Synthesis and study of oxadisilole-fused benzisoxazoles or naphthisoxazoles

Article abstract of DOI:10.1002/ejoc.201101583

Oxadisilole-fused benzisoxazoles or naphthisoxazoles were obtained through 1,3-dipolar cycloaddition of arynes with nitrile oxides in good yields at room temperature. Key to the procedure is the simultaneous in situ generation of reactive nitrile oxides f

Full text of DOI:10.1002/ejoc.201101583

FULL PAPER
DOI: 10.1002/ejoc.201101583
Synthesis and Study of Oxadisilole-Fused Benzisoxazoles or Naphthisoxazoles
Xuyan Ma,[a] Yali Chen,*[a] Yajuan Zhang,[a] Di Xu,[a] Weiguo Cao,[a,b] and Jie Chen[a]
Keywords: Cycloaddition / Nitrile oxide / Arynes / Isoxazoles / Heterocycles
Oxadisilole-fused benzisoxazoles or naphthisoxazoles were
obtained through 1,3-dipolar cycloaddition of arynes with ni-
trile oxides in good yields at room temperature. Key to the
procedure is the simultaneous in situ generation of reactive
nitrile oxides from arenecarbohydroximoyl chlorides and
aryne reactants from benzobis(oxadisilole) or 2,3-naphth-
oxadisilole. One oxadisilole-fused benzisoxazole is a new
precursor of a benzyne formed by a phenyliodination/fluor-
ide-induced elimination protocol. By using this benzyne, cy-
cloadducts were synthesized in good yields. The de-oxadisil-
ole reaction of some of the oxadisilole-fused benzisoxazoles
could be easily conducted with a 1.0
M solution of tetra-
butylammonium fluoride in THF at room temperature.
(trimethylsilyl)benzene has also been reported by Russell
and Winling.[14] Herein, we report an efficient approach to
the synthesis of oxadisilole-fused benzisoxazoles 6a–e or
naphthisoxazoles 10a–e by using benzobis(oxadisilole) 1 or
2,3-naphthoxadisilole 7 as benzyne 3 or naphthyne 9 pre-
cursors and arenecarbohydroximoyl chlorides 4a–e as start-
ing materials for nitrile oxides 5a–e at room temperature.
We also found that 6d could serve as a new precursor of
benzyne 12; trapping experiments were carried out with
various carbo- and heterocyclic dienes 13a–c to afford cy-
cloadducts 14a–c in good yields. Benzobis(oxadisilole) 1
can serve as the precursor for the stepwise generation of
1,4-benzdiyne 15. We found that the de-oxadisilole reaction
of 6a,d,e could be easily conducted with a 1.0 m solution
of tetrabutylammonium fluoride (TBAF) in THF at room
temperature.
Introduction
1,3-Dipolar cycloaddition reactions (1,3-DCRs), intro-
duced by Huisgen in the early 1960s,[1] have been largely
studied as useful synthetic strategies to obtain various het-
erocyclic systems.[2] The idea of synthesizing benzisoxazoles
by the 1,3-DCR of a benzyne with a nitrile oxide has been
reported previously.[3] Benzisoxazole derivatives are associ-
ated with various biological activities, such as antipsy-
chotic,[4] antitumor,[5] anticonvulsant,[6] antimicrobial,[7]
antithrombotic[8] and antidiabetic effects.[9] Aryne is an im-
portant intermediate and synthon in organic synthesis.[10]
However, most benzynes are commonly accessed in situ by
fluoride-promoted ortho-elimination of o-(trimethylsilyl)-
aryl triflates.[3] Aryne formation of benzoxadisilole by phen-
yliodination with o-bis(trimethylsilyl)benzene was also re-
ported by Kitamura and Yamane.[11] Recently, we have be-
come interested in the chemistry of arynes generated from
benzobis(oxadisilole), benzotris(oxadisilole) and 2,3-
naphthoxadisilole under very mild conditions. We found
that benzobis(oxadisiloles) could serve as the synthetic
equivalent of benzdiynes. Their applications to the synthesis
of functional acenes and benzoquinones have also been
reported.[12] The chemistry was further extended to the
synthesis of oxadisilole-fused benzo[d]isoxazoline and
naphtho[2,3-d]isoxazoline derivatives (or oxadisilole-fused
benzotriazole and naphthotriazole derivatives) by 1,3-DCR
of nitrones (or azides) with arynes.[13] The sequential gener-
ation of the aryne of 1,4-bis(benzyne) from 1,2,4,5-tetrakis-
Results and Discussion
Preparation of Oxadisilole-Fused Benzisoxazoles and
Naphthisoxazoles
The syntheses of oxadisilole-fused benzisoxazoles 6a–e
or naphthisoxazoles 10a–e are outlined in Schemes 1 and 2.
Arynes 3 and 9 were generated from benzobis(oxadisilole)
(1) and 2,3-naphthoxadisilole (7), respectively, through our
previously reported phenyliodination/fluoride-induced desi-
lylation protocol.[12a,12b] Trapping of benzyne
3 and
[a] Department of Chemistry, Shanghai University,
Shanghai 200444, P. R.China
naphthyne 9 at room temperature with nitrile oxides 5a–e
by 1,3-DCRs afforded 6a–e and 10a–e, respectively, in good
yields. The 1,3-dipolar nitrile oxides 5a–e are reactive inter-
mediates, commonly generated in situ from arenecarbo-
hydroximoyl chloride counterparts 4a–e, which undergo
rapid dehydrohalogenation upon exposure to a suitable
Fax: +86-21-66132797
E-mail: ylchen@staff.shu.edu.cn
[b] State Key Laboratory of Organometallic Chemistry,
Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences,
Shanghai 200032, P. R.China
1388
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 1388–1393

Oxadisilole-Fused Benzisoxazoles or Naphthisoxazoles
base.[15] Compounds 4a–e were prepared according to 87% (Table 1, Entry 7). Attempts to change the reaction
literature procedures.[16]
time to 1, 5 or 16 h gave the desired product 6d in 75, 81
Our investigation started with the reaction of nitrile ox- or 84% yield, respectively (Table 1, Entries 6, 8 or 9, respec-
ide 5d generated in situ from 4-chlorobenzenehydroximoyl tively).
chloride (4d) with oxadisilole-fused benzyne 3 generated in
situ from 1. Phenyliodination of 1 with a 1.5:3 mixture of
Table 1. Cycloaddition of the nitrile oxide 5d, generated from 4d,
phenyliodium
diacetate/trifluoromethanesulfonic
acid
with benzyne 3 generated from 1 (1 equiv.) by using different fluor-
(TfOH) took place readily at room temperature in dichloro-
methane (Scheme 1). Without isolation of the ring-opened
iodination intermediate 2, benzyne 3 could be generated in
situ upon treatment with a 1.0 m solution of TBAF in THF.
Trapping experiments were carried out with nitrile oxide 5d
generated in situ from 4d (0.42 equiv.) at room temperature
for 16 h to afford the oxadisilole-fused benzisoxazole 6d in
a yield of 82% in this three-step reaction (Scheme 1 and
Table 1, Entry 3). Nitrile oxide 5d is a reactive intermediate
commonly generated in situ by treatment of 4d with a base.
However, with diisopropylamine as the base and CsF as the
fluoride source, the desired product 6d could only be iso-
lated in 27% yield (Table 1, Entry 1). We observed that,
with triethylamine as the base and CsF as the fluoride
source, the yield of 6d slightly increased to 30% (Table 1,
Entry 2). The use of a solution of TBAF in THF as the
ide sources and bases at room temperature.
Entry
4d
[equiv.]
Fluoride source Base
Time Yield[a] of 6d
[h]
[%]
1
2
3
4
5
6
7
8
9
0.42
0.42
0.42
0.42
0.60
0.75
0.75
0.75
0.75
0.80
CsF
CsF
iPr2NH
Et3N
16
16
16
3
3
1
3
5
16
3
27
30
82
80
83
75
87
81
84
77
TBAF/THF
TBAF/THF
TBAF/THF
TBAF/THF
TBAF/THF
TBAF/THF
TBAF/THF
TBAF/THF
iPr2NH
iPr2NH
iPr2NH
iPr2NH
iPr2NH
iPr2NH
iPr2NH
iPr2NH
10
[a] Yields of purified products.
We further studied the 1,3-DCR of benzyne 3 generated
fluoride source and iPr2NH as the base gave benzisoxazole in situ from 1 with 5a–e generated in situ from 4a–e
6d in 80% yield at room temperature after 3 h (Table 1, En- (0.75 equiv.) at room temperature for 3 h. The oxadisilole-
try 4). In the present case, use of 0.60 or 0.80 equiv. of 4d fused benzisoxazoles 6a–e were formed in 70–89% yield
at room temperature for 3 h afforded the desired product (Scheme 1 and Table 2, Entries 1–5). As shown from the
6d in 83 or 77% yield, respectively (Table 1, Entry 5 or 10, yields, this 1,3-DCR of 5a–e with 3 is rather insensitive with
respectively). Finally, we found that use of 0.75 equiv. of 4d respect to the electronic nature (X = OCH3, CH3, H, Cl,
at room temperature for 3 h improved the yield of 6d to NO2) of the substituents on the benzene rings of 5a–e.
Scheme 1. Synthesis of the oxadisilole-fused benzisoxazoles 6a–e.
Scheme 2. Synthesis of the naphthisoxazoles 10a–e.
Eur. J. Org. Chem. 2012, 1388–1393
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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1389

X. Ma, Y. Chen, Y. Zhang, D. X., W. Cao, J. Chen
FULL PAPER
Furthermore, the 1,3-DCRs of 9 generated in situ from picted in Scheme 4, the stepwise generated 1,4-benzdiyne
the 7 with 5a–e generated in situ from 4a–e at room tem- was first treated with nitrile oxide 5d and then with other
perature were also investigated. To our delight, the 1,3-di- dienes 13a–c to build up a series of cycloadducts 14a–c.
polar nitrile oxides 5a–e successfully participated in the cy-
Table 3. Cycloaddition of dienes 13a–c with 12 generated from 6d.
cloaddition reaction with 9 at room temperature to afford
the corresponding naphthisoxazoles 10a–e in moderate to
good yields (Scheme 2 and Table 2, Entries 6–10).
Entry
Diene
X
Product
Yield[a] of 14 [%]
1
2
3
13a
13b
13c
O
N-Boc
CH2
14a
14b
14c
92
71
79
Table 2. Cycloaddition of 5a–e generated from 4a–e (0.75 equiv.)
with 3 or 9 generated from 1 (1 equiv.) or 7 (1 equiv.) at room tem-
perature.
[a] Yields of purified products.
Entry Arenecarbohydroximoyl
chloride
X
Aryne Product
Yield[a]
[%]
1
2
3
4
5
6
7
8
9
4a
4b
4c
4d
4e
4a
4b
4c
4d
4e
OCH3
CH3
H
3
3
3
3
3
9
9
9
9
9
6a
6b
6c
6d
6e
10a
10b
10c
10d
10e
89
82
70
87
71
87
75
54
84
34
Cl
NO2
OCH3
CH3
H
Cl
NO2
10
[a] Yields of purified products.
Benzyne 12 from the Oxadisilole-Fused Benzisoxazole 6d
The oxadisilole-fused benzisoxazole 6d is a new precur-
sor of benzyne 12 obtained by a phenyliodination/fluoride-
induced elimination protocol. Trapping experiments of 12
were carried out with various carbo- and heterocyclic dienes
13a–c. Cycloadducts 14a–c were synthesized by the Diels–
Alder reactions outlined in Scheme 3. Phenyliodination of
6d with a 3:4 mixture of PhI(OAc)2/TfOH took place read-
ily at room temperature in CH2Cl2. Without isolation of
intermediate 11 or 11Ј, benzyne 12 could be generated in
situ upon treatment with KF and a catalytic amount of
TBAF. Cycloadducts 14a–c were obtained by trapping ex-
periments of 12 with various dienes 13a–c [furan, N-(tert-
Scheme 4. Benzobis(oxadisilole) 1 as the synthetic equivalent of
1,4-benzdiyne 15 for the preparation of cycloadducts 14a–c.
De-oxadisilole Reaction of Oxadisilole-Fused
Benzisoxazoles 6a,d,e
We were delighted to find that benzisoxazole derivatives
butoxycarbonyl)pyrrole (N-Boc-pyrrole) and cyclopentadi- 16a,d,e could be easily obtained from oxadisilole-fused
ene] in good isolated yields (Scheme 3 and Table 3). With benzisoxazoles 6a,d,c with a 1.0 m solution of TBAF in
the generation of 12 from 6d, we have demonstrated that 1 THF by de-oxadisilole reactions. Reactions were completed
is a synthetic equivalent of 1,4-benzdiyne 15.[12b] As de- at room temperature within 2 h to give the target products
Scheme 3. Benzyne 12 generation and trapping experiments.
1390
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Eur. J. Org. Chem. 2012, 1388–1393

Oxadisilole-Fused Benzisoxazoles or Naphthisoxazoles
spectrometer in EI mode and are reported as m/z values. High-
resolution mass spectra were recorded with a Finnigan MAT-8430
instrument. Element analyses were performed at the Shanghai Uni-
versity.
16a,d,e in good yields (Scheme 5 and Table 4). This easy de-
oxadisilole reaction proceeded smoothly under the chosen
reaction conditions.
Oxadisilole-Fused Benzisoxazoles 6a–e and Naphthisoxazoles 10a–
e: TfOH (0.27 mL, 3.0 mmol) was added by means of a syringe to
a stirred solution of PhI(OAc)2 (493 mg, 1.5 mmol) in dichloro-
methane (10 mL) at 0 °C under N2. The mixture was stirred under
N2 at 0 °C for 0.5 h and at room temperature for 1.5 h. The clear
yellow solution was cooled again to 0 °C followed by dropwise ad-
dition of a solution of the benzobis(oxadisilole) 1 (or 2,3-naphth-
oxadisilole 7) (1.0 mmol) in dichloromethane (5 mL). The mixture
was stirred at 0 °C for 0.5 h and at room temperature for 3–6 h. The
clear yellow solution was cooled again to 0 °C, iPr2NH (0.35 mL,
2.5 mmol) and arenecarbohydroximoyl chlorides 4a–e (0.75 mmol)
were added followed by a solution of TBAF (1.0 m in THF, 4.5 mL,
4.5 mmol). The mixture was stirred under N2 at room temperature
for 3 h. The solvent was removed under reduced pressure. The
crude product was purified by column chromatography on silica gel
using a gradient of 5–10% EtOAc in PE (60–80 °C) as the eluent to
afford cycloadducts 6a–e and 10a–e.
Scheme 5. Synthesis of benzisoxazole derivatives 16a,d,e.
Table 4. Synthesis of 16a,d,e from 6a,d,e at room temperature.
Entry
Reactant
X
Product
Yield[a] of 16 [%]
1
2
3
6a
6d
6e
OCH3
Cl
NO2
16a
16d
16e
56
72
63
[a] Yields of purified products.
The structures of compounds 6a–e, 10a–e, 14a–c and
16a,d,e were established by 1H and 13C NMR spectroscopy,
MS, IR spectroscopy, elemental analysis and high-resolu-
tion (HR) MS.
3-(4-Methoxyphenyl)-5,6-oxadisilole-Fused Benzisoxazole (6a):
Yield: 237 mg, 89%. Colourless solid. M.p. 119–120 °C. H NMR
1
(500 MHz, CDCl3): δ = 0.43 (s, 6 H, SiMe2), 0.44 (s, 6 H, SiMe2),
3.91 (s, 3 H, OMe), 7.11 (d, J = 8.5 Hz, 2 H, Ar-H), 7.80 (d, J =
1.0 Hz, 1 H, Ar-H), 7.93 (d, J = 8.5 Hz, 2 H, Ar-H), 8.08 (d, J =
1.0 Hz, 1 H, Ar-H) ppm. 13C NMR (125 MHz, CDCl3): δ = 1.1,
1.5, 55.5, 112.4, 114.8, 121.5, 122.4, 125.3, 129.6, 142.4, 150.4,
Conclusions
156.9, 161.4, 164.9 ppm. IR (KBr): ν = 3443, 3042, 2953, 2849,
˜
1611, 1584, 1480, 1254, 1093, 927, 835, 795 cm–1. HRMS (MALDI-
TOF): calcd. for C18H21NO3Si2 [M + H]+ 356.1132; found
356.1133.
Oxadisilole-fused benzisoxazoles 6a–e or naphthisox-
azoles 10a–e were obtained through the 1,3-DCR of
benzyne (3) or naphthyne (9) generated in situ from benzo-
bis(oxadisilole) (1) or 2,3-naphthoxadisilole (7) with nitrile
3-(4-Methylphenyl)-5,6-oxadisilole-Fused Benzisoxazole (6b): Yield:
oxides 5a–e generated in situ from arenecarbohydroximoyl 209 mg, 82%. Colourless solid. M.p. 86–89 °C. 1H NMR
(500 MHz, CDCl3): δ = 0.42 (s, 6 H, SiMe2), 0.44 (s, 6 H, SiMe2),
2.47 (s, 3 H, Me), 7.40 (d, J = 8.0 Hz, 2 H, Ar-H), 7.81 (d, J =
0.5 Hz, 1 H, Ar-H), 7.87 (d, J = 8.0 Hz, 2 H, Ar-H), 8.07 (d, J =
0.5 Hz, 1 H, Ar-H) ppm. 13C NMR (125 MHz, CDCl3): δ = 1.1,
1.4, 21.6, 112.4, 122.4, 125.3, 126.2, 128.1, 130.0, 140.6, 142.4,
chlorides 4a–e in good yields at room temperature. Oxadi-
silole-fused benzisoxazole 6d is a new precursor of benzyne
12 through the phenyliodination/fluoride-induced elimi-
nation protocol. Cycloaddition of 12 with various dienes
13a–c afforded cycloadducts 14a–c in good yields. In the
overall transformations, benzobis(oxadisilole) (1) served as
a synthetic equivalent of 1,4-benzdiyne (15). We also found
an easy de-oxadisilole method for oxadisilole-fused benz-
isoxazoles 6a,d,e to give benzisoxazole derivatives 16a,d,e in
the presence of TBAF/THF in good yields at room tem-
perature. These reactions could offer great opportunities for
the synthesis of important heterocyclic compounds.
150.4, 157.2, 164.9 ppm. IR (KBr): ν = 3443, 3030, 2956, 1596,
˜
1433, 1256, 1086, 930, 794 cm–1. MS (EI): m/z (%) = 339 (100)
[M+], 324 (73). HRMS (MSI-TOF): calcd. for C18H21NO2Si2 [M
+ Na]+ 362.1009; found 362.1031.
3-Phenyl-5,6-oxadisilole-Fused Benzisoxazole (6c): Yield: 171 mg,
70%. Colourless solid. M.p. 102–105 °C. 1H NMR (500 MHz,
CDCl3): δ = 0.44 (s, 6 H, SiMe2), 0.45 (s, 6 H, SiMe2), 7.56–7.61
(m, 3 H, Ar-H), 7.83 (d, J = 1.0 Hz, 1 H, Ar-H), 7.98–8.00 (m, 2 H,
Ar-H), 8.10 (d, J = 1.0 Hz, 1 H, Ar-H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 1.1, 1.5, 112.5, 122.3, 125.3, 128.3, 129.1, 129.3, 130.4,
Experimental Section
142.6, 150.6, 157.3, 165.0 ppm. IR (KBr): ν = 3442, 3052, 2960,
˜
1598, 1447, 1252, 1092, 933, 796 cm–1. HRMS (MALDI-TOF):
calcd. for C17H19NO2Si2 [M + H]+ 326.1031; found 326.1027.
General Methods: Purification was effected by silica gel column
chromatography (200–300 mesh silica gel) using mixtures of rea-
gent-grade EtOAc/petroleum ether (PE, 60–80 °C) as the eluents.
3-(4-Chlorophenyl)-5,6-oxadisilole-Fused Benzisoxazole (6d): Yield:
235 mg, 87%. Colourless solid. M.p. 117–120 °C. 1H NMR
(500 MHz, CDCl3): δ = 0.43 (s, 6 H, SiMe2), 0.44 (s, 6 H, SiMe2),
7.57 (d, J = 8.5 Hz, 2 H, Ar-H), 7.82 (d, J = 0.5 Hz, 1 H, Ar-H),
7.92 (d, J = 8.5 Hz, 2 H, Ar-H), 8.04 (d, J = 0.5 Hz, 1 H, Ar-H)
ppm. 13C NMR (125 MHz, CDCl3): δ = 1.1, 1.5, 112.6, 122.0,
125.0, 127.6, 129.5, 129.6, 136.6, 142.9, 150.9, 156.4, 165.0 ppm.
1
NMR spectra were recorded at 500 MHz for H and 125 MHz for
13C with CDCl3 as the solvent by using a Bruker DRX-500 NMR
spectrometer. Chemical shifts are reported in ppm on the δ scale
relative to the residual resonance of CHCl3 (δ =7.26 ppm for H,
1
and 77.16 ppm for the central peak of the triplet in 13C). Coupling
constants (J) are reported in Hz. IR spectra were recorded with an
FTIR spectrometer and expressed in cm–1 (KBr disc). Low-resolu-
tion mass spectra were obtained with a Finnigan MAT SSQ-710
IR (KBr): ν = 3444, 3058, 2957, 1601, 1433, 1252, 1094, 942,
˜
794 cm–1. MS (EI): m/z (%)
=
359 (78) [M+], 344 (100).
Eur. J. Org. Chem. 2012, 1388–1393
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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X. Ma, Y. Chen, Y. Zhang, D. X., W. Cao, J. Chen
FULL PAPER
C17H18ClNO2Si2 (359.96): calcd. C 56.72, H 5.04, N 3.89; found C
56.43, H 5.04, N 3.86.
Cycloadducts 14a–c from Benzyne 12 Generated from Oxadisilole-
Fused Benzisoxazole 6d: Trifluoromethanesulfonic acid (0.36 mL,
4.0 mmol) was added by means of a syringe to a stirred solution
of PhI(OAc)2 (987 mg, 3.0 mmol) in dichloromethane (10 mL) at
0 °C. The mixture was stirred under N2 at 0 °C for 0.5 h and at
room temperature for 1.5 h. The clear yellow solution was cooled
again to 0 °C followed by dropwise addition of a solution of 6d
(359 mg, 1.0 mmol) in dichloromethane (5 mL). The mixture was
stirred at 0 °C for 0.5 h and at room temperature for 3 h. The clear
yellow solution was cooled again to 0 °C, the diene [furan
(0.76 mL, 10 mmol), N-(tert-butoxycarbonyl)pyrrole (1.6 mL,
10 mmol) or cyclopentadiene (0.82 mL, 10 mmol)] was added fol-
lowed by KF (232 mg, 4.0 mmol) and TBAF (1.0 m in THF,
0.2 mL, 0.2 mmol). The mixture was stirred under N2 at room tem-
perature for 16 h. The organic solvent was removed under reduced
pressure. The crude product was purified by column chromatog-
raphy on silica gel using a gradient of 10–15% EtOAc in PE (60–
80 °C) as the eluent to afford cycloadducts 14a–c.
3-(4-Nitrophenyl)-5,6-oxadisilole-Fused Benzisoxazole (6e): Yield:
197 mg, 71%. Colourless solid. M.p. 203–204 °C. 1H NMR
(500 MHz, CDCl3): δ = 0.44 (s, 6 H, SiMe2), 0.45 (s, 6 H, SiMe2),
7.87 (s, 1 H, Ar-H), 8.07 (s, 1 H, Ar-H), 8.19 (d, J = 9.0 Hz, 2 H,
Ar-H), 8.46 (d, J = 9.0 Hz, 2 H, Ar-H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 1.1, 1.5, 112.8, 121.5, 124.50, 124.58, 129.2, 135.4,
143.6, 149.0, 151.4, 155.5, 165.3 ppm. IR (KBr): ν = 3442, 3080,
˜
2959, 1601, 1522, 1250, 1087, 941, 795 cm–1. MS (EI): m/z (%) =
370 (18) [M+], 355 (65), 209 (100). C17H18N2O4Si2 (370.51): calcd.
C 55.11, H 4.90, N 7.56; found C 54.97, H 5.06, N 7.35.
3-(4-Methoxyphenyl)naphth[2,3-d]isoxazole (10a): Yield: 180 mg,
87%. Colourless solid. M.p. 188–189 °C. 1H NMR (500 MHz,
CDCl3): δ = 3.92 (s, 3 H, OMe), 7.13 (d, J = 8.5 Hz, 2 H, Ar-H),
7.48 (t, J = 7.5 Hz, 1 H, Ar-H), 7.58 (t, J = 7.5 Hz, 1 H, Ar-H),
7.98 (d, J = 8.5 Hz, 2 H, Ar-H), 8.02–8.04 (m, 3 H, Ar-H), 8.45 (s,
1 H, Ar-H) ppm. 13C NMR (125 MHz, CDCl3): δ = 55.6, 105.1,
114.8, 121.3, 122.0, 122.2, 124.8, 127.7, 128.1, 129.3, 129.7, 130.6,
3-(4-Chlorophenyl)-5,8-dihydro-5,8-epoxynaphth[2,3-d]isoxazole
1
(14a): Yield: 272 mg, 92%. Pale brown solid. M.p. 157–158 °C. H
134.2, 157.0, 160.1, 161.5 ppm. IR (KBr): ν = 3444, 3052, 2974,
˜
NMR (500 MHz, CDCl3): δ = 5.80 (d, J = 6.5 Hz, 2 H, O-C-H),
7.03–7.07 (m, 2 H, C=C-H), 7.48–7.50 (m, 3 H, Ar-H), 7.57 (s, 1 H,
Ar-H), 7.81 (d, J = 8.0 Hz, 2 H, Ar-H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 81.9, 82.2, 104.1, 112.4, 116.9, 127.5, 129.3, 129.5,
1608, 1463, 1255, 1030, 870, 753 cm–1. HRMS (MALDI-TOF):
calcd. for C18H13NO2 [M + H]+ 276.1019; found 276.1019.
3-(4-Methylphenyl)naphth[2,3-d]isoxazole (10b): Yield: 146 mg,
75%. Colourless solid. M.p. 158–159 °C. 1H NMR (500 MHz,
CDCl3): δ = 2.49 (s, 3 H, Me), 7.42 (d, J = 8.0 Hz, 2 H, Ar-H),
7.46–7.49 (m, 1 H, Ar-H), 7.56–7.59 (m, 1 H, Ar-H), 7.97–8.00 (m,
4 H, Ar-H), 8.02 (d, J = 8.0 Hz, 1 H, Ar-H), 8.45 (s, 1 H, Ar-H)
ppm. 13C NMR (125 MHz, CDCl3): δ = 21.7, 105.1, 122.0, 122.2,
124.8 126.1, 127.7, 128.1, 128.2, 129.4, 130.1, 130.6, 134.3, 140.9,
136.3, 142.1, 143.3, 144.9, 152.3, 156.7, 163.9 ppm. IR (KBr): ν =
˜
3444, 3023, 1599, 1464, 1336, 1090, 845 cm–1. MS (EI): m/z (%) =
295 (42) [M+], 266 (100); 267 (100). C17H10ClNO2 (295.72): calcd.
C 69.05, H 3.41, N 4.74; found C 69.14, H 3.44, N 4.75.
N-(tert-Butoxycarbonyl)-3-(4-chlorophenyl)-5,8-dihydro-5,8-imino-
naphth[2,3-d]isoxazole (14b): Yield: 280 mg, 71%. Pale yellow solid.
157.4, 160.2 ppm. IR (KBr): ν = 3447, 3052, 2920, 1611, 1505,
˜
1
M.p. 147–149 °C. H NMR (500 MHz, CDCl3): δ = 1.38 (s, 9 H,
1463, 1245, 1099, 870, 752 cm–1. MS (EI): m/z (%) = 259 (100)
[M+], 231 (64), 91 (16). C18H13NO (259.31): calcd. C 83.37, H 5.05,
N 5.40; found C 83.25, H 5.10, N 5.36.
CMe3), 5.58 (s, 2 H, N-C-H), 7.01 (s, 2 H, C=C-H), 7.50–7.52 (m,
3 H, Ar-H), 7.61 (s, 1 H, Ar-H), 7.82–7.84 (m, 2 H, Ar-H) ppm.
13C NMR (125 MHz, CDCl3): δ = 28.3, 66.2, 81.3, 104.6, 113.3,
116.8, 127.6, 129.4, 129.6, 136.5, 141.7, 144.4, 151.6, 154.9, 156.7,
3-Phenylnaphth[2,3-d]isoxazole (10c): Yield: 100 mg, 54%. Colour-
less solid. M.p. 139–140 °C. 1H NMR (500 MHz, CDCl3): δ =
7.47–7.51 (m, 1 H, Ar-H), 7.58–7.65 (m, 4 H, Ar-H), 7.99–8.09 (m,
5 H, Ar-H), 8.48 (s, 1 H, Ar-H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 105.2, 122.0, 124.9, 127.7, 127.8 128.2, 128.3, 129.2,
163.7 ppm. IR (KBr): ν = 3435, 3069, 2976, 1697, 1464, 1338, 1168,
˜
834 cm–1. HRMS: calcd. for C22H19N2O3Cl [M]+ 394.1085; found
394.1084.
3-(4-Chlorophenyl)-5,8-dihydro-5,8-methanonaphth[2,3-d]isoxazole
(14c): Yield: 232 mg, 79 %. Yellow oil. 1H NMR (500 MHz,
CDCl3): δ = 2.31 (d, J = 7.5 Hz, 1 H, CH2), 2.43 (d, J = 7.5 Hz, 1
H, CH2), 3.97 (s, 1 H, CH2-C-H), 3.99 (s, 1 H, CH2-C-H), 6.77–
6.82 (m, 2 H, C=C-H), 7.46 (s, 1 H, Ar-H), 7.50 (d, J = 8.5 Hz, 2
H, Ar-H), 7.55 (s, 1 H, Ar-H), 7.85 (d, J = 8.5 Hz, 2 H, Ar-H)
ppm. 13C NMR (125 MHz, CDCl3): δ = 49.6, 50.4, 68.6, 104.7,
113.1, 116.6, 128.1, 129.3, 129.4, 129.5, 129.6, 136.1, 142.2, 143.3,
129.36, 129.37, 130.6, 130.7, 134.3, 157.5, 160.2 ppm. IR (KBr): ν
˜
= 3443, 3052, 2964, 1633, 1501, 1462, 1246, 1100, 865, 748 cm–1.
HRMS (MALDI-TOF): calcd. for C17H11NO [M + H]+ 246.0917;
found 246.0913.
3-(4-Chlorophenyl)naphth[2,3-d]isoxazole (10d): Yield: 176 mg,
84%. Colourless solid. M.p. 175–176 °C. 1H NMR (500 MHz,
CDCl3): δ = 7.48–7.51 (m, 1 H, Ar-H), 7.51–7.61 (m, 3 H, Ar-H),
7.99–8.04 (m, 5 H, Ar-H), 8.42 (s, 1 H, Ar-H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 105.3, 121.5, 121.6, 125.0 127.4, 127.9,
128.1, 129.3, 129.5, 129.6, 130.7, 134.3, 136.8, 156.5, 160.2 ppm. IR
148.2, 155.9, 156.4, 163.8 ppm. IR (KBr): ν = 3386, 3048, 2935,
˜
1604, 1464, 1341, 1092, 834 cm–1. HRMS: calcd. for C18H12NOCl
[M]+ 293.0610; found 293.0607.
(KBr): ν = 3446, 3052, 2922, 1634, 1463, 1216, 1092, 826, 744 cm–1.
˜
Benzisoxazole Derivatives 16a,d,e from Oxadisilole-Fused Benzisox-
azole 6a,d,e: TBAF (1.0 m in THF, 2.0 mL, 2.0 mmol) was added
to a solution of oxadisilole-fused benzisoxazole derivatives 6a,d,e
(1.0 mmol) in dichloromethane (10 mL) under N2. The mixture was
stirred at room temperature for 2 h. The organic solvent was re-
moved under reduced pressure. The crude product was purified by
column chromatography on silica gel using a gradient of 5–10%
EtOAc in PE (60–80 °C) as the eluent to afford benzisoxazole de-
rivatives 16a,d,e.
HRMS (MALDI-TOF): calcd. for C17H10ClNO [M
280.0528; found 280.0524.
+
H]+
3-(4-Nitrophenyl)naphth[2,3-d]isoxazole (10e): Yield: 74 mg, 34%.
1
Pale brown solid. M.p. Ͼ271 °C. H NMR (500 MHz, DMSO): δ
= 7.60 (t, J = 7.5 Hz, 1 H, Ar-H), 7.71 (t, J = 7.5 Hz, 1 H, Ar-H),
8.17 (d, J = 8.0 Hz, 1 H, Ar-H), 8.26 (d, J = 8.0 Hz, 1 H, Ar-H),
8.40 (s, 1 H, Ar-H), 8.47–8.53 (m, 4 H, Ar-H), 8.95 (s, 1 H, Ar-H)
ppm. 13C NMR (125 MHz, DMSO): δ = 105.1, 120.3, 122.6, 124.5,
125.3, 128.0, 128.2, 129.46, 129.51, 130.6, 134.0, 134.1, 148.8, 3-(4-Methoxyphenyl)-1,2-benzisoxazole (16a): Yield: 126 mg, 56%.
155.7, 159.5 ppm. IR (KBr): ν = 3453, 3088, 1630, 1604, 1526,
Colourless solid. 1H NMR (500 MHz, CDCl3): δ = 3.90 (s, 3 H,
OMe), 7.08 (d, J = 8.5 Hz, 2 H, Ar-H), 7.37 (t, J = 7.5 Hz, 1 H,
Ar-H), 7.58 (t, J = 7.5 Hz, 1 H, Ar-H), 7.63 (d, J = 8.5 Hz, 1 H,
˜
1347, 853, 754 cm–1. HRMS (MALDI-TOF): calcd. for
C17H10N2O3 [M + H]+ 291.0769; found 291.0764.
1392
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© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 1388–1393

Oxadisilole-Fused Benzisoxazoles or Naphthisoxazoles
Ar-H), 7.92 (d, J = 8.5 Hz, 3 H, Ar-H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 55.6, 110.3, 114.7, 120.7, 121.5, 122.4, 123.9, 129.6,
129.8, 157.0, 161.3, 163.9 ppm. LRMS (EI): m/z (%) = 225 (100)
[M+], 197 (27), 105 (72).
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3-(4-Chlorophenyl)-1,2-benzisoxazole (16d): Yield: 165 mg, 72%.
Colourless solid. H NMR (500 MHz, CDCl3): δ = 7.39–7.42 (m,
1
1 H, Ar-H), 7.54–7.56 (m, 2 H, Ar-H), 7.60–7.63 (m, 1 H, Ar-H),
7.66–7.68 (m, 1 H, Ar-H), 7.89–7.93 (m, 3 H, Ar-H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 110.5, 120.3, 122.1, 124.2, 127.6,
129.4, 129.6, 130.1, 136.6, 156.5, 164.1 ppm. MS (EI): m/z (%) =
229 (100) [M+], 201 (41), 166 (37).
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3-(4-Nitrophenyl)-1,2-benzisoxazole (16e): Yield: 151 mg, 63%. Pale
brown solid. 1H NMR (500 MHz, DMSO): δ = 7.56 (t, J = 7.5 Hz,
1 H, Ar-H), 7.79 (t, J = 7.5 Hz, 1 H, Ar-H), 7.92 (d, J = 8.5 Hz, 1
H, Ar-H), 8.20 (d, J = 8.5 Hz, 1 H, Ar-H), 8.33 (d, J = 8.5 Hz, 2 H,
Ar-H), 8.45 (d, J = 8.5 Hz, 2 H, Ar-H) ppm. 13C NMR (125 MHz,
DMSO): δ = 110.4, 119.2, 122.5, 124.5, 125.0, 129.3, 131.0, 134.2,
148.6, 155.4, 163.5 ppm. MS (EI): m/z (%) = 240 (100) [M+], 212
(20), 194 (24).
Acknowledgments
Financial support from the National Natural Science Foundation
of China (no. 20872086) and the Shanghai Municipal Education
Commission (nos. 09YZ19 and J50102) are gratefully acknowl-
edged.
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Received: October 31, 2011
Published Online: January 16, 2012
Eur. J. Org. Chem. 2012, 1388–1393
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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