Unusual methylation reaction of gem-bromofluorospiropentanes with methyllithium

Article abstract of DOI:10.1016/j.tet.2009.05.032

A series of novel gem-bromofluorospiropentanes were synthesized and investigated in the reaction with methyllithium. Either substitution of the fluorine atom for a methyl group or rearrangement into methylated cyclobutene derivatives occurred under these

Full text of DOI:10.1016/j.tet.2009.05.032

Tetrahedron 65 (2009) 5693–5701
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Unusual methylation reaction of gem-bromofluorospiropentanes
with methyllithium
Elena B. Averina, Kseniya N. Sedenkova, Ilya S. Borisov, Yuri K. Grishin,
*
Tamara S. Kuznetsova , Nikolai S. Zefirov
Department of Chemistry, Moscow State University, Leninskie Gory, 119992 Moscow, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of novel gem-bromofluorospiropentanes were synthesized and investigated in the reaction with
methyllithium. Either substitution of the fluorine atom for a methyl group or rearrangement into
methylated cyclobutene derivatives occurred under these conditions.
Received 3 November 2008
Received in revised form 30 April 2009
Accepted 14 May 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Available online 21 May 2009
Keywords:
gem-Dihalogenospiropentanes
Carbenoid rearrangement
Alkyllithium reagents
Fluorine substitution
1. Introduction
model gem-bromofluorospiropentanes 11–20 and investigated
their reaction with methyllithium.
Previously we have reported an unusual skeletal rearrangement
of gem-dibromospiropentanes under treatment with methyl-
lithium at low temperatures (Scheme 1).1 In general, the reaction of
dibromides I with methyllithium gives corresponding allenes III as
major products (Scheme 1, route A). This transformation, so-called
Doering–Scattebol–Moore reaction, is well documented.2 We have
found that lowering the reaction temperature to ꢀ55 ꢁC favors the
formation of rearranged products IV–VII and disfavors the forma-
tion of allenes III.1 We have demonstrated the general character of
this process and found that the formation of ‘monomeric’ (IV, V;
Scheme 1, route B) or ‘dimeric’ (VI, VII; Scheme 1, route C) products
was possible depending on the substituents in the dibromocyclo-
propane fragment.3 In several cases we have also observed the
products of type VIII arised from the insertion of some in-
termediate into C–H bond of diethyl ether used as a solvent.4
The general mechanistic scheme was supposed to include the
nucleophilic attack of neighboring three-membered C–C bond at
intermediate Li–carbenoid II with Br as a leaving group.3c Studying
the reaction mechanism, we were interested in the influence of the
halogen atom nature on the direction of the dihalogenospiro-
pentane reactions with MeLi. Since no data concerning this prob-
lem was available,5 in this paper we have synthesized a series of
2. Results and discussion
Bromofluorospiropentanes 11–20 were synthesized in good
yields by the cycloaddition of bromofluorocarbene6 to corre-
sponding methylenecyclopropanes 1–10 (Table 1). The compounds
14–16 and 19 are obtained as mixtures of two diastereomeres (of
four possible ones for 14 and 15). Indeed, in NMR spectra of com-
pounds 14 and 15 we can see only two sets of signals, corre-
sponding just two diastereomeres (A and B). Thus, addition of
bromofluorocarbene to alkenes 4, 5 is in a sense a diaster-
eoselective process. Consideration of spin–spin coupling constants
JHH, JHF and JCF allowed us to determine relative configurations for
the diastereomeres 14 (A) and 14 (B) (Scheme 2). (The detailed
description of NMR parameters for 14 (A) and 14 (B) including re-
sults of iterative analysis of 1H spectrum is given in Experimental).
The stereospecificity of long-range coupling constant JHH for the
spiropentane has previously been pointed out.7 The sign and value
of 4JHH depend on the path of spin–spin interaction. We have found
that value of 4JHF also has a strong geometric dependence. Thus for
4
4
isomer 14 (A) JH5aF is equal ca. 9 Hz whereas other JHF for both
isomers 14 (A) and 14 (B) have value <1 Hz.
In the NMR spectra of bromofluorospiropentanes 16 and 19 we
can observe two sets of signals that corresponds two possible
diastereomeres. Basing on characteristic coupling constants JHF
* Corresponding author. Tel.: þ7 095 9393969; fax: þ7 095 9390290.
E-mail address: kuzn@org.chem.msu.ru (T.S. Kuznetsova).
4
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.05.032

5694
E.B. Averina et al. / Tetrahedron 65 (2009) 5693–5701
Br
R1
R1
Br
R2
R2
I
CH3Li (LiX)
Li
R1
R2
R2
R1
R1
X
R1
R1
R1
R1
R1
Br
R2
R2
R2
route B
route A
C
or
CH
R2
Br
R2
R2
H3C
OEt
III
IV, X=Br V, X=I
VIII
II
R2=H
X
C
R1
R1
R1
X
R1
VI, X=Br VII, X=I
Scheme 1.
Table 1
Synthesis of gem-bromofluorospiropentanes and their reaction with methyllithium
R1
R1 Br
R2
R3
R2
R3
R5
R6
F
R5
MeLi, Et2O
CHBr2F, 50%NaOH
TEBAC, CH2Cl2
products of fluorine substitution
or rearrangement, allenes
-10 - 0 °C
R6
R4
R4
21-34
1-10
11-20
Alkenes
gem-Bromofluorospiropentanes
Br
Yield (%)
59
Products
Yield (%)
90
F
Br
CH3
1
21
11
Br
F
Br CH3
53
92
25
45
2
22
12
Br
F
Br
CH3
3
23
13
CH3
Br
F
27
27
Ph
Ph
Br
24
52
Ph
C
Ph
4
14
25
CH3
Br
20
41
p-F-C6H4
26
F
Br
p-F-C6H4
35
p-F-C6H4
15
C
5
p-F-C6H4
27

E.B. Averina et al. / Tetrahedron 65 (2009) 5693–5701
5695
Table 1 (continued )
Alkenes
gem-Bromofluorospiropentanes
Yield (%)
Products
CH3
Yield (%)
Br
F
28
14
28
Br
65
C
6
16
29
CH3
Br
28
55
30
F
Br
39
C
7
17
31
CH3
CH3
Br
F
64
39
40
45
8
18
32
CH3
CH3
CH3
F
Br
Ph
Ph
CH3
CH3
Ph
33
9
19
H3C
F
Br
Ph
Ph
Ph
35
51
Ph
Ph
H3C
34
10
20
Ph
H5a
H5a
Ph
H4
H5s
H4
stability of bromofluorospiranes toward alkyllithium reagents rel-
ative to analogous dibromospiranes and thus they need more harsh
reaction conditions. The results of the reactions for compounds 11–
20 under the selected conditions are summarized in Table 1. The
structures of the products obtained (21–34, Table 1) were proved
unambiguously by NMR and mass spectra.
H2s
H2a
(1S,3R,4R)*-14 (A)
H5s
H2s
H2a
F
F
Br
Br
(1S,3S,4S)*-14 (B)
Scheme 2.
We have observed the following general features: (1) in the
case of compounds 11–13, containing internal dihalogenocyclo-
propane moiety, the only isolated products of the reaction were
the corresponding methylbromides 21–23. (2) In the case of ter-
minal bromofluorides 14–17 together with the formation of
methylation products 24, 26, 28, 30, allenes were formed by
a competing reaction path (Scheme 1, route A), i.e., the classical
variant of dihalogenocyclopropanes reaction with alkyllithium
was partially realized. (3) Bromofluorospiranes 18–20 reacted
with methyllithium to form the products of the above mentioned
rearrangement,1,3 namely the corresponding cyclobutenes 32–34.
However, in a sharp contrast with the reaction of analogous
dibromides with methyllithium,1,3 the resulting structures did not
contain halogen atom(s). In fact, structures 32 and 33 observed
here correspond to the previously obtained rearranged structures
of types IV–VII,1,3 but with a formal substitution of bromine atom
for methyl group(s). Thus, fluorine containing dihalogenospiro-
3
and JCF we have also determined relative configurations of stereo-
isomeres for compounds 16 and 19 (see Experimental).
It is obvious that in the majority of cases (compounds 14–16) we
observe preferential formation of less sterically hindered isomers,
where the bromine atom is maximally distant from the most bulky
substituents.
Dihalogenides 11–20 were treated with commercial MeLi free
from LiBr or LiI to avoid the formation of a mixture of Br- and I-
substituted molecules.3,4 The reactions of 11 and 18 with 1 equiv of
MeLi were at first performed at ꢀ55 ꢁC, because this temperature
favored the formation of the rearranged products of types IV and
VI.3c However, only the starting bromofluorospiranes 11 and 18
were observed at this temperature in the reaction mixture. Opti-
mizing the conditions for compounds 11 and 18, we found out that
the reactions between compounds 11–20 and 2 equiv of MeLi were
complete at ꢀ10 to 0 ꢁC. It seems to be the result of a greater
pentanes seem to possess
a characteristic feature to give

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E.B. Averina et al. / Tetrahedron 65 (2009) 5693–5701
methylation products. Moreover, the monomeric intermediate(s)
in the reaction of diphenylsubstituted bromofluorospiropentane
20 similarly undergo double methylation followed by cyclization
leading to the tricyclic molecule 34. The observed general sub-
stitution of fluorine atom for methyl group in cyclopropane
moiety is quite an unexpectable result.5
product formation. Consider first the fact of a smooth substitution
of fluorine for Me group (e.g., 11/21; Table 1). Known is the ex-
ample of analogous substitution of bromine atom for Ph group in
13,13-dibromodispiro[5.0.5.1]tridecane under the treatment with
an excess of PhLi and this phenylation was considered to be a sur-
prising result.11 The formation of bromophenylsubstituted cyclo-
propane moiety was explained by involving single electron transfer
(SET) mechanism12 and by the assumption of a fast coupling in
a caged radical pair.11 Application of this concept to our results
means that (i) the first step of the reaction Li–F exchange proceeds
faster than does Li–Br one and it leads to a caged radical ion pair Xa
(Scheme 3; intermediates X were suggested by applying Scheme IV
in Ref. 12c, using monomeric MeLi); (ii) coupling in a caged radical
pair (Meꢂ and ꢂC–Br) is extremely fast. This concept explains
the formation of monomethylated bromides 21–24, 26, 28, 30, but
The majority of literature data for the reaction of gem-bromo-
fluorocyclopropanes with alkyllithium reagents claims the forma-
tion of allenes as main products.8 At low temperature (about
ꢀ100 ꢁC) gem-bromofluorocyclopropanes are known to give fluoro-
lithium carbenoids with alkyllithium reagents, which can be
carboxylated.6a,9 However, when the reaction temperature was
increased, a complex mixture containing bromo- and fluorosub-
stituted cyclopropanes was detected.6a Thus, based upon literature
data, one cannot unambiguously state, which halogen–carbon bond
(C–F or C–Br) participates at the first step of the reaction at ꢀ10 ꢁC.
Only one example of an unusual reactivity of gem-bromo-
fluorosubstituted polyspirocyclopropanes is known.10 The treat-
ment of highly spirocyclopropanated fluorobromo-[15]-triangulane
with butyllithium at ꢀ10 to ꢀ5 ꢁC led to a remarkable skeletal
rearrangement accompanied by two consecutive cyclopropyl-
carbene to cyclobutene enlargements and incorporation of two
n-butyl groups resulting in a bicyclo[2.2.0]hexane derivative as the
main product.10
the general assumption of
a
fast Li–F exchange seems
questionable.6a,9,13
Moreover, the SET mechanism cannot explain the formation of
rearranged product(s), which arises from some ionic pathway(s)
and one needs to assume the carbenoid intermediates of type XI for
this process. Then, taking into account literature data6a,9 (via car-
boxylation of intermediate fluorolithium carbenoid) the formation
of intermediate fluorolithium cyclopropane carbenoid XIa (Scheme 3)
is also quite possible.
Contrary to the results given above our strained gem-bromo-
fluorosubstituted polyspirocyclopropanes 11–20 react with alkyl-
lithium reagents in an unusual manner. The reaction of these
substrates with methyllithium proceeded with the formal sub-
stitution of a fluorine atom, in some cases followed by either
transformation into allenes or by the rearrangement of carboca-
tionic type. This is a good example of the unusual reactivity of
polyspirocyclopropanes.
There is a principle question: which has to be solved for studied
gem-bromofluorocyclopropanes, which halogen atom undergoes
substitution by Li at the first step of the reaction. Indeed, any
mechanism proposed to explain the dependence of the product on
the halogen has to involve the halogen leaving at some stages of
It seems that initially formed fluorolithium cyclopropane car-
benoid XIa can react with the second molecule of methyllithium via
nucleophilic substitution of the fluorine with a methyl group to give
methyllithium intermediate XII (path a, Scheme 3). It may appear
that intermediate XII is formed according to metal assisted ioni-
zation (MAI)14 of the C–F bond in the carbenoid XIa as it is known
for cyclopropyl halogenolithium carbenoids.14c,15 Then the reaction
of XIa with alkyl bromide (starting dihalospiropentane IX) leads to
the methylated bromide XIII, which is the main pathway for many
cases (compounds 21–24, 26, 28, 30). Some bromofluorides (14–17)
react with methyllithium along two ways (a and b, Scheme 3)
forming methylated products (24, 26, 28, 30) as discussed above
and allenes (25, 27, 29, 31) via corresponding carbenes XIV. This
cage
Y
Br
R1
R1
R2
F
R1
R2
Me
Br
X-
MeLi
-MeBr
(MeLi)
R2
R
R
R
R
R
R
IX
XIII
Xa, X=F, Y=Br
Xb, X=Br, Y=F
R-Br
R1
R2
Y
Li
R
R1
R1
R2
Li
Me
R
MeLi
path a
path b
R2
R
R
R
R
XIa, Y=F
XIb, Y=Br
XII
XIV
R1
R
R
C
R2
XIV
Scheme 3.

E.B. Averina et al. / Tetrahedron 65 (2009) 5693–5701
5697
fact gives evidence that fluorocarbenoid precursors XIa undergo
both -elimination and methylation to give the products of path-
ways a and b (Scheme 3).
reactions, (b) a-elimination forming the allenes, (c) intramolecular
a
nucleophilic substitution of fluorine with C–C bond combined with
methylation which yielded the rearranged products 32–34.
The unusual reactivity of spiropentane bromofluorides IX in the
reactions with methyllithium can be explained by their ambiphilic
nature because fluorolithium carbenoids can act as both electro-
philic and nucleophilic agents. Nevertheless, the detailed mecha-
nism of this process is still a subject of further investigation.
The most interesting fact is that carbenoids generated from
bromofluorides 18–20 formed only rearranged products 32–34.
This can be explained as a result of intramolecular nucleophilic
attack at the carbenoid carbon by a neighbor C–C bond with cyclo-
propane ring opening followed by the isomerization of bicy-
clo[2.1.0]pentane derivative XVI into four-membered cyclic
intermediate XVII (Scheme 4). Apparently intermediates XVI and
XVII may be represented as carbon cationdfluorine anion tight ion
pairs and methyl group is incorporated in the structure XVII via its
reaction with methyllithium likewise nucleophilic substitution of
fluorine by methyl group proceeds in carbenoid XIa (Scheme 4).
This process leads to intermediate XVIII, which is lithium allylic
derivative and may be prone to [1,3]-sigmatropic migration of C–Li
bond to give the lithium derivative XIX. The sigmatropic tautom-
erism of allyl lithium derivatives (or even acceptance of pure ionic
structure) is well documented in literature.16 Cyclobutene in-
termediate XIX can react with either parent dihalospiropentane IX
or with methyl bromide giving rearranged products 33 or XX, re-
3. Experimental
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,
¼77.13 ppm). Mass
d
spectra were taken on a Finnigan MAT 95 XL spectrometer (70 eV)
using electron impact ionization (EI) and GC–MS coupling. MALDI-
TOF spectra were recorded in positive mode using Bruker Ultraflex
mass spectrometer with dithranol as a matrix. Accurate 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. Infrared spectra were recorded on
a Thermo Nicolet FTIR-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 chro-
matography was performed using silica gel 60 (230–400 mesh,
Merck). GLC analyses and separation were performed using silicone
E-301 (15% on Inerton AW). Petroleum ether used refers to the
fraction boiling at 40–60 ꢁC. All reagents except commercial prod-
ucts of satisfactory quality were purified by literature procedures
prior to use. Starting compounds: bicyclopropylidene (1),17 cyclo-
propylidenecyclobutane (2),18 cyclopropylidenecyclohexane (3),18
(2-methylenecyclopropyl)benzene (4),19,20 1-fluoro-4-(2-methyl-
spectively. If there are no substituents in a-position of the starting
dihalogenide IX the molecule of bromide XX reacts with lithium
intermediate XIX, yielding ‘dimeric’ rearranged product 32.
Consider now the formation of tricyclic compound 34. The most
probable intermediate for its formation is the corresponding
methylenecyclobutane derivative XVII (R1¼R2¼Ph). Thus, one may
accept the electrophilic substitution at the ortho-position of one
phenyl group and subsequent reaction with methyllithium and
methyl bromide (Scheme 4).
Thus, our experimental results demonstrate that in contrast
with gem-dibromospiropentanes the reactions of bromo-
fluorospiropentanes 11–20 with methyllithium at relatively high
temperatures (ꢀ10 to 0 ꢁC) proceed as the unexpected methylation
and may proceed via at least three pathways depending on the
substituents at the carbenoid center: (a) nucleophilic substitution
of fluorine with methyl group, which occurred in majority
enecyclopropyl)benzene
(5),20
1-methylenespiro[2.3]hexane
Li
Me
1) MeBr
2) MeLi
3) H2O
Li
Li
+
Li
F
F
R1
R2
F
Br
MeLi
-MeBr
-F-
R1=R2=Ph
R2
R2
R2
+
R1
R1
F
Me
R1
XVII
Ph
Ph
XVI
IX
X
XXI
34
MeLi
Li
Me
R2
Me
Me
R1
IX
R2
Br
Li
R1
R1
R2
XIX
XVIII
XX
R1=Ph
R1=R2=H
MeBr
XIX
R2=Me
Me
Me Me
Me
Me
33
Ph
32
Scheme 4.

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E.B. Averina et al. / Tetrahedron 65 (2009) 5693–5701
(6),20,21 9-methylenebicyclo[6.1.0]nonane (7),20 methylenecyclo-
propane (8),22 (1-cyclopropylideneethyl)benzene (9),23 1,10-(cyclo-
propylidenemethylene)dibenzene (10),23 were synthesized by
known procedures.
4JAE ꢀ0.74, 4JHF 8.95, CH2, A¼H5a), 1.437 (1H, 2JDE ꢀ7.36, 4JBD ꢀ0.68,
4JCD 0.86, 3JHF 3.25, CH2, D¼H2a),1.447 (1H, 2JAB ꢀ5.13, 3JBC 8.70, 4JBD
ꢀ0.68, 4JBE 0.98, CH2, B¼H5s), 1.555 (1H, 2JDE ꢀ7.36, 4JAE ꢀ0.74, 4JBE
4
3
3
3
0.98, JCE ꢀ0.71, JHF 12.32, CH2, E¼H2s), 2.482 (1H, JAC 5.54, JBC
8.70, 4JCD 0.86, 4JCE ꢀ0.71, 4JHF 0.55, CH, C¼H4), minor isomer (B),
d:
3.2. General procedure 1: addition of bromofluorocarbene to
alkenes 1–10
1.237 (1H, 2JAB ꢀ5.10, 3JAC 5.80, 4JAD ꢀ0.78, 4JAE ꢀ0.10, 4JHF 0.77, CH2,
A¼H5a), 1.317 (1H, 2JDE ꢀ7.33, 4JAD ꢀ0.78, 4JBD 0.94, 4JCD ꢀ0.71, 3JHF
3.60, CH2, D¼H2a), 1.633 (1H, 2JDE ꢀ7.33, 4JAE ꢀ0.10, 4JBE ꢀ0.65, 4JCE
3
2
3
4
A 50% aqueous solution (10 mL) of NaOH was added to
16.0 mmol of the corresponding alkene, 9.22 g (48.0 mmol) of
CHBr2F and 0.73 g (2.6 mmol) of TEBAC in 10 mL of dichloro-
methane at 0 ꢁC in 0.5 h. Then a drop of ethanol was added. The
reaction mixture was warmed up to room temperature and stirred
for 48 h. Then it was treated with 25 mL of cold water. The organic
phase was separated and the water phase extracted with
dichloromethane (3ꢃ50 mL). The combined organic fractions were
washed with 100 mL of water and dried over MgSO4. The solvent
was evaporated, the residue was distilled or purified by column
chromatography.
1.01, JHF 12.05, CH2, E¼H2s),1.644 (1H, JAB ꢀ5.10, JBC 8.68, JBD
4 4 3 3
0.94, JBE ꢀ0.65, JHF 0.94, CH2, B¼H5s), 2.331 (1H, JAC 5.80, JBC
8.68, 4JCD ꢀ0.71, 4JCE 1.01, 4JHF 0.90, CH, C¼H4), aromatic protons
d:
6.90–6.93 (m, 2H, Ph, A), 6.93–6.96 (m, 2H, Ph, B), 7.10–7.13 (m, 2H,
Ph, AþB), 7.16–7.20 (m, 4H, Ph, AþB). 13C NMR (101 MHz, CDCl3)
d:
17.0 (3JCF 3.6, CH2, B), 18.7 (CH2, A), 21.8 (2JCF 11.7, CH2, A), 22.0 (2JCF
11.7, CH2, B), 24.0 (3JCF 2.7, CH, A), 25.6 (3JCF 0.5, CH, B), 29.8 (2JCF 9.7,
C-spiro, A), 30.1 (2JCF 10.6, C-spiro, B), 84.4 (1JCF 306.3, CBrF, AþB),
84.4 (1JCF 305.0, CBrF, AþB), 126.4 (2CH, Ph, Aþ2CH, Ph, B), 126.5
(CH, Ph, AþCH, Ph, B), 128.5 (2CH, Ph, Aþ2CH, Ph, B), 139.0 (C, Ph,
A), 139.6 (C, Ph, B). 19F NMR (376 MHz, CDCl3)
d
: ꢀ134.56 (X part of
3
3
4
4
ABCDEX system, 1F, JHF 3.25, JHF 12.32, JHF 0.55, JHF 8.95, A),
ꢀ133.44 (X part of ABCDEX system,1F, 3JHF 3.60, 3JHF 12.05, 4JHF 0.77,
4JHF 0.94, 4JHF 0.90, B). Anal. Calcd for C11H10BrF: C, 54.80; H, 4.18%.
Found: C, 54.60; H, 4.02%.
3.3. 7-Bromo-7-fluorodispyro[2.0.2.1]heptane 11
Yield 1.80 g (59%), colorless liquid, bp 55–60 ꢁC/60 torr. IR (film):
n
3078, 2993, 1458, 1435, 1317, 1200, 1090, 1005, 964, 910, 866, 609,
510 cmꢀ1. 1H NMR (400 MHz, CDCl3)
d: 0.93–1.00 (m, 2H), 1.04–1.15
3.7. 1-Bromo-1-fluoro-4-(4-fluorophenyl)spiro[2.2]-
pentane 15
(m, 4H), 1.34–1.40 (m, 2H). 13C NMR (101 MHz, CDCl3) : 7.7 (1JCH
d
164, 2ꢃCH2), 9.1 (1JCH 163, 2ꢃCH2), 25.9 (2JCF 11, 2ꢃC-spiro), 90.8
(1JCF 312, CFBr). 19F NMR (376 MHz, CDCl3)
d
: ꢀ133.34 (t,1F, 4JHF 8.5).
Yield 1.82 g (44%), colorless liquid, Rf 0.4 (petroleum ether). Two
Anal. Calcd for C7H8BrF: C, 44.01; H, 4.22%. Found: C, 43.98; H,
4.03%.
isomers, A:B 1:0.9. IR (film):
n
3060, 3010, 2940, 2860, 1600, 1508,
: 1.33
1260, 1190, 1090, 840, 595 cmꢀ1. 1H NMR (400 MHz, CDCl3)
d
2
3
(ddd, 1H, JHH 5.2, 3JHH 5.4, JHF 8.7, CH2, A), 1.52–1.57 (m, 2H, CH2,
B), 1.70 (dd, 1H, 2JHH 5.2, 3JHH 8.5, CH2, A), 1.73–1.83 (m, 2H, CH2, A),
1.94–2.01 (m, 2H, CH2, B), 2.50 (dd,1H, 3JHH 5.6, 3JHH 8.5, CH, B), 2.75
3.4. 8-Bromo-8-fluorodispiro[2.0.3.1]octane 12
3
3
Yield 1.74 g (53%), colorless liquid, bp 114 ꢁC/60 torr. IR (film):
3080, 2998, 1445, 1315, 1020, 930, 824, 725, 606, 522 cmꢀ1. 1H NMR
(400 MHz, CDCl3) : 0.90–0.95 (m, 1H, CH2, c-Pr), 0.95–1.04 (m, 1H,
n
(dd, 1H, JHH 5.4, JHH 8.5, CH, A), 6.97–7.10 (m, 4H, CH, Ph, Aþ4H,
CH, Ph, B). 13C NMR (101 MHz, CDCl3) (AþB)
d
: 16.9 (3JCF 4, 1JCH 165,
d
CH2), 18.5 (1JCH 165, CH2), 21.7 (2JCF 12, 1JCH 163, CH2), 21.8 (2JCF 12,
1JCH 165, CH2), 23.3 (1JCH 162, CH, B), 24.9 (1JCH 163, CH), 29.9 (2JCF
10, C-spiro), 39.9 (2JCF 10, C-spiro), 84.1 (1JCF 305, 2CBrF), 115.3 (1JCH
163, 2CH, Ph), 115.5 (1JCH 163, 2CH, Ph), 127.9 (2JCF 7, 1JCH 160, 4CH,
Ph), 134.5 (C, Ph, A), 135.3 (C, Ph, B), 161.7 (1JCF 244, 2CF, Ph). 19F
CH2, c-Pr), 1.11–1.16 (m, 1H, CH2, c-Pr), 1.17–1.24 (m, 1H, CH2, c-Pr),
1.86–2.03 (m, 3H, CH2, c-Bu), 2.05–2.13 (m, 1H, CH2, c-Bu), 2.23–
2.32 (m, 1H, CH2, c-Bu), 2.33–2.42 (m, H, CH2, c-Bu). 13C NMR
(101 MHz, CDCl3) d: 7.4 (CH2), 9.0 (CH2), 15.42 (CH2), 23.0 (CH2),
3
3
4
26.8 (CH2), 29.2 (2JCF 10, C-spiro), 35.2 (2JCF 12, C-spiro), 92.8 (1JCF
NMR (376 MHz, CDCl3)
d
: ꢀ134.74 (ddd, 1F, JHF 3.4, JHF 12.2, JHF
311, CBrF). 19F NMR (376 MHz, CDCl3)
Anal. Calcd for C8H10BrF: C, 46.86; H, 4.92%. Found: C, 46.76; H,
5.07%.
d
: ꢀ136.10 (br d, 1F, 4JHF 8.6).
8.7, A), ꢀ133.77 (br dd, 1F, 3JHF 3.4, 3JHF 12.3, B), ꢀ117.20 to ꢀ117.31
(m,1F, Ph, Aþ1F, Ph, B). Anal. Calcd for C11H9BrF2: C, 50.99; H, 3.50%.
Found: C, 51.09; H, 3.60%.
3.5. 10-Bromo-10-fluorodispyro[2.0.5.1]decane 13
3.8. 1-Bromo-1-fluorodispiro[2.0.3.1]octane 16
Yield 3.28 g (86%), colorless oil, bp 115 ꢁC/8 torr. IR (film):
3002, 2850, 1452, 1380, 1250, 1010, 720, 609, 569 cmꢀ1 1H NMR
(400 MHz, CDCl3) : 0.83–0.88 (m, 1H, CH2, c-Pr), 0.94–1.02 (m, 1H,
CH2, c-Pr), 1.08–1.18 (m, 2H, CH2, c-Pr), 1.35–1.75 (m, 10H, 5ꢃCH2, c-
n
3076,
Yield 2.13 g (65%), colorless liquid, bp 110 ꢁC/110 torr. Two iso-
.
mers, (1S,3R)
1024, 910, 720, 610, 515 cmꢀ1. 1H NMR (400 MHz, CDCl3)
1H, 2JHH 5.4, 4JHF 8.3, C(8)H2, c-Pr, A), 1.09 (d, 1H, 2JHH 5.2, C(8)H2, c-
*
-A:(1S,3S)
*
-B¼5:1. IR (film):
n
3050, 2925, 2850, 1480,
d
d: 1.03 (dd,
Hex). 13C NMR (101 MHz, CDCl3)
d
: 5.7 (1JCH 164, CH2, c-Pr), 7.5 (1JCH
Pr, B), 1.13 (d, 1H, JHH 5.4, C(8)H2, c-Pr, A), 1.28 (d, 1H, JHH 5.2,
C(8)H2, c-Pr, B), 1.51 (dd, 1H, 2JHH 6.9, 3JHF 2.9, C(2)H2, c-Pr, A), 1.65
(dd, 1H, 2JHH 6.8, 3JHF 2.8, C(2)H2, c-Pr, B), 1.73 (dd, 1H, 2JHH 6.8, 3JHF
11.6, C(2)H2, c-Pr, B), 1.86 (dd, 1H, 2JHH 6.9, 3JHF 12.9, C(2)H2, c-Pr, A),
1.92–2.31 (m, 5H, CH2, c-Bu, Aþ5H, CH2, c-Bu, B), 2.34–2.43 (m, 1H,
CH2, c-Bu, A), 2.64–2.72 (m, 1H, CH2, c-Bu, B). 13C NMR (101 MHz,
2
2
163, CH2, c-Pr), 24.8 (1JCH 127, CH2, c-Hex), 25.2 (1JCH 127, CH2, c-
Hex), 25.9 (1JCH 130, CH2, c-Hex), 28.4 (1JCH 131, 2JCF 4, CH2, c-Hex),
30.0 (2JCF 10, C-spiro), 32.7 (2JCF 9, C-spiro), 33.1 (1JCH 127, CH2, c-
Hex), 97.7 (1JCF 310, CFBr). 19F NMR (376 MHz, CDCl3)
d
: ꢀ140.51 (br
d, 1F, 4JHF 8.9). Anal. Calcd for C10H14BrF: C, 51.52; H, 6.05%. Found:
C, 51.60; H, 6.15%.
CDCl3) d
: 16.8 (CH2, c-Bu, B), 17.0 (CH2, c-Bu, A), 18.0 (3JCF 3.0, CH2, c-
Pr, B), 21.3 (CH2, c-Pr, A), 21.8 (2JCF 11.7, CH2, c-Pr, A), 22.4 (2JCF 11.0,
CH2, c-Pr, B), 25.7 (CH2, c-Bu, B), 27.7 (CH2, c-Bu, A), 27.9 (C-spiro, B),
28.1 (3JCF 4.3, C-spiro, A), 29.1 (CH2, c-Bu, AþCH2, c-Bu, B), 30.0 (2JCF
10.2, C-spiro, A), 30.5 (2JCF 11.0, C-spiro, B), 85.4 (1JCF 307, CBrF, B),
3.6. 1-Bromo-1-fluoro-4-phenylspiro[2.2]pentane 14
Yield 2.01 g (52%), colorless liquid, bp 120 ꢁC/8 torr. Two iso-
mers, (1S,3R,4R)
*
-A:(1S,3S,4S)
*
-B¼1:0.9. IR (film):
n
3080, 3020,
86.5 (1JCF 305, CBrF, A). 19F NMR (376 MHz, CDCl3)
d
: ꢀ139.75 (ddd,
3000, 2835, 1600, 1580, 1450, 1350, 1200, 1010, 720, 610, 504 cmꢀ1
.
1F, 3JHF 2.9, 3JHF 12.9, 4JHF 8.3, A), ꢀ130.08 (dd, 1F, 3JHF 2.8, 3JHF 11.6,
B). Anal. Calcd for C8H10BrF: C, 46.86; H, 4.92%. Found: C, 49.93; H,
4.73%.
1H NMR (600 MHz, C6D6), alicyclic protons (ABCDE part of ABCDEX
system, X¼19F), major isomer (A),
d
: 1.038 (1H, 2JAB ꢀ5.13, 3JAC 5.54,

E.B. Averina et al. / Tetrahedron 65 (2009) 5693–5701
5699
3.9. 20-Bromo-20-fluorospiro[bicyclo[6.1.0]nonane-9,10-
cyclopropane] 17
10 mL of absolute ether at ꢀ55 ꢁC in argon. The reaction mixture was
warmed up to ꢀ10 ꢁC and stirred for 72 h. Then it was warmed up to
0 ꢁC and quenched with equal amount of cold water. The organic
phase was separated, the water phase extracted with ether
(3ꢃ3 mL). The combined organic fractions were washed with 5 mL
of water and dried over MgSO4. The solvent was evaporated, the
products were isolated by preparative column chromatography or
GLC (column 3000ꢃ5 mm, silicone E-301, 15% on Inerton AW).
Yield 1.54 g (39%), colorless liquid, Rf 0.5 (petroleum ether). IR
(film):
n
3045, 2995, 2923, 2854, 1467, 1163, 1061, 1024, 858, 815,
: 1.02–1.21 (m, 2H),1.24–
: 19.1
760, 710 cmꢀ1. 1H NMR (400 MHz, CDCl3)
d
1.32 (m, 2H), 1.39–1.88 (m, 12H). 13C NMR (101 MHz, CDCl3)
d
(2JCF 12, CH2, c-Pr), 22.9 (3JCF 2, CH, c-Pr), 23.7 (CH2, c-Oct), 24.3 (CH,
c-Pr), 24.7 (CH2, c-Oct), 26.5 (2CH2, c-Oct), 28.6 (CH2, c-Oct), 28.7
(CH2, c-Oct), 30.3 (2JCF 10, C-spiro), 85.3 (1JCF 305, CBrF). 19F NMR
3.14. 7-Bromo-7-methylbicyclo[2.0.2.1]heptane 2124
(376 MHz, CDCl3)
for C11H16BrF: C, 53.46; H, 6.53%. Found: C, 53.18; H, 6.60%.
d
: ꢀ129.98 (dd, 1F, 3JHF 2.5, 3JHF 11.7, B). Anal. calcd
Yield 0.67 g (90%), colorless liquid, Rf 0.5 (petroleum ether). IR
(film):
n
3070, 2990, 2870, 1470, 1380, 1200, 964, 912, 865,
605 cmꢀ1
.
1H NMR (400 MHz, CDCl3)
d
: 0.73–0.77 (m, 2H), 0.82–
3.10. 1-Bromo-1-fluorospyropentane 18
0.85 (m, 2H), 0.93–1.04 (m, 4H), 1.70 (s, CH3). 13C NMR (101 MHz,
CDCl3)
CH3), 26.9 (2ꢃC-spiro), 44.0 (CBr). MS (FAB): 187, 185 (2, Mꢀ1), 91
(100, MꢀBrꢀMe). MS (EI, 70 eV) m/z: 187 ([Mꢀ1]þ, 2),185 ([Mꢀ1]þ,
2), 173 (4), 171 (4), 107 ([MꢀBr]þ, 33), 91 (100), 79 (93), 65 (26), 51
(21), 41 (22), 39 (28).
Yield 1.69 g (64%), colorless liquid, bp 110–111 ꢁC. IR (film):
n
d
: 7.0 (1JCH 165, 2ꢃCH2), 8.5 (1JCH 159, 2ꢃCH2), 25.9 (1JCH 129,
3082, 3005, 1435, 1394, 1194, 1109, 1072, 1018, 930, 822, 594 cmꢀ1
.
1H NMR (400 MHz, CDCl3)
1.30–1.38 (m, 1H), 1.68 (dd, 1H, JHH 7.1, JHF 3.2), 1.91 (dd, 1H, JHH
7.1, 3JHF 12.4). 13C NMR (101 MHz, CDCl3) : 8.0 (1JCH 164, 3JCF 3, CH2),
9.7 (1JCH 165, CH2), 22.1 (2JCF 10, C-spiro), 23.0 (1JCH 165, 2JCF 12, CH2),
85.3 (1JCF 305, CFBr). 19F NMR (376 MHz, CDCl3)
d: 1.04–1.12 (m, 2H), 1.22–1.30 (m, 1H),
2
3
2
d
d
: ꢀ134.46 to
3.15. 8-Bromo-8-methyldispiro[2.0.3.1]octane 22
ꢀ134.53 (m, 1F). Anal. Calcd for C5H6BrF: C, 36.40; H, 3.67%. Found:
C, 36.67; H, 3.98%.
Yield 0.20 g (25%), colorless liquid, Rf 0.2 (petroleum ether). IR
(film):
NMR (400 MHz, CDCl3)
n
3075, 2996, 2870, 1465, 1378, 915, 820, 718, 609 cmꢀ1. 1H
3.11. 1-Bromo-1-fluoro-2-methyl-2-phenylspiro[2.2]-
pentane 19
d
: 0.81–0.84 (m, 1H, CH2, c-Pr), 0.89–0.92
(m, 1H, CH2, c-Pr), 0.93–0.98 (m, 2H, CH2, c-Pr), 1.65 (s, 3H, CH3),
1.92–2.01 (m, 4H, 2CH2, c-Bu), 2.23–2.28 (m, 1H, CH2, c-Bu), 2.38–
Yield 1.59 g (39%), colorless liquid, Rf 0.4 (petroleum ether). Two
2.44 (m, 1H, CH2, c-Bu). 13C NMR (101 MHz, CDCl3)
d: 7.1 (CH2), 8.7
isomers, (1R,2R)
3000, 2930, 2880, 1600, 1500, 1450, 1380, 1190, 1100, 1005, 980,
875, 780, 710, 640 cmꢀ1. 1H NMR (400 MHz, CDCl3)
: 1.10 (ddd, 1H,
*
-A:(1R,2R)
*
-B¼1:0.95. IR (film):
n 3070, 3030,
(CH2), 14.9 (CH2), 23.9 (CH2), 24.3 (CH3), 26.2 (C-spiro), 28.1 (CH2),
30.2 (C-spiro), 46.7 (CBr). MS MALDI-TOF calcd for C9H1379Br (Mþ):
200.02, found: 200.60; MS (EI, 70 eV) m/z: 174 ([MꢀC2H4]þ, 58),172
([MꢀC2H4]þ, 62), 159 (3), 157 (3), 121 (8), 105 (12), 93 (100), 91 (66),
79 (37), 77 (75), 65 (37), 55 (12), 53 (23), 41 (19), 39 (35). Anal. Calcd
for C9H13Br: C, 53.75; H, 6.52%. Found: C, 53.37; H, 6.75%.
d
CH2), 1.13–1.32 (m, 4H, CH2), 1.42–1.48 (m, 1H, CH2), 1.50–1.58 (m,
2H, CH2), 1.63 (d, 3H, 4JHF 2.0, CH3), 1.64 (d, 3H, 4JHF 2.5, CH3), 7.28–
7.41 (m, 5H, Ph, Aþ5H, Ph, B). 13C NMR (101 MHz, CDCl3)
d
: 6.2 (3JCF
4.0, CH2, B), 8.9 (CH2, A), 9.0 (3JCF 3.8, CH2, A), 10.8 (CH2, B), 20.4 (3JCF
5.1, CH3, B), 24.9 (3JCF 3.9, CH3, A), 30.9 (2JCF 8.4, C-spiro, A), 31.0 (2JCF
9.8, C-spiro, B), 34.5 (2JCF 9.8, C, A), 35.3 (2JCF 11.0, C, B), 94.0 (1JCF
314, CBrF), 94.9 (1JCF 308, CBrF), 127.0 (2CH, Ph), 128.3 (2CH, Ph),
128.3 (2CH, Ph), 128.4 (2CH, Ph), 128.4 (2CH, Ph), 138.9 (C, Ph), 141.9
3.16. 10-Bromo-10-methyldispyro[2.0.5.1]decane 2325
Yield 0.41 g (45%), colorless liquid, Rf 0.4 (petroleum ether). IR
n .
3070, 3000, 2856, 1462, 1380, 725, 612 cmꢀ1 1H NMR
(C, Ph). 19F NMR (376 MHz, CDCl3)
d
: ꢀ136.60 (br d, 1F, 4JHF 8.6, B),
(film):
(400 MHz, CDCl3)
CH2, c-Pr), 0.94–0.99 (m, 1H, CH2, c-Pr), 1.30–1.78 (m, 10H, CH2, c-Hex),
1.81 (s, 3H, CH3). 13C NMR (101 MHz, CDCl3)
: 5.6 (CH2, c-Pr), 7.3 (CH2,
ꢀ130.67 (br d, 1F, 4JHF 8.1, A). Anal. Calcd for C12H12BrF: C, 56.49; H,
d: 0.73–0.79 (m, 1H, CH2, c-Pr), 0.86–0.90 (m, 2H,
4.74%. Found: C, 56.70; H, 4.74%.
d
c-Pr), 24.3 (CH3), 25.4 (CH2, c-Hex), 25.6 (CH2, c-Hex), 26.0 (CH2, c-Hex),
29.5 (C-spiro), 30.1 (CH2, c-Hex), 30.9 (C-spiro), 35.0 (CH2, c-Hex), 50.9
(CBr). MS (EI, 70 eV) m/z: 230 (Mþ, 36), 228 (Mþ, 37), 149 ([MꢀBr]þ,
80), 119 (8), 107 (18), 91 (28), 81 (73), 67 (100), 55 (8), 41 (12).
3.12. 1-Bromo-1-fluoro-2,2-diphenylspiro[2.2]pentane 20
Yield 1.77 g (35%), colorless solid, mp 106–108 ꢁC, Rf 0.2 (pe-
troleum ether). IR (film):
n 3068, 3040, 2970, 2940, 2860, 1600,
1500,1470,1390,1180,1060, 715, 650, 605 cmꢀ1. 1H NMR (400 MHz,
CDCl3)
d
: 1.30 (ddd,1H, 2JHH 5.1, 3JHH 6.7, 3JHH 9.5, CH2),1.45 (ddd,1H,
3.17. 1-Bromo-1-methyl-4-phenylspiro[2.2]pentane 24
2JHH 5.0, 3JHH 6.4, 3JHH 9.5, CH2), 1.52 (dddd, 1H, 2JHH 5.0, 3JHH 6.7, 3JHH
9.1, 4JHF 0.9, CH2), 1.72 (dddd, 1H, 2JHH 5.1, 3JHH 6.4, 3JHH 9.1, 4JHF 9.0,
Yield 0.26 g (27%), two isomers, A:B 1:0.6, colorless oil, Rf 0.2
CH2), 7.24–7.38 (m, 10H, Ph). 13C NMR (101 MHz, CDCl3)
d
: 8.3 (3JCF
(petroleum ether). IR (film):
n
3078, 3020, 3000, 2850, 1600, 1458,
: 1.17 (d, 1H,
4, CH2), 11.3 (CH2), 32.0 (2JCF 9, C-spiro), 43.0 (2JCF 10, C), 93.3 (1JCF
312, CBrF), 127.2 (CH, Ph), 127.2 (CH, Ph), 128.2 (2CH, Ph), 128.5
(2CH, Ph), 129.3 (2CH, Ph), 129.5 (2CH, Ph), 139.0 (C, Ph), 141.0 (3JCF
4, C, Ph). MS (EI, 70 eV) m/z: 318 (Mþ, 12), 316 (Mþ, 12), 237
([MꢀBr]þ, 100), 222 (29), 203 (35), 159 (32), 115 (19), 109 (21), 91
1376, 1230, 720, 610 cmꢀ1. 1H NMR (400 MHz, CDCl3)
d
2JHH 5.8, CH2, B), 1.32 (d, 1H, 2JHH 5.8, CH2, A), 1.33 (dd, 1H, 2JHH 4.7,
3JHH 5.5, CH2, A), 1.37 (dd, 1H, 2JHH 4.9, 3JHH 5.0, CH2, B), 1.46 (d, 1H,
2JHH 5.8, CH2, A), 1.65 (d, 1H, 2JHH 5.8, CH2, B), 1.68 (dd, 1H, 2JHH 4.9,
3JHH 8.4, CH2, B), 1.76 (dd, 1H, 2JHH 4.7, 3JHH 8.4, CH2, A), 1.81 (s, 3H,
CH3, B), 1.86 (s, 3H, CH3, A), 2.45 (dd, 3JHH 5.5, 3JHH 8.4, CH, A), 2.53
(dd, 3JHH 5.0, 3JHH 8.4, CH, B), 7.08–7.12 (m, 2H, Ph, B), 7.16–7.19 (m,
2H, Ph, A), 7.20–7.25 (m, 2H, Ph, AþB), 7.28–7.35 (m, 4H, Ph, AþB).
(43). 19F NMR (376 MHz, CDCl3)
Calcd for C17H14BrF: C, 64.37; H, 4.95%. Found: C, 65.37; H, 4.75%.
d
: ꢀ128.15 (br d, 1F, 4JHF 9.0). Anal.
3.13. General procedure 2: reaction of gem-bromofluoro-
spiropentanes 11–20 with methyllithium
13C NMR (101 MHz, CDCl3) : 17.3 (1JCH 163, CH2, A), 19.3 (1JCH 163,
d
CH2, B), 22.0 (1JCH 161, CH2, B), 22.1 (1JCH 161, CH2, A), 23.8 (1JCH 166,
CH, B), 25.5 (1JCH 166, CH, A), 27.6 (1JCH 130, CH3, A), 27.7 (1JCH 129,
CH3, B), 31.6 (C-spiro, B), 31.8 (C-spiro, A), 36.9 (CBr, B), 37.5 (CBr, A),
125.9 (2CH, Ph), 126.0 (2CH, Ph), 126.5 (2CH, Ph), 128.3 (2CH, Ph),
A solution (5.4 mL) of 1.5 N (8.0 mmol) methyllithium in ether was
added dropwise to solution of 4.0 mmol bromofluorospiropentane in

5700
E.B. Averina et al. / Tetrahedron 65 (2009) 5693–5701
128.4 (2CH, Ph), 141.1 (C, Ph, A), 141.2 (C, Ph, B). Anal. Calcd for
C12H13Br: C, 60.78; H, 5.53%. Found: C, 60.68; H, 5.29%.
77 (42), 65 (15), 53 (20), 41 (22), 39 (28). Anal. Calcd for C9H13Br: C,
53.75; H, 6.52%. Found: C, 53.45; H, 6.82%.
3.18. (2-Vinylidenecyclopropyl)benzene 2526
3.22. 1-Ethenylidenespiro[2.3]hexane 29
Yield 0.15 g (27%), colorless liquid, Rf 0.4 (petroleum ether). IR
Yield 0.06 g (14%), colorless liquid, Rf 0.3 (petroleum ether). IR
(film):
865 cmꢀ1
2.11–2.17 (m, 1H, CH2), 3.00–3.07 (m, 1H, CH), 4.95–5.01 (m, 2H,
CH2]), 7.18–7.43 (m, 5H, Ph). 13C NMR (101 MHz, CDCl3)
: 18.1
n
3080, 3020, 3005, 2835, 1970, 1585, 1450, 1350, 1062,
(film):
NMR (400 MHz, CDCl3)
(m, 2H, CH2, c-Bu), 2.16–2.26 (m, 2H, CH2, c-Bu), 2.37–2.47 (m, 2H,
CH2, c-Bu), 4.81 (m, 2H, CH2]). 13C NMR (101 MHz, CDCl3)
: 16.8
n .
3068, 2995, 2897, 1958, 1470, 1440, 1062, 750 cmꢀ1 1H
.
1H NMR (400 MHz, CDCl3)
d
: 1.69–1.80 (m, 1H, CH2),
d: 1.57–1.62 (m, 2H, CH2, c-Pr), 2.00–2.15
d
d
(CH2), 25.1 (CH), 77.8 (CH2]), 81.0 (C]), 126.4 (CH, Ph), 126.6 (2CH,
Ph), 128.2 (2CH, Ph), 140.5 (C, Ph), 194.3 (]C]). MS MALDI-TOF
calcd for C11H10 (Mþ): 142.08, found: 141.98.
(1JCH 137, CH2, c-Bu), 21.5 (1JCH 163, CH2, c-Pr), 27.9 (C-spiro), 30.7
(1JCH 137, 2CH2, c-Bu), 76.2 (1JCH 168, CH2]), 83.4 (C]), 193.5
(]C]). MS (EI, 70 eV) m/z: 106 (Mþ, 3), 105 (31), 91 (100), 78 (94),
65 (25), 52 (36), 39 (28). Anal. Calcd for C8H10Br: C, 90.51; H, 9.49%.
Found: C, 90.19; H, 9.35%.
3.19. 1-Bromo-1-methyl-4-(4-fluorophenyl)spiro[2.2]-
pentane 26
3.23. 20-Bromo-20-methylspiro[bicyclo[6.1.0]nonane-9,10-
cyclopropane] 30
Yield 0.42 g (43%), two isomers, A:B 1:0.65, colorless oil, Rf 0.2
(petroleum ether). IR (film):
n
3060, 3010, 2955, 2868, 1600, 1508,
: 1.13 (d, 1H,
1260, 1180, 840, 593 cmꢀ1. 1H NMR (400 MHz, CDCl3)
d
Yield 0.27 g (28%), colorless liquid, Rf 0.5 (petroleum ether). IR
2JHH 6.0, CH2, B), 1.26–1.32 (m, 2H, CH2, Aþ1H, CH2, B), 1.41 (d, 1H,
2JHH 6.1, CH2, A), 1.61 (d, 1H, 2JHH 6.0, CH2, B), 1.63–1.70 (m, 1H, CH2,
B), 1.73 (dd, 2JHH 5.0, 3JHH 8.5, 1H, CH2, A), 1.79 (s, 3H, CH3, B), 1.84 (s,
3H, CH3, A), 2.41 (dd, 3JHH 5.3, 3JHH 8.5, 1H, CH, A), 2.76 (dd, 3JHH 5.6,
3JHH 8.6, 1H, CH, B), 6.95–7.21 (m, 4H, 4CH, Ph, Aþ4H, 4CH, Ph, B).
(film): n 3060, 2995, 2960, 2856, 1446, 1361, 1162, 1060, 858, 761,
521 cmꢀ1. 1H NMR (400 MHz, CDCl3) : 0.94 (d, 1H, 2JHH 5.4, CH2, c-
d
Pr), 1.03–1.19 (m, 2H), 1.25–1.31 (m, 1H), 1.25 (d, 1H, 2JHH 5.4, CH2, c-
Pr), 1.37–1.79 (m, 10H), 1.72 (s, 3H, CH3), 1.81–1.88 (m, 1H). 13C NMR
(101 MHz, CDCl3) d
: 19.2 (1JCH 162, CH2, c-Pr), 22.4 (1JCH 160, CH, c-
13C NMR (101 MHz, CDCl3)
d
: 17.0 (1JCH 162, CH2, A), 19.1 (1JCH 163,
Pr), 24.0 (1JCH 160, CH, c-Pr), 25.0 (1JCH 125, CH2, c-Oct), 25.1 (1JCH
125, CH2, c-Oct), 26.6 (1JCH 125, CH2, c-Oct), 26.7 (1JCH 125, CH2, c-
Oct), 27.8 (1JCH 128, CH3), 29.0 (1JCH 125, CH2, c-Oct), 29.1 (1JCH 125,
CH2, c-Oct), 31.5 (C-spiro), 38.3 (CBr). Anal. Calcd for C12H19Br: C,
59.27; H, 7.88%. Found: C, 59.42; H, 7.79%.
CH2, B), 21.9 (1JCH 164, CH2, B), 22.0 (1JCH 164, CH2, A), 24.3 (1JCH 162,
CH, B), 24.8 (1JCH 160, CH, A), 27.5 (1JCH 129, CH3, A), 27.7 (1JCH 129,
CH3, B), 31.4 (C-spiro, A), 31.6 (C-spiro, B), 36.6 (CBr, B), 37.7 (CBr, A),
115.1 (2JCF 13, 2CH, Ph, A), 115.2 (2JCF 13, 2CH, Ph, B), 127.3 (3JCF 7,
2CH, Ph), 127.9 (3JCF 7, 2CH, Ph), 136.7 (C, Ph, AþC, Ph, B), 161.6 (1JCF
243, CF, Ph, AþCF, Ph, B). MS (EI, 70 eV) m/z: 175 ([MꢀBr]þ,100),160
(19), 147 (28), 134 (80), 122 (46), 109 (13), 96 (6). HRMS (ESI) calcd
for C9H13Br (MꢀBr)þ: 175.0923, found: 175.0918.
3.24. 9-Vinylidenebicyclo[6.1.0]nonane 31
Yield 0.33 g (55%), colorless liquid, Rf 0.6 (petroleum ether). IR
(film):
NMR (400 MHz, CDCl3)
1.55–1.67 (m, 4H), 1.77–1.87 (m, 2H), 2.02–2.10 (m, 2H), 4.74 (t, 2H,
5JHH 3.8, CH2). 13C NMR (100 MHz, CDCl3)
: 25.8 (2CH), 26.0 (2CH2),
n
2935, 2870,1970,1470,1440,1340,1170,1062, 726 cmꢀ1. 1H
3.20. 1-Fluoro-4-(2-vinylidenecyclopropyl)benzene 27
d: 1.22–1.33 (m, 2H), 1.35–1.49 (m, 4H),
Yield 0.18 g (28%), colorless liquid, Rf 0.4 (petroleum ether). IR
d
(film):
785 cmꢀ1
2.09–2.15 (m, 1H, CH2), 2.98–3.03 (m, 1H, CH), 4.95–5.00 (m, 2H,
n
3065, 3020, 3000, 2840, 1956, 1578, 1457, 1360, 1080, 1045,
26.3 (2CH2), 29.1 (2CH2), 75.6 (]CH2), 83.7 (C]), 193.3 (]C]). MS
(EI, 70 eV) m/z: 148 (Mþ, 2), 147 (3), 133 (29), 119 (34), 105 (63), 91
(100), 79 (77), 67 (29), 55 (23), 41 (34), 39 (30). HRMS (ESI) calcd for
C11H16 (M)ꢀ: 148.1252, found: 148.1259.
.
1H NMR (400 MHz, CDCl3)
d
: 1.64–1.69 (m, 1H, CH2),
CH2]), 7.95–7.13 (m, 4H, 4CH, Ph). 13C NMR (101 MHz, CDCl3)
d:
18.0 (CH2), 24.3 (CH), 77.9 (CH2]), 81.3 (C]), 115.3 (2JCF 13, 2CH,
Ph), 127.9 (3JCF 7, 2CH, Ph), 161.8 (1JCF 244, CF, Ph), 194.4 (]C]). MS
(EI, 70 eV) m/z: 160 (Mþ, 35), 159 (100), 133 (37), 120 (6), 109 (9).
HRMS (ESI) calcd for C11H9F (MꢀH)ꢀ: 159.0610, found: 159.0614.
3.25. 1,10-Ethane-1,2-diylbis(2-methylcyclobutene) 32
Yield 0.26 g (40%), colorless oil, Rf 0.6 (petroleum ether). IR
(film):
n
2980, 2950, 2860, 1660, 1465, 1378, 1270, 1215, 1090, 1070,
: 1.61 (br s, 6H,
3.21. 1-Bromo-1-methyldispiro[2.0.3.1]octane 28
945, 880, 720, 650 cmꢀ1. 1H NMR (400 MHz, CDCl3)
d
CH3), 2.09 (br s, 4H), 2.22–2.29 (br m, 8H, c-Bu). 13C NMR (101 MHz,
Yield 0.23 g (28%), two isomers, A:B 1:0.8, colorless liquid, Rf 0.2
CDCl3)
d
: 13.8 (1JCH 125, 2ꢃCH3), 26.2 (1JCH 127, 2ꢃCH2), 27.7 (1JCH
(petroleum ether). IR (film):
n
3078, 3000, 2962, 2870, 1452, 1375,
137, 2ꢃCH2, c-Bu), 29.5 (1JCH 136, 2ꢃCH2, c-Bu), 136.1 (C]), 140.5
(C]). MS (EI, 70 eV) m/z: 162 (Mþ, 12), 147 (25), 133 (9), 119 (12),
105 (10), 91 (10), 81 (100), 79 (46), 67 (7), 53 (23), 41 (19), 39 (18).
Anal. Calcd for C12H18: C, 88.82; H, 11.18%. Found: C, 88.62; H, 11.10%.
1335, 1280, 962, 810, 725, 567 cmꢀ1. 1H NMR (400 MHz, CDCl3)
d:
0.75 (d, 2JHH 4.5, 1H, CH2, c-Pr, B), 0.98 (d, 2JHH 4.5, 1H, CH2, c-Pr, B),
0.99 (br s, 2H, CH2, c-Pr, B), 1.03 (d, 2JHH 5.3, 1H, CH2, c-Pr, A), 1.14 (d,
2JHH 5.3, 1H, CH2, c-Pr, A), 1.32 (d, 2JHH 5.6, 1H, CH2, c-Pr, A), 1.50 (d,
2JHH 5.6, 1H, CH2, c-Pr, A), 1.79 (s, 3H, CH3, B), 1.90 (s, 3H, CH3, A),
1.94–2.22 (m, 5H, CH2, c-Bu, Aþ5H, CH2, c-Bu, B), 2.23–2.29 (m, H,
CH2, c-Bu, A), 2.70–2.76 (m, H, CH2, c-Bu, B). 13C NMR (101 MHz,
3.26. (2-(2-Methylcyclobut-1-enyl)propan-2-yl)benzene 33
Yield 0.33 g (45%), colorless solid, Rf 0.3 (petroleum ether). IR
CDCl3)
d
: 16.9 (1JCH 142, CH2, c-Bu, B), 17.1 (1JCH 142, CH2, c-Bu, A),
(film):
n
3030, 3000, 2970, 2875, 1665, 1600, 1475, 1430, 1372, 1250,
18.0 (1JCH 161, CH2, c-Pr, B), 21.0 (1JCH 161, CH2, c-Pr, A), 22.0 (1JCH
161, CH2, c-Pr, A), 22.7 (1JCH 161, CH2, c-Pr, B), 26.2 (1JCH 137, CH2, c-
Bu, B), 27.5 (1JCH 129, CH3), 27.7 (1JCH 137, CH2, c-Bu, A), 28.5 (1JCH
128, CH3), 28.6 (C-spiro, B), 29.1 (C-spiro, A), 29.3 (1JCH 140, CH2, c-
Bu, B), 29.5 (1JCH 140, CH2, c-Bu, A), 30.2 (C-spiro, B), 30.7 (C-spiro,
A), 39.3 (CBr, B), 39.4 (CBr, A). MS (EI, 70 eV) m/z: 174 ([MꢀC2H4]þ,
3), 172 ([MꢀC2H4]þ, 3), 121 (9), 105 (28), 93 (69), 91 (42), 79 (100),
1170, 1145, 772, 730, 715, 685 cmꢀ1
.
1H NMR (400 MHz, CDCl3)
d:
1.48 (br s, 6H, 2CH3),1.57 (br s, 3H, CH3), 2.20–2.28 (br m, 4H, 2CH2),
7.18–7.24 (m, 1H, CH, Ph), 7.32–7.43 (m, 4H, 4CH, Ph). 13C NMR
(101 MHz, CDCl3) d
: 15.4 (1JCH 126, CH3), 25.8 (1JCH 137, CH2), 28.1
(1JCH 127, 2CH3), 28.9 (1JCH 137, CH2), 29.8 (C), 125.6 (CH, Ph), 126.3
(2CH, Ph), 128.0 (2CH, Ph), 135.1 (C, Ph), 146.6 (C]), 148.7 (C]). MS
(EI, 70 eV) m/z: 186 (Mþ, 12), 171 (100), 156 (12), 143 (48), 129 (21),

E.B. Averina et al. / Tetrahedron 65 (2009) 5693–5701
5701
Lysov, A. E.; Potekhin, K. A.; Zefirov, N. S. Dokl. Akad. Nauk (Russ.) 2000, 375,
481; Dokl. Chem. (Engl. Trans.) 2000, 375, 257; (c) Averina, E. B.; Karimov, R. R.;
Sedenkova, K. N.; Grishin, Y. K.; Kuznetzova, T. S.; Zefirov, N. S. Tetrahedron
2006, 62, 8814.
115 (11), 91 (23), 77 (9), 41 (10), 39 (5). Anal. Calcd for C14H18: C,
90.26; H, 9.74%. Found: C, 90.32; H, 9.71%.
4. (a) Averina, E. B.; Sedenkova, K. N.; Grishin, Y. K.; Kuznetsova, T. S.; Zefirov, N. S.
ARKIVOC 2008, IV, 71; (b) Sedenkova, K. N.; Averina, E. B.; Grishin, Y. K.; Kuz-
netsova, T. S.; Zefirov, N. S. Zh. Org. Khim. (Russ.) 2008, 44, 962; Russ. J. Org.
Chem. (Engl. Trans.) 2008, 44, 950.
3.27. 2a,7-Dimethyl-7-phenyl-2,2a,7,7a-tetrahydro-1H-
cyclobuta[a]indene 34
5. The case of substitution of the fluorine atom for butyl group in 7-bromo-7-
fluorobicyclo[2.0.2.1]heptane is mentioned as an unpublished result in a re-
view: de Meijere, A.; Kozhushkov, S. I. Chem. Rev. 2000, 100, 93.
6. (a) Mu¨ller, K.; Stier, F.; Weyerstahl, P. Chem. Ber. 1977, 110, 124; (b) Anke, L.;
Reinhard, D.; Weyerstahl, P. Liebigs Ann. Chem. 1981, 591.
7. Bechtold, W.; Goldstein, J. H. J. Am. Chem. Soc. 1981, 103, 4989.
8. (a) Azizoglu, A.; Demirkol, O.; Kilie, T.; Yildiz, Y. K. Tetrahedron 2007, 63,
2409; (b) Christl, M.; Braun, M.; Hartmut, F.; Groetsch, S.; Mu¨ller, G.; Leusser,
D.; Deuerlein, S.; Stalke, D.; Arnone, M.; Engels, B. Eur. J. Org. Chem. 2006,
Yield 0.50 g (51%), colorless oil, Rf 0.2 (petroleum ether). IR
(film):
1380, 1125, 1080, 940, 772, 750, 730, 675 cmꢀ1. 1H NMR (400 MHz,
CDCl3) : 0.94–1.02 (m, 1H, CH2), 1.43 (s, 3H, CH3), 1.45 (s, 3H, CH3),
n 3020, 2985, 2950, 2925, 2870, 1600, 1525, 1500, 1470, 1430,
d
1.61–1.72 (m, 1H, CH2), 1.91–2.01 (m, 1H, CH2), 2.36–2.47 (m, 1H,
CH2), 3.30–3.35 (m, 1H, CH), 7.18–7.24 (m, 1H, Ph), 7.25–7.38 (m, 6H,
Ph), 7.42–7.48 (m, 2H, Ph). 13C NMR (101 MHz, CDCl3) : 18.6 (1JCH
d
¨
¨
125, CH3), 23.0 (1JCH 138, CH2), 26.2 (1JCH 128, CH3), 28.9 (1JCH 138,
CH2), 48.4 (1JCH 138, CH), 52.3 (C), 57.9 (C), 125.5 (CH, Ph), 125.8 (CH,
Ph), 125.9 (CH, Ph), 126.5 (CH, Ph), 127.0 (CH, Ph), 127.6 (2CH, Ph),
127.7 (2CH, Ph), 143.3 (C, Ph), 146.7 (C, Ph), 151.5 (C, Ph). MS (EI,
70 eV) m/z: 248 (Mþ, 26), 233 (15), 220 (54), 205 (100),192 (20),178
(15), 143 (26), 128 (13), 115 (9), 91 (14), 77 (4). Anal. Calcd for
C19H20: C, 91.88; H, 8.12%. Found: C, 91.63; H, 8.34%.
5045; (c) Ozen, R.; Balci, M. Tetrahedron 2002, 58, 3079; (d) Algi, F.; Ozen, R.;
Balci, M. Tetrahedron Lett. 2002, 43, 3129; (e) Christl, M.; Braun, M.; Mu¨ller,
G. Angew. Chem. 1992, 104, 471; (f) Christl, M.; Braun, M. Chem. Ber. 1989,
122, 1939.
9. Gawronska, K.; Gawronski, J.; Walborsky, H. M. J. Org. Chem. 1991, 56, 2193.
10. de Meijere, A.; von Seebach, M.; Zo¨llner, S.; Kozhushkov, S. I.; Belov, V. N.; Boese,
R.; Haumann, T.; Benet-Buchholz, J.; Yufit, D. S.; Howard, A. K. Chem.dEur. J. 2001,
7, 4021.
11. Eccles, W.; Jasinski, M.; Kaszynski, P.; Zienkiewicz, K.; Stulgies, B.; Jankowiak, A.
J. Org. Chem. 2008, 73, 5732.
12. (a) Ward, H. R.; Lawler, R. G.; Loken, H. Y. J. Am. Chem. Soc. 1968, 90, 7359; (b)
Bailey, W. F.; Gagnier, R. P.; Patricia, J. J. J. Org. Chem. 1984, 49, 2098; (c) Bailey,
W. F.; Carson, M. W. J. Org. Chem. 1998, 63, 9960.
Acknowledgements
13. (a) Scho¨llkopf, U. Houben-Weyl. In Lithium-organische Verbindungen; Mu¨ller, E.,
Ed.; Thieme: Stutgart, 1970; 13/1, pp 87–255; (b) Braun, M. The Chemistry of
Organolithium Compounds. In Lithium Carbenoid; Rappoport, Z., Ed.; John
Wiley: Chichester, UK, 2004; pp 829–900.
14. (a) Duraisamy, M.; Walborsky, H. M. J. Am. Chem. Soc. 1984, 106, 5035; (b) Rachon,
J.; Goedken, V.; Walborsky, H. M. J. Am. Chem. Soc. 1986, 108, 7435; (c) Topolski,
M.; Duraisamy, M.; Rachon, J.; Gawronski, J.; Gawronska, K.; Goedken, V.;
Walborsky, H. M. J. Org. Chem. 1993, 58, 546.
We thank the Division of Chemistry and Materials Science RAS
(Program N 1) and the President’s grant ‘Support of Leading Sci-
entific School’ N 5538.2008.3 (academician N.S.Z.) and the Russian
Foundation for Basic Research (Project 09-03-00717-a) for financial
support of this work.
15. Kitatani, K.; Yamomoto, H.; Hiyama, T.; Nozaki, H. Bull. Chem. Soc. Jpn. 1977, 50,
2158.
References and notes
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