Gem-Bromochlorospiropentane reactivity toward methyllithium: An unusual carbenoid rearrangement

Article abstract of DOI:10.1016/j.tet.2010.07.054

A skeletal carbenoid rearrangement of the gem-bromochlorospiropentanes in the presence of methyllithium has been studied. The synthetic and mechanistic aspects of this rearrangement as well as the influence of the halogen atom nature on the reaction pathway are discussed.

Full text of DOI:10.1016/j.tet.2010.07.054

Tetrahedron 66 (2010) 8089e8094
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
gem-Bromochlorospiropentane reactivity toward methyllithium: an unusual
carbenoid rearrangement
*
Kseniya N. Sedenkova, Elena B. Averina, Yuri K. Grishin, Tamara S. Kuznetzova , Nikolai S. Zefirov
Department of Chemistry, Moscow State University, Leninskie Gory 1/3, 119991 Moscow, Russia Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 11 May 2010
Received in revised form 1 July 2010
Accepted 20 July 2010
Available online 24 July 2010
A skeletal carbenoid rearrangement of the gem-bromochlorospiropentanes in the presence of methyl-
lithium has been studied. The synthetic and mechanistic aspects of this rearrangement as well as the
influence of the halogen atom nature on the reaction pathway are discussed.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Carbenoids
Methyllithium
Spiro compounds
Halogenocyclobutenes
gem-Dihalogenospiropentanes
1. Introduction
R1
R1
R4
R1
R2
R3
R4
R1 Br
Br
Br
R6
R5
R2
R3
X
R6
R2
R3
R4
X=Br
X=F, Br R2
R3
R4
+ CH3Li
C
R5=R6=H
The reaction of gem-dihalogenocyclopropanes with alkyl-
lithium reagents is a traditional method for the synthesis of
substituted allenes (the DoeringeLaFlamme reaction).1 However,
gem-dihalogeno substituted spiropentanesdthe substrates con-
taining unique strained frameworkdwere found to react with
alkyllithium reagents in quite a different way.2 Recently we have
described our investigations of gem-dibromospiropentanes and
gem-bromofluorospiropentanes reactivity toward methyllithium.3,4
When treated with methyllithium at low temperature (ꢀ55 ꢁC),
dibromospiropentanes underwent carbocationic skeletal rear-
rangement leading to monomeric or dimeric bromocyclobutenes.2,3
On the other hand, the preferable pathway of gem-bromo-
fluorospiropentane reaction with methyllithium was the formal
substitution of the fluorine atom for a methyl group with the re-
tention of the spiropentane framework (Scheme 1).4
After we had established such a dramatic influence of the hal-
ogen atom on the reaction pathway, we decided to study a series of
mixed gem-bromochlorospiropentanes in the reaction with meth-
yllithium. Taking the previous results into consideration, we could
expect the formation of rearranged products in addition to the
substitution of one of the halogen atoms for a methyl group with
the gem-bromochlorospiropentanes. It is of interest to determine if
R5
X=Br
X=F
R1
R1
Br
Br
R2
R2
R3
CH3
R6
R3
R4
Br
R5 R6
R4
R5
Scheme 1. Reaction of gem-dihalogenospiropentanes with methyllithium.
the change in the nature of the halogen atom (Br, Cl, F) results in
a change of reactivity.
2. Results and discussion
A series of previously unknown gem-bromochlorospiropentanes
1e8 were obtained via bromochlorocarbene cycloaddition to the
corresponding alkylidenecyclopropanes under PTC conditions
(Table 1). According to literature data, the possible formation of
dibromospiropentanes as byproducts could be prevented by using
dibenzo-18-crown-6 as phase-transfer catalyst.5 Indeed, the target
bromochlorospiropentanes 1e8 were the sole products obtained
under these conditions.
gem-Bromochlorospiropentanes 1e8 were treated with meth-
yllithium at low temperature. We have previously shown ꢀ55 ꢁC to
be the most favorable temperature for gem-dibromospiropentane
skeletal rearrangement. However, gem-bromochlorospiropentanes
* Corresponding author. Tel.: þ7 095 9393969; fax: þ7 095 9390290; e-mail
address: kuzn@org.chem.msu.ru (T.S. Kuznetzova).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.07.054

8090
K.N. Sedenkova et al. / Tetrahedron 66 (2010) 8089e8094
Table 1
Reaction of unsubstituted gem-bromochlorospiropentane
1
Synthesis of gem-bromochlorospiropentanes
with methyllithium led to dimeric chlorocyclobutene 9 and bro-
mocyclobutene 10 in a ratio of 4:1 (Table 2). This ratio did not
change while lowering the temperature to ꢀ78 ꢁC. While using
butyllithium or tert-butyllithium instead of methyllithium we ob-
served only traces of the halogenocyclobutenes in the reaction
mixture, besides the products of polymerization or decomposition.
Basing on the earlier obtained data for gem-dihalogenospir-
opentane carbenoid rearrangement,3 we can suppose the following
method for cyclobutene formation (Scheme 2). In the first step, the
halogenophilic substitution of the bromine atom occurs leading to
chlorolithium carbenoid I. In the next step nucleophilic attack of
the CeC bond at the carbenoid center takes place giving the fused
species II, which isomerizes quickly into four-membered ring III.
Then lithium migration in the allylic system leads to alkyllithium
intermediate Va. Another halogenophilic reaction of Va with 1 re-
sults in alkylhalogenide VIa, whose interaction with alkyllithium
intermediate Va affords chlorocyclobutene 9.
R1
R1 Br
R2
R3
R6 CHBr2Cl, 50% NaOH
R2
R3
Cl
R5
R6
dibenzo-18-crown-6
CH2Cl2, 0-25oC
R4
R4 R5
1-8
No
gem-Bromochlorospiropentanes
Yielda (%)
1
2
3
4
5
6
7
8
R1¼R2¼R3¼R4¼R5¼R6¼H
54
72
62
62
55
70
77
56
R1¼Ph, R2¼R3¼R4¼R5¼R6¼H
R1eR2¼(CH2)3, R3¼R4¼R5¼R6¼H
R1eR2¼(CH2)5, R3¼R4¼R5¼R6¼H
R1eR2¼(CH2)3, R3eR4¼(CH2)3, R5¼R6¼H
R1eR3¼(CH2)4, R2¼R4¼R5¼R6¼H
R1eR3¼(CH2)6, R2¼R4¼R5¼R6¼H
R1eR2¼(CH2)2, R3eR4¼H, R5¼R6¼(CH2)2
a
Isolated yields.
Formation of bromocyclobutene 10 can result from the partial
substitution of the chlorine for bromine in ionic pair III. Chlorine
substitution at the first stage of reaction leading to bromolithium
carbenoid is unlikely, as the CeCl bond is more stable and less
yielded a large amount (up to 50%) of allenes under these condi-
tions and the best yields of the rearranged products were achieved
while carrying out the reaction at ꢀ65 ꢁC. The results are presented
in Table 2.
Table 2
Reaction of terminal gem-bromochlorospiropentanes 1e7 with methyllithium
R1
R1
R1
R4
R1
CH3Li (1,5 eq.), Et20 R2
R3
R4
9, 11, 13-17
ClCl
R1
R1
R2
Br
Br
Br
R2
R3
R2
R3
R2
R3
R4
Cl
H
R2
R3
R4
+
+
C
R3
R4
-65oC
R4
H
1-7
10, 12
Bromochlorospiropentanes
Halogenocyclobutenes
Yielda (%)
Allenes yieldb (%)
Cl
Br
Br
Cl
Cl
61c
d
Br
(4:1)
1
2a
10
9
Cl
Br
Br
Cl
Ph
Ph
Ph
Ph
Ph
Cl
Br
42c
(3:1)
21
2
3e
12
11
Cl Cl
Cl Cl
Cl Cl
Cl
Br
40
74
19
18
3
13a
13b
13c
Cl Cl
Cl
Br
4
14
Cl
Br
Cl
Cl
42
10
15
5
Cl Cl
Cl
Br
29
33
36
24
6
16
Cl
Br
Cl Cl
17
7
a
Isolated yields.
b
c
Allenes were not isolated, the yields refer to NMR data of reaction mixture.
The yields refer to the mixture of bromo- and chlorocyclobutenes.

K.N. Sedenkova et al. / Tetrahedron 66 (2010) 8089e8094
8091
Li
Cl
ClCl
Cl
Va
1
Cl
-LiBr
Li
Li
Br
Li
Cl-
Br
Li
+
Li
Cl
Cl
CH3Li
+
IVa
Va
VIa
9
Br-
-CH3Br
Cl-
-Cl-
Li
Br
Br
Br
Br
Br
1
I
II
III
Vb
Br
1
-LiBr
IVb
Vb
VIb
10
Scheme 2. Reaction of gem-bromochlorospiropentane 1 with methyllithium.
reactive toward methyllithium cf. the CeBr bond.6 Additional ex-
periments showed that gem-dichlorospiropentanes of similar
structure did not react with methyllithium under similar
conditions.
These results illustrate the differences in the stability of halo-
genolithium carbenoids VII (Scheme 4). Fluorolithium carbenoid
VIIc is stable enough toward nucleophilic attack of the CeC bond
that makes fluorine substitution by an external nucleophile (such
as methyllithium molecule) possible and leads to product 20 via
halogenophilic reaction of intermediate XIII with starting spi-
ropentane 22. Bromolithium carbenoid VIIb isomerizes faster than
any possible bimolecular reaction with methyllithium could occur
and bromocyclobutene 18b (X¼Br) is the sole product of the
reaction. For the chlorine containing carbenoid VIIa, that has in-
termediate stability, we observed the competition of both pro-
cesses and the formation of rearranged products 18a and 19 as well
as dispiro compound 20.
It is notable, that the formation of dimeric cyclobutenes is never
observed for dihalogenides containing internal dihalogenocyclo-
propane moiety. Halogenophilic reaction of allyllithium in-
termediate X or XII with a source of bromine, such as the starting
gem-dihalogenospiropentane or reaction with methyl bromide
results in the corresponding product 18 or 19. In contrast with in-
termediates VIa and VIb (Scheme 2) compounds 18 and 19 do not
interact with allyllithium particles X and XII, probably, due to
sterical hindrance.
The investigation of the carbenoid rearrangement of a new
series of mixed gem-bromochlorospiropentanes together with re-
cently studied gem-dibromo- and gem-bromofluorospiropentanes
gives new insight into the halogenolithium spiropentyl carbenoids
reactivity toward nucleophiles. The mechanism of the reaction can
be viewed as a carbocationic stepwise rearrangement, which
suggests the nucleophilic attack of CeC bond of the neighboring
spiro three-membered cycle on the carbenoid center.3 This process
leads to the formation of a series of carbocationic intermediates,
which ultimately yield cyclobutene products. The obtained results
demonstrate the substantial influence of the nature of the halogen
atom in lithium carbenoids on its transformation pathway. The
reactivity of gem-bromochlorospiropentanes is mainly similar to
the reactivity of gem-dibromospiropentanes (and not bromo-
fluorospiropentanes), and the difference in the stabilities of CeBr
and CeCl bonds results in the formation of chloro substituted
cyclobutenes as the major or the sole products of the reaction.
Moving ahead, we studied how the substituents in cyclopro-
pane moiety influence the reaction pathway and the products
(Table 2). Phenyl substituted bromochlorospiropentane 2 was
found to react with methyllithium giving a mixture of chloro- and
bromo-substituted products of rearrangement 11 and 12, chloro-
cyclobutene 11 being the major one. At the same time, spi-
rocycloalkyl substituted spiropentanes 3e5 and compounds 6 and
7, which contain 1,2-fused rings afforded chlorocyclobutenes
14e17 without the presence of bromocyclobutenes. This seems to
result from sterical hindrance, which prevents the exchange of
halogen atoms in the intermediate III (Scheme 2). In the reactions
of compound 6 and 7 the yield of allenes is higher and the yield of
chlorocyclobutenes is lower because in these cases CeC-bond
migration might be hindered by a fixed polycyclic structure.
An unexpected result was obtained for gem-bromochloro-
dispiroheptane 8, which contains the internal gem-bromochloro-
cyclopropane fragment. In the reaction of this substrate with
methyllithium we observed both possible reaction pathways, i.e.,
skeletal rearrangement, leading to cyclobutenes 18a and 19, and
methylationwith the retention of spiropentane moiety (product 20,
Scheme 3).
X
CH3
Br
Br X
Br CH3
CH3Li
+
+
Br
8, X=Cl
21, X=Br
22, X=F
18a, 25% 19, 26%
18b, 77%
20, 29%
90%
Scheme 3. Reaction of gem-dihalogenodispiroheptanes with methyllithium.
It is interesting to compare the results for the bromochloride 8
with the other gem-bromohalogenodispiroheptanes. The reactions
of dihalogenospiropentanes 21 and 22 with methyllithium were
studied in our previous works (Scheme 3).2a,3c,d,4
Li
Li
X-
X
X
X
8 or 21
Li
Br
X= Br, Cl
VIII
IX
Li
X
18a,b
CH3
Li
CH3
Br
Li X
Br X
CH3Li
-LiX
CH3Li
CH3
X=Cl
8
VIII
-CH3Br
8, X=Cl
21, X=Br
22, X=F
VIIa, X=Cl
VIIb, X=Br
VIIc, X=F
XI
XII
19
CH3Li
-LiX
X=Cl, F
Li CH3
Br CH3
8 or 22
XIII
20
Scheme 4. Proposed mechanism of the reaction of gem-dihalogenodispiroheptanes with methyllithium.

8092
K.N. Sedenkova et al. / Tetrahedron 66 (2010) 8089e8094
3. Experimental
(m, 4H, 4CH, Ph). 13C NMR (100.6 MHz, CDCl3)
d: 18.7 (CH2), 20.0
(CH2), 26.2 (CH), 26.9 (CH2CBrCl, AþCH2CBrCl, B), 27.4 (CH), 35.0
(Cspiro, AþCspiro, B), 47.1 (CBrCl), 47.2 (CBrCl), 126.5 (2CH, Ph,
Aþ2CH, Ph, B), 126.6 (CH, Ph, AþCH, Ph, B), 128.6 (2CH, Ph,
Aþ2CH, Ph, B), 139.4 (C, Ph), 139.64 (C, Ph). Anal. Calcd for
C11H10BrCl: C 51.30, H 3.91%. Found: C 51.18, H 4.07%.
3.1. General
NMR spectra were recorded on a Bruker DPX-400 spectrometer
(400.13 and 100.62 MHz for 1H and 13C, respectively) at room
temperature; chemical shifts
d were measured with reference to
the solvent (1H: CDCl3,
d
¼7.24 ppm; 13C: CDCl3,
d¼77.13 ppm). Mass
3.2.3. 1-Bromo-1-chlorodispiro[2.0.3.1]octane
(62%), colorless liquid, Rf 0.8 (petroleum ether). Two diastereomers,
A:B 1.25:1. IR (film): 3053, 2981, 2951, 2929, 2850, 1514, 1460,
(3). Yield
1.51 g
spectra were taken on a Finnigan MAT 95 XL spectrometer (70 eV)
using electron impact ionization (EI) and GCeMS coupling. Accu-
rate mass measurements (HRMS) were carried out using a Bruker
micro TOF-QÔ ESI-TOF mass spectrometer. Microanalyses were
performed on a Carlo Erba 1106 instrument at the Microanalytic
Laboratory, Department of Chemistry, Moscow State University.
Infrared spectra were recorded on a Thermo Nicolet FT IR-200
spectrometer. Analytical thin layer chromatography (TLC) was
carried out with Silufol silica gel plates (supported on aluminum);
the detection was done by UV lamp (254 and 365 nm) and chemical
staining (iodine vapor). Column chromatography was performed
using silica gel 60 (230e400 mesh, Merck). GLC analyses and sep-
aration were performed using silicone E-301 (15% on Inerton AW).
Petroleum ether used refers to the fraction boiling at 60e70 ꢁC. All
reagents except commercial products of satisfactory quality were
purified by literature procedures prior to use. Starting com-
pounds: methylenecyclopropane,7 (2-methylenecyclopropyl)
benzene,8 1-methylenespiro[2.3]hexane,9 1-methylenespiro[2.5]
octane,10 9-methylenedispiro[3.0.3.1]nonane,11 7-methylenebicyclo
[4.1.0]heptane,12 9-methylenebicyclo[6.1.0]nonane,12 1-tert-butoxy-
2-methylenecyclopropane,13 bicyclopropylidene14 were synthesized
by known procedures.
n
1429, 1400, 1259, 1117, 1080, 1043, 1012, 987, 897, 860, 717 cmꢀ1. 1H
NMR (400.1 MHz, CDCl3)
d
: 1.05 (d, 1H, 2JHH 5.5, CH2, cyePr, B), 1.07
2
2
(d, 1H, JHH 5.4, CH2, cyePr, A), 1.17 (d, 1H, JHH 5.4, CH2, cyePr, A),
1.27 (d, 1H, 2JHH 5.5, CH2, cyePr, B), 1.75 (d, 1H, 2JHH 6.1, CH2, cyePr,
2
2
B), 1.77 (d, 1H, JHH 6.1, CH2, cyePr, A), 1.88 (d, 1H, JHH 6.1, CH2,
cyePr, A), 1.92 (d, 1H, 2JHH 6.1, CH2, cyePr, B), 1.93e2.04 (m, 1H, CH2,
cyeBu, Aþ1H, CH2, cyeBu, B), 2.04e2.15 (m, 2H, CH2, cyeBu, Aþ2H,
CH2, cyeBu, B), 2.16e2.30 (m, 2H, CH2, cyeBu, Aþ2H, CH2, cyeBu,
B), 2.68e2.83 (m, 1H, CH2, cyeBu, Aþ1H, CH2, cyeBu, B). 13C NMR
(100.6 MHz, CDCl3) d
: 17.0 (1JCH 139, CH2, cyeBu, B), 17.1 (1JCH 139,
CH2, cyeBu, A), 19.8 (1JCH 161, CH2, cyePr, B), 21.6 (1JCH 162, CH2,
cyePr, A), 25.8 (1JCH 137, CH2, cyeBu, B), 26.3 (1JCH 138, CH2, cyeBu,
A), 27.1 (1JCH 165, CH2CBrCl, cyePr, A), 27.5 (1JCH 166, CH2CBrCl,
cyePr, B), 28.9 (1JCH 138, CH2, cyeBu, B), 29.3 (1JCH 137, CH2, cyeBu,
A), 32.3 (Cspiro), 32.6 (Cspiro), 32.6 (Cspiro), 33.0 (Cspiro), 48.5 (CBrCl,
B), 49.2 (CBrCl, A). Anal. Calcd for C8H10BrCl: C 43.38, H 4.55%.
Found: C 43.50, H 4.61%.
3.2.4. 1-Bromo-1-chlorodispiro[2.0.5.1]decane
(4). Yield
1.71 g
(62%), colorless liquid, Rf 0.8 (petroleum ether). Two diastereomers,
A:B 1.7:1. IR (film): n 3062, 2992, 2941, 2862, 1518, 1448, 1405, 1356,
3.2. General procedure 1: addition of bromochlorocarbene
to alkenes
1171, 1087, 1030, 952, 890, 860, 726, 720, 680, 500 cmꢀ1. 1H NMR
2
(400.1 MHz, CDCl3)
d
: 0.84 (d, 1H, JHH 4.5, CH2, cyePr, B), 0.86 (d,
1H, 2JHH 4.4, CH2, cyePr, A), 0.97 (d, 1H, 2JHH 4.4, CH2, cyePr, A), 1.06
(d, 1H, 2JHH 4.5, CH2, cyePr, B), 1.22e1.34 (m, 1H, CH2, cyePr, Aþ1H,
CH2, cyePr, B), 1.34e1.44 (m, 1H, CH2, cyePr, Aþ1H, CH2, cyePr, B),
1.47e1.69 (m, 6H, CH2, cyeHex, Aþ6H, CH2, cyeHex, B), 1.71e1.91
(m, 4H, CH2, cyeHex, Aþ4H, CH2, cyeHex, B). 13C NMR (100.6 MHz,
A 50% (w/w) aqueous solution of NaOH (22 mL) was added to
11.0 mmol of the corresponding alkene, CHBr2Cl (2.74 g, 13.1 mmol)
and dibenzo-18-crown-6 (0.1 g, 0.3 mmol) in dichloromethane
(22 mL) at 0 ꢁC over 0.5 h. The reaction mixture was warmed up to
room temperature and stirred for 24 h. Then it was treated with ice
(20 g). The organic phase was separated and the water phase
extracted with dichloromethane (3ꢂ10 mL). The combined organic
fractions were washed with water (50 mL) and dried over MgSO4.
The solvent was evaporated; the residue was distilled or purified by
preparative column chromatography.
CDCl3) d: 20.8 (CH2, cyePr, B), 22.7 (CH2, cyePr, A), 25.3 (CH2,
AþCH2, B), 25.7 (CH2, B), 25.9 (CH2, A), 26.0 (CH2, A), 26.1 (CH2, B),
26.7 (CH2, A), 26.9 (CH2, B), 32.3 (CH2, B), 32.4 (Cspiro, B), 32.5 (Cspiro
,
A), 32.6 (CH2, A), 33.7 (CH2, B), 34.0 (CH2, A), 35.6 (Cspiro, B), 36.0
(Cspiro, A), 47.4 (CBrCl, B), 48.6 (CBrCl, A). Anal. Calcd for C10H14BrCl:
C 48.12, H 5.65%. Found: C 47.99, H 5.51%.
3.2.1. 1-Bromo-1-chlorospiro[2.2]pentane (1). Yield 1.08 g (54%),
3.2.5. 1-Bromo-1-chlorotrispiro[2.0.34.0.38.03]undecane
1.59 g (55%), colorless liquid, Rf 0.8 (petroleum ether). 1H NMR
(5). Yield
colorless liquid, bp 80 ꢁC/140 Torr. IR (film):
n
3078, 3003, 2927,
1556, 1498, 1423, 1396, 1149, 1089, 1039, 1016, 899, 849, 719, 660,
640 cmꢀ1 1H NMR (400.1 MHz, CDCl3)
: 1.17e1.27 (m, 3H, CH2),
1.31e1.37 (m, 1H, CH2), 1.91e1.94 (m, 2H, CH2). 13C NMR
(400.1 MHz, CDCl3) d
: 1.66 (d, 1H, 2JHH 5.8, CH2, cyePr), 1.68 (d, 1H,
.
d
2JHH 5.8, CH2, cyePr), 1.80e1.89 (m, 2H, CH2, cyeBu), 1.93e2.19 (m,
8H, CH2, cyeBu), 2.44e2.59 (m, 2H, CH2, cyeBu). 13C NMR
(100.6 MHz, CDCl3)
d
: 10.1 (CH2), 11.3 (CH2), 27.2 (Cspiro), 28.1 (CH2),
(100.6 MHz, CDCl3) d
: 16.0 (1JCH 139, CH2, cyeBu), 16.1 (1JCH 139,
47.7 (CBrCl). MS (EI, 70 eV) m/z: 147 (6), 145 (6) [MꢀClþ], 103 (7),
101 (23) [MꢀBrþ], 66 (43), 65 (100), 63 (3), 51 (4), 40 (46), 39 (44),
38 (16). HRMS (EI): [MꢀBr]þ calcd for C5H635Cl 101.0158, found
101.0166.
CH2, cyeBu), 21.7 (1JCH 137, CH2, cyeBu), 22.3 (1JCH 136, CH2,
cyeBu), 24.8 (1JCH 136, CH2, cyeBu), 25.0 (1JCH 137, CH2, cyeBu),
25.9 (1JCH 165, CH2, cyePr), 34.7 (Cspiro), 35.6 (Cspiro), 36.2 (Cspiro),
49.7 (CBrCl). Anal. Calcd for C11H14BrCl: C 50.51, H 5.39%. Found: C
50.65, H 5.73%.
3.2.2. 1-Bromo-1-chloro-4-phenylspiro[2.2]pentane
2.04 g (72%), colorless oil, Rf 0.5 (petroleum ether). Two di-
astereomers, A:B 1:1. IR (film): 3078, 3062, 3030, 2993, 2925,
2852, 1604, 1493, 1452, 1348, 1207, 1099, 1072, 1053, 1030, 945,
926, 899, 866, 769, 751, 719, 698, 588, 550 cmꢀ1 1H NMR
: 1.57 (dd, 1H, JHH 5.4, JCH 5.6, CH2), 1.63
(2). Yield
3.2.6. 20-Bromo-20-chlorospiro[bicyclo[4.1.0]heptane-7,10-cyclopro-
pane] (6). Yield 1.81 g (70%), colorless liquid, Rf 0.5 (petroleum
n
ether). IR (film):
n
3020, 2938, 2867, 1463, 1381, 1150, 1060, 1049,
.
961, 847, 764, 727, 660, 568 cmꢀ1
.
1H NMR (400.1 MHz, CDCl3)
d:
2
3
(400.1 MHz, CDCl3)
d
3
1.15e1.25 (m, 2H, CH2), 1.26e1.35 (m, 2H, CH2), 1.42e1.52 (m, 2H,
CH2), 1.59 (ddd, 1H, 3JHH 1.6, 6.9, 8.7, CH), 1.73 (ddd, 1H, 3JHH 1.6, 6.9,
8.7, CH), 1.75 (br s, 2H, CH2, cyePr), 1.84e1.96 (m, 2H, CH2). 13C NMR
2
(dd, 1H, JHH 5.4, JCH 5.6, CH2), 1.85e1.91 (m, 1Hþ2H, CH2),
1.96e2.03 (m, 1H, CH2), 2.03e2.07 (m, 2H, CH2), 2.69 (dd, 1H,
3
3
3
3JHH¼5.6, JHH¼8.7, CH), 2.81 (dd, 1H, JHH¼5.6, JCH¼8.7, CH),
(100.6 MHz, CDCl3)
d
: 18.9 (1JCH 165, CH), 20.1 (1JCH 165, CH), 21.1
7.14e7.19 (m, 4H, 4CH, Ph), 7.21e7.33 (m, 2H, 2CH, Ph), 7.34e7.40
(1JCH 127, CH2, cyeHex), 21.2 (1JCH 127, CH2, cyeHex), 21.2 (1JCH 127,

K.N. Sedenkova et al. / Tetrahedron 66 (2010) 8089e8094
8093
CH2, cyeHex), 21.5 (1JCH 127, CH2, cyeHex), 25.1 (1JCH 165, CH2,
cyePr), 34.8 (Cspiro), 48.9 (CBrCl). Anal. Calcd for C9H12BrCl: C 45.89,
H 5.13%. Found: C 45.74, H 5.07%.
250 (21), 231 (9), 229 (31), 227 (16), 215 (20), 193 (16), 180 (20),
179 (31), 178 (26), 165 (23), 155 (37), 142 (23), 141 (100), 129 (32),
128 (50), 127 (34), 115 (56), 102 (16), 91 (42), 77 (19), 51 (10).
HRMS (TOF ESIꢀ): [M]þ calcd for C22H2035Cl2 354.0942, found
354.0931.
3.2.7. 20-Bromo-20-chlorospiro[bicyclo[6.1.0]nonane-9,10-cyclopro-
pane] (7). Yield 2.24 g (77%), colorless solid, Rf 0.7 (petroleum
ether), mp 35e36 ꢁC. IR (film):
n
3060, 2992, 2938, 2860, 1527,
1470, 1418, 1380, 1360, 1196, 1147, 1120, 1073, 1024, 972, 949,
823, 760, 745, 653, 583, 552 cmꢀ1. 1H NMR (400.1 MHz, CDCl3)
3.3.3. 2,20-Ethane-1,2-diylbis(1-chlorospiro[3.3]hept-1-ene) (13a),
2-chloro-1-[2-(1-chlorospiro[3.3]hept-1-en-2-yl)ethyl]spiro[3.3]
hept-1-ene (13b), 1,10-ethane-1,2-diylbis(2-chlorospiro[3.3]hept-1-
ene) (13c).y Yield 0.23 g (40%), colorless oil, Rf 0.7 (petroleum
d
:
1.02e1.15 (m, 2H, CH2), 1.36e1.54 (m, 6H, CH2), 1.57e1.65 (m, 2H,
CH2), 1.66 (s, 2H, CH2, cyePr), 1.68e1.76 (m, 2H, CH2), 1.77e1.84
ether). Three isomers, A:B:C 5:2.5:1. IR (film):
2880, 1661, 1469, 1440, 1385, 1302, 1229, 1193, 1088, 902, 760,
700 cmꢀ1 1H NMR (400.1 MHz, CDCl3)
: 1.73e1.84 (m, 6H),
n 3080, 2970, 2960,
(m, 2H, CH2). 13C NMR (100.6 MHz, CDCl3) : 24.4 (1JCH 165, CH2,
d
cyePr), 24.4 (1JCH 125, CH2, cyeOct), 24.7 (1JCH 125, CH2,
cyeOct), 24.8 (1JCH 158, CH), 26.1 (1JCH 160, CH), 26.5 (1JCH 126,
2CH2, cyeOct), 29.0 (1JCH 127, 2CH2, cyeOct), 35.2 (Cspiro), 48.1
(CBrCl). Anal. Calcd for C11H16BrCl: C 50.12, H 6.12%. Found: C
50.23, H 6.27%.
.
d
1.85e1.98 (m, 6H), 2.03e2.16 (m, 12H), 2.17e2.33 (m, 12H), 2.25
(s, 4H, B), 2.37 (s, 4H, C), 2.42 (s, 4H, B), 2.65 (s, 4H, C), 2.66 (s, 4H,
B), 2.68 (s, 4H, A). 13C NMR (100.6 MHz, CDCl3)
d: 15.8 (2CH2,
cyeBu, B), 16.3 (2CH2, cyeBu, A), 17.0 (2CH2, cyeBu, C), 22.7
(2CH2), 22.8 (2CH2), 24.2 (2CH2), 28.7 (2CH2), 28.8 (2CH2), 28.8
(4CH2), 29.7 (4CH2), 30.3 (4CH2), 42.4 (2Cspiro,) 42.7 (2Cspir-
oþ2Cspiro), 48.8 (2CH2), 49.2 (4CH2), 126.4 (C), 126.6 (C), 143.4 (C),
146.6 (C). HRMS (TOF ESIꢀ): [M]þ calcd for C16H2035Cl2 282.0942,
found 282.0947.
3.2.8. 7-Bromo-7-chlorodispiro[2.0.2.1]heptane (8). Yield 1.28 g
(56%), colorless solid, Rf 0.1 (petroleum ether), mp 48e50 ꢁC. IR
(film):
1123, 1058, 1038, 1023, 916, 897, 798, 670 cmꢀ1
(400.1 MHz, CDCl3) : 1.02e1.10 (m, 4H, CH2), 1.21e1.25 (m, 2H,
CH2), 1.33e1.38 (m, 2H, CH2). 13C NMR (100.6 MHz, CDCl3)
: 9.5
n
3085, 3009, 2969, 2937, 2862, 1566, 1465, 1382, 1321, 1158,
.
1H NMR
d
d
3.3.4. 1,10-Ethane-1,2-diylbis(2-chlorospiro[3.5]non-1-ene) (14). Yield
0.50 g (74%), colorless oil, Rf 0.8 (petroleum ether). 1H NMR
(2CH2), 10.6 (2CH2), 30.9 (2Cspiro), 55.7 (CBrCl). Anal. Calcd for
C7H8BrCl: C 40.52, H 3.89%. Found: C 40.61, H 3.78%.
(400.1 MHz, CDCl3)
CH2),1.43e1.79 (m,14H, CH2), 2.26 (s, 2H, CH2), 2.36 (s, 2H, CH2). 13
NMR (100.6 MHz, CDCl3)
: 22.7 (1JCH 127, 2CH2), 24.4 (1JCH 124,
d: 1.10e1.23 (m, 2H, CH2), 1.25e1.40 (m, 8H,
C
3.3. General procedure 2: reaction of gem-
d
bromochlorospiropentanes with methyllithium
4CH2), 25.5 (1JCH 124, 2CH2), 34.3 (1JCH 125, 4CH2), 46.5 (1JCH 140,
2CH2, cyeBu), 47.3 (2Cspiro), 120.5 (2C]), 150.5 (2CCl). MS (EI,
70 eV) m/z: 342 (1), 340 (5), 338 (8) [Mþ], 305 (4), 303 (11)
[MꢀClꢀHþ], 272 (4), 270 (7), 267 (8), 257 (7), 255 (10), 223 (8), 221
(20), 207 (5), 195 (9), 189 (12), 187 (16), 185 (9), 133 (63), 127 (29),
105 (53), 91 (100), 81 (22), 79 (32), 77 (26), 67 (35), 55 (24), 41 (24).
HRMS (TOF APCIþ): [MꢀCl]þ calcd for C20H2835Cl 303.1880, found
303.1885.
A solution of 1.5 M methyllithium (4.0 mL, 6.0 mmol) in ether was
added dropwise to solution of 4.0 mmol bromochlorospiropentane
in absolute ether (10 mL) at ꢀ65 ꢁC in argon. The reaction mixture
was stirred for 10 h. Then it was warmed up to 0 ꢁC and quenched
with an equal amount of cold water. The organic phase was sepa-
rated, the water phase extracted with ether (3ꢂ3 mL). The combined
organic fractions were washed with water (5 mL) and dried over
MgSO4. The solvent was evaporated; the products were isolated by
preparative column chromatography or GLC (column 3000ꢂ5 mm,
silicone E-301, 15% on Inerton AW).
3.3.5. 9,90-Ethane-1,2-diylbis(10-chlorodispiro[3.0.3.2]dec-9-ene)
(15). Yield 0.30 g (42%), colorless oil, Rf 0.8 (petroleum ether). 1H
NMR (400.1 MHz, CDCl3)
2.07e2.15 (m, 16H, CH2, cyeBu), 2.43 (s, 4H, CH2). 13C NMR
(100.6 MHz, CDCl3) : 15.2 (2CH2, cyeBu), 15.8 (2CH2, cyeBu), 22.8
d: 1.71e1.91 (m, 8H, CH2, cyeBu),
3.3.1. 1,10-Ethane-1,2-diylbis(2-chlorocyclobutene) (9). Yield 0.20 g
(40%), colorless liquid, Rf 0.6 (petroleum ether). 1H NMR
d
(2CH2), 26.6 (4CH2, cyeBu), 27.9 (4CH2, cyeBu), 54.2 (2Cspiro), 58.8
(2Cspiro), 127.3 (2C]), 144.6 (2CCl). MS (EI, 70 eV) m/z: 364 (1), 362
(2) [Mþ], 310 (2), 308 (21), 306 (32), 280 (60), 279 (16), 278 (97), 271
(15), 252 (23), 250 (37), 245 (23), 243 (63), 235 (19), 229 (9), 217
(30), 216 (17), 215 (75), 206 (23), 207 (49), 193 (16), 180 (32), 179
(55), 178 (27), 165 (35), 153 (20), 141 (16), 130 (16), 129 (23), 128
(26), 127 (31), 125 (66), 117 (72), 115 (87), 105 (21), 103 (36), 99 (19),
91 (96), 89 (100), 77 (50). Anal. Calcd for C22H2835Cl2: C 72.72, H
7.77%. Found: C 72.77, H 8.04%.
(400.1 MHz, CDCl3)
d
: 2.26 (br s, 4H, 2CH2), 2.33e2.38 (m, 4H, 2CH2,
cyeBu), 2.60e2.65 (m, 4H, 2CH2, cyeBu). 13C NMR (100.6 MHz,
CDCl3)
d
: 24.7 (1JCH 129, 2CH2), 27.6 (1JCH 141, 2CH2, cyeBu), 33.8
(1JCH 142, 2CH2, cyeBu), 119.9 (2C]), 142.7 (2CCl]). MS (EI, 70 eV)
m/z: 206 (1), 204 (6), 202 (9) [Mþ], 167 (22), 169 (8) [MꢀClþ], 103
(26), 102 (12), 101 (71), 91 (8), 80 (6), 77 (8), 66 (9), 65 (100), 51 (9),
39 (16). Anal. Calcd for C10H12Cl2: C 59.13, H 5.96%. Found: C 58.83,
H 6.09%.
3.3.2. 1,10-[Ethane-1,2-diylbis(2-chlorocyclobut-2-ene-3,1-diyl)]di-
benzene (11). Yield 0.22 g (25%), colorless oil, Rf 0.2 (petroleum
ether). Two diastereomers, A:B 1.1:1. 1H NMR (400.1 MHz, CDCl3)
3.3.6. 7,70-Ethane-1,2-diylbis(8-chlorobicyclo[4.2.0]oct-7-ene)
(16). Two isomers, A:B 1:1. Yield 0.18 g (29%), colorless liquid, Rf 0.7
(petroleum ether). 1H NMR (400.1 MHz, CDCl3)
d: 1.36e1.48 (m,
d
: 2.29e2.37 (m, 2H, CH2, Aþ2H, CH2, B), 2.46e2.54 (m, 4H, CH2,
12H, CH2, cyeHex), 1.48e1.62 (m, 12H, CH2, cyeHex), 1.62e1.73 (m,
8H, CH2, cyeHex), 2.14e2.25 (m, 4H, CH2, 2CH2, AþB), 2.29e2.40
(m, 4H, 2CH2, AþB), 2.75e2.80 (m, 4H, 4CH, AþB), 2.89e2.95
Aþ4H, CH2, B), 2.91e2.99 (m, 2H, CH2, Aþ2H, CH2, B), 4.05e4.09
(m, 2H, CH, Aþ2H, CH, B), 7.26e7.41 (m, 10H, CH, Ph, Aþ10H, CH,
Ph, B). 13C NMR (100.6 MHz, CDCl3)
d
: 24.6 (1JCH 130, 2CH2, B),
(m, 4H, 4CH, AþB). 13C NMR (100.6 MHz, CDCl3)
d
: 17.9 (1JCH 127,
24.7 (1JCH 130, 2CH2, A), 38.2 (1JCH 141, 2CH2, cyeBu, A), 38.2 (1JCH
141, 2CH2, cyeBu, B), 50.2 (1JCH 142, 2CH, cyeBu, A), 50.2 (1JCH
142, 2CH, cyeBu, B), 123.6 (C], AþC], B), 126.9 (1JCH 160, 4CH,
Ph, Aþ4CH, Ph, B), 126.9 (1JCH 160, 2CH, Ph, Aþ2CH, Ph, B), 128.6
(1JCH 160, 4CH, Ph, Aþ4CH, Ph, B), 139.8 (2C, Ph, A), 139.9 (2C, Ph,
B), 142.9 (2CCl, A), 143.0 (2CCl, B). MS (EI, 70 eV) m/z: 356 (0.5),
354 (1) [Mþ], 321 (1), 319 (3) [MꢀClþ], 318 (3), 283 (8), 252 (16),
4CH2), 18.2 (1JCH 127, 2CH2), 18.3 (1JCH 127, 2CH2), 22.1 (1JCH 127,
4CH2), 23.0 (1JCH 126, 2CH2), 23.0 (1JCH 127, 2CH2), 23.5 (1JCH 130,
2CH2), 23.6 (1JCH 128, 2CH2), 38.5 (1JCH 143, 2CH), 38.7 (1JCH 143,
y
The weak 13C signals of C]C fragment were not found for minor isomer C.

8094
K.N. Sedenkova et al. / Tetrahedron 66 (2010) 8089e8094
2CH), 44.3 (1JCH 143, 4CH), 123.6 (2C]), 123.7 (2C]), 144.9 (2CCl),
145.1 (2CCl). HRMS (TOF ESIþ): [MꢀCl]þ calcd for C18H2435Cl
275.1567, found 275.1544.
Acknowledgements
We thank the Russian Foundation for Basic Research (Project 09-
03-00717-a) and the Division of Chemistry and Materials Science
RAS (Program N 4) for financial support of this work.
Two isomers, A:B 1:1. Yield 0.24 g (33%), colorless oil, Rf 0.7
(petroleum ether). IR (film):
1452, 1360, 1119, 1028, 960, 719, 622 cmꢀ1
CDCl3)
: 1.25e1.87 (m, 24H, Aþ24H, B), 2.10e2.19 (m, 2H, Aþ2H, B),
n
2994, 2945, 2867, 1670, 1530, 1471,
.
1H NMR (400.1 MHz,
d
References and notes
2.23e2.35 (m, 2H, Aþ2H, B), 2.58e2.64 (m, 2H, Aþ2H, B),
2.73e2.78 (m, 2H, Aþ2H, B). 13C NMR (100.6 MHz, CDCl3)
d:
1. (a) Doering, W. v. E.; LaFlamme, P. M. Tetrahedron 1958, 2, 75; (b) Moore, W. R.;
Ward, H. R. J. Org. Chem. 1960, 25, 2073; (c) Skattebøl, L. Acta Chem. Scand. 1963,
17, 1683; (d) Hopf, H. In The Chemistry of Ketenes, Allenes and Related Compounds;
Patai, S., Ed.; Wiley: New York, NY, 1980; Part 2, Chapter 2, pp 779e901; (e)
Banwell, M. G.; Reum, M. E. In Advances in Strain in Organic Chemistry; Halton, B.,
Ed.; JAI: Greenwich,1991; Vol.1, pp 19e54; (f) Backes, J.; Brinker, U. H. In Houben-
Weyl; Regitz, M., Ed.; Cyclopropylidene; Thieme: Stutgart, 1989; Vol. E 19b,
pp 391e541; (g) Lee-Ruff, E. In Houben-Weyl; de Meijere, A., Ed.; Cyclo-
propylidene to Allene Rearrangement; Thieme: Stutgart, 1997; Vol.
pp 2388e2418; (h) Kostikov, R. R.; Molchanov, A. P.; Hopf, H. Top. Curr. Chem.1990,
155, 41; (i) Sydnes, L. K. Chem. Rev. 2003, 103, 1133.
2. (a) Lukin, K. A.; Zefirov, N. S.; Yufit, D. S.; Struchkov, Y. T. Tetrahedron 1992, 48,
9977; (b) Lukin, K. A.; Zefirov, N. S. Chemistry of Cyclopropyl Group In
Spiroannulated Cyclopropanes; Rappoport, Z., Ed.; John Wiley: Chichester, UK,
1995; pp 861e885.
22.5 (1JCH 124, 4CH2), 22.7 (1JCH 125, 4CH2), 25.0 (1JCH 124, 4CH2),
25.9 (1JCH 124, 4CH2), 26.3 (1JCH 126, 4CH2), 29.7 (1JCH 124, 4CH2),
30.0 (1JCH 123, 4CH2), 45.4 (1JCH 139, 2CH), 45.7 (1JCH 139, 2CH), 51.0
(1JCH 137, 4CH),123.8 (2C]), 123.9 (2C]), 143.5 (2CCl), 143.7 (2CCl).
MS (EI, 70 eV) m/z: 370 (1), 368 (3), 366 (5) [Mþ], 334 (2), 332 (6)
[MꢀClþ], 333 (7), 331 (21) [MꢀClꢀHþ], 295 (10), 235 (8), 199 (9),
185 (9), 181 (9), 161 (8), 147 (26), 145 (14), 131 (15), 129 (14), 127
(13), 119 (29), 117 (19), 115 (17), 105 (51), 93 (28), 91 (100), 81 (26),
67 (45), 65 (21), 55 (24). HRMS (TOF APCIþ): [M]þ calcd for
C22H3235Cl2 366.1881. Found 366.1860.
E 17c,
3. (a) Averina, E. B.; Kuznetsova, T. S.; Zefirov, A. N.; Koposov, A. E.; Grishin, Y. K.;
Zefirov, N. S. Mendeleev Commun. 1999, 101; (b) Averina, E. B.; Kuznetsova, T. S.;
Lysov, A. E.; Potekhin, K. A.; Zefirov, N. S. Dokl. Akad. Nauk 2000, 375, 481 (Russ.);
Dokl. Chem. 2000, 375, 257 (Eng. Trans.); (c) Averina, E. B.; Karimov, R. R.; Sed-
enkova, K. N.; Grishin, Y. K.; Kuznetzova, T. S.; Zefirov, N. S. Tetrahedron 2006, 62,
8814; (d) Averina, E. B.; Sedenkova, K. N.; Grishin, Y. K.; Kuznetsova, T. S.; Zefirov,
N. S. ARKIVOC 2008, IV, 71; (e) Sedenkova, K. N.; Averina, E. B.; Grishin, Y. K.;
Kuznetsova, T. S.; Zefirov, N. S. Zh. Org. Khim. 2008, 44, 962 (Russ.); Russ. J. Org.
Chem. 2008, 44, 950 (Eng. Trans.).
3.3.7. 1-(1-Bromocyclopropyl)-2-chlorocyclobutene (18a). Yield
0.18 g (25%), colorless liquid, Rf 0.6 (petroleum ether). 1H NMR
(400.1 MHz, CDCl3)
d: 1.25e1.29 (m, 2H, CH2, cyePr), 1.31e1.35 (m,
2H, CH2, cyePr), 2.43e2.46 (m, 2H, CH2, cyeBu), 2.54e2.57 (m, 2H,
CH2, cyeBu). 13C NMR (100.6 MHz, CDCl3)
d
: 16.5 (1JCH 166, 2CH2,
cyePr), 25.1 (CBr), 27.9 (1JCH 142, CH2, cyeBu), 32.5 (1JCH 143, CH2,
cyeBu), 120.1 (C]), 142.0 (CCl¼). MS (EI, 70 eV) m/z: 210 (2), 208
(11), 206 (10) [Mþ], 129 (14), 127 (51) [MꢀBrþ], 92 (24), 91 (100), 65
(23), 63 (9), 51 (12), 49 (10). HRMS (TOF ESIꢀ): [M]þ calcd for
C7H8Br35Cl 205.9498, found 205.9502.
4. Averina, E. B.; Sedenkova, K. N.; Borisov, I. S.; Grishin, Y. K.; Kuznetzova, T. S.;
Zefirov, N. S. Tetrahedron 2009, 65, 5693.
ꢀ
5. Fedorynski, M. Synthesis 1977, 783.
€
6. (a) Kobrich, G.; Goyert, W. Tetrahedron 1968, 24, 4327; (b) Borer, M.; Loosli, T.;
Minger, A.; Neuenschwander, M. Helv. Chim. Acta 1995, 78, 1311.
7. Binger, P.; Brinkmann, A.; Wedemann, P. Synthesis 2002, 1344.
8. (a) Kitatami, K.; Hiyama, T.; Nozaki, H. Bull. Chem. Soc. Jpn. 1977, 50, 3288; (b)
Arora, S.; Binger, P. Synthesis 1974, 801.
9. Al Dulayymi, J. R.; Baird, M. S. Tetrahedron Lett. 1995, 36, 3393.
10. Hamdouchi, C.; Topolski, M.; Goedken, V.; Walborsky, H. M. J. Org. Chem. 1993,
38, 3148.
11. Bee, L. K.; Everett, J. W.; Garratt, P. J. Tetrahedron 1977, 33, 2143.
12. Arora, S.; Binger, P. Synthesis 1974, 801.
13. Takeuchi, D.; Inoue, A.; Ishimaru, F.; Osakada, K. Macromolecules 2008, 41, 6339.
14. (a) de Meijere, A.; Kozhushkov, S. I.; Spaeth, T.; Zefirov, N. S. J. Org. Chem. 1993,
58, 502; (b) de Meijere, A.; Kozhushkov, S. I.; Spaeth, T. Org. Synth. 2002, 78, 142.
3.3.8. 1-(1-Bromocyclopropyl)-2-methylcyclobutene (19). Yield 0.19 g
(26%), colorless liquid, Rf 0.7 (petroleum ether). 1H NMR (400.1 MHz,
CDCl3)
d: 1.07e1.10 (m, 2H, CH2, cyePr), 1.21e1.25 (m, 2H, CH2,
cyePr), 1.79 (s, 3H, CH3), 2.19e2.22 (m, 2H, CH2, cyeBu), 2.29e2.33
(m, 2H, CH2, cyeBu). 13C NMR (100.6 MHz, CDCl3) : 14.6 (1JCH 126,
d
CH3), 16.1 (1JCH 165, 2CH2, cyePr), 27.0 (1JCH 138, CH2, cyeBu), 27.9
(CBr), 28.6 (1JCH 138, CH2, cyeBu), 139.1 (C]), 139.8 (C]). Anal.
Calcd for C8H11Br: C 51.36, H 5.93%. Found: C 51.18, H 6.08%.