Cyclopropyl building blocks in organic synthesis. Part 81: Striving for unusually strained oxiranes: Epoxidation of spirocyclopropanated methylenecyclopropanes

Article abstract of DOI:10.1016/S0040-4020(02)00695-6

1-Oxa[3]triangulane 13, the epoxide of methylenespiropentane, is thermally stable up to 300°C, but immediately rearranges to spiro[2.3]hexan-4-one (7) in the presence of lithium iodide at ambient temperature. The permethylated bicyclopropylidene 10 is sim

Full text of DOI:10.1016/S0040-4020(02)00695-6

Tetrahedron 58 (2002) 7001–7007
Cyclopropyl building blocks in organic synthesis. Part 81: Striving
for unusually strained oxiranes: epoxidation of
spirocyclopropanated methylenecyclopropanesq
Daniel Frank,a Sergei I. Kozhushkov,a Thomas Labahnb and Armin de Meijerea
,
*
a
¨
Institut fur Organische Chemie der Georg-August-Universitat Gottingen, Tammannstrasse 2, D-37077 Gottingen, Germany
Institut fur Anorganische Chemie der Georg-August-Universitat Gottingen, Tammannstrasse 4, D-37077 Gottingen, Germany
¨
¨
¨
b
¨
¨
¨
¨
Dedicated to Professor Waldemar Adam on the occasion of his 65th birthday
Received 28 March 2002; accepted 29 April 2002
Abstract—1-Oxa[3]triangulane 13, the epoxide of methylenespiropentane, is thermally stable up to 3008C, but immediately rearranges to
spiro[2.3]hexan-4-one (7) in the presence of lithium iodide at ambient temperature. The permethylated bicyclopropylidene 10 is simply less
reactive than the parent bicyclopropylidene (6a) towards dimethyldioxirane, but yields the isolable epoxide 11 (94%) with mCPBA. In
contrast, the partially or fully spirocyclopropanated bicyclopropylidenes 18, 20, and 22, upon treatment with mCPBA or dimethyldioxirane,
did not furnish the corresponding epoxides, but underwent oxidation with rearrangement to the corresponding cyclobutanones 19, 21 and 23
in yields of 59, 100 and 97%, respectively. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
does not necessarily apply to the corresponding hetero-
triangulanes 2. Oxaspiropentane (3a) and azaspiropentane
(3b) are both much more reactive8 than the hydrocarbon
spiropentane. Since little is known about the heterocyclic
analogues 2 of the higher [n ]triangulanes 1, we studied the
epoxidation of some spirocyclopropanated methylenecyclo-
propanes 4 and bicyclopropylidenes 5 and present our
results here.
The chemical properties of systems containing three-
membered rings may be profoundly different from those
of larger rings or acyclic analogs.2,3 The pronounced
tendency to undergo ring-opening reactions is a conse-
quence of the ring strain and the peculiar type of bonding in
cyclopropane and its heterocyclic analogues. The chemical
reactivity of a three-membered ring may even be enhanced
when it is either conjugated with an appropriate elec-
tronically active substituent4–6 or its overall strain7 is
increased by incorporation into an oligocyclic molecule in
such a way that it shares one atom (spirofusion) or two
(annelation) with another small ring, especially another
three-membered ring. Among such systems, the highly
strained, so-called [n]triangulanes 1, hydrocarbons which
consist of spiroannelated cyclopropane rings only, and their
functionally substituted derivatives, have been and still are
of special interest.8a It turns out that all of these
hydrocarbons are relatively stable towards heating and a
variety of chemical reagents in spite of their high overall
strain energies. The all-carbon [n]triangulanes therefore
have become one of the most convincing examples for the
notion that total strain energy of a molecule and kinetic
instability do not correlate at all.2,3 However, this principle
2. Results and discussion
q For Parts 79 and 80, see Ref. 1.
The simplest oxatriangulane—oxaspiropentane (3a)—can
readily be prepared by straightforward epoxidation of
methylenecyclopropane.9a–c The alternative approach to
oxaspiropentanes, especially to substituted ones, by
Keywords: alkenes; epoxidations; heterotriangulanes; peroxides; small ring
systems.
*
Corresponding author. Tel.: þ49-551-393232; fax: þ49-551-399475;
e-mail: armin.demeijere@chemie.uni-goettingen.de
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00695-6

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D. Frank et al. / Tetrahedron 58 (2002) 7001–7007
Scheme 1. Known preparations of higher oxa[n]triangulanes and their reactivity.
cyclopropanation of carbonyl compounds with sulfonium
cyclopropylides or stabilized cyclopropylcarbanions
has been exploited towards preparatively useful inter-
mediates.9e,f,10 The only higher oxatriangulanes that have
unequivocally been characterized, are the 7-oxa[3]triangu-
lanes 8a,b which were obtained by epoxidation of
bicyclopropylidene (6a) and its tetramethyl derivative 6b
(Scheme 1).9a,11,12 In contrast to methylenecyclopropane,
bicyclopropylidene (6a) reacts with meta-chloroperbenzoic
acid (mCPBA) spontaneously at 08C within 5 min.12,13 All of
the oxaspiropentanes (oxa[2]triangulanes) rapidly isomerize
to cyclobutanones under the catalysis of lithium iodide and
other Lewis acids, a fact which has found widespread
application in organic synthesis.9–12,14,15
of the intermediate 1-cyclopropylcyclopropyl cation to a
2-cyclopropylallyl cation is favored over the cyclopropyl-
carbinyl to cyclobutyl cation ring enlargement.
To start with, the possible epoxidation of permethylbi-
cyclopropylidene (10),16 which is more sterically congested
than its tetramethyl analogue 8b, was tested. Indeed, the
hydrocarbon 10 did not react at all with a twofold excess of
dimethyldioxirane,17 which was chosen as an epoxidizing
reagent that does not generate an acid, at room temperature
within 5 h. However, the epoxidation of 10 could be
achieved with mCPBA to furnish the permethyl-7-oxa-[3]-
triangulane 11 in 94% yield (Scheme 2).
The structure of the permethyl-7-oxa[3]triangulane 11 was
unequivocally established by X-ray crystal structure
analysis (Fig. 1).18 This displays the mutual repulsion of
the four endo-oriented methyl groups, yet the sum of van der
Waals radii of two nearest hydrogen atoms (2.40 A) in two
methyl groups on the different rings does not exceed the
˚
intramolecular distance (2.693 A). Anyhow, this leads to a
deformation of the oxaspiropentane units by bending (i.e.
buckling of the C2 axis which usually bisects the
cyclopropane and the oxirane rings, see Fig. 1) by 16.78
Bicyclopropylidene epoxide (8a), a 7-oxa[3]triangulane
(7-oxadispiro[2.0.2.1]heptane) is remarkably more stable
towards lithium iodide than the oxaspiropentanes, its
isomerization could be effected only at 758C.11a,12 Under
the same conditions, the sterically congested 1,1,5,5-
tetramethyloxa[3]triangulane 8b surprisingly does not
yield a cyclobutanone, but instead rearranges to 2,2-di-
methyl-1-(3-isoprenyl)cyclopropanol (9) (Scheme 1).9a One
can only speculate that in this unique case, the ring opening
˚
Scheme 2. (1) mCPBA, NaHCO3, CH2Cl2, 08C, 3 h; (2) C6D6, 1008C, 1.5 h; (3) dimethyldioxirane, acetone, 0–208C, 2–5 h; (4) CDCl3, 208C.

D. Frank et al. / Tetrahedron 58 (2002) 7001–7007
7003
could be purified by bulb-to-bulb distillation at 08C and
0.01 Torr in 92% yield and be assigned the structure of
1-oxa[3]triangulane 13 on the basis of its 1H and 13C NMR
spectra (Scheme 2). Surprisingly, this product did neither
undergo isomerization upon heating at 608C in CDCl3
solution, nor under flash vacuum pyrolysis conditions even
at 3008C. However, addition of a catalytic quantity of
lithium iodide to a solution of 13 in CDCl3 at ambient
temperature led to an immediate and quantitative rearrange-
ment of 13 into 7. Thus, the 1-oxa[3]triangulane 13
is remarkably less stable towards lithium iodide than
7-oxa[3]triangulane 8a and even less stable than oxaspiro-
pentane (3a) and its derivatives. It is most remarkable that
13 under LiI catalysis, rearranges to the same product 7 as
does 8a. For the most reasonable mechanistic interpretation
one has to assume an initial opening of the distal (with
respect to the spiropentane moiety) C–O bond in the
oxirane ring, the resulting zwitterion 15, which, by being a
cyclopropylcarbinyl cation ought to be a reasonably
stabilized species,20 would then undergo the well-known
cyclopropylcarbinyl to cyclobutyl cationic ring enlarge-
ment,21 and the resulting intermediate 16 would liberate LiI
again to yield 7 (Scheme 2). The ring enlargement of 15 to
16 proceeds regioselectively with migration of the distal
bond in the spiropentane moiety of 15 only. Alternatively,
the lithium iodide-complexed oxa[3]triangulane 17 could
undergo a concerted ring-enlarging 1,2-migration of a
proximal cyclopropyl bond in the spiropentane moiety
with opening of the oxirane ring and subsequent liberation
of LiI to give 7.
Figure 1. Molecular structure of permethyl-7-oxa[3]triangulane 11 in the
˚
crystal (selected interatomic distances are given in A).
18
(F¼163.38 for both moieties). This is more pronounced
than even in branched [15]triangulane (F¼168.38).16
However, the deformation of the oxaspiropentane units as
observed for the central spiropentane units in [15]triangu-
lane16 by twisting (i.e. rotation of the plane of cyclopropane
against that of the oxirane ring) is essentially negligible
(c¼89.4 and 89.88 for the left and right oxaspiropentane
unit, see Fig. 1).
This 7-oxa[3]triangulane 11 turned out to be rather stable at
1008C as well as towards lithium iodide upon heating at
608C in C6D6 solution for 0.5 h, but partially rearranged
upon heating with LiI in a sealed tube at 1008C, to yield
permethylspiro[2.3]hexan-4-one (12) (Scheme 2). The
isomer of 8a, the 1-oxa[3]triangulane 13, at first appeared
to be considerably less stable than 8a, as an attempted
epoxidation of methylenespiropentane (14) with either
buffered mCPBA or dimethyldioxirane on a small scale
with attempted purification by ‘bulb-to-bulb’ distillation (at
308C/0.2 Torr) only gave small amounts of the known
spiro[2.3]hexan-4-one (7)11a,12,19 (9 and 15%, respectively)
along with polymeric material. However, when performed
on a larger scale (650 mg–1.6 g), epoxidation of 14 with
mCPBA under buffered conditions did give a product which
Thus, one additional spirocyclopropane moiety attached to
an oxaspiropentane at either end apparently does not signifi-
cantly decrease the thermal stability of the corresponding
oxatriangulane 8a or 13, respectively. However, attempted
epoxidation of the mono-, bis- and tetrakis-spirocyclo-
propanated bicyclopropylidenes 18, 20 and 2222 furnished
exclusively the corresponding spirocyclopropanated
Scheme 3. Attempted epoxidations of spirocyclopropanated bicyclopropylidenes 18, 20 and 22 and further oxidation of the cyclobutanone 21. (1) mCPBA,
NaHCO3, CH2Cl2, 08C, 3 h; (2) dimethyldioxirane, acetone, 0–208C, 2–5 h.

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D. Frank et al. / Tetrahedron 58 (2002) 7001–7007
23 derived from the perspirocyclopropanated bicyclo-
propylidene 22 and of the g-butyrolactone 26 were
established by X-ray crystal structure analyses (Fig. 2).18
It is interesting to compare the structural features of 23 and
26 with those of the parent cyclobutanone26 and g-butyro-
lactone.27 The four-membered ring in 23 is almost planar
with an interplanar angle of 1.68 between the planes formed
by C3, C4, C5 and C3, C12, C5. This angle is significantly
smaller than that in the parent cyclobutanone (19.88), as
determined by microwave and nematic phase NMR
spectroscopy.26 The g-butyrolactone fragment in 26 is
virtually as close to being planar as g-butyrolactone itself.27
As far as bond lengths are concerned, only the outer sphere
cyclopropane rings in the [3]triangulane moieties of these
molecules can be reproduced accurately enough by the
previously derived general bond increment scheme for
triangulanes.28 The bond lengths in the spirocyclopropane
rings attached to the four-membered ring in 23 or five-
membered ring in 26 follow the rules put forward by
Allen.29 Due to the electron-withdrawing effect of the
carbonyl group in 23 and carbonyloxy substituent in 26 the
proximal and the distal bonds in the respective adjacent
spirocyclopropane ring are lengthened and shortened,
respectively.
Figure 2. Molecular structures of the spirocyclopropanated cyclobutanone
˚
23 and g-butyrolactone 26 in the crystal (bond lengths are given in A).
3. Conclusion
18
In conclusion, one can say that for the oxa[n ]triangulanes
some sort of correlation between increasing strain of the
molecules and their kinetic instability does exist. The
spiroannelation of every new cyclopropane moiety to an
[n ]triangulane skeleton increases the total strain energy by
cyclobutanone derivatives 19, 21 and 23, no matter whether
buffered mCPBA or dimethyldioxirane was used as an
oxidant (Scheme 3). This cannot be attributed to rearrange-
ment upon purification (column chromatography), as the
corresponding oxiranes could not even be detected in the
NMR spectra of the crude reaction mixtures. Thus, an
earlier report8,23 on the successful preparation of the
epoxide 24 from the perspirocyclopropanated bicyclo-
propylidene 22 was proved wrong.
at least 36.7 kcal mol21 30
but a strain-instability relation-
,
ship emerges more pronouncedly in the case of oxatriangu-
lanes 2. Viewing it from another angle, the oxidation of
oligocyclopropanated methylenecyclopropanes and bicyclo-
propylidenes with typical epoxidizing agents can be used as
an easy access to unusual oligospirocyclopropanated
cyclobutanones.
In fact, the material previously obtained on a very small
scale (4 mg)23 turned out to have the same 1H NMR
spectroscopic data as the cyclobutanone derivative 23,
which has now been unequivocally identified (see below).
Undoubtedly, the ring enlargement en route to 19, 21 and 23
occurs at the stage of a cyclopropyl cationic intermediate of
type 25. It is noteworthy that the cationic charge
preferentially develops on the cyclopropane moiety that
has additional spirocyclopropane rings attached. This is due
to the fact that a cyclopropyl cation is stabilized by
spirocyclopropane annelation.24 However, it is not obvious
whether the intermediates 25 are formed via the correspond-
ing oxiranes or directly from the alkene and the epoxidizing
reagent.25 Just like octamethylbicyclopropylidene (10), the
sterically significantly less congested alkenes 20 and 22
reacted faster with mCPBA than with dimethyldioxirane.
4. Experimental
4.1. General methods
Methylene chloride and acetone were purified by distillation
from P4O10 and K2CO3, respectively. Dimethyldioxirane
(DMDO),17 octamethylbicyclopropylidene (10),16 methyl-
enespiropentane (14),31 cyclopropylidenespiropentane
(18),32 7-cyclopropylidene-dispiro[2.0.2.1]heptane (20),32
and bis(dispiro[2.0.2.1]hept-7-ylidene) (22),16 were pre-
pared according to published procedures. All other
chemicals were used as commercially available (Merck,
Acro˜s, BASF, Bayer, Degussa AG, and Hu¨ls AG). Organic
extracts were dried with MgSO4.
With an excess of mCPBA, the cyclobutanone 21 rapidly
undergoes a subsequent Bayer–Villiger oxidation to give
the spirocyclopropanated g-butyrolactone 26 (Scheme 3).
This type of further oxidation was also observed in the
reaction of the parent bicyclopropylidene (6a) with ozone.11
1H and 13C NMR spectra were recorded at 250 (1H), and
62.9 [13C, additional distortionless enhancement by polari-
zation transfer (DEPT)] MHz with a Bruker AM 250
instrument in CDCl3 soln, with residual CHCl3 and
CDCl3, respectively, as internal reference (if not otherwise
specified); d in ppm, J in Hz. IR spectra were measured with
The structures of the spirocyclopropanated cyclobutanone

D. Frank et al. / Tetrahedron 58 (2002) 7001–7007
7005
1
a Bruker IFS 66 (FT-IR) spectrophotometer as KBr pellets
or oils between KBr plates. Mass spectra (EI-70 eV and
CI–NH3) were obtained on a Finnigan MAT 95 spectro-
meter. Melting points were measured with a Bu¨chi 510
capillary melting point apparatus and are uncorrected. TLC
analyses were performed using Macherey–Nagel precoated
sheets, 0.25 mm Sil G/UV254 and column chromatography
using Merck silica gel, grade 60, 230–400 mesh. The CH
analyses were carried out by the Mikroanalytisches
Laboratorium des Instituts fu¨r Organische Chemie der
did not result in any detectable changes in its H and 13C
NMR spectra.
(b) The crude product obtained from 14 (325 mg,
4.06 mmol), mCPBA (839 mg, 3.65 mmol) and NaHCO3
(2.52 g, 30 mmol) according to GP1, which was almost pure
13, was bulb-to-bulb distilled at 308C/0.2 Torr to give 711a,
12,18 (32 mg, 9.1%) as a colorless liquid. 1H NMR d: 3.03 (t,
J¼7.5 Hz, 2H, Cbut-CH2), 2.22 (t, J¼7.5 Hz, 2H, Cbut-
CH2), 1.35–1.30 (dd, J¼4.3, 7.7 Hz, 2H, 2Cpr-H), 1.11–
1.05 (dd, J¼4.3, 7.7 Hz, 2H, 2Cpr-H). 13C NMR d: 215.5
(C), 43.8 (CH2), 39.6 (C), 20.6 (CH2), 16.5 (2CH2).
¨ ¨
Universitat Gottingen.
4.2. General procedure (GP1) for the epoxidation of
alkenes 10, 14, 18, 20, and 22 with meta-chloro-
perbenzoic acid (mCPBA)
(c) Bulb-to-bulb distillation at 308C/0.2 Torr of the crude
product obtained from 14 (163 mg, 2.03 mmol) and DMDO
(2.88 mmol, 28.8 ml of a ca. 0.1 M solution in acetone)
according to GP2, also furnished 7 (29 mg, 15%).
To a well stirred suspension of NaHCO3 (1.26 g, 15 mmol)
in CH2Cl2 (90 ml) was added the corresponding alkene
(2.6 mmol) in CH2Cl2 (90 ml), and then a solution of
mCPBA (0.9 equiv., 75% purity) in CH2Cl2 (45 ml) was
added dropwise at 08C over a period of 15 min. After
stirring for an additional 1–3 h at 08C, the mixture was
poured into conc. NH4OH aq. solution (8 ml), the inorganic
layer was extracted with CH2Cl2 (3£20 ml), the combined
organic solutions were washed with sat. NH4Cl aq. solution
(3£15 ml), dried and concentrated under reduced pressure at
08C. The product was purified by column chromatography
on silica gel.
(d) To a solution of purified 13 (40 mg) in CDCl3 (0.5 ml) in
an NMR tube was added anhydrous lithium iodide as a
powder (10 mg). Upon vigorous shaking of the tube a
slightly exothermal reaction was observed. The immedi-
ately following NMR measurement indicated complete
transformation of 13 into 7.
4.3.2. 1,1,2,2,5,5,6,6-Octamethyl-7-oxadispiro[2.0.2.1]-
heptane (11) and 1,1,2,2,5,5,6,6-octamethylspiro[2.3]-
hexan-4-one (12). (a) The crude product mixture obtained
from permethylbicyclopropylidene (10) (500 mg, 2.6
mmol), mCPBA (1.076 g, 4.68 mmol, 1.8 equiv.) and
NaHCO3 (1.26 g, 15 mmol) was sublimed at 1008C/
0.1 Torr to give 11 (513 mg, 94%) as a colorless solid,
Rf¼0.33 (hexane/Et2O 30:1), mp 948C. 1H NMR (C6D6) d:
1.21 (s, 12H, 4CH3), 1.03 (s, 12H, 4CH3). 13C NMR (C6D6)
d: 72.2 (2C), 18.1 (4CH3), 17.9 (4C), 15.4 (4CH3). IR (KBr),
cm21: 2989, 2922, 1653, 1457, 1378, 1115, 1042, 952, 905,
766, 577, 637, 436. EI-MS m/z: 208 (1%, Mþ), 193 (3%,
Mþ2CH3), 178 (4%, Mþ22CH3), 163 (2%, Mþ23CH3),
125 (12%), 96 (44%), 84 (20%), 81 (100%), 69 (30%).
CI-MS m/z: 243 (42%, MþNH3þNHþ4 ), 226 (47%,
MþNHþ4 ), 209 (100%, MþHþ). HRMS (EI) calcd for
C14H24O (Mþ) 208.1827, found 208.1827.
4.3. General procedure (GP2) for the epoxidation of
alkenes 10, 14, 18, 20, and 22 with dimethyldioxirane
(DMDO)
To a solution of DMDO in acetone (5.76 mmol, 57.6 ml of
ca. 0.1 M solution) was added the corresponding alkene
(5.2 mmol) at 08C. After stirring for an additional 2 h, the
mixture was concentrated under appropriate pressure and
the residue was taken up with Et2O (30 ml), washed with
water (20 ml), brine (2£20 ml), dried, concentrated under
appropriate pressure at 08C and purified by column
chromatography, if not otherwise specified.
4.3.1. Spiro[2.3]heptan-4-one (7) and 1-oxadispiro[2.0.2.1]-
heptane (13). (a) The crude product obtained from 14
(650 mg, 8.11 mmol), mCPBA (1.68 g, 7.30 mmol) and
NaHCO3 (3.93 g, 46.8 mmol) according to GP1 was bulb-
to-bulb distilled (08C/0.01 Torr) to give almost pure 13
(643 mg, 92%) as a colorless oil. Attempted column
chromatography of 200 mg of 13 (45 g of silica gel,
25£3 cm column, pentane/Et2O 5:1, Rf¼0.23) resulted in
quantitative isolation of 13, but of the same purity. 1H NMR
d: 3.33 (d, J¼4.9 Hz, 1H, one of OCH2), 3.16 (d, J¼4.9 Hz,
1H, one of OCH2), 1.48 (d, J¼6.3 Hz, 1H, one of CH2), 1.39
(d, J¼6.3 Hz, 1H, one of CH2), 1.11–0.80 (m, 4H, 2CH2).
13C NMR d: 57.7 (C), 48.8 (CH2), 9.7 (CH2), 9.2 (C), 6.8
(CH2), 5.1 (CH2). IR (film), cm21: 3069, 3054, 2992,
1714, 1603, 1424, 1324, 1162, 1050, 998, 970, 929, 876,
858, 824, 627, 565, 454. EI-MS m/z: 96 (18%, Mþ), 95
(33%, Mþ2H), 81 (17%, Mþ2H–CH2), 67 (86%,
Mþ2H–CH2CH2), 66 (100%, Mþ22H–CH2CH2), 65
(54%), 54 (60%), 53 (84%), 43 (26%), 42 (21%), 41
(42%). Heating of the solution of 13 in CDCl3 (608C, 3 h) as
well as flash vacuum pyrolysis at 200 and 3008C/0.01 Torr
(b) Heating of a solution of purified 11 (40 mg) in C6D6
(0.5 ml) in an NMR tube with addition of lithium iodide as a
powder (10 mg) (608C, 0.5 h) did not result in any
detectable changes in its 1H NMR spectrum. However,
heating of this sample in a sealed tube at 1008C for 1.5 h
furnished a rearranged product (74% yield) which, accor-
1
ding to its H and 13C NMR spectra, had the structure of
1,1,2,2,5,5,6,6-octamethylspiro[2.3]hexan-4-one (12) (see
below).
(c) A solution of epoxide 11 (131 mg, 0.63 mmol) and LiI
(30 mg, 0.22 mmol) in anhydrous benzene (2 ml) was
heated at 1008C for 2 h in a sealed tube. After cooling to
ambient temperature, the solution was concentrated under
reduced pressure. Column chromatography (120 g of silica
gel, 3£35 cm column, hexane/Et2O 30:1) gave 12 (83 mg,
1
63%) as a colorless solid, Rf¼0.29, mp 288C. H NMR d:
1.20 (s, 6H, 2CH3), 1.18 (s, 6H, 2CH3), 1.16 (s, 6H, 2CH3),
0.99 (s, 6H, 2CH3). 13C NMR d: 220.1 (C), 59.5 (C), 57.9
(C), 41.7 (C), 36.7 (2 C), 23.2 (2CH3), 20.0 (2CH3), 18.3

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D. Frank et al. / Tetrahedron 58 (2002) 7001–7007
(2CH3), 18.0 (2CH3). IR (KBr), cm21: 3011, 2926, 2869,
1750, 1557, 1379, 1162, 1100, 1040, 994. EI-MS m/z: 208
(38%, Mþ), 193 (57%, Mþ2CH3), 165 (25%), 125 (64%),
109 (18%), 96 (100%), 84 (67%), 81 (97%), 69 (70%), 57
(20%). HRMS (EI) calcd for C14H24O (Mþ) 208.1827,
found 208.1827.
J¼4.7, 5.3, 9.5 Hz, 2H), 0.86–0.72 (m, 6H), 0.66–0.59
(ddd, J¼4.1, 5.5, 9.3 Hz, 2H), 0.31–0.27 (dd, J¼5.0,
6.5 Hz, 2H). 13C NMR d: 209.5 (C), 48.1 (C), 42.4 (C), 27.1
(2 C), 25.6 (C), 13.4 (2CH2), 4.3 (2CH2), 3.9 (2CH2), 3.2
(2CH2). IR (KBr), cm21: 3072, 2993, 1758, 1325, 1197,
1100, 1051, 1022, 982, 938, 876. CI-MS m/z: 235 (85%,
MþNH3þNHþ4 ), 218 (100%, MþNHþ4 ), 201 (5%, MþHþ).
4.3.3. Dispiro[3.0.2.1]octan-1-one (19). (a) Column chro-
matography (120 g of silica gel, 3.5£35 cm column,
pentane/Et2O 5:1) of the reaction mixture obtained from
cyclopropylidenespiropentane (18) (276 mg, 2.60 mmol),
mCPBA (538 mg, 2.34 mmol) and NaHCO3 (1.26 g,
15 mmol) according to GP1 gave 19 (168 mg, 59%) as a
colorless oil, Rf¼0.45. 1H NMR d: 3.07–2.94 (ddd, J¼6.0,
9.2, 17.5 Hz, 1H, one of Cbut-CH2), 2.92–2.79 (ddd, J¼5.7,
9.3, 17.5 Hz, 1H, one of Cbut-CH2), 2.33–2.23 (ddd, J¼5.8,
9.3, 11.2 Hz, 1H, one of Cbut-CH2), 2.17–2.06 (ddd, J¼6.0,
9.3, 11.2 Hz, 1H, one of Cbut-CH2), 1.90 (d, J¼4.0 Hz, 1H,
one of Cpr-CH2), 1.57 (d, J¼4.0 Hz, 1H, one of Cpr-CH2),
1.02–0.78 (m, 4H, 2Cpr-CH2). 13C NMR d: 215.1 (C), 45.6
(C), 43.6 (CH2), 25.2 (C), 23.4 (CH2), 19.4 (CH2), 6.2
(CH2), 4.7 (CH2). IR (film), cm21: 3072, 2985, 2870, 1767,
1533, 1437, 1394, 1249, 1176, 1144, 1108, 1071, 1024, 998,
956, 918, 878, 845, 828, 733. CI-MS m/z: 262 (5%,
2MþNHþ4 ), 157 (20%, MþNH3þNHþ4 ), 140 (100%,
MþNHþ4 ), 123 (5%, MþHþ).
(b) The reaction mixture obtained from 22 (980 mg,
5.32 mmol) and DMDO (20 mmol, 200 ml of a ca. 0.1 M
solution in acetone) according to GP2 contained, according
1
to its H NMR spectrum, less than 5% of 23.
4.3.6. 1-Oxatrispiro[4.0.2.0.2.0]undecan-2-one (26).
Column chromatography (70 g of silica gel, 20£3 cm
column, hexane/Et2O 5:1) of the reaction mixture obtained
from 20 (714 mg, 5.4 mmol), mCPBA (1.60 g, 7.0 mmol)
and NaHCO3 (1.26 g, 15 mmol) according to GP1, gave the
cyclobutanone 21 (48 mg, 6%, Rf¼0.40), and the lactone 26
(537 mg, 61%) as a colorless solid, Rf¼0.20, mp 105–
1
1088C. H NMR d: 2.59 (t, J¼8.4 Hz, 2H, COCH2), 2.26
(t, J¼8.4 Hz, 2H, CH2), 1.13–1.02 (m, 2H, Cpr-CH2),
0.94–0.85 (m, 4H, 2Cpr-CH2), 0.75–0.64 (m, 2H, Cpr-
CH2). 13C NMR d: 176.5 (C), 72.1 (C), 29.3 (CH2), 25.2
(CH2), 20.2 (2C), 5.8 (2CH2), 5.4 (2CH2). IR (KBr), cm21
:
3064, 2977, 2937, 2864, 1772, 1457, 1259, 1123, 1074,
1017, 796. CI-MS m/z: 199 (25%, MþNH3þNHþ4 ), 182
(100%, MþNHþ4 ).
(b) From 18 (552 mg, 5.20 mmol) and DMDO (5.76 mmol,
57.6 ml of a ca. 0.1 M solution in acetone) the cyclobuta-
none 19 (330 mg, 52%) was obtained according to GP2.
Acknowledgments
4.3.4. Trispiro[3.0.2.0.2.0]decan-1-one (21). (a) Column
chromatography (50 g of silica gel, 20£2 cm column,
hexane/Et2O 5:1) of the reaction mixture obtained from
7-cyclopropylidenedispiro[2.0.2.1]heptane (20) (340 mg,
2.57 mmol), mCPBA (314 mg, 1.36 mmol) and NaHCO3
(1.26 g, 15 mmol) according to GP1, gave 21 (201 mg,
100%) as a colorless solid, Rf¼0.40, mp 52–548C. 1H NMR
d: 2.71 (t, J¼7.6 Hz, 2H, Cbut-CH2), 2.04 (t, J¼7.6 Hz, 2H,
Cbut-CH2), 0.97–0.85 (m, 4H, 2Cpr-CH2), 0.82–0.77 (m,
2H, Cpr-CH2), 0.62–0.56 (m, 2H, Cpr-CH2). 13C NMR d:
214.6 (C), 50.1 (C), 43.1 (CH2), 29.4 (2C), 18.2 (CH2), 5.8
(2CH2), 4.5 (2CH2). IR (KBr), cm21: 3069, 2985, 2951,
2862, 1767, 1576, 1421, 1389, 1249, 1175, 1122, 1017, 948,
867, 750, 549. EI-MS m/z: 148 (5%, Mþ), 133 (5%), 119
(10%), 106 (18%), 105 (50%), 92 (32%), 91 (100%), 79
(35%), 77 (26%), 65 (16%), 63 (14%), 52 (18%), 51 (21%).
This work was supported by the Fonds der Chemischen
Industrie (Germany). The authors are indebted to the
companies BASF AG, Bayer AG, Chemetall GmbH, and
Degussa AG for generous gifts of chemicals. We are
¨
particularly grateful to Dr B. Knieriem, Universitat
Gottingen, for his careful reading of the final manuscript.
¨
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parameters refined, final R indices [I.2s(I )] R1¼0.0486,
wR2¼0.1380, Gof¼1.051, maximum and minimum residual
electron density 0.263 and 20.212 e A23. 26: C10H12O2
˚
(164.20), triclinic, a¼5.4056(11), b¼7.4357(15), c¼
˚
8. (a) Review: de Meijere, A.; Kozhushkov, S. I. Chem. Rev.
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11.1700(20) A, a¼77.41(3), b¼76.13(3), g¼78.23(3)8,
3
˚
V¼419.89(15) A , Z¼2, space group P21, T¼133(2) K,
r¼1.299 g cm23, F(000)¼176, intensities measured: 4353
(2umax¼49.368), independent: 1485 (Rint¼0.0657), 109 para-
meters refined, final R indices [I.2s(I )] R1¼0.0362,
wR2¼0.0966, Gof¼1.050, maximum and minimum residual
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electron density 0.195 and 20.154 e A23. Crystallographic
˚
data (excluding structure factors) for the structures reported in
this paper have been deposited as supplementary publication
no. CCDC-182317 (11), CCDC-182315 (23), and CCDC-
182316 (26) with the Cambridge Crystallographic Data
Centre. Copies of the data can be obtained free of charge on
application to The Director, CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK (fax: þ44-1223-336-033; e-mail:
deposit@ccdc.cam.ac.uk).
19. Denis, J. M.; Le Perchec, P.; Conia, J.-M. Tetrahedron 1977,
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12. de Meijere, A.; Erden, I.; Weber, W.; Kaufmann, D. J. Org.
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22. (a) Zollner, S.; Buchholz, H.; Boese, R.; Gleiter, R.; de
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6053–6059.
¨
16. de Meijere, A.; von Seebach, M.; Zollner, S.; Kozhushkov,
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¨ ¨
23. Zollner, S. Dissertation, Universitat Hamburg, 1991.
¨
24. Kozhushkov, S.; Spath, T.; Fiebig, T.; Galland, G.; Ruasse,
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M.-F.; Xavier, P.; Apeloig, Y.; de Meijere, A. J. Org. Chem.,
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18. Crystals of compounds were grown by slow evaporation of
their solutions in a mixture of Et2O and hexane (23 and 26) or
by sublimation at 1008C/0.1 Torr (11). The X-ray single
crystal data were collected on a Stoe IPDS II diffractometer
using graphite monochromated Mo Ka-radiation. The struc-
ture solutions and refinements on F 2 were performed with the
Bruker SHELXTL program suite. The hydrogen atoms in
structures 11, 23 and 26 were located in a difference Fourier
synthesis and refined isotropically. 11: C14H24O (208.33),
25. For example, the spiro[2.3]hexan-4-one (7) was formed in the
reaction of bicyclopropylidene (6a) with ozone (67% yield)
even at 2788C.12 In this case intermediate of the type 25 was
presumably formed directly from 6a and the oxidizing agent.
26. Cole, K. C.; Gilson, D. F. R. Can. J. Chem. 1976, 54,
657–664.
27. Brown, J. M.; Conn, A. D.; Pilcher, G.; Leitao, M. L. P.;
Meng-Yan, Y. J. Chem. Soc., Chem. Commun. 1989,
1817–1819.
˚
monoclinic, a¼16.2695(12), b¼6.4521(6), c¼12.5687(9) A,
3
˚
28. Boese, R.; Haumann, T.; Kozhushkov, S.; Jemmis, E. D.;
Kiran, B.; de Meijere, A. Liebigs Ann. 1996, 913–919.
29. Allen, F. H. Acta Crystallogr. B 1980, 36, 81–96.
30. Beckhaus, H.-D.; Ru¨chardt, C.; Kozhushkov, S. I.; Belov,
V. N.; Verevkin, S. P.; de Meijere, A. J. Am. Chem. Soc. 1995,
117, 11854–11860.
b¼97.406(6)8, V¼1308.36(18) A , Z¼4, space group P2(1)/c,
T¼133(2) K, r¼1.058 g cm23, F(000)¼464, intensities
measured: 12387 (2umax¼59.528), independent: 2225
(Rint¼0.0407), 144 parameters refined, final R indices
[I.2s(I)] R1¼0.0352, wR2¼0.0946, Gof¼1.073, maximum
and minimum residual electron density 0.208 and
23
˚
20.125 e A
31. de Meijere, A.; Kozhushkov, S. I.; Faber, D.; Bagutskii, V.;
Boese, R.; Haumann, T.; Walsh, R. Eur. J. Org. Chem. 2001,
3607–3614.
.
23: C14H16
O
(200.27), monoclinic,
˚
a¼12.814(3), b¼7.0866(14), c¼12.867(3) A, b¼109.40(3)8,
3
˚
V¼1102.1(4) A , Z¼4, space group P2(1)/c, T¼133(2) K,
r¼1.207 g cm23, F(000)¼432, intensities measured: 3478
32. de Meijere, A.; Kozhushkov, S. I.; Spaeth, T.; Zefirov, N. S.
J. Org. Chem. 1993, 58, 502–505.
(2umax¼49.568), independent: 1631 (Rint¼0.0823), 136