Prototropic Isomerization of 1-Oxaspiro[2.3]hexane-5-carbonitrile and Methyl 1-Oxaspiro[2.3]hexane-5-carboxylate into the Corresponding 3-Hydroxymethylbicyclo[1.1.0]butane-1-carboxylic Acid Derivatives

Article abstract of DOI:10.1023/A:1023434410844

Epoxy derivatives of 3-methylenecyclobutane-1-carbonitrile and methyl 3-methylenecyclobutane-1-carboxylate undergo isomerization into the corresponding 3-hydroxymethylbicyclobutane-1-carboxylic acid derivatives on treatment with lithium diisopropylamide in aprotic medium.

Full text of DOI:10.1023/A:1023434410844

Russian Journal of Organic Chemistry, Vol. 39, No. 1, 2003, pp. 33 39. Translated from Zhurnal Organicheskoi Khimii, Vol. 39, No. 1, 2003,
pp. 44 50.
Original Russian Text Copyright
2003 by Razin, Ulin.
Prototropic Isomerization of 1-Oxaspiro[2.3]hexane-
5-carbonitrile and Methyl 1-Oxaspiro[2.3]hexane-5-carboxylate
into the Corresponding 3-Hydroxymethylbicyclo[1.1.0]butane-
1-carboxylic Acid Derivatives*
V. V. Razin and N. V. Ulin
St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198904 Russia
Received July 10, 2002
Abstract Epoxy derivatives of 3-methylenecyclobutane-1-carbonitrile and methyl 3-methylenecyclobutane-
1-carboxylate undergo isomerization into the corresponding 3-hydroxymethylbicyclobutane-1-carboxylic acid
derivatives on treatment with lithium diisopropylamide in aprotic medium.
, -Epoxy sulfones, ketones, esters, and nitriles are
known [2] to undergo rearrangement into the corre-
sponding substituted cyclopropylcarbinols by the
action of bases. Gaoni [3] used this method of con-
struction of a three-membered carbon ring for the
synthesis of functionally substituted bicyclobutyl-
carbinols, starting from vinylcyclopropane derivatives
(Scheme 1).
C C bond is built up, so that the hydroxymethyl
group appears at the bridgehead position rather than
at the bridging carbon atom.
Scheme 2.
Scheme 1.
I, III, V, X = CN; II, IV, VI, X = CO2Me.
Let us consider each of the two steps of synthesis
of bicyclobutylmethanols I and II according to
Scheme 2. Initial methylenecyclobutanes III and IV
were converted into the corresponding spirooxiranes
V and VI in two ways (Scheme 3): (1) by successive
bromohydroxylation and dehydrobromination and
(2) by direct epoxidation. Bromohydroxylation of III
and IV was effected by the action of N-bromosuccin-
imide (NBS) in aqueous dioxane. In both cases, the
addition was highly regioselective (according to the
Markownikoff rule), and bromomethyl(hydroxy)cyclo-
butanes VII and VIII were obtained, respectively.
Each product was formed as an approximately equim-
olar mixture of two diastereoisomers: VIIa:VIIb =
1.28, VIIIa:VIIIb = 1.15. All diastereoisomers were
Following an analogous approach, in the present
work we made an attempt to synthesize bicyclobutyl-
carbinols with a different substitution pattern, namely
compounds I and II, on the basis of the methylene-
cyclobutane system (Scheme 2). As starting com-
pounds we used known 3-methylenecyclobutane-1-
carbonitrile (III) and methyl 3-methylenecyclobutane-
1-carboxylate (IV). Unlike Gaoni’s scheme, in our
case the central rather than the side bicyclobutane
____________
*
For preliminary communication, see [1].
1070-4280/03/3901-0033$25.00 2003 MAIK Nauka/Interperiodica

34
RAZIN, ULIN
Scheme 3.
V, VII, X = CN; VI, VIII, X = CO2Me.
isolated in the pure state by column chromatography
on silica gel.
figuration of substituted cyclobutane fragment does
not change during the dehydrobromination process.
1
Table 1 contains the H and 13C NMR spectral data
Direct epoxidation of methylenecyclobutanes III
and IV was performed in methylene chloride with
the system H2O2 CCl3CN, following the procedure
described in [5]. As a result, stereoisomeric mixtures
of spirooxiranes V and VI were obtained. The direct
epoxidation is characterized by higher diastereoselec-
tivity, as compared with the bromohydroxylation reac-
tion: the trans/cis ratio of the products was 19.0 for
nitrile V and 3.2 for ester VI. It should be noted that
epoxidation of cyclobutane III with m-chloroperoxy-
benzoic acid was less selective: the ratio of the trans
of compounds VIIa, VIIb, VIIIa, and VIIIb. For
comparison, the corresponding data are given for two
diastereoisomers of 3-hydroxy-3-methylcyclobutane-
1-carbonitrile (IXa and IXb) which were obtained
by hydroxymercuration hydrodemercuration of nitrile
III. These data ensure unambiguous assignment of the
structures of VII and VIII. Their configuration was
1
determined by comparing the H NMR spectra of
stereoisomers according to the recommendations of
[4]: compounds VIIa, VIIIa, and IXa were assigned
trans configuration, for their 1-H signal appears in
1
and cis isomers of nitrile V was 2.9. The H and 13C
a weaker field,
1-H(trans, cis)
0.4 ppm.
NMR spectra of compounds Va, Vb, and VIa, VIb
are given in Table 2. Here, the same arguments as
those underlying structure assignment of VII and VIII
are less convincing: 1-H(trans, cis) 0.2 ppm.
Isomerization of spiro epoxides Va, Vb, VIa, and
VIb into target bicyclobutylmethanols I and II was
effected by the action of 1.3 equiv of lithium diiso-
Nitriles VII were converted into spirooxiranes V
by treatment with potassium tert-butoxide, and ana-
logous transformation of esters VIII into epoxy
derivatives VI was effected by the action of sodium
hydride. The results of experiments with pure dia-
stereoisomers of VII and VIII showed that the con-
Table 1. 1H and 13C NMR spectra of substituted cyclobutanols VII IX
1H NMR spectrum, , ppm (J, Hz)
13C NMR spectrum, C, ppm
CH2Br
Comp.
no.
CH2Br
[CH3]
CN
1-H
2-H, 4-H
2.37 2.57
OH
OCH3
C1
C2, C4
37.7
C3
[CH3] [CO2CH3]
VIIa
3.16
3.60 s
3.10 br.s
3.17 br.s
13.9
72.2
42.4
122.0
quint (8)
VIIb
VIIIa
2.65 2.80 2.47 2.65
3.51 s
3.64 s
12.9
28.8
38.4
36.4
70.8
71.8
40.9
44.1
121.2
[175.7]
[51.9]
[175.0]
[51.9]
122.9
3.17
2.39 d (8)
2.67 br.s 3.69 s
quint (8)
VIIIb
2.59 2.78 2.33 2.45
3.55 s
3.35 br.s 3.67 s
28.4
37.4
70.0
42.2
IXa
IXb
3.05 3.19 2.34 2.56 [1.53 s] 2.25 br.s
2.59 2.71 2.34 2.56 [1.38 s] 2.25 br.s
14.1
12.7
40.8
42.2
71.9
69.7
[28.5]
[26.0]
121.9
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 1 2003

PROTOTROPIC ISOMERIZATION OF 1-OXASPIRO[2.3]HEXANE-5-CARBONITRILE
35
Table 2. 1H and 13C NMR spectra of substituted 1-oxaspiro[2.3]hexanes Va, Vb, VIa, and VIb
1H NMR spectrum, , ppm (J, Hz)
13C NMR spectrum, C, ppm
Comp.
no.
1-H
2-H, 4-H
CH2O
CH3O
C1
C2, C4
C3
CH2O CO2CH3 [CN]
Va
Vb
VIa
3.08 3.25
2.85 3.02 (3H), 2.67 2.83 (2H)
3.00 3.18 2.58 2.80
2.65 2.95
2.76 s
2.74 s
2.69 s 3.66 s
15.0
13.5
30.3
35.6
35.9
34.0
57.6
56.2
58.3
51.6
51.7
52.1
[122.1]
[121.0]
174.0
51.8
VIb
2.70 3.00 (3H), 2.36 2.55 (2H)
2.69 s 3.66 s
29.0
34.4
56.2
52.0
174.3
51.8
Table 3. 1H and 13C NMR spectra of substituted bicyclobutanes I, II, and X XIIIa
1H NMR spectrum, , ppm (J, Hz)
13C NMR spectrum, C, ppm
CH2O
Comp.
no.
endo-2-H, exo-2-H,
endo-4-Hb exo-4-Hb
CH2O
[CH3]
OH
[OCH3]
CN
C1
C2, C4
C3
[CH3]
[CO2CH3]
I
II
1.36
1.25
2.27
2.35
4.22 s
3.98 s
3.07 br.s
3.21 br.s
[3.65 s]
4.27 br.s
4.4
12.8
38.1
36.3
26.8
29.9
58.8
60.0
119.6
[51.8]
[172.2]
X
XI
XII
1.08
1.49
1.40
2.18
2.33
2.51
4.13 s
4.94 s
4.77 s
13.3
2.8
13.5
35.5
38.9
36.8
22.5
22.9
26.2
59.3
61.3
62.2
118.5
[171.1]
[51.9]
120.0
[3.65 s]
XIII
1.28
1.98
[1.72 s]
3.6
40.2
22.8
[12.4]
a
1
Other signals: H NMR, , ppm: X: 1.20 d (6H), 1.36 d (6H), 3.43 sept (1H), 4.75 sept (1H), CON[CH(CH3)2]2; XI: 7.40 7.65 (3H)
and 8.05 8.15 (2H) (PhCO); XII: 7.40 7.65 (3H) and 8.0 8.10 (2H) (PhCO); 13C NMR, C, ppm: X: 20.3, 20.7, 46.0, 50.3, 170.2
(CON[CH(CH3)2]2); XI: 128.3, 129.6, 133.2, 141.0, 165.8 (PhCO); XII: 128.2, 129.5, 133.0, 140.1, 165.8 (PhCO).
b
All 2-H and 4-H signals are broadened singlets.
propylamide in THF at 80 C. These conditions
ensured formation of compounds I and II as the only
products, regardless of configuration of the initial
epoxy derivative. With a larger excess of lithium
diisopropylamide, amide X was formed as by-product
in the two cases. The fraction of X was greater in the
reaction with ester VI. Each bicyclobutylmethanol, I
and II, was converted into the corresponding benzoyl
derivative (XI, X = CN; XII, X = CO2CH3).
of substituted bicyclobutane-1-carboxylic acid deriva-
tives I, II, XI XIII are characterized by upfield shift
of the C1 signal by about 15 ppm relative to the C1
signal in the spectra of respective cyclobutanecarbo-
xylic acid derivatives V IX. It should be emphasized
that the chemical shifts of C1 in nitriles I, XI, and
XIII have negative values.
1
Table 3 contains the H and 13C NMR spectral data
for bicyclobutane derivatives I, II, and X XII and
also the data reported in [6] for their known analog,
1
bicyclobutane XIII. The H NMR spectra charac-
teristically contain broadened singlets (2JHH 0 Hz)
from nonequivalent methylene protons of the bicyclo-
butane fragment; the corresponding difference in the
chemical shifts is about 1 ppm. The 13C NMR spectra
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 1 2003

36
RAZIN, ULIN
Taking into account the accessibility of nitrile III
Bromohydroxylation of 3-methylenecyclobutane-
1-carbonitrile (III). N-Bromosuccinimide, 2.7 g
(15 mmol), was added in small portions over a period
of 0.5 h to a solution of 1.4 g (15 mmol) of nitrile III
in 10 ml of aqueous dioxane (1:1) under continuous
stirring at 0 C. The cooling bath was removed, and
the mixture was stirred for 2 h at room temperature.
Diethyl ether, 30 ml, was added, and the organic layer
was separated, washed with water (3 10 ml), dried
over magnesium sulfate, and evaporated. The residue,
2.65 g, was a viscous liquid (yield 93%) consisting of
four components (according to the GLC data, 180 C);
below are given the retention time and the fraction
of each component: 1, 5.1 min, 50.0%; 2, 6.3 min,
5.5%; 3 9.0 min, 5.5%; 4 10.4 min, 39%. Components
1 and 4 were identified as compounds VIIa and VIIb,
respectively, and were separated by column chromato-
graphy on silica gel (the separation process was
monitored by GLC). Minor components 2 and 3 were
not isolated and identified. By analogy with the results
of bromomethoxylation of III and IV [13], these
products were tentatively assigned the structure of
diastereoisomeric anti-Markownikoff adducts (with no
regard to their configuration).
as the product of cycloaddition of acrylonitrile and
allene [7], the proposed procedure for synthesizing
bicyclobutylmethanols I and II on the basis of the
corresponding methylenecyclobutanes III and IV
according to Scheme 2 seems to be efficient and quite
reasonable. The key stage in this procedure, proto-
tropic isomerization of spirooxiranes V and VI into
bicyclobutanes I and II is irreversible, despite the
greater strain energy of the bicyclobutane system
(62.6 kcal/mol [8]), as compared to the 1-oxaspiro-
hexane system (56.7 kcal/mol [9]).
Scheme 4.
Presumably, the observed isomerization direction
(V, VI
I, II) is governed by the stage including
trans-3-Bromomethyl-3-hydroxycyclobutane-1-
carbonitrile (VIIa) (component 1). Viscous liquid.
Found, %: C 37.78, 37.93; H 4.39, 4.33; N 7.29, 7.24.
C6H8BrNO. Calculated, %: C 37.92; H 4.24; N 7.37.
transformation of carbanion A into alcoholate ion B;
the latter is more stable due to high electronegativity
of the oxygen atom. Aprotic medium and some excess
of a strong base are necessary conditions for the
cis-3-Bromomethyl-3-hydroxycyclobutane-1-
carbonitrile (VIIb) (component 4). mp 77 C. Found,
%: C 37.88, 37.90; H 4.35, 4.28; N 7.20, 7.34.
C6H8BrNO. Calculated, %: C 37.92; H 4.24; N 7.37.
process to be controlled by the transformation A
B
(Scheme 4).
EXPERIMENTAL
1
The H and 13C NMR spectra of nitriles VIIa and
The 1H and 13C NMR spectra of solutions in CDCl3
were recorded on a Bruker AM-200 spectrometer.
GLC analysis was performed on a Tsvet-101 chrom-
atograph equipped with a flame-ionization detector;
carrier gas nitrogen, flow rate 30 ml/min; glass
column, 2000 3 mm; stationary phase 3% of OV-17
on Inerton Super (0.16 0.2 mm). Silufol UV-254
plates were used for thin-layer chromatography; eluent
hexane ethyl acetate, 1:1. Column chromatography
was performed on silica gel L 40/100 m.
3-Methylenecyclobutane-1-carbonitrile (III), bp 65
66 C (21 mm), n2D0 1.4615 [7], methyl 3-methylene-
cyclobutane-1-carboxylate (IV), bp 57 60 C (20 mm),
n2D0 1.4490 [10], and 3-methylbicyclobutane-1-carbo-
nitrile (XIII) [6] were synthesized by known methods.
Potassium tert-butoxide was prepared as described in
[11], and butyllithium was obtained by the procedure
reported in [12].
VIIb are given in Table 1.
Bromohydroxylation of methyl 3-methylene-
cyclobutane-1-carboxylate (IV). N-Bromosuccin-
imide, 1.78 g (10 mmol), was added in small portions
over a period of 0.5 h to a solution of 1.26 g
(10 mmol) of ester IV in 8 ml of aqueous dioxane
(1:1) under continuous stirring at 0 C. The cooling
bath was removed, and the mixture was stirred for 1 h
at 20 C, diluted with 20 ml of water, and extracted
with diethyl ether (3 15 ml). The combined extracts
were washed with water (2 10 ml) and dried over
MgSO4. Removal of the solvent gave 2.1 g (94%) of
a product which, according to the GLC data (160 C),
was a mixture of four substances. Below are given
their retention times and fractions in the mixture: 1,
4.1 min, 50%; 2, 5.0 min, 3.0%; 3, 6.0 min, 3.5%;
4, 6.7 min, 43.5%. By column chromatography on
silica gel (under GLC monitoring), components 1
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 1 2003

PROTOTROPIC ISOMERIZATION OF 1-OXASPIRO[2.3]HEXANE-5-CARBONITRILE
37
(VIIIa) and 4 (VIIIb) were separated from minor
products 2 and 3.
Methyl trans-3-bromomethyl-3-hydroxycyclo-
butane-1-carboxylate (VIIIa) (component 1).
Viscous liquid. Found, %: C 37.91, 37.63; H 5.03,
5.15. C7H11BrO3. Calculated, %: C 37.69; H 4.97.
of 95:5 (GLC). bp 69 72 C (8 mm). Found, %:
C 66.29, 65.95; H 6.31, 6.52; N 12.71, 12.65.
C6H7NO. Calculated, %: C 66.04; H 6.47; N 12.84.
b. A solution of 2.60 g (12 mmol) of 80%
m-chloroperoxybenzoic acid in 60 ml of CH2Cl2 was
stirred for 30 min at 10 C. The precipitate of
m-chlorobenzoic acid was filtered off, and the filtrate
was added dropwise at 0 C to a solution of 0.93 g
(10 mmol) of nitrile III in 20 ml of CH2Cl2. The
mixture was stirred for 1 h at room temperature and
cooled to 15 C, the precipitate was filtered off, and
the filtrate was washed in succession with a 5% solu-
tion of sodium sulfite, a saturated solution of sodium
hydrogen carbonate, and water. It was then dried over
MgSO4 and evaporated to obtain 0.73 g (67%) of
Methyl cis-3-bromomethyl-3-hydroxycyclo-
butane-1-carboxylate (VIIIb) (component 4).
mp 58 C. Found, %: C 37.65, 37.85; H 4.91, 5.09.
C7H11BrO3. Calculated, %: C 37.69; H 4.97.
1
The H and 13C NMR spectra of esters VIIIa and
VIIIb are given in Table 1.
3-Hydroxy-3-methylcyclobutane-1-carbonitrile
(IXa/IXb). A solution of 4.15 g (13 mmol) of mer-
cury acetate in 30 ml of aqueous tetrahydrofuran (1:1)
was added with stirring to a solution of 1.2 g
(13 mmol) of nitrile III in 20 ml of a 2:1 THF H2O
mixture. The mixture was stirred for 18 h at room
temperature, 30 ml of a 6M aqueous solution of
NaOH and 0.75 g (20 mmol) of NaBH4 were added
in succession, and the mixture was stirred for 1 h.
It was then filtered, and the filtrate was extracted with
diethyl ether (3 30 ml). The combined extracts were
dried over MgSO4 and evaporated, and the residue
was distilled under reduced pressure. Yield 0.54 g
(38%). bp 85 C (2 mm). The product was a mixture
of diastereoisomers IXa and IXb at a ratio of 1.7:1
1
epoxy nitrile V. According to the H NMR data, the
product was a mixture of diastereoisomers Va and Vb
at a ratio of 2.9:1.
Epoxidation of ester (IV). Methyl trans- and cis-
1-oxaspiro[2.3]hexane-5-carboxylates VIa and VIb.
Following the above procedure (method a), from
1.26 g (10 mmol) of ester IV and 2.9 g (20 mmol) of
trichloroacetonitrile in 20 ml of CH2Cl2 and 2.5 ml
of 30% hydrogen peroxide (pH 7 8) we obtained
1.10 g (77%) of a mixture of epoxy esters VIa and
VIb at a ratio of 3.2:1 (1H NMR). bp 71 74 C
(12 mm). Found, %: C 59.20, 58.89; H 7.01, 6.95.
C7H10O3. Calculated, %: C 59.14; H 7.09.
1
(according to the H NMR data). Found, %: C 64.68,
Dehydrobromination of compounds VIIa and
VIIb. Potassium tert-butoxide, 1.2 mmol, was added
to a solution of 1 mmol of nitrile VIIa or VIIb in
5 ml of dry ether. The disappearance of the initial
compound was monitored by GLC. As a rule, it was
necessary to add 0.5 mmol more of potassium tert-
butoxide to complete the reaction. The reaction time
was about 3 h. The mixture was filtered through
a layer of silica gel using 1:1 pentane ether as eluent.
The eluate was dried over magnesium sulfate and
64.77; H 8.08, 8.21; N 12.45, 12.67. C6H9NO. Cal-
culated, %: C 64.84; H 8.15; N 12.60.
1
The H and 13C NMR spectra of nitriles IXa and
IXb, given in Table 1, were derived from the spectra
of their mixture.
Epoxidation of nitrile (III). trans- and cis-1-Oxa-
spiro[2.3]hexane-5-carbonitriles Va and Vb. a. To
a solution of 0.93 g (10 mmol) of nitrile III and 2.9 g
(20 mmol) of trichloroacetonitrile in 15 ml of CH2Cl2,
while stirring at 20 C, we added dropwise 2 ml of
30% hydrogen peroxide preliminarily adjusted to
pH 7 by addition of potassium hydrogen phosphate.
The mixture was stirred for 2 h, and the disappearance
of initial nitrile III was monitored by GLC. Usually,
it was necessary to add 0.5 ml more of H2O2 to com-
plete the reaction. The mixture was diluted with
hexane (15 ml), and the precipitate of trichloroacet-
amide was filtered off and washed with hexane. The
filtrate was washed with water, a 3% solution of
Na2SO3, and water again. It was then dried over
MgSO4 and evaporated, and the residue was distilled
under reduced pressure to obtain 0.67 g (61%) of
a mixture of epoxy derivatives Va and Vb at a ratio
evaporated to obtain spectrally (1H NMR) pure prod-
1
ucts Va (yield 85%) and Vb (89%). Their H and
13C NMR spectra are given in Table 2.
Dehydrobromination of compounds VIIIa and
VIIIb. Sodium hydride, 40 mg (1.2 mmol), was
added to a solution of 1 mmol of compound VIIIa or
VIIIb in 10 ml of dry ether, and the mixture was
stirred at 20 C until the initial compound disappeared
completely. Usually, an additional amount of sodium
hydride (15 20 mg) was necessary. The yields of
epoxy esters VIa and VIb were 83 and 77%, respec-
1
tively. Their H and 13C NMR spectra are given in
Table 2.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 1 2003

38
RAZIN, ULIN
Methyl 3-hydroxymethylbicyclo[1.1.0]butane-1-
in 2 ml of dry ether was added, the cooling bath was
removed, and the mixture was stirred for 10 15 min
(TLC). Water, 10 ml, a saturated solution of ammo-
nium chloride, 5 ml, and ether, 10 ml, were added,
and the organic phase was separated, washed with
a solution of sodium chloride, and dried over MgSO4.
Removal of the solvent left 0.35 g (86%) of an oily
liquid which contained alcohol I and a small amount
(less than 5%) of amide X. Chromatographically and
spectrally pure alcohol I was obtained by purification
of the crude product by column chromatography on
silica gel. Colorless liquid, Rf 0.23. Using standard
technique [14], alcohol I was converted into benzoyl
derivative XI which was purified by recrystallization
from hexane ether.
carboxylate (II). A 0.58 M solution of butyllithium
in pentane (4 mmol, 6.8 ml) was added in small
portions through a syringe to a solution of 0.43 g
(4.2 mmol) of diisopropylamine (preliminarily dis-
tilled over NaH) in 5 ml of dry ether, stirred under
dry nitrogen at 78 C. The mixture was stirred for
30 min, gradually raising the temperature to 20 C.
A solution of 0.44 g (3.1 mmol) of epoxy derivative
VIa in 3 ml of dry ether was added, the cooling bath
was removed, and the mixture was stirred for 3 h.
It was then treated with 10 ml of a saturated solution
of ammonium chloride, the organic phase was se-
parated, and the aqueous phase was extracted with
ether (2 10 ml). The extracts were combined with
the organic phase, washed with a solution of sodium
chloride, and dried over magnesium sulfate. Removal
of the solvent left an oily residue, 0.37 g (84%),
3-Benzoyloxymethylbicyclobutane-1-carbonitrile
(XI). mp 69 C. Found, %: C 72.98, 73.08; N 5.17,
5.30; N 6.67, 6.77. C13H11NO2. Calculated, %:
C 73.22; H 5.20; N 6.57.
1
which (according to the TLC and H NMR data)
contained alcohol II, Rf 0.25, with an impurity ( 5%)
of amide X, Rf 0.37. Following a similar procedure
with the same reactant ratio, alcohol II was obtained
from epoxy ester VIb in 80% yield. Chromatogra-
phically and spectrally pure alcohol II was obtained
by purification of the crude product by column
chromatography on silica gel; colorless liquid,
Rf 0.25. Using the standard technique [14], alcohol II
was converted into benzoyl derivative XII which was
purified by flash chromatography on silica gel.
1
The H and 13C NMR spectra of compounds I, II,
and X XIII are given in Table 3.
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Methyl 3-benzoyloxymethylbicyclobutane-1-car-
boxylate (XII). Rf 0.63; viscous noncrystallizable
liquid. Found, %: C 68.09, 68.37; H 5.59, 5.67.
C14H14O. Calculated, %: C 68.28; H 5.73.
N,N-Diisopropyl-3-hydroxymethylbicyclobutane-
1-carboxamide (X). When the isomerization of epoxy
esters VIa and VIb (see above) was carried out using
a threefold excess of lithium diisopropylamide, the
product, apart from alcohol II (Rf 0.25), contained
an appreciable amount (15%) of amide X, Rf 0.37.
The latter was isolated by column chromatography on
silica gel. mp 71 C. Found, %: C 68.03, 68.18;
H 9.89, 10.11; N 6.48, 6.51. C12H21NO2. Calculated,
%: C 68.21; H 10.02; N 6.63.
3-Hydroxymethylbicyclo[1.1.0]butane-1-carbo-
nitrile (I). A 0.6 M solution of butyllithium in
pentane (5 mmol, 0.85 ml) was added in small
portions through a syringe to a solution of 0.51 g
(5 mmol) of anhydrous diisopropylamine in 10 ml of
dry ether, stirred at 78 C under dry nitrogen. The
mixture was stirred for 30 min, gradually raising
the temperature to 25 C. A solution of 0.43 g
(3.7 mmol) of a mixture of compounds Va and Vb
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PROTOTROPIC ISOMERIZATION OF 1-OXASPIRO[2.3]HEXANE-5-CARBONITRILE
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