Cinchona-derived ammonium salts-catalyzed aza Diels-Alder reaction of Danishefsky's diene with imines

Article abstract of DOI:10.1016/j.tet.2010.12.002

Described is the efficiency of cinchona-derived quaternary ammonium salts as Lewis acid organocatalysts in aza Diels-Alder reaction of Danishefsky's diene 1 with imines 2 and 16, providing 1,2-dialkyl-2,3-dihydro-4-pyridinones 3 and cyclic dihydropyridone

Full text of DOI:10.1016/j.tet.2010.12.002

Tetrahedron 67 (2011) 1166e1170
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Cinchona-derived ammonium salts-catalyzed aza DielseAlder reaction of
Danishefsky’s diene with imines
,
Yohan Park a, Eunyoung Park a, Hyojun Jung a, Yeon-Ju Lee b, Sang-sup Jewa, Hyeung-geun Park a
*
a College of Pharmacy, Seoul National University, Seoul 151-742, Korea
b Marine Natural Products Chemistry Laboratory, Korea Ocean Research and Development Institute, Ansan 426-744, Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 October 2010
Received in revised form 1 December 2010
Accepted 2 December 2010
Available online 9 December 2010
Described is the efficiency of cinchona-derived quaternary ammonium salts as Lewis acid organo-
catalysts in aza DielseAlder reaction of Danishefsky’s diene 1 with imines 2 and 16, providing 1,2-di-
alkyl-2,3-dihydro-4-pyridinones 3 and cyclic dihydropyridones 17, respectively. Among the nine of
cinchonidine-derived quaternary ammonium catalysts prepared, N-20,30,40-trifluorobenzyl-O-benzylcin-
chonidinum bromide (6) exhibited the highest chemical yield (up to 99%). Systematic study on struc-
ture-catalytic efficiency relationship revealed that 20,30,40-trifluorobenzyl, quinuclidine, and quinoline
moieties are essential.
Keywords:
Cinchona ammonium catalyst
Aza DielseAlder reaction
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
under CH3CN at room temperature in the presence of tetrabutyl
ammonium salts as facile quaternary ammonium salts to optimize
Since the late of 19700s, lots of cinchona-derived catalysts have
been developed as practical catalysts and utilized in various useful
chemical reactions.1 Among them, cinchona-derived quaternary
ammonium salts, diversely modified by N-alkylation of cinchona
alkaloids, have successfully been applied to phase-transfer cata-
lytic reactions.2 During the last decade, we also have developed
polymeric or hydrogen bonding inducible functional group in-
corporated cinchona-derived quaternary ammonium catalysts and
successfully applied them to various useful synthetic reactions.3 In
continuation of our studies on broadening the scope of reactions
and the usefulness of cinchona-derived catalysts, we attempted to
apply them to the aza DielseAlder reaction of Danishefsky’s diene
1 with imines 2, which is the most powerful methodology for the
construction of nitrogen-containing six membered ring com-
pounds.4 Recent advances in these reactions have been made by
a number of Lewis acid-catalyzed versions in organic solvents or
aqueous media, including asymmetric versions using chiral cata-
lysts.5 In this article, we report a new synthetic method of the aza
DielseAlder reaction in the presence of cinchona-derived ammo-
nium salts as Lewis acid organocatalysts.
the reaction conditions of solvents and the counter anions of the
ammonium catalysts.
As shown in Table 1, only 10% of the cyclized product 3a was
obtained with no catalyst, which was in accordance with previous
results (entry 1).5j Interestingly, the chemical yields were quite
variable depending on the counter anions of the n-tetrabutyl
ammonium salts. TBAF, expected to facilitate the reaction by the
removal of the TMS group of 1, did not afford 3a (entry 2), but rather
unidentified products. The same results were obtained with other
solvents (H2O, THF; data are not shown). However, there was
a significant increase of chemical yield (entry 2e4) by changing of
the counter anion from fluoride to iodide, and TBAI exhibited the
best chemical yield (entry 4, 92%). It was speculated that a softer
counter anion could be more easily displaced by imine 2a to form
an activated transition state, which could give higher chemical
yields. The polarity of the solvents was also important (entry 4e7).
The more polar solvents showed the higher chemical yields (entry
4, CH3CN 92%; entry 7, CH2Cl2 22%), but aqueous solvents afforded
lower chemical yields than aprotic polar solvents (entry 5, H2O 80%;
entry 6, H2O/CH2Cl2 (1:1) 39%), which was in accordance with
previous results.6
2. Results and discussion
The reaction was monitored by 1H NMR for the determination of
the reaction mechanism, and it revealed that there was a Mannich
addition intermediate in addition to the further cyclized final
product 3a. After quenching the reaction mixture with 1.0 M HCl
during the work-up process, only the aza DielseAlder type cyclized
product 3a could be isolated. Based on these NMR studies,
this reaction seemed to be gone through the Mannich type
As a preliminary study, we performed the aza DielseAlder re-
action of Danishefsky’s diene 1 with N-benzylideneaniline (2a)
* Corresponding author. Tel.: þ82 2 880 8264; fax: þ82 2 880 9129; e-mail
address: hgpk@snu.ac.kr (H.-g. Park).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.12.002

Y. Park et al. / Tetrahedron 67 (2011) 1166e1170
1167
Table 1
Table 2
Optimization with the n-tetrabutyl ammoniums salts
Aza DielseAlder reaction with quaternary ammonium salts
OMe
Ph
OMe
R4N+X- (10 mol %)
Solvent, r.t.
Ph
Ph
Ph
N
N
catalyst (10 mol %)
N
+
+
O
Ph
solvent, r.t.
Ph
TMSO
TMSO
2a
1
1
2a
3a
OMe
+
Entry
Catalyst
Solvent
Time(h)
Yielda(%)
N+R4
Ph
Ph
Ph
N
N
1
2
3
4
5
6
7
8
4
5
6
6
6
7
8
9
10
11
12
13
14
15
MeCN
MeCN
MeCN
H2O
8
8
3
3
4.5
24
72
24
5
24
24
24
24
72
97
98
99
83
93
72
d
TMS
O
Ph
O
3a
CH2Cl2
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
Entry
Catalyst
Solvent
Time(h)
Yielda(%)
1
2
3
4
5
6
7
d
MeCN
MeCN
MeCN
MeCN
H2O
72
72
24
24
24
24
72
10
d
14
85
64
29
36
58
10
TBAF
TBAB
TBAI
TBAI
TBAI
TBAI
9
23
92
80
39
22
10
11
12
13
14
H2O/CH2Cl2 (1:1)
CH2Cl2
a
Isolated yield after acidic work-up.
a
Isolated yield after acidic work-up.
intermediate via the transition state by the chelation of the N-lone
pair on imine 2a with an ammonium cation (Table 1).
responsible for high chemical yield, non-cinchona type ammonium
salts (Fig. 2, 13e158) were prepared and evaluated for their catalytic
efficiency. N-20,30,40-trifluorobenzyl-N-tri-n-butylquternary am-
monium bromide (13, 36%) gave 1.6 times higher efficiency than
that of n-tetrabutyl ammonium bromide (TBAB, 23%), and even
higher catalytic efficiency was observed with N-20,30,40-tri-
fluorobenzylquinuclidine ammonium bromide (14, 58%). The
higher efficiency of 6 over that of 14 may indicate that the quinoline
ring contributes to form a more rigid conformation of the transition
Next we examined cinchonidinum quaternary ammonium salts.
Aza DielseAlder reaction of Danishefsky’s diene 1 with N-benzyli-
deneaniline (2a) was performed in the presence of various cin-
chonidinum quaternary ammonium salts (10 mol %) (Fig. 1, 46e12)
under CH3CN at room temperature. As shown in Table 2, the
chemical yields were quite variable depending on the structure of
the catalysts. A significant increase of chemical yield resulted from
the change of the counter anion from fluoride to bromide, which is
similar to the preliminary results (Table 1).7 The solvent also greatly
affected the chemical yields (entry 3e5) as well. Notably, the
chemical yields were dramatically dependent on the functional
groups on the N-benzyl group. The electron withdrawing group
(entry 3, 2,3,4-F3 99%; entry 10, 4-F 85%) yielded a higher chemical
yield than that of the electron donating group (entry 10, 4-Me 64%;
entry 11, 4-MeO 29%). Very high chemical yields were observed
with catalysts 4e6 and catalyst 6 (entry 3, 99%) exhibited the best
yield with a lower reaction time. To confirm the electronic effect
of the 2,3,4-F3 group and what part of the cinchonidine moiety is
state by a pep stacking interaction. Steric hindrance might lead to
lower chemical yields (13, 36%; 14, 58%; 15, 10%). The cumulative
results revealed that 20,30,40-trifluorobenzyl, quinuclidine, and
quinoline moieties play integral roles for the catalytic efficiency of 6.
F
F
+
N
Br-
F
F
F
F
N
Br
13
Br-
Br-
N+
O
Br-
N+
O
N+
OH
5
F
F
F
Br-
F
F
F
N
N+
N
F
F
F
F
N
N
4
6
F
F
F
F
F
15
Br-
F-
Cl-
N+
O
N+
O
N+
O
14
F
F
Fig. 2. Non-Cinchona-derived ammonium catalysts.
F
F
F
F
N
N
7
8
9
Catalyst 6 was chosen for further investigation for scope and
limitation in aza DielseAlder reaction of Danishefsky’s diene with
various trans-imines. As shown in Table 3, very high chemical yields
(80e99%) were observed. Much to our disappointment, no enan-
tioselectivity (<5% ee) was observed in 3. The low affinity of cin-
chona-derived catalysts with imines in the transition state is not
effective enough for the induction of enantioselectivity.
Br-
Br-
Br-
N+
O
N+
O
N+
O
F
Me
OMe
N
N
N
10
11
12
The substrate scope was extended to cyclic arylimines. Aza
DielseAlder reaction of 1 with 3,4-dihydroisoquinoline (16a9)in the
Fig. 1. Cinchona-derived ammonium catalysts.

1168
Y. Park et al. / Tetrahedron 67 (2011) 1166e1170
Table 3
(3). Catalyst 6 showed the highest chemical yield (up to 99%). Al-
Scope of imine substrates in aza DielseAlder reaction
though the reaction did not exhibit enantioselectivity, catalyst 6
successfully applied to the synthesis of polycyclicdihydropyridones
via aza DielseAlder reaction of 1 with cyclic imines, which can be
applied to the synthesis of biologically active aza polycyclic natural
products.
Br-
N+
F
OBn
OMe
F
F
R1
R2
N
R1
N
6 (10 mol %)
N
+
4. Experimental
4.1. General
O
R2
TMSO
CH3CN, r.t.
1
2
3
Entry
R1
R2
Time(h)
Yielda(%)
Infrared (IR) spectra were recorded on a JASCO FT/IR-300E
and PerkineElmer 1710 FT spectrometer. Nuclear magnetic res-
onance (1H NMR and 13C NMR) spectra were measured on
a JEOL JNM-LA 300 [300 MHz (1H), 75 MHz (13C)] spectrometer
and JEOL JNM-GSX 400 [400 MHz (1H), 100 MHz (13C)] spec-
trometer, using CHCl3-d or DMSO-d as a solvent, and were
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
4-CH3OPh
4-BrePh
Ph
Ph
Ph
Ph
Ph
Ph
3
5
8
8
5
5
5
3
4
8
99
99
98
97
99
99
95
99
99
80
4-CH3OPh
4-BrePh
4-NO2ePh
2-Furyl
2-Pyridyl
PheCH]CH
c-C6H11
reported in parts per million relative to CHCl3-d (
DMSO-d6
2.50) for 1H NMR and relative to the CHCl3-d (
77.23) or DMSO-d6 (d
39.50) resonance for 13C NMR. Coupling
d 7.24) or
(
d
d
10
Ph
constants (J) in 1H NMR are in Hz. Low-resolution mass spectra
(MS) were recorded on a VG Trio-2 GCeMS spectrometer. High-
resolution mass spectra (HRMS) were measured on a JEOL JMS-
AX 505wA, JEOL JMS-HX/HX 110A spectrometer. Melting points
a
Isolated yield after acidic work-up.
presence of catalyst 6 afforded dihydropyridone 17a10 in 50% yield
€
were measured on a Buchi B-540 melting point apparatus. For
(Scheme 1). In addition, 4,9-dihydro-3H-b
-carboline (16b11) pro-
thin layer chromatography (TLC) analysis, a Merck precoated TLC
plate (silica gel 60 GF254, 0.25 mm) was used. For column
chromatography, a Merck Kieselgel 60 (70e230 mesh) was used.
vided the corresponding dihydropyridone 17b12 in 54% yield. In our
knowledge, it was the first application to construct polycyc-
licdihydropyridone system by aza DielseAlder reaction. The dihy-
dropyridones 17a and 17b are essential skeleton of tetrabenazine13a
and tangutorine,13b respectively.
4.2. General procedure for ammonium salts-catalyzed aza
DieleAlder reaction in acetonitrile
Danishfsky’s diene (1) (90 mL) was added to N-benzylidienea-
OMe
N
N
niline (2a) (54 mg) with ammonium catalyst (10 mol %) in anhy-
drous acetonitrile (1 mL) and stirred at room temperature for 3 h.
The reaction mixture was quenched with 1.0 M HCl and diluted
with dichloromethane and (10 mL), washed with brine (2ꢀ10 mL),
dried over anhydrous MgSO4, filtered, and concentrated in vacuo.
The residue was purified by column chromatography (silica gel,
hexanes/EtOAc¼4:1) to afford 1,2-diphenyl-2,3-dihydro-4-pyr-
idinone (3a) as a yellow solid. Spectral data of 3 and 17 were con-
sistent with literature values.5g,10,12
Cat. 6 (10 mol %)
+
O
CH3CN, r.t.
4 h, 50%
TMSO
17a
1
16a
N
O
H
OCH3
OCH3
Tetrabenazine
4.2.1. 1,6,7,11b-Tetrahydro-pyrido[2,1-
NMR (300 MHz, CHCl3-d)
4.74 (dd, J1¼16.1 Hz, J2¼4.3 Hz, 1H), 3.65e3.59 (m, 1H), 3.43 (tꢀd,
J1¼12.0 Hz, J2¼3.1 Hz, 1H), 3.14 (tꢀd, J1¼15.9 Hz, J2¼5.1 Hz, 1H),
2.86e2.79 (m, 2H), 2.59e2.46 (m, 1H) ppm; 13C NMR (100 MHz,
a
]isoquinolin-2-one (17a10). 1H
7.28e7.14 (m, 5H), 5.06 (d, J¼7.5 Hz, 1H),
d
OMe
N
N
Cat. 6 (10 mol %)
+
O
CH3CN, r.t.
6 h, 54%
HN
HN
17b
TMSO
CHCl3-d)
d 192.7, 154.1, 134.9, 133.3, 129.0, 127.1, 127.0, 125.6, 98.5,
1
16b
56.6, 49.7, 43.9, 30.3 ppm.
HO
4.2.2. 6,7,12,12b-Tetrahydro-1H-indolo[2,3-
NMR (300 MHz, CHCl3-d)
a
]quinolizin-2-one (17b12). 1H
9.15 (s, 1H), 7.48 (d, J¼7.5 Hz, 1H), 7.38
H
N
d
H
(d, J¼8.0 Hz, 1H), 7.23e7.08 (m, 3H), 5.08 (d, J¼7.3 Hz, 1H), 4.83 (br
d, J¼14.4 Hz, 1H), 3.70 (dd, J1¼11.9 Hz, J2¼4.5 Hz, 1H), 3.49 (tꢀd,
J1¼11.9 Hz, J2¼4.2 Hz, 1H), 3.02e2.97 (m, 2H), 2.96e2.89 (m, 1H),
H
N
Tangutorine
H
2.59 (dd, J1¼15.7 Hz, J2¼15.7 Hz,1H) ppm; 13C NMR (100 MHz, CHCl3-d)
d
Scheme 1. Cyclic imines (16) in aza DielseAlder reaction.
192.5, 155.0, 136.7, 131.5, 126.4, 122.3, 119.7, 118.1, 111.5, 107.8, 98.2,
54.0, 50.9, 41.6, 22.1 ppm.
4.3. General procedure for anion exchange of cinchonidinium
catalyst7b
3. Conclusion
Cinchona-derived ammonium catalysts were prepared and ap-
plied to aza DielseAlder reaction of Danishefsky’s diene 1 with
various imines (2), providing 1,2-dialkyl-2,3-dihydro-4-pyridinones
After 1.0 M HF was added to amberlyst-A26 (OHꢁ) in a column,
the resin was rinsed with water three times for neutralization. 95%
aqueous EtOH and benzene was added and then it was dried at

Y. Park et al. / Tetrahedron 67 (2011) 1166e1170
1169
40 ꢂC in a vacuum oven (4 h). When the amberlyst-A26 (Fꢁ) was
generated and it was packed in the column, the catalyst 6 (100 mg)
was loaded and spilled by MeOH in the column. After evaporation
of the gained mixtures, the brown caramel was afforded (99%). In
the MS (FABꢁ) analysis, the peak of Brꢁ (79) disappeared and the Fꢁ
peak (19) appeared. For the chloride anion exchange, the same
procedure was used with 1.0 M HCl, a yellow solid was obtained,
and in MS (FABꢁ) analysis, the peak of Brꢁ (79) was disappeared
and the Clꢁ peak (35) was appeared.
1508, 1311, 1240, 1128, 1068, 818, 754 cmꢁ1; mp 155 ꢂC; HRMS (FAB)
calculated for [C37H36F3N2O]þ: 581.2780, found: 581.2789.
4.6.2. Catalyst 10. 1H NMR (400 MHz, DMSO-d6)
d
9.04 (d, J¼4.4 Hz,
1H), 8.30 (d, J¼8.3 Hz, 1H), 8.17 (d, J¼8.24 Hz, 1H), 7.90e7.86
(m, 1H), 7.82e7.79 (m, 2H), 7.73e7.71 (m, 2H), 7.58e7.54 (m, 2H),
7.48e7.37 (m, 5H), 6.52 (s, 1H), 5.10e5.02 (m, 1H), 4.89e4.86 (m,
2H), 4.60e4.52 (m, 1H) 3.99e3.94 (m, 2H), 3.40e3.38 (m, 1H),
3.29e3.16 (m, 2H), 2.35e2.28 (m, 1H), 1.98e1.91 (m, 2H), 1.76e1.70
(m, 2H), 1.53e1.47 (m, 1H), 1.27e1.07 (m, 2H), 0.70 (t, J¼7.2 Hz,
4.4. Representative procedure of N-benzylation to
hydrocinchonidine: catalyst 5
3H) ppm; 13C NMR (100 MHz, DMSO-d6)
d 150.2, 148.1, 141.1, 137.0,
136.2, 136.1, 129.9, 129.6, 128.6, 128.3, 128.1, 127.5, 125.2, 124.1,
123.6, 119.8, 116.0, 115.7, 70.2, 67.7, 62.3, 61.0, 50.7, 34.8, 25.1, 24.6,
23.7, 20.4, 11.1 ppm; IR (KBr) 3400, 2925, 1603, 1512, 1460, 1230,
1065, 843, 754 cmꢁ1; mp 148 ꢂC; HRMS (FAB) calculated for
[C33H36FN2O]þ: 495.2812, found: 495.2820.
Hydrocinchonidine (3.0 g, 10.1 mmol) with 20,30,40-trifluoro-
benzyl bromide (2.5 g, 11.1 mmol) in dichloromethane was stirred
at room temperature for 4 h. After evaporating dichloromethane,
the reaction mixture was columned by dichloromethane and
methanol in a 40:1 mixture. After column chromatography, the
solid was diluted with methanol (50 mL) and then added to ether
(400 mL) dropwise with stirring. The precipitated solid was filtered
and washed with ether (600 mL). The desired product was 4.8 g
(91% yield) as a light yellow solid. Spectral data were consistent
with literature values.3d
4.6.3. Catalyst 11. 1H NMR (400 MHz, DMSO-d6)
d
9.04 (d, J¼4.4 Hz,
1H), 8.28 (d, J¼8.2 Hz, 1H), 8.17 (d, J¼8.1 Hz, 1H), 7.90e7.87 (m, 1H),
7.81e7.78 (m, 2H), 7.58e7.53 (m, 2H), 7.50e7.40 (m, 5H), 7.38e7.36
(m, 2H), 6.51 (s, 1H), 4.99e4.93 (m, 1H), 4.84e4.69 (m, 2H), 4.57
(d, J¼11.1 Hz, 1H), 3.99e3.91 (m, 2H), 3.27e3.13 (m, 2H), 2.39
(s, 3H), 2.31e2.23 (m, 1H), 1.97e1.91 (m, 3H), 1.75e1.67 (m, 2H),
1.51e1.45 (m, 1H), 1.25e1.06 (m, 2H), 0.71 (t, J¼7.3 Hz, 3H) ppm; 13
C
4.5. Representative procedure of O-benzylation to
hydrocinchonidinium: catalyst 6
NMR (100 MHz, DMSO-d6) d 150.3, 148.1, 141.2, 139.9, 137.0, 133.6,
129.9, 129.7, 129.5, 129.1, 128.7, 128.4, 128.2, 127.5, 125.2, 124.6,
123.6, 119.9, 70.3, 67.6, 63.2, 61.1, 50.7, 34.8, 25.2, 24.7, 23.8, 20.9,
20.5, 11.2 ppm; IR (KBr) 3396, 2925, 1736, 1603, 1512, 1458, 1375,
1240, 1122, 1065, 816, 752 cmꢁ1; mp 145 ꢂC; HRMS (FAB) calculated
for [C34H39N2O]þ: 491.3062, found: 491.3056.
To a suspension of N-(20,30,40-Trifluoro)benzylhydro-cinchoni-
dinium bromide (1.0 g, 1.92 mmol) in dichloromethane (4 mL) was
added benzyl bromide (0.25 mL, 2.11 mmol) and 50% aqueous KOH
(0.65 mL, 5.76 mmol). The resulting mixture was stirred vigorously
at room temperature for 4 h, during, which time all of solids dis-
solved. The mixturewas diluted withwater (3mL) andwasextracted
with dichloromethane (3ꢀ10 mL). The combined organic extracts
were dried over MgSO4, filtered, and concentrated in vacuo. The
residue was purified by column chromatography (silica gel, CH2Cl2/
MeOH¼40:1) and diluted with methanol (20 mL), which was added
to ether (200 mL) by dropwise with stirring. The precipitated solid
was filtered and washed with ether (600 mL). The desired product
was afforded (1.06 g, 90% yield) as a light yellow solid. 1H NMR
4.6.4. Catalyst 12. 1H NMR (400 MHz, DMSO-d6)
d
9.04 (d, J¼4.4 Hz,
1H), 8.27 (d, J¼8.3 Hz, 1H), 8.17 (d, J¼8.2 Hz, 1H), 7.91e7.87 (m, 1H),
7.82e7.78 (m, 2H), 7.58e7.44 (m, 5H), 7.40e7.37 (m, 1H), 7.34e7.20
(m, 2H), 7.12 (d, J¼8.6 Hz, 2H), 6.50 (s, 1H), 5.04e5.01 (m, 1H),
4.88e4.84 (m, 1H), 4.81e4.75 (m, 1H), 4.56 (d, J¼11.1 Hz, 1H),
4.01e3.93 (m, 2H), 3.84 (s, 3H), 3.15e3.12 (m,1H), 2.30e2.26 (m,1H),
1.97e1.90 (m, 2H), 1.75e1.67 (m, 3H), 1.51e1.45 (m, 1H), 1.28e1.08
(m, 2H), 0.69 (t, J¼7.3 Hz, 3H) ppm; 13C NMR (100 MHz, DMSO- d6)
d
160.5,150.3,148.1,141.2,137.0,135.1,129.9,129.6,128.7,128.4,128.2,
(300 MHz, DMSO-d6)
d
9.05 (d, J¼4.5 Hz, 1H), 8.33 (d, J¼8.2 Hz, 1H),
128.0,127.5,125.2,123.5,119.9,119.3,114.3, 70.3, 67.4, 62.9, 60.9, 55.3,
50.5, 34.8, 25.2, 24.6, 23.8, 20.5, 11.2 ppm; IR (KBr) 3398, 2925, 1606,
1512, 1458, 1254, 1028, 827, 752 cmꢁ1; mp 143 ꢂC; HRMS (FAB) cal-
culated for [C34H39N2O2]þ: 507.3012, found: 507.3012.
8.18 (d, J¼8.4 Hz, 1H), 7.92e7.70 (m, 4H), 7.64e7.36 (m, 5H), 6.55 (s,
1H), 5.29 (d, J¼12.9 Hz,1H), 4.96 (d, J¼13.2 Hz,1H), 4.85 (d, J¼10.7Hz,
1H), 4.53(d, J¼10.8 Hz, 1H), 4.12e4.08 (m, 1H), 3.97e3.93 (m, 1H),
3.43e3.36 (m, 2H), 3.26e3.22 (m, 1H), 2.28e2.26 (m, 1H), 1.95 (s,
2H), 1.73e1.65 (m, 2H), 1.47e1.43 (m, 1H), 1.25e1.06 (m, 3H), 0.71 (t,
4.6.5. Catalyst 13. 1H NMR (300 MHz, DMSO-d6)
4.63 (s, 2H), 3.33e3.12 (m, 6H), 1.71 (m, 6H), 1.35e1.24 (m, 6H),
0.96e0.92 (m, 9H) ppm; 13C NMR (75 MHz, CHCl3-d)
153.9, 151.5,
d 7.54e7.46 (m, 2H),
J¼7.2Hz, 3H)ppm; 13CNMR (75MHz, DMSO-d6)
d150.2,148.0,140.8,
136.9,130.5,129.8,129.6,129.0,128.5,128.2,128.1,127.5,125.1,124.1,
119.9, 113.6, 113.5, 113.4, 113.1, 70.4, 67.3, 64.8, 61.1, 56.0, 51.0, 35.1,
25.2, 24.8, 23.5, 20.7, 11.1 ppm; IR (KBr) 3402, 2929,1622,1510,1311,
1240, 1128, 1066, 818, 754, 698 cmꢁ1; mp 152 ꢂC; HRMS (FAB) cal-
culated for [C33H34F3N2O]þ: 531.2623, found: 531.2616.
d
150.1, 141.1, 138.6, 129.7, 113.62, 113.59, 113.44, 113.41, 113.00, 112.96,
112.90, 59.5, 56.8, 30.1, 24.6,19.7,13.5 ppm; IR (KBr) 3755, 3460, 2962,
1626, 1510, 1383, 1309, 1163, 1065, 870, 750 cmꢁ1; mp 120 ꢂC; HRMS
(FAB) calculated for [C19H31F3N]þ: 330.2409, found: 330.2399.
4.6. Spectroscopic characterization of the ammonium
catalysts
4.6.6. Catalyst 14. 1H NMR (300 MHz, CHCl3-d)
7.14e7.05 (m, 1H), 5.07 (s, 2H), 3.78 (t, J¼7.8 Hz, 6H), 2.23e2.19 (m,
1H), 2.03e1.97 (m, 6H) ppm; 13C NMR (75 MHz, CHCl3-d)
153.8,
152.2, 151.3, 149.6, 141.1, 138.6, 129.7, 113.4, 113.2, 112.5, 59.3, 54.4,
23.9, 19.5 ppm; IR (KBr) 3408, 2949, 1626, 1506, 1389, 1309, 1255,
1167, 1072, 1009, 960, 831, 756, 681 cmꢁ1; mp 291 ꢂC; HRMS (FAB)
calculated for [C14H17F3N]þ: 256.1313, found: 256.1324.
d 7.94e7.86 (m, 1H),
d
4.6.1. Catalyst 7. 1H NMR (300 MHz, DMSO-d6)
d
9.08 (d, J¼4.4 Hz,
1H), 8.45 (d, J¼8.0 Hz, 1H), 8.18 (d, J¼8.4 Hz, 1H), 8.05e7.91 (m, 4H),
7.88e7.74 (m, 4H), 7.71e7.68 (m,1H), 7.59e7.56 (m, 1H), 7.54e7.53 (m,
3H),6.69(s,1H), 5.39(d, J¼12.6Hz,1H), 5.12(m, 2H), 4.71(d,J¼10.8Hz,
1H), 4.18e4.02 (m, 2H), 3.57e3.10 (m, 2H), 2.33e2.31 (m, 1H), 1.92 (s,
2H), 1.73e1.64 (m, 2H), 1.44e1.41 (m, 1H), 1.21e1.04 (m, 2H), 0.69 (t,
Acknowledgements
J¼7.1 Hz, 3H) ppm; 13C NMR (100 MHz, DMSO-d6)
d 150.3,148.1,140.8,
134.5, 132.8, 132.6, 130.3, 129.9, 129.7, 128.2, 127.9, 127.6, 127.5, 126.9,
126.4, 126.3, 126.2, 125.2, 123.8, 120.0, 113.5, 113.3, 113.2, 70.5, 67.6,
61.2, 56.3,51.0,35.1, 25.2,24.8,23.5, 20.6,11.2ppm;IR(KBr)2931,1628,
This study was supported by grants of the Korea Healthcare
technologyR&DProject,MinistryforHealth, Welfare&FamilyAffairs,
Republic of Korea (A092006) and the Seoul R&BD program (10541).

1170
Y. Park et al. / Tetrahedron 67 (2011) 1166e1170
Hetero dienophile additions to dienes In. Comprehensive Organic Synthesis;
Supplementary data
Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 5; p 401; (d)
Waldmann, H. Synthesis 1994, 535.
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2010.12.002.
5. For aza-DielseAlder reactions with Danishefsky’s diene: (a) Collin, J.; Jaber, N.;
Lannou, M. I. Tetrahedron Lett. 2001, 42, 7405; (b) Laurent-Robert, H.; Garrigues,
B.; Dubac, J. Synlett 2000, 1160; (c) Ali, T.; Chauhan, K. K.; Frost, C. G. Tetrahedron
Lett. 1999, 40, 5621; (d) Kobayashi, S.; Ishitani, H.; Nagayama, S. Synthesis 1995,
1195; (e) Kobayashi, S.; Ishitani, H.; Nagayama, S. Chem. Lett. 1995, 423;
(f) Kobayashi, S.; Manabe, K.; Mori, Y. Tetrahedron 2001, 57, 2537; (g) Yuan, Y.; Li,
X.; Ding, K. Org. Lett. 2002, 4, 3309; (h) Kobayashi, S.; Loncaric, C.; Manabe, K.
Chem. Commun. 2003, 5, 574; (i) Kobayashi, S.; Loncaric, C.; Manabe, K. Adv. Synth.
References and notes
1. For the multiple roles of Cinchona alkaloid and their derivatives in chemical
reactions, see: (a) Kacprzak, K.; Gawronski, J. Synthesis 2001, 961; (b) Taggi, A.
E.; Hafez, A. M.; Lectka, T. Acc. Chem. Res. 2003, 36, 10.
ꢀ
Catal. 2003, 345, 475; (j) Wilhelm, R.; Jurcík, V. Org. Biomol. Chem. 2005, 3, 239.
6. Corey, E. J.; Xu, F.; Noe, M. C. J. Am. Chem. Soc. 1997, 119, 12414.
7. (a) Colonna, S.; Re, A.; Gelbard, G.; Cesarotti, E. J. Chem. Soc. Perkin Trans. 1979,
2248; (b) Shioiri, T.; Ando, A.; Miura, T.; Tatematsu, T. Tetrahedron Lett. 1993,
34, 1507.
8. Ooi, T.; Kameda, M.; Maruoka, K. J. Am. Chem. Soc. 2003, 125, 5139.
9. Mohamed, M. A.; Yamada, K.-i.; Tomioka, K. Tetrahedron Lett. 2009, 50,
3436.
10. (a) Cicchi, S.; Revuelta, J.; Zanobini, A.; Betti, M.; Brandi, A. Synlett 2003, 2305;
(b) Revuelta, J.; Cicchi, S.; Brandi, A. J. Org. Chem. 2005, 70, 5636.
11. (a) Nicolaou, K. C.; Mathison, C. J. N.; Montagnon, T. Angew. Chem., Int. Ed. 2003,
42, 4077; (b) Nicolaou, K. C.; Mathison, C. J. N.; Montagnon, T. J. Am. Chem.
Soc. 2004, 126, 5192.
2. For recent reviews on phase-transfer catalysis, see: (a) Maruoka, K.; Ooi, T.
Chem. Rev. 2003, 103, 3013; (b) O’Donnell, M. J. Acc. Chem. Res. 2004, 37, 506;
(c) Lygo, B.; Andrews, B. I. Acc. Chem. Res. 2004, 37, 518; (d) Hashimoto, T.;
Maruoka, K. Chem. Rev. 2007, 107, 5656; (e) Jew, S.-s.; Park, H.-g. Chem. Commun.
2009, 7090.
3. For our recent reports on asymmetric phase-transfer catalysis with Cinchona
derivatives, see: (a) Jew, S.-s.; Jeong, B.-S.; Yoo, M.-S.; Huh, H.; Park, H.-g. Chem.
Commun. 2001, 1244; (b) Park, H.-g.; Jeong, B.-S.; Yoo, M.-S.; Park, M.-k.; Huh,
H.; Jew, S.-s. Tetrahedron Lett. 2001, 42, 4645; (c) Park, H.-g.; Jeong, B.-S.; Yoo,
M.-S.; Lee, J.-H.; Park, M.-k.; Lee, Y.-J.; Kim, M.-J.; Jew, S.-s. Angew. Chem., Int. Ed.
2002, 41, 3036; (d) Jew, S.-s.; Yoo, M.-S.; Jeong, B.-S.; Park, I. Y.; Park, H.-g. Org.
Lett. 2002, 4, 4245; (e) Yoo, M.-S.; Jeong, B.-S.; Lee, J.-H.; Park, H.-g.; Jew, S.-s
Org. Lett. 2005, 7, 1129; (f) Angew. Chem., Int. Ed.; Jew, S.-s., Lee, J.-H., Jeong, B.-S.,
Yoo, M.-S., Kim, M.-J., Lee, Y.-J., Lee, J., Choi, S.-h., Lee, K., Lah, M. S., Park, H.-g.,
Eds.; 2005; 44, p 1383.
12. Wolter, M.; Borm, C.; Merten, E.; Wartchow, R.; Winterfeldt, E. Eur. J. Org. Chem.
2001, 4051.
13. (a) Paek, S.-M.; Kim, N.-J.; Shin, D.; Jung, J.-K.; Jung, J.-W.; Chang, D.-J.; Moon,
H.; Suh, Y.-G. Chem.dEur. J. 2010, 16, 4623; (b) Nemoto, T.; Yamamoto, E.;
4. (a) Carruthers, W. Cycloaddition Reactions in Organic Synthesis; Pergamon:
Oxford, 1990; (b) Oppolazer, W. In Comprehensive Organic Synthesis; Pa-
quette, L. A., Ed.; Pergamon: Oxford, 1991; Vol. 5; p 315; (c) Weinreb, S. M.
ꢁ
Franzen, R.; Fukuyama, T.; Wu, R.; Fukamachi, T.; Kobayashi, H.; Hamada, Y.
Org. Lett. 2010, 12, 872.