Reactions of bromine-containing organozinc compounds derived from α,α-dibromo ketones with 2-arylmethylideneindan-1,3-diones and 5-arylmethylidene-2,2-dimethyl-1,3-dioxane-4,6-diones

Article abstract of DOI:10.1134/S1070428010040081

Bromine-containing organozinc compounds generated from 1,1-dibromo-3,3- dimethylbutan-2-one reacted with 2-arylmethylideneindan-1,3-diones and 5-arylmethylidene-2,2-dimethyl-1,3-dioxane-4,6-diones to give 3-aryl-2-(2,2-dimethylpropanoyl)spiro[cyclopropane

Full text of DOI:10.1134/S1070428010040081

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 4, pp. 499–502. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © V.V. Shchepin, Yu.G. Stepanyan, P.S. Silaichev, M.A. Ezhikova, M.I. Kodess, 2010, published in Zhurnal Organicheskoi Khimii,
2010, Vol. 46, No. 4, pp. 509–513.
Reactions of Bromine-Containing Organozinc Compounds
Derived from α,α-Dibromo Ketones with 2-Arylmethylidene-
indan-1,3-diones and 5-Arylmethylidene-2,2-dimethyl-
1,3-dioxane-4,6-diones
V. V. Shchepina, Yu. G. Stepanyana, P. S. Silaicheva, M. A. Ezhikovab, and M. I. Kodessb
a Perm State University, ul. Bukireva 15, Perm, 614990 Russia
e-mail: koh2@psu.ru
b Postovskii Institute of Organic Synthesis, Ural Division, Russian Academy of Sciences,
ul. S. Kovalevskoi 20, Yekaterinburg, 620219 Russia
Received December 2, 2008
Abstract—Bromine-containing organozinc compounds generated from 1,1-dibromo-3,3-dimethylbutan-2-one
reacted with 2-arylmethylideneindan-1,3-diones and 5-arylmethylidene-2,2-dimethyl-1,3-dioxane-4,6-diones to
give 3-aryl-2-(2,2-dimethylpropanoyl)spiro[cyclopropane-1,2′-indan]-1′,3′-diones and 1-aryl-6,6-dimethyl-2-
(2,2-dimethylpropanoyl)-5,7-dioxaspiro[2.5]octan-4,8-diones, respectively. Reactions of 2-arylmethylidene-
indan-1,3-diones with bromine-containing zinc enolates derived from 1-aryl-2,2-dibromopropan-1-ones and
2,2-dibromo-1,2,3,4-tetrahydronaphthalen-1-one resulted in the formation of 2-aroyl-3-aryl-2-methylspiro-
[cyclopropane-1,2′-indan]-1′,3′-diones and 2,3:8,9-dibenzo-12-phenyldispiro[4.0.5.1]dodecane-1,4,7-trione,
respectively.
DOI: 10.1134/S1070428010040081
We previously developed a procedure for the syn-
thesis of spirocyclopropanes via reaction of 3-aryl-2-
cyanoprop-2-enoic acid derivatives with zinc enolates
derived from 2,2-dibromo-1,2,3,4-tetrahydronaphtha-
len-1-one and 2,2-dibromoindan-1-one [1]. In the
present work we made an attempt to find out another
synthetic approach to cyclopropane derivatives having
one and two spiro carbon atoms. For this purpose, we
examined reactions of bromine-containing organozinc
compounds derived from α,α-dibromo ketones with
2-arylmethylideneindan-1,3-diones and 5-arylmethyli-
dene-2,2-dimethyl-1,3-dioxane-4,6-diones. In fact,
these reactions led to the formation of the correspond-
ing cyclopropanation products as shown in Scheme 1.
propane-1,2 ′ -indan]-1′,3′-diones VIIIa and VIIIb
(Scheme 1).
The structure of compounds VIa, VIb, VIIIa, and
VIIIb was confirmed by their elemental analyses and
1
IR and H NMR spectra. The IR spectra of VIa and
VIb characteristically contained absorption bands
belonging to stretching vibrations of the ketone and
ester carbonyl groups at 1700 and 1720–1730 cm–1,
1
respectively. In the H NMR spectra of these com-
pounds we observed a strong signal from 9 protons in
the tert-butyl group (δ 1.24–1.25 ppm), two methyl
proton singlets at δ 1.64–1.67 and 1.73–1.76 ppm, and
two protons in the cyclopropane ring at δ 3.90–
3.96 ppm. Compounds VIIIa and VIIIb displayed in
the IR spectra absorption bands at 1690 and 1705 cm–1
due to stretching vibrations of carbonyl groups.
Protons in the tert-butyl group resonated in the
1H NMR spectrum of VIIIa and VIIIb at δ 1.0–
1.01 ppm, and signals from two protons in the cyclo-
propane rings appeared at δ 3.59 ppm (VIIIa in
DMSO-d6) or at δ 3.51 and 3.54 ppm (VIIIb in
CDCl3). The spin–spin coupling constants for protons
Zinc enolate II preliminarily generated from 1,1-di-
bromo-3,3-dimethylbutan-2-one I added at the double
C=C bond in substrates IIIa, IIIb, IVa, and IVb to
give intermediates Va, Vb, VIIa, and VIIb which
underwent cyclization with formation of cyclopropana-
tion products, 1-aryl-6,6-dimethyl-2-(2,2-dimethylpro-
panoyl)-5,7-dioxaspiro[2.5]octane-4,8-diones VIa and
VIb and 3-aryl-2-(2,2-dimethylpropanoyl)spiro[cyclo-
499

SHCHEPIN et al.
500
Scheme 1.
O
OZnBr
Bu-t
Zn
Br
Br
Bu-t
Br
H
I
II
t-Bu
Br
Ar
H
t-Bu
O
O
O
H
ZnBr
O
O
O
O
O
II
Ar
O
O
–ZnBr2
Ar
O
Me
Me
Me
Me
O
O
O
Me
Me
IIIa, IIIb
Va, Vb
VIa, VIb
H
H
t-Bu
O
O
O
Br
O
t-Bu
ZnBr
II
Ar
Ar
O
–ZnBr2
Ar
O
O
O
IVa, IVb
VIIa, VIIb
VIIIa, VIIIb
III, V, VI, Ar = 4-ClC6H4 (a), 4-BrC6H4 (b); IV, VII, VIII, Ar′ = Ph (a), 4-FC6H4 (b).
1H NMR spectra. In the IR spectra of XIVa and XIVb,
in the cyclopropane ring in the spectrum of IIIb in
CDCl3 (3JHH = 9.9 Hz) indicates their mutual cis orien-
tation with respect to the cyclopropane ring plane.
absorption bands typical of carbonyl stretching vibra-
1
tions appeared at 1660 and 1690 cm–1. Their H NMR
spectra contained signals from protons in the methyl
group and CH proton in the cyclopropane ring at
δ 1.90–1.97 and 3.59–3.70 ppm, respectively. Com-
pounds XIVa and XIVb were isolated as a single
stereoisomer, as followed from the presence of only
one set of signals in the spectrum. Compound XVI
displayed carbonyl absorption bands at 1670 and
2-Arylmethylideneindan-1,3-diones IVa and IVb
reacted with zinc enolates derived from 1-aryl-2,2-di-
bromopropan-1-ones IXa and IXb and 2,2-dibromo-
1,2,3,4-tetrahydronaphthalen-1-one as shown in
Scheme 2. The reactions were carried out in diethyl
ether–tetrahydrofuran. Primary adducts XIIIa, XIIIb,
and XV underwent spontaneous cyclization to give
final products, 2-aroyl-3-aryl-2-methylspiro[cyclopro-
pane-1,2′-indan]-1′,3′-diones XIVa and XIVb and
2,3,8,9-dibenzo-12-phenyldispiro[4.0.5.1]dodecane-
1,4,7-trione (XVI), respectively.
1
1690 cm–1. In the H NMR spectrum of XVI, four
methylene protons resonated in the region δ 2.57–
3.10 ppm, and the signal at δ 3.85 ppm was assigned to
the cyclopropane ring proton. The spectrum of XVI
contained only one set of signals, indicating the pres-
ence of a single stereoisomer.
The structure of compounds XIVa, XIVb, and XVI
was confirmed by their elemental analyses and IR and
1
Compound XIVa was additionally studied by H
and 13C NMR spectroscopy, including two-dimen-
sional homo- and heteronuclear correlation techniques
Br
7
6'
4'
7'
8
O
6
7a'
1'
5'
1
1
(1H–13C HSQC, H–13C HMBC, H–1H NOESY; see
figure) with a view to determine steric configuration of
the isolated products. The arrangement of substituents
in the cyclopropane ring of XIVa was determined on
the basis of the Karplus dependence of the vicinal
Me
2
5
1
2'
3a'
4
3'
O
3
9
H
O
10
3
12
11
coupling constant JCH for the 3-H proton and carbon
atom in the substituents. Signals from vicinal carbon
atoms in the 13C NMR spectrum recorded without
decoupling from protons appeared as unresolved multi-
Structure of the 2-(4-bromobenzoyl)-2-methyl-3-phenylspiro-
[cyclopropane-1,2′-indan]-1′,3′-dione (XIVa) molecule with
atom numbering.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 4 2010

REACTIONS OF BROMINE-CONTAINING ORGANOZINC C OMPOUNDS
501
Scheme 2.
O
OZnBr
O
OZnBr
Ar
Br
Br
Br
Br
Zn
Zn
Br
Br
Ar
Me
IXa, IXb
Me
Xa, Xb
XI
XII
O
Me
O
H
Br
O
Me
Ar
ZnBr
O
Ar
Xa, Xb
Ar'
O
–ZnBr2
Ar'
Ar'
O
O
O
IVa, IVb
XIIIa, XIIIb
XIVa, XIVb
O
O
O
XII
ZnBr
H
Ph
–ZnBr2
O
Br
O
Ph
O
Ph
O
O
IVa
XV
XVI
Ar = 4-BrC6H4, Ar′ = Ph (a); Ar = Ar′ = 4-FC6H4 (b).
plets, and we succeeded in determining only the cou-
pling constant between 3-H and carbon atom in the
methyl group on C2: 3JCH = 6.2 Hz. The other coupling
constants were measured using 2D J-spectroscopy
with selective inverting pulse [2] acting on 3-H
(δ 3.71 ppm). Cross-sections of the resulting two-di-
mensional spectrum that are parallel to the F1 axis and
passing through signals of the corresponding carbon
atoms give one-dimensional spectra displaying only
CDCl3 (VIa, VIIIb, XIVb) or DMSO-d6 (VIIIa, XVI)
using hexamethyldisiloxane as internal reference. The
one- (1H, 13C) and two-dimensional NMR spectra
(NOESY, HSQC, HMBC) of compound XIVa were
recorded on a Bruker DRX-400 spectrometer
(400 MHz for 1H and 100 MHz for 13C) from solutions
in CDCl3 using tetramethylsilane as internal reference,
and the spectra of VIb in CDCl3 were measured on
a Tesla BS-567A instrument (100 MHz) using hexa-
methyldisiloxane as internal reference.
3
coupling constants with the 3-H proton: J(3-H, C1′) =
4.2, 3J(3-H, C3′) = 2.9, 3J(3-H, Me) = 6.1, 3J(3-H, CO) =
4.6 Hz. Comparison of the vicinal coupling constants
for compound XIVa with 3JCH values found by us pre-
viously for substituted cyclopropanes [1, 3] led us to
conclude that the 3-H proton and the methyl group on
C2 are arranged at the same side of the cyclopropane
ring plane. Among two carbonyl carbon atoms in the
indandione fragment, the C1′ atom [downfield signal,
1-Aryl-6,6-dimethyl-2-(2,2-dimethylpropanoyl)-
5,7-dioxaspiro[2.5]octane-4,8-diones VIa and VIb
(general procedure). 1,1-Dibromo-3,3-dimethylbutan-
2-one, 0.015 mol, was added to a mixture of 4 g of
metallic zinc prepared as fine turnings, 7 ml of diethyl
ether, and 10 ml of tetrahydrofuran. The mixture was
heated to initiate the reaction which then occurred
spontaneously. When the reaction was complete, the
mixture was heated for 15 min under reflux and
cooled, the liquid phase was separated by decanting,
0.01 mol of 5-arylmethylidene-2,2-dimethyl-1,3-di-
oxane-4.6-dione IIIa or IIIb was added, and the mix-
ture was heated for 30–40 min under reflux, cooled,
hydrolyzed with 5% acetic acid, and extracted with
benzene. The solvent was distilled off from the extract,
and the residue was recrystallized from ethyl acetate or
methanol.
3
δC 196.87 ppm, J(3-H, C1′) = 4.2 Hz] is oriented cis
with respect to 3-H, whereas the C3′ atom [upfield
3
signal, δC 194.14 ppm, J(3-H, C3') 2.9 Hz] is oriented
trans.
EXPERIMENTAL
The IR spectra were recorded on a Specord 75IR
spectrometer from samples dispersed in mineral oil.
1
The H NMR spectra were measured on a Mercury
Plus-300 instrument (300 MHz) from solutions in
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 4 2010

SHCHEPIN et al.
502
1-(4-Chlorophenyl)-6,6-dimethyl-2-(2,2-dimeth-
ylpropanoyl)-5,7-dioxaspiro[2.5]octane-4,8-dione
7.32 m (2H, 10-H), 7.41 d (2H, 7-H, J = 8.8 Hz),
7.64 d (2H, 6-H, J = 8.8 Hz), 7.75–7.85 m (3H, 4′-H,
5′-H, 6′-H), 8.03 d.t (1H, 7′-H, J = 7.3, 1.1 Hz).
13C NMR spectrum, δC, ppm: 19.57 (CH3), 47.27 (C2),
49.99 (C3), 50.25 (C1), 122.58 (C7′), 122.92 (C4′),
127.47 (C12), 127.60 (C11), 130.31 (C6), 130.76 (C10),
131.82 (C7), 131.91 (C9), 133.65 (C5), 135.32 and
134.99 (C5′, C6), 141.59 (C7a′), 142.57 (C3a′), 192.72
(C4), 194.14 (C3′), 196.87 (C1′). Found, %: C 67.38;
H 3.80. C25H17BrO3. Calculated, %: C 67.43; H 3.85.
(VIa). Yield 33%, mp 186–188°C. IR spectrum, ν,
1
cm–1: 1700, 1720. H NMR spectrum, δ, ppm: 1.25 s
(9H, t-Bu), 1.67 s (3H, CH3), 1.76 s (3H, CH3), 3.96 s
(2H, CH), 7.27–7.32 m (4H, C6H4). Found, %: C 62.51;
H 5.76. C19H21ClO5. Calculated, %: C 62.55; H 5.80.
1-(4-Bromophenyl)-6,6-dimethyl-2-(2,2-dimeth-
ylpropanoyl)-5,7-dioxaspiro[2.5]octane-4,8-dione
(VIb). Yield 36%, mp 197–198°C. IR spectrum, ν,
1
cm–1: 1700, 1730. H NMR spectrum, δ, ppm: 1.24 s
2-(4-Fluorobenzoyl)-3-(4-fluorophenyl)-2-methyl-
spiro[cyclopropane-1,2′-indan]-1′,3′-dione (XIVb).
Yield 51%, mp 148–150°C. IR spectrum, ν, cm–1:
(9H, t-Bu), 1.64 s (3H, CH3), 1.73 s (3H, CH3), 3.90 s
(2H, CH), 7.06–7.43 m (4H, C6H4). Found, %: C 55.71;
H 5.13. C19H21BrO5. Calculated, %: C 55.76; H 5.17.
1
1690, 1660. H NMR spectrum, δ, ppm: 1.90 s (3H,
CH3), 3.59 s (1H, CH), 6.82–7.73 m (12H, Harom).
Found, %: C 74.60; H 3.39. C26H18F2O2. Calculated,
%: C 74.62; H 4.01.
3-Aryl-2-(2,2-dimethylpropanoyl)spiro[cyclo-
propane-1,2′-indan]-1′,3′-diones VIIIa and VIIIb
(general procedure). 1,1-Dibromo-3,3-dimethylbutan-
2-one, 0.015 mol, was added to a mixture of 4 g of
metallic zinc prepared as fine turnings, 7 ml of diethyl
ether, and 10 ml of tetrahydrofuran. The mixture was
heated to initiate the reaction which then occurred
spontaneously. When the reaction was complete, the
mixture was heated for 15 min under reflux and
cooled, the liquid phase was separated by decanting,
0.01 mol of 2-arylmethylideneindan-1,3-dione IVa or
IVb and 5 ml of anhydrous toluene were added, and
the mixture was heated for 30–40 min under reflux,
cooled, hydrolyzed with 5% acetic acid, and extracted
with benzene. The solvent was distilled off from the
extract, and the residue was recrystallized from ethyl
acetate or methanol.
2,3:8,9-Dibenzo-12-phenyldispiro[4.0.5.1]dodeca-
2,8-diene-1,4,7-trione (XVI). 2,2-Dibromo-1,2,3,4-
tetrahydronaphthalen-1-one, 0.024 mol, was added to
a mixture of 2 g of fine zinc turnings, 7 ml of diethyl
ether, and 10 ml of tetrahydrofuran. The mixture was
heated to initiate the reaction which then occurred
spontaneously. When the reaction was complete, the
mixture was heated for 5 min under reflux and cooled,
the liquid phase was separated by decanting and trans-
ferred into a flask charged with 0.02 mol of 2-phenyl-
methylideneindan-1,3-dione (IVa), 10 ml of anhydrous
toluene was added, and the mixture was heated for
60 min under reflux. The mixture was cooled, hydro-
lyzed with 5% acetic acid, and extracted with diethyl
ether, the extract was dried over Na2SO4, the solvent
was distilled off, and the residue was recrystallized
from ethyl acetate. Yield 58%, mp 189–190°C. IR
2-(2,2-Dimethylpropanoyl)-3-phenylspiro[cyclo-
propane-1,2′-indan]-1′,3′-dione (VIIIa). Yield 37%,
mp 159–160°C. IR spectrum, ν, cm–1: 1990, 1705.
1H NMR spectrum, δ, ppm: 1.00 s (9H, t-Bu), 3.59 s
(2H, CH), 7.26–8.00 m (9H, Harom). Found, %: C 79.46;
H 6.02. C22H20O3. Calculated, %: C 79.50; H 6.06.
1
spectrum, ν, cm–1: 1690, 1670. H NMR spectrum, δ,
ppm: 2.57–3.10 m (4H, C6H4), 3.85 s (1H, CH), 7.19–
8.07 m (13H, Harom). Found, %: C 82.49; H 4.76.
C26H18O3. Calculated, %: C 82.52; H 4.79.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 07-03-96035).
2-(2,2-Dimethylpropanoyl)-3-(4-fluorophenyl)-
spiro[cyclopropane-1,2′-indan]-1′,3′-dione (VIIIb).
Yield 36%, mp 162–163°C. IR spectrum, ν, cm–1:
1
1690, 1750. H NMR spectrum, δ, ppm: 1.01 s (9H,
t-Bu), 3.51 d (1H, CH), 3.54 d (1H, CH, J = 9.9 Hz),
6.96–7.85 m (8H, Harom). Found, %: C 75.36; H 5.41.
C22H19FO3. Calculated, %: C 75.41; H 5.47.
REFERENCES
1. Shchepin, V.V., Stepanyan, Yu.G., Silaichev, P.S., Ezhi-
kova, M.A., and Kodess, M.I., Russ. J. Org. Chem., 2007,
vol. 43, p. 1002.
2. Braun, S., Kalinowski, H.-O., and Berger, S., 150 and
More Basic NMR Experiments: A Practical Course,
Weinheim: VCH, 1998, 2nd ed., p. 241.
3. Shchepin, V.V., Silaichev, P.S, Stepanyan, Yu.G., Ka-
lyuzhnyi, M.M., Russkikh, N.Yu., and Kodess, M.I.,
Russ. J. Org. Chem., 2006, vol. 42, p. 973.
Compounds XIVa and XIVb were synthesized
in a similar way.
2-(4-Bromobenzoyl)-2-methyl-3-phenylspiro-
[cyclopropane-1,2′-indan]-1′,3′-dione (XIVa). Yield
53%, mp 172–173°C. IR spectrum, ν, cm–1: 1690,
1
1660. H NMR spectrum, δ, ppm: 1.97 s (1H, CH3),
3.71 s (1H, 3-H), 7.16–7.20 m (3H, 11-H, 12-H),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 4 2010