Mild and efficient synthesis of indoles and isoquinolones via a nickel-catalyzed Larock-type heteroannulation reaction

Article abstract of DOI:10.1039/c8ob00795k

A simple and efficient approach for the preparation of substituted indoles and isoquinolones via a nickel-catalyzed Larock-type heteroannulation reaction is reported. This transformation employed air-stable and inexpensive Ni(dppp)Cl₂ as a precatalyst and Et₃N as a mild base. Moreover, the reaction occurs efficiently under mild conditions, and a wide range of substituted indoles and isoquinolones bearing various functional groups are obtained in moderate to excellent yields.

Full text of DOI:10.1039/c8ob00795k

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
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Mild and efficient synthesis of indoles and isoquinolones via a
nickel-catalyzed Larock-type heteroannulation reaction
Wei-Zhi Weng,‡ Jian Xie‡ and Bo Zhang*
Received 00th January 20xx,
Accepted 00th January 20xx
A simple and efficient approach for the preparation of substituted indoles and isoquinolones via a nickel-catalyzed Larock-
type heteroannulation reaction is reported. This transformation employed air-stable and inexpensive Ni(dppp)Cl2 as a
precatalyst and Et3N as a mild base. Moreover, the reaction occur efficiently under mild conditions, and a wide range of
substituted indoles and isoquinolones bearing various functional groups are obtained in moderate to excellent yields.
DOI: 10.1039/x0xx00000x
www.rsc.org/
develop cross-coupling reactions catalyzed by non-precious
Introduction
metals that
Previous reports:
R3
NR1
Conditions
NHR1
R2
R2
+
Nitrogen heterocycles, especially indoles and isoquinolones,
are ubiquitous structural motifs present in many natural
products, medicinally relevant compounds, and functional
materials.1,2 Because of the importance of these structures in
medicinal chemistry and drug discovery the development of
new and efficient synthetic methods for their preparation
continues to be a very active field of research in organic
chemistry.3 Pioneering work by Larock demonstrated an
efficient method for the preparation of substituted indoles via
a palladium-catalyzed heteroannulation reaction of ortho-
haloaniline derivatives with alkynes.4 From then on, this
methodology became an efficient synthetic platform for the
preparation of substituted indoles. The development of
approaches to couple ortho-haloaniline derivatives with
alkynes has been studied extensively in the past decades, and
recent progress has greatly expanded the scope of palladium-
catalyzed heteroannulation reaction.5 Apart from indoles, this
kind of Larock-type heteroannulation reaction was also
successfully applied to the construction of other nitrogen
heterocycles (Scheme 1, a).6 Nevertheless, in these processes,
the use of expensive palladium catalyst is not cost-efficient for
industrial use. Moreover, these approaches usually required
specialized ancillary ligands, high temperatures, and/or an
excess of the alkyne. In this regard, the development of a new
strategy to produce nitrogen heterocycles using inexpensive
metal catalytic systems and mild reaction conditions is still
attractive.
R3
I
R4
R4
nitrogen heterocycles
Conditions: a) Pd0, ligand, base, additive, 100-140 o
b) NiII, metal reductant, base, 80 oC
C
c) Ni0, ligand, tBuOLi, 100 o
C
This work:
R2
O
R3
R1
R3
R3
cat. Ni(dppp)Cl2
Et3N, CH3CN
N
NHR1
+
R2
R4
R2
or
N
R1
I
R4
40 o
C
R4
indoles
isoquinolones
Scheme 1 Preparation of substituted nitrogen heterocycles via a transition-
metal-catalyzed Larock-type heteroannulation reaction.
are typically catalyzed by precious metal catalysts.7 In
particular, the utilization of nickel catalysts in cross-coupling
reactions has received considerable attention, because nickel
is cheaper and significantly more abundant than its precious
metal counterparts (e.g., palladium).8 Notably, some studies
on the preparation of substituted indoles and isoquinolones
via a nickel-catalyzed Larock-type heteroannulation reaction
have been reported. In 2010, Cheng and co-workers developed
a
nickel-catalyzed heteroannulation reaction of ortho-
iodobenamides with alkynes to produce substituted
isoquinolones (Scheme 1, b).9 In 2011, Matsubara and co-
workers described a similar protocol to construct substituted
indoles (Scheme 1, c).10 However, the former approach
requires elevated temperatures and stoichiometric metal
reductant (Zn), and the latter approach suffers from harsh
reaction conditions and the use of strong base (tBuOLi) and
air/moisture-sensitive Ni(0) catalyst.
Recently, tremendous interest has been attracted to
With these limitations in mind, we sought to develop a
general, mild, and practical approach for the synthesis of these
useful nitrogen heterocycles. Along this line, we recently
developed a simple and cost-efficient nickel catalytic system
that can efficiently catalyze the formation of isoquinolines
starting from 2-haloaldimines and alkynes under very mild
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a
conditions.11 This nickel catalytic system uses air-stable and
inexpensive Ni(II) salt as a catalyst and Et3N as a mild base.
Encouraged by this work, we questioned whether indoles and
isoquinolones can be obtained by a nickel-catalyzed Larock-
type heteroannulation reaction using a simple Ni(II)/Et3N
system. Herein, we report a general and efficient nickel-
catalyzed Larock-type heteroannulation reaction to prepare
substituted indoles and isoquinolones under mild conditions
(Scheme 1). The new Larock-type heteroannulation variant can
be accomplished in moderate to excellent yields with a broad
substrate scope. The reaction employs inexpensive and
air/mosture-stable Ni(II) catalysts that are advantageous over
Ni(0). Importantly, this protocol operates efficiently without
the need for stoichiometric metal reductants and additional
ligands.
Reaction conditions: 1 (0.2 mmol), 2 (0.3 mmol), catalyst (10 mol%), and
base (0.4 mmol) in solvent (2.0 mL) at 40 oC under N2 for 12 h Isolated
yields. The reaction was conducted at room temperature. Using NiCl2,
Ni(acac)2, Ni(NO3)2•6H2O, Ni(OTf)2, or Ni(OAc)2•4H2O as a precatalyst.
dppp
bis(diphenylphosphino)ethane, dppf = 1,1'-bis(diphenylphosphino)ferrocene,
DBU 1,8-diazabicyclo[5.4.0]undec-7-ene, DABCO 1,4-
diazabicyclo[2.2.2]octane.
b
c
d
=
1,3-bis(diphenylphosphino)propane,
dppe
=
1,2-
=
=
found that this transformation could work in the presence of
Et3N, DABCO or iPrNEt, and Et3N performed best (Table 1,
entries 3-9). With Et3N as a base, several nickel sources were
then examined. Some nickel complexes with phosphine ligands,
such as Ni(dppe)Cl2, Ni(dppf)Cl2, and Ni(PPh3)Cl2, delivered
3 in
20-86% yields (Table 1, entries 10-12). However, the reaction
did not occur in the absence of a ligand (Table 1, entry 13).
Other solvents were also surveyed but consistently led to
lower conversion (Table 1, entries 14-20). No
3 was observed
when the reaction was carried out in the absence of a nickel
catalyst, thus confirming the catalytic effect of nickel salt
(Table 1, entry 21).
Results and discussion
Our studies started with the indolization reaction of N-(2-
With optimized experimental conditions established, the
scope of this indolization reaction was next explored. As
showed in Table 2, various electron-donating and electron-
withdrawing substituents at the 4- or 5-positions of the ortho-
iodophenyl)acetamide
1 and 1,2-diphenylethyne 2 in the
presence of Ni(dppp)Cl2 as a precatalyst and Et3N as a base in
CH3CN at room temperature for 12 h. Fortunately, we found
that the indole
3 was obtained in 75% yield (Table 1, entry 1).
iodoacetanilide electrophile were well tolerated
(4-14).
Upon slightly elevating reaction temperature, the yield of
3
Substitution at the 3-position of the aromatic ring resulted in
moderate yield, probably for steric reasons (15). Moreover,
naphthalene-derived substrate could also participate in the
reaction to deliver the desired product 16. Unfortunately, 2-
iodo-N-methylaniline failed to afford the desired product. We
then investigated the scope of alkyne coupling partners (Table
2). Symmetrical diaryl-substituted alkynes bearing electron-
donating or electron-withdrawing substituents consistently
could reach to 91% (Table 1, entry 2). Investigations were
continued by screening different bases, including Cs2CO3,
Na2CO3, K2CO3, DBU, 2,6-lutidine, DABCO, and iPrNEt, and we
Table 1 Optimization of the reaction conditionsa
afforded the desired indoles 17-21 in moderate to excellent
yields. A thiophene-derived internal alkyne also produced the
targeted product 22 in good yield. Besides diaryl-substituted
alkynes, symmetrical dialkyl-substituted alkynes could also
participate in our nickel-catalyzed Larock-type
Entry
1c
Catalyst
Base
Solvent
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
THF
Yieldb (%)
Ni(dppp)Cl2
Ni(dppp)Cl2
Ni(dppp)Cl2
Ni(dppp)Cl2
Ni(dppp)Cl2
Ni(dppp)Cl2
Ni(dppp)Cl2
Ni(dppp)Cl2
Ni(dppp)Cl2
Ni(dppe)Cl2
Ni(dppf)Cl2
Ni(PPh3)Cl2
NiX2
Et3N
75
91
0
2
Et3N
3
Cs2CO3
Na2CO3
K2CO3
DBU
2,6-lutidine
DABCO
iPrNEt
Et3N
4
trace
0
5
6
0
7
0
8
52
64
20
86
30
0
9
10
11
12
13d
14
15
16
17
18
19
20
21
Et3N
Et3N
Et3N
Ni(dppp)Cl2
Ni(dppp)Cl2
Ni(dppp)Cl2
Ni(dppp)Cl2
Ni(dppp)Cl2
Ni(dppp)Cl2
Ni(dppp)Cl2
none
Et3N
37
10
10
13
trace
trace
trace
0
Et3N
DCE
Et3N
DMSO
DMF
Et3N
Et3N
EtOAc
MeOH
toluene
CH3CN
Et3N
Et3N
Et3N
2 | J. Name., 2012, 00, 1-3
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Table 2 Scope of the nickel-catalyzed Larock-type heteroannulation reaction Table 3 Scope of the nickel-catalyzed Larock-type heteroannulation reaction
of ortho-iodoacetanilides with alkynesa,b
of ortho-iodobenzamides with alkynesa,b
O
O
R2
R4
R1
Ni(dppp)Cl2 (10 mol%)
N
R1
R3
(1.2 equiv)
R4
N
+
R2
H
Et3N (2.0 equiv)
CH3CN, 40 oC, 6 h
I
R3
R1 = 4-MeC6H4
O
O
O
N
R1
Ph
30, R = H, 95%
Me
R1
Ph
R
R1
Ph
N
N
31, R = Me, 97%
32, R = OMe, 98%
33, R = F, 96%
34, R = CO2Me, 82%
Me
Ph
Me
Ph
Ph
O
35, 49%
36, 75%
O
O
MeO
R1
R1
R1
Ph
O
O
N
N
N
MeO
Ph
Ph
F3C
Ph
37, 88%
Ph
38, 91%
Ph
39, 36%
R
O
O
O
N
R1
Ph
R
N
N
Ph
Ph
Ph
Ph
Ph
41, R = H, 94%
42, R = OMe, 92%
43, R = F, 91%
40, 98%
44, R = Me, 43%
45 R = benzyl, 20%
O
O
R1
R1
N
N
46, R = 4-Me, 94%
47, R = 4-OMe, 90%
48, R = 4-F, 97%
49, R = 4-Cl, 93%
50, R = 3-Me, 64%
R
S
a
Reactions were conducted on a 0.2 mmol scale following the reaction
R
S
conditions given in Table 1. b Isolated yields. c The reaction was conducted in
the presence of Ni(dppe)Cl2 (15 mol%) for 24 h. d Ratio of regioisomers.
52, R3 = R4 = Et, 97%
51, 90%
O
53, R3 = R4 = nPr, 92%
54, R3 = R4 = nBu, 90%
55, R3 = R4 = CH2OMe, 86%
56, R3 or R4 = Me or Ph, 93% (1.1:1)c
57, R3 or R4 = H or Ph, 91% (1:1)c
R1
R4
N
heteroannulation reaction to afford the corresponding
products in good yields (23-25). In addition, we investigated
R3
unsymmetrical alkynes and found that prop-1-yn-1-ylbenzene
and phenylacetylene reacted under optimized conditions with
complete regioselectivity to 26 and 28. The reaction conducted
with unsymmetrical dialkyl-substituted alkyne provided the
indole product 27 as a 1.3:1 regioisomeric mixture. The low
a Reactions were conducted on a 0.2 mmol scale. b Isolated yields. c Ratio of
regioisomers.
reactivity (41-43). However, substrates with a methyl or benzyl
protecting group reacted sluggishly to give the products in low
yields (44 and 45). Next, we examined the scope of alkyne
coupling partners (Table 3). Various symmetrical diaryl-
substituted alkynes and symmetrical dialkyl-substituted
alkynes with different functional groups underwent this facile
cyclization to deliver the corresponding isoquinolones in good
yields for 12, 15, 16, 26, and 28 were due to the incomplete
conversions of substrates.
To further probe the applicability of this protocol, we turned
out attention to the synthesis of isoquinolones. To our delight,
under the same reaction conditions, the reaction of 2-iodo-N-
to excellent yields (46-55). For unsymmetrical alkynes, we
(p-tolyl)benzamide 29 with 1,2-diphenylethyne
2 afforded the
found that prop-1-yn-1-ylbenzene and phenylacetylene
afforded the products as a 1:1 regioisomeric mixture (56 and
57). Compared to Cheng’s protocol,9 the advantages of the
current method include: (1) simple and mild reaction
conditions; (2) broad substrate scope; (3) a stoichiometric
amount of metal reductant is not required. These advantages
make this method very practical.
desired isoquinolone 30 in 95% yield. Intriguingly, the yield of
30 was not affected when the reaction was conducted with a
slight excess (1.2 equiv) of 1,2-diphenylethyne for 6 h. Under
this reaction condition, we examined the scope of this
transformation (Table 3). Ortho-iodobenzamides carrying
various substituents are suitable substrates, leading to the
corresponding isoquinolones 31-39 in good to excellent yields
To show the practical usefulness of this method, the nickel-
catalyzed Larock-type heteroannulation reaction has been
performed on a gram scale. As shown in Scheme 2, the indole
regardless of their electronic and steric properties.
Naphthalene-derived substrate coupled readily with 1,2-
diphenylethyne to give the isoquinolone 40. Moreover, the
phenyl protecting groups bearing electron-donating and
electron-withdrawing substituents did not hamper the
3
and isoquinolone 29 were prepared in 82% yield (1.27g) and
90% yield (1.39 g), respectively.
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Ph
I
Ni(dppp)Cl2 (10 mol%)
Ph
+
Ph
Ph
(a)
Et3N (2.0 equiv)
CH3CN, 40 oC 12 h
N
NHAc
Ac
1
2
3
TEMPO (2.0 equiv)
BHT (2.0 equiv)
0%
76%
Me
Me
O
O
N
Ni(dppp)Cl2 (10 mol%)
N
H
(b)
+
Ph
Ph
Et3N (2.0 equiv)
CH3CN, 40 oC, 6 h
I
Ph
Ph
29
2
30
TEMPO (2.0 equiv)
BHT (2.0 equiv)
0%
93%
Scheme 2 Gram-scale reactions.
Ph
To gain further insight into the reaction mechanism, some
control experiments were conducted. When TEMPO was
added as a radical scavenger, the desired transformations
were completely inhibited. However, when BHT was added
into the reactions, the targeted products were formed in good
yields, which is different from the result of TEMPO (Scheme 3a
and 3b). We hypothesized that TEMPO on one hand acts as a
radial scavenger, and on the other hand it might interact with
Ni(II) to stop these reactions. To probe whether these
reactions occur through a radical pathway, we performed
radical clock experiments and radical trapping experiments,
and found that no ring-opening products or radical adducts
were formed (for details see the Supporting Information).
These experimental results indicated that aryl radicals are not
likely involved in these reactions. Next, these reactions were
conducted in the presence of a catalytic amount of Ni(cod)2
(cod = 1,5-cyclooctadiene) and dppp, and the desired products
Ni(cod)2 (10 mol%)
dppp (15 mol%)
I
Ph
+
Ph
Ph
(c)
Et3N (2.0 equiv)
CH3CN, 40 oC, 12 h
N
NHAc
Ac
1
2
3, 97%
Me
Me
O
I
O
Ni(cod)2 (10 mol%)
dppp (15 mol%)
N
N
H
(d)
(e)
+
Ph
Ph
Et3N (2.0 equiv)
CH3CN, 40 oC, 6 h
Ph
Ph
29
2
30, 95%
Ph
I
Ni(dppp)Cl2 (10 mol%)
CH3CN, 40 oC, 12 h
Ph
+
Ph
Ph
N
NHAc
Ac
1
2
3
With Et3N (2.0 equiv)
Without Et3N
91%
0%
Me
Me
O
O
Ni(dppp)Cl2 (10 mol%)
CH3CN, 40 oC, 6 h
N
N
H
+
Ph
Ph
(f)
I
Ph
Ph
29
2
30
3
and 30 were obtained in excellent yields, thus indicating that
With Et3N (2.0 equiv)
Without Et3N
95%
0%
Ni(0) may be the active catalyst in the current reactions
(Scheme 3c and 3d). Furthermore, we found that the reactions
did not take place in the absence of Et3N, thus suggesting that
Et3N is key for the heteroannulation reaction to occur (Scheme
5e and 5f). According to these experimental observations and
Scheme 3 Mechanistic studies.
previous reports,4,5,9 we proposed
a plausible reaction
Conclusions
mechanism. The active Ni(0) catalyst is first formed by an in
situ reduction of Ni(II) with the help of Et3N,11,12 followed by
oxidative addition into the corresponding C-I bond to form
aryl-Ni(II)I species. Subsequent deprotonation of the amide
hydrogen by Et3N gives the five-membered ring nickelacycle
intermediate. Finally, coordinative insertion of alkyne,
followed by reductive elimination delivers the product. This
process allows the regeneration of the active Ni(0) catalyst.13
In summary, we have presented a simple and mild nickel-
catalyzed Larock-type heteroannulation reaction, in which the
air-stable and inexpensive Ni(dppp)Cl2 was used as
precatalyst and Et3N as mild base. Notably, neither
a
a
stoichiometric metal reductant nor additional ligand is
required in this process. This protocol provides an efficient
methodology to access a wide range of substituted indoles and
isoquinolones in moderate to excellent yields. These reactions
are easy to carry out and amenable to gram-scale synthesis.
Further studies on the mechanism and the synthetic
applications are currently ongoing.
Experimental
General information
All manipulations were conducted with a standard Schlenk
tube under a nitrogen atmosphere. Unless otherwise noted,
materials obtained from commercial suppliers were used
without further purification. Ortho-iodoacetanilides were
prepared according to
a
reported method.5c Ortho-
iodobenzamides were prepared according to a reported
method.9 Flash column chromatography was carried out on
4 | J. Name., 2012, 00, 1-3
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silica gel (200-300 mesh). Thin layer chromatography (TLC) was White solid (73.7 mg, 95%). Mp: 216-218 °C; 1H NMR (300
performed using silica gel 60 F254 plates. 1H NMR spectra were MHz, CDCl3) δ 8.57 (d, J = 7.5 Hz, 1H), 7.58-7.47 (m, 2H), 7.26-
recorded on
a
Bruker AV-300 spectrometer at room 7.12 (m, 6H), 6.99 (s, 4H), 6.89 (s, 5H), 2.21 (s, 3H); 13C NMR
temperature. Chemical shifts (in ppm) were referenced to (75 MHz, CDCl3) δ 162.7, 141.2, 137.6, 137.2, 136.8, 136.4,
tetramethylsilane (δ = 0 ppm) in CDCl3 as an internal standard. 134.9, 132.4, 131.6, 131.0, 129.2, 129.1, 128.2, 127.9, 127.1,
13C NMR spectra were obtained by the same NMR 127.0, 126.8, 126.7, 125.5, 118.6, 21.0; HRMS (ESI) calculated
spectrometer and were calibrated with CDCl3 (δ = 77.00 ppm). for C28H22NO [M+H]+ m/z 388.1696, found 388.1704.
Data for 1H NMR are reported as follows: chemical shifts (δ
ppm), multiplicity (s = singlet, d = doublet, t = triplet, q =
Acknowledgements
quartet, m = multiplet or unresolved, br s = broad singlet),
coupling constant (Hz) and integration. Data for 13C NMR are
This work is financially supported by the National Natural
reported in terms of chemical shift and multiplicity where
Science Foundation of China (21702230), the Natural Science
Foundation of Jiangsu Province (BK20160743), the Program
appropriate. Mass spectra were performed on an Aglient 6530
Q-TOF for HRMS. The yields were determined on a METTLER for Jiangsu Province Innovative Research Team, and the 111
Project (B16046).
TOLEDO ME 104 balance (accuracy: 0.1 mg). Melting points
(Mp) were determined on a SGW X-4B and are uncorrected.
General procedure for the synthesis of indoles via a nickel-
catalyzed Larock-type heteroannulation reaction of ortho-
iodoacetanilides with alkynes (GP1)
Notes and references
1
For some reviews, see: (a) J. A. Joule and K. Mills,
Heterocyclic Chemistry, Blackwell Science, Oxford, 2000; (b) T.
Eicher, S. Hauptmann and A. Speicher, The Chemistry of
Heterocycles, Wiley-VCH Verlag GmbH & Co, Weinheim, 2nd
edn, 2003; (c) T. Kawasaki and K. Higuchi, Nat. Prod. Rep.,
2005, 22, 761; (d) N. Saracoglu, Top. Heterocycl. Chem., 2007,
11, 145-178.
Ortho-iodoacetanilide (0.2 mmol, 1.0 equiv), alkyne (0.3 mmol,
1.5 equiv), Ni(dppp)Cl2 (0.02 mmol, 0.1 equiv), and Et3N (0.4
mmol, 2.0 equiv) were placed in a dry 10 mL Schlenk tube
under a nitrogen atmosphere. Dry CH3CN (2.0 mL) was added
with a syringe and the reaction mixture was stirred at 40 oC for
12 h monitored with TLC. After completion of the reaction, it
was transferred to a round-bottomed flask after dilution with
CH2Cl2. The solvent was removed under reduced pressure and
the residue was purified by flash column chromatography on
silica gel to afford the product.
2
For selected examples, see: (a) M. C. González, C. Zafra-Polo,
M. A. Blázquez, A. Serrano and D. Cortes, J. Nat. Prod., 1997,
60, 108; (b) T. Wang, Q. Xu, P. Yu, X. Liu and J. M. Cook, Org.
Lett., 2001, 3, 345; (c) F. Coelho, D. Veronese, E. C. S. Lopes
and R. C. Rossi, Tetrahedron Lett., 2003, 44, 5731; (d) M.
Nagarajan, A. Morrell, B. C. Fort, M. R. Meckley, S. Antony, G.
Kohlhagen, Y. Pommier and M. Cushman, J. Med. Chem.,
2004, 47, 5651; (e) A. L. Ruchelman, P. J. Houghton, N. Zhou,
A. Liu, L. F. Liu and E. J. LaVoie, J. Med. Chem., 2005, 48, 792;
(f) A. Cappelli, G. P. Mohr, G. Giuliani, S. Galeazzi, M. Anzini, L.
Mennuni, F. Ferrari, F. Makovec, E. M. Kleinrath, T. Langer, M.
General procedure for the synthesis of isoquinolones via a nickel-
catalyzed Larock-type heteroannulation reaction of ortho-
iodobenzamides with alkynes (GP2)
Ortho-iodobenzamide (0.20 mmol, 1.0 equiv), alkyne (0.24
mmol, 1.2 equiv), Ni(dppp)Cl2 (0.02 mmol, 0.1 equiv), and Et3N
(0.4 mmol, 2.0 equiv) were placed in a dry 10 mL Schlenk tube
under a nitrogen atmosphere. Dry CH3CN (2.0 mL) was added
with a syringe and the reaction mixture was stirred at 40 oC for
6 h monitored with TLC. After completion of the reaction, it
was transferred to a round-bottomed flask after dilution with
CH2Cl2. The solvent was removed under reduced pressure and
the residue was purified by flash column chromatography on
silica gel to afford the product.
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Characterisation data for representative products
1-(2,3-Diphenyl-1H-indol-1-yl)ethanone (3)
White solid (56.7 mg, 91%). Mp: 130-132 °C; 1H NMR (300
MHz, CDCl3) δ 8.46 (d, J = 8.4 Hz, 1H), 7.56 (dd, J = 7.8, 0.6 Hz,
1H), 7.43-7.20 (m, 12H), 1.99 (s, 3H); 13C NMR (75 MHz, CDCl3)
δ 171.6, 136.7, 134.9, 133.0, 132.9, 130.7, 130.0, 129.2, 128.6,
128.6, 128.2, 126.9, 125.5, 123.4, 123.3, 119.5, 116.2, 27.9;
HRMS (ESI) calculated for C22H18NO [M+H]+ m/z 312.1383,
found 312.1382.
4
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This journal is © The Royal Society of Chemistry 20xx
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Organic & Biomolecular Chemistry
Page 6 of 7
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DOI: 10.1039/C8OB00795K
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Page 7 of 7
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/C8OB00795K
Wei-Zhi Weng, Jian Xie and Bo Zhang*
Mild and efficient synthesis of indoles and
isoquinolones via a nickel-catalyzed Larock-type
heteroannulation reaction
A simple and mild approach for the preparation of substituted indoles
and isoquinolones via nickel-catalyzed Larock-type heteroannulation
reaction is reported
.