Synthesis of 3-Organoseleno-Substituted Quinolines through Cyclization of 2-Aminophenylprop-1-yn-3-ols Promoted by Iron(III) Chloride with Diorganyl Diselenides

Article abstract of DOI:10.1002/ejoc.201500766

We have described the application of iron(III) chloride and diorganyl diselenides as cooperative partners in the cyclization of (2-aminoaryl)-2-ynols for the regioselective synthesis of 3-organoseleno quinolines. The optimized reaction conditions were app

Full text of DOI:10.1002/ejoc.201500766

FULL PAPER
DOI: 10.1002/ejoc.201500766
Synthesis of 3-Organoseleno-Substituted Quinolines through Cyclization of
2
-Aminophenylprop-1-yn-3-ols Promoted by Iron(III) Chloride with Diorganyl
Diselenides
[a]
[a]
[a]
André Luiz Stein, Alisson Rodrigues Rosário, and Gilson Zeni*
Keywords: Synthetic methods / Nitrogen heterocycles / Cyclization / Regioselectivity / Selenium / Iron
We have described the application of iron(III) chloride and
tivity for six-membered quinoline products, which were
diorganyl diselenides as cooperative partners in the cycliza- formed by a 6-endo-dig ring closure, instead of a 5-exo-dig
tion of (2-aminoaryl)-2-ynols for the regioselective synthesis
of 3-organoseleno quinolines. The optimized reaction condi-
tions were applied to (2-aminoaryl)-2-ynols that contain a
wide range of functional groups, including electron-rich and
electron-poor substituents. The reaction showed regioselec-
process for the formation of indole products. In addition, we
also found that (2-aminoaryl)-2-ynols and a catalytic amount
of iron(III) chloride, in the absence of diorganyl diselenides,
afforded the corresponding quinoline derivatives without the
organoseleno moiety at the 3-position.
est.[12] The use of iron salts in organic synthesis has emerged
as a powerful method to promote the following transforma-
Introduction
In recent years, great progress has been made in the area
of organochalcogen chemistry, a subject of intensive re-
search in organic synthesis. Traditional methods to the in-
troduce an organochalcogen group into an organic struc-
ture have involved the use of nucleophilic, electrophilic,
and radical species. The incorporation of an organochal-
cogen moiety into an organic structure can result in the
tions: (i) cross-coupling reactions of Grignard reagents with
[13]
organic electrophiles,
(ii) carbon-heteroatom (i.e., C–N,
[14]
C–O, C–S) bond formation, (iii) heteroatom-heteroatom
and carbon-carbon bond formation, and (iv) the synthe-
sis of heterocyclic compounds. It has been reported that
[15]
[
1]
[2]
[16]
[
3]
iron has many advantages over other transition metals such
as its relative stability, abundance, low toxicity, economic
and ecological advantages, and excellent tolerance towards
3
2
formation of sp -, sp -, and sp-hybridized chemical bonds
and thus provide useful building blocks for further transfor-
mations. Thus far many methods have been reported that
use organochalcogen chemistry to form new carbon–car-
[17]
various functional groups.
[
4]
[5]
[6]
bon, carbon-lithium, carbon-halogen, and carbon-
[
7]
hydrogen bonds. Organochalcogen chemistry has also
[
8]
been proven useful in the synthesis of natural products.
Moreover, organochalcogens can exhibit pharmacological
Scheme 1.
[
9]
activity. For example, reports have shown that organo-
[
10]
chalcogen derivatives have potential use as anticancer,
anti-inflammatory, antibacterial, and antifungal agents.
[
11]
The quinoline structural motif is of particular interest,
Herein, we have developed a protocol for the synthesis of as it is found in a large number of natural products, many
3
-organoseleno quinolines 2 by employing the regioselective of which have biological activity.[18] Among the methods
cyclization of (2-aminoaryl)-2-ynols 1 promoted by the co- that have been used for their preparation, transition-metal-
operative action between iron(III) chloride and diorganyl catalyzed cyclizations of acyclic precursors are one of the
[
19]
diselenides (Scheme 1). Recently, the transformation of un- most promising. Similarly, electrophile-promoted nucleo-
saturated substrates into heterocycles by using iron salts philic cyclizations have also been recognized as a key syn-
and diorganyl dichalcogenides has received increasing inter- thetic process for their preparation.[20] Although most
methods described the use of transition-metal-catalyzed or
[
a] Laboratório de Síntese, Reatividade, Avaliação Farmacológica electrophile-promoted cyclizations for the preparation of
e Toxicológica de Organocalcogânios, CCNE, Universidade
quinolines, the cooperative action between iron(III) chlor-
Federal de Santa Maria,
Santa Maria, Rio Grande do Sul 97105-900, Brazil
E-mail: gzeni@ufsm.br
ide and diorganyl dichalcogenides has not yet been em-
ployed. The main advantage of this strategy includes the
ability of both iron(III) chloride and diorganyl dichalco-
genides to transform acyclic substrates into different hetero-
www.ufsm.br
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500766.
5640
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 5640–5648

Synthesis of 3-Organoseleno-Substituted Quinolines
cycles and incorporate new functionality into the final o-(2-aminoaryl)-2-ynol 1a was added, and the reaction was
structure, making heterocycles that are suitable for further conducted at 40 °C for the time indicated in Table 1. The
transformations.
initial screening of the iron source showed that the best re-
sults were obtained by using iron(III) chloride, which gave
3
-(phenylselenyl)quinoline (2a) in 68% yield along with
Results and Discussion
quinoline 3a in 13% yield (Table 1, Entry 5). Other iron
salts gave only quinoline 3a without the phenylselenyl group
at the 3-position (Table 1, Entries 1–4). No significant
change to the yield or selectivity was observed by lowering
the temperature, but the reaction was slower (Table 1, En-
try 6). The effect of changing the amounts of iron(III)
chloride and diphenyl diselenide were then evaluated. The
reaction was performed with 0.5, 0.75, and 1.5 equiv. of di-
phenyl diselenide, respectively, and the amount of iron(III)
chloride was kept constant at 1.5 equiv. Next, we varied the
amount of iron(III) chloride and kept the amount of di-
phenyl diselenide constant. As a result, we confirmed that
an iron(III) chloride/diphenyl diselenide ratio of 1.0:1.5 af-
forded the best yields (Table 1, Entries 5 and 7–12).
First, we explored the reaction conditions to promote the
cyclization of (2-aminoaryl)-2-ynols 1[ by screening pa-
rameters such as the molar ratio of the reagents, the tem-
perature, solvent, and iron source, that could affect the cy-
clization reaction (Table 1). Our study was initiated by tre-
21]
ating diphenyl diselenide with an iron source in CH Cl2
2
(3 mL) at room temperature for 15 min under argon. Then,
Table 1. Effect of different reaction parameters on the preparation
of 3-(phenylselenyl)quinoline (2a).[
a]
We suspected that the inert atmosphere would hamper
the oxidation of the selenolate anion into diphenyl diselen-
ide. To confirm this hypothesis, the reaction was carried
out under aerobic conditions (Table 1, Entry 13). However,
Entry Solvent
(PhSe)
2
Iron salt
Time % Yield these reaction conditions did not improve the yield of the
2a/3a[
b]
[equiv.] [equiv.]
[h]
desired product 2a, which implies that the cyclization reac-
tion requires both selenolate moieties in the starting reagent
to form the product in good yields. We assumed that the
coordination of one portion of diphenyl diselenide with
iron(III) chloride forms an intermediate, which promotes
the cyclization and the incorporation of PhSe into the het-
0
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
MeCN
toluene
DCE
CHCl
THF
EtOH
DMSO
2
2
2
2
2
2
2
2
2
2
2
2
2
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
2
2
2
2
2
2
2
2
2
2
2
2
2
1.0
1.0
1.0
1.0
1.0
1.0
0.5
0.75
1.5
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
Fe (1.5)
24
24
24
24
4
12
4
4
4
4
4
4
4
12
12
4
4
4
6
24
12
–/12
–/10
–/49
[
c]
Fe(acac)
3
(1.5)
FeCl
FeCl
FeCl
FeCl
FeCl
FeCl
FeCl
FeCl
FeCl
FeCl
FeCl
FeCl
FeCl
FeCl
FeCl
FeCl
FeCl
FeCl
FeCl
2
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
·4H
2
2
O (1.5)
O (1.5)
·6H
–/56
(1.5)
(1.5)
(1.5)
(1.5)
(1.5)
(1.0)
(2.0)
(3.0)
(1.5)
(1.5)
(1.5)
(1.5)
(1.5)
(1.5)
(1.5)
(1.5)
(1.5)
68:13
66:13
53:5
[
d]
–
erocycle. The other portion of selenolate anion (PhSe ) acts
as a base in the final step of the product formation
58:10
50:16
25:20
64:14
23:23
44:46
12:48
10:40
48:35
50:18
–/70
(Scheme 2, mechanism proposal). An investigation of vari-
0
1
2
3
4
5
6
7
8
9
0
1
ous solvents indicated that CH Cl was the most efficient
2
2
(Table 1, Entry 5). Other solvents such as MeCN, toluene,
[
e]
1,2-dichloroethane (DCE), and CHCl were less efficient
3
(
(
see Table 1, Entries 14–17), whereas tetrahydrofuran
THF), EtOH, dimethyl sulfoxide (DMSO), and 1,4-diox-
ane gave quinoline 3a as the sole product (Table 1, En-
tries 18–21).
3
–/70
–/10
–/58
In additional studies, we carried out experiments to find
parameters that could affect the cyclization reaction mecha-
nism. For example, when we ran the cyclization under the
optimized conditions (Table 1, Entry 5) in the presence of
the PhSeCl, previously prepared by the reaction of diphenyl
1,4-dioxane
[
a] The reaction was performed by the addition of diphenyl diselen-
ide to a solution of the iron salt in solvent (3 mL) at room tempera-
ture under argon. After 15 min, (2-aminoaryl)-2-ynol 1a
0.25 mmol) was added at this temperature, and the resulting mix-
ture was heated at 40 °C for the time indicated above. [b] Yield of iron(III) chloride and diphenyl diselenide, product 2a was
isolated products. [c] acac = acetylacetonate. [d] Reaction per-
obtained in 66% yield. These results indicate that the com-
[
22]
diselenide with thionyl chloride,
and the absence of
(
formed at room temperature. [e] Reaction carried out under air.
bination of iron(III) chloride and diphenyl diselenide could
Scheme 2. Proposed mechanism for the synthesis of 3-organoseleno quinolines 2.
Eur. J. Org. Chem. 2015, 5640–5648
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5641

A. L. Stein, A. R. Rosário, G. Zeni
FULL PAPER
lead to an in situ formation of PhSeCl, a selenium electro-
philic source, which could promote the cyclization. How-
ever, when the reaction of (2-aminoaryl)-2-ynol 1a was car-
ried out under the optimized reaction conditions by adding
PhSeCl instead of diphenyl diselenide, product 2a was ob-
tained only in 34% yield. In addition, the reaction of (2-
aminoaryl)-2-ynol 1a with iron(III) chloride in the absence
of diphenyl diselenide and PhSeCl gave quinoline 3a. When
FeCl and diphenyl diselenide were treated with quinoline
3
3a as the substrate under the optimized reaction conditions,
no amount of product 2a was formed. This implies that a
cyclization mediated by FeCl followed by an attack on the
3
C–Fe bond by diphenyl diselenide, which would act as an
electrophile source, does not occur. Finally, to check if HCl
could be liberated from FeCl acting as a catalyst, the reac-
3
tion was conducted in the presence of hydrochloric acid and
HCl (g), but only a trace amount of 3a was obtained. These
experiments clearly indicate that when diphenyl diselenide
is used as a reagent, the presence of an iron salt is necessary
to promote the cyclization of (2-aminoaryl)-2-ynol 1a and
that the cooperative action between diphenyl diselenide and
iron(III) chloride is essential to provide a good yield of the
cyclized product. With this information, we believed that
Scheme 3. Proposed mechanism for the synthesis of quinolines 3.
the cyclization of (2-aminoaryl)-2-ynols 1Ј to give 3-phen- quinolines 2g and 2h in low yields (Table 2, Entries 7 and
ylselenyl quinolines 2Ј involves iron(III) coordination with 8). In addition, the optimized reaction conditions were ap-
the oxygen atom of 1Ј and with one selenium atom of di- plied to dibenzyl diselenide, but they failed to afford the
phenyl diselenide, which activates the other selenium atom desired 3-(benzylselenyl)quinolines 2i (Table 2, Entry 9).
towards a nucleophilic attack by the alkyne to give selenir- This failure can be explained by the low stability of benzyl
anium ion I (Scheme 2). A nucleophilic anti attack of the selenides, which can undergo β-selenoxide elimination[23]
nitrogen atom on activated seleniranium ion I leads to dihy- during the purification or workup process to give the final
droquinoline II and a selenolate anion. Dehydration fol- product without a selenium group incorporated into the
lowed by deprotonation of the nitrogen atom by the sel- structure. We also found that using a dialkyl diselenide in
enolate anion gives 3-phenylselenyl quinoline 2Ј. For the the reaction worked well under the standard reaction condi-
formation of quinoline 3, we propose that the iron(III) tions and led to formation of the expected product in mod-
chloride acts as a Lewis acid to activate the triple bond erate yield (Table 2, Entry 10). The reaction with diphenyl
toward a nucleophilic attack by the nitrogen atom, giving disulfide did not give any of the desired product, whereas
quinoline 3 after dehydration (Scheme 3).
the use of diphenyl ditelluride gave the cyclized product in
The results in Table 1 indicate that the cyclization of (2- low yield (Table 2, Entries 11 and 12).
aminoaryl)-2-ynol 1a gave the desired 3-(phenylselenyl)-
Next, to elaborate on the general reactivity of the present
quinoline 2a in better yields when the reaction was carried protocol, we added functional groups to different positions
out by adding diphenyl diselenide (1.0 equiv.) to a solution of the (2-aminoaryl)-2-ynols 1. The experimental results
of iron(III) chloride (1.5 equiv.) in CH Cl (3 mL) at room show that the reactions of substrates with different substi-
2
2
temperature under argon. After 15 min, (2-aminoaryl)-2- tuted aryl groups directly bonded to the triple bond also
ynol 1a (0.25 mmol) was added at this temperature, and the worked well under the standard reaction conditions. How-
resulting mixture was heated at 40 °C for 4 h. These stan- ever, the presence of a p-methoxy substituent on the aryl
dard conditions were then applied to a variety of (2-amino- group gave the product in low yield (Table 2, Entries 13 and
aryl)-2-ynols 1 and diorganyl diselenides to investigate the 14). (2-Aminoaryl)-2-ynol 1d, which has an alkyl chain off
tolerance of the functional groups and their effects on the the alkyne, was also employed in the cyclization reaction
conversion (Table 2). We first investigated the influence of and afforded cyclized product 2o in 51% yield (Table 2, En-
various diorganyl diselenides on the yield of the cyclization. try 15). Changing the phenyl group at the propargyl posi-
The results indicate that the reaction is not sensitive to the tion to an aryl or methyl substituent did not affect the cycli-
electronic effects of the substituents on the aromatic ring zation, and 3-(arylselenyl)quinolines 2p–2r were obtained in
of the diaryl diselenides, as neutral, electron-donating, and moderated yields (Table 2, Entries 16–18). Finally, ex-
electron-withdrawing groups provided the 3-(arylselenyl)- tending the optimized conditions to (2-aminoaryl)-2-ynols
quinolines in similar yields (Table 2, Entries 1–6). In con- 1h and 1i, which have a Cl- and strongly electron-with-
trast, the steric hindrance of the methyl and methoxy drawing NO -substituted aromatic ring, gave good yields
2
groups at the ortho position of the aromatic ring exerted of the expected cyclized products (Table 2, Entries 19
significant negative effects and afforded 3-(arylselenyl)- and 20).
5642
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 5640–5648

Synthesis of 3-Organoseleno-Substituted Quinolines
Table 2. Synthesis of 3-organoseleno quinoline derivatives 2.[a]
[
(
a] The reaction was performed by adding diorganyl dichalcogenides (1.0 equiv.) to a solution of iron(III) chloride (1.5 equiv.) in CH
3 mL) at room temperature under argon. After 15 min, (2-aminoaryl)-2-ynols 1 (0.25 mmol) were added at this temperature, and the
resulting mixture was heated at 40 °C for 4 h. [b] Yield of isolated products. [c] The reaction was heated at 40 °C for 24 h.
2 2
Cl
After the result obtained in Table 1, Entry 18, in which the cyclization of (2-aminoaryl)-2-ynols 1 by using iron(III)
quinoline 3a was generated in 70% yield, we focused on chloride in the absence of the organoseleno source. For this
Eur. J. Org. Chem. 2015, 5640–5648
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5643

A. L. Stein, A. R. Rosário, G. Zeni
FULL PAPER
purpose, we systematically evaluated different parameters Table 3. Synthesis of quinoline derivatives 3.[a]
to determine the best reaction conditions by subjecting (2-
aminoaryl)-2-ynols 1a to the cyclization process (Support-
ing Information, Table S1) Thus, careful analysis of the re-
actions revealed that the best conditions for this cyclization
involved (2-aminoaryl)-2-ynol 1a (0.25 mmol) and a cata-
lytic amount of iron(III) chloride (30 mol-%) in CH Cl2
2
(3 mL) at 40 °C for 4 h. By using these conditions, we were
able to prepare quinoline 3a in 85% yield. To demonstrate
the efficiency of this protocol, we explored its generality
by extending the reaction to several (2-aminoaryl)-2-ynols
1
(Table 3). The corresponding quinolines 3 were produced
in good to excellent yields under the optimized conditions
Table 3). With regard to the scope of the substrate, we first
(
examined the aryl substituent directly bonded to the alkyne
moiety. Neutral and electron-donating groups on the aryl
unit such as p-methyl and p-methoxy afforded the corre-
sponding quinoline products in good yields (Table 3, En-
tries 2 and 3). However, the yield decreased considerably
when a straight chain alkyl group was bonded to the alkyne
(
Table 3, Entry 4). We then focused on the effect of other
substituents at the propargyl position of the (2-aminoaryl)-
-ynols. The presence of a p-tolyl, p-chlorophenyl, or
2
methyl group instead of a phenyl unit did not have a signifi-
cant influence on the yield (Table 3, Entries 5–7). The effect
of a substituent on the main aromatic ring of the (2-amino-
aryl)-2-ynols was also investigated. In this case, chloro-sub-
stituted compound 1h afforded quinoline 3h in 74% yield,
whereas nitro-substituted 1i gave a poor 49% yield of
quinoline 3i (Table 3, Entries 8 and 9).
An interesting feature of 3-organoseleno-substituted
quinolines is their ability to undergo chalcogen-lithium ex-
[24]
change reactions with lithium reagents. To introduce dif-
ferent functional groups at the 3-position of the quinoline
ring and improve the synthetic utility of our methodology,
a 3-organoseleno quinoline was treated with n-butyllithium
followed by the addition of an electrophile. As expected, the
reaction of n-butyllithium (1.0 equiv.) with 3-organoseleno
quinoline 1a (1.0 equiv.) in THF (3 mL) at –78 °C gave the
lithium intermediate,[ which upon the addition of an al-
dehyde or TMSCl (TMS = trimethylsilyl) afforded the cor-
responding secondary alcohol 4a and 3-(trimethylsilyl)quin-
oline (4b) in 76 and 73% yields, respectively (Scheme 4).
25]
[
(
a] The reaction was performed by adding (2-aminoaryl)-2-ynols 1
0.25 mmol) to a solution of iron(III) chloride (30 mol-%) in
CH Cl (3 mL) at room temperature under argon. After 15 min at
2
2
this temperature, the resulting mixture was heated at 40 °C for 4 h.
[b] Yield of isolated products. [c] A reaction time of 24 h was neces-
sary.
Scheme 4. Organoseleno-lithium exchange reaction of 3-organo-
seleno-substituted quinoline 2a.
5644
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 5640–5648

Synthesis of 3-Organoseleno-Substituted Quinolines
3
-(p-Methoxyphenylselenyl)-2,4-diphenylquinoline (2c): Yellow solid
Conclusions
1
(
0.053 g, 45% yield); m.p. 132–134 °C. H NMR (400 MHz,
In summary, we have shown that the cooperative action CDCl ): δ = 8.16 (d, J = 8.4 Hz, 1 H), 7.71–7.66 (m, 1 H), 7.53–
3
between iron(III) chloride and diorganyl diselenides can be 7.22 (m, 12 H), 6.75–6.42 (m, 4 H), 3.68 (s, 3 H) ppm. 1 C NMR
3
(
100 MHz, CDCl
34.2, 129.7, 129.6, 129.5, 129.1, 128.1, 127.9, 127.7, 127.6, 127.3,
26.6, 126.0, 122.8, 114.3, 55.2 ppm. MS (EI, 70 eV): m/z (%) =
67 (100), 360 (58), 278 (24), 176 (38), 151 (18). HRMS (ESI-TOF):
3
): δ = 162.6, 158.7, 153.8, 147.1, 142.2, 138.7,
efficiently used for the cyclization of (2-aminoaryl)-2-ynols
for the regioselective synthesis of 3-organoseleno quinol-
ines. The reaction showed high regioselectivity for six-mem-
bered quinoline products that were formed by a 6-endo-dig
instead of 5-exo-dig ring closure. The experiments revealed
1
1
4
calcd. for C28
H
21NOSe [M + H]+ 468.0867; found 468.0871.
that the selectivity favoring the former cyclization process 3-(p-Fluorophenylselenyl)-2,4-diphenylquinoline (2d): Yellow solid
1
(
0.068 g, 60% yield); m.p. 127–129 °C. H NMR (400 MHz,
CDCl ): δ = 8.17 (d, J = 8.4 Hz, 1 H), 7.69 (td, J = 6.4 and 1.7 Hz,
H), 7.52–7.21 (m, 12 H), 6.70–6.57 (m, 4 H) ppm. C NMR
100 MHz, CDCl ): δ = 162.4, 161.8 (d, J = 246 Hz), 153.9, 147.2,
is controlled by the iron intermediate. In addition, when the
reaction of the (2-aminoaryl)-2-ynols were carried out with
a catalytic amount of iron(III) chloride, in the absence of
the diorganyl diselenides, the quinolone derivatives without
the organoseleno group at the 3-position were exclusively
obtained. This result is significant because similar reaction
conditions were used to obtain two classes of quinolones.
3
1
3
1
(
1
1
2
3
42.0, 138.6, 134.2 (d, J = 8.1 Hz), 129.9, 129.6, 129.5, 129.0, 128.1,
28.0, 127.7, 127.2, 127.1, 127.0, 126.9, 126.6, 125.5, 115.6 (d, J =
1.3 Hz) ppm. MS (EI, 70 eV): m/z (%) = 454 (31), 360 (100), 278
(
32), 207 (78), 75 (18). HRMS (ESI-TOF): calcd. for C27H18FNSe
+
To introduce different functional groups at the 3-position [M + H] 456.0667; found 456.0671.
of the quinoline ring and improve the synthetic utility of
3
(
=
(
-(p-Chlorophenylselenyl)-2,4-diphenylquinoline (2e): Yellow oil
0.059 g, 50% yield). H NMR (400 MHz, CDCl
8.4 Hz, 1 H), 7.73–7.70 (m, 1 H), 7.51–7.40 (m, 7 H), 7.32–7.31
m, 3 H), 7.23–7.18 (m, 2 H), 6.88–6.84 (m, 2 H), 6.66–6.64 (m, 2
our methodology, the 3-organoseleno quinoline was treated
with n-butyllithium followed by the addition of an aldehyde
or TMSCl, which afforded the corresponding secondary
alcohol and 3-(trimethylsilyl)quinoline, respectively.
1
3
): δ = 8.18 (d, J
13
H) ppm. C NMR (100 MHz, CDCl
3
): δ = 162.4, 154.3, 147.3,
1
1
7
7
4
41.9, 138.5, 135.7, 133.2, 132.5, 131.0, 130.0, 129.6, 129.4, 129.0,
28.6, 128.1, 128.0, 127.6, 127.2, 126.9, 126.7, 124.9 ppm. MS (EI,
0 eV): m/z (%) = 471 (38), 392 (29), 281 (38), 207 (100), 176 (37),
Experimental Section
+
3 (58). HRMS (ESI-TOF): calcd. for C27
72.0371; found 472.0377.
H18ClNSe [M + H]
General Procedure for the Preparation of the 3-Organochalcogen
Quinoline Derivatives: To a Schlenk tube that contained dichloro-
methane (3 mL) under argon were added iron(III) chloride (99.99%
purity from commercial suppliers, 0.061 g, 1.5 equiv.) and dior-
ganyl dichalcogenides (0.25 mmol, 1.0 equiv.), and the resulting
mixture was stirred at room temperature for 15 min. After this time,
a solution of 2-aminophenylprop-1-yn-3-ol 1a–1j (0.25 mmol,
2
,4-Diphenyl-3-(m-trifluoromethylphenylselenyl)quinoline (2f): Yel-
1
low solid (0.073 g, 58% yield); m.p. 121–123 °C. H NMR
400 MHz, CDCl ): δ = 8.18 (d, J = 8.4 Hz, 1 H), 7.73 (td, J = 6.4
and 1.7 Hz, 1 H), 7.50–7.42 (m, 7 H), 7.31–7.21 (m, 6 H), 7.05–7.01
(
3
1
3
(
m, 1 H), 6.98–6.97 (m, 2 H) ppm. C NMR (100 MHz, CDCl
3
): δ
=
162.3, 154.3, 147.5, 147.8, 138.5, 135.4, 130.8 (q, J = 32.3 Hz),
1
.0 equiv.) in CH
for the desired time at 40 °C and then diluted with dichloromethane
20 mL). The resulting mixture was washed with a saturated solu-
tion of NaHCO (20 mL). The organic phase was separated, dried
with MgSO , and concentrated under vacuum. The residue was
purified by flash chromatography (hexane/acetate, 97:3).
2 2
Cl (1 mL) was added. The mixture was stirred
1
1
1
2
30.2, 129.7, 129.0, 128.8, 128.6 (q, J = 3.7 Hz), 128.2, 127.7, 127.2,
27.0, 126.7, 124.8, 123.5 (q, J = 272 Hz), 123.3 (q, J = 3.7 Hz),
21.5 ppm. MS (EI, 70 eV): m/z (%) = 505 (10), 360 (31), 281 (36),
(
3
18 3
07 (100), 133 (23). HRMS (ESI-TOF): calcd. for C28H F NSe
4
[
M + H]+ 506.0635; found 506.0640.
2
6
8
7
7
6
1
1
7
7
4
,4-Diphenyl-3-(phenylselenyl)quinoline (2a): Yellow solid (0.074 g, 2,4-Diphenyl-3-(2,4,6-trimethylphenylselenyl)quinoline (2g): Dark
1
1
8% yield); m.p. 132–134 °C. H NMR (400 MHz, CDCl
.17 (d, J = 8.1 Hz, 1 H), 7.68–7.63 (m, 1 H), 7.52–7.50 (m, 2 H), (400 MHz, CDCl
3
): δ = yellow solid (0.036 g, 30% yield); m.p. 111–113 °C. H NMR
): δ = 8.13 (d, J = 8.4 Hz, 1 H), 7.65 (t, J =
7.9 Hz, 1 H), 7.52–7.51 (m, 2 H), 7.37–7.29 (m, 8 H), 7.06 (d, J =
3
.45–7.43 (m, 1 H), 7.37–7.34 (m, 4 H), 7.28–7.26 (m, 3 H), 7.21–
1
3
.29 (m, 2 H), 6.98–6.94 (m, 1 H), 6.86 (t, J = 7.7 Hz, 2 H), 6.74–
7.9 Hz, 2 H), 6.48 (s, 2 H), 2.12 (s, 3 H), 1.77 (s, 6 H) ppm.
C
.73 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl
): δ = 162.7, 154.4, NMR (100 MHz, CDCl
3
): δ = 162.2, 151.1, 146.6, 142.4, 141.1,
3
47.2, 142.0, 138.6, 132.9, 131.6, 129.8, 129.4, 129.3, 128.9, 128.4,
27.9, 127.8, 127.4, 127.1, 126.7, 126.6, 126.2, 125.0 ppm. MS (EI,
138.4, 137.2, 130.5, 129.7, 129.1, 128.5, 128.4, 128.1, 128.0, 127.8,
127.7, 127.5, 126.6, 126.5, 125.9, 23.5, 20.6 ppm. MS (EI, 70 eV):
0 eV): m/z (%) = 437 (66), 359 (100), 280 (31), 252 (14), 176 (45), m/z (%) = 479 (9), 281 (18), 207 (100), 77 (9). HRMS (ESI-TOF):
7 (17). HRMS (ESI-TOF): calcd. for C27
38.0761; found 438.0766.
H
19NSe [M +H]+
calcd. for C30
H
25NSe [M + H]+ 480.1230; found 480.1234.
3-(o-Methoxyphenylselenyl)-2,4-diphenylquinoline (2h): Yellow oil
1
2
6
8
7
,4-Diphenyl-3-(p-tolylselenyl)quinoline (2b): Yellow solid (0.070 g, (0.041 g, 35% yield). H NMR (400 MHz, CDCl
3
): δ = 8.19 (d, J
1
2% yield); m.p. 115–117 °C. H NMR (400 MHz, CDCl
3
): δ = = 7.9 Hz, 1 H), 7.73–7.69 (td, J = 8.4 and 2.0 Hz, 1 H), 7.55–7.52
.18–8.16 (m, 1 H), 7.70–7.66 (m, 1 H), 7.52–7.48 (m, 2 H), 7.46–
.44 (m, 1 H), 7.41–7.39 (m, 4 H), 7.32–7.29 (m, 3 H), 7.23–7.20
(m, 2 H), 7.46–7.41 (m, 2 H), 7.40–7.36 (m, 3 H), 7.30–7.25 (m, 3
H), 7.22–7.20 (m, 2 H), 7.01–6.97 (m, 1 H), 6.62–6.55 (m, 2 H),
1
3
(
m, 2 H), 6.76 (d, J = 7.9 Hz, 2 H), 6.68–6.65 (m, 2 H), 2.17 (s, 3
6.50 (d, J = 8.2 Hz, 1 H), 3.51 (s, 3 H) ppm. C NMR (100 MHz,
CDCl ): δ = 163.2, 156.9, 155.0, 147.4, 142.0, 138.7, 131.6, 129.9,
13
H) ppm. C NMR (100 MHz, CDCl
3
): δ = 162.8, 154.3, 147.2,
3
1
1
7
42.1, 138.7, 136.2, 132.0, 129.8, 129.5, 129.4, 129.3, 129.1, 129.0,
28.0, 127.8, 127.5, 127.2, 126.7, 126.6, 126.4, 20.9 ppm. MS (EI,
129.6, 128.3, 128.9, 127.9, 127.8, 127.7, 127.4, 127.3, 127.2, 126.8,
126.7, 124.0, 122.8, 121.2, 110.3, 55.5 ppm. MS (EI, 70 eV): m/z
(%) = 467 (3), 271 (35), 207 (100), 133 (23), 73 (8). HRMS: calcd.
0 eV): m/z (%) = 451 (5), 374 (12), 207 (100), 73 (79). HRMS (ESI-
+
21NOSe [M + H]+ 468.0867; found 468.0872.
TOF): calcd. for C28
H
21NSe [M + H] 452.0917; found 452.0920.
for C28H
Eur. J. Org. Chem. 2015, 5640–5648
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5645

A. L. Stein, A. R. Rosário, G. Zeni
H
21NSe [M + H]+ 452.0917; found
FULL PAPER
3
-Butylselenyl-2,4-diphenylquinoline (2j): Yellow solid (0.056 g, 54%
(ESI-TOF): calcd. for C28
): δ = 8.17 (d, J 452.0923.
8.4 Hz, 1 H), 7.80–7.77 (m, 2 H), 7.70 (m, 1 H), 7.55–7.38 (m, 8
H), 7.36–7.34 (m, 2 H), 2.03 (t, J = 7.3 Hz, 2 H), 1.13 (quint, J =
.3 Hz, 2 H), 1.00 (sext, J = 7.3 Hz, 2 H), 0.65 (q, J = 7.3 Hz, 3
1
yield); m.p. 62–64 °C. H NMR (400 MHz, CDCl
=
3
4
-(p-Chlorophenyl)-2-phenyl-3-(phenylselenyl)quinoline (2q): Yellow
1
solid (0.055 g, 47% yield); m.p. 163–165 °C. H NMR (400 MHz,
CDCl ): δ = 8.18 (d, J = 8.4 Hz, 1 H), 7.76–7.69 (m, 1 H), 7.53–
.50 (m, 2 H), 7.43–7.41 (m, 2 H), 7.36–7.31 (m, 5 H), 7.11 (dt, J
7
13
3
H) ppm. C NMR (100 MHz, CDCl
3
): δ = 162.2, 153.9, 146.9,
7
=
1
1
7
42.3, 139.1, 129.8, 129.5, 129.4, 129.3, 128.2, 128.1, 127.9, 127.8,
27.0, 126.7, 126.4, 123.2, 31.8, 28.6, 22.5, 13.2 ppm. MS (EI,
0 eV): m/z (%) = 416 (7), 360 (100), 281 (41), 206 (68), 73 (29).
8.4 and 2.0 Hz, 2 H), 7.03 (tt, J = 7.5 and 1.8 Hz, 1 H), 6.92 (t,
1
3
J = 7.7 Hz, 2 H), 6.77–6.74 (m, 2 H) ppm. C NMR (100 MHz,
CDCl ): δ = 162.8, 153.0, 147.3, 141.9, 136.9, 134.0, 133.0, 131.8,
30.9, 130.1, 129.7, 129.0, 128.5, 128.3, 128.1, 127.7, 127.1, 127.0,
26.5, 126.3, 125.3 ppm. MS (EI, 70 eV): m/z (%) = 471 (26), 394
+
3
HRMS (ESI-TOF): calcd. for C25
found 418.1080.
H
23NSe [M + H] 418.1074;
1
1
2
2
1
,4-Diphenyl-3-(phenyltelluryl)quinoline (2l): Yellow oil (0.030 g, (36), 281 (37), 207 (100), 176 (24), 73 (58). HRMS (ESI-TOF):
1
H
18ClNSe [M + H]+ 472.0371; found 472.0379.
5% yield). H NMR (400 MHz, CDCl
3
): δ = 8.15 (d, J = 8.4 Hz,
calcd. for C27
H), 7.68 (td, J = 8.4 and 1.7 Hz, 1 H), 7.49–7.37 (m, 7 H), 7.30
4
-Methyl-2-phenyl-3-(phenylselenyl)quinoline (2r): Yellow solid
(
d, J = 2.0 Hz, 2 H), 7.29 (d, J = 1.7 Hz, 1 H), 7.20–7.18 (m, 2
1
(
0.056 g, 60% yield); m.p. 110–112 °C. H NMR (400 MHz,
CDCl ): δ = 8.16 (d, J = 8.1 Hz, 1 H), 8.03 (d, J = 7.9 Hz, 1 H),
.76–7.70 (m, 1 H), 7.59–7.55 (m, 1 H), 7.48–7.45 (m, 2 H), 7.37–
.34 (m, 3 H), 7.08–7.06 (m, 3 H), 7.01–6.98 (m, 2 H), 2.93 (s, 3
13
H), 7.08–7.01 (m, 3 H), 6.87 (t, J = 7.7 Hz, 2 H) ppm. C NMR
100 MHz, CDCl ): δ = 164.3, 157.0, 147.5, 144.1, 141.6, 137.4,
29.9, 129.5, 128.9, 128.8, 128.3, 128.1, 128.0, 127.9, 127.8, 127.6,
3
(
3
7
7
1
1
4
28.0, 126.8, 126.7, 117.5, 114.9 ppm. MS (EI, 70 eV): m/z (%) =
13
H) ppm. C NMR (100 MHz, CDCl
3
): δ = 163.2, 150.6, 146.9,
85 (18), 281 (50), 207 (100), 132 (23), 73 (63). HRMS (ESI-TOF):
1
1
3
42.6, 133.1, 130.2, 130.0, 129.8, 129.1, 128.9, 128.0, 127.6, 127.3,
26.7, 126.1, 124.9, 124.5, 20.1 ppm. MS (EI, 70 eV): m/z (%) =
74 (62), 340 (16), 281 (32), 206 (100), 132 (20), 73 (49). HRMS
+
calcd. for C27
H
19NTe [M + H] 488.0658; found 488.0663.
4
-Phenyl-3-(phenylselenyl)-2-(p-tolylphenyl)quinoline (2m): Yellow
+
1
(ESI-TOF): calcd. for C H NSe [M + H] 376.0604; found
solid (0.081 g, 72% yield); m.p. 125–127 °C. H NMR (400 MHz,
CDCl ): δ = 8.17 (d, J = 8.6 Hz, 1 H), 7.68 (td, J = 6.4 and 1.7 Hz,
22 17
376.0609.
3
1
2
2
1
1
2
H), 7.44–7.34 (m, 7 H), 7.19–7.16 (m, 2 H), 7.12 (d, J = 7.6 Hz,
H), 7.01–6.97 (m, 1 H), 6.89 (t, J = 7.5 Hz, 2 H), 6.76–6.74 (m,
6
-Chloro-2,4-diphenyl-3-(phenylselenyl)quinoline (2s): Yellow solid
1
(
0.073 g, 72% yield); m.p. 70–72 °C. H NMR (400 MHz, CDCl
3
):
H), 2.35 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl
3
): δ = 162.9,
δ = 8.10 (d, J = 8.9 Hz, 1 H), 7.63 (dd, J = 8.9 and 2.3 Hz, 1 H),
54.5, 147.3, 139.2, 138.7, 133.2, 131.6, 129.9, 129.5, 129.4, 128.9,
28.7, 128.5, 128.2, 127.9, 127.8, 127.2, 126.7, 126.6, 126.2, 125.1,
7
7
.50–7.48 (m, 2 H), 7.44–7.41 (m, 4 H), 7.31–7.28 (m, 3 H), 7.22–
.18 (m, 2 H), 7.01 (tt, J = 7.3 and 1.1 Hz, 1 H), 6.91–6.87 (m, 2
1.2 ppm. MS (EI, 70 eV): m/z (%) = 451 (2), 374 (5), 207 (100), 73
13
3
H), 6.74–6.71 (m, 2 H) ppm. C NMR (100 MHz, CDCl ): δ =
+
(77). HRMS (ESI-TOF): calcd. for C28
H
21NSe [M + H] 452.0917;
1
1
1
63.0, 153.5, 145.7, 141.8, 138.1, 132.8, 132.7, 132.1, 131.3, 130.8,
29.4, 129.0, 128.7, 128.4, 128.3, 128.1, 128.0, 127.7, 126.7, 126.6,
25.4 ppm. MS (EI, 70 eV): m/z (%) = 471 (94), 469 (50), 390 (25),
found 452.0920.
2
-(p-Methoxyphenyl)-4-phenyl-3-(phenylselenyl)quinoline (2n): Yel-
1
279 (33), 176 (35). HRMS (ESI-TOF): calcd. for C27H18ClNSe [M
+
low solid (0.035 g, 30% yield); m.p. 143–145 °C. H NMR
400 MHz, CDCl ): δ = 8.19 (d, J = 7.9 Hz, 1 H), 8.15 (dt, J = 8.9
and 2.2 Hz, 2 H), 7.85 (dd, J = 8.3 and 0.7 Hz, 1 H), 7.59–6.67 (m,
+
H] 472.0371; found 472.0375.
(
3
6-Nitro-2,4-diphenyl-3-(phenylselenyl)quinoline (2t): Yellow solid
1
1
1
6 H), 3.85 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl
56.3, 148.9, 148.8, 138.5, 132.2, 129.9, 129.5, 129.4, 128.9, 128.5,
28.3, 126.0, 125.5, 125.4, 118.8, 114.2, 55.3 ppm. MS (EI, 70 eV):
3
): δ = 160.8,
1
(
0.094 g, 78% yield); m.p. 197–199 °C. H NMR (400 MHz,
CDCl ): δ = 8.44 (dd, J = 9.1 and 2.5 Hz, 1 H), 8.41 (dd, J = 2.5
and 0.6 Hz, 1 H), 8.26 (dd, J = 9.1 and 0.6 Hz, 1 H), 7.55–7.45 (m,
3
m/z (%) = 467 (100), 390 (95), 267 (33), 207 (30), 163 (35). HRMS
5
1
H), 7.36–7.32 (m, 3 H), 7.25–7.22 (m, 2 H), 7.03 (tt, J = 7.4 and
+
(ESI-TOF): calcd. for C28
H
21NOSe [M + H] 468.0867; found
13
.2 Hz, 1 H), 6.92–6.88 (m, 2 H), 6.74–6.71 (m, 2 H) ppm.
): δ = 166.0, 155.7, 149.2, 145.8, 141.3,
37.2, 132.4, 132.0, 131.4, 129.4, 128.9, 128.8, 128.7, 128.6, 128.5,
128.4, 127.8, 126.9, 126.3, 123.5, 123.2 ppm. MS (EI, 70 eV): m/z
%) = 482 (68), 405 (30), 357 (19), 207 (100), 77 (29). HRMS (ESI-
C
468.0870.
NMR (100 MHz, CDCl
1
3
2
5
1
-Butyl-4-phenyl-3-(phenylselenyl)quinoline (2o): Brown oil (0.053 g,
1% yield). H NMR (400 MHz, CDCl
1
3
): δ = 8.13 (d, J = 8.4 Hz,
(
H), 7.71 (m, 1 H), 7.42–7.37 (m, 5 H), 7.16–7.01 (m, 7 H), 3.24
18 2 2
H N O
Se [M + H]+ 483.0612; found
TOF): calcd. for C27
483.0620.
(
7
t, J = 7.3 Hz, 2 H), 1.80 (quint, J = 7.3 Hz, 2 H), 1.42 (sext, J =
.3 Hz, 2 H), 0.91 (t, J = 7.3 Hz, 3 H) ppm. 13C NMR (100 MHz,
CDCl ): δ = 165.4, 155.0, 147.7, 139.0, 135.6, 129.9, 129.1, 129.0,
28.8, 127.8, 127.7, 127.0, 126.6, 126.0, 124.3, 39.4, 32.1, 22.8,
3.9 ppm. MS (EI, 70 eV): m/z (%) = 416 (4), 374 (54), 207 (100),
32 (20), 76 (49). HRMS (ESI-TOF): calcd. for C25 23NSe [M +
3
General Procedure for the Preparation of the Quinoline Derivatives
3: To a Schlenk tube that contained CH Cl (3 mL) under argon
1
1
1
2
2
were added iron(III) chloride (99.99% purity from commercial sup-
pliers, 0.012 g, 30 mol-%) and 2-aminophenylprop-1-yn-3-ol 1a–1j
(0.25 mmol), and the resulting mixture was stirred at room tem-
perature for 4 h. After this period of time, the mixture was diluted
with dichloromethane (20 mL), and the resulting mixture was
washed with a saturated solution of NaHCO
phase was separated, dried with MgSO , and concentrated under
vacuum. The residue was purified by flash chromatography (hex-
ane/acetate, 99:1).
H
+
H] 418.1074; found 418.1081.
2
-Phenyl-3-(phenylselenyl)-4-p-tolylquinoline (2p): Yellow oil
1
(0.062 g, 55% yield). H NMR (400 MHz, CDCl
3
): δ = 8.16 (d, J
3
(20 mL). The organic
=
8.4 Hz, 1 H), 7.69 (d, J = 7.5 Hz, 1 H), 7.50–7.39 (m, 4 H), 7.28–
4
7
1
3
1
1
.22 (m, 5 H), 7.12 (d, J = 7.9 Hz, 2 H), 7.01–6.97 (t, J = 7.3 Hz,
H), 6.90 (t, J = 7.3 Hz, 2 H), 6.74 (d, J = 7.9 Hz, 2 H), 2.43 (s,
H) ppm. 13C NMR (100 MHz, CDCl
): δ = 162.8, 154.6, 147.3,
3
42.1, 139.4, 137.7, 135.8, 133.1, 132.0, 129.8, 129.5, 129.0, 128.8,
28.5, 127.8, 127.5, 127.4, 126.9, 126.7, 126.2, 125.2, 21.3 ppm. MS
2,4-Diphenylquinoline (3a): Pale yellow solid (0.060 g, 85% yield);
m.p. 107–109 °C. H NMR (400 MHz, CDCl
1
3
): δ = 8.24 (d, J =
(EI, 70 eV): m/z (%) = 451 (4), 374 (10), 207 (100), 73 (78). HRMS
8.1 Hz, 1 H), 8.17 (d, J = 8.4 Hz, 2 H), 7.86 (d, J = 8.4 Hz, 1 H),
5646
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 5640–5648

Synthesis of 3-Organoseleno-Substituted Quinolines
7
.78 (s, 1 H), 7.68 (t, J = 8.1 Hz, 1 H), 7.50–7.39 (m, 9 H) ppm.
144.7, 139.8, 130.2, 129.3, 129.1, 128.7, 127.5, 127.2, 126.6, 126.0,
): δ = 156.7, 149.0, 148.7, 139.5, 138.3, 119.7, 18.9 ppm. MS (EI, 70 eV): m/z (%) = 219 (100), 218 (41),
30.0, 129.4, 129.4, 129.2, 128.7, 128.5, 128.3, 127.5, 126.2, 125.7, 204 (82), 176 (5), 108 (22). HRMS (ESI-TOF): calcd. for C16
25.5, 119.2 ppm. MS (EI, 70 eV): m/z (%) = 281 (75), 280 (100), [M + H]+ 220.1126; found 220.1130.
07 (13), 139 (16), 77 (5). HRMS (ESI-TOF): calcd. for C21
13
C NMR (100 MHz, CDCl
3
1
1
2
13
H N
15
H N
6
-Chloro-2,4-diphenylquinoline (3h): Yellow solid (0.058 g, 74%
[
M + H]+ 282.1283; found 282.1289.
1
3
yield); m.p. 127–129 °C. H NMR (400 MHz, CDCl ): δ = 8.19–
4
-Phenyl-2-(p-tolyl)quinoline (3b): Yellow solid (0.067 g, 91% yield);
8.15 (m, 3 H), 7.85 (d, J = 2.3 Hz, 1 H), 7.82 (s, 1 H), 7.97 (dd, J
1
13
m.p. 101–103 °C. H NMR (400 MHz, CDCl
3
): δ = 8.22 (d, J = = 8.9 and 2.3 Hz, 1 H), 7.58–7.44 (m, 8 H) ppm. C NMR
8.4 Hz, 1 H), 8.09 (d, J = 8.1 Hz, 2 H), 7.87 (d, J = 8.4 Hz, 1 H), (100 MHz, CDCl
3
): δ = 157.0, 148.4, 147.2, 139.2, 137.8, 132.2,
7
.78 (s, 1 H), 7.69 (dd, J = 7.0 and 1.2 Hz, 1 H), 7.55–7.40 (m, 6 131.7, 130.4, 129.6, 129.4, 128.9, 128.8, 128.7, 127.5, 126.5, 124.5,
13
H), 7.31 (d, J = 8.1 Hz, 2 H), 2.41 (s, 3 H) ppm. C NMR 120.0 ppm. MS (EI, 70 eV): m/z (%) = 316 (42), 314 (82), 207 (100),
(
100 MHz, CDCl
30.0, 129.5, 129.4, 129.3, 128.5, 128.3, 127.4, 126.1, 125.7, 125.6,
19.1, 21.2 ppm. MS (EI, 70 eV): m/z (%) = 295 (74), 294 (100),
17
01 (16), 139 (10), 73 (2). HRMS (ESI-TOF): calcd. for C22H N
3
): δ = 156.8, 149.0, 148.8, 139.7, 138.5, 136.8, 139 (30), 73 (31). HRMS (ESI-TOF): calcd. for C21
H
14ClN [M +
+
1
1
2
H] 316.0893; found 316.0898.
6
-Nitro-2,4-diphenylquinoline (3i): Yellow solid (0.040, 49% yield);
1
m.p. 206–208 °C. H NMR (400 MHz, CDCl
.5 Hz, 1 H), 8.48 (dd, J = 9.1 and 2.5 Hz, 1 H), 8.33 (d, J =
9.1 Hz, 1 H), 8.25–8.23 (m, 2 H), 7.97 (s, 1 H), 7.64–7.52 (m, 8
3
): δ = 8.85 (d, J =
[
M + H]+ 296.1439; found 296.1443.
2
2
-(p-Methoxy)-4-phenylquinoline (3c): Yellow solid (0.048 g, 62%
1
13
yield); m.p. 75–77 °C. H NMR (400 MHz, CDCl
7.9 Hz, 1 H), 8.15 (dt, J = 8.9 and 2.2 Hz, 2 H), 7.85 (dd, J = 145.4, 138.5, 136.9, 131.8, 130.4, 129.5, 129.3, 129.1, 129.0, 127.8,
.4 and 0.7 Hz, 1 H), 7.75 (s, 1 H), 7.68 (td, J = 8.4 and 1.6 Hz, 1 124.8, 123.0, 122.9, 120.7 ppm. MS (EI, 70 eV): m/z (%) = 326 (78),
H), 7.55–7.48 (m, 5 H), 7.41 (td, J = 8.1 and 1.2 Hz, 1 H), 7.02 279 (100), 202 (19), 176 (16), 139 (28). HRMS (ESI-TOF): calcd.
3 3
): δ = 8.19 (d, J H) ppm. C NMR (100 MHz, CDCl ): δ = 160.0, 151.3, 151.0,
=
8
13
[M + H]+ 327.1134; found 327.1145.
(
(
14 2 2
dt, J = 8.9 and 2.1 Hz, 2 H), 3.85 (s, 3 H) ppm. C NMR for C21H N O
100 MHz, CDCl
3
): δ = 160.8, 156.4, 149.0, 148.8, 138.5, 132.2,
29.9, 129.5, 129.4, 128.9, 128.5, 128.3, 125.9, 125.5, 125.4, 118.8,
14.2, 55.3 ppm. MS (EI, 70 eV): m/z (%) = 311 (14), 207 (100),
2
5
8
-(p-Chlorophenyl)-4-phenylquinoline (3j): Yellow solid (0.039 g,
0% yield); m.p. 104–106 °C. H NMR (400 MHz, CDCl
.21 (dd, J = 8.4 and 0.7 Hz, 1 H), 8.13 (dt, J = 8.7 and 2.0 Hz, 2
1
1
1
1
3
): δ =
32 (4), 73 (94). HRMS (ESI-TOF): calcd. for C22
H
17NO
H), 7.88 (dd, J = 8.4 and 0.7 Hz, 1 H), 7.75 (s, 1 H), 7.71 (td, J =
[
M + H]+ 312.1388; found 312.1392.
1
3
6
.8 and 1.5 Hz, 1 H), 7.54–7.43 (m, 8 H) ppm. C NMR
1
2
-Butyl-4-phenylquinoline (3d): Brown oil (0.020 g, 30% yield). H
(100 MHz, CDCl ): δ = 155.4, 149.3, 148.7, 139.5, 139.0, 138.2,
3
NMR (400 MHz, CDCl
.86 (dd, J = 8.4 and 1.2 Hz, 1 H), 7.67 (td, J = 7.0 and 1.2 Hz, 1
H), 7.55–7.46 (m, 5 H), 7.42 (td, J = 7.0 and 1.2 Hz, 1 H), 7.24 (s,
3
): δ = 8.11 (dd, J = 8.4 and 0.7 Hz, 1 H), 130.7, 129.6, 129.5, 129.0, 128.8, 128.6, 128.5, 126.5, 125.8, 125.6,
118.8 ppm. MS (EI, 70 eV): m/z (%) = 316 (45), 314 (100), 206 (20),
139 (33), 73 (11). HRMS (ESI-TOF): calcd. for C21 14ClN [M +
7
H
+
1
7
H), 3.01 (t, J = 7.3 Hz, 2 H), 1.88–1.80 (m, 2 H), 1.47 (sext, J = H] 316.0893; found 316.0898.
.3 Hz, 2 H), 0.97 (t, J = 7.3 Hz, 3 H) ppm. 13C NMR (100 MHz,
): δ = 162.6, 148.5, 148.4, 138.3, 129.5, 129.2, 129.1, 128.5,
28.2, 125.7, 125.6, 125.3, 121.6, 39.1, 32.2, 22.7, 13.9 ppm. MS
EI, 70 eV): m/z (%) = 261 (2), 219 (100), 178 (5), 108 (8), 73 (14).
General Procedure for the Preparation of Quinolines 4a and 4b: To
a two-necked round-bottomed flask that contained a solution of
CDCl
1
(
3
2a (0.25 mmol) in THF (2 mL) at –78 °C under argon was added
dropwise nBuLi (2.5 m solution in hexane, 0.25 mmol). The reac-
tion mixture was stirred for 15 min, and the appropriate electro-
phile (0.50 mmol) in THF (2 mL) at –78 °C was then added slowly.
The resulting mixture was stirred at room temperature for 2 h. Af-
+
HRMS (ESI-TOF): calcd. for C19H19N [M + H] 262.1596; found
262.1599.
2
-Phenyl-4-(p-tolyl)quinoline (3e): Yellow solid (0.053 g, 72% yield);
1
3
m.p. 100–102 °C. H NMR (400 MHz, CDCl ): δ = 8.23 (d, J = ter this time, the mixture was diluted in ethyl acetate (20 mL), and
8
7
7
.4 Hz, 1 H), 8.17 (d, J = 8.4 Hz, 2 H), 7.90 (d, J = 8.4 Hz, 1 H), the resulting solution was then washed with a saturated aqueous
.77 (s, 1 H), 7.68 (t, J = 8.1 Hz, 1 H), 7.49 (t, J = 7.6 Hz, 2 H),
.44–7.40 (m, 4 H), 7.31 (d, J = 7.6 Hz, 2 H), 2.44 (s, 3 H) ppm.
solution of NH
4
Cl (3ϫ 10 mL). The organic phases were sepa-
rated, and the combined organic extracts were dried with MgSO
4
1
3
3
C NMR (100 MHz, CDCl ): δ = 156.9, 149.3, 148.9, 139.8, 138.3, and concentrated under vacuum. The residue was purified by flash
1
1
1
2
35.6, 130.2, 129.5, 129.4, 129.3, 128.9, 127.6, 126.3, 126.0, 125.8,
chromatography (hexane/acetate, 9:1).
19.3, 21.3 ppm. MS (EI, 70 eV): m/z (%) = 295 (73), 201 (16),
(
4-Chlorophenyl)(2,4-diphenylquinolin-3-yl)methanol (4a): Pale yel-
45 (10), 73 (3). HRMS (ESI-TOF): calcd. for C22
96.1439; found 296.1444.
H
17N [M + H]+
1
low solid (0.080 g, 76% yield); m.p. 198–200 °C. H NMR
400 MHz, CDCl ): δ = 8.18 (d, J = 8.3 Hz, 1 H), 7.72 (td, J = 8.3
(
3
4
-(p-Chlorophenyl)-2-phenylquinoline (3f): Yellow oil (0.054 g, 69% and 1.2 Hz, 1 H), 7.50–7.39 (m, 4 H), 7.35–7.27 (m, 7 H), 7.00 (d,
1
yield). H NMR (400 MHz, CDCl
3
): δ = 8.23 (d, J = 8.4 Hz, 1 H),
J = 8.6 Hz, 2 H), 6.95 (d, J = 8.6 Hz, 1 H), 6.71 (d, J = 7.9 Hz, 2
1
3
8
7
.16 (d, J = 7.3 Hz, 2 H), 7.80 (d, J = 8.4 Hz, 1 H), 7.75 (s, 1 H),
H), 5.98 (d, J = 8.4 Hz, 1 H), 1.61 (s, 1 H) ppm. C NMR
(100 MHz, CDCl ): δ = 160.5, 148.9, 146.7, 142.6, 140.9, 136.1,
1
3
.70 (td, J = 8.4 and 1.2 Hz, 1 H), 7.52–7.42 (m, 8 H) ppm.
): δ = 156.8, 148.8, 147.8, 139.4, 136.8,
34.6, 130.8, 130.2, 129.6, 129.4, 128.8, 127.5, 126.5, 125.5, 125.2,
19.2 ppm. MS (EI, 70 eV): m/z (%) = 316 (6), 281 (23), 207 (100),
C
3
NMR (100 MHz, CDCl
3
132.3, 131.9, 129.9, 129.6, 129.5, 129.4, 128.9, 128.3, 128.2, 128.1,
128.0, 127.7, 126.7, 126.5, 126.3, 71.4 ppm. MS (EI, 70 eV): m/z
(%) = 422 (47), 421 (100), 344 (65), 280 (34), 154 (25). HRMS (ESI-
1
1
1
56 (50), 73 (39). HRMS (ESI-TOF): calcd. for C21
H
14ClN [M +
TOF): calcd. for C28H20ClNO 422.1312; found 422.1315.
+
H] 316.0893; found 316.0899.
2
,4-Diphenyl-3-(trimethylsilyl)quinoline (4b): Pale yellow solid
1
1
4
-Methyl-2-phenylquinoline (3g): Yellow oil (0.033 g, 60% yield). H
(0.065 g, 73% yield); m.p. 160–162 °C. H NMR (400 MHz,
): δ = 8.15 (d, J = 8.4 Hz, 1 H), 7.70–7.56 (m, 4 H), 7.51–
NMR (400 MHz, CDCl
.1 and 0.9 Hz, 1 H), 7.74–7.66 (m, 2 H), 7.56–7.44 (m 4 H), 2.74
s, 3 H) ppm. 13C NMR (100 MHz, CDCl
): δ = 157.0, 148.0, δ = 165.3, 157.6, 146.9, 145.1, 139.7, 131.1, 130.1, 129.8, 129.4,
3
): δ = 8.20–8.12 (m, 3 H), 7.97 (dd, J = CDCl
3
1
3
8
(
7.37 (m, 9 H), –0.36 (s, 9 H) ppm. C NMR (100 MHz, CDCl ):
3
3
Eur. J. Org. Chem. 2015, 5640–5648
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5647

A. L. Stein, A. R. Rosário, G. Zeni
FULL PAPER
1
29.3, 128.4, 128.2, 128.1, 128.0, 126.1, 126.0, 125.8, 2.3 ppm. MS
2004, 69, 3950; c) A. Fürstner, A. Leitner, M. Mendez, H.
Krause, J. Am. Chem. Soc. 2002, 124, 13856; d) A. Fürstner,
A. Leitner, Angew. Chem. Int. Ed. 2002, 41, 609; Angew. Chem.
(
(
EI, 70 eV): m/z (%) = 353 (16), 338 (100), 308 (12), 161 (18), 73
10). HRMS (ESI-TOF): calcd. for C24H23NSi [M + H] 354.1678;
+
2
002, 114, 632.
14] a) O. Bistri, A. Correa, C. Bolm, Angew. Chem. Int. Ed. 2008,
7, 586; Angew. Chem. 2008, 120, 596; b) A. Correa, M. Carril,
C. Bolm, Angew. Chem. Int. Ed. 2008, 47, 2880; Angew. Chem.
found 354.1682.
[
4
Acknowledgments
2
008, 120, 2922; c) A. Correa, C. Bolm, Angew. Chem. Int. Ed.
007, 46, 8862; Angew. Chem. 2007, 119, 9018; d) S. L. Buch-
2
The authors are grateful to Fundação de Amparo à Pesquisa do
Estado do Rio Grande do Sul (FAPERGS), Coordenação de Aper-
feiçoamento de Pessoal de Nível Superior (CAPES), and Conselho
Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for
the financial support. CNPq is also acknowledged for the fellow-
ships to A. R. R., A. L. S., and G. Z.
wald, C. Bolm, Angew. Chem. Int. Ed. 2009, 48, 5586; Angew.
Chem. 2009, 121, 5694.
[15] a) A. O. Abdelwareth, A. A. O. Sarhan, C. Bolm, Chem. Soc.
Rev. 2009, 38, 2730; b) A. Correa, O. G. Mancheno, C. Bolm,
Chem. Soc. Rev. 2008, 37, 1108.
[
16] K. C. Majumdar, N. De, T. Ghosh, B. Roy, Tetrahedron 2014,
0, 4827.
7
[
17] a) C. Bolm, Chem. 2009, 1, 420; b) C. Bolm, J. Legros, J. L.
[
1] a) V. L. Nunes, I. C. de Oliveira, O. S. D. Barros, Eur. J. Org.
Chem. 2014, 1525; b) S. Santoro, B. Battistelli, L. Testaferri,
M. Tiecco, C. Santi, Eur. J. Org. Chem. 2009, 4921; c) M.
Tiecco, L. Testaferri, F. Marini, S. Sternativo, F. Del Verme, C.
Santi, L. Bagnoli, A. Temperini, Tetrahedron 2008, 64, 3337;
d) C. Santi, S. Santoro, L. Testaferri, M. Tiecco, Synlett 2008,
Paih, L. Zani, Chem. Rev. 2004, 104, 6217.
[18] a) A. A. Joshi, C. L. Vishwanathan, Bioorg. Med. Chem. Lett.
2006, 16, 2613; b) C. Portela, C. M. M. Afonso, M. M. Pinta,
M. J. Ramos, Bioorg. Med. Chem. 2004, 12, 3313; c) S. W. El-
more, M. J. Coghlan, D. D. Anderson, J. K. Pratt, B. E. Green,
A. X. Wang, M. A. Stashko, C. W. Lin, C. M. Tyree, J. N.
Miner, P. B. Jacobson, D. M. Wilcox, B. C. Lane, J. Med.
Chem. 2001, 44, 4481; d) O. Billker, V. Lindo, M. Panico, A. E.
Etienne, T. Paxton, A. Dell, M. Rogers, R. E. Sinden, H. R.
Morris, Nature 1998, 392, 289; e) W. Peczynskaczoch, F. Pog-
nan, L. Kaczmarek, J. Boratynski, J. Med. Chem. 1994, 37,
3503.
[19] a) Y. K. Kumar, G. R. Kumar, T. J. Reddy, B. Sridhar, M. S.
Reddy, Org. Lett. 2015, 17, 2226; b) F. Couty, G. Evano, Synlett
2009, 3053; c) B. Gabriele, R. Mancuso, E. Lupinacci, R.
Spina, G. Salerno, L. Veltri, A. Dibenedetto, Tetrahedron 2009,
65, 8507; d) A. K. Verma, T. Kesharwani, J. Singh, V. Tandon,
R. C. Larock, Angew. Chem. Int. Ed. 2009, 48, 1138; Angew.
Chem. 2009, 121, 1158; e) B. Gabriele, R. Mancuso, G. Salerno,
E. Lupinacci, G. Ruffolo, M. Costa, J. Org. Chem. 2008, 73,
4971; f) R. Halim, P. J. Scammells, B. L. Flynn, Org. Lett. 2008,
10, 1967; g) M. J. Sandelier, P. DeShong, Org. Lett. 2007, 9,
3209; h) B. Jiang, Y.-G. Si, J. Org. Chem. 2002, 67, 9449.
[20] a) R. Halim, L. Aurelio, P. J. Scammells, B. L. Flynn, J. Org.
Chem. 2013, 78, 4708; b) A. C. Mantovani, T. A. C. Goulart,
D. F. Back, P. H. Menezes, G. Zeni, J. Org. Chem. 2014, 79,
10526; c) M. S. Reddy, N. Thirupathi, Y. K. Kumar, RSC Adv.
2012, 2, 3986; d) S. Ali, H.-T. Zhu, X.-F. Xia, K.-G. Ji, Y.-F.
Yang, X.-R. Song, Y.-M. Liang, Org. Lett. 2011, 13, 2598; e)
Z. Huo, I. D. Gridnev, Y. Yamamoto, J. Org. Chem. 2010, 75,
1266; f) K. O. Hessian, B. L. Flynn, Org. Lett. 2006, 8, 243; g)
X. Zhang, M. A. Campo, T. Yao, R. C. Larock, Org. Lett.
2005, 7, 763; h) X. Zhang, T. Yao, M. A. Campo, R. C. Larock,
Tetrahedron 2005, 66, 1177.
1471; e) C. Santi, S. Santoro, B. Battistelli, L. Testaferri, M.
Tiecco, Eur. J. Org. Chem. 2008, 5387.
[
[
2] C. Santi, S. Santoro, in: Organoselenium Chemistry: Synthesis
and Reactions (Ed.: T. Wirth), Wiley-VCH Verlag GmbH &
Co. KGaA, Weinheim, Germany, 2011, p. 1–51.
3] a) A. Ogawa, I. Ogawa, R. Obayashi, K. Umezu, M. Doi, T.
Hirao, J. Org. Chem. 1999, 64, 86; b) A. Ogawa, M. Doi, I.
Ogawa, T. Hirao, Angew. Chem. Int. Ed. 1999, 38, 2027; Angew.
Chem. 1999, 111, 2066.
[4] C. C. Silveira, A. L. Braga, A. S. Vieira, G. Zeni, J. Org. Chem.
2003, 68, 662.
[5] a) H. J. Reich, S. K. Shah, J. Am. Chem. Soc. 1975, 97, 3250;
b) D. Seebach, A. K. Beck, Angew. Chem. Int. Ed. Engl. 1974,
1
3, 806; Angew. Chem. 1974, 86, 859; c) D. Seebach, N. Peleties,
Chem. Ber. 1972, 105, 511.
[6] M. Sevrin, W. Dumont, L. Hevesi, A. Krief, Tetrahedron Lett.
1976, 30, 2647.
[
[
7] T. Mitamura, A. Ogawa, Org. Lett. 2009, 11, 2045.
8] G. Zeni, R. B. Panatieri, E. Lissner, P. H. Menezes, A. L.
Braga, H. A. Stefani, Org. Lett. 2001, 3, 819.
[
[
9] C. W. Nogueira, J. B. T. Rocha, Arch. Toxicol. 2011, 85, 1313.
10] D. G. Hilmey, M. Abe, M. I. Nelen, C. E. Stilts, G. A. Baker,
S. N. Baker, F. V. Bright, S. R. Davies, S. O. Gollnick, A. R.
Oseroff, S. L. Gibson, J. Med. Chem. 2002, 45, 449.
[
11] A. P. Pesarico, G. Sartori, C. F. A. dos Santos, J. S. S. Neto, V.
Bortolotto, R. C. V. Santos, C. W. Nogueira, M. Prigol, Micro-
biol. Res. 2013, 168, 563.
[
12] a) Z.-J. Yang, B.-L. Hu, C.-L. Deng, X.-G. Zhang, Adv. Synth.
Catal. 2014, 356, 1962; b) A. L. Stein, F. N. Bilheri, D. F. Back,
G. Zeni, Adv. Synth. Catal. 2014, 356, 501; c) A. Sperança, B.
Godoi, G. Zeni, J. Org. Chem. 2013, 78, 1630; d) A. Sperança,
B. Godoi, S. Pinton, D. F. Back, P. H. Menezes, G. Zeni, J.
Org. Chem. 2011, 76, 6789; e) L. Yu, L. Ren, R. Yi, Y. Wu, T.
Chen, R. Guo, J. Organomet. Chem. 2011, 696, 2228; f) H.-A.
Du, R.-Y. Tang, C.-L. Deng, Y. Liu, J.-H. Li, X.-G. Zhang,
Adv. Synth. Catal. 2011, 353, 2739; g) R. M. Gay, F. Manarin,
C. C. Schneider, D. A. Barancelli, M. D. Costa, G. Zeni, J. Org.
Chem. 2010, 75, 5701.
[21] The (2-aminoaryl)-2-ynols 1 were synthesized according to the
literature. For details, see: B. Gabriele, R. Mancuso, G. Sa-
lerno, G. Ruffolo, P. Plastina, J. Org. Chem. 2007, 72, 6873.
[22] W. J. E. Parr, J. Chem. Soc. Perkin Trans. 1 1981, 1, 3002.
[23] I. D. Entwistle, R. A. W. Johnstone, J. H. Varle, J. Chem. Soc.,
Chem. Commun. 1976, 61.
[24] G. Perin, E. J. Lenardão, R. G. Jacob, R. B. Panatieri, Chem.
Rev. 2009, 109, 1277.
[25] S. Dumouchel, F. Mongin, F. Trecourt, G. Queguiner, Tetrahe-
dron 2003, 59, 8629.
[
13] a) A. Fürstner, A. Schlecker, C. W. Lehmann, Chem. Commun.
Received: June 10, 2015
2007, 4277; b) G. Seidel, D. Laurich, A. Fürstner, J. Org. Chem.
Published Online: July 30, 2015
5648
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 5640–5648