Zinc(ii)-catalyzed intramolecular hydroarylation-redox cross-dehydrogenative coupling of N -propargylanilines with diverse carbon pronucleophiles: Facile access to functionalized tetrahydroquinolines

Article abstract of DOI:10.1039/d0cc02921a

Zinc(ii)-catalyzed intramolecular hydroarylation-redox cross-dehydrogenative coupling of N-propargylanilines with two types of carbon pronucleophiles (nitromethane as a sp3 carbon pronucleophile and phenylacetylenes as sp carbon pronucleophiles) proceeded to give the 2-substituted tetrahydroquinolines in good yields with 100percent atomic utilization without any additional external oxidants.

Full text of DOI:10.1039/d0cc02921a

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DOI: 10.1039/D0CC02921A
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Zinc(II)-catalyzed Intramolecular Hydroarylation-Redox Cross-
Dehydrogenative Coupling of N-Propargylanilines with Diverse
Carbon Pronucleophiles: Facile Access to Functionalized
Tetrahydroquinolines
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Guangzhe Li, *a,b Chengdong Wang, a Yueqing Li, a,b Kun Shao, b Guo Yu, c Shisheng Wang, a,b
Xiuhan Guo, a,b Weijie Zhao a,b and Hiroyuki Nakamura c
Zinc(II)-catalyzed
dehydrogenative coupling of N-propargylanilines with two types of carbon methods have been developed to access these 2-substituted
pronucleophiles (nitromethane as
sp3 carbon pronucleophile and tetrahydroquinoline motifs. The most broadly applicable
intramolecular
hydroarylation-redox
cross-
So far, a variety of convenient and versatile synthetic
a
phenylacetylenes as sp carbon pronucleophiles) proceeded to give the 2- methods of the ring construction include intramolecular
substituted tetrahydroquinolines in good yields with 100% atomic utilization cyclizations,[3] Povarov reaction,[4] and partial hydrogenations
without any additional external oxidants.
of quinolines.[5] Besides, the attack of nucleophiles to the
quinoline salts provides an efficient strategy for a direct access
to the 2-substituted 1,2-dihydroquinolines, which can be readily
converted to 2-substituted 1,2,3,4-tetrahydroquinolines
through hydrogenation (Scheme 1, eq 1).[6] Zinc(II)-catalyzed
intramolecular hydrogenation-redox cross-dehydrogenative
coupling (redox CDC) reaction of N-propargylaniline with indole
was firstly reported by our group for preparing 2-
indoltetrahydroquinoline compounds (Scheme 1, eq 2).[7]
Briefly, dihydroquinoline was generated from intramolecular
cyclization firstly, followed by isomerization to give an imine
cation, which would undergo nucleophilic addition with indole
(sp2 carbon nucleophile) to afford the final product. In this
reaction, three C-H bonds (two sp2 and one sp3) were activated
in one shot. With the propargylic triple bond in the molecule
acting as an internal oxidant to trap these hydrogens, there was
no additional external oxidant needed, and notably the atomic
Tetrahydroquinoline is one of the most important heterocyclic
compounds which are widely applied in the pharmaceutical and
agrochemical industries.[1] Particularly, 1,2,3,4-tetrahydro-
quinolines bearing a substitution at the C2-position possess key
role in a class of compounds widely present in natural products
and biologically active molecules with a broad bioactivity
spectrum, including antimalarial, antivirus, antifungal,
antitumor activities and acting on pharmacological targets such
as ion channels and membrane receptors (Figure 1).[2]
OH
O
R1
H
N
N
NH
Me
R2
O
CF3
O2N
N
H
O
O
R1 = H, R2 = OMe
Galipeine
Cuspareine
Galipinine
Mansil
(approved)
SL-251131
R
1 = R2 = OMe
(Clinical Phase I )
Anti-parkinson
R1 = R2 = OCH2O
Anti schistosomiasis
Antimalarial natural products
R2
O
(1) Nucleophilic addition to quinolinium salts:
R
NH
N
R1
N
O
N
[H]
Cat.
R1
R1
N
R1
+
Nu
O
N
N
R2
N
R2
Nu
N
R2
Nu
O
Agonists of the Melatonin
MT2 Receptor
X
NH2
F
Dopamine Receptor 3 ligand
MAO inhibitor
(2) Redox-CDC reaction of N-propargylanilines and carbon pronucleophiles:
R3
Figure 1. The chemical structures of representative natural and bioactive 2-substituted
tetrahydroquinolines.
R3
H
H
Zn or Cu-cat
R1
R1
Carbon Pronucleophiles
H
Nu)
(
H
N
Nu
N
sp2 indoles
ref. 
R2
R2
sp3 nitromethane this study
sp alkynes (this study)
-
H
H
Nu
R3
R3
R3
a. Department of Pharmacy, Schoo of Chemical Engineering, Dalian University of
Technology, No. 2 Linggong Road, Dalian 116024, China.
H
H
R2
[M]
R2
[M]
R2
[M]
+
H
b. State Key Laboratory of Fine Chemicals, Dalian University of Technology, No. 2
Linggong Road, Dalian 116024, China.
N
R1
N
R1
H
N
R1
c. Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo
Institute of Technology, Nagatsuta-cho, Midori-ku, Yokohama 226-8503, Japan.
Electronic Supplementary Information (ESI) available: See DOI: 10.1039/x0xx00000x
Scheme 1. The synthetic strategy of constructing 2-substituted tetrahydroquinolines.
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utilization was 100%. Inspired by these findings, we speculated 17% yield (Table 1, entry 6). The low conversiVoienw AmrtiicglehOtnlbinee
DOI: 10.1039/D0CC02921A
that the activation of these C-H bonds might take place among ascribed to the competitive intramolecular Friedel-Crafts
two sp3 and one sp2 carbons and/or among sp3, sp2, and sp alkylation reaction of an alkyl halide with benzene ring in the
carbons. Herein, we employed nitromethane (sp3 carbon presence of metallic Lewis acid. Then, the effect of substituents
nucleophile) and phenylacetylenes (sp carbon nucleophiles) as at the para position (R2 group) of aniline moiety was examined.
pronucleophiles in the redox CDC reaction with N- N-Benzyl-N-(2-propynyl)anilines (R1 = Bn, R3 = H) with various
propargylanilines, and constructed structurally diverse 2- functional groups at R2, such as electron-donating groups:
substituted tetrahydroquinolines.
methoxy (1g) and methyl (1h), electron-withdrawing groups:
Firstly, we chose N-benzyl-N-(2-propynyl)aniline) (1a) and chloro (1i) and fluoro (1j), also compatible with the reaction,
nitromethane (2) as the model substrates to examine the provided corresponding 2-substituted N-benzyl-1,2,3,4-
hydroarylation-redox CDC reaction. The reaction was tetrahydroquino-lines 3g-j (Table 1, entries 7-10) in moderate
performed in the presence of Zn(OAc)2 (20 mol%) at 100 oC for to good yields. Apart from that, the intramolecular
24 h under nitrogen atmosphere in neat conditions. hydroarylation-redox CDC reaction of N-propargylanilines
Disappointingly, the yield of final product 3a was only 10% having a substituent at R3 such as phenyl (1k), n-butyl (1l) and
(Table S1, entry 14 in the Supporting Information). However, methyl (1m) with nitromethane were examined to interestingly
from the screening of Lewis acid catalysts, it was surprisingly give respective product 3k-m in low to moderate yields with
found that the reaction was greatly accelerated by only 10 mol% trans diastereoselectivity (Table 1, entries 11-13).
of ZnBr2. Then the other parameters (e.g. catalyst concentration,
reaction temperature and solvents etc.) were further optimized. obtained
Thus, 2-nitromethyltetrahydroquinolines can be readily
from various N-(2-propynyl)anilines with
As shown in Table S1, the highest yield of target product 3a nitromethane through the intramolecular hydroarylation-redox
(65% isolated yield, Table S1, entry 15) was achieved in the CDC reaction. Nitroalkanes are known to be broadly versatile
o
presence of ZnBr2 (10 mol%) at 100 C for 24 h under nitrogen building groups in organic synthesis. Not only because of their
atmosphere in neat condition.
widely use in C-C bond formation, including nitro-aldol (Henry
Under this optimized reaction condition, the intramolecular reaction), Michael addition, and Diels-Alder reaction, but also
hydroarylation-redox CDC reaction with various N-propargyl- can the nitro group be converted into other different functional
anilines were evaluated. The results are summarized in Table 1. groups, such as the carbonyl groups by the Nef reaction and the
N-(2-propynyl)anilines (R2 = R3 = H) bearing various substituents amines by reduction.[8] As shown in Scheme 2, compound 3a
at R1, such as phenyl (1b), allyl (1c), methyl (1d) and methyl was reduced by Raney Ni to afford amine 4 as a crucial
acetate (1e) which underwent the intramolecular intermediate for the preparation of MT2 receptor agonist 5.[2c]
hydroarylation-redox CDC reaction with nitromethane (2) Similarly, the hydrogenation of 3a by Pd/C afforded amine 6
smoothly gave the corresponding N-substituted-1,2,3,4- which was treated with 1,1-carbonyldiimidazole (CDI) to give
tetrahydroquinolines 3b-e (Table 1, entries 2-5) in good yields. the corresponding tricyclic product 7, as a synthetic precursor
N-Ethylchloride-N-(2-propynyl)aniline 1f was converted to 3f in of MAO inhibitor, in 74% yield.[2d]
Table 1. Intramolecular hydroarylation-redox CDC reaction of various N-
propargylanilines with nitromethane.
b
a
(1)
NH2
NHCOMe
N
N
R3
Ph
Ph
NO2
5
98%
4
57%
R3
N
R2
R2
ZnBr2 (10 mol%)
Ph
c
d
+
CH3NO2
Neat, 100 o
24 h, N2
C
3a
NH2
NO2
N
(2)
N
H
N
N
R1
NH
R1
1
O
6
99%
7
74%
2
3
Reagents and conditions: (a) Raney Ni (30%),THF, H2, 6 atm, 30 oC,12 h;(b) THF,
acetic anhydride (1.5 eqv.), 30 oC, 2 h; (c) Pd/C (30%),CH3OH, H2, 30 oC, 6 h; (d)
CDI (2.4 eqv.), THF/DMF, N2
1
3
Entry
N-propargylaniline
Yield of [%]
1
2
3
4
5
6
R1
=
=
1a
3a
)
Bn
(
)
)
)
)
)
65 (
1b
3b
Ph
(
61 (
55 (
69 (
40 (
17 (
)
Scheme 2. Synthesis of important intermediates.
1c
3c
allyl
(
)
NO2
N
N
R1
1d
1e
3d
3e
Me
(
)
R1
CH2COOEt
(CH2)2Cl
(
)
Next, the intramolecular hydroarylation-redox CDC reaction
of N-benzyl-N-(2-propynyl)aniline (1a) with phenylacetylene
was examined in the presence of catalytic amount of ZnBr2 (20
mol%). It was particularly gratifying that this reaction
proceeded smoothly in 1,2-dichloroethane (DCM) for 24 h to
afford N-benzyl-2-ethylbenzene-1,2,3,4-tetrahydroquinoline
(9aa) in 80% yield (Table 2, entry 1). The screening of metal
Lewis acid catalysts showed that CuBr exhibited similar catalytic
effects with ZnBr2 (75% yield in Table S2, entry 1). Subsequent
assessment of the concentration of catalyst, the equivalent
ratio of phenylacetylene and the reaction temperature,
indicated that the optimal yield of target product 9aa was
1f
3f
)
(
)
R2
R2
1g
1h
OMe
Me
F
(
)
)
)
R2
3g
3h
47 (
52 (
44 (
70 (
)
)
7
8
(
NO2
N
1i
(
3i
3j
)
)
N
9
1j
( )
Cl
10
Ph
Ph
R3
R3
N
R3 = Ph
n-Bu (
(
)
15(dr = 9:1) (3k)
1k
11
12
13
NO2
N
3l
)
3m
1l
22(dr = 12:1) (
41(dr = 11:1) (
)
1m
)
Me
(
)
Ph
Ph
aRection conditios: 1 (0.25 mmol), 2 (0.5 ml) and ZnBr2 (10 mol%) were heated in a
closed vial tube under N2 atmosphere at 100 oC for 24 h.
2 | J. Name., 2012, 00, 1-3
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R1
o
gained in the presence of ZnBr2 (20 mol%) at 120 C for 24 h
under nitrogen atmosphere.
View Article Online
DOI: 10.1039/D0CC02921A
ZnBr2 (20 mol%)
DCE, 1 M, 120 oC, 24 h
R2
+
N
Me
After establishing optimized reaction conditions, we explored
the scopes of the N-(2-propynyl)anilines. N-(2-propynyl)anilines
(R2 = R3 = H) having diverse substituents at R1, such as phenyl
(1b), allyl (1c) and methyl (1d) proceeded smoothly with
8g
8h
R
R
1 = R2 = OMe
1 = R2 = OCH2O
1d
(3 equiv)
Pd/C (30%), H2 (6 atm)
R1
R2
N
R1
R2
N
phenylacetylene
to
afford
the
corresponding
2-
(1)
Me
CH3OH, rt, 6 h
Me
alkynyltetrahydoquinolines 9ba-9da in moderate to high yields
(Table 2, entries 2-4). N-Benzyl-N-(2-propynyl)anilines having
different functional groups at R2, such as the electron-donating
groups, methoxy (1g) and methyl (1h), and the electron-
withdrawing groups, chloro (1i) and fluoro (1j) groups, gave the
corresponding 2-alkynyltetrahydoquinolines 9ga–9ja in good
yields (Table 2, entries 5-8). The intramolecular hydroarylation-
redox CDC reaction was able to be employed to N-benzyl-N-(2-
propynyl)-anilines having substituents at R3, such as phenyl (1k),
n-butyl (1l) and methyl (1m) with 8a, and the corresponding 2-
alkynyltetrahydoquinolines 9ka-9ma were obtained in good
yields (Table 2, entries 9-11). The diastereomeric ratios of
products 9la and 9ma were approximately 5:1 as calculated
galipinine (10)
99%
9dg
9dh


60%
58%
cuspareine (11)
99%
Grubbs-II.cat.(4 mol%)
N
(2)
Ph
Toluene, 110 oC, 40 h
N
12
51%
9ca
Scheme 3. Synthesis of natural alkaloids and important intermediate.
The current zinc(II)-catalyzed intramolecular hydroarylation-
redox CDC reaction is useful for synthesis of
tetrahydroquinoline framework-containing natural products.
Galipinine and cuspareine, as natural alkaloids isolated from the
trunk bark of Galipea Officinalis Hancock (Rutaceae),[2a,2b] were
able to be synthesized from N-methyl-N-(2-propynyl)aniline
(1d) as shown in Scheme 3. The reaction of 1d with alkynes 8g
and 8h proceeded smoothly to give the desired 2-
alkynyltetrahydroquinolines 9dg and 9dh in 60% and 58%
yields,
respectively. Hydrogenation of 9dg and 9dh proceeded
quantitatively to afford (±)-galipinine (10) and (±)-cuspareine
(11) respectively (Scheme 3, eq 1). It should be noted that the
synthesis of these natural alkaloids only requires two steps from
readily available aniline such as 1d. Furthermore, 2-
phenylethynyl-N-allyl-1,2,3,4-tetrahydroquinoline 9ca obtained
from 1c and 8a underwent intramolecular olefin metathesis in
the presence of the Grubbs-II catalyst to afford the unique aza
tricyclic compound 12 (Scheme 3, eq 2).
1
from H NMR data. We explored the scopes of intramolecular
hydroarylation-redox CDC reaction with respect to the various
substituted aryl alkynes. It turned out that this reaction had an
excellent tolerance with various aromatic groups from electron-
rich
to
electron-deficient
ones,
and
giving
2-
alkynyltetrahydoquinolines 9ab-9af in 58-78% yields (Table 2,
entries 12-16).
Table 2. Intramolecular hydroarylation-redox CDC reaction of various N-
propargylanilines with alkynes.
R3
R3
R2
R2
ZnBr2. (20 mol%)
R4
+
DCE,1 M, 120 oC, 24 h
N
N
R1
R4
R1
1
8
9
(3 equiv)
8
9
1
Alkynes
Yield of [%]
Entry
N-propargylaniline
R1 = Bn (1a)
9aa
80 (
)
1
2
3
4
D
4
H/ (29%d)
1b
9ba
Ph
(
)
51 (
58 (
70 (
)
)
N
R1
D
H/ (52%d)
1c
9ca
allyl
Me
(
)
)
N
3
ZnBr2 (20 mol%)
1d
9da
)
(
R1
8a
8a
D
Ph
+
(1)
2
N
N
DCE,1M,
120 oC, 24 h
1
R2
R2
Ph
R2 = OMe (
)
Ph
Ph
1a
1g
5
6
7
8
9ga
9ha
58 (
52 (
61 (
56 (
)
1h
Me
F
(
(
(
)
N
8a
d- (3 equiv.)
9aa
%
61
d-
N
)
1i
)
D incorporation 93%
9ia
9ja
)
)
1j
Cl
)
D
D
H/ (16%d)
4
R3
D
H/ (10%d)
R3
ZnBr2 (20 mol%)
3
+
Ph
(2)
N
N
2
DCE, 1M,
120 oC, 24 h
R3
9
9ka
59 (dr = 8:1) (
67 (dr = 5:1) (
51 (dr = 5:1) (
)
1k
(
)
Ph
=
n-Bu
Me
1
Ph
10
11
N
N
9la
)
1l
Ph
(
)
8a
Ph
9ma
)
1m
(
)
1a
8a
9aa
d- 70%
d-
(3 equiv.)
D incorporation 99%
R4
D
4
H/ (56%d)
9ab
12
13
14
15
16
58 (
75 (
73 (
60 (
78 (
)
D
ZnBr2 (20 mol%)
9ac
3
)
R4
8b
MeO
=
Me
(
)
)
(3)
Ph
D
+
H/ (80%d)
D
N
9ad
)
8c
(
(
(
DCE, 1M,
120 oC, 24 h
N
N
1a
2
N
9ae
9af
)
8d
F
)
)
1
R4
Ph
Ph
)
8e
8f
Cl
Ph
COOMe (
)
1a'
8a
9aa
d- 70%
d-
(3 equiv.)
D incorporation 99%
aRection conditios: 1 (0.25 mmol), 8 (0.75 mmol, 3 equiv) and ZnBr2 (20 mol%) were
heated in dichloroethane in a closed vial tube under N2 atmosphere at 120 oC for
24 h.
Scheme 4. Deuterium labeling study for the intramolecular hydroarylation-redox CDC
reaction of N-propargylanilines and phenylacetylenes.
The deuterium labeling experiments were further carried
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
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3
(a) I. T. Alt, C. Guttroff, B. Plietker, Angew. Chem, 2017, 129,
out. As shown in Scheme 4, deuterium was incorporated at
C3 and C4 positions of d-9aa from both reactions of 1a with
d-8a (Scheme 4, eq 1) and d-1a with 8a (Scheme 4, eq 2),
suggesting that both terminal alkyne hydrogens (1a and 8a)
were readily exchanged into each other under the conditions.
Because deuterium was not incorporated at C2 position of d-
9aa, the allene intermediate suggested by Zhang et al. would
not be involved in the reaction mechanism (Scheme S3).[9]
Furthermore, the results that 80% and 56% of deuterium
was incorporated at C2 and C4 positions of d-9aa,
respectively, from the reaction of d-1a′ with 8a (Scheme 4,
eq 3) are consistent with our proposed mechanism shown in
Scheme 1, eq. 2.
View Article Online
10718; (b) Z. Pan, S. M. Pound, N. R.DROoI:n1d0l.1a0,3C9./DJ0. CDCo0u2g9l2a1sA,
Angew. Chem. Int. Ed, 2014, 53, 5170; (c) J. F. Briones and G.
S. Basarab, Chem. Commun, 2016, 52, 8541; (d) M.
Bakthadoss, A. Devaraj, D. Kannan, Eur. J. Org. Chem, 2014,
2014, 1505; (e) M. R. Porter, R. M. Shaker, C. Calcanas, J. J.
Topczewski, J. Am. Chem. Soc, 2018, 140, 1211; (f) H.
Borgohain, R. Devi, D. Dheer, B. J. Borah, R. Shankar, S. K. Das,
Eur. J. Org. Chem. 2017, 2017, 6671-6679. (g) D. Mo, L. L.
Anderson, Angew. Chem. Int. Ed, 2013, 52, 6722; (h) M. Yang,
B. Su, Y. Wang, K. Chen, X. Jiang, Y. Zhang, X. Zhang, G. Chen,
Y. Cheng, Z. Cao, Q. Guo, L. Wang, Z. Shi, Nat. Commun, 2014,
5,4707; (i) C. Wang, C. Chen, J. Zhang, J. Han, Q. Wang, K. Guo,
P. Liu, M. Guan, Y. Yao, Y. Zhao, Angew. Chem. Int. Ed, 2014,
53, 9884; (j) V. S. B. Damerla, C. Tulluri, R. Gundla, L. Naviri, U.
Adepally, P. S. Iyer, Y. L. N. Murthy, N. Prabhakar, S. Sen, Chem.
Asian J, 2012, 7, 2351; (k) Y. Chen, X. Zhang, H. Yuan, W. Wei,
M. Yan, Chem. Commun. 2013, 49, 10974; (l) Y. Han, W. Han,
X. Hou, X. Zhang, W. Yuan, Org. Lett, 2012, 43, 8916; (m) Y. K.
Kang, S. M. Kim, D. Y. Kim, J. Am. Chem. Soc, 2010, 132, 11847;
(n) Y. Zhao, Y. Hu, H. Wang, X. Li, B. Wan, J. Org. Chem, 2016,
81, 4412; (o) M. Bakthadoss, D. Kannan, J. Srinivasan, V.
Vinayagam, Org Biomol Chem, 2015, 46, 2870; (p) B. J. Barron,
W. Wong, P. Chiu, K. K. Hii, ACS Catal, 2016, 6, 4189; (q) S.
Rousseaux, B. Liégault, K. Fagnou, Chem. Sci, 2012, 3, 244; r)
J. J. Farndon, X. Ma, J. F. Bower, J. Am. Chem. Soc, 2017, 139,
14005.
In conclusion, we have developed
a zinc-catalyzed
intramolecular hydroarylation-redox CDC reaction of N-
propargyl anilines with two types of carbon pronucleophiles
(nitromethane as
a
sp3 carbon pronucleophile and
phenylacetylenes as sp carbon pronucleophiles) without using
any external oxidants for preparation of the 2-substituted and
2,4-disubstituted tetrahydroquinolines at 100% atomic
utilization rate. The reaction tolerates a wide range of
substrates. Not only the conversion between a plurality of
functional groups or a complex ring system construction, but
also the synthesis of 2-substituted tetrahydroquinoline
bioactive substance or natural products could be realized easily
and efficiently. The reaction mechanism that we previously
proposed was also verified by multiple deuterium labeling
experiments. Because the direct functionalization to
tetrahydroquinolines has not been fully established yet, we
believe that the current intramolecular hydroarylation-redox
CDC is one of the most efficient strategies for the construction
of functionalized tetrahydroquinolines.
4
(a) F. Shi, G. Xing, R. Zhu, W. Tan, S. Tu, Org. Lett, 2012, 15,
128; (b) L. He, M. Bekkaye, P. Retailleau, G. Masson, Org.
Lett, 2012, 14, 3158; (c) J. Lin, G. Zong, R. Du, J. Xiao, S. Liu,
Chem. Commun, 2012, 48, 7738; (d) K. L. Jensen, G. Dickmeiss,
B. S. Donslund, P. H. Poulsen, K. A. Jørgensen, Org. Lett, 2011,
13, 3678; (e) G. Bergonzini, L. Gramigna, A. Mazzanti, M.
Fochi, L. Bernardi, A. Ricci, Chem. Commun, 2010, 46, 327; (f)
H. Liu, G. Dagousset, G. Masson, P. Retailleau, J. Zhu, J. Am.
Chem. Soc, 2009, 131, 4598.
(a) L. Xu, K. H. Lam, J. Ji, J. Wu, Q. Fan, W. Lo, A. S. C. Chan,
Chem. Commun. (Cambridge), 2005, 1390; (b) P. Yang, Y.
Zhou, Tetrahedron: Asymmetry, 2004, 15, 1145; (c) W. Wang,
S. Lu, P. Yang, X. Han, Y. Zhou, J. Am. Chem. Soc, 2003, 125,
10536.
5
6
This work was supported by the National Natural Science
Foundation of China (Grant No. 21606036) and the
Fundamental Research Funds for the Central Universities
(DUT18LK11, DUT16RC(3)007).
(a) V. Sridharan, P. A. Suryavanshi, J. C. Menéndez, Chem. Rev,
2011, 111, 7157; (b) Y. Wang, Y. Liu, D. Zhang, H. Wei, M. Shi,
F. Wang, Angew. Chem. Int. Ed, 2016, 55, 3776.
7
8
G. Li, H. Nakamura, Angew. Chem. Int. Ed, 2016, 55, 6758.
(a) G. Rosini and R. Ballini, Synthesis, 1988, 833; (b) A. G. M.
Barrett and G. G. Graboski, Chem. Rev, 1986, 86, 751; (c) M.
Brindisi, S. Butini, S. Franceschini, S. Brogi, F. Trotta, S. Ros, A.
Cagnotto, M. Salmona, A. Casagni, M. Andreassi, S. Saponara,
B. Gorelli, P. Weikop, J. D. Mikkelsen, J. Scheel-Kruger, K.
Sandager-Nielsen, E. Novellino, G. Campiani, S. Gemma, J.
Med. Chem, 2014, 57, 9578; (d) A. L. Rodriguez, Y. Zhou, R.
Williams, C. David Weaver, P. N. Vinson, E. S. Dawson, T.
Steckler, H. Lavreysen, C. Mackie, J. M. Bartolomé, G. J.
Macdonald, J. Scott Daniels, C. M. Niswender, C. K. Jones, P.
Jeffrey Conn, C. W. Lindsley, S. R. Stauffer, Bioorg. Med. Chem.
Lett, 2012, 22, 7388; (e) T. Guo, H. Gu, D. W. Hobbs, L. L.
Rokosz, T. M. Stauffer, B. Jacob, J. W. Clader, Bioorg. Med.
Chem. Lett, 2007, 17, 3010.
Conflicts of interest
There are no conflicts to declare.
Notes and references
1
(a) V. Sridharan, P. A. Suryavanshi, J. C. Menendez, Chem. Rev,
2011, 111, 7157; (b) I. Muthukrishnan, V. Sridharan, J. C.
Menéndez, Chem. Rev, 2019, 119, 5057.
2
(a) P. J. Houghton, T. Z. Woldemariam, Y. Watanabe, M. Yates,
Planta Med, 1999, 65, 250; (b) I. Jacquemond-Collet, F.
Benoit-Vical, Mustofa, A. Valentin, E. Stanislas, M. Mallie, I.
Fouraste, Planta Med, 2002, 68, 68; (c) A. O'Byrne and P.
Evans, Tetrahedron, 2008, 64, 8067; (d) G. Spadoni, A. Bedini,
S. Lucarini, M. Mari, D. Caignard, J. A. Boutin, P. Delagrange,
V. Lucini, F. Scaglione, A. Lodola, F. Zanardi, D. Pala, M. Mor,
S. Rivara, J. Med. Chem, 2015, 58, 7512; (e) C. Banzatti, A.
Dellatorre, P. Melloni, D. PieraccioliI, P. Salvadori, J.
Heterocyclic Chem,1983, 20, 139; (f) S. M. El-Zoghby, S. A.
Ebied, Z. A. Kholy, A. A. Saad, G. A. Abdel-Tawab, N. A.
Hammouda and Y. A. El-Gohary, Biochem. Pharmacol, 1980,
29, 429.
9
H. Wang, M. Dong, C. Liu, D. Zhang, Catal. Sci. Technol, 2018,
8, 1997.
4 | J. Name., 2012, 00, 1-3
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Redox cross-dehydrogenative coupling of N-propargylanilineDsOI: w10.1i0t3h9/D0CC02921A
diverse carbon pronucleophiles offers a general and efficient synthetic
method to construct functionalized tetrahydroquinolines.

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DOI: 10.1039/D0CC02921A
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