Diels-Alder reaction of eight-membered cyclic siloxydienes

Article abstract of DOI:10.1016/j.tet.2008.09.053

Eight-membered cyclic siloxydienes, 2-(tert-butyldimethylsiloxy)-1-methyl-5-oxacycloocta-1,3-diene and 2-(tert-butyldimethylsiloxy)-5-oxacycloocta-1,3-diene, were prepared from δ-valerolactone, and their Diels-Alder reactions with various dienophiles are

Full text of DOI:10.1016/j.tet.2008.09.053

Tetrahedron 64 (2008) 11224–11229
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Diels–Alder reaction of eight-membered cyclic siloxydienes
*
Jun-ichi Matsuo , Shun Sasaki, Takaya Hoshikawa, Hiroyuki Ishibashi
Division of Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Eight-membered cyclic siloxydienes, 2-(tert-butyldimethylsiloxy)-1-methyl-5-oxacycloocta-1,3-diene
Received 20 August 2008
Received in revised form 17 September
2008
Accepted 17 September 2008
Available online 26 September 2008
and 2-(tert-butyldimethylsiloxy)-5-oxacycloocta-1,3-diene, were prepared from
their Diels–Alder reactions with various dienophiles are reported.
d-valerolactone, and
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Diels–Alder reaction
Siloxydiene
Eight-membered cyclic compound
8-endo-dig Cyclization
1. Introduction
d a-Phenylsulfenylation of 2 in the
-valerolactone5 (Scheme 1).
presence HMPA gave 3 in 66% yield, and nucleophilic addition6 of
lithium trimethylsilylacetylide to 3 followed by treatment with
saturated aqueous ammonium chloride gave trimethylsilylalkynyl
ketone and the corresponding desilylated product 4 in 73 and 16%
yields, respectively. Deprotection of the trimethylsilyl group of
ethynyl ketone by TBAF gave 4 in 88% yield. It was noted that when
the addition of lithium trimethylsilylacetylide to 3 was performed
in a small scale (0.54 mmol of 3), desilylated product 4 was directly
obtained in 93% yield by successive treatment with aqueous am-
monium chloride.
The Diels–Alder reaction is one of the most powerful methods
for constructing a cyclohexene ring in organic synthesis.1 Although
various types of dienes have been developed for the Diels–Alder
reaction,2 eight-membered cyclic dienes have rarely been
employed since they are very poor enophiles. For example, it is very
difficult to obtain the Diels–Alder adduct between cycloocta-1,3-
diene and maleic anhydride.3 It has also been reported that even
tetracyanoethylene (TCNE), which is a much more reactive dien-
ophile than maleic anhydride, reacted with cycloocta-1,3-diene too
slowly to determine the reaction rate.4 We considered that eight-
membered siloxydienes 1 would be a more reactive enophile in
Diels–Alder reactions than cycloocta-1,3-diene (Fig. 1). In order to
verify this hypothesis, we prepared eight-membered cyclic
siloxydienes 1 and investigated their reactivities in Diels–Alder
reactions with various dienophiles. We report here the results
obtained in the preparation and Diels–Alder reactions of 1.
Intramolecular 8-endo-dig cyclization of 4 by Schreiber’s pro-
cedure7 (the use of a stoichiometric amount of n-butyllithium in
the presence of HMPA) gave 5 in 22–56% yields depending on the
reaction scale. That is, the cyclization of 0.16 mmol of 4 gave 5 in
56% yield, whereas the same cyclization of 2.01 mmol of 4 gave 5 in
22% yield. We found that the use of a catalytic amount (0.2 equiv) of
n-butyllithium in the presence of HMPA constantly gave the desired
eight-membered enone 5 in 52–56% yields along with 3 in 10–22%
yields. The suitable concentration of 4 for this cyclization was found
to be 0.04 M, and a concentration lower than 0.04 M resulted in
2. Results and discussion
2.1. Preparation of eight-membered cyclic siloxydienes
8 and 16
Eight-membered siloxydiene 8 was prepared from a-methyl-d-
valerolactone 2, which was obtained by methylation of
* Corresponding author. Tel./fax: þ81 76 234 4439.
Figure 1. Eight-membered cyclic siloxydiene 1.
E-mail address: jimatsuo@p.kanazawa-u.ac.jp (J. Matsuo).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.09.053

J. Matsuo et al. / Tetrahedron 64 (2008) 11224–11229
11225
Scheme 3. Preparation of 16.
Scheme 1. Preparation of 8.
the desired product 14 was obtained in 82% yield. Direct de-
sulfurization of 14 proceeded with zinc and ammonium chloride to
give 15 in 55% yield, and eight-membered siloxydiene 16 was
obtained by silylation with KHMDS and TBSCl.
increased formation of 3. These results suggest that this cyclization
proceeds by the mechanism shown in Scheme 2. Alkoxide 9 gen-
erated by the reaction of 4 and a catalytic amount of n-butyllithium
is cyclized to 10, and 10 is protonated with unreacted 4 to give the
desired product 5 and the intermediate 9. The formation of 10
competes with the formation of 11 having a six-membered ring,
and 11 equilibrates with 3 and lithium acetylide. Under the con-
dition of a low concentration of 4 (lower than 0.04 M), it was dif-
ficult for intermolecular attack of lithium acetylide to 3 to take
place, and 3 was obtained in increased yields.
2.2. Diels–Alder reaction of eight-membered siloxydiene
8 and 16
The Diels–Alder reaction of 8 with tetracyanoethyene (TCNE)9 at
room temperature gave the corresponding Diels–Alder adduct 17
quantitatively (Scheme 4). The structure of 17 was confirmed by
HMBC correlations. It has been reported that [4þ2] and [2þ2] cy-
cloaddition competed in the reaction of TCNE and some substituted
1,3-butadienes.9 However, only [4þ2] cycloaddition proceeded ef-
ficiently in the reaction of 8 and TCNE.
Scheme 4. Diels–Alder reaction of 8 and TCNE.
Eight-membered siloxydiene 16 also reacted with TCNE
smoothly to afford the corresponding Diels–Alder adduct 18 in 88%
yield (Scheme 5).
Scheme 2. Possible mechanism for cyclization of 4 to 5.
Direct desulfurization of 5 to 7 by using zinc and ammonium
chloride8 did not proceed. Therefore, the phenylthio group of 5 was
removed to afford desulfurized enone 7 by oxidation of 5 with
mCPBA, followed by treatment of the resultant sulfoxide 6 with zinc
and ammonium chloride. tert-Butyldimethylsilyl (TBS) enol ether 8
was prepared from 7 in 92% yield by using KHMDS and TBSCl at
ꢀ10 ꢁC.
Similar to the synthesis of 8, eight-membered siloxydiene 16
was prepared from
d-valerolactone (Scheme 3). Bis-a-phenyl-
sulfenylation of -valerolactone gave 12 in 81% yield by using
d
Scheme 5. Diels–Alder reaction of 16 with TCNE.
2.1 equiv of LDA and S-phenyl benzenethiosulfonate. Compound 13,
which was obtained by nucleophilic addition of lithium trime-
thylsilylacetylide followed by desilylation with aqueous ammo-
nium chloride, was cyclized under the above-mentioned conditions
of employing 0.2 equiv of n-butyllithium in the presence of HMPA.
The cyclization of 13 proceeded more efficiently than that of 4 and
4-Phenyl-1,2,4-triazoline-3,5-dione (PTAD) 19, which is known
to be a better dienophile than TCNE,10 reacted with 8 in toluene at
0 ꢁC within 10 min. It was found that a major product was formed
along with some by-products, and it was difficult to purify the

11226
J. Matsuo et al. / Tetrahedron 64 (2008) 11224–11229
major product without its isomerization on silica gel or neutral
alumina. Therefore, the isomerization was led to completion by
treating the crude product with silica gel in dichloromethane at
room temperature to afford compound 22 in 30% yield (Scheme
6).11 The structure of 22 was determined by HMBC correlations and
NOE experiments. It was thought that the initial major product was
Diels–Alder adduct 20, and isomerization to 22 took place via in-
termediate 21, which was formed by silica gel-catalyzed ring-
opening of 20.
tetramethylsilane. Splitting patterns are designated as s, singlet; d,
doublet; t, triplet; q, quartet; sext, sextet; m, multiplet. 13C NMR
spectra were recorded on a JEOL JNM GSX500 (500 MHz) spec-
trometer with complete proton decoupling. Chemical shifts are
reported in parts per million relative to tetramethylsilane with the
solvent resonance as the internal standard CDCl3. High resolution
mass spectra (HRMS) were recorded on a JEOL JMS-SX-102A mass
spectrometer (EI). Elemental analyses were carried out on a Yanaco
CHN Corder MT-5. Analytical TLC was performed on Merck pre-
coated TLC plates (silica gel 60 GF254, 0.25 mm). Silica gel column
chromatography was carried out on silica gel 60N (Kanto Kagaku
Co., Ltd, spherical, neutral, 63–210 mm).
4.2. 2-Methyl-2-phenylsulfanylpentano-5-lactone (3)
To a stirred solution of diisopropylamine (5.93 mL, 42.3 mmol)
in dry THF (141 mL) was added n-butyllithium (1.66 M in hexane,
25.5 mL, 42.3 mmol) at ꢀ78 ꢁC and the resulting solution was
stirred at ꢀ78 ꢁC for 15 min. After the addition of HMPA (14.7 mL,
84.7 mmol),
a solution of a-methyl-d
-varelolactone5 (3.22 g,
28.2 mmol) in THF (10 mL) was added and the reaction mixture was
stirred at ꢀ78 ꢁC for 20 min. Then, a solution of S-phenyl benze-
nethiosulfonate14 (10.6 g, 42.3 mmol) in THF (10 mL) was added at
ꢀ78 ꢁC, and the reaction mixture was stirred at 0 ꢁC for 30 min and
at room temperature for 30 min. The reaction was quenched with
saturated aqueous ammonium chloride and the mixture was
extracted with ethyl acetate. The organic extracts were washed
with brine, dried over anhydrous sodium sulfate, filtered, and
concentrated. The crude product was purified by column chroma-
tography on silica gel (hexane/ethyl acetate¼10:1 then 3:1) to af-
ford 3 (4.52 g, 20.3 mmol, 72%) as colorless plates: mp 58.0–59.0 ꢁC
(hexane–ethyl acetate). 1H NMR (500 MHz, CDCl3)
d 1.45 (s, 3H),
Scheme 6. Diels–Alder reaction of 8 and PTAD (19).
1.84–1.90 (m, 1H), 2.04–2.15 (m, 1H), 2.16–2.32 (m, 2H), 4.32–4.36
(m,1H), 4.65–4.69 (m,1H), 7.33–7.42 (m, 3H), 7.49–7.51 (m, 2H); 13C
Eight-membered siloxydiene 8 did not react with maleic an-
hydride, N-phenylmaleimide, p-quinone, dimethyl acetylenedi-
carboxylate, and phenyl vinyl sulfone in refluxing toluene. It is
considered that highly electrophilic dienophiles such as TCNE and
PTAD12 react with eight-membered siloxydienes by an asynchro-
nous mechanism.13 On the other hand, less electrophilic
dienophiles such as maleic anhydride does not react with eight-
membered siloxydienes because the diene moiety of
eight-membered 1,3-dienes does not have planarity, which is re-
quired for a synchronous [4þ2] cycloaddition mechanism, which
works for less reactive dienophiles.
NMR (125 MHz, CDCl3)
d 20.7, 26.4, 34.0, 50.5, 69.3, 128.8, 129.9,
130.1, 137.2, 171.4; IR (CHCl3, cmꢀ1) 1720, 1269, 1119. Anal. Calcd for
C12H14O2S: C, 64.83; H, 6.35. Found: C, 64.55; H, 6.31.
4.3. 7-Hydroxy-4-methyl-4-phenylsulfanylhept-1-yn-3-
one (4)
Gram-scale preparation of 4. To a stirred solution of trime-
thylsilylacetylene (3.37 mL, 24.4 mmol) in dry THF (70 mL) was
added n-butyllithium (1.66 M in hexane, 14.7 mL, 24.4 mmol) at
ꢀ78 ꢁC, and the reaction mixture was stirred for 20 min. A solution
of 3 (4.51 g, 20.3 mmol) in dry THF (5 mL) was added to the reaction
mixture at ꢀ78 ꢁC and the reaction mixture was stirred at ꢀ78 ꢁC
for 15 min. A saturated aqueous ammonium chloride solution was
added to the reaction mixture, and the resulting mixture was stir-
red at room temperature for 20 min and extracted with ethyl ace-
tate. The combined organic extracts were washed with brine, dried
over anhydrous sodium sulfate, filtered, and concentrated. The
crude product was purified by column chromatography on silica gel
(hexane/ethyl acetate¼3:1) to afford the corresponding trime-
thylsilylethynyl ketone (4.76 g, 14.9 mmol, 73%) and 4 (0.79 g,
3.18 mmol, 16%).
3. Conclusion
We established a method for the preparation of eight-mem-
bered silyloxydienes 8 and 16 from d-valerolactone, and we found
that they were more reactive than cycloocta-1,3-diene for the Di-
els–Alder reaction with TCNE. It was also found that PTAD reacted
with 8 but the formed Diels–Alder adduct was considered to
isomerize easily to six-membered ketal 22. The reactivities of 8 and
16 in Diels–Alder reactions, which were disclosed by this research,
will offer a part of basic information for the Diels–Alder reaction of
medium-sized cyclic dienes.
To a stirred solution of thus-obtained trimethylsilylethynyl ke-
tone (4.74 g, 14.8 mmol) and methanol (5.98 mL, 148 mmol) in THF
(80 mL) was added at ꢀ20 ꢁC a solution of TBAF (1 M in THF,
5.91 mL, 5.91 mmol). The reaction mixture was stirred at ꢀ20 ꢁC for
15 min and 0 ꢁC for 15 min. The reaction was quenched by adding
a solution of saturated aqueous ammonium chloride solution and
the resulting mixture was extracted with ethyl acetate. The com-
bined organic extracts were washed with brine, dried over anhy-
drous sodium sulfate, filtered, and concentrated. The crude product
was purified by column chromatography on silica gel (hexane/ethyl
4. Experimental
4.1. General
All melting points were determined on a Yanagimoto micro
melting point apparatus and are uncorrected. Infrared (IR) spectra
were recorded on a Shimadzu FTIR-8100. 1H NMR spectra were
recorded on a JEOL JNM GSX500 (500 MHz) spectrometer; chem-
ical shifts
(d) are reported in parts per million relative to

J. Matsuo et al. / Tetrahedron 64 (2008) 11224–11229
11227
acetate¼2:1 then 1:1) to afford 4 (3.24 g, 13.0 mmol) as a pale
yellow oil. 1H NMR (500 MHz, CDCl3)
1.39 (s, 3H), 1.49–1.57 (m,
J¼7.8 Hz, 1H), 6.70 (d, J¼8.1 Hz, 1H); 13C NMR (125 MHz, CDCl3)
d
d )
18.9, 27.1, 27.8, 46.6, 68.9, 103.4, 153.7, 208.2; IR (CHCl3, cmꢀ1
1H), 1.69 (br s, 1H), 1.74–1.84 (m, 2H), 1.96–2.03 (m, 1H), 3.31 (s, 1H),
3.61–3.66 (m, 2H), 7.30–7.32 (m, 2H), 7.36–7.39 (m, 1H), 7.42–7.43
1661, 1620; HRMS (EI) calcd for C8H12O2 (m/z): 140.08373, found:
140.08330.
(m, 2H); 13C NMR (125 MHz, CDCl3)
d
19.8, 27.8, 32.3, 60.2, 62.6,
79.8, 79.9, 129.0, 129.6, 129.8, 136.9, 138.0, 184.0; IR (CHCl3, cmꢀ1
)
4.6. 2-(tert-Butyldimethylsiloxy)-1-methyl-5-oxacycloocta-
3299, 2097, 1669; HRMS (EI) calcd for C14H16O2S (m/z): 248.08710,
found: 248.08680.
1,3-diene (8)
Small scale preparation of 4. To a stirred solution of trime-
thylsilylacetylene (0.09 mL, 0.65 mmol) in dry THF (2 mL) was
added n-butyllithium (1.63 M in hexane, 0.39 mL, 0.64 mmol) at
ꢀ78 ꢁC, and the reaction mixture was stirred for 20 min. A solution
of 3 (119 mg, 0.535 mmol) in dry THF (1 mL) was added to the re-
action mixture at ꢀ78 ꢁC and the reaction mixture was stirred at
ꢀ78 ꢁC for 20 min. A saturated aqueous ammonium chloride so-
lution was added to the reaction mixture, and the same workup
procedure described above gave 4 (123.8 mg, 0.499 mmol, 93%).
To a stirred solution of 7 (155 mg,1.11 mmol) and TBSCl (201 mg,
1.33 mmol) in dry THF (5 mL) was added at ꢀ10 ꢁC a solution of
KHMDS (0.5 M in toluene, 2.65 mL, 1.33 mmol), and the mixture
was stirred at ꢀ10 ꢁC for 15 min. The reaction was quenched with
saturated aqueous ammonium chloride solution and the resulting
mixture was extracted with ethyl acetate. The combined organic
extracts were washed with brine, dried over anhydrous sodium
sulfate, filtered, and concentrated. The crude product was purified
by column chromatography on silica gel (hexane/ethyl
acetate¼55:1) to afford 8 (260 mg, 1.02 mmol, 92%) as a pale yellow
4.4. 8-Methyl-8-phenylsulfanyl-4-oxacyclooct-2-en-1-one (5)
oil. 1H NMR (500 MHz, CDCl3)
d 0.16 (s, 3H), 0.96 (s, 9H), 1.57 (br s,
2H), 2.30 (br s, 2H), 4.20 (br s, 2H), 4.41 (dd, J¼1.2, 8.5 Hz, 1H), 6.08
To a stirred solution of n-butyllithium (1.55 M in hexane,
0.93 mL, 1.44 mmol) in dry THF (150 mL) and HMPA (12.5 mL,
71.8 mmol) was added at ꢀ78 ꢁC a solution of 4 (1.79 g, 7.20 mmol)
in dry THF (50 mL), and the reaction mixture was stirred at room
temperature for 2 h. The reaction was quenched with saturated
aqueous ammonium solution and the mixture was extracted with
ethyl acetate. The combined organic extracts were washed with
brine, dried over anhydrous sodium sulfate, filtered, and concen-
trated. The crude product was purified by column chromatography
on silica gel (hexane/ethyl acetate¼10:1) to afford 3 (350 mg,
1.57 mmol, 22%) as a pale yellow oil and 5 (996 mg, 4.01 mmol,
56%) as colorless leaflets: mp 74.0–74.5 ꢁC (hexane–ethyl acetate).
(d, J¼7.9 Hz, 1H); 13C NMR (125 MHz, CDCl3)
ꢀ3.6, 16.2, 18.2, 22.4,
d
25.9, 29.3, 66.0, 100.7, 112.2, 142.5, 145.3; IR (CHCl3, cmꢀ1) 1630,
1119; HRMS (EI) calcd for C14H26O2Si (m/z): 254.17021, found:
254.17096.
4.7. Bis(2-phenylsulfanyl)pentano-5-lactone (12)
To a stirred solution of diisopropylamine (4.35 mL, 31.0 mmol)
in dry THF (74 mL) was added at ꢀ78 ꢁC a solution of n-butyllithium
(1.59 M in hexane, 19.5 mL, 31.0 mmol), and the reaction mixture
was stirred at the same temperature for 15 min. Then, a solution of
freshly distilled
d-valerolactone (1.48 g, 14.8 mmol) in dry THF
1H NMR (500 MHz, CDCl3)
d
1.33 (s, 3H), 1.84–1.96 (m, 2H), 2.07–
(5 mL) was added at ꢀ78 ꢁC and the mixture was stirred at ꢀ78 ꢁC
for 30 min. A solution of S-phenyl benzenethiosulfonate (7.77 g,
31.0 mmol) in dry THF (8 mL) was added at ꢀ78 ꢁC and the reaction
mixture was stirred at ꢀ20 ꢁC for 50 min. The reaction was
quenched with saturated aqueous ammonium chloride solution
and the resulting mixture was extracted with ethyl acetate. The
combined organic extracts were washed with brine, dried over
anhydrous sodium sulfate, filtered, and concentrated. The crude
product was purified by column chromatography on silica gel
(hexane/ethyl acetate¼5:1) to afford 12 (4.17 g, 13.2 mmol, 89%) as
colorless crystals: mp 126.5–127.0 ꢁC (hexane–ethyl acetate). 1H
2.15 (m, 1H), 2.35 (dt, J¼3.9, 13.9 Hz, 1H), 3.64 (dt, J¼2.4, 12.9 Hz,
1H), 4.13 (ddd, J¼1.2, 4.9, 12.7 Hz,1H), 5.06 (d, J¼8.1 Hz,1H), 6.61 (d,
J¼8.1 Hz, 1H), 7.32–7.43 (m, 5H); 13C NMR (125 MHz, CDCl3)
d 20.3,
26.5, 31.5, 60.3, 67.5, 100.9, 128.7, 129.8, 130.2, 137.4, 151.2, 199.2; IR
(CHCl3, cmꢀ1) 1657, 1624; HRMS (EI) calcd for C14H16O2S (m/z):
248.08710, found: 248.08725.
4.5. 8-Methyl-4-oxacyclooct-2-en-1-one (7)
To a stirred solution of 5 (420 mg, 1.69 mmol) in dichloro-
methane (10 mL) was added at ꢀ78 ꢁC a solution of mCPBA (65%,
450 mg, 1.69 mmol) in dichloromethane (2 mL) and the mixture
was stirred at ꢀ78 ꢁC for 1 h and at ꢀ20 ꢁC for 5 min. The reaction
was quenched with 10% aqueous sodium thiosulfate solution at
ꢀ20 ꢁC and the mixture was extracted with dichloromethane. The
combined organic extracts were washed with saturated aqueous
sodium hydrogencarbonate solution and brine, dried over anhy-
drous sodium sulfate, filtered, and concentrated. The crude product
was purified by column chromatography on silica gel (hexane/ethyl
acetate¼3:1 then 2:1 then 1:1) to afford 6 (349 mg, 1.32 mmol,
78%) as yellow oil. To a solution of 6 (340.6 mg, 1.29 mmol) in THF
(13 mL) was added activated zinc (5.02 g, 76.8 mmol) and saturated
aqueous ammonium chloride solution (13 mL) at room tempera-
ture, and the mixture was stirred at room temperature for 15 min.
The reaction mixture was filtered through a Celite pad and the
filtrate was extracted with ether. The combined organic extracts
were washed with saturated aqueous sodium hydrogencarbonate
solution and brine, dried over anhydrous sodium sulfate, filtered,
and concentrated. The crude product was purified by column
chromatography on silica gel (hexane/ether¼7:1) to afford 7
(154.2 mg, 1.10 mmol, 85%) as a pale yellow oil. 1H NMR (500 MHz,
NMR (500 MHz, CDCl3)
d
1.97 (sext, J¼6.1 Hz, 2H), 2.16 (t, J¼6.4 Hz,
2H), 4.36 (t, J¼6.1 Hz, 2H), 7.36–7.44 (m, 6H), 7.66–7.67 (m, 4H); 13C
NMR (125 MHz, CDCl3)
d 20.9, 33.6, 64.5, 69.7, 128.9, 129.9, 130.4,
136.6, 167.0; IR (CHCl3, cmꢀ1) 1278. Anal. Calcd for C17H18O2S2: C,
64.53; H, 5.10; N, 0.00. Found: C, 64.48; H, 5.10; N, 0.00.
4.8. 7-Hydroxy-bis(4-phenylsulfanyl)hept-1-yn-3-one (13)
To
a stirred solution of trimethylsilylacetylene (1.34 mL,
9.69 mmol) in dry THF (55 mL) was added n-butyllithium (1.66 M
in hexane, 6.09 mL, 10.1 mmol) at ꢀ78 ꢁC, and the mixture was
stirred for 15 min. A solution of 12 (2.66 g, 8.42 mmol) in dry THF
(5 mL) was then added at ꢀ78 ꢁC and the mixture was stirred at
ꢀ78 ꢁC for 15 min. Saturated aqueous ammonium chloride solution
was then added at ꢀ78 ꢁC and the mixture was stirred at room
temperature for 20 min. The resulting mixture was extracted with
ethyl acetate, and combined organic extracts were washed with
brine, dried over anhydrous sodium sulfate, filtered, and concen-
trated. The crude product was purified by column chromatography
on silica gel (hexane/ethyl acetate¼2:1) to afford 13 (2.61 g,
7.62 mmol, 90%) as a colorless oil. 1H NMR (500 MHz, CDCl3)
d 1.26
CDCl3)
d
1.17 (d, J¼7.3 Hz, 3H), 1.71–1.78 (m, 1H), 1.87–1.90 (m, 2H),
(br s, 1H), 1.77–1.80 (m, 2H), 1.88–1.95 (m, 2H), 3.40 (s, 1H), 3.49 (t,
1.99–2.07 (m, 1H), 2.53–2.60 (m, 1H), 3.93–4.02 (m, 2H), 4.91 (d,
J¼6.3 Hz, 2H), 7.33–7.41 (m, 6H), 7.61 (d, J¼7.6 Hz, 4H); 13C NMR

11228
J. Matsuo et al. / Tetrahedron 64 (2008) 11224–11229
(125 MHz, CDCl3)
d
27.7, 29.2, 62.3, 74.0, 79.9, 81.3, 129.1, 129.5,
4.12. 7-tert-Butyldimethylsiloxy-9,9,10,10-tetracyano-6-
methyl-2-oxabicyclo[4.2.2]dec-7-ene (17)
129.9, 136.1, 179.6; IR (CHCl3, cmꢀ1) 3299, 2099, 1669; HRMS (EI)
calcd for C19H18O2S2 (m/z): 342.07483, found: 342.07371.
A solution of TCNE (13.8 mg, 0.108 mmol) in toluene (1 mL) was
added 8 (17.6 mg, 69.2 mmol) at room temperature, and the
4.9. Bis(8-phenylsulfanyl)-4-oxacyclooct-2-en-1-one (14)
resulting yellow solution was stirred at room temperature for
30 min. After evaporation of the solvent, the crude product was
purified by column chromatography on silica gel (hexane/ethyl
To a stirred solution of n-butyllithium (1.66 M in hexane,
0.99 mL, 1.64 mmol) in dry THF (200 mL) and HMPA (14.3 mL,
82.2 mmol) was added a solution of 13 (2.816 g, 8.22 mmol) in dry
THF (6 mL) at ꢀ78 ꢁC, and the mixture was stirred at room tem-
perature for 1 h. The reaction was quenched with saturated aque-
ous ammonium chloride solution and the mixture was extracted
with ethyl acetate. The combined organic extracts were washed
with brine, dried over anhydrous sodium sulfate, filtered, and
concentrated. The crude product was purified by column chroma-
tography on silica gel (hexane/ethyl acetate¼10:1) to afford 14
(2.31 g, 6.75 mmol, 82%) as a white powder: mp 159.5–160.0 ꢁC
acetate¼30:1 then 5:1) to afford 17 (26.5 mg, 69.3
m
mol, quant) as
0.30
a white solid: mp 137.0–137.5 ꢁC. 1H NMR (500 MHz, CDCl3)
d
(s, 3H), 0.33 (s, 3H), 0.99 (s, 9H),1.65 (s, 3H), 1.70–1.78 (m, 1H), 1.93–
2.13 (m, 3H), 3.65–3.69 (m,1H), 3.94 (dd, J¼6.1, 12.8 Hz,1H), 4.96 (d,
J¼7.3 Hz, 1H), 5.20 (d, J¼7.9 Hz, 1H); 13C NMR (125 MHz, CDCl3)
d
ꢀ4.8, ꢀ4.8, 18.2, 25.4, 26.9, 27.3, 31.9, 36.1, 46.9, 47.2, 50.0, 63.0,
74.2, 94.4, 110.3, 110.6, 111.9, 113.1, 159.9; IR (CHCl3, cmꢀ1) 2253,
1649; HRMS (EI) calcd for C20H26O2N4Si (m/z): 382.18250, found:
382.18272.
(hexane–ethyl acetate). 1H NMR (500 MHz, CDCl3)
d 1.93 (br s, 2H),
2.10 (br s, 2H), 3.99 (br s, 2H), 4.97 (d, J¼8.1 Hz, 1H), 6.60 (d,
4.13. 7-tert-Butyldimethylsiloxy-9,9,10,10-tetracyano-2-
oxabicyclo[4.2.2]dec-7-ene (18)
J¼8.1 Hz, 1H), 7.36–7.43 (m, 6H), 7.71 (br s, 4H); 13C NMR (125 MHz,
CDCl3)
d 26.2, 28.6, 67.9, 78.3, 99.7, 128.8, 129.4, 131.2, 135.6, 151.8,
193.8; IR (CHCl3, cmꢀ1) 1661, 1624; HRMS (EI) calcd for C19H18O2S2
To the stirred solution of 16 (20.8 mg, 86.5 mmol) in toluene
(m/z): 342.07483, found: 342.07438.
(2 mL) was added tetracyanoethylene (16.7 mg, 0.13 mmol) at room
temperature, and the mixture was stirred at room temperature for
15 min. After the solvent was evaporated, the crude product was
purified by column chromatography on silica gel (hexane/ethyl
4.10. 4-Oxacyclooct-2-en-1-one (15)
To a stirred solution of 14 (2.10 g, 6.13 mmol) in THF (35 mL) was
added activated zinc (9.2 g, 141 mmol) and saturated aqueous
ammonium chloride solution (35 mL) at room temperature, and the
resulting suspension was stirred at room temperature for 15 min.
After filtration through a Celite pad, the filtrate was extracted with
diethyl ether. The combined organic extracts were washed with
saturated aqueous sodium hydrogencarbonate and brine, dried
over anhydrous sodium sulfate, filtered, and concentrated. The
crude product was purified by column chromatography on silica gel
(hexane/ether¼5:1 then 1:1) to afford 15 (342 mg, 2.71 mmol, 44%)
and a mixture containing a partially reduced compound (868 mg).
The mixture containing a partially reduced compound was treated
with zinc and ammonium chloride by the same procedure to give
15 (86 mg, 0.68 mmol, 11%) as a pale yellow oil. 1H NMR (500 MHz,
acetate¼5:1) to afford 18 (28.2 mg, 76.5
m
mol, 88%) as a white solid:
mp 107.5–108.0 ꢁC. 1H NMR (500 MHz, CDCl3)
d
0.30 (s, 3H), 0.32 (s,
3H), 0.97 (s, 9H), 1.81–1.89 (m,1H), 1.98–2.03 (m, 2H), 2.31–2.36 (m,
1H), 3.29 (dd, J¼2.4, 5.9 Hz, 1H), 3.67–3.72 (m, 1H), 3.92 (dt, J¼3.9,
13.4 Hz, 1H), 5.03 (d, J¼7.8 Hz, 1H), 5.21 (d, J¼7.6 Hz, 1H); 13C NMR
(125 MHz, CDCl3)
d
ꢀ4.7, ꢀ4.7, 17.9, 25.3, 26.1, 26.7, 42.3, 46.4, 47.6,
63.1, 75.0, 95.2, 110.1, 110.3, 112.3, 113.1, 158.6; IR (CHCl3, cmꢀ1
)
2253, 1661, 1256; HRMS (EI) calcd for C19H24O2N4Si (m/z):
368.16685, found: 368.16585.
4.14. ( )-(4aR
*
,8aR )-4a-tert-Butyldimethylsiloxy-8a-
*
methyloctahydro-5-oxa-N-phenyl-1,2-
cinnolinedicarboximide (22)
CDCl3)
d
1.88–1.99 (m, 4H), 2.53–2.55 (m, 2H), 4.09 (t, J¼5.6 Hz, 2H),
4.92 (d, J¼8.1 Hz, 1H), 6.74 (d, J¼8.1 Hz); 13C NMR (125 MHz, CDCl3)
To a solution of 8 (20.9 mg, 82.1
m
mol) in toluene (1 mL) was
added at 0 ꢁC a solution of PTAD (14.6 mg, 83.4
mmol) in toluene
d
19.0, 30.6, 42.0, 69.3, 104.3, 155.0, 204.0; IR (CHCl3, cmꢀ1) 1641,
(1 mL), and the resulting red solution was stirred at 0 ꢁC for 15 min.
After evaporation of the solvent, silica gel (1 g) and dichloro-
methane (3 mL) were added. The suspension was stirred at room
temperature for 20 min and it was filtered through a Celite pad. The
filtrate was concentrated and the crude product was purified by
column chromatography on silica gel (hexane/ethyl acetate¼7:1) to
afford 22 (10.7 mg, 24.9 mmol, 30%) as a white solid: mp 138.0–
1617, 1302; HRMS (EI) calcd for C7H10O2 (m/z): 126.06808, found:
126.06840.
4.11. 2-(tert-Butyldimethylsiloxy)-5-oxacycloocta-1,3-
diene (16)
143.0 ꢁC. 1H NMR (500 MHz, CDCl3)
d 0.23 (s, 3H), 0.27 (s, 3H), 0.97
To a stirred solution of 15 (59.3 mg, 0.47 mmol) and TBSCl
(77.9 mg, 0.517 mmol) in dry THF (2.5 mL) was added a solution of
KHMDS (0.5 M in toluene, 1.13 mL, 0.565 mmol) at ꢀ10 ꢁC, and the
reaction mixture was stirred at the same temperature for 15 min.
The reaction was quenched with saturated aqueous ammonium
chloride solution and the mixture was extracted with ether. The
combined organic extracts were washed with brine, dried over
anhydrous sodium sulfate, filtered, and concentrated. The crude
product was purified by column chromatography on silica gel
(hexane/ether¼50:1) to afford 16 (104 mg, 0.433 mmol, 92%) as
(s, 9H), 1.33 (s, 3H), 1.54–1.57 (m, 1H), 2.03–2.17 (m, 2H), 2.93–2.97
(m,1H), 3.68–3.72 (m,1H), 3.90–3.95 (m,1H), 5.25 (d, J¼8.3 Hz,1H),
6.98 (dd, J¼0.5, 8.3 Hz, 1H), 7.37–7.39 (m, 1H), 7.45–7.50 (m, 4H);
13C NMR (125 MHz, CDCl3)
d
ꢀ3.0, ꢀ2.5, 18.5, 21.2, 21.7, 25.9, 28.1,
60.8, 62.8, 94.0, 107.7, 117.8, 125.8, 128.3, 129.1, 130.9, 145.6, 149.8; IR
(CHCl3, cmꢀ1
)
1775, 1717, 1659, 1412; HRMS (EI) calcd for
C22H31O4N3Si (m/z): 429.20839, found: 429.20770.
a pale yellow oil. 1H NMR (500 MHz, CDCl3)
d
0.16 (s, 6H), 0.94 (s,
Acknowledgements
9H), 1.52–1.58 (m, 2H), 2.29–2.34 (m, 2H), 4.33 (t, J¼5.4 Hz, 2H),
4.36 (d, J¼8.3 Hz, 1H), 4.70 (t, J¼8.3 Hz, 1H), 6.14 (d, J¼8.3 Hz, 1H);
The authors are grateful for the financial support from the
Uehara Memorial Foundation and a Grant-in-Aid for Scientific Re-
search from the Ministry of Education, Culture, Sports, Science, and
Technology of Japan.
13C NMR (125 MHz, CDCl3)
d
ꢀ4.3, 18.1, 22.2, 24.0, 25.7, 66.5, 100.0,
104.9, 146.9, 150.2; IR (CHCl3, cmꢀ1) 1635, 1163, 1117; HRMS (EI)
calcd for C13H24O2Si (m/z): 240.15456, found: 240.15388.

J. Matsuo et al. / Tetrahedron 64 (2008) 11224–11229
11229
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