Relative Stabilities of Spirocyclopropanated Cyclopropyl Cations

Article abstract of DOI:10.1002/ejoc.200300440

Dispiro[2.0.2.1]hept-1-yl triflate (3), 7-bromo-7-phenyldispiro[2.0.2.1]heptane (4) and 7-chloro-7-phenylsulfanyldispiro[2.0.2.1]heptane (6) were prepared from bicyclopropylidene (5) in 50, 77 and 90% overall yield, respectively. 7-Bromo-7-cyclopropyldispiro[2.0.2.1]heptane (8) and 7-bromo-7-methyldispiro[2.0.2.1]heptane (11) were obtained by hydrobromination of 7-cyclopropylidene- (7) and 7-methylenedispiro[2.0.2.1]heptane (10) (78 and 95% yield, respectively). Methanolyses of triangulane derivatives 4, 6, and 8 as well as acetolysis of 6 all proceed with retention of the dispiro[2.0.2.1]heptane skeleton yielding the corresponding 7-substituted 7-methoxydispiro[2.0.2.1]heptanes 15, 21, and 23 as well as 7-acetoxy-7-phenylsulfanyldispiro[2.0.2.1]heptane 22 in 90, 100, 100 and 88% yield, respectively. Methanolysis of 1-bromo-1-cyclopropylcyclopropane (24) also gave mainly the ring-retained product 25 (66%) along with the ring-opened product 26 (33%). Apparently, an increasing number of spiro-annelated three-membered rings stabilizes a cyclopropyl cation against ring opening under solvolysis conditions. The rate of solvolysis, however, is only slightly affected by this spiroannelation, as the rate coefficient for the triflate 3 in sodium acetate-buffered methanol was determined to be k = 3.5 × 10 ^-4 s^-1 at 50 °C and 1.6 × 10^-4 s ^-1 at 40 °C which is virtually the same as that for cyclopropyl triflate itself (4.02 × 10^-4 s^-1 at 70 °C in acetone/H₂O 3:2). No reaction was observed for the bromotriangulane 11 in pure methanol, and solvolysis of 11 in aqueous methanol only led to products 27-30 which were formed by ring-enlarging and ring-opening rearrangements of the initially formed 7-dispiro[2.0.2.1]heptyl cation. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.

Full text of DOI:10.1002/ejoc.200300440

FULL PAPER
Relative Stabilities of Spirocyclopropanated Cyclopropyl Cations
Sergei I. Kozhushkov,[a] Thomas Späth,[a] Monica Kosa,[b] Yitzhak Apeloig,*[b]
Dmitrii S. Yufit,[c] and Armin de Meijere*[a]
Keywords: Ab initio calculations / Carbocations / Cyclopropanes / Solvolysis / Spiro compounds
Dispiro[2.0.2.1]hept-1-yl triflate (3), 7-bromo-7-phenyldispi-
ro[2.0.2.1]heptane (4) and 7-chloro-7-phenylsulfanyldispi-
the ring-opened product 26 (33%). Apparently, an increasing
number of spiro-annelated three-membered rings stabilizes
ro[2.0.2.1]heptane (6) were prepared from bicyclopropylid- a cyclopropyl cation against ring opening under solvolysis
ene (5) in 50, 77 and 90% overall yield, respectively. 7- conditions. The rate of solvolysis, however, is only slightly
Bromo-7-cyclopropyldispiro[2.0.2.1]heptane (8) and 7- affected by this spiroannelation, as the rate coefficient for the
bromo-7-methyldispiro[2.0.2.1]heptane (11) were obtained triflate 3 in sodium acetate-buffered methanol was deter-
by hydrobromination of 7-cyclopropylidene- (7) and 7- mined to be k = 3.5 × 10−4 s−1 at 50 °C and 1.6 × 10−4 s−1 at
methylenedispiro[2.0.2.1]heptane (10) (78 and 95% yield, re-
spectively). Methanolyses of triangulane derivatives 4, 6, and
8 as well as acetolysis of 6 all proceed with retention of the
dispiro[2.0.2.1]heptane skeleton yielding the corresponding
7-substituted 7-methoxydispiro[2.0.2.1]heptanes 15, 21, and
40 °C which is virtually the same as that for cyclopropyl tri-
flate itself (4.02 × 10−4 s−1 at 70 °C in acetone/H2O 3:2). No
reaction was observed for the bromotriangulane 11 in pure
methanol, and solvolysis of 11 in aqueous methanol only led
to products 27−30 which were formed by ring-enlarging
23 as well as 7-acetoxy-7-phenylsulfanyldispiro[2.0.2.1]hep- and ring-opening rearrangements of the initially formed 7-
tane 22 in 90, 100, 100 and 88% yield, respectively. Meth-
anolysis of 1-bromo-1-cyclopropylcyclopropane (24) also
gave mainly the ring-retained product 25 (66%) along with
dispiro[2.0.2.1]heptyl cation.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2003)
Introduction
by the β-bromo substituent, and this influence can only be
deduced from computations which may leave some uncer-
tainty as to the real structure of the intermediate cations.
More direct evidence may be extracted from kinetic and
product studies of solvolysis reactions of appropriate spiro-
cyclopropanated derivatives (cf. ref.[1]). So far, such studies
have been carried out only for spiropentane derivatives ac-
curately enough with respect to their mechanisms and the
structures of the respective intermediates. Thus, the kinetic
data for the solvolysis of spiropentyl chloride versus cyclo-
propyl chloride (k ϭ 7.1 ϫ 10Ϫ5 sϪ1 versus k ϭ 1.4 ϫ 10Ϫ5
The influence of different substituents upon the stability
of a cyclopropyl cation has been studied in great detail.[1]
The ring opening of the parent cyclopropyl to the allyl cat-
ion is known to proceed virtually without a measurable ac-
tivation energy.[1a] The latter, however, can be significantly
higher for appropriately substituted cyclopropyl cations. A
rather efficient stabilization at least towards ring opening
may, apparently, be achieved by one or two spiro-annelated
cyclopropane rings, as was corroborated by the recently de-
termined kinetics[2] for the bromination of various methyl-
enetriangulanes and cyclopropylidenetriangulanes.[3] How-
ever, the intermediate cation in an alkene bromination reac-
tion is always — but not to the same degree — influenced
sϪ1 [4]
indicated that the spiro-annelated three-membered
)
ring increases the rate only by a factor of five, whereas an
α-cyclopropyl substituent usually accelerates a solvolysis re-
action by factors of between 105 and 107.[1a] Moreover, a
ring expansion and ring opening were the predominant
transformation modes in solvolysis reactions of spiropen-
tane derivatives.[5,6] More recently, we have undertaken a
solvolysis study of various 7-substituted dispiro[2.0.2.1]hep-
tane ([3]triangulane) derivatives, and the results of this
study are reported here.
[a]
Institut für Organische Chemie der Georg-August-Universität
Göttingen,
Tammannstrasse 2, 37077 Göttingen, Germany
Fax: (internat.) ϩ 49-(0)551/399-475
E-mail: Armin.deMeijere@chemie.uni-goettingen.de
[b]
Lise Meitner Minerva Center for Computational Quantum
Chemistry, Technion
Technion City,
Ϫ Israel Institute of Technology,
Results and Discussion
The dispiro[2.0.2.1]heptyl derivatives 3, 4, 6, 8, and 11
were essentially all prepared starting from the readily avail-
able bicyclopropylidene (5)[7] (Scheme 1).
32000 Haifa, Israel
Fax: (internat.) ϩ 972-4/823-3735
E-mail: chrapel@techunix.technion.ac.il
Department of Chemistry, University of Durham,
Durham, South Rd., DH1 3LE, England
[c]
4234
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200300440
Eur. J. Org. Chem. 2003, 4234Ϫ4242

Relative Stabilities of Spirocyclopropanated Cyclopropyl Cations
FULL PAPER
nucleophilicity, in the presence of 2,6-lutidine, and also in
a 1.9:10 mixture of ethanol and hexafluoro-2-propanol. In
these cases, only the esters 14a and 14b arising from twofold
ring opening of the intermediate 7-dispiro[2.0.2.1]heptyl
cation were isolated (Scheme 2). Although the proportion
of the product 12a in which all three cyclopropane rings
had been retained was relatively small (19%), the hydrolysis
of spiropentyl triflate gave an even smaller amount of the
ring-retained product (5%).[5] The rate of solvolysis of the
triflate 3 in sodium acetate-buffered methanol was deter-
mined to be k ϭ 3.5 ϫ 10Ϫ4 sϪ1 at 50 °C and 1.6 ϫ 10Ϫ4
sϪ1 at 40 °C (see Exp. Sect.). In comparison to the rate for
cyclopropyl triflate itself (4.02 ϫ 10Ϫ4 sϪ1 at 70 °C in ace-
tone/H2O 3:2[13]) that of 3 is only two times higher when
adjusted to the same solvent (80% EtOH) and temperature
(70 °C). This is in line with Applequist’s observation for
spiropentyl chloride.[4] Each additional spirocyclopropane
ring accelerates the solvolysis reaction only by a factor of
1.4 to 5. It is also consistent with the observation that the
bromine additions to methylenetriangulanes and cyclopro-
pylidenetriangulanes proceed essentially with the same rate
as those to the corresponding oligomethyl-substituted ethyl-
enes.[2] However, the proportions of ring-retained and ring-
opened products from cyclopropyl and spiropentyl chloride
as well as dispiro[2.0.2.1]heptyl triflate 3 ranged from 0%
for cyclopropyl and spiropentyl chloride[14] to 19% for 3
Scheme 1. Preparation of 7-(trifluoromethylsulfonyloxy)[3]triangu-
lane 3 and 7,7-disubstituted dispiro[2.0.2.1]heptanes ([3]triangu-
lanes) 4, 6, 8 and 11: a) Bu3SnH, Et2O, 25 °C, 3 h; b) (1) tBuLi,
THF, Ϫ78 °C, 2 h; (2) O2, Ϫ78 °C, 1 h; (3) Tf2O, Ϫ90Ǟ20 °C;
c) CHBr3, KOH (powder), TEBACl, CH2Cl2, 0Ǟ20 °C, 5 h; d)
PhCHBr2, tBuOK, pentane, 20 °C, 48 h; e) PhSCHCl2, 50%
NaOH, CH2Cl2, 20 °C, 48 h; f) HBr, pentane, Ϫ30 °C
The dispiro[2.0.2.1]hept-7-yl triflate (3) could not be ob- (Scheme 2). On the other hand, 2,2,3,3-tetramethyl-1-phe-
tained along the route developed by Applequist for the nylcyclopropyl bromide (16) upon solvolysis in methanol at
preparation of spiropentyl triflate[5] [addition of chloro(2- 65 °C underwent complete ring opening to yield only the
chloroethoxy)carbene onto 5 followed by deprotection with 1,3-butadiene derivative 17 without incorporation of a
PhLi and esterification with Tf2O], as the lithium alkoxide methoxy group (cf. ref.[20] in[1c]) (Scheme 2).
of 7-hydroxidispiro[2.0.2.1]heptane turned out to be rather
With its rather well carbocation-stabilizing α-phenyl
unstable (cf. ref.[8]). However, reductive monodebromin- group, the bromotriangulane 4 undergoes methanolysis
ation of the dibromocarbene adduct 1 of bicyclopropyl- with complete retention of the dispiro[2.0.2.1]heptane skele-
idene[9] with tributyltin hydride gave the corresponding ton to yield the methoxy derivative 15 (90% isolated). For
monobromide 2, which cleanly underwent bromine-lithium comparison, hydrolysis of 1-phenylspiropentyl bromide has
exchange upon treatment with tert-butyllithium at low tem- been reported to also proceed with 92% retention of the
perature (Ϫ78 °C). Subsequent reaction with oxygen and spiropentyl moiety at 25 °C.[5]
trapping of the intermediate lithium dispiro[2.0.2.1]hept-7-
The cation-stabilizing effect of a phenylsulfanyl group is
yl oxide with triflic anhydride at low temperature gave the known to be particularly powerful,[1,11b] and in agreement
triflate 3 in 56% overall yield (Scheme 1). The addition of with this the methanolysis as well as acetolysis of 7-phenyl-
bromo(phenyl)carbene[10] and chloro(phenylsulfanyl)car- sulfanyldispiro[2.0.2.1]hept-7-yl chloride (6) proceeded very
bene[11] to 5 furnished 7-bromo-7-phenyl- (4) and 7-bromo- smoothly with complete retention of the triangulane skele-
7-(phenylsulfanyl)[3]triangulane (6) in 77 and 90% yield, ton in the products 21 and 22 (Scheme 2). Even upon at-
respectively. Hydrobromination of 7-cyclopropylidene[3]tri- tempted recrystallization from methanol, 6 was completely
angulane (7) and 7-methylene[3]triangulane (10), which solvolyzed to 21. For comparison, methanolysis of 1-
were prepared in three and two steps, respectively, from bi- chloro-1-(phenylsulfanyl)-2,2,3,3-tetramethylcyclopropane
cyclopropylidene (5),[3,12] gave 7-bromo-7-cyclopropyl[3]tri- (18) under these conditions has been reported to proceed
angulane (8; 78% yield) along with its regioisomer 9 (9% with only 43% conservation of the cyclopropane ring
yield) and 7-bromo-7-methyl[3]triangulane (11; 95% yield), (Scheme 2).[11b]
respectively (Scheme 1).
An α-cyclopropyl group is known to have the largest sta-
The products from the solvolysis of the triflate 3 in etha- bilizing effect of any α-alkyl substituent on a carbocation,[1]
nol (buffered with sodium acetate) were mainly the allyl and methanolysis of 7-bromo-7-cyclopropyldispiro[2.0.2.1]-
ethers 13a (8%) and 14a (45%) arising from single and two- heptane (8) accordingly proceeded without ring opening to
fold ring opening of the intermediate cation, respectively, yield only the methyl ether 23 (88% isolated) (Scheme 3).
along with 19% of the ring-retained dispiroheptyl ethyl This demonstrates that the two spirocyclopropane groups
ether 12a. For comparison, the triflate 3 was also solvolyzed in 8 significantly contribute to the — at least kinetic —
in hexafluoro-2-propanol, which is known for its low stability of the intermediate cyclopropyl cation, since 1-
Eur. J. Org. Chem. 2003, 4234Ϫ4242
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4235

S. I. Kozhushkov, T. Späth, M. Kosa, Y. Apeloig, D. S. Yufit, A. de Meijere
FULL PAPER
11 at 65 °C in aqueous methanol (1:2) did result in solvo-
lysis, however a set of three ketones 27Ϫ29 along with two
diastereomeric dimethoxy-substituted dienes (E)- and (Z)-
30 was formed (Scheme 4).
Scheme 4. Solvolysis of 7-bromo-7-methyl[3]triangulane (11): a)
MeOH/H2O, 2:1, 65 °C, 74 h
Since the ketones 27 and 28 have similar spectroscopic
characteristics and identical molecular masses, the structure
of the known compound 27[16] was rigorously proved by
an X-ray crystal structure analysis of its tosylhydrazone 31
(Figure 1A). There are two crystallographically indepen-
dent molecules of 31[17] in the unit cell, one of which is
disordered over two positions with distinctively different
orientations of the cyclopropyl group. Both molecules have
similar conformations of the tosylhydrazone moiety with
Scheme 2. Products of alcoholysis of triflate 3 and of solvolyses of
various [3]triangulane derivatives 4, 6, and their tetramethylcyclo-
propane analogues 16, 18: a) EtOH, NaOAc and/or (CF3)2CHOH,
2,6-lutidine, 40 °C, 1 h; b) MeOH, 65 °C, 10 minϪ24 h; c) MeOH,
MeONa (2 equiv.), 80 °C, 2 h; d) HOAc, NaOAc, 110 °C, 1 h
torsional angles NϪSϪCϪC ϭ Ϫ66.1(2)° as well as
77.4(2)° and NϪNϪSϪC ϭ Ϫ54.4(2)° as well as 60.2(2)°,
which are typical for arylsulfonamides.[18a] The orientations
of the cyclopropyl group relative to the cyclobutane ring is
different in the independent molecules of 31 (Figure 1B)
and can be described by torsional angles τ (C3···C1ϪC6-
center of C7ϪC8 bond) of Ϫ66.6°, Ϫ54.6° and 56.7°. Inter-
estingly, there are only two other structures in the CCDC
data file in which a cyclopropylcyclobutane moiety is not
part of a three-dimensional framework.[18b] Both of these
structures contain a number of bulky substituents on the
four-membered ring, and two out of three cyclopropyl
groups in these compounds adopt an s-trans-conformation
with a τ angle of about 180°. These examples imply almost
unhindered rotation around the CϪC bond between two
cycles. The independent molecules of 31 in the unit cell
form dimers, connected by pairs of NϪH···O hydrogen
bromo-1-cyclopropylcyclopropane (24)[12,15] undergoes
methanolysis to give both the ring-retained 25 and the ring-
opened product 26 in 98% yield with a ratio of 2:1
(Scheme 3).
˚
bonds with N···O distances of 2.968(3) and 2.991(3) A,
respectively (Figure 1A). In the packing of these dimers in
the crystal (Figure 1C), a number of weak CH···O(N) inter-
actions play a significant role.
Among the solvolysis products 27Ϫ30, only the dimeth-
oxy-substituted butadienes (E)- and (Z)-30 (7% total) may
have been formed by initial cyclopropyl to allyl cation ring
opening of the intermediate 35 (Scheme 5). Most probably,
Scheme 3. Methanolysis of 7-bromo[3]triangulane (8) and 1-
bromo-1-cyclopropylcyclopropane (24): a) MeOH, 65 °C, 30 min;
b) MeOH, 65 °C, 14 days
Contrary to this, the methyl-substituted analogue of 8,7- ketones 27Ϫ29 resulted by acid-catalyzed rearrangements
bromo-7-methyl[3]triangulane (11) remained unchanged of the intermediate protonated alcohols 33 and 38. Pro-
after heating in refluxing methanol for 14 days. Heating of tonation of 33 at the quaternary carbon C7 with opening
4236
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 4234Ϫ4242

Relative Stabilities of Spirocyclopropanated Cyclopropyl Cations
FULL PAPER
Figure 1. Molecular structure of the tosylhydrazone of 2-cyclopropyl-2-methylcyclobutanone (31) in the crystal (A), schematic represen-
tation of three conformations of cyclopropylcyclobutane fragment in 31 (B) and crystal packing of 31 (C)[17]
of the bridgehead-bridgehead bond leads to 34, the pro- Conclusion
tonated form of ketone 28 (mode a), whereas protonation
of 33 at the spirocarbon yields 32, the protonated major
The carbocations generated from cyclopropyl substrates
ketone 27 (mode b). Such acid-catalyzed ring-opening re- have been classified in three categories:[1a] (1) open planar
arrangements of cyclopropanols are well documented.[19] structures arising from concerted ionization and ring open-
The protonated cyclopropanols 38 and 33, in turn, must ing, (2) half-opened, and (3) closed structures. The latter
have been formed by nucleophilic attack of water on the two are non-planar and result whenever the disrotatory ring
initially formed carbocation 35 and the bicyclopentyl opening is retarded or prevented for reasons of steric con-
bridgehead cation 36, respectively. Quite remarkably, the gestion or increasing ring strain. The cations arising from
latter would have originated from the former by the well- 7-dispiro[2.0.2.1]heptyl derivatives apparently belong to the
known ring-enlarging cyclopropylmethyl to cyclobutyl cat- second two types, depending on the nature of the additional
ion rearrangement.[20,21] The intermediate protonated al- substituent in the 7-position. Even the kinetically stabilizing
cohols 33 and 38 may also have been formed by nucleo- effect of the two α-spirocyclopropane rings, which does not
philic attack of the water solvent on the bicyclobutonium- significantly influence the rate of solvolysis, in most cases
type cation common to both 35 and 36, but from different causes the solvolysis products to be formed without ring
sides.[20a]
opening. The intermediate from 8 actually is a particular
Unfortunately, nothing is known about solvolysis reac- tricyclopropylmethyl cation, one in which two of the cyclo-
tions of bicyclo[2.1.0]pentyl and/or bicyclo[3.1.0]hexyl de- propyl groups are rigidly held in a bisected orientation, but
rivatives with a leaving group at the bridgehead position.
www.eurjoc.org
with a drastically decreased bonding angle which causes ad-
Eur. J. Org. Chem. 2003, 4234Ϫ4242
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4237

S. I. Kozhushkov, T. Späth, M. Kosa, Y. Apeloig, D. S. Yufit, A. de Meijere
FULL PAPER
MP2/6-311ϩG(2d,p) level of theory at the optimized
B3LYP/6-31G(d,p) geometries. All calculations were per-
formed with the Gaussian 98 package of programs.[22] All
energy values are calculated at the MP2/6-311ϩG(2d,p)//
B3LYP/6-31G(d,p) level of theory and are given in kcal
molϪ1
.
The results are shown in Figure 3, where ∆E1‡ values are
the ring-opening barriers according to Equation (1), ∆E2
values are the thermodynamic driving forces for ring open-
ing according to Equation (2), and ∆E3 values are the
thermodynamic stabilities in the gas phase according to the
isodesmic Equation (3). Positive values of ∆E2 indicate that
this cyclopropyl cation is thermodynamically more stable
than the corresponding allyl cation.
Scheme 5. Mechanistic rationalization for the formation of com-
pounds 27Ϫ30
ditional angle strain in the central three-membered ring.
The accumulated experimental evidence leads one to ar-
range the variously substituted and spirocyclopropanated
cyclopropyl cations according to their relative stabilities as
shown in Figure 2.
Figure 3. Relative kinetic and thermodynamic stabilities of vari-
ously substituted and spirocyclopropanated cyclopropyl cations ac-
cording to MP2/6-311ϩG(2d,p)//B3LYP/6-31G(d,p) calculations
(all values in kcal·molϪ1); the parent cyclopropyl cation 52 is not
a minimum but a transition structure connecting two equivalent
forms of the corresponding allyl cation
Figure 2. The apparent relative kinetic stabilities of variously sub-
stituted and spirocyclopropanated cyclopropyl cations
This experimentally derived stability sequence was pro-
The computed barrier for the ring opening of the cyclo-
bed by computations. All structures were optimized at the propyl ring, which leads to the kinetic stability order of the
B3LYP/6-31G(d,p) level of theory. Vibrational frequency cations 42Ϫ47, 50, 51, corresponds very nicely to the exper-
calculations at this level of theory were used to characterize imentally derived one, based on the product distribution be-
each of the stationary points as either a minimum (zero tween ring-retaining products and ring-opened products.
imaginary frequencies) or transition state (one imaginary The calculated high barrier for the ring opening of cation
frequency). Single point energies were calculated at the 42 should make this the most stable kinetically, and this
4238
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 4234Ϫ4242

Relative Stabilities of Spirocyclopropanated Cyclopropyl Cations
FULL PAPER
1
colorless liquid, b.p. 81 °C (8 Torr). H NMR: δ ϭ 0.75Ϫ0.85 (m,
2 H, CH2), 0.86Ϫ1.02 (m, 4 H, 2 CH2), 1.07Ϫ1.20 (m, 2 H, CH2),
3.65 (s, 1 H, CHBr) ppm. 13C NMR: δ ϭ 6.9, 8.6 (2 CH2), 32.8
(CH), 21.6 (2 C) ppm. MS (EI), m/z (%) ϭ 93 (21) [Mϩ Ϫ Br], 92
(15), 91 (100) [C7H7ϩ], 66 (7), 65 (32) [C5H5ϩ]. C7H9Br (173.05):
calcd. C 48.58, H 5.24, Br 46.18; found C 48.77, H 5.41, Br 46.11.
was really observed experimentally. However, the results for
cyclopropyl cation 46 are not in line with its chemical be-
havior under solvolytic conditions (see Scheme 3). We be-
lieve that this can be attributed to solvation effects which
are not included in the calculations, as the latter simulate
the situation in the gas phase only. The 7-dispiro-
[2.0.2.1]heptyl cation (47) is rather unstable thermo-
dynamically, yet the small positive value of ∆H϶ in such
cations (0.4 kcal molϪ1 in the case of 47) presumably causes
the unusual reactivity of the bromide 11 upon solvolysis
(Schemes 4, 5).
7-(Trifluoromethanesulfonyloxy)dispiro[2.0.2.1]heptane (3): A 1.8 
solution of tBuLi in pentane (14.2 mL, 25.6 mmol) was added
dropwise at Ϫ78 °C within 1.5 h to a stirred solution of the bro-
mide 2 (4.0 g, 23.11 mmol) in anhydrous THF (100 mL). After stir-
ring for an additional 30 min, a strong stream of dry oxygen was
passed through the reaction mixture at this temp. for 1 h. The mix-
ture was stirred for an additional 30 min, cooled to Ϫ90 °C, and
trifluoromethanesulfonic anhydride (6.51 g, 3.78 mL, 23.07 mmol)
was added slowly. The mixture was allowed to warm to ambient
temperature, poured into ice-cold water (200 mL) and quickly ex-
It is interesting to note that the energy differences be-
tween the cyclic and the ring-opened cations, ∆E2, which
denote the thermodynamic driving force for ring opening,
do not correspond to the barriers for ring opening and
therefore cannot be used to predict the kinetic stabilities tracted with Et2O (3 ϫ 100 mL). The combined organic extracts
were washed with sat. aq. NH4Cl solution (3 ϫ 50 mL), water and
brine (50 mL each), dried and concentrated under reduced press-
ure. The residue was purified by flash column chromatography
(100 g of silica gel, 35 ϫ 4 cm column, pentane) to give 3 (3.84 g,
towards ring opening of substituted cyclopropyl cations.
This is yet another case where the Hammond postulate is
misleading.
1
68%) as a colorless oil, Rf ϭ 0.70. H NMR: δ ϭ 0.82Ϫ0.97 (m, 4
H, 2 CH2), 1.10Ϫ1.25 (m, 4 H, 2 CH2), 4.85 (s, 1 H, CHOTf) ppm.
13C NMR: δ ϭ 5.2, 7.1 (2 CH2), 71.4 (CH), 18.4 (2 C), 118.6 (q,
J ϭ 320 Hz, CF3) ppm. 19F NMR: δ ϭ 87.5 ppm. MS (EI), m/z
(%) ϭ 91 (100) [C7H7ϩ], 81 (75), 79 (80), 69 (90), 53 (100).
C8H9F3O3S (242.22): calcd. C 39.67, H 3.75; found C 39.89, H
3.89.
Experimental Section
General: 1H and 13C NMR: Spectra were recorded at 250 (1H),
and 62.9 [13C, additional DEPT (Distortionless Enhancement by
Polarization Transfer)] MHz on Bruker AM 250 instrument in
CDCl3 soln, CHCl3/CDCl3 as internal reference; δ in ppm, J in
Hz. IR: PerkinϪElmer 298. FT-IR: Bruker IFS 66, measured as
KBr pellets, oils between KBr plates. MS (EI): Finnigan MAT 95
spectrometer (70 eV). M. p.: Büchi 510 capillary melting point ap-
paratus, uncorrected. GC analyses: Siemens Sichromat 1Ϫ4, 25 m
capillary column CP-SIL-5-CB, if not otherwise specified. GC sep-
arations: Intersmat 130 instrument, 20% SE-30 on Chromaton
7-Bromo-7-phenyldispiro[2.0.2.1]heptane (4): A solution of α,α-di-
bromotoluene (4.25 g, 2.81 mL, 17.0 mmol) in pentane (10 mL) at
0 °C was added dropwise within 1 h to a suspension of tBuOK
(4.0 g, 35.6 mmol) in anhydrous pentane (30 mL) containing bi-
cyclopropylidene (5) (3.0 g, 3.51 mL, 37.4 mmol). The resulting
mixture was vigorously stirred at ambient temperature over a per-
iod of 2 days, then diluted with pentane (100 mL), filtered through
a pad of celite (20 g) and concentrated under reduced pressure. Col-
umn chromatography of the residue (130 g of silica gel, 30 ϫ 5 cm
column, pentane) gave 4 (3.26 g, 77%) as a colorless oil, Rf ϭ 0.60.
1H NMR: δ ϭ 1.03Ϫ1.12 (m, 4 H, 2 CH2), 1.20Ϫ1.27 (m, 4 H, 2
CH2), 7.21Ϫ7.47 (m, 5 H, C6H5) ppm. 13C NMR: δ ϭ 9.4, 9.6 (2
CH2), 127.5, 128.0 (2 CH), 126.9 (CH), 29.9 (2 C), 48.1, 141.3 (C)
ppm. MS (EI), m/z (%) ϭ 250/248 (0.5/0.5) [Mϩ], 222/220 (4/4)
[Mϩ Ϫ C2H4], 221/219 (2.5/2.5) [Mϩ Ϫ C2H5], 171 (37), 169 (50)
[Mϩ Ϫ Br], 154 (34), 141 (100) [Mϩ Ϫ Br Ϫ C2H4], 115 (40), 91
(20) [C7H7ϩ]. MS (HR-EI): 248.0200 (C13H13Br, calcd. 248.0200).
C13H13Br (249.14): calcd. C 62.67, H 5.26; found C 62.44, H 5.30.
WϪAWϪDMCS, 2000
ϫ
8.2 mm Teflon column. TLC:
MachereyϪNagel precoated sheets, 0.25 mm Sil G/UV254. Column
chromatography: Merck silica gel, grade 60, 230Ϫ400 mesh. Start-
ing materials: Anhydrous diethyl ether and THF were obtained by
distillation from sodium benzophenone ketyl, methanol and etha-
nol from magnesium alkoxides, and dichloromethane from P4O10.
Pentane was shaken with conc. sulfuric acid for 12 h, then with a
0.5  solution of KMnO4 in 3  H2SO4 for 24 h, washed with
diluted aq. solution of oxalic acid, aq. 5% NaHCO3 solution, dried
(MgSO4) and distilled from P4O10. 7,7-Dibromodispiro-
[2.0.2.1]heptane (1),[9a] bicyclopropylidene (5),[12,15] 7-cyclopro-
pylidene-dispiro[2.0.2.1]heptane
(7),[12]
7-methylenedispiro-
[2.0.2.1]heptane (10),[23] 1-bromo-1-phenyl-2,2,3,3-tetramethylcy-
clopropane (16),[10a] 1-bromo-1-cyclopropylcyclopropane (24),[12,15]
and dichloromethylphenyl sulfide[24] were prepared according to
the published procedure. All other chemicals were used as commer-
cially available (Merck, Acro˜s, BASF, Bayer, Hoechst, Degussa AG,
and Hüls AG). All reactions were performed under argon. Organic
extracts were dried with MgSO4.
7-Chloro-7-(phenylsulfanyl)dispiro[2.0.2.1]heptane (6):
A
50%
NaOH solution (80 mL) was added slowly at 0 °C to a vigorously
stirred solution of bicyclopropylidene (5; 8.01 g, 9.38 mL,
100 mmol), TEBACl (500 mg) and dichloromethylphenyl sulfide
(14.0 g, 72.5 mmol) in dichloromethane (100 mL), and the reaction
mixture was vigorously stirred at ambient temperature for an ad-
ditional 2 days. After the phases had separated, the inorganic phase
was extracted with CH2Cl2 (2 ϫ 100 mL), the combined organic
phases were washed with sat. NH4Cl solution (2 ϫ 50 mL), water
Preparation of the Substrates for Solvolysis
7-Bromodispiro[2.0.2.1]heptane (2): Bu3SnH (46.3 g, 42.8 mL, and brine (100 mL each), dried and concentrated under reduced
159 mmol) was added dropwise within 3 h to a stirred solution of pressure. As the product was neither stable towards silica gel nor
the dibromide 1 (40.0 g, 159 mmol) in anhydrous Et2O (100 mL) towards heating, the residue was dissolved in pentane (100 mL),
maintaining the temperature at 20Ϫ25 °C inside the flask. The re-
action mixture was ‘‘bulb-to-bulb’’ distilled into a cold (Ϫ78 °C)
trap under reduced pressure (0.1 Torr), and the content of the trap
was distilled under reduced pressure to give 2 (22.6 g, 82%) as a
cooled to Ϫ30 °C overnight and quickly filtered to give 6 (15.4 g,
90%) as yellow crystals, m.p. 72 °C. IR (KBr): ν˜ ϭ 3064 cmϪ1
,
1
2987, 1582, 1571, 1477, 1440, 1413, 1024, 1009, 802, 744, 689. H
NMR: δ ϭ 0.89Ϫ0.95 (m, 4 H, 2 CH2), 1.12Ϫ1.25 (m, 4 H, 2 CH2),
Eur. J. Org. Chem. 2003, 4234Ϫ4242
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4239

S. I. Kozhushkov, T. Späth, M. Kosa, Y. Apeloig, D. S. Yufit, A. de Meijere
7.05Ϫ7.25 (m, 5 H, C6H5) ppm. 13C NMR: δ ϭ 7.7, 8.0 (2 CH2),
pressure (0.1 Torr). The content of the trap (500 mg, 72%), accord-
FULL PAPER
127.8, 128.8 (2 CH), 126.2 (CH), 31.0 (2 C), 57.0, 134.3 (C) ppm. ing to its 1H NMR spectrum, was a mixture of 7-ethoxydispiro-
MS (EI), m/z (%) ϭ 238/236 (7/20) [Mϩ], 201 (11) [Mϩ Ϫ Cl], 168 [2.0.2.1]heptane (12a), [(1Ј-ethoxycyclopropyl)methylene]cyclopro-
(3), 167 (11), 161/159 (33/100) [Mϩ Ϫ C6H5], 129/127 (5/14) [Mϩ pane (13a) and 3-cyclopropylidene-2-(ethoxymethyl)propene (14a)
Ϫ SC6H5], 123 (21), 109 (10), 91 (46) [C7H7ϩ]. C13H13ClS (236.75): in a 2.38:1:5.63 ratio. The pure samples were obtained by prepara-
calcd. C 65.95, H 5.53, Cl 14.97; found C 65.82, H 5.72, Cl 15.09.
tive GC.
1
12a: H NMR: δ ϭ 0.61Ϫ0.69 (m, 2 H, CH2), 0.69Ϫ0.78 (m, 2 H,
7-Bromo-7-cyclopropyldispiro[2.0.2.1]heptane (8) and 7-(1Ј-Bromo-
cyclo-propyl)dispiro[2.0.2.1]heptane (9): A 0.3  solution of HBr in
pentane (10 mL, 3 mmol) was added at Ϫ30 °C over 30 min to
a stirred solution of 7-cyclopropylidenedispiro[2.0.2.1]heptane (7)
(200 mg, 1.51 mmol) in olefin- and water-free pentane (50 mL). The
reaction mixture was stirred at Ϫ30 °C for 1 h, and then treated
with NaHCO3 (500 mg) at this temp. After 30 min of additional
stirring, the mixture was poured into an ice-cold 5% NaHCO3 solu-
tion (50 mL), and the water layer was extracted with pentane (2 ϫ
50 mL). The combined organic phases were washed with brine be-
fore they were dried and concentrated under reduced pressure to
give 280 mg (87%) of 8 and 9 as a 9.6:1 mixture that could not be
separated because compounds 8, 9 are unstable towards silica gel.
8: 1H NMR: δ ϭ 0.46Ϫ0.53 (m, 2 H, CH2), 0.54Ϫ0.60 (m, 2 H,
CH2), 0.76Ϫ0.83 (m, 2 H, CH2), 0.84Ϫ0.90 (m, 2 H, CH2),
0.92Ϫ0.98 (m, 2 H, CH2), 1.12Ϫ1.19 (m, 2 H, CH2), 1.37Ϫ1.45
(m, 1 H, CH) ppm. 13C NMR: δ ϭ 4.78, 7.81, 7.83 (2 CH2), 25.21
(CH), 19.62 (2 C), 51.73 (C) ppm. IR (film): ν˜ ϭ 2940 cmϪ1, 2860,
2800, 1015, 820, 770, 750, 635. GC-MS (EI), m/z (%) ϭ 213/211
(0.3/0.3) [Mϩ Ϫ H], 131 (9) [Mϩ Ϫ H Ϫ HBr], 117 (34), 105 (83)
[Mϩ Ϫ Br Ϫ C2H4], 79 (33), 69 (100).
CH2), 0.87Ϫ0.95 (m, 2 H, CH2), 0.99Ϫ1.08 (m, 2 H, CH2), 1.19 (t,
J ϭ 7.0 Hz, 3 H, CH3), 3.55 (q, J ϭ 7.0 Hz, 2 H CH2), 3.65 (s, 1
H, CH) ppm. 13C NMR: δ ϭ 15.3 (CH3), 3.6, 6.1 (2 CH2), 65.8
(CH2), 62.2 (CH), 18.6 (2 C) ppm.
1
13a: H NMR: δ ϭ 0.74Ϫ0.81 (m, 2 H, CH2), 0.93Ϫ1.02 (m, 4 H,
2 CH2), 1.09Ϫ1.18 (m, 2 H, CH2), 1.16 (t, J ϭ 7.0 Hz, 3 H, CH3),
3.51 (q, J ϭ 7.0 Hz, 2 H CH2), 5.89 (br. s, 1 H, ϭCH) ppm. 13C
NMR: δ ϭ 15.5 (CH3), 13.6 (2 CH2), 0.5, 2.9, 63.0 (CH2), 119.3
(CH), 63.21, 120.6 (C) ppm.
1
14a: H NMR: δ ϭ 1.04Ϫ1.12 (m, 2 H, CH2), 1.18Ϫ1.28 (m, 2 H,
CH2), 1.22 (t, J ϭ 7.0 Hz, 3 H, CH3), 3.53 (q, J ϭ 7.0 Hz, 2 H
CH2), 4.22 (s, 2 H OCH2), 5.16 (br. s, 1 H, ϭCH2) 5.22 (br. s, 1
H, ϭCH2), 6.45 (s, 1 H, ϭCH) ppm. 13C NMR: δ ϭ 15.2 (CH3),
1.2, 4.5, 66.0, 71.0, 113.9 (CH2), 118.1 (CH), 124.1, 143.3 (C) ppm.
b) In Hexafluoro-2-propanol: From a mixture of 3 (750 mg,
3.1 mmol), 2,6-lutidine (750 mg, 0.82 mL, 7 mmol), hexafluoro-2-
propanol (5 mL) and water (0.15 mL), 3-cyclopropylidene-2-[(hexa-
fluoroisopropyloxy)methyl]propene (14b) (81 mg, 10%) was ob-
tained under the conditions of the preceding experiment after pre-
1
parative GC separation: H NMR: δ ϭ 1.05Ϫ1.15 (m, 2 H, CH2),
1.17Ϫ1.32 (m, 2 H, CH2), 4.18 (sept, J ϭ 6.25 Hz, 1 H, OCH),
4.59 (s, 2 H OCH2), 5.29 (br. s, 1 H, ϭCH2) 5.33 (br. s, 1 H, ϭ
CH2), 6.45 (s, 1 H, ϭCH) ppm. 13C NMR: δ ϭ 122.5 (d, J ϭ
295.6 Hz, 2 CF3), 1.0, 5.4, 74.1, 117.8 (CH2), 118.1 (CH), 126.5,
143.3 (C) ppm.
1
9: H NMR: δ ϭ 0.45Ϫ0.61 (m, 4 H, 2 CH2), 0.75Ϫ0.97 (m, 6 H,
3 CH2), 1.12Ϫ1.19 (m, 2 H, CH2), 1.32Ϫ1.47 (m, 1 H, CH) ppm.
13C NMR: δ ϭ 7.82 (4 CH2), 4.71 (2 CH2), 25.25 (CH), 19.59 (2
C), 51.60 (C) ppm.
c) In a Hexafluoro-2-propanol/Ethanol Mixture: From a mixture of
3 (1.00 g, 4.13 mmol), 2,6-lutidine (643 mg, 0.70 mL, 6 mmol),
EtOH (1.50 g, 1.91 mL, 32.6 mmol) and hexafluoro2-propanol
(10 mL), compounds 14b (yield 14%) and 14a (yield 41%) were
obtained under the conditions of the preceding experiment after
2 h of stirring at 25 °C. The yields were determined from the 1H
NMR spectrum of the mixture obtained after ‘‘bulb-to-bulb’’ distil-
lation.
7-Bromo-7-methyldispiro[2.0.2.1]heptane (11): Hydrogen bromide
(2.29 g, 28.26 mmol) was condensed at Ϫ78 °C into a stirred solu-
tion
of
7-methylenedispiro[2.0.2.1]heptane
(10)
(2.00 g,
18.84 mmol) in anhydrous pentane (40 mL). The reaction mixture
was warmed to Ϫ30 °C over a period of 30 min, stirred for an
additional 30 min at this temp., poured into ice-cold sat. aq.
NaHCO3 solution (200 mL) and then extracted with pentane (2 ϫ
50 mL). The combined organic extracts were washed with brine
(50 mL), dried and concentrated under reduced pressure. The resi-
due was distilled under reduced pressure to give 11 (3.35 g, 95%)
as a colorless liquid, b.p. 40 °C (0.5 Torr), which solidified upon
7-Methoxy-7-phenyldispiro[2.0.2.1]heptane (15): The reaction mix-
ture obtained from 4 (1.58 g, 6.34 mmol) after 24 h at reflux tem-
perature according to GP1, was purified by flash column chroma-
tography (60 g of silica gel, 35 ϫ 3 cm column, pentane/Et2O 40:1)
to give 15 (1.14 g, 90%) as a colorless oil, Rf ϭ 0.30. 1H NMR:
δ ϭ 0.68Ϫ0.90 (m, 4 H, 2 CH2), 0.90Ϫ1.01 (m, 2 H, CH2),
1.26Ϫ1.37 (m, 2 H, CH2), 3.45 (s, 3 H, OMe), 7.14Ϫ7.24 (m, 1 H,
C6H5), 7.29Ϫ7.38 (m, 4 H, C6H5) ppm. 13C NMR: δ ϭ 55.4 (CH3),
5.8, 6.0 (2 CH2), 125.9 (3 CH), 127.8 (2 CH), 26.4 (2 C), 67.9, 140.3
(C) ppm. MS (EI), m/z (%) ϭ 199 (60) [Mϩ Ϫ H], 185 (100) [Mϩ
Ϫ CH3], 171 (230) [Mϩ Ϫ C2H4 Ϫ H], 157 (50) [Mϩ Ϫ COCH3],
128 (45), 115 (30) [Mϩ Ϫ COC4H9], 105 (38), 91 (20) [C7H7ϩ], 77
(60) [C6H5ϩ].
1
standing at 0 °C, m.p. 28Ϫ29 °C. H NMR: δ ϭ 0.74Ϫ0.81 (m, 2
H, CH2), 0.82Ϫ1.11 (m, 6 H, 3 CH2), 1.73 (s, 3 H, CH3) ppm. 13C
NMR: δ ϭ 7.1, 8.6 (2 CH2), 27.0 (CH3), 26.8 (2 C), 44.1 (C) ppm.
C8H11Br (187.08): calcd. C 51.36, H 5.93, Br 42.71; found C 51.27,
H 5.76, Br 42.56.
General Procedure 1 (GP1) for the Methanolysis of Compounds 3, 4,
6, 8, 11, 16, 24: A solution of the substrate (6 mmol) in anhydrous
methanol (20 mL) was heated under reflux with GC monitoring
for the indicated time. After completion of the reaction, the mixture
was poured into an ice-cold solution of NaHCO3 (10 g) in water
(100 mL) and extracted with Et2O (3 ϫ 50 mL). The combined
organic extracts were washed with brine (50 mL), dried and con-
centrated under reduced pressure. The residue was purified as de-
scribed below.
2,4-Dimethyl-3-phenylpenta-1,3-diene (17): The residue (1.16 g,
85%) obtained from 1-bromo-1-phenyl-2,2,3,3-tetramethylcyclo-
propane (16) (2.00 g, 7.90 mmol) after 24 h under reflux according
to GP1 consisted of essentially pure 17 as revealed by its spectro-
scopic data.[25]
Solvolysis of the Triflate 3. a) In Ethanol: A mixture of 3 (1.210 g,
5 mmol), NaOAc (575 mg, 7 mmol) and anhydrous ethanol
(10 mL) was stirred at 40 °C with GC monitoring. After 1 h, the
mixture was worked up according to GP1. The residue was ‘‘bulb-
to-bulb’’ distilled at 20 °C into a cold (Ϫ78 °C) trap under reduced
7-Methoxy-7-(phenylsulfanyl)dispiro[2.0.2.1]heptane (21): The reac-
tion mixture obtained from 6 (1.50 g, 6.34 mmol) after 10 min un-
der reflux according to GP1 was taken up in methanol and cooled
to Ϫ60 °C. The precipitate was quickly filtered off to give 21
4240
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 4234Ϫ4242

Relative Stabilities of Spirocyclopropanated Cyclopropyl Cations
FULL PAPER
(1.46 g, 99%) as a colorless solid, m.p. 66 °C. 1H NMR: δ ϭ 5.16 (s, 1 H, ϭCH2), 5.61 (t, J ϭ 7.0 Hz, 1 H, ϭCH) ppm. 13C
0.69Ϫ0.73 (m, 2 H, CH2), 0.88Ϫ0.92 (m, 2 H, CH2), 0.96Ϫ1.01 NMR: δ ϭ 14.1, 57.9, 58.6 (CH3), 29.1, 72.0, 73.9, 112.7 (CH2),
(m, 2 H, CH2), 1.26Ϫ1.30 (m, 2 H, CH2), 3.45 (s, 3 H, OMe), 123.9 (CH), 134.2, 145.0 (C) ppm.
7.11Ϫ7.14 (m, 1 H, C6H5), 7.20Ϫ7.29 (m, 4 H, C6H5) ppm. 13C Z-30: Oil, Rf ϭ 0.08. 1H NMR: δ ϭ 1.82 (s, 3 H, CH3), 2.33Ϫ2.48
NMR: δ ϭ 54.2 (CH3), 5.69, 5.74 (2 CH2), 127.6, 128.6 (2 CH),
125.3 (CH), 27.3 (2 C), 73.7, 135.8 (C) ppm. MS (EI), m/z (%) ϭ 2 H, OCH2), 3.45 (t, J ϭ 7.1 Hz, 2 H, OCH2), 5.05 (s, 1 H, ϭCH2),
231 (6) [Mϩ Ϫ H], 217 (11) [Mϩ Ϫ CH3], 155 (100) [Mϩ Ϫ C6H5], 5.10 (s, 1 H, ϭCH2), 5.71 (t, J ϭ 7.1 Hz, 1 H, ϭCH) ppm. 13C
123 (13), 91 (14) [C7H7ϩ]. C14H16OS (232.33): calcd. C 72.37, H NMR: δ ϭ 10.8, 55.8, 58.5 (CH3), 27.1, 71.1, 71.9, 113.6 (CH2),
(m, 2 H, CH2), 3.29 (s, 3 H, OCH3), 3.30 (s, 3 H, OCH3), 3.35 (s,
6.94; found C 72.47, H 7.05.
123.9 (CH), 133.1, 146.1 (C) ppm.
7-Cyclopropyl-7-methoxydispiro[2.0.2.1]heptane (23): The residue
Tosylhydrazone of 2-Cyclopropyl-2-methylcyclobutanone (31): Ke-
(0.416 g, 88%) obtained from 8 (0.614 g, 2.88 mmol) after 30 min tone 27 (200 mg, 1.61 mmol) was added to a solution of tosylhydra-
under reflux according to GP1 consisted of essentially pure 23 as
revealed by its spectroscopic data. H NMR: δ ϭ 0.33Ϫ0.42 (m, 2
zine (300 mg, 1.61 mmol) in hot methanol (3 mL), and the resulting
mixture was kept at 0 °C overnight. The precipitate was collected
1
H, CH2), 0.45Ϫ0.70 (m, 6 H, 3 CH2), 0.80Ϫ0.90 (m, 2 H, CH2), on a filter to give 31 (407 mg, 86%) as a white powder, m.p.
0.95Ϫ1.05 (m, 2 H, CH2), 1.12Ϫ1.25 (m, 1 H, CH), 3.42 (s, 3 H, 130Ϫ131 °C. 1H NMR: δ ϭ Ϫ0.20 to Ϫ0.15 (m, 1 H, CH2),
OMe) ppm. 13C NMR: δ ϭ 54.5 (CH3), 2.0, 3.6, 4.9 (2 CH2), 12.0 0.16Ϫ0.27 (m, 3 H, CH2), 0.77Ϫ0.87 (m, 1 H, CH), 1.21 (s, 3 H,
(CH), 21.1 (2 C), 66.5 (C) ppm.
CH3), 1.54Ϫ1.78 (m, 2 H, CH2), 2.43 (s, 3 H, CH3), 2.48Ϫ2.65 (m,
2 H, CH2), 7.25 (s, 1 H, NH), 7.35 (d, J ϭ 6.3 Hz, 2 H, Ar-H),
7.79 (d, J ϭ 6.3 Hz, 2 H, Ar-H) ppm. 13C NMR: δ ϭ 21.6, 23.2
(CH3), 0.9, 1.2, 26.0, 27.4 (CH2), 127.8, 129.5 (2 CH), 17.9 (CH),
51.7, 135.1, 143.9, 166.0 (C) ppm.
7-Acetoxy-7-(phenylsulfanyl)dispiro[2.0.2.1]heptane (22): Com-
pound 6 (1.50 g, 6.34 mmol) was added in one portion to a stirred
mixture of acetic acid (3.0 g, 2.86 mL, 50 mmol) and sodium acet-
ate (4.10 g, 50 mmol) at 110 °C. After stirring for an additional 1 h,
the mixture was cooled to ambient temperature, poured into ice-
cold water (100 mL) and worked up according to GP1 but with
Et2O extraction. The residue was recrystallized from pentane at
Ϫ30 °C to give 1.62 g (100%) of 22 as a colorless solid. An analyti-
Determination of Rate Constants for the Methanolysis of 3: The
solvolysis reaction of 3 was monitored by 19F NMR spec-
troscopy[26] using a Varian VXR 500 instrument. A solution of 3
(10 mg) and NaOAc (20 mg) in a mixture of methanol (0.6 mL)
cal sample was obtained by crystallization from MeOH/H2O. M.p. and [D4]methanol (10 µL) was thermostatted within 5 min, and 19
F
1
76 °C. H NMR: δ ϭ 0.72Ϫ0.76 (m, 2 H, CH2), 0.80Ϫ0.84 (m, 2 NMR spectra were recorded every 5 min. The rate constants were
H, CH2), 1.04Ϫ1.08 (m, 2 H, CH2), 1.16Ϫ1.20 (m, 2 H, CH2), 2.12
determined by integration of the 19F signals for the starting mate-
(s, 3 H, CH3), 7.13Ϫ7.18 (m, 1 H, C6H5), 7.22Ϫ7.27 (m, 4 H, C6H5) rial (δ ϭ 88.40 ppm with C6F6 as internal standard) and the trifluo-
ppm. 13C NMR: δ ϭ 21.3 (CH3), 5.8, 6.5 (2 CH2), 127.6, 128.7 (2 romethylsulfonate anion (∆δ ϭ 3.25 ppm). The determined values
CH), 125.7 (CH), 27.4 (2 C), 68.9, 135.6, 169.7 (C) ppm.
C15H16O2S (260.33): calcd. C 69.20, H 6.20; found C 69.04, H 6.03.
were equal to k ϭ 3.5 ϫ 10Ϫ4 sϪ1 at 50 °C and 1.6 ϫ 10Ϫ4 sϪ1 at
40 °C.
Methanolysis of 7-Bromo-7-methyldispiro[2.0.2.1]heptane (11):
From the residue (922 mg), which was obtained from 11 (1.182 g,
6.32 mmol) after stirring for 74 h at 65 °C in a mixture of MeOH
and H2O (2:1, 24 mL) according to GP1, 2-cyclopropyl-2-methyl-
cyclobutanone (27; 359 mg, 46%), 7-methylspiro[2.4]heptan-4-one
(28; 38 mg, 5%), 1-(bicyclopropyl-1-yl)ethanone (29; 252 mg, 32%),
(Z)-6-methoxy-2-(methoxymethyl)hexa-1,3-diene [(Z)-30; 24 mg,
2%] and (E)-6-methoxy-2-(methoxymethyl)hexa-1,3-diene [(E)-30;
55 mg, 5%] along with 98 mg (8%) of the starting material 11 were
isolated by column chromatography (40 g of silica gel, 30 ϫ 2 cm
column, pentane/Et2O 10:1.5). 11: Rf ϭ 0.67.
Acknowledgments
This work was supported by the Niedersächsisches Ministerium für
Wissenschaft und Kunst (Niedersachsen-Israel Research Cooper-
ation Program), the Fonds der Chemischen Industrie (Germany) as
well as EPSRC (UK). The authors are indebted to the companies
BASF AG, Bayer AG, Chemetall GmbH, Degussa AG, and Hüls
AG for generous gifts of chemicals. We are particularly grateful to
Dr. B. Knieriem, Universität Göttingen, for his careful proof-
reading of the final manuscript.
27:[16] Oil, Rf ϭ 0.42. 1H NMR: δ ϭ 0.01Ϫ0.14 (m, 1 H, CH2),
0.27Ϫ0.32 (m, 1 H, CH2), 0.33Ϫ0.44 (m, 2 H, CH2), 0.81Ϫ0.85
(m, 1 H, CH), 1.17 (s, 3 H, CH3), 1.56Ϫ1.65 (m, 2 H, CH2),
2.79Ϫ2.85 (m, 2 H, CH2) ppm. 13C NMR: δ ϭ 21.2 (CH3), 1.0,
1.2, 21.9, 42.4 (CH2), 15.6 (CH), 64.0, 214.5 (C) ppm.
[1]
Reviews: [1a] G. Boche, H. M. Walborsky, Cyclopropane Derived
Reactive Intermediates (Eds.: S. Patai, Z. Rappoport), Wiley,
[1b]
Chichester, 1990, pp. 117Ϫ173.
E. C. Friedrich, in The
Chemistry of the Cyclopropyl Group (Ed.: Z. Rappoport),
Wiley, Chichester, 1987, pp. 633Ϫ700. [1c]U. Schöllkopf, Angew.
28: Oil, Rf ϭ 0.38. 1H NMR: δ ϭ 0.37Ϫ0.45 (m, 2 H, CH2),
0.79Ϫ0.85 (m, 2 H, CH2), 1.26 (d, J ϭ 7.2 Hz, 3 H, CH3),
Chem. 1968, 80, 601Ϫ613; Angew. Chem. Int. Ed. Engl. 1968,
7, 588Ϫ598. For a more recent study see:
E. T. Vilar, S. de la Moya Gerero, J. O. Barcina, P. C. Gomez,
J. Org. Chem. 1999, 64, 5611Ϫ5619.
[1d]
´
A. G. Martınez,
1.58Ϫ1.71 (m, 2 H, CH2), 2.81Ϫ2.90 (m, 3 H, CH2, CH) ppm. 13
C
´
NMR: δ ϭ 21.5 (CH3), 4.3, 4.9, 23.9, 42.0 (CH2), 19.1 (CH), 69.5,
209.4 (C) ppm. C8H12O (124.18): calcd. C 77.37, H 9.74; found C
77.18, H 9.81.
[2]
S. I. Kozhushkov, T. Späth, T. Fiebig, B. Galland, M.-F. Ru-
asse, P. Xavier, Y. Apeloig, A. de Meijere, J. Org. Chem. 2002,
67, 4100Ϫ4114.
1
29: Oil, Rf ϭ 0.25. H NMR: δ ϭ Ϫ0.05 to Ϫ0.02 (m, 2 H, CH2),
[3]
[4]
A. de Meijere, S. I. Kozhushkov, Chem. Rev. 2000, 100,
0.41Ϫ0.55 (m, 4 H, 2 CH2), 0.93Ϫ0.97 (m, 2 H, CH2), 1.31Ϫ1.42
(m, 1 H, CH), 2.25 (s, 3 H, CH3) ppm. 13C NMR: δ ϭ 27.6 (CH3),
3.2, 14.6 (2 CH2), 11.9 (CH), 32.0, 210.5 (C) ppm. C8H12O
(124.18): calcd. C 77.37, H 9.74; found C 77.25, H 9.69.
93Ϫ142.
[4a] J. A. Landgrebe, D. E. Applequist, J. Am. Chem. Soc. 1964,
[4b]
86, 1536Ϫ1542.
D. E. Applequist, J. A. Landgrebe, J. Am.
Chem. Soc. 1964, 86, 1543Ϫ1549.
E-30: Oil, Rf ϭ 0.17. 1H NMR: δ ϭ 1.80 (s, 3 H, CH3), 2.32Ϫ2.46
(m, 2 H, CH2), 3.31 (s, 3 H, OCH3), 3.33 (s, 3 H, OCH3), 3.38 (s,
2 H, OCH2), 3.43 (t, J ϭ 7.0 Hz, 2 H, OCH2), 5.11 (s, 1 H, ϭCH2),
[5]
[6]
D. E. Applequist, G. W. Nickel, J. Org. Chem. 1979, 44,
321Ϫ325.
For a brief summary of these results see also ref..[3]
Eur. J. Org. Chem. 2003, 4234Ϫ4242
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4241

S. I. Kozhushkov, T. Späth, M. Kosa, Y. Apeloig, D. S. Yufit, A. de Meijere
FULL PAPER
For reviews on bicyclopropylidene chemistry see: [7a] A. de Me-
ijere, S. I. Kozhushkov, A. F. Khlebnikov, Zh. Org. Khim. 1996,
32, 1607Ϫ1626; Russ. J. Org. Chem. (Engl. Transl.) 1996, 32,
R1 ϭ 0.0627 for 362 refined parameters and 5042 reflections
with I Ն 2σ(I), wR2 (all data) ϭ 0.1887, GOF ϭ 1.062, maxi-
mum and minimum residual electron density 0.833 (in the
vicinity of disordered atoms of one of the independent mol-
[7]
1555Ϫ1575. [7b] A. de Meijere, S. I. Kozhushkov, A. F. Khlebni-
[7c]
˚
kov, Top. Curr. Chem. 2000, 207, 89Ϫ147.
I. Kozhushkov, Eur. J. Org. Chem. 2000, 3809Ϫ3822.
A. de Meijere, S.
ecules) and Ϫ0.472 e·AϪ3. CCDC-214664 contains the sup-
[7d]
A. de
plementary crystallographic data for this paper. These data can
be obtained free of charge at www.ccdc.cam.ac.uk/conts/
retrieving.html [or from the Cambridge Crystallographic Data
Centre, 12, Union Road, Cambridge CB2 1EZ, UK; Fax: (in-
ternat.) ϩ44-1223/336-033; E-mail: deposit@ccdc.cam.ac.uk].
Meijere, S. I. Kozhushkov, T. Späth, M. von Seebach, S. Löhr,
H. Nüske, T. Pohlmann, M. Es-Sayed, S. Bräse, Pure Appl.
Chem. 2000, 72, 1745Ϫ1756.
A. de Meijere, S. I. Kozhushkov, D. S. Yufit, R. Boese, T. Hau-
mann, D. L. Pole, P. K. Sharma, J. Warkentin, Liebigs Ann.
1996, 601Ϫ612.
K. A. Lukin, N. S. Zefirov, D. S. Yufit, Yu. T. Struchkov,
L. Fitjer, J.-M. Conia,
Angew. Chem. 1973, 85, 832Ϫ833; Angew. Chem. Int. Ed. Engl.
[8]
[18] [18a]
A. Kalman, M. Czugler, G. Argay, Acta Crystallogr., Sect.
[18b]
B 1981, 37, 868Ϫ877.
N. A. Donskaya, A. G. Bessmert-
[9] [9a]
nykh, O. E. Grushina, S. V. Lindeman, V. I. Petrov, Yu. Y.
Struchkov, Yu. S. Shabarov, Zh. Org. Chim. 1987, 23,
2369Ϫ2377. [18c] N. A. Donskaya, Yu. K. Grishin, B. A. Lukov-
[9b]
Tetrahedron 1992, 48, 9977Ϫ9984.
skii, I. P. Beletskaya, Zh. Org. Chim. 1994, 30, 19Ϫ24.
1973, 12, 761Ϫ762.
[19]
[19a]
[10] [10a]
Reviews:
D. H. Gibson, C. H. DePuy, Chem. Rev. 1974,
R. A. Moss, R. Gerstl, Tetrahedron 1966, 22, 2637Ϫ2647.
C. Wentrup in Methoden der Organischen Chemie
[19b]
[10b]
74, 605Ϫ623.
I. Ryu, S. Murai, in Methods of Organic
Chemistry (Houben-Weyl) (Ed.: A. de Meijere), Thieme,
Stuttgart, 1997, Vol. E 17c, pp. 1985Ϫ2040.
(Houben-Weyl), E 19b/Teil 1 (Ed.: M. Regitz), pp. 981Ϫ999.
[10d]
[10c]R. A. Moss, Tetrahedron Lett. 1967, 4905Ϫ4909.
K.
[20] [20a]
Review: G. A. Olah, V. P. Reddy, G. K. S. Prakash, Chem.
Steinbeck, J. Klein, Angew. Chem. 1981, 93, 787; Angew. Chem.
Int. Ed. Engl. 1981, 20, 773.
[20b]
Rev. 1992, 92, 69Ϫ95.
For a recent study see also: D. N.
Kevill, M. H. Abduljaber, J. Org. Chem. 2000, 65, 2548Ϫ2554.
For synthetic applications of this rearrangement see reviews:
[21a] L. Fitjer, in Methods of Organic Chemistry (Houben-Weyl)
(Ed.: A. de Meijere), Thieme, Stuttgart, 1997, Vol. E 17e, pp.
251Ϫ316. [21b] A. J. H. Klunder, B. Zwanenburg, in Methods of
[11] [11a] U. Schöllkopf, F. P. Woerner, E. Wiskott, Chem. Ber. 1966,
[21]
[11b]
99, 806Ϫ811.
U. Schöllkopf, E. Ruban, P. Tonne, K. Rie-
del, Tetrahedron Lett. 1970, 5077Ϫ5080.
A. de Meijere, S. I. Kozhushkov, T. Spaeth, N. S. Zefirov, J.
Org. Chem. 1993, 58, 502Ϫ505.
X. Creary, J. Am. Chem. Soc. 1976, 98, 6608Ϫ6613.
D. E. Applequist, W. A. Bernett, Tetrahedron Lett. 1968,
3005Ϫ3007.
A. de Meijere, S. I. Kozhushkov, T. Späth, Org. Synth. 2000,
78, 142Ϫ151.
Only 1H NMR spectra have been reported in two previous
[12]
Organic Chemistry (Houben-Weyl) (Ed.: A. de Meijere), Thie-
[13]
[14]
[21c]
me, Stuttgart, 1997, Vol. E 17c, pp. 2419Ϫ2437.
J. Salaün,
in The Chemistry of the Cyclopropyl Group (Eds.: S. Patai, Z.
Rappoport), Wiley, New York, 1987, Vol. 2, pp. 809Ϫ878.
Gaussian 98, Revision A.11.3, M. J. Frisch, G. W. Trucks, H.
B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, V.
G. Zakrzewski, J. A. Montgomery, Jr., R. E. Stratmann, J. C.
Burant, S. Dapprich, J. M. Millam, A. D. Daniels, K. N. Ku-
din, M. C. Strain, O. Farkas, J. Tomasi, V. Barone, M. Cossi,
R. Cammi, B. Mennucci, C. Pomelli, C. Adamo, S. Clifford, J.
Ochterski, G. A. Petersson, P. Y. Ayala, Q. Cui, K. Morokuma,
N. Rega, P. Salvador, J. J. Dannenberg, D. K. Malick, A. D.
Rabuck, K. Raghavachari, J. B. Foresman, J. Cioslowski, J. V.
Ortiz, A. G. Baboul, B. B. Stefanov, G. Liu, A. Liashenko, P.
Piskorz, I. Komaromi, R. Gomperts, R. L. Martin, D. J. Fox,
T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, M.
Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W.
Wong, J. L. Andres, C. Gonzalez, M. Head-Gordon, E. S. Re-
plogle, and J. A. Pople, Gaussian, Inc., Pittsburgh PA, 2002.
I. Erden, Synth. Commun. 1986, 16, 117Ϫ122.
[15]
[16]
[22]
[16a]
publications:
B. M. Trost, M. J. Bogdanowicz, J. Am.
[16b]
Chem. Soc. 1973, 95, 5321Ϫ5334.
G. Rousseau, P. Le Per-
chec, J. M. Conia, Tetrahedron 1976, 32, 2533Ϫ2537.
[17]
The crystals of 31 were obtained by slow evaporation of its
solution in hexane/Et2O. The X-ray data were collected at
120.0 K on a Bruker SMART CCD 1 K diffractometer [λ(Mo-
Kα), graphite monochromator, ω-scan, 0.3°/frame] equipped
with an Oxford Cryostream LT-device. At 120.0(2) K crystal
of 31 (C15H20N2O2S, M ϭ 292.39, crystal size 0.22 ϫ 0.20 ϫ
0.11 mm3) is monoclinic, a ϭ 9.6680(3), b ϭ 22.6816(8), c ϭ
3
˚
˚
14.3919(5) A, β ϭ 93.51(2)°, V ϭ 3150.0(2) A , Z ϭ 8, space
group P21/c, ρ ϭ 1.233 Mg/m3. A total of 27025 intensities
were measured: (θmax ϭ 27.5°), yielding 7232 independent re-
flections (Rint ϭ 0.0525). The structure was solved by direct
methods and refined by full-matrix least-squares on F2 for all
data. Non-hydrogen atoms (except the disordered ones) were
refined with anisotropic displacement parameters, H-atoms
were placed in calculated positions and refined in ‘‘riding mo-
de’’, H-atoms of amino groups were refined isotropically. Final
[23]
[24]
T. Teraji, I. Moritani, E. Tsuda, J. Chem. Soc., D 1971,
3252Ϫ3257.
[25]
[26]
R. V. Bommett, P. R. Jenkins, J. Chem. Soc., Perkin Trans. 1
1989, 413Ϫ418.
X. Creary, Y.-X. Wang, J. Org. Chem. 1992, 57, 4761Ϫ4765.
Received July 15, 2003
4242
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 4234Ϫ4242