Synthesis of aryl-substituted quinoline derivatives via bronsted acid-catalyzed [4+2] aza Diels-Alder reaction

Article abstract of DOI:10.1246/cl.2004.922

CF₃SO₃H-catalyzed [4+2] aza Diels-Alder reaction of aldimines with silyl enol ethers, and subsequent in situ oxidation furnished quinoline derivatives in good to excellent yields, wherein use of CF ₃SO₃H as a Br

Full text of DOI:10.1246/cl.2004.922

922
Chemistry Letters Vol.33, No.7 (2004)
Synthesis of Aryl-substituted Quinoline Derivatives via
Brꢀnsted Acid-catalyzed [4+2] Aza Diels–Alder Reaction
Takahiko Akiyama,Ã Saeko Nakashima, Koji Yokota, and Kohei Fuchibe
Department of Chemistry, Gakushuin University, Mejiro, Toshima-ku, Tokyo 171-8588
(Received April 27, 2004; CL-040483)
Table 1. Effect of Brꢀnsted acida
CF3SO3H-catalyzed [4+2] aza Diels–Alder reaction of aldi-
mines with silyl enol ethers, and subsequent in situ oxidation fur-
nished quinoline derivatives in good to excellent yields, wherein
use of CF3SO3H as a Brꢀnsted acid is critical for the cyclization
reaction.
Brꢀnsted
acid
Yield of
3/%
Yield of
4/%
Yield of
5/%
Entry
b
1
2
3
4
5
6
7
8
HBF4
HBF4 OEt2
88
90
39
89
70
25
0
0
0
0
0
0
0
0
0
12
20
69
.
CF3CO2H
CSA
0
The aza Diels–Alder reaction of N-aryl aldimine with elec-
tron-rich alkene provides useful method for the preparation of
quinoline and tetrahydroquinoline derivatives,1 which are pre-
c
HPF6
FSO3H
11
51
53
26
d
HClO4
CF3SO3H
cursors of the nitrogen containing natural products. A number
4
of Lewis acid catalysts such as InCl3,2 BiCl3,3 BF3 OEt2,
0
.
Yb(OTf)3,5 LiClO4,6 as well as Brꢀnsted acid catalysts such as
CF3CO2H,7 TsOH,8 PPh3HClO4,9 CF3CH2OH,10 and photo-
chemical conditions11 have been developed for the aza Diels–Al-
der reaction.
aAldimine 1 (1.0 equiv.) and silyl enol ether 2 (1.5 equiv.)
were treated with Brꢀnsted acid (10 mol %) in CH3CN at
room temperature. b50% aq solution, c60% aq solution.
d70% aq solution.
We already reported that Brꢀnsted acid catalyzed the Man-
nich-type reaction of silyl enolates with aldimines to give ꢀ-ami-
no carbonyl compounds in excellent yields.12,13 For example,
treatment of aldimine 1 with silyl enol ether 2 in the presence
of aq HBF4 (10 mol %) in CH3CN furnished ꢀ-amino ketone 3
in a high yield. In the course of the reaction, we have found that
use of CF3SO3H in place of HBF4 dramatically changed the re-
action course; aza Diels–Alder reaction took place smoothly to
afford a mixture of tetrahydroquinoline 4 and quinoline 5.14,15
We wish to report herein intriguing effect of the Brꢀnsted acid
on the cyclization reaction and its application to one-pot synthe-
sis of quinoline derivatives.
Table 2. Effect of solventa
Yield of
3/%
Yield of
4/%
Yield of
5/%
Entry
Solvent
1
2
3
4
5
CH2Cl2
Et2O
CH3CN
CH3CN-H2Ob
i-PrOH
0
62
0
87
96
11
7
26
0
69
21
69
0
0
0
aAldimine 1 (1.0 equiv.) and silyl enol ether 2 (1.5 equiv.)
were treated with CF3SO3H (10 mol %) at room temperature.
b1.5 molar equivalent of H2O based on imine was added.
ArNH
O
OMe
cat.
solvent afforded a mixture of 4 and 5,16 whereas protic solvent
furnished 3 exclusively.
Ph
Ph
HBF4
N
3
Above results are summarized as follows; i) use of stronger
Brꢀnsted acid gave cycloadducts 4 and 5 preferentially, ii) use of
protic solvent furnished Mannich adduct 3, iii) addition of excess
amount of water gave 3. Effects of the Brꢀnsted acid and solvent
are explained as follows; Brꢀnsted acid-catalyzed addition of sil-
yl enolate 2 with imine 1 generates an intermediate 6 (Figure 1).
The nucleophilic attack of some nucleophile in the medium on
the silicon atom would give 3, whereas intramolecular addition
of enamine to the oxonium ion furnishes 4. When weaker
Brꢀnsted acid was used, corresponding conjugate base would at-
cat.
Ph
OMe
+
1
+
OMe
CF3SO3H
HN
Ph
OTMS
Ph
N
Ph
Ph
Ph
OTMS
4
5
2
In the first place, we studied the effect of Brꢀnsted acid in
the reaction of 1 and 2 in CH3CN and the results are shown in
Table 1. Aqueous HBF4 afforded ꢀ-amino ketone 3 exclusively
(Entry 1). In order to elucidate the effect of H2O present, anhy-
.
drous HBF4 OEt2 was employed but 3 was obtained exclusively
OMe
(Entry 2). Anhydrous camphor sulfonic acid gave 3 in a high
yield (Entry 4). Use of aq HPF6 resulted in the formation of
the mixture of 3 and 4 (Entry 5). Interestingly, use of HClO4
or CF3SO3H suppressed the formation of 3, and gave 4 and 5
in good combined yields (Entries 7, 8).
H
N
Ph
Ph
O
TMS
6
X
Next, effect of the solvent was examined by use of 10 mol %
of CF3SO3H as a Brꢀnsted acid catalyst (Table 2). Use of aprotic
Figure 1.
Copyright ꢀ 2004 The Chemical Society of Japan

Chemistry Letters Vol.33, No.7 (2004)
923
57, 6099 (2001).
tack the silicon atom to give 3. In contrast, conjugate base of
stronger Brꢀnsted acid is less nucleophilic and the attack on
the silicon atom is suppressed. Water also acted as a nucleophile
toward silicon atom, thus interrupting the formation of 4.17
Next, one-pot synthesis of quinoline derivative was exam-
ined. Although oxidizing agents such as DDQ, I2, and CAN were
not effective, Mn(OAc)3 turned out to be effective for the syn-
thesis of quinoline derivatives. Treatment of aldimine and silyl
enol ether (2.0 equiv.) with CF3SO3H (10 mol %) in CH3CN at
room temperature for 3 h, and subsequent oxidation of the mix-
ture with Mn(OAc)3 (2.0 equiv.) in AcOH at room temperature
overnight furnished numerous kinds of quinoline derivatives in
good to excellent yields (Figure 2).18
2
3
G. Babu and P. T. Perumal, Tetrahedron Lett., 39, 3225 (1998).
H. Laurent-Robert, B. Garrigues, and J. Dubac, Synlett, 2000,
1160.
´
B. Crousse, J.-P. Begue, and D. Bonnet-Delpon, Tetrahedron
Lett., 39, 5765 (1998).
a) S. Kobayashi, H. Ishitani, and S. Nagayama, Chem. Lett.,
1995, 423. b) Y. Makioka, T. Shindo, Y. Taniguchi, K. Takaki,
and Y. Fujiwara, Synthesis, 1995, 801. c) Y. Ma, C. Qian,
M. Xie, and J. Sun, J. Org. Chem., 64, 6462 (1999). d) D.
Cheng, J. Zhou, E. Saiah, and G. Beaton, Org. Lett., 4, 4411
(2002).
J. S. Yadav, B. V. S. Reddy, C. V. Rao, and R. Srinivas,
Synlett, 2002, 993.
P. A. Grieco and A. Bahsas, Tetrahedron Lett., 29, 5855
(1988).
Y. Nomura, M. Kimura, Y. Takeuchi, and S. Tomoda, Chem.
Lett., 1978, 267.
R. Nagarajan, S. Chitra, and P. T. Perumal, Tetrahedron, 57,
3419 (2001).
4
5
6
7
8
9
OTMS
1) CF3SO3H
2) Mn(OAc)3
N
N
Ar2
R
Ar2
+
R
Ar1
Ar1
2
1
10 M. V. Spanedda, V. D. Hoang, B. Crousse, D. Bonnet-Delpon,
and J.-P. Begue, Tetrahedron Lett., 44, 217 (2003).
11 W. Zhang, X. Jia, L. Yang, and Z.-L. Liu, Tetrahedron Lett.,
43, 9433 (2002).
12 T. Akiyama, J. Takaya, and H. Kagoshima, Synlett, 1999,
1045; T. Akiyama, J. Takaya, and H. Kagoshima, Tetrahedron
Lett., 42, 4025 (2001); T. Akiyama, J. Takaya, and H.
Kagoshima, Adv. Synth. Catal., 344, 338 (2002); T. Akiyama,
J. Itoh, and K. Fuchibe, Synlett, 2002, 1269; T. Akiyama, J.
Itoh, K. Yokota, and K. Fuchibe, Angew. Chem., Int. Ed., 43,
1566 (2004).
13 For the Brꢀnsted acid-catalyzed aza Diels–Alder reaction, see;
T. Akiyama, J. Takaya, and H. Kagoshima, Tetrahedron Lett.,
40, 7831 (1999).
14 Lewis acid promoted aza Diels-Alder reaction of N-aryl
aldimine and silyl enol ether has been reported. See, Ref. 5b.
15 For recent examples of the preparation of quinolines, K. Sangu,
K. Fuchibe, and T. Akiyama, Org. Lett., 6, 353 (2004); B. R.
McNaughton and B. L. Miller, Org. Lett., 5, 4257 (2003),
and references cited therein.
Me
OMe
N
N
N
Ph
Ph
Ph
Ph
Ph
Ph
Ph
100%
93%
90%
Cl
MeO
N
N
N
Ph
Ph
Ph
Ph
Me
96%
N
90%
85%
N
Ph
Ph
16 The structure of 5 was determined by comparison of the
1H NMR spectra with the literature data.19
Cl
OMe
94%
17 pKa values of Brꢀnsted acids follow; HBF4 (À0:44),20 HClO4
88%
N
(À10).21
OMe
OMe
18 Typical experimental procedure (2,4-diphenylquinoline), To a
solution of benzylideneaniline (40.2 mg, 0.222 mmol) and ꢁ-
trimethylsiloxystyrene (88 mL, 0.444 mmol) in CH3CN
(1 mL) was added a CH3CN solution of CF3SO3H (98 mL,
0.021 mmol) (0.226 mol/L solution of CF3SO3H in CH3CN)
at room temperature. After being stirred at the temperature
N
Ph
71%
Ph
Me
O2N
.
80%
for 3 h, Mn(OAc)3 2H2O (120.1 mg, 0.448 mmol) and AcOH
(3 mL) were added. The mixture was stirred at the temperature
for 24 h. After removing the solid by filtration over Celite, the
filtrate was neutralized by addition of sat. NaHCO3 solution.
The filtrate was extracted with CH2Cl2 and the combined
extracts were washed with sat. NaHCO3 solution and brine.
Removing the solvent in vacuo gave crude material. Purifica-
tion of the crude material with p-TLC (hexane:ethyl acetate
= 7:1/v:v) furnished 2,4-diphenylquinoline (62.4 mg, 0.221
mmol) in a quantitative yield.
Figure 2. One-pot synthesis of quinolines.
In conclusion, we have found an intriguing effect of the
Brꢀnsted acid leading to quinoline derivative by [4+2] cycload-
dition reaction of silyl enol ether and aldimines. Subsequent
Mn(OAc)3 mediated oxidation in one pot conditions furnished
quinoline derivatives in good to excellent yields.
References and Notes
19 T. Nishio and Y. Omote, J. Chem. Soc., Perkin Trans. 1, 1983,
1773.
20 T. N. Sudakova and V. V. Krasnoshchekov, Zh. Neorg. Khim.,
23, 1506 (1978).
21 W. N. White, T. Vogelmann, M. Morse, and H. S. White,
J. Org. Chem., 42, 162 (1977).
1
D. L. Boger, S. M. Weinreb, ‘‘Hetero Diels-Alder Methodolo-
gy in Organic Synthesis,’’ Academic, San Diego (1987),
Chap. 2 and 9; S. M. Weinreb, in ‘‘Heterodienophile Additions
to Dienes,’’ ed. by B. M. Trost and I. Fleming, Oxford (1991)
Vol. 5, p 401; P. Buonora, J.-C. Olsen, and T. Oh, Tetrahedron,
Published on the web (Advance View) June 21, 2004; DOI 10.1246/cl.2004.922