The First Domino Reduction/Imine Formation/Intramolecular Aza-Diels–Alder Reaction for the Diastereoselective Preparation of Tetrahydrochromano[4,3-b]quinolines

Article abstract of DOI:10.1002/ejoc.201600976

The first domino reduction/imine formation/intramolecular aza-Diels–Alder reaction is reported. Tetrahydrochromano[4,3-b]quinolines are formed with high exo-E-anti selectivity and yields up to 87 % when a nitrobenzene and a 2-(cinnamyloxy)benzaldehyde are reacted in aqueous citric acid by using iron as a reductant and montmorillonite K10 as a catalyst. The domino process starts with the in situ reduction of the nitrobenzene to the corresponding aniline, which is followed by imine formation and terminated by an intramolecular aza-Diels–Alder reaction.

Full text of DOI:10.1002/ejoc.201600976

A Journal of
Accepted Article
Title: The First Domino Reduction / Imine Formation / Intramolecular Aza-Diels-Alder
Reaction for the Diastereoselective Preparation of Tetrahydrochromano[4,3-
b]quinolines
Authors: Hans-Georg Imrich; Uwe Beifuss; Ju¨rgen Conrad
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201600976
Link to VoR: http://dx.doi.org/10.1002/ejoc.201600976
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European Journal of Organic Chemistry
10.1002/ejoc.201600976
FULL PAPER
The First Domino Reduction / Imine Formation / Intramolecular
Aza-Diels–Alder Reaction for the Diastereoselective Preparation
of Tetrahydrochromano[4,3-b]quinolines
Hans-Georg Imrich,[a] Jürgen Conrad,[a] and Uwe Beifuss*[a]
Dedicated to Professor Junjappa Hiriyakkanavar on the occasion of his 80th birthday
The first domino reduction / imine formation / intramolecular aza-
Diels–Alder reaction is reported. Tetrahydrochromano[4,3-
b]quinolines are formed with high exo-E-anti selectivity and with
yields up to 87% when a nitrobenzene and a 2-(cinnamyloxy)-
benzaldehyde are reacted in aqueous citric acid using iron as a
reductant and montmorillonite K10 as a catalyst. The domino
process starts with the in situ reduction of the nitrobenzene to the
corresponding aniline, is followed by imine formation and terminated
by an intramolecular aza-Diels–Alder reaction.
activity against MDA-MB-231 and MCF-7 breast cancer cell
lines.[19]
The synthesis of tetrahydroquinolines can be achieved by
numerous methods, including the domino reduction
/
intramolecular reductive amination of 2-nitroarylketones,[20c] the
domino reduction / intramolecular Michael addition of ω-(2-
nitroaryl) substituted α,β-unsaturated esters[20b,d] and the
reductive cyclization of 2-nitrochalcones.[20a] Another important
method for the construction of tetrahydroquinolines is the aza-
Diels–Alder reaction of electron poor 2-azabutadienes with
electron rich dienophiles. This transformation which is also
known as the Povarov reaction allows for the efficient and
selective preparation of tetrahydroquinolines and related
skeletons.[21,22] Since the required 2-azabutadienes are rather
sensitive to moisture,[23] it is advantageous when they are
prepared in situ. This can be achieved for example by reacting
an aniline with a carbonyl compound in the presence of the
dienophile under the conditions of the Povarov reaction.[21,22]
This three component reaction can be catalysed / promoted by
numerous Brønsted[22a–c] and Lewis acids[22d–g] to deliver the
resulting tetrahydroquinolines. Since anilines are usually
obtained from the corresponding nitrobenzenes by reduction[24]
and many anilines are known to be sensitive towards
oxidation[25] it is highly attractive to combine the reduction of the
nitrobenzenes to the anilines, their condensation with carbonyls
to imines and their intermolecular Povarov reaction with
dienophiles to a one-pot reaction.
Introduction
N-Heterocycles are structural motifs of a great number of
natural as well as unnatural biologically active compounds.[1]
This is the reason for the continuing interest in the development
of new and efficient methods for their selective synthesis.[2]
Among others, N-heterocycles can be constructed by reductive
cyclization of nitro compounds.[3–16] Initially, reduction of the nitro
group occurs and forms a nitroso group and/or a nitrene, an N-
hydroxylamino or an amino group as an intermediate. This is
followed by the actual ring closure. Using nitro compounds as
substrates, numerous five membered N-heterocycles such as
pyrroles,[3] pyrrolidin-2-ones,[4] pyrrolin-N-oxides,[5] indoles,[6]
indeno[1,2-b]indoles,[7] carbazoles,[8] hexahydrocarbazoles,[9]
2H-indazoles,[10] and isoxazolidines,[11] can be synthesized.
Among the best known methods for the synthesis of indoles, for
example, are the indole syntheses according to Leimburger-
Batcho,[6d] Bartoli and Reissert,[6a] the transition metal catalysed
reductive N-heteroannulation of o-nitrostyrenes[6b,c] and the
Cadogan cyclization.[6e] Six membered N-heterocycles such as
dihydropyridin-4-ones,[12] quinolines,[13] tetrahydroquinolines,[14]
tetrahydroquinoxalines[15] and dihydrobenzoxazines[16] can also
be obtained by reductive cyclizations of nitroaromatics.
Recently, we have reported that this type of three-
component reaction between a nitrobenzene, a benzaldehyde
and cyclopentadiene can be achieved (Scheme 1a).[26] The
reactions were performed in aqueous citric acid under mild
reaction conditions using iron as a reductant and montmorillonite
K10 as a catalyst and delivered the products of a domino
reduction / imine formation / intermolecular aza-Diels–Alder
reaction with high endo-selectivities and high yields.
The preparation of tetrahydroquinolines and related ring
systems is particularly relevant, because many compounds with
this skeleton display pronounced biological activities.[17] In
addition, tetrahydroquinolines are also of interest for several
industrial applications.[18]
We wondered whether it is also possible to combine the in
situ reduction of a nitrobenzene to an aniline with the reaction of
an ω-unsaturated aldehyde to an imine and its subsequent
intramolecular aza-Diels–Alder reaction. Here, we present the
first examples of the domino reduction / imine formation /
intramolecular aza-Diels–Alder reaction (Scheme 1b).
A number of tetrahydroquinoline derivatives, namely the
tetrahydrochromano[4,3-b]quinolines, show antiproliferative
[a]
Bioorganische Chemie, Institut für Chemie, Universität Hohenheim,
Garbenstraße 30, D-70599 Stuttgart, Germany
E-mail: ubeifuss@uni-hohenheim.de
https://bioorganische-chemie.uni-hohenheim.de/
Supporting information for this article is available on the WWW under
http://dx.doi.org/xx.xxx/ejoc.xxxxxxxxx.
1
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European Journal of Organic Chemistry
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FULL PAPER
(a) Our previous work:
Reduction
Fe, citric acid
m ontmorillonite K10
O
Imine formation
H
H
Intermolecular
Povarov Reaction
OHC
O
H2
O
H
+
H
+
R2
N
N
H
NO2
H
H
H
O
R2
R1
NO2
R1
1a
2a
3a
Table 1. Optimization of the reaction conditions of the montmorillonite K10-
Reduction
catalyzed
reaction
between
nitrobenzene
(1a)
and
2-
Ph
(cinnamyloxy)benzaldehyde (2a).[a]
(b) This work:
Imine formation
Intramolecular
Povarov Reaction
H
H
Ph
O
O
OHC
Yield of 3a
Entry
Fe
Citric
Clay
T
Time
N
H
+
R1
[equiv.]
acid
[wt-%]
[°C]
[h]
[%]
R1
NO2
R2
R2
[equiv.]
Scheme 1. Intermolecular and intramolecular versions of the Povarov reaction
using nitrobenzenes as substrates.
1
4
4
4
4
4
4
4
4
3
-
4
4
4
4
4
4
4
4
3
4
-
10
10
10
10
10
10
10
7
40
60
70
80
80
80
100
80
80
80
80
80
4
4
4
2
3
4
4
4
4
4
4
4
2
73
82
78
86
87
85
81
84
-
2
3
Results and Discussion
4
The reaction between nitrobenzene (1a) and 2-
(cinnamyloxy)benzaldehyde (2a) to the tetrahydrochromano[4,3-
b]quinoline 3a was used to demonstrate the feasibility of this
transformation. The reason was that the corresponding
transformation between aniline (4a) and 2-(cinnamyloxy)-
benzaldehyde (2a) in the presence of an excess of a strong
Brønsted acid (10 equiv. trifluoroacetic acid) in an organic
solvent (acetonitrile) is known to deliver 3a.[27a] In order to
establish that the imine formation / aza-Diels–Alder reaction
between aniline (4a) and 2a to the tetrahydrochromano[4,3-
b]quinoline 3a can also be catalysed by montmorillonite K10,
equimolar amounts of 4a and 2a were reacted with
montmorillonite K10 (10 wt-%) in aqueous citric acid for 4 h at
40 °C. The cycloadduct 3a was formed; its yield, however,
amounted to only 3%. Despite of the disappointingly low yield of
the experiment with aniline (4a), the reaction between equimolar
amounts of nitrobenzene (1a) and the aldehyde 2a in the
presence of Fe (4 equiv.) as reductant and montmorillonite K10
(10 wt-%) as catalyst in aqueous citric acid for 4 h at 40 °C was
performed. The positive result of this experiment was that the
desired cycloadduct 3a was formed at all. However, the yield of
3a was only 2% (Table 1, entry 1). After some experimentation,
we found that the yield of 3a could be improved dramatically by
simply raising the reaction temperature. Already at 60 °C the
yield of 3a amounted to 73% (Table 1, entry 2). A further
improvement of the yield to 82% and 87% could be achieved by
increasing the reaction temperature to 70 °C and 80 °C (Table 1,
entries 3 and 6). However, a further increase of the reaction
temperature to 100 °C had no positive effect on the outcome of
the transformation (Table 1, entry 7). Next, the reaction time was
shortened. While a reduction of the reaction time from 4 h to 3 h
had no significant effect on the yield, it decreased to 78% upon
halving the reaction time (Table 1, entries 4 and 5). Further
experiments addressed the reduction of the amount of
montmorillonite K10 to 7 wt-% (Table 1, entry 8) and that of citric
acid to 3 equiv. (Table 1, entry 9). Under both conditions, the
yields were higher than 80%, but the yield of Table 1, entry 6
could not be exceeded.
5
6
7
8
9
13
13
20
-
10
11
12
4
4
-
4
-
[a] Reactions were performed using 2 mmol of nitrobenzene (1a) and 2 mmol
of 2a in 15 mL aqueous citric acid in a sealed flask (25 mL).
Finally, three control experiments established that the
cycloadduct was not formed at all in the absence of a) Fe, b)
montmorillonite K10 and c) citric acid (Table 1, entries 10–12).
The results from the control experiments support the assumption
that the reduction of nitrobenzene (1a) to aniline (4a) is achieved
using Fe as reducing reagent in combination with citric acid as
chelating agent under aqueous conditions. Aniline then reacts
with the unsaturated aldehyde 2a to the corresponding imine,
which undergoes a montmorillonite K10-catalyzed Povarov
reaction to the cycloadduct 3a. In summary, the
tetrahydrochromano[4,3-b]quinoline 3a could be obtained in
diastereomerically pure form in 87% yield by reacting
nitrobenzene (1a) and 2-(cinnamyloxy)benzaldehyde (2a) under
the conditions of Table 1, entry 6. The optimization experiments
clearly demonstrated that the reduction of nitrobenzene (1a) to
aniline (4a), the imine formation between 4a and aldehyde 2a,
and the intramolecular aza-Diels–Alder reaction can be
combined to a one-pot process. The efficiency of the method
reported here can be seen from the fact that the yield of
cycloadduct 3a from the reaction between equimolar amounts of
aniline (4a) and 2-(cinnamyloxy)benzaldehyde (2a) in the
2
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European Journal of Organic Chemistry
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presence of 10 wt-% montmorillonite K10 as catalyst in aqueous
citric acid for 4 h at 80 °C amounts to 84%. This means that it is
in the same range as the yield of the reaction between
nitrobenzene (1a) and aldehyde 2a under the conditions of
Table 1, entry 6.
products of the domino reduction / imine formation / aza-Diels–
Alder reaction, were formed exclusively in
a
highly
diastereoselective manner with yields between 80 and 82%
(Table 2, 3j–l). It should be noticed that all reactions can be run
in an aqueous solvent system under mild conditions and that the
crude products are almost free of any side products. The
cycloadducts were obtained in high purity (~95%) after workup
and column filtration on silica gel. Analytically pure samples
were obtained by crystallization or flash chromatography.
With optimized reaction conditions at hand the influence of
the substrate structures on yield and diastereoselectivity of the
domino reaction was studied (Table 2). First, the structure of the
nitrobenzene was addressed. For this purpose, 2-(cinnamyloxy)-
benzaldehyde (2a) was reacted with a number of o- and p-
substituted nitrobenzenes 1b–i under optimized reaction
conditions. Irrespective of the substitution pattern of the
nitrobenzenes, the products of the domino reduction / imine
formation / aza-Diels–Alder reaction were isolated exclusively.
The yields of the diastereomerically pure cycloadducts were
ranging between 69% and 83% (Table 2, 3b–i). These
experiments demonstrated that the transformation tolerates a
number of substituents, including alkyl, methoxy, fluoro, chloro,
bromo, and nitrile groups in the o- and p-position of
nitrobenzenes.
H
Ph
H
H
H
reduction
O
OHC
2
imine formation
O
Ph
O
Ph
+
N
R1
R2
N
R2
R1
R1
NO2
H
H
exo-E-anti
R2
1
3
7
Scheme 2. Proposed reaction mechanism for the formation of
tetrahydrochromano[4,3-b]quinolines 3.
It is assumed that the transformations can be classified as
a domino reduction / imine formation / intramolecular aza-Diels–
Alder reaction with inverse electron demand (Scheme 2). After
selective reduction of the nitrobenzene 1, the resulting aniline 4
Fe (4 equiv.)
undergoes condensation with the aldehyde
2
to the
citric acid (4 equiv.)
montmorillonite K10 (10 wt-% )
H2O, 80 °C, 4h
Ph
corresponding imine or iminium ion. It can be assumed that they
adopt the E-configuration, since E-imines and E-iminium salts
are known to be more stable than the corresponding Z-
isomers.[28] The formation of the C=N double bond is followed by
the intramolecular aza-Diels–Alder reaction that yields the trans-
trans diastereomer with an equatorial phenyl group at C-7
exclusively. The high degree of diastereoselectivity – only one
out of four diastereomers is formed – is attributed to the fact that
the cyclization proceeds via the exo-E-anti transition state
structure 7 with an E-configuration of both the C=N bond of the
diene and the C=C bond of the dienophile.
H
H
O
+
O
OHC
R1
NO2
N
H
R1
R2
1a-i
2a-d
3b-l
R2
Table 2. Reaction of nitrobenzenes 1a-i with 2-(cinnamyloxy)benzaldehydes
2a-d.[a]
Ph
Ph
Ph
Ph
H
H
H
H
M eO
NC
O
O
O
O
N
H
N
H
N
H
N
H
H
H
H
H
3c, 73%
3d, 72%
3e, 76%
Ph
3b, 76%
Ph
Ph
Ph
H
H
H
H
H
Cl
F
Br
O
O
O
O
N
H
N
H
N
H
N
H
H
H
H
 = 2.40 ppm
(dddd, 3 x J ~ 11.0 Hz, J = 3.9 Hz)
Br
3i, 73%
3g, 78%
3h, 69%
3f, 83%
H
Ph
Ph
H
Ph
H
H
H
H
6a
Ph
O
O
O
Br
6
7
O
N
H
N
N
H
N
H
H
H
12a
H
3j, 81%
3k, 80%
3l, 82%
Br
Cl
H
H
 = 3.96 ppm
(dd, 2 x J ~ 11.1 Hz)
H
 = 3.97 ppm
(d, J = 11.8 Hz)
[a] Reactions were performed using 2 mmol of the nitrobenzene 1, 2 mmol of
the 2-cinnamyloxybenzaldehyde 2 and 15 mL aqueous citric acid in a sealed
flask (25 mL).
 = 4.55 ppm
(d, J = 10.4 Hz)
Figure 1. Relative configuration of 3h.
In a second set of experiments the reactions between
The cyclization
products
3
were isolated in
nitrobenzene (1a) and
a number of 2-(cinnamyloxy)benz-
diastereomerically pure form by column filtration on silica gel of
the crude products followed by crystallization. In no case, an
additional diastereomer could be detected. The structures of all
Povarov products were unambiguously established by mass
spectrometry and NMR spectroscopy. The full assignment of the
1H and 13C chemical shifts was achieved by evaluating their
gCOSY, gHSQC and gHMBC spectra (Figures 1, 2). Compound
aldehydes 2a-d carrying different substituents on the benz-
aldehyde moiety were studied. The required 2-(cinnamyloxy)-
benzaldehydes 2b-d were obtained by Williamson ether
synthesis of the substituted salicylic aldehydes 5b-d with
cinnamyl chloride (6) under basic conditions in high yields (see
Experimental Section). The reactions between 1a and 2b-d were
performed under the optimized reaction conditions. Again, the
3
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European Journal of Organic Chemistry
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3h is particularly suitable for the determination of the relative
configuration of the cycloadducts since all 16 proton signals in
the 1H NMR are well separated. Analysis of the gCOSY
spectrum revealed four spin systems. In addition to three
aromatic spin systems there is one spin system consisting of the
four aliphatic protons 6-H(ax), 6-H(eq), 6a-H, 7-H and 12a-H.
The proton 6a-H resonates at δ = 2.40 ppm as dddd with
coupling constants of J = 3.9 (3J 6a-H, 6-Heq), ~ 11 (3J 6a-H, 6-Hax), ~
intramolecular aza-Diels–Alder reactions. The domino reaction
can be performed with numerous functionalized nitrobenzenes
and a number of 2-(cinnamyloxy)benzaldehydes.
11 (3J
7-H) and ~ 11 (3J
12-H) Hz. The large vicinal
6a-H,
6a-H,
Experimental Section
3
3
coupling constants J
~ 11 Hz and J
~ 11 Hz
6a-H, 12-H
6a-H, 7-H
indicate the positions of 6a-H, 7-H and 12-H as axial. This
proves the trans arrangement of both rings as well as the
equatorial position of the phenyl group at C-7 unequivocally.
General Remarks: Nitrobenzene (1a) and solvents used for extraction
and purification were distilled prior to use. Iron powder was treated with
diluted aqueous HCl, washed with water and acetone and dried in vacuo.
All other reagents were used without further purification. Reaction
temperatures are reported as bath temperatures. Thin-layer
chromatography (TLC) was performed on TLC silica gel 60 F254
.
H
Compounds were visualized with UV light ( = 254 nm) and by immersion
in a KMnO4 solution followed by heating. Products were purified by flash
chromatography on silica gel, 0.04-0.053 mm mesh (Macherey–Nagel &
Co), or by crystallization. Melting points were recorded with a Büchi B-
545 melting point apparatus with open capillary tubes and are
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
O
H
H
H
H
Br
Br
Br
O
H
O
H
uncorrected. IR spectra were measured with
a Bruker Alfa FTIR
H
H
H
H
H
H
H
N
H
N
H
H
N
H
spectrometer. UV/Vis spectra were recorded with a Varian Cary 50
instrument. 1H and 13C NMR spectra were recorded at 500/125 or 300/75
MHz using Varian Unity Inova spectrometers, with CDCl3 or CD3COCD3
as the solvents. The 1H and 13C chemical shifts were referenced to
residual signals at δH/C = 7.26/77.00 ppm (CDCl3) and δH/C = 2.05/29.9
(CD3COCD3). HSQC-, HMBC- and COSY-spectra were recorded with
Varian Unity Inova spectrometers at 300 and 500 MHz. Coupling
constants J [Hz] were directly taken from the spectra and are not
averaged. Splitting patterns are designated as s (singlet), d (doublet), t
(triplet), q (quartet), m (multiplet), app d (apparent dublett), app t
(apparent triplett) and br (broad). 1D and 2D homonuclear NMR spectra
were measured with standard pulse sequences. Copies of the NMR
spectra were prepared using SpinWorks.[29] Low-resolution electron
impact mass spectra (MS) and exact mass electron impact mass spectra
(HRMS) were obtained at 70 eV using a double focusing sector field
mass spectrometer (Finnigan MAT 95). Intensities are reported as
percentages relative to the base peak (I = 100%).
H
H
H
H
H
H
H
H
H
H
H
ROESY
HMBC
COSY
Figure 2. Selected COSY, ROESY and HMBC correlations of 3h.
HMBC- and ROESY spectra allowed for the unequivocal
assignment of all 13C NMR signals as well as the connectivities
(Figure 2). In this regard, the HMBC correlations of 11-H to C-7a,
8-H to C-11a, 7-H to C-11a, 12a-H to C-12b, 1-H to C-4a and 4-
to C-12b were particularly significant. The structural
assignment is well supported by the ROESY correlations of NH
H
to 11-H, 12a-H to 1-H, 7-H to 8-H and 7a-H to 2’-H.
General
(Cinnamyloxy)benzaldehydes
Procedure
I
for
2
the
Preparation
of
2-
5
from 2-Hydroxybenzaldehydes
Conclusions
and Cinnamyl Chloride (6): 2-Hydroxybenzaldehyde 5 (100 mmol),
cinnamyl chloride (6) (110 mmol), K2CO3 (150 mmol), KI (15 mmol) and
N,N-dimethylformamide (75 mL) were stirred at room temperature for 3d.
Then, water (100 mL) was added. The mixture was extracted with ethyl
acetate (3 × 50 mL). The combined organic layers were washed with
brine (3 × 50 mL) and water (50 mL). The solvent was removed under
reduced pressure. The residue was dissolved in dichloromethane and
filtered over silica gel. Crystallization of the crude product from i-propanol
gave analytically pure 2-(cinnamyloxy)benzaldehyde 2.
In conclusion, the domino reduction / imine formation /
intramolecular aza-Diels–Alder reaction is reported for the first
time. The reaction between nitrobenzenes and ω-unsaturated
aldehydes, i.e. 2-(cinnamyloxy)benzaldehydes, in the presence
of iron as reductant and catalytic amounts of montmorillonite
K10 in aqueous citric acid at 80 °C produces trans-fused
tetrahydrochromano[4,3-b]quinolines exclusively and with yields
between 69% and 87%. It is assumed that the sequence of
reactions starts with the iron-mediated reduction of the
nitrobenzene. The resulting aniline reacts with the ω-
unsaturated aldehyde to the corresponding imine which in turn
undergoes an intramolecular aza-Diels–Alder reaction. This
Povarov type reaction is catalysed by montmorillonite K10,
proceeds via an exo-E-anti transition state structure and delivers
the trans-fused tetrahydrochromano[4,3-b]quinolines in dia-
stereomerically pure form. The new method allows the
replacement of anilines with nitrobenzenes as substrates for
2-(Cinnamyloxy)benzaldehyde (2a):[30a] K2CO3 (20.9 g, 151.2 mmol),
KI (253 mg, 1.5 mmol), 2-hydroxybenzaldehyde (5a) (12.3 g, 101 mmol)
and cinnamyl chloride (6) (16.8 g, 110 mmol) were used according to
general procedure I. After workup, 2-(cinnamyloxy)benzaldehyde (2a)
was obtained (21.9 g, 91.9 mmol, 92 %) as a colourless solid. Rf = 0.29
(petroleum ether/dichloromethane, 1:1), m.p. 54–55 °C (ref.[30a] m.p. 51–
52 °C). 1H NMR (300 MHz, CDCl3): δ = 4.83 (dd, J = 5.7, J = 1.4 Hz, 2 H),
6.43 (dt, J = 16.0, J = 5.7 Hz, 1 H), 6.77 (dt, J = 16.0, J = 1.4 Hz, 1 H),
7.01–7.08 (m, 2 H), 7.25–7.38 (m, 3 H), 7.43 (app d, J = 8.0 Hz, 2 H),
7.55 (ddd, 2 × J ≈ 7.4, J = 1.9 Hz, 1 H), 7.87 (dd, J = 7.9, J = 1.9 Hz, 1 H),
10.58 (s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 69.1, 112.9, 120.9,
4
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European Journal of Organic Chemistry
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FULL PAPER
123.4, 125.1, 126.6, 128.1, 128.5, 128.7, 133.5, 135.8, 136.1, 161.0,
(6aRS,7SR,12aRS)-6a,7,12,12a-Tetrahydro-7-phenyl-6H-
189.8 ppm. MS (EI): m/z (%) = 238 (8) [M]+, 209 (11), 115 (100), 91 (18).
chromeno[4,3-b]quinoline (3a):[27a] Iron powder (447 mg, 8.0 mmol),
citric acid monohydrate (1.68 g, 8.0 mmol), montmorillonite K10 (305 mg),
nitrobenzene (1a) (247 mg, 2.0 mmol) and 2-(cinnamyloxy)benzaldehyde
(2a) (476 mg, 2.0 mmol) were used according to general procedure II.
After workup and column filtration on silica gel (petroleum
2-(Cinnamyloxy)-5-methylbenzaldehyde (2b):[30b] K2CO3 (2.07 g, 15.0
mmol), KI (28 mg, 0.15 mmol), 2-hydroxy-5-methylbenzaldehyde (5b)
(1.37 g, 10.1 mmol) and cinnamyl chloride (6) (1.69 g, 11.0 mmol) were
used according to general procedure I. Crystallization of the crude
product from i-propanol gave 2-(cinnamyloxy)-5-methylbenzaldehyde
(2b) (1.88 g, 7.47 mmol, 74%) as a colourless solid. Rf = 0.35 (petroleum
ether/dichloromethane
=
1:1),
(6aRS,7SR,12aRS)-6a,7,12,12a-
tetrahydro-7-phenyl-6H-chromeno[4,3-b]quinoline (3a) was obtained (545
mg, 1.74 mmol, 87%). Crystallization from methanol gave 3a in
analytically pure form as a colourless solid. Rf = 0.29 (petroleum
1
ether/dichloromethane, 1:1), m.p. 58–59 °C; H NMR (500 MHz, CDCl3):
ether/dichloromethane, 1:1), m.p. 168–170 °C. IR: = 3363, 3026, 2974,
δ = 2.32 (s, 3 H), 4.82 (dd, J = 5.7, J = 1.4 Hz, 2 H), 6.42 (dt, J = 16.0, J
= 5.7 Hz, 1 H), 6.75 (dt, J = 16.0, J = 1.5 Hz, 1 H), 6.94 (d, J = 8.5 Hz, 1
H), 7.28 (app t, J = 7.3 Hz, 1 H), 7.32–7.36 (m, 3 H), 7.42 (app d, J = 8.0
Hz, 2 H), 7.67 (d, J = 2.6 Hz, 1 H), 10.54 (s, 1 H) ppm. 13C NMR (125
MHz, CDCl3): δ = 20.2, 69.2, 113.0, 123.6, 124.8, 126.6, 128.1, 128.5,
128.6, 130.3, 133.4, 136.1, 136.5, 159.1, 189.9 ppm. MS (EI): m/z (%) =
252 (36) [M]+, 234 (29), 224 (31), 209 (27), 191 (14), 161 (26), 133 (21),
115 (100), 105 (24), 91 (32), 77 (19).
2892, 2858, 1599, 1577, 1486, 1451, 1421, 1354, 1306, 1232, 1204,
1141, 1126, 1075, 1040, 1017, 897, 856, 818, 776, 746, 724, 705, 675,
640, 625, 551, 506 cm-1. 1H NMR (500 MHz, CDCl3): δ = 2.49 (dddd, 3J6a-
3
3
3
≈ 11.2, J6a-H,6-H(ax) ≈ 11.2, J6a-H,12a-H ≈ 11.2, J6a-H,6-H(eq) = 3.8 Hz, 1
H,7-H
H, 6a-H), 3.85 (d, 3J7-H,6a-H = 11.6 Hz, 1 H, 7-H), 3.87 (dd, 2J6-H(ax),6-H(eq)
11.1, J6-H(ax),6a-H ≈ 11.1 Hz, 1 H, 6-H(ax)), 4.05 (dd, J6-H(eq),6-H(ax) ≈ 11.0,
3J6-H(eq),6a-H = 3.6 Hz, 1 H, 6-H(eq)), 4.38 (brs, 1 H, N-H), 4.50 (d, J12a-
≈
3
3
3
= 10.3 Hz, 1 H, 12a-H), 6.62–6.66 (m, 2 H, 8-H and 9-H), 6.76 (d,
H,6a-H
3J11-H,10-H = 8.0 Hz, 1 H, 11-H), 6.83 (d, 3J4-H,3-H = 8.0 Hz, 1 H, 4-H), 7.00
(dd, 3J2-H,1-H ≈ 7.6, 3J2-H,3-H ≈ 7.6 Hz, 1 H, 2-H), 7.04–7.08 (m, 1 H, 10-H),
7.16–7.22 (m, 3 H, 3-H, 2’-H and 6’-H), 7.29 (app t, J = 7.3 Hz, 1 H, 4’-H),
7.31–7.36 (m, 3 H, 1-H, 3’-H and 5’-H) ppm. 13C NMR (125 MHz, CDCl3):
δ = 41.1 (C-6a), 47.0 (C-7), 52.1 (C-12a), 67.6 (C-6), 116.0 (C-11), 117.0
(C-4), 118.9 (C-9), 120.7 (C-2), 122.6 (C-12b), 124.7 (C-1), 125.4 (C-7a),
127.1 (C-4’), 127.3 (C-10), 128.67 (C-3 or C-3’ and C-5’), 128.73 (C-3 or
C-3’ and C-5’), 129.1 (C-2’ and C-6’), 130.4 (C-8), 142.9 (C-1’), 144.4 (C-
11a), 154.1 (C-4a) ppm. MS (EI) m/z (%) = 313 (100), [M]+, 280 (14), 254
(6), 232 (37), 206 (15), 180 (12), 154 (18), 139 (12).
5-Chloro-2-(cinnamyloxy)benzaldehyde (2c):[30b] K2CO3 (3.14 g, 22.7
mmol), KI (42 mg, 0.25 mmol), 5-chloro-2-hydroxybenzaldehyde (5c)
(2.35 g, 15.0 mmol) and cinnamyl chloride (6) (2.53 g, 16.6 mmol) were
used according to general procedure I. Crystallization of the crude
product from i-propanol gave 5-chloro-2-(cinnamyloxy)benzaldehyde (2c)
(3.52 g, 12.9 mmol, 86%) as a colourless solid. Rf = 0.39 (petroleum
1
ether/dichloromethane, 1:1), m.p. 94–95 °C. H NMR (300 MHz, CDCl3):
δ = 4.82 (dd, J = 5.8, J = 1.3 Hz, 2 H), 6.40 (dt, J = 15.9, J = 5.8 Hz, 1 H),
6.76 (dt, J = 16.0, J = 1.5 Hz, 1 H), 7.00 (d, J = 8.9 Hz, 1 H), 7.25–7.45
(m, 5 H), 7.48 (dd, J = 8.9, J = 2.8 Hz, 1 H), 7.81 (d, J = 2.8 Hz, 1 H),
10.49 (s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 69.6, 114.6, 122.9,
126.0, 126.6, 128.0, 128.3, 128.7, 134.0, 135.3, 135.9, 159.4, 188.4 ppm.
MS (EI): m/z (%) = 272 (23) [M]+, 237 (31), 209 (61), 181 (32), 153 (21),
125 (21), 115 (100), 91 (34).
(6aRS,7SR,12aRS)-6a,7,12,12a-Tetrahydro-9-methyl-7-phenyl-6H-
chromeno[4,3-b]quinoline (3b): Iron powder (447 mg, 8.0 mmol), citric
acid monohydrate (1.68 g, 8.0 mmol), montmorillonite K10 (301 mg), 4-
nitrotoluene (1b) (275 mg, 2.0 mmol) and 2-(cinnamyloxy)benzaldehyde
(2a) (477 mg, 2.0 mmol) were used according to general procedure II.
After workup and column filtration on silica gel (petroleum
5-Bromo-2-(cinnamyloxy)benzaldehyde (2d):[30a] K2CO3 (6.36 g, 46
mmol), KI (78 mg, 0.47 mmol), 5-bromo-2-hydroxybenzaldehyde (5d)
(6.15 g, 30.6 mmol) and cinnamyl chloride (6) (5.13 g, 33.6 mmol) were
used according to general procedure I. Crystallization of the crude
product from i-propanol gave 5-bromo-2-(cinnamyloxy)benzaldehyde
(2d) (8.72 g, 27.5 mmol, 90%) as a colourless solid. Rf = 0.31 (petroleum
ether/dichloromethane, 7:3), m.p. 101–104 °C (ref.[30a] m.p. 69–71 °C).
1H NMR (300 MHz, CDCl3): δ = 4.81 (dd, J = 5.8, J = 1.4 Hz, 2 H), 6.40
(dt, J = 16.0, J = 5.8 Hz, 1 H), 6.76 (dt, J = 16.0, J = 1.5 Hz, 1 H), 6.95 (d,
J = 8.9 Hz, 1 H), 7.25–7.44 (m, 6 H), 7.62 (dd, J = 8.9, J = 2.7 Hz, 1 H),
7.95 (d, J = 2.6 Hz, 1 H), 10.47 (s, 1 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 69.5, 113.7, 115.0, 122.8, 126.4, 126.6, 128.3, 128.7, 131.0, 134.0,
135.9, 138.2, 159.8, 188.3 ppm. MS (EI): m/z (%) = 316 (73) [M]+, 287
(14), 237 (75), 208 (65), 191 (29), 178 (18), 165 (16), 131 (19), 115 (100),
91 (25), 77 (12).
ether/dichloromethane
=
1:1),
(6aRS,7SR,12aRS)-6a,7,12,12a-
tetrahydro-9-methyl-7-phenyl-6H-chromeno[4,3-b]quinoline (3b) was
obtained (498 mg, 1.52 mmol, 76%). Crystallization from methanol gave
3b in analytically pure form as a colourless solid. Rf = 0.25 (petroleum
ether/dichloromethane, 1:1), m.p. 207–209 °C. IR: = 2897, 1611, 1580,
1493, 1447, 1350, 1314, 1288, 1227, 1204, 1156, 1135, 1079, 1064,
1041, 1015, 943, 898, 881, 828, 806, 786, 755, 725, 705, 674, 648, 624,
551, 522, cm-1. UV (CH3CN): λmax (log ε) = 305 (3.37), 283 (3.59), 262
(3.97) nm. 1H NMR (500 MHz, CDCl3): δ = 2.11 (s, 3 H, CH3), 2.46 (dddd,
3J6a-H,7-H ≈ 11.6, 3J6a-H,6-H(ax) ≈ 11.6, 3J6a-H,12a-H ≈ 11.6, 3J6a-H,6-H(eq) = 3.7 Hz,
1 H, 6a-H), 3.81 (d, 3J7-H,6a-H = 11.5 Hz, 1 H, 7-H), 3.87 (dd, 2J6-H(ax),6-H(eq)
≈ 11.2, 3J6-H(ax),6a-H ≈ 11.2 Hz, 1 H, 6-H(ax), 4.04 (dd, 2J6-H(eq),6-H(ax) = 11.0,
3
3J6-H(eq),6a-H = 3.6 Hz, 1 H, 6-H(eq)), 4.25 (brs, 1 H, N-H), 4.45 (d, J12a-
3
= 10.3 Hz, 1 H, 12a-H), 6.46 (s, 1 H, 8-H), 6.71 (d, J11-H,10-H = 8.1
H,6a-H
Hz, 1 H, 11-H), 6.83 (dd, 3J4-H,3-H = 8.2, 4J4-H,2-H = 1.1 Hz, 1 H, 4-H), 6.89
(dd, J10-H,11-H = 8.2, J10-H,8-H = 1.9 Hz, 1 H, 10-H), 7.00 (ddd, J2-H,1-H
General Procedure II for the Domino Reactions between Nitroarenes
1 and 2-(Cinnamyloxy)benzaldehydes 2: A 25 mL screw-capped round
bottom flask was equipped with a magnetic stirring bar and charged with
iron powder (447 mg, 8 mmol), citric acid monohydrate (1.682 g, 8 mmol),
montmorillonite K10 (300 mg), water (15 mL), the nitroarene 1 (2 mmol),
and the 2-(cinnamyloxy)benzaldehyde 2 (2 mmol). The sealed reaction
flask was stirred at 80 °C for 4 h. Each hour the reaction flask was
shaken and sonicated for a few seconds using an ultrasonic bath. The
reaction mixture was filtered with suction; the filter cake was washed with
water (3 × 50 mL) and then extracted with hot acetone (3 × 50 mL). The
combined organic extracts were evaporated under reduced pressure.
The residue thus obtained was dissolved in dichloromethane (100 mL)
and filtered over silica gel. Analytically pure compounds were obtained by
crystallization or flash chromatography on silica gel.
3
4
3
≈
3
4
7.6, J2-H,3-H ≈ 7.6, J2-H,4-H = 1.2 Hz, 1 H, 2-H), 7.16–7.23 (m, 3 H, 3’-H,
2’-H and 6’-H), 7.29 (app t, J = 7.2 Hz, 1 H, 4’-H), 7.32–7.39 (m, 3 H, 1-H,
3’-H and 5’-H) ppm. 13C NMR (125 MHz, CDCl3): δ = 20.5 (CH3), 41.4 (C-
6a), 47.0 (C-7), 52.3 (C-12a), 67.6 (C-6), 116.3 (C-11), 116.9 (C-4),
120.7 (C-2), 122.8 (C-12b), 124.8 (C-1), 125.5 (C-7a), 127.0 (C-4’), 128.1
(C-10), 128.3 (C-9), 128.6 (C-3 or C-3’ and C-5’), 128.7 (C-3 or C-3’ and
C-5’), 129.1 (C-2’ and C-6’), 130.9 (C-8), 142.1 (C-11a), 143.0 (C-1’) ppm.
MS (EI): m/z (%) = 327 (100) [M]+, 308 (4), 246 (7), 220 (18), 194 (9),
153 (3), 131 (7). HRMS (EI): calcd. for C23H21NO [M]+ 327.1618; found
327.1623.
5
This article is protected by copyright. All rights reserved

European Journal of Organic Chemistry
10.1002/ejoc.201600976
FULL PAPER
(6aRS,7SR,12aRS)-6a,7,12,12a-Tetrahydro-11-methyl-7-phenyl-6H-
chromeno[4,3-b]quinoline (3c): Iron powder (449 mg, 8.0 mmol), citric
acid monohydrate (1.68 g, 8.0 mmol), montmorillonite K10 (300 mg), 2-
nitrotoluene (1c) (274 mg, 2.0 mmol) and 2-(cinnamyloxy)benzaldehyde
(2a) (476 mg, 2.0 mmol) were used according to general procedure II.
After workup and column chromatography on silica gel (petroleum
2’ and C-6’), 142.7 (C-1’), 138.2 (C-11a), 153.0 (C-9), 154.1 (C-4a) ppm.
MS (EI): m/z (%) = 343 (100) [M]+, 326 (4), 264 (8), 236 (6), 210 (5), 131
(3), 69 (4), 55 (7). HRMS (EI): calcd. for C23H21NO2 [M]+ 343.1567; found
343.1563.
(6aRS,7SR,12aRS)-6a,7,12,12a-Tetrahydro-7-phenyl-6H-
ether/dichloromethane
=
1:1),
(6aRS,7SR,12aRS)-6a,7,12,12a-
chromeno[4,3-b]quinoline-9-carbonitrile (3e): Iron powder (449 mg,
8.0 mmol), citric acid monohydrate (1.68 g, 8.0 mmol), montmorillonite
K10 (300 mg), 4-nitrobenzonitrile (1e) (297 mg, 2 mmol) and 2-
(cinnamyloxy)benzaldehyde (2a) (476 mg, 2.0 mmol) were used
according to general procedure II. After workup and column filtration on
silica gel (petroleum ether/dichloromethane = 1:1), (6aRS,7SR,12aRS)-
6a,7,12,12a-tetrahydro-7-phenyl-6H-chromeno[4,3-b]quinoline-9-
carbonitrile (3e) was obtained (514 mg, 1.52 mmol, 76%). Crystallization
from i-propanol gave 3e in analytically pure form as a colourless solid. Rf
tetrahydro-11-methyl-7-phenyl-6H-chromeno[4,3-b]quinoline (3c) (478
mg, 1.46 mmol, 73%) was obtained. Crystallization from i-propanol gave
3c in analytically pure form as a colourless solid. Rf = 0.53 (petroleum
ether/dichloromethane, 1:1), m.p. 169–170 °C. IR: = 3029, 2898, 1595,
1579, 1486, 1464, 1447, 1356, 1314, 1244, 1226, 1141, 1094, 1078,
1041, 1020, 1009, 946, 919, 883, 842, 797, 776, 761, 746, 701, 673, 626,
554, 517 cm-1. UV (CH3CN): λmax = (log ε) 283 (3.69), 276 (3.68), 249
(3.97) nm. 1H NMR (500 MHz, CDCl3): δ = 2.29 (s, 3 H, CH3), 2.47 (dddd,
3J6a-H,7-H ≈ 11.3, 3J6a-H,6-H(ax) ≈ 11.3, 3J6a-H,12a-H ≈ 11.3, 3J6a-H,6-H(eq) = 3.6 Hz,
1 H, 6a-H), 3.87 (d, 3J7-H,6a-H = 11.6 Hz, 1 H, 7-H), 3.88 (dd, 2J6-H(ax),6-H(eq)
≈ 11.2, 3J6-H(ax),6a-H ≈ 11.2 Hz, 1 H, 6-H(ax)), 4.05 (dd, 2J6-H(eq),6-H(ax) = 11.0,
= 0.10 (petroleum ether/dichloromethane, 1:1), m.p. 241–243 °C. IR: =
3362, 3031, 2212, 1607, 1582, 1504, 1480, 1464, 1446, 1342, 1320,
1251, 1225, 1194, 1137, 1066, 1045, 1017, 943, 888, 827, 816, 779, 746,
700, 677, 653, 626, 588, 567, 541, 509 cm-1. UV (CH3CN): λmax (log ε) =
357 (2.91), 303 (4.01), 272 (4.02) nm. 1H NMR (500 MHz, CD3COCD3): δ
3J6-H(eq),6a-H = 3.6 Hz, 1 H, 6-H(eq)), 4.50 (d, J12a-H,6a-H = 10.4 Hz, 1 H,
3
3
3
3
12a-H), 6.54 (d, J8-H,9-H = 7.8 Hz, 1 H, 8-H), 6.59 (dd, J9-H,8-H ≈ 7.3, J9-
3
4
3
3
3
3
≈ 7.3 Hz, 1 H, 9-H), 6.85 (dd, J4-H,3-H = 8.3, J4-H,2-H = 1.2 Hz, 1 H,
H,10-H
= 2.46 (dddd, J6a-H,7-H ≈ 11.5, J6a-H,12a-H ≈ 11.5, J6a-H,6-H(ax) ≈ 11.5, J6a-
4-H), 6.98 (ddd, 3J10-H,9-H = 7.2, 2 × J ≈ 0.8 Hz, 1 H, 10-H), 7.03 (ddd, 3J2-
H,1-H ≈ 7.5, 3J2-H,3-H ≈ 7.5, 4J2-H,4-H = 1.2 Hz, 1 H, 2-H), 7.17 (app d, J = 7.9
2
3
= 3.7 Hz, 1 H, 6a-H), 3.91 (dd, J6-H(eq),6-H(ax) = 11.1, J6-H(eq),6a-H
=
H,6-H(eq)
3.7 Hz, 1 H, 6-H(eq)), 3.99 (dd, 2J6-H(ax),6-H(eq) ≈ 11.2, 3J6-H(ax),6a-H ≈ 11.2 Hz,
1 H, 6-H(ax)), 4.02 (d, 3J7-H,6a-H = 11.4 Hz, 1 H, 7-H), 4.71 (d, 3J12a-H,6a-H
Hz, 2 H, 2’-H and 6’-H), 7.22 (ddd, 3J3-H,2-H ≈ 7.8, 3J3-H,4-H ≈ 7.8, 4J3-H,1-H
=
=
1.6 Hz, 1 H, 3-H), 7.28 (app t, J = 7.3 Hz, 1 H, 4’-H), 7.34 (app t, J = 7.5
Hz, 2 H, 3’-H and 5’-H), 7.42 (ddd, 3J1-H,2-H = 7.7, 2 × J ≈ 1.3 Hz, 1 H, 1-
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 17.4 (CH3), 40.9 (C-6a), 47.3
(C-7), 52.1 (C-12a), 67.7 (C-6), 117.1 (C-4), 118.4 (C-9), 120.8 (C-2),
122.9 (C-12b), 123.3 (C-11), 124.7 (C-1), 125.3 (C-7a), 127.0 (C-4’),
128.3 (C-8 or C-10), 128.4 (C-8 or C-10), 128.71 (C-3 or C-3’ and C-5’),
128.72 (C-3 or C-3’ and C-5’), 129.1 (C-2’ and C-6’), 142.3 (C-11a),
143.1 (C-1’), 154.2 (C-4a) ppm. MS (EI): m/z (%) = 327 (100) [M]+, 248
(11), 220 (25), 194 (14), 165 (9), 131 (10), 115 (6), 91 (9), 77 (7). HRMS
(EI): calcd. for C23H21NO [M]+ 327.1618; found 327.1607.
10.2 Hz, 1 H, 12a-H), 6.65 (brs, 1 H, N-H) 6.75 (s, 1 H; 8-H), 6.78 (dd,
3J4-H,3-H = 8.3, 4J4-H,2-H = 0.8 Hz, 1 H, 4-H), 6.97 (ddd, overlapped, 3J2-H,1-H
4
≈ 7.6, 3J2-H,3-H ≈ 7.6 Hz, J2-H,4-H ≈ 0.9 Hz, 1 H, 2-H), 6.97 (d, overlapped,
3J11-H,10-H = 8.4 Hz, 1 H, 11-H), 7.19 (dd, 3J3-H,2-H ≈ 7.7, 3J3-H,4-H ≈ 7.7 Hz, 1
H, 3-H), 7.31 (d, overlapped, 3J10-H,11-H = 8.3 Hz, 1 H, 10-H), 7.31 (app d,
overlapped, 2 H, 2’-H and 6’-H), 7.36 (app t, J = 7.4 Hz, 1 H, 4’-H), 7.44
(app t, J = 7.6 Hz, 2 H, 3’-H and 5’-H), 7.59 (d, 3J1-H,2-H = 7.8 Hz, 1 H, 1-
H) ppm. 13C NMR (125 MHz, CD3COCD3): δ = 40.7 (C-6a), 46.8 (C-12a),
52.5 (C-7), 68.1 (C-6), 99.8 (C-9), 116.3 (C-11), 117.6 (C-4), 121.4 (C-2),
123.2 (C-12b), 126.2 (C-7a), 126.5 (C-1), 128.4 (C-4’), 129.5 (C-3), 130.0
(C-2’, C-3’, C-5’ and C-6’), 131.9 (C-10), 134.7 (C-8), 142.8 (C-1’), 150.2
(C-11a), 155.0 (C-4a) ppm. MS (EI): m/z (%) = 338 (100) [M]+, 259 (13),
231 (26), 205 (12), 190 (9), 131 (29), 91 (8), 77 (8). HRMS (EI): calcd. for
C23H18N2O [M]+ 338.1414; found 338.1410.
(6aRS,7SR,12aRS)-6a,7,12,12a-Tetrahydro-9-methoxy-7-phenyl-6H-
chromeno[4,3-b]quinoline (3d): Iron powder (446 mg, 8.0 mmol), citric
acid monohydrate (1.68 g, 8.0 mmol), montmorillonite K10 (303 mg), 4-
methoxynitrobenzene
(1d)
(307
mg,
2.0
mmol)
and
2-
(cinnamyloxy)benzaldehyde (2a) (475 mg, 2.0 mmol) were used
according to general procedure II. After workup and column filtration on
silica gel (petroleum ether/dichloromethane = 1:1), (6aRS,7SR,12aRS)-
6a,7,12,12a-tetrahydro-9-methoxy-7-phenyl-6H-chromeno[4,3-
(6aRS,7SR,12aRS)-9-Fluoro-6a,7,12,12a-tetrahydro-7-phenyl-6H-
chromeno[4,3-b]quinoline (3f): Iron powder (448 mg, 8.0 mmol), citric
acid monohydrate (1.68 g, 8.0 mmol), montmorillonite K10 (300 mg), 4-
fluoronitrobenzene
(1f)
(283
mg,
2.0
mmol)
and
2-
b]quinoline (3d) was obtained (494 mg, 1.44 mmol, 72%). Crystallization
from i-propanol gave 3d in analytically pure form as a colourless solid. Rf
= 0.11 (petroleum ether/dichloromethane, 1:1), m.p. 185–186 °C. IR: =
(cinnamyloxy)benzaldehyde (2a) (477 mg, 2.0 mmol) were used
according to general procedure II. After workup and column filtration on
silica gel (petroleum ether/dichloromethane = 1:1), (6aRS,7SR,12aRS)-9-
fluoro-6a,7,12,12a-tetrahydro-7-phenyl-6H-chromeno[4,3-b]quinoline (3f)
was obtained (550 mg, 1.66 mmol, 83%). Crystallization from i-propanol
gave 3f in analytically pure form as a colourless solid. Rf = 0.62
3024, 2892, 1607, 1580, 1493, 1437, 1313, 1266, 1226, 1151, 1138,
1083, 1063, 1036, 1013, 943, 921, 900, 849, 826, 805, 785, 755, 746,
726, 705, 675, 648, 625, 569, 557, 531 cm-1. UV (CH3CN): λmax (log ε) =
358 (3.04), 317 (3.54), 249 (3.98) nm. 1H NMR (500 MHz, CDCl3): δ =
2.43 (dddd, 3J6a-H, 6-H(ax) ≈ 11.3, 3J6a-H,7-H ≈ 11.3, 3J6a-H,12a-H ≈ 11.3, 3J6a-H,6-
H(eq) = 3.7 Hz, 1 H, 6a-H), 3.59 (s, 3 H, OCH3), 3.80 (d, 3J7-H,6a-H = 11.5 Hz,
(petroleum ether/dichloromethane, 7:3), m.p. 170–172 °C; IR: = 3025,
2983, 2862, 1605, 1580, 1493, 1475, 1463, 1451, 1356, 1312, 1259,
1230, 1205, 1189, 1135, 1079, 1056, 1042, 1015, 958, 932, 920, 871,
829, 811, 762, 743, 711, 699, 645, 615, 548, 516 cm-1. UV (CH3CN): λmax
(log ε) = 250 (4.01) nm. 1H NMR (500 MHz, CD3COCD3): δ = 2.39 (dddd,
2
3
1 H, 7-H), 3.87 (dd, J6-H(ax),6-H(eq) ≈ 11.2, J6-H(ax),6a-H ≈ 11.2 Hz, 1 H, 6-
H(ax)), 4.06 (dd, 2J6-H(eq),6-H(ax) = 11.0, 3J6-H(eq),6a-H = 3.7 Hz, 1 H, 6-H(eq)),
3
3
3
3
3J6a-H,7a-H ≈ 10.5, J6a-H,6-H(ax) ≈ 10.5, J6a-H,12a-H ≈ 10.5, J6a-H,6-H(eq) = 4.3
4.07 (brs, 1 H, N-H), 4.41 (d, J12a-H,6a-H = 10.4 Hz, 1 H, 12a-H), 6.23 (d,
4J8-H,10-H = 2.6 Hz, 1 H, 8-H), 6.70 (dd, 3J10-H,11-H = 8.6, 4J10-H,8-H = 2.7 Hz,
1 H, 10-H), 6.76 (d, 3J11-H,10-H = 8.7 Hz, 1 H, 11-H), 6.83 (dd, 3J4-H,3-H = 8.2,
4J4-H,2-H = 1.0 Hz, 1 H, 4-H), 7.00 (ddd, 3J2-H,1-H ≈ 7.5, 3J2-H,3-H ≈ 7.5, 4J2-H,4-
H = 1.1 Hz, 1 H, 2-H), 7.16–7.22 (m, 3 H, 3-H, 2’-H and 5’-H), 7.28 (app t,
1 H, 4’-H), 7.34 (app t, 2 H, 3’-H and 5’-H), 7.38 (d, 3J1-H,2-H = 7.7 Hz, 1 H,
1-H) ppm. 13C NMR (125 MHz, CDCl3): δ = 41.2 (C-6a), 47.2 (C-7), 52.5
(C-12a), 55.5 (OCH3), 67.6 (C-6), 113.4 (C-10), 115.7 (C-8), 116.9 (C-4),
117.7 (C-11), 120.7 (C-2), 122.9 (C-12b), 125.0 (C-1), 127.1 (C-4’ and C-
7a), 128.6 (C-3 or C-3’ and C-5’), 128.7 (C-3 or C-3’ and C-5’), 129.1 (C-
2
3
Hz, 1 H, 6a-H), 3.93 (dd, J6-H(eq),6-H(ax) = 11.0, J6-H(eq),6a-H = 4.4 Hz, 1 H,
6-H(eq)), 3.97 (d, J7-H,6a-H = 11.7 Hz, 1 H, 7-H), 3.97 (dd, 2J6-H(ax),6-
3
3
3
H(eq) ≈ 10.9, J6-H(ax),6a-H ≈ 10.9 Hz, 1 H, 6-H(ax)), 4.51 (d, J12a-H,6a-H
=
3
4
10.9 Hz, 1 H, 12a-H), 5.67 (brs, 1 H, N-H), 6.24 (dd, J8-H,9-F = 10.1, J8-
= 2.9 Hz, 1 H, 8-H), 6.76 (dd, 3J4-H,3-H = 8.1, J4-H,2-H = 1.2 Hz, 1 H,
4
H,10-H
3
3
4
4-H), 6.78 (ddd, J10-H,9-F = 8.3, J10-H,11-H = 8.3, J10-H,8-H = 3.0 Hz, 1 H,
10-H), 6.87 (dd, 3J11-H,10H = 8.9, 4J11-H,9-F = 5.1 Hz, 1 H, 11-H), 6.95 (ddd,
3J2-H,1-H ≈ 7.6, 3J2-H,3-H ≈ 7.6, 4J2-H,4-H = 1.3 Hz, 1 H, 2-H), 7.16 (ddd, 3J3-H,2-
H ≈ 7.3, 3J3-H,4-H ≈ 7.3, 4J3-H,1-H = 1.7 Hz, 1 H, 3-H), 7.33 (app t, J = 7.4 Hz,
6
This article is protected by copyright. All rights reserved

European Journal of Organic Chemistry
10.1002/ejoc.201600976
FULL PAPER
3
3
1 H, 4’-H), 7.41 (app t, J = 7.1 Hz, 2 H, 3’-H and 5’-H), 7.27 (app d, J =
8.2 Hz, 2 H, 2’-H and 6’-H), 7.59 (ddd, 3J1-H,2-H = 7.7, 2 × J ≈ 1.4 Hz, 1 H,
1-H) ppm. 13C NMR (125 MHz, CD3COCD3): δ = 41.8 (C-6a), 47.4 (C-7),
H, 6-H(ax), 3.97 (d, J7-H,6a-H = 11.8 Hz, 1 H, 7-H), 4.55 (d, J12a-H,6a-H
=
10.4 Hz, 1 H, 12a-H), 5.93 (brs, 1 H, N-H), 6.60 (s, 1 H, 8-H), 6.76 (dd,
3J4-H,3-H = 8.2, 4J4-H,2-H = 0.8 Hz, 1 H, 4-H), 6.83 (d, 3J11-H,10-H = 8.6 Hz, 1 H,
11-H), 6.95 (ddd, J2-H,1-H ≈ 7.5 Hz, J2-H,3-H ≈ 7.5, J2-H,4-H = 1.0 Hz, 1 H,
2-H), 7.10 (dd, J10-H,11-H = 8.6, J10-H,8-H = 2.3 Hz, 1 H, 10-H), 7.17 (dd,
3J3-H,2-H ≈ 7.7, J3-H,4-H ≈ 7.7 Hz, 1 H, 3-H), 7.28 (app d, J = 7.2 Hz, 2 H,
3
3
4
52.9 (C-12a), 68.1 (C-6), 114.6 (d, 2JCF = 22.6 Hz, C-10), 116.5 (d, 2JCF
=
3
3
4
22.6 Hz, C-8), 117.4 (C-4), 117.9 (d, JCF = 7.5 Hz, C-11), 121.3 (C-2),
124.2 (C-12b), 126.8 (C-1), 127.4 (d, JCF = 6.2 Hz, C-7a), 128.1 (C-4’),
3
3
129.3 (C-3), 129.8 (C-3’ and C-5’), 130.0 (C-2’ and C-6’), 143.0 (d, 4JCF
=
2’-H and 6’-H), 7.34 (app t, J = 7.4 Hz, 1 H, 4’-H), 7.41 (app t, J = 7.4 Hz,
3
1.9 Hz, C-11a), 143.9 (C-1’), 156.9 (d, JCF = 233.6 Hz, C-9), 157.6 (C-4a)
ppm. MS (EI): m/z (%) = 331 (100) [M]+, 252 (12), 224 (21), 198 (10), 183
(6), 131 (9). HRMS (EI): calcd. for C22H18NOF [M]+ 331.1367; found
331.1381.
2 H, 3’-H and 5’-H), 7.58 (d, J1-H,2-H = 7.8 Hz, 1 H, 1-H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 41.6 (C-6a), 47.2 (C-7), 52.6 (C-12a), 68.1 (C-6),
109.6 (C-9), 117.4 (C-4), 118.4 (C-11), 121.3 (C-2), 123.9 (C-12b), 126.7
(C-1), 128.2 (C-7a), 128.8 (C-4’), 129.3 (C-3), 129.8 (C-3’ and C-5’),
130.0 (C-2’ and C-6’), 130.6 (C-10), 133.0 (C-8), 143.6 (C-1’), 145.8 (C-
11a), 155.0 (C-4a) ppm. MS (EI): m/z (%) = 391 (100) [M]+, 312 (8), 284
(13), 260 (6), 204 (6), 165 (7), 131 (15). HRMS (EI): calcd. for
C22H18BrNO [M]+ 391.0566; found 391.0545.
(6aRS,7SR,12aRS)-9-Chloro-6a,7,12,12a-tetrahydro-7-phenyl-6H-
chromeno[4,3-b]quinoline (3g): Iron powder (449 mg, 8.0 mmol), citric
acid monohydrate (1.69 g, 8.0 mmol), montmorillonite K10 (304 mg), 4-
chloronitrobenzene
(1g)
(315
mg,
2.0
mmol)
and
2-
(cinnamyloxy)benzaldehyde (2a) (476 mg, 2.0 mmol) were used
according to general procedure II. After workup and column filtration on
(6aRS,7SR,12aRS)-11-Bromo-6a,7,12,12a-tetrahydro-7-phenyl-6H-
chromeno[4,3-b]quinoline (3i): Iron powder (449 mg, 8.0 mmol), citric
acid monohydrate (1.70 g, 8.1 mmol), montmorillonite K10 (303 mg), 2-
silica gel (petroleum ether/dichloromethane
=
1:1), 9-chloro-
(6aRS,7SR,12aRS)-6a,7,12,12a-tetrahydro-7-phenyl-6H-chromeno[4,3-
b]quinoline (3g) was obtained (543 mg, 1.56 mmol, 78%). Crystallization
from dichloromethane/petroleum ether gave 3g in analytically pure form
as a colourless solid. Rf = 0.38 (petroleum ether/dichloromethane, 1:1),
bromonitrobenzene
(1i)
(404
mg,
2.0
mmol)
and
2-
(cinnamyloxy)benzaldehyde (2a) (477 mg, 2.0 mmol) were used
according to general procedure II. After workup and column filtration on
silica gel (petroleum ether/dichloromethane = 1:1), (6aRS,7SR,12aRS)-
11-bromo-6a,7,12,12a-tetrahydro-7-phenyl-6H-chromeno[4,3-b]quinoline
(3i) was obtained (573 mg, 1.46 mmol, 73%). Crystallization from
petroleum ether gave 3i in analytically pure form as a colourless solid. Rf
m.p. 173–174 °C. IR: = 2897, 1598, 1581, 1478, 1449, 1349, 1313,
1288, 1260, 1227, 1156, 1126, 1095, 1080, 1061, 1042, 1017, 944, 921,
901, 874, 827, 804, 779, 753, 727, 706, 663, 644, 621, 550, 512 cm-1.
1
UV (CH3CN): λmax (log ε): 310 (3.39), 260 (4.10) nm. H NMR (500 MHz,
= 0.46 (petroleum ether/dichloromethane, 1:1), m.p. 202–204 °C. IR: =
3
3
3
CDCl3): δ = 2.45 (dddd, J6a-H,6-H(ax) ≈ 11.4, J6a-H,7-H ≈ 11.4, J6a-H,12a-H
≈
3024, 2892, 1607, 1580, 1493, 1437, 1313, 1266, 1227, 1151, 1138,
1083, 1063, 1036, 1013, 943, 921, 900, 849, 826, 805, 784, 755, 746,
725, 705, 675, 624, 569, 556, 531, 453 cm-1. UV (CH3CN): λmax (log ε) =
302 (3.48), 284 (3.62), 275 (3.63), 251 (3.94) nm. 1H NMR (500 MHz,
11.4, 3J6a-H,6-H(eq) = 3.5 Hz, 1 H, 6a-H), 3.79 (d, 3J7-H,6a-H = 11.5 Hz, 1 H, 7-
H), 3.85 (dd, J6-H(ax),6-H(eq) ≈ 11.2, J6-H(ax),6a-H ≈ 11.2 Hz, 1 H, 6-H(ax)),
2
3
2
3
4.02 (dd, J6-H(eq),6-H(ax) = 11.0, J6-H(eq),6a-H = 3.5 Hz, 1 H, 6-H(eq)), 4.38
(brs, 1 H, N-H), 4.47 (d, 3J2a-H,6a-H = 10.4 Hz, 1 H, 12a-H), 6.60 (d, 4J8-H,10-
CDCl3): δ = 2.50 (dddd, J6a-H,7-H ≈ 11.4, J6a-H,6-H(ax) ≈ 11.4, J6a-H,12a-H
≈
3
3
3
3
= 2.2 Hz, 1 H, 8-H), 6.68 (d, J11-H,10-H = 8.6 Hz, 1 H, 11-H), 6.83 (dd,
3J4-H,3-H = 8.2, J4-H,2-H = 1.1 Hz, 1 H, 4-H), 6.98–7.03 (m, 2 H, 2-H and
10-H), 7.16 (app d, J = 6.9 Hz, 2 H, 2’-H and 6’-H), 7.20 (dd, J3-H,2-H
7.7, J3-H,4-H ≈ 7.7 Hz, 1 H, 3-H), 7.31 (app t, J = 7.6 Hz, 1 H, 4’-H), 7.32
11.4, 3J6a-H,6-H(eq) = 3.6 Hz, 1 H, 6a-H), 3.86 (d, 3J7-H,6a-H = 11.7 Hz, 1 H, 7-
H
4
2
3
H), 3.87 (dd, J6-H(ax),6-H(eq) ≈ 11.2, J6-H(ax),6a-H ≈ 11.2 Hz, 1 H, 6-H(ax),
4.04 (dd, 2J6-H(eq),6-H(ax) = 11.0, 3J6-H(eq),6a-H = 3.7 Hz, 1 H, 6-H(eq), 4.54 (d,
3J12a-H,6a-H = 10.3 Hz, 1 H, 12a-H), 5.07 (brs, 1 H, N-H), 6.48 (dd, 3J9-H,8-H
3
≈
3
3
3
3
(d, overlapped, J1-H,2-H = 7.1 Hz, 1 H, 1-H), 7.36 (app t, J = 7.6 Hz, 2 H,
≈ 7.8, J9-H,10-H ≈ 7.8 Hz, 1 H, 9-H), 6.59 (ddd, J8-H,9-H = 7.7, 2 × J ≈ 1.2
3’-H and 5’-H) ppm. 13C NMR (125 MHz, CDCl3): δ = 40.7 (C-6a), 46.9
(C-7), 52.1 (C-12a), 67.4 (C-6), 117.08 (C-4 or C-11), 117.13 (C-4 or C-
11), 120.8 (C-2), 122.2 (C-12b), 123.5 (C-9), 124.6 (C-1), 127.0 (C-7a),
127.38 (C-10), 127.40 (C-4’), 128.8 (C-3), 129.0 (overlapped, C-2’, C-3’,
C-5’ and C-6’), 129.9 (C-8), 141.9 (C-1’), 143.0 (C-11a), 154.0 (C-4a)
ppm. MS (EI): m/z (%) = 347 (100) [M]+, 308 (9), 268 (14), 240 (14), 214
(9), 154 (12). HRMS (EI): calcd. for C22H18ClNO [M]+ 347.1071; found
347.1065.
Hz, 1 H, 8-H), 6.85 (dd, J4-H,3-H = 8.2, J4-H,2-H = 1.2 Hz, 1 H, 4-H), 7.04
3
4
3
3
(ddd, J2-H,1-H ≈ 7.6, J2-H,3-H ≈ 7.6, 4J2-H,4-H = 1.3 Hz, 1 H, 2-H), 7.17 (app
d, J = 8.2 Hz, 2 H, 2’-H, 6’-H), 7.22 (ddd, 3J3-H,2-H ≈ 7.7, 3J3-H,4-H ≈ 7.7, 4J3-
= 1.6 Hz, 1 H, 3-H), 7.30 (app t, J = 7.3 Hz, 1 H, 4’-H), 7.33 (d
H,1-H
overlapped, 1 H, 10-H), 7.35 (app t, J = 7.3 Hz, 2 H, 3’-H and 5’-H), 7.40
3
(ddd J1-H,2-H = 7.7, 2 × J ≈ 1.3 Hz, 1 H, 1-H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 40.7 (C-6a), 47.3 (C-7), 52.1 (C-12a), 67.5 (C-6), 110.3 (C-
11), 117.0 (C-4), 118.7 (C-9), 120.9 (C-2), 122.0 (C-12b), 124.5 (C-1),
126.7 (C-7a), 127.3 (C-4’), 128.85 (C-3 or C-3’ and C-5’), 128.87 (C-3 or
C-3’ and C-5’), 129.0 (C-2’ and C-6’), 129.6 (C-8), 130.6 (C-10), 141.6
(C-11a), 142.3 (C-1’), 153.9 (C-4a) ppm. MS (EI): m/z (%) = 391 (100)
[M]+, 312 (9), 284 (15), 260 (4), 234 (4), 204 (7), 180 (13), 165 (7), 131
(10). HRMS (EI): calcd. for C22H18BrNO [M]+ 391.0566; found 391.0557.
(6aRS,7SR,12aRS)-9-Bromo-6a,7,12,12a-tetrahydro-7-phenyl-6H-
chromeno[4,3-b]quinoline (3h): Iron powder (447 mg, 8.0 mmol), citric
acid monohydrate (1.68 g, 8.0 mmol), montmorillonite K10 (301 mg), 4-
bromonitrobenzene
(1h)
(405
mg,
2.0
mmol)
and
2-
(cinnamyloxy)benzaldehyde (2a) (475 mg, 2.0 mmol) were used
according to general procedure II. After workup and column filtration on
silica gel (petroleum ether/dichloromethane = 1:1), (6aRS,7SR,12aRS)-9-
bromo-6a,7,12,12a-tetrahydro-7-phenyl-6H-chromeno[4,3-b]quinoline
(3h) was obtained (542 mg, 1.38 mmol, 69%). Crystallization from i-
propanol gave 3h in analytically pure form as a colourless solid. Rf = 0.37
(6aRS,7SR,12aRS)-6a,7,12,12a-Tetrahydro-2-methyl-7-phenyl-6H-
chromeno[4,3-b]quinoline (3j): Iron powder (447 mg, 8.0 mmol), citric
acid monohydrate (1.69 g, 8.0 mmol), montmorillonite K10 (300 mg),
nitrobenzene (1a) (247 mg, 2.0 mmol) and 2-cinnamyloxy-5-
methylbenzaldehyde (2b) (505 mg, 2.0 mmol) were used according to
general procedure II. After workup and column filtration on silica gel
(petroleum ether/dichloromethane, 1:1), m.p. 167–168 °C. IR: = 3026,
2897, 1582, 1477, 1449, 1379, 1350, 1313, 1288, 1256, 1288, 1256,
1228, 1204, 1156, 1127, 1077, 1059, 1043, 1018, 943, 920, 900, 886,
871, 853, 826, 804, 777, 705, 652, 619, 551, 509 cm-1. UV (CH3CN): λmax
(petroleum
ether/dichloromethane
=
1:1),
(6aRS,7SR,12aRS)-
6a,7,12,12a-tetrahydro-2-methyl-7-phenyl-6H-chromeno[4,3-b]quinoline
(3j) was obtained (530 mg, 1.62 mmol, 81%). Crystallization from i-
propanol gave 3j in analytically pure form as a colourless solid. Rf = 0.45
(petroleum ether/dichloromethane, 1:1), m.p. 205–206 °C. IR: = 3392,
3025, 1598, 1515, 1492, 1439, 1320, 1269, 1249, 1222, 1203, 1152,
1126, 1087, 1072, 1029, 991, 967, 883, 866, 806, 744, 704, 688, 620,
1
(log ) = 310 (3.36), 261 (4.13) nm. H NMR (500 MHz, CD3COCD3): δ =
2.40 (dddd, 3J6a-H,7a-H ≈ 11.1, 3J6a-H,6-H(ax) ≈ 11.1, 3J6a-H,12a-H ≈ 11.1, 3J6a-H,6-
H(eq) = 3.9 Hz, 1 H, 6a-H), 3.90 (dd, 2J6-H(eq),(6-H(ax) = 11.0, 3J6-H(eq),6a-H = 3.9
Hz, 1 H, 6-H(eq)), 3.96 (dd, 2J6-H(ax),6-H(eq) ≈ 11.1, 3J6-H(ax),6a-H ≈ 11.1 Hz, 1
7
This article is protected by copyright. All rights reserved

European Journal of Organic Chemistry
10.1002/ejoc.201600976
FULL PAPER
1
573, 532, 509 cm-1. UV (CH3CN): λmax (log ε) = 291 (3.76), 251 (4.02) nm.
540, 524 cm-1. UV (CH3CN): λmax (log ε) = 294 (3.68), 232 (4.16) nm. H
3
3
1H NMR (500 MHz, CD3COCD3): δ = 2.27 (s, 3 H, CH3), 2.33–2.41 (m, 1
NMR (500 MHz, CDCl3): δ = 2.45 (dddd, J6a-H,7-H ≈ 11.2, J6a-H,6-H(ax) ≈
3
H, 6a-H), 3.88–3.93 (m, 2 H, 6-H(ax) and 6-H(eq)), 3.93 (d, J7-H,6a-H
=
11.2, 3J6a-H,12a-H ≈ 11.2, 3J6a-H,6-H(eq) = 3.6 Hz, 1 H, 6a-H), 3.83 (d, 3J7-H,6a-H
= 11.9 Hz, 1 H, 7-H), 3.84 (dd, 2J6-H(ax),6-H(eq) ≈ 11.4, 3J6-H(ax), 6a-H ≈ 11.4 Hz,
1 H, 6-H(ax)), 4.05 (dd, 2J6-H(eq),6-H(ax) = 11.1, 3J6-H(eq),6a-H = 3.6 Hz, 1 H, 6-
11.8 Hz, 1 H, 7-H), 4.49 (d, 3J12a-H,6a-H = 10.3 Hz, 1 H, 12a-H), 5.67 (brs,
1 H, N-H), 6.48–6.54 (m, 2 H, 8-H and 9-H), 6.64 (d, 3J4-H,3-H = 8.3 Hz, 1
3
3
H, 4-H), 6.84 (d, J11-H,10-H = 8.2 Hz, 1 H, 11-H), 6.94–6.99 (m, 2 H, 3-H
H(eq)), 4.30 (brs, 1 H, N-H), 4.45 (d, J12a-H,6a-H = 10.4 Hz, 1 H, 12a-H),
3
3
3
and 10-H), 7.24 (app d, J = 7.2 Hz, 2 H, 2’-H and 6’-H), 7.29 (app t, J =
7.3 Hz, 1 H, 4’-H), 7.41 (s, 1 H, 1-H), 7.37 (app t, J = 7.4 Hz, 2 H, 3’-H
and 5’-H) ppm. 13C NMR (125 MHz, CD3COCD3): δ = 20.8 (CH3), 42.4
(C-6a), 47.5 (C-7), 53.0 (C-12a), 68.8 (C-6), 116.6 (C-11), 117.1 (C-4),
118.6 (C-9), 123.9 (C-12b), 125.8 (C-7a), 127.1 (C-1), 127.78 (C-4’ or C-
10), 127.80 (C-4’ or C-10), 129.6 (C-3’ and C-5’), 129.7 (C-3), 130.0 (C-2’
and C-6’), 130.2 (C-2), 130.8 (C-8), 144.7 (C-1’), 146.6 (C-11a), 152.9
(C-4a) ppm. MS (EI): m/z (%) = 327 (100) [M]+, 312 (7), 248 (14), 220
(18), 180 (15), 145 (15), 115 (9), 91 (9). HRMS (EI): calcd. for C23H21NO
[M]+ 327.1618; found 327.1607.
6.63 (d, J8-H,9-H = 7.2 Hz, 1 H, 8-H), 6.66 (dd, J9-H,8-H ≈ 7.5, J9-H,10-H ≈
7.5 Hz, 1 H, 9-H), 6.71 (d, J4-H,3-H = 8.8 Hz, 1 H, 4-H), 6.80 (d, 3J11-H,10-H
3
= 7.9 Hz, 1 H, 11-H), 7.08 (ddd, 3J10-H,9-H ≈ 7.5, 3J10-H,11-H ≈ 7.5, 4J10-H,8-H
=
1.5 Hz, 1 H, 10-H), 7.17 (app d, J = 7.1 Hz, 2 H, 2’-H and 6’-H), 7.26–
7.31 (m, 2 H, 3-H and 4’-H), 7.35 (app t, J = 7.2 Hz, 2 H, 3’-H and 5’-H),
7.35 (s, 1 H, 1-H) ppm. 13C NMR (125 MHz, CDCl3): δ = 40.7 (C-6a),
46.9 (C-7), 51.9 (C-12a), 67.8 (C-6), 112.8 (C-2), 116.3 (C-11), 118.8 (C-
4), 119.3 (C-9), 124.8 (C-12b), 125.4 (C-7a), 127.2 (C-4’), 127.5 (C-10),
127.8 (C-1), 128.8 (C-3’ and C-5’), 129.1 (C-2’ and C-6’), 130.4 (C-8),
131.5 (C-3), 142.6 (C-1’), 144.0 (C-11a), 153.3 (C-4a) ppm. MS (EI): m/z
(%) = 391 (100) [M]+, 312 (28), 284 (11), 234 (13), 206 (34), 180 (30),
165 (18), 139 (16), 91 (13), 77 (14). HRMS (EI) calcd. for C22H18NOBr
[M]+ 391.0566; found 391.0537.
(6aRS,7SR,12aRS)-2-Chloro-6a,7,12,12a-tetrahydro-7-phenyl-6H-
chromeno[4,3-b]quinoline (3k): Iron powder (448 mg, 8.0 mmol), citric
acid monohydrate (1.68 g, 8.0 mmol), montmorillonite K10 (300 mg),
nitrobenzene
(1a)
(248 mg, 2.0 mmol) and 5-chloro-2-
Supporting Information (see footnote on the first page of this article):
1H and 13C NMR spectra for compounds 2a–d and 3a–l.
(cinnamyloxy)benzaldehyde (2c) (547 mg, 2.0 mmol) were used
according to general procedure II. After workup and column filtration on
silica gel (petroleum ether/dichloromethane = 7:3), (6aRS,7SR,12aRS)-2-
chloro-6a,7,12,12a-tetrahydro-7-phenyl-6H-chromeno[4,3-b]quinoline
(3k) was obtained (556 mg, 1.60 mmol, 80%). Crystallization from i-
propanol gave 3k in analytically pure form as a colourless solid. Rf = 0.50
Acknowledgements
We thank M. Wolf and Dipl.-Biol. C. Braunberger for recording of
NMR spectra and Dr. A. Mikhael (Institut für Chemie, Universität
Hohenheim) as well as Dipl.-Ing. (FH) J. Trinkner (Institut für
Organische Chemie, Universität Stuttgart) for recording of mass
spectra.
(petroleum ether/dichloromethane, 7:3), m.p. 160–161 °C. IR: = 3391,
3025, 2978, 2854, 1603, 1581, 1477, 1407, 1350, 1310, 1268, 1236,
1220, 1204, 1146, 1101, 1058, 1021, 934, 896, 874, 856, 817, 777, 749,
729, 702, 645, 605, 559, 544, 529 cm-1. UV (CH3CN): λmax (log ε) = 294
3
(3.67), 232 (4.11) nm. 1H NMR (500 MHz, CDCl3): δ = 2.46 (dddd, J6a-
3
3
3
≈ 11.2, J6a-H,6-H(ax) ≈ 11.2, J6a-H,12a-H ≈ 11.2, J6a-H,6-H(eq) = 3.5 Hz, 1
H,7-H
H, 6a-H), 3.83 (d, 3J7-H,6a-H = 11.7 Hz, 1 H, 7-H), 3.85 (dd, 2J6-H(ax),6-H(eq)
≈
3
2
Keywords: Domino reactions • Nitrogen heterocycles • Oxygen
heterocycles • Reduction
11.2, J6-H(ax),6a-H ≈ 11.2 Hz, 1 H, 6-H(ax)), 4.05 (dd, J6-H(eq),6-H(ax) = 11.0,
3J6-H(eq),6a-H = 3.7 Hz, 1 H, 6-H(eq)), 4.32 (brs, 1 H, N-H), 4.45 (d, J12a-
3
3
= 10.4 Hz, 1 H, 12a-H), 6.63 (d, J8-H,9-H = 7.4 Hz, 1 H, 8-H), 6.66
(ddd, J9-H,8-H ≈ 7.5, J9-H,10-H ≈ 7.5, J9-H,11-H = 1.1 Hz, 1 H, 9-H), 6.76 (d,
3J4-H,3-H = 8.4 Hz, 1 H, 4-H), 6.80 (d, 3J11-H,10-H = 7.9 Hz, 1 H, 11-H), 7.08
H,6a-H
3
3
4
[1]
a) N. Saracoglu, Top. Heterocycl. Chem. 2007, 11, 145; b) T. Eicher, S.
Hauptmann, A. Speicher, The Chemistry of Heterocycles, Wiley VCH,
Weinheim, 2nd edn, 2003; c) J. A. Joule, K. Mills, Heterocyclic
Chemistry, Blackwell Science, Oxford, 2000; d) E. C. Taylor, J. E.
Saxton, The Chemistry of Heterocyclic Compounds, Wiley-Interscience,
New York, 1983; e) E. Vitaku, D. T. Smith, D. T. J. T. Njardson, J. Med.
Chem. 2014, 57, 10257; f) M. González, H. Cerecetto, A. Monge, Top.
Heterocycl. Chem. 2007, 11, 179.
3
3
4
(ddd, J10-H,9-H ≈ 7.4, J10-H,11-H ~ 7.4, J10-H,8-H = 1.5 Hz, 1 H, 10-H), 7.14
(dd, 3J3-H,4-H = 8.7, 4J3-H,1-H = 2.4 Hz, 1 H, 3-H), 7.17 (app d, J = 7.1 Hz, 2
H, 2’-H and 6’-H), 7.29 (app t, J = 7.3 Hz, 1 H, 4’-H), 7.33 (s, 1 H, 1-H),
7.35 (app t, J = 7.1 Hz, 2 H, 3’-H and 5’-H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 40.8 (C-6a), 46.9 (C-7), 52.0 (C-12a), 67.8 (C-6), 116.3 (C-
11), 118.4 (C-4), 119.3 (C-9), 124.2 (C-12b), 124.8 (C-1), 125.4 (C-7a),
125.6 (C-2), 127.2 (C-4’), 127.4 (C-10), 128.6 (C-3), 128.8 (C-3’ and C-
5’), 129.1 (C-2’ and C-6’), 130.4 (C-8), 142.6 (C-1’), 144.0 (C-11a), 152.7
(C-4a) ppm. MS (EI): m/z (%) = 347 (100) [M]+, 268 (15), 240 (13), 206
(20), 180 (24), 165 (27), 152 (9), 115 (9), 77 (12); HRMS (EI): calcd. for
C22H18NOCl [M]+ 347.1071; found 347.1073.
[2]
For reviews on the synthesis of N-heterocyclic compounds, see: a) N.
Kaur, Synth. Commun. 2015, 45, 1145; b) B. Zhang, A. Studer, Chem.
Soc. Rev., 2015, 44, 3505; c) J. Yu, H. Fu, Rep. Org. Chem. 2015, 5, 1;
d) C.-V. T. Vo, J. W. Bode, J. Org. Chem. 2014, 79, 2809; e) C. Allais,
J.-M. Grassot, J. Rodriguez, T. Constantieux, Chem. Rev. 2014, 114,
10829; f) Y. Yamamoto, Chem. Soc. Rev. 2014, 43, 1575; g) K. C.
Majumdar, N. De, T. Ghosh, B. Roy, Tetrahedron 2014, 70, 4827.
H. Lee, B. H. Kim, Tetrahedron 2013, 69, 6698.
(6aRS,7SR,12aRS)-2-Bromo-6a,7,12,12a-tetrahydro-7-phenyl-6H-
chromeno[4,3-b]quinoline (3l): Iron powder (447 mg, 8.0 mmol), citric
acid monohydrate (1.68 g, 8.0 mmol), montmorillonite K10 (301 mg),
nitrobenzene (1a) (247 mg, 2.01 mmol) and 5-bromo-2-
(cinnamyloxy)benzaldehyde (2d) (634 mg, 2.0 mmol) were used
according to general procedure II. After workup and column filtration on
silica gel (petroleum ether/dichloromethane = 1:1), (6aRS,7SR,12aRS)-2-
bromo-6a,7,12,12a-tetrahydro-7-phenyl-6H-chromeno[4,3-b]quinoline (3l)
was obtained (643 mg, 1.64 mmol, 82%). Crystallization from i-propanol
gave 3l in analytically pure form as a colorless solid. Rf = 0.40 (petroleum
[3]
[4]
a) J. L. O. Domingos, E. C. Lima, A. G. Dias, P. R. R. Costa,
Tetrahedron: Asymmetry 2004, 15, 2313; b) C. Meisterhans, A. Linden,
M. Hesse, Helv. Chim. Acta 2003, 86, 644.
[5]
[6]
J. Xu, X. Li, J. Wu, W.-M. Dei, Tetrahedron 2014, 70, 6384.
a) A. Ricci, M. Fochi, Angew. Chem. Int. Ed. 2003, 42, 1444; b) B. C.
Söderberg, J. A. Shriver, J. Org. Chem. 1997, 62, 5838; c) M. Akazome,
T. Kondo, Y. Watanabe, J. Org. Chem. 1994, 59, 3375; d) R. D. Clark,
D. B. Repke, Heterocycles 1984, 22, 195; e) J. I. G. Cadogan,
Synthesis 1969, 11.
ether/dichloromethane, 1:1), m.p. 172–173 °C. IR: = 3386, 3023, 2977,
2853, 1603, 1582, 1477, 1403, 1350, 1310, 1270, 1235, 1204, 1134,
1092, 1058, 1021, 931, 856, 816, 777, 749, 726, 702, 644, 630, 597, 558,
[7]
F. J. Reboredo, M. Treus, J. C. Estévez, L. Castedo, R. J. Estévez,
Synlett 2002, 999.
8
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FULL PAPER
[8]
[9]
A. W. Freeman, M. Urvoy, M. E. Criswell, J. Org. Chem. 2005, 70, 5014.
S. S. Labadie, C. Parmer, Synth. Commun. 2011, 41, 1752.
R. Palnati, L. R. Singh, A. Upadhyay, S. R. Avula, A. Kumar, R. Kant,
Green Chem. 2015, 17, 3766; e) G. L. Xi, Z.-Q. Liu, Eur. J. Med. Chem.
2015, 95, 416; f) J. S. B. Forero, E. M. De Carvalho, J. J. Junior, F. M.
Da Silva, Curr. Org. Synth. 2015, 12, 102; g) C. R. Borel, L. C. A.
Barbosa, C. R. Á. Maltha, S. A. Fernandes, Tetrahedron Lett. 2015, 56,
662; h) J. Yu, H.-J. Jiang, Y. Zhou, S.-W. Luo, L.-Z. Gong, Angew.
Chem. Int. Ed. 2015, 54, 11209; i) R. K. Kawade, D. B. Huple, R.-J. Lin,
R.-S. Liu, Chem. Commun. 2015, 51, 6625; j) C. Huo, H. Xie, M. Wu, X.
Jia, X. Wang, F. Chen, J. Tang, Chem. Eur. J. 2015, 21, 5723; k) L.-P.
Li, X. Cai, Y. Xiang, Y. Zhang, J. Song, D.-C. Yang, Z. Guan, Y.-H. He,
Green Chem. 2015, 17, 3148; l) Y. Wang, F. Peng, J. Liu, C. Huo, X.
Wang, X. Jia, J. Org. Chem. 2015, 80, 609; m) J. Liu, F. Liu, Y. Zhu, X.
Ma, X. Jia, Org. Lett. 2015, 17, 1409; n) X. Jia, F. Peng, C. Qing, C.
Huo, Y. Wang, X. Wang, Tetrahedron Lett. 2013, 54, 4950.
[10] a) N. E. Genung, L. Wei, G. E. Aspnes, Org. Lett. 2014, 16, 3114; b) A.
H. Moustafa, C. C. Malakar, N. Aljaar, E. Merişor, J. Conrad, U. Beifuss,
Synlett 2013, 1573; c) D. Sawant, R. Kumar, P. R. Maulik, B. Kundu,
Org. Lett. 2006, 8, 1525.
[11] a) L. Tian, G.-Y. Xu, Y. Ye, L.-Z. Liu, Synthesis 2003, 1329; b) H. Inone,
S. Tamura, J. Chem. Soc. Chem. Commun. 1985, 141.
[12] P. J. Alaimo, R. O’Brien III, A. W. Johnson, S. R. Slauson, J. M. O’Brien,
E. L. Tyson, A.-L. Marshall, C. E. Ottinger, J. G. Chacon, L. Wallace, C.
Y. Paulino, S. Connell, Org. Lett. 2008, 10, 5111.
[13] a) L. He, J.-Q. Wang, Y. Gong, Y.-M. Liu, Y. Cao, H.-Y. He, K.-N. Fan,
Angew. Chem. Int. Ed. 2011, 50, 10216; b) R. Bujok, A. Kwast, P.
Cmoch, Z. Wróbel, Tetrahedron 2010, 66, 698; c) C. S. Cho, T. K. Kim,
B. T. Kim, T.-J. Kim, S. C. Shim, J. Organomet. Chem. 2002, 650, 65;
d) C. Boix, J. M. De la Fuente, M. Poliako, New J. Chem. 1999, 23, 641.
[14] a) L. Chen, Z. Li, C.-J. Li, Synlett 2003, 732; b) K. H. Park, H. S. Joo, S.
W. Kim, M. S. Park, P. S. Shin, Tetrahedron Lett. 1999, 40, 1145; c) K.
H. Park, H. S. Joo, K. I. Ahn, K. Jun, Tetrahedron Lett. 1995, 36, 5943.
[15] E. Merişor, J. Conrad, S. Mika, U. Beifuss, Synlett 2007, 2033.
[16] a) A. Hakki, R. Dillert, D. W. Bahnemann, ACS Catal. 2013, 3, 565; b)
E. Merişor, J. Conrad, I. Klaiber, U. Beifuss, Angew. Chem. Int. Ed.
2007, 46, 3353; c) R. A. Bunce, D. M. Herron, L. Y. Hale, J.
Heterocyclic Chem. 2003, 40, 1031.
[23] V. Lucchini, M. Prato, G. Scorrano, P. Tecilla, J. Org. Chem. 1988, 53,
2251.
[24] For recent examples on the reduction of nitroarenes to anilines, see: a)
H. Genc, Catal. Commun. 2015, 67, 64; b) A. Shukla, R. K. Singha, T.
Sasaki, R. Bal, Green Chem. 2015, 17, 785; c) W.-J. Liu, K. Tian, H.
Jiang, Green Chem. 2015, 17, 821; d) Z. Zhao, H. Yang, J. Mol Catal.
A: Chem. 2015, 398, 268; e) X. Liu, X. Ma, S. Liu, Y. Liu, C. Xia, RCS
Adv. 2015, 5, 36423.
[25] L. Horner, J. Dehnert, Chem. Ber. 1963, 786.
[26] H.-G. Imrich, J. Conrad, D. Bubrin, U. Beifuss, J. Org. Chem. 2015, 80,
2319.
[17] a) A. R. Katritzky, S. Rachwal, B. Rachwal, Tetrahedron 1996, 52,
15031; b) S. Nishiyama, J. F. Cheng, X. L. Tao, S. Yamamura,
Tetrahedron Lett. 1991, 32, 4151; c) N. B. Perry, J. W. Blunt, M. H. G.
Munro, T. Higa, R. Sakai, J. Org. Chem. 1988, 53, 4127.
[27] For intramolecular Povarov reactions based on transformations
between anilines and salicylaldehyde ether-derived unsaturated
aldehydes, see: a) M. R. Spaller, W. T. Thielemann, P. E. Brennan, P.
A. Bartlett, J. Comb. Chem. 2002, 4, 516; b) V. Gaddam, R. Meesala, R.
Nagarajan, Synthesis 2007, 2504; c) M. Anniyappan, D. Muralidharan,
P. T. Perumal, Tetrahedron Lett. 2003, 44, 3653; d) G. Sabitha, E. V.
Reddy, Y. S. Yadav, Synthesis 2001, 1979; e) W. Jones, A. S.
Kieselyov, Tetrahedron Lett. 2000, 41, 2309.
[18] V. Sridharan, P. A. Suryavanshi, J. C. Menéndez, Chem. Rev. 2011,
111, 7157.
[19] K. Nagaiah, A. Venkatesham, R. Srinivasa Rao, V. Saddanapu, J. S.
Yadav, S. J. Basha, V. A S. Sarma,. B. Sridhar, A. Addlagatta, Bioorg.
Med. Chem. Lett. 2010, 20, 3259.
[20] a) A. Patti, S. Pedotti, Tetrahedron 2010, 66, 5607; b) R. A. Bunce, B.
Nammalwar, L. M. Slaughter, J. Heterocycl. Chem. 2009, 46, 854; c) R.
A. Bunce, J. E. Schammerhorn, L. M. Slaughter, J. Heterocycl. Chem.
2007, 44, 1051; d) R. A. Bunce, D. M. Herron, M. L. Ackerman, J. Org.
Chem. 2000, 65, 2847.
[28] a) L.-X. Dai, Y-R. Lin, X.-L. Hou, Y.-G. Zhou, Pure Appl. Chem. 1999,
71, 1033; b) G. Merényi, G. Wettermark, Chem. Phys. 1973, 1, 340.
[29] K. Marat, SpinWorks 4.0.1.0; University of Manitoba: Winnipeg, 2013.
[30] a) A. A. Kudale, D. O. Miller, L. N. Dawe, G. J. Bodwell, Org. Biomol.
Chem. 2011, 9, 7196; b) L. M. Jaramillo-Gómez, J. Martin, L. A. Rios, J.
Chil. Chem. Soc. 2007, 52, 1277.
[21] For reviews on the Povarov reaction, see: a) M. Fochi, L. Caruana, L.
Bernardi, Synthesis 2014, 135; b) G. Masson, C. Lalli, M. Benohoud, G.
Dagousset, Chem. Soc. Rev. 2013, 42, 902; c) V. V. Kouznetsov,
Tetrahedron 2009, 65, 2721; d) K. A. Jørgensen, Angew. Chem. Int. Ed.
2000, 39, 3558; e) L. S. Povarov, Russ. Chem. Rev. 1967, 36, 656.
[22] For recent examples of Povarov reactions, see: a) H.-X. Luo, Y.-H. Niu,
X.-P. Cao, X.-S. Ye, Adv. Synth. Catal. 2015, 357, 2893; b) Q. Gao, S.
Liu, X. Wu, J. Zhang, A. Wu, J. Org. Chem. 2015, 80, 5984; c) J. Pasha,
B. Kandagatla, S. Sen, G. P. K. Seerapu, S. Bujji, D. Haldar, S. Nanduri,
S. Oruganti, Tetrahedron Lett. 2015, 56, 2289; d) K. V. Sashidhara, G.
9
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One-Pot Reactions
Hans-Georg Imrich, Jürgen Conrad,
Uwe Beifuss*
Ph
1. Reduction
H
2. Imine formation
3. Intramolecular
aza-Diels-Alder
Ph
O
O
OHC
N
+
R1
H
Yields up to 87%
12 examples
H
Page No. – Page No.
R1
NO2
R2
R2
Only exo-E-anti products
The First Domino Reduction / Imine
Formation / Intramolecular Aza-Diels–
Alder Reaction for the
Diastereoselective Preparation of
Tetrahydrochromano[4,3-b]quinolines
Domino reduction / imine formation / intramolecular aza-Diels–Alder reaction
delivers tetrahydrochromano[4,3-b]quinolines with high exo-E-anti selectivity and
with yields up to 87% by reacting nitrobenzenes and a 2-(cinnamyloxy)-
benzaldehyde in aqueous citric acid using iron as a reductant and montmorillonite
K10 as a catalyst.
10
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