Highly stereoselective intramolecular diels-alder reaction of decatrienoates activated by t-butoxycarbonyl, chloro, and sulfonyl groups at the terminal position

Article abstract of DOI:10.1246/bcsj.81.1308

Highly stereoselective intramolecular Diels-Alder (IMDA) reaction of decatrienoates has been achieved by using a more sterically hindered ester group, i.e., i-butoxycarbonyl, or electron-withdrawing hetero substituents. i.e., chloro and phenylsulfonyl, as terminal activating groups. A remarkable olefin isomerization of the Diels-Alder cycloadduct bearing a phenylsulfonyl group occurred upon heating it for a few hours and it was found that the isomerization can be catalyzed by Bronsted acid.

Full text of DOI:10.1246/bcsj.81.1308

1308 Bull. Chem. Soc. Jpn. Vol. 81, No. 10, 1308–1314 (2008)
Ó 2008 The Chemical Society of Japan
Highly Stereoselective Intramolecular Diels–Alder Reaction
of Decatrienoates Activated by t-Butoxycarbonyl, Chloro,
and Sulfonyl Groups at the Terminal Position#
ꢀ1
Seiichi Inoue, Chunji Yin,1 Hiroko Kosugi,2 Atsuko Nabeta,2
Yoko Sakai,1 Kiyoshi Honda,2 and Yujiro Hoshino1
1Graduate School of Environment and Information Sciences, Yokohama National University,
79-7 Tokiwadai, Hodogaya-ku, Yokohama 240-8501
2Graduate School of Engineering, Yokohama National University,
79-5 Tokiwadai, Hodogaya-ku, Yokohama 240-8501
Received April 18, 2008; E-mail: s-inoue@ynu.ac.jp
Highly stereoselective intramolecular Diels–Alder (IMDA) reaction of decatrienoates has been achieved by using a
more sterically hindered ester group, i.e., t-butoxycarbonyl, or electron-withdrawing hetero substituents, i.e., chloro and
phenylsulfonyl, as terminal activating groups. A remarkable olefin isomerization of the Diels–Alder cycloadduct bearing
a phenylsulfonyl group occurred upon heating it for a few hours and it was found that the isomerization can be catalyzed
by Brønsted acid.
The intramolecular Diels–Alder (IMDA) reaction is a pow-
erful tool for the stereocontrolled construction of polycyclic
Results and Discussion
frameworks from relatively simple precursors.1 Recently, ex-
tensive efforts have been focused upon the stereochemistry
of the fused ring junction in IMDA reaction of the ester-teth-
ered deca-1,3,9-trienoate (=3,5-hexadienyl acrylate) deriva-
tives 1, which can generally give cis fused 3,4,4a,7,8,8a-hexa-
hydro-1H-2-benzopyran-1-ones (cis-2) in good, if not to say
satisfactory, stereoselectivity (Scheme 1).2
Hence, it has been applied to the synthesis of a variety
of complex molecules including natural products such as eleu-
therobin,3 lycorine,2d and stenine.4 Although decatrienoates
with terminally activated dienophiles are expected to be good
substrates in IMDA reactions, expanded examination of their
reactivity and selectivity with respect to various activating
groups except acetyl2b,5 or ester2h groups are scarce.6 In view
of further transformations in natural product synthesis,
heteroatom-containing groups such as sulfonyl and chloro
are more attractive activating groups. To explore access to
cis-2 in high selectivity we have now examined thoroughly
the IMDA reaction of 1 having various dienophile-activating
groups.
The results of heat-promoted IMDA reaction of 1a–1c
combined with literature results are shown in Table 1. Heating
acetyl-activated 1a5 gave two diastereomeric lactones: cis-2a
predominantly along with trans-2a in minor amount (Table 1,
Entry 1). Cycloaddition of enol silyl ether 1b and 1c also
yielded two isomeric products (Table 1, Entries 2–4) and the
selectivity was slightly improved in DMF (Table 1, Entry 3
vs. Entry 2). These results in hand and in literature indicate
that the reaction preferentially proceeds via endo boat-like
transition state A among the two competing diastereomeric
transition states (Scheme 2).1c,1d,2
The selectivity for cycloadducts cis-2 increased as the
terminal dienophile activating substituent changed along the
series COMe < CO2Et (or CO2Me) < H < i-Pr. Especially,
trienoate derivatives with unsaturated electron-withdrawing
substituents (e.g., COMe, CO2Me, and CO2Et) exhibited lower
selectivity than others. In these cases, exo boat-like transition
state B seems to competitively participate in the reaction due
to stabilizing attractive electrostatic and/or secondary orbital
interactions between the endo-oriented terminal carbonyl
group and the diene unit in the transition state, promoting
enhanced formation of the minor trans isomer. Therefore, the
O
R1
R1
O
O
H
H
R1
heat
O
7
O
O
+
4a
R4
1
3
R2
R4
R4
R2
R2
4
H
H
R3
R3
R3
1
cis-2
trans-2
Scheme 1. IMDA reaction of deca-1,3,9-trienoates.
Published on the web October 10, 2008; doi:10.1246/bcsj.81.1308

S. Inoue et al.
Bull. Chem. Soc. Jpn. Vol. 81, No. 10 (2008) 1309
Table 1. Thermal IMDA Reaction of Activated 1,3,9-Decatrienoates 1a–1g
Entry
1
R1
R2
R3
R4
Temp
/ꢁC
Time
/h
Yield
/%a)
2
cis/trans
1c)
2c)
3c)
4c)
5f)
6f)
7g)
8g)
1ab)
1b
1b
1c
1d
1e
COMe
COMe
COMe
CO2Et
H
CO2Me
COMe
i-Pr
Me
Me
Me
Me
H
H
H
H
H
H
H
H
H
H
Me
Me
H
OTIPS
OTIPS
OTBS
H
H
H
H
135d)
100d)
100e)
135d)
132
110
125
220
7
21
12
16
47
22
5
57
94
88
89
70
82
52
43
2a
2b
2b
2c
2d
2e
2f
cis-2g
74:26
70:30
73:27
80:20
92:8
83:17
60:40
cis only
1f
1g
20
a) Isolated yield after purification. b) 1a is a mixture of E and Z isomers (60:40) at C3 position. c) The reaction
was carried out in 0.01–0.1 M (M = mol dmꢂ3) solution for 1a–1c. d) In xylene. e) In N,N-dimethylform-
amide. f) Reference 2h. g) Reference 2b.
R3
O
HO
R1
O
O
O
O
a
H
H
R4
R
+
O
R2
O
O
Me
HO
Me
3
4
R4
R2
H
R1
O
R3
R1
R
R
O
b
endo-boat A
cis-2
O
O
O
H
O
O
Me
OSi
5
1
R2
Si = t-BuMe2Si
R1
R4
R4
h: R = CO2t-Bu; i: R = Cl; j: R = SO2Ph
H
R2
R3
R3
H
Scheme 3. Syntheses of triene 1h, 1i, and 1j. (a) DCC,
DMAP or EDC, DMAP (5h 58%, 5i 54%, 5j 88%). (b)
TBSOTf, Et3N (1h 74%, 1i 78%, 1j 87%).
exo-boat B
trans-2
Scheme 2. Transition states for decatrienoates 1.
selectivity for cis-2 was decreased by increasing the endo sta-
bilizing interactions (i.e., COMe > CO2Et > H).7 It is also
clear from the data of Table 1 that some terminal dienophile
substituents certainly play a significant influence in determin-
ing the cis stereoselectivity of the IMDA reaction. The deca-
trienoate 1g with an isopropyl group (Table 1, Entry 8) cycliz-
es to give cis fused bicyclic lactones exclusively. As shown in
Scheme 2, the exo boat-like transition state B apparently has
repulsive nonbonded interactions between substituent R1 and
the diene unit, thereby promoting this cyclization to proceed
by way of endo boat-like transition state A.
Table 2. Thermal IMDA Reaction of Activated 1,3,9-Deca-
trienoates 1h–1ja)
O
R
O
H
R
heat
O
O
Me
Me
OSi
OSi
H
Si = t-BuMe2Si
1
cis-2
Time
/h
Entry
1
R
Temp
/ꢁC
2
Yield
/%b)
It is anticipated from the above results that a bulky carbon-
yl-based substituent will enhance cis selective cyclization via
transition state A. Besides carbonyl-based activating groups
for the dienophile moiety, terminal electro-negative and/or
bulky hetero substituents will be also promising for cis favored
cyclization, and these hetero substituents are important for fur-
ther manipulation of the C8 position of the cycloadducts.6b,8
Then, we turned our attention to the IMDA reaction of t-bu-
toxycarbonyl-, chloro-, and phenylsulfonyl-activated triene
systems. In Scheme 3 is outlined synthesis of the ester-tethered
trienes 1h,9a,9b 1i,9c and 1j9d,9e via ester 5. Esterification of
(E)-3-chloroacrylic acid (3i) with 6-hydroxyenone 410 was un-
expectedly sluggish when using EDC, whereas acid 3h and 3j
underwent esterification with 4 either using DCC or EDC.
The results of thermal cyclization of 1h–1j are summarized
in Table 2. As anticipated, t-butoxycarbonyl-activated 1h pro-
vided only cycloadduct cis-2h with the 3-methyl group in anti
1
1h
1i
1j
CO2t-Bu
Cl
SO2Ph
115c)
175e)
100c)
15
1.5
3
cis-2h
cis-2i
cis-2j
86
68
95
2d)
3
a) The reaction was carried out in 0.01–0.1 M solution. b) Iso-
lated yield after purification. c) In toluene. d) Diphenylamine
(1.2 equiv) was added as a hydrogen chloride scavenger. e) In
1,2-dichlorobenzene.
(equatorial) orientation to the angular hydrogens. The IMDA
reactions of chlorotrienoate 1i also afforded cycloadduct as a
single isomer, although higher temperature for complete con-
version of the starting triene and addition of amine (as a
hydrogen chloride scavenger)6b were necessary. Interestingly,
phenylsulfonyl-activated 1j afforded cis-2j exclusively in high
yield in relatively short reaction period. These results suggest
that if optically active alcohol 4 is used as one of the starting
compounds, enantiomerically pure cycloadducts cis-2 having

1310 Bull. Chem. Soc. Jpn. Vol. 81, No. 10 (2008)
Highly Stereoselective IMDA Reaction
Table 3. 1H NMR Data for C8a–H in 2a–2c, and 2h–2j (in
CDCl3)
O
SO2Ph
H
8
O
8a
2
ꢂ cis
ꢂ trans
2a 3.16 (dd, J ¼ 9:2, 3.6 Hz) 2.83 (dd, J ¼ 12:2, 10.9 Hz)
2b 3.16 (dd, J ¼ 8:5, 3.7 Hz) 2.71 (dd, J ¼ 12:2, 11.3 Hz)
2c 3.19 (dd, J ¼ 8:8, 3.2 Hz) 2.69 (dd, J ¼ 12:2, 11.2 Hz)
Me
OTBS
H
Figure 2. The structure of 6.
2h 3.15 (dd, J ¼ 8:6, 3.0 Hz)
—
—
—
2i
2.92 (dd, J ¼ 8:3, 2.4 Hz)
Table 4. Intermolecular Diels–Alder Reaction of Substitut-
ed Butadiene and 2-Alken-5-olide
2j 3.55 (d, J ¼ 7:8 Hz)
O
R2
R3
Intermolecular
Diels-Alder reaction
O
+
R1
O
H
O
H
H
R2
R3
R2
R3
O
+
O
R1
R1
H
C
D
R1
CH3
R2
H
R3
H
C/D
Yield/% Ref.
Figure 1. X-ray crystal analysis of 2j. The H atoms re-
moved for clarity.
>20:1
42
82
12a
12b
PhthN(PhCH2)CH CH2Ph OTMS 100:0
four chiral centers can be obtained.
The stereochemistry of the cycloadducts 2a–2c and 2h–2j
was assigned primarily on the basis of their 400-MHz 1H NMR
spectra, the proton ꢀ to the lactone carbonyl (C8a–H) of these
compounds being particularly useful for assigning stereochem-
istry of the ring fusion. As illustrated in Table 3, in the cis
fused 2a–2c, 2h, and 2i, these signals appear as a doublet of
doublets (J8a{4a ¼ 8:3{9:2 Hz and J8a{8 ¼ 2:4{3:7 Hz), for
trans fused 2a–2c those protons also appear as a doublet of
doublets with two large coupling constants (J8a{4a ¼ 12:2 Hz
and J8a{8 ¼ 10:9{11:3 Hz). In contrast, for cis fused cycload-
duct 2j, this signal appears as a doublet (J8a{4a ¼ 7:8 Hz). It
seems likely that the H–C8a–C8–H dihedral angle approaches
90ꢁ, simplifying the C8a–H signal to a doublet. These assign-
ments are further corroborated by the COSY and especially
NOE experiments; in the latter case, a strong correlation was
observed between the proton ꢀ to the lactone oxygen and both
of the ring juncture protons in cis fused 2 and with only the
proton ꢀ to the carbonyl in trans fused 2. Fortunately, 2j could
be crystallized and was submitted to single-crystal X-ray anal-
ysis, the result of which is shown in Figure 1.
the product (Figure 2). It is quite interesting that neither the
proton ꢀ to the sulfonyl group nor the proton ꢀ to the lactone
carbonyl were epimerized under the reaction conditions.
The reaction should have at least two characteristics. At
first, the structure of 6 would be thought to be alternatively ob-
tainable from intermolecular Diels–Alder reaction of substitut-
ed butadiene and 2-alken-5-olide. However, 6 has trans stereo-
chemistry between the methyl group and the angular hydro-
gens (Type D in Table 4), therefore 6 belongs to type D com-
pounds, diastereomers of type C compounds which are
predominant or exclusive products of intermolecular Diels–
Alder reactions, as exemplified in Table 4.12 Secondly the re-
action is quite straightforward and exhibits very clear double-
bond isomerization which has not been so often reported in the
literature.13
We then performed reaction of cycloadduct cis-2j under
close examination under several conditions (Table 5). When
heated in toluene at 100 ꢁC for 4 h, cis-2j afforded the isomer
6 in high yield along with a small amount of 8 and 9 (Table 5,
Entry 1). We thought it likely that a trace amount of PhSO2H
generated by splitting off under thermal conditions with
formation of 9 might have catalyzed isomerization of cis-2j
to provide 6. Then cis-2j was treated with 0.12 equiv of p-tol-
uenesulfonic acid for 2 h to produce isomer 6 in 87% yield
(Table 5, Entry 2). When cis-2j was heated in the presence
of 6 equiv of triethylamine for 15 h, it was recovered un-
changed in 84% yield along with diene 7 in 6% yield (Table 5,
Entry 3). It is worth to note that in 1H NMR spectra of 7,
two hydrogens at C7 showed very large long range coupling
(J ¼ 10:5, 7.8 Hz) between the hydrogen at C4a.14
Experimental results showed that the sterically demanding
phenylsulfonyl group in 1j did not affect the IMDA reactivity
affording a single cycloadduct having the same relative stereo-
chemistry as cis-2a–2g. Instead, whilst we were studying the
IMDA reaction of 1j, a rather strange behavior was observed
when 1j was heated in toluene at 100 ꢁC for a prolonged period
(9 h). In this case, a single compound, accompanied by trace
amounts of unknown by-products,11 was obtained in 76%
yield, which exhibited upfield shift of the olefinic proton on
1
the cyclohexene ring in H NMR spectra (4.43 and 4.66 ppm
for 6 and cis-2j, respectively, in CDCl3). We at first anticipat-
ed that epimerization should have taken place at C8 or C8a po-
sitions as was proposed in the case of 2a.5 Extensive 2D NMR
experiments, however, allowed us to assign structure 6 for
It is quite obvious from the experiments that 6 is thermody-
namically a more stable isomer compared to IMDA product
cis-2j. This is in sharp contrast to 5ꢁ-3-ketosteroids and 2-dec-
alone, where ꢀ3-enol ether (steroid numbering) and 1,2-enol

S. Inoue et al.
Bull. Chem. Soc. Jpn. Vol. 81, No. 10 (2008) 1311
Table 5. Isomerization of Bicyclic Lactone 2ja)
on a Perkin-Elmer Paragon 1000 Fourier transform IR spectrom-
1
eter. H and 13C NMR spectra were measured on a JEOL JNM-
O
EX 270 (270 MHz) or a JEOL JNM-ALS 400 (400 MHz) spec-
trometers using internal tetramethylsilane as standard. High-
resolution mass spectra were recorded on a JEOL JMS-700 mass
spectrometer.
additive
O
2j
6
+
Me
+
OSi
H
(E)-1-Methyl-5-oxo-3-hexen-1-yl (E)-4-Oxo-2-pentenoate (5b).
To a solution of (E)-4-oxo-2-pentenoic acid (2.54 g, 22.1 mmol),
N,N0-dicyclohexylcarbodiimide (DCC, 4.17 g, 20.2 mmol) and 4-
(dimethylamino)pyridine (DMAP, 0.17 g, 1.4 mmol) in dichloro-
methane (120 mL) was added (E)-6-hydroxy-3-hepten-2-one (4,
2.17 g, 16.9 mmol). The reaction mixture was stirred for 12 h at
room temperature and the precipitated N,N0-dicyclohexylurea
was filtered off over celite, the filtrate was washed with water
and dried over magnesium sulfate. The solvent was removed un-
der reduced pressure and purification by column chromatography
(hexane/AcOEt = 7:3) afforded the title compound (2.36 g, 62%)
as a colorless oil. IR (neat, cmꢂ1): 2981, 2936, 1723, 1701, 1681,
1631, 1427, 1362, 1292, 1259, 1182, 982; 1H NMR (270 MHz,
CDCl3): ꢂ 7.01 (1H, d, J ¼ 16:2 Hz, OOCCH=CH), 6.72 (1H,
dt, J ¼ 15:8, 7.3 Hz, CH2CH=CH), 6.63 (1H, d, J ¼ 16:2 Hz,
OOCCH=CH), 6.14 (1H, d, J ¼ 15:8 Hz, CH2CH=CH), 5.17
(1H, app sextet, J ¼ 6:3 Hz, CHCH3), 2.56–2.50 (2H, m,
CH2CH=CH), 2.37 (3H, s, COCH3), 2.25 (3H, s, COCH3), 1.33
(3H, d, J ¼ 6:3 Hz, CHCH3); 13C NMR (67 MHz, CDCl3): ꢂ
197.6, 197.0 (COCH3), 164.4 (COO), 141.6, 139.8, 133.4, 131.1
(OOCCH=CH and CH2CH=CH), 70.2 (CHCH3), 38.4 (CH2),
27.9, 26.8 (COCH3), 19.5 (CHCH3); HRMS (FAB+) m=z calcd
for C12H17O4 ðM þ HÞþ: 225.1127. Found: 225.1129.
7
SO2Ph
O
O
O
H
H
O
O
+
Me
Me
O
H
8
9
Si = t-BuMe2Si
Entry
Additive
Time
Yield/%b)
/h
6
7
8
9
2j
1
2
—
p-TsOH
(0.12 equiv)
Et3N
(6 equiv)
4
2
90
87
—
—
2c)
0.3c)
3c)
3c)
—
—
3
15
—
6
—
—
84
a) The reaction was carried out in 0.01–0.1 M toluene solution
at 100 ꢁC. b) Isolated yield after purification except otherwise
noted. c) Yields were determined by H NMR analysis.
1
ether (decaline numbering), respectively, were produced pre-
dominantly under thermodynamically controlled conditions.15
Relative stability of double-bond isomers of silyl enol ethers
in our system may be influenced by the fused lactone ring
which contains oxygen and sp2-carbon atoms. Inspection of
the crystallographic structure indicates that the hydrogen at
C5 lies close to the equatorial hydrogen at C4 and that C7
and C8 positions have eclipsed conformation. This conforma-
tional strain energy may be released by isomerization from 2j
to 6. A similar acid-catalyzed thermal isomerization was also
observed with cis-2b and it gave isomerized products possess-
ing the same skeleton as 6 in 32% yield, although concurrent
formation of ketone like 8 (17% yield) was observed along
with the recovery of cis-2b in 16%.
In conclusion, we have explored stereoselectivity and reac-
tivity of the IMDA cyclization of variously substituted deca-
trienoates under thermal conditions and found that, compared
to acetyl and ethoxycarbonyl analogues, t-butoxycarbonyl-
and phenylsulfonyl-activated trienoate 1h and 1j exhibited
both increased reactivity and exclusive endo boat-like product
selectivity and chloro-substituted 1i showed complete stereo-
selectivity but moderate reactivity. Unexpectedly, cis-2j was
found to easily undergo isomerization as to the position of
the double bond in the presence of a catalytic amount of
Brønsted acid. Cycloadducts from the IMDA reaction which
appeared in the text seem to be valuable for the synthesis of
complex natural products and other functional materials.
By a procedure similar to the preparation of 5b, esters 5c and
5i were prepared from the corresponding acrylic acids 3c and
3i, respectively, with 4.
t-Butyl (E)-1-Methyl-5-oxo-3-hexen-1-yl (E)-2-Butenedioate
(5h). To a solution of t-butyl hydrogen fumarate (3h, 0.16 g, 0.94
mmol), DMAP (11 mg, 0.09 mol), and N-[3-(dimethylamino)prop-
yl]-N0-ethylcarbodiimide hydrochloride (EDC HCl, 0.20 g, 1.04
ꢃ
mmol) in dichloromethane (11 mL) was added (E)-6-hydroxy-3-
hepten-2-one (4, 0.11 g, 0.86 mol) at 10 ꢁC. The resulting solution
was kept at 10 ꢁC for 3 h. Then, the solvent was removed in vacuo,
the concentrate was diluted with AcOEt (40 mL) and made acidic
with 0.5 M hydrochloric acid (ca. pH 3). The mixture was washed
with 0.5 M NaHCO3 solution, brine, dried over magnesium
sulfate, filtered and the solvent removed under reduced pressure.
Purification by column chromatography (hexane/AcOEt 6:1 to
1:1) yielded the title compound (0.14 g, 58%) as a colorless oil.
IR (neat, cmꢂ1): 2981, 2935, 1716, 1678, 1645, 1428, 1369,
1
1302, 1261, 1151, 1062, 980, 848; H NMR (400 MHz, CDCl3):
ꢂ 6.73–6.63 (3H, m, COOCH=CH, CH2CH=CH), 6.07 (1H, d,
J ¼ 15:9 Hz, CH2CH=CH), 5.10 (1H, app sextet, J ¼ 6:3 Hz
CHCH3), 2.51–2.47 (2H, m, CH2CH=CH), 2.20 (3H, s, COCH3),
1.46 (9H, s, t-Bu), 1.27 (3H, d, J ¼ 6:3 Hz, CHCH3); 13C NMR
(67 MHz, CDCl3): ꢂ 197.8 (COCH3), 164.3, 163.7 (OOCCH=CH,
COOt-Bu), 141.8, 135.7, 133.6, 132.2 (OOCCH=CH and
CH2CH=CH), 81.9 (OC(CH3)3), 70.1 (CHCH3), 38.6 (CH2CH=
CH), 27.9 (OC(CH3)3), 27.0 (COCH3), 19.7 (CHCH3); HRMS
(FAB+) m=z calcd for C15H23O5 ðM þ HÞþ: 283.1545. Found:
283.1542.
By a procedure similar to the preparation of 5h, 5j was pre-
pared from the corresponding acrylic acid 3j and 4.
(E)-1-Methyl-5-(triisopropylsiloxy)-3,5-hexadien-1-yl (E)-4-
Oxo-2-pentenoate (1b). To a solution of compound 5b (0.49 g,
2.2 mmol) and TIPSOTf (0.58 mL, 2.4 mmol) in benzene (25 mL)
Experimental
Solvents were freshly distilled from the appropriate drying
agents before use. Reactions were conducted under an atmosphere
of dry N2 unless noted otherwise. Column chromatography was
performed using Kieselgel 60 (230–400 mesh) silica gel. All
melting points are uncorrected, and were measured on a Buchi
¨
535 micromelting point apparatus. IR spectra were recorded

1312 Bull. Chem. Soc. Jpn. Vol. 81, No. 10 (2008)
Highly Stereoselective IMDA Reaction
was added dropwise Et3N (0.35 mL, 2.8 mmol) under Ar atmo-
sphere at 0 ꢁC. The resulting solution was allowed to warm to room
temperature and left while stirring for 1 h. The mixture was wash-
ed with brine (30 mL) and the organic layers were dried over mag-
nesium sulfate, filtered and the solvent removed under reduced
pressure. Purification by column chromatography (hexane/AcOEt
9:1, +3% NEt3) yielded the title compound (0.72 g, 86%) as a col-
orless oil. IR (neat, cmꢂ1): 2945, 2867, 1725, 1704, 1688, 1593,
1464, 1361, 1324, 1290, 1258, 1180, 1026, 884, 681; 1H NMR
(270 MHz, CDCl3): ꢂ 6.98 (1H, d, J ¼ 16:0 Hz, OOCCH=CH),
6.61 (1H, d, J ¼ 16:0 Hz, OOCCH=CH), 6.06–5.90 (2H, m,
CH2CH=CH), 5.08 (1H, app sextet, J ¼ 6:3 Hz, CHCH3), 4.27
(1H, s, C=CHH), 4.21 (1H, s, C=CHH), 2.45–2.37 (2H, m,
CH2CH=CH), 2.35 (3H, s, COCH3), 1.28 (3H, d, J ¼ 6:3 Hz,
CHCH3), 1.26–1.13 (3H, m, SiCH(CH3)2), 1.10–1.05 (18H, m,
SiCH(CH3)2).
methyl-1-oxo-3,4,4a,7,8,8a-hexahydro-1H-2-benzopyran-8-car-
Ã
Ã
Ã
Ã
boxylate (cis-2c) and Ethyl (3R ,4aS ,8R ,8aR )-6-(t-Butyldi-
methylsiloxy)-3-methyl-1-oxo-3,4,4a,7,8,8a-hexahydro-1H-2-
benzopyran-8-carboxylate (trans-2c). cis-2c: Yield: 71%, col-
orless oil; IR (neat, cmꢂ1): 2955, 2931, 2858, 1737, 1673, 1472,
1464, 1388, 1369, 1281, 1261, 1198, 1178, 1035, 912, 839;
1H NMR (400 MHz, CDCl3): ꢂ 4.61 (1H, br s, H-5), 4.44 (1H,
dqd, J ¼ 12:2, 6.1, 2.1 Hz, H-3), 4.41–4.09 (2H, m, OCH2CH3),
3.29 (1H, dt, J ¼ 6:2, 3.2 Hz, H-8), 3.19 (1H, dd, J ¼ 8:8,
3.2 Hz, H-8a), 3.09–2.55 (1H, m, H-4a), 2.52 (1H, dd, J ¼ 17:2,
6.2 Hz, H-7ꢁ), 2.41 (1H, br d, J ¼ 17:2 Hz, H-7ꢀ), 2.19 (1H,
ddd, J ¼ 14:1, 9.0, 2.1 Hz, H-4ꢁ), 1.33 (3H, d, J ¼ 6:1 Hz,
CHCH3), 1.28–1.15 (1H, m, H-4ꢀ), 1.24 (3H, t, J ¼ 7:1 Hz,
OCH2CH3), 0.88 (9H, s, Sit-Bu), 0.09 (3H, s, SiCH3), 0.08
(3H, s, SiCH3); 13C NMR (67 MHz, CDCl3): ꢂ 173.0 (C-1),
172.9 (COOCH2CH3), 148.4 (C-6), 106.4 (C-5), 73.1 (C-3),
61.0 (OCH2), 39.0, 37.9, 37.8, 28.2, 27.9, (C-8, C-8a, C-4a,
C-7, C-4), 25.6 (SiC(CH3)3), 20.9 (CHCH3), 18.0 (SiC(CH3)3),
14.2 (CH2CH3), ꢂ4:3, ꢂ4:4 (SiCH3); HRMS (FAB+) calcd for
C19H33O5Si ½M þ Hꢄþ: 369.2097. Found m=z: 369.2099.
By a procedure similar to the preparation of 1b, 1c, and 1h–1j
was prepared from the corresponding trienoates.
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(3R ,4aR ,8R ,8aR )-8-Acetyl-3-methyl-6-(triisopropylsil-
oxy)-3,4,4a,7,8,8a-hexahydro-1H-2-benzopyran-1-one (cis-2b)
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and (3R ,4aS ,8R ,8aR )-8-Acetyl-3-methyl-6-(triisopropyl-
siloxy)-3,4,4a,7,8,8a-hexahydro-1H-2-benzopyran-1-one (trans-
2b). A solution of trienoate 1b (0.71 g, 1.9 mmol) in DMF (93
mL) was heated at 100 ꢁC for 12 h. Then, the reaction mixture
was cooled and brine (120 mL) and ether (120 mL) were added.
The organic layer was separated and the aqueous layer was extract-
ed with ether. The combined organic layers were washed with
brine and dried over sodium sulfate, filtered and the solvent re-
moved under reduced pressure. Purification by column chromatog-
raphy (hexane/AcOEt 3:1) gave the title compound cis-2b (0.46 g,
65%) with compound trans-2b (0.17 g, 23%) as a colorless oil.
cis-2b: IR (neat, cmꢂ1): 2943, 2866, 1734, 1714, 1676, 1463,
1391, 1371, 1271, 1201, 1173, 1064, 909, 884; 1H NMR (400
MHz, CDCl3): ꢂ 4.54 (1H, br s, H-5), 4.41 (1H, dqd, J ¼ 12:2,
6.1, 1.7 Hz, H-3), 3.19 (1H, dt, J ¼ 6:3, 3.7 Hz, H-8), 3.16 (1H,
dd, J ¼ 8:5, 3.7 Hz, H-8a), 2.99–2.93 (1H, m, H-4a), 2.57 (1H,
dd, J ¼ 17:5, 6.3 Hz, H-7ꢁ), 2.27 (1H, dd, J ¼ 17:5, 3.7 Hz,
H-7ꢀ), 2.12 (3H, s, COCH3), 2.08 (1H, ddd, J ¼ 13:9, 8.3,
1.7 Hz, H-4ꢁ), 1.24 (3H, d, J ¼ 6:1 Hz, CHCH3), 1.14–1.05
(1H, m, H-4ꢀ), 1.05–0.99 (3H, m, SiCH(CH3)2), 0.95 (18H, d,
J ¼ 6:3 Hz, SiCH(CH3)2); 13C NMR (67 MHz, CDCl3): ꢂ 208.1
(C=O), 173.3 (C-1), 147.9 (C-6), 105.1 (C-5), 73.1 (C-3), 46.6
(C-8), 37.8, 37.0, 28.4, 28.2 (C-4a, C-8a, C-4, C-7), 27.7
(COCH3), 20.7 (OCHCH3), 17.8 (SiCH(CH3)2), 12.4 (SiCH-
(CH3)2); HRMS (FAB+) m=z calcd for C21H37O4Si ðM þ HÞþ:
381.2461. Found: 381.2457.
trans-2c: Yield: 18%, colorless oil; IR (neat, cmꢂ1): 2955,
2933, 2898, 2858, 1739, 1668, 1364, 1316, 1256, 1196, 1124,
1049, 838, 781; 1H NMR (400 MHz, CDCl3): ꢂ 4.74 (1H, br s,
H-5), 4.59 (1H, ddq, J ¼ 9:7, 6.3, 6.1 Hz, H-3), 4.25–4.15 (2H,
m, OCH2CH3), 2.80 (1H, td, J ¼ 11:2, 6.1 Hz, H-8), 2.69 (1H,
dd, J ¼ 12:2, 11.2 Hz, H-8a), 2.60–2.51 (1H, m, H-4a), 2.35
(1H, dd, J ¼ 17:1, 6.1 Hz, H-7ꢁ), 2.24 (1H, dd, J ¼ 17:1,
11.2 Hz, H-7ꢀ), 1.95 (1H, dt, J ¼ 13:4, 9.7 Hz, H-4ꢁ), 1.70
(1H, ddd, J ¼ 13:4, 9.3, 6.3 Hz, H-4ꢀ), 1.38 (3H, d, J ¼ 6:1 Hz,
CHCH3), 1.28 (3H, t, J ¼ 7:1 Hz, OCH2CH3), 0.91 (9H, s, Si-
t-Bu), 0.14 (6H, s, SiCH3); 13C NMR (67 MHz, CDCl3): ꢂ
174.2, 173.5 (C-1 and COOCH2CH3), 148.8 (C-6), 105.8 (C-5),
72.7 (C-3), 60.9 (OCH2CH3), 42.0, 40.7 (C-8 and C-8a), 36.6,
33.0, 31.4 (C-4a, C-7, C-4), 25.6 (SiC(CH3)3), 21.2 (CHCH3),
18.0 (SiC(CH3)3), 14.2 (OCH2CH3), ꢂ4:3, ꢂ4:5 (SiCH3); HRMS
(FAB+) m=z calcd for C19H33O5Si, ðM þ HÞþ: 369.2097. Found:
369.2093.
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t-Butyl (3R ,4aR ,8R ,8aR )-6-(t-Butyldimethylsiloxy)-3-
methyl-1-oxo-3,4,4a,7,8,8a-hexahydro-1H-2-benzopyran-8-car-
boxylate (cis-2h): Yield: 86%, colorless oil; IR (neat, cmꢂ1):
2956, 2932, 2859, 1731, 1672, 1473, 1369, 1258, 1200, 1176,
867, 841; 1H NMR (400 MHz, CDCl3): ꢂ 4.59 (1H, br s, H-5),
4.43 (1H, dqd, J ¼ 12:2, 6.3, 2.3 Hz, H-3), 3.22 (1H, dt, J ¼
5:9, 3.0 Hz, H-8), 3.15 (1H, dd, J ¼ 8:6, 3.0 Hz, H-8a), 3.10–
3.02 (1H, m, H-4a), 2.49 (1H, dd, J ¼ 17:4, 5.9 Hz, H-7ꢁ), 2.36
(1H, br d, J ¼ 17:4 Hz, H-7ꢀ), 2.19 (1H, ddd, J ¼ 14:2, 9.2,
2.3 Hz, H-4ꢁ), 1.43 (9H, s, Ot-Bu), 1.33 (3H, d, J ¼ 6:3 Hz,
CHCH3), 1.26–1.16 (1H, m, H-4ꢀ), 0.88 (9H, s, Sit-Bu), 0.10
(3H, s, SiCH3), 0.09 (3H, s, SiCH3); 13C NMR (67 MHz, CDCl3):
ꢂ 173.1 (C-1), 172.1 (COOt-Bu), 148.6 (C-6), 106.0 (C-5), 80.9
(OC(CH3)3), 72.9 (C-3), 39.7, 38.0, 37.8, 28.1, 27.9 (C-8, C-8a,
C-4a, C-7, C-4), 27.8 (OC(CH3)3), 25.5 (SiC(CH3)3), 20.8
(CHCH3), 17.9 (SiC(CH3)3), ꢂ4:4 (SiCH3), ꢂ4:5 (SiCH3);
HRMS (FAB+) m=z calcd for C21H37O5Si ðM þ HÞþ: 397.2410.
Found: 397.2405.
trans-2b: IR (neat, cmꢂ1): 2945, 2867, 1745, 1717, 1667,
1464, 1385, 1353, 1306, 1201, 1123, 1056, 883; 1H NMR (400
MHz, CDCl3): ꢂ 4.72 (1H, br s, H-5), 4.54 (1H, ddq, J ¼ 9:5,
6.3, 6.1 Hz, H-3), 2.99 (1H, td, J ¼ 11:3, 5.9 Hz, H-8), 2.71
(1H, dd, J ¼ 12:2, 11.3 Hz, H-8a), 2.54–2.46 (1H, m, H-4a),
2.33 (3H, s, COCH3), 2.28 (1H, dd, J ¼ 17:1, 5.9 Hz, H-7ꢁ),
2.07 (1H, dt, J ¼ 13:4, 9.5 Hz, H-4ꢁ), 1.91 (1H, dd, J ¼ 17:1,
11.3 Hz, H-7ꢀ), 1.65 (1H, ddd, J ¼ 13:4, 9.5, 6.3 Hz, H-4ꢀ),
1.34 (3H, d, J ¼ 6:1 Hz, CHCH3), 1.17–1.07 (3H, m, SiCH-
(CH3)2), 1.03 (18H, d, J ¼ 6:6 Hz, SiCH(CH3)2); 13C NMR (67
MHz, CDCl3): ꢂ 210.3 (C=O), 174.0 (C-1), 149.0 (C-6),
104.8 (C-5), 72.7 (C-3), 46.4 (C-8), 42.6, 36.5, 32.5, 31.7, 30.3
(C-4a, C-8a, C-4, C-7, COCH3), 21.2 (OCHCH3), 17.9 (SiCH-
(CH3)2), 12.6 SiCH(CH3)2); HRMS (FAB+) m=z calcd for
C21H37O4Si ðM þ HÞþ: 381.2461. Found: 381.2462.
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(3R ,4aR ,8R ,8aR )-6-(t-Butyldimethylsiloxy)-8-chloro-3-
methyl-3,4,4a,7,8,8a-hexahydro-1H-2-benzopyran-1-one (cis-2i).
A solution of 1i (0.23g, 0.69 mmol) in 1,2-dichlorobenzene (5 mL)
was added dropwise to a solution of diphenylamine (0.14 g, 0.83
mmol) in the same solvent (35mL) under reflux. The reaction mix-
ture was refluxed and monitored by TLC. After completion of the
reaction (1.5 h), the reaction was cooled and the 1,2-dichlorobenzene
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Ethyl (3R ,4aR ,8R ,8aR )-6-(t-Butyldimethylsiloxy)-3-

S. Inoue et al.
Bull. Chem. Soc. Jpn. Vol. 81, No. 10 (2008) 1313
was removed by short column (hexane/AcOEt 8:1). The resulting
oil was purified by column chromatography (hexane/AcOEt 20:1)
to give the title compound (0.16 g, 68%) as a light-yellow oil. IR
(neat, cmꢂ1): 2931, 2895, 2858, 1738, 1674, 1473, 1379, 1297,
1240, 1194, 1063, 920, 837, 781, 686; 1H NMR (400 MHz, CDCl3):
m, Ph), 4.68 (1H, dqd, J ¼ 11:7, 6.1, 3.4 Hz, H-3), 4.12 (1H, dt,
J ¼ 6:6, 3.5 Hz, H-8), 3.89 (1H, br d, J ¼ 7:6 Hz, H-8a), 3.37–
3.27 (1H, m, H-4a), 2.79 (1H, dd, J ¼ 16:1, 6.6 Hz, H-7ꢁ), 2.62
(1H, dd, J ¼ 16:1, 3.5 Hz, H-7ꢀ), 2.50–2.42 (2H, m, H-4ꢁ,
H-5ꢁ), 2.04 (dd, J ¼ 15:1, 13.2 Hz, H-5ꢀ), 1.60–1.55 (1H, m,
H-4ꢀ), 1.44 (3H, d, J ¼ 6:1 Hz, CHCH3).
ꢂ
4.81 (1H, dt, J ¼ 4:6, 2.4 Hz, H-8), 4.71 (1H, br s, H-5), 4.41
(1H, dqd, J ¼ 12:2, 6.1, 2.2Hz, H-3), 3.35–3.31 (1H, m, H-4a),
3.02 (dd, J ¼ 18:3, 4.6Hz, H-7 ), 2.92 (1H, dd, J ¼ 8:3, 2.4 Hz,
H-8a), 2.34 (1H, ddd, J ¼ 14:2, 10.0, 2.2 Hz, H-4 ), 2.24 (1H,
br d, J ¼ 18:3 Hz, H-7 ), 1.36 (1H, d, J ¼ 6:1 Hz, CHCH3),
1.34–1.25 (1H, m, H-4 ), 0.90 (9H, s, Sit-Bu), 0.13 (3H, s, SiCH3),
0.12 (3H, s, SiCH3); 13C NMR (67 MHz, CDCl3):
171.6 (C-1),
Compound 9: White crystals; IR (KBr, cmꢂ1): 2976, 2934,
1714, 1698, 1643, 1614, 1450, 1392, 1356, 1307, 1258, 1206,
1106, 1039, 1014, 949, 731; 1H NMR (400 MHz, CDCl3): ꢂ
7.35 (1H, dt, J ¼ 5:1, 2.9 Hz, H-8), 4.54 (1H, dqd, J ¼ 11:7,
6.3, 3.9 Hz, H-3), 3.21 (1H, ddd, J ¼ 23:2, 5.1, 3.4 Hz, H-7ꢁ),
3.03 (1H, dt, J ¼ 23:2, 2.9 Hz, H-7ꢀ), 2.93–2.84 (1H, m, H-4a),
2.65 (1H, dd, J ¼ 14:9, 3.4 Hz, H-5ꢁ), 2.26 (1H, dd, J ¼ 14:9,
12.4 Hz, H-5ꢀ), 2.08 (1H, dd, J ¼ 13:9, 3.9 Hz, H-4ꢁ), 1.61–
1.52 (1H, m, H-4ꢀ), 1.44 (3H, d, J ¼ 6:3 Hz, CHCH3).
ꢁ
ꢁ
ꢀ
ꢀ
ꢂ
146.0 (C-6), 106.4 (C-5), 72.9 (C-3), 54.1 (C-8), 42.6 (C-4), 37.4
(C-8a), 34.8 (C-4a), 26.5 (C-7), 25.7 (SiC(CH3)3), 20.7 (CHCH3),
18.0 (SiC(CH3)3), ꢂ4:5 (SiCH3), ꢂ4:7 (SiCH3); HRMS (FAB+)
m=z calcd for C16H28O3ClSi ðM þ HÞþ: 331.1497. Found:
331.1496.
Table 5, Entry 2. To a solution of cycloadduct 2j (61 mg,
0.14 mmol) in toluene (14 mL) was added p-toluenesulfonic acid
(1.9 mg, 0.017 mmol) and the mixture was heated at 100 ꢁC for
2 h. The cooled reaction mixture was washed with saturated
NaHCO3 solution followed by brine. The organic layer was dried
over magnesium sulfate, filtered and the solvent removed under
reduced pressure, then was purified by column chromatography
(hexane/AcOEt 4:1 to 1:1) to give white solid 6 (53 mg, 87%)
and a mixture of 8 (0.15 mg, 0.3%) and 9 (0.65 mg, 3%).
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(3R ,4aR ,8R ,8aR )-6-(t-Butyldimethylsiloxy)-3-methyl-8-
phenylsulfonyl-3,4,4a,7,8,8a-hexahydro-1H-2-benzopyran-1-one
(cis-2j): Yield: 95%, colorless crystals, mp 119.6–120.2 ꢁC; IR
(KBr, cmꢂ1): 3055, 2994, 2932, 2859, 1744, 1727, 1682, 1447,
1370, 1309, 1252, 1182, 1143, 1061, 916, 842, 778; 1H NMR
(400 MHz, CDCl3): ꢂ 7.92–7.55 (5H, m, Ph), 4.66 (1H, br s, H-
5), 4.51 (1H, dqd, J ¼ 11:8, 6.1, 2.3 Hz, H-3), 4.01 (1H, d, J ¼
7:9 Hz, H-8), 3.55 (1H, d, J ¼ 7:8 Hz, H-8a), 3.37–3.30 (1H, m,
H-4a), 2.55 (1H, dd, J ¼ 19:0, 7.9 Hz, H-7ꢁ), 2.36 (1H, ddd,
J ¼ 13:0, 10.2, 2.3 Hz, H-4ꢁ), 2.21 (1H, d, J ¼ 19:0 Hz, H-7ꢀ),
1.37 (3H, d, J ¼ 6:1 Hz, CHCH3), 1.30 (1H, ddd, J ¼ 13:0,
11.8, 7.8 Hz, H-4ꢀ), 0.89 (9H, s, Sit-Bu), 0.14 (3H, s, SiCH3),
0.12 (3H, s, SiCH3); 13C NMR (67 MHz, CDCl3): ꢂ 172.0
(C-1), 145.8 (C-6), 137.7, 134.0, 129.2, 128.3 (Ph), 107.2
(C-5), 73.1 (C-3), 58.6 (C-8), 37.7 (C-4), 34.7 (C-8a), 27.5
(C-4a), 25.5 (SiC(CH3)3), 25.0 (C-7), 20.6 (CHCH3), 17.9
(SiC(CH3)3), ꢂ4:4 (SiCH3), ꢂ4:5 (SiCH3); Anal. Calcd for
C22H32O5SSi: C, 60.52; H, 7.39%. Found: C, 60.47; H, 7.56%.
Table 5, Entry 3. To a solution of cycloadduct 2j (36 mg,
0.083 mmol) in toluene (8 mL) was added triethylamine (0.069
mL, 0.50 mmol) and the mixture was heated at 100 ꢁC for 15 h.
The cooled reaction mixture was washed with saturated NH4Cl
solution followed by brine. The organic layer was dried over mag-
nesium sulfate, filtered and the solvent removed under reduced
pressure, then was purified by column chromatography (hexane/
ꢀ
ꢀ
AcOEt 5:1 to 4:1) to give 2j (30 mg, 83%) and (3R ,4aR )-6-
(t-butyldimethylsiloxy)-3-methyl-3,4,4a,7-tetrahydro-1H-2-benzo-
pyran-1-one (7) (1.4 mg, 6%) as colorless solids.
Compound 7: White crystals; IR (KBr, cmꢂ1): 2957, 2931,
2859, 1714, 1677, 1472, 1377, 1266, 1218, 1141, 1057, 906,
864, 779; 1H NMR (400 MHz, CDCl3): ꢂ 7.04 (1H, dt, J ¼ 4:9,
2.3 Hz, H-8), 4.75 (1H, t, J ¼ 2:3 Hz, H-5), 4.57 (1H, dqd,
J ¼ 11:9, 6.3, 3.2 Hz, H-3), 3.32–3.22 (1H, m, H-4a), 2.91 (1H,
ddt, J ¼ 23:2, 10.5, 2.5 Hz, H-7ꢁ), 2.82 (1H, ddd, J ¼ 23:2, 7.8,
4.9 Hz, H-7ꢀ), 2.01 (1H, dt, J ¼ 13:4, 3.2 Hz, H-4ꢁ), 1.39 (3H,
d, J ¼ 6:3 Hz, CHCH3), 1.32 (1H, ddd, J ¼ 14:6, 11.9, 4.6 Hz,
H-4ꢀ), 0.92 (9H, s, Sit-Bu), 0.16 (6H, s, SiCH3); 13C NMR
(67 MHz, CDCl3): ꢂ 165.1 (C-1), 148.0 (C-6), 137.0, 127.3
(C-8 and C-8a), 103.6 (C-5), 76.8 (C-3), 39.0, 34.6, 32.1 (C-4a,
C-7, C-4), 25.6 (SiC(CH3)3), 22.0 (CH3), 18.0 (SiC(CH3)3),
ꢂ4:4 (SiCH3).
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(3R ,4aR ,8R ,8aR )-6-(t-Butyldimethylsiloxy)-3-methyl-
8-phenylsulfonyl-3,4,4a,5,8,8a-hexahydro-1H-2-benzopyran-1-
one (6). A solution of cycloadduct cis-2j (0.144 g, 0.33 mmol) in
toluene (33 mL) was heated at 100 ꢁC for 4 h. The reaction solvent
was removed under reduced pressure and the crude product was
purified by column chromatography (hexane/AcOEt 4:1 to 1:1)
to give the title compound 6 (0.13 g, 90%) and a mixture of
ꢀ
ꢀ
ꢀ
ꢀ
(3R ,4aR ,8R ,8aR )-3-methyl-8-phenylsulfonyl-3,4,4a,5,7,8,8a-
heptahydro-1H-2-benzopyran-1,6-dione (8) (2.1 mg, 2%) and
ꢀ
ꢀ
(3R ,4aR )-3-methyl-3,4,4a,5,7-pentahydro-1H-2-benzopyran-1,6-
dione (9) (2.0 mg, 3%).
Compound 6: White crystals, mp 135.5–136.5 ꢁC; IR (KBr,
cmꢂ1): 3066, 2932, 2859, 1744, 1664, 1447, 1375, 1305, 1256,
Experimental Procedure for X-ray Crystallography of
cis-2j. A suitable single crystal cis-2j was obtained by recrystal-
lization from hexane/AcOEt (5:1). The data were collected at
ꢂ180 ꢁC on a Rigaku AFC-7R automated four-circle diffractome-
ter by using graphite-monochromated Cu Kꢀ radiation (ꢃ ¼
1
1200, 1146, 914, 834, 785; H NMR (400 MHz, CDCl3): ꢂ 7.92–
7.57 (5H, m, Ph), 4.61–4.52 (1H, m, H-3), 4.43 (1H, d, J ¼
4:7 Hz, H-7), 4.39 (1H, d, J ¼ 4:7 Hz, H-8), 3.57 (1H, d, J ¼
6:1 Hz, H-8a), 3.02–2.91 (1H, m, H-4a), 2.38 (1H, ddd, J ¼
14:4, 10.3, 4.4 Hz, H-4ꢁ), 2.17 (1H, dd, J ¼ 17:7, 6.1 Hz,
H-5ꢁ), 1.81 (1H, dd, J ¼ 17:7, 12.0 Hz, H-5ꢀ), 1.39 (3H, d, J ¼
6:1 Hz, CHCH3), 1.35–1.26 (1H, m, H-4ꢀ), 0.87 (9H, s, Sit-Bu),
0.08 (3H, s, SiCH3), 0.05 (3H, s, SiCH3); 13C NMR (67 MHz,
CDCl3): ꢂ 171.7 (C-1), 155.9 (C-6), 137.4, 134.0, 129.2, 128.9
(Ph), 93.6 (C-7), 73.3 (C-3), 60.9 (C-8), 36.6, 35.7, 35.6, 25.7
(C-8a, C-4a, C-5, C-4), 25.4 (SiC(CH3)3), 20.9 (CHCH3), 17.8
(SiC(CH3)3), ꢂ4:5 (SiCH3), ꢂ4:7 (SiCH3); HRMS (FAB+) m=z
calcd for C22H33O5SiS ðM þ HÞþ: 437.1818. Found: 437.1820.
Compound 8: 1H NMR (400 MHz, CDCl3): ꢂ 7.92–7.60 (5H,
˚
1:5418 A). A summary of the cell parameters, data collection
conditions, and refinement results are given in Table 6.
The structures were solved by direct methods and expanded us-
ing Fourier techniques.16 All calculations were performed using
the teXsan crystallographic software package.17 Crystallographic
data have been deposited with the Cambridge Crystallographic
Data Centre: Deposition number CCDC-656299 for compound
cis-2j. Copies of the data can be obtained free of charge via
http://www.ccdc.cam.ac.uk/conts/retrieving.html (or from the
Cambridge Crystallographic Data Centre, 12, Union Road, Cam-

1314 Bull. Chem. Soc. Jpn. Vol. 81, No. 10 (2008)
Highly Stereoselective IMDA Reaction
Table 6. Summary of Crystal Data for Compound cis-2j
Soc., Perkin Trans. 1 1996, 571. e) A. Saito, H. Ito, T. Taguchi,
Org. Lett. 2002, 4, 4619. f) H. Yanai, A. Saito, T. Taguchi, Tetra-
hedron 2005, 61, 7087. For theoretical discussions of the transi-
tion states in the IMDA reaction of 1,3,9-decatrienoates, see: g)
D. J. Tantillo, K. N. Houk, M. E. Jung, J. Org. Chem. 2001, 66,
1938. h) E. L. Pearson, L. C. H. Kwan, C. I. Turner, G. A. Jones,
A. C. Willis, M. N. Paddon-Row, M. S. Sherburn, J. Org. Chem.
2006, 71, 6099.
Empirical formula
Formula weight
Crystal color, description
Crystal size/mm3
Crystal system
C22H32O5SSi
436.64
colorless, prismatic
0:2 ꢅ 0:2 ꢅ 0:1
Triclinic
ꢁ
Space group
˚
P1(#2)
a/A
˚
14.344(8)
17.00(1)
10.413(3)
102.40(3)
92.89(3)
66.53(4)
2273(1)
4
`
a) N. Ritter, P. Metz, Synlett 2003, 2422. b) H. Bruyere,
S. Samaritani, S. Ballereau, A. Tomas, J. Royer, Synlett 2005,
3
b/A
˚
c/A
1421, and references cited therein.
4 a) C. Y. Chen, D. J. Hart, J. Org. Chem. 1990, 55, 6236.
b) C. Y. Chen, D. J. Hart, J. Org. Chem. 1993, 58, 3840.
ꢀ/deg
ꢁ/deg
ꢄ/deg
5
6
K. Mori, A. K. Gupta, Tetrahedron 1985, 41, 5295.
For examples of IMDA reactions of trienoates with termi-
3
˚
V/A R ¼ 0:04
Z
nally activated dienophiles, see: a) L. Strekowski, S. Kong, M. A.
Battiste, J. Org. Chem. 1988, 53, 901. b) E. J. Corey, R. L.
Danheiser, S. Chandrasekaran, G. E. Keck, B. Gopalan, S. D.
Larsen, P. Siret, J.-L. Gras, J. Am. Chem. Soc. 1978, 100, 8034.
c) G. Lorvelec, M. Vaultier, Tetrahedron Lett. 1998, 39, 5185.
Dcalcd/g cmꢂ3
F000
ꢅ(Cu Kꢀ)/cmꢂ1
2ꢆmax/deg
No. of measured reflns
Unique relns
Observed reflns
1.276
936.00
2.017
67.94
8670
6474
7
This trend parallels observations previously established
in the decatriene system. W. R. Roush, A. P. Essenfeld, J. S.
523
Warmus, Tetrahedron Lett. 1987, 28, 2447.
R
Rw
0.0395
0.0675
1.466
0.0252
0.38
8
D. Craig, D. A. Fischer, O. Kemal, T. Plessner, Tetra-
hedron Lett. 1988, 29, 6369.
t-Butyl hydrogen fumarate (3h): a) B. Neises, W. Steglich,
GOF
Max Shift/error in final cycle
9
Org. Synth. 1985, 63, 183. b) S. E. Denmark, A. Thoraresen,
D. S. Middleton, J. Am. Chem. Soc. 1996, 118, 8266. (E)-3-
Chloroacrylic acid (3i): c) A. N. Kurtz, W. E. Billups, R. B.
Greenlee, H. F. Hamil, W. T. Pace, J. Org. Chem. 1965, 30,
3141. (E)-3-Phenylsulfonylacrylic acid (3j): d) P. J. Bradley,
D. H. Grayson, J. Chem. Soc., Perkin Trans. 1 2002, 1794.
e) V. N. Mikhailova, N. K. Kau, A. D. Bulat, J. Org. Chem. USSR
1969, 5, 1421.
10 A. P. Kozikowski, T. R. Nieduzak, T. Konoike, J. P.
Springer, J. Am. Chem. Soc. 1987, 109, 5167.
11 The structures of these by-products were not determined at
this stage, but a later isomerization experiment of cis-2j revealed
that the byproducts of the cyclization of 1j were 8 and 9 by com-
parison with the isolated compounds.
ꢂ3
˚
Max peak in diff Fourier map/e Aꢂ3
˚
Min peak in diff Fourier map/e A
ꢂ0:39
bridge, CB2 1EZ, UK; Fax: +44 1223 336033; e-mail: deposit@
ccdc.cam.ac.uk).
We thank Dr. Nobuto Minowa of Meiji Seika Co., Ltd.,
Japan for X-ray crystallographic analysis of cis-2j. This work
was partly supported by a Sasakawa Scientific Research Grant
from The Japan Science Society (to C. Yin), and Cooperative
Research Fund from Graduate School of Environment and
Information Sciences, Y. N. U.
12 a) J. A. Findlay, J. M. Matsoukas, J. Krepinsky, Can. J.
Chem. 1976, 54, 3419. b) E. Demont, A. Eatherton, C. S.
Frampton, I. Kahn, S. Redshaw, Synlett 2004, 684. c) E. C.
Angell, F. Fringuelli, L. Minuti, F. Pizzo, B. Porter, A. Taticchi,
E. Wenkert, J. Org. Chem. 1985, 50, 4686.
Supporting Information
Spectroscopic data of 5c, 5i, 5j, 1c, 1h, 1i, and 1j. This material
is available free of charge on the web at http://www.csj.jp/
journals/bcsj/.
13 a) A. Deyine, G. Dujardin, M. Mammeri, J. M. Poirier,
Synth. Commun. 1998, 28, 1817. b) K. Ishihara, H. Nakamura,
S. Nakamura, H. Yamamoto, J. Org. Chem. 1998, 63, 6444, and
references cited therein.
References
# This paper is dedicated to the memory of Professor
Yoshihiko Ito.
1
For related reviews on IMDA reactions, see: a) E. Ciganek,
14 a) L. J. Durham, J. Studebaker, M. J. Perkins, Chem.
Commun. (London) 1965, 19, 456. b) E. W. Garbisch, Jr., M. G.
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3828. b) M. Sobukawa, M. Nakajima, K. Koga, Tetrahedron:
Asymmetry 1990, 1, 295.
16 DIRDIF 94: P. T. Beurskens, G. Admiraal, G. Beurskens,
W. P. Bosman, R. de Gelder, R. Israel, J. M. M. Smits, The
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2
For some examples, see: a) S. F. Martin, S. A. Williamson,
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Structure Corporation, 1985 and 2004.