Intramolecular Aza-Diels-Alder Cyclization of a Dimerized Citral with Anilines Catalyzed by InCl3

Article abstract of DOI:10.1002/jccs.201500112

A series of aza-polycyles containing octahydroacridine core were prepared via an intramolecular aza-Diels-Alder reaction of a dimerized citral with various aromatic amines. This reaction is efficiently catalyzed by InCl₃ at ambient temperature

Full text of DOI:10.1002/jccs.201500112

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Article
Intramolecular Aza-Diels-Alder Cyclization of a Dimerized Citral with Anilines
Catalyzed by InCl3
Yijang Chen, Mani Ramanathan* and Shiuh-Tzung Liu*
Department of Chemistry, National Taiwan University, 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan
(Received: Mar. 23, 2015; Accepted: Jun. 26, 2015; Published Online: Sept. 7, 2015; DOI: 10.1002/jccs.201500112)
A series of aza-polycyles containing octahydroacridine core were prepared via an intramolecular
aza-Diels-Alder reaction of a dimerized citral with various aromatic amines. This reaction is efficiently
catalyzed by InCl3 at ambient temperature to afford the corresponding cyclized products in moderate to
good yields.
Keywords: Aza-Diels-Alder Reaction; Indium chloride; Acridine.
INTRODUCTION
The hetero Diels-Alder reaction is a versatile tool for
presence of proline or NaH to yield 1,2,4-trisubstituted
cyclohexadienal 1 (Eqn. 1).21 We speculated that molecules
of this kind could serve as a suitable substrate in the aza
Diels-Alder reaction and provide molecular complexities
and structural diversities especially in a Lewis acid cata-
lyzed one pot protocol. We prepared compound 1 in a
multi-gram scale reaction under NaH promoted conditions.
the construction of hetero-polycyclic systems and complex
organic skeletons,1 especially in the intramolecular ver-
sions for construction of multiple ring systems. Among
various intramolecular cycloadditions, the aza-Diels-Alder
reaction between N-arylimines and electron rich dienophile
is a useful method for constructing nitrogen containing
heterocycles,2,3 such as tetrahydroquinolines,4 octohydro-
acridines,5 and others.6
Octahydroacridine systems are an important class of
biologically active molecules and inhibitors of gastric acid
secretion.7 The use of aza-Diels-Alder method leading to
this framework has been achieved with various Lewis acids
such as SnCl4,8 TiCl3,9 BiCl3,10 solid supported ZnCl2.11 In
addition, ionic liquids were found to efficiently accelerate
the cycloaddition.12,13
To study the intrinsic aspects of 1 towards the aza
Diels-Alder reaction, we conducted a reaction between
equimolar amounts of 1 and aniline 2a (R = H) in presence
of a catalytic amount InCl3 (20 mol%) (Scheme 1). Fortu-
nately, the tetracyclic adduct 3a was obtained as the only
isolated product with high trans-selectivity in 42% yield.
Dichloromethane was the best choice of the solvent as di-
ethyl ether, tetrahydrofuran, hexanes, were found to be less
efficient. Performing the reaction in dry acetonitrile gave a
similar yield. Structural characterization of 3a was estab-
lished by the NMR spectroscopy. 1H and 13C NMR shifts
corresponding to the octahydroacridine core were similar
to those reported data.13 Chemical shifts corresponding to
the aliphatic side chain at C-3 position are essentially simi-
lar to those in 1. Signals for the aromatic protons of 3a are
in the range of d 6.55 ~ 7.21 with the expected splitting pat-
terns. Both protons at C-1 and C-2 show a complicated
splitting pattern, indicating a long-range H-H coupling.
InCl3 has been known to be an efficient catalyst for a
variety of transformation such as Mukaiyama aldol reac-
tion,14 imino Diels-Alder reaction,15 Mannich-type reac-
tion,16 reductive Friedel-Craft alkylation,17 rearrangement
of epoxides,18 preparation and reactions of allylindium re-
agents,19 Diels-Alder reaction in water.20 Apart from these
remarkable applications, InCl3 is a readily available, eco-
nomically moderate and found to maintain its catalytic
ability even in the presence of amines and water. We herein
report the synthesis of functionalized octahydroacridine
derivatives via an efficient intramolecular aza-Diels-Alder
reaction of a dimerized citral catalyzed by InCl3.
RESULTS AND DISCUSSION
Citral is known to undergo self-condensation in the
* Corresponding author. Tel: +8862 33661661; Fax: + 8862 33668670; Email: stliu@ntu.edu.tw & Tel: +8862 33663831; Fax: +8862
33668670; Email: chemkid97@gmail.com
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Chen et al.
The trans-fusion at C-6a and C-12a was amply supported
by the H-H coupling value J = 10 Hz, which is similar to
those reported for octahydroacridines in trans isomers.13
with halogens, methoxycarbonyl, ethoxycabonyl and
acetyl groups at para-positions (entries 3f~3j) were exam-
ined and provided satisfactory yields. Naphthylamine was
readily reacted with 1 under the similar conditions, resulting
in a better yield (74%, entry 3k) probably due to the reactiv-
ity of the additional aromatic ring.
Aza-Diels-Alder reaction of 1 with anilines
Scheme 1
The efficiency of this reaction was found to be influ-
enced strongly by steric and electronic variations on the an-
iline substrates. The reactions with electron-withdrawing
functional groups such as 3,5-bis(trifluoromethyl)aniline,
2-amino-4-chlorobenzoic acid, p-nitroaniline and steri-
cally crowded 2-aminobiphenyl resulted the products in
poor yields (less than 10%).
With this result in hand, screening the scope of aryl
amines with a wide range of functional groups and sub-
stituents was investigated. As shown in the Scheme 2, vari-
ous anilines underwent the reaction smoothly to afford the
desired products. The reaction was not hampered by me-
thyl substituents at para- or the 3,5-meta positions (entries
3b, 3c). For the substrate m-toluidine yielded a regio-iso-
meric mixture in a ratio of 1: 0.7, which could not be sepa-
rated by column chromatography (entries 3d and 3d’).
We next examined the possibility for the Diels-Al-
der reaction with 3. Thus, 3a was treated with maleic an-
hydride in toluene under refluxing conditions for 12h.
Thermal Diels-Alder reaction proceeded smoothly in an
intermolecular fashion producing the pentacyclic product
4 in 31% isolated yield, thus offering a straightforward
route to generate complexity and diversity of molecules
(Eqn. 2). Characterization of the isolated pentacyclic
product 4 was unambiguously elucidated via NMR-spec-
troscopic methods. The reaction was observed to be
diastereoselctive to provide the cis-isomer exclusively.
The assignment of cis ring fusion at the newly formed ring
was established by the H-H coupling constant of 8.5 Hz
between them, as observed in Diels-Alder cycloadditions
of similar systems.22
Substrate scope with various aryl aminesa
Scheme 2
In summary, we have demonstrated a versatile proto-
col for the preparation of novel series of aza-polycyclic
compounds by means of aza Diels-Alder cycloaddition em-
ploying dimerized citral 1 as a convenient substrate. This
method describes a synthesis of octahydroacridine deriva-
tives in high trans-selectivity. The use of economically af-
fordable InCl3 makes this protocol simple, convenient, and
operationally practical. Further functionalization through
intermolecular Diels-Alder reaction increases the com-
plexity and may find application in natural product synthe-
sis and drug chemistry.
Aniline with an isopropyl group at para-position fur-
nished the corresponding adduct in 48% yield accompa-
nied with some unidentified products presumably due to
the oligomerization (entry 3e). To investigate the func-
tional group tolerance of this strategy, a series of anilines
762
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Aza-Diels-Alder Reaction
EXPERIMENTAL
1.67 (s, 3H), 1.61 (s, 3H), 1.45-1.56 (m, 4H), 1.34 (s, 3H), 1.16 (s,
3H), 0.99 (s, 3H); 13C NMR (100 MHz, CDCl3) d 142.8, 142.3,
136.7, 131.6, 131.0, 126.5, 126.4, 124.1, 117.5, 117.4, 114.8,
114.6, 49.8, 47.4, 44.2, 41.2, 37.1, 35.5, 35.2, 26.8, 26.7, 26.0,
25.7, 22.8, 20.8, 17.7; HRMS-ESI (TOF) for C26H36N [M+H]+:
calcd m/z = 362.2848, found 362.2845.
General: All aniline derivatives were purchased from
commercial sources and used without further purification. The re-
actions were performed under nitrogen atmosphere. Anhydrous
CH2Cl2 was obtained by distillation over calcium hydride imme-
diately before use. For chromatographic purification silica gel
(70-230 mm) was used. The identification of the final compounds
was confirmed by 1H-NMR, 13C-NMR and ESI-HRMS spectrom-
etry. NMR experiments were recorded on a 400 MHz instrument
using TMS as internal standard.
trans-4a,7,7,9-Tetramethyl-3-(4-methylpent-3-en-1-
yl)-4,4a,5, 6,6a,7,12,12a-octahydrobenzo[c]acridine (3b):
Brown oil (20 mg, 31%). 1H NMR (400 MHz, CDCl3) d 7.01 (s,
1H), 6.78 (d, J = 8 Hz, 1H), 6.49 (d, J = 8 Hz, 1H), 5.76 (d, J = 6
Hz, 1H), 5.67 (m, 1H), 5.11 (m, 1H), 3.85 (bs, 1H, -N-H), 3.73 (d,
J = 9.2 Hz, 1H), 2.22 (s, 3H), 2.10-2.15 (m, 5H), 1.80-1.84 (m,
1H), 1.73-1.76 (m, 1H), 1.67 (s, 3H), 1.61 (s, 3H), 1.43-1.48 (m,
4H), 1.33 (s, 3H), 1.15 (s, 3H), 1.00 (s, 3H); 13C NMR (100
MHz,): d 142.5, 140.4, 136.7, 131.6, 131.1, 127.2, 127.0, 126.5,
124.1, 117.5, 115.2, 114.8, 49.8, 47.6, 44.2, 41.1, 37.1, 35.5, 35.2,
27.1, 27.0, 26.0, 25.7, 22.8, 20.8, 20.7, 17.8; HRMS-ESI (TOF)
for C27H38N [M+H]+: calcd m/z = 376.3004, found 376.3006.
trans-4a,7,7,8,10-Pentamethyl-3-(4-methylpent-3-en-
1-yl)-4,4a, 5,6,6a,7,12,12a-octahydrobenzo[c]acridine (3c):
Orange oil (30 mg, 44%). 1H NMR (400 MHz, CDCl3) d 6.33 (s,
1H), 6.29 (s, 1H), 5.75 (dd, J = 5.6, 2.4 Hz, 1H), 5.67 (m, 1H),
5.11 (m, 1H), 3.67 (d, J = 10.4 Hz, 1H), 2.44 (s, 3H), 2.17 (s, 3H),
2.07-2.12 (m, 5H), 1.74-1.78 (m,1H), 1.72-1.73 (m, 1H), 1.67 (s,
3H), 1.62 (s, 3H), 1.53-1.56 (m, 4H), 1.45 (s, 3H), 1.27 (s, 3H),
0.97 (s, 3H); 13C NMR (100 MHz) d 143.8, 142.4, 137.3, 136.8,
135.8, 131.6, 126.6, 124.1, 123.9, 117.5, 114.8, 114.7, 50.1, 48.7,
43.8, 40.7, 37.1, 36.3, 35.0, 26.5, 26.0, 25.7, 23.7, 23.6, 22.8,
20.5, 20.4, 17.8; HRMS-ESI (TOF) for C28H40N [M+H]+: calcd
m/z = 390.3161, found 390.3163.
Preparation of 6-methyl-4,6-bis(4-methyl-3-penenyl)-
1,3-cyclohexadiene-1-carboxaldehyde (1): To a solution of so-
dium hydride (60% in mineral oil, 700 mg, mmol) in anhydrous
diethyl ether (100 mL) was added citral (5.6 mL, 32.8 mmol)
slowly under nitrogen atmosphere. After being refluxed for 30
min, the reaction mixture was allowed to stir at room temperature
for 2 h. The mixture was quenched with ice water and extracted
with ether (2 ´ 30 mL). The organic extracts were washed with
brine (30 mL) and dried over anhydrous MgSO4 before being con-
centrated under reduced pressure. Further purification by flash
column chromatography yielded the title compound 1 (4.0 g,
96%) as viscous oil. IR (KBr): 1670 cm-1 (nco); H NMR (400
1
MHz, CDCl3) d 9.34 (s, 1H), 6.59 (d, J = 5.7 Hz, 1H), 5.85 (d, J =
5.7 Hz, 1H), 4.96-5.03 (m, 2H), 2.26-2.31 (m, 1H), 2.22-2.12 (m,
3H), 1.93-1.97 (m, 1H), 1.70-1.85 (m, 4H), 1.61 (s, 3H), 1.58 (s,
3H), 1.54 (s, 3H), 1.46 (s, 3H), 1.27-1.33 (m, 1H), 1.12 (s, 3H);
13C NMR (100 MHz, CDCl3) d 17.5, 17.7, 23.8, 25.2, 25.6 (3C),
36.2, 37.7, 38.3, 41.9, 117.9, 123.2, 124.7, 131.1, 132.3, 141.4,
145.8, 150.7, 193.2. The spectral data are similar to the reported
ones.23
General procedure for the aza Diels-Alder adducts:
InCl3 (0.2 eq.) was added to a mixture of 1 (1 eq.) and appropriate
aniline (1.0 eq.) in anhydrous CH2Cl2 (5 mL). The reaction mix-
ture was stirred at room temperature for 17-19 h. On completion
as indicated by TLC, the reaction mixture was quenched with wa-
ter and extracted with CH2Cl2 (3 ´ 5 mL). The organic layer was
dried over anhydrous MgSO4 before being concentrated under re-
duced pressure. The crude product was purified by silica gel flash
column chromatography with elution of ethyl acetate: hexane
(0:1 to 1:6) containing 1% triethylamine.
trans-4a,7, 7,10-Tetramethyl-3-(4-methylpent-3-en-1-
yl)-4, 4a, 5,6,6a,7, 12,12a-octahydrobenzo[c]acridine (3d):
Yellow oil (35.7 mg, 55%): a regioisomeric mixture in 1:0.7 ra-
tio). Major isomer:1H NMR (400 MHz, CDCl3) d 7.10 (d, J = 7.8
Hz, 1H),6.49 (dd, J = 7.8, 1.2 Hz, 1H), 6.40 (s, 1H), 5.74 (dd, J =
5.6, 1.5 Hz, 1H), 5.66 (dd, J = 5.6, 1.5 Hz, 1H), 5.10 (m, 1H), 3.96
(bs, 1H, - N-H), 3.75 (d, J = 10.2 Hz, 1H), 2.20 (s, 3H), 2.09-2.15
(m, 5H), 1.78-1.81(m, 1H),1.71-1.75 (m, 1H), 1.67 (s, 3H), 1.60
(s, 3H), 1.40-1.55 (m, 4H), 1.32 (s, 3H), 1.13 (s, 3H), 0.97 (s, 3H);
13C NMR (100 MHz) d 143.9, 142.7, 137.4, 131.6, 128.3, 127.9,
126.4, 124.1, 118.4, 117.5, 115.4, 114.8, 49.9, 47.6, 44.2, 41.2,
37.1, 35.3, 35.2, 29.7, 26.8, 26.0, 25.6, 22.8, 20.9, 20.8, 17.7;
Minor isomer:1H NMR (400 MHz, CDCl3) d 6.84 (t, J = 7.4 Hz,
1H), 6.50 (d, J = 7.4 Hz, 1H), 6.43 (d, J = 7.4 Hz, 1H), 5.75 (d, J =
5.7 Hz, 1H), 5.66-5.67 (m, 1H), 5.08-5.12 (m, 1H), 3.95 (bs, 1H,
-N-H), 3.69 (d, J = 10.6 Hz, 1H), 2.49 (s, 3H), 2.04-2.18 (m, 5H),
1.85-1.87 (m, 1H), 1.72-1.74 (m, 1H), 1.65 (s, 3H), 1.62 (s, 3H),
trans-4a,7,7-Trimethyl-3-(4-methylpent-3-en-1-yl)-4,4a,
5,6,6a, 7,12,12a-octahydrobenzo[c]acridine (3a): Brown oil
(26.3 mg, 42%).1H NMR (400 MHz, CDCl3) d 7.21 (dd, J = 7.8,
1.2 Hz, 1H), 6.96 (dt, J = 8, 1.2 Hz, 1H), 6.66 (td, J = 8, 1.2 Hz,
1H), 6.55 (dd, J = 8, 1.2 Hz, 1H), 5.76 (dd, J = 5.6, 2 Hz, 1H), 5.67
(m, 1H), 5.11 (m, 1H), 4.00 (bs, 1H, -N-H), 3.76 (d, J = 10 Hz,
1H), 2.07-2.19 (m, 5H), 1.81-1.83 (m, 1H), 1.73-1.77 (m, 1H),
J. Chin. Chem. Soc. 2015, 62, 761-765
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1.50-1.60 (m, 4H), 1.45 (s, 3H), 1.28 (s, 3H), 0.99 (s, 3H); 13C
NMR (100 MHz, CDCl3) d 142.3, 141.5, 137.4, 136.8, 131.6,
127.5, 126.3, 124.1, 122.8, 117.5, 114.8, 114.3, 50.1, 48.7, 43.8,
40.7, 37.1, 36.5, 36.3, 35.0, 29.7, 26.4, 26.0, 23.5, 22.8, 20.5,
17.5; HRMS-ESI (TOF) for C27H38N [M+H]+: calcd m/z =
376.3004, found 376.3006.
(3h): Yellow oil (27.5 mg, 39%).1H NMR (400 MHz, CDCl3) d
7.90 (d, J = 1.6 Hz, 1H), 7.59 (dd, J = 8, 1.6 Hz, 1H), 6.49 (d, J = 8
Hz, 1H), 5.69 (m, 1H), 5.66 (m, 1H), 5.09 (m, 1H), 4.65 (bs, 1H,
-N-H), 3.82 (d, J = 10.4 Hz, 1H), 2.47 (s, 3H), 2.09-2.17 (m, 5H),
1.83-1.88 (m, 1H), 1.71-1.81 (m, 1H), 1.66 (s, 3H), 1.60 (s, 3H),
1.41-1.47 (m, 4H), 1.39 (s, 3H), 1.11 (s, 3H), 0.99 (s, 3H); 13C
NMR (100 MHz) d 196.4, 147.3, 141.5, 137.2, 131.6, 129.7,
128.5, 127.1, 126.5, 124.0, 117.1, 114.3, 113.2, 50.2, 46.9, 44.3,
41.5, 37.0, 35.3, 26.0 (2C), 25.9, 25.8, 25.7, 23.0, 22.9, 20.9,
17.7; HRMS-ESI (TOF) for C28H38NO [M+H]+: calcd m/z =
404.2953, found 404.2959.
trans-9-Isopropyl-4a,7,7-trimethyl-3-(4-methylpent-
3-en-1-yl)-4,4a,5,6,6a,7,12,12a-octahydrobenzo[c]acridine (3e):
Dark brown oil (34 mg, 48%). 1H NMR (400 MHz, CDCl3) d 7.06
(s, 1H), 6.85 (d, 1H, J = 8 Hz), 6.53 (d, 1H, J = 8 Hz), 5.77 (dd, J =
2, 5.6 Hz, 1H), 5.66 (m, 1H), 5.11 (m, 1H), 3.74 (d, J = 10 Hz,
1H), 2.79 (septet, J = 6.8 Hz, 1H), 2.07-2.19 (m, 5H), 1.79-1.88
(m, 1H), 1.72-1.76 (m, 1H), 1.68 (s, 3H), 1.62 (s, 3H), 1.44-1.50
(m, 4H), 1.32 (s, 3H), 1.19 (d, J = 6.8 Hz, 6H), 1.16 (s, 3H), 0.98
(s, 3H); 13C NMR (100 MHz, CDCl3): d 142.8, 141.0, 138.1,
136.9, 131.8, 131.2, 124.8, 124.6, 124.4, 117.8, 115.3, 114.9,
50.1, 47.9, 44.4, 41.4, 41.3, 37.3, 35.9, 35.5, 33.7, 27.2 (2C), 26.3,
26.0, 24.6, 23.1, 21.1, 18.0; HRMS-ESI (TOF) for C29H42N
[M+H]+: calcd m/z = 404.3317, found 404.3319.
trans-Methyl-4a,7,7-trimethyl-3-(4-methylpent-3-en-
1-yl)-4,4a, 5,6,6a,7,12,12a-octahydrobenzo[c]acridine-9-car-
boxylate (3i): Yellow oil (36.4 mg, 50%). IR (KBr): 1706 cm-1
(nco); 1H NMR (400 MHz, CDCl3) d 7.92 (d, J = 1.6 Hz, 1H), 7.64
(dd, J = 8, 1.6 Hz, 1H), 6.49 (d, J = 8 Hz, 1H), 5.69 (m, 1H), 5.66
(m, 1H), 5.09 (m, 1H), 4.54 (bs, 1H, -N-H), 3.82 (s, 3H), 3.81 (m,
1H), 2.09-2.17 (m, 5H), 1.82-1.87 (m, 1 H), 1.76-1.77 (m, 1H),
1.67 (s, 3H), 1.60 (s, 3H), 1.42-1.50 (m, 4H), 1.36 (s, 3H), 1.11 (s,
3H), 0.98 (s, 3H); 13C NMR (100 MHz) d 167.6, 147.0, 141.6,
137.1, 131.6, 129.6, 128.8, 128.3, 124.0, 117.9, 117.2, 114.3,
113.5, 51.4, 50.1, 46.9, 44.3, 41.5, 37.0, 37.0, 35.3, 26.0, 26.0,
25.9, 25.7, 22.8, 20.9, 17.7; HRMS-ESI (TOF) for C28H38NO
[M+H]+: calcd m/z = 420.2903, found 420.2900.
trans-9-Chloro-4a,7,7-trimethyl-3-(4-methylpent-3-
en-1-yl)-4,4a, 5,6,6a,7,12,12a-octahydrobenzo[c]acridine (3f):
Yellow oil (32 mg, 46%). 1H NMR (400 MHz, CDCl3) d 7.14 (d, J
= 2.4 Hz, 1H), 6.90 (dd, J = 8.4, 2.4 Hz, 1H), 6.47 (d, J = 8.4 Hz,
1H), 5.72 (dd, J = 5.6, 2 Hz, 1H), 5.66 (m, 1H), 5.10 (m, 1H), 4.02
(bs, 1H, -N-H), 3.73 (d, J = 10.4 Hz, 1H), 2.10-2.17 (m,
5H),1.79-1.85 (m, 1H), 1.73-1.79 (m, 1H), 1.67 (s, 3H), 1.60 (s,
3H), 1.46-1.58 (m, 4H), 1.30 (s, 3H), 1.14 (s, 3H), 0.97 (s, 3H);
13C NMR (100MHz) d 142.0, 141.4, 136.9, 132.6, 131.6, 126.4,
126.3, 124.0, 121.8, 117.4, 115.9, 114.7, 49.9, 47.0, 44.2, 41.2,
37.1, 35.7, 35.2, 26.6, 26.5, 26.0, 25.7, 22.8, 20.8, 17.8;
HRMS-ESI (TOF) for C26H35NCl [M+H]+: calcd m/z = 396.2458,
found 396.2448.
trans-Ethyl 4a,7,7-trimethyl-3-(4-methylpent-3-en-1-
yl)-4, 4a,5, 6,6a,7,12,12a-octahydrobenzo[c]acridine-9-car-
boxylate (3j): Yellow oil (27.4 mg, 50%). IR (KBr): 1711 cm-1
(nco); 1H NMR (400 MHz, CDCl3) d 7.93 (d, J = 1.6 Hz, 1H), 7.65
(dd, J = 8, 1.6 Hz, 1H), 6.49 (d, J = 8 Hz, 1H), 5.70 (d, J = 5.6 Hz,
1H), 5.65 (m, 1H), 5.09 (m, 1H), 4.51 (s, 1H, -N-H), 4.29 (q, J =
7.2 Hz, 2H), 3.81 (d, J = 10.4 Hz, 1H), 2.09-2.17 (m, 5H),
1.85-1.88 (m, 1H), 1.75-1.82 (m, 1H), 1.67 (s, 3H), 1.60 (s, 3H),
1.42-1.54 (m, 4H), 1.38 (s, 3H), 1.36 (t, J = 7.2 Hz, 3H), 1.12 (s,
3H), 0.99 (s, 3H); 13C NMR (100 MHz) d 167.1, 146.9, 141.7,
137.1, 131.6, 129.7, 128.7, 128.3, 127.2, 124.0, 117.2, 114.4,
113.5, 60.1, 50.1, 47.0, 44.3, 41.5, 37.0, 37.0, 35.3, 26.1, 26.0,
25.9, 25.7, 22.9, 20.9, 17.7, 14.5; HRMS-ESI (TOF) for
C29H40NO2 [M+H]+: calcd m/z = 434.3059, found 434.3062.
trans-4a,7,7-Trimethyl-3-(4-methylpent-3-en-1-yl)-4,4a,
5,6,6a, 7,14,14a-octahydrodibenzo[c,h]acridine (3k): Brown
oil (53.2 mg, 74%). 1H NMR (400 MHz, CDCl3) d 7.89 (d, J = 8
Hz, 1H), 7.73 (d, J = 8 Hz, 1H), 7.36-7.44 (m, 1H), 7.36-7.44 (m,
1H), 7.36-7.44 (m, 1H), 7.23 (d, J = 8 Hz, 1H), 6.10 (dd, J = 5.6,
1.6 Hz, 1H), 5.77 (m, 1H), 5.15 (m, 1H), 4.45 (bs,1H, -N-H), 3.87
(d, J = 9.6 Hz, 1H), 2.14-2.26 (m, 5H), 1.86-1.88 (m, 1H), 1.70 (s,
3H), 1.64 (s, 3H), 1.48-1.61 (m, 4H), 1.41 (s, 3H), 1.25 (s, 3H),
1.05 (s, 3H); 13C NMR (100MHz) d 142.6, 137.0, 136.8, 132.6,
trans-9-Bromo-4a,7,7-trimethyl-3-(4-methylpent-3-
en-1-yl)-4, 4a,5,6,6a,7,12,12a-octahydrobenzo[c]acridine
(3g): Yellow oil (36.5 mg, 48%). 1H NMR (400 MHz, CDCl3) d
7.27 (d, J = 2.4 Hz, 1H), 7.03 (dd, J = 8, 2.4 Hz, 1H), 6.43 (d, J = 8
Hz, 1H), 5.72 (dd, J = 5.6, 2 Hz, 1H), 5.66 (m, 1H),5.10 (m, 1H),
4.04 (bs, 1H, -N-H), 3.73 (d, J = 10 Hz, 1H), 2.09-2.32 (m, 5H),
1.79-1.82 (m, 1H), 1.73-1.77 (m, 1H), 1.67 (s, 3H), 1.60 (s, 3H),
1.38-1.53 (m, 4H), 1.31 (s, 3H), 1.12 (s, 3H), 0.97 (s, 3H); 13C
NMR (100 MHz) d 141.9, 141.8, 137.0, 133.1, 131.6, 129.3,
129.1, 124.0, 117.4, 116.4, 114.7, 108.9, 49.9, 47.0, 44.2, 41.2,
37.1, 35.7, 35.2, 26.6, 26.5, 26.0, 25.7, 22.7, 20.8, 17.8;
HRMS-ESI (TOF) for C26H35NBr [M+H]+: calcd m/z = 440.1953,
found 440.1945.
trans-4a,7,7-Trimethyl-3-(4-methylpent-3-en-1-yl)-4,
4a,5,6,6a, 7,12,12a-octahydrobenzo[c]acridin-9-yl)ethanone
764
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J. Chin. Chem. Soc. 2015, 62, 761-765

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Aza-Diels-Alder Reaction
1999, 40, 7211. (d) Motorina, I. A.; Grierson, D. S. Tetrahe-
dron Lett. 1999, 40, 7215. (e) Boruah, R. C.; Ahmed, S.;
Sharma, U.; Sandhu, J. S. J. Org. Chem. 2000, 65, 922.
4. (a) Povarov, L. S. Russ. Chem. Rev. 1967, 36, 656. (b)
Makioka, Y.; Shindo, T.; Taniguchi, Y.; Takaki, K.; Fujiwara,
Y. Synthesis 1995, 801. (c) Yamanaka, M.; Nishida, A.;
Nakagana, M. Org. Lett. 2000, 2, 159. (e) Ishitani, H.;
Kobayashi, S. Tetrahedron Lett. 1996, 37, 7357. (d) Grieco,
P. A.; Bahsas, A. Tetrahedron Lett. 1988, 29, 5855. (e)
Bortolotti, B.; Leardini, R.; Nanni, D.; Zanardi, G. Tetrahe-
dron 1993, 49, 10157.
131.6, 128.2, 125.6, 125.2, 125.1, 124.9, 124.1, 124.0, 120.1,
117.8, 117.6, 115.3, 49.8, 47.6, 44.3, 41.1, 37.1, 35.8, 35.4, 27.3,
26.7, 26.0, 25.7, 22.7, 20.8, 17.8; HRMS-ESI (TOF) for C30H38N
[M+H]+: calcd m/z = 412.3004, found 412.3003.
trans-5a,8,8-Trimethyl-4-(4-methylpent-3-en-1-yl)-3a,
4,5,5a,6, 7,7a,8, 13,13a-decahydro-4,13b-ethenoisobenzofuro
[5,4-c]acri-dine-1,3-dione (4): A mixture of 3a (42 mg, 0.121
mmol) and maleic anhydride (15 mg, 0.157 mmol) in anhydrous
toluene (2 mL) was heated under refluxing for 12h. Solvent was
removed under reduced pressure and the crude product was puri-
fied by silica gel column chromatography to give 4 as a sponge
material (17 mg, 31%). 1H NMR (400 MHz, CDCl3) d 7.12 (d, J =
7.8 Hz, 1H), 6.90 (dt, J = 7.8, 1.4 Hz, 1H), 6.55 (dt, J = 8.2, 1.4
Hz, 1H), 6.51 (d, J = 8.2 Hz, 2H), 6.25 (bs, 1H), 5.90 (d, J = 8.2,
1H), 5.10 (t, J = 7 Hz, 1H), 3.76 (d, J = 10.2 Hz, 1H), 3.48 (d, J =
8.5 Hz, 1H), 3.07 (d, J = 8.5 Hz, 1H), 2.09-2.19 (m, 1H),
1.90-1.98 (m, 1H), 1.77-1.83 (m, 2H), 1.64 (s, 3H, Me), 1.60-1.61
(m, 3H), 1.58 (s, 3H, Me), 1.35-1.38 (m, 2H), 1.29-1.32 (m, 2H),
1.27 (s, 3H), 1.12 (s, 3H), 1.11 (s, 3H); 13C NMR (400 MHz,
CDCl3) d 175.7, 169.6, 143.9, 133.8 (2C), 132.2, 129.9, 126.7,
125.6, 123.7, 116.76, 114.86, 51.9, 51.3, 49.6, 49.0, 48.1, 44.7,
40.7, 40.5, 37.7, 35.4, 35.0, 26.9, 26.6, 25.7, 25.2, 22.7, 19.9,
17.7; HRMS-ESI (TOF) for C30H38NO3 [M+H]+: calcd m/z =
460.2852, found 460.2846.
5. (a) Temme, O.; Laschat, S. J. Chem. Soc. Perkin Trans 1
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ACKNOWLEDGEMENTS
We thank the Ministry of Science and Technology,
Taiwan for the financial support (MOST103-2113-M-
002-002-MY3) and undergraduate research project.
13. Yadav, J. S.; Reddy, B. V. S.; Chetia, L.; Srinivasulu, G.;
Kunwar, A. C. Tetrahedron Lett. 2005, 46, 1039.
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J. Chin. Chem. Soc. 2015, 62, 761-765
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