Unexpected formation of 4-arylcyclopentane-1,1,3,3-tetracarboxylates in GaCl3-catalyzed reaction of 2-arylcyclopropane-1,1-dicarboxylates with tetrasubstituted 1-pyrazolines

Article abstract of DOI:10.1016/j.mencom.2012.06.002

Gallium trichloride-catalyzed reaction between 2-arylcyclopropane-1,1- dicarboxylates and 3,3,5,5-tetrasubstituted 1-pyrazolines affords 4-arylcyclopentane-1,1,3,3-tetracarboxylates, which originate from cycloaddition of the two molecules of the starting

Full text of DOI:10.1016/j.mencom.2012.06.002

Mendeleev
Communications
Mendeleev Commun., 2012, 22, 181–183
Unexpected formation of 4-arylcyclopentane-1,1,3,3-tetracarboxylates
in GaCl3-catalyzed reaction of 2-arylcyclopropane-1,1-dicarboxylates
with tetrasubstituted 1-pyrazolines
Roman A. Novikov, Yury V. Tomilov* and Oleg M. Nefedov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation.
Fax: +7 499 135 5328; e-mail: tom@ioc.ac.ru
DOI: 10.1016/j.mencom.2012.06.002
Gallium trichloride-catalyzed reaction between 2-arylcyclopropane-1,1-dicarboxylates and 3,3,5,5-tetrasubstituted 1-pyrazolines affords
4-arylcyclopentane-1,1,3,3-tetracarboxylates, which originate from cycloaddition of the two molecules of the starting cyclopropane
with the loss of one arylidene fragment subtracted by the 1-pyrazoline.
We have recently shown1 that scandium or ytterbium triflate-
catalyzed reactions between 2-arylcyclopropane-1,1-dicarboxylates
(usually referred to as donor-acceptor cyclopropanes2) and
2-pyrazolines give 1,2-diazabicyclo[3.3.0]octanes as the major
products. The similar reactions with 1-pyrazolines containing at
least one hydrogen atom in 3- or 5-position mostly afford N-sub-
stituted 2-pyrazolines. The same products are also formed if an
equimolar amount of GaCl3 is used and the reaction is carried
out at 0–5°C.1
On the other hand, studies on the chemical behaviour of
donor-acceptor cyclopropanes on contact with various Lewis acids
revealed a few unusual pathways of their dimerization,2–5 for
instance, conversion of 2-arylcyclopropane-1,1-dicarboxylates 1
to polysubstituted cyclopentanes E,E- and E,Z-2 in yields above
70% (Scheme 1).3,4
CO2Me
CO2Me
GaCl3
(30 mol%)
Me
CO2Me
Me
+
MeO2C
CH2Cl2, 80 °C,
3 h, sealed tube
N
N
Ar
1a–j
2 : 1
E,Z-3
MeO2C CO2Me
Me
CO2Me
MeO2C
Me
N
+
N
H
CO2Me
CO2Me
Ar
Ar
4a–j
5a–j
Scheme 2
moiety, which is trapped by a molecule of pyrazoline 3 to produce
azomethineimine 5a. No such reactions involving fragmentation
of the cyclopropane ring on treatment with Lewis acids have
been reported so far. Unfortunately, we failed to isolate the
pure azomethineimine 5a, since such attempts resulted in its
fast hydrolysis to give benzaldehyde and the corresponding
pyrazolidine.
When other Lewis acids were applied, e.g. EtAlCl2 or scandium
or ytterbium triflates, the conversion of cyclopropane 1a to pro-
ducts 4 and 5 did not occur at all. Similarly, they were not formed
MeO2C CO2Me
CO2Me
Sn(OTf)2 or Yb(OTf)3
(5 mol%), PhCl, 132 °C
CO2Me
CO2Me
CO2Me
or
Ar
Ar
GaCl3 (20 mol%), CH2Cl2,
room temperature, 30 min
Ar
1
2
Scheme 1
Herein, we studied the Lewis acid-catalyzed reaction of 2-aryl-
cyclopropane-1,1-dicarboxylates 1 in the presence of dialkyl
3,5-dimethyl-1-pyrazoline-3,5-dicarboxylates 3 containing no
hydrogen atoms in 3- or 5-positions of the heterocycle. Such a
substitution pattern in pyrazoline was found to be the crucial factor
determining the new type of transformation of cyclopropanes 1.
In fact, heating of cyclopropane 1a with pyrazoline E-3 in the
presence of 30 mol% anhydrous GaCl3 in dichloromethane in a
sealed tube at 80°C gave 4-phenylcyclopentane-1,1,3,3-tetracar-
boxylate 4a (Scheme 2, Ar = Ph) in up to 60% yields.† Unlike the
dimerization products of donor-acceptor cyclopropanes described
previously,3–5 compound 4a is not a true dimer, though it is
formed from two cyclopropanedicarboxylate molecules. The
transformation is accompanied by elimination of one CH–Ph
General procedure. All operations were performed under a dry argon
atmosphere. Solid GaCl3 (0.3 mmol) in one portion was added to a solu-
tion of cyclopropane 1 (1 mmol) and pyrazoline 3 (0.5 mmol) in 5 ml of
anhydrous dichloromethane at room temperature with vigorous stirring.
The reaction mixture was heated at 80°C under a slight pressure in a
sealed tube and was stirred during 3 h. After that, an aqueous solution of
HCl (5%) was added to the mixture at room temperature until pH 3 was
achieved, and the reaction mixture was extracted with dichloromethane
(3×10 ml). The extract was dried with MgSO4 and the solvent was removed
in vacuo. The residue was subjected to column chromatography on silica
gel (benzene–EtOAc, 20:1) to afford pure cyclopentanes 4 as thick colour-
less oils in yields indicated in Table 1.
Tetramethyl 4-phenylcyclopentane-1,1,3,3-tetracarboxylate 4a. Yield,
60%. 1H NMR, d: 2.64 (ddd, 1H, Ha-5, 2J 13.5 Hz, 3J 6.8 Hz, 4J 1.7 Hz),
2.88 (dd, 1H, Hb-5, 2J 13.5 Hz, 3J 13.0 Hz), 3.01 (dd, 1H, Ha-2, 2J 14.5 Hz,
4J 1.7 Hz), 3.17 (s, 3H, C3O2Me), 3.20 (d, 1H, Hb-2, 2J 14.5 Hz), 3.78, 3.79
†
1H and 13C NMR spectra were recorded on Bruker AMX-400 (400.1
3
and 100.6 MHz, respectively) and Bruker AVANCE II 300 (300 and
75 MHz, respectively) spectrometers in CDCl3 containing 0.05% TMS
as the internal standard. 19F NMR spectra were recorded on Bruker
AVANCE II 300 (282.4 MHz); standard, CFCl3. Assignments of 1H and
13C signals were made with the aid of 1D DEPT-135 and 2D COSY,
NOESY, HSQC and HMBC spectra.
and 3.82 (all s, 3×3H, 3OMe), 4.16 (dd, 1H, H-4, J 13.0 and 6.8 Hz),
7.23–7.37 (m, 5H, Ph). 13C NMR, d: 38.8 (C5H2), 41.4 (C2H2), 49.2 (C4H),
52.2, 52.7, 53.0 and 53.2 (4OMe), 58.8 (C1), 64.6 (C3), 127.4 (p-CH),
128.3 and 128.7 (2o-CH, 2m-CH), 138.1 (i-C), 170.4, 171.1, 171.9 and
172.0 (4COO). HRMS, m/z: 401.1202 (calc. for C19H22O8, m/z: 401.1207
[M+Na]+).
© 2012 Mendeleev Communications. All rights reserved.
– 181 –

Mendeleev Commun., 2012, 22, 181–183
Table 1 Formation of 4-arylcyclopentane-1,1,3,3-tetracarboxylates 4 in
when other nitrogen-containing compounds (azobenzene, pyridine,
or triethylamine) were used in place of pyrazoline 3. The reaction
using other 1-pyrazolines containing a hydrogen atom in the
a-position with respect to the N=N bond occurred by the path-
ways described previously1 without fragmentation of the starting
reactants. Thus, the system comprising 1-pyrazoline 3 and GaCl3
proved to be specific, ensuring the formation of compounds 4 and 5.
Note that both the individual E- and Z-isomers of pyrazoline 3
or their mixture (~3.5:1) prepared by 1,3-dipolar cycloaddition
of methyl diazopropionate to methyl methacrylate6 were equally
efficient in the reaction.
The discovered method for synthesizing cyclopentanetetra-
carboxylate 4a from 1a is well reproducible for other 2-arylcyclo-
propane-1,1-dicarboxylates 1b–j (Table 1).† The reactions with
cyclopropanes 1b–d containing halogen atoms in the ortho- and
meta-positions of the benzene ring occurred most readily. Similar
reactions proceeded with naphthyl-substituted substrates 1i,j. All
the 4-arylcyclopentane-1,1,3,3-tetracarboxylates 4a–j obtained
manifest a characteristic upfield shift of protons of one of the
methoxy groups (dH 3.13–3.27, and even higher, viz., 2.83 and
3.03, for naphthyl-substituted derivatives 4i,j). This arrangement
of signals is typical of the cis-CO2Me group at C3, which is located
above the plane of the adjacent benzene ring within its ‘negative
cone’ of anisotropy.
the GaCl3-catalyzed reaction of 2-arylcyclopropane-1,1-dicarboxylates 1
with pyrazoline E-3.a
Entry
Reagent
Ar
Product
Yield (%)b
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
1g
1h
1i
Ph
4a
4b
4c
4d
4e
4f
4g
4h
4i
60
91
86
80
57
68
69
65
50
48
2-ClC6H4
3-ClC6H4
3-BrC6H4
4-MeC6H4
4-FC6H4
4-ClC6H4
4-BrC6H4
1-naphthyl
2-naphthyl
10
1j
4j
a Reaction conditions: 1:3:GaCl3 = 1:0.5:0.3, CH2Cl2, sealed tube, 80°C,
3 h. The optimum time and temperature were determined by NMR monitoring
the reaction in an NMR tube. b Isolated yields.
The proposed mechanism of this process is outlined in
Scheme 3. First, cyclopropanedicarboxylate 1 on contact with
gallium trichloride is opened to give bipolar intermediate I, which
adds to a molecule of pyrazoline 2 to produce intermediate II.
No migration of substituents at the heterocycle can occur in
intermediate II, so it adds a second molecule 1 to form bipolar
intermediate III. Intramolecular SN2 attack by a malonyl anion
on the sterically free CH2 group in III results in splitting of
the latter to afford cyclopentane 4 and azomethineimine 5. The
nucleophilic attack occurs on the methylene group, whereas attack
on the methine C atom appears unlike due to considerable steric
hindrance. The resulting azomethine 5 is unstable under acidic
conditions and is hydrolyzed during the workup of the reaction
mixture to give pyrazolidine 6 and the corresponding benz-
aldehydes 7.
Note that cyclopentanes 4 cannot be obtained by direct [2+3]-
cycloaddition of cyclopropanedicarboxylates 1 to methylidene-
malonate, since donor-acceptor cyclopropanes readily add to
electron-rich double bonds,7 but do not react with electron-
deficient ones. In this study, we suggested a ‘bypass’ route for
synthesizing cyclopentanes 4 by oxidative doubling of readily
available cyclopropanedicarboxylates 1. During the doubling
of cyclopropanedicarboxylates, the second molecule of cyclo-
propane 1 is synthetically equivalent to methylidenemalonate.
In summary, we have discovered a new unusual reaction of
2-arylcyclopropane-1,1-dicarboxylates with a 3,3,5,5-tetrasub-
stituted 1-pyrazoline in the presence of catalytic amounts of
GaCl3 to give 4-arylcyclopentane-1,1,3,3-tetracarboxylates in
high yields. In this case, 1-pyrazoline acts as the oxidant, causing
Tetramethyl 4-(2-chlorophenyl)cyclopentane-1,1,3,3-tetracarboxylate
4b.Yield, 91%. IR (CHCl3, n/cm–1): 3020, 2976, 1956, 2896, 2846, 1734
1
(br., O=CO), 1521, 1479, 1436, 1393, 1256. H NMR, d: 2.67 (dd, 1H,
Ha-5, 2J 14.0 Hz, 3J 10.4 Hz), 2.89 (ddd, 1H, Hb-5, 2J 14.0 Hz, 3J 8.1 Hz,
4J 1.3 Hz), 3.05 (dd, 1H, Ha-2, 2J 14.5 Hz, 4J 1.3 Hz), 3.27 (s, 3H, C3O2Me),
3.28 (d, 1H, Hb-2, 2J 14.5 Hz), 3.73, 3.76 and 3.78 (all s, 3×3H, 3OMe),
4.83 (dd, 1H, H-4, 3J 10.4 and 8.1 Hz), 7.14 (ddd, 1H, C6H4, 3J 7.8 and
7.6 Hz, 4J1.6 Hz), 7.19 (ddd, 1H, C6H4, 3J7.7 and 7.6 Hz, 4J 1.5 Hz), 7.27 (dd,
1H, C6H4, 3J 7.7 Hz, 4J 1.6 Hz), 7.35 (dd, 1H, C6H4, 3J 7.8 Hz, 4J 1.5 Hz).
13C NMR, d: 40.9 (C5H2), 41.9 (C2H2), 45.0 (C4H), 52.3, 53.1 and 53.2
(1C, 1C and 2C, 4OMe), 58.9 (C1), 64.9 (C3), 126.7, 128.4, 129.2 and 129.7
(4CH, C6H4), 135.3 (CCl), 137.5 (i-C), 169.9, 171.2, 171.4 and 171.6
(4COO). MS, m/z (%): 377 (11), 317 (24), 261 (11), 257 (10), 155 (13),
149 (11), 115 (20), 113 (24), 103 (7), 89 (7), 77 (8), 59 (100). HRMS,
m/z: 435.0809 (calc. for C19H2135ClO8, m/z: 435.0817 [M+Na]+).
Tetramethyl 4-(3-chlorophenyl)cyclopentane-1,1,3,3-tetracarboxylate
4c. Yield, 86%. 1H NMR, d: 2.58 (ddd, 1H, Ha-5, 2J 13.5 Hz, 3J 6.8 Hz,
4J 1.6 Hz), 2.80 (dd, 1H, Hb-5, 2J 13.5 Hz, 3J 13.1 Hz), 2.96 (dd, 1H, Ha-2,
2J 14.5 Hz, 4J 1.6 Hz), 3.13 (s, 3H, C3O2Me), 3.16 (d, 1H, Hb-2, 2J 14.5 Hz),
3.75, 3.76 and 3.79 (all s, 3×3H, 3OMe), 4.07 (dd, 1H, H-4, 3J 13.1 and
6.8 Hz), 7.17–7.24 (m, 3H, C6H4), 7.31 (m, 1H, H2', C6H4). 13C NMR, d:
38.7 (C5H2), 41.4 (C2H2), 48.9 (C4H), 52.4, 53.0, 53.1 and 53.2 (4OMe),
58.6 (C1), 64.5 (C3), 127.0, 127.7, 128.8 and 129.3 (4CH, C6H4), 134.0
(CCl), 140.2 (i-C), 170.3, 170.9, 171.6 and 171.9 (4COO). MS, m/z (%):
414 (2) and 412 (5) [M]+, 383 (1) and 381 (3) [M–OMe]+, 354 (6) and
352 (16) [M–HCO2Me]+, 349 (7), 322 (18), 321 (11), 320 (54), 292 (19),
263 (18), 262 (11), 261 (64), 260 (8), 233 (24), 205 (12), 175 (17), 155
(17), 149 (18), 141 (16), 139 (32), 115 (27), 113 (30), 71 (25), 59 (100).
HRMS, m/z: 435.0809 (calc. for C19H2135ClO8, m/z: 435.0817 [M+Na]+).
Tetramethyl 4-(4-fluorophenyl)cyclopentane-1,1,3,3-tetracarboxylate
4f. Yield, 68%. IR (CHCl3, n/cm–1): 3020, 2956, 2928, 2853, 1733 (br.,
O=CO), 1686, 1654, 1646, 1602, 1513, 1474, 1436, 1347, 1263, 1223.
1H NMR, d: 2.58 (ddd, 1H, Ha-5, 2J 13.4 Hz, 3J 6.7 Hz, 4J 1.6 Hz), 2.81
Tetramethyl 4-(1-naphthyl)cyclopentane-1,1,3,3-tetracarboxylate 4i.
Yield, 50%. IR (CHCl3, n/cm–1): 3023, 2955, 1732 (br., O=CO), 1599,
1515, 1435, 1255, 1227. 1H NMR, d: 2.83 (s, 3H, C3O2Me), 2.85 (dd, 1H,
Ha-5, 2J 13.7 Hz, 3J 10.7 Hz), 2.92 (ddd, 1H, Hb-5, 2J 13.7 Hz, 3J 7.9 Hz,
4J 1.6 Hz), 3.08 (dd, 1H, Ha-2, 2J 14.4 Hz, 4J 1.6 Hz), 3.40 (d, 1H, Hb-2,
2J 14.4 Hz), 3.72, 3.80 and 3.81 (all s, 3×3H, 3OMe), 5.21 (dd, 1H,
H-4, 3J 10.7 and 7.9 Hz), 7.36–7.44 (m, 2H, 1-naphthyl), 7.46 (ddd, 1H,
1-naphthyl, 3J 8.0 and 6.9 Hz, 4J 1.0 Hz), 7.55 (ddd, 1H, 1-naphthyl, 3J 8.5
and 6.8 Hz, 4J 1.4 Hz), 7.72 (br.dd, 1H, 1-naphthyl, 3J 6.9 Hz, 4J 2.2 Hz),
7.81 (br.d, 1H, 1-naphthyl, 3J 8.1 Hz), 8.50 (br.d, 1H, 1-naphthyl, 3J 8.6 Hz).
13C NMR, d: 41.7, 42.0 and 43.0 (C5H2, C2H2 and C4H), 52.0, 53.17 and
53.23 (1C, 1C and 2C, 4OMe), 59.4 (C1), 65.5 (C3), 124.5, 125.1, 125.4,
125.7, 126.2, 128.1 and 128.7 (7CH, 1-naphthyl), 132.7, 133.9 and 136.2
(3C, 1-naphthyl), 170.0, 171.3, 171.8 and 172.2 (4COO). MS, m/z (%):
428 (13) [M]+, 397 (0.1) [M–OMe]+, 368 (3) [M–HCO2Me]+, 337 (10),
277 (31), 224 (22), 220 (19), 219 (19), 217 (31), 189 (66), 179 (21), 165
(100), 152 (34), 145 (20), 128 (15), 113 (25), 59 (97). HRMS, m/z: 451.1346
(calc. for C23H24O8, m/z: 451.1346 [M+Na]+).
2
3
2
(dd, 1H, Hb-5, J 13.4 Hz, J 13.2 Hz), 2.97 (dd, 1H, Ha-2, J 14.5 Hz,
4J 1.6 Hz), 3.15 (d, 1H, Hb-2, 2J 14.5 Hz), 3.20, 3.75, 3.76 and 3.80 (all s,
4×3H, 4OMe), 4.10 (dd, 1H, H-4, J 13.2 and 6.7 Hz), 6.95 (m, 2H,
3
2m-CH, 3JHF 8.7 Hz), 7.31 (m, 2H, 2o-CH, 4JHF 5.5 Hz). 13C NMR, d: 38.8
(C5H2), 41.4 (C2H2), 48.5 (C4H), 52.3, 52.9, 53.1 and 53.2 (4OMe), 58.7
(C1), 64.5 (C3), 114.9 (2m-CH, 2JCF 21.2 Hz), 130.3 (2o-CH, 3JCF 7.9 Hz),
133.7 (i-C, 4JCF 3.3 Hz), 162.2 (p-CF, 1JCF 246 Hz), 170.4, 171.0, 171.8
and 172.0 (4COO). 19F NMR, d: –116.0 (tt, 1F, 3JHF 8.7 Hz, 4JHF 5.5 Hz).
MS, m/z(%): 396 (0.2) [M]+, 365 (0.2) [M–OMe]+, 336 (6) [M–HCO2Me]+,
304 (18), 276 (8), 245 (25), 217 (19), 159 (15), 133 (25), 123 (35), 113 (14),
95 (14), 59 (100). HRMS, m/z: 419.1104, 435.0848 (calc. for C19H21FO8,
m/z: 419.1113 [M+Na]+, 435.0852 [M+K]+).
For characteristics of compounds 4d,e,g,h,j, see Online Supplementary
Materials.
– 182 –

Mendeleev Commun., 2012, 22, 181–183
Me
CO2Me
Me
OMe
O
Ar
MeO2C
N
N
CO2Me
CO2Me
GaCl3
3
MeO
O
O
I
Ar
1
Ar
H
7
CO2Me
Me
+
Me
CO2Me
Me
Me
MeO2C
N
MeO2C
N
HN NH
GaCl3
6
OMe
O
Ar
MeO
H+/H2O
Me
CO2Me
Me
O
Ga
Cl3
MeO2C
Me
CO2Me
Me
MeO2C CO2Me
N
N
II
MeO2C
Ar
Ar
N
H
N
+
OMe
CO2Me
CO2Me
Ar
MeO2C
MeO2C
CO2Me
CO2Me
Ar
O
5
4
Ar
GaCl3
1
O
MeO
III
Scheme 3
the fragmentation of the resulting dimeric intermediate III (see
Scheme 3) with elimination of the arylidene moiety as azo-
methineimine.
2 M. Ya. Mel’nikov, E. M. Budynina, O. A. Ivanova and I. V. Trushkov,
Mendeleev Commun., 2011, 21, 293.
3 R. A. Novikov,V.A. Korolev,V. P. Timofeev andYu.V. Tomilov, Tetrahedron
Lett., 2011, 52, 4996.
4 A. O. Chagarovskiy, O. A. Ivanova, E. M. Budynina, I. V. Trushkov and
M. Ya Melnikov, Tetrahedron Lett., 2011, 52, 4421.
This work was supported by the Russian Federation President
Council for Grants (Program for State Support of Leading Scientific
Schools of the Russian Federation, grant no. NSh-8242.2010.3)
and the Division of Chemistry and Materials Sciences of the Russian
Academy of Sciences (Program for Basic Research ‘Theoretical
and Experimental Study of the Nature of Chemical Bonds and
Mechanisms of Important Chemical Reactions and Processes’).
5 (a) O. A. Ivanova, E. M. Budynina, A. O. Chagarovskiy, I. V. Trushkov
and M. Ya. Melnikov, J. Org. Chem., 2011, 76, 8852; (b) O. A. Ivanova,
E. M. Budynina, A. O. Chagarovskiy, E. R. Rakhmankulov, I. V. Trushkov,
A. V. Semeykin, N. L. Shimanovskii and M.Ya. Melnikov, Chem. Eur. J.,
2011, 17, 11738.
6 R. A. Novikov, D. N. Platonov, V. A. Dokichev, Yu. V. Tomilov and
O. M. Nefedov, Izv. Akad. Nauk, Ser. Khim., 2010, 963 (Russ. Chem.
Bull., Int. Ed., 2010, 59, 984).
Online Supplementary Materials
Supplementary data associated with this article can be found
in the online version at doi:10.1016/j.mencom.2012.06.002.
7 (a) H. U. Reissig and R. Zimmer, Chem. Rev., 2003, 103, 1151; (b) M.Yu
and B. L. Pagenkopf, Tetrahedron, 2005, 61, 321; (c) F. de Simone and
J. Waser, Synthesis, 2009, 20, 3353.
References
1 (a)Yu. V. Tomilov, R. A. Novikov and O. M. Nefedov, Tetrahedron, 2010,
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Mendeleev Commun., 2012, 22, 87.
Received: 5th March 2012; Com. 12/3887
– 183 –