A concise synthesis of quinolinium, and biquinolinium salts and biquinolines from benzylic azides and alkenes promoted by copper(II) species

Article abstract of DOI:10.1039/c6ra11840b

A novel copper-promoted multiple aza-[4 + 2] cycloaddition reaction of N-methyleneanilines in situ generated from benzylic azide and alkenes afforded quinolinium salts, biquinolinium salts, biquinolines or substituted quinolines depending on the substitution on the phenyl ring of benzylic azide. The reaction of para substituted benzylic azides and 2 equivalents of alkenes afforded the corresponding substituted quinolinium salts, while benzylic azides without a para substituent provided biquinolinium salts. The copper-promoted cycloaddition reaction also allows biquinoline products to be obtained from ortho-substituted benzylic azides. These reactions work well with both terminal and internal alkenes. Unsymmetrical internal alkene reactions proceed with high regioselectivity. The reaction is likely started by Lewis acidic Cu^II-assisted rearrangement of benzylic azide to N-methyleneaniline, followed by a [4 + 2] cycloaddition with alkene. Detailed mechanistic studies suggest that the biquinoline and biquinolinium salts are likely formed via radical processes.

Full text of DOI:10.1039/c6ra11840b

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DOI: 10.1039/C6RA11840B
RSC Advances
ARTICLE
A Concise Synthesis of Quinolinium, and Biquinolinium Salts and
Biquinolines from Benzylic Azides and Alkenes Promoted by
Copper(II) Species
Received 00th January 20xx,
Accepted 00th January 20xx
Wei-Chen Chen, Parthasarathy Gandeepan, Chia-Hung Tsai, Ching-Zong Luo, Pachaiyappan
Rajamalli and Chien-Hong Cheng*
DOI: 10.1039/x0xx00000x
www.rsc.org/
A novel copper-promoted multiple aza-[4 + 2] cycloaddition reaction of N-methyleneanilines in situ generated from benzylic
azide and alkenes afforded quinolinium salts, biquinolinium salts, biquinolines or substituted quinolines depending on the
substitution on the phenyl ring of benzylic azide. The reaction of para substituted benzylic azides and 2 equivalents of
alkenes afforded the corresponding substituted quinolinium salts, while benzylic azides without a para substituent provided
biquinolinium salts. The copper-promoted cycloaddition reaction also allows to get biquinoline products from ortho-
substituted benzylic azides. These reactions work well with both terminal and internal alkenes. Unsymmetrical internal
II
alkenes proceed with high regioselectivity. The reaction likely started by Lewis acidic Cu -assisted rearrangement of benzylic
azide to N-methyleneaniline, followed by a [4 + 2] cycloaddition with alkene. Detailed mechanistic studies suggest that the
biquinoline and biquinolinium salts are likely formed via radical processes.
straightforward route to the diversely substituted quinolinium
salts.9
Introduction
In this manuscript, we report a convenient method to access
Lewis acid (LA) mediated aza-[4 + 2] cycloaddition reaction of
-azadiene and electron rich alkenes is an important tool to
highly substituted quinolinium salts from benzyl azides and
2
II
alkenes via a Cu -promoted double aza-[4 + 2] cycloaddition
1
construct nitrogen heterocycles. In particular, the Povarov
reactions (Scheme 1).
2
reaction (PR) a [4 + 2] cycloaddition of N-arylimines and
alkenes is a known effective method for the synthesis of
tetrahydroquinolines (THQs), which can be easily transformed
3
to quinolines by dehydrogenation. Generally, Povarov reaction
is performed using either a protic or Lewis acid as the catalyst
and a N-arylimine as azadiene, and electron-rich alkenes, such as
cyclic and acyclic enol ethers, enamides, enamines, and
4
conjugated dienes as a dienophile. Recently, arylmethyl azide
was also shown to be a suitable substrate to undergo [4 + 2]
5
annulation with alkene to afford THQs. In addition to neutral
nitrogen heterocycles, the synthesis of cationic N-heterocycles
also received great attention owing to the various biological
6
activities and materials applications. In particular, applications
of quinolinium salts in biological studies demands new synthetic
methods for the synthesis of a wide range of substituted
7
quinolinium salts. A well-known method to these compounds
8
involves the reaction of quinolines with alkyl halides. However,
the method is limited by the availability of substrates. Our
continuing interest in the synthesis of N-heterocyclic salts has
encouraged us to tackle this problem and to develop a
II
Scheme 1 Cu -Promoted multiple aza-[4 + 2] cycloaddition reactions.
Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan.
E-mail: chcheng@mx.nthu.edu.tw; Fax: +886-3-5724698; Tel: +886-3-5721454.
Results and discussion
The reaction of 4-methylbenzyl azide (1a) and styrene (2a) in the
presence of Cu(II) salt gave dihydro-1H-pyridoquinolinium salt
†
Electronic Supplementary Information (ESI) available: General experimental
1 13
procedures, characterization details and H and C NMR spectra of new
compounds. CCDC 1434531-1434533. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/x0xx00000x.
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3aa), which possesses an unusual fused tricyclic structure (eq 1) cycloaddition reaction to give 3ad in 61% yield. Trea ent of β-
tmAr
DOI: 10.1039/C6RA11840B
consisting of one p-toluidine, two styrene and two methylene methylstyrene (2e) with 1a gave the expected quinolinium salt
units. In order to optimize the reaction, we performed a series of 3ae in 69% yield. Interestingly, the reaction of allylbenzene (2f
studies by varying the oxidant, solvent, the ratio of the substrates
)
and the reaction temperature and time. After an extensive
screening, we found that treatment of 1a (0.64 mmol), 2a (0.32
mmol), CuSO
mmol) in CH
aa in 89% isolated yield and the reaction condition was denoted
4
(1.12 mmol), NaBF
4
2
(0.20 mmol), and H O (2.22
3
NO (3 mL) at 100 C for 24 h gave the product
2
3
as condition A (see Supporting Information, Table S1 for the
detailed optimization studies). In view of the excess amount of
copper(II) salt used in condition A, we try to reduce the amount
of copper salt by using various inorganic and organic oxidants
along with catalytic amount of CuSO
to give 3aa (see Table S2). The results of this screening reveal
that by using (NH as the oxidant, CuSO can be reduced
4
in the reaction of 1a and
2
a
4
)
2
S
2
O
8
4
to a catalytic amount of 0.08 mmol, a decrease of 14 times
compared to that of condition A. As a result, treatment of 1a
(
(
(
0.64 mmol), 2a (0.32 mmol), CuSO
4
(0.08 mmol), (NH
4
)
2
S
2
O
8
0.4 mmol), NaBF (0.2 mmol), and H
4
2
O (2.22 mmol) in MeNO
2
3 mL) at 100 C for 24 h afford 3aa in 77% isolated yield. This
optimized catalytic condition is referred as condition B. We also
examined the effect of different metal salt on the product yield
III
II
III
under reaction condition B; among the Fe -, Fe -, and In -salts
tested, none of them is as active as CuSO .(Table S3).
4
Next, we probe the scope of the copper promoted double aza-
4+2] cycloaddition reaction to form quinolinium salts. Various
[
substituted benzyl azides (1a-i) were treated with styrene 2a
under both conditions A and B and their results are shown in
Scheme 2. Thus, the reaction of p-iPr, p-OMe, p-Ph, p-Cl, p-F
substituted benzyl azides (1a-f) with 2a afforded the expected
quinolinium salts 3ba-fa in good yields. 3,4-Disubstituted
benzyl azide 1g was also effectively transformed into the
respective quinolinium salt 3ga in 65% yield. The reaction of
ortho substituted benzyl azide 1h gave a single [4 + 2]
cycloaddition product, quinoline 3ha’, presumably due to the
presence of the ortho methyl group in 1h that prevents a second Scheme 2 Scope of benzyl azides in quinolinium salts formation. a Condition A: azide 1
(
0.64 mmol), styrene 2a (0.32 mmol), CuSO
2.22 mmol) in MeNO
(3 mL) at 100 C for 24 h. b Condition B: azide 1 (0.64 mmol),
(0.08 mmol), NaBF (0.2 mmol), (NH (0.4 mmol),
(3 mL) at 100 C for 24 h. c Isolated yields are calculated
4 4 2
(1.12 mmol), NaBF (0.20 mmol), and H O
[
4 + 2] cycloaddition to give a quinolinium salt. Benzyl azide (1i)
(
2
containing a methyl substituent at the benzylic position failed to
undergo the expected [4 + 2] cycloaddition product (product
styrene 2a (0.32 mmol), CuSO
4
4
4 2 2 8
) S O
and H O (2.22 mmol) in MeNO
2
2
3
ia). Similarly, the benzylic azides containing strong electron based on 3a, 0.16 mmol, as the upper limit (100%).
withdrawing groups such as p-CF
3 2
, p-NO , p-CN were
ineffective under the reaction conditions.
with 1a gave quinolinium salt 3af’ in 74% yield with elimination
The copper-catalyzed synthesis of quinolinium salts from benzyl
azides were effective with different alkenes (Scheme 3). Thus the
reaction of 4-Me-, and 4-Br substituted styrenes afforded
products 3ab and 3ac in good yields. In addition to vinyl arenes,
simple alkyl alkene 2d also effective in the double aza-
of a benzyl group at the quinoline ring. The structure of 3af’ was
confirmed by X-ray structure analysis.10 Similarly, -
methylstyrene (2g) reacted with 1a to give 3ag’ with the
elimination of a methyl group.
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(
1
(
(
0.4 mmol), and H
a (0.64 mmol), alkene 2 (0.32 mmol), CuSO
2.22 mmol) in MeNO
0.16 mmol) as the limiting reagent.
2
O (2.22 mmol) in MeNO
2
(3 mL) at 100 C for 24 h. b Condition A: azide
(1.12 mmol), NaBF (0.2 mmol), and H O
4 4 2
Interestingly, treatment of benzyl azide (1j) with 2a under
conditions A and B gave the biquinolinium salt product 4ja in
View Article Online
DOI: 10.1039/C6RA11840B
(3 mL) at 100 C for 24 h. c Isolated yields are given based on 2a
2
5
% yield (eq 2) instead of 3ja. The structure of 4ja was
unambiguously confirmed by X-ray structure analysis.10 To
different alkenes with 2a (Scheme 4). 4-Bromostyrene (2c
)
effectively underwent multiple cycloadditions to give 4jc in 69%
yield. Luckily, hept-1-ene (2d) also gave biquinolinium cation in
50% yield. However, the reaction of other alkenes 2f-g with
benzyl azide (1j) resulted in inseparable complex mixtures.
Interestingly, the reaction of ortho substituted benzylic azide
such as 2-methylbenzyl azide (1k) and styrene (2a) afforded 6,6'-
biquinolinyl derivative 5ka in 80% yield (Scheme 5). The
structure was confirmed by its H and 13C NMR, HRMS, and
single crystal X-ray analysis.10 Similarly, 2-bromobenzylic azide
1
(
1l) gave product 5la in 20% yield. Other vinylic substrates 2c
and 2d reacted effectively with 1k to give products 5kc and 5kd
in 74 and 53% yields, respectively. The reaction also proceeded
smoothly with β-methyl styrene (2e) giving 5ke in 54% yield.
On the other hand, the use of allylbenzene (2f) as olefin substrate
for the reaction with 1k, afforded product 5kf’ instead of 5kf in
improve the yield of 4ja, we conducted a series of optimization
studies and found that treatment of 1j (0.64 mmol), 2a (0.32
mmol), and Cu(BF ) ·6H O (0.80 mmol) in CH NO at 100 C
4 2 2 3 2
for 24 h offered 4ja in 70% isolated yield (see Table S4). With
the optimized conditions in hand, we tested the reaction of
66% yield. The benzyl group in 2f was cleaved during this
copper-promoted reaction, similar to the reaction of 1a with 2f
to give product 3af’ (Scheme 3).
Scheme 4 Scope of alkenes in the synthesis of biquinolinium salts. a Reaction conditions:
benzylic azide 1 (0.64 mmol), alkene 2 (0.32 mmol), and Cu(BF
MeNO
(3 mL) at 100 C for 24 h. b Isolated yields calculated based on alkene (0.16 mmol)
as the limit.
4 2 2
) ·6H O (0.80 mmol) in
2
To understand the mechanism of this multiple aza-[4 + 2]
cycloaddition reaction, several controlled experiments were
performed as shown in Scheme 6. The reaction of 1a and 2a
under reaction condition A, but with an extra addition of 1
Scheme 3 Scope of alkenes in the quinolinium salts formation. a Condition B: azide 1a
equivalent
of
radical
scavenger
2,2,6,6-
(
0.64 mmol), alkene 2 (0.32 mmol), CuSO
4
(0.08 mmol), NaBF
4
(0.2 mmol), (NH
4
)
2
S
2
O
8
tetramethylpiperidinyloxy (TEMPO), is blocked nearly
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completely affording 3aa in less than 10% yield. Next, we used showed 50% deuterium incorporation at the two ad cent
leja
DOI: 10.1039/C6RA11840B
pre-formed 4-methyl-N-methyleneaniline (1A) with 2a under the carbons connected to the quinoline nitrogen atom. The result
reaction conditions to give 3aa in 25% yield. The result indicates suggests that both N-carbons of 3aa are from the CH group of
1a. In addition, two molecules of 1a are required for the
formation of a molecule of 3aa. Next, we treated 4-phenyl-
,2,3,4-tetrahydroquinoline (1B) with formaldehyde and styrene
2
that N-aryl imine is a possible intermediate in situ formed from
1
II
(
2a) in the presence of Cu -salt to give product 4ja in 87% yield.
Similarly, treatment of 1B in the presence of Cu(BF ·6H
gave 6,6’-biquinoline derivative 5B in 45% yield along with 17%
-phenylquinoline (1C). Finally, we treated 1C with styrene and
formaldehyde under the reaction conditions and neither dimer
4
)
2
2
O
4
product
(
Schemes 4 and 5
)
nor quinolinium product (Schemes 2
and 3) was observed.
Scheme 5 Synthesis of substituted biquinolines. a Reaction conditions: benzylic azide 1
(
0.64 mmol), alkene 2 (0.32 mmol), and Cu(BF
00 C for 24 h. b Isolated yields calculated based on alkene (0.16 mmol) as limiting
reagent.
4 2 2 2
) ·6H O (0.80 mmol) in MeNO (3 mL) at
1
benzylic azides under the reaction conditions. Furthermore, we Scheme 6 Mechanistic studies.
conducted the reaction of D1-1a with 2a and the product
2
D -3aa
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Based on the mechanistic studies and known literature a reaction using 4-methyl benzyl azide (1a) and ally enzene (2f)
lbie
DOI: 10.1039/C6RA11840B
plausible mechanism for the multiple aza-[4 + 2] cycloaddition is proposed as shown in Scheme 7. It is expected that
Scheme 7 Plausible Reaction Mechanism for the Synthesis of Quinolinium Cations.
Scheme 8 Possible Reaction Mechanism for the Formation of Biquinolinium Cations.
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4
-methyl-N-methyleneaniline (
I
) is formed in situ from benzylic
View Article Online
DOI: 10.1039/C6RA11840B
azide.5,11 A dual [4 + 2] cycloaddition of in situ formed imine
intermediate with alkene 2f affords julolidine derivative VI 4,12,13
.
1
.0
.8
Copper-mediated multiple single electron transfer (SET)
oxidation process offers the final quinolinium cation. During the
aromatization process of julolidine VI, a benzyl group instead of
a hydrogen is eliminated. The cationic product 3ag is stabilized
by the non-nucleophilic anion BF
important for the present reaction. Because the cascade reaction
involves a second aza-[4 + 2] cycloaddtion of imine cation
with alkene, the formation of this imine cation needs one
molecule of HCHO, which is generated from the reaction of N-
2
methyleneaniline I with H O.
3aa
ja
3aa
ja
4
0.2
4
0
.6,14 The presence of H
0.6
4
2
O is
0
.1
.0
0
.4
.2
V
0
0
0.0
A possible pathway for the formation of 6,6’-biquinolinium
cation is depicted in Scheme 8. It follows similar steps shown in
Scheme 7 up to the formation of 1,2,3,4-tetrahydro quinoline
derivative IV’. Then oxidative dimerization of IV’ to give dimer
300
400
500
Wavelength, nm
Figure 1. The absorption and emission spectra of compounds 3aa and 4ja at a
concentration of 1  10-5 m in CH
Cl .
2 2
II
IX’ likely proceeds via a series of Cu induced SET processes,
nucleophilic addition, deprotonation and protonation.15 Further
condensation of IX’ with formaldehyde released from the CuII-
catalyzed decomposition of benzyl azide give di-iminium ions
X’. Again, aza-cycloaddition reaction with 2a offers XI’. CuII-
Conclusions
In summary, we have successfully demonstrated a copper
promoted multiple aza-[4 + 2] cycloaddition reactions between
benzylic azides and alkenes. Three different types of products
including quinolinium cations, biquinolinium cations, and
biquinolines are formed from para-substituted, unsubstituted,
and ortho-substituted benzylic azides, respectively. A wide range
of functional groups on the benzylic azides can be tolerated.
Moreover, high regioselectivity can be achieved with
unsymmetrical alkenes. The reaction mechanism involves a
Lewis acidic copper promoted rearrangement of benzylic azide
to N-arylimine, followed by aza-[4 + 2] cycloaddition with
alkene to provide 1,2,3,4-tetrahydroquinoline product, which
further undergoes condensation with formaldehyde followed by
another [4 + 2] cycloaddition with alkene to give the julolidine
derivative. The mechanistic studies suggest that the oxidation of
oxidation via a SET process in the presence of stabilizing BF
anion provides the final product 4ja. While the ortho substituted
benzylic azides gave 6,6’-biquinoline product (Scheme 5) from
4
5
II
intermediate IX’ through Cu -oxidation (Scheme 7).
The new quinolinium and biquinolinium salts exhibit strong
photoluminescence properties. A preliminary studies were
performed using 3aa and 4ja to understand the fluorescence
properties in solution. As shown in Figure 1, the quinolinium
salts 3aa and 4ja showed blue emissions. In addition, the
fluorescence intensity of these compounds is very high
prompting us to determine their fluorescence quantum yields
(
Ф
f
)
using 9,10-diphenylanthracene as the reference.16
Surprisingly, Ф of >99% for 3aa and 80% for 4ja were observed
f
in dichloromethane solution. It is worth to mention that this type
of fluorescent molecules highly useful in nonlinear optical
1,2,3,4-tetrahydroquinoline to aromatic quinoline moiety goes
(
NLO) applications, fluorescent stains for biological studies,
through a copper mediated SET process. However, further
detailed mechanistic studies are needed to elucidate the exact
reaction mechanism, which is ongoing in our laboratory.
particle size analysis and chemosensors.7,17 Moreover, these
compounds also can be potential candidates as dopants for
efficient solution-process organic light emitting diodes
(
OLEDs).18
Experimental section
General information
Unless otherwise stated, all reactions were performed under a
nitrogen atmosphere on a dual-manifold Schlenk line and in
oven-dried glassware. All reagents were purchased
commercially and used without further purification. Reagent
grade nitromethane was used as such from Alfa Aesar without
further purification. NMR spectra ( H and 13C) were measured
on a Bruker Avance III 400 MHz spectrometer. High resolution
1
(
HR) mass data were measured with a JEOL JMS-700
spectrometer. Infrared spectra were recorded on a HORIBA FT-
IR 720 using KBr plates. UV-visible absorption and
Fluorescence spectra were measured using Hitachi U-3300
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spectrophotometer and Hitachi F-7000 spectrophotometer, General procedure for the synthesis of substituted
DOI: 10.1039/C6RA11840B
respectively.
biquinolines 5
A sealed tube containing Cu(BF
4
)
2
.6H
2
O (276 mg, 0.80 mmol)
General procedure for the synthesis of substituted benzylic
azides5b
was dissolved in MeNO
substituted benzyl azide
and additional MeNO
2
(2 mL) under nitrogen gas. Then, ortho-
(0.64 mmol), alkene (0.32 mmol)
(1 mL) were added to the system via
1
2
Substituted benzyl bromide (1.0 equiv) and sodium azide (1.5
equiv) were dissolved in DMF (2.0 mL/mmol) and stirred at
room temperature for overnight. At the end of the reaction, the
mixture was diluted with water and extracted with diethyl ether.
2
syringe sequentially. The reaction was allowed to stir at 100 °C
for 24 h. When the reaction was completed, the mixture was
diluted with CH
and washed several times with CH
2
Cl
2
(10 mL) and filtered through a Celite pad
Cl (50 mL). The combined
4
The combined organic solution was dried over MgSO and
2
2
concentrated in vacuo and the crude product was purified by a
silica gel column (n-hexane/EtOAc, 90:10) to afford the
substituted benzyl azide.
filtrate was concentrated in vacuo and the residue was purified
by column chromatography on a silica gel column using n-
hexane/ethyl acetate (95:5) as eluent to afford the desired pure
product 5.
General procedure for the synthesis of quinolinium salts 3
Condition A: A sealed tube that contained CuSO
mmol) and NaBF (24 mg, 0.2 mmol) was evacuated and purged
with nitrogen gas three times. MeNO (2.0 mL) was then added
to the tube, and the suspension was stirred for 2 min at ambient
temperature. Then, para-substituted benzylic azide (0.64
mmol), alkene (0.32 mmol), H O (40 L, 2.22 mmol), and
additional MeNO (1 mL) were added to the system via syringe
sequentially. The reaction was stirred at 100°C for 24 h. At the
end of the reaction, the mixture was diluted with CH Cl (10
mL), filtered through a Celite pad, and washed three times with
CH Cl (3  20 mL). The combined filtrate was concentrated in
4
(178 mg, 1.12
4
Acknowledgements
We thank the Ministry of Science and Technology of the
Republic of China (MOST-104-2633-M-007-001) for support of
this research.
2
1
2
2
2
Notes and references
2
2
1
D. L. Boger and S. M. Weinreb, Hetero Diels-Alder
Methodology in Organic Syntheses, ed. H. H. Wasserman,
Academic Press, New York, 1987.
2
2
vacuo and the mixture was purified by a silica gel column using
DCM/MeOH (95:5) as eluent to afford the desired pure product
2
3
S. Kobayashi and K. A. Jørgensen, Cycloaddition Reactions in
Organic Synthesis, Wiley-VCH: Weinheim, Germany, 2002.
(a) F. Shi, G.-J. Xing, Z.-L. Tao, S.-W. Luo, S.-J. Tu and L.-Z.
Gong, J. Org. Chem. 2012, 77, 6970; (b) A. Bunescu, Q. Wang
and J. Zhu, Org. Lett. 2014, 16, 1756; (c) L. R. Domingo, M.
3
.
Condition B: A sealed tube that contained CuSO
mmol), NaBF (24 mg, 0.20 mmol) and (NH
mmol) was evacuated and purged with nitrogen gas three times.
MeNO (2.0 mL) was then added to the tube, and the suspension
was stirred for 2 min at ambient temperature. Then, para-
4
(13 mg, 0.080
4
) S O (92 mg, 0.40
4 2 2 8
J. Aurell, J. A. Sáez and S. M. Mekelleche, RSC Adv. 2014,
5268.
For selected examples, see: (a) N. Shindoh, H. Tokuyama, Y.
Takemoto and K. Takasu, J. Org. Chem. 2008, 73, 7451; (b)
M.-G. Shen, C. Cai and W.-B. Yi, J. Heterocycl. Chem. 2009,
4,
2
2
4
substituted benzylic azide
1
(0.64 mmol), alkene
2
(0.32 mmol),
4
6
, 796; (c) P. Gandeepan, P. Rajamalli and C.-H. Cheng,
Asian J. Org. Chem. 2014, , 303; (d) J. B. Simões, Â. De
Fátima, A. A. Sabino, L. C. Almeida Barbosa and S. A.
Fernandes, RSC Adv. 2014, , 18612.
(a) J. Tummatorn, P. Poonsilp, P. Nimnual, J. Janprasit, C.
Thongsornkleeb and S. Ruchirawat, J. Org. Chem. 2015, 80
H
2
O (40 L, 2.22 mmol) and additional MeNO
2
(1 mL) were
3
added to the system via syringe sequentially. The reaction was
stirred at 100°C for 24 h. At the end of the reaction, the mixture
4
5
6
was diluted with CH
and washed three times with CH
2
Cl
2
(10 mL), filtered through a Celite pad,
Cl (3  20 mL). The combined
,
2
2
4
516; (b), C.-Z. Luo, P. Gandeepan, Y.-C. Wu, W.-C. Chen
filtrate was concentrated in vacuo and the mixture was purified
by a silica gel column using DCM/MeOH (95:5) as eluent to
and C.-H. Cheng, RSC Adv. 2015, 5, 106012; (c) K. Suman, L.
Srinu and S. Thennarasu, Org. Lett., 2014, 16, 3732.
afford the desired pure product
3
.
a) J. Jayakumar, K. Parthasarathy and C.-H. Cheng, Angew.
Chem. Int. Ed. 2012, 51, 197; (b) C.-Z. Luo, P. Gandeepan, J.
Jayakumar, K. Parthasarathy, Y.-W. Chang and C.-H. Cheng,
Chem. Eur. J. 2013, 19, 14181; (c) K. Muralirajan and C.-H.
Cheng, Chem. Eur. J. 2013, 19, 6198; (d) C.-Z. Luo, P.
Gandeepan and C.-H. Cheng, Chem. Commun. 2013, 49, 8528;
(e) N. Senthilkumar, P. Gandeepan, J. Jayakumar and C.-H.
Cheng, Chem. Commun. 2014, 50, 3106; (g) C.-Z. Luo, J.
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General procedure for the synthesis of biquinolinium salts 4
A sealed tube containing Cu(BF ·6H O (276 mg, 0.80 mmol)
was dissolved in MeNO (2 mL) under nitrogen gas. Then,
unsubstituted benzylic azide (0.64 mmol), alkene (0.32
mmol) and additional MeNO (1 mL) were added to the system
via syringe sequentially. The reaction was allowed to stir at 100
C for 24 h. When the reaction was completed, the mixture was
diluted with CH Cl (10 mL) and filtered through a Celite pad
and washed several times with CH Cl (50 mL). The combined
4
)
2
2
2
1
2
2
°
7
For applications of quinolinium slats, see: (a) B. M. Gutsulyak,
Russ. Chem. Rev. 1972, 41, 187; (b) I. I. Sidorchuk, R. F.
Stadniichuk, E. I. Tishchenko and L. T. Bordyakovskaya,
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2
2
2
2
filtrate was concentrated in vacuo and the residue was purified
by column chromatography on a silica gel column using
DCM/MeOH (95:5) as eluent to afford the desired pure product
4
.
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Please Rd So Cn oA tda vd aj un sc te ms argins
Page 8 of 9
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View Article Online
DOI: 10.1039/C6RA11840B
Graphical Abstract:
A Concise Synthesis of Quinolinium, and Biquinolinium Salts and
Biquinolines from Benzylic Azides and Alkenes Promoted by
Copper(II) Species
Wei-Chen Chen, Parthasarathy Gandeepan, Chia-Hung Tsai, Ching-Zong Luo, Pachaiyappan
Rajamalli and Chien-Hong Cheng*
A copper promoted multiple aza-[4 + 2] cycloaddition reactions between benzylic azides and
alkenes are described. Four different products including quinolinium and biquinolinium
cations, and biquinolines and quinolines can be formed depending on the substituents on the
benzylic azides.