New synthesis of t-butyl 1,2-dihydro-1-oxaazulene-3-carboxylates using lithium trimethylsilyldiazomethane

Article abstract of DOI:10.3987/COM-05-10504

Lithium trimethylsilyldiazomethane reacts with t-butylaryloxypyruvates to give t-butyl 1,2-dihydro-1-oxaazulene-3-carboxylates via alkylidenecarbene intermediates.

Full text of DOI:10.3987/COM-05-10504

HETEROCYCLES, Vol. 65, No. 11, 2005
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HETEROCYCLES, Vol. 65, No. 11, 2005, pp. 2667
Received, 6th July, 2005, Accepted, 18th August, 2005, Published online, 19th August, 2005
NEW SYNTHESIS OF t-BUTYL 1,2-DIHYDRO-1-OXAAZULENE-3-
CARBOXYLATES USING LITHIUM TRIMETHYLSILYLDIAZO-
METHANE
Susumu Tsuchida, Yoshiyuki Hari, and Toyohiko Aoyama*
Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1
Tanabe-dori, Mizuho, Nagoya 467-8603, Japan. E-mail: aoyama@phar.nagoya-
cu.ac.jp
Abstract
–
Lithium trimethylsilyldiazomethane reacts with t-butyl
aryloxypyruvates to give t-butyl 1,2-dihydro-1-oxaazulene-3-carboxylates via
alkylidenecarbene intermediates.
Alkylidenecarbenes are attractive intermediates in organic synthesis.1 We have already demonstrated that
the lithium salt of trimethylsilyldiazomethane (TMSC(Li)N2) smoothly reacts with carbonyl compounds
to generate alkylidenecarbenes which undergo various types of reactions to give homologous alkynes,
aldehydes, and heterocycles.2 Furthermore, we have found that TMSC(Li)N2 chemoselectively reacts with
4-aryl-2-oxobutanoates3 and N-methylanilides of α-keto acids4 at the carbonyl moiety giving 2,3-
dihydroazulenes and 1-aza-1,2-dihydroazulen-2-ones via intramolecular cycloaddition of the generated
alkylidenecarbenes to a benzene ring, followed by ring expansion, respectively (Scheme 1). Our
continuous interest in this area has led us to investigate the reaction of aryloxypyruvates with
TMSC(Li)N2 giving 1,2-dihydro-1-oxaazulene derivatives. In this paper, the details are described.
Scheme 1.

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Scheme 2. Reagents and conditions. i, t-butyl glycidate (1.1-2.2 eq.), NaH (0.3–1.0 eq.), t-BuOMe,
rt–reflux, 43–65 h, 34–67 %; ii, Dess-Martin periodinane (3.0 eq.), CH2Cl2, rt, 3 h, 59–87 %. R1, R2, R3 =
H, H, H (a); H, Me, H (b); H, MeO, H (c); H, Br, H (d); H, CF3, H (e); Me, H, Me (f).
Table 1. Examination of reaction conditions.
Entry
TMSC(metal)N2
Solvent
Et2O
THF
i-Pr2O
t-BuOMe
Conditions
Yield
19 %
–
1
2
3
4
5
6
7
8
9
TMSC(Li)N2 (1.2 eq.) a
TMSC(Li)N2 (1.2 eq.) a
TMSC(Li)N2 (1.2 eq.) a
TMSC(Li)N2 (1.2 eq.) a
TMSC(Li)N2 (1.2 eq.) a
TMSC(Na)N2 (1.2 eq.) b
TMSC(K)N2 (1.2 eq.) c
TMSC(MgBr)N2 (1.2 eq.) d
TMSC(Li)N2 (2.0 eq.) a
TMSC(Li)N2 (2.0 eq.) e
–78 °C, 1 h → reflux, 2 h
–78 °C, 1 h → 40 °C, 2 h
–78 °C, 1 h → 40 °C, 2 h
–78 °C, 1 h → 40 °C, 2 h
f
8 %
6 %
Et2O-TMEDA (1.2 eq.) –78 °C, 1 h → reflux, 2 h
– f (85 %) g
4 %
Et2O
Et2O
Et2O
Et2O
Et2O
–78 °C, 1 h → reflux, 2 h
–78 °C, 1 h → reflux, 2 h
–78 °C, 1 h → reflux, 2 h
–78 °C, 1 h → reflux, 2 h
–78 °C, 1 h → reflux, 2 h
f
–
– f (42 %) g
28 %
10
27 %
a
Prepared from TMSCHN2 and LDA. b Prepared from TMSCHN2 and NaHMDS. c Prepared from TMSCHN2 and
KHMDS. d Prepared from TMSCHN2, LDA and MgBr2. e Prepared from TMSCHN2 and n-BuLi. f Not obtained.
g
Obtained the aldol product (5).
The synthesis of t-butyl aryloxypyruvates (1) as substrates is shown in Scheme 2. The epoxy-opening
reaction of t-butyl glycidate5 by phenols (2) yielded α-hydroxy esters (3), which were oxidized by Dess-
Martin periodinane giving the desired 1.
The reaction conditions were optimized on the basis of reaction using t-butyl phenoxypyruvate (1a)
(Table 1). Treatment of 1a with TMSC(Li)N2 (1.2 eq.), prepared from TMSCHN2 and LDA, in Et2O gave
the desired t-butyl 1,2-dihydro-1-oxaazulene-3-carboxylate (4a) in 19 % yield (Entry 1). Et2O was found
to be the solvent of choice though THF, i-Pr2O and t-BuOMe were also tried (Entries 1-4). Interestingly,
reaction in Et2O containing TMEDA as an additive afforded the aldol product (5), and 4a was not
obtained at all (Entry 5). This result was probably due to an increase in basicity of TMSC(Li)N2 by the
addition of TMEDA. As shown in Entries 6–8, in this reaction, other metal salts of TMSCHN2 such as
TMSC(Na)N2, TMSC(K)N2 and TMSC(MgBr)N2 were quite ineffective. When two equivalents of
TMSC(Li)N2 were used, the best result was obtained and the yield of 4a increased to 28 % (Entry 9).6 The
use of n-BuLi, instead of LDA, for the preparation of TMSC(Li)N2 was also applicable in this reaction
(Entry 10).

HETEROCYCLES, Vol. 65, No. 11, 2005
2669
Table 2. The synthesis of t-butyl 1,2-dihydro-1-oxaazulene-3-carboxylates.
Entry
R1
H
H
H
H
R2
H
Me
MeO
Br
CF3
H
R3
H
H
H
H
Substrate
Yield
28 %
31 %
23 %
28 %
22 %
20 % b
1 a
2
1a
1b
1c
1d
1e
1f
3
4
5
H
Me
H
Me
6
a Shown in Entry 9 of Table 1. b Obtained a mixture of 4f and its isomer (1.7:1).
Next, reactions using other t-butyl aryloxypyruvates were carried out under the optimized reaction
conditions described above (Table 2). Various aryloxypyruvates bearing methyl (1b), methoxy (1c),
bromo (1d) and trifluoromethyl groups (1e) at the 4-position of the benzene ring reacted with
TMSC(Li)N2 to give the desired 4b-e in 22-31 % yields (Entries 2-5). In these cases, substituents on the
benzene ring of 1 had no effect on the yields of 4. Reaction with (3,5-dimethylphenoxy)pyruvate (1f) also
proceeded but the product was a mixture of 4f and its isomer (concerning the position of double bonds) in
20 % yield (Entry 6). Unfortunately, reaction with N,N-diisopropyl-phenoxypyruvamide7 or
phenoxypropan-2-one gave a complex mixture and the desired 1,2-dihydro-1-oxaazulene derivative was
not obtained.
In conclusion, we have found that the reaction of t-butyl aryloxypyruvates with lithium
trimethylsilyldiazomethane gave t-butyl 1,2-dihydro-1-oxaazulene-3-carboxylates bearing substituents on
the 7-membered ring. Although the yield was still unsatisfactory, this synthetic method allows us to easily
synthesize t-butyl 1,2-dihydro-1-oxaazulene-3-carboxylates from t-butyl acrylate.
EXPERIMENTAL
All melting points were measured on a Yanagimoto micro melting points apparatus and are uncorrected.
1 13
IR spectra were recorded on a SHIMADZU FTIR-8400S spectrophotometer. H and C NMR spectra
were recorded on a JEOL JNM-EX-270 spectrometer (1H, 270 MHz; C, 67.8 MHz). MS spectra were
13
recorded on a JEOL JMS-SX-102A spectrometer.
t-Butyl 2-hydroxy-3-phenoxypropioate (3a). To a stirred solution of phenol (1.88 g, 20 mmol) in t-butyl
methyl ether (4 mL) were added NaH (400 mg, 60 % dispersion in oil, 10 mmol) and t-butyl glycidate
(3.17 g, 22 mmol) under argon atmosphere. After being stirred at 45 °C for 43 h, the mixture was
quenched with H2O and extracted with EtOAc (2 times). The organic extracts were washed with water
and saturated brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by Kugelrohr

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distillation (1.0 mmHg, 150 °C) to give 3a (3.17 g, 67 %). Colorless needles, mp 67-68 °C (Et2O-hexane).
IR (nujol): 3018, 1734 cm-1. 1H NMR (CDCl3) δ: 1.48 (s, 9H), 3.21 (d, 1H, J = 6.5 Hz), 4.18-4.28 (m, 2H),
4.36-4.40 (m, 1H), 6.89-6.91 (m, 3H), 7.25-7.31 (m, 1H). 13C NMR (CDCl3) δ: 28.0, 69.8, 70.3, 83.0,
114.6, 121.1, 129.0, 158.4, 171.2. MS (EI): m/z 238 (M+), 94 (bp). HRMS calcd for C13H18O4: 238.1205,
found: 238.1216.
t-Butyl 2-hydroxy-3-(4-methylphenoxy)propioate (3b). Prepared from 4-methylphenol (541 mg, 5.0
mmol) and t-butyl glycidate (865 mg, 6.0 mmol). The residue was purified by Kugelrohr distillation (1.2
mmHg, 140 °C) to give 3b (516 mg, 41 %). Colorless crystals, mp 98-100 °C (hexane). IR (nujol): 3439,
1734 cm-1. 1H NMR (CDCl3) δ: 1.47 (s, 9H), 2.28 (s, 3H), 3.21(br s, 1H), 4.14-4.24 (m, 2H), 4.35-4.37 (m,
1H), 6.80 (d, 2H, J = 8.4 Hz), 7.07 (d, 2H, J = 8.4 Hz). 13C NMR (CDCl3) δ: 20.6, 28.1, 70.0, 70.3, 83.1,
114.5, 129.8, 130.4, 156.3, 171.3. MS (EI): m/z 252 (M+), 108 (bp). HRMS calcd for C14H20O4: 252.1362,
found: 252.1368.
t-Butyl 2-hydroxy-3-(4-methoxyphenoxy)propioate (3c). Prepared from 4-methoxyphenol (621 mg, 5.0
mmol) and t-butyl glycidate (865 mg, 6.0 mmol). The residue was purified by Kugelrohr distillation (1.0
mmHg, 150 °C) to give 3c (644 mg, 48 %). Colorless needles, mp 74-75 °C (Et2O-hexane). IR (nujol):
1
3439, 1740 cm-1. H NMR (CDCl3) δ: 1.48 (s, 9H), 3.21 (d, 1H, J = 6.1 Hz), 3.77 (s, 3H), 4.16-4.19 (m,
2H), 4.30-4.35 (m, 1H), 6.79 (d, 2H, J = 8.4 Hz), 7.07 (d, 2H, J = 8.7 Hz). 13C NMR (CDCl3) δ: 28.1, 55.7,
70.4, 70.7, 83.1, 114.5, 115.7, 152.6, 154.0, 171.3. MS (EI): m/z 268 (M+), 212 (bp). HRMS calcd for
C14H20O5: 268.1311, found: 268.1309.
t-Butyl 3-(4-bromophenoxy)-2-hydroxypropioate (3d). Prepared from 4-bromophenol (346 mg, 5.0
mmol) and t-butyl glycidate (634 g, 4.4 mmol). The residue was purified by Kugelrohr distillation (1.4
mmHg, 168 °C) to give 3d (263 mg, 42 %). White powder, mp 96-97 °C. IR (nujol): 3434, 1732 cm-1. 1H
NMR (CDCl3) δ: 1.47 (s, 9H), 3.21 (d, 1H, J = 6.5 Hz), 4.14-4.24 (m, 2H), 4.36 (br s, 1H), 6.78 (d, 2H, J
= 8.3 Hz), 7.37 (d, 2H, J = 8.3 Hz). 13C NMR (CDCl3) δ: 28.1, 70.1, 70.2, 83.3, 113.4, 116.4, 132.2, 157.6,
171.0. MS (EI): m/z 318 (M+), 316 (M+), 57 (bp). HRMS calcd for C13H17O479Br: 317.0310, found:
317.0337.
t-Butyl
2-hydroxy-3-(4-trifluoromethylphenoxy)propioate
(3e).
Prepared
from
4-
trifluoromethylphenol (811 mg, 5.0 mmol) and t-butyl glycidate (865 mg, 6.0 mmol). The residue was
purified by Kugelrohr distillation (1.4 mmHg, 168 °C) to give 3e (513 mg, 34 %). Colorless crystals, mp
121-122 °C (Et2O). IR (nujol): 3437, 1730 cm-1. 1H NMR (CDCl3) δ: 1.57 (s, 9H), 3.27 (br s, 1H), 4.22-
4.32 (m, 2H), 4.38-4.42 (m, 1H), 6.96 (d, 2H, J = 8.7 Hz), 7.54 (d, 2H, J = 8.7 Hz). 13C NMR (CDCl3) δ:
28.0, 70.0, 70.1, 83.5, 114.5, 115.4, 126.8, 126.9, 160.8, 170.9. MS (EI): m/z 306 (M+), 162 (bp). HRMS
calcd for C14H17O4F3: 306.1079, found: 306.1087.

HETEROCYCLES, Vol. 65, No. 11, 2005
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t-Butyl 3-(3,5-dimethylphenoxy)-2-hydroxypropioate (3f). Prepared from 3,5-dimethylphenol (611 mg,
5.0 mmol) and t-butyl glycidate (793 g, 5.5 mmol). The residue was purified by Kugelrohr distillation
1
(1.1 mmHg, 155 °C) to give 3f (559 mg, 42 %). Colorless oil. IR (neat): 3434, 1736 cm-1. H NMR
(CDCl3) δ: 1.48 (s, 9H), 2.28 (s, 6H), 3.19 (d, 1H, J = 6.6 Hz) 4.13-4.23 (m, 2H), 4.35 (t, 1H, J = 3.0 Hz),
13
6.53 (s, 2H), 6.61 (s, 2H). C NMR (CDCl3) δ: 21.4, 28.0, 69.7, 70.3, 112.3, 122.9, 139.0, 158.4, 171.3.
MS (EI): m/z 266 (M+), 122 (bp). HRMS calcd for C15H22O4: 266.1518, found: 266.1526.
t-Butyl phenoxypyruvate (1a). To a solution of t-butyl 2-hydroxy-3-phenoxypropioate (2a) (218 mg,
0.91 mmol) in CH2Cl2 (4 mL) was added Dess-Martin periodinane (1.16 g, 2.74 mmol) and the mixture
was stirred at rt for 3 h. After the mixture was diluted by Et2O, a 1:1 mixture of saturated NaHCO3 aq. and
saturated Na2S2O3 aq. was added and the mixture was further stirred overnight. The mixture was extracted
with Et2O (3 times). The organic extracts were washed with water and saturated brine, dried over Na2SO4,
and concentrated in vacuo. The residue was purified by column chromatography on silica gel (Fuji Sylisia
BW-200MH, hexane:EtOAc = 7:1) to give 1a (183 mg, 85 %). Pale yellow oil. IR (neat): 1746, 1734 cm-1.
1H NMR (CDCl3) δ: 1.56 (s, 9H), 5.09 (s, 2H), 6.91 (d, 2H, J = 8.1 Hz), 7.01 (t, 1H, J = 7.6 Hz), 7.27-
13
7.33 (m, 2H). C NMR (CDCl3) δ: 27.9, 70.9, 85.1, 114.8, 121.9, 129.5, 157.4, 159.3, 189.7. MS (EI):
m/z 236 (M+), 107 (bp). HRMS calcd for C13H16O4: 236.1049, found: 236.1056.
t-Butyl (4-methylphenoxy)pyruvate (1b). Prepared from 2b (510 mg, 2.0 mmol) and Dess-Martin
periodinane (2.57 g, 6.1 mmol). The residue was purified by column chromatography on silica gel (Fuji
Sylisia BW-200MH, hexane:EtOAc = 7:1) to give 1b (437 mg, 86 %). Pale yellow oil. IR (neat): 1755,
1720 cm-1. 1H NMR (CDCl3) δ: 1.56 (s, 9H), 2.29 (s, 3H), 5.04 (s, 2H), 6.81 (d, 2H, J = 8.4 Hz), 7.08 (d,
2H, J = 8.4 Hz). 13C NMR (CDCl3) δ: 20.6, 27.8, 71.3, 85.0, 114.7, 129.9, 131.2, 155.4, 159.4, 189.9. MS
(EI): m/z 250 (M+), 121 (bp). HRMS calcd for C14H18O4: 250.1205, found: 250.1200.
t-Butyl (4-methoxyphenoxy)pyruvate (1c). Prepared from 2c (553 mg, 2.1 mmol) and Dess-Martin
periodinane (2.62 g, 6.2 mmol). The residue was purified by column chromatography on silica gel (Fuji
Sylisia BW-200MH, hexane:EtOAc = 7:1) to give 1c (430 mg, 78 %). Yellow oil. IR (neat): 1749, 1734
cm-1. 1H NMR (CDCl3) δ: 1.56 (s, 9H), 3.77 (s, 3H), 5.09 (s, 2H), 6.80-6.87 (m, 4H). 13C NMR (CDCl3) δ:
27.9, 55.7, 72.0, 85.0, 114.6, 116.1, 151.7, 154.6, 159.3, 190.1. MS (EI): m/z 266 (M+), 210 (M+- tBu), 57
(bp). HRMS calcd for C14H18O5: 266.1154, found: 266.1154.
t-Butyl (4-bromophenoxy)pyruvate (1d). Prepared from 2d (266 mg, 0.84 mmol) and Dess-Martin
periodinane (1.07 g, 2.5 mmol). The residue was purified by column chromatography on silica gel (Fuji
Sylisia BW-200MH, hexane:EtOAc = 7:1) to give 1d (227 mg, 86 %). Pale yellow oil. IR (neat): 1747,
1
1732 cm-1. H NMR (CDCl3) δ: 1.56 (s, 9H), 5.07 (s, 2H), 6.79 (d, 2H, J = 9.1 Hz), 7.39 (d, 2H, J = 9.1
13
Hz). C NMR (CDCl3) δ: 27.9, 71.1, 85.3, 114.2, 116.5, 132.3, 156.6, 159.1, 189.1. MS (EI): m/z 316
79
(M+), 314 (M+), 57 (bp). HRMS calcd for C13H15O4 Br: 314.0154, found: 314.0152.

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HETEROCYCLES, Vol. 65, No. 11, 2005
t-Butyl (4-trifluoromethylphenoxy)pyruvate (1e). Prepared from 2e (500 mg, 1.6 mmol) and Dess-
Martin periodinane (2.08 g, 4.9 mmol). The residue was purified by column chromatography on silica gel
(Fuji Sylisia BW-200MH, hexane:EtOAc = 7:1) to give 1e (295 mg, 59 %). Colorless crystals, mp 78-
79 °C (hexane). IR (nujol): 1751 cm-1. 1H NMR (CDCl3) δ: 1.57 (s, 9H), 5.15 (s, 2H), 6.97 (d, 2H, J = 8.6
13
Hz), 7.56 (d, 2H, J = 8.6 Hz). C NMR (CDCl3) δ: 27.9, 70.7, 85.4, 114.7, 122.1, 123.8, 124.3, 126.1,
t
159.0, 159.8, 188.7. MS (EI): m/z 304 (M+), 248 (M+- Bu), 175 (bp). HRMS calcd for C14H17O4F3:
304.0922, found: 304.0929.
t-Butyl (3,5-dimethylphenoxy)pyruvate (1f). Prepared from 2f (175 mg, 0.66 mmol) and Dess-Martin
periodinane (936 mg, 2.0 mmol). The residue was purified by column chromatography on silica gel (Fuji
Sylisia BW-200MH, hexane:EtOAc = 7:1) to give 1f (121 mg, 70 %). Yellow needles, mp 84-85 °C
(Et2O-hexane). IR (nujol): 1751, 1726 cm-1. 1H NMR (CDCl3) δ: 1.56 (s, 9H), 2.28 (s, 6H), 5.04 (s, 2H),
13
6.53 (s, 2H), 6.65 (s, 1H). C NMR (CDCl3) δ: 21.5, 27.9, 70.9, 85.0, 112.5, 123.7, 139.3, 157.5, 159.4,
t
190.0. MS (EI): m/z 264 (M+), 135 (M+-COCO2 Bu), 57 (bp). HRMS calcd for C15H20O4: 264.1362,
found: 264.1368.
t-Butyl 1,2-dihydro-1-oxaazulene-3-carboxylate (4a). To a stirred solution of diisopropylamine (95 mg,
0.94 mmol) in Et2O (4 mL) was added dropwise n-butyllithium (1.60 M in hexane solution, 0.59 mL, 0.94
mmol) at -78 °C under argon atmosphere, and the mixture was stirred for 20 min. TMSCHN2 (1.55 M in
hexane solution, 0.60 mL, 0.94 mmol) was added dropwise at –78 °C, and the mixture was stirred for 10
min. A solution of t-butyl phenoxypyruvate (3a) (111 mg, 0.47 mmol) in Et2O (0.6 mL) was added
dropwise. This mixture was stirred at -78 °C for 1 h, then refluxed for 2 h. After being quenched with
H2O, the mixture was extracted with EtOAc (3 times). The organic extracts were washed with water and
saturated brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by column
chromatography on silica gel (Fuji Sylisia BW-200MH, hexane:EtOAc = 30:1) to give 4a (29 mg, 27 %).
1
Red oil. IR (neat): 1686 cm-1. H NMR (CDCl3) δ: 1.46 (s, 9H), 5.36 (s, 2H), 5.63 (d, 1H, J = 9.3 Hz),
5.79 (dd, 1H, J = 8.2 and 11.0 Hz), 6.12 (dd, 1H, J = 9.3 and 11.0 Hz), 6.23 (dd, 1H, J = 8.2 and 11.9 Hz),
7.22 (d, 1H, J = 11.9 Hz). 13C NMR (CDCl3) δ: 27.8, 78.1, 79.7, 104.9, 112.7, 123.3, 123.8, 133.5, 134.4,
144.6, 162.1, 172.1. MS (EI): m/z 232 (M+), 176 (M+-tBu), 131(bp). HRMS calcd for C14H16O3: 232.1100,
found: 232.1100.
t-Butyl 4-(t-butoxycarbonyl)-3,5-diphenoxy-4-hydroxy-2-oxopentanoate (5). Prepared from 3a (61
mg, 0.26 mmol), TMSC(Li)N2 (0.31 mmol) and TMEDA (36 mg, 0.31 mmol). The residue was purified
by column chromatography on silica gel (Fuji Sylisia BW-200MH, hexane:EtOAc = 30:1) to give 5 (52
1
mg, 85 %). Colorless needles, mp 127-128 °C (Et2O). IR (nujol): 3522, 1747, 1728 cm-1. H NMR
(CD2Cl2) δ: 1.36 (s, 9H), 1.42 (s, 9H), 3.99 (br s, 1H), 4.30 (d, 1H, J = 9.6 Hz), 4.34 (d, 1H, J = 9.6 Hz),
13
5.71 (s, 1H), 6.87-7.02 (m, 6H), 7.29 (m, 4H). C NMR (CD2Cl2) δ: 27.8, 27.8, 69.8, 79.2, 79.5, 84.3,

HETEROCYCLES, Vol. 65, No. 11, 2005
2673
85.0, 114.8, 115.1, 121.5, 122.2, 129.3, 129.5, 156.9, 158.0, 161.0, 168.9, 191.3. MS (FAB): m/z 473
(MH+). Anal. Calcd for C26H32O8: C, 66.09; H, 6.83. Found: C, 65.79; H, 6.85.
t-Butyl 1,2-dihydro-6-methyl-1-oxaazulene-3-carboxylate (4b). Prepared from 3b (132 mg, 0.53
mmol) and TMSC(Li)N2 (1.1 mmol). The residue was purified by column chromatography on silica gel
(Fuji Sylisia BW-200MH, hexane:EtOAc = 30:1) to give 4b (41 mg, 31 %). Red solid, mp 46-48 °C. IR
(nujol): 1682 cm-1. 1H NMR (CD2Cl2) δ: 1.46 (s, 9H), 1.90 (s, 3H), 5.32 (s, 2H), 5.56 (d, 1H, J = 9.3 Hz),
6.03 (d, 1H, J = 9.3 Hz), 6.20 (d, 1H, J = 12.2 Hz), 7.23 (d, 1H, J = 12.2 Hz). 13C NMR (CD2Cl2) δ: 25.3,
27.8, 77.5, 79.6, 104.3, 112.2, 123.4, 130.7, 132.4, 137.8, 143.9, 162.3, 169.8. MS (EI): m/z 246 (M+),
190 (bp). HRMS calcd for C15H18O3: 246.1256, found: 246.1257.
t-Butyl 1,2-dihydro-6-methoxy-1-oxaazulene-3-carboxylate (4c). Prepared from 3c (99 mg, 0.37
mmol) and TMSC(Li)N2 (0.75 mmol). The residue was purified by column chromatography on silica gel
(Fuji Sylisia BW-200MH, hexane:EtOAc = 30:1) to give 4c (23 mg, 23 %). Red solid, mp; 73-74 °C. IR
(nujol): 1678 cm-1. 1H NMR (CD2Cl2) δ: 1.47 (s, 9H), 3.56 (s, 3H), 5.28 (s, 2H), 5.51 (d, 1H, J = 9.4 Hz),
5.63 (d, 1H, J = 9.4 Hz), 6.19 (d, 1H, J = 12.8 Hz), 7.36 (d, 1H, J = 12.8 Hz). 13C NMR (CD2Cl2) δ: 27.8,
54.7, 76.9, 79.7, 101.8, 106.5, 113.0, 124.1, 132.0, 142.5, 154.8, 162.3, 165.4. MS (EI): m/z 262 (M+),
205 (bp). HRMS calcd for C15H18O4: 262.1205, found: 262.1205.
t-Butyl 6-bromo-1,2-dihydro-1-oxaazulene-3-carboxylate (4d). Prepared from 3d (172 mg, 0.55
mmol) and TMSC(Li)N2 (1.1 mmol). The residue was purified by column chromatography on silica gel
(Fuji Sylisia BW-200MH, hexane:EtOAc = 30:1) to give 4d (48 mg, 28 %). Red solid, mp 121-123 °C.
IR (nujol): 1688 cm-1. 1H NMR (CD2Cl2) δ: 1.47 (s, 9H), 5.33 (s, 2H), 5.40 (d, 1H, J = 9.7 Hz), 6.40 (d,
1H, J = 11.7 Hz), 6.51 (d, 1H, J = 9.7 Hz), 7.08 (d, 1H, J = 11.7 Hz). 13C NMR (CD2Cl2) δ: 27.7, 78.0,
80.4, 102.9, 115.7, 116.5, 123.6, 134.9, 137.8, 142.4, 161.7, 171.4. MS (EI): m/z 312 (M+), 310 (M+), 254
79
(bp). HRMS calcd for C14H15O3 Br: 310.0205, found: 310.0202.
t-Butyl 1,2-dihydro-1-oxa-6-trifluoromethylazulene-3-carboxylate (4e). Prepared from 3e (273 mg,
0.90 mmol) and TMSC(Li)N2 (1.8 mmol). The residue was purified by column chromatography on silica
gel (Fuji Sylisia BW-200MH, hexane:EtOAc = 30:1) to give 4e (60 mg, 22 %). Red solid, mp <30 °C. IR
(nujol): 1659 cm-1. 1H NMR (CD2Cl2) δ: 1.47 (s, 9H), 5.39 (s, 2H), 5.58 (d, 1H, J = 9.6 Hz), 6.24 (d, 1H, J
= 12.5 Hz), 6.55 (d, 1H, J = 9.6 Hz), 7.27 (d, 1H, J = 12.5 Hz). 13C NMR (CD2Cl2) δ: 27.7, 78.6, 80.8,
t
101.8, 124.3, 128.6, 128.7, 132.8, 142.4, 161.5, 174.7. MS (EI): m/z 300 (M+), 244 (M+- Bu), 199 (bp).
HRMS calcd for C15H15O3F3: 300.0973; found: 300.0979.
t-Butyl 1,2-dihydro-3,5-dimethyl-1-oxaazulene-3-carboxylate (4f). Prepared from 3f (86 mg, 0.33
mmol) and TMSC(Li)N2 (0.65 mmol). The residue was purified by column chromatography on silica gel
(Fuji Sylisia BW-200MH, hexane:EtOAc = 30:1) to give a mixture of 4f and its isomer (17 mg, 20 %, 4f :
1
its isomer = 1.7 : 1). Red oil. IR (nujol): 1688 cm-1. 4f, H NMR (CD2Cl2) δ: 1.70 (s, 9H), 2.27 (s, 3H),

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HETEROCYCLES, Vol. 65, No. 11, 2005
2.30 (s, 3H), 5.30 (s, 2H), 5.62 (s, 1H), 5.72 (s, 1H), 7.17 (s, 1H);its isomer, 1H NMR (CD2Cl2) δ: 1.54 (s,
9H), 1.95 (s, 3H), 2.00 (s, 3H), 4.86 (s, 2H), 6.54 (s, 1H), 6.63 (s, 1H), 7.55 (s, 1H). MS (EI): m/z 260
(M+), 203 (M+- tBu), 159 (bp). HRMS calcd for C16H20O3: 260.1412; found: 260.1414.
ACKNOWLEDGEMENTS
This work was financially supported by a Grant-in-Aid for Scientific Research (KAKENHI) (to T.A.),
and a Grant-in-Aid from The Fujisawa Foundation (to Y.H.).
REFERENCES AND NOTES
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