Cycloaddition of C,C-disubstituted ketonitrones with acceptor methylenecyclopropanes and subsequent rearrangement cascade of 5-spirocyclopropane-isoxazolidines

Article abstract of DOI:10.1002/ejoc.201200039

A new reaction cascade to give tricyclic cores of 2,4-dihydro-1H-azeto[1,2- a]quinolines (benzocarbacephems) and pyrrolo[1,2-a]quinolines starting from acyclic N-aryl ketonitrones and acceptor ring substituted methylenecyclopropanes has been reported. This reaction includes 1,3-dipolar cycloaddition of N-aryl-C,C-diaryl or N-aryl-C,C-bis(methoxycarbonyl) nitrones 1 to the double bond of dimethyl methylenecyclopropane-1,2-dicarboxylate 2 or benzylidenecyclopropane-1,1-dicarboxylate 3, followed by Brandi-Guarna rearrangement of the initially formed 5-spirocyclopropane-isoxazolidine cycloadducts to give 2,4-dihydro-1H-azeto[1,2-a]quinolines 4 or pyrrolo[1,2-a]quinolines 6. 1,3-Dipolar cycloaddition of acceptor ring-substituted methylenecyclopropanes and trisubstituted N,C,C-triaryl- and N-aryl-C,C-bis(methoxycarbonyl)nitrones proceed with the formation of new polycycliccompounds with azeto[1,2-a]quinoline or pyrrolo[1,2-a]quinoline cores. Copyright

Full text of DOI:10.1002/ejoc.201200039

FULL PAPER
DOI: 10.1002/ejoc.201200039
Cycloaddition of C,C-Disubstituted Ketonitrones with Acceptor
Methylenecyclopropanes and Subsequent Rearrangement Cascade of
5-Spirocyclopropane-isoxazolidines
Tung Q. Tran,[a] Vyacheslav V. Diev,[b] Galina L. Starova,[a] Vladislav V. Gurzhiy,[a] and
Alexander P. Molchanov*[a]
Keywords: Cycloaddition / Rearrangement / Nitrones / Small ring systems / Methylenecyclopropanes
A new reaction cascade to give tricyclic cores of 2,4-dihydro-
1H-azeto[1,2-a]quinolines (benzocarbacephems) and pyr-
rolo[1,2-a]quinolines starting from acyclic N-aryl keto-
nitrones and acceptor ring substituted methylenecyclo-
propanes has been reported. This reaction includes 1,3-di-
polar cycloaddition of N-aryl-C,C-diaryl or N-aryl-C,C-bis-
(methoxycarbonyl) nitrones 1 to the double bond of dimethyl
methylenecyclopropane-1,2-dicarboxylate 2 or benzylidene-
cyclopropane-1,1-dicarboxylate 3, followed by Brandi–
Guarna rearrangement of the initially formed 5-spirocyclo-
propane-isoxazolidine cycloadducts to give 2,4-dihydro-1H-
azeto[1,2-a]quinolines 4 or pyrrolo[1,2-a]quinolines 6.
Introduction
Different transformations of methylenecyclopropanes,
for instance ring expansion, cycloadditions, and ring-open-
ing reactions have been intensively studied during past dec-
ades.[1–4] The release of strain energy in methylenecyclo-
propanes causes significant enhancement of their reactivity
in a number of reactions where simple alkenes (e.g. alkyl-
substituted ethylenes) are not active. In many cases initially
formed cycloadducts possess high strain energy. This may
facilitate subsequent cascade transformations of the initially
formed products.[1a,4]
1,3-Dipolar cycloaddition of nitrones to the double car-
bon–carbon bond of methylenecyclopropanes is one of the
most extensively studied cycloaddition reactions of methyl-
enecyclopropanes due to rich chemistry of spirocyclo-
propane cycloadducts formed in these reactions.[4f,4k,5] In
most cases 5-spirocyclopropane-isoxazolidine regioisomers
are formed predominantly or exclusively (Scheme 1). 5-
Spirocyclopropane-isoxazolidines contain a highly strained
spirocyclopropane ring and a comparatively weak adjacent
N–O bond that facilitates subsequent Brandi–Guarna re-
arrangement with the formation of piperidin-4-ones and a
number of related products (Scheme 1).[6] Rich chemistry of
transformations of 5-spirocyclopropane-isoxazolidines was
exploited in the synthesis of different azaheterocycles, e.g.
tetrahydropyridones, benzoazocinones, azetidinones.[7]
Scheme 1. Dipolar cycloaddition of nitrones and methylenecyclo-
propanes.
Regioselectivity of 1,3-dipolar cycloaddition reactions in
general is determined by electronic structure of reactants,
steric factors or combinations of both.[5,8] It was shown pre-
viously that electronic structure of methylenecyclopropanes
can be altered by ring substitution with acceptor groups
such as carboxylic functions or ester groups. This causes
changes of the reactivity of acceptor-substituted cyclo-
propenes and methylenecyclopropanes in the 1,3-dipolar
cycloaddition reactions with carbonyl ylides and nitro-
nes.[9,10] In particular, in reactions between acceptor ring-
substituted methylenecylopropanes and C,N-diarylnitrones
thermally stable regioisomeric 4-spirocyclopropane-isox-
azolidines are formed[9,10] instead of regioisomeric 5-spiro-
cyclopropane-isoxazolidines observed for unsubstituted or
alkyl-substituted methylenecyclopropanes.[4f,4k]
[a] Department of Chemistry, Saint Petersburg State University,
Universitetsky pr. 26, 198504 Saint Petersburg, Russian
Federation
In this paper we report a study of the reaction between
N,C,C-trisubstituted nitrones 1 and ring acceptor-substi-
tuted dimethyl methylenecyclopropane-1,2-dicarboxylate 2
or arylmethylidenecyclopropane-1,1-dicarboxylates 3a–c.
E-mail: s.lab.@pobox.spbu.ru
[b] Department of Chemistry, University of Southern California,
Los Angeles, CA 90089, U.S.A.
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200039.
2054
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 2054–2061

Cycloaddition of Nitrones to Methylenecyclopropanes
The increased steric hindrance of N,C,C-trisubstituted better yields of the products 4e–g up to 54%. Minor side
nitrones causes inversion of the regioselectivity of the 1,3- products 5e–g can also be isolated from crude reaction mix-
dipolar cycloaddition reaction with the formation of 5-spi- tures (yields 10–16%).
rocyclopropane-isoxazolidines. N-Aryl-substituted 5-spiro-
The structure of products 4 were established on the basis
cyclopropane-isoxazolidines cannot be isolated and un- of their spectroscopic data and X-ray data for compounds
dergo a previously unknown reaction cascade with the for- 4c and 4e (Figure 1).
mation of products containing tricyclic frameworks of
benzocarbacepham and pyrrolo[1,2-a]quinolines – struc-
tural moieties of antibiotics and biologically active com-
pounds.[11,12]
Results and Discussion
Methylenecyclopropanes 2 and 3 represent vicinal and
geminal ring-substituted materials that are easily accessible
in gram quantities by known procedures.[13] In initial ex-
periments, ester 2 was heated in toluene at 110 °C for 70–
90 hours in the presence of slight excess (1.1 equiv.) of tri-
Figure 1. ORTEP diagram for 4c (left) and 4e (right). Hydrogen
atoms omitted.
arylnitrones 1a–d. Azetoquinolines 4a–d were isolated by
chromatography on silica gel in modest yields 2–20%
(Scheme 2, Table 1). Use of different reaction conditions
(temperature, reaction time) did not change yields signifi-
cantly. The reaction yields are limited by the thermal sta-
bility of triarylnitrones. Feist’s ester 2 can be recovered from
reaction mixtures (up to 70%). The formation of products
4 is surprising since cycloaddition of C,N-disubstituted
nitrones to the same methylenecyclopropanes 2 and 3
give only isomeric 4-spirocyclopropane-isoxazolidines
(Scheme 2).[9,10]
Cycloaddition reactions between geminal acceptor sub-
stituted methylenecyclopropanes 3a–c and nitrones 1e–h
proceed under similar conditions (toluene, 110 °C, 2–5 days
until disappearance of starting materials by TLC) with the
formation of pyrrolo[1,2-a]quinolines 6a–d in good yields
of up to 81% (Scheme 3, Table 2). The structure of products
6 were established on the basis of their spectroscopic data
and X-ray data for compound 6a (Figure 2).
Scheme 3. Reaction between nitrones 1e–h and methylenecyclo-
propane 3a–c.
Table 2. Reaction scope of the reaction in Scheme 3.
Entry
R3
R4
Product
Isolated yield
[%]
Scheme 2. Reaction between nitrones 1a–g and methylenecyclo-
propane 2.
1
2
3
4
5
6
7
8
H
Cl
Me
MeO
H
H
H
H
H
Me
Me
Me
Me
Cl
Cl
Cl
6a
6b
6c
6d
6e
6f
6g
6h
6i
81
66
78
51
64
64
68
32
67
48
43
Table 1. Reaction scope of the reaction in Scheme 2.
Entry
R1
R2
Time
[h]
Product Isolated yield
[%]
Cl
Me
MeO
H
Cl
Me
1
2
3
4
5
6
7
1a, H
1b, Cl
1c, Me
Ph
Ph
Ph
91
80
70
77
70
66
74
4a
4b
4c
4d
4e
4f
14 (19[a]
3
)
9
10
11
20 (41)[a]
6j
6k
1d, MeO Ph
2
1e, H
1f, Cl
1g, Me
CO2Me
CO2Me
CO2Me
42
40
54
Previous literature data suggest that the presence of an
aryl group at the nitrogen atom of nitrones can play an
important role in directing reaction towards formation of
eight-membered azocines vs. six-membered tetrahydropyr-
4g
[a] Yield based on the recovered ester 2.
By varying the structure of trisubstituted nitrones we idines.[7] The N-methyl-substituted nitrone 7 has been cho-
found that more electrophilic ketonitrones 1e–g gave much sen to study the role of the substitution at the nitrogen atom
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A. P. Molchanov et al.
FULL PAPER
data allows to conclude that the formation of products 4
and 6 is driven by the presence of N-aryl substituents since
no similar products were observed in the reaction with N-
methyl nitrone 7.
In line with literature data, the initial formation of ther-
mally unstable 5-spirocyclopropane-isoxazolidines can be
proposed in cycloaddition reactions between methylenecy-
clopropanes 2, 3 and nitrones 1.[4f]
Regioselectivity in the 1,3-dipolar cycloaddition with
nitrones can be controlled by frontier molecular orbitals in-
teractions or by use of sterically demanded substrates.[8]
The X-ray structure of triphenylnitrone 1a shows significant
out-of-plane rotation of both C,C-phenyl rings that makes
trisubstituted nitrones sterically overcrowded at the carbon
atom of a nitrone dipole.[14] Thus, the inversion of the regio-
chemical results studied for the systems in this paper rela-
tive to the previously reported cycloaddition reactions of
the same methylenecyclopropanes 2 and 3 can be explained
by taking into account steric factors.
Figure 2. X-ray structure of 6a. Hydrogen atoms omitted for clar-
ity.
of nitrones on the reaction outcome. The 1,3-dipolar cyclo-
addition reaction between 7 and Feist’s ester 2 (benzene,
80 °C, 4–5 d) leads to the formation of the corresponding 5-
spirocyclopropane-isoxazolidine cycloadduct 8 (yield 79%)
together with small amounts of 9 (yield 3%) (Scheme 4).
The initial slow step in the studied reactions is a “nor-
mal” 1,3-dipolar cycloaddition of methylenecyclopropanes
with nitrones to form 5-spirocyclopropane-isoxazolidine cy-
cloadducts I (Scheme 5). These cycloadducts I are thermally
unstable and can undergo a thermally induced Brandi–Gu-
arna rearrangement.[6] The biradicals III can undergo ring
closure to form either six-membered piperidinones 5 or
eight-membered azocinones IV. For the reaction between 2
and 1g, the corresponding azocinone intermediate IVg can
1
Analysis of the crude reaction mixture by H NMR spec-
troscopy does not show the presence of signals of possible
4-spirocyclopropane-isoxazolidine cycloadducts or any
other side products. Product 9 can be also obtained by heat-
ing cycloadduct 8 in p-xylene (Scheme 4). The obtained
1
be detected by H NMR after heating the reaction mixture
for only 10 h.
The presence of acceptor ester groups in the eight mem-
bered rings of intermediates IV may facilitate transannular
nucleophilic attack of a lone pair of nitrogen atom to a
carbonyl group to form azetoquinolines 4.[15–17] Note, that
azocinone IVg undergo complete conversion to 4g by
addition of catalytic amounts of trifluoroacetic acid
(Scheme 6).
Scheme 4. Reaction between nitrone 7 and methylenecyclopropane
2.
Scheme 5. Proposed mechanism for the reaction between nitrones 1 and methylenecyclopropane 2.
2056
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Eur. J. Org. Chem. 2012, 2054–2061

Cycloaddition of Nitrones to Methylenecyclopropanes
Scheme 6. Isomerization of azocinone IVg into azetoquinoline 4g.
Scheme 7. Proposed mechanism for the reaction between nitrones 1 and methylenecyclopropanes 3.
phenone. Dimethyl methylenecyclopropane-1,2-dicarboxylate 2, di-
Azetoquinolines can also be proposed as intermediates
for the reaction of methylenecylopropane 3 with geminal
ester groups (Scheme 7). In this case the proposed azeto-
quinoline intermediates can undergo ring opening and cy-
clocondensation to give pyrroloquinolines 6.
Frameworks of both azetoquinolines 4 and pyrroloquin-
olines 6 are pharmaceutically relevant. Previous examples
of the formation of benzocarbacephem cores included dif-
ferent cyclizations of the substituted azetidinones or the use
of bicyclic heterocycles for further functionalization.[18] In
the current approach, tricyclic benzocarbacephem cores can
be obtained in one-pot procedure directly from acyclic
nitrones and methylenecyclopropanes. This process can be
characterized as rather efficient, taking into account com-
plexity of the described reaction cascade.
methyl 2-benzylidenecyclopropane-1,1-dicarboxylate 3 and nitro-
nes 1 were prepared following known procedures.[13] Reaction pro-
gress was monitoring using thin-layer chromatography. 1H and 13
C
NMR spectra were recorded in CDCl3 or [D6]DMSO (300 and
75 MHz accordingly). IR spectra were recorded in 1–5% CHCl3
solutions.
General Procedure: A mixture of methylenecyclopropanedicarbox-
ylate 2 (2 mmol) and the corresponding nitrone 1a–g (1.1 equiv.)
was heated at reflux in dry toluene for 66–91 h. The solvent was
removed under reduced pressure, and products were isolated by
chromatography of the residue on silica gel eluting with petroleum
ether/ethyl acetate mixtures followed by crystallization from eth-
anol.
Dimethyl 1,1-Diphenyl-2,4-dihydro-1H-azeto[1,2-a]quinoline-3,4-di-
carboxylate (4a): Obtained from 510 mg (3 mmol) of the ester 2
and 982 mg (3.6 mmol) of the nitrone 1a. Yield of 4a 180 mg
(14%). White solid, m.p. 187–189 °C. Rf = 0.53 (EtOAc/hexane =
Conclusions
1:2). IR: ν = 3060, 2960, 1730 (s), 1680 (s), 1600, 1490, 1440, 1380,
˜
1
1310, 1120, 1080 cm–1. H NMR ([D6]DMSO): δ = 3.57 (s, 3 H),
Reactions between acceptor ring-substituted methylene-
cyclopropanes 2 and 3 and trisubstituted N,C,C-triaryl and
N-aryl-C,C-bis(methoxycarbonyl)nitrones 1 proceed with
the formation of 2,4-dihydro-1H-azeto[1,2-a]quinolines and
pyrrolo[1,2-a]quinolines in moderate to good yields. The in-
creased steric demand of trisubstituted nitrones changes re-
giochemical outcome, so that 5-spirocyclopropane-isoxazol-
idines are formed or can be postulated as intermediate cy-
cloadducts in the studied reactions. A proposed mechanism
for the reaction includes Brandi–Guarna rearrangement of
the initially formed cycloadducts followed by transannular
cyclization of the intermediate azocinones.
3.64 (s, 3 H), 3.80 (d, J = 16.7 Hz, 1 H), 3.96 (d, J = 16.7 Hz, 1
H), 4.88 (s, 1 H), 6.10–6.13 (m, 1 H), 6.94–7.04 (m, 4 H), 7.30–7.53
(m, 9 H) ppm. 13C NMR (CDCl3): δ = 44.0 (CH), 48.8 (CH2), 51.4
(CH3), 52.8 (CH3), 91.0 (C), 113.6 (CH), 120.6 (C), 123.6 (CH),
127.1 (CH), 128.0 (CH), 128.1 (CH), 128.7 (CH), 128.9 (CH), 129.0
(CH), 130.4 (CH), 136.2 (C), 140.0 (C), 141.9 (C), 156.2 (C), 167.5
(CO), 173.5 (CO) ppm. C27H23NO4 (425.48): calcd. C 76.22, H
5.45, N 3.29; found C 76.09, H 5.48, N 3.10.
Dimethyl 6-Chloro-1,1-diphenyl-2,4-dihydro-1H-azeto[1,2-a]quinol-
ine-3,4-dicarboxylate (4b): Obtained from 552 mg (3.2 mmol) of the
ester 2 and 1.0 g (3.3 mmol) of the nitrone 1b. Yield of 4b 39 mg
(3%). Yellowish oil. R = 0.58 (EtOAc/hexane = 1:2). IR: ν = 3055,
˜
f
2970, 1745 (s), 1690 (s), 1610, 1500, 1455, 1380, 1300, 1110 cm–1.
1H NMR (CDCl3): δ = 3.72 (s, 3 H), 3.76 (s, 3 H), 3.88 (d, J =
16.0 Hz, 1 H), 3.98 (d, J = 16.0 Hz, 1 H), 4.95 (s, 1 H), 6.09 (d, J
= 8.4 Hz, 1 H), 6.84–6.88 (m, 1 H), 7.11–7.13 (m, 3 H), 7.41–7.47
(m, 8 H) ppm. 13C NMR (CDCl3): δ = 43.9 (CH), 48.7 (CH2), 51.6
Experimental Section
General: All reactions were performed in anhydrous solvents under
an argon atmosphere. Toluene was distilled from Na/benzo-
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A. P. Molchanov et al.
FULL PAPER
(CH3), 53.0 (CH3), 91.0 (C), 114.5 (CH), 122.2 (C), 126.9 (CH), 1100, 1080 cm–1. 1H NMR (CDCl3): δ = 3.06 (d, J = 16.7 Hz, 1
127.9 (CH), 128.2 (CH), 128.3 (CH), 128.5 (C), 128.9 (CH), 129.0 H), 3.47 (s, 3 H), 3.52 (s, 3 H), 3.60 (d, J = 16.7 Hz, 1 H), 3.71 (s,
(CH), 129.1 (CH), 130.3 (CH), 134.9 (C), 139.4 (C), 141.6 (C), 3 H), 3.77 (s, 3 H), 5.23 (s, 1 H), 7.12 (m, 1 H), 7.24–7.34 (m, 4
156.2 (C), 167.3 (CO), 173.0 (CO) ppm. HRMS (ESI): Found
H), 12.17 (s, 1 H) ppm. 13C NMR (CDCl3): δ = 38.2 (CH2), 52.3
941.2357 [2M + Na]+. Calcd. for C27H22ClNO4: 941.2372 [2M + (CH3), 52.5 (CH3), 53.3 (CH3), 53.4 (CH3), 60.9 (CH), 71.9 (C),
Na]+.
97.3 (C), 125.8 (CH), 126.9 (CH), 129.1 (CH), 146.2 (C), 168.5 (C),
170.0 (C), 170.3 (C), 170.5 (C), 172.3 (C) ppm. C19H21NO9
(407.37): calcd. C 56.02, H 5.20, N 3.44; found C 56.09, H 5.23, N
3.53.
Dimethyl 6-Methyl-1,1-diphenyl-2,4-dihydro-1H-azeto[1,2-a]quinol-
ine-3,4-dicarboxylate (4c): Obtained from 170 mg (1 mmol) of the
ester 2 and 373 mg (1.3 mmol) of the nitrone 1c. Yield of 4c 86 mg
(20%). White solid, m.p. 183–185 °C. Rf = 0.54 (EtOAc/hexane =
Tetramethyl 6-Chloro-2H-azeto[1,2-a]quinoline-1,1,3,4(4H)-tetra-
carboxylate (4f) and Tetramethyl 1-(4-Chlorophenyl)-4-hydroxy-1,2-
dihydro-1H-pyridine-2,2,5,6-tetracarboxylate (5f): Obtained from
340 mg (2 mmol) of the ester 2 and 706 mg (2.6 mmol) of the
nitrone 1f. Yield of 4f 340 mg (40%). White solid, m.p. 154 °C. Rf
1:2). IR: ν = 3050, 2960, 1740 (s), 1670 (s), 1610, 1530, 1450, 1370,
˜
1245, 1095 cm–1. 1H NMR (CDCl3): δ = 2.24 (s, 3 H), 3.70 (s, 3
H), 3.75 (s, 3 H), 3.87 (d, J = 16.0 Hz, 1 H), 3.96 (d, J = 16.0 Hz,
1 H), 4.95 (s, 1 H), 6.07 (d, J = 8.0 Hz, 1 H), 6.70–6.72 (m, 1 H),
7.13–7.47 (m, 11 H) ppm. 13C NMR (CDCl3): δ = 21.2 (CH3), 44.1
(CH), 48.9 (CH2), 51.3 (CH3), 52.8 (CH3), 90.5 (C), 113.4 (CH),
120.6 (C), 127.1 (CH), 127.9 (CH), 128.1 (CH), 128.6 (CH), 128.7
(CH), 128.9 (CH), 129.0 (CH), 130.9 (CH), 133.2 (C), 133.7 (C),
139.9 (C), 142.0 (C), 156.2 (C), 167.6 (CO), 173.7 (CO) ppm.
C28H25NO4 (439.51): calcd. C 76.52, H 5.73, N 3.19; found C
76.58, H 5.73, N 3.00.
= 0.28 (EtOAc/hexane = 1:2). IR: ν = 3060, 2970, 1750 (s), 1710
˜
1
(s), 1610, 1500, 1452, 1380, 1300, 1160, 1140, 1110, 1090 cm–1. H
NMR (CDCl3): δ = 3.65 (d, J = 16.0 Hz, 1 H), 3.71 (s, 3 H), 3.74
(s, 3 H), 3.77 (s, 3 H), 3.92 (d, J = 16.0 Hz, 1 H), 3.93 (s, 3 H),
4.85 (s, 1 H), 6.87 (d, J = 9.1 Hz, 1 H), 7.16 (dd, J = 9.1, 2.2 Hz,
1 H), 7.41 (d, J = 2.2 Hz, 1 H) ppm. 13C NMR (CDCl3): δ = 39.0
(CH2), 43.6 (CH), 51.7 (CH3), 53.1 (CH3), 53.9 (CH3), 54.0 (CH3),
73.2 (C), 93.6 (C), 114.6 (CH), 121.7 (C), 128.7 (CH), 129.5 (C),
130.4 (CH), 134.6 (C), 153.8 (C), 166.5 (CO), 166.9 (CO), 167.5
(CO), 172.5 (CO) ppm. C19H18ClNO8 (423.81): calcd. C 53.85, H
4.28, N 3.31; found C 53.99, H 4.07, N 3.39.
Some crystallographic data for compound 4c: Colorless crystals,
C28H25NO4, M = 439.49, monoclinic, space group P21/c, a =
11.4824(11), b = 8.6216(9), c = 23.963(3) Å, β = 103.020(2), V =
2311.3(4) Å3, Z = 4, T = 293 K. Selected bond lengths and angles:
C1–N9 1.4969(15), C1–C2 1.5503(9), C2–C2a 1.5308(9),C2a–C3
1.3346(16), C2a–N9 1.3665(16), N9–C1–C2 86.50, C2a–C2–C1 86.37,
N9–C2a–C2 92.06, C2a–N9–C1 94.74.
Product 5f: Yield 130 mg (15%). White solid, m.p. 116–117 °C. Rf
= 0.33 (EtOAc/hexane = 1:2). IR: ν = 3480 (br.), 3060, 2970, 1750
˜
(s), 1682 (s), 1640, 1615, 1510, 1460, 1372, 1320, 1285, 1195, 1100,
1070 cm–1. 1H NMR (CDCl3): δ = 3.04 (d, J = 16.7 Hz, 1 H), 3.50
(s, 3 H), 3.52 (s, 3 H), 3.56 (d, J = 16.7 Hz, 1 H), 3.70 (s, 3 H),
3.76 (s, 3 H), 5.15 (s, 1 H), 7.22 (d, J = 9.0 Hz, 2 H), 7.29 (d, J =
9.0 Hz, 2 H), 12.15 (s, 1 H) ppm. 13C NMR (CDCl3): δ = 38.1
(CH2), 52.3 (CH3), 52.6 (CH3), 53.4 (CH3), 53.5 (CH3), 60.9 (CH),
71.9 (C), 97.0 (C), 128.5 (CH), 129.2 (CH), 131.3 (C), 144.7 (C),
168.3 (C), 169.8 (C), 170.1 (C), 170.3 (C), 172.0 (C) ppm.
C19H20ClNO9 (441.82): calcd. C 51.65, H 4.56, N 3.17; found C
52.07, H 4.45, N 3.29.
Dimethyl 6-Methoxy-1,1-diphenyl-2,4-dihydro-1H-azeto[1,2-a]quin-
oline-3,4-dicarboxylate (4d): Obtained from 255 mg (1.5 mmol) the
ester 2 and 591 mg (1.9 mmol) of the nitrone 1d. Yield of 4d 14 mg
(2%). Yellowish oil. R = 0.38 (EtOAc/hexane = 1:2). IR: ν = 3055,
˜
f
2942, 1740 (s), 1672 (s), 1610, 1510, 1450, 1380, 1270, 1093 cm–1.
1H NMR (CDCl3): δ = 3.71 (s, 3 H), 3.73 (s, 3 H), 3.75 (s, 3 H),
3.87 (d, J = 16.0 Hz, 1 H), 3.96 (d, J = 16.0 Hz, 1 H), 4.88 (s, 1
H), 6.12 (d, J = 8.7 Hz, 1 H), 6.47 (dd, J = 16.0, 2.9 Hz, 1 H), 7.00
(d, J = 2.9 Hz, 1 H), 7.12–7.45 (m, 10 H) ppm. 13C NMR (CDCl3):
δ = 44.4 (CH), 48.9 (CH2), 51.4 (CH3), 52.9 (CH3), 55.9 (CH3),
89.6 (C), 113.6 (CH), 114.5 (CH), 115.8 (CH), 122.0 (C), 127.1
(CH), 127.9 (CH), 128.1 (CH), 128.9 (CH), 129.0 (CH), 129.9 (C),
139.9 (C), 142.0 (C), 156.2 (C), 173.5 (CO) ppm. HRMS (ESI):
found 933.3325 [2M + Na]+; Calcd. for C28H25NO5: 933.3363 [2M
+ Na]+.
Tetramethyl 6-Methyl-2H-azeto[1,2-a]quinoline-1,1,3,4(4H)-tetra-
carboxylate (4g) and Tetramethyl 4-Hydroxy-1-(4-methylphenyl)-
1,2-dihydro-1H-pyridine-2,2,5,6-tetracarboxylate (5g): Obtained
from 340 mg (2 mmol) of the ester 2 and 653 mg (2.6 mmol) of the
nitrone 1g. Yield of 4g 430 mg (54%). White solid, m.p. 144–
145 °C. R = 0.26 (EtOAc/hexane = 1:2). IR: ν = 3050, 2970, 1750
˜
f
(s), 1700 (s), 1628, 1520, 1450, 1380, 1310, 1270, 1165, 1140, 1100
Tetramethyl 2H-Azeto[1,2-a]quinoline-1,1,3,4(4H)-tetracarboxylate
(4e) and Tetramethyl 4-hydroxy-1-phenyl-1,2-dihydro-1H-pyridine-
2,2,5,6-tetracarboxylate (5e): Obtained from 340 mg (2 mmol) of
the ester 2 and 616 mg (2.6 mmol) of the nitrone 1e. Yield of 4e
327 mg (42%). White solid, m.p. 127–128 °C. Rf = 0.25 (EtOAc/
1
cm–1. H NMR (C6D6): δ = 2.08 (s, 3 H), 3.15 (s, 3 H), 3.34 (s, 3
H), 3.39 (s, 3 H), 3.56 (s, 3 H), 3.68 (d, J = 16.0 Hz, 1 H), 3.81 (d,
J = 16.0 Hz, 1 H), 5.30 (s, 1 H), 6.89 (dd, J = 8.0, 1.5 Hz, 1 H),
7.24 (d, J = 8.0 Hz, 1 H), 7.37 (s, 1 H) ppm. 13C NMR (CDCl3):
δ = 21.3 (CH3), 39.0 (CH2), 43.7 (CH), 51.5 (CH3), 52.9 (CH3),
53.8 (CH3), 53.9 (CH3), 73.0 (C), 93.2 (C), 113.2 (CH), 119.9 (C),
129.2 (CH), 130.8 (CH), 133.4 (C), 134.2 (C), 154.2 (C), 166.9
(CO), 167.2 (CO), 167.8 (CO), 173.2 (CO) ppm. C20H21NO8
(403.39): calcd. C 59.55, H 5.25, N 3.47; found C 59.88, H 5.23, N
3.73.
hexane = 1:2). IR: ν = 3060, 2970, 1752 (s), 1702 (s), 1620, 1505,
˜
1451, 1385, 1330, 1312, 1280, 1160, 1140, 1090 cm–1. 1H NMR
([D6]DMSO): δ = 3.57 (s, 3 H), 3.64 (s, 3 H), 3.68 (s, 3 H), 3.73 (d,
J = 16.0 Hz, 1 H), 3.86 (s, 3 H), 3.93 (d, J = 16.0 Hz, 1 H), 4.82
(s, 1 H), 6.80 (d, J = 8.0 Hz, 1 H), 7.08 (m, 1 H), 7.25 (m, 1 H),
7.39 (d, J = 7.5 Hz, 1 H) ppm. 13C NMR (CDCl3): δ = 39.0 (CH2),
43.7 (CH), 51.6 (CH3), 52.9 (CH3), 53.8 (CH3), 53.9 (CH3), 73.1
(C), 93.5 (C), 113.3 (CH), 120.0 (C), 124.6 (CH), 128.6 (CH), 130.5
(CH), 135.8 (C), 154.2 (C), 166.8 (CO), 167.1 (CO), 167.7 (CO),
173.0 (CO) ppm. C19H19NO8 (389.36): calcd. C 58.61, H 4.92, N
3.60; found C 58.65, H 4.92, N 3.60.
Product 5g: Yield 130 mg (16%). White solid, m.p. 97–99 °C. Rf =
0.32 (EtOAc/hexane = 1:2). IR: ν = 3480 (br.), 3055, 2970, 1750
˜
(s), 1683 (s), 1635, 1530, 1460, 1320, 1280, 1190, 1100, 1072 cm–1.
1H NMR (CDCl3): δ = 2.29 (s, 3 H), 3.03 (d, J = 17.0 Hz, 1 H),
3.45 (s, 3 H), 3.50 (s, 3 H), 3.57 (d, J = 17.0 Hz, 1 H), 3.70 (s, 3
H), 3.75 (s, 3 H), 5.19 (s, 1 H), 7.06 (d, J = 8.0 Hz, 2 H), 7.26 (d,
J = 8.0 Hz, 2 H), 12.18 (s, 1 H) ppm. 13C NMR (CDCl3): δ = 21.4
(CH3), 38.1 (CH2), 52.3 (CH3), 52.5 (CH3), 53.3 (CH3), 54.0 (CH3),
Product 5e: Yield 81 mg (10%). White solid, m.p. 134–135 °C. Rf
= 0.30 (EtOAc/hexane = 1:2). IR: ν = 3475 (broad), 3060, 2970,
˜
1750 (s), 1682 (s), 1640, 1610, 1510, 1460, 1375, 1320, 1285, 1195,
2058
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© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 2054–2061

Cycloaddition of Nitrones to Methylenecyclopropanes
61.2 (CH), 72.0 (C), 97.2 (C), 127.9 (CH), 129.7 (CH), 136.0 (C), and 240 mg (1.0 mmol) of the nitrone 1e, time 100 h, yield of 6e
143.3 (C), 168.4 (C), 170.1 (C), 170.2 (C), 170.5 (C), 172.3 (C) ppm. 288 mg (64%). Yellow solid, m.p. 166 °C. Rf = 0.28 (EtOAc/hexane
C20H23NO9 (421.40): calcd. C 57.00, H 5.50, N 3.32; found C
57.28, H 5.46, N 3.66.
= 1:2). IR: ν = 3034, 2954, 1745 (s), 1723 (s), 1493, 1434, 1363,
˜
1270, 1144, 1055 cm–1. 1H NMR (CDCl3): δ = 2.45 (s,3 H), 3.79
(s, 6 H), 3.83 (s, 3 H), 5.98 (s, 1 H), 7.20–7.50 (m, 6 H), 7.64 (d, J
= 6.5 Hz, 1 H), 8.93 (d, J = 8.7 Hz, 1 H) ppm. 13C NMR (CDCl3):
δ = 21.9 (CH3), 52.8 (OCH3), 54.2 (2OCH3), 58.9 (C), 111.8 (CH),
117.5 (CH), 117.9 (C), 124.5 (C), 124.9 (CH), 126.5 (C), 129.8
(2CH), 130.4 (CH), 130.5 (CH), 133.9 (C), 137.1 (C), 141.1 (C),
150.1 (C), 163.0 (CO), 163.7 (CO), 169.1 (2CO) ppm. C25H21NO7
(447.44): calcd. C 67.11, H 4.73, N 3.13; found C 67.47, H 4.38, N
3.19.
Trimethyl 1-Oxo-3-phenyl-1H-pyrrolo[1,2-a]quinoline-2,5,5-tricarb-
oxylate (6a): Obtained from 246 mg (1.0 mmol) of the ester 3 and
261 mg (1.1 mmol) of the nitrone 1e, time 130 h, yield of 6a 350 mg
(81%). Yellow solid, m.p. 158–159 °C. Rf = 0.31 (EtOAc/hexane =
1:2). IR: ν = 3058, 2970, 1750 (s), 1725 (s), 1620, 1510, 1480, 1450,
˜
1
1380, 1285, 1190, 1165, 1050 cm–1. H NMR (CDCl3): δ = 3.79 (s,
6 H), 3.82 (s, 3 H), 5.96 (s, 1 H), 7.24 (m, 1 H), 7.44–7.54 (6 H),
7.65 (d, J = 8.6 Hz, 1 H), 8.94 (d, J = 8.0 Hz, 1 H) ppm. 13C NMR
(CDCl3): δ = 52.8 (CH3), 54.2 (2CH3), 58.9 (C), 112.0 (CH), 117.5
(CH), 117.9 (C), 125.0 (CH), 128.9 (CH), 129.4 (C), 129.8 (CH),
130.4 (CH), 130.6 (CH), 130.7 (CH), 133.8 (C), 137.0 (C), 149.9
(C), 162.8 (CO), 163.6 (CO), 169.1 (CO) ppm. C24H19NO7 (433.42):
calcd. C 66.51, H 4.42, N 3.23; found C 66.53, H 4.30, N 3.32.
Trimethyl
7-Chloro-1-oxo-3-(4-tolyl)-1H-pyrrolo[1,2-a]quinoline-
2,5,5-tricarboxylate (6f): Obtained from 260 mg (1.0 mmol) of the
ester 3b and 300 mg (1.1 mmol) of the nitrone 1f, time 88 h, yield of
6f 310 mg (64%). Yellow solid, m.p. 205–206 °C. Rf = 0.27 (EtOAc/
hexane = 1:2). IR: ν = 3030, 2950, 1742 (s), 1720 (s), 1490, 1438,
˜
1
1365, 1274, 1140, 1050 cm–1. H NMR (CDCl3): δ = 2.46 (s,3 H),
Trimethyl
7-Chloro-1-oxo-3-phenyl-1H-pyrrolo[1,2-a]quinoline-
3.81 (s, 6 H), 3.83 (s, 3 H), 5.93 (s, 1 H), 7.33 (d, J = 8.0 Hz, 2 H),
7.39 (d, J = 8.0 Hz, 2 H), 7.39 (d, J = 8.0 Hz, 2 H), 7.43 (dd, J =
9.4, 2.1 Hz, 1 H), 7.63 (d, J = 2.1 Hz, 1 H), 8.90 (d, J = 9.4 Hz, 1
H) ppm. 13C NMR (CDCl3): δ = 21.9 (CH3), 52.8 (OCH3), 52.4 (2
OCH3), 58.8 (C), 111.4 (CH), 118.8 (CH), 119.5 (C), 124.5 (C),
126.3 (C), 129.7 (CH), 129.8 (CH), 130.1 (C), 130.4 (CH), 130.5
(CH), 132.5 (C), 136.8 (C), 141.3 (C), 150.2 (C), 162.8 (CO), 163.6
(CO), 168.7 (2 CO) ppm. C25H20ClNO7 (481.89): calcd. C 62.31,
H 4.18, N 2.91; found C 62.16, H 4.30, N 2.84.
2,5,5-tricarboxylate (6b): Obtained from 246 mg (1.0 mmol) of the
ester 3 and 299 mg (1.1 mmol) of the nitrone 1f, time 117 h, yield of
6b 300 mg (64%). Yellow solid, m.p. 177–178 °C. Rf = 0.37 (EtOAc/
hexane = 1:2). IR: ν = 3042, 2990, 1750 (s), 1720 (s), 1630, 1505,
˜
1
1450, 1380, 1280, 1185, 1165, 1060 cm–1. H NMR (CDCl3): δ =
3.81 (s, 6 H), 3.82 (s, 3 H), 5.94 (s, 1 H), 7.43 (dd, J = 7.3, 7.5 Hz,
1 H), 7.47–7.50 (2 H), 7.52–7.56 (3 H), 7.64 (d, J = 2.9 Hz, 1 H),
8.90 (d, J = 8.7 Hz, 1 H) ppm. 13C NMR (CDCl3): δ = 52.9 (CH3),
54.5 (2CH3), 58.8 (C), 111.6 (CH), 118.8 (CH), 119.5 (C), 125.0
(C), 129.0 (CH), 129.2 (C), 129.8 (CH), 130.2 (C), 130.5 (CH),
130.6 (CH), 130.8 (CH), 132.4 (C), 136.8 (C), 150.0 (C), 162.6
(CO), 163.5 (CO), 168.6 (CO) ppm. C24H18ClNO7 (467.86): calcd.
C 61.61, H 3.88, N 2.99; found C 61.63, H 3.66, N 3.08.
Trimethyl 1-Oxo-3,7-bis(4-tolyl)-1H-pyrrolo[1,2-a]quinoline-2,5,5-
tricarboxylate (6g): Obtained from 260 mg (1.0 mmol) of the ester
3b and 276 mg (1.1 mmol) of the nitrone 1g, time 100 h, yield of
6g 315 mg (68%). Yellow solid, m.p. 193–194 °C. Rf = 0.20 (EtOAc/
hexane = 1:3). IR: ν = 3030, 2950, 1745 (s), 1727 (s), 1490, 1430,
˜
Trimethyl
7-Methyl-1-oxo-3-phenyl-1H-pyrrolo[1,2-a]quinoline-
1
1360, 1275, 1140, 1060 cm–1. H NMR (CDCl3): δ = 2.37 (s, 3 H),
2,5,5-tricarboxylate (6c): Obtained from 246 mg (1.0 mmol) of the
ester 3 and 276 mg (1.1 mmol) of the nitrone 1g, time 130 h, yield
of 6c 350 mg (78%). Yellow solid, m.p. 175–177 °C. Rf = 0.31
2.46 (s, 3 H), 3.79 (s, 6 H), 3.83 (s, 3 H), 5.95 (s, 1 H), 7.25 (d, J =
1.5 Hz, 1 H), 7.33 (d, J = 8.0 Hz, 2 H), 7.39 (d, J = 8.0 Hz, 2 H),
7.40 (m, 1 H), 8.80 (d, J = 8.0 Hz, 1 H) ppm. 13C NMR (CDCl3):
δ = 21.5 (CH3), 21.9 (CH3), 52.7 (OCH3), 54.2 (2 OCH3), 58.9 (C),
111.7 (CH), 117.7 (C), 124.5 (C), 126.5 (C), 129.7 (CH), 129.8
(CH), 130.6 (C), 131.2 (CH), 131.5 (C), 134.6 (C), 137.1 (C), 141.0
(C), 149.9 (C), 163.6 (CO), 169.2 (2*CO) ppm. C26H23NO7
(461.47): calcd. C 67.67, H 5.02, N 3.04; found C 67.48, H 5.03, N
3.17.
(EtOAc/hexane = 1:2). IR: ν = 3060, 2970, 1747 (s), 1720 (s), 1630,
˜
1520, 1450, 1380, 1270, 1200, 1165, 1060 cm–1. 1H NMR (CDCl3):
δ = 2.38 (s, 3 H), 3.81 (s, 6 H), 3.82 (s, 3 H), 5.94 (s, 1 H), 7.27
(dd, J = 8.7, 1.5 Hz, 1 H), 7.42 (d, J = 1.5 Hz, 1 H), 7.47–7.55 (5
H), 8.81 (d, J = 8.7 Hz, 1 H) ppm. 13C NMR (CDCl3): δ = 21.5
(CH3), 52.8 (CH3), 54.2 (2CH3), 58.9 (C), 111.9 (CH), 117.4 (CH),
117.7 (C), 125.0 (C), 128.9 (CH), 129.5 (C), 129.8 (CH), 130.6
(CH), 131.2 (CH), 131.5 (C), 134.6 (C), 137.1 (C), 149.8 (C), 162.9
(CO), 163.4 (CO), 169.2 (CO) ppm. C25H21NO7 (447.44): calcd. C
67.11, H 4.73, N 3.13; found C 67.39, H 4.64, N 3.37.
Trimethyl 7-Methoxy-1-oxo-3-(4-tolyl)-1H-pyrrolo[1,2-a]quinoline-
2,5,5-tricarboxylate (6h): Obtained from 260 mg (1.0 mmol) of the
ester 3b and 277 mg (1.0 mmol) of the nitrone 1h, time 90 h, yield
of 6h 155 mg (32%). Yellow solid, m.p. 215 °C (dec.). Rf = 0.22
Trimethyl
7-Methoxy-1-oxo-3-phenyl-1H-pyrrolo[1,2-a]quinoline-
(EtOAc/hexane = 1:2). IR: ν = 3007, 2958, 1748 (s), 1723 (s), 1503,
˜
2,5,5-tricarboxylate (6d): Obtained from 246 mg (1.0 mmol) of the
ester 3 and 276 mg (1.1 mmol) of the nitrone 1h, time 50 h, yield of
6d 235 mg (51%). Yellow solid, m.p. 153–154 °C. Rf = 0.23 (EtOAc/
1436, 1366, 1280, 1144, 1086, 1052, 1029 cm–1. 1H NMR (CDCl3):
δ = 2.46 (s, 3 H), 3.79 (s, 3 H), 3.83 (s, 3 H), 3.84 (s, 3 H), 5.93 (s,
1 H), 7.02 (dd, J = 9.2, 2.6 Hz, 1 H), 7.18 (d, J = 2.6 Hz, 1 H),
7.32 (d, J = 8.0 Hz, 2 H), 7.39 (d, J = 8.0 Hz, 2 H), 8.87 (d, J =
9.2 Hz, 1 H) ppm. 13C NMR (CDCl3): δ = 21.9 (CH3), 52.7
(OCH3), 54.2 (2 OCH3), 55.5 (OCH3), 59.1 (C), 111.3 (CH), 115.7
(CH), 118.7 (CH), 124.5 (C), 126.5 (C), 127.7 (C), 129.6 (CH),
129.8 (CH), 137.1 (C), 140.9 (C), 156.4 (CO), 163.0 (CO), 163.4
(CO), 169.0 (2 CO) ppm. C26H23NO8 (477.47): calcd. C 65.40, H
4.86, N 2.93; found C 65.68, H 5.04, N 3.16.
hexane = 1:2). IR: ν = 3055, 2970, 1745 (s), 1715 (s), 1690, 1630,
˜
1517, 1448, 1380, 1290, 1270, 1200, 1160, 1100, 1070 cm–1. 1H
NMR (CDCl3): δ = 3.77 (s, 6 H), 3.80 (s, 3 H), 3.83(s, 3 H), 5.90
(s, 1 H), 7.00 (dd, 1 H, J = 8.7, 2.9 Hz), 7.16 (d, 1 H, J = 2.9 Hz),
7.46–7.53 (5 H), 8.86 (d, 1 H, J = 8.7 Hz) ppm. 13C NMR (CDCl3):
δ = 52.8 (CH3), 54.2 (2CH3), 55.9 (CH3), 59.1 (C), 111.5 (CH),
115.7 (CH), 115.8 (CH), 118.7 (CH), 119.2 (C), 124.9 (C), 127.6
(C), 128.9 (CH), 129.5 (C), 129.8 (CH), 130.6 (CH), 137.1 (C),
149.6 (C), 156.4 (C), 162.9 (CO), 163.3 (CO), 169.0 (CO) ppm.
C25H21NO7 (447.44): calcd. C 64.79, H 4.57, N 3.02; found C
64.77, H 4.35, N 3.18.
Trimethyl
3-(4-Chlorophenyl)-1-oxo-1H-pyrrolo[1,2-a]quinoline-
2,5,5-tricarboxylate (6i): Obtained from 260 mg (1.0 mmol) of the
ester 3c and 240 mg (1.0 mmol) of the nitrone 1e, time 120 h, yield
of 6i 315 mg (67%). Yellow solid, m.p. 197 °C. Rf = 0.22 (EtOAc/
Trimethyl
1-Oxo-3-(4-tolyl)-1H-pyrrolo[1,2-a]quinoline-2,5,5-tri-
carboxylate (6e): Obtained from 260 mg (1.0 mmol) of the ester 3b
hexane = 1:2). IR: ν = 2954, 1749 (s), 1740 (s), 1504, 1437, 1369,
˜
Eur. J. Org. Chem. 2012, 2054–2061
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2059

A. P. Molchanov et al.
FULL PAPER
1231, 1144, 1037 cm–1. H NMR (CDCl3): δ = 3.80 (s, 6 H), 3.84
1
169.9 (C), 170.4 (C), 172.2 (C) ppm. C14H19NO9 (345.31): calcd. C
(s, 3 H), 5.92 (s, 1 H), 7.20–7.30 (m, 1 H), 7.40–7.50 (m, 5 H), 7.65 48.70, H 5.55, N 4.06; found C 48.77, H 5.56, N 4.63.
(dd, J = 8.0, 2.4 Hz, 1 H), 8.92 (d, J = 8.0 Hz, 1 H) ppm. 13C
NMR (CDCl3): δ = 21.5 (CH3), 52.9 (OCH3), 54.2 (2 OCH3), 58.9
CCDC-778712 (for 4c), -778713 (for 4e) and -778714 (for 6a) con-
tain the supplementary crystallographic data for this paper. These
(C), 112.0 (CH), 117.4 (CH), 117.6 (C), 125.1 (C), 127.8 (C), 129.3
data can be obtained free of charge from The Cambridge Crystallo-
(CH), 130.7 (CH), 131.2 (2 CH), 131.3 (C), 134.8 (C), 136.9 (C),
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
137.0 (C), 148.8 (C), 162.7 (2 CO), 163.1 (CO), 169.0 (2 CO) ppm.
Supporting Information (see footnote on the first page of this arti-
cle): 1H and 13C spectra of all new compounds, X-ray crystal struc-
tures for 4c, 4e and 6a.
C25H21NO7 (447.44): calcd. C 67.11, H 4.73, N 3.13; found C
67.47, H 4.38, N 3.19.
Trimethyl 3,7-Dichloro-1-oxo-1H-pyrrolo[1,2-a]quinoline-2,5,5-tri-
carboxylate (6j): Obtained from 260 mg (1.0 mmol) of the ester 3c
and 300 mg (1.1 mmol) of the nitrone 1f, time 90 h, yield of 6j
208 mg (43%). Yellow solid, m.p. 222 °C. Rf = 0.24 (EtOAc/hexane
Acknowledgments
= 1:3). IR: ν = 3031, 2952, 1759 (s), 1745 (s), 1491, 1437, 1369,
˜
T. Q. T. is grateful to the Ministry of Education and Training of
Vietnam for partial support.
1
1245, 1144, 1037 cm–1. H NMR (CDCl3): δ = 3.81 (s, 6 H), 3.83
(s, 3 H), 5.90 (s, 1 H), 7.44 (m, 1 H), 7.44 (d, J = 7.0 Hz, 2 H),
7.52 (d, J = 7.0 Hz, 2 H), 7.64 (d, J = 2.2 Hz, 1 H), 8.89 (d, J =
9.4 Hz, 1 H) ppm. 13C NMR (CDCl3): δ = 52.9 (OCH3), 54.5 (2
OCH3), 58.7 (C), 111.6 (CH), 118.8 (CH), 119.4 (C), 125.1 (C),
127.5 (C), 129.4 (CH), 130.3 (C), 130.5 (CH), 130.6 (CH), 131.2
(CH), 132.3 (C), 136.6 (C), 137.2 (C), 149.1 (C), 162.4 (CO), 163.2
(CO), 168.5 (2*CO) ppm. C24H17Cl2NO7 (502.31): calcd. C 57.39,
H 3.41, N 2.79; found C 57.58, H 3.30, N 2.87.
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Trimethyl
3-(4-Chlorophenyl)-7-(4-tolyl)-1-oxo-1H-pyrrolo[1,2-
a]quinoline-2,5,5-tricarboxylate (6k): Obtained from 260 mg
(1.0 mmol) of the ester 3c and 276 mg (1.1 mmol) of the nitrone
1g, time 90 h, yield of 6f 207 mg (43%). Yellow solid, m.p. 168 °C.
R = 0.30 (EtOAc/hexane = 1:2). IR: ν = 2954, 1749 (s), 1740 (s),
˜
f
1504, 1437, 1369, 1231, 1144, 1039 cm–1. H NMR (CDCl3): δ =
1
2.38 (s,3 H), 3.80 (s, 6 H), 3.84 (s, 3 H), 5.89 (s, 1 H), 7.27 (d, J =
8.0 Hz, 1 H), 7.40–7.55 (m, 5 H), 8.77 (d, J = 8.7 Hz, 1 H) ppm.
13C NMR (CDCl3): δ = 21.5 (CH3), 52.9 (OCH3), 54.2 (2*OCH3),
58.9 (C), 112.0 (CH), 117.4 (CH), 117.6 (C), 125.1 (C), 127.8 (C),
129.3 (CH), 130.7 (CH), 131.2 (2*CH), 131.3 (C), 134.8 (C), 136.9
(C), 137.0 (C), 148.8 (C), 162.7 (CO), 163.1 (CO), 169. (2*CO)
ppm. C25H20ClNO7 (481.89): calcd. C 62.31, H 4.18, N 2.91; found
C 62.16, H 4.30, N 2.84.
Tetramethyl
5-Methyl-4-oxa-5-azaspiro[2.4]heptan-1,2,6,6-tetra-
carboxylate (8) and Tetramethyl 4-Hydroxy-1-methyl-3,6-dihydro-
1H-pyridine-2,2,5,6-tetracarboxylate (9): Obtained from 1 mmol
(170 mg) of the ester 2 and 1.1 mmol (192 mg) nitrone 7 refluxing
in 4 mL of benzene during 106 h. Benzene was evaporated and resi-
due was separated on silica gel (eluent: ethyl acetate/hexane = 1:2),
the product was crystallized from ethanol. Yield of 8 272 mg
(79%). White solid, m.p. 100–101 °C. Rf = 0.39 (EtOAc/hexane =
1:1). IR (KBr): ν = 2956, 1760 (s), 1729 (s), 1614, 1437, 1340, 1274,
˜
1233, 1202, 1148 cm–1. 1H NMR (CDCl3): δ = 2.46 (d, J = 6.5 Hz,
1 H), 2.81 (s, 3 H), 2.86 (d, J = 6.5 Hz, 1 H), 3.03 (d, J = 14.5 Hz,
1 H), 3.10 (d, J = 14.5 Hz, 1 H), 3.73 (s, 3 H), 3.74 (s, 3 H), 3.80
(s, 3 H), 3.82 (s, 3 H) ppm. 13C NMR (CDCl3): δ = 30.1 (CH),
32.7 (CH), 41.0 (CH2), 41.3 (CH3), 52.7 (CH3), 52.8 (CH3), 53.4
(2CH3), 70.7 (C), 76.9 (C), 167.4 (CO), 167.6 (CO), 167.7 (CO),
170.1 (CO) ppm. C14H19NO9 (345.31): calcd. C 48.70, H 5.55, N
4.06; found C 48.95, H 5.66, N 4.26.
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Lautens, W. Klute, W. Tam, Chem. Rev. 1996, 96, 49; b) A.
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0.34 (EtOAc/hexane = 1:2). IR: ν = 3470 (broad), 2973, 1740 (s),
˜
1678 (s), 1638 (s), 1610, 1450, 1440, 1307, 1275, 1250, 1180, 1110
1
cm–1. H NMR (CDCl3): δ = 2.68 (s, 3 H), 2.89 (d, J = 16.7 Hz, 1
H), 3.18 (d, J = 16.7 Hz, 1 H), 3.71 (s, 3 H), 3.74 (s, 3 H), 3.78 (s,
3 H), 3.80 (s, 3 H), 4.23 (s, 1 H), 12.06 (s, 1 H) ppm. 13C (CDCl3):
δ = 36.8 (CH2), 39.3 (CH3), 52.2 (CH3), 52.6 (CH3), 53.2 (CH3),
53.4 (CH3), 62.1 (CH), 71.2 (C), 96.3 (C), 169.4 (C), 169.5 (C),
2060
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© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 2054–2061

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Received: January 12, 2012
Published Online: February 24, 2012
Eur. J. Org. Chem. 2012, 2054–2061
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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