An effective Diels-Alder reaction of vinyl allenols with dienophiles

Article abstract of DOI:10.1002/ejoc.201001148

Vinyl allenols obtained from reaction of aldehydes with vinyl propargyl bromide and indium underwent Diels-Alder reactions with a variety of symmetric and unsymmetric dienophiles in dichloromethane or toluene regioselectively, producing cyclohexenylmethyl

Full text of DOI:10.1002/ejoc.201001148

FULL PAPER
DOI: 10.1002/ejoc.201001148
An Effective Diels–Alder Reaction of Vinyl Allenols with Dienophiles
Subin Choi,[a] Hoon Hwang,[a] and Phil Ho Lee*[a]
Keywords: Alcohols / Cycloaddition / Indium / Allenes / Regioselectivity
Vinyl allenols obtained from reaction of aldehydes with vinyl
propargyl bromide and indium underwent Diels–Alder reac-
tions with a variety of symmetric and unsymmetric dieno-
philes in dichloromethane or toluene regioselectively, pro-
ducing cyclohexenylmethyl alcohols possessing an exo meth-
ylene moiety in good to excellent yield.
Introduction
Allene having two adjacent double bonds is a very inter-
esting functional group due to its hybrid character of hav-
ing both carbon–carbon double and triple bonds.[1] Espe-
cially, vinyl allene compounds (allene having a vinyl group:
1,2,4-pentatriene) have been recognized as versatile building
blocks in organic synthesis.[1] These compounds have been
used in Diels–Alder reactions[2] as well as in transition-
metal-catalyzed organic reactions.[3] However, because vinyl
allenes are generally less stable than their isomeric enynes
and because synthetic methods to selectively prepare a vari-
ety of vinyl allenes are difficult, their applications to organic
synthesis have been limited. Therefore, the development of
a synthetic method for preparing compounds having a func-
tionalized vinyl allene moiety such as vinyl allenol and vinyl
allenamine and its application to Diels–Alder reactions and
transition-metal-catalyzed organic reactions is required. Al-
though vinyl allenes have been used as the diene moiety in
Diels–Alder reactions,[2] as far as we are aware, the use of
vinyl allenols as the diene moiety in Diels–Alder reactions
has not been reported. Because so much is now known
about the Diels–Alder reaction,[4] successful use of vinyl al-
lenols as diene moieties in Diels–Alder reactions would
prove useful in the synthesis of cyclohexenylmethyl alcohols
having an exo methylene moiety. We have recently demon-
strated that a variety of organoindium reagents generated
in situ from indium and allyl and propargyl halides are ef-
fective nucleophiles in Pd-catalyzed cross-coupling and ad-
dition reactions.[5] In continuation of our studies on prepar-
ative methods of vinyl allenols with organoindium reagents
and their applications,[6] we herein describe an efficient
Diels–Alder reaction of vinyl allenols with a range of dieno-
philes to give cyclohexenylmethyl alcohols having an exo
methylene moiety (Scheme 1).
Scheme 1. Diels–Alder reaction of vinyl allenol with dienophile.
Results and Discussion
First, vinyl allenols 3 were produced in good to excellent
yields from reaction of aldehydes with organoindium rea-
gents generated in situ from vinyl propargyl bromide (2)
and indium (Scheme 2).[6] For example, compound 3a was
regioselectively prepared in 81% yield from reaction of but-
anal (1 equiv.) with 2 (1 equiv.) and indium (1 equiv.) in the
presence of lithium iodide (1 equiv.) in THF at 25 °C for
Scheme 2. Synthesis of vinyl allenol via selective 1,2,4-pentatriene-
3-ylation to aldehydes.
[a] Department of Chemistry and Institute for Molecular Science
and Fusion Technology, Kangwon National University,
Chuncheon 200-701, Republic of Korea
Fax: +82-33-253-7582
E-mail: phlee@kangwon.ac.kr
Scheme 3. Dienophiles.
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S. Choi, H. Hwang, P. H. Lee
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Table 1. Diels–Alder reaction of vinyl allenol with dienophile.
[a] Reaction temperature: CH2Cl2, 25 °C; toluene, 80 °C. [b] Isolated yield. Diastereomeric ratio is given in parentheses, as determined by
1H NMR spectroscopy. Dienophile 4 (2 equiv.) was used. [c] Dienophile 4 (4 equiv.) was used. [d] Dienophile 4 (6 equiv.) was used.
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An Effective Diels–Alder Reaction of Vinyl Allenols with Dienophiles
2 h under a nitrogen atmosphere. Vinyl allenols 3b, 3c, and tons (δ = 5.16 and 5.07 ppm), respectively. Encouraged by
3d were selectively obtained by treatment of the corre- these results, we next examined the influence of the electron
sponding aldehyde with 2 and indium.
density of the aromatic rings on the reactivity of vinyl all-
Next, Diels–Alder reactions of vinyl allenols 3 with enol. Vinyl allenol 3c possessing a 4-methoxycarbonyl
dienophiles 4 (Scheme 3) were examined to obtain cyclo- group as an electron-withdrawing group on its aromatic ring
hexenylmethyl alcohols 5 possessing an exo methylene moi- was treated with 4c in dichloromethane at 25 °C for 1.5 h,
ety. The results are summarized in Table 1. Reaction of vi- providing corresponding adduct 5l (93%, 1:2.5dr; Table 1,
nyl allenol 3a with tetra(cyano)ethylene (4a) produced Entry 10). The diastereomeric ratio of 5l was determined
Diels–Alder adduct 5a in 90% yield in dichloromethane at from the integration ratio of the vinylic protons (δ = 6.21
25 °C after 1.5 h (Table 1, Entry 1). In addition, exposure and 6.09 ppm) on the cyclohexenyl moiety. Corresponding
of 3a to N-methylmaleimide (4b) produced 5b in 92% yield adduct 5m was obtained in 90% yields from the Diels–Alder
in dichloromethane at 25 °C after 1 h (Table 1, Entry 2). A reaction of 4a with vinyl allenol 3d possessing a 4-methoxy
coupling constant of the allylic proton at the bridgehead group as an electron-donating group on its aromatic ring in
carbon is 8.76 Hz, indicating that the stereoisomer of the dichloromethane at 25 °C after 3 h (Table 1, Entry 11).
bicyclic ring is cis. The diastereomeric ratio of 5b (1:1.5dr) Reaction of 3d with 4e proceeded smoothly to produce ad-
was determined from the integration ratio of the exo meth- duct 5n in 86% yield (1:1.8dr) in toluene at 80 °C for 3.5 h
ylene protons (four singlets: δ = 5.57, 5.41, 5.34, and (Table 1, Entry 12). These results imply that the reactivity of
5.27 ppm). Because Diels–Alder reactions of vinyl allenes 3c obtained from 4-methoxycarbonylbenzaldehyde is higher
with dienophiles proceed generally under harsh conditions than that of 3d obtained from 4-methoxybenzaldehyde. The
(high temperature),[2g] it is noteworthy that the present diastereomeric ratio of 5n was determined from the integra-
Diels–Alder reactions proceed smoothly under mild reac- tion ratio of the exo methylene protons (δ = 4.82 and
tion conditions (room temperature). Treatment of 3b with 4.75 ppm) on the cyclohexenyl moiety.
4a afforded the corresponding adduct 5c in 96% yield in
dichloromethane (Table 1, Entry 3). Subjecting 3b to 4b
gave adduct 5d in 97% (1:1.1dr) yield in dichloromethane
(Table 1, Entry 4). The diastereomeric ratio of 5d was deter-
mined from the integration ratio of the benzylic and N-
methyl protons. Although reaction of 3b with 4c produced
Diels–Alder adduct 5e in 50% (1:4dr) yield (dichlorometh-
ane, 25 °C, 4 h), use of toluene as solvent provided 5e in
92% (1:4.4dr) yield (80 °C, 3 h; Table 1, Entry 5). The dia-
stereomeric ratio of 5e was determined from the integration
ratio of the vinylic protons (δ = 6.23 and 6.15 ppm) on the
cyclohexenyl moiety. We were pleased to obtain 5f in 62%
(1:2dr) yield by subjecting 3b to dimethyl fumarate (4d) in
toluene (Table 1, Entry 6). The diastereomeric ratio of 5f
was determined from the integration ratio of the exo meth-
ylene protons (δ = 5.16 and 5.11 ppm). In the case of
naphthoquinone (4e), toluene gave a better result (78%,
1:1.8dr) than dichloromethane (35%, 1:1.3dr; Table 1, En-
try 7). The diastereomeric ratio of 5g was determined from
the integration ratio of the vinylic protons (δ = 6.13 and
6.04 ppm) on the cyclohexenyl moiety. Reaction of 3b with
methyl vinyl ketone (4f, 4 equiv.) produced cyclohexenyl-
methyl alcohol 5h (74%, 1:2dr) and 5i (6%, 1:5dr) in dichloro-
methane at 25 °C after 3 h (Table 1, Entry 8). These results
indicate that the electron-rich central carbon of vinyl allene
preferentially adds to the more electron-deficient
carbon of the dienophile (Scheme 4). The diastereomeric
ratios of 5h and 5i were determined from the integration
ratio of the benzylic protons (δ = 5.53 and 5.50 ppm) and
the exo methylene protons (δ = 5.18 and 5.12 ppm), respec-
tively. With ethyl acrylate (4g, 6 equiv.), adducts 5j and 5k
were obtained in 62% (1:1.3dr) and 7% (1:1.4dr) yield,
respectively, in toluene at 80 °C for 3 h (Table 1, Entry 9).
The diastereomeric ratios of 5j and 5k were determined from
the integration ratio of the vinylic protons (δ = 6.07 and
Scheme 4. Diels–Alder reaction of 3b with 4f.
Conclusions
In summary, cyclohexenylmethyl alcohols possessing an
exo methylene moiety were regioselectively produced from
Diels–Alder reactions of vinyl allenols, derived from selec-
tive addition reactions of organoindium reagents generated
in situ from vinyl propargyl bromide and indium to alde-
hydes, with a variety of dienophiles in good to excellent
yields in dichloromethane or toluene.
Experimental Section
General: Reactions were carried out in oven-dried glassware under
a nitrogen atmosphere. All commercial reagents were used without
purification, and all solvents were reaction grade. CH2Cl2 was
freshly distilled from CaH2. Toluene was freshly distilled from so-
dium under a nitrogen atmosphere. All reaction mixtures were
magnetically stirred and were monitored by thin-layer chromatog-
raphy by using Merck silica gel 60 F254 precoated glass plates,
which were visualized with UV light and developed by using either
iodine or a solution of anisaldehyde. Flash column chromatography
6.02 ppm) on the cyclohexenyl moiety and the benzylic pro- was carried out by using Merck silica gel 60 (0.040–0.063 mm, 230–
Eur. J. Org. Chem. 2011, 1351–1356
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S. Choi, H. Hwang, P. H. Lee
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400 mesh). H and 13C NMR spectra were recorded with a Bruker
1
CDCl3, 25 °C): δ = 179.8, 177.5, 141.5, 141.0, 134.1, 128.9, 128.3,
DPX FT (300 or 400 MHz) spectrometer. Deuterated chloroform
was used as the solvent, and chemical shift values (δ) are reported
in parts per million relative to the residual signals of this solvent
(δ = 7.24 for 1H and δ = 77.0 for 13C). Infrared spectra were re-
corded with a JASCO FT/IR-460 plus FTIR spectrometer as either
a thin film pressed between two sodium chloride plates or as a
solid suspended in a potassium bromide disk. High-resolution mass
spectra were recorded with a Jeol JMS 700 high-resolution mass
spectrometer.
126.7, 126.0, 116.5, 75.0, 47.4, 39.1, 25.8, 23.1 ppm. Data for the
minor isomer: H NMR (300 MHz, CDCl3, 25 °C): δ = 7.36–7.17
1
(m, 5 H, ArH), 6.19 (d, J = 6.4 Hz, 1 H, CH), 5.44 (s, 1 H, CH),
5.35 (s, 1 H, CH), 5.32 (s, 1 H, CH), 3.61 (t, J = 9.1 Hz, 1 H, s, 1
H, CH), 3.14 (q, J = 7.6 Hz, 1 H, s, 1 H, CH), 2.74 (s, 3 H, NCH3).
2.88–2.72 (m, 1 H, CH2), 2.44–2.27 (m, 1 H, CH2), 2.20 (s, 1 H,
OH) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ = 179.8, 176.8,
142.4, 142.0, 134.5, 128.8, 128.3, 127.2, 123.3, 116.0, 74.3, 48.0,
39.6, 25.6, 23.5 ppm. IR (film): ν = 3036, 2934, 1747, 1067, 884,
˜
708 cm–1. M.p. 97–99 °C. HRMS (EI): calcd. for C17H17N4O3
4-(1-Hydroxybutyl)-3-methylenecyclohex-4-ene-1,1,2,2-tetracarbo-
nitrile (5a): Yellow oil. 1H NMR (300 MHz, CDCl3, 25 °C): δ =
6.14 (t, J = 3.3 Hz, 2 H, CH2=), 6.07 (d, J = 2.0 Hz, 1 H, CH),
4.54 (s, 1 H, CH), 3.29 (d, J = 4.7 Hz, 2 H, CH2), 2.11 (d, J =
3.6 Hz, 1 H, OH), 1.70–1.33 (m, 4 H, CH2), 0.96 (t, J = 7.3 Hz, 3
H, CH3) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ = 138.2,
128.4, 123.2, 119.4, 110.8, 110.7, 109.9, 109.8, 71.4, 45.8, 40.0, 38.5,
283.1208; found 283.1206.
5-[Hydroxy(phenyl)methyl]-4-methylene-3a,4,7,7a-tetrahydroiso-
benzofuran-1,3-dione (5e): Yellow solid. 1H NMR (300 MHz,
CDCl3, 25 °C): δ = 7.38–7.22 (m, 5 H, ArH), 6.16 (s, 1 H, CH),
5.43 (s, 1 H, CH), 5.36 (d, J = 10.1 Hz, 2 H, CH2=), 3.90 (d, J =
9.4 Hz, 1 H, CH), 3.45 (td, J = 8.5, 3.5 Hz, 1 H, CH), 2.85–2.73
(m, 1 H, CH2), 2.58–2.43 (m, 1 H, CH2), 2.30 (s, 1 H, OH) ppm.
13C NMR (100 MHz, CDCl3, 25 °C): δ = 173.6, 171.4, 141.8, 140.2,
131.2, 129.1, 128.5, 127.3, 125.6, 117.6, 74.5, 46.7, 39.6, 23.0 ppm.
33.2, 14.6, 14.2 ppm. IR (film): ν = 3329, 3067, 2247, 1642, 1024,
˜
899 cm–1. HRMS (EI): calcd. for C15H14N4O 266.1168; found
266.1169.
1
Data for the minor isomer: H NMR (300 MHz, CDCl3, 25 °C): δ
5-(1-Hydroxybutyl)-2-methyl-4-methylene-3a,4,7,7a-tetrahydro-1H-
isoindole-1,3(2H)-dione (5b): A mixture of 3-vinyl-1,2-heptadien-4-
ol (3a; 36.1 mg, 0.5 mmol) and N-methylmaleimide (4b; 111.1 mg,
1.0 mmol) in CH2Cl2 (2.0 mL) at room temperature using a test
tube. After being stirred for 1 h, the solvent was removed under
reduced pressure. The product was purified by silica gel column
chromatography (EtOAc/hexane, 1:2) to give 5b (115 mg, 92%) as
= 7.38–7.22 (m, 5 H, ArH), 6.23 (s, 1 H, CH), 5.48 (s, 1 H, CH),
5.36 (d, J = 10.1 Hz, 2 H, CH2=), 3.90 (d, J = 9.4 Hz, 1 H, CH),
3.45 (td, J = 8.5, 3.5 Hz 1 H, CH), 2.85–2.73 (m, 1 H, CH2), 2.58–
2.43 (m, 1 H, CH2), 2.30 (s, 1 H, OH) ppm. 13C NMR (100 MHz,
CDCl3, 25 °C): δ = 173.8, 171.7, 141.8, 140.3, 131.5, 129.2, 128.6,
127.0, 124.5, 117.4, 74.2, 47.1, 39.9, 23.0 ppm. IR (film): ν = 3066,
˜
1778, 1718, 1046, 898, 711 cm–1. M.p. 83–85 °C. HRMS (EI): calcd.
for C16H14O4 270.0892; found 270.0889.
1
a yellow oil. H NMR (300 MHz, CDCl3, 25 °C): δ = 5.90 (d, J =
3.5 Hz, 1 H, CH2), 5.57 (s, 1 H, CH2=), 5.41(s, 1 H, CH2=), 4.27
(t, J = 6.5 Hz, 1 H, CH), 3.69 (d, J = 8.8 Hz, 1 H, CH), 3.23–3.15
(m, 1 H, CH), 2.95 (s, 3 H, NCH3), 2.83–2.68 (m, 1 H, CH2), 2.39–
2.23 (m, 1 H, CH2), 1.86 (s, 1 H, OH), 1.65–1.48 (m, 2 H, CH2),
1.41–1.05 (m, 2 H, CH2), 0.90 (t, J = 7.4 Hz, 3 H, CH3) ppm. 13C
NMR (100 MHz, CDCl3, 25 °C): δ = 179.9, 177.7, 141.8, 134.2,
125.2, 116.2, 73.8, 47.9, 39.3, 37.7, 25.7, 23.5, 19.6, 14.3 ppm. Data
for the minor isomer: 1H NMR (300 MHz, CDCl3, 25 °C): δ = 5.95
(d, J = 6.7 Hz, 1 H, CH2), 5.34 (s, 1 H, CH2=), 5.27 (s, 1 H, CH2=),
4.48 (s, 1 H, CH), 3.69 (d, J = 8.8 Hz, 1 H, CH), 3.23–3.15 (m, 1
H, CH), 2.95 (s, 3 H, NCH3), 2.83–2.68 (m, 1 H, CH2), 2.39–2.23
(m, 1 H, CH2), 1.77 (s, 1 H, OH), 1.65–1.48 (m, 2 H, CH2), 1.41–
1.05 (m, 2 H, CH2), 0.90 (t, J = 7.4 Hz, 3 H, CH3) ppm. 13C NMR
(100 MHz, CDCl3, 25 °C): δ = 180.0, 177.6, 142.8, 135.4, 121.8,
114.9, 71.2, 48.3, 39.4, 38.4, 25.6, 23.4, 18.7, 14.2 ppm. IR (film):
Dimethyl 4-[Hydroxy(phenyl)methyl]-3-methylenecyclohex-4-ene-
1,2-dicarboxylate (5f): Yellow oil. 1H NMR (300 MHz, CDCl3,
25 °C): δ = 7.34–7.23 (m, 5 H, ArH), 6.02 (s, 1 H, CH), 5.53 (s, 1
H, CH), 5.15 (s, 1 H, CH2=), 4.90 (s, 1 H, CH2=), 3.70 (s, 3 H,
OCH3), 3.68 (s, 1 H, CH), 3.67 (s, 3 H, OCH3), 3.22 (q, J = 6.7 Hz,
1 H, CH), 2.68–2.49 (m, 2 H, CH2), 2.20 (s, 1 H, OH) ppm. 13C
NMR (100 MHz, CDCl3, 25 °C): δ = 174.3, 173.3, 142.6, 137.9,
136.8, 128.9, 128.1, 127.3, 126.8, 114.2, 74.0, 52.6, 49.6, 41.8,
26.8 ppm. Data for the minor isomer: 1H NMR (300 MHz, CDCl3,
25 °C): δ = 7.34–7.23 (m, 5 H, ArH), 6.06 (s, 1 H, CH), 5.53 (s, 1
H, CH), 5.11 (s, 1 H, CH2=), 4.90 (s, 1 H, CH2=), 3.70 (s, 3 H,
OCH3), 3.67 (s, 3 H, OCH3), 3.64 (s, 1 H, CH), 3.22 (q, J = 6.7 Hz,
1 H, CH), 2.68–2.49 (m, 2 H, CH2), 2.20 (s, 1 H, OH) ppm. 13C
NMR (100 MHz, CDCl3, 25 °C): δ = 174.3, 173.3, 142.7, 137.9,
136.7, 128.8, 128.1, 127.2, 126.6, 114.3, 74.1, 52.5, 49.6, 41.7,
ν = 3397, 2957, 2874, 1679, 1067, 911, 816 cm–1. HRMS (EI):
˜
calcd. for C14H19NO3 249.1365; found 249.1361.
36.7 ppm. IR (film): ν = 3074, 1772, 1741, 1603, 1498, 1377, 1222,
˜
910, 812 cm–1. HRMS (EI): calcd. for C18H20O5 316.1311; found
316.1313.
4-[Hydroxy(phenyl)methyl]-3-methylenecyclohex-4-ene-1,1-2,2-tetra-
carbonitrile (5c): Yellow solid. 1H NMR (300 MHz, CDCl3, 25 °C):
δ = 7.43–7.31 (m, 5 H, ArH), 6.40 (t, J = 4.0 Hz, 1 H, CH), 6.00
(s, 1 H, CH2=), 5.78 (d, J = 2.4 Hz, 1 H, CH2=), 5.53 (s, 1 H, CH),
3.39 (d, J = 4.1 Hz, 2 H, CH2), 1.28 (s, 1 H, OH) ppm. 13C NMR
(100 MHz, CDCl3, 25 °C): δ = 140.2, 136.1, 129.8, 1219.6, 127.7,
127.2, 124.7, 120.9, 110.9, 110.7, 109.7, 109.6, 73.8, 45.7, 40.0,
2-[Hydroxy(phenyl)methyl]-1-methylene-1,4,4a,9a-tetrahydroanthr-
acene-9,10-dione (5g): A mixture of 1-phenyl-2-vinyl-2,3-butadien-
1-ol (3b; 86.1 mg, 0.5 mmol) and 1,4-naphthoquinone (4e;
158.2 mg, 1.0 mmol) in toluene (2.0 mL) was heated at 80 °C for
3 h. The solvent was removed under reduced pressure. The product
was purified by silica gel column chromatography (EtOAc/hexane,
1:2) to give 5g (128.8 mg, 78 %) as a brown solid. 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 8.04–7.95 (m, 2 H, ArH), 7.76–7.67
(m, 2 H, ArH), 7.36–7.22 (m, 5 H, ArH), 6.03 (t, J = 4.0 Hz, 1 H,
CH), 5.55 (s, 1 H, CH), 5.24 (s, 1 H, CH2=), 4.8 (s, 1 H, CH2=),
4.0 (t, J = 6.2 Hz 1 H, CH), 3.49 (quint., J = 5.4 Hz, 1 H, CH),
33.5 ppm. IR (film): ν = 3068, 2281, 2248, 1602, 1489, 1376, 760,
˜
709 cm–1. M.p. 117–119 °C. HRMS (EI): calcd. for C18H12N4O
300.1011; found 300.1013.
5-[Hydroxy(phenyl)methyl]-2-methyl-4-methylene-3a,4,7,7a-tetra-
1
hydro-1H-isoindole-1,3(2H)-dione (5d): Pale yellow solid. H NMR
(300 MHz, CDCl3, 25 °C): δ = 7.36–7.17 (m, 5 H, ArH), 5.96 (d,
J = 5.4 Hz, 1 H, CH), 5.39 (s, 1 H, CH), 5.31 (s, 1 H, CH2=), 5.27 2.83–2.65 (m, 1 H, CH2), 2.56–2.39 (m, 1 H, CH2), 2.56–2.39 (m,
(s, 1 H, CH2=), 3.61 (t, J = 9.1 Hz, 1 H, CH), 3.14 (q, J = 7.6 Hz, 1 H, OH) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ = 196.9,
1 H, CH), 2.92 (s, 3 H, NCH3). 2.88–2.72 (m, 1 H, CH2), 2.44– 142.4, 138.5, 135.7, 135.3, 134.8, 134.7, 129.2, 128.8, 128.1, 127.8,
2.27 (m, 1 H, CH2), 2.20 (s, 1 H, OH) ppm. 13C NMR (100 MHz, 127.4, 127.3, 73.7, 48.0, 26.3 ppm. Data for the minor isomer: H
1
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An Effective Diels–Alder Reaction of Vinyl Allenols with Dienophiles
NMR (300 MHz, CDCl3, 25 °C): δ = 8.04–7.95 (m, 2 H, ArH), = 7.39–7.26 (m, 5 H, ArH), 5.92 (s, 1 H, CH), 5.52 (s, 1 H, CH),
7.76–7.67 (m, 2 H, ArH), 7.36–7.22 (m, 5 H, ArH), 6.03 (t, J = 5.16 (s, 1 H, CH2=), 4.91 (s, 1 H, CH2=), 4.14 (q, J = 7.3 Hz, 2 H,
4.0 Hz, 1 H, CH), 5.51 (s, 1 H, CH), 5.13 (s, 1 H, CH2=), 4.75 (s,
CO2CH2), 3.30 (t, J = 4.3 Hz, 1 H, CH), 2.74–2.42 (m, 4 H, CH2),
2.15 (d, J = 3.5 Hz, 1 H, OH), 1.25 (td, J = 7.1, 2.1 Hz, 3 H, CH3)
1 H, CH2=), 4.0 (t, J = 6.2 Hz 1 H, CH), 3.49 (quint., J = 5.4 Hz,
1 H, CH), 2.83–2.65 (m, 1 H, CH2), 2.56–2.39 (m, 1 H, CH2), 2.56– ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ = 169.8, 144.0, 143.5,
2.39 (m, 1 H, OH) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ =
142.4, 128.8, 127.7, 127.2, 127.1, 122.3, 72.0, 62.7, 48.2, 36.6, 26.1,
197.5, 142.6, 137.8, 135.6, 135.3, 134.9, 134.5, 128.9, 128.6, 128.2,
14.6 ppm. Data for the minor isomer: 1H NMR (300 MHz, CDCl3,
127.7, 127.4, 127.3, 74.2, 55.4, 26.2 ppm. IR (film): ν = 3396, 3351, 25 °C): δ = 7.39–7.26 (m, 5 H, ArH), 6.07 (s, 1 H, CH), 5.54 (s, 1
˜
3082, 2903, 1936, 1688, 1272, 897, 707 cm–1. M.p. 82–83 °C. H, CH), 5.07 (s, 1 H, CH2=), 4.91 (s, 1 H, CH2=), 4.14 (q, J =
HRMS (EI): calcd. for C22H18O3 330.1256; found 330.1256.
7.3 Hz, 2 H, CO2CH2CH3), 3.30 (t, J = 4.3 Hz, 1 H, CH), 2.74–
2.42 (m, 4 H, CH2), 2.11 (d, J = 4.0 Hz, 1 H, OH), 1.25 (td, J =
7.1, 2.1 Hz, 3 H, CH3) ppm. 13C NMR (100 MHz, CDCl3, 25 °C):
δ = 169.9, 144.2, 143.2, 142.2, 128.7, 127.6, 127.2, 126.8, 121.1,
1-{4-[Hydroxy(phenyl)methyl]-5-methylenecyclohex-3-enyl}ethanone
(5h): Pale yellow oil. 1H NMR (300 MHz, CDCl3, 25 °C): δ = 7.38–
7.23 (m, 5 H, ArH), 6.03 (t, J = 4.2 Hz, 1 H, CH), 5.50 (s, 1 H,
CH), 4.94 (s, 1 H, CH2=), 4.86 (s, 1 H, CH2=), 2.82–2.70 (m, 1 H,
CH), 2.57 (d, J = 3.2 Hz, 1 H, OH), 2.47–2.32 (m, 4 H, CH2), 2.17
(s, 3 H, CH3) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ = 210.8,
143.1, 139.8, 138.8, 128.8, 128.0, 127.8, 127.3, 127.2, 111.7, 73.9,
47.9, 35.2, 28.4, 28.0 ppm. Data for the minor isomer: 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 7.38–7.23 (m, 5 H, ArH), 6.07 (t, J
= 4.2 Hz, 1 H, CH), 5.53 (s, 1 H, CH), 4.95 (s, 1 H, CH2=), 4.86
(s, 1 H, CH2=), 2.82–2.70 (m, 1 H, CH), 2.61 (d, J = 3.1 Hz, 1 H,
OH), 2.47–2.32 (m, 4 H, CH2), 2.17 (s, 3 H, CH3) ppm. 13C NMR
(100 MHz, CDCl3, 25 °C): δ = 210.8, 143.1, 139.8, 138.6, 128.8,
71.9, 62.5, 48.2, 36.6, 26.3, 14.4 ppm. IR (film): ν = 3349, 3074,
˜
2998, 1212, 899.712 cm–1. HRMS (EI): calcd. for C17H20O3
272.1412; found 272.1412.
Methyl 4-[Hydroxy(4-methylene-1,3-dioxo-1,3,3a,4,7,7a-hexahy-
1
droisobenzofuran-5-yl)methyl]benzoate (5l): Yellow solid. H NMR
(300 MHz, CDCl3, 25 °C): δ = 7.97 (d, J = 8.1 Hz, 2 H, ArH), 7.38
(d, J = 8.3 Hz, 2 H, ArH), 6.09 (s, 1 H, CH), 5.50 (s, 1 H, CH),
5.37 (d, J = 10.7 Hz, 2 H, CH2=), 3.94 (d, J = 9.8 Hz, 2 H, CH),
3.89 (s, 3 H, OCH3), 3.49 (q, J = 7.0 Hz, 1 H, OH), 2.83–2.71 (m,
1 H, CH2), 2.57–2.44 (m, 1 H, CH2) ppm. 13C NMR (100 MHz,
CDCl3, 25 °C): δ = 173.6, 171.3, 167.3, 164.6, 146.8, 137.0, 131.1,
130.3, 127.1, 126.7, 117.8, 74.3, 52.6, 46.7, 39.6, 23.0 ppm. Data
for the minor isomer: 1H NMR (300 MHz, CDCl3, 25 °C): δ = 7.61
(d, J = 7.9 Hz, 2 H, ArH), 7.33 (d, J = 8.3 Hz, 2 H, ArH), 6.20 (s,
1 H, CH), 5.53 (s, 1 H, CH), 5.37 (d, J = 5.2 Hz, 2 H, CH2=), 3.94
(d, J = 9.8 Hz, 2 H, CH), 3.88 (s, 3 H, OCH3), 3.49 (q, J = 7.0 Hz,
1 H, OH), 2.83–2.71 (m, 1 H, CH2), 2.57–2.44 (m, 1 H, CH2) ppm.
13C NMR (100 MHz, CDCl3, 25 °C): δ = 173.7, 171.1, 167.3, 164.6,
146.9, 140.0, 131.3, 130.3, 126.9, 125.5, 117.7, 73.9, 52.6, 47.0, 39.8,
127.4, 127.3, 111.6, 73.9, 47.9, 35.2, 38.4, 28.0 ppm. IR (film): ν =
˜
3351, 2995, 2918, 1688, 1213, 1020, 899, 710 cm–1. HRMS (EI):
calcd. for C16H18O2 242.1307; found 242.1306.
4-(1-Hydroxybutyl)-3-methylenecyclohex-4-ene-1,1,2,2-tetracarbo-
1
nitrile (5i): Pale yellow oil. H NMR (300 MHz, CDCl3, 25 °C): δ
= 7.34–7.20 (m, 5 H, ArH), 5.89 (s, 1 H, CH), 5.49 (s, 1 H, CH),
5.18 (s, 1 H, CH2=), 4.85 (s, 1 H, CH2=), 3.18 (t, J = 4.5 Hz, 1 H,
CH), 2.29–2.10 (m, 3 H, CH2), 2.05 (s, 1 H, OH), 2.02 (s, 3 H,
CH3), 1.77–1.71 (m, 1 H, CH2) ppm. 13C NMR (100 MHz, CDCl3,
25 °C): δ = 208.6, 206.0, 138.4, 136.6, 129.0, 127.3, 126.5, 125.7,
112.7, 73.4, 29.9, 27.0, 23.1, 22.2 ppm. Data for the minor isomer:
1H NMR (300 MHz, CDCl3, 25 °C): δ = 7.34–7.20 (m, 5 H, ArH),
6.06 (s, 1 H, CH), 5.49 (s, 1 H, CH), 5.12 (s, 1 H, CH2=), 4.85 (s,
1 H, CH2=), 3.14 (t, J = 5.0 Hz, 1 H, CH), 2.29–2.10 (m, 3 H,
CH2), 1.92 (s, 1 H, OH), 1.81 (s, 3 H, CH3), 1.77–1.71 (m, 1 H,
CH2) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ = 208.6, 206.0,
141.3, 136.1, 127.6, 127.4, 126.7, 125.8, 72.7, 54.4, 26.9, 22.8,
23.0 ppm. IR (film): ν = 3459, 3055, 2953, 1610, 1778, 1046, 897,
˜
710 cm–1. M.p. 132–134 °C. HRMS (EI): calcd. for C18H16O6
328.0947; found 328.0949.
4-[Hydroxy(4-methoxyphenyl)methyl]-3-methylenecyclohex-4-ene-
1,1,2,2-tetracarbonitrile (5m): Beige solid. 1H NMR (300 MHz,
CDCl3, 25 °C): δ = 7.25 (d, J = 7.4 Hz, 2 H, ArH), 6.91 (d, J =
8.8 Hz, 2 H, ArH), 6.45 (t, J = 4.0 Hz, 1 H, CH), 6.00 (s, 1 H,
CH), 5.73 (d, J = 2.5 Hz, 1 H, CH2=), 5.50 (s, 1 H, CH2=), 3.81
(s, 3 H, OCH3), 3.41 (d, J = 4.0 Hz, 2 H, CH2) ppm. 13C NMR
(100 MHz, CDCl3, 25 °C): δ = 159.9, 152.6, 142.6, 136.1, 128.8,
128.5, 123.0, 122.2, 117.4, 115.4, 111.2, 109.9, 71.0, 56.6, 33.4, 22.7,
22.0 ppm. IR (film): ν = 3352, 2995, 2919, 1689, 1213, 1020, 899,
˜
709 cm–1. HRMS (EI): calcd. for C16H18O2 242.1307; found
242.1306.
21.8 ppm. IR (film): ν = 3419, 3002, 2837, 2248, 1940, 1610,
˜
Ethyl 3-[Hydroxy(phenyl)methyl]-2-methylenecyclohex-3-enecarbox-
ylate (5j): Pale yellow oil. 1H NMR (300 MHz, CDCl3, 25 °C): δ =
7.39–7.26 (m, 5 H, ArH), 6.02 (s, 1 H, CH), 5.52 (s, 1 H, CH), 4.93
(s, 1 H, CH2=), 4.86 (s, 1 H, CH2=), 4.14 (q, J = 7.3 Hz, 2 H,
CO2CH2), 2.74–2.42 (m, 5 H, CH2), 2.15 (d, J = 3.5 Hz, 1 H, OH),
1.25 (td, J = 7.1, 2.1 Hz, 3 H, CH3) ppm. 13C NMR (100 MHz,
CDCl3, 25 °C): δ = 169.8, 144.0, 143.5, 142.4, 128.8, 127.7, 127.2,
127.1, 122.3, 72.0, 62.7, 48.2, 36.6, 26.1, 14.6 ppm. Data for the
907 cm–1 M.p. 105–107 °C. HRMS (EI): calcd. for C18H12N4O
330.1117; found 330.1115.
2-[Hydroxy(4-methoxyphenyl)methyl]-1-methylene-1,4,4a,9a-tetra-
hydroanthracene-9,10-dione (5n): Brown solid. 1H NMR (300 MHz,
CDCl3, 25 °C): δ = 8.08–7.97 (m, 2 H, ArH), 7.80–7.69 (m, 2 H,
ArH), 7.29–7.20 (m, 2 H, ArH), 6.89–6.83 (m, 2 H, ArH), 6.07 (t,
J = 4.0 Hz, 1 H, CH), 5.54 (s, 1 H, CH), 5.23 (s, 1 H, CH2=), 4.82
(s, 1 H, CH2=), 4.01 (d, J = 5.2 Hz, 1 H, CH), 3.80 (s, 3 H, OCH3),
3.56 (m, 1 H, CH), 2.89–2.68 (m, 1 H, CH2), 2.57–2.43 (m, 1 H,
CH2), 2.03 (s, 1 H, OH) ppm. 13C NMR (100 MHz, CDCl3, 25 °C):
δ = 199.8, 189.9, 161.1, 144.3, 143.2, 138.2, 137.7, 133.6, 133.3,
133.2, 129.7, 125.9, 124.7, 114.6, 114.5, 110.1, 74.1, 63.3, 54.8, 46.9,
23.8 ppm. Data for the minor isomer: 1H NMR (300 MHz, CDCl3,
25 °C): δ = 8.08–7.97 (m, 2 H, ArH), 7.80–7.69 (m, 2 H, ArH),
7.29–7.20 (m, 2 H, ArH), 6.89–6.83 (m, 2 H, ArH), 6.22 (t, J =
4.0 Hz, 1 H, CH), 5.48 (s, 1 H, CH), 5.07 (s, 1 H, CH2=), 4.75 (s,
1
minor isomer: H NMR (300 MHz, CDCl3, 25 °C): δ = 7.39–7.26
(m, 5 H, ArH), 6.07 (s, 1 H, CH), 5.54 (s, 1 H, CH), 4.93 (s, 1 H,
CH2 =), 4. 86 (s, 1 H, CH2 =), 4.14 (q, J = 7.3 Hz, 2 H,
CO2CH2CH3), 2.74–2.42 (m, 5 H, CH2), 2.11 (d, J = 4.0 Hz, 1 H,
OH), 1.25 (td, J = 7.1, 2.1 Hz, 3 H, CH3) ppm. 13C NMR
(100 MHz, CDCl3, 25 °C): δ = 169.9, 144.2, 143.2, 142.2, 128.7,
127.6, 127.2, 126.8, 121.1, 71.9, 62.5, 48.2, 36.6, 26.3, 14.4 ppm. IR
(film): ν = 3349, 3074, 2998, 1212, 899.712 cm–1. HRMS (EI):
˜
calcd. for C17H20O3 272.1412; found 272.1412.
Ethyl 3-[Hydroxy(phenyl)methyl]-2-methylenecyclohex-3-enecarbox- 1 H, CH2=), 4.04 (d, J = 5.0 Hz, 1 H, CH), 3.79 (s, 3 H, OCH3),
1
ylate (5k): Pale yellow oil. H NMR (300 MHz, CDCl3, 25 °C): δ
3.56 (m, 1 H, CH), 2.89–2.68 (m, 1 H, CH2), 2.57–2.43 (m, 1 H,
Eur. J. Org. Chem. 2011, 1351–1356
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1355

S. Choi, H. Hwang, P. H. Lee
FULL PAPER
CH2), 1.86 (s, 1 H, OH) ppm. 13C NMR (100 MHz, CDCl3, 25 °C):
δ = 199.7, 189.8, 161.1, 144.1, 143.2, 138.0, 137.9, 133.7, 133.4,
133.1, 129.4, 125.8, 124.7, 114.5, 114.2, 110.1, 74.2, 63.1, 54.6, 46.6,
Kang, J. Am. Chem. Soc. 2006, 128, 1139–1146; e) H. Funami,
H. Kusama, N. Iwasawa, Angew. Chem. Int. Ed. 2007, 46, 909–
911.
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Pergamon Press, Oxford, U.K., 1990; b) W. Oppolzer in Com-
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L. A. Paquette), Pergamon Press, Oxford, U.K., 1991, vol. 5,
p. 315; c) C. O. Kappe, S. S. Murphree, A. Padwa, Tetrahedron
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˜
905, 708 cm–1. M.p. 99–100 °C. HRMS (EI): calcd. for C23H20O4
360.1362; found 360.1365.
Acknowledgments
This work was supported by the National Research Laboratory
Program funded by the Ministry of Education, Science and Tech-
nology (MEST) and by the National Research Foundation (NRF)
of Korea, grant-funded by the Korean government (MEST) (2009-
0087013). Following are results of a study on the “Human Re-
source Development Center for Economic Region Leading Indus-
try“ Project, supported by MEST and NRF. This work was sup-
ported by the second phase of the Brain Korea 21 Program in 2009.
Dr. Sung Hong Kim at the Korea Basic Science Institute (KBSI,
Daegu) is thanked for obtaining the MS data. The NMR spectro-
scopic data were obtained from the central instrumental facility in
Kangwon National University.
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Received: August 16, 2010
Published Online: January 12, 2011
1356
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 1351–1356