Cyclobutylidenecyclopropane: New synthesis and use in 1,3-dipolar cycloadditions - A direct route to spirocyclopropane-annulated azepinone derivatives

Article abstract of DOI:10.1002/1099-0690(200110)2001:20<3789::AID-EJOC3789>3.0.CO;2-O

Cyclobutylidenecyclopropane (7) was prepared in multigram quantities by a new three-step sequence starting from ethyl cyclobutanecarboxylate (4) (39% overall yield). 1,3-Dipolar cycloadditions of phenyl- (9), pyridyl- (10), and the newly prepared (four st

Full text of DOI:10.1002/1099-0690(200110)2001:20<3789::AID-EJOC3789>3.0.CO;2-O

FULL PAPER
Cyclobutylidenecyclopropane: New Synthesis and Use in 1,3-Dipolar
Cycloadditions ؊ A Direct Route to Spirocyclopropane-Annulated Azepinone
Derivatives[‡]
Armin de Meijere,*[a] Malte von Seebach,[a] Sergei I. Kozhushkov,[a] Roland Boese,[b]
Dieter Bläser,[b] Stefano Cicchi,[c] Tula Dimoulas,[c] and Alberto Brandi*[c]
Keywords: Cycloadditions / Rearrangements / Small ring systems / Spiro compounds
Cyclobutylidenecyclopropane (7) was prepared in multigram
quantities by a new three-step sequence starting from ethyl
cyclobutanecarboxylate (4) (39% overall yield). 1,3-Dipolar
84, and 48% yields, respectively. Under flash vacuum pyro-
lysis conditions, the cycloadducts 15−17 underwent thermal
rearrangement with opening of the four-membered ring, to
cycloadditions of phenyl- (9), pyridyl- (10), and the newly afford the spirocyclopropanated azepinones 21−23 in 32, 30,
prepared (four steps, 43% overall yield) spirocyclic nitrone and 19% yields, respectively. In the case of 17, the indolizidi-
11 onto 7 resulted in the regioselective formation of the cor- none 25 was also isolated (13% yield). Mechanistically this
responding adducts 15−17, with the spirobutane moieties
adjacent to the oxygen atom in the oxazolidine rings, in 52,
rearrangement is interpreted in terms of a cyclobutylmethyl-
to-penten-5-yl radical rearrangement.
Introduction
Highly strained alkenes, such as those containing an exo-
cyclic double bond on a small ring, have attracted the at-
tention of researchers because of their peculiar structural
features and reactivities.[1,2] The high strain energies that
characterize these molecules confer high reactivities to-
wards many cyclophiles in various addition reactions.[3] In
recent years we have shown how highly strained methylene-
cyclopropanes readily undergo 1,3-dipolar cycloadditions
with nitrones, affording spirocyclopropane-isoxazolidines A
(Scheme 1).[4] The presence of residual strain in such com-
pounds, together with the weak NϪO bond adjacent to one
of the spirocyclopropane rings, makes further elaboration
of these substrates possible by simple thermal treatment,
to yield spirocyclopropane-annulated pyridones as the main
products.[4] The same overall result can also be achieved
more conveniently by performing the 1,3-dipolar cycloaddi-
tion at a higher temperature directly.
Scheme 1. Thermal transformations of spirocyclopropane-isoxazol-
idines A
Some of these compounds alkylate DNA,[5] in a manner
reminiscent of the activity of natural sesquiterpenes of the
illudin[6] and ptaquiloside[7] families. Recently, some of
these pyridones have been transformed into octahydro-2-
pyrindine
derivatives
through
sequential
[‡]
Cyclopropyl Building Blocks for Organic Synthesis, 72. Ϫ Part
WittigϪHornerϪEmmons olefination and vinylcyclopro-
pane-to-cyclopentene rearrangement.[8] Here we present an
extension of the basic methodology to the synthesis of spir-
ocyclopropane-annulated azepinones, based on the cycload-
dition of nitrones to cyclobutylidenecyclopropane (7), pre-
pared according to a new procedure more convenient than
those reported previously.
71: A. de Meijere, S. I. Kozhushkov, D. Faber, V. Bagutskii,
R. Boese, T. Haumann, R. Walsh, Eur. J. Org. Chem. 2001,
3607Ϫ3614. Ϫ Part 70: S. Löhr, A. de Meijere, Synlett 2001,
489Ϫ492.
Institut für Organische Chemie der Georg-August-Universität
Göttingen,
Tammannstrasse 2, 37077 Göttingen, Germany
Fax: (internat.) ϩ 49-(0)551/399475
E-mail: Armin.deMeijere@chemie.uni-goettingen.de
Institut für Anorganische Chemie der UniversitätϪGH Essen,
Universitätstrasse 3Ϫ5, 45117 Essen, Germany
[a]
[b]
[c]
Dipartimento di Chimica Organica ‘‘U. Schiff’’, and Centro di Results and Discussion
Studio sulla Chimica e la Struttura dei Composti Eterociclici e
`
loro Applicazioni, C.N.R., Universita di Firenze,
The most practical previous synthesis of cyclobutylidene-
cyclopropane (7) on a preparative scale was by Wittig
Via G. Capponi 9, 50121 Firenze, Italy
E-mail: brandi@chimorg.unifi.it
Eur. J. Org. Chem. 2001, 3789Ϫ3795
WILEY-VCH Verlag GmbH, 69451 Weinheim, 2001
1434Ϫ193X/01/1020Ϫ3789 $ 17.50ϩ.50/0
3789

A. de Meijere et al.
FULL PAPER
olefination of cyclobutanone with the ylide generated from
cyclopropyltriphenylphosphonium bromide.[9] This route,
although affording 7 in good yield, suffered from the neces-
sity of using starting materials that were either not readily
available or expensive.[10] A new, alternative synthesis of 7
starts from commercially available ethyl cyclobutanecarb-
oxylate (4), adopting a strategy previously developed for the
synthesis of bicyclopropylidene (Scheme 2).[11]
Scheme 3. Preparation of the nitrone 11: a) CrO3, H2SO4, 20 °C,
12 h; b) (CH2OH)2, Me3SiCl, 20 °C, 24 h; c) NH2OH·HCl, Et3N,
80 °C, 4 h; d) HgO, CH2Cl2, 20 °C, 4 h
Scheme 2. Preparation of cyclobutylidenecyclopropane: a) EtMgBr,
Ti(iPrO)4, Et2O, 20 °C, 3 h; b) TsCl, Py, 0Ϫ5 °C, 7 d; c) tBuOK,
DMSO, 20 °C, 2 d
On application of Kulinkovich reaction conditions,[12] the
ester 4 was transformed almost quantitatively into 1-cyclo-
butylcyclopropanol (5).[13] The alcohol 5 was converted into
its tosylate 6, which was dehydrotosylated with potassium
tert-butoxide in DMSO. After 2 d at ambient temperature,
a mixture of the methylenecyclopropane 7 and the isomeric
1-cyclopropylcyclobutene (8), in a ratio of 8:1, was isolated
in 52% yield. Prolonged (2 d) stirring of this mixture of 7
and 8 under these conditions resulted in complete isomeriz-
ation, and 1-cyclopropylcyclobutene (8) was obtained as a
single product in 56% yield, or 30% yield from 6. Cyclobu-
tylidenecyclopropane (7) prepared by this route may, how-
ever, be used for many synthetic purposes without separa-
tion from 8,[14] and this new method is thus significantly
more convenient than those reported previously (cf. ref.[9]).
The reactions between cyclobutylidenecyclopropane (7)
and nitrones 9؊11 provided the isoxazolidines 15؊17 in
moderate to good yields (48Ϫ84%). All three reactions pro-
ceeded with a high degree of regioselectivity, each affording
the corresponding 5-spirocyclobutaneisoxazolidine as a
single product. Structure assignment was possible on the
basis of the 13C NMR spectra, because all compounds
showed a signal typical of the isoxazolidine quaternary car-
bon atom adjacent to the oxygen atom at δ ϭ 84Ϫ85. This
signal was assigned to the carbon atom in the cyclobutane
ring, because it appeared at least 15 ppm downfield from
the analogous carbon signal of a spirocyclopropane group
in a corresponding product from bicyclopropylidene.[18]
This high regioselectivity is in accordance with results previ-
ously observed in 1,3-dipolar cycloadditions to methylene-
cyclopropane (18)[18] and methylenecyclobutane (19).[19]
While methylenecyclopropane (18) yields mixtures of 4- and
5-substituted isoxazolidines, methylenecyclobutane (19) ex-
clusively affords 5-spirocyclobutane-isoxazolidines.[19]
1,3-Dipolar cycloadditions onto 7 were performed with
the three model nitrones 9, 10, and 11. Nitrones 9 and 10[15]
were chosen as simple, open-chain nitrones, with 10 af-
fording a higher hydrophilicity in the final product. Nitrone
To explain observed regioselectivity in a 1,3-dipolar
11, not known in the literature, was prepared in four steps cycloaddition, it is usual to consider the HOMOϪLUMO
from commercially available 1,4-dibromobutan-2-ol (12) interactions of the dipole and the dipolarophile and the
(Scheme 3). Oxidation of 12 and protection of the ketone magnitudes of the atomic coefficients at the terminal posi-
as an ethylene acetal 13, followed by cyclizing nucleophilic tions of the reagents.[20] The HOMO and LUMO energies
substitution[16] to yield N-hydroxypyrrolidine 14 and sub- and atomic orbital coefficients for compounds 7, 18, 19,
sequent oxidation with mercuric oxide afforded the nitrone and pyrroline N-oxide (20) as a model nitrone were calcu-
11 in 28% overall yield. The presence of the dioxolane lated by ab initio (up to the STO 6-311G level) and DFT
group apparently induces the oxidation to proceed regiose- methods (LSDA/VWN/DN level[21]), using the SPARTAN
lectively, to afford a single regioisomer.[17]
program package.[22] According to these data, however, the
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Cyclobutylidenecyclopropane: New Synthesis and Use in 1,3-Dipolar Cycloadditions
FULL PAPER
Figure 1. Structure of cyclobutylidenecyclopropane (7) in the crystal[23] (the bond lengths and standard deviations are given in A) and
two possible transition structures for the 1,3-dipolar cycloaddition of a nitrone to 7
˚
observed regioselectivities cannot be justified by more fav-
orable frontier orbital interactions, as demonstrated by the
calculated values of ∆E between the frontier orbitals of the
alkenes 18, 19 and the nitrone 20. Moreover, the polariza-
tion of atomic orbitals in the HOMOs and LUMOs of al-
kenes 7, 18, and 19, although indicating the correct regiose-
lectivity, appears too small to be significant.
The experimentally observed results might be attributable
to the greater steric bulk of the planar or slightly puckered
cyclobutyl, relative to the cyclopropyl group with its smaller
bond angle, which might favor an approach of 7 with its
cyclobutyl group towards the sterically less congested oxy-
gen end of the nitrone, as in transition structure B in Fig-
ure 1. To test this interpretation, the structure of 7 was de-
termined by an X-ray crystal structure analysis (Fig-
ure 1).[23] The cyclobutane ring did indeed turn out to be
only very slightly puckered, with dihedral angles between
the planes defined by C1, C2, C3 and C1, C2A, C3 and
between the planes defined by C2, C1, C2A and C2, C3,
C2A of 5.3 and 5.4°, respectively. The four carbon atoms
Scheme 4. Thermal rearrangements of isoxazolidines 15Ϫ17 and
mechanistic interpretation: a) FVT, 600 °C, 10Ϫ3 mbar
C2, C2A, C5, and C5A and C1, C4 of the double bond are
almost completely coplanar (the interplanar angle between
C2, C1, C2A and C5, C4, C5A is only 2.6°). Nevertheless,
the difference in energies between the two different trans-
ition states B and C (Figure 1), but with a planar four-mem-
Analysis of the crude reaction mixtures revealed only the
bered ring, related to the two possible regioisomeric prod- expected azepinones 21 and 22 for substances 15 and 16.
ucts, was computed (at the STO 3G level of theory) as The rearrangement process, analogously to that proposed
∆Ea ϭ 1.8 kcal·molϪ1. Assuming that the preexponential for the cyclopropane-annulated substituted isoxazolid-
factors in the Arrhenius equations for both cycloaddition ines,[18] starts with the homolytic cleavage of the NϪO bond
directions are identical, a ∆Ea of 1.8 kcal·molϪ1 would and is followed by the opening of the adjacent small ring
correspond to rate coefficients ratio of kB/kC ഠ 11.4 at 100 in the intermediate diradical 26 to give 27, which eventually
°C (373.15 K).
closes to form the seven-membered ring (Scheme 4).
Thermal rearrangements of the isoxazolidines 15Ϫ17 Whereas the thermal rearrangement of simple 5-spirocyclo-
could only be effected under conditions much harsher than butane-isoxazolidines also resulted in the formation of
those used for the corresponding spirocyclopropane-annu- open-chain products,[18] due to the concomitant shift of one
lated analogs.[18] Upon flash vacuum thermolysis of 15Ϫ17 hydrogen atom in the intermediate diradical, the crude reac-
at 600 °C and 10Ϫ3 mbar, the azepinones 21Ϫ23[19] were tion mixtures from 15 and 16 did not contain any products
obtained, but accompanied by considerable amounts of de- of low molecular mass other than 21 and 22, respectively.
composition products (Scheme 4).
This may be attributed to the presence of the spirocyclopro-
Eur. J. Org. Chem. 2001, 3789Ϫ3795
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A. de Meijere et al.
FULL PAPER
CaH2. All other chemicals were used as commercially available
pane group, which reduces the rotational freedom of the
1,7-diradical carbon skeleton in 27, favoring ring-closure,
as also observed in previous examples.[4]
˜
(Merck, Acros, BASF, Bayer, Hoechst, Degussa AG, and Hüls
AG). Organic extracts were dried with MgSO4.
However, the crude pyrolysate obtained from compound
17 contained not only the expected azepinone derivative 23
(19%), but also a noncyclized product (16%) identified as
1-Cyclobutylcyclopropanol (5): Ethylmagnesium bromide (0.980
mol, 276 mL of a 3.55  solution in Et2O) was added over a period
of 3 h to a well-stirred solution of ethyl cyclobutanecarboxylate
the pyrroline derivative 24, together with the indolizidinone (4)[10c] (56.47 g, 0.441 mol) and titanium tetraisopropoxide
1
(26.3 mL, 88.2 mmol, 20 mol %) in anhydrous diethyl ether
(200 mL). The temperature was maintained between 20 and 25 °C
with a water bath. After the addition was complete, the mixture was
stirred for an additional 0.5 h at the same temp. and then cooled to
Ϫ5 °C. The reaction was quenched by careful addition of ice-cold
10% aqueous sulfuric acid (500 mL) while the temperature was
maintained between Ϫ5 and 0 °C with an acetone/dry ice bath. The
mixture was stirred at 0 °C for an additional 1 h, and the inorganic
phase was extracted with Et2O (100 mL). The combined ethereal
phases were washed with saturated NaHCO3 (2 ϫ 200 mL) and
25 (13%). The indolizidinone 25 was identified from its H
NMR spectrum, which showed a doublet at δ ϭ 1.21 for
the methyl group, and its 13C NMR spectrum, with all sig-
nals in agreement with the proposed structure. The forma-
tion of these two side products can be explained by assum-
ing an isomerization of the diradical 27 to 28 by means of
a 1,2-H shift and a subsequent 1,5-H shift to give 24, or
ring-closure to 25. Alternatively, 24 might be formed dir-
ectly from 27 through a 1,6-H shift (Scheme 4). The differ-
ence between the reaction mode of compound 17 and that brine (200 mL), dried, and concentrated under water-aspirator va-
cuum at 20 °C to give 48.92 g (99%) of 1-cyclobutylcyclopropanol.
of compounds 15 and 16 must be associated with the pres-
ence of the additional rings in the skeleton. These may ham-
per the closure of the seven-membered ring even more than
usual, due to additional geometric restraints in the diradical
intermediate. Isomerization processes can therefore com-
pete with the cyclization of the original diradical 27. This
Its spectroscopic data are identical to those reported.[12]
1-Cyclobutyl-1-(p-tolylsulfonyloxy)cyclopropane (6): p-Toluenesul-
fonyl chloride (87.32 g, 0.458 mol) was added in portions at 0 °C
to a solution of the alcohol 5 (48.92 g, 0.436 mol) in anhydrous
pyridine (500 mL). The resulting mixture was kept at 5 °C for 7 d,
type of radical isomerization of 27, producing 25, is unpre- diluted with ice-cold water (1000 mL), and extracted with dichloro-
methane (3 ϫ 300 mL). The combined organic phases were washed
with 5% HCl solution (400 mL), saturated NaHCO3 (2 ϫ 200 mL),
and brine (200 mL), dried, and concentrated under reduced pres-
sure to give 6 (98.94 g, 85%) as a light brown solid, which was used
without further purification. An analytical sample was purified by
column chromatography on silica gel (eluent hexane/Et2O, 4:1) and
then recrystallized from Et2O, m.p. 46Ϫ47 °C, Rf ϭ 0.38. Ϫ 1H
NMR: δ ϭ 0.74 and 1.04 (m, 4 H, CH2, cy-Pr), 1.49Ϫ1.96 (m, 6
H, CH2, cy-Bu), 2.43 (s, 3 H, CH3), 3.08Ϫ3.22 (m, 1 H, CH, cy-
Bu), 7.30 (d, J ϭ 8.2 Hz, 2 H, C6H4), 7.74 (d, J ϭ 8.2 Hz, 2 H,
C6H4). Ϫ 13C NMR: δ ϭ 8.43 (2 CH2), 17.30 (CH2), 21.57 (CH3),
24.93 (2 CH2), 37.87 (CH), 69.89 (C), 127.31, 129.59 (2 CH),
135.70, 144.29 (C). Ϫ MS (EI): m/z (%) ϭ 266 (0.1) [Mϩ], 155
(50) [C7H7O2Sϩ], 139 (14) [C7H7OSϩ], 91 (78) [C7H7ϩ], 83 (100)
[C5H7Oϩ], 65 (17) [C5H5ϩ], 55 (94) [C5H7Oϩ Ϫ CO]. Ϫ C14H18O3S
(266.40): calcd. C 63.13, H 6.81; found C 63.18, H 6.87.
cedented in the thermal rearrangements of spiroisoxazolid-
ines.[24]
Conclusion
The novel cycloaddition-rearrangement process with
cyclobutylidenecyclopropane (7) constitutes a straightfor-
ward approach, albeit with modest overall yields, to highly
substituted azepinones characterized by an α-oxospirocy-
clopropane moiety. Since this reactive unit has been found
to be important for biological activity,[5] or as a starting
point for further synthetic elaboration,[8] the overall strat-
egy can now be extended to the introduction of seven-mem-
bered rings into more complex heterocyclic structures.
Cyclobutylidenecyclopropane (7) and 1-Cyclopropylcyclobutene (8):
The tosylate 6 (88.43 g, 0.332 mol) was added in portions to a
solution of potassium tert-butoxide (44.66 g, 0.398 mol) in DMSO
(0.5 L). The temperature was maintained between 20 and 25 °C
with an ice bath, and the resulting solution was then stirred for
24 h under nitrogen in the closed apparatus at ambient temp. After
this, all the volatile material was ‘‘bulb-to-bulb’’ distilled into a cold
trap under reduced pressure (0.1 Torr), at ambient flask temp. The
residue was stirred under the same conditions for an additional
24 h, and the ‘‘bulb-to-bulb’’ distillation procedure was repeated.
The combined contents of the cold trap were washed with ice-cold
water, saturated NH4Cl solution, and brine (100 mL each), dried,
and distilled directly from MgSO4 under reduced pressure to give
a mixture of 7 and 8 (16.15 g, 52%) in a ratio of 8:1, according to
the 1H NMR spectrum, b.p. 54Ϫ59 °C (110 mbar). The spectro-
scopic data of 7 and 8 were identical to those reported.[9a,9b]
Experimental Section
General Remarks: All operations were carried out under an inert
gas. Ϫ 1H and 13C NMR spectra were recorded at 200 or 250 MHz
(1H) and 50.3 or 62.9 MHz [13C, additional DEPT (Distortionless
Enhancement by Polarization Transfer)] with Varian Gemini or
Bruker AM 250 spectrometers, respectively, in CDCl3 solution un-
less otherwise stated; δ in ppm, TMS as internal reference. Ϫ IR:
PerkinϪElmer 881 spectrophotometer, measured as KBr pellets or
as oils between KBr plates. Ϫ Mass spectra (EI): QMD 1000 Carlo
Erba instrument, by GC or direct inlet (70 eV); (CI): Finnigan
MAT 95 spectrometer (70 eV).
Ϫ
Elemental analyses:
PerkinϪElmer 240 C or PerkinϪElmer 2400 instruments. Ϫ Rf
values refer to TLC on 0.25 mm precoated silica gel plates (Merck
F254) with the same eluent as used for the separation of the com-
pound by flash column chromatography. Ϫ Melting points (m.p.):
Büchi 510 capillary melting point apparatus, values uncorrected. Ϫ
Anhydrous diethyl ether and toluene were obtained by distillation
from sodium benzophenone ketyl, pyridine and DMSO from
2-(2-Bromoethyl)-2-(bromomethyl)-1,3-dioxolane (13): A solution of
CrO3 (4.57 g, 45.7 mmol) and 96% H2SO4 (8.5 mL) in water
(62 mL) was added dropwise with ice-bath cooling to a solution of
1,4-dibromobutan-2-ol (12) (3.0 g, 13 mmol) in acetone (150 mL).
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Cyclobutylidenecyclopropane: New Synthesis and Use in 1,3-Dipolar Cycloadditions
FULL PAPER
The reaction mixture was stirred overnight at ambient temp., then
NMR: δ ϭ 0.10Ϫ0.22 (m, 1 H, cy-Pr), 0.36Ϫ0.41 (m, 1 H, cy-Pr),
diluted with water (250 mL), and extracted with CH2Cl2 (2 ϫ 0.53Ϫ0.61 (m, 1 H, cy-Pr), 0.84Ϫ0.98 (m, 1 H, cy-Pr), 1.33Ϫ1.44
100 mL). The organic phase was washed with brine, dried with
Na2SO4, and concentrated to afford crude 1,4-dibromobutan-2-
one, which was used without further purification.[25] Trimethylsilyl
chloride (0.57 mL, 4.48 mmol) was added under nitrogen to a solu-
(m, 1 H, cy-Bu), 1.83Ϫ2.01 (m, 1 H, cy-Bu), 2.04Ϫ2.22 (m, 2 H,
cy-Bu), 2.22Ϫ2.43 (m, 2 H, cy-Bu), 2.76 (s, 3 H, CH3), 3.60 (s, 1
H, CH), 7.23Ϫ7.31 (m, 5 H, C6H5). Ϫ 13C NMR: δ ϭ 6.6, 6.8
(CH2, cy-Pr), 13.5, 32.1, 33.7 (CH2, cy-Bu), 37.6 (C, cy-Pr), 44.4
tion of this ketone (3.37 g, 14.7 mmol) in anhydrous ethylene (CH3), 78.4 (CH), 84.4 (C, cy-Bu), 127.6, 128.0 (2 CH), 128.5 (CH),
glycol, and the resulting solution was stirred at ambient temper-
137.1 (C). Ϫ IR: ν ϭ 3069 cmϪ1, 2992, 2962, 1428, 1356, 1297,
˜
ature for 24 h. The reaction was quenched with a 5% NaHCO3 1220, 1139. Ϫ MS (EI): m/z (%) ϭ 229 (49) [Mϩ], 201 (100) [Mϩ
solution (100 mL) and the mixture was extracted with diethyl ether Ϫ C2H4], 158 (32), 118 (25), 91 (18), 77 (9) [C6H5ϩ]. Ϫ C15H19NO
(2 ϫ 100 mL). The organic phase was washed with brine (50 mL),
dried, and concentrated under reduced pressure. The crude product
was purified by filtration through a short pad of silica gel, eluting
with petroleum ether/diethyl ether (4:1), to afford 2.85 g (71%) of
(229.31): calcd. C 78.57, H 8.35, N 6.11; found C 78.75, H 8.34,
N 6.20.
9-Methyl-10-(2-pyridyl)-8-oxa-9-azadispiro[2.0.3.3]decane
(16):
Compounds 10 (0.816 g, 6 mmol) and 7 (0.846 g, 9 mmol) gave
1.16 g (84%) of 16 as a slightly yellow oil, Rf (CH2Cl2) ϭ 0.33. Ϫ
1H NMR: δ ϭ 0.03Ϫ0.14 (m, 1 H, cy-Pr), 0.45Ϫ0.54 (m, 1 H, cy-
Pr), 0.62Ϫ0.73 (m, 1 H, cy-Pr), 0.77Ϫ0.84 (m, 1 H, cy-Pr),
1.22Ϫ1.31 (m, 1 H, cy-Bu), 1.76Ϫ1.88 (m, 1 H, cy-Bu), 1.91Ϫ2.00
(m, 2 H, cy-Bu), 2.10Ϫ2.31 (m, 2 H, cy-Bu), 2.75 (s, 3 H, CH3),
3.81 (s, 1 H, CH), 7.16 (t, J ϭ 6.1 Hz, 1 H, C5H4N), 7.43 (d, J ϭ
7.5 Hz, 1 H, C5H4N), 7.60 (t, J ϭ 7.6 Hz, 1 H, C5H4N), 8.41 (d,
J ϭ 7.4 Hz, 1 H, C5H4N). Ϫ 13C NMR: δ ϭ 5.8, 7.5 (CH2, cy-Pr),
13.6, 32.5, 33.3 (CH2, cy-Bu), 37.2 (C, cy-Pr), 45.3 (CH3), 78.7
(CH), 84.8 (C, cy-Bu), 122.3, 122.9, 136.4, 148.5 (CH, C5H4N),
158.6 (C). Ϫ IR: ν˜ ϭ 3074 cmϪ1, 2991, 1684, 1433, 1263, 1137. Ϫ
MS (CI): m/z (%) ϭ 248 (1) [M ϩ NH4ϩ], 245 (6) [Mϩ ϩ 15], 231
(100) [M ϩ Hϩ]. Ϫ C14H18N2O (230.31): calcd. C 73.02, H 7.88,
N 12.16; found C 72.66, H 7.89, N 12.39.
1
the pure acetal 13 as a colorless oil, Rf ϭ 0.51. Ϫ H NMR: δ ϭ
2.49Ϫ2.36 (m, 2 H, CH2) 3.46Ϫ3.35 (m, 4 H, 2 CH2Br), 3.94Ϫ4.12
(m, 4 H, 2 CH2O). Ϫ IR: ν ϭ 2979 cmϪ1, 1425, 1346, 1290, 1217.
˜
Ϫ MS (EI): m/z (%) ϭ 181 (64), 179 (100), 167 (47), 121 (59), 107
(70), 55 (59). Ϫ C6H10Br2O2 (273.95): calcd. C 26.31, H 3.68; found
C 26.45, H 3.85.
1,4-Dioxa-7-azaspiro[4.4]nonan-7-ol (14): A solution of the acetal
13 (1.175 g, 4.29 mmol) and hydroxylamine hydrochloride (0.82 g,
11.8 mmol) in Et3N (10 mL) was heated under reflux for 4 h under
nitrogen. The resulting suspension was then concentrated under re-
duced pressure, and the residue was thoroughly washed with diethyl
ether (100 mL). The ethereal extract was concentrated, and the res-
idue purified by flash column chromatography, eluting with ethyl
acetate, to afford 0.256 g (41%) of pyrrolidine 14 as a slightly yellow
oil, Rf ϭ 0.28. Ϫ 1H NMR: δ ϭ 1.94Ϫ2.12 (m, 2 H, CH2),
3.03Ϫ3.15 (m, 4 H, 2 NCH2), 3.85 (br. s, 4 H, 2 OCH2). Ϫ 13C
NMR: δ ϭ 34.8 (CH2), 57.5, 66.8 (CH2N), 64.5 (2 CH2O), 114.8
Dispiro Compound 17: Compounds 11 (0.38 g, 2.6 mmol) and 7
(0.414 g, 4.4 mmol) gave 0.296 g (48%) of 17 as a slightly yellow
1
oil, Rf (CH2Cl2/CH3OH 15:1) ϭ 0.37. Ϫ H NMR: δ ϭ 0.51Ϫ0.59
(C). Ϫ IR: ν ϭ 2991 cmϪ1, 1356, 1215, 1090, 1010. Ϫ MS (EI): m/
˜
(m, 1 H, cy-Pr), 0.64Ϫ0.92 (m, 2 H, cy-Pr), 0.96Ϫ1.03 (m, 1 H, cy-
Pr), 1.11Ϫ1.29 (m, 1 H, cy-Bu), 1.55Ϫ1.97 (m, 3 H, cy-Bu),
2.11Ϫ2.34 (m, 4 H, cy-Bu ϩ CH2), 3.12 (s, 1 H, CH), 3.15Ϫ3.37
(m, 2 H, CH2N), 3.75Ϫ3.98 (m, 4 H, 2 CH2O). Ϫ 13C NMR: δ ϭ
4.5, 9.5 (CH2, cy-Pr), 13.0, 32.5, 33.9 (CH2, cy-Bu), 32.8 (C, cy-
Pr), 35.2 (CH2), 53.9 (CH3), 63.9, 65.4 (CH2O), 77.5 (CH), 85.2
z (%) ϭ 143 (10) [Mϩ Ϫ 2 H], 128 (27), 113 (46), 99 (63), 86 (78),
84 (100), 71 (37). Ϫ C6H11NO3 (145.16): calcd. C 49.65, H 7.64, N
9.65; found C 49.64, H 7.79, N 10.00.
1,4-Dioxa-7-azaspiro[4.4]non-6-ene N-Oxide (11): Yellow HgO
(5.06 g, 23.4 mmol) was added in one portion to an ice-cooled solu-
tion of N-hydroxypyrrolidine 14 (0.41 g, 2.8 mmol) in CH2Cl2
(12 mL). The resulting suspension was stirred at ambient temp. for
4 h, filtered through a short pad of Celite, and concentrated under
reduced pressure. The crude product was purified by filtration
through a short pad of silica gel, eluting with ethyl acetate/meth-
anol (10:1), to yield 0.39 g (96%) of nitrone 11 as a colorless solid,
(C, cy-Bu), 117.0 (C). Ϫ IR: ν ϭ 2992 cmϪ1, 2950, 1430, 1305,
˜
1263. Ϫ MS (EI): m/z (%) ϭ 122 (26), 109 (37), 99 (82), 94 (42),
86 (100), 84 (58), 80 (52), 67 (41), 55 (52). Ϫ C13H19NO3 (237.30):
calcd. C 65.80, H 8.07, N 5.90; found C 66.12, H 7.89, N 5.95.
Thermal Rearrangement of Adducts 15؊17. ؊ General Procedure
(GP) 2: The respective adducts 15Ϫ17 (0.5Ϫ1 mmol) were heated
at 100Ϫ120 °C under vacuum (10Ϫ3 mbar), and the vapors allowed
to pass through a quartz tube preheated to 600 °C by a furnace
(heating path length ca. 15 cm). The vapors were collected in a
liquid nitrogen cooled trap, as red-yellow oils. The crude reaction
mixture was separated by flash column chromatography.
1
Rf ϭ 0.34. Ϫ H NMR: δ ϭ 2.44Ϫ2.52 (m, 2 H, CH2), 3.97Ϫ4.01
(m, 6 H, 2 CH2O and CH2N), 6.82 (t, J ϭ 2.0 Hz, 1 H, ϭCH). Ϫ
13C NMR: δ ϭ 33.1 (CH2), 60.6 (NCH2), 65.3 (2 OCH2), 113.6
(C), 132.2 (ϭCH). Ϫ IR: ν˜ ϭ 2965 cmϪ1, 1584, 1350, 1309, 1102.
Ϫ MS (EI): m/z (%) ϭ 143 (21) [Mϩ], 115 (24) [Mϩ Ϫ C2H4], 113
(89) [Mϩ Ϫ NO], 85 (29), 84 (62), 83 (62), 71 (100), 55 (39), 53
(82). Ϫ C6H9NO3 (143.14): calcd. C 50.34, H 6.34, N 9.78; found
C 50.38, H 6.75, N 9.69.
5-Methyl-4-phenyl-5-azaspiro[2.6]nonan-9-one (21): Compound 15
(96 mg, 0.42 mmol) gave 31 mg (32%) of 21 as a slightly yellow oil,
1
Rf (CH2Cl2) ϭ 0.37. Ϫ H NMR: δ ϭ 0.71Ϫ0.79 (m, 1 H, cy-Pr),
1.25Ϫ1.37 (m, 2 H, cy-Pr), 1.44Ϫ1.53 (m, 1 H, cy-Pr), 2.05Ϫ2.22
(m, 1 H, CH2), 2.51Ϫ2.60 (m, 1 H, CH2), 2.62 (s, 3 H, CH3),
2.72Ϫ2.81 (m, 2 H, CH2), 2.84Ϫ2.95 (m, 1 H, CH2N), 3.15Ϫ3.23
(m, 1 H, CH2N), 3.83 (s, 1 H, CH), 7.21Ϫ7.48 (m, 5 H, C6H5). Ϫ
13C NMR: δ ϭ 16.1, 20.2 (CH2, cy-Pr), 21.7, 41.9, 50.7 (CH2), 31.2
(C, cy-Pr), 43.0 (CH3), 69.9 (CH), 127.2, 128.2 (2 CH), 128.5 (CH),
140.8, 213.1 (C). Ϫ IR: ν˜ ϭ 3054 cmϪ1, 2987, 1676, 1422. Ϫ MS
(EI): m/z (%) ϭ 229 (45) [Mϩ], 160 (45), 152 (62) [Mϩ Ϫ C6H5],
132 (82), 118 (69), 86 (81), 84 (100), 77 (54) [C6H5ϩ], 51 (86). Ϫ
1,3-Dipolar Cycloadditions of Nitrones 9؊11 to Cyclopropylidenecy-
clobutane (7). ؊ General Procedure (GP) 1: A solution of the re-
spective nitrone (2Ϫ6 mmol) and cyclobutylidenecyclopropane (7)
(1.5Ϫ1.7 equiv.) in toluene (5 mL) was heated in a sealed vial at
100 °C for 6 d. The solution was concentrated under reduced pres-
sure, and the crude product was purified by flash column chroma-
tography.
9-Methyl-10-phenyl-8-oxa-9-azadispiro[2.0.3.3]decane (15): Com-
pounds 9 (0.811 g, 6 mmol) and 7 (0.846 g, 9 mmol) gave 0.717 g C15H19NO (229.32): calcd. C 78.56, H 8.35, N 6.11; found C 78.66,
(52%) of 15 as a slightly yellow oil, Rf (CH2Cl2) ϭ 0.42. Ϫ 1H
H 8.08, N 6.36.
Eur. J. Org. Chem. 2001, 3789Ϫ3795
3793

A. de Meijere et al.
FULL PAPER
5-Methyl-4-(2-pyridyl)-5-azaspiro[2.6]nonan-9-one (22): Compound
the Bayer AG through generous gifts of chemicals. T. D. acknow-
16 (230 mg, 1 mmol) gave 69 mg (30%) of 22 as a slightly yellow ledges the receipt of a SOCRATES program student mobility sti-
1
oil, Rf (CH2Cl2/MeOH 40:1) ϭ 0.26. Ϫ H NMR: δ ϭ 0.63Ϫ0.67 pend. The authors are grateful to Dr. Burkhard Knieriem, Univer-
(m, 1 H, cy-Pr), 0.70Ϫ0.74 (m, 1 H, cy-Pr), 1.18Ϫ1.23 (m, 1 H, cy- sität Göttingen, for his careful proofreading of the final manu-
Pr), 1.42Ϫ1.46 (m, 1 H, cy-Pr), 1.55Ϫ1.62 (m, 1 H, CH2), script.
2.11Ϫ2.19 (m, 1 H, CH2), 2.57 (s, 3 H, CH3), 2.81 (t, J ϭ 6.8 Hz,
2 H, CH2), 2.90 (dt, J ϭ 3.8, 4.5 Hz, 1 H, CH2N), 3.06Ϫ3.12 (m,
1 H, CH2N), 3.88 (s, 1 H, CHN), 7.14Ϫ7.16 (m, 1 H, C5H4N), 7.47
(d, J ϭ 7.8 Hz, 1 H, C5H4N), 7.64 (td, J ϭ 1.8, 7.8 Hz, 1 H,
[1]
[1a] R. Gleiter, R. Haider, J.-M. Conia, J.-P. Barnier, A. de Mei-
C5H4N), 8.54Ϫ8.56 (m, 1 H, C5H4N). Ϫ 13C NMR: δ ϭ 15.6, 21.0
(CH2, cy-Pr), 32.2 (C, cy-Pr), 42.6 (CH3), 21.3, 42.9, 50.1 (CH2),
72.5 (CH), 122.5, 123.7, 136.6, 149.1 (CH), 160.5, 212.1 (C). Ϫ IR:
ν˜ ϭ 3058 cmϪ1, 2992, 2941, 1673, 1432. Ϫ MS (EI): m/z (%) ϭ 230
(4) [Mϩ], 202 (12) [Mϩ Ϫ C2H4], 174 (69) [Mϩ Ϫ CO Ϫ C2H4],
152 (31), 132 (51), 117 (16), 93 (16), 86 (63), 84 (100), 79 (15), 78
(24) [C5H4Nϩ], 70 (63). Ϫ MS (HR-EI): 230.1419 (C14H18N2O,
calcd. 230.1419).
jere, W. Weber, J. Chem. Soc., Chem. Commun. 1979, 130Ϫ132.
[1b]
Ϫ
M. Eckert-Maksic, Z. B. Maksic, A. Skancke, P. N.
Skancke, J. Phys. Chem. 1987, 91, 2786Ϫ2790. Ϫ [1c] M. Traet-
teberg, A. Simon, A. de Meijere, J. Mol. Struct. 1984, 118,
333Ϫ343.
[2]
[3]
Review: A. de Meijere, S. I. Kozhushkov, Chem. Rev. 2000,
100, 93Ϫ142.
Review: A. de Meijere, S. I. Kozhushkov, A. F. Khlebnikov,
Top. Curr. Chem. 2000, 207, 89Ϫ147.
[4] [4a]
Thermal Rearrangement of Adduct 17: Compound 17 (80 mg,
0.34 mmol) gave 15 mg (19%) of 23, 13 mg (16%) of 24, and 10 mg
(13%) of 25 as slightly yellow oils.
C. Zorn, A. Goti, A. Brandi, K. Johnsen, M. Noltemeyer,
S. I. Kozhushkov, A. de Meijere, J. Org. Chem. 1999, 64,
755Ϫ763. Ϫ [4b] B. Anichini, A. Goti, A. Brandi, S. I. Kozhush-
[4c]
kov, A. de Meijere, Chem. Commun. 1997, 261Ϫ262. Ϫ
A.
Spiro Compound 23: Rf (ethyl acetate/petroleum ether, 1:1) ϭ 0.23.
Goti, B. Anichini, A. Brandi, S. I. Kozhushkov, C. Gratkowski,
1
Ϫ H NMR: δ ϭ 0.66Ϫ0.73 (m, 1 H, cy-Pr), 0.99Ϫ1.07 (m, 1 H,
A. de Meijere, J. Org. Chem. 1996, 61, 1665Ϫ1672.
[5] [5a]
A. Goti, B. Anichini, A. Brandi, A. de Meijere, L. Citti, S.
cy-Pr), 1.12Ϫ1.28 (m, 1 H, cy-Pr), 1.34Ϫ1.47 (m, 1 H, cy-Pr),
1.83Ϫ1.99 (m, 4 H, 2 CH2), 2.52Ϫ2.65 (m, 2 H, CH2), 2.76 (s, 1
H, NCH), 2.69Ϫ2.86 (m, 2 H, CH2N), 3.00Ϫ3.12 (m, 2 H, CH2N),
3.82Ϫ3.96 (m, 4 H, 2 CH2O). Ϫ 13C NMR: δ ϭ 9.8, 17.6 (CH2,
cy-Pr), 31.8 (C, cy-Pr), 23.9, 35.4, 40.8, 50.8, 52.6, 63.9, 65.2 (CH2),
[5b]
Nevischi, Tetrahedron Lett. 1995, 36, 5811Ϫ5814. Ϫ
C.
Zorn, B. Anichini, A. Goti, A. Brandi, S. I. Kozhushkov, A.
de Meijere, L. Citti, J. Org. Chem. 1999, 64, 7846Ϫ7855.
T. Kushida, M. Uesugi, Y. Sugiura, H. Kigoshi, H. Tanaka,
J. Hirokawa, M. Ojika, K. Yamada, J. Am. Chem. Soc. 1994,
116, 479Ϫ486.
[6]
71.1 (CHN), 116.5, 211.3 (C). Ϫ IR: ν ϭ 2993 cmϪ1, 2979, 1686.
˜
Ϫ MS (EI): m/z (%) ϭ 237 (40) [Mϩ], 165 (38) [Mϩ Ϫ C3H4O2],
151 (100) [Mϩ Ϫ C4H6O2], 137 (50) [Mϩ Ϫ C3H4O2 Ϫ C2H4], 122
(39), 109 (75), 85 (71). Ϫ MS (HR-EI): 237.1364 (C13H19NO3,
calcd. 237.1361).
[7] [7a]
M. J. Kelner, T. McMorris, W. T. Beck, J. M. Zamora, R.
[7b]
Taetle, Cancer Res. 1987, 47, 3186Ϫ3189. Ϫ
M. J. Kelner,
T. C. McMorris, R. Taetle, J. Natl. Cancer Inst. 1990, 82,
[7c]
1562Ϫ1565. Ϫ
T. C. McMorris, M. J. Kelner, W. Wang,
L. A. Estes, M. A. Montoya, R. Taetle, J. Org. Chem. 1992,
57, 6876Ϫ6883.
1-[1-(1,4-Dioxa-7-azaspiro[4.4]non-6-en-6-yl)cyclopropyl]butan-1-
one (24): Rf (ethyl acetate/petroleum ether, 1:1) ϭ 0.51. Ϫ 1H
NMR: δ ϭ 0.87 (t, J ϭ 7.5 Hz, 3 H, CH3), 0.84Ϫ0.94 (m, 1 H, cy-
Pr), 1.22Ϫ1.34 (m, 3 H, cy-Pr), 1.52Ϫ1.63 (m, 2 H, CH2), 2.11 (t,
J ϭ 6.6 Hz, 2 H, CH2), 2.59 (t, J ϭ 7.4 Hz, 2 H, CH2), 3.88 (t, J ϭ
6.6 Hz, 2 H, CH2N), 3.94 (m, 4 H, 2 CH2O). Ϫ 13C NMR: δ ϭ
17.4 (CH3), 14.6 (2 CH2, cy-Pr), 29.7 (C, cy-Pr), 13.7, 35.5, 43.0,
[8]
A. Brandi, S. Cicchi, M. Brandl, S. I. Kozhushkov, A. de Mei-
jere, Synlett 2001, 433Ϫ435.
[9] [9a]
A. Maercker, V. E. E. Daub, Tetrahedron 1994, 50,
[9b]
2439Ϫ2458. Ϫ
C. J. M. van den Heuvel, A. Hofland, J. C.
van Velzen, H. Steinberg, Th. J. de Boer, J. R. Neth. Chem.
[9c]
Soc. 1984, 103, 233Ϫ240. Ϫ
N. S. Zefirov, K. A. Lukin, A.
Yu. Timofeeva, Zh. Org. Khim. 1987, 23, 2545Ϫ2548; J. Org.
˜
55.7 (CH2), 65.7 (2 CH2), 117.7, 174.6, 206.9 (C). Ϫ IR: ν ϭ 2964
Chem. USSR (Engl. Transl.) 1987, 23, 2246Ϫ2248.
cmϪ1, 1697, 1639. Ϫ C13H19NO3 (237.29) calcd. C 65.80, H 8.07,
[10] [10a]
Cyclobutanone is commercially available (at a cost of ca.
N 5.90; found C 65.62, H 8.25, N 5.54.
US$ 140.Ϫ per 5 g) or can be prepared in three steps from
1,3-dibromopropane; cf.: L. Fitjer, U. Quabeck, Synthesis 1987,
Spiro Compound 25: Rf (ethyl acetate/petroleum ether, 1:1) ϭ 0.23.
Ϫ H NMR: δ ϭ 0.79Ϫ0.81 (m, 1 H, cy-Pr), 0.99Ϫ1.03 (m, 1 H,
[10b]
299Ϫ300. Ϫ
Cyclopropyltriphenylphosphonium bromide
1
is commercially available (at a cost of ca. US$ 67.Ϫ per 25 g)
cy-Pr), 1.21 (d, J ϭ 6.7 Hz, 3 H, CH3), 1.23Ϫ1.26 (m, 1 H, cy-Pr),
1.29Ϫ1.33 (m, 1 H, cy-Pr), 1.87Ϫ1.96 (m, 2 H, CH2), 2.19 (dd, J ϭ
2.4, 17.5 Hz, 1 H, CH2), 2.56 (dd, J ϭ 12.2, 17.5 Hz, 1 H,
CH2), 2.72Ϫ2.75 (m, 1 H, CH2N), 2.98 (s, 1 H, CHN), 2.99Ϫ3.04
(m, 1 H, CH2N), 3.33Ϫ3.40 (m, 1 H, CH), 3.82Ϫ3.97 (m, 4 H, 2
CH2O). Ϫ 13C NMR: δ ϭ 10.4, 17.7 (CH2, cy-Pr), 19.0 (CH3), 30.1
(C, cy-Pr), 52.2, 69.3 (CH), 35.1, 43.2, 44.8 (CH2), 65.2 (2 CH2),
or can be prepared in two steps from 1,3-dibromopropane and
triphenylphosphane; cf.: A. Maercker, V. E. E. Daub, Tetrahed-
[10c]
ron 1994, 50, 2439Ϫ2458. Ϫ
Ethyl cyclobutanecarboxylate
is commercially available (at a cost of ca. US$ 120.Ϫ per 25 g)
or can be prepared in two steps from allyl bromide and diethyl
malonate; cf.: D. H. Hunter, V. Patel, R. A. Perry, Can. J.
Chem. 1980, 58, 2271Ϫ2277.
[11] [11a]
A. de Meijere, S. I. Kozhushkov, T. Spaeth, N. S. Zefirov,
115.5, 209.0 (C). Ϫ IR: ν ϭ 2928 cmϪ1, 1699, 1384. Ϫ C13H19NO3
˜
[11b]
J. Org. Chem. 1993, 58, 502Ϫ505. Ϫ
A. de Meijere, S. I.
(237.29) calcd. C 65.80, H 8.07, N 5.90; found C 66.02, H 8.34,
N 5.95.
Kozhushkov, T. Späth, Org. Synth. 2000, 78, 142Ϫ151.
[12]
[12a]
Reviews:
O. G. Kulinkovich, A. de Meijere, Chem. Rev.
[12b]
2000, 100, 2789Ϫ2834. Ϫ
B. Breit, J. Prakt. Chem. 2000,
[12c]
342, 211Ϫ214. Ϫ
F. Sato, H. Urabe, S. Okamoto, Chem.
Rev. 2000, 100, 2835Ϫ2886. Ϫ [12d] F. Sato, H. Urabe, S. Okam-
oto, Synlett 2000, 753Ϫ775.
Acknowledgments
This work was supported financially by Murst (Ministero dell’Uni-
[13]
[14]
J. Bargluenga, J. L. Fernandez-Simon, J. M. Concellon, M.
Yus, Synthesis 1987, 584Ϫ586.
Cyclobutylidenecyclopropane (7) can be separated from the by-
product 8 by preparative gas chromatography.
`
versita e la Ricerca Scientifica e Tecnologica Ϫ Cofin 2000), Italy,
and the Fonds der Chemischen Industrie, Germany, as well as by
3794
Eur. J. Org. Chem. 2001, 3789Ϫ3795

Cyclobutylidenecyclopropane: New Synthesis and Use in 1,3-Dipolar Cycloadditions
FULL PAPER
[15]
Nitrones 9 and 10 were synthesized by treatment of N-methyl-
hydroxylamine with the corresponding aldehydes. For a general
reference on nitrone syntheses see: D. Döpp, H. Döpp,
Methoden Org. Chem. (Houben-Weyl) 1990, vol. E 14b/part 2,
p. 1372Ϫ1544.
circle diffractometer, and the crystal formation detected using
graphite-monochromated Mo-Kα radiation. Correction for the
cylindrical shape of the crystals (0.3 mm diameter) was applied
for 7. The structure solutions and refinements on F2 were per-
formed with the Bruker AXS SHELXTL program suite (Ver-
sion 5.10). The hydrogen atoms were located in difference
Fourier maps and refined as riding groups with the 1.2-fold
isotropic displacement parameter of the corresponding C atom.
[16]
F. M. Cordero, F. Machetti, F. De Sarlo, A. Brandi, Gazz.
Chim. Ital. 1997, 127, 25Ϫ29.
[17] [17a]
A. Goti, S. Cicchi, V. Fedi, L. Nannelli, A. Brandi, J. Org.
[17b]
Chem. 1997, 62, 3119Ϫ3125. Ϫ
J. J. Tufariello, G. E. Lee,
C7H10 (94.15), monoclinic, a ϭ 4.0933(8), b ϭ 9.5034(18), c ϭ
3
˚
˚
J. Am. Chem. Soc. 1980, 102, 373Ϫ374.
A. Brandi, Y. Dürüst, F. M. Cordero, F. De Sarlo, J. Org.
Chem. 1992, 57, 5666Ϫ5670.
7.5436(15) A, β ϭ 91.876(5)°, V ϭ 293.29(10) A , Z ϭ 2, space
group P21/m, T ϭ 183(2) K, ρ ϭ 1.066 g cmϪ3, F(000) ϭ 104,
µ ϭ 0.059 mmϪ1, intensities measured: 742 (3.45° Յ θ Յ
28.22°), independent: 526 (Rint ϭ 0.0091), observed: 468 [Fo ϭ
4σ(F)], 38 parameters refined, R1 ϭ 0.0471, wR2 (final [I Ͼ
2σ(I)]) ϭ 0.1322, Goof ϭ 1.083, maximum residual electron
[18]
[19] [19a]
A. Brandi, F. M. Cordero, F. De Sarlo, R. Gandolfi, A.
[19b]
Rastelli, M. Bagatti, Tetrahedron 1992, 48, 3323Ϫ3334. Ϫ
A. Goti, A. Brandi, F. De Sarlo, A. Guarna, Tetrahedron 1992,
48, 5283Ϫ5300.
Ϫ3
˚
density 0.203 and Ϫ0.187
e
A
.
Crystallographic data
[20]
[21]
[22]
I. Fleming, Frontier Orbitals and Organic Chemical Reactions,
Wiley, London, 1976.
S. H. Vosko, L. Wilk, M. Nusair, Can. J. Phys. 1980, 58,
1200Ϫ1211.
Calculations were performed with the SPARTAN 5.1 package,
Wavefunction, Inc., 18401 Von Karman Ave., Ste. 370, Irvine,
CA 92612, USA.
Crystal Structure Determination of 7: The crystal of cyclobu-
tylidenecyclopropane (7) was grown in situ at 195 K with the
Optical Heating and Crystallization Device (OHCD), using a
miniature zone melting procedure with focused IR laser light
[R. Boese, M. Nussbaumer, in: Organic Crystal Chemistry (Ed.:
D. W. Jones), Oxford University Press, Oxford, 1994, pp.
20Ϫ37]. The device was mounted on a Nicolet R3m/V four-
(excluding structure factors) for the structures reported in
this paper have been deposited as supplementary publication
no. CCDC-162633 with the Cambridge Crystallographic
Data Centre. Copies of the data can be obtained free of
charge on application to CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK [Fax: (internat.) ϩ 44-1223/336-033; E-mail:
deposit@ccdc.cam.ac.uk].
[23]
[24] [24a]
A. Brandi, F. M. Cordero, F. De Sarlo, A. Goti, A. Gu-
[24b]
arna, Synlett 1993, 1Ϫ8. Ϫ
A. Goti, F. M. Cordero, A.
Brandi, Top. Curr. Chem. 1996, 178, 1Ϫ97.
J. R. Catch, D. F. Elliott, D. H. Hey, E. R. H. Jones, J. Chem.
Soc. 1948, 278Ϫ281.
[25]
Received April 26, 2001
[O01207]
Eur. J. Org. Chem. 2001, 3789Ϫ3795
3795