Ethylenediamine diacetate (EDDA)-catalyzed one-pot synthesis of tetrahydroquinolines by domino Knoevenagel/hetero Diels-Alder reactions from 1,3-dicarbonyls

Article abstract of DOI:10.1016/j.tet.2008.05.053

This paper describes new and efficient synthetic approaches for biologically interesting tetrahydroquinoline analogues. The key strategies involve the ethylenediamine diacetate-catalyzed cyclization of 1,3-dicarbonyls to aminobenzaldehydes through domino Knoevenagel/hetero Diels-Alder reactions. These reactions provide a rapid route for the synthesis of novel polycycles with the tetrahydroquinoline moiety.

Full text of DOI:10.1016/j.tet.2008.05.053

Tetrahedron 64 (2008) 7338–7346
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Tetrahedron
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Ethylenediamine diacetate (EDDA)-catalyzed one-pot synthesis of
tetrahydroquinolines by domino Knoevenagel/hetero Diels–Alder
reactions from 1,3-dicarbonyls
*
Yong Rok Lee , Thai Viet Hung
School of Chemical Engineering and Technology, Yeungnam University, Gyeongsan 712-749, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 23 April 2008
Received in revised form 10 May 2008
Accepted 12 May 2008
Available online 15 May 2008
This paper describes new and efficient synthetic approaches for biologically interesting tetrahy-
droquinoline analogues. The key strategies involve the ethylenediamine diacetate-catalyzed cyclization
of 1,3-dicarbonyls to aminobenzaldehydes through domino Knoevenagel/hetero Diels–Alder reactions.
These reactions provide a rapid route for the synthesis of novel polycycles with the tetrahydroquinoline
moiety.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Tetrahydroquinoline
Knoevenagel/hetero Diels–Alder reaction
1,3-Dicarbonyls
Aminobenzaldehydes
1. Introduction
TFA and p-TsOH,6 and lanthanide triflates including Ln(OTf)3,
Sc(OTf)3, and Yb(OTf)3.7 Montmorillonite KSF,8 GdCl3,9 ZrCl4,10
13
Tetrahydroquinolines with a variety of substituents show a wide
range of psychotropic, anti-allergic, anti-inflammatory, and estro-
genic activities.1 A number of methodologies for synthesizing tet-
rahydroquinones with substituents have been reported. Among
these, hetero Diels–Alder reactions between N-aldimines and
electron-rich dienophiles are a powerful synthetic tool for pre-
paring tetrahydroquinoline derivatives.2 First, intermolecular im-
ino Diels–Alder reactions using a three-component condensation of
N-anilines with benzaldehydes to electron-rich olefins provided
tetrahydroquinolines with a variety of substituents (Scheme 1).3
These reactions have been studied extensively using Lewis acids,
such as InCl3,3 FeCl3/NaI,4 and BF3$OEt2,5 Brønsted acids, such as
LiBF4,11 SbCl3,12 and LiClO4 have been used as catalysts in the
synthesis of tetrahydroquinolines. These strategies allow for the
facile synthesis of tetrahydroquinoline derivatives. However, these
reactions mainly give a mixture of diastereomers as products.
Second, intramolecular imino Diels–Alder reactions between N-
arylamines and O-allyl derivatives of salicylaldehyde also provide
multiple opportunities for synthesizing tetrahydroquinolines
(Scheme 2). These reactions have been also catalyzed by TFA,14
BiCl3,15 LiClO4,16 and triphenylphosphonium perchlorate.17 How-
ever, these reactions often produce a mixture of diastereomers,
require strong acidic conditions and long reaction times, and pro-
duce products in low yields.
H
H
H
H
O
O
O
O
+
O
O
catalyst
+
+
catalyst
+
O
+
NH2
N
H
N
H
O
NH2
N
H
N
H
H
Scheme 2.
Scheme 1.
Domino Knoevenagel/hetero Diels–Alder reactions have been
used extensively for the synthesis of heterocyclic compounds.18
These reactions provide a rapid synthetic route for assembling
polycyclic structures.19 The simplicity and utility of these reactions
for the synthesis of polycycles prompted us to examine the use of
* Corresponding author. Tel.: þ82 53 810 2529; fax: þ82 53 810 4631.
E-mail address: yrlee@yu.ac.kr (Y.R. Lee).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.05.053

Y.R. Lee, T.V. Hung / Tetrahedron 64 (2008) 7338–7346
7339
R
O
N
n
n
n X
X
X
n
X
R
n
R
X
+
+
O
O
O
O
O
O
O
O
R
O
O
R
X=CH2, O, NMe
n=0,1
R=H, prenyl, geranyl
N
N
N
N
Scheme 3.
Table 1
these reactions. The scope and limitation of these reactions in the
synthesis of tetrahydroquinoline derivatives were investigated.
There are no reports on domino Knoevenagel/hetero Diels–Alder
cyclizations between 1,3-dicarbonyls and N,N-dialkylated
aminobenzaldehydes.
Reaction of 1,3-cyclohexanedione (6) with aminobenzaldehyde 3 under several
conditions
O
Recently, the Brønsted acids and bases have demonstrated their
potent to serve as active catalysts for a variety of synthetically
useful reactions in organic chemistry.20 In particular, we have de-
veloped a new and useful methodology for preparing a variety of
benzopyrans using ethylenediamine diacetate (EDDA) as effective
Brønsted acid and base catalysts.21 These reactions involve a formal
N
O
H
O
H
3
2 equiv
condition
O
O
N
6
7
Condition
Yield (%)
[3þ3]-cycloaddition through a 6p-electrocyclization. This meth-
InCl3 (20 mol %)
Yb(OTf)3 (20 mol %)
Pyridine (excess)
EDDA (20 mol %)
Acetonitrile, reflux, 12 h
Acetonitrile, reflux, 12 h
140 ꢀC, 24 h
Methylene chloride,
rt, 24 h
Benzene, reflux, 24 h
Xylene, reflux, 24 h
Ethyl acetate,
0
10
0
odology provides a rapid route for synthesizing benzopyran de-
rivatives with a variety of substituents on the pyranyl ring.22
As a part of an ongoing study into the synthetic efficacy of this
methodology, this study investigated EDDA-catalyzed domino
Knoevenagel/hetero Diels–Alder reactions of cyclic 1,3-dicarbonyls
and 2-aminobenzaldehydes to afford tetrahydroquinolines, as
shown in Scheme 3. We report the efficient one-pot synthesis of
tetrahydroquinoline analogues with a variety of substituents on the
pyranyl rings.
33
EDDA (20 mol %)
EDDA (20 mol %)
EDDA (20 mol %)
42
75
60
rt, 24 h
triflate (20 mol %) afforded product 7 in only 10% yield. No products
were obtained using pyridine as the reactant and solvent at 140 ꢀC
for 24 h. However, adduct 7 was obtained using ethylenediamine
2. Results and discussion
As starting materials, N-methyl-N-prenyl-2-aminobenz-
aldehyde (3), N-methyl-N-geranyl-2-aminobenzaldehyde (4), and
N-methyl-N-farnesyl-2-aminobenzaldehyde (5) were first pre-
pared from 1-methylquinolinium iodide (1) in a two-step reaction,
as shown in Scheme 4. Treatment of methylquinolinium iodide (1)
with hydrogen peroxide in aqueous sodium hydroxide afforded
N-methyl-2-aminobenzaldehyde (2) in 84% yield.23 A reaction of
N-methyl-2-aminobenzaldehyde (2) with prenyl bromide in the
presence of NaH in DMF gave N-methyl-N-prenyl-2-amino-
benzaldehyde (3) in 84% yield. Similarly, treatment of compound 2
with geranyl bromide gave compound 4 in 75% yield. On the other
hand, a reaction with trans,trans-farnesyl bromide afforded com-
pound 5 in 70% yield.
diacetate (20 mol %) as
a catalyst. This reaction is solvent-
dependent with the best yield (75%) being obtained in refluxing
xylene for 24 h.
Compound 7 was easily separated by column chromatography
and the cis-stereochemistry of compound 7 was confirmed based
on the coupling constant of 1H NMR and by a direct comparison
with reported data.19c,24 The signal of the benzylic methine on the
pyranyl ring in compound 7 appears as a doublet (J¼6.0 Hz) at
d
3.91. In the cis-fused cycloadducts of these types of other known
tetracycles, the signals of benzylic methine are observed as a
doublet with a coupling constant J¼4–6 Hz, whereas those of trans-
fused adducts appear as a doublet with a coupling constant
J¼9–11 Hz.19c,24
The stereospecificity of compound 7 may be explained by the
endo-transition structure as shown in Scheme 5. In the process of
the hetero Diels–Alder reaction, the endo-transition structure must
have been more favorable than the exo-transition structure due to
an sp2-geminal effect according to the phenomenon of 1,3-allylic
strain.25 This is in agreement with Tietze’s work, who reported the
synthesis of tetracycles using intramolecular hetero Diels–Alder
cycloaddition of 1,3-dicarbonyl compounds and O-allyl ether of
salicylic aldehydes.26
R
O
O
N
R
Br
H2O2
-/H O
NaH
+
OH
84%
2
N
DMF
NH
I-
1
2
3 R=H, 84%
4 R=prenyl, 75%
5 R=geranyl, 70%
In order to extend the utility of this methodology, further re-
actions of several types of cyclic 1,3-dicarbonyls were carried out in
the presence of ethylenediamine diacetate (20 mol %) in refluxing
xylene for 12–24 h. The results are summarized in Table 2. First, the
reactions of symmetrical cyclic 1,3-dicarbonyl compounds were
examined. A reaction of 1,3-cyclopentanedione (8) of a five-mem-
bered ring with 2.0 equiv of N-methyl-N-prenyl-2-amino-
benzaldehyde (3) in refluxing xylene for 12 h afforded adduct 16 in
Scheme 4.
To produce a variety of tetrahydroquinoline analogues, reaction
of 1,3-cyclohexanedione (6) with 2.0 equiv of N,N-methylprenyl-2-
aminobenzaldehyde (3) was attempted under several conditions
(Table 1). Indium(III) chloride (20 mol %) as a Lewis acid catalyst in
refluxing acetonitrile gave no adduct, whereas ytterbium(III)

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Y.R. Lee, T.V. Hung / Tetrahedron 64 (2008) 7338–7346
O
O
O
H
O
N
O
+
H
O
O
N
3
6
N
7
favored conformation
endo
O
O
O
O
H
H
N
N
7a
exo
Scheme 5.
85% yield (entry 1). Similarly, a reaction of 5,5-dimethyl-1,3-
cyclohexanedione (9) with 3 gave adduct 17 in 83% yield, whereas
and cis-stereochemistry of compound 18 were confirmed by X-ray
single crystal analysis, as shown in Figure 1. The cycloaddition re-
actions were also successful with other unsymmetrical cyclic 1,3-
dicarbonyls. A reaction of 4-hydroxycoumarin (11) with compound
a
reaction with 3-hydroxy-1H-phenalen-1-one (10) afforded
product 18 in 76% yield (entries 2 and 3). In particular, the structure
Table 2
Reactions of symmetrical or unsymmetrical 1,3-dicarbonyls with aminobenzaldehyde 3a
Entry
1
1,3-Dicarbonyls
Aminoaldehyde
Time (h)
12
Product
Yield (%)
85
O
O
O
H
H
H
8
9
3
16
17
O
O
O
N
N
O
H
2
3
12
83
O
O
H
O
O
O
H
3
10
3
12
18
19
20
76
O
O
N
N
N
O
H
O
H
60
4
11
3
24
O
O
OH
O
O
H
H
24

Y.R. Lee, T.V. Hung / Tetrahedron 64 (2008) 7338–7346
7341
Table 2 (continued )
Entry
1,3-Dicarbonyls
Aminoaldehyde
Time (h)
Product
Yield (%)
O
H
O
H
O
21
58
N
5
12
3
24
O
O
OH
O
O
H
O
H
22
22
N
O
H
O
H
O
23
54
N
6
13
3
24
O
O
OH
O
O
H
O
24
20
H
N
N
H
O
H
O
7
14
3
24
25
75
N
O
OH
N
O
O
H
O
H
26
57
N
O
8
15
3
12
OH
O
O
O
O
H
27
32
H
N
a
Conditions: starting material (1.0 mmol) and 3 (2.0 mmol) under EDDA (20 mol %) in refluxing xylene.

7342
Y.R. Lee, T.V. Hung / Tetrahedron 64 (2008) 7338–7346
of compounds 26 and 27 can be explained by the sequence through
intermediates 26a and 27b as shown in Scheme 6.
O
N
O
O
O
O
+
OH
O
N
O
O
N
O
3
15
26a
27a
O
O
O
O
O
O
H
H
H
H
27
N
N
26
Scheme 6.
Based on these successful results, additional domino Knoeve-
nagel/intramolecular hetero Diels–Alder reactions between cyclic
1,3-dicarbonyl compounds and aminobenzaldehydes 4–5 with
geranyl or farnesyl group were examined (Table 3). A reaction of
1,3-cyclohexanedione (6) with aminobenzaldehyde
4 using
20 mol % of ethylenediamine diacetate as a catalyst in refluxing
xylene for 24 h gave product 28 (68%), whereas a reaction with
aminobenzaldehyde 5 afforded product 29 in 65% yield (entries 1
and 2). Similarly, treatment of compound
9 with amino-
Figure 1. X-ray structure of compound 18.
benzaldehyde 4 or 5 in the presence of 20 mol % of ethylenediamine
diacetate in refluxing xylene for 24 h gave product 30 (72%) or 31
(68%) (entries 3 and 4), respectively. These reactions provide a rapid
route for the synthesis of tetrahydroquinolines with long chain
substituents on the pyranyl ring.
In conclusion, we report a new and efficient methodology for
synthesizing biologically interesting tetrahydroquinoline de-
rivatives via domino Knoevenagel/hetero Diels–Alder reactions
from 1,3-dicarbonyls and aminoaldehydes. These reactions provide
a rapid route for the synthesis of novel types of polycycles with the
tetrahydroquinoline moiety.
3 in refluxing xylene for 24 h afforded two regioisomers 19 and 20
in 60 and 24% yields, respectively (entry 4). These two compounds
were easily separated by column chromatography and were
assigned by the spectral data. In the IR spectra, the ester carbonyl
absorption of compound 19 was observed at 1705 cmꢁ1, whereas
the carbonyl absorption was observed at 1618 cmꢁ1 in the case of
compound 20. Further support for distinguishing between the
coumarin and chromone structures came from the carbonyl carbon
in the 13C NMR spectrum, which appeared at
19 with a coumarin skeleton, and at 177.9 for compound 20 with
d 162.7 for compound
d
3. Experimental section
3.1. General
a chromene moiety. Similarly, reactions of 4-hydroxycoumarins 12
and 13 with substituents on the benzene ring gave also products
21–24 (entries 5 and 6) in moderate yields. Interestingly, in the
cases of entries 5 and 6 with substituents such as methyl and di-
methyl on the benzene ring, the yield and selectivity of the
obtained products were somewhat decreased. Unlike 4-hydroxy-
coumarins 11–13, 4-hydroxy-2-quinolone (14) gave product 25 in
75% yield as a sole compound. In order to examine the usefulness of
these reactions, the other reaction using 2-hydroxy-1,4-naph-
thoquinone (15) was studied. Treatment of compound 15 with 3 in
refluxing xylene for 12 h provided two products 26 and 27 in 57
and 32% yields, respectively. The products were easily separated by
column chromatography and the structures of two isomers were
determined from their spectroscopic data. The 1H NMR spectrum of
compound 26 showed the aromatic protons of symmetrical 1,4-
All the experiments were carried out in a nitrogen atmosphere.
Merck precoated silica gel plates (Art. 5554) with a fluorescent
indicator were used for analytical TLC. Flash column chromato-
graphy was performed using silica gel 9385 (Merck). The 1H NMR
and 13C NMR spectra were recorded on a Bruker Model ARX (300
and 75 MHz, respectively) spectrometer in CDCl3 using
d¼7.24 and
77.0 ppm as the solvent chemical shift. The IR spectra were recor-
ded on a Jasco FTIR 5300 spectrophotometer. The HRMS and MS
spectra were carried out at the Korea Basic Science Institute.
3.2. N-Methyl-2-aminobenzaldehyde (2)
naphthoquinone moiety as two parts with chemical shifts at
8.04 (2H, m) and 7.71–7.61 (2H, m), whereas compound 27 showed
aromatic peaks separately as four parts at
d 8.09–
To a stirred mixture of potassium hydroxide (8.30 g, 0.148 mol)
in water (30 mL) and 1,2-dichloroethane (30 mL) at 0 ꢀC was added
hydrogen peroxide (6.4 mL, 35%, 0.074 mol) in water (4 mL). 1-
Methylquinolinium iodide (1) (4.065 g, 0.015 mol) in water (10 mL)
was added dropwise over 45 min at 0 ꢀC, which was then stirred at
room temperature for 48 h. Thiodiethanol (0.5 g) was added and
the layers were separated. The aqueous phase was extracted with
d
8.07 (1H, d, J¼7.5 Hz),
7.84 (1H, d, J¼7.8 Hz), 7.64 (1H, dd, J¼7.8, 7.5 Hz), 7.51 (1H, dd, J¼7.5,
7.5 Hz) due to unsymmetrical 1,2-naphthoquinone skeleton. The
13C NMR spectra of compound 26 showed two signals at
d
184.2 and
179.9 due to the presence of two carbonyl groups, and compound
27 showed two carbonyl signals at 179.8 and 179.0. The formation
d

Y.R. Lee, T.V. Hung / Tetrahedron 64 (2008) 7338–7346
7343
Table 3
Reactions of 1,3-dicarbonys with aminobenzaldehydes 4–5a
Entry
1,3-Dicarbonyls
Aminoaldehyde
Time (h)
Product
Yield (%)
O
O
H
O
H
1
6
6
4
5
24
28
29
68
O
O
N
O
O
H
O
H
2
24
24
24
65
72
68
N
O
O
O
H
H
3
9
4
30
O
N
O
O
H
O
H
4
9
5
31
O
N
a
Conditions: starting materials (1.0 mmol) and aminobenzaldehydes 4–5 (2.0 mmol) under EDDA (20 mol %) in refluxing xylene.
dichloromethane (30 mLꢂ3), washed with water (30 mL) and sat-
urated sodium sulfite solution (30 mL), dried over MgSO4, and
evaporated. The residue was purified by column chromatography
on silica gel (hexane/ethyl acetate, 20:1) to give 2 (1.703 g, 84%) as
geranyl bromide (3.539 g, 16.3 mmol) in DMF (3 mL) was added
dropwise. The reaction mixture was stirred at room temperature
for 12 h and water (30 mL) was added slowly at 0 ꢀC. The mixture
was extracted with ethyl acetate (30 mLꢂ3), washed with water
(30 mL) and saturated NH4Cl solution (30 mL), dried over MgSO4,
and evaporated. The residue was purified by column chromatog-
raphy on silica gel (hexane/ethyl acetate, 20:1) to give 4 (3.012 g,
an oil: 1H NMR (300 MHz, CDCl3)
d
9.80 (1H, s), 7.45 (1H, dd, J¼7.8,
1.5 Hz), 7.42–7.38 (1H, m), 6.70–6.66 (1H, m), 6.66 (1H, d, J¼8.9 Hz),
2.92 (3H, d, J¼5.5 Hz); IR (neat) 3345, 2908, 2829, 2744, 1658, 1577,
869, 752 cmꢁ1; m/z (EI) 135 (Mþ, 59), 134 (100), 119 (20), 105 (35);
HRMS m/z (Mþ) calcd for C8H9NO: 135.0684. Found: 135.0687.
75%) as an oil: 1H NMR (300 MHz, CDCl3)
d 10.3 (1H, s), 7.76 (1H, dd,
J¼7.7, 1.7 Hz), 7.45 (1H, ddd, J¼7.2, 7.2, 1.7 Hz), 7.06–6.98 (2H, m),
5.30–5.26 (1H, m), 5.06–5.02 (1H, m), 3.69 (2H, d, J¼6.7 Hz), 2.81
(3H, s), 2.05–2.01 (4H, m), 1.67 (3H, s), 1.59 (3H, s), 1.58 (3H, s); IR
(neat) 2968, 2924, 1688, 1597, 1483, 1453, 1381, 1283, 1190, 1107,
932, 831, 764 cmꢁ1; HRMS m/z (Mþ) calcd for C18H25NO: 271.1936.
Found: 271.1934.
3.3. N-Methyl-N-prenyl-2-aminobenzaldehyde (3)
To a solution of 2 (2.0 g, 14.8 mmol) in DMF (20 mL) was added
sodium hydride (1.776 g, 60%, 44.4 mmol) at 0 ꢀC. After 20 min,
prenyl bromide (2.426 g, 16.3 mmol) in DMF (3 mL) was added
dropwise. The reaction mixture was stirred at room temperature
for 12 h and water (30 mL) was added slowly at 0 ꢀC. The reaction
mixture was extracted with ethyl acetate (30 mLꢂ3), washed with
water (30 mL) and saturated NH4Cl solution (30 mL), dried over
MgSO4, and evaporated. The residue was purified by column
chromatography on silica gel (hexane/ethyl acetate, 20:1) to give 3
3.5. N-Methyl-N-farnesyl-2-aminobenzaldehyde (5)
To a solution of 2 (2.0 g, 14.8 mmol) in DMF (20 mL) was added
sodium hydride (1.776 g, 60%, 44.4 mmol) at 0 ꢀC. After 20 min,
trans,trans-farnesyl bromide (4.650 g, 16.3 mmol) in DMF (3 mL)
was added dropwise. The reaction mixture was stirred at room
temperature for 12 h and water (30 mL) was added slowly at 0 ꢀC.
The mixture was extracted with ethyl acetate (30 mLꢂ3), washed
with water (30 mL) and saturated NH4Cl solution (30 mL), dried
over MgSO4, and evaporated. The residue was purified by column
chromatography on silica gel (hexane/ethyl acetate, 20:1) to give 5
(2.527 g, 84%) as an oil: 1H NMR (300 MHz, CDCl3)
d 10.23 (1H, s),
7.75 (1H, dd, J¼7.7, 1.7 Hz), 7.47–7.43 (1H, m), 7.07–6.97 (2H, m),
5.29–5.26 (1H, m), 3.67 (2H, d, J¼6.7 Hz), 2.80 (3H, s), 1.71 (3H, s),
1.59 (3H, s); IR (neat) 2855, 1686, 1597, 1483, 1453, 1381, 1283, 1192,
1080, 928, 831, 764 cmꢁ1; HRMS m/z (Mþ) calcd for C13H17NO:
203.1310. Found: 203.1312.
(3.517 g, 70%) as an oil: 1H NMR (300 MHz, CDCl3)
d 10.23 (1H, s),
7.77 (1H, dd, J¼7.7, 1.7 Hz), 7.46 (1H, ddd, J¼7.2, 7.2, 1.7 Hz), 7.10–
7.02 (2H, m), 5.38–5.27 (1H, m), 5.12–5.01 (2H, m), 3.95 (2H, s,
J¼6.7 Hz), 2.85 (3H, s), 2.13–1.96 (8H, m), 1.64 (6H, s), 1.57 (6H, s); IR
3.4. N-Methyl-N-geranyl-2-aminobenzaldehyde (4)
To a solution of 2 (2.0 g, 14.8 mmol) in DMF (20 mL) was added
sodium hydride (1.776 g, 60%, 44.4 mmol) at 0 ꢀC. After 20 min,
(neat) 2967, 1688, 1597, 1484, 1453, 1381, 1283, 1109, 831, 761 cmꢁ1
;
HRMS m/z (Mþ) calcd for C23H33NO: 339.2562. Found: 339.2560.

7344
Y.R. Lee, T.V. Hung / Tetrahedron 64 (2008) 7338–7346
3.6. General procedure for the synthesis of
tetrahydroquinolines
J¼8.0 Hz), 4.34 (1H, d, J¼6.1 Hz), 3.61 (1H, dd, J¼11.8, 8.4 Hz), 2.91
(1H, dd, J¼11.8, 8.4 Hz), 2.87 (3H, s), 2.62–2.55 (1H, m), 1.52 (3H, s),
1.08 (3H, s); IR (KBr) 2903, 1632, 1574, 1508, 1417, 1377, 1298, 1242,
1223, 1121, 1024, 937, 785, 742 cmꢁ1; HRMS m/z (Mþ) calcd for
Ethylenediamine diacetate (36 mg, 0.2 mmol) was then added
to a solution of cyclic 1,3-diketones (1.0 mmol) and amino-
benzaldehydes (2.0 mmol) in xylene (10 mL) at room temperature.
The reaction mixture was stirred in refluxing xylene for 12–24 h.
The removal of the solvent under reduced pressure left an oily
residue, which was then purified by column chromatography on
silica gel to give the products.
C26H23NO2: 381.1729. Found: 381.1730.
3.6.5. Compounds 19 and 20
A reaction of compound 11 (162 mg,1.0 mmol) with N-methyl-N-
prenyl-2-aminobenzaldehyde (3) (406 mg, 2.0 mmol) in refluxing
xylene (10 mL) for 24 h and purification by column chromatography
on silica gel (hexane/ethyl acetate, 7:1) afforded compounds 19
(208 mg, 60%) and 20 (83 mg, 24%).
3.6.1. Compound 7
A reaction of compound 6 (112 mg, 1.0 mmol) with N-methyl-N-
prenyl-2-aminobenzaldehyde (3) (406 mg, 2.0 mmol) in refluxing
xylene (10 mL) for 24 h and purification by column chromatography
on silica gel (hexane/ethyl acetate, 7:1) afforded compound 7
Compound 19: mp 170–172 ꢀC; 1H NMR (300 MHz, CDCl3)
d 7.96
(1H, d, J¼7.8 Hz), 7.65 (1H, dd, J¼7.8, 7.5 Hz), 7.47–7.37 (2H, m),
7.34–7.24 (2H, m), 6.87 (1H, dd, J¼7.5, 7.2 Hz), 6.76 (1H, d, J¼7.8 Hz),
4.27 (1H, d, J¼4.2 Hz), 3.69 (1H, dd, J¼11.4, 8.3 Hz), 3.06 (1H, dd,
J¼11.4, 8.3 Hz), 2.99 (3H, s), 2.73–2.68 (1H, m), 1.65 (3H, s), 1.26 (3H,
(223 mg, 75%) as an oil: 1H NMR (300 MHz, CDCl3)
d 7.05 (1H, dd,
J¼7.8, 7.5 Hz), 6.8 (1H, d, J¼7.5 Hz), 6.64 (1H, dd, J¼8.0, 7.8 Hz), 6.54
(1H, d, J¼8.0 Hz), 3.91 (1H, d, J¼6.0 Hz), 3.49 (1H, dd, J¼11.9, 8.0 Hz),
2.86–2.80 (4H, m), 2.58–2.50 (1H, m), 2.41–2.37 (2H, m), 2.35–2.29
(2H, m), 2.03–1.97 (2H, m), 1.32 (3H, s), 0.92 (3H, m); IR (neat) 2943,
1649, 1612, 1503, 1454, 1379, 1262, 1171, 1125, 1086, 1047, 1001, 928,
853, 748 cmꢁ1; m/z (EI) 297 (Mþ, 100), 296 (19), 282 (13), 255 (17),
254 (84), 242 (13), 241 (36), 198 (11),186 (40), 185 (15),184 (12), 144
(24);HRMS m/z (Mþ)calcd forC19H23NO2:297.1729. Found:297.1731.
s); 13C NMR (75 MHz, CDCl3)
d 162.7, 159.1, 152.7, 146.7, 131.5, 128.1,
127.3, 124.0, 123.5, 122.8, 117.7, 116.3, 115.8, 110.9, 101.0, 81.2, 51.0,
40.7, 38.6, 31.7, 28.0, 23.0; IR (KBr) 2978, 2847, 1705, 1626, 1574,
1495, 1454, 1393, 1279, 1136, 1086, 1038, 972, 897, 855, 748 cmꢁ1
;
m/z (EI) 347 (Mþ, 100), 346 (11), 305 (11), 304 (51), 291 (19), 186
(39), 185 (15), 184 (12), 160 (22), 149 (15), 144 (25), 129 (17), 121
(11), 83 (11), 71 (13), 69 (18), 57 (19), 55 (14); HRMS m/z (Mþ) calcd
for C22H21NO3: 347.1521. Found: 347.1523.
Compound 20: 1H NMR (300 MHz, CDCl3)
d 8.21 (1H, d,
3.6.2. Compound 16
J¼8.2 Hz), 7.56 (1H, dd, J¼8.2, 7.8 Hz), 7.38–7.33 (2H, m), 7.11–7.07
(2H, m), 6.69 (1H, dd, J¼7.2, 7.0 Hz), 6.60 (1H, d, J¼8.2 Hz), 4.33 (1H,
d, J¼6.2 Hz), 3.61 (1H, dd, J¼12.0, 7.8 Hz), 2.95 (1H, dd, J¼12.0,
A reaction of compound 8 (146 mg, 1.0 mmol) with N-methyl-N-
prenyl-2-aminobenzaldehyde (3) (406 mg, 2.0 mmol) in refluxing
xylene (10 mL) for 12 h and purification by column chromatogra-
phy on silica gel (hexane/ethyl acetate, 5:1) afforded compound 16
7.8 Hz), 2.87 (3H, s), 2.55–2.49 (1H, m), 1.51 (3H, s), 1.14 (3H, s); 13
C
NMR (75 MHz, CDCl3) d 177.9, 162.9, 153.0, 146.3, 132.7, 128.2, 127.2,
(203 mg, 85%) as an oil: 1H NMR (300 MHz, CDCl3)
d
7.52 (1H, d,
126.0, 124.8, 124.3, 122.8, 118.1, 116.9, 111.0, 97.4, 85.1, 51.1, 40.9,
38.9, 30.8, 28.2, 22.9; IR (neat) 2982, 1618, 1564, 1499, 1468, 1414,
1302, 1121, 1086, 972, 824, 758 cmꢁ1; m/z (EI) 347 (Mþ, 100), 346
(20), 332 (13), 305 (19), 304 (88), 292 (20), 291 (58), 278 (13), 249
(10), 186 (33), 185 (11),184 (20), 172 (16), 161 (16),160 (19),158 (14),
144 (39),130 (17),128 (10),121 (29),118 (32), 91 (13), 77 (14); HRMS
m/z (Mþ) calcd for C22H21NO3: 347.1521. Found: 347.1519.
J¼7.8 Hz), 7.09 (1H, dd, J¼7.8, 7.5 Hz), 6.72 (1H, dd, J¼7.6, 7.5 Hz),
6.60 (1H, d, J¼7.6 Hz), 3.84 (1H, d, J¼4.0 Hz), 3.35 (1H, dd, J¼11.7,
4.8 Hz), 2.93 (1H, dd, J¼11.7, 4.8 Hz), 2.87 (3H, s), 2.47–2.46 (2H, m),
2.39–2.34 (2H, m), 2.17–2.12 (1H, m), 1.39 (3H, s), 1.33 (3H, s); IR
(neat) 2926, 1689, 1609, 1510, 1435, 1381, 1302, 1278, 1201, 1144,
1121, 1082, 1020, 907, 858, 810, 741 cmꢁ1; m/z (EI) 283 (Mþ, 100),
282 (13), 240 (52), 228 (11), 227 (24), 203 (19), 198 (16), 186 (31),
184 (11), 158 (12), 145 (12), 144 (32), 143 (11); HRMS m/z (Mþ) calcd
for C18H21NO2: 283.1572. Found: 283.1774.
3.6.6. Compounds 21 and 22
A reaction of compound 12 (176 mg,1.0 mmol) with N-methyl-N-
prenyl-2-aminobenzaldehyde (3) (406 mg, 2.0 mmol) in refluxing
xylene (10 mL) for 24 h and purification by column chromatography
on silica gel (hexane/ethyl acetate, 5:1) afforded compounds 21
(209 mg, 58%) and 22 (83 mg, 22%).
3.6.3. Compound 17
A reaction of compound 9 (140 mg, 1.0 mmol) with N-methyl-N-
prenyl-2-aminobenzaldehyde (3) (406 mg, 2.0 mmol) in refluxing
xylene (10 mL) for 12 h and purification by column chromatogra-
phy on silica gel (hexane/ethyl acetate, 7:1) afforded compound 17
(270 mg, 83%) as an solid: mp 128–130 ꢀC; 1H NMR (300 MHz,
Compound 21: mp 172–174 ꢀC; 1H NMR (300 MHz, CDCl3)
d 7.58
(1H, s), 7.33–7.05 (4H, m), 6.72 (1H, dd, J¼7.5, 7.2 Hz), 6.62 (1H, d,
J¼8.1 Hz), 4.11 (1H, d, J¼5.7 Hz), 3.54 (1H, dd, J¼11.4, 8.7 Hz), 2.90
(1H, dd, J¼11.4, 8.7 Hz), 2.96 (3H, s), 2.58–2.52 (1H, m), 2.40 (3H, s),
1.50 (3H, s), 1.11 (3H, s); IR (KBr) 2980, 1709, 1626, 1582, 1499, 1385,
1277, 1121, 1090, 1047, 1011, 924, 820, 735 cmꢁ1; HRMS m/z (Mþ)
calcd for C23H23NO3: 361.1678. Found: 361.1674.
CDCl3)
d
7.05 (1H, dd, J¼7.5, 7.4 Hz), 6.7 (1H, d, J¼7.4 Hz), 6.65 (1H,
dd, J¼8.0, 7.5 Hz), 6.54 (1H, d, J¼8.0 Hz), 3.90 (1H, d, J¼6.0 Hz), 3.47
(1H, dd, J¼11.8, 8.1 Hz), 2.85–2.80 (4H, m), 2.44–2.22 (5H, m), 1.32
(3H, s), 1.12 (3H, s), 1.06 (3H, s), 0.93 (3H, m); IR (KBr) 2957, 2893,
1639, 1610, 1508, 1375, 1339, 1298, 1127, 1092, 1030, 862, 745 cmꢁ1
;
Compound 22: 1H NMR (300 MHz, CDCl3)
d 7.92 (1H, s), 7.32
m/z (EI) 325 (Mþ, 100), 324 (19), 310 (15), 283 (21), 282 (93), 270
(14), 269 (39), 186 (37), 185 (14), 184 (11), 144 (22); HRMS m/z (Mþ)
calcd for C21H27NO2: 325.2042. Found: 325.2045.
(1H, d, J¼8.4 Hz), 7.17 (1H, d, J¼8.4 Hz), 7.03–6.98 (2H, m), 6.59 (1H,
dd, J¼7.2, 7.0 Hz), 6.51 (1H, d, J¼7.8 Hz), 4.24 (1H, d, J¼5.7 Hz), 3.53
(1H, dd, J¼11.4, 8.7 Hz), 2.85 (1H, dd, J¼11.4, 8.7 Hz), 2.79 (3H, s),
2.47–2.42 (1H, m), 2.34 (3H, s), 1.43 (3H, s), 1.05 (3H, s); IR (neat)
2982,1615, 1568,1454, 1397, 1298, 1208,1121, 818, 735 cmꢁ1; HRMS
m/z (Mþ) calcd for C23H23NO3: 361.1678. Found: 361.1682.
3.6.4. Compound 18
A reaction of compound 10 (196 mg,1.0 mmol) with N-methyl-N-
prenyl-2-aminobenzaldehyde (3) (406 mg, 2.0 mmol) in refluxing
xylene (10 mL) for 12 h and purification by column chromatography
on silica gel (hexane/ethyl acetate, 7:1) afforded compound 18
(290 mg, 76%) as a solid: mp 196–198 ꢀC; 1H NMR (300 MHz, CDCl3)
3.6.7. Compounds 23 and 24
A reaction of compound 13 (190 mg,1.0 mmol) with N-methyl-N-
prenyl-2-aminobenzaldehyde (3) (406 mg, 2.0 mmol) in refluxing
xylene (10 mL) for 24 h and purification by column chromatography
on silica gel (hexane/ethyl acetate, 5:1) afforded compounds 23
(203 mg, 54%) and 24 (75 mg, 20%).
d
8.61 (1H, d, J¼7.4 Hz), 8.21 (1H, d, J¼7.4 Hz), 8.09 (1H, d, J¼8.0 Hz),
7.99 (1H, d, J¼8.0 Hz), 7.69 (1H, dd, J¼8.0, 7.4 Hz), 7.58 (1H, d, J¼8.0,
7.4 Hz), 7.11–7.05 (2H, m), 6.67 (1H, dd, J¼7.5, 7.3 Hz), 6.61 (1H, d,

Y.R. Lee, T.V. Hung / Tetrahedron 64 (2008) 7338–7346
7345
Compound 23: mp 175–177 ꢀC; 1H NMR (300 MHz, CDCl3)
d
7.51
(249 mg, 68%) as an oil: 1H NMR (300 MHz, CDCl3)
d
7.08 (1H, dd,
(1H, s), 7.16–7.09 (2H, m), 7.08 (1H, s), 6.70 (1H, dd, J¼7.5, 7.4 Hz),
6.59 (1H, d, J¼8.1 Hz), 4.08 (1H, d, J¼5.8 Hz), 3.53 (1H, dd, J¼11.8,
8.2 Hz), 2.89 (1H, dd, J¼11.8, 8.2 Hz), 2.84 (3H, s), 2.57–2.50 (1H, m),
2.32 (3H, s), 2.29 (3H, s),1.49 (3H, s),1.09 (3H, s); IR (KBr) 2978,1709,
J¼8.0, 7.4 Hz), 6.90 (1H, d, J¼7.4 Hz), 6.66 (1H, dd, J¼8.0, 7.4 Hz),
6.56 (1H, d, J¼8.0 Hz), 5.10–5.05 (1H, m), 3.91 (1H, d, J¼6.0 Hz), 3.45
(1H, dd, J¼11.8, 8.2 Hz), 2.86–2.79 (4H, m), 2.58–2.47 (1H, m), 2.45–
2.33 (4H, m), 2.05–1.96 (4H, m), 1.67 (3H, s), 1.59 (3H, s), 1.53 (2H,
m), 0.90 (3H, s); IR (neat) 2959, 1653, 1618, 1504, 1452, 1377, 1140,
754 cmꢁ1; m/z (EI) 365 (Mþ, 100), 297 (11), 296 (51), 294 (19), 282
(12), 264 (13), 255 (16), 254 (68), 242 (13), 241 (32), 212 (10), 198
(11), 184 (29), 144 (29); HRMS m/z (Mþ) calcd for C24H31NO2:
365.2355. Found: 365.2353.
1628, 1572, 1503, 1454, 1387, 1186, 1123, 1088, 1034, 864, 779 cmꢁ1
;
HRMS m/z (Mþ) calcd for C24H25NO3: 375.1834. Found: 375.1836.
Compound 24: 1H NMR (300 MHz, CDCl3)
d 7.94 (1H, s), 7.15 (1H,
s), 7.127–7.05 (2H, m), 6.67 (1H, dd, J¼7.4, 7.0 Hz), 6.59 (1H, d,
J¼8.2 Hz), 4.31 (1H, d, J¼6.1 Hz), 3.61 (1H, dd, J¼12.0, 7.8 Hz), 2.92
(1H, dd, J¼12.0, 7.8 Hz), 2.87 (3H, s), 2.56–2.52 (1H, m), 2.35 (3H, s),
2.32 (3H, s), 1.50 (3H, s),1.11 (3H, s); IR (neat) 2980,1618,1559,1501,
1464, 1435, 1391, 1300, 1200, 1123, 976, 874, 737 cmꢁ1; HRMS m/z
(Mþ) calcd for C24H25NO3: 375.1834. Found: 375.1832.
3.6.11. Compound 29
A reaction of compound 6 (112 mg, 1.0 mmol) with N-methyl-N-
farnesyl-2-aminobenzaldehyde (5) (679 mg, 2.0 mmol) in refluxing
xylene (10 mL) for 24 h and purification by column chromatogra-
phy on silica gel (hexane/ethyl acetate, 5:1) afforded compound 29
3.6.8. Compound 25
A reaction of compound 14 (175 mg,1.0 mmol) with N-methyl-N-
prenyl-2-aminobenzaldehyde (3) (406 mg, 2.0 mmol) in refluxing
xylene (10 mL) for 24 h and purification by column chromatography
on silica gel (hexane/ethyl acetate, 10:1) afforded compound 25
(270 mg, 75%) as a solid: mp 178–180 ꢀC; 1H NMR (300 MHz, CDCl3)
(282 mg, 65%) as an oil: 1H NMR (300 MHz, CDCl3)
d 7.06 (1H, dd,
J¼7.8, 7.5 Hz), 6.91 (1H, d, J¼7.5 Hz), 6.67 (1H, dd, J¼7.8, 7.5 Hz),
6.58 (1H, d, J¼7.8 Hz), 5.15–5.05 (2H, m), 3.91 (1H, d, J¼6.3 Hz), 3.46
(1H, dd, J¼11.4, 9.3 Hz), 2.83 (3H, s), 2.80 (1H, dd, J¼11.4, 9.3 Hz),
2.60–2.47 (1H, m), 2.46–2.33 (2H, m), 2.05–1.96 (10H, m), 1.65 (3H,
s), 1.64–1.58 (2H, m), 1.58 (6H, s), 0.91 (3H, s); IR (neat) 2924, 1651,
1615, 1505, 1453, 1379. 1262, 1101, 802, 748 cmꢁ1; m/z (EI) 433 (Mþ,
74), 365 (17), 364 (63), 322 (15), 296 (35), 254 (33), 241 (22), 184
(18), 182 (41), 167 (100), 144 (19), 69 (14); HRMS m/z (Mþ) calcd for
d
7.98 (1H, dd, J¼8.1, 1.5 Hz), 7.55 (1H, ddd, J¼7.2, 7.0, 1.8 Hz), 7.34
(1H, d, J¼8.4 Hz), 7.21–7.18 (1H, m), 7.12–7.07 (2H, m), 6.75–6.68 (2H,
m), 4.23 (1H, d, J¼6.3 Hz), 3.84–3.54 (5H, m), 2.92 (3H, s), 2.59–2.52
(1H, m), 1.47 (3H, s), 1.03 (3H, s); IR (KBr) 2978, 1632, 1503, 1462,
1385, 1327, 1196, 1119, 1044, 754 cmꢁ1; m/z (EI) 360 (Mþ, 100), 359
(15), 345 (25), 318 (18), 317 (74), 305 (14), 304 (24), 226 (29),186 (15),
144 (18), 129 (11), 57 (10); HRMS m/z (Mþ) calcd for C23H24N2O2:
360.1838. Found: 360.1841.
C29H39NO2: 433.2981. Found: 433.2983.
3.6.12. Compound 30
A reaction of compound 9 (140 mg, 1.0 mmol) with N-methyl-N-
geranyl-2-aminobenzaldehyde (4) (543 mg, 2.0 mmol) in refluxing
xylene (10 mL) for 24 h and purification by column chromatogra-
phy on silica gel (hexane/ethyl acetate, 5:1) afforded compound 30
3.6.9. Compounds 26 and 27
A reaction of compound 15 (174 mg,1.0 mmol) with N-methyl-N-
prenyl-2-aminobenzaldehyde (3) (406 mg, 2.0 mmol) in refluxing
xylene (10 mL) for 12 h and purification by column chromatography
on silica gel (hexane/ethyl acetate, 10:1) afforded compounds 26
(205 mg, 57%) and 24 (115 mg, 32%).
(283 mg, 72%) as an oil: 1H NMR (300 MHz, CDCl3)
d 7.07 (1H, dd,
J¼7.7, 7.4 Hz), 6.90 (1H, d, J¼7.4 Hz), 6.72–6.62 (2H, m), 5.09–5.05
(1H, m), 3.92 (1H, d, J¼6.1 Hz), 3.46 (1H, dd, J¼11.8, 8.3 Hz), 2.85
(3H, s), 2.82 (1H, dd, J¼11.3, 8.3 Hz), 2.57–2.31 (2H, m), 2.46–2.19
(4H, m), 2.07–1.99 (3H, m), 1.67 (3H, s), 1.59 (3H, s), 1.12 (3H, s), 1.07
(3H, s), 0.91 (3H, s); IR (neat) 2959, 2928, 1505, 1453, 1377, 1298,
1242, 1161, 1140, 748 cmꢁ1; m/z (EI) 393 (Mþ, 100), 325 (13), 324
(53), 322 (19), 310 (13), 292 (12), 283 (17), 282 (59), 270 (14), 269
(33), 254 (27), 240 (12), 184 (28), 144 (28); HRMS m/z (Mþ) calcd for
Compound 26: mp 169–171 ꢀC; 1H NMR (300 MHz, CDCl3)
d
8.09–8.04 (2H, m), 7.71–7.61 (2H, m), 7.13–7.04 (2H, m), 6.70 (1H,
dd, J¼7.5, 7.2 Hz), 6.60 (1H, d, J¼8.1 Hz), 4.24 (1H, d, J¼5.7 Hz), 3.48
(1H, dd, J¼11.4, 8.1 Hz), 2.94 (1H, dd, J¼11.4, 8.1 Hz), 2.84 (3H, s),
2.46–2.41 (1H, m), 1.48 (3H, s), 1.14 (3H, s); 13C NMR (75 MHz,
CDCl3)
d
184.2, 179.9, 154.4, 146.7, 134.0, 132.8, 132.5, 131.0, 129.0,
C26H35NO2: 393.2668. Found: 393.2670.
127.6,126.4,126.1,124.2,121.1,117.7,111.0, 81.2, 50.9, 40.5, 38.6, 31.8,
27.6, 23.4; IR (KBr) 2930, 1680, 1612, 1500, 1370, 1273, 1125, 982,
727 cmꢁ1; m/z (EI) 359 (Mþ, 100), 358 (49), 317 (21), 316 (48), 278
(21), 263 (16), 227 (46), 144 (44), 120 (12), 77 (13); HRMS m/z (Mþ)
calcd for C23H21NO3: 359.1521. Found: 359.1524.
3.6.13. Compound 31
A reaction of compound 9 (140 mg, 1.0 mmol) with N-methyl-N-
farnesyl-2-aminobenzaldehyde (5) (679 mg, 2.0 mmol) in refluxing
xylene (10 mL) for 24 h and purification by column chromatogra-
phy on silica gel (hexane/ethyl acetate, 5:1) afforded compound 31
Compound 27: 1H NMR (300 MHz, CDCl3)
d 8.07 (1H, d,
J¼7.5 Hz), 7.84 (1H, d, J¼7.8 Hz), 7.64 (1H, dd, J¼7.8, 7.5 Hz), 7.51
(1H, dd, J¼7.5, 7.5 Hz), 7.08 (1H, dd, J¼8.0, 7.5 Hz), 6.99 (1H, d,
J¼7.5 Hz), 6.66 (1H, dd, J¼8.0, 7.5 Hz), 6.60 (1H, d, J¼8.0 Hz), 4.21
(1H, d, J¼6.3 Hz), 3.55 (1H, dd, J¼12.0, 9.0 Hz), 2.96 (1H, dd, J¼12.0,
(314 mg, 68%) as an oil: 1H NMR (300 MHz, CDCl3)
d 7.07 (1H, dd,
J¼7.8, 7.5 Hz), 6.89 (1H, d, J¼7.5 Hz), 6.70 (1H, dd, J¼7.8, 7.5 Hz),
6.61 (1H, d, J¼7.8 Hz), 5.11–5.04 (2H, m), 3.92 (1H, d, J¼6.0 Hz), 3.47
(1H, dd, J¼11.7, 8.4 Hz), 2.84 (3H, s), 2.82 (1H, dd, J¼11.7, 8.4 Hz),
2.44–2.37 (2H, m), 2.31–2.28 (4H, m), 2.08–1.94 (7H, m), 1.66 (3H,
s), 1.63 (3H, s), 1.59 (3H, s), 1.13 (3H, s), 1.07 (3H, s), 0.91 (3H, s); IR
(neat) 2926, 1653, 1618, 1504, 1452, 1377, 1298, 1242, 1161, 1140,
748 cmꢁ1; m/z (EI) 461 (Mþ, 100), 393 (32), 392 (89), 324 (49), 322
(28), 283 (14), 282 (48), 270 (16), 269 (29), 184 (23), 149 (28), 144
(210), 69 (18); HRMS m/z (Mþ) calcd for C31H43NO2: 461.3294.
Found: 461.3291.
9.0 Hz), 2.86 (3H, s), 2.53–2.47 (1H, m), 1.53 (3H, s), 1.15 (3H, s); 13
C
NMR (75 MHz, CDCl3) d 179.8, 179.0, 161.7, 146.5, 134.7, 132.6, 130.9,
130.5, 129.7, 128.6, 127.4, 124.6, 123.7, 117.8, 114.6, 110.9, 82.5, 51.0,
40.3, 38.7, 30.5, 28.2, 23.4; IR (neat) 2930, 1647, 1602, 1568, 1502,
1454, 1373, 1290, 1122, 1089, 735 cmꢁ1; m/z (EI) 359 (Mþ, 100), 358
(30), 317 (19), 316 (72), 304 (19), 274 (21), 259 (31), 231 (21), 203
(17), 186 (30), 144 (41), 120 (27); HRMS m/z (Mþ) calcd for
C
23H21NO3: 359.1521. Found: 359.1518.
3.6.10. Compound 28
Acknowledgements
A reaction of compound 6 (112 mg, 1.0 mmol) with N-methyl-N-
geranyl-2-aminobenzaldehyde (4) (543 mg, 2.0 mmol) in refluxing
xylene (10 mL) for 24 h and purification by column chromatogra-
phy on silica gel (hexane/ethyl acetate, 5:1) afforded compound 28
This study was supported by grant No. RTI04-01-04 from the
Regional Technology Innovation Program of the Ministry of Com-
merce, Industry, and Energy (MOCIE).

7346
Y.R. Lee, T.V. Hung / Tetrahedron 64 (2008) 7338–7346
11. Yadav, J. S.; Reddy, B. V. S.; Madhuri, C. R.; Sabitha, G. Synthesis 2001, 1065.
References and notes
12. Maiti, G.; Kundu, P. Tetrahedron Lett. 2006, 47, 5733.
13. Yadav, J. S.; Reddy, B. V. S.; Srinivas, R.; Madhuri, C.; Ramalingam, T. Synlett
2001, 240.
14. Jones, W.; Kiselyoy, A. S. Tetrahedron Lett. 2000, 41, 2309.
15. Sabitha, G.; Reddy, E. V.; Yadav, J. S. Synthesis 2001, 1979.
16. Yadav, J. S.; Reddy, B. V. S.; Venkateswara Rao, C.; Srinivas, R. Synlett 2002, 993.
17. Anniyappan, M.; Muralidharan, D.; Perumal, P. T. Tetrahedron Lett. 2003, 44,
3653.
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