Reactivities of methylenetriangulanes and spirocyclopropanated bicyclopropylidenes toward bromine. Relative stabilities of spirocyclopropanated versus methyl-substituted bromonium ions

Article abstract of DOI:10.1021/jo0162686

The bromine additions to methylenecyclopropane (1), bicyclopropylidene (2), and spirocyclopro-panated methylenecyclopropanes and bicyclopropylidenes 3-6 in methanol at 25 °C proceed essentially with the same rate as those to the corresponding oligomethyl-substituted ethylenes. An increasing number of spiroannelated three-membered rings enhances the rate of bromination and stabilizes the intermediate cyclopropyl bromonium cations against ring opening in the course of bromine addition. Calculations at the B3LYP/6-311G(d,p) level show that unsymmetrical bromonium ions are the intermediates, and that they are stabilized by the spiroannelation with cyclopropane rings. The bromonium ion derived from 1 is less stable by 6.3 kcal mol^-1 than that from isobutene. One or two spirocyclopropane rings as in 3 and 4 stabilize the corresponding bromonium ion by 9.6 and 16.4 kcal mol^-1, respectively, while one or two α-cyclopropyl substituents as in ethenylcyclopropane (7) and 1,1-dicyclopropylethene (8) stabilize the corresponding bromonium ions by 13 and 29 kcal mol^-1, respectively. The experimental bromination rates of all the studied alkenes correlate reasonably well (r² = 0.93) with calculated relative energies of the corresponding bromonium ions. The correlation is even better within the series of methylenecyclopropanes 1, 3, and 4 (r² = 0.974) and bicyclopropylidenes 2, 5, and 6 (r² = 0.999). The experimental bromination rates also correlate fairly well with the first ionization energies of the corresponding alkenes 1-12 (with r² = 0.963) and 13-19 (with r² = 0.991). The calculated preferred nucleophilic attack of a water molecule at both the C^1′ and C¹ atoms of representative bromonium ions conforms well to the experimentally observed product distribution.

Full text of DOI:10.1021/jo0162686

4
100
J . Org. Chem. 2002, 67, 4100-4114
Rea ctivities of Meth ylen etr ia n gu la n es a n d Sp ir ocyclop r op a n a ted
Bicyclop r op ylid en es tow a r d Br om in e. Rela tive Sta bilities of
Sp ir ocyclop r op a n a ted ver su s Meth yl-Su bstitu ted Br om on iu m Ion s
†
†
†
‡
Sergei Kozhushkov, Thomas Sp a¨ th, Torsten Fiebig, Bernard Galland,
,
‡
§
,§
,†
Marie-Francoise Ruasse,* Prince Xavier, Yitzhak Apeloig,* and Armin de Meijere*
Institut f u¨ r Organische Chemie der Georg-August-Universit a¨ t G o¨ ttingen, Tammannstrasse 2,
D-37077 G o¨ ttingen, Germany, Institut de Topologie et de Dynamique des Syst e` mes de l’Universit e´ Paris
-Denis Diderot, associ e´ au CNRS, URA 34, 1 rue Guy de la Brosse, F-75005 Paris, France, and
7
Department of Chemistry and the Lise Meitner Minerva Center for Computational Quantum Chemistry,
TechnionsIsrael Institute of Technology, Technion City, 32000 Haifa, Israel
Armin.deMeijere@chemie.uni-goettingen.de
Received November 6, 2001
The bromine additions to methylenecyclopropane (1), bicyclopropylidene (2), and spirocyclopro-
panated methylenecyclopropanes and bicyclopropylidenes 3-6 in methanol at 25 °C proceed
essentially with the same rate as those to the corresponding oligomethyl-substituted ethylenes.
An increasing number of spiroannelated three-membered rings enhances the rate of bromination
and stabilizes the intermediate cyclopropyl bromonium cations against ring opening in the course
of bromine addition. Calculations at the B3LYP/6-311G(d,p) level show that unsymmetrical
bromonium ions are the intermediates, and that they are stabilized by the spiroannelation with
-
1
cyclopropane rings. The bromonium ion derived from 1 is less stable by 6.3 kcal mol than that
from isobutene. One or two spirocyclopropane rings as in 3 and 4 stabilize the corresponding
-1
bromonium ion by 9.6 and 16.4 kcal mol , respectively, while one or two R-cyclopropyl substituents
as in ethenylcyclopropane (7) and 1,1-dicyclopropylethene (8) stabilize the corresponding bromonium
-
1
ions by 13 and 29 kcal mol , respectively. The experimental bromination rates of all the studied
2
alkenes correlate reasonably well (r ) 0.93) with calculated relative energies of the corresponding
bromonium ions. The correlation is even better within the series of methylenecyclopropanes 1, 3,
2
2
and 4 (r ) 0.974) and bicyclopropylidenes 2, 5, and 6 (r ) 0.999). The experimental bromination
rates also correlate fairly well with the first ionization energies of the corresponding alkenes 1-12
2
2
(
with r ) 0.963) and 13-19 (with r ) 0.991). The calculated preferred nucleophilic attack of a
water molecule at both the C and C atoms of representative bromonium ions conforms well to
the experimentally observed product distribution.
1′ 1
In tr od u ction
Understanding the influence of strain in organic
molecules upon their reactivity is of fundamental impor-
tance for theoretical as well as experimental studies.
Methylenecyclopropane (1), bicyclopropylidene (2), and
their spirocyclopropanated analogues 3-6 are among the
most highly strained alkenes and thus exhibit an en-
hanced reactivity toward a wide range of electrophiles
and cyclophiles. A correlation of their reactivities with
their inherent strain would therefore be of special inter-
est. A large variety of chemical transformations have
1
2
been performed with hydrocarbons 1 and 2; e.g., cyclo-
additions to compounds 3-6 were used as key steps in
the preparation of linear and branched triangulanes.3
*
To whom correspondence should be addressed. Phone: ++49-(0)-
5
51 39 3231. Fax: ++49-(0)551 39 9475.
†
Institut f u¨ r Organische Chemie der Georg-August-Universit a¨ t
G o¨ ttingen.
‡
Institut de Topologie et de Dynamique des Syst e` mes de l’Universit e´
Paris 7-Denis Diderot. E-mail: ruasse@as2100.itodys.jussieu.fr (M.-
F.R.).
§
TechnionsIsrael Institute of Technology. Fax: ++(972-4) 823
3
735. E-mail: chrapel@techunix.technion.ac.il.
(1) Reviews: (a) Binger, P.; B u¨ ch, H. M. Top. Curr. Chem. 1987,
1
35, 77-151. (b) Binger, P.; Schmidt, T. In Houben-Weyl, Carbocyclic
Three-Membered Ring Compounds; de Meijere, A., Ed.; Thieme:
Stuttgart, 1997; Vol. E 17c, pp 2217-2294. (c) Brandi, A.; Goti, A.
Chem. Rev. 1998, 98, 589-635.
4
However, one of the simplest reactions sthe electro-
philic addition of halogens onto the double bondshas
1
0.1021/jo0162686 CCC: $22.00 © 2002 American Chemical Society
Published on Web 05/18/2002

Relative Stabilities of Bromonium Ions
J . Org. Chem., Vol. 67, No. 12, 2002 4101
never been investigated for this family of hydrocarbons,
at least not with respect to its quantitative implications
Ta ble 1. Ra te Coefficien ts (kBr 2) for th e Ad d ition of
Br om in e to Hyd r oca r bon s 1-6, 9, a n d 12 in Meth a n ol a t
2
5 °C a n d F ir st Ion iza tion En er gies (IEs) of 1-6, 9, a n d
2 a s Ta k en fr om He(I) P h otoelectr on Sp ectr a (P ES)
5
a-f
(
qualitative results for 1
and substituted methylene-
1
5
g-p
cyclopropanes
have been reported). Electrophilic ha-
logenations of alkenes are some of the classical reactions
in organic chemistry, and their mechanisms are well
documented by various investigations on kinetics and
6
products. Comparison of the steric and electronic effects
caused by substitution at the doubly bonded carbon
atoms of various alkenes were carried out by independent
7
8
rate studies of chlorination, bromination, and iodina-
9
tion. In bromination, the steric effects were found to be
smaller than electronic effects, regardless of the degree
of substitution at the double bond.8,10 In contrast to the
great amount of experimental work devoted to this
reaction, theoretical studies especially on the nature of
chloronium11 and bromonium ions are scarce.
12
(2) Reviews: (a) de Meijere, A.; Kozhushkov, S. I.; Khlebnikov, A.
F. Zh. Org. Khim. 1996, 32, 1607-1626; Russ. J . Org. Chem. (Engl.
Transl.) 1996, 32, 1555-1575. (b) de Meijere, A.; Kozhushkov, S. I.;
Khlebnikov, A. F. Top. Curr. Chem. 2000, 207, 89-147. (c) de Meijere,
A.; Kozhushkov, S. I. Eur. J . Org. Chem. 2000, 3809-3822.
(3) Reviews: (a) de Meijere, A.; Kozhushkov, S. In Advances in
Strain in Organic Chemistry; Halton, B., Ed.; J AI Press Ltd.: Green-
wich, CT, 1995; Vol. 4, pp 225-282. (b) de Meijere, A.; Kozhushkov, S.
I. Chem. Rev. 2000, 100, 93-142 and references therein.
(
4) Herges, R. Angew. Chem. 1995, 107, 57-59; Angew. Chem., Int.
Ed. Engl. 1995, 34, 51-53.
(
5) (a) K o¨ ster, R.; Arora, S.; Binger, P. Synthesis 1971, 322-323.
(
1
1
b) K o¨ ster, R.; Arora, S.; Binger, P. Liebigs Ann. Chem. 1973, 1619-
627. (c) Sala u¨ n, J .; Garnier, B.; Conia, J .-M. Tetrahedron 1974, 30,
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a Due to serious overlapping of bands the PES of 4 is not readily
interpretable.
Soc. Chim. Fr. 1963, 1444-1448. (e) Anderson, B. C. J . Org. Chem.
1
1
962, 27, 2720-2724. (f) Volta, L.; Stirling, C. J . M. Chem. Commun.
998, 2481-2482. (g) Derocque, J .-L.; Sunderman, F.-B.; Youssif, N.;
To quantify the nucleophilicities of the double bonds
in 1-6, we have investigated experimentally the rates
of bromine addition and have evaluated computationally
the relative stabilities of the respective intermediate
bromonium ions. For comparison, the cyclopropyl-sub-
stituted alkenes 9 and 12 also have been probed. The
products of all these reactions were characterized to
reveal the relative stabilities of the intermediate cations
as a function of the number and position of spiro-
annelated or attached cyclopropyl groups.
Hanack, M. Liebigs Ann. Chem. 1973, 419-431. (h) Sala u¨ n, J .; Hanack,
M. J . Org. Chem. 1975, 40, 1994-1998. (i) Hanack, M. J .; B a¨ ssler, T.;
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C.; Drach, J . C.; Zemlicka, J . J . Med. Chem. 1998, 26, 5257-5264. (o)
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Meijere, A., Ed.; Thieme: Stuttgart, 1997; Vol. E 17b, pp 1507-1544.
(
6) (a) Schmid, G. H. In The chemistry of double-bonded functional
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Resu lts a n d Discu ssion
1
(
Br om in a tion Ra te Coefficien ts. Kin etic Effects of
Sp ir oa n n ela ted a n d Atta ch ed Cyclop r op yl Gr ou p s.
The rate coefficients, kBr2, of free bromine addition to
alkenes 1-6, 9, and 12 (Table 1) were measured in
methanol by following bromine uptake spectrophoto-
C.; Bellucci, G. J . Am. Chem. Soc. 1997, 119, 12492-12502. (d) Brown,
R. S. Acc. Chem. Res. 1997, 30, 131-137.
(
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D. J . Am. Chem. Soc. 1965, 87, 1297-1307.
metrically13 for rate coefficients smaller than 10 mol
5
-1
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R o¨ lling, M.; Winguth, L.; Dietrich, P.; Doring, C.-E.; Hauthal, H. G.;
Wiedenh o¨ ft, A. J . Prakt. Chem. 1969, 311, 238-255. (b) Cerichelli, G.;
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I. G. J . Mol. Struct.: THEOCHEM 1981, 85, 153-158. (f) Poirier, R.
A.; DeMar e´ , G. R.; Yates, K.; Csizmadia, I. G. J . Mol. Struct.:
THEOCHEM 1983, 94, 137-141. (g) Nichols, J .; Tralka, T.; Goering,
B. K.; Wilcox, C. F.; Ganem, B. Tetrahedron 1996, 52, 3355-3364. (h)
Coxon, J . M.; Smith, W. B. J . Org. Chem. 2000, 65, 2192-2194. (i)
Brown, R. S.; Nagorski, R. W.; Bennet, A. J .; McClung, R. E. D.; Aarts,
G. H. M.; Klobukowski, M.; McDonald, R.; Santarsiero, B. D. J . Am.
Chem. Soc. 1994, 116, 2448-2456. (j) Hamilton, T. P.; Schaefer, H.
F., III. J . Am. Chem. Soc. 1990, 112, 8260-8265.
5
1
2
1
2, 5167-5171. (c) Fukuzumi, S.; Kochi, J . K. J . Am. Chem. Soc. 1981,
03, 2783-2791. (d) Dubois, J . E.; Schwarcz, A. Tetrahedron Lett. 1964,
167-2173. (e) Dubois, J . E.; Barbier, G. Tetrahedron Lett. 1965,
217-1225.
(
9) Cvetanovi c´ , R. J .; Duncan F. J .; Falconer, W. E.; Sunder, W. A.
J . Am. Chem. Soc. 1966, 88, 1602-1610.
10) Nelson, D. J .; Cooper, P. J .; Soundararajan, R. J . Am. Chem.
Soc. 1989, 111, 1414-1418.
11) (a) Rodriquez, C. F.; Bohme, D. K.; Hopkinson, A. C. J . Am.
(
(
Chem. Soc. 1993, 115, 3263-3269. (b) Yamabe, S.; Tsuji, T.; Hirao, K.
Chem. Phys. Lett. 1988, 146, 236-242. (c) McManus, S. P. J . Org.
Chem. 1982, 47, 3070-3075. (d) McManus, S. P.; Worley, S. D.
Tetrahedron Lett. 1977, 555-558. (e) Hopkinson, A. C.; Lien, M. H.;
Yates, K.; Csizmadia, I. G. Theor. Chim. Acta 1977, 44, 385-398. (f)
Dargelos, A.; Liotard, D.; Chaillet, M. Tetrahedron 1972, 28, 5595-
(13) (a) Connors, K. A. Chemical Kineticssthe Study of Reaction
Rates in Solution; VCH: Weinheim, 1990. (b) Dubois, J .-E.; Herzog,
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Spectrochim. Acta 1967, 23A, 2279-2288.
5
605.

4
102 J . Org. Chem., Vol. 67, No. 12, 2002
Kozhushkov et al.
Ta ble 2. Ra te Coefficien ts (kBr ) for th e Ad d ition of
The successive spirocyclopropanation of the three-
membered rings in 1 and 2 leads to significant accelera-
tions of the bromination for compounds 3-6, despite a
certain increase in steric congestion.2 The kinetic effects
of the spiroannelated cyclopropane rings are roughly
additive. On going from 1 to 3, the rate increases by a
factor of 16, and on going to 4 the second spirocyclopro-
pane group causes an additional rate increase by a factor
of 33. The same effect is observed in the bicyclopropyli-
dene series 2, 5, and 6 in which the acceleration factors
are 35 and 21 successively. These additivities show
unambiguously that there is no steric retardation due to
the spiroannelated cyclopropane groups. The effects of
these spiroannelations are markedly smaller than the
mean effect of a methyl group (factor of 60) in the series
of methylated ethylenes. The effect of a cyclopropyl
substituent as in 9 and 12 is completely different, with
2
Br om in e to Eth ylen e a n d Meth yl-Su bstitu ted Eth ylen es
in Meth a n ol a t 25 °C a n d F ir st IEs of th e Alk en es a s
Ta k en fr om He(I) P ES
,25
6
a drastic acceleration of 2 × 10 being observed when two
cyclopropyl groups are attached to 1, and tricyclopropyl-
ethylene (9) reacts slightly more slowly than 12.
The rate coefficients in Tables 1 and 2 were measured
in the presence of several different bromide ion concen-
a
From ref 21. Q ) kBr /kBr3-. b From ref 22. c From ref 23.
2
L s- and amperometrically14 in the higher reactivity
range (Table 1). Methanol has been chosen as the
reaction medium since numerous kinetic data for the
1
-2
-1
trations (2 × 10 to 2 × 10 M) and extrapolated to
-
[
Br ] ) 0. Under these conditions, two brominating
bromination of a large variety of ethylenic compounds
species, free bromine and tribromide ion, related to each
other by an equilibrium (eq 1), can competitively react
are at present available in this solvent.6
b,21
A comparison
of the new rate data for cyclopropanated methylenecyclo-
propanes with those of approximately analogously meth-
yl-substituted ethylenes (Table 2)21 shows that the reac-
tivity ranges of the two series of alkenes are rather
similar and spread over a range of roughly 6 orders of
magnitude. This contrasts with the correlation between
the rate of bromination and the number of methyl groups
in methylated ethylenes. Thus, the nucleophilicity of the
double bond in 1 closely resembles that of propene; the
reactivity of 2 is very close to that of isobutene (15) or
26
with a given compound. The kinetic terms for the free
bromine addition and those related to the tribromide ion
addition or bromide-assisted bromine addition can be
26
obtained separately, according to the usual equation (eq
2
)
-
-
Br + Br a Br
(1)
(2)
2
3
-
-
kexp(1 + K[Br ]) ) R + â[Br ]
2
-butene (16), and the bis(spirocyclopropane)-annelated
bicyclopropylidene 6 reacts approximately at the same
rate as tetramethylethylene (19). Accordingly, the acti-
vating effect of a three-membered ring geminally linked
to a double bond is similar to that of a single methyl
substituent.
in which K is the bromine-tribromide equilibrium con-
stant (eq 1), R is the rate coefficient kBr2 for the bromine
addition, and â is the salt effect coefficient. From this
coefficient, the rate coefficients “kBr3 ” are readily obtained
-
since, with the hypothesis that the bromide ion effect
arises mainly from the competition between free bromine
and tribromide ion additions, â ) KkBr3. In Tables 1 and
The influence of cyclopropyl substituents attached to
the double bond as in alkenes 9 and 12 is more significant
as shown by the bromination rate of 12, which is close to
2, Q is the kBr2/kBr3 ratio, which expresses the alkene
-
9
-1
-1 24
the diffusion control limit (5 × 10 mol L s ).
selectivity for the two brominating species. Nevertheless,
there has been a controversy27 about the mechanism to
(
14) (a) Poupard, D.; Ruasse, M.-F.; Dubois, J .-E. J . Electroanal.
which the â coefficient is to be related. It is now well-
Chem. 1983, 152, 77-85. (b) Ruasse, M.-F.; Poupard, D.; Dubois, J .-
E. Int. J . Chem. Kinet. 1983, 15, 855-866. (c) Poupard, D. Ph.D. Thesis,
University of Paris VII, Paris, France, 1981.
27,28
established
that Q values smaller than 15 correspond
better to bromide-assisted bromine addition, kinetically
equivalent to the tribromide addition. The Q values
obtained for the reactions of alkenes 1-6, 9, and 12 are
significantly greater than 15 (except for that of 12 with
Q ) 9) and are in the same range as those observed for
the methyl-substituted ethylenes. Therefore, at least for
alkenes 1-5, the bromide-assisted bromine addition does
not contribute significantly to the experimental bromi-
nation rates. The reason why Q for 12 is very small is
unclear since small Q values are generally obtained for
poorly reactive double bonds for which the assisted
(
(
15) Gleiter, R. Top. Curr. Chem. 1979, 86, 197-285.
16) Gleiter, R.; Haider, R.; Conia, J .-M.; Barnier, J .-P.; de Meijere,
A.; Weber, W. J . Chem. Soc., Chem. Commun. 1979, 130-132.
17) Gleiter, R.; de Meijere, A.; Kozhushkov, S. I. Unpublished
results.
(
(18) (a) Z o¨ llner, S. Dissertation, Universit a¨ t Hamburg, Hamburg,
Germany, 1991. (b) Z o¨ llner, S.; Gleiter, R.; Kozhushkov, S. I.; de
Meijere, A. Unpublished results. (c) Z o¨ llner, S.; Buchholz, H.; Boese,
R.; Gleiter, R.; de Meijere, A. Angew. Chem. 1991, 103, 1544-1546;
Angew. Chem., Int. Ed. Engl. 1991, 30, 1518-1520.
(
19) Nishida, S.; Moritani, I.; Teraji, T. J . Chem. Soc., Chem.
Commun. 1972, 1114.
20) Gleiter, R.; Eckert-Maksic, M.; de Meijere, A. Unpublished
results.
(
(
21) (a) Ruasse, M.-F.; Zhang, B.-L. J . Org. Chem. 1984, 49, 3207-
3
3
210. (b) Ruasse, M.-F.; Lefebvre, E. J . Org. Chem. 1984, 49, 3210-
212.
(25) Boese, R.; Haumann, T.; J emmis, E. D.; Kiran, B.; Kozhushkov,
S. I.; de Meijere, A. Liebigs Ann. 1996, 913-919.
(26) Bartlett, P. D.; Tarbell, D. S. J . Am. Chem. Soc. 1936, 58, 466-
474.
(27) Dubois, J .-E.; Bienven u¨ e-Go e¨ tz, E. Bull. Soc. Chim. Fr. 1968,
2094-2098.
(28) Dubois, J .-E.; Huynh, X. Q. Tetrahedron Lett. 1971, 3369-3372.
(
22) Carlier, P.; Hernandez, R.; Masclet, P.; Mouvier, G. J . Electron
Spectrosc. 1974, 5, 1103-1114.
23) Bienvenue-Go e¨ tz, E.; Dubois, J .-E. Tetrahedron 1978, 34, 2021-
026.
24) Ruasse, M.-F. Isr. J . Chem. 1985, 26, 414-419.
(
2
(

Relative Stabilities of Bromonium Ions
J . Org. Chem., Vol. 67, No. 12, 2002 4103
Ta ble 3. KSIEs in th e Br om in a tion of Sever a l
Cyclop r op yl-Gr ou p -Con ta in in g Alk en es, Mea su r ed a t
Sch em e 1
2
5 °C
kMeOH/kMeODa
kMeOH/kEtOHb
mc
2
3
5
6
9
4
5
9
1.18 ( 0.07
1.37 ( 0.09
1.90 ( 0.05
2.14 ( 0.15
1.90 ( 1.2
30.6
20.4
32.0
(0.30)d
d
(0.34)
(0.30)d
0.96
e
e
e
1
1
1
1.35
0.92
0.96
a
KSIE. b kEtOH measured in 97.5% aqueous ethanol. c Coeffi-
cients of the Grunwald-Winstein equation for solvent kinetic
d
effects using YBr- solvent parameters, from ref 30. Estimated
e
from kMeOH/kEtOH ratios. From ref 21.
Sch em e 2
mechanism is favored, yet 12 is highly reactive. The high
Q value for 6 can be interpreted in terms of a marked
steric effect on the kBr3 pathway and/or a very high rate
-
for the free bromine addition since it is known29 that both
effects increase the Q values strongly.
Some kinetic solvent isotope effects (Table 3) have also
been measured with respect to estimating the magnitude
of charge development in the rate-limiting transition
states of the bromine addition to these cyclopropyl-group-
containing alkenes. In the lowest reactivity range, the
kinetic solvent isotope effects (KSIEs), kMeOH/kMeOD, have
been determined for the reactions of alkenes 2 and 3 by
measuring the rate coefficients in MeOD, kMeOD(2) ) (4.34
33
itself by rearrangement. Nucleophilic assistance of the
3
-1
-1
(
0.3) × 10 mol L s and kMeOD(3) ) (4.0 ( 0.2) × 10
34
polar solvent methanol apparently prevents the ring
-
1
-1
mol L s , respectively (Table 3). Whereas for 3 this
KSIE is in the usual range for alkene brominations,31
that for 2 is noticeably smaller. In the higher reactivity
range, the effect of changing the solvent from methanol
to 97.5% aqueous ethanol on the reactivity of 5, 6, and 9
+
opening and ring enlargement of 1‚Br to yield isobutene
derivatives of type 21 or cyclobutane derivatives of type
via nucleophilic attack of bromide anion (Scheme 1b).
In the case of 2, the formation of a cyclopropyl cation
6c
2
2
+
fragment as in 2‚Br is inevitable (Scheme 2). Therefore,
5
7
[
(
k
EtOH ) (8.58 ( 0.03) × 10 , (1.63 ( 0.08) × 10 , and
side by side with the direct trapping products 24 (73%)
and 25 (17%), the tetrabromo-substituted 2-methyl-2-
pentene derivative 28 (7%) was also formed. The tetra-
substituted alkene 28 must arise via ring opening of the
8 -1 -1
1.6 ( 0.2) × 10 mol L s , respectively] is surprisingly
small as compared to that generally observed for acyclic
alkenes.21 These results, analogous to those previously
3
2
obtained in the solvolysis of analogous substrates, will
be discussed below (vide infra).
+
33
cyclopropyl cation moiety in 2‚Br to an allyl cation, 26,
and subsequent bromine addition to the allyl bromide 27
with concurrent cyclopropylcarbinyl to homoallyl cation
rearrangement. Two additional minor products (about
P r od u ct Distr ibu tion in th e Br om in a tion of Hy-
d r oca r bon s 1-6 in Meth a n ol. Previously, the bromi-
5
a-f
2 4
nation of 1 in aprotic solvents (pentane, Et O, CCl )
1
.5% each) could not be identified. Upon bromination of
in pentane at -30 °C, 1,1′-bis(1-bromocyclopropyl) (24)
was isolated as the sole product in 83% yield.
In contrast to the brominations of 1 and 2, that of
methylenespiropentane (3) yielded predominantly the
two ring-opening products 31 (20%) and 32 (32%), both
resulting from a cyclopropylcarbinyl to homoallyl cation
ring opening in the first intermediate 3‚Br and subse-
quent bromine addition to the intermediate (bromovinyl)-
has been reported to yield, in addition to the regular
bromine adduct 20, the two isomeric dibromides 21 and
2
3
2
2 in varying proportions depending on the solvent and
the temperature (Scheme 1a, the yields from GC analyses
of the reaction mixtures).
In contrast to this, the bromination of 1 in methanol
in the presence of 0.42 M sodium bromide yielded only
two products, 20 and 23, in a ratio of 2.7:1. The fact that
no product with the isobutene skeleton of type 21 was
formed indicates that in methanol only the (1-bromo-
+
cyclopropane 30 (Scheme 3). The formation of 30 from
‚Br can also be rationalized by an S
+
3
N
2′-type attack of
+
cyclopropyl)methyl cation 1‚Br is additionally stabilized
by solvation and therefore has no tendency to stabilize
(
33) (a) Boche, G.; Walborsky, H. M. In Cyclopropane Derived
Reactive Intermediates; Patai, S., Rappoport, Z., Eds.; Wiley: Chich-
ester, U.K., 1990; pp 117-173 and references therein. (b) Friedrich,
E. C. In The Chemistry of the Cyclopropyl Group; Rappoport, Z., Ed.;
Wiley: Chichester, U.K., 1987; pp 633-700. (c) Sch o¨ llkopf, U. Angew.
Chem. 1968, 80, 603-613; Angew. Chem., Int. Ed. Engl. 1968, 7, 588-
(
29) (a) Ruasse, M.-F.; Argile, A. J . Org. Chem. 1983, 48, 202-208.
(
b) Ruasse, M.-F.; Dubois, J .-E. J . Am. Chem. Soc. 1984, 106, 3230-
3
5
1
234.
(30) Bentley, T. W.; Carter, G. E. J . Am. Chem. Soc. 1982, 104,
741-5747.
(
598. (d) High-level ab initio and DFT calculations show that cyclopropyl
+
31) Ruasse, M.-F.; Motallebi, S.; Galland, B. J . Am. Chem. Soc.
cation is not a stationary point on the C
3
H
5
PES, and consequently
-1
991, 113, 3440-3446.
32) (a) Creary, X. J . Am. Chem. Soc. 1976, 98, 6608-6613. (b)
Landgrebe, J . A.; Applequist, D. E. J . Am. Chem. Soc. 1964, 86, 1536-
542. (c) Sp a¨ th, T. Dissertation, Universit a¨ t G o¨ ttingen, G o¨ ttingen,
there is no barrier to ring opening. The allyl cation is 32-36 kcal mol
more stable. Arnold, P. A.; Carpenter, B. K. Chem. Phys. Lett. 2000,
328, 90-96.
(
1
(34) (a) Stølevik, R.; Bakken, P. J . Mol. Struct. 1989, 197, 137-
142. (b) Buchholz, H. Dissertation, Universit a¨ t Hamburg, Hamburg,
Germany, 1992.
Germany, 1995. (d) Sp a¨ th, T.; Kozhushkov, S. I.; Albrecht, K.; Apeloig,
Y.; de Meijere, A. To be published.

4
104 J . Org. Chem., Vol. 67, No. 12, 2002
Kozhushkov et al.
Sch em e 3
Sch em e 5
Sch em e 4
Ta ble 4. P r od u ct Distr ibu tion s in th e Br om in a tion of
Meth ylen ecyclop r op a n e Der iva tives 1-6 in Meth a n ol in
th e P r esen ce of 0.42 M Sod iu m Br om id e
nonrearranged adductsa
rearranged adductsb
alkene
DB
MBR
MBâ
A
B
C
bromide on 3‚Br + with simultaneous ring opening. The
actually isolated products 31 and 32 must arise from the
methanol trapping of the cationic intermediate in the
1
2
3
4
5
73
73
48
28
32
17
27
17
c
7
52
14
23
48
83
49
bromine addition to 30. Subsequent S
N
1 displacement of
c
the bromine R to the methoxy group then yields the
dimethyl acetal 32; fragmentation of the R-bromoether
or its hydrolysis gives the R-bromoketone 31. The rear-
6
a
DB ) dibromide, MBR ) anti-Markovnikov-type methoxybro-
mide, derived from (bromocyclopropyl)carbinyl cation intermedi-
+
rangement of 3‚Br competitive with its bromine trap-
ates, and MBâ ) Markovnikov-type methoxybromide, formally
derived from (bromomethyl)cyclopropyl cation intermediates.
product formally derived from the cyclopropyl to allyl cation
rearrangement of the (bromomethyl)cyclopropyl cation, B )
product derived from the cyclopropylcarbinyl to homoallyl rear-
b
ping is apparently favored by the additional strain
A
)
release from its spiropentyl unit in analogy to results
from the solvolysis of methylspiropentane derivatives.3
The bromination of 7-methylenedispiro[2.0.2.1]heptane
rangement, and C ) product formally derived from ring enlarge-
(4) also gave an important fraction of a rearrangement
ment of the (bromocyclopropyl)carbinyl cation. c Plus 3-5% uni-
product, in this case the cyclobutanone 33 (49%) along
with the addition products 34 (28%) and 35 (23%)
dentified products.
(
Scheme 4). In this system, strain release is more
38, which upon further bromination/solvolysis eventually
gives the acetal 39.
favorably accomplished by ring enlargement of the
intermediate bromocyclopropylmethyl to a bromocyclo-
butyl cation, which is trapped by bromide ion or metha-
nol. The isolated cyclobutanone 33 is obviously the
hydrolysis product of an initially formed gem-dibromide,
R-bromoether, or dimethyl acetal (cf. ).
Bromination of the monospirocyclopropanated bicyclo-
propylidene 5 in methanol gave the three main products
Finally, 7-cyclopropylidenedispiro[2.0.2.1]heptane (6)
upon bromination in methanol gave only the two products
40 and 41, both derived from an intermediate bromo-
+
cyclopropyl cation, 6‚Br , which must be very efficiently
3
b
stabilized by the two adjacent spirocyclopropane groups
and one R-cyclopropyl substituent. However, the fact that
6 upon hydrobromination, in addition to 42 (90%), also
gives the bromide 43 in 10% yield indicates that the
alternative dispiroheptyl-substituted cyclopropyl cation
intermediate can also be formed.
3
6, 37, and 39 in 32%, 48%, and 15% isolated yield,
respectively, along with 4% an unidentified compound.
According to a gas chromatogram of the crude reaction
mixture, the proportions of 36, 37, and 39 were 30:50.5:
Considering the product distributions (Table 4) for the
bromine additions to methylenecyclopropane derivatives
1-6 in methanol, one can identify three trends.
(1) With an increasing number of spiroannelated three-
membered rings on 1, the total amount of products with
retained cyclopropane rings decreases, while increasing
spiroannelation on 2 leads to an increasing total amount
of nonrearranged products. Corresponding results have
been reported for the bromination in pentane, which for
compounds 4 and 6 proceeds without ring opening, i.e.,
1
5.5 (Scheme 5). Apparently, all three products are
derived from the (1′-bromospiropentyl)-substituted spiro-
pentyl cation 5‚Br , which must be the thermodynami-
cally favored and more long-lived intermediate. The two
major products 36 and 37 (together 80%) were obviously
formed directly via 5‚Br . The remaining product 39
must be derived from thesprobably nucleophile-assisteds
+
+
cyclopropyl to homoallyl ring-opening rearrangement of
5
+
‚Br to an intermediate bromomethylenecyclopropane,

Relative Stabilities of Bromonium Ions
contrary to hydrocarbons 1 and 2 (see above).3 Hydro-
J . Org. Chem., Vol. 67, No. 12, 2002 4105
,18
stationary points as either a minimum (zero imaginary
frequencies) or a transition state (one imaginary fre-
quency).
5
b
bromination of 1 also occurs with ring opening and that
of 4 and 6 without ring opening.3 In the case of 6, the
regioselectivity of 9:1 in favor of the “Markovnikov”-type
product 42 is remarkable (Scheme 5).
,18
Str u ctu r es of Br om on iu m Ion s. The structures of
+
+
bromonium ions 1‚Br -19‚Br were calculated, and the
4
0
(2) On going from 1 to 3 and 4, the predominating
geometries of most of them are shown in Figure 1. The
reactive intermediate changes from the cyclopropylcarbi-
nyl to the cyclopropyl-type cation. The intermediates
formed from 2, 5, and 6 inevitably are cyclopropyl-type
cations, but spiroannelation of cyclopropane rings ap-
parently stabilizes such cations kinetically and thus leads
to a regioselective methoxybromination of 5 and 6 to give
intermediate in the bromination of ethylene is a C -
2
v
+
symmetric bromonium ion, 13‚Br , with relatively long
C-Br bonds of 2.053 Å (compared to 1.929 Å in CH Br),
3
thus enclosing a very acute C-Br-C bond angle of 41.4°.
This structure is in good agreement with previous ab
initio calculations at the MCSCF level (effective core
potentials with an uncontracted basis set composition of
5s5p were used), which reports C-Br bond lengths of
2.069 Å and a C-Br-C bond angle of 41.2°.1 Hamilton
and Schaefer carried out both SCF and CISD calculations
using a DZ+d basis set, and their calculated C-Br bond
lengths were 2.053 and 2.025 Å, respectively.1 The good
agreement between these high-level ab initio calcula-
tions1 and the current DFT calculations supports the
reliability of the B3LYP/6-311G(d,p) calculations for
describing these species. The intermediate from tetra-
3
7 and 41, respectively.
3) The ratio of products with and without a methoxy
group (24:25 ≈ 4:1, 34:35 ≈ 1:1, 36:37 ≈ 1:1.6, 40:41 ≈
:5) demonstrates that the lifetime of the cationic inter-
(
2i
1
mediates increases with an increasing number of cyclo-
propane rings directly attached to the double bond or
spiroannelated at the cyclopropane ring of the core unit
2j
2i,j
(the longer the lifetime, the more important the methanol
trapping of free intermediates and the less important the
formation of dibromide by internal ion pair collapse).
Steric effects may also contribute to controlling this
product ratio as the larger bromide ion may less easily
get close to this cation than the smaller methanol
molecule. According to MM2 calculations, 1,1′-dibromo-
bicyclopropyl (24),3 for example, should exist as a
gauche conformer only, whereas unsubstituted bicyclo-
propyl exists as an equilibrium mixture of gauche and
s-trans conformers.35 The rotational barrier for the di-
bromide 40 was calculated by the MM2 method to be 14.1
kcal/mol,3 although a freezing of the conformational
changes could not be detected for 40 down to -90 °C.
+
methylethylene, the bromonium ion 19‚Br , has signifi-
cantly longer C-Br bonds of 2.176 Å, and a correspond-
ingly smaller C-Br-C bond angle of 39.8°.
+
The calculated geometry of 19‚Br may be compared
4a
with crystallographic data on the bromonium ion of
adamantylideneadamantane, which revealed an average
C-Br bond length of 2.11 Å and an average C-Br-C
12i
bond angle of 41.3°, in reasonable agreement with the
+
calculations for 19‚Br .
4b
+
The bromonium ion 15‚Br resulting from isobutene
is highly unsymmetrical with a relatively short C-Br
3
bond of 2.001 Å (1.929 Å in CH Br) to the primary carbon
Com p u ta tion a l Stu d ies
+
(
solid line in the structure of 15‚Br in Figure 1) and a
Calculations using density functional theory (DFT)36
significantly longer C-Br bond of 2.382 Å to the tertiary
+
carbon (dashed line in the structure of 15‚Br in Figure
on the structures and energies of the methylenecyclo-
propanes 1-6, the cyclopropyl-substituted alkenes 7-12,
the simple acyclic alkenes 13-19, and their bromonium
+
1
). This is the expected structure 15‚Br , as it places a
higher positive charge (+0.57, Figure 2) on the tertiary
CMe group than on the primary CH
+
+
37
2
2
group (+0.12). The
ions 1‚Br -19‚Br were carried out. The geometries
+
+
central C-C bond distances in 13‚Br , 15‚Br , and 19‚
of all the molecules were optimized using the hybrid
+
Br of 1.451, 1.464, and 1.482 Å, respectively, are
density functional method at the B3LYP//6-311G(d,p)
level of theory.3
8,39
significantly longer than that of a CdC double bond
Vibrational frequency calculations at
(1.333 Å in Me
2 2
CdCH ), indicating that these species are
this level of theory were used to characterize each of the
better described as bromonium ions rather than as
4
1
π-complexes.
(
35) Bastiansen, O.; de Meijere, A. Acta Chem. Scand. 1966, 20,
The spirocyclic bromonium ion 1‚Br + from methyl-
5
1
16-521; Hagen, K.; Hagen, G.; Traetteberg, M. Acta Chem. Scand.
972, 26, 3649-3661.
(
+
enecyclopropane is much more symmetrical than 15‚Br ,
36) (a) Parr, R. G.; Yang, W. Density Functional Theory of Atoms
the C-Br distances being 2.034 Å to the primary carbon
and Molecules; Oxford University Press: New York, 1989. (b) Koch,
W.; Holthausen, M. C. A Chemist’s Guide to Density Functional Theory;
Wiley-VCH: Weinheim, Germany, 2000.
and 2.149 Å to the tertiary carbon, and the calculated
positive charge on the primary CH group (+0.23) is
2
(37) The Gaussian series of programs was used. GAUSSIAN 98,
revision A.7: Frisch, M. J .; Trucks, G. W.; Schlegel, H. B.; Scuseria,
G. E.; Robb, M. A.; Cheeseman, J . R.; Zakrzewski, V. G.; Montgomery,
J . A., J r.; Stratmann, R. E.; Burant, J . C.; Dapprich, S.; Millam, J . M.;
Daniels, A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J .;
Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo,
C.; Clifford, S.; Ochterski, J .; Petersson, G. A.; Ayala, P. Y.; Cui, Q.;
Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.;
Foresman, J . B.; Cioslowski, J .; Ortiz, J . V.; Baboul, A. G.; Stefanov,
B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.;
Martin, R. L.; Fox, D. J .; Keith, T.; Al-Laham, M. A.; Peng, C. Y.;
Nanayakkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P. M. W.;
J ohnson, B.; Chen, W.; Wong, M. W.; Andres, J . L.; Gonzalez, C.; Head-
Gordon, M.; Replogle, E. S.; Pople, J . A., Gaussian, Inc., Pittsburgh,
PA, 1998.
somewhat smaller than on the cyclopropyl group (+0.34,
see Figure 2). The C-C bond length (1.440 Å) is slightly
+
shorter than in 15‚Br , but again much longer than in
the corresponding alkene 1 (1.318 Å). The spiroannelation
of a cyclopropane ring as in 3 has a strong effect on the
+
structure of the corresponding bromonium ion 3‚Br ,
which is highly unsymmetrical with a short C-Br bond
of 1.993 Å to the primary carbon and a very long C-Br
bond of 2.521 Å to the tertiary carbon; the C-C-Br bond
angle is 92.9°. This structure is in line with the fact that
(
38) (a) Becke, A. D. J . Chem. Phys. 1993, 98, 5648-5652. (b) Lee,
C. T.; Yang, W. T.; Parr, R. G. Phys. Rev. 1988, B37, 785-789.
39) (a) McLean, A. D.; Chandler, G. S. J . Chem. Phys. 1980, 72,
639-5648. (b) Krishnan, R.; Binkley, J . S.; Seeger, R.; Pople, J . A. J .
Chem. Phys. 1980, 72, 650-654.
(40) No attempt was made to locate the weakly bound π-complexes
(
2
between the alkenes and Br .
5
(41) Olah, G. A. Carbocations and Electrophilic Reactions; Wiley:
New York, 1973; pp 113-116.

4
106 J . Org. Chem., Vol. 67, No. 12, 2002
Kozhushkov et al.
F igu r e 1. Calculated [B3LYP/6-311G(d,p)] geometries (bond lengths in angstroms, bond angles in degrees) of bromonium cations.
a cyclopropyl substituent strongly stabilizes an adjacent
positively charged center42 and thus favors an unsym-
metrical structure that places a larger positive charge
also is not symmetrical, and this results from the
different orientations of the cyclopropyl rings relative to
the CBrC ring, which reduce the symmetry of the
+
43
at the cyclopropyl carbon, as shown in structure 3‚Br
bromonium ion.
+
(
Figure 2). In analogy to 3‚Br , the bromonium ion 4‚
Br om in a tion Ra tes. Th eor y vs Exp er im en t. To
quantify the nucleophilicity of the double bond in the
various alkenes 1-12, the energy changes (∆E) for the
+
Br , which has two spiroannelated cyclopropane rings,
is also highly unsymmetrical (the C-Br bond lengths are
.986 Å for C -Br and 2.599 Å for C -Br), the positive
1
′
7
+
1
addition of Br to these alkenes were calculated (see
charge at the cyclopropyl carbon being strongly stabilized
by the two adjacent spirocyclopropane rings.
Table 5).44 For comparison, ∆E values were also com-
puted for the analogous methyl-substituted ethylenes
+
The bromonium ion 2‚Br from bicyclopropylidene is
13-19.
again symmetrical with C-Br bond distances of 2.091
In the gas phase, the addition of Br+ to all alkenes is,
Å, shorter by 0.085 Å than in the tetramethylethylene
-1
as expected, highly exothermic, e.g., by -103.0 kcal mol
+
analogue 19‚Br . The bromonium ions of the spirocyclo-
+
+
propanated bicyclopropylidenes, 5‚Br and 6‚Br , are
highly unsymmetrical with one short and one long C-Br
(
43) The highly unsymmetrical structure of 10‚Br + results from the
1
fact that the cyclopropyl rings attached to C rotate into a bisected
conformation, which strongly stabilizes the positive charge at this site.
For steric reasons the four cyclopropyl groups cannot simultaneously
adopt the preferred bisected conformation.
+
+
bond (Figure 1) in analogy to 3‚Br and 4‚Br . The
+
bromonium ion 10‚Br from tetracyclopropylethylene
(
44) Initially, an attempt was made to quantify the nucleophilicity
(
42) Smith, M. B.; March, J . March’s Advanced Organic Chemistry.
of the double bond by calculating the proton affinities of these alkenes.
However, no correlation was found between the bromination rates and
the proton affinities.
Reactions, Mechanisms, and Structure, 5th ed.; Wiley: New York, 2001;
Chapter 5, pp 222-223.

Relative Stabilities of Bromonium Ions
J . Org. Chem., Vol. 67, No. 12, 2002 4107
F igu r e 2. Calculated [B3LYP/6-311G(d,p)] NPA charges of bromonium cations. [∑q(H) denotes the sum of the charges on the
+
+
hydrogens in the fragments which are pointed at by the arrows (e.g., in 5‚Br it refers to one cyclopropyl ring and in 10‚Br to
two rings).
Ta ble 5. Ca lcu la ted En er gies [B3LYP /6-311G(d ,p ) + ZP E,
Ta ble 6. Ca lcu la ted En er gies [B3LYP /6-311G(d ,p ) + ZP E]
-
1
+
+
k ca l m ol ] for th e Ad d ition of Br to Va r iou s Alk en es
of Br Exch a n ge Accor d in g to Eq 3 for Alk en es 1-6
1
-19 a n d th e Cor r esp on d in g Exp er im en ta l Br om in a tion
Alk
1
2
3
4
5
6
Ra te Con sta n ts (kBr ) for th e Ad d ition of Br om in e to
2
E (kcal mol-1) 6.3 -3.3 -3.2 -10.0 -11.6 -18.2
∆
Alk en es 1-19 in Meth a n ol a t 25 °C
alkene ∆Ea
∆∆Eb log kBr2 alkene ∆Ea
∆∆Ec log kBr2
exchange equations, such as eq 3, in which Alk denotes
1
2
3
4
5
6
7
8
9
0
1
2
-114.2 -0.0 2.56
-123.8 -9.7 4.67
-123.7 -9.6 3.77
-130.5 -16.4 5.29
-132.1 -17.9 6.21
-138.7 -24.5 7.53
-126.9 -12.8
13
14
15
16
17
18
19
7
-103.0
0.0 0.67
+
+
-112.2 -9.2 2.61
-120.5 -17.5 4.57
-119.6 -16.7 4.38
-119.4 -16.4
15‚Br + Alk f 15 + Alk ‚Br
(3)
an alkene (e.g., 1-6) and Alk ‚Br + denotes its bromonium
ion. Equation 3, for example, compares the Br addition
energies of several alkenes (Alk ) relative to that of 15,
and the calculated energy values are given in Table 6.
Similarly, the ∆∆E values in Table 5 give the energies
of similar Br transfer reactions relative to that of 1 (left
half of Table 5) or relative to that of ethylene (13) (right
half of Table 5).
+
-126.1 -23.2 6.11
-131.0 -28.0 7.09
-126.9 -24.0
-143.1 -40.1
-142.2 -39.2 8.48
-140.9 -37.9
-143.1 -28.9
-142.2 -28.0 8.48
-140.9 -26.7
8
9
10
+
1
1
1
-141.2 -27.0
-153.7 -39.5 8.90
a
Energy changes for the addition of Br+ to the alkene. b Arith-
metic difference in the calculated ∆E relative to that of 1.
Arithmetic difference in the calculated ∆E relative to that of 13.
The ∆E values for the addition of Br+ to the methyl-
substituted ethylenes 13-19 show a straightforward
correlation with the number of methyl groups connected
to the double bond. The ∆∆E value [i.e., the stability (in
this paper the term stability refers to thermodynamic
stability) of a particular bromonium ion relative to that
c
for ethylene. For calibration against solution results, it
is useful to compare the calculated ∆E values for the
alkenes of interest relative to that of a reference system.
+
+
-1
This is conveniently done by the use of isodesmic Br
of the parent 13‚Br ] for propene is by 9.2 kcal mol

4
108 J . Org. Chem., Vol. 67, No. 12, 2002
Kozhushkov et al.
lower than for ethylene, and that for isobutene is lower
the calculated ∆∆E for these two alkenes (eq 3, Alk ) 1)
-
1
+
-1
yet by another 8.3 kcal mol (i.e., 15‚Br is more stable
is 6.3 kcal mol
corresponding to a predicted rate
-
1
+
4.5
by 17.5 kcal mol than 13‚Br ). Substitution of ethylene
enhancement of 10 . Similarly, 3 and 4 are predicted
7
12
with a third and a fourth methyl group stabilizes the
bromonium ion further by ca. 6 and 5 kcal mol
by their calculated ∆∆E values to react 10 and 10 ,
respectively, faster than 1, while actually they are
brominated only 16 and 537 times, respectively, faster
than 1 (Table 5). These large differences between the
∆∆E values calculated for the gas phase and the actual
rate enhancements observed are due to at least two major
factors: (a) solvation effects, which in solution signifi-
cantly reduce the magnitude of the substituent effects
on the bromination rates relative to that in the gas phase,
and (b) the fact that only part of the electronic and steric
effects, operating in the bromonium ions, are experienced
also in the transition states. The slope of the correlation
line in Figure 3 of -0.171 gives a qualitative measure of
these effects. Namely, the effect of the substituents is
reduced in the experiments by a factor of 5.5 in terms of
-
1
,
respectively. The mean stabilizing effect of each methyl
-1
substituent on the bromonium ion is thus ca. 7 kcal mol .
+
The bromonium ion 1‚Br derived from 1 is less stable
-
1
+
by 6.3 kcal mol than the bromonium ion 15‚Br derived
4
5
from isobutene (eq 3, Alk ) 1). A spiroannelated
cyclopropane ring as in 3 and 4 stabilizes the bromonium
+
-1
ion versus 1‚Br by 9.6 kcal mol for the first ring (i.e.,
+
-1
3
‚Br ) and by an additional 6.8 kcal mol for the second
+
-1
ring (Table 5), so that 4‚Br is 10 kcal mol more stable
+
than 15‚Br (eq 3, Alk ) 4). The stabilizing effect by a
spirocyclopropane ring is similar on going from the
+
bromonium ion of bicyclopropylidene, 2‚Br , to that of
+
cyclopropylidenespiropentane, 5‚Br , and cyclopropylidene-
+
5.5
dispiro[2.0.2.1]heptane, 6‚Br , for which the stabilizing
energy and by a factor of ca. 10 in terms of rates
-1
effect is 8.2 kcal mol for the first ring and an additional
relative to that of the fully developed respective bromo-
nium ions in the gas phase. The relatively small slope
suggests a relatively “early” transition state with only
little “bromonium ion character” and/or a leveling of the
substituent effects by the solvent. This is in line with
previous conclusions of various experimental studies (see
below).
-
1
6
.6 kcal mol
for the second ring (Table 5). Thus,
spiroannelation of a cyclopropane ring in the R-position
to the double bond of a methylenecyclopropane or bicyclo-
propylidene stabilizes the bromonium ion on the average
-
1
by 8-9 kcal mol for the first ring, and by yet another
-
1
ca. 7 kcal mol for the second ring (Table 5). Direct
substitution of ethylene by cyclopropyl groups as in 7-10
or on the methylene group of methylenecyclopropane as
in 11 and 12 leads to a much larger stabilization of the
The good correlation according to eq 4 means that
substituents which strongly stabilize a bromonium ion
will also significantly enhance the bromination rate for
-
1
+
bromonium ion, e.g., by as much as 27.0 kcal mol for
the corresponding alkene. For instance, 12‚Br is more
+
-1
+
-1
one R-cyclopropyl group in 11‚Br and by 39.5 kcal mol
stable than 1‚Br by 39.5 kcal mol , and correspondingly
for two groups in 12‚Br + relative to 1‚Br +.
12 is brominated 2 × 10 times faster than 1 (Table 5).
6
The calculated energies (according to eq 3 or the ∆∆E
values in Table 5) correlate with the relative rates of
bromination of the corresponding alkene46 (correlation
coefficient 0.927 according to eq 4, Figure 3). The quality
of the correlation is particularly impressive considering
the wide variety of alkenes included, and the fact that
the calculations are related directly only to the gas phase,
neglecting solvation effects. The correlation coefficient
improves significantly when only structurally related
alkenes are included as done in Figure 4. Thus, when
only the methyl-substituted ethylenes are considered,
according to eq 5, the correlation coefficient is as high as
Both the calculations and the experiments point to a
much larger effect of an R-cyclopropyl substituent than
that of a spirocyclopropane group or a methyl substituent.
The influence of cyclopropyl substituents on the double
bond of ethylene is somewhat different from that on the
double bond of methylenecyclopropanes 11 and 12. For
ethylene, successive R-substitution with up to two cyclo-
propyl groups enhances the rate drastically whereas a
third and a fourth cyclopropyl substituent retards the
rate slightly. This kinetic series is also nicely reproduced
by the calculations of the corresponding bromonium ions.
The first R-cyclopropyl substituent on ethylene leads to
-
1
0
.998 (Figure 4a). Similarly, for the bicyclopropylidenes
a stabilization of the bromonium ion by 23.9 kcal mol
(Table 5), and the second stabilizes the bromonium ion
2
, 5, and 6, the correlation coefficient is 0.999, and for
-
1
-1
the methylenecyclopropanes 1, 3, and 4, it is 0.974
Figure 4b).
further by 16.2 kcal mol (total effect of 40.1 kcal mol ).
The effect is similar in the methylenecyclopropanes 11
and 12, where the stabilization by the first and second
(
-
1
log kBr2 ) -0.171∆∆E + 2.956
log kBr2 ) -0.233∆∆E + 0.570
(4)
(5)
cyclopropyl groups is 27.0 and 39.5 kcal mol , respec-
tively (Table 5). In contrast, substitution on ethylene by
a third and a fourth R-cyclopropyl group on ethylene
-
1
destabilizes the bromonium ion by 0.9 and 1.3 kcal mol
,
A calculated ∆∆E of 1.36 kcal mol-1 between two
respectively. This rate retardation can be reasonably
attributed to rate-decreasing steric and σ-electron-
withdrawing effects of the additional cyclopropyl groups
with inappropriate orientations which override the rate-
increasing electron-donating effects of the cyclopropyl
groups.
transition states is reflected in a rate enhancement by a
factor of 10 at 25 °C. Comparison of the calculated ∆∆E
values and the experimental bromination rates in metha-
nol shows that the actual rate changes observed in
solution are much smaller than the calculated ones. For
example, 15 is brominated 102 times faster than 1, while
2
A fairly good linear relationship (Figure 5, r ) 0.934)
is also found between the bromination rate coefficients
of the alkenes and their first ionization energies as taken
(
45) As the two bromonium ions have the same number of carbon
+
22
47
atoms, “size effects” are not important. Similarly, 2‚Br is less stable
from their PE spectra. An analogous relationship has
previously been observed for acyclic alkenes with linear
n-alkyl substituents and attributed to the absence of any
steric control in the bromination rates.
+
-1
than 19‚Br by 7.2 kcal mol
46) The same qualitative behavior was obtained also when ∆E and
∆E values were replaced by the corresponding ∆G and ∆∆G values
although in Figure 2 the correlation coefficient was somewhat lower.
.
(
∆

Relative Stabilities of Bromonium Ions
J . Org. Chem., Vol. 67, No. 12, 2002 4109
Sch em e 6
Sch em e 7
F igu r e 3. Measured rates of bromination of alkenes 2-19
versus their calculated ∆∆E values [B3LYP/6-311G(d,p) +
ZPE] relative to the energy of 1.
2
cyclopropanated alkenes 1-12 (eq 7 with r ) 0.963) are
considered separately.
log kBr2 ) -2.936(IE) + 31.424
log kBr2 ) -5.007(IE) + 49.879
(6)
(7)
Br om in a tion P r od u cts. Th eor y vs Exp er im en t . As
it is well established that cyclopropyl cations undergo
3
3
ring opening to the more stable allyl cations, the fact
that the major bromination products of most methyl-
enecyclopropanes contain an intact central ring indicates
that simple cyclopropyl cations 44 are not intermediates
in these reactions, and that their solvation makes their
reaction with methanol faster than their rearrangement.
Indeed, the calculations show that the reaction interme-
diates are not simple bromine-substituted cyclopropyl
cations 44, but bridged bromonium ions of type 46
(
Scheme 6). Even though some of the calculated bromo-
+
F igu r e 4. Measured rates of bromination versus calculated
nium ions are highly unsymmetrical (e.g., 3‚Br ), there
is still a significant interaction between the bromine and
the adjacent positively charged cyclopropyl center. 1‚Br
is calculated to be 8.6 kcal mol less stable than its
∆
∆E values [B3LYP/6-311G(d,p) + ZPE]: (a) methyl-substi-
tuted ethylenes 13-19 relative to ethylene and (b) methyl-
+
enecyclopropane series (1, 3, 4) and bicyclopropylidene series
-1
(2, 5, 6) relative to isobutene.
corresponding allyl cation 45 (m ) n ) 0), but a small
-
1
barrier of 1.6 kcal mol for ring opening slows the
rearrangement. In solution the barrier for ring opening
is probably higher.
As to the attack of a nucleophile on a bromonium ion,
it is reasonable that it will occur at the carbon atom
which carries the highest positive charge. The calculated
natural population analysis (NPA) charge distributions
(
given in Figure 2) show that for all unsymmetrical
4
(7)
bromonium ions the charge on C (see atom numbering
in Figure 1 and Scheme 7) is positive while it is negative
1
′
+
+
+
+
on C . E.g., for 3‚Br , 4‚Br , 6‚Br , and 15‚Br the
charges on C4 are +0.29, +0.33, + 0.35, and +0.30,
(7)
1
′
respectively, and the charges on C are -0.43, -0.45,
0.18, and -0.40, respectively. Thus, in such ions, where
-
1
′
4(7)
the C -Br bond is substantially shorter than the C
-
4
(7)
Br bond, and the positive charge on C
is larger than
1
′
on C , attack is expected to occur preferably at the more
highly charged C4 (Scheme 7). In agreement with these
qualitative theoretical considerations, in the bromination
(7)
F igu r e 5. Measured rates of bromination of various alkenes
versus their π-IEs.
In the same way as for the rate-calculated energy
relationships, better correlations are obtained when
methylethylenes 13-19 (eq 6 with r ) 0.991) and
(
47) (a) Dubois, J .-E.; Chr e´ tien, J . R. J . Am. Chem. Soc. 1978, 100,
506-3513. (b) Chr e´ tien, J . R.; Coudert, J .-D.; Ruasse, M.-F. J . Org.
Chem. 1993, 58, 1917-1921.
3
2

4
110 J . Org. Chem., Vol. 67, No. 12, 2002
Kozhushkov et al.
+
of, e.g., 4 and 6 via the highly unsymmetrical ions 4‚Br ,
+
4(7)
6
‚Br , products of a nucleophilic attack at C
were
observed (i.e., 35 and 41 in Schemes 4 and 5). Further-
more, as the charge at the cyclopropyl C4 (and the
groups attached to it) increases, the driving force for ring
opening increases, and some charge is also transferred
(7)
1
to C , increasing its reactivity toward nucleophiles. In
agreement with these qualitative theoretical consider-
+
ations, the bromination of 3 (via unsymmetrical 3‚Br )
yields products that result from cyclopropyl ring opening
1
as well as from nucleophilic attack at C (see Scheme 3).
It is noteworthy that the calculated structures of the
bromonium ions, more specifically their asymmetry, is
in complete agreement with the structures used in
Schemes 1-5 to rationalize the observed products.
The only case where the nucleophilic attack occurs at
1
′
+
C is observed in the bromination of 1 (via 1‚Br ), which
produces 23 in a yield of 27%, and no product resulting
1
4
7
from an attack at C (corresponding to C in 3 and C in
, respectively) is observed. This experimental result
4
seems to contradict the calculated charge distribution.
However, a hint for this exceptional behavior can already
be found in the very small positive charge of +0.06 on
1
+
+
C
in 1‚Br . Furthermore, in 1‚Br the total positive
1′
2
charge on C H is considerably larger than found in all
+
other bromonium ions (e.g., +0.23 in 1‚Br vs +0.08 in
+
+
3
‚Br or +0.02 in 4‚Br ), while the total positive charge
1(4/7)
on the fragment that contains C
is significantly
+
smaller in 1‚Br than that in all other bromonium ions
+
(
3
for example, it is +0.34 in 1‚Br vs +0.7 and +0.8 in
+
+
‚Br and 4‚Br , respectively, Figure 2). A theoretical
quantitative rationalization for the exceptional behavior
+
of 1‚Br is given below.
To account more quantitatively for the various prod-
ucts obtained in the brominations, the transition states
1
′
1(4/7)
1
for nucleophilic attack at C , C
, and C (see Scheme
7
), as well as for ring opening, would have to be
calculated. As such calculations are very resource de-
manding, they were conducted only for the parent 13‚
+
+
Br , for the dimethyl-substituted 15‚Br , and for the
+
methylenecyclopropane-derived bromonium ion 1‚Br ,
which behaves differently than the other bromonium
ions. A water molecule was chosen as an appropriate
model for the attacking nucleophile.48
According to the calculated profiles for these reactions
Figure 6), the first step involves the exothermic forma-
F igu r e 6. Calculated [B3LYP/6-311G(d,p)] energy profiles
(
(kcal mol-1) for the attack of water at C1′ and C
1
of (a) 13‚Br ,
+
+
+
tion of a bromonium ion-water complex, and this is
(b) 15‚Br , and (c) 1‚Br .
followed by a transition state (TS) that leads to the
-
1
1
+
endothermic by 7.4 kcal mol , while the attack at C is
products. For the parent bromonium ion 13‚Br , the
-
1
+
-1
exothermic by 7.4 kcal mol . Furthermore, with 15‚Br
1′
formation of the complex is exothermic by 21.8 kcal mol
the TS corresponding to attack at C involves a high
(
relative to the isolated reactants), and the TS that
-
1
-
1
barrier of 11.1 kcal mol , but the TS corresponding to
attack at C has a low barrier of 5.0 kcal mol . Thus,
for 15‚Br , nucleophilic attack at C is predicted to be
strongly preferred over attack at C , both thermody-
namically and kinetically (Figure 6b). As pointed out
above, this preference can also be related to the higher
positive charge (+0.30) placed on the tertiary C of 15‚
Br . The theoretical finding is in good agreement with
follows involves a barrier of 6 kcal mol , leading to a
product which is very close in energy to that of the
1
-1
+
1
complex (Figure 6a). Water attack on the unsymmetrical
1
′
+
1
(
2
5‚Br exhibits a very different potential energy surface
1
Figure 6b). While water attack at C is exothermic by
-
1
1.5 kcal mol (relative to the isolated reactants), the
1
1
′
attack at C is calculated to be endothermic by ca. 1 kcal
+
-
1
mol
.
the experimental observation that bromination of iso-
butene in methanol gives the Markovnikov-type product
The same conclusion is valid if the bromonium ion-
water complex is taken as the reference point; the
reaction leading to products via water attack at C1′ is
Me
2 2
C(OMe)CH Br in 85% yield, and none of the isomer
1
′ 47b
corresponding to nucleophilic attack at C .
In the case of 1‚Br , water addition to either C or C
is exothermic (Figure 6c). Addition to C leading to 51
+
1′
1
(48) We note that this model in which only one water molecule
1
models the solvent is extremely simplified, but we assume that some
insight can nevertheless be gained by the calculations detailed below.
-
1
(Scheme 8) is exothermic by 27.5 kcal mol (relative to

Relative Stabilities of Bromonium Ions
J . Org. Chem., Vol. 67, No. 12, 2002 4111
Sch em e 8
argue against the possibility that the product-forming
step (i.e., return) is rate limiting.4
9-51
(3) The transition states of the rate-limiting formation
of the ionic intermediates are very early, resembling more
the initial states than the unsymmetrical bromonium
ions in which the strain could be released. This conclusion
3
1
is supported by the small m values and KSIEs (Table
) found for the reaction of most cyclopropanated alkenes.
3
It is also supported by the comparison of the correlations
between rates and calculated energies of the bromonium
ions (eq 4 and Figure 3) and those between rates and
ionization potentials (eqs 6 and 7, Figure 5). In particular,
the fact that the bromination rates correlate fairly well
with IEs implies no change in strain energies on going
from the initial to transition states because IE measures
a vertical process in which changes in geometry are
minimal. Charge development, “less than normal”, in
early transition states has been suggested previously for
the solvolysis of cyclopropyl triflates32 on the basis of their
m values, as unusually small as those observed here for
bromination of analogous substrates. This interpretation
agrees with our conclusion.
the reactants), while addition to C1′ leading to the
-1
isomeric 53 is exothermic by only 18.5 kcal mol (Figure
1
6
c). Thus, the product resulting from attack at C is
favored thermodynamically. The same conclusion is valid
also if the bromonium ion-water complex is taken as the
reference point; the reactions leading from the complexes
(4) Nucleophilic solvation of the rate-limiting transition
c,51
4
9 and 54 to 51 and 53 are exothermic by 6.5 and 4.0
states6
is supported by all the kinetic, product, and
-
1
+
kcal mol , respectively (Figure 6c). However, for 1‚Br ,
the transition state leading to 51 is calculated to have
an energy barrier of 2.3 kcal mol , whereas the transi-
computational results. The very large stabilization af-
forded by water complexation of the bromonium ion
suggests that the reaction pathway does not go through
unsolvated, naked ions but goes directly from the alkenes
to the solvated intermediates. This implies that the
solvent participates nucleophilically in their formation.
The never large amount of rearranged products also
supports the solvent participation. The methanol trap-
ping of the intermediates is fast as compared to their
rearrangement, showing that methanol is involved in the
kinetically formed intermediate. These solvated inter-
mediates are, therefore, very short-lived. Rearrangement
is observed only when the positive charge is delocalized
into cyclopropyl rings, as, for example, with 3 and 4.
Moreover, the small but significant rearrangement for
the bromination of 1 in pentane but not in methanol
-
1
tion state leading to 53 has a very low barrier of 0.4 kcal
-
1
1′
mol . This lower barrier for attack at C is consistent
with the formation of product 23 (in 27% yield) in the
bromination of 1 in methanol, and the absence of
products of type 50. Thus, the product formation from 1
is kinetically controlled. This solves the apparent con-
tradiction pointed out above between the calculated
+
charge distributions in 1‚Br and the observed products.
Finally, it is of interest to compare in the addition of
+
water to 1‚Br the geometries of the bromonium ion-
water complexes and the transition states leading to
products. Both the complex and the TS appear “later”
1
on the reaction coordinate for attack at C compared to
1
′
+
1′
attack at C . The C---OH
2
distance is 2.572 Å in the C
(Scheme 1) is another support for the contribution of
1
complex 54 and 1.572 Å in the C complex 49. Similarly,
nucleophilic solvation in the formation of the correspond-
ing ionic intermediate. All these results are consistent
with the small kinetic solvent effects, observed in bro-
mination and in solvolysis of these alkenes.
in the corresponding transition states these distances are
2
.217 and 1.598 Å, respectively (Figure 7).
Con clu sion s
(5) The absence of a significant contribution of the
strain energies of these strained alkenes to their reac-
tivities and to their product formation52 results mainly
from the nucleophilic assistance of the solvent in the
formation and the reaction of the unsymmetrical bromo-
Several conclusions of interest for the bromination
6
mechanism of these highly strained methylenecyclopro-
panes and their spiroannelated analogues emerge from
the comparison of the kinetic, product, and computational
studies.
(
1) Strain does not contribute much to the reactivity
(49) (a) Slebocka-Tilk, H.; Gallagher, D.; Brown, R. S. J . Org. Chem.
996, 61, 3458-3466. (b) Slebocka-Tilk, H.; Motabelli, S.; Nagorski,
R. W.; Turner, P.; Brown, R. S.; McDonald, R. J . Am. Chem. Soc. 1995,
1
and to the product formation. The rates are neither
markedly smaller nor markedly larger than those ob-
served for acyclic methylethylenes. The rearranged prod-
ucts expected from a significant strain release are either
absent or formed in amounts similar to those of the
unrearranged products (Table 4).
1
17, 8769-8776.
(50) Bellucci, G.; Bianchini, R.; Chiappe, C.; Brown, R. S.; Slebocka-
Tilk, H. J . Am. Chem. Soc. 1991, 113, 8012-8016.
(51) Bentley, T. W.; Schleyer, P. v. R. Adv. Phys. Org. Chem. 1977,
1
4, 1-67.
(52) However, the resulting products are less strained than the
starting alkenes. This release of strain can be evaluated qualitatively
from the known strain energies of cyclopropane (28.1 kcal/mol), and
those of compounds 1 (41.7 kcal/mol), 2 (77.4 kcal/mol), and 3 (74.6
kcal/mol), assuming the validity of an additivity scheme for strain
energy increments (for details see refs 2 and 3). For theoretical
consideration of this question also see: J ohnson, W. T. G.; Borden, W.
T. J . Am. Chem. Soc. 1997, 119, 5930-5933.
(
2) The rate-limiting step of the bromination is the
formation of the unsymmetrical bromonium ions, not the
product-forming step. The small barrier calculated for the
trapping of intermediate 1‚Br (Figure 6c) and the
relatively small positive charge on the bromine atom
x

4
112 J . Org. Chem., Vol. 67, No. 12, 2002
Kozhushkov et al.
F igu r e 7. Calculated [B3LYP/6-311G(d,p)] geometries (bond lengths in angstroms) of bromonium ion-water complexes, transition
1
′
+
1
+
states, and products of water attack at (a) C of 1‚Br and (b) C of 1‚Br .
nium ions and probably, but at a smaller extent, in their
bromine bridging.
Exp er im en ta l Section
Gen er a l Rem a r k s. 1H and 13C NMR spectra were mea-
The successive spirocyclopropanation of the three-
membered rings in 1 and 2 leads to significant stabili-
zations of the corresponding bromonium ion and thus to
significant acceleration of the bromination reaction de-
spite the marked increase in strain. The methylene-
cyclopropane (1, 3, 4, 11, 12) series and bicyclopropyli-
dene (2, 5, 6) series show similar reactivity ranges for
sured in CDCl solution, CHCl /CDCl as internal reference,
3
3
3
1
13
δ in parts per million, J in hertz at 250 ( H) and 62.9 [ C,
additional DEPT (distortionless enhancement by polarization
transfer)] MHz. FT-IR spectra were recorded for KBr pellets
and oils between NaCl plates. MS (EI) spectra were recorded
at 70 eV. Melting points are uncorrected. GC analyses were
done on a 25 m capillary column CP-SIL-5-CB. TLC chromato-
grams were obtained using precoated sheets and 0.25 mm Sil
G/UV254. For chromatographic separations, silica gel 60 (230-
400 mesh) was used. Anhydrous methanol was prepared by
distillation from magnesium methoxide. The starting materials
+
the addition of Br . A good linear correlation is found
between the calculated stabilities of bromonium ions and
the experimentally measured rates of bromination of the
corresponding alkenes.

Relative Stabilities of Bromonium Ions
J . Org. Chem., Vol. 67, No. 12, 2002 4113
-
Ta ble 7. E Va lu es a s a F u n ction of th e Wa velen gth a n d
solution in methanol, a corresponding Br
3
concentration was
th e Br om in e Con cen tr a tion
produced, and the absorbance variations were registered. After
injection of some microliters of a concentrated alkene solution,
the absorbance decrease as a function of time gave the kinetic
signal. For the reactions under pseudo-first-order conditions,
the concentrations of the alkene exceeded those of bromine at
least by a factor of 10. The exact concentration of the alkene
was calculated using eq 8, where mal,sol is the exact quantity
λ
nm)
[NaBr]
ꢀ
(mol L-1)
(L mol-1 cm-1
(
solvent
)
2
70
70
45
[D1]methanol
0.029
30780
41730
43930
44670
45770
47918
1769
0
0
.011
.204
2
3
methanol
methanol
0.058
0
0
.114
.216
mal,sol
1
0
[
alkene] )
minj
(8)
0.056
mal,sol + mMeOH M + V
a
cell
0
0
.105
.208
1883
1818
of alkene in its mother solution, mMeOH the mass of methanol
used in the preparation of concentrated olefin solution, Mal the
molecular weight of olefin, Vcell the cell volume, and minj the
injected mass of mother alkene solution. For the reactions
under second-order conditions, the concentration of alkene was
about half the bromine concentration. After the registration
of the course of the absorbance curve, a known quantity of 2,3-
dimethylbut-2-ene was added to determine the final bromine
concentrations. The rate constants were evaluated from the
kinetic curve.
Gen er a l P r oced u r e (GP 1) for th e Ad d ition of Br om in e
to Hyd r oca r bon s 1-6 in Meth a n ol. To a stirred solution
of NaBr (3.0 g, 29.2 mmol) in anhydrous methanol (70 mL)
was added bromine (4.0 g, 1.29 mL, 25 mmol) in one portion
in the absence of light and moisture at 25 °C. Stirring was
continued for 2 min, and then a solution of the alkene (12.5
mmol) in MeOH (2 mL) was added at the indicated tempera-
ture. After being stirred for 2 min, the mixture was poured
1
,5a 2,53 3,54 4,55 5, 6,53a 7,56 and 857 were prepared according
to reported procedures. Olefin- and water-free pentane was
5
8
prepared by the common method. All other chemicals were
used as commercially available. Organic extracts were dried
over MgSO
Kin etic Mea su r em en ts. Ethanol p.a., methanol p.a., 2,3-
dimethylbut-2-ene, 99+%, and [D ]methanol were used as
commercially available. Sodium bromide (Suprapur) was dried
at atmospheric pressure at 120 °C for 24 h. All solutions were
used as freshly prepared within a maximum of 3 h after
preparation.
4
.
1
1
. Cou loa m p er om etr ic Mea su r em en ts. The measuring
cell (capacity about 100 mL) equipped with a motor-driven
glass stirrer, electrolysis circuit, and amperometric detector
circuit was used under isothermal conditions (25 ( 0.1 °C).
The electrolysis circuit consisting of two Metrohm electrolysis
2
electrodes (25 mm platinum plates) was connected with a
into an ice-cold solution of Na
in water (100 mL) and quickly extracted with pentane (3 ×
0 mL). The combined organic phases were washed with a 5%
NaHCO solution, water, and brine before they were dried and
2 2 3 3
S O (5 g) and NaHCO (10 g)
constant-current source (0.1-250 mA range) and stopwatch.
The amperometric detector circuit was a three-electrode po-
tentiostatic assembly involving a working electrode (polished
platinum disks of 2 or 5 mm diameter spinning at 2000 r/min),
a reference calomel electrode in satd NaCl/MeOH (EtOH)
solution, and an auxiliary glass-sealed platinum electrode. The
potential applied between the working and reference electrodes
5
3
concentrated under reduced pressure. The residue was sepa-
rated by flash column chromatography (75 g of silica gel,
column 30 × 3 cm). Taking into account the instability and
sensitivity of the products to silica gel, their relative ratio was
determined using NMR spectrometry before chromatographic
separation.
was that of the bromine diffusion plateau in methanol (ein
200 mV) or ethanol (ein ) +250 mV). The current detector
circuit was a current follower amplifier with a small bias
)
+
1
-Br om o-1-(br om om eth yl)cyclopr opan e (20) an d 1-Br o-
1
4a
current and small false-zero potential. The output signal was
registered with a recorder and oscilloscope. The cell was filled
with 45-50 mL of MeOH/NaBr solution, and the potential was
applied on the amperometric circuit. After thermostabilization
and compensation of a residual current, the predetermined
quantity of bromine was produced with the electrolysis circuit.
The constant of proportionality R that varied from 12 to 47
mol‚A/L in the course of measurements was averaged using
the amperometric signal. Then a solution of the alkene (half
as much as bromine) was injected into the cell solution. The
second-order rate constant was calculated from the kinetic
curve.
m o-1-(m eth oxym eth yl)cyclop r op a n e (23). From methyl-
5b
enecyclopropane (1) (1.0 g, 18.49 mmol), compounds 20 (0.753
g, 19%) and 23 (0.210 g, 7%) were obtained according to GP 1
after column chromatography (eluent pentane).
13
Data for 20: C NMR δ 18.50 (2 CH
2
), 43.72 (CH
2
), 32.08
), 3.40
); C NMR δ 58.69 (CH ),
), 46.09 (C).
-Br om o-1-(1′-b r om ocyclop r op yl)cyclop r op a n e (24),
C). Data for 23: 1H NMR δ 0.79-0.90 (m, 4 H, 2 CH
(
(
1
2
13
s, 3 H, OCH
3
), 3.48 (s, 2 H, CH
), 79.76 (CH
2
3
4.26 (2 CH
2
2
1
1
1
-(1′-Br om ocyclopr opyl)-1-m eth oxycyclopr opan e (25), an d
,3,5-Tr ibr om o-2-(br om om eth yl)p en t-2-en e (28). From bi-
cyclopropylidene (2) (1.0 g, 12.48 mmol), compounds 24 (2.115
g, 71%), 25 (0.383 g, 16%), and 28 (0.352 g, 7%) were obtained
according to GP 1 after column chromatography (eluent
2
2
. UV Sp ectr oscop y. The measurements were performed
using a spectrometer connected with data acquisition. The
measuring cell of capacity 2.5 mL and 1 cm in thickness was
equipped with a magnetic stirrer and thermostated. ꢀ values
were averaged as a function of wavelength and concentration
of bromide using the prepared bromine/tribromide solution
pentane/Et O, 100:1). Data for
1
24: R ) 0.8; mp 37-38 °C; H NMR δ 1.02-1.08 (m, 4 H,
f
1
3
2 CH ), 1.32-1.39 (m, 4 H, 2 CH ); C NMR δ 19.53 (4 CH ),
41.77 (2 C); MS (EI) m/z (rel intens) 242/240/238 (M , 3/5/2),
214/212/210 (M - C H , 14/30/14), 161/159 (M - Br, 27/27),
133/131 (M - Br - C
Anal. Calcd for C
H, 3.35.
2
2
2
+
+
+
(Table 7).
2
4
+
+
The measuring cell and reference cell were filled with 2.2
2
H
2
4
2
, 15/15), 80 (M - Br , 60), 79 (100).
: C, 30.03; H, 3.36. Found: C, 30.16;
mL of a corresponding NaBr/MeOH solution. After thermo-
stabilization and calibration of absorbance to zero, Br was
injected by quickly dipping a capillary tube filled with a 10%
6
H
8
Br
2
1
Data for 25: R
.81-0.88 (m, 2 H, CH
m, 2 H, CH ), 3.43 (s, 3 H, OCH
4.39, 15.26 (2 CH ), 35.72, 66.50 (C).
Data for 28: R ) 0.50; H NMR δ 3.16 (t, 2 H, J ) 6.8 Hz,
CH ), 3.61 (t, 2 H, J ) 6.8 Hz, CH Br), 4.22 (s, 2 H, CH Br),
4.32 (s, 2 H, CH
Br); 13C NMR δ 27.83, 28.76, 32.52, 40.69
CH ), 130.19, 135.16 (C).
-Br om o-1-(br om om eth yl)sp ir op en ta n e (29), 1′-(Br o-
m om eth yl)cyclop r op yl Br om om eth yl k eton e (31), a n d 1′-
Br om om eth yl)cyclop r op yl Br om om eth yl Keton e Di-
f
) 0.15; H NMR δ 0.61-0.69 (m, 2 H, CH
2
),
0
(
1
2
), 0.91-0.98 (m, 2 H, CH
2
), 1.16-1.23
1
3
2
3
); C NMR δ 55.05 (CH
3
),
(53) (a) de Meijere, A.; Kozhushkov, S. I.; Spaeth, T.; Zefirov, N. S.
2
J . Org. Chem. 1993, 58, 502-505. (b) de Meijere, A.; Kozhushkov, S.
I.; Sp a¨ th, T. J . Org. Synth. 2000, 78, 142-151.
1
f
(
(
(
54) Arora, S.; Binger, P. Synthesis 1974, 801-803.
2
2
2
55) Erden, I. Synth. Commun. 1986, 16, 117-121.
2
56) Donskaya, N. A.; Akhachinskaya, T. V.; Shabarov, Yu. S. Zh.
(
2
Org. Khim. 1976, 12, 1596-1597; J . Org. Chem. USSR (Engl. Transl.)
1
1
976, 12, 1572-1573.
57) Teraji, T.; Moritani, I.; Tsuda, E.; Nishida, S. J . Chem. Soc. C
971, 3252-3257.
58) Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory
Chemicals; Pergamon Press: New York, 1987.
(
(
1
(
m eth yl Aceta l (32). From methylenespiropentane (3) (1.0 g,
12.48 mmol), compounds 29 (0.825 g, 28%), 31 (0.623 g, 19%),

4
114 J . Org. Chem., Vol. 67, No. 12, 2002
Kozhushkov et al.
and 32 (0.432 g, 12%) were obtained according to GP 1 after
column chromatography (eluent pentane/Et O, 40:1).
) 0.55; H NMR δ 0.85-1.10 (m, 3
cyclopropyl H), 1.23-1.41 (m, 1 cyclopropyl H), 1.48 (d, 1 H, J
11.0 Hz, CH ), 1.70 (d, 1 H, J ) 11.0 Hz, CH ), 3.69 (d, 1 H,
J ) 11.0 Hz, CH Br), 3.84 (d, 1 H, J ) 11.0 Hz, CH
Br); 13
NMR δ 7.29, 8.88, 24.43, 43.84 (CH ), 25.33, 39.64 (C).
and 41 (0.849 g, 46%) were obtained according to GP 1 after
2
column chromatography (eluent pentane/Et
2
O, 40:1).
1
Data for 29:
R
f
Data for 40: R ) 0.85; bp 80 °C (0.2 Torr); mp 83-85 °C
f
1
[MeOH, then sublimation at 80 °C (0.2 Torr)];
H NMR δ 0.75-
)
2
2
0.83 (m, 2 H, CH ), 0.95-1.00 (m, 4 H, 2 CH ), 1.20-1.25 (m,
2
2
2
2
C
2 H, CH ), 1.27-1.37 (m, 4 H, 2 CH ); C NMR δ 7.68, 8.31,
18.04 (2 CH ), 28.17 (2 C), 42.29, 54.70 (C). Anal. Calcd for
2
2
13
2
2
1
Data for 31: R
f
) 0.15; H NMR δ 1.13-1.21 (m, 2 H, CH
2
),
C H Br : C, 41.13; H, 4.14. Found: C, 41.23; H, 4.12.
1
0
12
2
1
CH
1
.63-1.70 (m, 2 H, CH
2
), 3.74 (s, 2 H, CH
2
Br), 4.20 (s, 2 H,
Data for 41: R
f
) 0.35; bp 55 °C (0.2 mm); mp 24-25 °C
pentane); H NMR δ 0.60-0.74 (m, 4 H, 2 CH ), 0.98-1.05
m, 2 H, CH ), 1.05-1.15 (m, 4 H, 2 CH ), 1.17-1.23 (m, 2 H,
), 3.45 (s, 3 H, OCH ); C NMR δ 54.94 (CH ), 4.17, 4.87,
4.41 (2 CH ), 23.33 (2 C), 35.46, 74.20 (C); MS (CI) m/z (rel
intens) 279/277 (M + NH
1
3
2
Br); C NMR δ 22.10 (2 CH
2
), 30.67, 36.58 (CH
2
), 32.54,
),
1
(
(
2
99.45 (C).
2
2
1
Data for 32: R
f
) 0.30; H NMR δ 0.62-0.68 (m, 2 H, CH
), 3.20 (s, 6 H, 2 OCH ), 3.54 (s, 2 H,
Br); C NMR δ 48.63 (2 CH ), 12.79
), 31.70, 39.66 (CH ), 22.42, 98.88 (C).
Dispiro[2.0.2.2]octan-7-one (33),7-Bromo-7-(bromomethyl)-
2
13
CH
2
3
3
1
CH
(
.32-1.38 (m, 2 H, CH
Br), 3.73 (s, 2 H, CH
2 CH
2
3
1
2
1
3
2
2
3
+
+
4
+ NH
00/100), 230/228 (M - CH , 4/4). Anal. Calcd for C11
BrO: C, 54.34; H, 6.22. Found: C, 54.61; H, 6.27.
-Br om o-7-cyclopr op yldispir o[2.0.2.1]h epta n e (42) a n d
-(1′-Br om ocyclop r op yl)d isp ir o[2.0.2.1]h ep ta n e (43). To
3
, 8/8), 262/260 (M + NH
4
,
2
2
+
1
2
H
15
-
d isp ir o[2.0.2.1]h ep t a n e (34), a n d 7-(Br om om et h yl)-7-
7
m eth oxyd isp ir o[2.0.2.1]h ep ta n e (35). From 4 (1.06 g, 9.98
7
5
9
mmol), compounds 33 (0.296 g, 24%), 34 (0.375 g, 14%), and
5 (0.245 g, 11%) were obtained according to GP 1 after column
chromatography (eluent pentane/Et O, 40:1).
) 0.30; C NMR δ 8.13, 14.27 (2 CH
), 18.38, 43.08, 213.19 (C).
a stirred solution of 6 (200 mg, 1.51 mmol) in olefin- and water-
free pentane (50 mL) was added a 0.3 M solution of HBr in
pentane (10 mL, 3 mmol) over 30 min at -30 °C. The reaction
mixture was stirred over a period of 1 h and treated with
3
2
1
3
Data for 33: R
CH
Data for 34: R
CH ), 1.00-1.10 (m, 2 H, CH
f
2
), 52.69
(
2
NaHCO
additional stirring, the mixture was poured into an ice-cold
% NaHCO solution (50 mL), and the water layer was
3
(500 mg) at this temperature. After 30 min of
1
f
) 0.90; H NMR δ 0.81-0.98 (m, 4 H, 2
), 1.20-1.38 (m, 2 H, CH ), 3.82
), 43.11 (CH ),
2
2
2
5
3
1
3
(s, 2 H, CH
2
Br); C NMR δ 6.73, 8.24 (2 CH
2
2
extracted with pentane (2 × 50 mL). The combined organic
phases were washed with brine before they were dried and
concentrated under reduced pressure to give 280 mg (87%) of
-
1
2
1
2
8.76 (2 C), 45.86 (C); IR (film, cm ) 3072, 2988, 1421, 1229,
162, 1012, 961, 923, 888, 711; MS (EI) m/z (rel intens) 268/
+
+
66/264 (M , 0.3/0.7/0.3), 187/185 (M - Br, 6/7), 121 (10), 106
4
2 and 43 as a 10:1 mixture that could hardly be separated
(
100), 105 (38), 91 (83), 77 (46).
because compounds 42 and 43 were unstable toward silica gel.
1
Data for 35: R
.79-0.88 (m, 2 H, CH
), 3.40 (s, 3 H, OCH
NMR δ 54.92 (CH ), 3.94, 4.95 (2 CH
f
2
) 0.40; H NMR δ 0.51-0.61 (m, 2 H, CH ),
1
Data for 42: H NMR δ 0.46-0.53 (m, 2 H, CH
2
), 0.54-
0
(
2
), 1.02-1.11 (m, 2 H, CH
), 3.75 (s, 2 H, CH
2
), 37.04 (CH ), 24.63 (2
2
), 1.12-1.21
Br); 13
C
0.60 (m, 2 H, CH
2
), 0.76-0.83 (m, 2 H, CH
2
), 0.84-0.90 (m, 2
m, 2 H, CH
2
3
2
H, CH ), 0.92-0.98 (m, 2 H, CH
2
2
), 1.12-1.19 (m, 2 H, CH
2
),
),
3
2
1
3
+
1.37-1.45 (m, 1 H, CH); C NMR δ 4.78, 7.81, 7.83 (2 CH
-1
2
C), 64.52 (C); MS (EI) m/z (rel intens) 218/216 (M , 0.4/0.4),
+
+
+
25.21 (CH), 19.62 (2 C), 51.73 (C); IR (film, cm ) 2940, 2860,
1
37 (M - Br, 20), 122 (M - Br - CH
3
, 10), 109 (M - Br -
+
+
2800, 1015, 820, 770, 750, 635; GC-MS (EI) m/z (rel intens)
C
2
H
4
, 38), 105 (M - Br - HOCH
100).
-Br om o-1-(1′-b r om ocyclop r op yl)sp ir op en t a n e (36),
3
, 98), 91 (C
7
H
7
, 22), 79
+
+
2
1
13/211 (M - H, 0.3/0.3), 131 (M - H - HBr, 9), 117 (34),
+
(
05 (M - Br - C
2 4
H , 83), 79 (33), 69 (100).
1
Data for 43: 1H NMR δ 0.45-0.61 (m, 4 H, 2 CH
), 0.75-
), 1.32-1.47 (m,
), 4.71 (2 CH ), 25.25 (CH),
1
1
-(1′-Br om ocyclopr opyl)-1-m eth oxyspir open tan e (37), an d
′-Br om ocyclop r op yl 1′-(Br om om eth yl)cyclop r op yl Ke-
2
0
1
1
.97 (m, 6 H, 3 CH
2
), 1.12-1.19 (m, 2 H, CH
2
H, CH); 13C NMR δ 7.82 (4 CH
ton e Dim eth yl Aceta l (39). From cyclopropylidenespiropen-
tane (5) (1.327 g, 12.5 mmol), compounds 36 (1.079 g, 32%),
2
2
9.59 (2 C), 51.60 (C).
3
7 (1.313 g, 48%), and 39 (0.600 g, 15%) were obtained
according to GP 1 after column chromatography (eluent
pentane/Et O, 40:1).
Data for 36: R
Ack n ow led gm en t. This work was supported by the
Deutsche Forschungsgemeinschaft (Project Me 405/15-
), the Fonds der Chemischen Industrie, the Nieder-
2
f
) 0.56; bp 50 °C (0.2 Torr); mp 28-30 °C
3
1
(
MeOH); H NMR δ 0.80-1.19 (m, 4 cyclopropyl H), 1.20-1.44
s a¨ chsisches Ministerium f u¨ r Wissenschaft und Kunst
(Niedersachsen-Israel Research Cooperation Program),
and the companies BASF, Bayer, Degussa, Hoechst, and
H u¨ ls AG through generous gifts of chemicals. T.S. is
grateful to the Konrad-Adenauer Foundation for a
graduate student fellowship and T.F. for financial
support by the Erasmus Exchange Program. We are
indebted to Dr. Miriam Karni, TechnionsIsrael Insti-
tute of Technology, for helpful discussion and to Prof.
R. Gleiter, Heidelberg, for the measurement of several
PE spectra and the possibility to use these data prior
to publication. A.d.M. is indebted to the French Minis-
tere de l’Education Nationale, de la Recherche et de la
Technique (MENRT) for the Alexander von Humboldt-
Gay Lussac Award, which significantly enhanced the
collaboration between the groups in G o¨ ttingen and in
Paris. We are grateful to Dr. B. Knieriem for his careful
reading of the manuscript.
(
m, 5 cyclopropyl H), 1.57 (d, 1 H, J ) 6.0 Hz, 1 cyclopropyl
1
3
2
H); C NMR δ 7.93, 8.89, 18.61, 18.92, 25.66 (CH ), 25.20,
+
4
1.76, 48.49 (C); MS (EI) m/z (rel intens) 267/265/263 (M -
+
+
H, 5/10/5), 185/183 (M - H - HBr, 43/38), 105 (M - HBr -
+
+
Br, 100), 91 (M - HBr - Br - CH
2
, 51), 81/79 (Br , 40/35).
Anal. Calcd for C
H, 3.78.
8
H
10Br
2
: C, 36.13; H, 3.79. Found: C, 36.24;
1
Data for 37: R
f
) 0.22; bp 90 °C (3 Torr); H NMR δ 0.63-
0
0
.74 (m, 2 cyclopropyl H), 0.77-0.82 (m, 2 cyclopropyl H),
.93-1.03 (m, 2 cyclopropyl H), 1.06-1.15 (m, 3 cyclopropyl
13
H), 1.19- 1.24 (m, 1 cyclopropyl H), 3.43 (s, 3 H, OCH
NMR δ 55.03 (CH
3
+
C
3
);
C
3
), 4.17, 5.05, 13.55, 15.38, 17.29 (CH ), 21.68,
2
+
4
5.18, 67.39 (C); MS (CI) m/z (rel intens) 253/251 (M + NH
+
NH
H
3
, 10/10), 236/234 (M + NH
4
, 100/100). Anal. Calcd for
9
13BrO: C, 49.79; H, 6.04. Found: C, 49.89; H, 6.13.
1
Data for 39:
R
f
) 0.37; H NMR δ 0.62-0.67 (m, 2
cyclopropyl H), 0.97-1.06 (m, 2 cyclopropyl H), 1.26-1.42 (m,
2
2
1
cyclopropyl H), 1.50-1.56 (m, 2 cyclopropyl H), 3.21 (s, 6 H,
1
3
OCH
3
), 3.63 (br s, 2 H, CH
2
Br); C NMR δ 49.14 (2 CH
3
),
3.62, 14.11, 17.62, 19.28, 40.57 (CH
2
), 23.53, 33.07, 98.25 (C);
+
MS (EI) m/z (rel intens) 330/328/326 (M , 0.3/0.6/0.3), 316/314/
+
+
3
12 (M - CH
-Br om o-7-(1′-b r om ocyclop r op yl)d isp ir o[2.0.2.1]h ep -
tan e (40) an d 7-(1′-Br om ocyclopr opyl)-7-m eth oxydispir o-
2.0.2.1]h eptan e (41). From 7-cyclopropylidenedispiro[2.0.2.1]-
heptane (6) (1.0 g, 7.56 mmol), compounds 40 (0.204 g, 9%)
2
, 2/4/2), 299/297/295 (M - OCH
3
, 49/100/50).
Su p p or tin g In for m a tion Ava ila ble: Fully optimized
7
+
+
Cartesian coordinates of structures 1-19 and 1‚Br -19‚Br ,
their calculated total and zero-point vibrational energies, and
a figure of the fully optimized important geometrical param-
eters of structures 1-19. This material is available free of
charge via the Internet at http://pubs.acs.org.
[
(59) Denis, J . M.; Le Perchec, P.; Conia, J . M. Tetrahedron 1977,
3
3, 399-408.
J O0162686