6. (a) L. Zhou and Y. Zhang, Synth. Commun., 1998, 28, 3249. (b) A.
Hamid, A. Elomrib and A. Daïch, Tetrahedron Lett., 2006, 47, 1777.
(c) V. Singh, S. Hutait and S. Batra, Eur. J. Org. Chem., 2009, 3454.
(d) T. Tomioka, Y. Takahashi and T. Maejima, Org. Biomol. Chem.,
2012, 10, 5113. (e) S. Dhiman, H. Kumar Saini, N. Kumar
Nandwana, D. Kumar and A. Kumar, RSC Adv., 2016, 6, 23987.
7. (a) G. Vo and G. F. Hartwig, J. Am. Chem. Soc., 2009, 131, 11049.
(b) D. Maiti, B. P. Fors, J. L. Henderson, Y. Nakamura and S. L.
Buchwald, Chem. Sci., 2011, 2, 57. (c) S. Fantasia, J. Windisch and
M. Scalone, Adv. Synth. Catal., 2013, 355, 627. (d) S. Ge, R. A.
Green and J. F. Hartwig, J. Am. Chem. Soc., 2014, 136, 1617. (e) C.
W. Cheung, D. S. Surry and S. L. Buchwald, Org. Lett., 2013, 15,
3734.
8. (a) P. J. Manley and M. T. Bilodeau, Org. Lett., 2002, 4, 3127. (b) T.
Storz, Org. Process Res. Dev., 2004, 8, 663. (c) J. Yin, B. Xiang, M.
A. Huffman, C. E. Raab and I. W. Davies, J. Org. Chem., 2007, 72,
4554. (d) G. Li, C. Jia and K. Sun, Org. Lett., 2013, 15, 5198. (e) C.
Zhu, M. Yi, D. Wei, X. Chen, Y. Wu and X. Cui, Org. Lett., 2014, 16,
1840.
9. (a) B. Liu, H. Gao, Y. Yu, W. Wu and H. Jiang, J. Org. Chem., 2013,
78, 10319. (b) L. Zhang, L. Zheng, B. Guo and R. Hua, J. Org. Chem.,
2014, 79, 11541. (c) G. R. Kumar, Y. K. Kumar, R. Kant and M. S.
Reddy, Beilstein J. Org. Chem., 2014, 10, 1255. (d) B. Jiang, L. Hu
and W. Gui, RSC Adv., 2014, 4, 13850. (e) Q. Zheng, Q. Ding, C.
15. CCDC 1578030 (3a) contains the supplementary crystallographic
data. These data can also be obtained free of charge from The
Cambridge
Crystallographic
Data
Centre
via
http://www.ccdc.cam.ac.uk/data_request/cif.
16. (a) B. Guyen, C. M. Schultes, P. Hazel, J. Mann and S. Neidle, Org.
Biomol. Chem., 2004, 2, 981. (b) Y. O. Boahen and J. Mann, Chem.
Nat. Compd., 2014, 50, 494. (c) H. Lee, C. Chang, C. Su, H. Huang,
M. Mehndiratta, Y. Chao, C. Hsu, S. Kumar, T. Sung, Y. Huang, Y. Li,
C. Yang and J. B. Liou, Eur. J. Med. Chem., 2016, 122, 92.
17. Y. Wen, L. Huang, H. Jiang and H. Chen, J. Org. Chem., 2012, 77,
2029.
18. (a) D. J. Watson, E. D. Dowdy, W. Li, J. Wang and R. Polniaszek,
Tetrahedron Lett., 2001, 42, 1827. (b) K. D. Schleicher and T. F.
Jamison, Org. Lett., 2007, 9, 875.
19. (a) C. He, J. Hao, H. Xu, Y. Mo, H. Liu, J. Han and A. Lei, Chem.
Commun., 2012, 48, 11073. (b) S. Manna, K. Matcha and A. P.
Antonchick, Angew. Chem., Int. Ed., 2014, 53, 8163. (c) J. Zhou, B.
Li, F. Hu and B. Shi, Org. Lett., 2013, 15, 3460.
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Pd
X
XH
R2
R2
R3
[Pd]
R1
N
+
C
NH2
R1
R3
X = O or NTs
R2 = H or Et
N
N
H
High atom and step economy
C-X, C-C, C=N Bond formations
Excellent chemo- and regioselectivities
A novel strategy for the synthesis of heterocyclic fused 2-aminoquinolines via
palladium-catalyzed tandem cyclization of o-alkynylanilines and isocyanides has been
developed.