A general α-cyanoformylation using α-litho-β-ethoxyacrylonitrile: Application to the syntheses of new 6-cyano-2,4-bis(phenylthio)-and 4-cyano-2,6-bis(phenylthio)hepta-2,4,6-trienals

Article abstract of DOI:10.1039/b105894k

A new α-cyanoformylation of aldehydes and ketones proceeds in good to high yields using α-lithioacrylonitrile. This novel α-cyanoformylation is successfully applied to the preparation of two kinds of hepta-2,4,6-trienals, bearing a 6-cyano group (10) and a 4-cyano group (12).

Full text of DOI:10.1039/b105894k

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A general ꢀ-cyanoformylation using ꢀ-litho-ꢁ-ethoxyacrylonitrile:
application to the syntheses of new 6-cyano-2,4-bis(phenylthio)-
and 4-cyano-2,6-bis(phenylthio)hepta-2,4,6-trienals
1
Mitsuhiro Yoshimatsu,* Sachiko Yamaguchi and Yoshiaki Matsubara
Department of Chemistry, Faculty of Education, Gifu University, Yanagido 1-1, Gifu 501-1193,
Japan
Received (in Cambridge, UK) 4th July 2001, Accepted 24th August 2001
First published as an Advance Article on the web 4th October 2001
A new α-cyanoformylation of aldehydes and ketones proceeds in good to high yields using α-lithioacrylonitrile. This
novel α-cyanoformylation is successfully applied to the preparation of two kinds of hepta-2,4,6-trienals, bearing a
6-cyano group (10) and a 4-cyano group (12).
α-Cyanocinnamaldehydes have been one of the most important
classes of synthons for the syntheses of various biologically
active and heterocyclic compounds.1
Mostly, the cyanoethenes have been synthesized from the
Knoevenagel condensation using active methylene compounds
such as malonodinitrile,2 cyanoacetate,3 and cyanoacetic acid,
and their derivatives.4 However, cyanoacetaldehyde is highly
reactive to base, so that Knoevenagel conditions are not suit-
Fig. 1
able for the preparation of α-cyanoacrolein derivatives. There
are a few other synthetic approaches to α-cyanoacrolein; for
example, the oxidation of 2-cyanoprop-1-en-3-ols with PCC,5
with lithium 2,2,6,6-tetramethylpiperidide (LTMP) at Ϫ78 ЊC,
and successive reaction with benzaldehyde gave (Z)-2-cyano-3-
and the reduction of ethylenemalonodinitriles with DIBAL-H.6
ethoxy-1-phenylprop-3-en-1-ol 2a in 65% yield. We next
examined the dehydration of 2a with several kinds of acid and
found that trifluoromethanesulfonic acid trimethylsilyl ester
(TMSOTf ) was effective for the olefination process. Reaction
of 2a with TMSOTf afforded (E)-2-cyano-3-phenylprop-2-enal
3a as a single stereoisomer. The stereostructures of 2a and 3a
were determined by NOE experiments as shown in Fig. 1. α-
Cyanoformylation of various aldehydes proceeded in good to
high yields (Table 1, Entries 2–5). The easily enolizable 4-tert-
butylcyclohexanone gave 2f exclusively, and the successive
dehydration with TMSOTf afforded 3f in high yield; however,
the reaction with cyclohex-2-enone was accompanied by a
Michael addition product 4 (Entry 7). The bulky benzophenone
also gave the cyanoolefination product 3h in good yield (Entry
8). This novel olefination has been found to be applicable to the
various aldehydes and ketones tested.
Advantages of this olefination include introducing the cyano
group, which is less hindered and is strongly capable of
electron-withdrawing, retaining the formyl group, which could
be easily converted to other useful functional groups. Our
next approaches are the tandem α-cyanoformylation or the
preparations of the photo-sensitive hepta-2,4,6-trienal, which
would undergo the tandem cyclization to afford the oxabi-
cyclo[3.3.0]octa-3,7-diene. Our previous report has shown that
the photoreaction of 2,4,6-tris(phenylthio)-2,4,6-heptatrienal
afforded the new heterocycles, 2-oxa- or aza-bicyclic com-
pounds.10 First, a tandem olefination was examined as shown
in Scheme 2. Reaction of 2b with α-lithiated acrylonitrile gave
Recently, a convenient α-cyanoformylation of aromatic alde-
hydes with 3,3-dimethoxypropiononitrile–NaOMe and succes-
sive hydration with 6 M HCl has been reported; however, this
method has not been further investigated.1b
Results and discussion
Recently, we have reported a versatile olefination of carbonyl
compounds using 2-alkoxy-1-chalcogen-substituted alkenyl-
lithiums. In particular, we have shown the following two types
of olefinations: (i) a formyl olefination bearing a chalcogen
functional group at the α-position of the formyl group,7 and
(ii) a perfluoroacyl olefination bearing a chalcogen or non-
chalcogen functional group at the α-position to the perfluoro-
acyl group.8 Since β-alkoxyacrylonitriles have been easily and
regioselectively lithiated,9 a general olefination process using
its alkenyllithium will provide a novel α-cyanoformylation
(Scheme 1). As far as we know, no one has reported the general
Scheme 1
α-cyanoformylation of carbonyl compounds. If the olefination
using β-alkoxyacrylonitrile is accomplished, it will provide use-
ful synthons for the preparation of bioactive or heterocyclic
compounds. Here, we report the novel α-cyanoformylation of
carbonyl compounds and their application to the syntheses of
new cyano-substituted hepta-2,4,6-trienals.
2,4-dicyano-1-ethoxy-6,6-dimethylhepta-1,4-dien-3-ol
5
in
35% yield; however, attempted dehydration with TMSOTf to
give the aldehyde 6 did not succeed.
Next, we attempted to prepare the cyano-substituted hepta-
2,4,6-trienals. α-Thioformylation of 2b with PhSCH᎐CHOEt–
᎐
β-Ethoxyacrylonitrile 1 was easily lithiated by treatment
n-BuLi afforded the penta-2,4-dienal 8 via the intermediate
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J. Chem. Soc., Perkin Trans. 1, 2001, 2560–2565
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b105894k

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Table 1 α-Cyanoformyl olefination of aldehydes and ketones
Carbonyl compound
Entry
R1
R2
Alcohol (% yield)
Product (% yield)
1
2
3
4
5
6
7
8
Ph
H
H
H
Me
H
(Z)-2a (65)
(Z)-2b (quant.)
(Z)-2c (54)
(Z)-2d (76)
(Z)-2e (55)
2f (59)
(E)-3a (91)
(E)-3b (91)
(E)-3c (83)
(E)-3d (99)
(E)-3e (99)
3f (99)
tBu
Phenylethynyl
(E)-PhCH᎐CH
᎐
tBuCH᎐C(SPh)
᎐
(CH2)2CH(t-Bu)(CH2)2
CH᎐CH(CH2)3
Ph
2g (28)a
3g (99)
᎐
Ph
(Z)-2h (53)
3h (99)
a
was also produced.
Scheme 2 Reagents and conditions: i, 1, LTMP, Ϫ78 ЊC; ii, TMSOTf. Ϫ78 ЊC; iii, PhSCH᎐CHOEt, n-BuLi, Ϫ78 ЊC.
᎐
alcohol 7 in good yield. The second olefination afforded the
desired hepta-2,4,6-trienal 10. Furthermore, we conducted the
olefination of 3e in order to prepare the 4-cyano-substituted
hepta-2,4,6-trienal 12. The 4-cyano-2,6-bis(phenylthio)hepta-
2,4,6-trienal 12 was obtained in moderate yield; however,
α-cyanoformylation of 13 did not produce the trienal 16, but
instead gave 3-tert-butyl-2-(1-cyano-2-ethoxyethenyl)-1,4-bis-
(phenylthio)cyclopenta-1,3-diene 15 via cationic cyclization.
The reaction of 8 with α-lithioacrylonitrile gave the hepta-
1,4,6-trien-3-ol 17; however, treatment of 17 with TMSOTf
did not give the desired trienal 19, but instead the cyclized 2-
oxabicyclo[3.3.0]octa-3,7-diene 18 (Scheme 3). The structure
was determined by the existence of the two cyano groups in
the IR spectrum, which showed ν 2040 and 2160 cmϪ1; by the
existence of the two characteristic kinds of methine protons
and the olefinic protons in the 1H NMR spectrum, which
exhibited δ 2.88 (t, J 2 Hz, 5-H), 3.54 (t, J 2 Hz, 6-H), 6.42 (d,
J 2 Hz, 3-H), 6.95 (d, J 2 Hz, 8-H), which is determined by the
correlations of the H–H COSY (Fig. 2); and the molecular
formula C19H18N2OS (m/z 322). The stereochemistry of 18 was
J. Chem. Soc., Perkin Trans. 1, 2001, 2560–2565
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aceutical University. 1H and 13C NMR spectra were determined
with a Varian Inova 400 (400 MHz) spectrometer at the Center
of Instrumentation of Gifu University. Chemical shifts (δ) are
expressed in parts per million (ppm) with respect to tetrameth-
ylsilane as internal standard. Splitting patterns are designated
as follows: s = singlet, d = doublet, t = triplet, q = quartet.
J-Values are given in Hz. IR spectra of solids (KBr) and
liquids (film) were recorded on a JASCO IR A-100 infrared
spectrometer. EI Mass spectra (MS) were obtained using a
JMS-SX102A spectrometer with a direct-insertion probe at
an ionization voltage of 70 eV. Ether refers to diethyl ether.
Fig. 2
Preparation of 3-ethoxy-2-cyanoprop-2-en-1-ols 2a–i, 5, 14, 17
using ꢀ-lithio-2-ethoxyacrylonitrile: typical procedure
(Z )-2-Cyano-3-ethoxy-1-phenylprop-2-en-1-ol 2a. Under an
Ar atmosphere, a THF (2.00 ml) solution of 3-ethoxyacrylo-
nitrile 1 (0.30 g, 3.10 mmol) was added dropwise to a THF
(5.00 ml) solution of lithium 2,2,6,6-tetramethylpiperidide
[prepared from n-BuLi (3.10 ml, 4.65 mmol) and 2,2,6,6-
tetramethylpiperidine (0.88 g, 6.20 mmol)] at Ϫ78 ЊC. Then, a
THF (1.00 ml) solution of benzaldehyde (0.49 g, 4.65 mmol)
was added dropwise to the reaction mixture. The whole was
poured into water (50.0 ml), the organic layer was separated,
and the aqueous layer was extracted with ether. The combined
organic layer was dried over MgSO4. The solvent was removed
under reduced pressure. The residue was purified by preparative
TLC on silica gel and development with AcOEt–hexane (1 : 5)
to give the title compound 2a (0.41 g, 65%) as a yellow oil, IR
(film; cmϪ1) 3600–3100 (OH), 2170 (CN); 1H NMR (400 MHz;
CDCl3) δ 1.30 (3H, t, J 7, Me), 3.02 (1H, br s, OH), 4.04 (2H, q,
J 7, OCH2), 5.71 (1H, s, 1-H), 6.85 (1H, s, olefinic H), 7.25–7.34
(3H, m, ArH), 7.41–7.44 (2H, m, ArH); 13C NMR (100 MHz;
CDCl3) δ 15.30 (q), 66.68 (d), 71.41 (t), 97.58 (s), 117.85 (s),
125.78 (2d), 128.01 (2d), 128.58 (2d), 141.34 (s), 158.78 (d); MS
m/z 203 (Mϩ) (Calc. for C12H13NO2: C, 70.92; H, 6.45; N, 6.89.
Found: C, 70.58; H, 6.53; N, 7.02%).
Fig. 3
Scheme 3 Reagents and conditions: i, 1, LTMP, Ϫ78 ЊC; ii, TMSOTf,
Ϫ78 ЊC.
determined by NOE experiments (Fig. 3). Irradiation of 5-H at
δ 2.88 increased the intensity of the t-Bu group, not that of 6-H.
The plausible mechanism for formation of the oxabicyclic
compound is considered to be the same as that in the previous
report; however, the fact that the 2,6-dicyano-4-(phenylthio)-
hepta-2,4,6-trienal 19 could not be isolated, and instead directly
afforded the 2-oxabicyclo[3.3.0]octa-3,7-diene 18, shows that
the cyano group at the 2-position of the trienal accelerates this
tandem cyclization of the hepta-2,4,6-trienals. We also per-
formed the photocyclizations of the hepta-2,4,6-trienals 12 and
10; however, the 2-oxabicyclic compounds gave rise to only low
yields or a complex mixture (Scheme 4).
(Z )-2-Cyano-1-ethoxy-4,4-dimethylpent-en-3-ol 2b. A brown
oil, IR (film; cmϪ1) 3820–3080 (OH), 2240 (CN); 1H NMR
(400 MHz; CDCl3) δ 0.98 (9H, s, Me × 3), 1.32 (3H, t, J 7,
Me), 2.11 (1H, d, J 6, OH), 4.06 (2H, q, J 7, OCH2), 4.27 (1H,
d, J 6, 3-H), 6.92 (1H, s, olefinic H); 13C NMR (100 MHz;
CDCl3) δ 15.45 (q), 25.78 (3q), 36.95 (s), 71.30 (t), 73.32 (d),
95.04 (s), 119.14 (s), 159.45 (d); MS m/z 183 (Mϩ). (Calc. for
C10H17NO2: C, 65.54; H, 9.35; N, 7.64. Found: C, 65.14; H,
9.49; N, 7.62%).
(Z )-2-Cyano-1-ethoxy-5-phenylpent-1-en-4-yn-3-ol
2c.
Yellow needles, mp 30 ЊC; IR (film; cmϪ1) 3800–3150 (OH),
2230 (CN); 1H NMR (400 MHz; CDCl3) δ 1.36 (3H, t, J 7, Me),
2.68 (1H, d, J 6, OH), 4.13 (2H, q, J 7, OCH2), 5.56 (1H, d, J 6,
3-H), 6.95 (1H, d, J 1, olefinic H), 7.26–7.38 (3H, m, ArH),
7.43–7.52 (2H, m, ArH); 13C NMR (100 MHz; CDCl3) δ 15.35
(q), 56.53 (t), 71.90 (d), 86.32 (s), 95.40 (s), 117.47 (s), 122.11 (s),
124.66 (s), 128.45 (2d), 128.99 (d), 132.10 (2d), 159.69 (d); MS
m/z 227 (Mϩ) (Calc. for C14H13NO2: C, 73.99; H, 5.77; N, 6.16.
Found: C, 73.66; H, 5.85; N, 6.15%).
Scheme 4 Conditions: i, MeCN, hν (500–600 nm).
In summary, α-cyanoformylation is considered to be one of
the good methods for the preparation of various α-cyano-
acrolein derivatives. In addition, we could carry out syntheses
of some cyano-substituted hepta-2,4,6-trienals. Now we are
examining other transformations of the new 2,4,6-trienals and
their derivatives. These results will be reported elsewhere.
(1Z,4E )-2-Cyano-1-ethoxy-3-methyl-5-phenylpenta-1,4-dien-
3-ol 2d. Yellow needles, mp 30 ЊC; IR (film; cmϪ1) 3650–3150
1
(OH), 2220 (CN); H NMR (400 MHz; CDCl3) δ 1.31 (3H, t,
J 7, Me), 1.63 (3H, s, Me), 3.33 (1H, s, OH), 4.05–4.10 (2H, m,
OCH2), 6.36 (1H, d, J 16, 4-H), 6.63 (1H, d, J 16, 5-H), 6.88
(1H, s, 1-H), 7.22–7.39 (5H, m, ArH); 13C NMR (100 MHz;
CDCl3) δ 15.40 (q), 28.14 (q), 72.05 (t), 72.49 (s), 100.17 (s),
118.30 (s), 126.76 (2d), 127.79 (d), 127.88 (d), 128.73 (2d),
133.37 (d), 136.58 (s), 158.52 (d); MS m/z 200 (Mϩ Ϫ Ph), 166
(Mϩ Ϫ OH, CN) (Calc. for C15H17NO2: C, 74.05; H, 7.04; N,
5.76. Found: C, 74.30; H, 6.83; N, 6.01%).
Experimental
Mps were determined on a Yanagimoto micro-melting-point
apparatus and are uncorrected. Elemental analyses were per-
formed at the Microanalytical Laboratory of Gifu Pharm-
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J. Chem. Soc., Perkin Trans. 1, 2001, 2560–2565

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(1Z,4E )-2-Cyano-1-ethoxy-6,6-dimethyl-4-(phenylthio)hepta-
1,4-dien-3-ol 2e. Mp 96–97 ЊC, IR (film; cmϪ1) 3600–3300 (OH),
2240 (CN); 1H NMR (400 MHz; CDCl3) δ 1.21 (3H, t, J 7, Me),
1.30 (9H, s, Me × 3), 2.37 (1H, d, J 5, OH), 3.92–3.99 (2H, m,
OCH2), 4.94 (1H, d, J 5, 3-H), 6.62 (1H, d, J 1, 5-H), 6.87 (1H,
s, 1-H), 7.15–7.29 (5H, m, ArH); 13C NMR (100 MHz; CDCl3)
δ 15.28 (q), 30.76 (3q), 33.77 (s), 67.53 (d), 71.29 (t), 96.56 (s),
117.47 (s), 126.22 (d), 128.83 (2d), 129.09 (2d), 129.55 (s),
135.52 (s), 148.70 (d), 160.10 (d); MS m/z 317 (Mϩ) (Calc. for
C18H23NO2S: C, 68.11; H, 7.30; N, 4.11. Found: C, 67.82; H,
7.36; N, 4.27%).
(1Z,4E )-2,4-Dicyano-1-ethoxy-6,6-dimethylhepta-1,4-dien-3-
ol 5. A brown oil, IR (film; cmϪ1) 3750–3100 (OH), 2220 (CN);
1H NMR (400 MHz; CDCl3) δ 1.26 (9H, s, Me × 3), 1.37 (3H, t,
J 7, Me), 3.11 (1H, s, OH), 4.15 (2H, q, J 7, OCH2), 5.19 (1H, s,
olefinic H), 6.61 (1H, d, J 1, CH), 7.05 (1H, s, olefinic H); 13C
NMR (100 MHz; CDCl3) δ 15.37 (q), 29.62 (3q), 34.41 (s),
66.21 (d), 72.12 (t), 94.26 (s), 110.84 (s), 116.29 (s), 116.77 (s),
157.64 (d), 160.79 (d) (Calc. for C13H18N2O2: M, 234.1368.
Found: Mϩ, 234.1352).
Hydrolysis of 2-cyano-3-ethoxyprop-2-en-1-ols 2a–h. Typical
procedure
(Z )- and (E )-4-tert-Butyl-1-(1-cyano-2-ethoxyethenyl)cyclo-
hexanol 2f. The Z-isomer was obtained as colorless prisms,
Trimethylsilyl trifluoromethanesulfonate (TMSOTf ) (0.36 ml,
2.00 mmol) was added dropwise to a CH2Cl2 (2.00 ml) solution
of 2a (0.20 g, 1.00 mmol) at Ϫ78 ЊC under an Ar atmosphere.
After stirring for 10 min, the reaction mixture was poured into
saturated aq. NaHCO3 (50 ml). The organic layer was separated
and the aqueous layer was extracted with CHCl3. The com-
bined organic layer was dried over MgSO4. The solvent was
removed under reduced pressure, and the residue was crystal-
lized from hexane. The orange powder was filtered off and
recrystallized from ether–hexane to give (E)-2-cyano-3-phenyl-
prop-2-enal 3a (0.14 g, 91%) as colorless needles, mp 85–86 ЊC;
1
mp 64–66 ЊC; IR (film; cmϪ1) 3650–3300 (OH), 2210 (CN); H
NMR (400 MHz; CDCl3) δ 0.87 (9H, s, Me × 3), 1.01–1.02
(1H, m, 4-H), 1.36 (3H, t, J 7, Me), 1.42–1.46 (2H, m, CH2),
1.58–1.61 (2H, m, CH2), 1.65–1.72 (2H, m, CH2), 1.95–1.99
(2H, m, CH2), 2.76 (1H, s, OH), 4.09 (2H, q, J 7, OCH2), 6.82
(1H, s, olefinic H); 13C NMR (100 MHz; CDCl3) δ 15.38 (q),
22.23 (2t), 27.64 (3q), 32.52 (s), 37.17 (2t), 47.26 (d), 71.20 (s),
71.85 (t), 102.53 (s), 118.57 (s), 158.22 (d); MS m/z 251 (Mϩ)
(Calc. for C15H25NO2: C, 71.67; H, 10.02; N, 5.57. Found:
C, 71.39; H, 10.28; N, 5.50%).
1
IR (KBr; cmϪ1) 2220 (CN), 1690 (CO); H NMR (400 MHz;
The E-isomer was obtained as a brown oil, IR (film; cmϪ1
)
CDCl3) δ 7.54–7.65 (3H, m, ArH), 7.97 (1H, s, olefinic H), 8.04–
8.06 (2H, m, ArH), 9.61 (1H, s, CHO); 13C NMR (100 MHz;
CDCl3) δ 112.54 (s), 114.25 (s), 129.69 (2d), 131.38 (s), 131.51
(2d), 134.52 (d), 159.59 (d), 187.27 (d); MS m/z 157 (Mϩ) (Calc.
for C10H7NO: C, 76.42; H, 4.49; N, 8.91. Found: C, 76.27;
H, 4.59; N, 8.98%).
3700–3130 (OH), 2220 (CN); 1H NMR (400 MHz; CDCl3)
δ 0.85 (9H, s, Me × 3), 1.00–1.25 (3H, m, 4-H and CH2), 1.37
(3H, t, J 7, Me), 1.39–1.56 (2H, m, CH2), 1.73–1.76 (2H, m,
CH2), 2.32–2.41 (2H, m, CH2), 2.71 (1H, br s, OH), 4.13 (2H, q,
J 7, OCH2), 6.91 (1H, s, olefinic H); 13C NMR (100 MHz;
CDCl3) δ 15.44 (q), 24.72 (2t), 27.72 (3q), 32.38 (s), 38.52 (2t),
47.08 (d), 72.05 (t), 72.44 (s), 98.45 (s), 119.56 (s), 160.47 (d);
MS m/z 251 (Mϩ).
(E )-2-Cyano-4,4-dimethylpent-2-enal 3b. White powder,
1
mp 30 ЊC; IR (KBr; cmϪ1) 2240 (CN), 1710 (CO); H NMR
(400 MHz; CDCl3) δ 1.37 (9H, s, Me × 3), 7.36 (1H, s, olefinic
H), 9.40 (1H, s CHO); 13C NMR (100 MHz; CDCl3) δ 28.91
(3q), 36.22 (s), 94.57 (s), 112.80 (s), 177.49 (d), 187.43 (d); MS
m/z 138 (Mϩ) (Calc. for C8H11NO: C, 70.04; H, 8.08; N, 10.21.
Found: C, 69.88; H, 8.23; N, 10.10%).
(E )- and (Z )-1-(1-Cyano-2-ethoxyethenyl)cyclohex-2-en-1-ol
2g. A yellow oil, E : Z = 80 : 20; IR (film; cmϪ1) 3750–3150
(OH), 2230 (CN); H NMR (400 MHz; CDCl3) δ 1.34 (t, J 7,
1
Z-Me), 1.37 (t, J 7, E-Me), 1.65–2.07 (m, E- and Z-CH2), 2.68
(br s, Z-OH), 3.12 (s, E-OH), 4.07 (q, J 7, Z-OCH2), 4.12 (q, J 7,
E-OCH2), 5.61 (m, Z-CH), 5.82 (d, J 10, E-CH), 5.88–5.98 (m,
(E )-2-Cyano-5-phenylpent-2-en-4-ynal 3c. Colorless needles
(from ether–hexane), mp 59–60 ЊC; IR (KBr; cmϪ1) 2190 (CN),
1690 (CO); 1H NMR (400 MHz; CDCl3) δ 7.34 (1H, s, olefinic
H), 7.41–7.53 (3H, m, ArH), 7.62–7.65 (2H, m, ArH), 9.55
(1H, s, CHO); 13C NMR (100 MHz; CDCl3) δ 85.76 (s), 113.02
(s), 116.42 (s), 120.61 (s), 123.22 (s), 129.05 (2d), 131.88 (d),
133.37 (2d), 140.02 (d), 185.33 (d); MS m/z 181 (Mϩ) (Calc. for
C12H7NO: C, 79.55; H, 3.89; N, 7.73. Found: C, 79.31; H, 3.99;
N, 7.71%).
E- and Z-CH), 6.89 (s, E-olefinic H), 6.98 (s, Z-olefinic H); 13
C
NMR (100 MHz; CDCl3) δ 15.29 (E-q), 18.84 (Z-t), 24.72 (E-t),
24.84 (Z-t), 35.71 (E-t), 36.37 (Z-t), 69.42 (Z-s), 69.64 (E-s),
70.69 (Z-t), 71.90 (E-t), 97.84 (Z-s), 100.84 (E-s), 116.07 (Z-s),
118.58 (E-s), 129.68 (Z-d), 129.73 (E-d), 131.01 (E-d), 132.33
(Z-d), 158.86 (E-d), 160.41 (Z-d); MS m/z 193 (Mϩ) (Calc. for
C11H15NO2: C, 68.37; H, 7.82; N, 7.25. Found: C, 67.98; H,
7.87; N, 7.33%).
(E )-3-(1-Cyano-2-ethoxyethenyl)cyclohexanone 4. A yellow
oil, IR (film; cmϪ1) 2230 (CN), 1720 (CO); 1H NMR (400 MHz;
CDCl3) δ 1.33 (3H, t, J 7, Me), 1.67–1.80 (2H, m, CH2), 1.88–
1.91 (1H, m, CH2), 2.11–2.19 (2H, m, CH2), 2.28–2.40 (3H, m,
CH2), 2.94–3.02 (1H, m, 3-H), 4.07 (2H, q, J 7, OCH2), 6.86
(1H, s, olefinic H); 13C NMR (100 MHz; CDCl3) δ 15.24 (q),
24.95 (t), 34.34 (d), 40.85 (t), 45.87 (t), 95.61 (s), 118.27 (s),
158.12 (d), 209.74 (s); MS m/z 193 (Mϩ) (Calc. for C11H15NO2:
C, 68.37; H, 7.82; N, 7.25. Found: C, 67.93; H, 7.97; N, 7.15%).
(2E,4E )-2-Cyano-3-methyl-5-phenylpenta-2,4-dienal
3d.
Yellow needles, mp 56–58 ЊC; IR (KBr; cmϪ1) 2230 (CN), 1680
1
(CO); H NMR (400 MHz; CDCl3) δ 2.60 (3H, s, Me), 7.43–
7.49 (4H, m, ArH and 4-H), 7.56 (1H, d, J 16, 5-H), 7.62–7.64
(2H, m, ArH), 10.04 (1H, s, CHO); 13C NMR (100 MHz;
CDCl3) δ 14.55 (q), 114.86 (s), 127.23 (d), 128.79 (2d), 129.43
(2d), 131.46 (d), 134.85 (s), 143.71 (d), 185.34; MS m/z 197 (Mϩ)
(Calc. for C13H11NO: C, 79.17; H, 5.62; N, 7.10. Found: C,
79.01; H, 5.72; N, 7.10%).
(E )- and (Z)-2-Cyano-3-ethoxy-1,1-diphenylprop-2-en-1-ol
(2E,4E )-2-Cyano-6,6-dimethyl-4-(phenylthio)hepta-2,4-dienal
3e. Brown powder, mp 68–72 ЊC; IR (KBr; cmϪ1) 2230 (CN),
1700 (CO); 1H NMR (400 MHz; CDCl3) δ 1.38 (9H, s, Me × 3),
7.14 (1H, s, 3-H), 7.23–7.32 (5H, m, ArH), 7.42 (1H, s, 5-H),
9.27 (1H, s, CHO); 13C NMR (100 MHz; CDCl3) δ 30.07 (3q),
113.29 (s), 114.85 (s), 127.19 (d), 127.41 (s), 129.02 (2d), 129.62
(2d), 133.98 (s), 162.92 (d), 163.99 (d), 186.48 (d) (Calc. for
C16H17NOS: M, 271.1031. Found: Mϩ, 271.1022).
2h. E : Z = 95 : 5, White powder, mp 57–60 ЊC; IR (KBr; cmϪ1
)
3630–3500 (OH), 2210 (CN); 1H NMR (400 MHz; CDCl3)
δ 1.13 (t, J 7, E-Me), 1.25 (t, J 7, Z-Me), 2.03 (s, E-OH), 2.15
(s, Z-OH), 3.97 (q, J 7, E-OCH2), 4.11 (q, J 7, Z-OCH2), 6.63
(s, Z-olefinic H), 7.01 (s, E-olefinic H), 7.25–7.41 (m, E- and
Z-ArH); 13C NMR of (E)-2h (100 MHz; CDCl3) δ 15.27 (q),
72.19 (t), 79.34 (s), 102.09 (s), 118.47 (s), 127.20 (4d), 128.07
(2d), 128.21 (4d), 144.45 (2s), 159.13 (d); MS m/z 279 (Mϩ)
(Calc. for C18H17NO2: C, 77.40; H, 6.13; N, 5.01. Found: C,
77.37; H, 6.16; N, 4.98%).
2-(4-tert-Butylcyclohexylidene)-2-cyanoethanal
3f.
Pale
yellow powder, mp 103–105 ЊC; IR (KBr; cmϪ1) 2230 (CN),
J. Chem. Soc., Perkin Trans. 1, 2001, 2560–2565
2563

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1670 (CO); 1H NMR (400 MHz; CDCl3) δ 0.90 (9H, s, Me × 3),
1.28–1.48 (3H, m, CH and CH2), 2.14–2.18 (2H, m, CH2), 2.26–
2.44 (2H, m, CH2), 3.13–3.14 (1H, m, CH2), 3.17–3.18 (1H, m,
CH2), 9.95 (1H, s, CHO); 13C NMR (100 MHz; CDCl3) δ 27.60
(3q), 29.37 (d), 30.75 (s), 37.13 (2t), 47.41 (2t), 112.55 (s), 114.06
(s), 181.91 (s), 184.16 (d); MS m/z 205 (Mϩ) (Calc. for
C13H19NO: C, 76.06; H, 9.33; N, 6.82. Found: C, 75.78; H,
9.35; N, 6.75%).
added dropwise to a THF (2.00 ml) solution of PhSCLi᎐
᎐
CHOEt [prepared from PhSCH᎐CHOEt (0.16 g, 0.86 mmol)
᎐
and n-BuLi (0.43 ml, 0.65 mmol)] at Ϫ78 ЊC. The work-up
procedure afforded the title compound 9 (65 mg, 32%) as a
1
yellow oil, IR (film; cmϪ1) 3650–3150 (OH), 2230 (CN); H
NMR (400 MHz; CDCl3) δ 1.14 (9H, s, Me × 3), 1.24 (3H,
t, J 7, Me), 2.81 (1H, d, J 7, OH), 3.89–4.00 (2H, m, OCH2),
5.22 (1H, d, J 5, CH), 5.96 (1H, d, J 1, olefinic H), 6.55 (1H, t,
J 1, olefinic H), 6.80 (1H, t, J 12, CH), 7.09–7.39 (6H, m,
ArH), 7.42–7.45 (4H, m, ArH); 13C NMR (100 MHz; CDCl3)
δ 15.43 (q), 29.49 (3q), 34.59 (s), 69.83 (t), 70.72 (d), 107.28 (s),
108.48 (s), 116.64 (s), 126.10 (d), 126.74 (d), 127.17 (2d), 128.99
(2d), 129.04 (2d), 129.94 (d), 130.15 (2d), 134.79 (s), 137.94 (s),
138.16 (s), 157.51 (d), 163.06 (d); MS m/z 452 (Mϩ ϩ 1).
This compound was too labile to be isolated at room tem-
perature, so it was taken to the next (hydration) step without
purification.
(E )-2-Cyano-2-(cyclohex-2-enylidene)ethanal 3g. A brown
oil, E : Z = 59 : 41; IR (film; cmϪ1) 2230 (CN), 1670 (CO);
1H NMR (400 MHz; CDCl3) δ 1.89–1.98 (m, CH2), 2.42–2.47
(m, CH2), 2.86–2.89 (m, CH2), 3.06–3.09 (m, CH2), 6.80–6.91
(m, olefinic H), 7.31–7.35 (m, olefinic H), 9.98 (s, E-CHO),
10.00 (s, Z-CHO); MS m/z 146 (Mϩ Ϫ 1) (Calc. for C9H9-
NO: C, 73.45; H, 6.16; N, 9.52. Found: C, 73.19; H, 6.23;
N, 9.48%).
Hydration of 9. TMSOTf (0.10 ml, 0.55 mmol) was added
dropwise to a CH2Cl2 (2.00 ml) solution of 9 (50 mg,
0.11 mmol) at Ϫ78 ЊC. The work-up procedure afforded
(2Z,4Z,6Z)-6-cyano-8,8-dimethyl-2,4-bis(phenylthio)nona-
2-Cyano-3,3-diphenylprop-2-enal 3h. Pale yellow needles, mp
1
140–142 ЊC; IR (KBr; cmϪ1) 2230 (CN), 1670 (CO); H NMR
(400 MHz; CDCl3) δ 7.26–7.28 (2H, m, ArH), 7.45–7.63 (8H,
m, ArH), 9.42 (1H, s, CHO); 13C NMR (100 MHz; CDCl3)
δ 113.34 (s), 115.58 (s), 128.91 (2d), 128.95 (2d), 130.80 (2d),
131.70 (2d), 132.20 (d), 132.71 (d), 135.81 (s), 137.66 (s), 173.34
(s), 187.12 (d); MS m/z 233 (Mϩ) (Calc. for C16H11NO: C, 82.38;
H, 4.75; N, 6.00. Found: C, 82.20; H, 4.73; N, 5.91%).
2,4,6-trienal 10 (22 mg, 49%) as a yellow oil, IR (film; cmϪ1
)
2240 (CN), 1710 (CO); 1H NMR (400 MHz; CDCl3) δ 1.32 (9H,
s, Me × 3), 6.45 (1H, s, olefinic H), 6.55 (1H, d, J 1, olefinic H),
6.62 (1H, d, J 1, olefinic H), 7.07–7.10 (2H, m, ArH), 7.20–7.31
(6H, m, ArH), 7.36–7.38 (2H, m, ArH), 9.18 (1H, s, CHO);
13C NMR (100 MHz; CDCl3) δ 29.60 (3q), 35.29 (s), 108.55 (s),
116.01 (s), 127.57 (d), 127.94 (d), 129.35 (2d), 129.48 (2d),
130.09 (2d), 131.44 (2d), 133.20 (s), 136.16 (d), 137.80 (s),
148.12 (d), 166.41 (d), 189.11 (d) (Calc. for C24H23NO2S2: M,
421.1170. Found: Mϩ, 421.1168).
Preparation of (2Z,4Z,6Z )-6-cyano-8,8-dimethyl-2,4-bis(phenyl-
thio)nona-2,4,6-trienal 10
(1E,4E )-4-Cyano-1-ethoxy-6,6-dimethyl-2-(phenylthio)hepta-
1,4-dien-3-ol 7. Under an Ar atmosphere, a THF (1.50 ml)
solution of (E)-2-cyano-4,4-dimethylpent-1-en-3-ol 2b (0.14 g,
1.00 mmol) was added dropwise to a THF (2.00 ml) solution
Preparation of (2Z,4Z,6Z )-4-cyano-8,8-dimethyl-2,6-bis(phenyl-
thio)nona-2,4,6-trienal 12
of PhSCLi᎐CHOEt [prepared from 2-ethoxyvinyl phenyl
᎐
sulfide (0.27 g, 1.50 mmol) and n-BuLi (0.80 ml, 1.20 mmol)]
at Ϫ78 ЊC. After stirring for 10 min, the reaction mixture was
poured into water (50 ml). The organic layer was separated and
the aqueous layer was extracted with ether. The combined
organic layer was dried over MgSO4. The solvent was removed
under reduced pressure. The residue was purified by preparative
TLC on silica gel and development with AcOEt–n-hexane
(1 : 5) to give the title compound 7 (0.17 g, 52%) as a yellow oil,
(1E,4E,6Z )-4-Cyano-1-ethoxy-8,8-dimethyl-2,6-bis(phenyl-
thio)nona-1,4,6-trien-3-ol 11. Under an Ar atmosphere, a THF
(1.00 ml) solution of 2-cyano-6,6-dimethyl-4-(phenylthio)-
hepta-2,4-dienal 3e (0.27 g, 1.00 mmol) was added dropwise to
a THF (5.00 ml) solution of PhSCLi᎐CHOEt [prepared from
᎐
PhSCH᎐CHOEt (0.36 g, 2.00 mmol) and n-BuLi (1.00 ml,
᎐
1.50 mmol)] at Ϫ78 ЊC. The work-up procedure afforded the
1
IR (film; cmϪ1) 3700–3200 (OH), 2240 (CN); H NMR (400
title compound 11 (0.25 g, 55%) as a brown oil, IR (film; cmϪ1
)
1
MHz; CDCl3) δ 1.04 (9H, s, Me × 3), 1.37 (3H, t, J 7, Me), 3.28
(1H, d, J 9, OH), 4.06 (2H, q, J 7, OCH2), 5.14 (1H, dd, J 9 and
1, CH), 6.28 (1H, d, J 1, olefinic H), 6.85 (1H, s, olefinic H),
7.13–7.16 (1H, m, ArH), 7.22–7.27 (2H, m, ArH), 7.31–7.34
(2H, m, ArH); 13C NMR (100 MHz; CDCl3) δ 15.41 (q), 29.34
(3q), 33.98 (s), 70.23 (t), 71.17 (d), 107.93 (s), 112.29 (s), 116.82
(s), 126.16 (d), 127.24 (2d), 129.08 (2d), 137.08 (s), 156.14 (d),
156.92 (d) (Calc. for C18H23NO2S: M, 317.1449. Found:
Mϩ, 317.1444).
3480 (OH), 2250 (CN); H NMR (400 MHz; CDCl3) δ 1.27
(9H, s, Me × 3), 1.32 (3H, t, J 7, Me), 2.92 (1H, d, J 8, OH), 3.98
(2H, q, J 7, CH2), 5.03 (1H, d, J 8, CH), 6.25 (1H, s, olefinic H),
6.48 (1H, s, olefinic H), 6.75 (1H, s, olefinic H), 7.12–7.29 (10H,
m, ArH); 13C NMR (100 MHz; CDCl3) δ 15.46 (q), 30.36 (3q),
34.59 (s), 70.34 (t), 107.97 (s), 116.30 (s), 116.73 (s), 126.44
(s), 126.48 (d), 126.57 (d), 127.57 (2d), 129.21 (2d), 129.24
(2d), 129.64 (2d), 134.80 (s), 137.02 (s), 145.59 (d), 153.44 (d),
156.64 (d) (Calc. for C26H29NO2S2: M, 451.1640. Found: Mϩ,
451.1631).
(2Z,4Z )-4-Cyano-6,6-dimethyl-2-(phenylthio)hepta-2,4-dienal
8. TMSOTf (0.06 ml, 0.32 mmol) was added dropwise to a
CH2Cl2 (2.00 ml) solution of 7 (0.10 g, 0.32 mmol) at Ϫ78 ЊC.
The mixture was stirred for 10 min. The work-up procedure
afforded the title compound 8 (76 mg, 88%) as a yellow powder,
mp 64–68 ЊC; IR (film; cmϪ1) 2250 (CN), 1710 (CO); 1H NMR
(400 MHz; CDCl3) δ 1.32 (9H, s, Me × 3), 6.91 (1H, s, olefinic
H), 7.20 (1H, s, olefinic H), 7.21–7.34 (5H, m, ArH), 9.34 (1H,
s, CHO); 13C NMR (100 MHz; CDCl3) δ 29.40 (3q), 35.67 (s),
108.20 (s), 115.35 (s), 127.66 (d), 129.50 (2d), 130.43 (2d),
132.98 (s), 135.62 (s), 142.83 (d), 170.44 (d), 189.84 (d) (Calc.
for C16H17NOS: M, 271.1031. Found: Mϩ, 271.1020).
(2Z,4Z,6Z )-4-Cyano-8,8-dimethyl-2,6-bis(phenylthio)nona-
2,4,6-trienal 12. TMSOTf (0.04 ml, 0.22 mmol) was added
dropwise to a CH2Cl2 (2.00 ml) solution of 11 (0.10 g,
0.22 mmol) at Ϫ78 ЊC. The work-up procedure afforded the title
compound 12 (39 mg, 44%) as a yellow powder, mp 95–98 ЊC
1
(decomp.); IR (film; cmϪ1) 2230 (CN), 1700 (CO); H NMR
(400 MHz; CDCl3) δ 1.36 (9H, s, Me3), 6.80 (1H, s, olefinic H),
7.02 (1H, d, J 1, olefinic H), 7.04 (1H, d, J 1, olefinic H), 7.14–
7.30 (10H, m, ArH), 9.24 (1H, s, CHO); 13C NMR (100 MHz;
CDCl3) δ 30.29 (3q), 35.23 (s), 109.56 (s), 115.76 (s), 127.20 (d),
127.35 (s), 127.78 (d), 129.49 (2d), 129.54 (2d), 129.94 (2d),
130.55 (2d), 132.84 (s), 134.17 (s), 136.31 (s), 140.71 (d), 156.59
(d), 156.86 (d), 189.55 (d); MS m/z 405 (Mϩ) (Calc. for
C24H23NOS2: C, 71.08; H, 5.72; N, 3.45. Found: C, 70.85; H,
5.68; N, 3.41%).
(1E,4Z,6Z )-6-Cyano-1-ethoxy-8,8-dimethyl-2,4-bis(phenyl-
thio)nona-1,4,6-trien-3-ol 9. Under an Ar atmosphere, a THF
(1.50 ml) solution of compound 8 (0.12 g, 0.43 mmol) was
2564
J. Chem. Soc., Perkin Trans. 1, 2001, 2560–2565

View Article Online
Attempted preparation of (2E,4Z,6Z )-2-cyano-8,8-dimethyl-4,6-
bis(phenylthio)nona-2,4,6-trienal 16
olefinic H), 6.95 (1H, d, J 2, olefinic H), 7.39–7.50 (3H, m,
ArH), 7.55–7.58 (2H, m, ArH); 13C NMR (100 MHz; CDCl3)
δ 28.13 (3q), 34.96 (s), 53.32 (d), 65.61 (d), 92.61 (s), 108.79 (s),
113.97 (s), 116.08 (s), 120.92 (s), 128.30 (s), 129.76 (2d), 130.53
(d), 135.86 (2d), 144.73 (d), 156.48 (d); MS m/z 322 (Mϩ) (Calc.
for C19H18N2OS: 70.98; H, 5.63; N, 8.69. Found: C, 70.59;
H, 5.60; N, 8.53%).
Preparation of (1Z,4Z,6Z )-2-cyano-1-ethoxy-8,8-dimethyl-
4,6-bis(phenylthio)nona-1,4,6-trien-3-ol 14. Under an Ar atmos-
phere, a THF (1.00 ml) solution of 3-ethoxyacrylonitrile 1
(0.29 g, 3.00 mmol) was added dropwise to a THF (5.00 ml)
solution of lithium 2,2,6,6-tetramethylpiperidide [prepared
from 2,2,6,6-tetramethylpiperidine (0.17 g, 1.20 mmol) and n-
BuLi (0.80 ml, 1.20 mmol)] at Ϫ78 ЊC. After 10 min of stirring,
a THF (1.00 ml) solution of 6,6-dimethyl-2,4-bis(phenyl-
thio)hepta-2,4-dienal 13 (0.51 g, 1.50 mmol) was added drop-
wise to the reaction mixture. The work-up procedure afforded
the title compound 14 (0.16 g, 23%) as a yellow oil, IR (film;
Photoreaction of (2Z,4Z,6Z )-4-cyano-8,8-dimethyl-2,6-bis-
(phenylthio)nona-2,4,6-trienal 12
Under an Ar atmosphere, a MeCN (150 ml) solution of 12
(60 mg, 0.15 mmol) was stirred for 2 days under irradiation with
a 40 W fluorescent daylight lamp. The solvent was removed
under reduced pressure. The residue was purified by preparative
TLC on silica gel with AcOEt–n-hexane (1 : 10) as developer to
give (1R*,5R*,6S*)-6-tert-butyl-1-cyano-4,7-bis(phenylthio)-2-
oxabicylo[3.3.0]octa-3,7-diene 20 (6 mg, 9%) as a white powder,
IR (film; cmϪ1) 2250 (CN); 1H NMR (400 MHz; CDCl3) δ 0.91
(9H, s, Me × 3), 2.90 (1H, t, J 1, CH), 3.74 (1H, t, J 1, CH), 4.91
(1H, d, J 1, olefinic H), 6.55 (1H, d, J 2, olefinic H), 7.12–7.44
(10H, m, ArH) (Calc. for C24H23NOS2: M, 405.1121. Found:
Mϩ, 405.1137).
1
cmϪ1) 3450 (OH), 2230 (CN); H NMR (400 MHz; CDCl3)
δ 1.09 (9H, s, Me × 3), 1.32 (3H, t, J 7, Me), 2.92 (1H, d, J 8,
OH), 3.98 (2H, q, J 7, CH2), 5.03 (1H, d, J 8, CH), 6.25 (1H, s,
olefinic H), 6.48 (1H, s, olefinic H), 6.75 (1H, s, olefinic H),
7.12–7.29 (10H, m, ArH); 13C NMR (100 MHz; CDCl3) δ 15.46
(q), 30.36 (3q), 34.59 (s), 70.34 (t), 107.97 (s), 116.30 (s), 116.73
(s), 126.44 (s), 126.48 (d), 126.57 (d), 127.57 (2d), 129.21 (2d),
129.24 (2d), 129.64 (2d), 134.80 (s), 137.02 (s), 145.59 (d),
153.44 (d), 156.64 (d) (Calc. for C26H29NO2S2: M, 451.1640.
Found: Mϩ, 451.1650).
Acknowledgements
Reaction of 14 with TMSOTf. TMSOTf (0.06 ml, 0.11 mmol)
was added dropwise to a CH2Cl2 (2.0 ml) solution of 14 (0.05 g,
0.11 mmol) at Ϫ78 ЊC. The work-up procedure afforded 2-tert-
butyl-3-[(Z)-1-cyano-2-ethoxyethenyl]-1,4-bis(phenylthio)cyclo-
pentadiene 15 (0.05 g, 10%) as a yellow oil, IR (film; cmϪ1) 2200
The support of a part of this work by the Ministry of Edu-
cation, Science and Culture, Japan, is gratefully acknowledged.
1
References
(CN); H NMR (400 MHz; CDCl3) δ 1.36 (9H, s, Me × 3),
1.44 (3H, t, J 7, Me), 2.68 (2H, s, CH2), 4.42 (2H, q, J 7, OCH2),
5.89 (1H, s, olefinic H), 7.13–7.44 (10H, m, ArH) (Calc. for
C26H27NOS2: M, 433.1534. Found: M, 433.1538).
1 (a) M. Aiai, M. B. Floc’h, A. Robert and P. Le Grel, Synthesis, 1996,
403; S. Hbaieb, T. Ben Ayed and H. Amri, Synth. Commun., 1997,
27, 2825; I. Beltaief, S. Hbaieb, R. Besbes, H. Amri, M. Villieras and
J. Villieras, Synthesis, 1998, 1765; E. M. Campi, K. Dyall, G. Fallon,
W. R. Jackson, P. Perlmutter and A. J. Smallridge, Synthesis, 1990,
855; (b) A. J. Elliott, P. E. Morris, S. L. Petty and C. H. Williams,
J. Org. Chem., 1997, 62, 8071; (c) A. J. Elliott, D. A. Walsh and
P. E. Morris, PCT Int. Appl., WO 97 21 653, 1997 (Chem. Abstr.,
1997, 127, 121751v); J. A. Ciller, N. Martin, C. Seoane and
J. L. Soto, J. Chem. Soc., Perkin Trans. 1, 1985, 2581; A. Herbert
(BASF A.-G.), Ger. Offen., 2 623 170, 1977 (Chem. Abstr., 1978, 88,
62159j).
2 G. Jones, Org. React., 1967, 15, 204; F. Freeman, Chem. Rev.,
1980, 80, 329; A. Fatiadi, Synthesis, 1978, 165; E. Campaigne
and S. W. Schneller, Synthesis, 1976, 705; G. G. Yakobson and
N. E. Akhmetova, Synthesis, 1983, 169.
3 G. Haffer, U. Eder, G. Neef, G. Sauer and R. Wiechert, Chem. Ber.,
1978, 111, 1533; J. H. Clark, Chem. Rev., 1980, 80, 429; M. M.
Gugelchuk, D. J. Hart and Y.-M. Tsai, J. Org. Chem., 1981, 46, 3671.
4 J. S. K. Brunskill, A. De and D. F. Ewing, J. Chem. Soc.,
Perkin Trans. 1, 1978, 629; J. L. Soto, C. Aparicio, C. Seoane
and J. A. Valdes, Heterocycles, 1983, 20, 2393; S. M. Fahmy and
R. M. Mohareb, Liebigs Ann. Chem., 1985, 1492.
Attempted preparation of 2,6-dicyano-8,8-dimethyl-4-(phenyl-
thio)nona-2,4,6-trienal 19
(1Z,4Z,6Z )-2,6-Dicyano-1-ethoxy-8,8-dimethyl-4-(phenyl-
thio)nona-1,4,6-trien-3-ol 17. Under an Ar atmosphere, a THF
(1.00 ml) solution of 3-ethoxyacrylonitrile 1 (0.08 g, 0.83 mmol)
was added dropwise to a THF solution of lithium 2,2,6,6-
tetramethylpiperidide [prepared from 2,2,6,6-tetramethyl-
piperidine (0.117 g, 0.83 mmol) and n-BuLi (0.48 ml, 0.72
mmol)] at Ϫ78 ЊC. Then, a THF (1.50 ml) solution of (2Z,4Z)-
4-cyano-6,6-dimethyl-2-(phenylthio)hepta-2,4-dienal 8 (0.15 g,
0.55 mmol) was added dropwise to the reaction mixture. The
work-up procedure afforded the title compound 17 (53 mg,
26%) as a brown oil, IR (film; cmϪ1) 3750–3150 (OH), 2240
(CN); 1H NMR (400 MHz; CDCl3) δ 1.21 (3H, t, J 7, Me), 1.25
(9H, s, Me × 3), 2.17 (1H, s, OH), 3.99 (2H, q, J 7, OCH2), 5.10
(1H, s, CH), 6.52 (1H, d, J 1, olefinic H), 6.82 (1H, t, J 1,
olefinic H), 6.92 (1H, s, CH), 7.22–7.37 (5H, m, ArH); 13C
NMR (100 MHz; CDCl3) δ 15.27 (q), 29.56 (3q), 34.87 (s),
66.84 (d), 71.58 (t), 95.30 (s), 107.50 (s), 116.48 (s), 117.37
(s), 127.36 (d), 129.22 (2d), 129.64 (d), 130.84 (2d), 133.43 (s),
137.02 (s), 160.52 (d), 164.53 (d) (Calc. for C21H24N2O2S:
M, 368.1558. Found: Mϩ, 368.1551).
5 D. Basavaiah, N. Kumaragurubaran and K. Padmaja, Synlett, 1999,
1630.
6 H. Higuchi, M. Kondo, H. Yonehara, J. Ojima and M. Iyoda, Bull.
Chem. Soc. Jpn., 1989, 62, 1188.
7 I. Vlattas, L. D. Vecchia and A. O. Lee, J. Am. Chem. Soc., 1976, 98,
2009; M. Yoshimatsu, K. Oguri, K. Ikeda and S. Gotoh, J. Org.
Chem., 1998, 63, 4475; M. Yoshimatsu, S. Gotoh, K. Ikeda and
M. Komori, J. Org. Chem., 1998, 63, 6619.
8 M. Yoshimatsu, T. Sugimoto, N. Okada and S. Kinoshita, J. Org.
Chem., 1999, 64, 5162; Y. Matsubara and M. Yoshimatsu, J. Org.
Chem., 2000, 65, 4456; M. Yoshimatsu and M. Hibino, Chem.
Pharm. Bull., 2000, 48, 1395.
9 R. R. Schmidt and H. Speer, Tetrahedron Lett., 1981, 22, 4259;
R. R. Schmidt and R. Hirsenkorn, Tetrahedron, 1983, 39, 2043;
R. R. Schmidt and H. Speer, Synthesis, 1979, 797; R. R. Schmidt,
J. Talbiersky and P. Russegger, Tetrahedron Lett., 1979, 4273;
R. R. Schmidt and J. Talbiersky, Angew. Chem., 1977, 89, 891.
10 M. Yoshimatsu, S. Gotoh, G. Tanabe and O. Muraoka, Chem.
Commun., 1999, 909.
Reaction of 17 with TMSOTf. TMSOTf (0.06 ml, 0.32 mmol)
was added dropwise to a CH2Cl2 (2.00 ml) solution of 17
(0.100 g, 0.27 mmol) at Ϫ78 ЊC. The reaction mixture was
poured into saturated aq. NaHCO3 (50.0 ml). The work-up
procedure afforded (1R*,5S*,6S*)-6-tert-butyl-4,7-dicyano-1-
(phenylthio)-2-oxabicyclo[3.3.0]octa-3,7-diene 18 (8 mg, 9%) as
colorless needles, mp 118–120 ЊC; IR (film; cmϪ1) 2160 (CN),
2040 (CN); 1H NMR (400 MHz; CDCl3) δ 1.14 (9H, s, Me × 3),
2.88 (1H, t, J 2, CH), 3.54 (1H, t, J 2, CH), 6.42 (1H, d, J 2,
J. Chem. Soc., Perkin Trans. 1, 2001, 2560–2565
2565