Revisiting the Gold-Catalyzed Dimerization of 2-Ethynylanilines: A Room-Temperature and Silver-Free Protocol for the Synthesis of Multifunctional Quinolines

Article abstract of DOI:10.1055/s-0035-1561305

A room temperature and silver-free protocol for the formation of quinolines from 2-ethynylanilines through a dimerization event was achieved using a dinuclear gold catalyst, Au₂(BIPHEP)(NTf₂)₂. The reaction is inherently modular, allowing for the incorporation of peripheral substituents at any site of the quinoline product. The reaction is readily applied to other heterocyles also as exemplified by the preparation of naphthyridines. Competition reactions to determine the reactivity of dissimilar alkynes demonstrated that the product ratio of dimerization vs intermolecular addition is rather dependent on the electronic nature of aryl substituent on the alkynes. However, control experiments with substrates possessing internal alkynes resulted in cycloisomerization instead of expected dimerization, which is indicative of possible steric influence of the alkyne terminus in the reaction outcome.

Full text of DOI:10.1055/s-0035-1561305

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2016, 48, A–J
paper
A
C. Praveen, P. T. Perumal
Paper
Synthesis
Revisiting the Gold-Catalyzed Dimerization of 2-Ethynylanilines:
A Room-Temperature and Silver-Free Protocol for the Synthesis of
Multifunctional Quinolines
Chandrasekar Praveen*a
P. T. Perumalb
R1
Me
R1
NH2
R2
R2
R3
R4
R3
[Au2(BIPHEP)(NTf2)2] (2.5 mol%)
NH2
+
R4
R3
a Functional Materials Division, CSIR-Central Electrochemical
Research Institute, Karaikudi 630006, India
chandrasekar.praveen@gmail.com
b Organic Chemistry Division, CSIR-Central Leather Research
Institute, Adyar, Chennai 600020, India
R3
N
NH2
R1
(CH2Cl)2, 25 °C, 6 h
R4
20 examples
up to 96% yield
R4
R2
R1
'intermolecular dimerization'
R1, R2, R3, R4 = H, Me, MeO, Br, Cl, F,
CN, CO2Me, NO2, CPh3
R2
Dedicated to Professors Vèronique Michelet and Virginie
Ratovelomanana-Vidal with friendship and respect for their
contributions to transition-metal catalysis.
Received: 11.10.2015
Accepted after revision: 02.12.2015
Published online: 07.01.2016
species and behave ‘softer’ than simple gold(III) salts. They
are generally formed in situ via cationization of a gold(I)
complex (usually R3PAuCl) by means of halide abstraction
with a silver co-catalyst (AgOTf, AgNTf2, AgBF4, AgSbF6,
AgClO4, AgPF6).5 Early gold complexes featured phosphine
ligands predominantly such as PPh3 and these were joined
recently by N-Heterocyclic Carbenes (NHCs). Thanks to
their unique electronic and steric properties, carbene li-
gands offer highly valuable features for gold catalysis.6 It
has been suggested that the selectivity in catalytic applica-
tions in Au-NHC systems may very well be controlled as a
function of backbone substitutions, flexible N-substituents,
and ligand sterics. The main features brought by NHC coor-
dination are thermal stability of the resulting complex and
increased electron-donating abilities compared to the ubiq-
uitous tertiary phosphine family. Additionally, they possess
unprecedented σ-donation and steric bulk that enhances
the stability of catalytic intermediates. Another possibility
to use the most active and stable gold catalysts is their liga-
tion with a special class of NHCs called N-Heterocyclic Oxo-
Carbenes (NHOCs),7 Nitrogen Acyclic Carbenes (NACs),8 and
NHC-gold(I) hydroxide complexes ([Au(OH)NHC]).9 These
new generation AuNHCs exhibit improved catalytic activity
as compared to the typical gold catalysts and they have
been shown to be effective in numerous transformations
with quite promising TONs. Towards this end, the develop-
ment of state-of-the-art gold catalysts continues to emerge
in the literature and application towards existing or novel
organic transformations becomes highly attractive.
DOI: 10.1055/s-0035-1561305; Art ID: ss-2015-t0598-op
Abstract A room temperature and silver-free protocol for the forma-
tion of quinolines from 2-ethynylanilines through a dimerization event
was achieved using a dinuclear gold catalyst, Au2(BIPHEP)(NTf2)2. The
reaction is inherently modular, allowing for the incorporation of periph-
eral substituents at any site of the quinoline product. The reaction is
readily applied to other heterocyles also as exemplified by the prepara-
tion of naphthyridines. Competition reactions to determine the reactiv-
ity of dissimilar alkynes demonstrated that the product ratio of di-
merization vs intermolecular addition is rather dependent on the
electronic nature of aryl substituent on the alkynes. However, control
experiments with substrates possessing internal alkynes resulted in cy-
cloisomerization instead of expected dimerization, which is indicative
of possible steric influence of the alkyne terminus in the reaction out-
come.
Key words 2-ethynylanilines, dimerization, quinolines, atom-economy,
dinuclear gold complex, silver-free approach, competition reactions
The last decade has witnessed the upsurge of homoge-
neous gold catalysis in synthetic chemistry mainly because
of its unique ability to activate C≡C bond leading to the evo-
lution of powerful methods to efficiently assemble diverse
structures.1 From what has been learned from the litera-
ture, a wide array of gold(I) and gold(III) catalysts with dif-
ferent ligands is commercially available by now or can be
readily synthesized at the bench.2 Practically, the most con-
venient catalysts are gold complexes [AuLL′]X and [AuLX]
with weakly coordinating neutral (L′) or anionic ligands (X),
which could enter catalytic cycles by associative ligand ex-
change with the substrate.3 The properties of the catalysts
can be easily tuned sterically or electronically depending
on the ligand.4 For example, cationic gold(I) species are re-
garded as the most powerful catalysts for the electrophilic
activation of alkynes toward nucleophiles due to the lower
LUMO properties and poor back-donation of cationic gold
On the other hand, Sakai et al. in their seminal work de-
scribed the unusual dimerization of 2-ethynylanilines pro-
10
moted by InBr3 (Scheme 1). As part of our research en-
deavor in gold catalysis,11 we have previously communicat-
ed that the same reaction could be successfully realized
using a catalytic quantity of AuCl3 along with AgOTf as co-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

B
C. Praveen, P. T. Perumal
Paper
Synthesis
and practical difficulties associated with handling moisture
sensitive silver salts limited their synthetic utility. Follow-
ing our gold-catalyzed protocol, Shelton et al. in 2010
showcased the use of heterobimetallic catalyst of the type
CpRu(PPh3)Cl(μ-dppm)AuI in this dimerization reaction13
(Scheme 1). In continuation of our previous communication
concerning an original gold(III)/silver(I) based catalytic sys-
tem allowing the dimerization of a broad range of 2-ethy-
nylaniline substrates, we wish to report herein our endeav-
ors towards the discovery of an efficient dinuclear gold cat-
alytic system with no silver co-catalyst allowing the room
temperature dimerization of 2-ethynylanilines.
Shelton et al. (ref. 13)
CpRu(PPh3)Cl(μ-dppm)AuI (1 mol%)
CH2Cl2, reflux, 24 h
Me
N
InBr3 (1.0 equiv)
MeOH, reflux, 24 h
NH2
2
Sakai et al. (ref. 10)
R
NH2
R
R
The synthetic route to the requisite precursors is out-
lined in Scheme 2. At the outset, various substituted ani-
lines were subjected to Barluenga iodination, which afford-
ed 2-iodoanilines in quantitative yields.14 Sonogashira
coupling of the resulting iodoanilines with trimethylsilyl-
AuCl3 (5 mol%)/AgOTf (10 mol%)
MeCN, reflux
previous work (ref. 11a)
Scheme 1 Dimerization of 2-ethynylanilines
acetylene15
afforded
2-(trimethylsilylethynyl)anilines,
which upon subsequent desilylation under basic condi-
catalyst11a (Scheme 1). The Au/Ag catalytic systems allowed,
with good to excellent yields, the preparation of a broad va-
riety of quinolines, an important heterocyclic core possess-
ing multifarious medicinal applications.12 Whilst the for-
mer method suffers from the use of stoichiometric quantity
of InBr3, the shortcoming of latter is the rather harsh reac-
tion conditions generated by elevated temperature (84 °C)
tion16 led to 2-ethynylanilines 1a–t.
We embarked on our search for conditions to perform
dimerization reaction drawing precedence from our earlier
work, in which AuCl3/AgOTf was used as catalyst and aceto-
nitrile was used as solvent (see, Scheme 1). Several points
regarding the optimization of conversion of 1a to 2a are
worth noting. (i) Solvents like MeOH, EtOH, THF, MeNO2,
SiMe3
Pd(PPh3)2Cl2 (5 mol%)
CuI (5 mol%), Et3N
R
R
R
R
I
nBu4NF (1.0 equiv)
IPy2BF4 (1.0 equiv)
THF, r.t., 2 h
HBF4 or TFA (2.0 equiv)
CH2Cl2, r.t.
TMS≡CH (1.1 equiv)
NH2
NH2
NH2
NH2
1a–r
6 h, r.t.
Scheme 2 Synthesis of 2-ethynylanilines 1a–r
Me
NH2
L[Au] (5 mol%)
(CH2Cl)2, 25 °C
+
2
N
H
N
NH2
2a
1a
3a
L1: Ar = Ph; R1 = tBu; R2 = H (Johnpos)
iPr
iPr
iPr
L2: Ar = 2,4,6-triisopropyl; R1 = tBu; R2 = H (tBuXPhos)
L3: Ar = 2,6-dimethoxy; R1 = Cy (SPhos); R2 = H
L4: Ar = 2,4,6-triisopropyl; R1 = Cy (XPhos); R2 = H
R12P
Ar
N
N
L9 =
iPr
L5: Ar = 2-NMe2; R1 = Cy; R2 = H (DavePhos)
R2
L6: Ar =2,4,6-triisopropyl; R1 = Cy; R2 = 3,5-dimethoxy (BrettPhos)
L7: Ar =2,4,6-triisopropyl; R1 = Ad; R2 = 3,5-dimethoxy (AdBrettPhos)
; R1 = Ad; R2 = H (Mor-Dalphos)
N
O
L8: Ar =
Scheme 3 Optimization of reaction conditions
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

C
C. Praveen, P. T. Perumal
Paper
Synthesis
and MeCN were avoided on the basis of their coordinating
ability to the catalyst, which could eventually decrease the
π-aciditity of the catalyst. (ii) Therefore, we preferred to use
halogenated solvents and in particular 1,2-dichloroethane,
since it offers an additional advantage of performing the re-
action at high temperature. (iii) In order to avoid use of the
silver co-catalyst, we envisaged to use only the stable gold
complexes possessing non-nucleophilic anions. (iv) Simple
gold(III) salts are known to cyclize 2-ethynylanilines to in-
doles;17 to restrict this side reaction gold(I) catalysts with
bulky ligands were screened. Towards this end, the model
substrate 1a (0.5 M/1,2-DCE) was submitted to catalytic
amounts (5 mol%) of different gold complexes at 25 °C
(Scheme 3). The data presented in Table 1 highlight the key
findings of our initial search for the dimerization reaction.
It can be seen there that when 1a was reacted with
Gagosz’s catalyst (Ph3PAuNTf2),18 the reaction takes place,
but the conversion of 1a to 2a was too slow to constitute
good catalytic system (Table 1, entry 1). t-Bu3PAuNTf2 and
Ph3PAuOTf also proved to be rather ineffective as there is
hardly any conversion to 2a (entries 2 and 3). Given the no-
table ability to hydroaminate alkynes, Ph3PAuMe in combi-
nation with heteropolyacids was also tested,19 though de-
composition was observed. Switching to gold(I) catalyst
having sterically encumbered phosphine ligand such as
JohnPos (L1), DavePhos (L5), and MorDalphos (L8) the con-
version towards 2a increased at the expense of 3a (entries
5, 6, 11, 14, and 15), whereas in the case of t-BuxPhos (L2),
SPhos (L3), and BrettPhos (L6) most of the starting materi-
als remain unconsumed (entries 7–9 and 12). With XPhos
(L4) and AdBrettPhos (L7), the expected dimerization
turned out to be a complete failure with no product being
formed (entries 10 and 13). The influence of NHC-ligand
was also studied by employing Ipr carbene (L9), where it
was noticed that the conversion turned only in favor of 3a
(entries 16 and 17). At this point, we investigated the use of
chloronium-bridged dinuclear gold catalysts20 such as
[(Ph3PAu)2Cl]BF4 and [(Mes3PAu)2Cl]BF4 and were pleased to
witness a significant amelioration in the formation of 2a
(entries 18 and 19). Encouragingly, the bimetallic gold cata-
lyst possessing BIPHEP ligand21 showed inferior results in
terms of conversion ratio of 2a:3a reaching 71:4 (entry 20).
An increase in the reaction temperature using the same cat-
alyst resulted in decreased conversion of 2a to 52% (entry
21). Much to our delight, by increasing the substrate con-
centration to 1 M, an almost complete conversion towards
2a was observed, with an isolated yield of 89% (entry 22). A
further improvement was achieved by reducing the catalyt-
ic loading to 2.5 mol% to realize a full conversion, thereby
furnishing the desired product in 94% yield (entry 23). Fi-
nally, the reaction with oxonium bridged trinuclear gold
catalyst, [Ph3PAu]3OBF4 led to lower conversion of 2a (entry
24).
Table 1 Catalyst Screening for the Dimerization of 1a
Entry
L[Au]
Ph3PAuNTf2
Time (h)
1a/2a/3a,a yield (%)b
1
2
24
24
24
12
24
24
36
24
24
48
36
36
48
36
24
48
24
24
24
24
2
60/10/30
67/0/33
t-Bu3PAuNTf2
Ph3PAuOTf
3
50/0/50
4
Ph3PAuMe/H3[PW12O40
L1Au(MeCN)SbF6
L1AuNTf2
]
degradationc
60/28/12
62/30/8
5
6
7
L2Au(MeCN)SbF6
L3Au(MeCN)SbF6
L3AuNTf2
81/10/9
8
79/9/12
9
72/13/15
89/0/11
10
11
12
13
14
15
16
17
18
19
20
21d
22e
23e,f
24
L4AuNTf2
L5AuNTf2
55/28/17
73/7/20
L6AuNTf2
L7AuNTf2
78/0/22
L8Au(MeCN)SbF6
L8AuNTf2
24/31/45
14/33/53
38/25/37
43/16/41
26/50/24
24/58/18
25/71/4
L9AuOH
L9Au(MeCN)BF4
[(Ph3PAu)2Cl]BF4
[(Mes3PAu)2Cl]BF4
Au2(BIPHEP)(NTf2)2
Au2(BIPHEP)(NTf2)2
Au2(BIPHEP)(NTf2)2
Au2(BIPHEP)(NTf2)2
[Ph3PAu]3OBF4
16/52/32
4/96/0, 89
0/100/0, 94
21/40/39
6
6
24
a Determined by HPLC of the crude reaction mixture.
b Isolated yields after column chromatography.
c Sevaral unidentified by-products were also detected.
d Reaction was performed at reflux.
e Reaction performed at 1 M in substrate.
f Amount of catalyst used: 2.5 mol%.
Having established the optimal conditions, the scope of
the methodology was explored by subjecting a range of 2-
ethynylanilines (Scheme 4). Tolerance toward a wide range
of functionalities (electron-withdrawing and -releasing
groups) on the 2-ethynylaniline was demonstrated by ob-
taining the corresponding quinolines in moderate to excel-
lent yields (Table 2). It is pertinent to note that substrates
having electron releasing groups afforded good to excellent
yields of the products (Table 2, entries 1, 2, 7, 8, 10, 17, and
18). In contrast, electron-withdrawing groups led to some-
what lower yields (entries 3-6, 9, 11–13, and 16). This vari-
ability in yields observed with respect to the electronic na-
ture of the substituents can be explained by looking at the
diminished reactivity of electron-deficient anilines towards
hydroamination.22 The current protocol is amenable to sub-
strates containing peripheral substituents at all positions
(R1, R2, R3, and R4) with respect to the alkyne residue,
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

D
C. Praveen, P. T. Perumal
Paper
Synthesis
R1
Me
N
R1
R2
R3
R2
R3
NH2
[Au2(BIPHEP)(NTf2)2] (2.5 mol%)
(CH2Cl)2, 25 °C, 6 h
R4
R3
2
NH2
R4
R4
R1
2a–r
R2
1a–r
Scheme 4 Dimerization under optimized conditions
whereas an ortho-substitution (R1) was not reported in pre-
vious disclosures.10,11a,13 The quinolines 2a–r formed were
With the scope towards the synthesis of quinolines ex-
plored, our attention was turned to the preparation of 1,8-
naphthyridines, a structural motif with pharmacological
significance.23 The synthetic precursors, 2-amino-3-ethyn-
ylpyridines 1s and 1t were prepared by literature proce-
dure24 and subsequently subjected to our reaction condi-
tions (Scheme 5). Owing to the high polar nature of 1s and
1t, the reaction was performed at reflux temperature to
achieve homogenity and found only a moderate yield of the
corresponding naphthyridine products 2s and 2t.
1
characterized by IR, H NMR, 13C NMR, and mass spectros-
copy. As an illustrative example, the IR spectrum of com-
pound 2a exhibited broad peak at 3452 cm–1 revealing the
presence of NH2 functionality. The 1H NMR spectra of com-
pound 2a recorded in CDCl3 showed fourteen protons. A
singlet peak at δH = 2.74 indicated the presence of aryl-CH3
protons. The appearance of a broad singlet corresponding to
two protons at δH = 6.15, indicated the presence of NH2
group (D2O exchangeable). In 13C NMR spectra, a peak at δC
= 19.1 was attributed to the aryl-CH3 group. Further in
mass spectrum, the molecular ion peak (M+ + 1) appeared
at m/z = 235, which is exactly double the value of the corre-
sponding monomer (m/z = 117), confirmed the formation
of the product 2a.
Me
[Au2(BIPHEP)(NTf2)2]
(2.5 mol%)
R
R
NH2
(CH2Cl)2, reflux, 6 h
N
NH2
N
N
N
2s, 52%
2t, 41%
1s, R = Me
1t, R = NO2
R
Scheme 5 Synthesis of 1,8-naphthyridines
Table 2 Synthesis of Substituted Quinolines 2a–r
Entry
R1
R2
R3
R4
Producta Yield (%)b
We next sought out to operate the gold(I)-catalyzed in-
termolecular reactivity between two dissimilar alkynes as
depicted in Scheme 6. Accordingly, a mixture of 2-ethy-
nylaniline (1a) with different terminal alkynes 4a–f in an
equimolar ratio was subjected to these reaction conditions.
Two main products were isolated, the expected dimerized
product 2a accompanied by the addition product 5a–f.25
Alkynes of different electronic nature exert a profound ef-
fect on the selectivity of competitive dimerization versus
intermolecular addition. Interestingly, electron-donating
substituents on the phenyl ring (p-tolyl 4b, p-anisyl 4c, and
m-tolyl 4f) favor the predominant formation of intermolec-
ular addition products (5b, 5c, and 5f), whereas electron-
withdrawing groups (4-ClC6H4 4d and 2-ClC6H4 4e) and hy-
drogen (4a) favor the dimerization products (5a, 5d, and
5e). This trend can be rationalized in terms of enhancement
of electron density at the triple bond by electron-donating
substituents, which interacts with Lewis acidic gold(I) cata-
lyst with ease. Such observations are also consistent with
the increased reactivity of electron-rich substrates towards
dimerization reaction in which high yields were observed
(Table 2, entries 1, 2, 7, 8, 10, 17, and 18).
1
2
H
H
H
H
2a
2b
2c
2d
2e
2f
94
89
64
70
81
79
87
95
73
96
77
75
60
76
64
74
90
86
H
Me
F
H
H
3
H
H
H
4
H
NO2
Cl
H
H
5
H
H
H
6
H
CN
H
H
H
7
H
MeO
Me
H
H
2g
2h
2i
8
H
Me
Br
H
9
H
Cl
10
11
12
13
14
15
16
17
18
H
Me
Me
Br
H
Me
Cl
2j
H
H
2k
2l
H
H
Br
H
NO2
CO2Me
CPh3
CO2Me
H
H
MeO
MeO
MeO
Me
Me
H
2m
2n
2o
2p
2q
2r
H
H
H
H
H
H
Me
Me
H
H
H
A clue to understand the steric influence of the alkyne
residue was gleaned from a study of the gold(I)-catalyzed
reaction of substrate possessing internal alkyne such as 2-
a Products were characterized by IR and NMR spectroscopy, and mass spec-
trometry.
b Isolated yield after column chromatography.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

E
C. Praveen, P. T. Perumal
Paper
Synthesis
Isolated yield (%)
Me
N
Me
[Au2(BIPHEP)(NTf2)2]
2a/5a = 33/53
2a/5b = 24/65
2a/5c = 23/64
2a/5d = 47/29
2a/5e = 52/26
2a/5f = 30/58
(2.5 mol%)
+
NH2
+
NH2
Ar
(CH2Cl)2, 25 °C, 6 h
N
Ar
1a
4a–f
2a
5a–f
4a: Ar = Ph; 4b: Ar = p-tolyl; 4c: Ar = p-anisyl;
4d: Ar = p-ClC6H4; 4e: Ar = o-ClC6H4; 4f: Ar = m-tolyl
Scheme 6 Gold(I)-catalyzed competitive reactions
Et
N
Me
Et
[Au2(BIPHEP)(NTf2)2]
Me
NH2
N
Me
H2N
(2.5 mol%)
2u'
2u
(CH2Cl)2, 25 °C, 6 h
NH2
1u
Me
87%
N
H
3b
Scheme 7 Control experiment using internal alkyne 1u
(prop-1-ynyl)aniline (1u) (Scheme 7). However, the expect-
ed products 2u and 2u′ were not observed. Conversely, the
cycloisomerization product 3b was formed solely. Although
not conclusive, this study suggests that the dimerization
process is not induced in more sterically hindered and less
reactive internal alkynes and happens to occur only if no
substituent is present at the alkyne terminus.
Based on this observation, a plausible mechanistic de-
scription for the dimerization process is shown in Scheme
8. According to which, activation of alkyne 1′ by gold(I)
forms π-complex 1a′, which allows the nucleophilic attack
of NH2 group of another alkyne 1 to form vinyl-gold inter-
mediate 1b′. Species 1b′ undergoes proto-deauration to fur-
nish intermediate 1c′. The latter is activated by gold(I)
again, and a subsequent cyclization occurs to afford the in-
termediate 1d′. Proto-deauration of 1d′ regenerates the
gold(I) catalyst and delivers 1e′, which upon proton trans-
position affords the dimerized product 2.
Through dimerization of 2-ethynylanilines under the
catalysis of dinuclear gold catalyst Au2(BIPHEP)(NTf2)2, a
room temperature and silver-free synthesis of quinolines
was established. This protocol possesses broad substrate
scope and the chemical yields are generally good to excel-
lent. Not only limited to quinolines, the methodology is also
amenable to the synthesis of structurally related naphthyri-
dines. Reaction between two dissimilar alkynes was also
made possible in a competitive mode and two different
products (i.e., dimerization and intermolecular addition)
R1
+
R1
[AuL]+
R2
1'
NH2
+
1
R2
1a'
NH2
Me
N
1
R1
R1
[AuL]+
R1
[AuL]
[AuL]
R2
R2
N
R2
R1
2
1e'
N
R2
1b'
[AuL]+
H2
R1
N
H
1d'
N
R2
H
1c'
Scheme 8 Tentative mechanism for the dimerization
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

F
C. Praveen, P. T. Perumal
Paper
Synthesis
can be generated. The product ratio of dimerization versus
intermolecular addition is rather dependent on the elec-
tronic nature of aryl substituents on the alkynes. Reaction
with internal alkyne 1u offered cycloisomerized product
instead of the expected dimerization product. Our future
investigation will be towards elucidating the exact reaction
mechanism and on the application of this methodology to
the synthesis of natural products having pharmacological
significance.
13C NMR (125 MHz, CDCl3): δ = 159.0, 147.4, 146.7, 144.8, 130.2,
129.9, 129.5, 129.4, 126.5, 126.0, 123.7, 121.9, 121.2, 117.5, 117.3,
19.1.
MS (ESI): m/z = 235 [M + H+].
Anal. Calcd for C16H14N2: C, 82.02; H, 6.02; N, 11.96. Found: C, 81.91;
H, 6.05; N, 12.04.
2-(4,6-Dimethylquinolin-2-yl)-4-methylphenylamine (2b)
Yield: 234 mg (89%); yellow solid; mp 146–148 °C.
IR (KBr): 3425, 3327, 1604, 1423, 1216, 1119, 899, 726 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.92 (d, J = 8.0 Hz, 1 H), 7.61 (s, 1 H),
7.71 (s, 1 H), 7.50 (dd, J1 = 8.0 Hz, J2 = 1.5 Hz, 1 H), 7.00 (d, J = 8.1 Hz, 1
H), 7.48 (s, 1 H), 6.71 (d, J = 8.1 Hz, 1 H), 5.89 (br s, 2 H), 2.69 (s, 3 H),
2.54 (s, 3 H), 2.32 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 158.2, 145.3, 144.7, 144.0, 135.6,
131.3, 130.7, 130.0, 129.1, 126.5, 126.4, 122.6, 122.0, 121.2, 117.4,
21.8, 20.7, 19.1.
All commercially available solvents and reagents were dried and puri-
fied by standard purification procedures. Gold complexes were pur-
chased from Sigma-Aldrich and Strem chemicals, USA. Bench stable
Au2(BIPHEP)(NTf2)2 complex was prepared from Au2(BIPHEP)Cl2 and
AgNTf2 according to the procedure of Bandini et al.21 Solutions in or-
ganic solvents were dried with anhydrous Na2SO4. Solvents were
evaporated under reduced pressure. Melting points were obtained us-
ing open capillaries and are uncorrected. IR spectra were recorded on
a PerkinElmer FTIR spectrophotometer as KBr pellets for solid com-
pounds and neat sample for liquid compounds. GC analyses were per-
formed on a Hewlett-Packard 5890 series II instrument connected to
a Merck D-2500 or D-2000 integrator with a flame-ionization detec-
tor. HPLC analyses were performed on Waters instruments (Waters
486 detector, 717 autosampler equipped with Daicel column (46 mm
i.d. × 25 cm). 1H and 13C NMR spectra were obtained in DMSO-d6 and
CDCl3 on a JEOL spectrometer at 500 and 125 MHz, respectively. Pro-
ton chemical shifts (δ) are relative to TMS (δ = 0.00) as internal stan-
dard and expressed in parts per million. The number of protons (n)
for a given resonance is indicated as n H. Standard abbreviations are
used to denote spin multiplicities. Coupling constants (J) are given in
hertz. Elemental analyses were recorded using a Thermo Finnigan
FLASH EA 1112CHN analyzer. All compounds gave C, H and N analysis
within ± 0.4% of the theoretical values. Column chromatography was
performed using a mixture of PE and EtOAc on silica gel (100–200
mesh, Sisco Research Laboratories, India). Analytical TLC was per-
formed on precoated plastic sheets of silica gel G/UV-254 of 0.2 mm
thickness (Macherey-Nagel, Germany) using analytical grade solvents
and visualized with I2 spray (10% w/w I2 in silica gel), UV light (λ =
254 and 365 nm) and alkaline KMnO4 solution.
MS (ESI): m/z = 263 [M + H+].
Anal. Calcd for C18H18N2: C, 82.41; H, 6.92; N, 10.68. Found: C, 82.50;
H, 6.89; N, 10.62.
2-(6-Fluoro-4-methyl-2-quinolinyl)-4-fluorophenylamine (2c)
Yield: 173 mg (64%); yellow solid; mp 117–119 °C.
IR (KBr): 3466, 3347, 1453, 1286, 909, 786 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 8.00 (dd, J1 = 9.0 Hz, J2 = 4.0 Hz, 1 H),
7.56–7.58 (m, 2 H), 7.45 (td, J1 = 9.0 Hz, J2 = 2.6 Hz, 1 H), 7.35 (dd, J1 =
9.0 Hz, J2 = 2.6 Hz, 1 H), 6.93 (td, J1 = 9.0 Hz, J2 = 2.6 Hz, 1 H), 6.84 (dd,
J1 = 9.0 Hz, J2 = 4.0 Hz, 1 H), 5.88 (br s, 2 H), 2.71 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 160.4 (d, JC,F = 245.0 Hz), 157.1, 156.4,
154.6, 144.5 (d, JC,F = 5.9 Hz), 143.5 (d, JC,F = 32.4 Hz), 131.7 (d, JC,F = 9.5
Hz), 127.3 (d, JC,F = 9.7 Hz), 122.0 (d, JC,F = 6.8 Hz), 119.3 (d, JC,F = 25.0
Hz), 121.5, 118.1 (d, J = 6.7 Hz), 117.0 (d, JC,F = 22.0 Hz), 115.3 (d, JC,F
23.9 Hz), 107.3 (d, JC,F = 22.0 Hz), 19.2.
=
MS (ESI): m/z = 271 [M + H+].
Anal. Calcd for C16H12F2N2: C, 71.10; H, 4.48; N, 10.36. Found: C, 70.97;
H, 4.52; N, 10.41.
2-(4-Methyl-6-nitroquinolin-2-yl)-4-nitrophenylamine (2d)
Yield: 227 mg (70%); yellow solid; mp 244–246 °C.
Dimerization of 1a; Typical Procedure
IR (KBr): 3481, 3367, 1556, 1444, 1354, 1247, 899, 701 cm–1
.
In a screw cap vial at 25 °C, under an argon atmosphere was charged
Au2(BIPHEP)(NTf2)2 (37.2 mg (2.5 mol%). To this was added a freshly
prepared solution of 2-ethynylaniline (1a; 117 mg, 1 mmol) in anhy-
drous 1,2-dichloroethane (1 mL) and stirred at 25 °C for 6 h. Then the
reaction mixture was quenched with H2O (5 mL) and extracted with
CH2Cl2 (3 × 5 mL). The combined organic extracts were dried (Na2SO4),
filtered, and concentrated under reduced pressure. The crude materi-
al was purified by column chromatography (silica gel) using cyclohex-
ane–EtOAc eluent system to afford the desired dimerization product
2a.
1H NMR (500 MHz, DMSO-d6): δ = 9.06 (d, J = 2.6 Hz, 1 H), 8.85 (s, 1
H), 8.52 (dd, J1 = 9.2 Hz, J2 = 2.5 Hz, 1 H), 8.29 (d, J = 9.1 Hz, 1 H), 8.09
(dd, J1 = 9.1 Hz, J2 = 2.5 Hz, 1 H), 6.94 (d, J = 2.6 Hz, 1 H), 6.84 (d, J = 8.9
Hz, 1 H), 6.51 (br s, 2 H), 2.58 (s, 3 H).
13C NMR (125 MHz, DMSO-d6): δ = 154.8, 153.0, 148.9, 145.5, 114.8,
135.5, 131.2, 130.8, 127.1, 126.7, 125.8, 122.2, 121.4, 119.6, 113.3,
15.0.
MS (ESI): m/z = 325 [M + H+].
Anal. Calcd for C16H12N4O4: C, 59.26; H, 3.73; N, 17.28. Found: 59.35;
H, 3.71; N, 17.22.
2-(4-Methylquinolin-2-yl)phenylamine (2a)
Yield: 220 mg (94%); yellow solid; mp 78–80 °C.
2-(6-Chloro-4-methyl-2-quinolinyl)-4-chlorophenylamine (2e)
IR (KBr): 3454, 3330, 1612, 1447, 1242, 1157, 947, 751 cm–1
.
Yield: 247 mg (81%); yellow solid; mp 147–149 °C.
1H NMR (500 MHz, CDCl3): δ = 8.04 (d, J = 8.4 Hz, 1 H), 7.96 (d, J = 8.4
Hz, 1 H), 7.66–7.69 (m, 3 H), 7.52 (t, J = 6.9 Hz, 1 H), 7.19 (t, J = 8.1 Hz,
1 H), 6.80 (q, J = 12.2 Hz, 2 H), 6.15 (br s, 2 H), 2.74 (s, 3 H).
IR (KBr): 3413, 3351, 1438, 1268, 865, 766 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

G
C. Praveen, P. T. Perumal
Paper
Synthesis
1H NMR (500 MHz, CDCl3): δ = 7.99 (s, 1 H), 7.93 (s, 1 H), 7.63–7.69
(m, 2 H), 7.13 (d, J = 8.4 Hz, 1 H), 6.72 (d, J = 8.4 Hz, 1 H), 6.57 (d, J = 9.2
Hz, 1 H), 6.16 (br s, 2 H), 2.68 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 157.8, 148.8, 146.1, 144.4, 134.2,
132.0, 129.0, 127.4, 125.4, 122.9, 121.9, 121.5, 120.1, 118.6, 102.4,
19.0.
IR (thin film): 3512, 3487, 1602, 1287, 950, 802 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.99 (s, 1 H), 7.79 (d, J = 2.3 Hz, 1 H),
7.70 (s, 1 H), 7.44 (d, J = 2.3 Hz, 1 H), 6.79 (br s, 2 H), 7.90 (d, J = 1.5 Hz,
1 H), 2.69 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 163.0, 156.8, 152.3, 143.8, 138.0,
132.8, 132.5, 131.4, 130.1, 128.2, 125.2, 121.4, 121.1, 119.7, 110.7,
26.8.
MS (ESI): m/z = 303 [M + H+], 305 [M + 2 + H+], 307 [M + 4 + H+].
Anal. Calcd for C16H12Cl2N2: C, 63.38; H, 3.99; N, 9.24. Found: C, 63.52;
H, 3.92; N, 9.15.
MS (ESI): m/z = 461 [M + H+], 463 [M + 2 + H+], 465 [M + 4 + H+].
Anal. Calcd for C16H10Br2Cl2N2: C, 41.69; H, 2.19; N, 6.08. Found: C,
41.85; H, 2.15; N, 6.00.
2-(2-Amino-5-cyanophenyl)-4-methylquinoline-6-carbonitrile
(2f)
2,4-Dimethyl-6-(6,8-dimethyl-4-methyl-2-quinolinyl)phenyl-
amine (2j)
Yield: 225 mg (79%); yellow solid; mp 296–298 °C.
IR (KBr): 3487, 3356, 2266, 1403, 1277, 857, 772 cm–1
.
Yield: 278 mg (96%); yellow oil.
1H NMR (500 MHz, DMSO-d6): δ = 8.67 (s, 1 H), 8.38 (s, 1 H), 8.20–
8.24 (m, 2 H), 8.04 (d, J = 9.0 Hz, 1 H), 7.50 (d, J = 9.0 Hz, 1 H), 6.94 (d,
J = 9.2 Hz, 1 H), 6.02 (br s, 2 H), 2.77 (s, 3 H).
13C NMR (125 MHz, DMSO-d6): δ = 159.0, 152.4, 146.8, 146.0, 134.5,
1332.2, 130.6, 130.2, 129.9, 125.3, 121.0, 119.9, 118.6, 117.0, 116.9,
108.1, 95.8, 17.8.
IR (thin film): 3447, 3298, 1511, 1205, 915, 789 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.72 (s, 1 H), 7.63 (s, 1 H), 7.51 (s, 1 H),
7.43 (s, 1 H), 7.01 (s, 1 H), 6.45 (br s, 2 H), 2.81 (s, 3 H), 2.74 (s, 3 H),
2.56 (s, 3 H), 2.37 (s, 3 H), 2.29 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 157.0, 144.0, 143.4, 136.4, 135.1,
132.1, 131.0, 127.9, 124.3, 124.0, 121.0, 120.7, 119.9, 118.0, 21.9, 21.5,
19.5, 18.8, 18.0.
MS (ESI): m/z = 285 [M + H+].
Anal. Calcd for C18H12N4: C, 76.04; H, 4.25; N, 19.71. Found: C, 75.95;
H, 4.29; N, 19.76.
MS (ESI): m/z = 291 [M + H+].
Anal. Calcd for C20H22N2: C, 82.72; H, 7.64; N, 9.65. Found: C, 82.87; H,
7.59; N, 9.55.
2-(7-Methoxy-4-methyl-2-quinolinyl)-5-methoxyphenylamine
(2g)
2-Chloro-6-(6-chloro-4,8-dimethylquinolin-2-yl)-4-methylphe-
nylamine (2k)
Yield: 256 mg (87%); yellow solid; mp 124–126 °C.
IR (KBr): 3456, 3367, 1403, 1216, 809, 716 cm–1
.
Yield: 256 mg (77%); yellow oil.
1H NMR (500 MHz, CDCl3): δ = 7.85 (d, J = 9.2 Hz, 1 H), 7.62 (d, J = 9.2
Hz, 1 H), 7.47 (s, 1 H), 7.34 (d, J = 2.4 Hz, 1 H), 7.14 (dd, J1 = 9.2 Hz, J2 =
2.5 Hz, 1 H), 6.38 (dd, J1 = 9.2 Hz, J2 = 2.5 Hz, 1 H), 6.33 (br s, 2 H), 6.30
(d, J = 2.6 Hz, 1 H), 3.95 (s, 3 H), 3.82 (s, 3 H), 2.68 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 161.5, 160.2, 159.2, 149.2, 148.5,
144.3, 131.1, 124.6, 121.2, 118.8, 118.0, 115.2, 107.5, 104.2, 101.3,
55.5, 55.2, 19.0.
IR (thin film): 3361, 3300, 1600, 1147, 841 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 8.13 (s, 1 H), 7.81 (s, 1 H), 7.66 (s, 1 H),
7.63 (s, 1 H), 6.97 (s, 1 H), 5.10 (br s, 2 H), 2.57 (s, 3 H), 2.52 (s, 3 H),
2.42 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 151.0, 143.5, 141.1, 137.2, 135.0,
131.9, 130.4, 128.3, 127.5, 125.4, 124.5, 123.3, 117.7, 108.4, 100.0,
21.3, 19.9, 19.4.
MS (ESI): m/z = 295 [M + H+].
MS (ESI): m/z = 331 [M + H+], 333 [M + 2 + H+], 335 [M + 4 + H+].
Anal. Calcd for C18H18N2O2: C, 73.45; H, 6.16; N, 9.52. Found: C, 73.52;
H, 6.14; N, 9.49.
Anal. Calcd for C18H16Cl2N2: C, 65.27; H, 4.87; N, 8.46. Found: C, 65.48;
H, 4.95; N, 8.39.
2-(4,6,7-Trimethyl-2-quinolinyl)-4,5-dimethylphenylamine (2h)
2,4-Dibromo-6-(6,8-dibromo-4-methyl-2-quinolinyl)phenyl-
amine (2l)
Yield: 275 mg (95%); yellow solid; mp 184–186 °C.
IR (KBr): 3466, 3327, 1423, 1256, 899, 766 cm–1
.
Yield: 415 mg (75%); yellow solid; mp 186–188 °C.
1H NMR (500 MHz, CDCl3): δ = 7.78 (s, 1 H), 7.66 (s, 1 H), 7.55 (s, 1 H),
7.43 (s, 1 H), 6.61 (s, 1 H), 5.97 (br s, 2 H), 2.69 (s, 3 H), 2.46 (s, 3 H),
2.44 (s, 3 H), 2.24 (s, 3 H), 2.22 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 158.1, 145.9, 143.3, 140.1, 139.0,
138.6, 135.3, 130.3, 128.8, 125.3, 124.8, 123.0, 120.1, 119.9, 118.6,
20.3, 20.2, 19.7, 19.1, 19.0.
IR (KBr): 3751, 3413, 2956, 2430, 1457, 766 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 8.71 (s, 1 H), 8.19 (d, J = 2.3 Hz, 1 H),
8.14 (d, J = 2.3 Hz, 1 H), 7.65 (d, J = 2.2 Hz, 1 H), 7.10 (d, J = 2.3 Hz, 1 H),
4.12 (br s, 2 H), 2.51 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 162.8, 152.1, 143.2, 141.6, 136.0,
134.9, 132.1, 131.4, 129.9, 126.7, 126.6, 124.7, 120.7, 110.1, 109.2,
26.9.
MS (ESI): m/z = 291 [M+ + H+].
Anal. Calcd for C20H22N2: C, 82.72; H, 7.64; N, 9.65. Found: C, 82.85; H,
7.59; N, 9.58.
MS (ESI) m/z = 551 [M + H+], 553 [M + 2 + H+], 555 [M + 4 + H+].
Anal. Calcd for C16H10Br4N2: C, 34.95; H, 1.83; N, 5.09. Found: C, 35.07;
H, 1.78; N, 5.00.
4-Bromo-2-(6-bromo-8-chloro-4-methylquinolin-2-yl)-6-chloro-
phenylamine (2i)
Yield: 338 mg (73%); yellow oil.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

H
C. Praveen, P. T. Perumal
Paper
Synthesis
2-Methoxy-6-(8-methoxy-4-methyl-6-nitroquinolin-2-yl)-4-ni-
trophenylamine (2m)
Anal. Calcd for C22H22N2O4: C, 69.83; H, 5.86; N, 7.40. Found: C, 70.09;
H, 5.79; N, 7.32.
Yield: 230 mg (60%); brown solid; mp 264–266 °C.
3,5-Dimethyl-2-(4,5,7-trimethylquinolin-2-yl)aniline (2q)
IR (KBr): 3369, 2924, 1615, 1501, 1323, 1093, 740 cm–1
.
Yield: 261 mg (90%); pale yellow solid; mp 114–116 °C.
1H NMR (500 MHz, DMSO-d6): δ = 8.71 (s, 1 H), 8.55 (s, 1 H), 7.80 (s, 1
H), 7.67 (s, 2 H), 6.12 (br s, 2 H), 4.07 (s, 3 H), 3.93 (s, 3 H), 2.47 (s, 3
H).
13C NMR (125 MHz, DMSO-d6): δ = 157.1, 153.7, 146.2, 145.9, 145.5,
144.2, 141.9, 135.9, 129.1, 121.0, 119.2, 113.4, 105.5, 101.6, 100.0,
60.3, 57.0, 21.2.
IR (KBr): 3436, 3277, 1513, 1207, 918, 799 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.62 (s, 1 H), 7.41 (s, 1 H), 6.97 (s, 1 H),
6.53 (s, 1 H), 6.07 (br s, 2 H), 2.59 (s, 3 H), 2.54 (s, 3 H), 2.37, (s, 3 H),
2.34 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 158.2, 145.7, 143.0, 140.5, 139.2,
138.1, 135.1, 130.1, 128.8, 125.0, 124.4, 123.0, 120.0, 119.9, 118.5,
20.2, 20.1, 19.7, 19.0, 18.9.
MS (ESI): m/z = 385 [M + H+].
Anal. Calcd for C18H16N4O6: C, 56.25; H, 4.20; N, 14.58. Found: C,
56.45; H, 4.12; N, 14.49.
MS (ESI): m/z = 291 [M + H+].
Anal. Calcd for C20H22N2: C, 82.72; H, 7.64; N, 9.65. Found: C, 83.01; H,
7.56; N, 9.45.
Methyl 2-(2-Amino-3-methoxy-5-methoxycarbonylphenyl)-
8-methoxy-4-methylquinoline-6-carboxylate (2n)
Yield: 312 mg (76%); colorless solid; mp 156–158 °C.
2-(4,5-Dimethylquinolin-2-yl)-3-methylaniline (2r)
IR (KBr): 3394, 2955, 1677, 1081, 756 cm–1
.
Yield: 225 mg (86%); pale yellow solid; mp 139–141 °C.
IR (KBr): 3319, 3021, 1525, 1199, 904, 754 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 8.14 (s, 1 H), 8.06 (s, 1 H), 7.41 (s, 1 H),
7.31 (s, 1 H), 7.21 (d, J = 3.05 Hz, 1 H), 6.58 (br s, 2 H), 3.96 (s, 3 H),
3.91 (s, 3 H), 3.89 (s, 3 H), 3.88 (s, 3 H), 2.60 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 168.4, 166.9, 150.1, 146.6, 145.7,
145.3, 131.2, 128.4, 127.1, 125.0, 122.5, 117.3, 116.1, 115.5, 112.9,
104.3, 102.4, 55.9, 55.5, 51.9, 29.7, 28.1.
1H NMR (500 MHz, CDCl3): δ = 7.88 (d, J = 8.1 Hz, 1 H), 7.65 (t, J = 7.6
Hz, 1 H), 7.50 (d, J = 7.6 Hz, 1 H), 7.22 (t, J = 8.1 Hz, 1 H), 7.01 (s, 1 H),
6.78 (d, J = 7.6 Hz, 1 H), 6.64 (d, J = 8.1 Hz, 1 H), 6.07 (br s, 2 H), 2.63 (s,
3 H), 2.55 (s, 3 H), 2.50 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 158.5, 145.5, 144.3, 144.5, 135.1,
131.9, 130.0, 130.1, 129.2, 126.5, 126.3, 122.5, 122.0, 121.2, 117.4,
21.7, 20.3, 18.9.
MS (ESI): m/z = 411 [M + H+].
Anal. Calcd for C22H22N2O6: C, 64.38; H, 5.40; N, 6.83. Found: C, 64.52;
H, 5.35; N, 6.77.
MS (ESI): m/z = 263 [M + H+].
Anal. Calcd for C18H18N2: C, 82.41; H, 6.92; N, 10.68. Found: C, 82.25;
H, 6.96; N, 10.80.
2-Methoxy-6-(8-methoxy-4-methyl-6-tritylquinolin-2-yl)-4-tri-
tylaniline (2o)
Yield: 498 mg (64%); colorless solid; mp 144–146 °C.
3-(4,6-Dimethyl-1,8-naphthyridin-2-yl)-5-methylpyridin-2-amine
(2s)
IR (KBr): 3375, 2989, 1601, 1165, 920, 781 cm–1
.
Yield: 137 mg (52%); yellow solid; mp 227–229 °C.
1H NMR (500 MHz, CDCl3): δ = 7.90 (s, 1 H), 7.78–7.67 (m, 7 H), 7.55
(s, 1 H), 7.52–7.35 (m, 12 H), 7.31–7.24 (m, 6 H), 7.20–7.12 (m, 6 H),
7.01 (s, 1 H), 6.99 (s, 1 H), 6.96 (s, 1 H), 5.99 (br s, 2 H), 3.89 (s, 3 H),
3.85 (s, 3 H), 2.64 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 155.5, 149.6, 148.6, 144.4, 138.1,
136.4, 135.8, 132.9, 130.3, 129.7, 126.6, 125.8, 122.9, 122.5, 121.8,
121.5, 120.8, 120.1, 117.1, 111.9, 111.1, 102.6, 64.9, 64.3, 55.5, 54.9,
19.8.
IR (KBr): 3444, 2975, 1311, 947, 729 cm–1
.
1H NMR (500 MHz, DMSO-d6): δ = 8.99 (s, 1 H), 8.41 (s, 1 H), 7.80 (s, 1
H), 7.34 (s, 1 H), 7.01 (s, 1 H), 4.62 (br s, 2 H), 2.42 (s, 3 H), 2.37 (s, 3
H), 2.35 (s, 3 H).
13C NMR (125 MHz, DMSO-d6): δ = 153.6, 150.8, 150.3, 149.9, 147.2,
146.5, 135.0, 134.3, 133.8, 123.9, 121.2, 115.1, 112.3, 21.1, 18.9, 18.7.
MS (ESI): m/z = 265 [M + H+].
MS (ESI): m/z = 779 [M + H+].
Anal. Calcd for C16H16N4: C, 72.70; H, 6.10; N, 21.20. Found: C, 72.97;
H, 6.13; N, 20.90.
Anal. Calcd for C56H46N2O2: C, 86.34; H, 5.95; N, 3.60. Found: C, 85.99;
H, 6.00; N, 3.66.
3-(4-Methyl-6-nitro[1,8]naphthyridin-2-yl)-5-nitropyridin-2-yl-
amine (2t)
Methyl 2-[2-Amino-5-(methoxycarbonyl)-3-methylphenyl]-4,8-
dimethylquinoline-6-carboxylate (2p)
Yield: 134 mg (41%); yellow solid; mp 251–253 °C.
Yield: 280 mg (74%); yellow solid; mp 174–176 °C.
IR (KBr): 3450, 2961, 1599, 1400, 1218, 950, 715 cm–1
.
IR (KBr): 3401, 2988, 1599, 1175, 928, 791 cm–1
.
1H NMR (500 MHz, DMSO-d6): δ = 9.04 (s, 1 H), 8.83 (s, 1 H), 7.70 (s, 1
H), 7.52 (s, 1 H), 6.70 (s, 1 H), 4.57 (br s, 2 H), 2.46 (s, 3 H).
13C NMR (125 MHz, DMSO-d6): δ = 163.3, 147.0, 139.3, 135.8, 134.5,
132.6, 132.0, 131.9, 129.3, 129.2, 125.1, 103.2, 100.5, 20.6.
1H NMR (500 MHz, CDCl3): δ = 8.13 (s, 1 H), 8.01 (s, 1 H), 7.79 (s, 1 H),
7.44 (s, 1 H), 7.05 (s, 1 H), 3.95 (s, 3 H), 3.89 (s, 3 H), 2.66 (s, 3 H), 2.25
(s, 3 H), 2.20 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 168.8, 167.9, 156.8, 156.5, 150.1,
148.2, 137.9, 130.0, 127.1, 125.7, 122.8, 121.6, 120.5, 120.3, 117.7,
53.2, 51.4, 20.1, 19.1, 17.7.
MS (ESI): m/z = 327 [M + H+].
Anal. Calcd for C14H10N6O4: C, 51.54; H, 3.09; N, 25.76. Found: C,
51.75; H, 3.00; N, 25.68.
MS (ESI): m/z = 379 [M + H+].
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

I
C. Praveen, P. T. Perumal
Paper
Synthesis
Competitive Dimerization of 1a with Phenylacetylene (4a); Typical
Procedure
1H NMR (500 MHz, CDCl3): δ = 8.18 (d, J = 8.4 Hz, 1 H), 8.05 (d, J = 8.2
Hz, 1 H), 7.74–7.50 (m, 5 H), 7.42–7.35 (m, 2 H), 2.77 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 157.2, 148.0, 143.9, 139.9, 132.4,
131.7, 130.3, 130.1, 129.7, 129.3, 127.3, 127.1, 126.5, 123.7, 123.4,
18.8.
In a screw cap vial at 25 °C, under an argon atmosphere was charged
Au2(BIPHEP)(NTf2)2 (37.2 mg, 2.5 mol%). To this was added a freshly
mixed solution of 2-ethynylaniline (1a; 117 mg, 1 mmol), phenylacet-
ylene (4a; 102 mg, 1 mmol) in anhydrous 1,2-dichloroethane (1 mL)
and stirred at 25 °C for 6 h. Then the reaction mixture was quenched
with H2O (5 mL) and extracted with CH2Cl2 (3 × 5 mL). The combined
organic extracts were dried (Na2SO4), filtered, and concentrated un-
der reduced pressure. The crude material was purified by column
chromatography (silica gel) using cyclohexane–EtOAc eluent system
to separate the dimerization product 2a and the addition product 5a.
MS (ESI): m/z = 254 [M + H+], 256 [M + 2 + H+].
4-Methyl-2-(m-tolyl)quinoline (5f)
Yield: 135 mg (58%); yellow liquid.
IR (KBr): 3059, 2922, 1580, 1573, 1484, 804, 747 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 8.18 (d, J = 8.3 Hz, 1 H), 8.01–7.99 (m, 2
H), 7.91 (d, J = 7.5 Hz, 1 H), 7.74–7.71 (m, 2 H), 7.54 (t, J = 7.4 Hz, 1 H),
7.41 (t, J = 7.5 Hz, 1 H), 7.28–7.26 (m, 1 H), 2.77 (s, 3 H), 2.48 (s, 3 H).
4-Methyl-2-phenylquinoline (5a)
Yield: 116 mg (53%); yellow paste.
IR (KBr): 3040, 1590, 1544, 1565, 1444, 1406, 1345, 765, 728, 699 cm–1
1H NMR (500 MHz, CDCl3): δ = 8.22–8.16 (m, 3 H), 8.00 (d, J = 8.4 Hz, 1
H), 7.75–7.70 (m, 2 H), 7.57–7.44 (m, 4 H), 2.78 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 157.3, 148.3, 144.7, 139.9, 138.4,
130.4, 130.0, 129.3, 128.7, 128.3, 127.3, 126.0, 124.7, 123.6, 119.9,
21.6, 18.9.
.
MS (ESI): m/z = 234 [M + H+].
13C NMR (125 MHz, CDCl3): δ = 157.0, 148.2, 144.8, 139.9, 130.3,
129.3, 129.2, 128.8, 127.5, 127.3, 126.0, 123.6, 119.6, 18.8.
MS (ESI): m/z = 220 [M + H+].
Acknowledgment
C.P. acknowledges the Department of Science and Technology (DST),
India for providing INSPIRE faculty award (IFA14-MS27). C.P. also
thanks Dr. Vijayamohanan K. Pillai, Director, CSIR-CECRI and Dr. D.
Jeyakumar, Head, Functional Materials Division, CSIR-CECRI for their
constant support and encouragement.
4-Methyl-2-(p-tolyl)quinoline (5b)
Yield: 151 mg (65%); yellow paste.
IR (KBr): 3055, 2920, 1587, 1571, 1485, 1344, 814, 750 cm–1
1H NMR (500 MHz, CDCl3): δ = 8.16 (d, J = 8.3 Hz, 1 H), 8.06 (d, J = 7.6
Hz, 2 H), 7.99 (d, J = 8.2 Hz, 1 H), 7.71–7.69 (m, 2 H), 7.55–7.51 (m, 1
H), 7.33 (d, J = 7.6 Hz, 2 H), 2.76 (s, 3 H), 2.44 (s, 3 H).
.
Supporting Information
13C NMR (125 MHz, CDCl3): δ = 157.0, 148.3, 144.6, 139.2, 137.1,
Supporting information for this article is available online at
130.3, 129.5, 129.2, 127.4, 127.2, 125.8, 123.6, 119.6, 21.3, 18.9.
http://dx.doi.org/10.1055/s-0035-1561305.
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MS (ESI): m/z = 234 [M + H+].
2-(4-Methoxyphenyl)-4-methylquinoline (5c)
References
Yield: 159 mg (64%); pale yellow solid; mp 59–61 °C.
(1) (a) Dorel, R.; Echavarren, A. M. Chem. Rev. 2015, 115, 9028.
(b) Jiménez-Núñez, E.; Echavarren, A. Chem. Commun. 2007,
333.
(2) (a) Marion, N.; Nolan, S. P. Chem. Soc. Rev. 2008, 37, 1776.
(b) Nolan, S. P. Acc. Chem. Res. 2011, 44, 91. (c) Muñoz, M. P.;
Adrio, J.; Carretero, J. C.; Echavarren, A. M. Organometallics
2005, 24, 1293. (d) Hashmi, A. S. K.; Bührle, M. Aldrichimica Acta
2010, 43, 27.
IR (KBr): 3060, 1589, 1488, 1431, 1355, 1200, 1044, 771, 705 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 8.13 (d, J = 8.5 Hz, 3 H), 7.98 (d, J = 8.2
Hz, 1 H), 7.72–7.68 (m, 2 H), 7.52 (t, J = 7.4 Hz, 1 H), 7.04 (d, J = 8.6 Hz,
2 H), 3.89 (s, 3 H), 2.76 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 160.7, 156.7, 148.2, 144.6, 132.4,
130.1, 129.3, 128.9, 127.0, 125.7, 123.6, 119.3, 114.2, 55.4, 19.0.
MS (ESI): m/z = 250 [M + H+].
(3) (a) Jia, M.; Bandini, M. ACS Catal. 2015, 5, 1638. (b) Lu, Z.; Han,
J.; Hammond, G. B.; Xu, B. Org. Lett. 2015, 17, 4534.
(4) Wang, W.; Hammond, G.; Xu, B. J. Am. Chem. Soc. 2012, 134,
5697.
(5) Gorin, D. J.; Sherry, B. D.; Toste, F. D. Chem. Rev. 2008, 108, 3351.
(6) (a) de Frémont, P.; Scott, N. M.; Stevens, E. D.; Nolan, S. P.
Organometallics 2005, 24, 2411. (b) Gu, P.; Xu, Q.; Shi, M. Tetra-
hedron Lett. 2014, 55, 577.
2-(4-Chlorophenyl)-4-methylquinoline (5d)
Yield: 74 mg (29%); colorless solid; mp 93–95 °C..
IR (KBr): 3061, 1589, 1545, 1073, 878, 793, 773, 711 cm–1
1H NMR (500 MHz, CDCl3): δ = 8.17–8.10 (m, 3 H), 8.00 (d, J = 8.2 Hz, 1
H), 7.75–7.68 (m, 2 H), 7.57–7.48 (m, 3 H), 2.77 (s, 3 H).
.
(7) (a) Hashmi, A. S. K.; Lothschütz, C.; Böhling, C.; Hengst, T.;
Hubbert, C.; Rominger, F. Adv. Synth. Catal. 2010, 352, 3001.
(b) Hashmi, A. S. K.; Lothschütz, C.; Graf, K.; Haffner, T.;
Schuster, A.; Rominger, F. Adv. Synth. Catal. 2011, 353, 1407.
(8) Jaimes, M. C. B.; Böhling, C. R. N.; Serrano-Becerra, J. M.;
Hashmi, A. S. K. Angew. Chem. Int. Ed. 2013, 52, 7963.
(9) Gaillard, S.; Cazin, C. S. J.; Nolan, S. P. Acc. Chem. Res. 2012, 45,
778.
13C NMR (125 MHz, CDCl3): δ = 155.7, 148.2, 145.0, 138.2, 135.4,
130.3, 129.5, 128.9, 128.8, 127.3, 126.2, 123.6, 119.3, 18.9.
MS (ESI): m/z = 254 [M + H+], 256 [M + 2 + H+].
2-(2-Chlorophenyl)-4-methylquinoline (5e)
Yield: 66 mg (26%); colorless solid; mp 112–114 °C.
IR (KBr): 3029, 1575, 1522, 1050, 800, 706 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

J
C. Praveen, P. T. Perumal
Paper
Synthesis
(10) (a) Sakai, N.; Annaka, K.; Konakahara, T. J. Org. Chem. 2006, 71,
3653. (b) Sakai, N.; Annaka, K.; Fujita, A.; Sato, A.; Konakahara,
T. J. Org. Chem. 2008, 73, 4160.
(16) Koradin, C.; Dohle, W.; Rodriguez, A. L.; Schmid, B.; Knochel, P.
Tetrahedron 2003, 59, 1571.
(17) (a) Miyazaki, Y.; Kobayashi, S. J. Comb. Chem. 2008, 10, 355.
(b) Ambrogio, I.; Arcadi, A.; Cacchi, S.; Fabrizi, G.; Marinelli, F.
Synlett 2007, 1775. (c) Alfonsi, M.; Arcadi, A.; Aschi, M.; Bianchi,
G.; Marinelli, F. J. Org. Chem. 2005, 70, 2265. (d) Nakamura, I.;
Yamagishi, U.; Song, D.; Konta, S.; Yamamoto, Y. Angew. Chem.
Int. Ed. 2007, 46, 2284.
(18) Mézailles, N.; Richard, L.; Gagosz, F. Org. Lett. 2005, 7, 4133.
(19) Hashmi, A. S. K.; Blanco, M. C. Eur. J. Org. Chem. 2006, 4340.
(20) (a) Uson, R.; Laguna, A.; Castrillo, M. V. Synth. React. Inorg. Met.-
Org. Chem. 1979, 9, 317. (b) Bayler, A.; Bauer, A.; Schmidbaur, H.
Chem. Ber./Recl. 1997, 130, 115.
(11) (a) Praveen, C.; Jegatheesan, S.; Perumal, P. T. Synlett 2009,
2795. (b) Praveen, C.; Kiruthiga, P.; Perumal, P. T. Synlett 2009,
1990. (c) Praveen, C.; Kalyanasundaram, A.; Perumal, P. T.
Synlett 2010, 777. (d) Praveen, C.; Sagayaraj, Y. W.; Perumal, P. T.
Tetrahedron Lett. 2009, 50, 644. (e) Praveen, C.; Karthikeyan, K.;
Perumal, P. T. Tetrahedron 2009, 65, 9244. (f) Praveen, C.;
Perumal, P. T. Synlett 2011, 521. (g) Praveen, C.; Ayyanar, A.;
Perumal, P. T. Bioorg. Med. Chem. Lett. 2011, 21, 4170.
(h) Praveen, C.; Perumal, P. T. Chin. J. Catal. 2016, 37, in press;
DOI: 10.1016/S1872-2067(15)60994-9.
(12) (a) Chen, Y. L.; Fang, K. C.; Sheu, J. Y.; Hsu, S. L.; Tzeng, C. C.
J. Med. Chem. 2001, 44, 2374. (b) Michael, J. P. Nat. Prod. Rep.
2007, 24, 223.
(13) Shelton, P. A.; Hilliard, C. R.; Swindling, M.; McElwee-White, L.
ARKIVOC 2010, viii, 160.
(21) Bandini, M.; Monari, M.; Romaniello, A.; Tragni, M. Chem. Eur. J.
2010, 12, 14272.
(22) Widenhoefer, R. A.; Han, X. Eur. J. Org. Chem. 2006, 4555.
(23) Roma, G.; Braccio, M. D.; Grossi, G.; Mattioli, F.; Ghia, M. Eur. J.
Med. Chem. 2000, 1021.
(14) Ezquerra, J.; Pedregal, C.; Lamas, C. J. Org. Chem. 1996, 61, 5804.
(15) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975,
16, 4467.
(24) Pearson, S. E.; Nandan, S. Synthesis 2005, 2503.
(25) Kozlov, N. G.; Basalaeva, L. I. Russ. J. Org. Chem. 2003, 39, 718.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J