Reaction of methyl 1-bromocycloalkanecarboxylates with zinc and ethyl 5-aryl-3-oxo-2,2-diethylpent-4-enoates

Article abstract of DOI:10.1134/S1070363212050155

Methyl 1-bromoalkanecarboxylates react with zinc and ethyl 5-aryl-3-oxo-2,2-diethylpent-4-enoates to form ethyl 2-(10-aryl-6-oxo-7- oxaspiro[4.5]dec-8-en-8-yl)-2-ethylbutanoates and ethyl 2-(5-aryl-1-oxo-2- oxaspiro[5.5]undec-3-en-3-yl)-2-ethylbutanoates.

Full text of DOI:10.1134/S1070363212050155

ISSN 1070-3632, Russian Journal of General Chemistry, 2012, Vol. 82, No. 5, pp. 891–894. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © N.F. Kirillov, E.A. Nikiforova, P.A. Slepukhin, M.I. Vakhrin, 2012, published in Zhurnal Obshchei Khimii, 2012, Vol. 82, No. 5,
pp. 788–792.
Reaction of Methyl 1-Bromocycloalkanecarboxylates
with Zinc and Ethyl 5-Aryl-3-oxo-2,2-diethylpent-4-enoates
N. F. Kirillova, E. A. Nikiforovaa, P. A. Slepukhinb, and M. I. Vakhrina
a Perm’ State University, ul. Bukireva 15, Perm’, 614990 Russia
e-mail: kirillov@psu.ru
b Postovsky Institute of Organic Synthesis, Ural Branch, Russian Academy of Sciences, Yekaterinburg, Russia
Received February 21, 2011
Abstract—Methyl 1-bromoalkanecarboxylates react with zinc and ethyl 5-aryl-3-oxo-2,2-diethylpent-4-
enoates to form ethyl 2-(10-aryl-6-oxo-7-oxaspiro[4.5]dec-8-en-8-yl)-2-ethylbutanoates and ethyl 2-(5-aryl-1-
oxo-2-oxaspiro[5.5]undec-3-en-3-yl)-2-ethylbutanoates.
DOI: 10.1134/S1070363212050155
The Reformatsky reagents add to α,β-unsaturated
ketones in the 1,2- as well as in the 1,4-positions of the
conjugated system. The products of 1,4-addition undergo
cyclization to unsaturated lactones, the dihydropyran-
2-one derivatives [1, 2].
5-aryl-3-oxo-2,2-diethylpent-4-enoates IIIa–IIIf. Our
studies showed that organozinc reagents add to
compounds IIIa–IIIf in the 1,4 position of –C=C-C=O
fragment to form the intermediates IVa–IVd and Va–
Vf. In the course of the reaction these intermediates
due to attack of the oxygen atom on the ester carbonyl
carbon atom undergo cyclization to substituted
spyrodihydropyran-2-ones, in particular, to ethyl 2-
(10-aryl-6-oxo-7-oxaspiro[4.5]dec-8-en-8-yl)-2-ethyl-
butanoates VIa–VId and ethyl 2-(5-aryl-1-oxo-2-oxa-
spiro[5.5]undec-3-en-3-yl)-2-ethylbutanoates VIIa–VIIf.
In both cases a bromozincmethylate molecule is
liberated.
It was established previously that in the reactions of
alicyclic Reformatsky reagents with 1,3-diarylprop-2-
en-1-ones substituted spirodihydropyranones were
formed [3, 4]. Developing these studies we have
investigated the reactions of Reformatsky reagents
prepared from methyl 1-bromocyclopentane I and 1-
bromocyclohexane II-carboxylates and zinc with ethyl
Br
COOMe
(CH2)n
I, II
O
(CH2)n
C2H5
O
Ar
Ar
O
(CH2)n
COOC2H5
C2H5
Zn,
OMe
OZnBr
C2H5
Ar
C2H5
COOC2H5
C2H5
VIa−VId, VIIa−VIIf
IIIа−IIIf
−MeOZnBr
O
C
C
COOC2H5
C2H5
IVa−IVd, Va−Vf
I, IV, VI: n = 1; II, V, VII: n = 2; III–VII: Ar = Ph (а), 4-МеС6Н4 (b), 4-BrC6H4 (c), 4-ClC6H4 (d); III, V, VII: Ar = 3-
BrC6H4 (e), 2-FC6H4 (f).
891

892
KIRILLOV et al.
Fig. 1. General view of compound VIIc according to X-ray
Fig. 2. General view of compound VIa according to X-ray
data.
data.
The composition and structure of the compounds
obtained were confirmed by elemental analysis and the
IR and H NMR spectroscopy. In the IR spectra of
C5C10C13C14 66.26°. For compound VIIc these values
are C5C6C9C10 175.37°, C5C6C11C12 –66.00°.
1
EXPERIMENTAL
compounds VIa–VId and VIIa–VIIf characteristic
bands of C=C bonds at 1675–1690 cm–1 and of the
ester and lactonic carbonyls at 1735–1750 cm–1 and
IR spectra of compounds VIa–VId and VIIa–VIIf
1
1755–1775 cm–1 respectively were observed. H NMR
were recorded on a Specord-75IR spectrometer as
1
mulls in mineral oil. H NMR spectra were taken on a
spectra contain one set of signals among which the
doublets of dihydropyran cycle protons at 3.22–3.38
Mercury Plus-300 (300 MHz) spectrometer in CDCl3
with reference TMS.
1
and 5.35–5.41 ppm are most characteristic. In the H
NMR spectra of compounds VIa–VId unlike the
spectra of substances VIIa–VIIf signals of methylene
protons of the ethoxy groups give clearly expressed
10-component multiplet with the integral intensity
corresponding to two protons. At the saturation of the
resonance of methylene protons of the ethoxy group of
compound VIc the signal of the methylene group
proton converts in two doublets with chemical shifts of
4.19 and 4.23 ppm and the coupling constant J = 15.0 Hz.
It shows that these protons are nonequivalent.
XRD studies were carried out on an automatic
Xcalibur
3
diffractometer with CCD detector
according to the standard procedure [MoK radiation,
295(2) K, graphite monochromator, w-scanning]. For
the analysis of compound VIIc the colorless single
crystal of dimensions 0.31×0.23×0.13 mm was used,
and in the case of compound VIa the colorless single
crystal of dimensions 0.25×0.20×0.15 mm was
studied. The correction for the extinction of compound
VIIc was made analytically using the polyhedron
crystal model [5]. For compound VIa no correction
was made. Solving and refining of structures was
carried out by SHELXL-97 software [6]. The
structures were solved by the direct method and
refined by the full-matrix root-mean-square method
with respect to F2 in the anisotropic approximation for
all non-hydrogen atoms. Hydrogen atoms were
revealed by the peaks of spatial electronic density and
included in refining in the isotropic approximation in
the rider model. Main crystallographic data and the
parameters of refining of structures are listed in the
table.
Structure of the compounds VIa and VIIc was
established by the XRD study. It was shown that these
substances crystallize in centrosymmetric group of the
P21/c symmetry of the monoclinic crystal system with
close parameters of the unit cells. Interatomic distances
and bond angles of the cyclic esters synthesized are
close to the standard values. General view and
numbering of atoms in the structural experiment are
presented in Figs. 1, 2. The symmetry of ethyl sub-
stituents in the side chain of dihydropyran ring in both
compounds is distorted. Corresponding torsion angles
for compound VIa are C5C10C11C12 178.07°,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 5 2012

REACTION OF METHYL 1-BROMOCYCLOALKANECARBOXYLATES
Main parameters of the X-ray experiments
893
Compound
VIIc
VIа
Formula
Molecular weight
Crystal system
Space group
a, Å
b, Å
c, Å
α, deg
C24H31BrO4
463.40
Monoclinic
P21/с
11.1706(3)
12.9526(3)
15.9457(4)
90
C23H30O4
370.47
Monoclinic
P21/с
15.4759(7)
11.2863(11)
12.6735(8)
90
β, deg
94.611(2)
107.711(5)
γ, deg
90
90
2108.7(3)
V, Å3
2299.69(10)
Z
4
1.338
1.813
4
1.167
0.078
dcalc, g cm–3
μ, mm–1
Scanning range, deg
2.80 ≤ θ ≤ 30.52
13349/6606 (0.0141)
3815
2.76 ≤ θ ≤ 28.30
10328/5024 (0.0205)
2534
Number of measured independent reflections (Rint)
Number of reflections with I > 2σ(I)
Completeness (for θ, deg)
Number of refined parameters
S
97.3% (26.00)
271
98.2% (26.00)
247
1.001
1.008
R1 [by I > 2σ(I)]
0.0323
0.0458
wR2 [by I > 2σ(I)]
0.0773
0.1278
R1 (by all reflections)
wR2 (by all reflections)
Δe/e Å–3
0.0625
0.0804
0.358/–0.464
0.0948
0.1390
0.277/–0.242
1
X-ray data were deposited in the Cambridge center
of crystallographic data, CCDC numbers 842114 and
842115. These data are accessible free and may be
requested by the address www.ccdc.cam.ac.uk/
data_request/cif.
(C=O)est, 1779 (C=O)lact. H NMR spectrum, δ, ppm:
0.79 t. 0.82 t (6H, 2CH2CH3, J 7.5 Hz), 1.27 t (3H,
OCH2CH3, J 7.5 Hz), 1.18–2.09 m [12H, (CH2)4,
2CH2CH3], 3.26 d (1H, C19H, J 6.3 Hz), 4.13–4.25 m
(2H, OCH2CH3), 5.41 d (1H, =C9H, J 6.3 Hz), 7.11 d,
7.25 t, 7.27 t (5H, Ph, J 8.1 Hz). Found, %: C 74.78, H
8.02. C23H30O4. Calculated, %: C 74.56, H 8.16.
Ethyl 2-(10-aryl-6-oxo-7-oxaspiro[4.5]dec-8-en-
8-yl)-2-ethylbutanoates VIa–VId and ethyl 2-(5-
aryl-1-oxo-2-oxaspiro[5.5]undec-3-en-3-yl)-2-ethyl-
butanoates VIIa–VIIf. A mixture of 23 mg-equiv of
fine zinc turnings, the catalytic amount of mercury
chloride, 5 mmol of ethyl 5-aryl-3-oxo-2,2-diethyl-
pent-4-enoate, 5.3 mmol of methyl 1-bromo-
cyclopentane- or methyl 1-bromocyclohexanecar-
boxylate, 20 ml of benzene, 5 ml of ethyl acetate, and
1 ml of HMPA was boiled for 4 h, cooled, decanted
from the excess of zinc, and decomposed with 5%
hydrochloric acid. Organic layer was separated, and
water layer was two times extracted with ethyl acetate.
After drying the extract over anhydrous sodium sulfate
solvents were removed and compounds VIa–VId or
VIIa–VIIf were crystallized from ethanol.
Ethyl 2-[10-(4-methylphenyl)-6-oxo-7-oxaspiro
[4.5]dec-8-en-8-yl]-2-ethylbutanoate (VIb). Yield
0.83 g (43%), mp 123–124°C. IR spectrum, ν, cm–1:
1
1695 (C=C), 1735 (C=O)est , 1775 (C=O)lact. H NMR
spectrum, δ, ppm: 0.78 t, 0.82 t (6H, 2CH2CH3, J 7.2 Hz),
1.27 t (3H, OCH2CH3, J 6.9 Hz), 1.26–2.06 m [12H,
(CH2)4, 2CH2CH3], 2.30 s (3H, Me), 3.22 d (1H, C10H,
J 6.0 Hz), 4.13–4.25 m (2H, OCH2CH3). 5.39 d (1H,
=C9H, J 6.0 Hz), 7.00 d, 7.07 d (4H, 4-MeC6H4, J 8.1 Hz).
Found, %: C 75.18, H 8.23. C24H32O4. Calculated, %:
C 74.97, H 8.39.
Ethyl 2-[10-(4-bromophenyl)-6-oxo-7-oxaspiro-
[4.5]dec-8-en-8-yl]-2-ethylbutanoate (VIc). Yield
1.08 g (48%), mp 91–92°C. IR spectrum, ν, cm–1: 1680
(C=C), 1740 (C=O)est, 1775 (C=O)lact. H NMR spec-
trum, δ, ppm: 0.78 t, 0.82 t (6H, 2CH2CH3, J 7.5 Hz),
1.27 t (3H, OCH2CH3, J 7.2 Hz), 1.21–2.09 m [12H,
1
Ethyl 2-(6-oxo-10-phenyl-7-oxaspiro[4.5]dec-8-
en-8-yl)-2-ethylbutanoate (VIa). Yield 0.78 g (42%),
mp 74–75°C. IR spectrum, ν, cm–1: 1690 (C=C), 1740
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 5 2012

894
KIRILLOV et al.
Ethyl
(CH2)4, 2CH2CH3], 3.22 d (1H, C10H, J 6.3 Hz), 4.14–
4.25 m (2H, OCH2CH3), 5.38 d (1H, =C9H, J 6.3 Hz),
6.99 d, 7.39 d (4H, 4-BrC6H4, J 8.4 Hz). Found, %: C
61.69; H 6.29, Br 17.55. C23H29BrO4. Calculated, %: C
61.47, H 6.50, Br 17.78.
2-[5-(4-chlorophenyl)-1-oxo-2-oxaspiro-
[5.5]yndec-3-en-3-yl]-2-ethylbutanoate (VIId). Yield
0.82 g (39%), mp 83–84°C. IR spectrum, ν, cm–1: 1695
1
(C=C), 1745 (C=O)est, 1765 (C=O)lact. H NMR spec-
trum, δ, ppm: 0.77 t, 0.82 t (6H, 2CH2CH3, J 7.5 Hz),
1.25 t (3H, OCH2CH3, J 7.2 Hz), 0.98–2.12 m [14H,
(CH2)5, 2CH2CH3], 3.37 d (1H, C5H, J 6.3 Hz), 4.17 q
(2H, OCH2CH3, J 7.2 Hz). 5.28 d (1H, =C4H, J 6.3 Hz),
7.03 d, 7.24 d(4H, 4-ClC6H4, J 8.4 Hz). Found, %: C
68.96, H 7.67, Cl 8.29. C24H31ClO4. Calculated, %: C
68.80, H 7.46, Cl 8.46.
Ethyl 2-[6-oxo-10-(4-chlorophenyl)-7-oxaspiro-
[4.5]dec-8-en-8-yl]-2-ethylbutanoate (VId). Yield
0.97 g (47%), mp 98–99°C. IR spectrum, ν, cm–1: 1680
1
(C=C), 1740 (C=O)est, 1755 (C=O)lact. H NMR spec-
trum, δ, ppm: 0.78 t, 0.82 t (6H, 2CH2CH3, J 7.5 Hz),
1.27 t (3H, OCH2CH3, J 7.2 Hz), 1.21–2.08 m [12H,
(CH2)4, 2CH2CH3], 3.24 d (1H, C10H, J 6.0 Hz), 4.14–
4.25 m (2H, OCH2CH3). 5.38 d (1H, =C9H, J 6.0 Hz),
7.05 d, 7.24 d (4H, 4-ClC6H4, J 8.7 Hz). Found, %: C
68.44, H 7.06, Cl 8.53 C23H29ClO4. Calculated, %: C
68.22, H 7.22, Cl 8.76.
Ethyl 2-[5-(3-bromorophenyl)-1-oxo-2-oxaspiro-
[5.5]yndec-3-en-3-yl]-2-ethylbutanoate (VIIe). Yield
1.00 g (43%), mp 97–98°C. IR spectrum, ν, cm–1: 1690
1
(C=C), 1750 (C=O)est, 1775 (C=O)lact. H NMR spec-
trum, δ, ppm: 0.79 t, 0.83 t (6H, 2CH2CH3, J 7.2 Hz),
1.25 t (3H, OCH2CH3, J 6.9 Hz), 1.05–2.13 m [14H,
(CH2)5, 2CH2CH3], 3.34 d (1H, C5H, J 6.6 Hz), 4.19 q
(2H, OCH2CH3, J 6.9 Hz). 5.27 d (1H, =C4H, J 6.6 Hz),
7.03 d, 7.14 t, 7.26 s, 7.36 d (4H, 3-BrC6H4, J 7.8 Hz).
Found, %: C 62.46, H 6.89, Br 17.53. C24H31BrO4.
Calculated, %: C 62.20, H 6.74, Br 17.24.
Ethyl 2-(1-oxo-5-phenyl-2-oxaspiro[5.5]yndec-3-
en-3-yl)-2-ethylbutanoate (VIIa). Yield 0.88 g (46%),
mp 85–86°C. IR spectrum, ν, cm–1: 1690 (C=C), 1745
(C=O)est, 1775 (C=O)lact. H NMR spectrum, δ, ppm:
0.77 t, 0.81 t (6H, 2CH2CH3, J 7.5 Hz), 1.24 t (3H,
1
OCH2CH3, J 7.5 Hz), 0.95–2.10 m [14H, (CH2)5, 2CH2·
Ethyl 2-[1-oxo-5-(2-fluorophenyl)-2-oxaspiro[5.5]-
yndec-3-en-3-yl]-2-ethylbutanoate (VIIf). Yield 1.05 g
(52%), mp 83–84°C. IR spectrum, ν, cm–1: 1675
CH3], 3.35 d (1H, C5H, J 6.5 Hz), 4.13 q (2H,
OCH2CH3). 5.25 d (1H, =C4H, J 6.5 Hz), 6.92–7.27 m
(5H, Ph). Found, %: C 75.22, H 8.51. C24H32O4.
Calculated, %: C 74.97, H 8.39.
1
(C=C), 1740 (C=O)est, 1770 (C=O)lact. H NMR spec-
trum, δ, ppm: 0.78 t, 0.82 t (6H, 2CH2CH3, J 7.5 Hz),
1.25 t (3H, OCH2CH3, J 7.2 Hz), 0.98–2.12 m [14H,
(CH2)5, 2CH2CH3], 3.38 d (1H, C5H, J 6.6 Hz), 4.18 q
(2H, OCH2CH3, J 7.2 Hz). 5.30 d (1H, =C4H, J 6.6 Hz),
6.92–7.10 m (4H, 2-FC6H4, J 7.8 Hz). Found, %: C
71.39, H 7.94. C24H31FO4. Calculated, %: C 71.62, H 7.76.
Ethyl 2-[5-(4-methylphenyl)-1-oxo-2-oxaspiro-
[5.5]yndec-3-en-3-yl]-2-ethylbutanoate (VIIb). Yield
0.82 g (41%), mp 112–113°C. IR spectrum, ν, cm–1:
1695 (C=C), 1750 (C=O)est,1765 (C=O)lact. 1H NMR spec-
trum, δ, ppm: 0.77 t, 0.81 t (6H, 2CH2CH3, J 7.5 Hz),
1.25 t (3H, OCH2CH3, J 7.2 Hz), 1.00–2.10 m [14H,
(CH2)5, 2CH2CH3], 2.30 s (2H, Me), 3.35 d (1H, C5H,
J 6.3 Hz), 4.17 q (2H, OCH2CH3, J 7.2 Hz), 5.29 d
(1H, =C4H, J 6.3 Hz), 6.98 d, 7.07 d (4H, 4-MeC6H4, J
8.4 Hz). Found, %: C 75.48, H 8.71. C25H34O4.
Calculated, %: C 74.34, H 8.60.
ACKNOWLEDGMENTS
The work was carried out with the financial support
of Russian Foundation for Basic Research (grant no.
11-03-96014) and Ministry of Education and Science
of Russian Federation (project 1.12.11).
REFERENCES
Ethyl 2-[5-(4-bromophenyl)-1-oxo-2-oxaspiro-
[5.5]undec-3-en-3-yl]-2-ethylbutanoate (VIIc). Yield
1.09 g (47%), mp 84–85°C. IR spectrum, ν, cm–1: 1690
1. Ocampo, R. and Dolbier, W.R., Tetrahedron, 2004,
vol. 60, p. 9325.
1
2. Furstner, A., Synthesis, 1989, p. 571.
(C=C), 1750 (C=O)est, 1765 (C=O)lact. H NMR spec-
3. Kirillov, N.F. and Gavrilov, A.G., Zh. Obshch. Khim.,
2008, vol. 78, no. 7, p. 1189.
4. Kirillov, N.F. and Gavrilov, A.G., Zh. Org. Khim.,
2008, vol. 44, no. 7, p. 975.
5. Clark, R.C. and Reid, J.S., Acta Cryst. A, 1995, vol. 51,
trum, δ, ppm: 0.77 t, 0.82 t (6H, 2CH2CH3, J 7.5 Hz),
1.25 t (3H, OCH2CH3, J 7.2 Hz), 0.90–2.12 m [14H,
(CH2)5, 2CH2CH3], 3.36 d (1H, C5H, J 6.6 Hz), 4.17 q
(2H, OCH2CH3, J 7.2 Hz). 5.28 d (1H, =C4H, J 6.6 Hz),
6.97 d, 7.39 d (4H, 4-BrC6H4, J 8.4 Hz). Found, %: C
62.42, H 6.55, Br 17.03. C24H31BrO4. Calculated, %: C
62.20, H 6.74, Br 17.24.
p. 887.
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 5 2012