Tetrahedron 72 (2016) 7715e7721
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Catching a-aminoalkyl radicals: cyclization between tertiary
alkylanilines and alkenes
Zengqiang Song a, b, Andrey P. Antonchick a, b, *
a
b
€ r Molekulare Physiologie, Abteilung Chemische Biologie, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany
Max-Planck-Institut fu
€t Dortmund, Fakulta
€t Chemie und Chemische Biologie, Chemische Biologie, Otto-Hahn-Strasse 4a, 44227 Dortmund, Germany
Technische Universita
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 28 February 2016
Received in revised form 11 April 2016
Accepted 20 April 2016
Available online 22 April 2016
A practical synthesis of polycyclic heterocycles by radical annulation of tertiary arylamine derivatives is
described. Radical annulation occurs via formation of a-aminoalkyl radicals. The reaction is initiated by
tetrabutylammonium iodide using tert-butyl hydroperoxide as oxidant. The developed method allows
functionalization of diverse tertiary alkylanilines with different alkenes.
Ó 2016 Elsevier Ltd. All rights reserved.
Keywords:
Radical
Cyclization
Iodide
Amine
Peroxide
1. Introduction
Direct C(sp3)eH bond functionalization is a straightforward and
challenging way to synthesize compounds of interest. Due to the
significance of heteroatoms in natural products and bioactive
compounds, direct C(sp3)eH bond functionalization is attracting
intensive attention of chemists all over the world.1 Recently, radical
reactions have been found application in direct C(sp3)eH bond
functionalization. The radical functionalizations are initiated by
forming a radical cation on heteroatom or a radical at the a-position
of the heteroatom.2,3 The lone electron pair on nitrogen in tertiary
amines are very common participators in direct C(sp3)eH bond
functionalizations. These methods are based on single electron
transfer from nitrogen, to form a nitrogen radical cation. Afterwards, the radical cation generates an iminium ion A by two different pathways (Scheme 1). The first pathway is hydrogen
abstraction, the other pathway is deprotonation followed by a single electron transfer via carbon centred a-aminoalkyl radicals B
(Scheme 1, path A and path B). The application of iminium ions as
electrophiles in various transformations was subject of intensive
studies.4 The application of a-aminoalkyl radical B in synthesis is
limited due to the fast oxidation to iminium ion A under oxidative
reaction conditions. This problem is especially pronounced for
* Corresponding author. Tel.: þ49 231 755 3871; e-mail address: andrey.
antonchick@mpi-dortmund.mpg.de (A.P. Antonchick).
http://dx.doi.org/10.1016/j.tet.2016.04.052
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.
electron-poor amines due to the need of strong oxidants. The development of CeC bond forming method via C(sp3)eH bond functionalization of amines is highly desired. Here we report a C(sp3)eH
bond functionalization of tertiary arylamines via formation of carbon centred radicals in the synthesis of complex polycyclic products via radical annulation.
Scheme 1. Activation of tertiary aniline by single electron transfer.
In the recent years, MacMillan, Yoon and other research groups
reported impressive results on addition reactions with tertiary
anilines via a-aminoalkyl radicals using photoredox catalysis.5 The
application of a-aminoalkyl radicals in annulation for the synthesis
of complex products is less studied.6 Swan and Roy reported cyclization reactions using tertiary anilines with N-phenyl maleimides using benzoyl peroxide as catalyst at low temperature.7
Miura’s group achieved the same reactions using Mn(NO3)28 and
7716
Z. Song, A.P. Antonchick / Tetrahedron 72 (2016) 7715e7721
CuCl29 as single electron oxidants. Bian’s group accomplished these
transformation using ruthenium or iridium complexes as catalysts.10 Recently, Shen’s group11 and Zhang’s group12 used photoredox catalysis to report similar transformations. However, the
limited substrate scope due to the electron character of the reactants, especially for the strong electron deficient aniline, is still
a challenge which needs to be solved for this kind of reactions.
Therefore, the development of a general method of annulation with
broad substrate scope is desired. Having continuous interest in the
synthesis of bioactive heterocycles,13 we were interested in the
direct synthesis of the pyrrolo[3,4-c]quinolone scaffold which is
present in natural products and bioactive compounds (Fig. 1).14 In
result of extensive elucidation of the reaction conditions, we found
that a-aminoalkyl radicals can be formed in the presence of KI and
TBHP (tert-butyl hydroperoxide) which is a classic way to form
iminium ions.15
Table 1
Optimization of reaction conditionsa
Entry
Solvent
Catalyst (mol %)
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
9
10
11
12c
13
14
15
16
MeCN
MeCN
MeCN
MeCN
THF
Dioxane
MeOH
CHCl3
Toluene
DCE
EtOAc
DCE
DCE
DCE
DCE
DCE
KI (20)
TBAI (20)
I2 (20)
NIS (20)
KI (20)
KI (20)
KI (20)
KI (20)
KI (20)
KI (20)
KI (20)
KI (20)
KI (10)
KI (5)
TBAI (10)
d
1
1
1
1
12
0.5
0.5
12
12
2
0.5
8
2
3
2
12
62
59
56
50
52
67
Messy
80
63
90
69
84
89
87
91
72
a
Reaction conditions: 1a (0.1 mmol), 2a (0.2 mmol), TBHP (70% in H2O, 4 equiv),
catalyst (mol %) in solvent (1.0 mL) at 70 C.
b
Yield refers to isolated products after column chromatography.
c
TBHP (70%, in H2O) 2 equiv was used.
Fig. 1. Bioactive compounds based on pyrrolo[3,4-c]quinolones.
2. Results and discussion
We started our exploration focussing on the reaction between
N-phenyl maleimide (1a) and N,N-dimethyl aniline (2a) (Table 1).
To our delight, the proposed product 3a was obtained in 62% yield
using KI (20 mol %) as catalyst and TBHP (70% in H2O, 4 equiv) as
oxidant at 70 C in MeCN (Table 1, entry 1). Encouraged by this
result, we optimized the reaction conditions to improve the yield of
3a. Among different iodide reagents, KI and TBAI (tetrabutylammonium iodide) were most efficient for the radical reaction
(entries 1e4). The best yield of 90% was obtained using DCE (1,2dichloroethane) as solvent among others (entries 5e11). When
reducing the amount of TBHP to 2 equiv, yield of 3a became lower
(entry 12). Reduction of the loading of KI (from 20 mol % to 5 mol %)
led to a prolonged reaction time without strong effect on the yield
(entries 10, 13, 14). Remarkably, this reaction was completed in 2 h
with the highest yield using TBAI as catalyst (entry 15). The product
(3a) was isolated with 72% yield using 4 equiv of TBHP in the absence of iodide after 12 h (entry 16).
With the optimal reaction conditions established, we examined
the substrate scope of the reaction. First of all, various electron-rich
and electron-poor N,N-dimethylanilines were examined. The
corresponding products of radical annulation with N-phenylmaleimide were obtained with moderate to excellent yields (Table
2, compounds 3ben). It was found that ortho-substituted N,Ndimethylanilines also furnished the corresponding products with
moderate to good yields (compounds 3jel). Notably, the electrondeficient N,N-dimethyl-3,5-bis(trifluoromethyl)aniline also gave
the desired product with acceptable yield (product 3n). Subsequently, we investigated the scope of various maleimides under
these conditions (compounds 3oer). It was found that aliphatic as
well as aromatic groups at the nitrogen of maleimides were tolerated and the desired products were formed in good to excellent
yields. Furthermore, the application of maleimide without substituent on nitrogen led to the desired product 3s with 78% yield.
Maleic anhydride was also subjected to this process. Unfortunately,
the corresponding product was obtained only in trace amounts.
Intriguingly, diethyl fumarate provided the desired tetrahydroquinoline 3t with high diastereoselectivity. However, using dimethyl maleate as substrate, just trace amounts of the desired
product was detected after 12 h.
Next, we turned our attention to anilines with different aliphatic
and aromatic substituents on nitrogen. To our delight, the radical
cyclization of N-methyl-N-phenylaniline with N-phenylmaleimide
provides the desired product 3u with good yield. Notably, a benzyl
group on the aniline nitrogen was tolerated, the reaction with Nbenzyl-N-methylaniline occurs exclusively at the methyl part of
aniline (product 3v). The same selectivity was observed using Nbutyl-N-methylaniline (product 3w). Moreover, anilines with two
identical aliphatic groups provided the corresponding products in
good to excellent yields. However, the formation of two diastereomers was observed (products 3xez). Unfortunately, the
application of N-aryl tetrahydroisoquinolines as substrates did not
provide the corresponding products.
A plausible mechanism was proposed on the basis of the results
described above and the related literature (Scheme 2).7e12,16 Initially, tert-butoxyl and tert-butylperoxyl radicals are formed by the
tert-butylperoxide and iodide ion in the redox recycle. A single
Z. Song, A.P. Antonchick / Tetrahedron 72 (2016) 7715e7721
Table 2
Scope of cyclization of N,N-dimethylanilines and maleimidesa
7717
t-BuOOH
t-BuO
1/2 I2
I
H2O
HO
+
t-BuOO
+
N
t-BuOOH + HO
t-BuO or t-BuOO
t-BuO or t-BuOO
2a
N
t-BuO or t-BuOO
N
t-BuOH or t-BuOOH
I
II
1a
H O
N
O
H O
t-BuO or t-BuOO
N Ph
N
H O
N Ph
N
N
H O
O
t-BuOH or t-BuOOH
3a
IV
III
Scheme 2. Proposed mechanism.
3. Conclusions
In summary, we presented a novel and environmentally benign
method of cyclization between electron-deficient alkenes and tertiary alkylanilines. The a-aminoalkyl radical as reaction intermediates were formed under a TBAI/TBHP system without
formation of corresponding iminium ions. A broad range of tricyclic
products with good to excellent yields was smoothly formed under
the developed reaction conditions.
4. Experimental
4.1. General information
a
Reaction conditions: 1 (0.1 mmol), 2 (0.2 mmol), TBAI (10 mol%), TBHP (70 % in
H2O, 4 eq) in DCE (1 mL) at 70 C.
b
TBHP (70 %, in H2O, 2 equiv) used.
c
Using diethyl fumarate instead of maleimide.
d
Major isomer is shown and minor regioisomer is shown with star.
electron transfer (SET) from N,N-dimethylaniline to tert-butoxyl or
tert-butylperoxyl radical followed by deprotonation forms the aaminoalkyl radical II. Subsequently, radical II as a nucleophile attacks maleimide 1a which forms intermediate III which cyclizes to
IV. Finally, the desired product 3a is formed by oxidation and
deprotonation of intermediate IV.
Unless otherwise noted, all commercially available compounds
were used as provided without further purification. Solvents for
chromatography were technical grade. Dry solvents were purified
by the Solvent Purification System M-BRAUN Glovebox Technology
SPS-800. Analytical thin layer chromatography (TLC) was performed on Merck silica gel aluminium plates with F-254 indicator,
visualized by irradiation with UV light. Column chromatography
was performed using silica gel Merck 60 (particle size
0.040e0.063 mm). Solvent mixtures are understood as volume/
volume.
1
H NMR and 13C NMR were recorded on a Bruker DRX400
(400 MHz), DRX500 (500 MHz) and DRX600 (600 MHz) spectrometer in CDCl3 (d¼7.26 ppm for 1H, d¼77.16 ppm for 13C) and in
CD3CN (d¼1.940 ppm for 1H, d¼1.320, 118.260 ppm for 13C). Data
are reported in the following order: chemical shift (d) in ppm;
multiplicities are indicated s (singlet), d (doublet), t (triplet), q
(quartet), m (multiplet); coupling constants (J) are given in Hertz
(Hz). High resolution mass spectra were recorded on an LTQ Orbitrap mass spectrometer coupled to an Acceka HPLC-System (HPLC
column: Hypersyl GOLD, 50 mm1 mm, 1.9 mm). Fourier transform
infrared spectroscopy (FT-IR) spectra were obtained with a Bruker
Tensor 27 spectrometer (ATR, neat) and are reported in terms of
frequency of absorption (cm1). Chemical yields refer to isolated
7718
Z. Song, A.P. Antonchick / Tetrahedron 72 (2016) 7715e7721
pure substances. Tertiary anilines were prepared according to literature procedures, others were purchased from chemical
companies.
4.2. General procedure
To a screw cap reaction vial, maleimide (0.1 mmol, 1equiv),
tertiary aniline (0.2 mmol, 2 equiv), tertbutyl ammonium iodide
3.69 mg (TBAI, 10 mol %), TBHP 55 mL (70% in H2O, 0.4 mmol,
4 equiv) and DCE (1 mL) were added. The reaction mixture was
heated to 70 C. The reaction progress was monitored by thin layer
chromatography (ethyl acetate/petroleum ether mixture) and
GCeMS. Upon completion, the crude reaction mixture was concentrated under reduced pressure and subsequently purified by
flash column chromatography over silica using ethyl acetate/petroleum ether as eluent system.
4.3. Spectroscopic data of compounds 3
4.3.1. (3aR*,9bS*)-5-Methyl-2-phenyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3a). Light yellow amorphous
solid (91% yield). 1H NMR (400 MHz, CDCl3) d 7.55e7.53 (m, 1H),
7.46e7.41 (m, 2H), 7.38e7.34 (m, 1H), 7.29e7.23 (m, 3H), 6.92 (ddd,
J¼7.5, 7.5, 1.1 Hz, 1H), 6.76e6.75 (m, 1H), 4.17 (d, J¼9.6 Hz, 1H), 3.62
(dd, J¼11.5, 2.8 Hz, 1H), 3.54 (ddd, J¼9.6, 4.4, 2.8 Hz, 1H), 3.13 (dd,
J¼11.5, 4.4 Hz, 1H), 2.85 (s, 3H) ppm; 13C NMR (101 MHz, CDCl3)
d 177.80, 175.88, 148.63, 132.15, 130.47, 129.12, 128.82, 128.63,
126.49, 119.79, 118.67, 112.66, 50.81, 43.72, 42.28, 39.56 ppm; FTIR:
ṽ¼1708, 1598, 1497, 1392, 1197, 1180 cm1; HRMS: calcd for [MþH]þ
C18H17O2N2: 293.12845, found: 293.12911.
4.3.2. (3aR*,9bS*)-5,8-Dimethyl-2-phenyl-3a,4,5,9b-tetrahydro-1Hpyrrolo[3,4-c]quinoline-1,3(2H)-dione (3b). Light brown amorphous
solid (94% yield). 1H NMR (300 MHz, CDCl3) d 7.45e7.32 (m, 4H),
7.28e7.25 (m, 2H), 7.03 (dd, J¼8.3, 1.9 Hz, 1H), 6.65 (d, J¼8.3 Hz, 1H),
4.11 (d, J¼9.6 Hz, 1H), 3.58 (dd, J¼11.3, 2.7 Hz, 1H), 3.51 (ddd, J¼9.6,
4.3, 2.7 Hz, 1H), 3.05 (dd, J¼11.3, 4.3 Hz, 1H), 2.80 (s, 3H), 2.30 (s, 3H)
ppm; 13C NMR (75 MHz, CDCl3) d 177.95, 176.00, 146.46, 132.12,
130.93, 129.36, 129.11, 128.62, 126.49, 118.63, 112.68, 51.06, 43.68,
42.29, 39.71, 20.57 ppm; FT-IR: ṽ¼1711, 1508, 1395, 1192, 806 cm1;
HRMS: calcd for [MþH]þ C19H19O2N2: 307.14410, found: 307.14528.
4.3.3. (3aR*,9bS*)-8-Ethyl-5-methyl-2-phenyl-3a,4,5,9b-tetrahydro1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3c). Light brown amorphous solid (79% yield). 1H NMR (300 MHz, CDCl3) d 7.43e7.30 (m,
4H), 7.27e7.23 (m, 2H), 7.05 (dd, J¼8.3, 1.8 Hz, 1H), 6.65 (d, J¼8.3 Hz,
1H), 4.11 (d, J¼9.5 Hz, 1H), 3.56 (dd, J¼11.3, 2.7 Hz, 1H), 3.52e3.46
(m, 1H), 3.05 (dd, J¼11.3, 4.3 Hz, 1H), 2.79 (s, 3H), 2.58 (q, J¼7.6 Hz,
2H), 1.20 (t, J¼7.6 Hz, 3H) ppm; 13C NMR (75 MHz, CDCl3) d 177.95,
175.99, 146.62, 135.59, 132.11, 129.86, 129.10, 128.60, 128.10, 126.48,
118.61, 112.65, 50.98, 43.66, 42.29, 39.69, 28.02, 15.87 ppm; FT-IR:
ṽ¼1708, 1506, 1396, 1319, 1194, 810 cm1; HRMS: calcd for [MþH]þ
C20H21O2N2: 321.15975, found: 321.16016.
4.3.4. (3aR*,9bS*)-8-Fluoro-5-methyl-2-phenyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3d). Brown amorphous solid (81% yield). 1H NMR (500 MHz, CDCl3) d 7.48e7.45 (m,
2H), 7.41e7.38 (m, 1H), 7.32e7.29 (m, 3H), 6.99e6.95 (m, 1H), 6.70
(dd, J¼9.0, 4.6 Hz, 1H), 4.14 (d, J¼9.6 Hz, 1H), 3.61 (dd, J¼11.5, 2.8 Hz,
1H), 3.56 (ddd, J¼9.6, 4.3, 2.8 Hz, 1H), 3.11 (dd, J¼11.5, 4.3 Hz, 1H),
2.84 (s, 3H) ppm; 13C NMR (126 MHz, CDCl3) d 177.51, 175.29, 156.81
(d, J¼238.8 Hz), 145.10, 132.04, 129.19, 128.75, 126.47, 120.18 (d,
J¼7.8 Hz), 117.13 (d, J¼23.4 Hz), 115.23 (d, J¼21.9 Hz), 113.54 (d,
J¼7.5 Hz), 51.20, 43.57, 42.37, 39.89 ppm; FT-IR: ṽ¼1705, 1503, 1392,
1320, 1246, 1191 cm1; HRMS: calcd for [MþH]þ C18H16O2N2F:
311.11903, found: 311.11982.
4.3.5. (3aR*,9bS*)-8-Bromo-5-methyl-2-phenyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3e). Light yellow
amorphous solid (86% yield). 1H NMR (300 MHz, CDCl3) d 7.63e7.62
(m, 1H), 7.45e7.22 (m, 6H), 6.59 (d, J¼8.8 Hz, 1H), 4.08 (d, J¼9.5 Hz,
1H), 3.59 (dd, J¼11.5, 2.8 Hz, 1H), 3.52 (ddd, J¼9.5, 4.3, 2.8 Hz, 1H),
3.09 (dd, J¼11.5, 4.3 Hz, 1H), 2.80 (s, 3H) ppm; 13C NMR (75 MHz,
CDCl3) d 177.40, 175.27, 147.61, 132.83, 131.92, 131.56, 129.18, 128.76,
126.41, 120.49, 114.36, 111.79, 50.48, 43.40, 41.89, 39.58 ppm; FT-IR:
ṽ¼2924, 1710, 1593, 1495, 1371, 1176 cm1; HRMS: calcd for [MþH]þ
C18H16O2N279Br: 371.03897, found: 371.04033; C18H16O2N281Br:
373.03692, found: 373.03816.
4.3.6. (3aR*,9bS*)-8-Iodo-5-methyl-2-phenyl-3a,4,5,9b-tetrahydro1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3f). Brown amorphous
solid (77% yield). 1H NMR (500 MHz, CDCl3) d 7.81e7.80 (m, 1H),
7.49 (dd, J¼8.6, 2.0 Hz, 1H), 7.46e7.42 (m, 2H), 7.38e7.35 (m, 1H),
7.28e7.26 (m, 2H), 6.50 (d, J¼8.7 Hz, 1H), 4.09 (d, J¼9.6 Hz, 1H), 3.60
(dd, J¼11.6, 2.8 Hz, 1H), 3.52 (ddd, J¼9.6, 4.3, 2.8 Hz, 1H), 3.12 (dd,
J¼11.6, 4.3 Hz, 1H), 2.81 (s, 3H) ppm; 13C NMR (126 MHz, CDCl3)
d 177.29, 175.23, 148.21, 138.57, 137.51, 131.98, 129.16, 128.74, 126.41,
120.90, 114.89, 81.30, 50.37, 43.39, 41.70, 39.46 ppm; FT-IR: ṽ¼1709,
1493, 1369, 1319, 1177, 1101 cm1; HRMS: calcd for [MþH]þ
C18H16O2N2I: 419.02510, found: 419.02558.
4.3.7. (3aR*,9bS*)-Methyl
5-methyl-1,3-dioxo-2-phenyl2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,4-c]quinoline-8-carboxylate
(3g). Yellow amorphous solid (45% yield). 1H NMR (500 MHz,
CDCl3) d 8.22 (d, J¼1.2 Hz, 1H), 7.91 (dd, J¼8.7, 1.9 Hz, 1H), 7.44e7.41
(m, 2H), 7.37e7.34 (m, 1H), 7.27e7.25 (m, 2H), 6.74 (d, J¼8.7 Hz, 1H),
4.19 (d, J¼9.6 Hz, 1H), 3.88 (s, 3H), 3.68 (dd, J¼11.7, 2.9 Hz, 1H), 3.58
(ddd, J¼9.6, 4.3, 2.9 Hz, 1H), 3.25 (dd, J¼11.7, 4.3 Hz, 1H), 2.93 (s, 3H)
ppm; 13C NMR (126 MHz, CDCl3) d 177.16, 175.35, 166.98, 151.81,
132.06, 131.97, 130.84, 129.15, 128.73, 126.38, 120.98, 117.43, 112.13,
51.92, 49.83, 43.20, 41.82, 39.52 ppm; FT-IR: ṽ¼1706, 1607, 1498,
1374, 1275, 1177 cm1; HRMS: calcd for [MþH]þ C20H19O4N2:
351.13393, found: 351.13477.
4.3.8. (3aR*,9bS*)-9-Methoxy-5-methyl-2-phenyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3h) [A-major product]
and
(3aR*,9bS*)-7-methoxy-5-methyl-2-phenyl-3a,4,5,9btetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3h) [B-minor
product]. Brown amorphous solid (91% yield). [A-major product]
1
H NMR (500 MHz, CDCl3) d 7.44e7.41 (m, 2H), 7.36e7.33 (m, 1H),
7.30e7.28 (m, 2H), 7.20e7.17 (m, 1H), 6.56 (d, J¼8.3 Hz, 1H), 6.42 (d,
J¼8.2 Hz, 1H), 4.78 (d, J¼9.9 Hz, 1H), 3.91 (s, 3H), 3.56 (dd, J¼11.4,
1.8 Hz, 1H), 3.49 (ddd, J¼9.9, 4.9, 1.8 Hz, 1H), 2.98 (dd, J¼11.4, 4.9 Hz,
1H), 2.80 (s, 3H) ppm; 13C NMR (126 MHz, CDCl3) d 178.64, 175.51,
158.82, 151.01, 132.38, 129.07, 129.00, 128.54, 126.61, 109.23, 105.93,
103.74, 56.36, 52.72, 44.34, 39.86, 36.82 ppm; FT-IR: ṽ¼1705, 1597,
1495, 1389, 1184, 1061 cm1; HRMS: calcd for [MþH]þ C19H19O3N2:
323.13902, found: 323.13990. [B-minor product] 1H NMR
(500 MHz, CDCl3) d 7.46e7.41 (m, 3H), 7.37e7.34 (m, 1H), 7.27e7.26
(m, 2H), 6.48e6.46 (m, 1H), 6.31 (d, J¼2.3 Hz, 1H), 4.11 (d, J¼9.6 Hz,
1H), 3.80 (s, 3H), 3.61 (dd, J¼11.5, 2.8 Hz, 1H), 3.52 (ddd, J¼9.6, 4.4,
2.8 Hz, 1H), 3.14 (dd, J¼11.5, 4.4 Hz, 1H), 2.83 (s, 3H) ppm; 13C NMR
(126 MHz, CDCl3) d 177.75, 176.21, 160.43, 149.52, 132.17, 131.25,
129.14, 128.64, 126.51, 111.17, 104.51, 99.91, 55.43, 50.61, 43.32,
41.60, 39.69 ppm; HRMS: calcd for [MþH]þ C19H19O3N2: 323.13902,
found: 323.14017.
4.3.9. (3aR*,9bS*)-9-Acetyl-5-methyl-2-phenyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3i) [A-major product]
and (3aR*,9bS*)-7-acetyl-5-methyl-2-phenyl-3a,4,5,9b-tetrahydro-
Z. Song, A.P. Antonchick / Tetrahedron 72 (2016) 7715e7721
1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3i) [B-minor product]. Brown amorphous solid (76% yield). [A-major product] 1H NMR
(500 MHz, CDCl3) d 7.45e7.42 (m, 2H), 7.38e7.35 (m, 1H), 7.31e7.25
(m, 3H), 7.17 (dd, J¼7.6, 0.8 Hz, 1H), 6.88 (d, J¼8.1 Hz, 1H), 5.57 (d,
J¼9.9 Hz, 1H), 3.62 (dd, J¼11.5, 2.5 Hz, 1H), 3.56 (ddd, J¼9.9, 4.6,
2.5 Hz, 1H), 3.18 (dd, J¼11.5, 4.6 Hz, 1H), 2.89 (s, 3H), 2.71 (s, 3H)
ppm; 13C NMR (75 MHz, CDCl3) d 204.82, 178.20, 176.07, 149.88,
141.26, 132.02, 129.23, 128.77, 128.10, 126.51, 119.66, 116.80, 115.33,
51.04, 43.56, 40.05, 36.94, 30.46 ppm; FT-IR: ṽ¼1703, 1588, 1490,
1333, 1212, 1168 cm1; HRMS: calcd for [MþH]þ C20H19O3N2:
335.13902, found: 335.14033. [B-minor product] 1H NMR
(500 MHz, CDCl3) d 7.62 (d, J¼7.9 Hz, 1H), 7.47e7.42 (m, 3H),
7.38e7.34 (m, 2H), 7.26e7.25 (m, 2H), 4.22 (d, J¼9.6 Hz, 1H), 3.66
(dd, J¼11.6, 2.7 Hz, 1H), 3.57 (ddd, J¼9.6, 4.4, 2.7 Hz, 1H), 3.16 (dd,
J¼11.6, 4.4 Hz, 1H), 2.92 (s, 3H), 2.59 (s, 3H) ppm; 13C NMR (75 MHz,
CDCl3) d 198.38, 177.42, 175.17, 148.84, 137.51, 131.92, 130.60, 129.23,
128.84, 126.44, 123.86, 120.27, 111.64, 50.65, 43.53, 42.41, 39.68,
26.88 ppm; FT-IR: ṽ¼1699, 1500, 1391, 1282, 1170, 752, 696 cm1;
HRMS: calcd for [MþH]þ C20H19O3N2: 335.13902, found:
335.13952.
4.3.10. (3aR*,9bS*)-6-Benzyl-5-methyl-2-phenyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3j). Light yellow
amorphous solid (51% yield). 1H NMR (500 MHz, CDCl3) d 7.63 (d,
J¼7.5 Hz, 1H), 7.48e7.46 (m, 2H), 7.41e7.38 (m, 1H), 7.30e7.26 (m,
4H), 7.22e7.17 (m, 3H), 7.10 (t, J¼7.6 Hz, 1H), 7.03 (d, J¼7.5 Hz, 1H),
4.22 (d, J¼9.0 Hz, 1H), 4.08 (s, 2H), 3.61e3.51 (m, 2H), 3.43 (dd,
J¼13.8, 6.6 Hz, 1H), 2.74 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3)
d 177.94, 175.86, 146.57, 141.14, 136.16, 132.07, 130.59, 129.33, 129.15,
129.03, 128.83, 128.53, 126.39, 126.12, 124.55, 123.67, 51.49, 43.32,
41.63, 38.82, 36.32 ppm; FT-IR: ṽ¼1707, 1496, 1378, 1174, 909 cm1;
HRMS: calcd for [MþH]þ C25H23O2N2: 383.17540, found: 383.17681.
4.3.11. (3aR*,9bS*)-5-Methyl-2,6-diphenyl-3a,4,5,9b-tetrahydro-1Hpyrrolo[3,4-c]quinoline-1,3(2H)-dione (3k). Brown amorphous solid
(63% yield). 1H NMR (500 MHz, CDCl3) d 7.70 (dd, J¼7.5, 1.0 Hz, 1H),
7.52e7.50 (m, 2H), 7.48e7.46 (m, 2H), 7.42e7.37 (m, 3H), 7.35e7.27
(m, 3H), 7.22e7.15 (m, 2H), 4.22 (d, J¼8.5 Hz, 1H), 3.57e3.49 (m,
2H), 3.46e3.42 (m, 1H), 2.38 (s, 3H) ppm; 13C NMR (126 MHz,
CDCl3) d 177.69, 175.87, 145.90, 140.53, 135.71, 132.15, 131.06, 130.33,
129.29, 128.95, 128.78, 128.44, 127.08, 126.44, 123.42, 122.80, 50.98,
42.36, 42.14, 39.62 ppm; FT-IR: ṽ¼1708, 1497, 1378, 1172, 908,
821 cm1; HRMS: calcd for [MþH]þ C24H21O2N2: 369.15975, found:
369.16082.
4.3.12. (3aR*,9bS*)-6-Benzoyl-5-methyl-2-phenyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3l). Yellow amorphous solid (45% yield). 1H NMR (500 MHz, CDCl3) d 7.82e7.80 (m,
2H), 7.77 (d, J¼7.6 Hz, 1H), 7.58e7.56 (m, 1H), 7.48e7.42 (m, 4H),
7.41e7.38 (m, 1H), 7.29e7.24 (m, 3H), 7.05 (t, J¼7.6 Hz, 1H), 4.23 (d,
J¼9.2 Hz, 1H), 3.56e3.51 (m, 1H), 3.41e3.40 (m, 2H), 2.69 (s, 3H)
ppm; 13C NMR (126 MHz, CDCl3) d 197.56, 177.28, 175.61, 146.85,
137.57, 133.32, 133.01, 132.02, 130.45, 130.09, 129.71, 129.31, 128.86,
128.51, 126.41, 121.84, 120.95, 50.20, 44.05, 42.13, 41.52 ppm; FT-IR:
ṽ¼1709, 1497, 1375, 1174, 669 cm1; HRMS: calcd for [MþH]þ
C25H21O3N2: 397.15467, found: 397.15523.
4.3.13. (3aR*,9bS*)-7,8,9-Trimethoxy-5-methyl-2-phenyl-3a,4,5,9btetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3m). Brown
amorphous solid (93% yield). 1H NMR (500 MHz, CDCl3) d 7.45e7.42
(m, 2H), 7.37e7.34 (m, 1H), 7.30e7.28 (m, 2H), 6.11 (s, 1H), 4.66 (d,
J¼9.9 Hz, 1H), 4.11 (s, 3H), 3.87 (s, 3H), 3.82 (s, 3H), 3.53 (dd, J¼11.4,
1.5 Hz, 1H), 3.47 (ddd, J¼9.9, 5.0, 1.5 Hz, 1H), 2.92 (dd, J¼11.4, 5.0 Hz,
1H), 2.78 (s, 3H) ppm; 13C NMR (126 MHz, CDCl3) d 178.74, 175.99,
7719
153.56, 153.00, 146.59, 135.91, 132.33, 129.15, 128.63, 126.61, 106.62,
93.45, 61.76, 60.87, 56.20, 53.33, 44.39, 39.74, 37.14 ppm; FT-IR:
ṽ¼1708, 1599, 1495, 1372, 1180, 1113, 1029 cm1; HRMS: calcd for
[MþH]þ C21H23O5N2: 383.16015, found: 383.16114.
4.3.14. (3aR*,9bS*)-5-Methyl-2-phenyl-7,9-bis(trifluoromethyl)3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione
(3n). Light yellow amorphous solid (40% yield). 1H NMR (500 MHz,
CDCl3) d 7.55 (s, 1H), 7.47e7.44 (m, 2H), 7.40e7.37 (m, 1H),
7.30e7.28 (m, 2H), 7.19 (s, 1H), 4.74 (d, J¼9.6 Hz, 1H), 3.66e3.62 (m,
2H), 3.04 (dd, J¼11.8, 5.9 Hz, 1H), 2.90 (s, 3H) ppm; 13C NMR
(151 MHz, CDCl3) d 177.66, 173.53, 152.61, 134.35, 131.88, 131.63 (q,
J¼31.1 Hz), 131.09 (q, J¼33.3 Hz), 129.28, 129.01, 128.13, 126.40,
126.22, 124.27, 123.57 (q, J¼274.33), 123.50 (q, J¼273.1), 119.97,
115.10e115.03 (m), 113.00e112.98 (m), 53.98, 46.01, 40.08 (d,
J¼1.4 Hz), 39.86 ppm; FT-IR: ṽ¼1715, 1483, 1390, 1348, 1273, 1123,
1007 cm1; HRMS: calcd for [MþH]þ C20H15O2N2F6: 429.10322,
found: 429.10435.
4.3.15. (3aR*,9bS*)-2-(4-Bromophenyl)-5-methyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3o). Brown amorphous solid (68% yield). 1H NMR (500 MHz, CDCl3) d 7.56e7.51 (m,
3H), 7.26e7.22 (m, 1H), 7.20e7.18 (m, 2H), 6.91 (ddd, J¼7.5, 7.5,
1.0 Hz, 1H), 6.75e6.74 (m, 1H), 4.15 (d, J¼9.6 Hz, 1H), 3.60 (dd,
J¼11.5, 2.6 Hz, 1H), 3.53 (ddd, J¼9.6, 4.4, 2.6 Hz, 1H), 3.11 (dd, J¼11.5,
4.4 Hz, 1H), 2.84 (s, 3H) ppm; 13C NMR (126 MHz, CDCl3) d 177.47,
175.55, 148.61, 132.28, 131.12, 130.43, 128.92, 127.98, 122.42, 119.89,
118.47, 112.74, 50.75, 43.75, 42.27, 39.57 ppm; FT-IR: ṽ¼1710, 1488,
1396, 1198, 812 cm1; HRMS: calcd for [MþH]þ C18H16O2N279Br:
371.03897, found: 371.03996; HRMS: calcd for [MþH]þ
C18H16O2N281Br: 373.03692, found: 373.03747.
4.3.16. (3aR*,9bS*)-2,5-Dimethyl-3a,4,5,9b-tetrahydro-1H-pyrrolo
[3,4-c]quinoline-1,3(2H)-dione (3p). Light brown amorphous solid
(62% yield). 1H NMR (500 MHz, CDCl3) d 7.49e7.47 (m, 1H),
7.23e7.19 (m, 1H), 6.89 (ddd, J¼7.5, 7.5, 1.0 Hz, 1H), 6.71e6.69 (m,
1H), 4.00 (d, J¼9.4 Hz, 1H), 3.53 (dd, J¼11.5, 2.4 Hz, 1H), 3.36 (ddd,
J¼9.4, 4.3, 2.4 Hz, 1H), 3.04 (dd, J¼11.5, 4.3 Hz, 1H), 2.99 (s, 3H), 2.80
(s, 3H) ppm; 13C NMR (126 MHz, CDCl3) d 178.85, 176.92, 148.50,
130.33, 128.72, 119.78, 118.86, 112.63, 50.62, 43.72, 42.16, 39.54,
25.48 ppm; FT-IR: ṽ¼1693, 1435, 1314, 1095, 1020 cm1; HRMS:
calcd for [MþH]þ C13H15O2N2: 231.11280, found: 231.11355.
4.3.17. (3aR*,9bS*)-5-Methyl-2-propyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3q). Brown amorphous solid
(66% yield). 1H NMR (500 MHz, CDCl3) d 7.48e7.46 (m, 1H),
7.22e7.19 (m, 1H), 6.90e6.87 (m, 1H), 6.71e6.69 (m, 1H), 3.97 (d,
J¼9.4 Hz, 1H), 3.51e3.42 (m, 3H), 3.35 (ddd, J¼9.3, 4.4, 2.7 Hz, 1H),
3.03 (dd, J¼11.5, 4.4 Hz, 1H), 2.80 (s, 3H), 1.60e1.52 (m, 2H), 0.82 (t,
J¼7.5 Hz, 3H) ppm; 13C NMR (126 MHz, CDCl3) d 178.86, 176.90,
148.56, 130.34, 128.64, 119.75, 119.13, 112.54, 50.90, 43.65, 42.14,
40.95, 39.47, 21.00, 11.13 ppm; FT-IR: ṽ¼1696, 1498, 1400, 1324,
1201, 1122, 1094, 1043 cm1; HRMS: calcd for [MþH]þ C15H19O2N2:
259.14410, found: 259.14461.
4.3.18. (3aR*,9bS*)-2-Cyclohexyl-5-methyl-3a,4,5,9b-tetrahydro-1Hpyrrolo[3,4-c]quinoline-1,3(2H)-dione (3r). Brown amorphous solid
(87% yield). 1H NMR (500 MHz, CDCl3) d 7.48e7.46 (m, 1H),
7.22e7.18 (m, 1H), 6.90e6.87 (m, 1H), 6.71e6.69 (m, 1H), 3.97e3.89
(m, 2H), 3.45 (dd, J¼11.4, 2.9 Hz, 1H), 3.28 (ddd, J¼9.3, 4.6, 2.9 Hz,
1H), 3.03 (dd, J¼11.4, 4.6 Hz, 1H), 2.79 (s, 3H), 2.17e2.02 (m, 2H),
1.79e1.76 (m, 2H), 1.63e1.61 (m, 1H), 1.56e1.51 (m, 2H), 1.32e1.25
(m, 2H), 1.23e1.14 (m, 1H) ppm; 13C NMR (126 MHz, CDCl3)
d 178.82, 176.96, 148.52, 130.34, 128.56, 119.61, 119.17, 112.50, 52.33,
7720
Z. Song, A.P. Antonchick / Tetrahedron 72 (2016) 7715e7721
50.97, 43.21, 41.88, 39.52, 29.00, 28.89, 25.96, 25.91, 25.19 ppm; FTIR: ṽ¼2929, 1695, 1601, 1498, 1450, 1366, 1184, 1132 cm1; HRMS:
calcd for [MþH]þ C18H23O2N2: 299.17540, found: 299.17594.
4.3.19. (3aR*,9bS*)-5-Methyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]
quinoline-1,3(2H)-dione (3s). Light brown amorphous solid (78%
yield). 1H NMR (300 MHz, CD3CN) d 8.99 (brs, 1H), 7.35e7.32 (m, 1H),
7.22e7.16 (m, 1H), 6.84 (ddd, J¼7.5, 7.5, 1.1 Hz, 1H), 6.77e6.74 (m, 1H),
4.00 (d, J¼9.5 Hz, 1H), 3.44e3.37 (m, 2H), 2.90 (dd, J¼11.5, 4.5 Hz,
1H), 2.76 (s, 3H) ppm; 13C NMR (75 MHz, CD3CN) d 180.38, 178.37,
149.92, 131.08, 129.22, 120.75, 120.09, 113.44, 51.59, 45.57, 44.14,
39.81 ppm; FT-IR: ṽ¼3179, 1768, 1700, 1497, 1308, 1176, 1042 cm1;
HRMS: calcd for [MþH]þ C12H13O2N2: 217.09715, found: 217.09746.
4.3.20. (3R*,4R*)-Diethyl 1-methyl-1,2,3,4-tetrahydroquinoline-3,4dicarboxylate (3t). Light green amorphous solid (60% yield). 1H
NMR (500 MHz, CDCl3) d 7.22 (d, J¼7.6 Hz, 1H), 7.16e7.12 (m, 1H),
6.70e6.64 (m, 2H), 4.23e4.12 (m, 5H), 3.56e3.51 (m, 1H),
3.43e3.37 (m, 2H), 2.92 (s, 3H), 1.29 (t, J¼7.1 Hz, 3H), 1.23 (t,
J¼7.1 Hz, 3H) ppm; 13C NMR (151 MHz, CDCl3) d 173.19, 172.09,
145.61, 129.16, 128.51, 118.14, 117.57, 112.22, 61.36, 61.24, 50.37,
44.82, 41.18, 39.60, 14.32, 14.27 ppm; FT-IR: ṽ¼2980, 1728, 1602,
1504, 1181, 1025 cm1; HRMS: calcd for [MþH]þ C16H22O4N:
292.15433, found: 292.15505.
4.3.21. (3aR*,9bS*)-2,5-Diphenyl-3a,4,5,9b-tetrahydro-1H-pyrrolo
[3,4-c]quinoline-1,3(2H)-dione (3u). Yellow amorphous solid (67%
yield). 1H NMR (500 MHz, CDCl3) d 7.60 (d, J¼7.5 Hz, 1H), 7.43e7.40
(m, 2H), 7.37e7.32 (m, 3H), 7.19e7.17 (m, 2H), 7.12e7.08 (m, 4H),
6.97 (ddd, J¼7.5, 7.5, 1.1 Hz, 1H), 6.78e6.77 (m, 1H), 4.24 (d,
J¼9.4 Hz, 1H), 4.20 (dd, J¼12.0, 3.1 Hz, 1H), 3.70 (dd, J¼12.0, 4.5 Hz,
1H), 3.65 (ddd, J¼9.4, 4.5, 3.1 Hz, 1H) ppm; 13C NMR (126 MHz,
CDCl3) d 177.18, 175.73, 146.54, 146.33, 132.09, 130.87, 129.70, 129.19,
128.72, 128.47, 126.48, 124.02, 123.10, 121.60, 120.68, 117.45, 48.54,
44.70, 42.54 ppm; FT-IR: ṽ¼1705, 1592, 1491, 1390, 1181 cm1;
HRMS: calcd for [MþH]þ C23H19O2N2: 355.14410, found: 355.14520.
4.3.22. (3aR*,9bS*)-5-Benzyl-2-phenyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3v). Brown amorphous solid
(46% yield). 1H NMR (500 MHz, CDCl3) d 7.55 (d, J¼7.5 Hz, 1H), 7.46
(t, J¼7.7 Hz, 2H), 7.40e7.37 (m, 1H), 7.31e7.23 (m, 7H), 7.16e7.13 (m,
1H), 6.89 (t, J¼7.5 Hz, 1H), 6.75e6.74 (m, 1H), 4.48 (d, J¼15.3 Hz,
1H), 4.29 (d, J¼15.3 Hz, 1H), 4.20 (d, J¼9.5 Hz, 1H), 3.69 (dd, J¼11.7,
2.9 Hz, 1H), 3.56 (ddd, J¼9.5, 4.2, 2.9 Hz, 1H), 3.28 (dd, J¼11.7, 4.2 Hz,
1H) ppm; 13C NMR (126 MHz, CDCl3) d 177.55, 175.89, 147.60, 137.80,
132.22, 130.70, 129.22, 128.74, 128.70, 127.58, 127.48, 126.48, 119.93,
119.04, 113.66, 55.59, 49.18, 44.25, 42.57 ppm; FT-IR: ṽ¼1708, 1598,
1496, 1386, 1200 cm1; HRMS: calcd for [MþH]þ C24H21O2N2:
369.15975, found: 369.16074.
4.3.23. (3aR*,9bS*)-5-Butyl-2-phenyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3w). Brown amorphous solid
(65% yield). 1H NMR (500 MHz, CDCl3) d 7.51 (d, J¼7.5 Hz, 1H),
7.44e7.41 (m, 2H), 7.37e7.34 (m, 1H), 7.26e7.25 (m, 2H), 7.22e7.19
(m, 1H), 6.85 (ddd, J¼7.5, 7.5, 0.8 Hz, 1H), 6.76e6.75 (m, 1H), 4.13 (d,
J¼9.5 Hz, 1H), 3.66 (dd, J¼11.7, 2.9 Hz, 1H), 3.55e3.52 (m, 1H),
3.31e3.25 (m, 1H), 3.19 (dd, J¼11.7, 4.3 Hz, 1H), 3.13e3.07 (m, 1H),
1.65e1.50 (m, 2H), 1.36 (q, 7.4 Hz, 2H), 0.94 (t, J¼7.4 Hz, 3H) ppm;
13
C NMR (126 MHz, CDCl3) d 177.85, 175.95, 147.66, 132.20, 130.82,
129.15, 128.69, 128.63, 126.47, 119.15, 118.70, 112.72, 50.75, 48.46,
44.20, 42.50, 28.38, 20.50, 14.02 ppm; FT-IR: ṽ¼1709, 1598, 1496,
1374, 1175 cm1; HRMS: calcd for [MþH]þ C21H23O2N2: 335.17540,
found: 335.17657.
4.3.24. (3aR*,4R*,9bS*)-5-Ethyl-4-methyl-2-phenyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3x) [A-minor
product] and (3aR*,4S*,9bS*)-5-ethyl-4-methyl-2-phenyl-3a,4,5,9btetrahydro-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3x) [B-major
product]. White amorphous solid (63% yield). [A-minor product]
1
H NMR (500 MHz, CDCl3) d 7.49 (d, J¼7.4 Hz, 1H), 7.45e7.42 (m, 2H),
7.37e7.34 (m, 1H), 7.27e7.24 (m, 2H), 7.23e7.19 (m, 1H), 6.86e6.83
(m, 1H), 6.73e6.72 (m, 1H), 4.18e4.12 (m, 2H), 3.43e3.34 (m, 2H),
3.03e2.96 (m, 1H), 1.23 (t, J¼7.1 Hz, 3H), 1.11 (d, J¼6.7 Hz, 3H) ppm;
13
C NMR (126 MHz, CDCl3) d 177.64, 176.02, 144.39, 132.19, 130.17,
129.13, 129.02, 128.58, 126.44, 118.87, 118.60, 113.54, 51.69, 50.14,
43.65, 41.28, 15.07, 13.46 ppm; FT-IR: ṽ¼1705, 1598, 1496, 1381,
1165 cm1; HRMS: calcd for [MþH]þ C20H21O2N2: 321.15975, found:
321.16133. [B-major product] 1H NMR (500 MHz, CDCl3) d 7.48 (d,
J¼7.4 Hz, 1H), 7.43e7.40 (m, 2H), 7.36e7.33 (m, 1H), 7.26e7.23 (m,
2H), 7.21e7.18 (m, 1H), 6.84e6.81 (m, 1H), 6.70e6.69 (m, 1H),
4.16e4.10 (m, 2H), 3.41e3.32 (m, 2H), 3.01e2.94 (m, 1H), 1.21 (t,
J¼7.1 Hz, 3H), 1.09 (d, J¼6.7 Hz, 3H) ppm; 13C NMR (126 MHz, CDCl3)
d 177.65, 176.02, 132.19, 130.16, 129.13, 129.01, 128.58, 126.44, 118.81,
118.58, 113.54, 51.69, 50.15, 43.68, 41.29, 15.07, 13.46 ppm; HRMS:
calcd for [MþH]þ C20H21O2N2: 321.15975, found: 321.16136.
4.3.25. (3aR*,3bS*,11bS*)-2-Phenyl-3a,3b,4,5,6,11b-hexahydro-1Hdipyrrolo[1,2-a:30 ,40 -c]quinoline-1,3(2H)-dione (3y) [A-minor product] and (3aR*,3bR*,11bS*)-2-phenyl-3a,3b,4,5,6,11b-hexahydro-1Hdipyrrolo[1,2-a:30 ,40 -c]quinoline-1,3(2H)-dione (3y) [B-major product]. White amorphous solid (93% yield). [A-minor product] 1H
NMR (500 MHz, CDCl3) d 7.78 (d, J¼7.7 Hz, 1H), 7.49e7.46 (m, 2H),
7.41e7.38 (m, 1H), 7.31e7.29 (m, 2H), 7.26e7.23 (m, 1H), 6.90 (ddd,
J¼7.6, 7.6, 0.9 Hz, 1H), 6.69e6.68 (m, 1H), 4.13 (d, J¼8.1 Hz, 1H),
3.56e3.51 (m, 1H), 3.20e3.10 (m, 2H), 2.97e2.92 (m, 1H), 2.47e2.43
(m, 1H), 2.20e2.16 (m, 1H), 2.13e1.98 (m, 2H) ppm; 13C NMR
(126 MHz, CDCl3) d 175.90, 175.65, 144.81, 132.03, 130.80, 129.30,
128.76, 128.70, 126.58, 118.43, 116.02, 112.86, 58.60, 47.25, 46.09,
41.64, 31.44, 22.66 ppm; FT-IR: ṽ¼1699, 1600, 1501, 1458, 1375,
1158 cm1; HRMS: calcd for [MþH]þ C20H19O2N2: 319.14410;
found: 319.14568. [B-major product] 1H NMR (500 MHz, CDCl3)
d 7.54 (d, J¼7.5 Hz, 1H), 7.42e7.39 (m, 2H), 7.35e7.32 (m, 1H),
7.22e7.19 (m, 3H), 6.86 (ddd, J¼7.5, 7.5, 0.9 Hz, 1H), 6.65e6.63 (m,
1H), 4.22 (d, J¼9.2 Hz, 1H), 3.65 (dd, J¼9.2, 3.9 Hz, 1H), 3.51e3.47
(m, 1H), 3.30e3.26 (m, 1H), 3.00e2.90 (m, 2H), 2.15e2.07 (m, 2H),
2.00e1.94 (m, 1H) ppm; 13C NMR (126 MHz, CDCl3) d 176.14, 175.69,
147.86, 132.07, 129.99, 129.05, 128.69, 128.54, 126.59, 119.20, 118.36,
112.83, 59.15, 48.04, 45.93, 44.47, 26.45, 23.45 ppm; HRMS: calcd
for [MþH]þ C20H19O2N2: 319.14410, found: 319.14567.
4.3.26. (3aS*,12aS*,12bR*)-2-Phenyl-9,10,11,12,12a,12b-hexahydropyrido[1,2-a]pyrrolo[3,4-c]quinoline-1,3(2H,3aH)-dione
and
(3aS*,12aR*,12bR*)-2-phenyl-9,10,11,12,12a,12b-hexahydropyrido[1,2a]pyrrolo[3,4-c]quinoline-1,3(2H,3aH)-dione (3z). Brown amorphous solid (73% yield). 1H NMR (500 MHz, CDCl3, # denotes major
signals, * denotes minor signals) d 7.66e7.62#* (m), 7.46e7.41#*
(m), 7.39e7.34#* (m), 7.28e7.21 #* (m), 6.92e6.84#* (m),
4.12e4.10#* (m), 3.96e3.94#* (m), 3.78e3.76* (m), 3.59e3.56#
(m), 3.50e3.46# (m), 3.24* (d, J¼6.4 Hz), 3.03* (t, J¼12.0 Hz), 2.83#
(td, J¼12.9, 3.0 Hz), 2.11# (qd, J¼12.8, 3.9 Hz), 1.88e1.86#* (m),
1.76e1.62#* (m), 1.54e1.47#* (m) ppm; 13C NMR (126 MHz, CDCl3)
d major and minor isomers: 175.98, 175.80, 146.26, 132.07, 131.98,
130.89, 130.38, 129.19, 129.12, 128.93, 128.66, 128.61, 126.54, 126.50,
119.20, 117.07, 114.11, 56.57, 56.33, 49.46, 44.89, 41.59, 40.30, 25.71,
24.69, 22.53, 20.90 ppm; FT-IR: ṽ¼1705, 1598, 1494, 1376,
1137 cm1; HRMS: calcd for [MþH]þ C21H21O2N2: 333.15975,
found: 333.16138.
Acknowledgements
Z.S. thanks the China Scholarship Council (CSC) for a doctoral
fellowship. We gratefully acknowledge Prof. Dr. Herbert Waldmann
Z. Song, A.P. Antonchick / Tetrahedron 72 (2016) 7715e7721
for his generous support. This work was supported by the MaxPlanck-Gesellschaft.
Supplementary data
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2016.04.052.
These data include MOL files and InChiKeys of the most important
compounds described in this article.
5.
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