Eleuthesides and their analogs: III. Reaction of Red-Al with γ,δ-epoxy nitriles

Article abstract of DOI:10.1134/S1070428013070051

Oxiranyl-substituted cycloalkenecarbonitriles obtained by the Beckmann fragmentation of oximes derived from levoglucosenone adducts with 1,3-butadiene, isoprene, cyclohexadiene, and cyclopentadiene were subjected to Red-Al reduction with opening of the ep

Full text of DOI:10.1134/S1070428013070051

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 7, pp. 986–994. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © Yu.A. Khalilova, O.Yu. Doronina, B.T. Sharipov, L.V. Spirikhin, F.A. Valeev, 2013, published in Zhurnal Organicheskoi Khimii,
2013, Vol. 49, No. 7, pp. 1002–1010.
Eleuthesides and Their Analogs:
III.* Reaction of Red-Al with γ,δ-Epoxy Nitriles
Yu. A. Khalilova, O. Yu. Doronina, B. T. Sharipov, L. V. Spirikhin, and F. A. Valeev
Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences,
pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia
e-mail: sinvmet@anrb.ru
Received July 10, 2012
Abstract—Oxiranyl-substituted cycloalkenecarbonitriles obtained by the Beckmann fragmentation of oximes
derived from levoglucosenone adducts with 1,3-butadiene, isoprene, cyclohexadiene, and cyclopentadiene were
subjected to Red-Al reduction with opening of the epoxide ring. The reactions with 1,3-butadiene, isoprene,
and cyclohexadiene derivatives were accompanied by cyclopropane ring closure and reduction of the cyano
group to aldehyde, whereas the cyclopentadiene derivative underwent hydrogenolysis of the oxirane fragment.
DOI: 10.1134/S1070428013070051
We found previously [2] that reductive opening of
the oxirane ring in epoxy nitrile I, including the reac-
tion with Red-Al under anhydrous conditions, yields
secondary alcohol II, the cyano group remaining un-
changed. Treatment of I with Red-Al in the presence of
water was accompanied by cyclopropane ring closure
and reduction of the cyano group to aldehyde [2]. We
have found no published data on the reduction of
nitriles to aldehydes by the action of Red-Al.
reaction in the absence of water involved reductive de-
chlorination with formation of hydroxy nitrile II, i.e.,
the result was analogous to oxirane ring opening in
compound I under anhydrous conditions (Scheme 1).
Presumably, the presence of a small amount of
water favors the reaction to proceed toward formation
of carbanion which initiates cyclopropanation or facili-
tates reduction of the cyano group. Furthermore, the
formation of three-membered carbocycle may also
activate the cyano group, leading to its reduction to
aldehyde.
Our attempts to obtain aldehyde from cyanoalkyl
formate III having no oxirane fragment were unsuc-
cessful. Treatment of III with Red-Al–H2O (15 :1)
resulted in hydrolysis of the ester moiety, whereas the
With a view to elucidate the reaction mechanism,
epoxy nitrile I was treated with lithium diisopropyl-
Scheme 1.
Me
H
H
O
Red-Al, THF, 0°C
OH
CN
CN
H
H
Me
Me
Cl
I
II
Cl
H
H
H
Red-Al, H2O, THF, 0°C
99%
Red-Al, THF, 0°C
94%
II
OH
CN
OCHO
CN
H
Me
Me
IV
III
* For communication II, see [1].
986

ELEUTHESIDES AND THEIR ANALOGS: III.
987
Scheme 2.
H
H
H
H
H
H
OH
OTBS
OH
TBSCl, Imidazole
CH2Cl2
(1) Red-Al, THF, 0°C
(2) THF, HCl/H2O
LDA, THF
68%
I
100%
87%
CN
CN
CHO
Me
Me
Me
V
VI
VII
amide (LDA) to obtain in good yield hydroxy nitrile V.
The hydroxy group in V was protected by treatment
with tert-butyldimethylsilyl chloride (TBSCl), the
resulting ether VI was reduced with Red-Al, and
subsequent removal of the TBS protection afforded
hydroxy aldehyde VII (Scheme 2). Thus, the first step
in the reaction of I with Red-Al is cyclopropane ring
closure, and in the second step excess Red-Al reduces
the activated cyano group to aldehyde.
We tried to extend the scope of the discovered
transformation of (1R,2R,6S)-2-methyl-6-[(2S)-oxiran-
2-yl]cyclohex-3-ene-1-carbonitrile (I) into
(1S,2R,6R,7S)-7-hydroxymethyl-2-methylbicyclo-
[4.1.0]hept-3-ene-1-carbaldehyde (VII) [2] by the
action of Red-Al with a view to obtain new synthetic
blocks useful for the synthesis of eleutheside analogs.
For this purpose we used Diels–Alder adducts VIII–
XI derived from levoglucosenone and butadiene [3],
isoprene [4], cyclopentadiene [5], and cyclohexadiene.
The initial epoxy nitriles were synthesized according
to a scheme analogous to that reported for the pipery-
lene adduct [2]. The oximation of VIII–XI was more
efficient as compared to the piperylene adduct, and
oximes XII–XV were isolated in 95–98% yield
(Scheme 3).
chloro cyano formates XVI and XVIII in 83 and 62%
yield, respectively. The yield of XVII from oxime
XIII was appreciably lower, 49%. In addition, we
isolated from the reaction mixture 7% of hydroxy
formate XX. Chloro formate XIX was isolated in even
poorer yield (32%), while the major product was
γ-lactone XXI (40%). The oxirane ring in chloro
formates XVI, XVII, and XIX was smoothly formed
upon treatment with potassium hydroxide in aqueous
ethanol (Scheme 4). Under analogous conditions,
chloro formate XVIII gave rise to chlorohydrin XXV
and γ-lactone XXVI, the latter being formed as a result
of hydrolysis of the cyano group. Acid hydrolysis of
XVIII (HCl/H2O) afforded only 83% of chlorohydrin
XXV, and the latter was converted into epoxide
XXVII in 94% yield (cf. [2]).
From epoxy nitriles XXII–XXIV we obtained
hydroxy aldehydes XXVIII–XXX (Scheme 5). In the
reaction with XXII, we also succeeded in isolating
from aqueous solution of the reaction mixture 36% of
amino diol XXXI. Under analogous conditions, epoxy
nitrile XXVII unexpectedly gave rise to nitrile XXXII
as reductive deoxygenation product. It is known that
closure of endo-cyclopropane ring in norbornene
systems is fairly difficult [6]; therefore, the oxirane
ring opening step is likely to be accompanied by
hydrogenolysis (cf. [7]).
The second-order Beckmann rearrangement of
oximes XII and XIV by the action of SOCl2 afforded
Scheme 3.
O
O
( )n
R
O
O
NH2OH·HCl, pyridine
SOCl2, CH2Cl2
OCHO
O
NOH
CN
( )n
( )n
Cl
R
R
VIII–XI
XII–XV
XVI–XIX
Cl
H
Me
+
OH
+
OCHO
O
CN
H
O
XX
XXI
VIII, XII, XVI, R = H, n = 0; IX, XIII, XVII, R = Me, n = 0; X, XIV, XVIII, R = H, n = 1; XI, XV, XIX, R = H, n = 2.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 7 2013

KHALILOVA et al.
988
Scheme 4.
( )n
R
KOH, EtOH–H2O
XVI, XVII, XIX
O
CN
XXII–XXIV
KOH, EtOH–H2O
or THF, HCl/H2O
MeONa, CHCl3
OH
+
XVIII
XXV
O
Cl
O
CN
Cl
CN
O
XXV
XXVI
XXVII
XXII, R = H, n = 0; XXIII, R = Me, n = 0; XXIV, R = H, n = 2.
Scheme 5.
OH
( )n
H
(1) Red-Al, THF
(2) 3% HCl/H2O
H
XXII–XXIV
+
OH
H
CHO
H
NH2
OH
XXVIII–XXX
XXXI
(1) Red-Al, THF
(2) 3% HCl/H2O
XXVII
+
Me
Me
CN
CN OH
XXXII
XXXIII
XXVIII, R = H, n = 0; XXIX, R = Me, n = 0; XXX, R = H, n = 2.
Thus, unlike the reduction–ring opening of the
piperylene adduct by the action of Red-Al, the yields
of the corresponding products from adducts XXII–
XXIV derived from butadiene, isoprene, and cyclo-
hexadiene are appreciably lower, whereas no cyclo-
propane derivative is formed from oxiranylnorbornene
XXVII.
plates (Sorbpolimer closed corporation, Krasnodar,
Russia). The melting points were measured on
a Boetius PHMK 05 apparatus. The elemental com-
positions were determined on a Euro 2000 CHNS(O)
analyzer. The optical rotations were measured with
a Perkin Elmer 341 polarimeter. Commercial Red-Al
(a 70% solution in toluene, Lancaster) was used.
(1R,2R,6S)-6-[(1R)-1-Hydroxyethyl]-2-methyl-
cyclohex-3-ene-1-carbonitrile (II). A solution of
0.53 g (2.33 mmol) of compound III in 20.0 ml of
THF was cooled to 0°C, 1.4 ml (4.66 mmol) of Red-Al
was added under argon, and the mixture was stirred for
2 h at 0°C, treated with 6% aqueous HCl to dissolve
the precipitate, and extracted with ethyl acetate (3×
20 ml). The extracts were combined and dried over
MgSO4, the solvent was distilled off on a rotary evap-
orator, and the residue was subjected to chromatog-
raphy on silica gel. Yield 0.362 g (94%), oily sub-
stance, [α]D20 = –81.59° (c = 1.0, CHCl3), Rf 0.5 (petro-
leum ether–EtOAc, 3:1). IR spectrum, ν, cm–1: 3400,
3025, 2980, 2890, 2240, 1470, 1390, 1310, 1250,
EXPERIMENTAL
The H and 13C NMR spectra were recorded on
a Bruker AM-300 spectrometer at 300 and 75.47 MHz,
respectively, and on a Bruker Avance III instrument
1
1
(500 MHz for H) using CDCl3 as solvent unless
otherwise stated. The IR spectra were measured on
UR-20 and Specord M-80 instruments from films or
mineral oil mulls. The mass spectra were obtained on
a Hewlett Packard GC/MS system consisting of
an HP 6890 chromatograph coupled with an HP 5973
mass-selective detector. Analytical thin-layer chroma-
tography was performed on Sorbfil PTSKh-AF-A
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 7 2013

ELEUTHESIDES AND THEIR ANALOGS: III.
989
1100, 1010, 950, 890, 760. 1H NMR spectrum, δ, ppm:
1.22 d (3H, CH3, J = 7.2 Hz), 1.28 d (3H, 1′-CH3, J =
6.2 Hz), 1.73 d.d.d.d (1H, 6-H, J = 9.5, 9.5, 5.5,
2.7 Hz), 1.94 m and 2.06 m (1H each, 5-H), 2.48 m
(1H, 2-H), 3.46 d.d (1H, 1-H, J = 4.1, 3.8 Hz), 3.75 d.q
(1H, 1′-H, J = 9.5, 6.2 Hz), 5.45 d (1H, 3-H, J =
10.1 Hz), 5.73 m (1H, 4-H). 13C NMR spectrum, δC,
ppm: 18.89 (CH3), 21.52 (CH3), 25.05 (C5), 32.25 (C1),
34.14 (C6), 43.61 (C2), 68.91 (C1′), 119.0 (CN), 125.73
(C4), 129.80 (C3). Mass spectrum: m/z 166 [M + H]+.
Found, %: C 73.45; H 9.62; N 7.76. C10H15NO. Cal-
culated, %: C 72.69; H 9.15; N 8.48. M 165.2322.
the residue was subjected to chromatography on silica
gel. Yield 0.135 g (68%), oily substance, Rf 0.4 (petro-
leum ether–EtOAc, 1:1). IR spectrum, ν, cm–1: 3417,
1
2933, 2231, 1438, 1013, 717. H NMR spectrum, δ,
ppm: 1.22 d (3H, CH3, J = 7.4 Hz), 1.89 m (1H, 6- H),
1.78 m (1H, 7-H), 2.28 br.d and 2.54 br.d (1H each,
5-H, J = 19.2 Hz), 2.85 m (1H, 2-H), 3.66 d.d (1H,
1′-HA, J = 11.6, 7.9 Hz), 3.88 d.d (1H, 1′-HB, J = 7.9,
6.4 Hz), 5.42 m (1H, 4-H), 5.62 br.d (1H, 3-H, J =
9.0 Hz). 13C NMR spectrum, δC, ppm: 16.09 (C1),
18.71 (C6), 19.48 (C5), 20.20 (CH3), 28.83 (C7), 29.79
(C2), 56.52 (C1′), 123.82 (C4), 128.19 (C3), 124.42
(CN). Found, %: C 73.49; H 8.03; N 8.60. C10H13NO.
Calculated, %: C 73.59; H 8.03; N 8.58.
(1R,2R,6S)-6-[(1S)-2-Chloro-1-hydroxyethyl]-2-
methylcyclohex-3-ene-1-carbonitrile (IV). A solution
of 0.59 ml (1.98 mmol) of Red-Al in 10.0 ml of THF
was cooled to 0°C, 0.003 ml (0.165 mmol) of water
was added, the mixture was stirred for 1 h at room
temperature, and a solution of 0.15 g (0.66 mmol) of
compound III in 10.0 ml of THF was added. When the
reaction was complete, the mixture was treated with
5% aqueous HCl to weakly acidic reaction and extract-
ed with ethyl acetate (3×30 ml), the extracts were
combined, dried over MgSO4, and concentrated on
a rotary evaporator, and the residue was subjected to
chromatography on silica gel. Yield 0.130 g (99%),
oily substance, [α]D20 = –56.65° (c = 1.0, CHCl3), Rf =
(2R,6R,7S)-7-(tert-Butyldimethylsilyloxy)-2-
methylbicyclo[4.1.0]hept-3-ene-1-carbonitrile (VI).
Compound V, 0.116 g (0.7 mmol), was dissolved in
5.0 ml of methylene chloride, 0.121 g (0.84 mmol) of
TBSCl and 0.116 g (1.7 mmol) of imidazole were
added, and the mixture was stirred for 30 min. When
the reaction was complete, the mixture was treated
with water and extracted with methylene chloride
(3×10 ml). The extracts were combined, dried over
MgSO4, and concentrated, and the residue was sub-
jected to chromatography on silica gel. Yield 0.198 g
(100%), oily substance, [α]D20 = –27.6° (c = 2.0,
CHCl3), Rf 0.7 (petroleum ether–EtOAc, 3:1). IR spec-
trum, ν, cm–1: 3378, 2930, 2232, 1708, 1464, 1091,
1
0.23 (petroleum ether–EtOAc, 3:1). H NMR spec-
trum, δ, ppm: 1.21 d (3H, CH3, J = 7.3 Hz), 2.03 m
(3H, 5-H, 6-H), 2.50 m (1H, 2-H), 3.20–3.43 br.s (1H,
OH), 3.43 d (1H, 1-H, J = 5.0 Hz), 3.58 d.d (1H, 2′-HA,
J = 11.9, 6.1 Hz), 3.80 m (2H, 1′-H, 2′-HB), 5.48 d (1H,
3-H, J = 9.9 Hz), 5.72 d.d.d (1H, 4-H, J = 9.9, 7.1,
2.7 Hz). 13C NMR spectrum, δC, ppm: 18.91 (CH3),
24.44 (C5), 29.64 (C2), 34.05 (C6), 39.62 (C1), 48.54
(C2′), 72.09 (C1′), 118.62 (CN), 124.92 (C4), 130.14
(C3). Mass spectrum: m/z 200 [M + H]+. Found, %:
C 60.31; H 6.98; Cl 17.92; N 7.15. C10H14ClNO.
Calculated, %: C 60.15; H 7.07; Cl 17.76; N 7.01.
M 199.677.
1
837, 670. H NMR spectrum, δ, ppm: 0.0 s (6H,
SiCH3), 0.87 s (9H, t-Bu), 1.18 d (3H, CH3, J =
7.3 Hz), 1.68 m (1H, 7-H), 1.82 m (1H, 6-H), 2.24 br.d
and 2.46 br.d (1H each, 5-H, J = 21.2 Hz), 2.82 m (1H,
2-H), 3.60 d.d (1H, 1′-HA, J = 11.1, 7.8 Hz), 3.75 d.d
(1H, 1′-HB, J = 7.8, 6.5 Hz), 5.58 br.d (1H, 4-H, J =
13
10.4 Hz), 5.90 br.d (1H, 3-H, J = 10.4 Hz). C NMR
spectrum, δC, ppm: –5.45 (SiCH3), 19.79 (C1), 20.40
(C6), 20.56 (CH3), 24.85 (C5), 25.57 [(CH3)3C], 29.88
(C2), 30.28 (C7), 57.62 (C1′), 124.08 (C4), 124.74 (CN)
129.68 (C3). Found, %: C 69.25; H 9.82; N 5.05;
Si 10.12. C16H27NOSi. Calculated, %: C 69.26; H 9.81;
N 5.05; Si 10.12.
(2R,6R,7S)-7-(Hydroxymethyl)-2-methylbicyclo-
[4.1.0]hept-3-ene-1-carbonitrile (V). A solution of
0.21 ml (1.5 mmol) of diisopropylamine in 5.0 ml of
THF was cooled to –1 to 0°C, 0.7 ml (1.6 mmol) of
a 2.3 M solution of butyllithium in hexane was added
under argon, the mixture was stirred for 20 min, and
a solution of 0.2 g (1.2 mmol) of epoxy nitrile I in
10.0 ml of THF was added. When the reaction was
complete (TLC), the mixture was treated with
3% aqueous HCl and extracted with ethyl acetate
(3×10 ml). The extracts were combined, dried over
MgSO4, and concentrated on a rotary evaporator, and
(1S,2R,6R,7S)-7-Hydroxymethyl-2-methylbicy-
clo[4.1.0]hept-3-ene-1-carbaldehyde (VII). A solu-
tion of 0.13 g (0.47 mmol) of silyl ether VI in 10.0 ml
of THF was cooled to 0°C, and 0.14 ml (0.7 mmol) of
Red-Al was added to the solution under argon. When
the reaction was complete (TLC), the mixture was
treated with 6% aqueous HCl until the precipitate
dissolved completely, and the product was extracted
into ethyl acetate (3×20 ml). The extracts were com-
bined, dried over MgSO4, and concentrated on a rotary
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KHALILOVA et al.
990
evaporator, and the residue was subjected to hydrolysis
in a mixture of 2.5 ml of THF, 0.25 ml of water, and
0.25 ml of concentrated aqueous HCl. When the reac-
tion was complete (TLC), the mixture was neutralized
with a saturated solution of NaHCO3 and extracted
with ethyl acetate (3×10 ml), the combined extracts
were dried over MgSO4 and concentrated, and the
residue was purified by chromatography on silica gel.
Yield 0.068 g (87%), colorless crystals, mp 85.7°C,
[α]D20 = –105.2° (c = 1.0, CHCl3), Rf 0.3 (petroleum
ether–EtOAc, 3:1). IR spectrum, ν, cm–1: 3400, 2970,
synthesized in a similar way from 1.9 g (9.0 mmol) of
compound IX. Yield 1.9 g (95%), colorless crystals,
mp 88°C, [α]D20 = –13.0° (c = 1.0, CHCl3), Rf = 0.57
(petroleum ether–EtOAc, 3:1). IR spectrum, ν, cm–1:
1
3417, 2968, 2927, 1726, 1444, 1170, 1114. H NMR
spectrum, δ, ppm: 1.60 s (3H, CH3), 1.80 d.d (1H, 6-H,
J = 17.3, 6.2 Hz), 2.00–2.30 m (2H, 2-H, 3-H), 2.30 d
(1H, 3-H, J = 16.5 Hz), 2.46 m (1H, 6-H), 3.40 t (1H,
7-H, J = 6.2 Hz), 3.87 d.d (1H, exo-11-H, J = 7.2,
5.2 Hz), 4.38 d (1H, 1-H, J = 5.2 Hz), 4.40 d (1H,
endo-11-H, J = 7.2 Hz), 5.29 br.s (1H, 5-H), 6.44 s
(1H, 9-H), 7.92 br.s (1H, NOH). 13C NMR spectrum,
δC, ppm: 22.89 (C6), 23.60 (CH3), 28.41 (C3), 29.97
(C7), 29.40 (C2), 67.53 (C11), 77.19 (C1), 92.61 (C9),
117.40 (C5), 131.58 (C4), 155.03 (C8). Mass spectrum:
m/z 210 [M + H]+. Found, %: C 63.42; H 9.28; N 6.20.
C11H15NO3. Calculated, %: C 63.41; H 9.31; N 6.16.
M 209.2417.
1
1640, 1700, 1370, 1070, 920. H NMR spectrum, δ,
ppm: 1.07 d.d.d (3H, CH3, J = 2.4, 2.7, 7.3 Hz),
1.72 d.d (1H, 6-H, J = 7.3, 9.7 Hz), 1.81 d.d.d (1H,
7-H, J = 6.1, 8.1, 9.7 Hz), 2.35 d.d (1H, 5-HA, J = 4.7,
19.2 Hz), 2.50 d.d (1H, 5-HB, J = 7.3, 19.2 Hz),
3.25 d.d.d (1H, 2-H, J = 2.4, 2.7, 7.3 Hz), 3.80 d.d
(1H, 8-HB, J = 8.1, 11.2 Hz), 3.92 d.d.d (1H, 8-HB, J =
6.1, 8.1, 11.2 Hz), 5.50 d.d.d.d (1H, 4-H, J = 2.4, 4.7,
6.0, 10.3 Hz), 5.57 d.d.d (1H, 3-H, J = 2.4, 2.7, 3.0 Hz),
8.80 s (1H, CHO). 13C NMR spectrum, δC, ppm: 19.27
(CH3), 19.81 (C6), 20.47 (C5), 25.13 (C7), 27.69 (C2),
38.56 (C1), 57.81 (C8), 122.96 (C4), 129.96 (C3),
201.80 (CHO). Found, %: C 72.26; H 8.49. C10H14O2.
Calculated, %: C 72.25; H 8.50.
(1S,2S,3S,6R,7R,9R)-10,12-Dioxatetracyclo-
[7.2.1.13,6.02,7]tridec-4-en-8-one syn-oxime (XIV)
was synthesized in a similar way from 5.0 g
(27.0 mmol) of X. Yield 5.2 g (97%), oily substance,
[α]D20 = –50° (c = 0.58, CHCl3), Rf 0.38 (petroleum
ether–EtOAc, 3:1). IR spectrum, ν, cm–1: 3433, 2860,
1
1750–1608, 1456. H NMR spectrum, δ, ppm: 1.34 d
(1S,2S,7R,9R)-10,12-Dioxatricyclo[7.2.1.02,7]-
dodec-4-en-8-one syn-oxime (XII). Hydroxylamine
hydrochloride, 6.5 g (93.9 mmol), was added under
stirring to a solution of 5.0 g (27.6 mmol) of com-
pound VIII in 50.0 ml of pyridine. The mixture was
stirred for 30 min, ethyl acetate was added, and the
mixture was washed with water. The product was ex-
tracted into ethyl acetate (3×10 ml), and the combined
extracts were dried over MgSO4 and concentrated on
a rotary evaporator. Yield 5.2 g (97%), colorless crys-
tals, mp 118°C, [α]D20 = +10.3° (c = 1.0, CHCl3), Rf =
0.5 (petroleum ether–EtOAc, 3:1). IR spectrum, ν,
cm–1: 3280, 2970, 2820, 1458, 964. 1H NMR spectrum,
δ, ppm: 1.95–2.06 m (2H, 6-H), 2.07–2.19 m (2H,
3-H), 2.36–2.54 m (1H, 2-H), 3.14 t (1H, 7-H, J =
6.2 Hz), 3.92 d.d (1H, exo-11-H, J = 7.0, 5.1 Hz),
4.08 d (1H, endo-11-H, J = 7.0 Hz), 4.41 d (1H, 1-H,
J = 5.1 Hz), 5.62 m (2H, 4-H, 5-H), 6.50 s (1H, 9-H).
13C NMR spectrum, δC, ppm: 22.63 (C6), 23.50 (C3),
30.48 (C7), 38.92 (C2), 67.53 (C11), 77.23 (C1), 92.63
(C9), 123.33 (C4), 124.81 (C5), 155.20 (C8). Mass spec-
trum: m/z 196 [M + H]+. Found, %: C 61.91; H 9.00;
N 6.50. C10H13NO3. Calculated, %: C 61.53; H 6.71;
N 7.18. M 195.2152.
(1H, 13-HA, J = 8.6 Hz), 1.45 d.t (1H, 13-HB, J = 8.6,
1.8 Hz), 2.20 d.d (1H, 2-H, J = 9.4, 3.1 Hz), 2.94 br.s
(1H, 3-H), 3.05 d.d (1H, 7-H, J = 9.4, 4.1 Hz),
3.25 br.s (1H, 6-H), 3.72 d (1H, endo-11-H, J =
6.9 Hz), 3.78 d.d (1H, exo-11-H, J = 6.9, 5.0 Hz),
4.54 d (1H, 1-H, J = 5.0 Hz), 6.08 d.d (1H, 4-H, J =
5.6, 2.0 Hz), 6.30 m (1H, 5-H), 6.28 s (1H, 9-H),
8.20 br.s (1H, NOH). 13C NMR spectrum, δC, ppm:
36.62 (C2), 46.62 (C3), 46.99 (C7), 48.20 (C6), 49.07
(C13), 69.72 (C11), 74.80 (C1), 90.34 (C9), 134.36 (C4),
135.08 (C5), 154.70 (C8). Mass spectrum: m/z 208
[M + H – CHO]+. Found, %: C 63.80; H 8.50; N 6.30.
C11H13NO3. Calculated, %: C 63.98; H 8.50; N 6.22.
M 207.2259.
(1S,2S,3S,6R,7R,9R)-10,12-Dioxatetracyclo-
[7.2.2.11,9.02,7]tetradec-4-en-8-one syn-oxime (XV)
was synthesized in a similar way from 1.0 g
(4.8 mmol) of XI. Yield 1.1 g (98%), colorless crys-
tals, mp 119°C, [α]D20 = –348.7° (c = 1.0, CHCl3),
Rf 0.26 (petroleum ether–EtOAc, 3:1). IR spectrum, ν,
cm–1: 3264, 2941, 1724, 1377, 1175, 1117, 903, 688.
1H NMR spectrum, δ, ppm: 1.20–1.40 m (2H, 13-H),
1.44–1.62 m (2H, 14-H), 1.84 d (1H, 2-H, J = 9.6 Hz),
2.59 m (1H, 3-H), 2.84 d.d (1H, 7-H, J = 9.6, 3.3 Hz),
3.05 m (1H, 6-H), 3.68 d (1H, endo-11-H, J = 7.0 Hz),
3.82 d.d (1H, exo-11-H, J = 7.0, 5.0 Hz), 4.42 d (1H,
(1S,2S,7R,9R)-4-Methyl-10,12-dioxatricyclo-
[7.2.1.02,7]dodec-4-en-8-one syn-oxime (XIII) was
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ELEUTHESIDES AND THEIR ANALOGS: III.
991
1-H, J = 5.0 Hz), 6.12 d.d (1H, 4-H, J = 7.6, 7.0 Hz),
6.42 d.d (1H, 5-H, J = 7.6, 6.9 Hz), 6.27 s (1H, 9-H),
8.62 br.s (1H, NOH). 13C NMR spectrum, δC, ppm:
22.78 (C13), 27.06 (C14), 35.35 (C2), 35.87 (C3), 37.64
(C6), 42.04 (C7), 67.70 (C11), 77.02 (C1), 91.04 (C9),
131.69 (C4), 133.64 (C5), 155.38 (C8). Mass spectrum:
m/z 222 [M + H]+. Found, %: C 63.10; H 8.60; N 6.30.
C12H15NO3. Calculated, %: C 63.14; H 6.83; N 6.33.
M 221.2524.
spectrum: m/z 245 [M + H + H2O]+. Found, %:
C 58.00; H 6.22; Cl 15.60; N 6.15. C11H14ClNO2.
Calculated, %: C 58.03; H 6.20; Cl 15.57; N 6.15.
M 227.6871.
(1S)-2-Hydroxy-1-[(1S,6R)-3-methyl-6-cyanocy-
clohex-3-en-1-yl]ethyl formate (XX). Oily substance,
[α]D20 = –6.2° (c = 1.0, CHCl3), Rf 0.25 (petroleum
ether–EtOAc, 3:1). IR spectrum, ν, cm–1: 3464, 2914,
1
1724, 1176. H NMR spectrum, δ, ppm: 1.72 s (3H,
(1S)-2-Chloro-1-[(1S,6R)-6-cyanocyclohex-3-en-
1-yl]ethyl formate (XVI). A solution of 1.8 ml
(78.6 mmol) of thionyl chloride in 5.0 ml of methylene
chloride was added to a solution of 5.1 g (26.2 mmol)
of oxime XII in 30.0 ml of methylene chloride, cooled
to 0°C. The mixture was stirred for 1 h at 0°C (TLC)
and treated with a saturated aqueous solution of
NaHCO3 (until neutral reaction), the organic phase was
separated, and the aqueous phase was extracted with
methylene chloride (3×10 ml). The extracts were com-
bined with the organic phase, dried over MgSO4, and
concentrated on a rotary evaporator. Yield 4.6 g (83%),
colorless crystals, mp 46.6°C, [α]D20 = –65.6° (c = 0.5,
CHCl3), Rf 0.6 (petroleum ether–EtOAc, 3:1). IR spec-
trum, ν, cm–1: 1742, 1330. 1H NMR spectrum, δ, ppm:
2.02–2.26 m (2H, CH2), 2.31–2.48 m (3H, CH, CH2),
3.16 d (1H, 6′-H, J = 2.0 Hz), 3.68 d.d (1H, 2-HA, J =
12.7, 3.1 Hz), 3.92 d.d (1H, 2-H-B, J = 12.7, 2.6 Hz),
5.12 d.d (1H, 1-H, J = 9.6, 3.1 Hz), 5.71 br.s (1H,
4′-H), 5.80 br.s (1H, 3′-H), 8.14 s (1H, OCHO).
13C NMR spectrum, δC, ppm: 24.10 (C2′), 25.86 (C6′),
28.23 (C5′), 35.81 (C1′), 43.57 (C2), 73.10 (C1), 119.65
(CN), 123.25 (C3′), 125.37 (C4′), 159.94 (OCHO).
Found, %: C 56.10; H 5.65; Cl 15.59; N 6.56.
C10H12ClNO2. Calculated, %: C 56.21; H 5.66;
Cl 16.59; N 6.56.
CH3), 1.90–2.09 m (3H, CH2, CH), 2.28–2.49 m (2H,
CH2), 3.50 t (1H, 6′-H, J = 2.4 Hz), 3.85 d.d (1H, 1-H,
J = 6.5, 1.7 Hz), 4.14 d.d (1H, 2-HA, J = 11.6, 6.5 Hz),
4.48 d.d (1H, 2-HB, J = 11.6, 1.7 Hz), 5.43 br.s (1H,
4′-H), 8.16 s (1H, OCHO). 13C NMR spectrum, δC,
ppm: 23.19 (CH3), 25.73 (C6′), 27.99 (C2′), 29.31 (C3′),
38.08 (C1′), 65.51 (C2), 70.51 (C1), 117.40 (C4′), 120.6
(CN), 132.94 (C3′), 161.13 (OCHO). Found, %:
C 63.14; H 7.20; N 6.80. C11H15NO3. Calculated, %:
C 63.14; H 7.23; N 6.69.
(1S)-2-Chloro-1-[(1S,2S,3R,4R)-3-cyanobicyclo-
[2.2.1]hept-5-en-2-yl]ethyl formate (XVIII) was syn-
thesized in a similar way from 6.0 g (30.0 mmol) of
oxime XIV. Yield 4.0 g (62%), colorless crystals,
mp 45.5°C, [α]D20 = –42.6° (c = 1.15, CHCl3), Rf 0.6
(petroleum ether–EtOAc, 4:1). IR spectrum, ν, cm–1:
2891–2866, 2235, 1724, 1712, 1458, 1172, 1151.
1H NMR spectrum, δ, ppm: 1.46 d.t (1H, 7′-HA, J =
1.9, 9.4 Hz), 1.65 d.t (1H, 7′-HB, J = 9.4, 1.6 Hz),
3.00 d.t (1H, 2′-H, J = 10.8, 9.1, 3.1 Hz), 3.08 br.s (1H,
4′-H), 3.15 d.d (1H, 3′-H, J = 9.1, 3.6 Hz), 3.30 br.s
(1H, 1′-H), 3.70 d.d (1H, 2-HA, J = 12.9, 1.9 Hz),
4.01 d.d (1H, 2-HB, J = 12.9, 2.2 Hz), 4.73 d.t (1H,
1-H, J = 10.8, 2.2, 1.9 Hz), 6.23 d.d (1H, 6′-H, J = 5.5,
2.8 Hz), 6.44 d.d (1H, 5′-H, J = 5.5, 3.0 Hz), 8.03 s
(1H, OCHO). 13C NMR spectrum, δC, ppm: 31.33
(C3′), 44.10 (C2′), 44.21 (C4′), 44.97 (C2), 46.50 (C1′),
48.63 (C7′), 73.36 (C1), 120.01 (CN), 134.66 (C6′),
136.41 (C5′), 159.77 (OCHO). Mass spectrum: m/z 198
[M + H – CHO]+. Found, %: C 58.50; H 6.00;
Cl 15.17; N 6.16. C11H12ClNO2. Calculated, %:
C 58.54; H 5.36; Cl 15.17; N 6.21. M 225.6712.
Following an analogous procedure, from 4.3 g
(20.0 mmol) of oxime XIII we obtained 2.3 g (49%) of
formate XVII and 0.3 g (7%) of alcohol XX.
(1S)-2-Chloro-1-[(1S,6R)-3-methyl-6-cyanocyclo-
hex-3-en-1-yl]ethyl formate (XVII). Colorless crys-
tals, mp. 66°C, [α]D20 = –47.8° (c = 1.0, CHCl3), Rf 0.6
(petroleum ether–EtOAc, 3:1). IR spectrum, ν, cm–1:
Following an analogous procedure, from 0.734 g
(3.1 mmol) of oxime XV we obtained 0.243 g (32%)
of formate XIX and 0.244 g (40%) of lactone XXI.
1
2920, 1728, 1433, 1163, 781, 756. H NMR spectrum,
δ, ppm: 1.67 s (3H, CH3), 1.97 m (2H, CH2), 2.34 m
(3H, CH2, CH), 3.8 m (1H, 6′-H), 3.67 d.d (1H, 2-HA,
J = 12.67, 3.1 Hz), 3.89 d.d (1H, 2-HB, J = 12.67,
3.1 Hz), 5.08 d.t (1H, 1-H, J = 9.6, 3.1 Hz), 5.37 m
(1H, 4′-H), 8.12 s (1H, OCHO). 13C NMR spectrum,
δC, ppm: 23.09 (CH3), 25.52 (C6′), 28.06 (C2′), 28.62
(C5′), 36.06 (C1′), 43.47(C2), 72.88 (C1), 117.24 (C4′),
119.64 (CN), 132.52 (C3′), 159.77 (OCHO). Mass
(1S)-2-Chloro-1-[(1S,2S,3R,4R)-3-cyanobicyclo-
[2.2.2]oct-5-en-2-yl]ethyl formate (XIX). Colorless
crystals, mp 39°C, [α]D20 = –82.1° (c = 1.0, CHCl3),
Rf 0.5 (petroleum ether–EtOAc, 3:1). IR spectrum, ν,
1
cm–1: 2800, 1714, 1458, 1139, 721, 372. H NMR
spectrum, δ, ppm: 1.32 m (2H, 7-H, 8-H), 1.58 m (2H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 7 2013

KHALILOVA et al.
992
7-H, 8-H), 2.56 t (1H, 2′-H, J = 9.2, 9.2 Hz), 2.63 m
(1H, 1′-H), 3.0 m (1H, 4′-H), 3.02 m (1H, 3′-H),
3.73 d.d (1H, 2-H, J = 13.0, 2.9 Hz), 3.97 d.d (1H,
2-H, J = 13.0, 2.7 Hz), 4.87 (1H, 1-H), 6.30 t (1H,
5′-H, J = 7.1, 6.9 Hz), 6.40 t (1H, 6′-H, J = 7.1,
27.72 (C2), 38.41 (C6), 46.56 (C2′), 52.98 (C1′), 120.02
(CN), 122.98 (C3), 125.54 (C4). Mass spectrum:
m/z 162 [M + H]+. Found, %: C 72.40; H 7.43; N 9.39.
C9H11NO. Calculated, %: C 72.46; H 7.43; N 9.39.
M 149.1898.
13
7.0 Hz), 8.00 s (1H, OCHO). C NMR spectrum, δC,
(1R,6S)-4-Methyl-6-[(1R)-oxiran-1-yl]cyclohex-
3-ene-1-carbonitrile (XXIII) was synthesized in
a similar way from 2.3 g (10.0 mmol) of XVII. Yield
ppm: 23.08 (C7′), 25.20 (C8′), 30.06 (C3′), 32.57 (C4′),
33.95 (C2′), 41.17 (C1′), 44.65 (C2), 74.09 (C1), 120.67
(CN), 132.94 (C6′), 133.22 (C5′), 160.25 (OCHO).
Mass spectrum: m/z 212 [M + H – CHO]+. Found, %:
C 60.10; H 5.86; Cl 14.60; N 5.89. C12H14ClNO2.
Calculated, %: C 60.13; H 5.89; Cl 14.79; N 5.84.
M 239.6978.
1.2 g (76%), colorless crystals, mp 16°C, [α]D20
=
–31.8° (c = 1.0, CHCl3), Rf 0.53 (petroleum ether–
EtOAc, 3:1). IR spectrum, ν, cm–1: 3560, 2970, 2918,
1
2852, 1770, 1436, 871, 783. H NMR spectrum, δ,
ppm: 1.48–1.57 m (1H, 2-HA), 1.68 s (3H, CH3),
1.95 d.d (1H, 5-HA, J = 17.7, 4.8 Hz), 2.10 m (1H,
2-HB), 2.30–2.38 m (2H, 5-HB, 2′-HA), 2.57 d.d (1H,
6-H, J = 5.5, 2.5 Hz), 2.82 t (1H, 1-H, J = 4.2 Hz),
2.97 d.d.d (1H, 2′-HB, J = 11.2, 7.2, 3.3 Hz), 3.15 d.d.d
(1H, 1′-H, J = 7.2, 5.3, 2.9 Hz), 5.35 s (1H, 3-H).
13C NMR spectrum, δC, ppm: 22.63 (CH3), 23.53 (C5),
26.83 (C1), 28.26 (C2), 38.38 (C6), 46.03 (C2′), 52.58
(C1′), 117.0 (C3), 119.84 (CN), 132.54 (C4). Mass spec-
trum: m/z 164 [M + H]+. Found, %: C 73.09; H 8.00;
N 8.58. C10H13NO. Calculated, %: C 73.59; H 8.03;
N 8.58. M 163.2164.
(1S,2S,3S,6R,7R)-5-Hydroxymethyl-4-oxatri-
cyclo[5.2.2.02,6]undec-8-en-5-one (XXI). Colorless
crystals, mp 80°C, [α]D20 = –10.5° (c = 1.0, CHCl3),
Rf 0.1 (petroleum ether–EtOAc, 3:1). IR spectrum, ν,
1
cm–1: 3375, 2926, 1747, 1460, 1192, 719. H NMR
spectrum, δ, ppm: 1.23–1.36 m (2H, 10-H, 11-H),
1.48–1.60 m (2H, 10-H, 11-H), 2.55 d.d (1H, 2-H, J =
4.2, 3.3 Hz), 2.70 d.d (1H, 1-H, J = 7.0, 4.2 Hz),
2.80 d.d (1H, 6-H, J = 10.0, 2.4 Hz), 2.95 d.d (1H,
7-H, J = 7.0, 2.4 Hz), 3.10 br.s (1H, OH), 3.60 d.d (1H,
1′-HA, J = 12.3, 4.1 Hz), 3.80 d.d (1H, 1′-HB, J = 12.3,
2.8 Hz), 4.08 m (1H, 3-H), 5.26 d.d (1H, 9-H, J = 7.1,
7.0 Hz), 6.31 d.d (1H, 8-H, J = 7.1, 7.0 Hz). 13C NMR
spectrum, δC, ppm: 23.33 (C10), 23.50 (C11), 31.64
(C7), 32.98 (C1), 40.42 (C2), 46.26 (C6), 64.22 (C1′),
85.33 (C3), 133.0 (C9), 134.11 (C8), 179.64 (C=O).
Found, %: C 68.10; H 7.20. C11H14O3. Calculated, %:
C 68.02; H 7.27.
(1S,2R,3S,4S)-3-[(1R)-Oxiran-1-yl]bicyclo[2.2.2]-
oct-5-ene-2-carbonitrile (XXIV) was synthesized in
a similar way from 0.243 g (1.0 mmol) of XIX. Yield
0.133 g (63%), colorless crystals, mp. 75°C, [α]D20
=
–120.6° (c = 1.0, CHCl3), Rf 0.33 (petroleum ether–
EtOAc, 3:1). IR spectrum, ν, cm–1: 1458, 1377, 1174,
1
875, 725, 443. H NMR spectrum, δ, ppm: 1.22–
(1R,6S)-6-[(1R)-Oxiran-1-yl]cyclohex-3-ene-1-
carbonitrile (XXII). A solution of 4.5 g (21.1 mmol)
of formate XVI and 4.8 g of potassium hydroxide in
a mixture of 16.1 ml of water and 32.2 ml of ethanol
was stirred for 30 min (TLC). The mixture was
neutralized with 10% aqueous HCl to pH 7 and ex-
tracted with ethyl acetate (3×10 ml), the extracts were
combined, washed with brine, dried over MgSO4, and
concentrated, and the residue was subjected to chroma-
tography on silica gel. Yield 3.0 g (95%), colorless
crystals, mp 18°C, [α]D20 = –79.5° (c = 1.0, CHCl3),
Rf 0.4 (petroleum ether–EtOAc, 7:1). IR spectrum, ν,
cm–1: 2926, 2300, 1770, 1433, 921, 864, 673. 1H NMR
spectrum, δ, ppm: 1.55 m (1H, 6-H), 2.13–2.28 m (2H,
CH2), 2.42 m (2H, CH2), 2.61 d.d (1H, 1-H, J = 4.7,
2.5 Hz), 2.86 d.d (1H, 2′-HA, J = 10.8, 4.2 Hz),
3.0 d.d.d (1H, 2′-HB, J = 10.8, 6.6, 2.8 Hz), 3.22 d.d
(1H, 1′-H, J = 5.96, 2.8 Hz), 5.66 d.d (1H, 3-H, J =
10.3, 2.6 Hz), 5.78 d.d (1H, 4-H, J = 10.3, 2.3 Hz).
13C NMR spectrum, δC, ppm: 23.86 (C5), 27.35 (C1),
1.38 m (2H, 7-H, 8-H), 1.47–1.52 m (2H, 7-H, 8-H),
1.72 t.d (1H, 3′-H, J = 9.7, 9.6, 1.6 Hz), 2.09 d.d.d
(1H, 1-H, J = 9.6, 3.2, 2.4 Hz), 2.56 d.d (1H, 2-HA, J =
4.8, 2.4 Hz), 2.61 m (1H, 4′-H), 2.82 d.d (1H, 2-HB,
J = 4.8, 3.2 Hz), 2.99 d (1H, 1′-H, J = 2.6 Hz), 3.35 d.d
(1H, 2′-H, J = 9.7, 2.6 Hz), 6.39 m (2H, 5′-H, 6′-H).
13C NMR spectrum, δC, ppm: 23.60 (C8′), 24.80 (C7′),
31.59 (C2′), 33.14 (C1′), 35.54 (C3′), 44.35 (C4′), 47.14
(C2), 54.07 (C1), 120.45 (CN), 132.30 (C5′), 134.24
(C6′). Found, %: C 75.46; H 7.48; N 7.40. C11H13NO.
Calculated, %: C 75.40; H 7.48; N 7.99.
Hydrolysis of compound XVIII. a. As described
above for the hydrolysis of XVI, from 3.8 g
(17.0 mmol) of formate XVIII we obtained 2.2 g of
a mixture of chlorohydrin XXV (56%) and lactone
XXVI (17%).
b. Compound XVIII, 0.2 g (1.0 mmol), was dis-
solved in 2.7 ml of THF, and 0.27 ml of water and
0.27 ml of concentrated aqueous HCl were added.
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ELEUTHESIDES AND THEIR ANALOGS: III.
993
When the reaction was complete (TLC), the mixture
was neutralized with a saturated aqueous solution of
NaHCO3 and extracted with ethyl acetate (3×10 ml),
the combined extracts were dried over MgSO4 and
concentrated, and the residue was purified by chroma-
tography on silica gel. Yield of XXV 0.144 g (83%).
(petroleum ether–EtOAc, 3:1). IR spectrum, ν, cm–1:
3414, 2760, 2240, 1458, 1377, 1342, 875, 737.
1H NMR spectrum, δ, ppm: 1.29 m (1H, 7-HA),
1.55 d.t (1H, 7-HB, J = 10.8, 2.0 Hz), 1.97 d.t (1H,
3-H, J = 9.0, 3.3, 2.6 Hz), 2.57 d.d (1H, 2′-HA, J = 4.9,
2.6 Hz), 2,68 d.d.d (1H, 1′-H, J = 9.0, 4.0, 2.6 Hz),
2.78 d.d (1H, 2′-HB, J = 4.0, 4.9 Hz), 2.98 br.s (1H,
4-H), 3.13 d.d (1H, 2-H, J = 9.0, 3.6 Hz), 3.26 br.s
(1H, 1-H), 6.31 d.d (1H, 6-H, J = 5.6, 2.9 Hz), 6.37 d.d
(1H, 5-H, J = 5.6, 3.1 Hz). 13C NMR spectrum, δC,
ppm: 31.68 (C2), 45.22 (C3), 46.00 (C1), 46.15 (C2′),
46.96 (C4), 48.70 (C7), 51.98 (C1′), 119.81 (CN),
134.51 (C6), 135.29 (C5). Mass spectrum: m/z 162
[M + H]+. Found, %: C 74.68; H 7.12; N 8.39.
C10H11NO. Calculated, %: C 74.51; H 6.88; N 8.69.
M 161.2005.
(1R,2R,3S,4S)-3-[(1S)-2-Chloro-1-hydroxyethyl]-
bicyclo[2.2.1]hept-5-ene-2-carbonitrile (XXV). Oily
substance, Rf 0.3 (petroleum ether–EtOAc, 3:1).
1H NMR spectrum, δ, ppm: 1.60 d (1H, 7-HA, J =
9.0 Hz), 1.39 d (1H, 7-HB, J = 9.0 Hz), 2.55 d.t (1H,
3-H, J = 9.1, 9.1, 3.1 Hz), 2.92 br.s (1H, 4-H), 3.02 br.s
(1H, OH), 3.16 d.d (1H, 2-H, J = 9.1, 3.2 Hz), 3.24 br.s
(1H, 1-H), 3.50 m (1H, 2′-HA), 3.58 d.d (1H, 2′-HB, J =
13.7, 3.3 Hz), 3.75 d.d.d (1H, 1′-H, J = 9.1, 3.6,
3.3 Hz), 6.18 m (1H, 5-H), 6.38 d.d (1H, 6-H, J = 5.4,
2.7 Hz). 13C NMR spectrum, δC, ppm: 32.07 (C2),
44.50 (C3), 46.40 (C1), 47.90 (C4), 48.94 (C2′), 49.51
(C7), 71.81 (C1′), 121.18 (CN), 134.94 (C6), 136.15
(C5), 159.77 (OCHO). Found, %: C 60.70; H 6.19;
Cl 17.90; N 7.10. C10H12ClNO. Calculated, %:
C 60.76; H 6.12; Cl 17.94; N 7.09.
(1S,6R,7S)-7-Hydroxymethylbicyclo[4.1.0]hept-
3-ene-1-carbaldehyde (XXVIII). Red-Al, 0.59 ml
(3.0 mmol), was dissolved at 0°C under argon in
7.0 ml of THF, 0.004 ml (1.5 mmol) of water was
added, the mixture was stirred for 5 min, and a solution
of 0.151 g (1.0 mmol) of compound XXII in 5.0 ml of
THF was added dropwise. When the reaction was
complete (TLC), the mixture was treated with
3% aqueous HCl to dissolve the precipitate, the prod-
uct was extracted into ethyl acetate (3×2 ml), the com-
bined extracts were dried over MgSO4 and concentrat-
ed, and the residue was subjected to chromatography
on silica gel to isolate 0.032 g (21%) of aldehyde
XXVIII and 0.105 g (36%) of diol XXXI.
(1S,2S,3S,6R,7R)-3-Chloromethyl-4-oxatricyclo-
[5.2.1.02.6]dec-8-en-5-one (XXVI). Colorless crystals,
mp. 56°C, [α]D20 = –84.4° (c = 1.0, CHCl3), Rf 0.2
(petroleum ether–EtOAc, 3:1). IR spectrum, ν, cm–1:
2960, 2852, 1751, 1458, 1178, 1037, 966, 742.
1H NMR spectrum, δ, ppm: 1.46 d (1H, 10-HA, J =
8.4 Hz), 1.66 d (1H, 10-HB, J = 8.4 Hz), 3.00 m (1H,
2-H), 3.15 m (1H, 7-H), 3.30 br.s (1H, 1-H), 3.33 m
(1H, 6-H), 3.62 br.s and 3.64 br.s (1H each, 1′-H),
4.18 d.d.d (1H, 3-H, J = 7.1, 4.2, 2.9 Hz), 6.24 d.d
(1H, 9-H, J = 5.5, 2.9 Hz), 6.32 d.d (1H, 8-H, J = 5.5,
2.9 Hz). 13C NMR spectrum, δC, ppm: 44.27 (C2),
45.25 (C1), 45.65 (C7), 47.1 (C1′), 48.34 (C6), 51.38
(C10), 79.92 (C3), 134.46 (C9), 136.60 (C8), 176.86
(C=O). Mass spectrum: m/z 199 [M + H]+. Found, %:
C 60.45; H 5.60; Cl 17.85. C10H11ClO. Calculated, %:
C 60.46; H 5.58; Cl 17.85. M 198.6458.
Aldehyde XXVIII. Oily substance, [α]D20 = –54°
(c = 1.0, CHCl3), Rf 0.2 (petroleum ether–EtOAc, 2:1).
IR spectrum, ν, cm–1: 3400, 2889, 1776, 1697, 1147,
1
756, 665. H NMR spectrum, δ, ppm: 0.87 m (1H,
7-H), 1.60 br.s (1H, OH), 1.75 m (1H, 6-H), 2.10 d.d
(1H, 2-HA, J = 9.6, 2.10 Hz), 2.28 br.d (1H, 5-HB, J =
9.3 Hz), 2.55 d.d.d (1H, 5-HA, J = 9.3, 1.5, 1.0 Hz),
3.10 d.t (1H, 2-HB, J = 9.6 Hz), 3.67 d.d (1H, 1′-HA,
J = 11.5, 6.7 Hz), 3.75 d.d (1H, 1′-HB, J = 11.5,
6.2 Hz), 5.09 d (1H, 4-H, J = 10.0, 1.0 Hz), 5.18 d.d
(1H, 3-H, J = 10.0, 2.6 Hz), 8.81 s (1H, CHO).
13C NMR spectrum, δC, ppm: 18.35 (C2), 19.88 (C5),
29.20 (C7), 29.68 (C6), 31.96 (C1), 57.76 (C1′), 123.37
(C3), 123.71 (C4), 102.13 (CHO). Found, %: C 71.09;
H 7.80. C9H12O2. Calculated, %: C 71.03; H 7.95.
(1R,2R,3S,4S)-3-[(1S)-Oxiran-1-yl]bicyclo[2.2.1]-
hept-5-ene-2-carbonitrile (XXVII). A solution of
3.2 g (16.0 mmol) of chlorohydrin XXV in 30.0 ml of
chloroform was cooled to 0°C, and a solution of
sodium methoxide prepared from 0.37 g (16.0 mmol)
of sodium and 17.8 ml of methanol was added. The
mixture was stirred for 30 min (TLC), treated with
water, and extracted with ethyl acetate (3×10 ml). The
extract was dried over MgSO4, the solvent was dis-
tilled off, and the residue was subjected to chromatog-
raphy on silica gel. Yield 2.4 g (94%), colorless crys-
tals, mp 96°C, [α]D20 = –80.3° (c = 1.9, CHCl3), Rf 0.49
(1S,6R,7S)-7-Hydroxymethyl-4-methylbicyclo-
[4.1.0]hept-3-ene-1-carbaldehyde (XXIX) was syn-
thesized in a similar way from 0.5 g (3.1 mmol) of
XXIII. Yield 0.107 g (21%), oily substance, [α]D20
=
–18.1° (c = 1.0, CHCl3), Rf 0.25 (petroleum ether–
EtOAc, 1:1). IR spectrum, ν, cm–1: 3446, 3396, 2962,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 7 2013

KHALILOVA et al.
994
1
2922, 2854, 1701, 1685, 1438, 1055. H NMR spec-
trum, δ, ppm: 2.08 s (3H, CH3), 2.21 m (1H, 7-H),
2.22 m (1H, 6-H), 2.54 m (2H, 2-HA, 5-HB), 2.85 d.d
(1H, 5-HA), 3.52 d.d (1H, 2-HB, J = 2.2 Hz), 4.05 d.d
(1H, 1′-HB, J = 11.5, 7.3 Hz), 4.13 d.d (1H, 1′-HA, J =
11.5, 6.4 Hz), 5.65 d (1H, 3-H, J = 1.0 Hz), 9.25 s (1H,
CHO). 13C NMR spectrum, δC, ppm: 19.06 (C2), 20.86
(CH3), 23.16 (C6), 24.63 (C5), 29.25 (C7), 31.81 (C1),
57.49 (C1′), 118.11 (C3), 130.17 (C4), 201.89 (CHO).
Mass spectrum: m/z 167 [M + H]+. Found, %: C 72.36;
H 8.50. C10H14O2. Calculated, %: C 72.26; H 8.49.
M 166.217.
leum ether–EtOAc, 2:1). IR spectrum, ν, cm–1: 3850,
2981, 2300, 1334, 864, 848, 725. H NMR spectrum,
1
δ, ppm: 1.68 (3H, CH3, J = 7.5 Hz), 1.70 m (1H,
7-HA), 2.14 d.d (1H, 1′-HA, J = 4.7, 2.9 Hz), 2.38 d.d
(1H, 7-HB, J = 8.3, 1.5 Hz), 2.52 d.d (1H, 1′-HB, J =
4.7, 6.5 Hz), 2.65 d.d.d (1H, 3-H, J = 6.5, 4.7, 2.9 Hz),
2.75 d.d (1H, 2-H, J = 4.7, 4.1 Hz), 3.10 br.d (1H, 4-H,
J = 1.5 Hz), 3.25 br.s (1H, 1-H), 6.23 d (1H, 6-H, J =
13
5.7 Hz), 6.28 d (1H, 5-H, J = 5.7 Hz). C NMR spec-
trum, δC, ppm: 30.57 (CH3), 45.50 (C2), 45.63 (C1′),
47.97 (C3), 48.23 (C7), 49.13 (C1), 52.76 (C4), 122.43
(CN), 134.92 (C5), 135.56 (C6). Found, %: C 81.56;
H 8.90; N 9.51. C10H13N. Calculated, %: C 81.59;
H 8.90; N 9.51.
(1S,2S,3S,4R,5R)-3-(Hydroxymethyl)tricyclo-
[3.2.2.02,4]non-6-ene-2-carbaldehyde (XXX) was
synthesized in a similar way from 0.124 g (0.7 mmol)
of XXIV. Yield 0.107 g (7%), oily substance, [α]D20 =
–20° (c = 0.3, CHCl3), Rf 0.82 (petroleum ether–
EtOAc, 6:1). IR spectrum, ν, cm–1: 2953, 2924, 1724,
(1R,2R,3S,4R)-3-[(1R)-1-Hydroxyethyl]bicyclo-
[2.2.1]hept-5-ene-2-carbonitrile (XXXIII). Oily sub-
stance, Rf 0.17 (petroleum ether–EtOAc, 2: 1).
1H NMR spectrum, δ, ppm: 1.62 d (3H, CH3, J =
6.2 Hz), 1.62 d.t (1H, 7-HA, J = 9.0, 1.9, 1.9 Hz),
1.70 d.t (1H, 7-HB, J = 9.0, 1.7, 1.7 Hz), 2.16 d.d (1H,
2-H, J = 4.6, 1.8 Hz), 2.32 d.d (1H, 3-H, J = 6.2,
4.6 Hz), 2.90 br.s (1H, 4-H), 3.15 d.d (1H, 1′-H, J =
6.2, 6.2 Hz), 3.24 br.s (1H, 1-H), 6.05 d.d (1H, 5-H,
J = 5.6, 2.8 Hz), 6.17 d.d (1H, 6-H, J = 5.6, 3.0 Hz).
Found, %: C 73.60; H 8.10; N 8.60. C10H13NO. Cal-
culated, %: C 73.59; H 8.03; N 8.58.
1
1710, 1182, 1039, 754. H NMR spectrum, δ, ppm:
1.20–1.32 m (2H, 8-H), 1.40–1.52 m (2H, 9-H),
1.70 m (1H, 6-H), 1.40 m (1H, 7-H), 2.20 m (1H, 5-H),
2.35 d (1H, 2-H, J = 7.0 Hz), 3.55 d.d (1H, 1′-HA, J =
11.4, 5.8 Hz), 3.75 d.d (1H, 1′-HB, J = 11.4, 2.8 Hz),
6.23 t (1H, 4-H, J = 7.0, 6.9 Hz), 6.42 t (1H, 3-H, J =
7.0, 7.0 Hz), 9.98 s (1H, CHO). 13C NMR spectrum,
δC, ppm: 21.94 (C8), 26.74 (C9), 31.39 (C7), 33.52 (C6),
38.13 (C5), 42.87 (C1), 42.89 (C2), 50.39 (C1′), 134.19
(C3), 135.88 (C4), 102.13 (CHO). Found, %: C 74.20;
H 8.00. C11H14O2. Calculated, %: C 74.13; H 7.92.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 11-03-97024-r_povolzh’e_a) and by the Federal
Grant-in-Aid Program “Human Capital for Science and
Education in Innovative Russia” (state contract
no. 14.740.11.0367).
(1S)-1-[(1S,6S)-6-(Aminomethyl)cyclohex-3-en-
1-yl]ethane-1,2-diol (XXXI). Colorless crystals, mp.
126°C, [α]D20 = +30.1° (c = 1.0, EtOH), Rf 0.5 (EtOH).
IR spectrum, ν, cm–1: 3329, 2855, 1637, 1467, 1394,
1
1055, 687. H NMR spectrum (CD3OD), δ, ppm:
REFERENCES
2.06 m (3H, 5′-H, 6′-H), 2.41 m (2H, 2′-H), 2.62 d.d.d
(1H, 1′-H, J = 6.7, 5.9, 4.6 Hz), 2.93 t (1H, CH2NH2,
J = 11.2, 11.2 Hz), 3.43 d.d (1H, CH2NH2, J = 11.2,
8.2 Hz), 3.75 d.d.d (1H, 1-H, J = 9.2, 4.6, 4.6 Hz),
3.85 d.d (1H, 2-HA, J = 11.4, 9.2 Hz), 3.91 d.d (1H,
2-HB, J = 11.4, 4.6 Hz), 4.90 br.s (3H, NH2, OH),
1. Khalilova, Yu.A., Krasnoslobodtseva, O.Yu., Shari-
pov, B.T., Spirikhin, L.V., and Valeev, F.A., Russ. J. Org.
Chem., 2012, vol. 48, p. 513.
2. Kondrova, Yu.A., Krasnoslobodtseva, O.Yu., Spiri-
khin, L.V., and Valeev, F.A., Russ. J. Org. Chem., 2010,
vol. 46, 1151.
13
5.66 m (1H, 4′-H), 5.72 m (1H, 3′-H). C NMR spec-
trum, δC, ppm: 21.55 (C2′), 24.76 (C5′), 36.61 (C1′),
37.15 (C6′), 48.02 (CH2NH2), 60.25 (C2), 68.52 (C1),
125.49 (C3′), 125.68 (C4′). Found, %: C 63.10;
H 10.00; N 8.28. C9H17NO2. Calculated, %: C 63.13;
H 10.01; N 8.18.
3. Isobe, M., Fukami, N., Nishikawa, T., and Goto, T.,
Heterocycles, 1987, vol. 25, p. 521.
4. Valeev, F.A., Gaisina, I.N., and Miftakhov, M.S., Izv.
Akad. Nauk, Ser. Khim., 1996, p. 2047.
5. Miftakhov, M.S., Valeev, F.A., and Gaisina, I.P., Usp.
Khim., 1994, vol. 63, p. 922.
Following an analogous procedure, from 0.2 g
(1.2 mmol) of compound XXVII we obtained 0.07 g
(38%) of XXXII and 0.03 g (15%) of XXXIII.
6. Simmons, H.E., Blanchard, E.P., and Smith, R.D., J. Am.
Chem. Soc., 1964, vol. 86, p. 1347.
(1S,2S,3S,4R)-3-Ethylbicyclo[2.2.1]hept-5-ene-2-
carbonitrile (XXXII). Oily substance, Rf 0.3 (petro-
7. Bly, R.S. and Konizer, G.B., J. Org. Chem., 1969, vol. 34,
p. 2346.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 7 2013