Facile synthesis of 2-azaazulenes from thiobenzoyl isocyanates using trimethylsilyldiazomethane

Article abstract of DOI:10.1016/j.tet.2007.11.107

The reaction of trimethylsilyldiazomethane with thiobenzoyl isocyanates, in situ generated from thiazole-4,5-diones, yielded diazoketones, which were converted into 2-azaazulenes by the intramolecular Buchner reaction.

Full text of DOI:10.1016/j.tet.2007.11.107

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 1753e1758
www.elsevier.com/locate/tet
Facile synthesis of 2-azaazulenes from thiobenzoyl isocyanates
using trimethylsilyldiazomethane
*
Mikio Morita, Yoshiyuki Hari, Tomoe Iguchi, Toyohiko Aoyama
Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho, Nagoya 467-8603, Japan
Received 13 November 2007; accepted 30 November 2007
Available online 5 December 2007
Abstract
The reaction of trimethylsilyldiazomethane with thiobenzoyl isocyanates, in situ generated from thiazole-4,5-diones, yielded diazoketones,
which were converted into 2-azaazulenes by the intramolecular Buchner reaction.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
O
OTMS
O
N
i
ii
N
NCO
R
R
O
Our interest in trimethylsilyldiazomethane (TMSCHN2) as
a synthetic reagent originated from the hazardous nature of di-
azomethane (CH2N2), which has been widely used in various
organic reactions.1 TMSCHN2 is stable and safe in contrast
to labile and explosive diazomethane. We have already dem-
onstrated that TMSCHN2 can be effectively used not only as
a C1-unit introducing reagent and a [CeNeN]azole synthon
in place of diazomethane but also as an alkylidene carbene
generator from carbonyl compounds.2 Recently, for example,
we have succeeded in the synthesis of multi-substituted furans
and bicyclic pyridones by the reaction of TMSCHN2 with acyl
isocyanates, followed by DielseAlder reaction of the resulting
4-trimethylsiloxyoxazoles with dimethyl acetylenedicarboxy-
late and N-phenylmaleimide in one-pot, respectively (Scheme
1).3 The key point of the one-pot synthesis was the in situ gen-
eration of 4-trimethylsiloxyoxazoles, the electron-rich hetero-
dienes, by the reaction of TMSCHN2 with acyl isocyanates.
From the results, we thought that thiophenes via 4-trimethyl-
siloxythiazoles could be synthesized if thioacyl isocyanates
in place of acyl isocyanates are used as substrates. However,
interestingly, we found that the reaction of TMSCHN2 with
thiobenzoyl isocyanates proceeded in a different mode and
the N-diazoacetylbenzimido derivatives were formed, and
R
O
O
iv
iii
Ph
R
N
MeOOC
R
COOMe
O
O
N
O
H
Scheme 1. Reaction of TMSCHN2 with acyl isocyanate. (i) TMSCHN2
(1.2 equiv). (ii) H2O. (iii) DMAD (2 equiv). (iv) N-Phenylmaleimide
(1.2 equiv); CSA (0.1 equiv).
almost no 4-trimethylsiloxythiazoles were detected.4 The
N-diazoacetylbenzimido derivatives obtained seemed to be
good substrates for intramolecular Buchner reaction giving
2-azaazulenes.5 In this paper, we would like to describe the de-
tails of our results for the synthesis of 2-azaazulenes from
thiobenzoyl isocyanates using TMSCHN2.
2. Results and discussion
Reaction of TMSCHN2 with thiobenzoyl isocyanate 2a, in
situ generated from the thiazole-4,5-dione 1a by pyrolysis ac-
cording to the known procedure,6 was examined (Table 1).
Thiobenzoyl isocyanate 2a smoothly reacted with 1.2 equiv
of TMSCHN2 at 0 ꢀC in o-xylene, but the product was the si-
lyldiazoketone 3a resulting from 2 equiv of TMSCHN2 and
* Corresponding author. Tel./fax: þ81 52 836 3439.
E-mail address: aoyama@phar.nagoya-cu.ac.jp (T. Aoyama).
0040-4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.11.107

1754
M. Morita et al. / Tetrahedron 64 (2008) 1753e1758
Table 1
Reaction of thiobenzoyl isocyanate with TMSCHN2
of the reaction conditions was carried out to selectively obtain
4a. Various additives such as silica gel, AcOH, p-TsOH or
i-Pr2NEt, etc. were examined to convert 3a to 4a. As the re-
sult, after the reaction, treatment of the reaction mixture
with i-Pr2NEt led to the complete conversion of 3a to 4a in
one-pot and 4a was obtained in 75% yield as a sole isolable
product (entry 6 in Table 1).
Next, the reaction conditions of intramolecular Bucher
reaction were examined using 4a as a substrate (Table 2).
Several copper catalysts such as CuCl, Cu(OTf)2, and Cu(hfa-
cac)2, often used for Buchner reaction and other diazo-related
reactions,10 were less effective (entries 2e4). Eventually,
Rh2(OAc)4/o-xylene system gave the best result (82%)
(entry 7).
Under the optimized reaction conditions shown in entry 6
of Table 1 and entry 7 of Table 2, the synthesis of 2-azaazu-
lenes from thiobenzoyl isocyanates was examined (Table 3).
Various thiobenzoyl isocyanates smoothly reacted with
TMSCHN2 to give the corresponding diazoketones 4beh in
good yields though in some cases the yields are relatively
low. Subsequent conversion of 4 to 2-azaazulenes 5 was exam-
ined. Diazoketones 4b and 4c bearing substituents at the 4-po-
sition on benzene ring smoothly underwent the Buchner
reaction to afford the corresponding 2-azaazulenes 5b and 5c
in moderate to good yields (entries 2 and 3). In these reactions,
the effect of substituents was observed. Thus, the methoxy
group, an electron-donating group, accelerated the reaction
rate and gave the high yield of the product, while the chloro
group, an electron-withdrawing group, depressed both the re-
action rate and the yield (entries 2 and 3). These results may
be explained by the property of carbenoids. Thus, carbenoids
are highly electron-deficient species; therefore, the electron-
donating group on benzene ring accelerates the insertion reac-
tion of a carbenoid to a CeC double bond of benzene ring.
Analogously, the Buchner reaction of other diazoketones 4d
and 4f afforded the corresponding 2-azaazulenes 5d and 5f
though the yields were low (entries 4 and 6).11 In the case
of the 3-methyl derivative 4e, the reaction smoothly pro-
ceeded, but the 2-azaazulene (54%) obtained was an unsepar-
able mixture of 5-methyl-2-azaazulene 5e and its regioisomer
(entry 5). Interestingly, in the case of the 3-methoxy derivative
4g, the ring-expansion reaction proceeded in a different mode,
TMS
S
O
TMSCHN2
(2.4 equiv.)
S
S
O
Solvent
O
N2
N
N
NCO
Ph
reflux
5 min
0 °C to rt, 3 h
R
1a
2a
3a: R=TMS
4a: R=H
Entry
Solvent
Yield (%) of 3a and 4a
1a
2
o-Xylene
o-Xylene
58 (3a, 58)
76 (3a, 56; 4a, 20)
47 (4a, 47)
3
1,4-Dioxane
n-Heptane
Toluene
4
55 (3a, 26; 4a, 29)
74 (3a, 50; 4a, 24)
75 (4a, 75)
5
6b
a
Toluene
TMSCHN2 (1.2 equiv) was used.
b
Before work-up, i-Pr2NEt (10 equiv) was added and the mixture was
stirred at rt for 1 day.
1 equiv of 2a and the expected 4-trimethylsiloxythiazole was
hardly detected (entry 1). In this reaction, 2 equiv of
TMSCHN2 was required to complete the reaction. Therefore,
increase of TMSCHN2 to 2.4 equiv improved the yield (76%)
though a separable mixture of 3a and the desilylated diazoke-
tone 4a was obtained in 56% and 20% yield (entry 2).7 Similar
result was obtained by the use of toluene as a solvent (entry 5).
Other solvent such as 1,4-dioxane and n-heptane gave less sat-
isfactory results (entries 3 and 4). We thought that diazoke-
tones 3a and 4a could be used as substrates for
intramolecular Buchner reaction giving 2-azaazulenes. Thus,
the intramolecular Buchner reaction with 3a and 4a were indi-
vidually carried out under typical reaction conditions using
Rh2(OAc)4 as a catalyst (Scheme 2). As expected, the diazoke-
tone 4a smoothly underwent the Buchner reaction giving the
2-azaazulene 5a in moderate yield, while the reaction with
the silyldiazoketone 3a proceeded in a different mode and
the stable sulfonium ylide 6a was obtained as a sole isolable
product.8 It is known that there is equilibrium between E-
and Z-configurations in thioimidates,9 in which the E-form
might undergo Buchner reaction and the Z-form might lead
to the sulfonium ylide formation. Although the reason of the
difference of the reaction modes between 3a and 4a is not
clear to date, as one of the possibilities, the steric repulsion be-
tween the trimethylsilyl group and the benzene ring might
bring 3a to Z-configuration affording 6a. Thus, reexamination
Table 2
Intramolecular Buchner reaction of 4a
Catalyst
Conditions
4a
5a
TMS
Rh2(OAc)4
(5 mol%)
TMS
TMS
RhL2
O
S
TMS
Ph
Z-conformer
S
3a
O
Entry
Catalyst
Conditions
Yield (%) of 5a
(CH2Cl)2
reflux, 30 min
N
N
1
2
3
4
5
6
7
a
Rh2(OAc)4 (3 mol %)
CuCl (10 mol %)
Cu(OTf)2 (10 mol %)
(CH2Cl)2, rt
Toluene, 80 ꢀC
(CH2Cl)2, rt
CH2Cl2, rt
53
6a (83 %)
ndb
Trace
10
S
TMS
Ph
S
a
Rh2(OAc)4
(3 mol%)
Cu(hfacac)2 (3 mol %)
TMS
4a
Rh2(OAc)4 (3 mol %)
Rh2(OAc)4 (3 mol %)
Rh2(OAc)4 (3 mol %)
CH2Cl2, rt
Toluene, rt
o-Xylene, rt
69
55
N
N
(CH2Cl)2
rt, 4h
L2Rh
O
82
OH
E-conformer
5a (53 %)
hfacac, Hexafluoroacetylacetonate.
Not detected.
b
Scheme 2. Decomposition of diazoketones 3a and 4a catalyzed by Rh2(OAc)4.

M. Morita et al. / Tetrahedron 64 (2008) 1753e1758
1755
Table 3
Synthesis of 2-azaazulenes
TMS
O
O
i) Toluene, reflux, 5 min;
ii) TMSCHN2 (2.4 equiv.)
0 °C to rt, 3 h
R1
R1
S
R1
R4
S
R1
R4
S
TMS
OH
R2
S
R2
R3
O
TMS
R2
R3
R2
R3
N
Rh2(OAc)4 (3 mol%)
2
N
R3
N
N
N
iii) i-Pr2NEt (10 equiv.)
rt, 1d
o-xylene
rt, Time
R4
R4
OH
1
4
5
7
Entry
Substrate
Yield (%) of 4
Time
Yield (%) of 5 (or 7)
1
2
3
4
5
6
7
8
1a (R1¼R2¼R3¼R4¼H)
75 (4a)
73 (4b)
30 (4c)
32 (4d)
70 (4e)
60 (4f)
39 (4g)
65 (4h)
1 h
82 (5a)
47 (5b)
88 (5c)
26 (5d)
54a (5e)
12 (5f)
11 (7g)
44 (7h)
1b (R1¼R2¼H, R3¼Cl, R4¼H)
12 h
30 min
3 h
1c (R1¼R2¼H, R3¼MeO, R4¼H)
1d (R1¼Me, R2¼R3¼R4¼H)
1e (R1¼H, R2¼Me, R3¼R4¼H)
1f (R1¼H, R2¼Me, R3¼H, R4¼Me)
1g (R1¼H, R2¼MeO, R3¼R4¼H)
2 h
3 h
15 min
2 h
1h (R1¼H, R2¼MeO, R3¼H, R4¼MeO)
A mixture of 5-methyl-2-azaazulene 5e and its regioisomer (R1¼R2¼R3¼H, R4¼Me) was obtained (major/minor¼ca. 2.5:1).
a
and the isoquinoline 7g was obtained as a sole isolable product
though the yield was low (entry 7). Another 3-methoxy deriv-
ative 4h also gave 7h in moderate yield (entry 8). These results
are similar to those of the intramolecular Buchner reaction of
the carbon analogues, 1-diazo-4-(3-methoxyphenyl)butan-2-
ones, giving 2-tetralones.12
our knowledge, there are only several reports for the synthesis
of 2-azaazulenes.15 Therefore, our present method using
TMSCHN2 will provide a new approach to the synthesis of
2-azaazulenes.
4. Experimental
The reaction mechanism for the formation of 5 and 7 may
be as follows (Scheme 3). Initially, insertion of the carbenoid
to the CeC double bond of benzene ring affords the norcara-
diene intermediate, which is then isomerized to 5. In the case
of the 3-methoxy derivatives, the electron-donating methoxy
group remarkably affects the isomerization mode and 7 is
formed.12a
4.1. General
IR spectra were measured on a SHIMADZU FTIR-8100
1
diffraction grating IR spectrophotometer. H and 13C NMR
spectra were measured on a JEOL JNM-EX-270 NMR spec-
1
trometer, operating at 270 MHz for H NMR and at 68 MHz
for 13C NMR. H and 13C NMR spectra were reported in
1
3. Conclusion
d units, parts per million (ppm) downfield from tetramethyl-
silane (d¼0). EIMS and FABMS spectra were measured on
a JEOL JMS-SX-102A instrument. All reactions were per-
formed under an argon atmosphere. H2O was used without pu-
rification. Toluene, o-xylene, CH2Cl2, and 1,2-dichloroethane
were distilled from CaH2. Silica gel column chromatography
was performed on Fuji Silysia BW200 or BW820MH silica
gel. Thiobenzamides were purchased from commercial
suppliers or synthesized from the corresponding benzamides
In summary, we found that the reaction of TMSCHN2 with
thiobenzoyl isocyanates generated from thiazole-4,5-diones
and followed by intramolecular Buchner reaction of the result-
ing diazoketones gave 2-azaazulenes. 2-Azaazulenes, one of
the aza analogues of azulenes, will be fascinating targets13 be-
cause they may have attractive biological activities such as
anti-inflammatory and anti-allergic activity of azulenes.14 To
TMS
S
R1
N
Rh2(OAc)4
R2
R3
4a-f
O
5a-f
H
R4
TMS
N
S
TMS
O
S
O
Rh2(OAc)4
O
N
4g and 4h
O
7g and 7h
H
R4
R4
R4=H or OMe
Scheme 3. Possible reaction mechanism.

1756
M. Morita et al. / Tetrahedron 64 (2008) 1753e1758
by Lawesson’s reagent. 2-Phenylthiazole-4,5-dione 1a,16
2-(4-chlorophenyl)thiazole-4,5-dione 1b,16 2-(4-methoxyphe-
nyl)thiazole-4,5-dione 1c,16 and 2-(3-methoxyphenyl)thi-
azole-4,5-dione 1h17 were already reported.
was extracted with EtOAc (50 mLꢂ3). The combined organic
layer was dried over Na2SO4 and concentrated in vacuo. The
residue was purified by silica gel chromatography (hexane/
EtOAc¼15:1 to 5:1) to give 3a (56%) and 4a (20%).
4.2. Preparation of thiazoline-4,5-diones 1aeh: general
procedure
4.3.1. (Trimethylsilyl)methyl N-2-diazo-2-(trimethylsilyl)-
ethanoylbenzimidothioate (3a)
A yellow solid. Mp 58e60 ꢀC (EtOAc). IR (neat): n¼2924,
1
To a solution of thiobenzamide (1.0 mmol) in acetone
(10 mL) was added dropwise oxalyl chloride (1.0 mmol) at
0 ꢀC, and the mixture was stirred for 5 min at the same temper-
ature. The formed precipitate was collected by filtration and
washed with acetone to give the following products.
2105, 1626, 1600 cmꢁ1. H NMR (CDCl3): d¼0.15 (s, 9H),
0.19 (s, 9H), 2.27 (s, 2H), 7.31e7.49 (m, 3H), 7.53e7.58 (m,
2H). 13C NMR (CDCl3): d¼ꢁ1.60, ꢁ1.57, 17.26, 126.98,
128.25, 130.78, 136.27, 172.81, 179.37. FABMS: m/z¼364
(MHþ). Anal. Calcd for C16H25N3OSSi2: C, 52.85; H, 6.93;
N, 11.56. Found: C, 53.07; H, 6.66; N, 11.64.
4.2.1. 2-(2-Methylphenyl)thiazole-4,5-dione (1d)
Yield 30%. A yellow solid. Mp 104e106 ꢀC (decomposed,
4.3.2. (Trimethylsilyl)methyl N-2-diazoethanoyl-
benzimidothioate (4a)
acetone). IR (Nujol): n¼1734 cmꢁ1
.
1H NMR (CDCl3):
1
d¼2.81 (s, 3H), 7.42e7.49 (m, 2H), 7.60e7.68 (m, 1H), 7.95
(d, 1H, J¼9.2 Hz). 13C NMR (CDCl3): d¼23.55, 126.71,
130.77, 131.85, 133.17, 135.70, 142.54, 171.53, 184.91, 190.57.
FABMS: m/z¼206 (Mþþ1). Anal. Calcd for C10H7NO2S: C,
58.52; H, 3.44; N, 6.82. Found: C, 58.70; H, 3.57; N, 6.98.
An orange oil. IR (neat): n¼2954, 2104, 1637 cmꢁ1. H
NMR (CDCl3): d¼0.16 (s, 9H), 2.26 (s, 2H), 4.77 (s, 1H),
7.35e7.50 (m, 3H), 7.52e7.57 (m, 2H). 13C NMR (CDCl3):
d¼ꢁ1.56, 17.38, 51.09, 126.98, 128.46, 130.97, 136.04, 176.49.
EIMS: m/z¼263 (MþꢁN2). FABMS: m/z¼292 (MHþ). HRMS
(MþꢁN2): calcd for C13H17NOSSi: 263.0800; found: 263.0798.
4.2.2. 2-(3-Methylphenyl)thiazole-4,5-dione (1e)
Yield 46%. A yellow solid. Mp 108e109 ꢀC (decomposed,
4.4. One-pot preparation of diazoketones 4aeg: general
procedure
1
acetone). IR (Nujol): n¼1734 cmꢁ1. H NMR (CDCl3): d¼
2.50 (s, 3H), 7.52 (t, 1H, J¼7.6 Hz), 7.65 (d, 1H, J¼7.8 Hz),
8.02 (d, 1H, J¼7.8 Hz), 8.05 (s, 1H). 13C NMR (CDCl3): d¼
21.31, 127.34, 129.38, 130.11, 131.85, 138.78, 139.72, 171.25,
173.54, 190.90. FABMS: m/z¼206 (MHþ). Anal. Calcd for
C10H7NO2S: C, 58.52; H, 3.44; N, 6.82. Found: C, 58.30; H,
3.50; N, 7.01.
A solution of 1,3-thiazole-4,5-diones 1 (0.50 mmol) in tol-
uene (8 mL) was refluxed with stirring for 5 min. After cool-
ing to 0 ꢀC, a solution of TMSCHN2 in hexane (1.2 mmol)
was added, and the mixture was stirred at 0 ꢀC for 1 h and
at rt for 2 h. Then, i-Pr2NEt (5.0 mmol) was added, and the
mixture was stirred at rt for 1 day. The resulting mixture
was poured into water (30 mL), and the aqueous layer was ex-
tracted with EtOAc (50 mLꢂ3). The combined extracts were
dried over Na2SO4 and concentrated in vacuo. Purification
by silica gel chromatography using hexaneeEtOAc system
gave the following products.
4.2.3. 2-(3,5-Dimethylphenyl)thiazole-4,5-dione (1f)
Yield 79%. A yellow solid. Mp 126e127 ꢀC (decomposed,
1
acetone). IR (Nujol): n¼1732 cmꢁ1. H NMR (CDCl3): d¼
2.45 (s, 6H), 7.46 (s, 1H), 7.85 (s, 2H). 13C NMR (CDCl3): d¼
21.21, 127.67, 131.77, 139.49, 139.94, 171.35, 184.23, 190.98.
FABMS: m/z¼220 (MHþ). Anal. Calcd for C11H9NO2S: C,
60.26; H, 4.14; N, 6.39. Found: C, 59.97; H, 4.38; N, 6.27.
4.4.1. (Trimethylsilyl)methyl 4-chloro-N-2-diazoethanoyl-
benzimidothioate (4b)
4.2.4. 2-(3,5-Dimethoxyphenyl)thiazole-4,5-dione (1g)
Yield 34%. A yellow solid. Mp 121e125 ꢀC (decomposed,
Yield 47%. A brown oil. IR (neat): n¼2956, 2106,
1
1601 cmꢁ1. H NMR (CDCl3): d¼0.16 (s, 9H), 2.25 (s, 2H),
1
acetone). IR (Nujol): n¼1755 cmꢁ1. H NMR (CDCl3): d¼
4.80 (s, 1H), 7.37 (d, 2H, J¼8.6 Hz), 7.50 (d, 2H, J¼
8.9 Hz). 13C NMR (CDCl3): d¼ꢁ1.54, 17.50, 51.26, 128.44,
128.78, 134.40, 137.21, 176.20. EIMS: m/z¼297 and 299
3.89 (s, 6H), 6.88 (t, 1H, J¼2.2 Hz), 7.36 (d, 2H, J¼2.2 Hz).
13C NMR (CDCl3): d¼55.95, 104.94, 107.32, 110.39, 133.58,
161.10, 171.30, 190.86. FABMS: m/z¼252 (MHþ). Anal.
Calcd for C11H9NO4S: C, 52.58; H, 3.61; N, 5.57. Found: C,
52.69; H, 3.64; N, 5.57.
(MþꢁN2). FABMS: m/z¼326 and 328 (MHþ). HRMS
35
16
(MþꢁN2): calcd for C13H ClNOSSi: 297.0410; found:
297.0402.
4.3. Reaction of thiobenzoyl isocyanate 2a with TMSCHN2
4.4.2. (Trimethylsilyl)methyl N-2-diazoethanoyl-4-methoxy-
benzimidothioate (4c)
A solution of 1a (100 mg, 0.52 mmol) in o-xylene (8 mL)
was refluxed with stirring for 5 min. After cooling to 0 ꢀC, a so-
lution of TMSCHN2 in hexane (1.5 M, 0.86 mL, 1.3 mmol)
was added, and the mixture was stirred at rt for 3 h. Then,
the mixture was poured into water (30 mL), and the mixture
Yield 30%. A yellow oil. IR (neat): n¼2954, 2104,
1
1605 cmꢁ1. H NMR (CDCl3): d¼0.15 (s, 9H), 2.24 (s, 2H),
3.83 (s, 3H), 4.76 (s, 1H), 6.89 (d, 2H, J¼8.6 Hz), 7.56
(d, 2H, J¼8.9 Hz). 13C NMR (CDCl3): d¼ꢁ1.46,
17.50, 51.10, 55.43, 113.89, 128.46, 129.06, 161.83, 176.84.

M. Morita et al. / Tetrahedron 64 (2008) 1753e1758
1757
EIMS: m/z¼293 (MþꢁN2). FABMS: m/z¼322 (MHþ). HRMS
(MꢁNþ2 ): calcd for C14H19NO2SSi: 293.0906; found: 293.0903.
for 30 min. After cooling to rt, the solvent was removed in va-
cuo. The residue was purified by column chromatography on
silica gel using hexane/EtOAc (30:1) to give the title com-
pound (48.5 mg, 83%) as a yellow oil. IR (neat): n¼
2.25 (s, 2H), 7.38e7.50 (m, 3H), 8.02e8.10 (m, 2H). 13C
NMR (CDCl3): d¼ꢁ1.70, ꢁ1.01, 22.90, 126.38, 127.56,
128.51, 130.00, 143.04, 152.51, 163.37. EIMS: m/z¼335
(Mþ). HRMS (Mþ): calcd for C16H25NOSSi2: 335.1196;
found: 335.1199.
4.4.3. (Trimethylsilyl)methyl N-2-diazoethanoyl-2-methyl-
benzimidothioate (4d)
1
2956 cmꢁ1. H NMR (CDCl3): d¼0.16 (s, 9H), 0.38 (s, 9H),
Yield 32%. A yellow oil. IR (neat): n¼2956, 2105,
1
1644 cmꢁ1. H NMR (CDCl3): d¼0.14 (s, 9H), 2.25 (s, 2H),
2.37 (s, 3H), 4.79 (br s, 1H), 7.13e7.35 (m, 4H). 13C NMR
(CDCl3): d¼ꢁ1.52, 17.13, 19.59, 51.19, 125.30, 126.58,
129.63, 130.31, 134.44, 136.28, 176.22. EIMS: m/z¼277
(MþꢁN2). FABMS: m/z¼306 (MHþ). HRMS (MþꢁN2):
calcd for C14H19NOSSi: 277.0966; found: 277.0966.
4.5. Intramolecular Buchner reaction of diazoketones 4aeh:
general procedure
4.4.4. (Trimethylsilyl)methyl N-2-diazoethanoyl-3-methyl-
benzimidothioate (4e)
A mixture of 4 (0.5 mmol) and Rh2(OAc)4 (3 mol %) in
o-xylene (5 mL) was stirred at rt for 3 h. Then, the solvent
was removed in vacuo, and the residue was purified by silica
gel chromatography using hexaneeEtOAc system to give the
following products.
Yield 70%. A brown oil. IR (neat): n¼2955, 2104,
1
1597 cmꢁ1. H NMR (CDCl3): d¼0.16 (s, 9H), 2.25 (s, 2H),
2.37 (s, 3H), 4.76 (s, 1H), 7.25e7.35 (m, 4H). 13C NMR
(CDCl3): d¼ꢁ1.49, 17.46, 21.46, 51.11, 124.18, 127.49,
128.41, 131.83, 136.14, 138.39, 176.54. EIMS: m/z¼277
(MþꢁN2). FABMS: m/z¼306 (MHþ). HRMS (MþꢁN2):
calcd for C14H19NOSSi: 277.0966; found: 277.0957.
4.5.1. 3-[(Trimethylsilyl)methylthio]cyclohepta[c]pyrrol-1-ol
(5a)
Yield 82%. Black amorphous. IR (Nujol): n¼1685,
1
4.4.5. (Trimethylsilyl)methyl N-2-diazoethanoyl-3,5-dimethyl-
benzimidothioate (4f)
1633 cmꢁ1. H NMR (CDCl3): d¼0.10 (s, 9H), 2.14 (s, 2H),
5.58 (dd, 1H, J¼8.4, 11.1 Hz), 5.85 (dd, 1H, J¼7.6, 11.1 Hz),
6.16 (dd, 1H, J¼8.4, 11.3 Hz), 6.79 (d, 1H, J¼11.3 Hz), 6.91
(d, 1H, J¼7.6 Hz), 10.66 (br, 1H). 13C NMR (CDCl3): d¼
ꢁ1.76, 20.62, 120.81, 121.96, 122.61, 126.27, 135.61, 135.75,
135.97, 140.48, 165.91. EIMS: m/z¼263 (Mþ). HRMS (Mþ):
calcd for C13H17NOSSi: 263.0800; found: 263.0805.
Yield 60%. A yellow oil. IR (neat): n¼2955, 2104,
1
1591 cmꢁ1. H NMR (CDCl3): d¼0.15 (s, 9H), 2.24 (s, 2H),
2.33 (s, 3Hꢂ2), 4.76 (s, 1H), 7.08 (s, 1H), 7.13 (s, 2H). 13C
NMR (CDCl3): d¼ꢁ1.46, 17.44, 21.39, 51.17, 124.64, 132.82,
136.12, 138.29, 176.69. EIMS: m/z¼291 (MþꢁN2). FABMS:
m/z¼320 (MHþ). HRMS (MþꢁN2): calcd for C15H21NOSSi:
291.1113; found: 291.1114.
4.5.2. 6-Chloro-3-[(trimethylsilyl)methylthio]cyclohepta[c]-
pyrrol-1-ol (5b)
4.4.6. (Trimethylsilyl)methyl N-2-diazoethanoyl-3-methoxy-
benzimidothioate (4g)
Yield 47%. A dark green solid. Mp 149e152 ꢀC (EtOAc).
1
IR (Nujol): n¼1683, 1634 cmꢁ1. H NMR (CDCl3): d¼0.13
Yield 39%. A yellow oil. IR (neat): n¼2956, 2105,
(s, 9H), 2.07 (s, 2H), 5.64 (d, 1H, J¼12.2 Hz), 6.08 (d, 1H,
J¼8.6 Hz), 6.65e6.70 (m, 2H), 8.51 (br, 1H). 13C NMR
(CDCl3): d¼ꢁ1.76, 20.14, 119.41, 124.36, 124.57, 124.61,
131.94, 134.54, 135.01, 147.24, 166.05. EIMS: m/z¼297 and
299 (Mþ). HRMS (Mþ): calcd for C13H16ClNOSSi:
297.0410; found: 297.0404.
1
1622 cmꢁ1. H NMR (CDCl3): d¼0.13 (s, 9H), 2.24 (s, 2H),
3.81 (s, 3H), 4.78 (s, 1H), 6.95e7.02 (m, 1H), 7.05e7.13 (m,
2H), 7.30 (t, 1H, J¼8.1 Hz). 13C NMR (CDCl3): d¼ꢁ1.38,
17.40, 51.07, 55.32, 112.31, 116.91, 119.32, 129.62, 137.28,
159.28, 176.53. EIMS: m/z¼293 (MþꢁN2). FABMS:
m/z¼322 (MHþ). HRMS (MþꢁN2): calcd for C14H19NO2SSi:
293.0906; found: 293.0898.
4.5.3. 6-Methoxy-3-[(trimethylsilyl)methylthio]cyclohepta[c]-
pyrrol-1-ol (5c)
4.4.7. (Trimethylsilyl)methyl N-2-diazoethanoyl-3,
5-dimethoxybenzimidothioate (4h)
Yield 88%. A dark green solid. Mp 174e176 ꢀC (EtOAc).
IR (Nujol): n¼1674 cmꢁ1. 1H NMR (CDCl3): d¼0.12 (s, 9H),
2.08 (s, 2H), 3.71 (s, 3H), 5.75 (d, 1H, J¼9.2 Hz), 5.65 (d, 1H,
J¼11.9 Hz), 7.00 (d, 1H, J¼12.2 Hz), 7.14 (d, 1H, J¼8.1 Hz),
8.59 (br, 1H). 13C NMR (CDCl3): d¼ꢁ1.71, 21.65, 55.62,
99.92, 120.06, 121.04, 121.42, 127.03, 135.01, 135.44,
165.72, 169.33. EIMS: m/z¼293 (Mþ). HRMS (Mþ): calcd
for C14H19NO2SSi: 293.0906; found: 293.0903.
Yield 65%. An orange oil. IR (neat): n¼2957, 2105,
1
1593 cmꢁ1. H NMR (CDCl3): d¼0.15 (s, 9H), 2.23 (s, 2H),
3.79 (s, 6H), 4.79 (s, 1H), 6.53 (s, 1H), 6.67 (s, 2H). 13C NMR
(CDCl3): d¼ꢁ1.57, 17.28, 51.00, 55.42, 102.96, 105.00,
137.74, 160.44, 176.54. EIMS: m/z¼323 (MþꢁN2). FABMS:
m/z¼352 (MHþ). HRMS (MþꢁN2): calcd for C15H21NO3SSi:
323.1013; found: 323.1012.
4.5.4. 4-Methyl-3-[(trimethylsilyl)methylthio]cyclohepta[c]-
pyrrol-1-ol (5d)
4.4.8. S-Ylide (6a)
A mixture of 3a (63 mg, 0.17 mmol) and Rh2(OAc)4 (3 mg,
0.007 mmol) in 1,2-dichloroethane was refluxed with stirring
Yield 26%. Black amorphous. IR (Nujol): n¼2955, 1674,
1
1626 cmꢁ1. H NMR (CDCl3): d¼0.13 (s, 9H), 2.23 (s, 2H),

1758
M. Morita et al. / Tetrahedron 64 (2008) 1753e1758
2.38 (s, 3H), 5.64 (d, 1H, J¼8.6 Hz), 5.91 (dd, 1H, J¼7.8,
10.8 Hz), 6.22 (t, 1H, J¼10.3 Hz), 7.07 (d, 1H, J¼7.6 Hz),
9.74 (br, 1H). 13C NMR (CDCl3): d¼ꢁ1.66, 22.69, 26.96,
120.61, 120.68, 124.54, 125.81, 134.77, 135.42, 139.96, 148.14,
165.61. EIMS: m/z¼277 (Mþ). HRMS (Mþ): calcd for
C14H19NOSSi: 277.0957; found: 277.0956.
References and notes
1. For reviews on TMSCHN2, see: (a) Hodnett, N. S. Synlett 2003, 2095e
2096; (b) Shioiri, T.; Aoyama, T. Science of Synthesis; Fleming, I., Ed.;
Georg Thieme: Stuttgart, 2002; Vol. 4, p 569; (c) Shioiri, T.; Aoyama,
T. J. Synth. Org. Chem., Jpn. 1996, 54, 918e928; (d) Shioiri, T.; Aoyama,
T. Advances in the Use of Synthons in Organic Chemistry; Dondoni, A.,
Ed.; JAI: London, 1993; Vol. 1, p 51.
2. For our recent application of TMSCHN2, see: (a) Hari, Y.; Kanie, T.;
Aoyama, T. Tetrahedron Lett. 2006, 47, 1137e1139; (b) Hari, Y.; Kanie,
T.; Miyagi, T.; Aoyama, T. Synthesis 2006, 1249e1252; (c) Hari, Y.;
Tsuchida, S.; Aoyama, T. Tetrahedron Lett. 2006, 47, 1977e1980; (d)
Tsuchida, S.; Hari, Y.; Aoyama, T. Heterocycles 2005, 65, 2667e2674;
(e)Miyagi, T.;Hari, Y.; Aoyama, T. TetrahedronLett. 2004, 45, 6303e6305.
3. (a) Hari, Y.; Iguchi, T.; Aoyama, T. Synthesis 2004, 1359e1362; (b) Hari,
Y.; Iguchi, T.; Aoyama, T. Synthesis 2005, 2147e2150.
4. The synthesis of thiazolones from diazo compounds and thiobenzoyl iso-
cyanate was reported. See: (a) Tsuge, O.; Shinaki, I.; Koga, M. Bull.
Chem. Soc. Jpn. 1972, 45, 3657e3660; (b) Goerdeler, J.; Schimpf, R.
Chem. Ber. 1973, 106, 1496e1500.
4.5.5. A mixture of 5-methyl-3-[(trimethylsilyl)methylthio]-
cyclohepta[c]pyrrol-1-ol (5e) and 7-methyl-3-[(trimethyl-
silyl)methylthio]cyclohepta[c]pyrrol-1-ol
Yield 54% (major/minor¼ca. 2.5:1). Brown amorphous. IR
(Nujol): n¼1681, 1634 cmꢁ1
.
1H NMR (CDCl3): major:
d¼0.13 (s, 9H), 1.91 (s, 3H), 2.09 (s, 2H), 5.89 (dd, 1H, J¼
7.8, 11.9 Hz), 6.05e6.14 (m, 1H), 6.67e6.75 (m, 1H), 6.90
(d, 1H, J¼1.1 Hz), 9.32 (br, 1H). Minor: d¼0.12 (s, 3H),
1.96 (s, 3H), 2.08 (s, 2H), 5.60 (dd, 1H, J¼8.4, 11.3 Hz),
6.05e6.14 (m, 1H), 6.67e6.75 (m, 1H), 6.88 (d, 1H, J¼
1.1 Hz), 9.32 (br, 1H). EIMS: m/z¼277 (Mþ). HRMS (Mþ):
calcd for C14H19NOSSi: 277.0957; found: 277.0955.
5. Buchner, E. Chem. Ber. 1896, 29, 106e109.
6. (a) Goerdeler, J.; Weiss, R. Chem. Ber. 1967, 100, 1627e1632; (b) Weiss,
R. Chem. Ber. 1967, 100, 685e689; (c) Tsuge, O.; Kanemasa, S.; Tashiro,
M. Tetrahedron 1968, 24, 5205e5214.
4.5.6. 5,7-Dimethyl-3-[(trimethylsilyl)methylthio]cyclohepta-
[c]pyrrol-1-ol (5f)
7. The diazoketone 4a seemed to be formed by protodesilylation of 3a with
water during the purification by silica gel column chromatography.
8. For a review on the S-ylide formation, see: Padwa, A.; Hornbuckle, S. F.
Chem. Rev. 1991, 91, 263e309.
Yield 12%. Black amorphous. IR (Nujol): n¼3221,
1
1715 cmꢁ1. H NMR (CDCl3): d¼0.12 (s, 9H), 1.91 (s, 3H),
9. (a) Walter, W.; Meese, C. O. Chem. Ber. 1976, 109, 922e946; (b) Walter,
W.; Meese, C. O. Chem. Ber. 1977, 110, 2463e2479.
1.98 (s, 3H), 2.09 (s, 2H), 6.03 (s, 1H), 6.64 (s, 1H), 6.90 (s,
1H), 9.45 (s, 1H). 13C NMR (CDCl3): d¼ꢁ1.70, 21.06, 26.08,
26.80, 118.25, 121.08, 129.45, 131.01, 134.46, 134.77, 137.05,
140.16, 165.73. EIMS: m/z¼291 (Mþ). HRMS (Mþ): calcd for
C15H21NOSSi: 291.1113; found: 291.1123.
10. (a) CuCl:Constantino,A.;Linstrumelle,G.;Julia,S.Bull. Soc. Chim. Fr. 1970,
907e912; Scott, L. T.; Minton, M. A.; Kirms, M. A. J. Am. Chem. Soc. 1980,
102, 6311e6314; (b) Cu(hfacac)2: Pusino, A.; Saba, A. Tetrahedron 1986, 42,
4319e4324; (c) Cu(OTf)2: Yadav, J. S.; Reddy, B. V. S.; Gupta, M. K.;
Prabhakar, A.; Jagadeesh, B. Chem. Commun. 2004, 2124e2125.
11. The low yields were presumably due to decomposition of the resulting 5d
and 5f during the purification by silica gel column chromatography be-
cause of their relative lability.
4.5.7. 7-Methoxy-1-[(trimethylsilyl)methylthio]isoquinolin-
3-ol (7g)
Yield 11%. A yellow oil. IR (neat): n¼2956, 1636 cmꢁ1. 1H
NMR (CDCl3): d¼0.18 (s, 9H), 2.47 (s, 2H), 3.93 (s, 3H), 6.47
(s, 1H), 7.22 (dd, 1H, J¼2.2, 8.9 Hz), 7.33 (d, 1H, J¼2.2 Hz),
7.52 (d, 1H, J¼8.9 Hz). 13C NMR (CDCl3): d¼ꢁ1.36, 15.19,
55.52, 96.24, 102.38, 123.74, 124.42, 127.47, 134.73, 155.95,
156.48, 157.57. EIMS: m/z¼293 (Mþ). HRMS (Mþ): calcd for
C14H19NO2SSi: 293.0906; found: 293.0909.
12. (a) Marguire, A. R.; O’Leary, P.; Harrington, F.; Lawrence, S. E.; Blake,
A. J. J. Org. Chem. 2001, 66, 7166e7177; (b) Kennedy, M.; Mckervey,
M. A.; Maguire, A. R.; Tuladhar, S. M.; Twohig, M. F. J. Chem. Soc.,
Perkin Trans. 1 1990, 1047e1054.
13. Many researches about drug discovery of azaazulenes were reported. For
example: (a) 1-Azaazulenes:Chem. Pharm. Bull. 1994, 42, 2491e2499;
(b) 1,3-Diaazaazulenes: Satake, N.; Zhou, Q.; Kosakai, K.; Nimura, M.;
Shibata, S. Eur. J. Pharmacol. 1994, 251, 1e7; (c) 1,2-Diazaazulenes:
Imafuku, K.; Aradono, K.; Uono, T.; Ogawa, K.; Matsushita, Y. Chem.
Pharm. Bull. 1992, 40, 1606e1609.
4.5.8. 5,7-Dimethoxy-1-[(trimethylsilyl)methylthio]-
isoquinolin-3-ol (7h)
14. Many studies about synthesis of biologically active azulenes were re-
ported. For example: (a) Fujio, K.; Kobayashi, H.; Ozeki, S.; Fujimori,
K. Chem. Lett. 2006, 35, 1272e1273; (b) Rekka, E.; Chrysselis, M.;
Siskou, I.; Kourounakis, A. Chem. Pharm. Bull. 2002, 50, 904e907; (c)
Noguchi, K.; Kase, J.; Saitoh, M.; Masumiya, H.; Saitoh, M.; Nakazawa,
T.; Tanaka, Y.; Tanaka, H.; Hashimoto, K.; Shigenobu, K. Pharmacology
2002, 64, 36e42; (d) Hong, B.-C.; Jiang, Y.-F.; Kumar, E. S. Bioorg. Med.
Chem. Lett. 2001, 11, 1981e1984; (e) Yokota, M.; Uchibori, S.; Hayashi,
H.; Koyama, R.; Kosakai, K.; Wakabayashi, S.; Tomiyama, T. Bioorg.
Med. Chem. 1996, 4, 575e591; (f) Asato, A. E.; Peng, A.; Hossain,
M. Z.; Mirzadegan, T.; Bertram, J. S. J. Med. Chem. 1993, 36, 3137e
3147; (g) Tomiyama, T.; Yokota, M.; Wakabayashi, S.; Kosakai, K.; Yana-
gisawa, T. J. Med. Chem. 1993, 36, 791e800.
Yield 44%. A yellow solid. Mp 103e106 ꢀC (EtOAc). IR
1
(Nujol): n¼1641 cmꢁ1. H NMR (CDCl3): d¼0.19 (s, 9H),
2.46 (s, 2H), 3.83 (s, 3Hꢂ2), 6.56 (d, 1H, J¼1.6 Hz), 6.89
(d, 1H, J¼1.6 Hz), 6.98 (s, 1H). 13C NMR (CDCl3): d¼
ꢁ1.46, 15.37, 55.49, 55.63, 92.43, 93.92, 101.40, 123.56,
128.60, 154.98, 156.22, 156.55, 156.91. EIMS: m/z¼323 (Mþ).
HRMS (Mþ): calcd for C15H21NO3SSi: 323.1012; found:
323.1014.
15. (a) Kreher, R.; Vogt, G.; Schultz, M. L. Angew. Chem., Int. Ed. Engl.
1975, 14, 821; (b) Jones, R. A.; Singh, S. Heterocycles 1976, 4, 969e
972; (c) Seitz, G.; The, H. S. Synthesis 1984, 119e121.
16. Goerdeler, J.; Schenk, H. Chem. Ber. 1965, 98, 2954e2965.
17. Kehrbach, W.; Mlinaric, M.; Ziegler, D.; Brueckner, R.; Bielenberg, W.
U.S. Patent 5,547,967, 1996.
Acknowledgements
This work was financially supported by a Grant-in-Aid for
Scientific Research (KAKENHI). M.M. was financially sup-
ported by Pfizer Japan Inc.