Synthesis of Functionalized Quinolines from 4-(o-Nitroaryl)-Substituted 3-Acyl-4,5-Dihydrofurans: Reductive Cyclization and C=C Bond Cleavage

Article abstract of DOI:10.1002/ejoc.201700256

A new synthetic approach to functionalized quinolines was developed based on the application of Zn–AcOH system as a simple and efficient reductive agent towards 4-(o-nitroaryl)-3-acyl-substituted 4,5-dihydrofurans. Reduction of 3-carbonyl-substituted dihy

Full text of DOI:10.1002/ejoc.201700256

A Journal of
Accepted Article
Title: Synthesis of Functionalized Quinolines from 4-(o-Nitroaryl)-
substituted 3-Acyl-4,5-dihydrofurans: Reductive Cyclization and
C=C Double Bond Cleavage
Authors: Sergey Zaytsev, Elena Villemson, Konstantin Ivanov,
Ekaterina Budynina, and Mikhail Melnikov
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201700256
Link to VoR: http://dx.doi.org/10.1002/ejoc.201700256
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European Journal of Organic Chemistry
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Synthesis of Functionalized Quinolines from 4-(o-Nitroaryl)-
substituted 3-Acyl-4,5-dihydrofurans: Reductive Cyclization and
C=C Double Bond Cleavage
[a]
[a]
[a]
[a]
Sergey V. Zaytsev, Elena V. Villemson, Konstantin L. Ivanov, Ekaterina M. Budynina,* and
Mikhail Ya. Melnikov[a]
Abstract: A new synthetic approach to functionalized quinolines was
developed based on the application of Zn-AcOH system as a simple
and efficient reductive agent towards 4-(o-nitroaryl)-3-acyl-
substituted 4,5-dihydrofurans. Reduction of 3-carbonyl-substituted
dihydrofurans is accomplished by C=C double bond cleavage in the
dihydrofuran ring and 1,6-cyclization leading to 3,4-dihydroquinolines.
The latter can be easily oxidized to quinolines or reduced to
tetrahydroquinolines. For dihydrofuran-3-carboxylates, reduction
proceeds with retention of the dihydrofuran ring and affords a
tricyclic dihydrofuroquinoline core under harsher conditions. The
proposed general reaction pattern was supported by results of DFT
quinoline-like cores provides manifold opportunities towards
further modification and functionalization of the synthesized
compounds.
calculations. Moreover,
a similar reductive system can be
successfully applied in the conversion of dihydrofuran acyclic
precursors, -(o-nitroaryl) α,β-unsaturated carbonyl compounds, into
quinoline derivatives.
Figure 1. Selected examples of quinoline-derived medicines.
Introduction
Quinoline-derived natural and artificial structures attract great
interest mostly due to their broad and manifold bioactivity.[1–8]
Among bioactive quinoline compounds, anticancer alkaloid
Camptothecin and its synthetic analogs, antimalarial Quinine,
Mefloquine, Chloroquine, antibacterial quinolone Ciprofloxacin
and its analogs are widely used as medicines (Figure 1).
Currently, in order to furnish wide structural and functional
diversity of quinoline-based compounds, classical approaches
(
such as Skraup, Doebner-von Miller, Friedländer, Pfitzinger,
Conrad-Limpach, Combes reactions) are used along with
relevant novel methods in order to assemble the quinoline core
and introduce desirable substituents into the pre-existing
bicycle.[9–20] In this context, we report a new synthesis of
Scheme 1. Opportunities for quinoline assembly presented in this work.
quinoline-based structures via intramolecular reduction-triggered
transformations[21,22] of 4-(o-nitroaryl)-3-acyl-substituted 4,5-
Results and Discussion
dihydrofurans. The method allows for the synthesis of
functionalized quinolones, 1,2,3,4-tetrahydro- and 3,4-
dihydroquinolines as well as tricyclic dihydrofuroquinoline
derivatives (Scheme 1). The presence of various functions, such
as carbonyl, alcohol or amino groups, in different positions of the
For the synthesis of the initial 4-(o-nitroaryl)-3-acyl-substituted
4,5-dihydrofurans 4 and 5, we employed a simple two-step
procedure based on Knoevenagel condensation, followed by
Corey-Chaykovsky reaction (Scheme 2).[23] In the first step, we
used commercial 2-nitrobenzaldehyde 1a or its derivatives 1b-d
which can be obtained in actual laboratory conditions via
nitration of the corresponding benzaldehydes.[24,25] The choice of
their 1,3-dicarbonyl counterparts was based on one essential
requirement: the presence of at least one keto-group which can
[
a]
Department of Chemistry, Moscow State University
Leninskie gory 1-3 Moscow 119991 Russia
E-mail: ekatbud@kinet.chem.msu.ru
Homepage: www.budynina.com
steer the transformation of alkene
2 or 3 towards 4,5-
dihydrofurans instead of cyclopropanes under Corey-
Supporting information for this article is given via a link at the end of
the document.
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European Journal of Organic Chemistry
10.1002/ejoc.201700256
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Chaykovsky reaction conditions. Therefore, acetylacetone and
methyl acetoacetate were applied.
as well, whereas complete conversion was only observed after
two-hour heating in EtOH under reflux. Therefore, further
experiments were carried out with the more appropriate Zn-
AcOH in EtOH.
The presence of a nitro group in Knoevenagel alkenes 2 and
3
determines their considerable lability under typical Corey-
Chaykovsky conditions which leads to significant reduction in
chemoselectivity for the formation of dihydrofurans 4 and 5 due
to oligo- and polymerization. A brief survey of reaction conditions
has allowed us to reveal the optimal ones (Scheme 2). We have
succeeded in preparation of 4 and 5 in reasonable yields upon
carrying out this reaction at 020 C for 20 min, whereas further
decrease in temperature or duration did not provide complete
conversion of alkenes 2 and 3 into 4 and 5, respectively.
Similarly to 4a, keto-derivatives 4b-d yield dihydroquinolines
6b-d under identical conditions (Scheme 3). Formally, the
reduction of 4a-d can be visualized as a domino-process
proceeding via initial formation of anilines I-1 whose
intramolecular reaction with the carbonyl group leads to imine
ring closure (I-2) and dihydrofuran ring opening.
Scheme 3. Reduction of 3-keto-derived dihydrofurans 4a-d.
Dihydroquinolines 6a-d were found to be quite unstable,
rapidly decomposing on silica gel during purification attempts.
Moreover, imines
corresponding tetrahydroquinolines
6
readily disproportionate to form the
and quinolines 8.
7
Nevertheless, we characterized 6a-d as crude products and
then transformed them into their stable derivatives (Scheme 4).
Thus, the reduction of
6
with NaBH
4
readily furnished
tetrahydroquinolines 7a-d. Alternatively, dehydrogenation of 6 in
the presence of Pd/C led to aromatization of the bicyclic system
and formation of stable quinolines 8a-d.
Scheme 2. Synthesis of parent dihydrofurans 4 and 5.
In order to elucidate appropriate reductive conditions,
several simple Fe or Zn-based systems were examined, with
dihydrofuran 4a employed as a model substrate. Fe-HCl in
EtOH-H
2
O under reflux, quite common in the reduction of
nitroarenes,[
26]
proved to be too harsh for 4a, affording a
complex mixture of unidentified products. The use of Zn-HCl at
ambient temperature leads to a significant decrease in reaction
time without noticeable enhancement in chemoselectivity.
Replacement of a strong Brønsted acid, HCl, by weaker AcOH
allowed us to achieve chemoselective reduction of 4a. At
ambient temperature, slow conversion was observed, while
heating the reaction mixture in EtOH under reflux provided
complete conversion of 4a in 10 min. Unexpectedly, this reaction
resulted in dihydroquinoline 6a (Scheme 3). The Zn-NH
4
Cl
system was found to be suitable for transformation of 4a into 6a
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European Journal of Organic Chemistry
10.1002/ejoc.201700256
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Scheme 4. Reduction and dehydrogenation of 6 into tetrahydroquinolines 7
and quinolines 8.
Tetrahydroquinolines 7 were formed as mixtures of two
diastereomers with the prevalence of 2,4-cis-isomers supported
1
by NMR spectral data. Thus, in H NMR spectra of 7 two Haxial
-
H
axial 3J (ca. 11–13 Hz) are observed for the major isomers, while
only one such constant is revealed for each of the minor isomers
Table 1). Additionally, in NOESY spectra of 7d, strong cross-
(
peaks between two methine protons arise for the major isomers.
DFT method
ΔH298 [kcal/mol]
B3LYP/def2-SVP
B3LYP/def2-TZVP
M06-2X/def2-SVP
0.8
2.0
1.9
Table 1. Relative configurations and stabilities for major and minor
isomers of tetrahydroquinoline 7a
NMR data
The use of identical conditions for the reduction of ester-
substituted dihydrofurans 5 resulted in stable aniline derivatives
9

1
(Scheme 5) which, apparently, did not undergo spontaneous
-lactamization due to lower electrophilicity of CO R vs. COR.
,6-Cyclization into quinolone derivatives 10 was found to
2
proceed under harsher conditions (when filtered reaction
mixtures were heated in a microwave reactor at 150 C upon
zinc removal). It is noteworthy that in the instances when acetic
acid was removed after reduction, intramolecular amidation did
not proceed up to 180 C. Despite harsh conditions, 1,6-
cyclization of 9 to quinolones 10 was not accompanied by
dihydrofuran ring opening in contrast with 4-to-6 transformation.
DFT method
ΔH298 [kcal/mol]
B3LYP/def2-SVP
B3LYP/def2-TZVP
M06-2X/def2-SVP
1.1
1.2
1.3
According to the results of DFT calculations, the minor trans-
a is more stable than the major cis-7a (Table 1). This can be
7
2
ascribed to the equatorial location of the bulky CH OAc group at
C-4 in cis-7a which is less favorable for tetralin-like bicycles due
to the interaction between this group and H-5.[27] Therefore, the
origin of this diastereoselectivity can be related to the
conformation of the initial imine 6a (Table 2). The major cis-7a
may be derived via a hydride attack on the more stable
conformer of imine a-6a with the CH
axially (this minimizes the interaction between this group and H-
). The alternative hydride attack on the less stable conformer of
imine e-6a, where bulky CH OAc at C-4 occupies the less
2
OAc group at C-4 located
5
2
favorable equatorial position, can afford both cis- and trans-7a.
Table 2. Origin of diastereoselectivity of 6a-to-7a transformation and
relative stabilities of conformers a-6a and e-6a
Scheme 5. Reduction of dihydrofuran-3-carboxylates 5.
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European Journal of Organic Chemistry
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FULL PAPER
40
30
20
10
0
3
1.4
3.5
2
4.4
2
17.6
1
9.8
9
.3
-
10
20
-
12.3
16.0
-
-
Scheme 6. Energy profiles (B3LYP/def2-SVP/COSMO EtOH) for ring opening in protonated hydrates of imine (I3, green path) and amide (I3’, red path).
To better understand the difference in reactivities of ketones
2
an NO -free analog of dihydrofuran 4a, 1-(2-methyl-4-phenyl-
4
and esters 5 we carried out DFT calculations of energy
4,5-dihydrofuran-3-yl)ethan-1-one, in EtOH in the presence of
Zn-AcOH for 1 h did not cause its any detectable conversion.
Meanwhile, the prolong heating of NO -free dihydrofuran of type
2
barriers for C–C bond cleavage in hypothetic species I3 and I3’
Scheme 6).[ These species can be yielded by I2a (Scheme 3)
28]
(
or 10a (Scheme 5) via hydration of dihydrofuran rings in them
under acidic conditions. We supposed that I3 and I3’ are more
probable intermediates for C–C bond cleavage in comparison
with hydrated forms of initial dihydrofurans 4 and 5.
4 in the presence of a strong Brønsted acids (e.g., HCl) led to
dihydrofuran ring opening.[29]
Table 3. H
3
O+ affinities of I2a and 10a defined as ΔG of corresponding
We succeeded in optimizing the corresponding transition
states TS1 and TS1’ for C–C bond cleavage in I3 and I3’ in the
gas phase and EtOH, using the COSMO model. This allowed us
to calculate two energy profiles for the transformation of cations
I3 and I3’ into protonated final dihydroquinolines I5 and I5’. We
revealed the highest stationary points of the calculated pathways
that correspond to transition states TS2 and TS2’. These
transition states are related to the rotation along C=O bond in
the protonated esters I4 and I4’, leading to spontaneous
intramolecular proton transfer with irreversible formation of I5
and I5’. The calculated pathways indicate possibility of C–C
bond cleavage in both cases while for I3’ this process is much
slower. This may be due to more efficient delocalization of the
positive charge in protonated amide I3’ vs. protonated imine I3.
The differences in reactivity can also be explained
thermodynamically by referring to different basicities of the
hydrated intermediate imine I2a and final amide 10a. It is
reactions (B3LYP/def2-SVP/COSMO EtOH).
Reaction
Δ
r
G
298 [kcal/mol]
O+ → I3
O+ → I3’
I2a + H
10a + H
3
-24.6
3
-9.3
10a + I3 → I2a + I3’
15.3
Therefore, the difference in reactivities of ketones 4, leading
to bicyclic dihydroquinoline derivatives 6, and esters 5, affording
tricyclic dihydrofuroquinolone 10, is ensured by both
thermodynamic and kinetic factors. On the one hand, the
basicity of imine is higher than that of amide and, thus, under the
same acidic conditions, imine I2 provides higher concentration of
the protonated hydrates I3. On the other hand, due to less
effective delocalization of the positive charge in I3 vs. I3’, the
former is more prone towards C–C bond cleavage affording
dihydroquinoline 6 as the final product (Scheme 7).
obvious that the basicity of imine is higher than that of amide.
+
The calculated values of the corresponding H
3
O affinities for I2a
and 10a are given in Table 3. They allowed us to hypothesize
that the use of a relatively weak Brønsted acid (e.g., AcOH)
would not afford sufficient concentrations of I3’ to provide a
noticeable C–C bond cleavage rate. In particular, the heating of
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European Journal of Organic Chemistry
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FULL PAPER
Scheme 7. Proposed mechanism for reductive transformations of ketones 4 and esters 5.
Additionally, we examined the efficiency of Zn-AcOH when
applied to Knoevenagel alkenes and (precursors of
dihydrofurans 4 and 5). We found that, under similar conditions,
the reaction of alkenes 2,3 proceeds with exceptional
the corresponding keto- and ester-derivatives. DFT calculations
supported the proposed reaction pathway that includes the
hydration of the C=C double bond followed by its cleavage,
which is enforced by additional activation via protonation of the
hydrated intermediate.
2
3
2
chemoselectivity, manifesting as a cascade of NO -reduction /
intramolecular imination and yielding the corresponding
functionalized quinolines 11,12 (Scheme 8).[30,31]
Additionally, Zn-AcOH was proved to be effective in the
reductive transformation of Knoevenagel alkenes, acting as
dihydrofuran precursors, into quinoline derivatives.
Experimental Section
General information
NMR spectra were acquired either on Bruker Avance 400 MHz or on
Bruker Avance 600 MHz spectrometers at room temperature; the
1
chemical shifts  were measured in ppm with respect to solvent ( Н:
13
CDCl
3
,  = 7.27 ppm; C: CDCl ,  = 77.0 ppm). Splitting patterns are
3
designated as s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; dd,
double doublet. Coupling constants (J) are given in Hertz. The structures
of compounds were elucidated with the aid of 1D NMR ( H, 13C) and 2D
1
NMR ( H- H COSY, 1H-13C HSQC and HMBC) spectroscopy. High
resolution and accurate mass measurements were carried out using a
BrukermicroTOF-QTM ESI-TOF (Electro Spray Ionization / Time of Flight)
and Thermo ScientificTM LTQ Orbitrap mass spectrometers. Analytical
thin layer chromatography (TLC) was carried out with silica gel plates
1
1
(silica gel 60, F254, supported on aluminium); the revelation was done by
UV lamp (365 nm).
Scheme 8. Reductive transformation of alkenes 2 and 3 into quinolines 11 and
12.
All the calculations reported in this paper have been performed within
density functional theory,[32] using the hybrid functionals B3LYP[33,34] or
M06-2X.[35]
A
standard def2-SVP or def2-TZVP basis sets,[36] as
Conclusions
[37]
implemented in the ORCA 3.0 suite of programs, have been used in all
cases together with the RIJCOSX approximation.[38] Preliminary
geometry optimization of the various stereoisomers and conformers of
I2a and 10a was made in order to select the most stable ones.
Frequency analysis was carried out to check whether optimized
structures were local minima or transition states. No imaginary
frequencies were found for local minima, and only one imaginary
frequency was found for each transition state. The solvent effects were
estimated using the continuous solvation model COSMO[39] with ethanol
as a solvent. All the energetic characteristics of reactions were computed
assuming zero-point energy correction.
In conclusion, we have developed a new technique for the
synthesis of functionalized quinoline derivatives via reduction of
4
-(o-nitroaryl)-3-acyl-substituted 4,5-dihydrofurans with a simple
Zn-AcOH reductive system. 3-Keto-derived 4,5-dihydrofurans
yield 3,4-dihydroquinolines via a domino reaction involving NO
2
reduction, 1,6-cyclization and C=C double bond cleavage in the
dihydrofuran fragment, whereas 4,5-dihydrofuran-3-carboxylates
afford dihydrofuroquinolines, retaining the dihydrofuran ring.
Apparently, the difference in reactivity is related to the
discrepancy in basicities of imines vs. amides, originating from
GP-I. General procedure for synthesis of alkenes 2 and 3
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European Journal of Organic Chemistry
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Alkenes 2 and 3 were synthesized via Knoevenagel condensation under
piperidinium acetate catalysis. Mixture of corresponding o-
nitrobenzaldehyde 1 (33 mmol) acetylacetone or methyl acetoacetate (33
mmol), piperidine (3.3 mmol) and acetic acid (6.6 mmol) in benzene (25
mL) was heated under reflux with 15-mL Dean-Stark trap for 2 h. After
cooling to the ambient temperature, reaction mixture was washed twice
concentrated under reduced pressure. Product 10 was purified by
column chromatography (SiO
2
, petroleum ether – ethyl acetate 4:1).
-(2-Nitrobenzylidene)pentane-2,4-dione (2a)[40] was obtained from 1a
3
and acetylacetone according to GP-I. Yield 76%.
R
f
0.30
),
1
(
dichloromethane). Н NMR (CDCl
3
, 600 MHz)  = 2.11 (s, 3H, CH
3
with brine, dried with Na
Residue was purified by column chromatography (Al
dichloromethane 1:1).
2
SO
4
and concentrated under reduced pressure.
), 7.38 (br. d, 3J 7.6 Hz, 1H, Ar), 7.57–7.61 (m, 1H, Ar),
2
.48 (s, 3H, CH
.63–7.68 (m, 1H, Ar), 7.91 (s, 1 H, CH=), 8.22 (dd, J 8.2, J 1.2 Hz, 1H,
, 150 MHz)  = 26.8 (CH ), 31.7 (CH ), 125.2 (CH),
29.9 (C), 130.5 (CH), 131.2 (CH), 134.1 (CH), 137.8 (CH), 144.2 (C),
147.0 (C), 196.3 (C=O), 202.8 (C=O).
3
2 3
O , petroleum ether
3
4
7
-
Ar). 13С NMR (CDCl
3
3
3
1
GP-II. General procedure for synthesis of dihydrofurans 4 and 5
Dihydrofurans and were synthesized under Corey-Chaykovsky
reaction conditions. To suspension of NaH (7.5 mmol, 60% suspension in
mineral oil) in dry DMF (14 mL) Me SOI (7.5 mmol) was added in one
4
5
3-(5-Bromo-2-nitrobenzylidene)pentane-2,4-dione (2b) was obtained
3
from 1b and acetylacetone according to GP-I. Yield 54%. R 0.28
f
portion under inert atmosphere. After stirring for 20 min at ambient
temperature, reaction mixture was cooled in ice-water bath and then
alkene 2 or 3 (6.8 mmol) was added in one portion under vigorous stirring.
Cooling bath was taken away and the mixture was stirred for additional
dichloromethane : petroleum ether; 1:1). 1Н NMR (CDCl
3
, 600 MHz)  =
(
), 7.49–7.50 (m, 1H, Ar), 7.69 (dd, 3
2
.15 (s, 3H, CH
3
), 2.46 (s, 3H, CH
3
J
.8, J 2.2 Hz, 1H, Ar), 7.81 (s, 1H, CH=), 8.07 (d, J 8.8 Hz, 1H, Ar). 13С
4
3
8
NMR (CDCl
3 3 3
, 150 MHz)  = 26.8 (CH ), 31.7 (CH ), 128.6 (CH), 129.1
2
0 min, quenched with ice water (15 mL) and extracted with EtOAc (330
mL). Combined organic fractions were washed with water (515 mL),
dried with Na SO and concentrated under reduced pressure. Residue
(
1
C), 131.8 (C), 133.4 (CH), 133.7 (CH), 136.8 (CH), 144.5 (C), 145.7 (C),
96.3 (C=O), 201.9 (C=O). HRMS ESI: m/z = 311.9858 [M + H]+
2
4
(
311.9866 calcd for C12H11BrNO
4
).
was purified by column chromatography (Al
dichloromethane 1:1).
2 3
O , petroleum ether -
3-(4,5-Dimethoxy-2-nitrobenzylidene)pentane-2,4-dione (2c) was
obtained from 1c and acetylacetone according to GP-I. Yield 75%. R
f
GP-III. General procedure for reduction of dihydrofurans 4 and 5
.77 (ethyl acetate : dichloromethane; 1:10). 1Н NMR (CDCl
0

OCH
3
, 600 MHz)
), 3.91 (s, 3H,
), 6.76 (s, 1H, CH), 7.68 (s, 1H, CH), 7.86 (s, 1H, CH). 13С NMR
, 150 MHz)  = 26.5 (CH ), 31.7 (CH ), 56.5 (OCH ), 56.6 (OCH ),
To solution of dihydrofuran 4 or 5 (1 mmol) in EtOH (10 mL) Zn dust (10
mmol) and AcOH (5 mmol) were successively added under vigorous
stirring. Resulting suspension was heated under reflux for 10 min. After
cooling to ambient temperature, reaction mixture was diluted with brine
3 3 3
= 2.03 (s, 3H, CH ), 2.39 (s, 3H, CH ), 3.85 (s, 3H, OCH
3
(
CDCl
3
3
3
3
3
1
1
2
08.0 (CH), 112.7 (CH), 123.9 (C), 138.1 (CH), 139.7 (C), 143.5 (C),
(10 mL) and extracted with EtOAc (320 mL). Combined organic
49.6 (C), 153.3 (C), 196.5 (C=O), 203.8 (C=O). HRMS ESI: m/z =
fractions were washed twice with water, dried with Na SO and
2
4
+
94.0967 [M + H] (294.0972 calcd for C14
H16NO
6
).
concentrated under reduced pressure. Crude product 6 was used in the
next steps without purification. Product 9 can be purified by column
3
(
-((6-Nitrobenzo[d][1,3]dioxol-5-yl)methylene)pentane-2,4-dione
chromatography (SiO
purification.
2
, ethyl acetate) or used in the next steps without
2d)[30] was obtained from 1d and acetylacetone according to GP-I. Yield
0.81 (ethyl acetate : dichloromethane; 1:10). 1Н NMR (CDCl
), 2.42 (s, 3H, CH ), 6.15 (s, 2H, OCH O),
65%. R
600 MHz)  = 2.12 (s, 3H, CH
.70 (s, 1H, CH), 7.64 (s, 1H, CH), 7.81 (s, 1H, CH). 13С NMR (CDCl
6
150 MHz)  = 26.5 (CH ), 31.6 (CH ), 103.6 (OCH O), 105.7 (CH), 109.4
f
3
,
3
3
2
GP-IV. General procedure for reduction of dihydroquinolines 6
3
,
To solution of crude dihydroquinoline 6 (GP-III) in MeOH (10 mL) NaBH
4
3
3
2
(57 mg, 1.5 mmol) was added in one portion. Resulting suspension was
(CH), 126.3 (C), 138.3 (CH), 141.4 (C), 143.2 (C), 149.0 (C), 152.3 (C),
stirred under ambient conditions for 4 h, then diluted with brine (10 mL)
and extracted with EtOAc (320 mL). Combined organic fractions were
196.3 (C=O), 202.8 (C=O).
2 4
dried with Na SO and concentrated under reduced pressure. Product 7
3
-(3,4,5-Trimethoxy-2-nitrobenzylidene)pentane-2,4-dione (2e) was
was purified by column chromatography (SiO
acetate 4:1).
2
, petroleum ether – ethyl
obtained from 1e and acetylacetone according to GP-I. Yield 71%. R
f
0

OCH
.66 (ethyl acetate : dichloromethane; 1:20). 1Н NMR (CDCl
= 2.18 (s, 3H, CH ), 2.36 (s, 3H, CH ), 3.84 (s, 3H, OCH ), 3.91 (s, 3H,
), 6.67 (s, 1H, CH), 7.35 (s, 1H, CH=). 13С
), 3.98 (s, 3H, OCH
, 150 MHz)  = 26.3 (1JCH 128 Hz, CH
NMR (CDCl
), 56.3 (1JCH 146 Hz, OCH ), 61.1 (1JCH 146 Hz, OCH
CH
46 Hz, OCH
3
, 600 MHz)
3
3
3
GP-V. General procedure for dehydrogenation of dihydroquinolines
6
To solution of crude dihydroquinoline 6 (GP-III) in toluene (10 mL) 10%-
Pd/C (100 mg) was added in one portion. Resulted suspension was
stirred at 130 C for 4 h. After cooling to ambient temperature, reaction
3
3
), 31.7 (1JCH 128 Hz,
3
3
), 62.4 (1JCH
3
3
3
1
1
3
), 107.7 (CH), 122.2 (C), 133.1 (CH=), 138.7 (C), 143.7 (C),
45.6 (C), 146.9 (C), 155.1 (C), 196.0 (C=O), 204.0 (C=O). HRMS ESI:
mixture was diluted with EtOAc (10 mL), passed through thing SiO
and concentrated under reduced pressure. Product 8 was purified by
column chromatography (SiO , petroleum ether – ethyl acetate 1:1).
2
layer
+
m/z = 324.1080 [M + H] (324.1078 calcd for C15
7
H18NO ).
2
3
-(2,3,4-Trimethoxy-6-nitrobenzylidene)pentane-2,4-dione (2f) was
obtained from 1f and acetylacetone according to GP-I. Yield 69%. R 0.57
ethyl acetate : dichloromethane; 1:20). 1Н NMR (CDCl
, 600 MHz)  =
), 3.75 (s, 3H, OCH ), 3.90 (s, 3H,
), 7.53 (s, 1H, CH), 7.61 (s, 1H, CH). 13С NMR
), 29.9 (CH ), 56.3 (OCH ), 61.0 (OCH ),
), 104.5 (CH), 118.5 (C), 135.7 (CH=), 142.2 (C), 143.7 (C),
f
GP-VI. General procedure for two-step transformation of 5 into 10
Reaction mixture obtaining from dihydrofuran 5, Zn dust and AcOH in
EtOH according to GP-III was heated under reflux for 10 min. After
cooling to ambient temperature, the resulting suspension was filtered,
precipitate was washed with EtOH (22mL), filtrate was put into
microwave vial and heated in microwave reactor at 150 C for 40 min.
After cooling to ambient temperature, reaction mixture was diluted with
brine (10 mL) and extracted with EtOAc (320 mL). Combined organic
(
3
2.22 (s, 3H, CH
3
), 2.47 (s, 3H, CH
3
3
OCH
), 3.92 (s, 3H, OCH
3 3
(
6
1
CDCl
3
, 150 MHz)  = 26.9 (CH
1.2 (OCH
3
3
3
3
3
47.2 (C), 150.1 (C), 153.3 (C), 197.0 (C=O), 200.9 (C=O). HRMS ESI:
+
m/z = 324.1079 [M + H] (324.1078 calcd for C15
7
H18NO ).
2 4
fractions were washed twice with water, dried with Na SO and
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201700256
FULL PAPER
Methyl 2-(2-nitrobenzylidene)-3-oxobutyrate (3a)[41] was obtained from
CH
CH
), 29.1 (1JCH 127 Hz, CH
), 44.2 (1JCH 142 Hz, CH), 77.6 (1JCH 154 Hz,
3
3
1
a and methyl acetoacetate according to GP-I. Yield 85%; dr A:B = 60:40.
0.38 (dichloromethane). 1Н NMR (CDCl
, 600 MHz)  = 2.15 (s, 3H,
, A), 3.54 (s, 3H, OCH , A), 3.81 (s, 3H, OCH
2
), 114.3 (C), 126.2 (CH), 128.6 (C), 131.1 (CH), 131.4 (CH), 140.3
R
f
3
(C), 147.5 (C), 171.2 (C), 192.9 (C=O). HRMS ESI: m/z = 326.0020 [M +
+
CH
3
, B), 2.42 (s, 3H, CH
3
3
3
,
H] (326.0022 calcd for C13
H
13BrNO
4
).
B), 7.29 (br. d, J 7.5 Hz, 1H, Ar, B), 7.37 (br. d, 3J 7.5 Hz, 1H, Ar, A),
3
7
.51–7.53 (m, 1H, Ar, B), 7.53–7.55 (m, 1H, Ar, A), 7.58–7.60 (m, 1H, Ar,
B), 7.61–7.64 (m, 1H, Ar, A), 8.00 (s, 1 H, CH=, B), 8.03 (s, 1 H, CH=, A),
.13 (d, 3J 8.1 Hz, 1H, Ar, B), 8.16 (dd, 3J 8.1 Hz, 1H, Ar, A). 13С NMR
CDCl , 150 MHz)  = 26.8 (CH , A), 30.9 (CH , B), 52.0 (OCH , A), 52.4
OCH , B), 124.8 (CH, B), 124.9 (CH, A), 129.6 (CH, A), 129.8 (C, B),
30.1 (CH, B), 130.2 (CH, A), 130.3 (C, A), 130.7 (CH, B), 133.73 (CH,
B), 133.75 (CH, A), 135.5 (C, B), 136.0 (C, A), 139.4 (CH, A), 140.2 (CH,
B), 146.7 (C, A), 146.9 (C, B), 164.1 (CO Me, B), 166.0 (CO Me, A),
94.3 (C=O, A), 200.1 (C=O, B).
1
-(4-(4,5-Dimethoxy-2-nitrophenyl)-2-methyl-4,5-dihydrofuran-3-
yl)ethanone (4c) was obtained from 2с according to GP-II. Yield 58%. R
f
8
(
(
1
0
2
4
CH
.42 (dichloromethane). Н NMR (CDCl
3
, 600 MHz)  = 1.93 (s, 3H, CH
), 3.85 (s, 3H, OCH ), 3.91 (s, 3H, OCH
.22 (dd, 2J 9.6, J 5.0 Hz, 1H, CH ), 4.92 (dd, 2J 9.6, 3J 10.8 Hz, 1H,
), 5.02 (ddq, J 5.0, 10.8, J 0.9 Hz, 1H, CH), 6.66 (s, 1H, Ar), 7.57 (s,
, 150 MHz)  = 15.2 (CH ), 29.1 (CH ), 44.4
), 56.3 (OCH ), 78.3 (CH ), 108.3 (CH), 109.4 (CH),
13.6 (C), 133.1 (C), 140.8 (C), 147.7 (C), 153.5 (C), 171.4 (C), 194.1
3
),
),
3
3
3
3
.36 (d, 5J 0.9 Hz, 3H, CH
3
3
3
3
3
2
1
3
5
2
H, Ar). 13С NMR (CDCl
1
3
3
3
2
2
(CH), 56.2 (OCH
3
3
2
1
1
(
C
C=O). HRMS ESI: m/z = 308.1132 [M + H]+ (308.1129 calcd for
).
Methyl 2-(4,5-dimethoxy-2-nitrobenzylidene)-3-oxobutyrate (3b) was
obtained from 1b and methyl acetoacetate according to GP-I. Yield 83%;
15
H18NO
6
dr A:B = 61:39. R
CDCl , 600 MHz)  = 2.19 (s, 3H, CH
H, OCH , B), 3.88 (s, 3H, OCH , A), 3.93 (s, 3H, OCH
, B), 3.98 (s, 3H, OCH , A), 3.99 (s, 3H, OCH , B), 6.82 (s, 1H, CH,
f
0.79 (ethyl acetate : dichloromethane; 1:10). 1Н NMR
, A), 2.49 (s, 3H, CH , B), 3.66 (s,
, A), 3.94 (s, 3H,
1
-(2-Methyl-4-(6-nitrobenzo[d][1,3]dioxol-5-yl)-4,5-dihydrofuran-3-
(
3
OCH
3
3
3
yl)ethanone (4d) was obtained from 2d according to GP-II. Yield 55%. R
f
3
3
3
1
0
.40 (dichloromethane). Н NMR (CDCl
3
, 600 MHz)  = 2.01 (s, 3H, CH
3 2
3
),
), 4.88
), 4.89 (ddq, 3J 3.7, 10.7, 5J 1.1 Hz 1H,
O), 6.08 (d, 2J 1.2 Hz, 1H, OCH
O),
.68 (s, 1H, Ar), 7.47 (s, 1H, Ar). 13С NMR (CDCl
, 150 MHz)  = 15.3
1JCH 130 Hz, CH ), 29.2 (1JCH 127 Hz, CH ), 44.6 (1JCH 141 Hz, CH),
8.2 (1JCH 155 Hz, CH ), 103.0 (1JCH 176 Hz, OCH
O), 105.7 (CH), 107.1
3
3
3
.36 (d, 5J 1.1 Hz, 3H, CH
), 4.21 (dd, 2J 8.7, J 3.7 Hz 1H, CH
3
2
A), 6.91 (s, 1H, CH, B), 7.76 (s, 1H, CH, A), 7.78 (s, 1H, CH, B), 8.08 (s,
H, CH, B), 8.09 (s, 1H, CH, A). 13С NMR (CDCl
, 150 MHz)  = 26.7
CH ), 31.4 (CH ), 52.5 (OCH ), 52.7 (OCH ), 56.5 (2× OCH ), 56.62
OCH ), 56.64 (OCH ), 107.9 (CH), 108.0 (CH), 111.2 (CH), 112.8 (CH),
24.0 (C), 124.5 (C), 135.1 (C), 136.0 (C), 139.5 (CH), 139.9 (C), 140.0
C), 140.3 (CH), 149.6 (C), 149.7 (C), 153.2 (C), 153.3 (C), 164.4
dd, 2J 8.7, 3J 10.7 Hz 1H, CH
2
(
1
3
CH), 6.07 (d, 2J 1.2 Hz, 1H, OCH
2
2
(
(
3
3
3
3
3
6
(
7
3
3
3
3
3
1
2
2
(
(
3
(
1
CH), 114.2 (C), 135.6 (C), 142.5 (C), 146.8 (C), 152.4 (C), 171.4 (C),
CO
2
Me), 166.9 (CO
2
Me), 194.7 (C=O), 201.6 (C=O). HRMS ESI: m/z =
93.6 (C=O). HRMS ESI: m/z = 292.0820 [M + H]+ (292.0816 calcd for
+
10.0923 [M + H] (310.0921 calcd for C14
H16NO
7
).
C
14 14
H O
6
N).
Methyl
oxobutobutyrate (3c) was obtained from 1c and methyl acetoacetate
according to GP-I. Yield 79%; dr A:B = 58:42. R 0.82 (ethyl acetate :
dichloromethane; 1:10). 1Н NMR (CDCl
, 600 MHz) A  = 2.41 (s, 3H,
CH ), 3.64 (s, 3H, OCH ), 6.14 (s, 2H, OCH O), 6.75 (s, 1H, CH), 7.61 (s,
H, CH), 7.92 (s, 1H, CH); B  = 2.21 (s, 3H, CH ), 3.84 (s, 3H, OCH ),
2-((6-nitrobenzo[d][1,3]dioxol-5-yl)methylene)-3-
Methyl
2-methyl-4-(2-nitrophenyl)-4,5-dihydrofuran-3-carboxylate
(
5a) was obtained from 3a according to GP-II. Yield 57%. R
f
0.85 (ethyl
f
1
5
acetate : petroleum ether; 1:1). Н NMR (CDCl
3
, 600 MHz)  = 2.36 (d, J
3
), 3.34 (dd, 2J 9.8, J 4.9 Hz 1H,
3
1.2 Hz, 3H, CH ), 3.53 (s, 3H, OCH
3
3
3
3
2
2
CH ), 4.85 (ddq, J 9.8, 10.9, J 1.2 Hz 1H, CH), 4.93 (dd, J 9.8, J 10.9
3
5
2
3
1
3
3
3
4
3
4
Hz 1H, CH
2
), 7.36 (dd, J 7.8, J 1.4 Hz, 1H, Ar), 7.39 (ddd, J 7.4, 8.1, J
6
.15 (s, 2H, OCH
2
O), 6.68 (s, 1H, CH), 7.63 (s, 1H, CH), 7.96 (s, 1H, CH).
3
4
5
1
.4 Hz, 1H, Ar), 7.56–7.59 (m, 1H, Ar), 7.95 (ddd, J 7.8, J 1.4, J 0.4 Hz,
1
3С NMR (CDCl
1
), 52.5 (1JCH
3
, 150 MHz) A  = 26.7 ( JCH 129 Hz, CH
3
H, Ar). 13С NMR (CDCl
1
1
3
, 150 MHz)  = 14.3 ( JCH 129 Hz, CH
3
), 43.5
), 78.2 (1JCH 154 Hz, CH
),
1
148 Hz, OCH
3
), 104.0 ( JCH 177 Hz, OCH
2
O), 105.5 (CH), 108.1 (CH),
1JCH 143 Hz, CH), 50.9 ( JCH 146 Hz, OCH
1
(
3
2
1
26.6 (C), 135.4 (C), 140.4 (CH), 141.5 (C), 148.9 (C), 152.2 (C), 166.2
104.3 (C), 124.5 (CH), 127.6 (CH), 128.5 (CH), 133.4 (CH), 138.6 (C),
1
), 52.6 (1JCH 148 Hz,
(
CO
2
Me), 194.4 (C=O); B  = 31.2 ( JCH 129 Hz, CH
3
+
148.9 (C), 165.6 (C), 171.6 (C). HRMS ESI: m/z = 264.0868 [M + H]
1
OCH
3
), 103.6 ( JCH 177 Hz, OCH
2
O), 105.6 (CH), 109.5 (CH), 126.4 (C),
Me),
00.5 (C=O). HRMS ESI: m/z = 294.0609 [M + H]+ (294.0608 calcd for
).
(
264.0866 calcd for C13
5
H14NO ).
1
2
34.8 (C), 139.9 (CH), 141.6 (C), 148.8 (C), 152.1 (C), 164.3 (CO
2
Methyl 4-(4,5-dimethoxy-2-nitrophenyl)-2-methyl-4,5-dihydrofuran-3-
carboxylate (5b) was obtained from 3b according to GP-II. Yield 55%. R
13 7
C H12NO
f
1
0
2
.55 (ethyl acetate : petroleum ether; 1:1). Н NMR (CDCl
3
, 600 MHz)  =
1-(2-Methyl-4-(2-nitrophenyl)-4,5-dihydrofuran-3-yl)ethanone
(4a)
.38 (d, 5J 1.1 Hz, 3H, CH
3
), 3.56 (s, 3H, OCH
3
), 3.90 (s, 3H, OCH
3
),
was obtained from 2a according to GP-II. Yield 60%.
R
f
0.35
2
3
2
3
.94 (s, 3H, OCH
3
), 4.29 (dd, J 8.9, J 4.3 Hz, 1H, CH
2
), 4.97 (dd, J 8.9,
1
(dichloromethane). Н NMR (CDCl
3
, 600 MHz)  = 1.97 (s, 3H, CH
3
),
),
3
3
5
J 10.9 Hz, 1H, CH
2
), 5.01 (ddq, J 4.3, 10.9, J 1.1 Hz, 1H, CH), 6.71 (s,
, 150 MHz)  = 14.3 (CH ), 43.7
), 78.2 (CH ), 104.0 (C),
2
3
.39 (br.s, 3H, CH ), 4.24–4.33 (m, 1H, CH), 4.87–4.95 (m, 2H, CH
2
H, Ar), 7.58 (s, 1H, Ar). 13С NMR (CDCl
1
3
3
3
4
3
4
7.33 (dd, J 7.9, J 1.3 Hz, 1H, Ar), 7.41 (ddd, J 7.6, 7.9, J 1.3 Hz, 1H,
(CH), 50.9 (OCH ), 56.2 (OCH ), 56.3 (OCH
3
3
3
2
3
4
3
4
Ar), 7.58 (ddd, J 7.6, 8.1, J 1.1 Hz, 1H, Ar), 7.95 (dd, J 8.1, J 1.1 Hz,
H, Ar). 13С NMR (CDCl , 150 MHz)  = 15.4 (1JCH 129 Hz, CH
), 29.2
1JCH 128 Hz, CH ), 44.4 (1JCH 141 Hz, CH), 78.2 ( JCH 154 Hz, CH
),
1
08.0 (CH), 109.4 (CH), 133.6 (C), 141.0 (C), 147.5 (C), 153.4 (C), 165.7
1
(
3
3
C), 171.5 (C). HRMS ESI: m/z = 324.1074 [M + H]+ (324.1078 calcd for
).
(
1
3
2
15 7
C H18NO
1
1
14.1 (C), 124.8 (CH), 128.0 (CH), 128.6 (CH), 133.7 (CH), 138.2 (C),
48.9 (C), 171.4 (C), 193.9 (C=O). HRMS ESI: m/z = 248.0924 [M + H]+
Methyl 2-methyl-4-(6-nitrobenzo[d][1,3]dioxol-5-yl)-4,5-dihydrofuran-
(
248.0917 calcd for C13
H
14NO
4
).
3
-carboxylate (5c) was obtained from 3c according to GP-II. Yield 60%.
1
5
R
f
0.32 (dichloromethane). Н NMR (CDCl
), 4.27 (dd, 2J 9.1, J 4.2 Hz, 1H, CH
), 3.58 (s, 3H, CH
.88 (ddq, 3J 4.2, 10.8, J 1.1 Hz, 1H, CH), 4.92 (dd, 2J 9.1, 3J 10.8 Hz,
3
, 600 MHz)  = 2.36 (d, J 1.1
1
-(4-(5-Bromo-2-nitrophenyl)-2-methyl-4,5-dihydrofuran-3-
3
Hz, 3H, CH
4
1
3
3
2
),
yl)ethanone (4b) was obtained from 2b according to GP-II. Yield 58%. R
0
2
f
5
1
.40 (dichloromethane). Н NMR (CDCl
.38 (d, 5J 0.7 Hz, 3H, CH
3
, 600 MHz)  = 2.08 (s, 3H, CH
3
),
2
2
H, CH
2
), 6.10 (d, J 1.3 Hz, 1H, CH
2
), 6.11 (d, J 1.3 Hz, 1H, CH
, 150 MHz)  = 14.4 (CH
), 102.9 (OCH O), 104.1 (C), 105.5
CH), 107.1 (CH), 136.0 (C), 142.5 (C), 146.6 (C), 152.2 (C), 165.6 (C),
2
), 6.74
3
), 4.22–4.27 (m, 1H, CH), 4.84–4.89 (m, 2H,
s, 1H, Ar), 7.48 (s, 1H, Ar). 13С NMR (CDCl
3.9 (CH), 50.9 (OCH ), 78.2 (CH
(
4
3
3
),
4
3
4
CH
(
2
), 7.37 (d, J 2.1 Hz, 1H, Ar), 7.50 (dd, J 8.7, J 2.1 Hz, 1H, Ar), 7.79
3
2
2
d, J 8.7 Hz, 1H, Ar). 13С NMR (CDCl , 150 MHz)  = 15.4 (1JCH 130 Hz,
3
3
(
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201700256
FULL PAPER
1
C
71.9 (C). HRMS ESI: m/z = 308.0767 [M + H]+ (308.0765 calcd for
).
1H, Ar), 7.10 (d, 3J 7.7 Hz, 1H, Ar). 13С NMR (CDCl
20.9 (CH ), 22.6 (CH ), 35.26 (CH), 35.29 (CH ), 46.8 (CH), 67.6 (CH
14.4 (CH), 117.4 (CH), 120.8 (C), 126.8 (CH), 127.3 (CH), 145.4 (C),
71.2 (MeCO ); B  = 21.0 (CH ), 22.59 (CH ), 31.4 (CH ), 35.3 (CH),
), 114.1 (CH), 116.9 (CH), 119.3 (C), 127.6 (CH),
30.0 (CH), 144.9 (C), 171.0 (MeCO ). HRMS ESI: m/z = 220.1329 [M +
3
, 150 MHz) A  =
),
14
H
14NO
7
3
3
2
2
1
1
2
3
3
2
(
2-Methyl-3,4-dihydroquinolin-4-yl)methyl acetate (6a) was obtained
from 4a according to GP-III. 1Н NMR (CDCl
, 400 MHz)  = 2.07 (s, 3H,
CH ), 2.33 (br.s, 3H, CH ), 2.54–2.55 (m, 2H, CH ), 3.11–3.18 (m, 1H,
42.2 (CH), 68.4 (CH
2
3
1
2
3
3
2
+
2
3
2
3
2
H] (220.1332 calcd for C13H18NO ).
CH), 4.01 (dd, J 11.1, J 8.2 Hz, 1H, CH
2
), 4.14 (dd, J 11.1, J 5.7 Hz,
), 7.16–7.22 (m, 2H, Ar), 7.29–7.33 (m, 1H, Ar), 7.38–7.45 (m,
H, Ar). 13С NMR (CDCl , 150 MHz)  = 20.5 (1JCH 129 Hz, CH
), 27.5
), 30.6 (1JCH 129 Hz, CH ), 33.3 (1JCH 134 Hz, CH),
5.3 (1JCH 149 Hz, CH
), 125.7 (C), 126.1 (CH), 126.5 (CH), 127.3 (CH),
1
H, CH
2
1
(
3
3
(6-Bromo-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)methyl
(7b) was obtained from 6b according to GP-IV. Yield 32% (two-step yield
starting from dihydrofuran 4b); dr A:B = 71:29. R 0.35 (ethyl acetate :
petroleum ether; 1:4). 1Н NMR (CDCl , 600 MHz) A  = 1.230 (d, 3J 6.2
Hz, 3H, CH ), 2.06 (ddd,
), 1.41 (ddd, 2J 12.9, 3J 11.3, 12.6 Hz, 1H, CH
2J 12.9, 3J 2.6, 5.7 Hz, 1H, CH
), 2.099 (s, 1H, CH ), 3.17–3.22 (m, 1H,
acetate
1JCH 127 Hz, CH
3
2
6
1
2
f
28.1 (CH), 143.3 (C), 169.3 (C), 170.5 (C). HRMS ESI: m/z = 218.1179
3
+
[M + H] (218.1176 calcd for C13
2
H16NO ).
3
2
2
3
CHAr), 3.41 (dqd, 3J 2.6, 6.2, 11.3 Hz, 1H, CHN), 3.77 (br.s, 1H, NH),
(
6-Bromo-2-methyl-3,4-dihydroquinolin-4-yl)methyl acetate (6b) was
4.18 (dd, 2J 11.1, 3J 7.1 Hz, 1H, CH
), 4.46 (dd, 2J 11.1, 3J 5.2 Hz, 1H,
1
2
obtained from 4b according to GP-III. Н NMR (CDCl
3
, 600 MHz)  = 2.05
3
4
2
3
CH
2
), 6.383 (d, J 8.5 Hz, 1H, Ar), 7.068–7.087 (m, 1H, Ar), 7.25 (dd, J
(
2
2
s, 3H, CH
3
), 2.22 (br.s, 3H, CH
3
), 2.43 (dd, J 17.2, J 6.9 Hz, 1H, CH
2
),
2.3, J 1.1 Hz, 1H, Ar); B  = 1.225 (d, J 6.2 Hz, 3H, CH
3
), 1.55 (ddd, 2J
5
3
.46 (dd, 2J 17.2, 3J 4.7 Hz, 1H, CH
2
), 3.05–3.09 (m, 1H, CH), 3.96 (dd,
3
2
3
3
2
3
13.4, J 5.4, 11.4 Hz, 1H, CH
2
), 1.91 (ddd, J 13.4, J 2.3, 2.8 Hz, 1H,
2 2
J 11.1, J 8.0 Hz, 1H, CH ), 4.09 (dd, J 11.1, J 5.9 Hz, 1H, CH ), 7.18
3
d, 3J 8.3 Hz, 1H, Ar), 7.28 (br.d, 4J 2.3 Hz, 1H, Ar), 7.39 (dd, 3J 8.3, 4
CH ), 2.103 (s, 3H, CH
2
3
), 3.05–3.09 (m, 1H, CHAr), 3.42 (dqd, J 2.9, 6.1,
(
J
),
2
3
.3 Hz, 1H, Ar). 3С NMR (CDCl
7.8 ( JCH 127 Hz, CH
5.2 ( JCH 149 Hz, CH
31.3 (CH), 142.6 (C), 169.8 (C), 170.7 (C). HRMS ESI: m/z = 296.0279
1
, 150 MHz)  = 20.7 (1JCH 130 Hz, CH
11.4 Hz, 1H, CHN), 3.77 (br.s, 1H, NH), 4.09 (dd, J 11.0, J 9.5 Hz, 1H,
2
2
6
1
3
3
2
3
3
1
), 30.6 (1JCH 130 Hz, CH
1
CH
7.072–7.091 (m, 1H, Ar), 7.18 (dd, 4J 2.3, 5J 0.5 Hz, 1H, Ar). 13С NMR
CDCl , 150 MHz) A  = 21.0 (CH ), 22.5 (CH ), 34.8 (CH ), 35.4 (CH),
46.9 (CH), 67.3 (CH ), 109.0 (C), 115.9 (CH), 123.1 (C), 129.6 (CH),
30.1 (CH), 144.4 (C), 171.1 (MeCO ); B  = 21.0 (CH ), 22.4 (CH ),
1.2 (CH ), 35.3 (CH), 42.4 (CH), 68.0 (CH ), 108.2 (C), 115.7 (CH),
2 2
), 4.21 (dd, J 11.0, J 5.7 Hz, 1H, CH ), 6.380 (d, J 8.5 Hz, 1H, Ar),
3
2
), 33.4 ( JCH 133 Hz, CH),
1
2
), 119.6 (C), 128.0 (CH), 128.1 (C), 130.4 (CH),
(
3
3
3
2
+
2
[M + H] (296.0281 calcd for C13
2
H15BrNO ).
1
3
2
3
3
2
2
(
(
6,7-Dimethoxy-2-methyl-3,4-dihydroquinolin-4-yl)methyl
acetate
6c) was obtained from 4c according to GP-III. 1Н NMR (CDCl
121.4 (C), 130.4 (CH), 132.5 (CH), 143.9 (C), 170.9 (MeCO
2
). HRMS
3
, 600
+
2
3
ESI: m/z = 298.0443 [M + H] (298.0437 calcd for C13
H17BrNO
2
).
MHz)  = 2.06 (s, 3H, CH
Hz, 1H, C(3)H
3
), 2.22 (s, 3H, C(2’)H
), 2.48 (dd, J 17.1, J 4.0 Hz, 1H, C(3)H
3
), 2.43 (dd, J 17.1, J 7.2
2
3
2
2
), 3.01–3.06 (m,
), 3.91 (dd, J 11.1,
2
(6,7-Dimethoxy-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)methyl
acetate (7c) was obtained from 6c according to GP-IV. Yield 40% (two-
1
H, C(4)H), 3.876 (s, 3H, OCH ), 3.880 (s, 3H, OCH
3
3
3
2
3
J 8.6 Hz, 1H, C(1’)H
2
), 4.10 (dd, J 11.1, J 5.7 Hz, 1H, C(1’)H
2
), 6.66 (s,
, 150 MHz)  = 20.9 (CH ), 27.7
), 56.2 (OCH ), 65.6
H, Ar), 6.92 (s, 1H, Ar). 13С NMR (CDCl
step yield starting from dihydrofuran 4c); dr A:B = 60:40. R
f
0.58 (ethyl
, 600 MHz) A  = 1.170 (d,
), 1.38 (ddd, J 12.7, J 11.4, 12.8 Hz, 1H, CH ), 2.025
), 3.13–3.18 (m,
1
3
3
1
acetate : petroleum ether; 1:2). Н NMR (CDCl
3
(
(
(
(
C(2’)H
C(1’)H
3
), 30.8 (C(3)H
2
), 33.5 (C(4)H), 55.9 (OCH
3
3
3
2
3
J 6.1 Hz, 3H, CH
3
2
2
), 110.2 (CH), 110.4 (CH), 117.4 (C), 137.5 (C), 147.4 (C), 148.5
2
3
Me). HRMS ESI: m/z = 278.1387 [M + H]+
(ddd, J 12.7, J 2.3, 6.2 Hz, 1H, CH
2
), 2.033 (s, 1H, CH
3
C), 166.9 (C(2)), 170.8 (CO
4
278.1387 calcd for C15 20NO ).
2
3
1
3
1
1
H, CHAr), 3.33 (dqd, J 2.3, 6.1, 11.4 Hz, 1H, CHN), 3.49 (br.s, 1H, NH),
H
.738 (s, 3H, OCH
3
), 3.744 (s, 3H, OCH
3
), 4.14 (dd, 2J 10.9, 3J 7.3 Hz,
), 4.39 (dd, J 10.9, J 5.0 Hz, 1H, CH ), 6.09 (s, 1H, Ar), 6.69 (s,
H, Ar); B  = 1.166 (d, 3J 6.1 Hz, 3H, CH ), 1.52 (ddd, 2J 13.4, 3J 5.7,
), 1.87 (ddd, 2J 13.4, 3J 1.9, 2.5 Hz, 1H, CH
), 2.05 (s,
), 2.96–2.99 (m, 1H, CHAr), 3.33 (dqd, 3J 2.6, 6.1, 11.5 Hz, 1H,
CHN), 3.49 (br.s, 1H, NH), 3.736 (s, 3H, OCH ), 3.75 (s, 3H, OCH ), 4.03
), 4.21 (dd, 2J 10.9, 3J 5.3 Hz, 1H, CH
),
6.07 (s, 1H, Ar), 6.60 (s, 1H, Ar). , 150 MHz) A  = 20.75
13С NMR (CDCl
2
3
H, CH
2
2
(6-Methyl-7,8-dihydro-[1,3]dioxolo[4,5-g]quinolin-8-yl)methyl acetate
(
6d) was obtained from 4d according to GP-III. 1Н NMR (CDCl
3
3
, 400
), 2.38 (dd, J 17.2, J
2
3
11.4 Hz, 1H, CH
2
2
MHz)  = 2.05 (s, 3H, C CH
.8 Hz, 1H, C(3)H
3
), 2.20 (s, 3H, C(2’)H
), 2.44 (dd, J 17.2, J 3.8 Hz, 1H, C(3)H
3
2
3
3H, CH
3
6
(
2
2
), 2.94–3.01
m, 1H, C(4)H), 3.90 (dd, 2J 11.0, 3J 8.3 Hz, 1H, C(4’)H
), 4.03 (dd, 2
J
3
3
2
2
3
3
(dd, J 10.9, J 9.9 Hz, 1H, CH
2
2
1
(
1.0, J 5.9 Hz, 1H, C(4’)H
2
), 5.93 (s, 2H, OCH
2
O), 6.61 (s, 1H, Ar), 6.83
, 100 MHz)  = 20.8 (CH ), 27.6 (C(2’)H ),
), 101.1 (OCH O), 107.3 (CH),
s, 1H, Ar). 13С NMR (CDCl
3
3
3
3
(1
3
J
CH 129 Hz, CH
), 22.32 (1JCH 126 Hz, CH
1
3
3
), 34.9 ( JCH 127 Hz, CH),
3
1
1
0.6 (C(3)H
2
), 33.8 (C(4)H), 65.5 (C(4’)H
2
2
1
), 47.0 (1JCH 134 Hz, CH), 55.5 ( JCH 144 Hz,
1
5.6 ( JCH 128 Hz, CH
), 56.6 (1JCH 144 Hz, OCH ), 67.8 (1JCH 148 Hz, CH
OCH ), 99.4 (CH),
3 3 2
2
07.5 (CH), 119.1 (C), 119.4 (C), 145.8 (C), 147.1 (C), 167.0 (C(2)),
70.8 (CO
+
2
Me). HRMS ESI: m/z = 262.1070 [M + H] (262.1074 calcd for
1

11.5 (CH), 113.9 (C), 139.7 (C), 141.3 (C), 148.5 (C), 170.9 (MeCO
2
); B
14 4
C H16NO ).
= 20.79 (1JCH 129 Hz, CH
), 22.25 (1JCH 126 Hz, CH
), 31.7 ( JCH 128
1
3
3
1
Hz, CH
Hz, OCH
2
), 34.8 (1JCH 127 Hz, CH), 42.3 (1JCH 136 Hz, CH), 55.5 ( JCH 144
2
-Methyl-1,2,3,4-tetrahydroquinolin-4-yl)methyl acetate (7a) was
obtained from 6a according to GP-IV. Yield 38% (two-step yield starting
from dihydrofuran 4a); dr A:B = 71:29. R 0.25 (ethyl acetate : petroleum
ether; 1:4). 1Н NMR (CDCl , 600 MHz) A  = 1.243 (d, 3J 6.2 Hz, 3H,
), 56.5 (1JCH 143 Hz, OCH ), 68.3 (1JCH 147 Hz, CH
3
3
2
), 99.0
(
(
CH), 110.5 (C), 112.2 (CH), 139.1 (C), 141.1 (C), 148.6 (C), 170.8
). HRMS ESI: m/z = 280.1538 [M + H]+ (280.1543 calcd for
MeCO
).
f
2
3
15 4
C H22NO
CH
CH
3
), 1.47 (ddd, 2J 12.8, 3J 11.7, 12.3 Hz, 1H, CH
), 2.10 (s, 3H, CH
2
), 2.08–2.12 (m, 1H,
3
2
3
), 3.23–3.28 (m, 1H, CHAr), 3.45 (dqd, J 2.5, 6.2,
2
3
(6-Methyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]quinolin-8-yl)methyl
acetate (7d) was obtained from 6d according to GP-IV. Yield 38% (two-
12.3 Hz, 1H, CHN), 3.78 (br.s, 1H, NH), 4.22 (dd, J 10.9, J 7.4 Hz, 1H,
), 4.54 (dd, 2J 10.9, 3J 4.9 Hz, 1H, CH
), 6.53 (d, 3J 8.0 Hz, 1H, Ar),
CH
2
2
step yield starting from dihydrofuran 4d); dr A:B = 76:24. R
f
0.62 (ethyl
3
6.67–6.70 (m, 1H, Ar), 7.02–7.04 (m, 1H, Ar), 7.17 (d, J 7.8 Hz, 1H, Ar);
1
3
), 1.60 (ddd, 2J 13.3, 3J 5.4, 11.6 Hz,
acetate : petroleum ether; 1:2). Н NMR (CDCl
3
, 600 MHz) A  = 1.21 (d,
), 2.04
), 3.13–3.19 (m,
B  = 1.241 (d, J 6.2 Hz, 3H, CH
3
3
2
3
2
3
J 6.2 Hz, 3H, CH
3
), 1.40 (ddd, J 12.8, J 11.3, 12.9 Hz, 1H, CH
2
1
3
4
H, CH
2 2 3
), 1.96 (ddd, J 13.3, J 2.1, 2.6 Hz, 1H, CH ), 2.12 (s, 3H, CH ),
3
(
ddd, 2J 12.8, J 2.5, 6.0 Hz, 1H, CH
2
), 2.08 (s, 1H, CH
3
.10–3.14 (m, 1H, CHAr), 3.43–3.48 (m, 1H, CHN), 3.79 (br.s, 1H, NH),
.14 (dd, 2J 11.0, J 10.0 Hz, 1H, CH
3
3
2
3
1H, CHAr), 3.33 (dqd, J 2.5, 6.2, 11.3 Hz, 1H, CHN), 3.46 (br.s, 1H, NH),
2
), 4.26 (dd, J 11.0, J 5.4 Hz, 1H,
4.13 (dd, 2J 11.0, 3J 7.0 Hz, 1H, CH ), 4.37 (dd, 2J 11.0, 3J 5.2 Hz, 1H,
), 6.52 (d, 3J 8.0 Hz, 1H, Ar), 6.64–6.67 (m, 1H, Ar), 7.01–7.04 (m,
2
CH
2
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201700256
FULL PAPER
CH
2
), 5.81 (d, 2J 1.4 Hz, 1H, OCH
2
O), 5.82 (d, 2J 1.4 Hz, 1H, OCH
2
O),
14.2 (1JCH 129 Hz, CH
3 2
OCH ), 106.8 (C), 116.5 (CH), 119.3 (CH),
127.2 (CH), 127.3 (CH), 129.3 (C), 143.8 (C), 166.2 (C), 168.9 (C).
HRMS ESI: m/z = 234.1129 [M + H] (234.1125 calcd for C13
3
), 41.8 (1JCH 135 Hz, CH), 50.7 (1JCH 146 Hz,
4
3
), 77.8 (1JCH 151 Hz, CH
6.12 (s, 1H, Ar), 6.69 (d, J 0.9 Hz, 1H, Ar); B  = 1.20 (d, J 6.1 Hz, 3H,
2
3
4
2
CH
3
), 1.54 (dddd, J 13.4, J 5.6, 11.5, J 0.7 Hz, 1H, CH
2
), 1.88 (ddd, J
3.4, 3J 2.0, 2.6 Hz, 1H, CH
+
1
2
), 2.09 (s, 3H, CH
3
), 2.96–3.00 (m, 1H,
3
H16NO ).
3
CHAr), 3.36 (dqd, J 2.6, 6.1, 11.5 Hz, 1H, CHN), 3.46 (br.s, 1H, NH),
4
.07 (dd, 2J 11.1, 3J 9.6 Hz, 1H, CH
Hz, 1H, CH
), 5.80 (d, 2J 1.4 Hz, 1H, OCH
OCH
O), 6.10 (s, 1H, Ar), 6.58 (d, 4J 0.6 Hz, 1H, Ar). 13С NMR (CDCl
50 MHz) A  = 20.97 (CH ), 22.41 (CH ), 35.39 (CH), 35.6 (CH ), 47.2
CH), 68.2 (CH ), 96.7 (CH), 100.35 (OCH O), 106.9 (CH), 113.1 (C),
40.1 (C), 140.4 (C), 146.5 (C), 171.10 (MeCO ); B  = 20.98 (CH ),
2.38 (CH ), 31.7 (CH ), 35.42 (CH), 42.5 (CH), 68.6 (CH ), 96.3 (CH),
00.41 (OCH O), 109.3 (CH), 111.2 (C), 139.6 (C), 139.8 (C), 147.0 (C),
70.97 (MeCO
). HRMS ESI: m/z = 264.1228 [M + H]+ (264.1230 calcd
).
2
), 4.27 (ddd, 2J 11.1, 3J 5.4, 4J 0.7
Methyl 4-(2-amino-4,5-dimethoxyphenyl)-2-methyl-4,5-dihydrofuran-
O), 5.81 (d, 2J 1.4 Hz, 1H,
2
2
3
R
-carboxylate (9b) was obtained from 5b according to GP-III. Yield 73%.
2
3
,
1
5
f
0.58 (ethyl acetate). Н NMR (CDCl
3
, 600 MHz)  = 2.28 (d, J 1.1 Hz,
), 3.80 (s, 3H, OCH ),
), 4.39 (ddq, J 4.2, 10.3, J 1.1 Hz, 1H, CH), 4.46 (dd,
1
(
1
2
1
1
3
3
2
3H, CH
3
), 3.64 (s, 3H, OCH ), 3.78 (s, 3H, OCH
3
3
3
2
2
3
5
3
.82 (br.s, 2H, NH
2
2
3
2
3
2
3
J 9.5, J 4.2 Hz, 1H, CH
2
), 4.69 (dd, J 9.5, J 10.3 Hz, 1H, CH
2
), 6.25 (s,
3
2
2
1
H, Ar), 6.62 (s, 1H, Ar). 13С NMR (CDCl , 150 MHz)  = 14.4 (1JCH 130
Hz, CH
3
2
), 41.8 (1JCH 135 Hz, CH), 51.0 ( JCH 146 Hz, OCH
), 56.8 (1JCH 144 Hz, OCH ), 77.9 (1JCH 151 Hz, CH
3 2
44 Hz, OCH ),
1
), 55.7 (1JCH
3
3
2
1
1
3
for C14H18NO
4
01.8 (CH), 107.4 (C), 111.9 (CH), 121.0 (C), 137.8 (C), 142.8 (C), 148.6
+
(C), 166.4 (C), 168.6 (C). HRMS ESI: m/z = 294.1341 [M + H] (294.1336
(
2-Methylquinolin-4-yl)methyl acetate (8a) was obtained from 6a
according to GP-V. Yield 60% (two-step yield starting from dihydrofuran
a). R , 400
0.48 (ethyl acetate : petroleum ether; 1:1). 1Н NMR (CDCl
MHz)  = 2.15 (s, 3H, CH ), 2.72 (s, 3H, CH ), 5.51 (s, 2H, CH ), 7.28 (s,
H, Ar), 7.47–7.51 (m, 1H, Ar), 7.65–7.69 (m, 1H, Ar), 7.85 (d, J 8.4 Hz,
calcd for C15
H
20NO
5
).
4
f
3
Methyl
4-(6-aminobenzo[d][1,3]dioxol-5-yl)-2-methyl-4,5-
3
3
2
dihydrofuran-3-carboxylate (9c) was obtained from 5c according to
3
1
1
1
GP-III. Yield 65%. R
f
0.71 (ethyl acetate). Н NMR (CDCl
3
, 600 MHz)  =
), 3.83 (br.s, 2H, NH ),
.38 (ddq, J 3.9, 9.6, J 1.1 Hz, 1H, CH), 4.40 (dd, J 8.9, J 3.9 Hz, 1H,
), 4.67 (dd, 2J 8.9, 3J 9.6 Hz, 1H, CH ), 5.81 (d, 2J 1.5 Hz, 2H,
O), 5.83 (d, 2J 1.5 Hz, 2H, OCH
O), 6.25 (s, 1H, Ar), 6.59 (s, 1H,
, 150 MHz)  = 14.4 (1JCH 130 Hz, CH ), 41.7 (1JCH
), 78.1 (1JCH 151 Hz, CH
), 98.9
O), 106.9 (CH), 107.5 (C), 112.2 (C),
H, Ar), 8.03 (d, J 8.4 Hz, 1H, Ar). 13С NMR (CDCl
3
3
, 100 MHz)  = 20.8
.27 (d, 5J 1.1 Hz, 3H, CH
2
4
3
), 3.65 (s, 3H, OCH
3
2
(CH
3
), 25.3 (CH ), 62.5 (CH ), 120.6 (CH), 122.6 (CH), 124.1 (C), 126.0
3
2
3
5
2
3
(CH), 129.3 (2×CH), 140.7 (C), 147.8 (C), 158.7 (C), 170.4 (MeCO
2
).
CH
2
2
+
HRMS ESI: m/z = 216.1022 [M + H] (216.1019 calcd for C13
2
H14NO ).
OCH
2
2
Ar). 3С NMR (CDCl
1
3
1
3
(
6-Bromo-2-methylquinolin-4-yl)methyl acetate (8b) was obtained
from 6b according to GP-V. Yield 45% (two-step yield starting from
dihydrofuran 4b). R
0.53 (ethyl acetate : petroleum ether; 1:1). 1Н NMR
135 Hz, CH), 51.0 ( JCH 147 Hz, OCH
(CH), 100.6 (1JCH 172 Hz, OCH
3
2
2
f
138.3 (C), 141.3 (C), 146.5 (C), 166.4 (C), 168.8 (C). HRMS ESI: m/z =
278.1020 [M + H] (278.1023 calcd for C14
+
(CDCl
3
, 400 MHz)  = 2.20 (s, 3H, CH
), 7.34 (s, 1H, Ar), 7.77 (dd, J 9.0, J 2.1 Hz, 1H, Ar), 7.92 (d, J 9.0
3
), 2.73 (s, 3H, CH
3
), 5.49 (s, 2H,
H
16NO
5
).
3
4
3
CH
2
Hz, 1H, Ar), 8.05 (d, 4J 2.1 Hz, 1H, Ar). 13С NMR (CDCl
, 100 MHz)  =
), 120.2 (C), 121.6 (CH), 125.3 (CH),
25.6 (C), 131.1 (CH), 132.9 (CH), 140.1 (C), 146.4 (C), 159.4 (C), 170.5
). HRMS ESI: m/z = 294.0127 [M + H]+ (294.0124 calcd for
13BrNO ).
3
3
-Methyl-5,9b-dihydrofuro[3,4-c]quinolin-4(1H)-one
obtained from 5a according to GP-VI. Yield 45% (two-step yield starting
0.60 (ethyl acetate : petroleum ether; 1:1). 1Н
from dihydrofuran 5a). R
(10a)
was
2
1
(
C
3 3 2
0.9 (CH ), 25.4 (CH ), 62.4 (CH
f
MeCO
2
5
2
NMR (CDCl
3
3
3
, 600 MHz)  = 2.27 (d, J 2.2 Hz, 3H, CH ), 4.50 (dd, J 7.9,
13
H
2
2
3
J 11.9 Hz, 1H, CH
H, CH
), 6.82 (dd, 3J 7.9, 4J 1.0 Hz, 1H, Ar), 6.94 (br.d, 3J 7.5 Hz, 1H,
Ar), 7.00–7.02 (m, 1H, Ar), 7.17–7.20 (m, 1H, Ar), 8.53 (br.s, 1H, NH).
13С NMR (CDCl , 150 MHz)  = 13.6 (1JCH 130 Hz, CH ), 41.7 (1JCH 136
Hz, CH), 76.4 (1JCH 154 Hz, CH
), 101.3 (C), 115.4 (CH), 122.7 (CH),
2
), 4.53–4.58 (m, 1H, CH), 5.08 (dd, J 7.9, J 9.5 Hz,
1
2
(
6,7-Dimethoxy-2-methylquinolin-4-yl)methyl acetate (8c) was
obtained from 6с according to GP-V. Yield 55% (two-step yield starting
from dihydrofuran 4с). R
0.34 (ethyl acetate : petroleum ether; 1:1). 1
NMR (CDCl , 600 MHz)  = 2.18 (s, 3H, CH
H, OCH ), 4.02 (s, 3H, OCH
3
3
f
Н
2
3
3
), 2.69 (s, 3H, CH
3
), 4.00 (s,
124.7 (C), 125.4 (CH), 127.7 (CH), 137.8 (C), 164.8 (C), 166.4 (C).
HRMS ESI: m/z = 202.0861 [M + H] (202.0863 calcd for C12
+
3
3
3
), 5.49 (s, 2H, CH
2
), 7.09 (s, 1H, Ar), 7.20
H
12NO
2
).
(
s, 1H, Ar), 7.40 (s, 1H, Ar). 13С NMR (CDCl
3
, 150 MHz)  = 20.9 (1JCH
), 62.9
), 100.8 (CH), 108.3 (CH), 119.1 (CH), 119.4 (C), 139.1
1
29 Hz, CH
3
), 25.0 (1JCH 127 Hz, CH
3
), 56.0 (1JCH 145 Hz, 2OCH
3
7,8-Dimethoxy-3-methyl-5,9b-dihydrofuro[3,4-c]quinolin-4(1H)-one
(
(
1JCH 148 Hz, CH
2
(10b) was obtained from 5b according to GP-VI. Yield 42% (two-step
C), 145.1 (C), 149.3 (C), 152.2 (C), 156.5 (C), 170.6 (MeCO
2
). HRMS
f
yield starting from dihydrofuran 5b). R 0.19 (ethyl acetate : petroleum
+
ESI: m/z = 276.1229 [M + H] (276.1230 calcd for C15
4
H18NO ).
ether; 1:1). 1Н NMR (CDCl
.78 (OCH ), 3.80 (OCH
, 600 MHz)  = 2.23 (d, 5J 2.2 Hz, 3H, CH
), 4.38 (dd, J 8.2, 3J 12.2 Hz, 1H, CH
3
3
),
2
3
3
3
2
), 4.43–
), 6.38 (s, 1H, Ar),
, 150 MHz)  = 13.4
), 76.6 (CH ), 100.2 (CH),
2
3
(
6-Methyl-[1,3]dioxolo[4,5-g]quinolin-8-yl)methyl acetate (8d) was
obtained from 6d according to GP-V. Yield 52% (two-step yield starting
from dihydrofuran 4d). R
0.39 (ethyl acetate : petroleum ether; 1:1). 1
NMR (CDCl , 600 MHz)  = 2.17 (s, 3H, CH ), 2.68 (s, 3H, CH ), 5.41 (s,
H, CH ), 6.11 (s, 2H, OCH O), 7.16 (s, 1H, Ar), 7.18 (s, 1H, Ar), 7.37
br.s, 1H, Ar). 13С NMR (CDCl
, 150 MHz)  = 20.9 (CH ), 24.8 (CH ),
3.1 (CH ), 98.7 (CH), 101.8 (OCH O), 106.0 (CH), 119.5 (CH), 121.0
4.48 (m, 1H, CH), 4.98 (dd, J 8.2, J 9.6 Hz, 1H, CH
6.51 (s, 1H, Ar), 9.62 (br.s, 1H, NH). 13С NMR (CDCl
(CH ), 41.4 (CH), 55.7 (OCH ), 56.4 (OCH
2
3
f
Н
3
3
3
2
3
3
3
101.6 (C), 109.1 (CH), 115.6 (C), 131.4 (C), 144.6 (C), 148.5 (C), 164.8
(C), 166.0 (C). HRMS ESI: m/z = 262.1071 [M + H]+ (262.1074 calcd for
C H16NO ).
14 4
2
(
6
2
2
3
3
3
2
2
(
C), 139.8 (C), 146.3 (C), 147.7 (C), 150.5 (C), 156.4 (C), 170.6 (MeCO
2
).
3
-Methyl-5,10b-dihydro-[1,3]dioxolo[4,5-g]furo[3,4-c]quinolin-4(1H)-
one (10c) was obtained from 5c according to GP-VI. Yield 41% (two-step
yield starting from dihydrofuran 5c). R 0.25 (ethyl acetate : petroleum
ether; 1:1). 1Н NMR (CDCl , 600 MHz)  = 2.26 (d, 5J 2.2 Hz, 3H, CH
),
4.38 (dd, 2J 8.0, 3J 12.1 Hz, 1H, CH
), 4.43–4.48 (m, 1H, CH), 4.99 (dd,
+
HRMS ESI: m/z = 246.0763 [M + H] (246.0761 calcd for C13
4
H12NO ).
f
Methyl 4-(2-aminophenyl)-2-methyl-4,5-dihydrofuran-3-carboxylate
9a) was obtained from 5a according to GP-III. Yield 66%. R 0.78 (ethyl
acetate). 1Н NMR (CDCl
, 600 MHz)  = 2.31 (s, 3H, CH ), 3.63 (s, 3H,
OCH ), 4.01 (br.s, 2H, NH ), 4.43–4.47 (m, 2H, CH , CH), 4.68–4.72 (m,
H, CH
), 6.66 (d, 3J 7.8 Hz, 1H, Ar), 6.78–6.80 (m, 1H, Ar), 7.03–7.05
m, 1H, Ar), 7.95 (d, 3J 7.8 Hz, 1H, Ar). 13С NMR (CDCl
, 150 MHz)  =
3
3
(
f
2
2
3
3
3
J 8.0, J 9.7 Hz, 1H, CH
2
), 5.91 (s, 1H, OCH
2
O), 6.38 (s, 1H, Ar), 6.45 (s,
, 150 MHz)  = 13.6 (CH ),
), 97.7 (CH), 101.2 (OCH O), 105.5 (CH), 116.9 (C),
1H, Ar), 9.17 (br.s, 1H, NH). 13С NMR (CDCl
3
2
2
3
3
1
(
2
41.7 (CH), 76.7 (CH
2
2
3
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European Journal of Organic Chemistry
10.1002/ejoc.201700256
FULL PAPER
1
31.9 (C), 143.3 (C), 146.9 (C), 164.9 (C), 166.7 (C). HRMS ESI: m/z =
Methyl 6-methyl-[1,3]dioxolo[4,5-g]quinoline-7-carboxylate (12b) was
+
246.0761 [M + H] (246.0761 calcd for C13
H12NO
4
).
obtained from 3d accordong to GP-III. Yield 57%. R
petroleum ether; 1:1). 1Н NMR (CDCl
, 600 MHz)  = 2.92 (s, 3H, CH
.95 (s, 3H, OCH ), 6.13 (s, 2H, OCH O), 7.06 (s, 1H, Ar), 7.32 (s, 1H,
Ar), 8.54 (s, 1H, Ar). 13С NMR (CDCl , 150 MHz)  = 25.3 (1JCH 129 Hz,
CH O), 103.1
), 52.2 (1JCH 147 Hz, OCH ), 102.0 (1JCH 174 Hz, OCH
(CH), 105.1 (CH), 121.4 (C), 122.5 (C), 138.6 (CH), 147.4 (C), 147.8 (C),
f
0.69 (ethyl acetate :
3
3
),
3
3
2
1-(6-Bromo-2-methylquinolin-3-yl)ethan-1-one (11a) was obtained
3
from 2b accordong to GP-III. Yield 41%. R
petroleum ether; 1:1). 1Н NMR (CDCl
f
0.77 (ethyl acetate :
, 600 MHz)  = 2.71 (s, 3H, CH
), 7.84 (dd, J 8.9, J 2.2 Hz, 1H, Ar), 7.91 (d, J 8.9 Hz,
3
),
3
3
2
3
3
4
3
2
1
1
1
1
.89 (s, 3H, CH
3
H, Ar), 8.02 (d, 4J 2.2 Hz, 1H, Ar), 8.36 (s, 1H, Ar). 13С NMR (CDCl
50 MHz)  = 25.3 (CH ), 29.1 (CH ), 120.1 (C), 126.5 (C), 129.9 (CH),
152.6 (C), 156.7 (C), 167.0 (CO
2
Me). HRMS ESI: m/z = 246.0763 [M +
3
,
+
H] (246.0761 calcd for C13
H12NO
4
).
3
3
30.1 (CH), 131.7 (C), 134.7 (CH), 136.5 (CH), 146.6 (C), 157.7 (C),
99.4 (C=O). HRMS ESI: m/z = 264.0025 [M + H]+ (264.0019 calcd for
12 4
C H11BrNO ).
Acknowledgements
1
-(6,7-Dimethoxy-2-methylquinolin-3-yl)ethan-1-one (11b)[42] was
obtained from 2c accordong to GP-III. Yield 50%. R 0.52 (ethyl acetate :
petroleum ether; 1:1). 1Н NMR (CDCl
, 600 MHz)  = 2.68 (s, 3H, CH ),
.87 (s, 3H, CH ), 4.01 (s, 3H, OCH ), 4.03 (s, 3H, OCH ), 7.07 (s, 1H,
Ar), 7.36 (s, 1H, Ar), 8.35 (s, 1H, Ar). 13С NMR (CDCl
, 150 MHz)  =
5.4 (1JCH 129 Hz, CH ), 29.0 (1JCH 128 Hz, CH ), 56.0 (1JCH 145 Hz,
OCH ), 105.5 (CH), 107.3 (CH), 120.9 (C),
), 56.2 (1JCH 146 Hz, OCH
29.0 (C), 136.6 (CH), 145.7 (C), 149.8 (C), 154.3 (C), 155.7 (C), 199.6
C=O).
This research was supported by a grant 15-33-20442 from the
Russian Foundation for Basic Research.
f
3
3
2
3
3
3
3
Keywords: dihydrofurans • quinolines • reduction •
dehydrogenation • C=C bond cleavage
2
3
3
3
3
1
(
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-(6-Methyl-[1,3]dioxolo[4,5-g]quinolin-7-yl)ethan-1-one (11c)[30] was
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petroleum ether; 1:1). 1Н NMR (CDCl
, 600 MHz)  = 2.64 (s, 3H, CH ),
O), 7.02 (s, 1H, Ar), 7.27 (s, 1H, Ar),
, 150 MHz)  = 25.3 (1JCH 128 Hz, CH
),
), 102.0 (1JCH 175 Hz, OCH
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.24 (s, 1H, Ar). 13С NMR (CDCl
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3 2
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335–355.
3
3
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(CH), 122.2 (C), 129.1 (C), 137.0 (CH), 147.0 (C), 147.8 (C), 152.5 (C),
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1-(6,7,8-Trimethoxy-2-methylquinolin-3-yl)ethan-1-one (11d) was
3
obtained from 2e accordong to GP-III. Yield 46%. R
petroleum ether; 1:1). 1Н NMR (CDCl
, 400 MHz)  = 2.68 (s, 3H, CH
), 4.06 (s, 3H, OCH ), 4.16 (s, 3H,
), 6.90 (s, 1H, Ar), 8.33 (s, 1H, Ar). 13С NMR (CDCl
, 150 MHz)  =
), 29.2 (CH ), 56.0 (OCH ), 61.5 (OCH ), 62.2 (OCH ), 101.5
CH), 122.9 (C), 130.4 (C), 136.9 (CH), 139.9 (C), 146.0 (C), 147.3 (C),
53.1 (C), 154.7 (C), 200.0 (C=O). HRMS ESI: m/z = 276.1237 [M + H]+
276.1230 calcd for C15 ).
f
0.44 (ethyl acetate :
[
[
7]
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3
3
),
2.90 (s, 3H, CH
3
), 3.98 (s, 3H, OCH
3
3
OCH
3
3
25.8 (CH
3
3
3
3
3
[
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(
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H18NO
4
1
-(5,6,7-Trimethoxy-2-methylquinolin-3-yl)ethanone
0.40 (ethyl acetate :
, 400 MHz)  = 2.70 (s, 3H, CH ),
), 4.01 (s, 3H, OCH ), 4.12 (s, 3H,
), 7.18 (s, 1H, Ar), 8.70 (s, 1H, Ar). 13С NMR (CDCl
, 150 MHz)  =
), 29.1 (CH ), 56.3 (OCH ), 61.3 (OCH ), 61.7 (OCH ), 103.3
CH), 116.4 (C), 128.5 (C), 133.1 (CH), 140.3 (C), 146.2 (C), 147.4 (C),
57.6 (C), 158.1 (C), 199.7 (C=O). HRMS ESI: m/z = 276.1231 [M + H]+
276.1230 calcd for C15 ).
(11e)
was
obtained from 2f accordong to GP-III. Yield 49%. R
petroleum ether; 1:1). 1Н NMR (CDCl
f
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2.87 (s, 3H, CH
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(
1
(
H18NO
4
8
[
Methyl 6,7-dimethoxy-2-methylquinoline-3-carboxylate (12a) was
obtained from 3c accordong to GP-III. Yield 53%. R 0.63 (ethyl acetate :
, 600 MHz)  = 2.95 (s, 3H, CH ),
), 7.01 (s, 1H,
, 150 MHz)  =
), 105.5 (CH), 107.1
CH), 121.1 (C), 121.4 (C), 138.2 (CH), 146.1 (C), 149.8 (C), 154.4 (C),
56.7 (C), 167.1 (CO
Me). HRMS ESI: m/z = 262.1077 [M + H]+
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3
3
3
3
.96 (s, 3H, OCH
3
), 4.01 (s, 3H, OCH
), 4.05 (s, 3H, OCH
3
Ar), 7.38 (s, 1H, Ar), 8.62 (s, 1H, Ar). 13С NMR (CDCl
5.4 (CH ), 52.2 (OCH ), 56.1 (OCH ), 56.3 (OCH
3
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3
3
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Title
((Insert TOC Graphic here: max.
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Quinoline derivatives
Sergey V. Zaytsev, Elena V. Villemson,
Konstantin L. Ivanov, Ekaterina M.
Budynina,* and Mikhail Ya. Melnikov
Page No. – Page No.
A new simple approach to functionalized quinolines was developed via reduction of
Synthesis of Functionalized
Quinolines from 4-(o-Nitroaryl)-
substituted 3-Acyl-4,5-dihydrofurans:
Reductive Cyclization and C=C
Double Bond Cleavage
4-(o-nitroaryl)-3-acyl-substituted 4,5-dihydrofurans with a Zn-AcOH system.
According to DFT, the difference in reactivities of 3-keto vs. 3-ester derivatives,
affording bicyclic dihydroquinolines or tricyclic dihydrofuroquinolones, respectively,
is ensured by both thermodynamic and kinetic factors.
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