Synthesis of alkoxy- and phenylsulfanyl-substituted 1,1-dihalospiro[2.2] pentanes and their reactivity toward methyllithium

Article abstract of DOI:10.1134/S1070428012100016

A number of new alkoxy- and phenylsulfanyl-substituted 1,1-dihalospiro[2.2] pentanes bearing different halogen atoms were synthesized. 1,1-Dihalo-4-tert- butoxyspiro[2.2]pentanes reacted with methyllithium at -55 to -10°C to give exclusively 1-tert-butoxy-2-vinylidenecyclopropane. The reaction of 1-bromo-1-fluoro-4-phenylsulfanylspiro[2,2]pentane with methyllithium resulted in replacement of the fluorine atom by methyl group. Pleiades Publishing, Ltd., 2012.

Full text of DOI:10.1134/S1070428012100016

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 10, pp. 1265–1271. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © K.N. Sedenkova, E.B. Averina, I.S. Borisov, Yu.K. Grishin, V.B. Rybakov, T.S. Kuznetsova, N.S. Zefirov, 2012, published in Zhurnal
Organicheskoi Khimii, 2012, Vol. 48, No. 10, pp. 1271–1277.
Synthesis of Alkoxy- and Phenylsulfanyl-Substituted
1,1-Dihalospiro[2.2]pentanes and Their Reactivity
toward Methyllithium
K. N. Sedenkovaa, b, E. B. Averinaa, b, I. S. Borisova, Yu. K. Grishina, V. B. Rybakova,
T. S. Kuznetsovaa, b, and N. S. Zefirova, b
a Faculty of Chemistry, Moscow State University, Leninskie gory 1, Moscow, 119991 Russia
e-mail: elaver@org.chem.msu.ru
b Institute of Physiologically Active Compounds, Russian Academy of Sciences,
Chernogolovka, Moscow oblast, Russia
Received March 7, 2012
Abstract—A number of new alkoxy- and phenylsulfanyl-substituted 1,1-dihalospiro[2.2]pentanes bearing
different halogen atoms were synthesized. 1,1-Dihalo-4-tert-butoxyspiro[2.2]pentanes reacted with methyl-
lithium at –55 to –10°C to give exclusively 1-tert-butoxy-2-vinylidenecyclopropane. The reaction of 1-bromo-
1-fluoro-4-phenylsulfanylspiro[2,2]pentane with methyllithium resulted in replacement of the fluorine atom by
methyl group.
DOI: 10.1134/S1070428012100016
Reactions of geminal dihalocyclopropanes with
alkyllithiums underlie a classical procedure for the
preparation of substituted allenes [1]. However, while
studying chemical properties of polyspirocyclo-
propanes (triangulanes) we found that gem-dihalo-
spiropentanes reacted with methyllithium in an unex-
pected fashion. Only a small amount of allene was
formed at –55°C, whereas the major products were
those resulting from unusual skeletal rearrangement
(Scheme 1) [2]. The product structure depended on the
nature of halogen atoms and other substituents in the
initial spiropentane. Reactions of diiodo-, dibromo-,
and bromochlorospiropentanes with MeLi afforded
monomeric or dimeric halocyclobutenes [3, 4], and the
main reaction pathway of gem-bromofluorospiro-
pentanes was formal replacement of the fluorine atom
Scheme 1.
R1
R4
Hlg2
R5
R2
R3
Et2O
R6
Hlg1 = Hlg2 = Br
R5 = R6
≠
H
R4
R1
Hlg1 = Hlg2 = I, Br
Hlg1 = Br, Hlg2 = Cl
R5 = R6 = H
Me
R1 Br
OEt
R3
R2
R1 Hlg1
Hlg2
R2
R3
Me
R6
R2
R3
Hlg2
R6
+
MeLi
Hlg1 = Br, Hlg2 = F
R4 R5
R1
R4 R5
R1
Hlg2
R2
R3
R5
R6
R2
R3
Hlg1 = Hlg2 = I, Br
Hlg1 = Br, Hlg2 = Cl
R5R6 = (CH2)2
Hlg1
·
Hlg1, Hlg2 = I, Br, Cl, F
R4
R4
1265

SEDENKOVA et al.
1266
by methyl group with formation of 1-halo-1-methyl-
spiropentanes [5] (Scheme 1).
It is known that classical nucleophilic substitution
reactions are not typical for strained carbocycles [8].
Products of formal nucleophilic substitution in three-
membered rings were described mainly for bromo-
cyclopropanes; they are usually formed as a result of
1,2-elimination of HBr and subsequent addition of
nucleophile at the strained double bond in cyclo-
propene intermediate [9]. Such two-step sequence was
proposed for the first time for the reaction of methyl
bromocyclopropanecarboxylate with t-BuOK in
t-BuOH [10]. In our case the reaction of phenoxy-sub-
stituted cyclopropane IV with potassium tert-butoxide
is likely to involve elimination of phenol molecule
with formation of highly reactive chloro(methyl)cyclo-
propene A which takes up t-BuOH molecule generated
during the process to give intermediate B, and dehy-
drochlorination of the latter leads to methylidene-
cyclopropane V. Thus we have revealed previously
unknown formal nucleophilic substitution of phenoxy
group in cyclopropane ring by the action of potassium
tert-butoxide.
We previously studied reactions of methyllithium
with a large series of gem-dihalospiropentanes having
various alkyl, cycloalkyl, and aryl substituents in the
spiropentane fragment. The obtained results allowed us
to propose a general scheme for the dihalotriangulane
rearrangement [3, 6]. In continuation of these studies,
in the present work we tried to involve in reaction with
methyllithium a number of new gem-dihalospiropen-
tanes having electron-donor heteroatom substituents.
Br
Hlg
PhX
Hlg = Br, Cl, F; X = O, S.
A conventional method for the preparation of such
dihalospiropentanes is based on [1+2]-cycloaddition
of dihalocarbenes to 2-phenoxy- and 2-phenylsulfanyl-
cyclopropanes I and II. Various methylidenecyclo-
propanes were previously synthesized in two steps
including addition of chloro(methyl)carbene to the
double bond of the corresponding alkene and subse-
quent dehydrohalogenation of the adduct [7]. We made
an attempt to obtain methylidenecyclopropane I in
such a way and found that the first step smoothly
afforded 1-chloro-1-methyl-2-phenoxycyclopropane
(IV) in a high yield (Scheme 2). However, the sub-
sequent dehydrohalogenation of IV with potassium
tert-butoxide in DMSO unexpectedly produced tert-
butoxy-substituted methylidenecyclopropane V as the
only product, i.e., formal nucleophilic replacement of
the phenoxy group by tert-butoxy occurred. We failed
to change the reaction direction toward formation of
target compound I by varying the conditions (tempera-
ture, solvent, reactant ratio, and order of their addition)
or using other bases instead of potassium tert-butoxide
[KOH, NaOEt, (Me3Si)2NNa].
Sulfanyl derivative II was prepared as described in
[11] from lithiated methylidenecyclopropane and di-
phenyl disulfide (Scheme 3). Substituted methylidene-
cyclopropanes II and V were brought into [1 +2]-
cycloaddition reactions with various dihalocarbenes.
The addition of dibromocarbene to methylidenecyclo-
propane V was carried out under the Doering–
Hoffmann reaction conditions [12], while mixed di-
halocarbenes, i.e., those having two different halogen
atoms, reacted with V according to Makosza [13] (see
table). tert-Butoxy-substituted dihalospiropentanes
VIa–VIc were isolated in good or satisfactory yields
1
and were characterized by H and 13C NMR spectra
and elemental analyses (Scheme 4).
Phenylsulfanyl derivative II turned out to be low
reactive toward dihalocarbenes. The reaction of II with
dibromocarbene under different conditions gave no
target dibromospiropentane. Moreover, the major prod-
uct formed in the Makosza reaction was tetrabromide
Scheme 2.
CH2
MeCHCl2
BuLi, Et2O
–40 to –30°C
Cl
t-BuOK
DMSO
PhO
Me
I
PhO
CH2
CH2
PhO
IV, 88%
Cl
Me
Cl
III
t-BuOH
–PhOH
–HCl
Me
t-BuO
t-BuO
V, 48%
A
B
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 10 2012

SYNTHESIS OF ALKOXY- AND PHENYLSULFANYL-SUBSTITUTED
1267
Scheme 3.
Reaction conditions and yields of 1-bromo-1-halo-4-tert-
butoxyspiro[2.2]pentanes VIa–VIc
BuLi, THF
–10°C
PhS–SPh
THF, –78°C
CH2
CH2
CH2
Compound
Reaction conditions
Yield,a %
no.
Li
PhS
II, 17%
VIa
t-BuOK, petroleum ether
56
67
40
50% NaOH, CH2Cl2, dibenzo-
18-crown-6
VIb
VIc
Scheme 4.
Br
50% NaOH, CH2Cl2, BTEAC
Hlg
CHBr2Hlg, base
a
After chromatographic isolation.
V
t-BuO
ment products of the cyclobutane series were formed
in reactions of tert-butoxy-substituted dihalospiropen-
tanes VIa–VIc, while the only reaction pathway was
that leading to allene IX (Scheme 6).
VIa–VIc
Hlg = Br (a), Cl (b), F (c).
VII which may be regarded as product of formal ad-
dition of carbon tetrabromide to the double bond of
alkene II (Scheme 5). The structure of VII was unam-
biguously determined by X-ray analysis (see figure).
Scheme 6.
MeLi, Et2O
·
CH2
VIa–VIc
t-BuO
Scheme 5.
IX
CBr3
CHBr3, 50% NaOH
CH2Cl2, BTEAC
The reaction of phenylsulfanyl derivative VIII with
methyllithium afforded exclusively bromo(methyl)-
spiropentane X as formal product of replacement of the
fluorine atom by methyl group (Scheme 7).
Br
PhS
VII, 35%
II
F
CHBr2F, 50% NaOH
CH2Cl2, BTEAC
Br
Scheme 7.
Me
Br
PhS
MeLi, Et2O
VIII
VIII, 52%
PhS
In keeping with published data, analogous tetra-
bromides were formed in reactions of sterically hin-
dered or electrophilic alkenes with bromoform under
phase transfer catalysis [14]. It was presumed that
generation of dibromocarbene is accompanied by
formation of carbon tetrabromide which then adds to
the double bond of alkene according to the radical
mechanism [15]. We never observed formation of
tetrabromo-substituted adducts while preparing various
gem-dibromospiropentanes from substituted methyli-
denecyclopropanes [3]; therefore, the presence of
a bulky phenylsulfanyl substituent in molecule II con-
siderably reduces its reactivity in [1+2]-cycloaddition
processes. We succeeded in obtaining the desired
spiropentane adduct VIII only by reaction of alkene II
with less bulky bromofluorocarbene (Scheme 5).
X, 40%
To conclude, we have studied the reactivity of
a number of gem-dihalospiropentanes having various
halogen atoms and heteroatom substituents toward
Br4
Br3
C12
C11
C33
Br1
C1
C32
C34
Br2
C3
C2
C31
C35
C36
S31
New gem-dihalospiropentanes VIa–VIc and VIII
were brought into reaction with methyllithium under
the conditions described previously, which were varied
depending on the halogen nature [3–5]. No rearrange-
Structure of the molecule of 1-bromo-1-(2,2,2-tribromo-
ethyl)-2-phenylsulfanylcyclopropane (VII) according to the
X-ray diffraction data.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 10 2012

SEDENKOVA et al.
1268
3
methyllithium at low temperature and found that the
presence of a bulky alkoxy substituent in the spiro-
pentane fragment hampers carbenoid skeletal rear-
rangement and forces the reaction to follow exclu-
sively the carbene path with formation of allenes.
1-Bromo-1-fluoro-4-phenylsulfanylspiro[2.2]pentane
reacts with methyllithium to give only product of
formal replacement of the fluorine atom by methyl
group without rearrangement. Thus the examined
dihalospiropentanes do not tend to undergo carbenoid
skeletal rearrangement.
4J = 2.0, 2.6), 2.93 d.d.d.d (1H, CH, J = 7.7, 4.2, 4J =
2.1, 2.3), 5.58–5.61 m and 5.66–5.68 m (1H each,
3
4
=CH2), 7.20 t.t (1H, Harom, J = 7.4, J = 1.2), 7.31–
7.36 m (2H, Harom), 7.42–7.46 m (2H, Harom). 13C NMR
spectrum, δC, ppm (J, Hz): 14.32 (CH2, 1J = 164.6, 2J =
9.6, 3.8), 15.66 (CH, J = 180.1), 106.49 (=CH2, 1J =
1
2
162.8, J = 2.8, 5.2), 125.70 (CHarom), 127.37 (2C,
CHarom), 129.07 (2C, CHarom), 132.09 (C=), 138.22
(Carom). Found: m/z 163.0576 [M + H]+. C10H10S. Cal-
culated: [M + H] 163.0581.
1-Chloro-1-methyl-2-phenoxycyclopropane (IV).
A solution of 9.70 g (0.081 mol) of vinyloxybenzene
and 12.02 g (0.122 mol) of 1,1-dichloroethane in 45 ml
of anhydrous diethyl ether was cooled to –40°C, a so-
lution of 0.130 mol of butyllithium (81.0 ml of a 1.6 M
solution in hexane) was added over a period of 1.5 h
under argon. The mixture was stirred for 4 h at room
temperature and treated with 80 ml of water, the
organic layer was separated, and the aqueous phase
was extracted with diethyl ether (3×50 ml). The ex-
tracts were combined with the organic phase, washed
with a saturated solution of sodium chloride, and dried
over MgSO4. The solvent was distilled off under
reduced pressure, and the residue was distilled in
a vacuum. Yield 13.0 g (88%), mixture of stereo-
isomers A and B (2:1). Colorless liquid, bp 127°C
(2 mm), Rf 0.75 (petroleum ether–ethyl acetate, 5:1).
1H NMR spectrum, δ, ppm (J, Hz), isomer A: 1.17 d.d
EXPERIMENTAL
The H and 13C NMR spectra were recorded on
1
a Bruker Avance-400 instrument at 400 and 100 MHz,
respectively, from solutions in CDCl3 using the solvent
signals as reference (δ 7.24 ppm, δC 77.10 ppm). The
mass spectra (electron impact, 70 eV) were obtained
on a Finnigan MAT ITD-700 mass spectrometer. The
high-resolution mass spectra (positive ion detection)
were run on Bruker micrOTOF II (ESI) and JEOL
GCmate instruments (70 eV). The X-ray analysis of
a single crystal of compound VII was performed at
room temperature on an Enraf–Nonius CAD-4 auto-
matic diffractometer (λAgKα irradiation, graphite
monochromator, ω-scanning). The progress of reac-
tions and the purity of products were monitored by
TLC on Silufol UV-254 plates. Silica gel Merck (40–
60 μm) was used for preparative column chroma-
tography.
2
3
2
(1H, CH2, J = 7.8, J = 4.2), 1.51 d.d (1H, CH2, J =
7.8, 3J = 8.0), 1.61 s (3H, CH3), 3.96 d.d (1H, CH, 3J =
4.2, 8.0), 7.02–7.07 m (3H, Ph), 7.33–7.38 m (2H, Ph);
isomer B: 1.25–1.30 m (1H, CH2), 1.36 d.d (1H, CH2,
2J = 7.7, 3J = 4.4), 1.74 s (3H, CH3), 3.96 d.d (1H, CH,
3J = 4.4, 7.4), 7.02–7.07 m (3H, Ph), 7.33–7.38 m (2H,
Ph). 13C NMR spectrum, δC, ppm (J, Hz), isomer A:
[(2-Methylidenecyclopropyl)sulfanyl]benzene
(II). A solution of 0.021 mol of butyllithium (8.75 ml
of a 1.6 M solution in hexane) in 20 ml of anhydrous
THF was cooled to –10°C, a solution of 1.08 g
(0.020 mol) of methylidenecyclopropane in 4 ml of
anhydrous THF was added dropwise, the mixture was
stirred for 1 h at 0°C and cooled to –78°C, and a solu-
tion of 2.89 g (0.020 mol) of benzenesulfenyl chloride
in 6 ml of anhydrous THF was added. The mixture was
allowed to warm up to 0°C and treated with an equal
volume of ice water, the organic phase was separated,
the aqueous phase was extracted with diethyl ether
(3×20 ml), the extracts were combined with the or-
ganic phase, washed with water (3×20 ml), and dried
over MgSO4, the solvent was distilled off under
reduced pressure, and the product was isolated by
column chromatography. Yield 0.55 g (17%), colorless
1
1
20.92 (CH3, J = 129), 22.81 (CH2, J = 162), 41.81
(C1), 60.92 (CH, J = 189), 114.76 (2C, CHarom, J =
1
1
1
159), 121.65 (CHarom, J = 160), 129.63 (2C, CHarom
,
1J = 159), 158.19 (Carom); isomer B: 22.42 (CH2, J =
1
164), 26.05 (CH3, J = 128), 42.36 (C1), 58.48 (CH,
1
1J = 184), 114.90 (2C, CHarom, J = 159), 121.65
1
1
1
(CHarom, J = 160), 129.48 (CHarom, J = 159), 158.23
(Carom). Found, %: C 65.71; H 5.89. C10H11ClO. Cal-
culated, %: C 65.76; H 6.07.
1-tert-Butoxy-2-methylidenecyclopropane (V).
A solution of 5.61 g (50 mmol) of potassium tert-
butoxide in 20 ml of DMSO was heated to 40°C,
6.02 g (33 mmol) of chloro(methyl)cyclopropane IV
was added under argon over a period of 1 h, and the
mixture was stirred for 4 h at room temperature and
treated with an equal volume of ice water. The organic
1
liquid, Rf 0.2 (petroleum ether). H NMR spectrum, δ,
2
3
ppm (J, Hz): 1.42 d.d.d.d (1H, CH2, J = 9.3, J = 4.2,
4J = 2.1, 2.7), 1.88 d.d.d.d (1H, CH2, 2J = 9.3, 3J = 7.7,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 10 2012

SYNTHESIS OF ALKOXY- AND PHENYLSULFANYL-SUBSTITUTED
1269
phase was separated, the aqueous phase was extracted
with diethyl ether (3×20 ml), the extracts were com-
bined with the organic phase, washed with water
(3×20 ml), and dried over MgSO4, the solvent was
distilled off under reduced pressure, and the residue
was distilled in a vacuum. Yield 1.99 g (48%), color-
solvent was distilled off under reduced pressure, and
the residue was purified by column chromatography.
The product was a mixture of stereoisomers A and B at
a ratio of 1:1. Yield 1.87 g (67%), colorless liquid,
1
Rf 0.5 (petroleum ether–ethyl acetate, 1:1). H NMR
spectrum, δ, ppm (J, Hz): 1.26 s and 1.27 s (9H each,
t-Bu), 1.29–1.33 m (2H), 1.34–1.37 m (1H), 1.49–
1.52 m (1H), 1.96–2.03 m (4H), 3.72 d.d.d (1H, CH,
1
less liquid, bp 58–60°C (60 mm). H NMR spectrum,
δ, ppm: 1.21–1.27 m (1H, CH2,), 1.30 s (9H, t-Bu),
1.39–1.46 m (1H, CH2), 3.65–3.70 m (1H, CH),
5.52 br.s and 5.67 br.s (1H each, CH2=). 13C NMR
3
4
2
2J = 3.9, J = 6.8, J = 1.4), 3.85 d.d.d (1H, CH, J =
3.9, J = 6.7, J = 1.3). 13C NMR spectrum, δC, ppm
(J, Hz): 16.85 (CH2, J = 163), 18.15 (CH2, J = 163),
27.27 (CH2, J = 165), 27.31 (CH2, J = 165), 28.23
and 28.28 (CH3, J = 125), 30.75 and 30.81 (Cspiro),
47.23 and 47.84 (CBrCl), 53.77 (CH, J = 183), 54.90
(CH, J = 184), 75.12 and 75.17 (CMe3). Found, %:
3
4
1
1
1
spectrum, δC, ppm (J, Hz): 12.91 (CH2, J = 161),
1
1
1
1
28.23 (CH3, J = 126), 46.25 (C1, J = 181), 75.03
(CMe3), 106.68 (CH2=, 1J = 161), 133.80 (C2). Found,
%: C 76.07; H 11.37. C8H14O. Calculated, %: C 76.14;
H 11.18.
1
1
1
C 42.47; H 5.63. C9H14BrClO. Calculated, %: C 42.63;
H 5.57.
1,1-Dibromo-4-tert-butoxyspiro[2.2]pentane
(VIa). A mixture of 1.39 g (11 mmol) of alkene V and
2.9 g (26 mmol) of potassium tert-butoxide in 10 ml
of petroleum ether was cooled to 0°C, 3.34 g (1.2 ml,
13 mmol) of bromoform was added dropwise under
stirring. The mixture was allowed to warm up to room
temperature, stirred for 72 h, and treated with an equal
volume of ice water. The organic phase was separated,
the aqueous phase was extracted with diethyl ether
(3×10 ml), the extracts were combined with the or-
ganic phase, washed with water (3×10 ml), and dried
over MgSO4, the solvent was distilled off under
reduced pressure, and the residue was purified by
column chromatography. Yield 1.84 g (56%), colorless
Bromofluorospiropentanes VIc and VIII (general
procedure). A mixture of 16 mmol of alkene II or V,
9.22 g (48 mmol) of dibromofluoromethane, and
0.73 g (2.6 mmol) of benzyl(triethyl)ammonium chlo-
ride in 10 ml of methylene chloride was cooled to 0°C,
10 ml of 50% aqueous sodium hydroxide was added
dropwise under stirring, and a drop of ethanol was then
added. The mixture was stirred for 48 h at room tem-
perature and treated with an equal volume of ice water.
The organic phase was separated, the aqueous phase
was extracted with methylene chloride (3 ×20 ml),
the extracts were combined with the organic phase,
washed with water (3×20 ml), and dried over MgSO4,
the solvent was distilled off under reduced pressure,
and the residue was purified by column chroma-
tography.
1
oily substance, Rf 0.2 (petroleum ether). H NMR
spectrum, δ, ppm (J, Hz): 1.27 s (9H, t-Bu), 1.35 d.d.d
2
3
4
(1H, CH2, J = 4.0, J = 6.1, J = 0.5), 1.39–1.42 m
2
4
(1H, CH2), 2.06 d.d (1H, CH2, J = 6.7, J = 1.4),
2.11 br.d (1H, CH2, 2J = 6.7), 3.77 d.d.d (1H, CH, 3J =
4.0, 6.7, 4J = 1.4). 13C NMR spectrum, δC, ppm (J, Hz):
18.78 (CH2, J = 163), 28.14 (CH2, J = 166), 28.31
(CH3, J = 126), 30.41 (Cspiro), 31.33 (Cspiro), 55.56
H5a
H4
H5s
SPh
1
1
1
H2s
H2a
2s
H5a
SPh
H5s
H4
F
H
1
(CH, J = 182), 75.21 (CMe3). Found, %: C 36.26;
H2a
F
H 4.75. C9H14Br2O. Calculated, %: C 36.27; H 4.74.
Br
Br
A
B
1-Bromo-1-chloro-4-tert-butoxyspiro[2.2]pen-
tane (VIb). A mixture of 1.39 g (11 mmol) of alkene
V, 2.74 g (13 mmol) of dibromochloromethane, and
0.1 g (0.3 mmol) of dibenzo-18-crown-6 in 22 ml of
methylene chloride was cooled to 0°C, 22 ml of
50% aqueous sodium hydroxide was added dropwise
under stirring, and the mixture was stirred for 24 h at
room temperature and poured onto ice (20 g). The
organic phase was separated, the aqueous phase was
extracted with methylene chloride (3×10 ml), the ex-
tracts were combined with the organic phase, washed
with water (3×10 ml), and dried over MgSO4, the
1-Bromo-1-fluoro-4-phenylsulfanylspiro[2.2]-
pentane (VIc) was obtained from 2.59 g of alkene II.
The product was a mixture of two stereoisomers A and
B at a ratio of 1:0.8. Yield 2.17 g (52%), colorless oily
substance, Rf 0.1 (petroleum ether). H NMR spec-
trum,* δ, ppm (J, Hz): isomer A: 1.10 br.d.d.d (1H,
1
2
3
4
5-Ha, J = 5.3, J5a,4 = 4.8, JHF = 8.6), 1.42–1.47 m
* The NMR spectra were recorded in CDCl3–C6D6 (1:2) to avoid
overlap of signals from protons in the cyclopropane fragment of
the two isomers.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 10 2012

SEDENKOVA et al.
(2H, 5-Hs, 2-Ha), 1.77 br.d.d (1H, 2-Hs, 2J = 7.8, 3JHF
1270
=
of ice water. The organic phase was separated, the
aqueous phase was extracted with methylene chloride
(3×4 ml), the extracts were combined with the organic
phase, washed with water (3×4 ml), and dried over
MgSO4, the solvent was distilled off under reduced
pressure, and the residue was purified by column
chromatography. Yield 0.11 g (35%), colorless crys-
tals, mp 51°C, Rf 0.1 (petroleum ether). 1H NMR spec-
3
3
12.8), 2.82 d.d (1H, 4-H, J5a,4 = 4.8, J5s,4 = 8.1),
7.17–7.23 m (1H, Harom), 7.27–7.34 m (2H, Harom),
7.36–7.41 m (2H, Harom); isomer B: 1.25 d.d (1H, 5-Ha,
2J = 5.2, J5a,4 = 5.1), 1.51 d.d (1H, 2-Ha, J = 7.9,
3
2
3JHF = 4.2), 1.65 d.d (1H, 5-Hs, J = 5.2, J5s,4 = 8.0),
2
3
1.68 br.d.d (1H, 2-Hs, 2J = 7.9, 3JHF = 12.1), 2.66 d.d.d
3
3
4
(1H, 4-H, J5a,4 = 5.1, J5s,4 = 8.0, JHF = 1.3), 7.17–
7.23 m (1H, Harom), 7.27–7.34 m (2H, Harom), 7.36–
7.41 m (2H, Harom). 13C NMR spectrum, δC, ppm
2
trum, δ, ppm (J, Hz): 1.95 d.d.d (1H, 3-H, J = 7.9,
4
2
3
3J = 9.7, J = 1.4), 2.04 d.d (1H, 3-H, J = 7.9, J =
(J, Hz): isomer A: 17.78 (C5), 21.02 (C4, JCF = 2.2),
6.6), 2.91 d.d (1H, 2-H, J = 9.7, 6.6), 3.68 d (1H,
3
3
22.14 (C2, JCF 11.8), 29.80 (Cspiro, JCF = 10.4), 83.45
(C1, 1JCF = 305), 125.65 (CHarom), 126.73 (2C, CHarom),
129.03 (2C, CHarom), 136.34 (Carom); isomer B: 16.64
1-CH2, 2J = 16.7), 3.90 d.d (1H, 1-CH2, 2J = 16.7, 4J =
2
2
3
4
1.4), 7.23 t.t (1H, Harom, J = 7.1, J = 1.4), 7.30–
7.40 m (4H, Harom). 13C NMR spectrum, δC, ppm
(C5, JCF = 2.2), 21.84 (C2, JCF = 11.2), 22.81 (C4),
(J, Hz): 22.30 (C3, JCH = 167), 30.29 (1-CH2, JCH
=
3
2
1
1
29.58 (Cspiro, JCF = 10.0), 83.17 (C1, JCF = 306),
125.88 (CHarom), 127.56 (2C, CHarom), 128.91 (2C,
CHarom), 136.09 (Carom). Found: m/z 271.9676 [M]+.
C11H10BrFS. Calculated: M 271.9671.
184), 34.67 (CBr3), 35.81 (C1), 60.89 (C2, 1JCH = 135),
2
1
1
125.82 (CHarom, JCH = 165), 126.39 (2C, CHarom
,
1JCH = 161), 129.38 (2C, CHarom, JCH = 162), 136.13
(Carom). Mass spectrum (EI), m/z (Irel, %): 498 (2), 496
(7), 494 (10), 492 (7), 491 (2) [M + H]+, 417 (23), 415
(69), 413 (69), 411 (23) [M + H – Br]+, 335 (6), 333
(12), 331 (6) [M + H – 2Br] +, 305 (10), 303 (10) , 255
(40), 253 (52), 251 (27), 229 (27), 227 (28), 222 (34),
218 (19), 201 (15), 199 (15), 173 (63), 147 (100), 109
(86), 91 (45), 65 (75), 50 (51), 45 (57), 39 (41).
C11H10Br4S. M 493.88.
1
1-Bromo-4-tert-butoxy-1-fluorospiro[2.2]pentane
(VIII) was obtained from 2.02 g of alkene V. The
product was a mixture of two stereoisomers A and B at
a ratio of 1:0.7. Yield 1.52 g (40%), colorless liquid,
1
Rf 0.5 (petroleum ether). H NMR spectrum, δ, ppm
(J, Hz): 1.13–1.19 m (2H, CH2), 1.25 s (9H, t-Bu, B),
1.26 s (9H, t-Bu, A), 1.33–1.37 m (1H, CH2), 1.47–
1.53 m (1H, CH2), 1.71–1.76 m (2H, CH2), 1.93–
Reaction of dihalospiropentanes VIa–VIc and
VIII with methyllithium (general procedure). A solu-
tion of 5.0 mmol of compound VIa, VIb, VIc, or VIII
in 10 ml of diethyl ether was cooled to –55 (VIa, VIb)
or –10°C (VIc, VIII), 5.0 ml (7.5 mmol) of a 1.5 N
solution of methyllithium in diethyl ether was added
dropwise, and the mixture was stirred for 1 h at the
same temperature. The mixture was then allowed to
warm up to 0°C and treated with an equal volume of
ice water. The organic phase was separated, the aque-
ous phase was extracted with diethyl ether (3×5 ml),
the extracts were combined with the organic phase,
washed with 10 ml of water, and dried over MgSO4,
the solvent was distilled off under reduced pressure,
and the residue was purified by column chroma-
tography.
2
3
2.03 m (2H, CH2), 3.63 d.d.d (1H, CH, J = 3.9, J =
6.7, J = 1.5, B), 3.83–3.87 m (1H, CH, A). 13C NMR
4
spectrum, δC, ppm (J, Hz): 15.02 (CH2, 1JCH2 = 164, B),
1
16.63 (CH2, JCH = 163, A), 22.15 (CH2, JCF = 11.8,
1JCH = 165, B), 22.37 (CH2, JCF = 11.8, JCH = 165,
2
1
1
1
A), 28.07 (CH3, JCH = 123, A), 28.19 (CH3, JCH
=
1
123, B), 29.70 (Cspiro, A, B), 51.85 (CH, JCH = 166,
A), 53.50 (CH, 1JCH = 166, B), 74.97 (CMe3, B), 75.16
1
(CMe3, A), 84.03 (CBrF, JCF = 305), 85.11 (CBrF,
1JCF = 303). Found, %: C 45.77; H 5.94. C9H14BrFO.
Calculated, %: C 45.59; H 5.95.
1-Bromo-1-(2,2,2-tribromoethyl)-2-phenylsul-
fanylcyclopropane (VII).** A mixture of 0.10 g
(0.62 mmol) of alkene II, 0.78 g (3.1 mmol) of CHBr3,
and 0.02 g (0.01 mmol) of BTEAC in 3 ml of meth-
ylene chloride was cooled to 0°C, 2.5 ml of 50%
aqueous sodium hydroxide was added dropwise under
stirring, and a drop of ethanol was then added. The
mixture was allowed to warm up to room temperature,
stirred for 10 days, and treated with an equal volume
1-tert-Butoxy-2-vinylidenecyclopropane (IX) was
obtained from 1.03 g of VIa (yield 0.48 g, 69%),
0.87 g of VIb (0.33 g, 48%), or 0.81 g of VIc (0.39 g,
57%). Colorless oily substance, Rf 0.7 (petroleum
1
ether). H NMR spectrum, δ, ppm: 1.28 s (9H, t-Bu),
1.70–1.78 m and 1.80–1.87 m (1H each, CH2), 3.94–
3.98 m (1H, CH), 4.78–4.84 m and 4.85–4.91 m (1H
each, CH2=). 13C NMR spectrum, δC, ppm (J, Hz):
** The CIF file containing complete crystallographic data for
compound IX (entry no. CCDC 854970) is available from
www.ccdc.cam.ac.uk/data_request/cif.
1
1
16.28 (CH2, JCH = 165), 28.14 (CH3, JCH = 125),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 10 2012

SYNTHESIS OF ALKOXY- AND PHENYLSULFANYL-SUBSTITUTED
1271
1
2. Lukin, K.A., Zefirov, N.S., Yufit, D.S., and Struch-
51.03 (CH, JCH = 184), 75.81 (CMe3), 76.38 (CH2=,
1JCH 167), 79.24 (C2), 194.54 (=C=). Found:
m/z 138.1045 [M]+. C9H14O. Calculated: M 138.1045.
kov, Y.T., Tetrahedron, 1992, vol. 48, p. 9977.
3. Averina, E.B., Karimov, R.R., Sedenkova, K.N.,
Grishin, Yu.K., Kuznetzova, T.S., and Zefirov, N.S.,
Tetrahedron, 2006, vol. 62, p. 8814; Sedenkova, K.N.,
Averina, E.B., Grishin, Yu.K., Kuznetsova, T.S., and
Zefirov, N.S., Russ. J. Org. Chem., 2008, vol. 44,
p. 958; Averina, E.B., Sedenkova, K.N., Grishin, Yu.K.,
Kuznetzova, T.S., and Zefirov, N.S., Arkivoc, 2008,
part (iv), p. 71.
4. Sedenkova, K.N., Averina, E.B., Grishin, Yu.K., Kuzne-
tsova, T.S., and Zefirov, N.S., Tetrahedron, 2010,
vol. 66, p. 8089.
5. Averina, E.B., Sedenkova, K.N., Borisov, I.S., Gri-
shin, Yu.K., Kuznetsova, T.S., and Zefirov, N.S., Tetra-
hedron, 2009, vol. 65, p. 5693.
6. Zefirov, N.S. and Kuznetsova, T.S., Synlett, 2011,
p. 2299; Sedenkova, K.N., Averina, E.B., Gri-
shin, Yu.K., Rybakov, V.B., Kuznetzova, T.S., and
Zefirov, N.S., Eur. J. Org. Chem., 2010, p. 2145.
7. Zefirov, N.S., Kozhushkov, S.I., Kuznetsova, T.S.,
Kokoreva, O.V., Lukin, K.A., and Tratch, S.S., J. Am.
Chem. Soc., 1990, vol. 112, p. 7702.
8. Turkenburg, L.A.M., de Wolf, W.H., Bickelhaupt, F.,
Stam, C.H., and Konijn, M., J. Am. Chem. Soc., 1982,
vol. 104, p. 3471.
9. Banning, J.E., Prosser, A.R., Alnasleh, B.K.,
Smarker, J., Rubina, M., and Rubin, M., J. Org. Chem.,
2011, vol. 76, p. 3968.
1-Bromo-1-methyl-4-phenylsulfanylspiro[2.2]-
pentane (X) was obtained from 1.37 g of bromo-
fluorospiropentane VIII. The product was a mixture of
two stereoisomers A and B at a ratio of 1:0.5. Yield
0.54 g (40%), colorless oily substance, Rf 0.1 (petro-
leum ether). 1H NMR spectrum, δ, ppm (J, Hz): isomer
A: 1.32–1.39 m (2H, CH2), 1.40 d and 1.62 d (1H
each, CH2, 2J = 6.1), 1.77 s (3H, CH3), 2.77 d.d.d (1H,
3
4
CH, J = 7.3, 4.2, J = 1.3), 7.08–7.45 m (5H, Ph);
isomer B: 1.32–1.39 m (2H, CH2), 1.34 d and 1.57 d
2
(1H each, CH2, J = 6.0), 1.74 s (3H, CH3), 2.83 d.d
3
(1H, CH, J = 7.3, 4.2), 7.08–7.45 m (5H, Ph).
13C NMR spectrum, δC, ppm (J, Hz): isomer A: 16.89
(C5, J = 166), 22.09 (C2, JCH = 158), 22.64 (C4, J =
1
1
1
1
164), 27.77 (CH3, J = 130), 29.82 (Cspiro), 126.21
(CHarom), 128.04 (2C, CHarom), 128.86 (2C, CHarom),
137.09 (Carom); isomer B: 19.05 (C5, J = 160), 21.27
1
(C4, J = 163), 22.01 (C2, J = 163), 27.56 (CH3, J =
127), 29.49 (Cspiro), 126.01 (CHarom), 127.87 (2C,
CHarom), 128.80 (2C, CHarom), 137.09 (Carom). Found:
m/z 271.9676 [M]+. C12H13BrS. Calculated:
M 271.9671.
1
1
1
This study was performed under financial support
by the Russian Foundation for Basic Research (project
nos. 09-03-00717-a, 11-03-01040-a) and by the Chem-
istry and Materials Science Department of the Russian
Academy of Sciences (program no. 1 “Theoretical and
Experimental Study on the Nature of Chemical Bond
and Mechanisms of the Most Important Chemical
Reactions and Processes”).
10. Wiberg, K.B., Barnes, R.K., and Albin, J., J. Am. Chem.
Soc., 1957, vol. 79, p. 4994.
11. De Meijere, A., Kozhushkov, S.I., and Zefirov, N.S.,
Synthesis, 1993, p. 681.
12. Doering, W.v.E. and Hoffmann, A.K., J. Am. Chem.
Soc., 1954, vol. 76, p. 6162.
13. Mąkosza, M. and Wawrzyniewicz, M., Tetrahedron
Lett., 1969, vol. 10, p. 4659.
14. Dehmlow, E.V. and Lissel, M., Chem. Ber., 1978,
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 10 2012