Novel formation of oxazepino[4,5-a]quinolines by tandem 1,3-dipolar and insertion reaction of quinoline N-oxides with arynes

Article abstract of DOI:10.1246/bcsj.20120325

By combination of 1,3-dipolar cycloaddition and N-O single bond insertion, tandem synthesis of dibenzo[1,4]-oxazepino[4,5-a]quinolines was accomplished. Reaction of quinoline N-oxides with arynes afforded 2-(2-hydroxyphenyl) quinolines and 7-membered pentacyclic oxazepino[4,5-a]quinolines.

Full text of DOI:10.1246/bcsj.20120325

© 2013 The Chemical Society of Japan
Bull. Chem. Soc. Jpn. Vol. 86, No. 5, 615-619 (2013)
615
Novel Formation of Oxazepino[4,5-a]quinolines by Tandem 1,3-Dipolar
and Insertion Reaction of Quinoline N-Oxides with Arynes
Kentaro Okuma,* Koki Hirano, Chisato Shioga, Noriyoshi Nagahora, and Kosei Shioji
Department of Chemistry, Fukuoka University, Jonan-ku, Fukuoka 814-0180
Received November 21, 2012; E-mail: kokuma@fukuoka-u.ac.jp
By combination of 1,3-dipolar cycloaddition and N-O single bond insertion, tandem synthesis of dibenzo[1,4]-
oxazepino[4,5-a]quinolines was accomplished. Reaction of quinoline N-oxides with arynes afforded 2-(2-hydroxyphen-
yl)quinolines and 7-membered pentacyclic oxazepino[4,5-a]quinolines.
1,3-Dipolar cylcloaddition of arynes is one of the most
useful reaction in organic synthesis which allows easy access
to heterocycles.1 Huisgen et al. reported the reaction of
nitrones with benzyne, which resulted in the formation of
benzisoxazolines in almost quantitative yields.2 Approaches
to benzisoxazolines and benzisoxazoles by reactions of amine
N-oxides (nitrones and nitrile oxides) with benzyne were
investigated for more than fifty years.2,3 This type of reaction
still focused attention due to the biological and pharmacolog-
ical activities of benzisoxazolines and benzisoxazoles.4 Reac-
tion of aromatic amine N-oxides with arynes derived from
benzenediazonium 2-carboxylate or 2-(trimethylsilyl)phenyl
triflate (1a) was also reported. Abramovitch and Shinkai
reported that the reaction of pyridine N-oxide (2) with benzyne
generated from benzenediazonium carboxylate gave 3-(2-hy-
droxyphenyl)pyridine (3) and 2-(2-hydroxyphenyl)pyridine (4)
in 21 and 6% yields, respectively.5 Larock et al. reported the
same reaction by using triflate 1a as a benzyne precursor, which
resulted in the isolation of 3 in 88% yield.6 They suggested that
the reaction would proceed through three-membered cyclic
intermediate 5 (Scheme 1).
quinoid form 8, which has higher energy than that of inter-
mediate 5. Thus, the product of this reaction would not be 3-(2-
hydroxylphenyl)quinoline (9) but 2-(2-hydroxylphenyl)quino-
line (10). Additionally, there is a possibility that initial 1,3-
dipolar cycloadduct 7 reacts with additional benzyne to give
previously unknown oxazepines (11) (Scheme 2).
Recently, we have reported the synthesis of 2-substituted
quinoline N-oxides by the reaction of 2-alkenylnitrobenzene
with Fe/HCl.7 These results prompted us to investigate the
reaction of N-oxides 6 with arynes. Herein, we report novel
formation of pentacyclic oxazepines from N-oxides 6 and
arynes.
Results and Discussion
We started by optimizing the reaction conditions using an
unsubstituted benzyne precursor 1a and quinoline N-oxide (6a)
(Table 1). Treatment of N-oxide 6a with triflate 1a (1.2 equiv)
and CsF (2.4 equiv) in acetonitrile at rt resulted in the forma-
tion of 2-(2-hydroxyphenyl)quinoline (10a) and dibenzo[1,4]-
oxazepino[4,5-a]quinoline 11a in 54% and 9% yields, respec-
tively (Entry 1). When 2.2 equiv of triflate 1a was used, 10a
and 11a were obtained in 19% and 33% yields, respectively
(Entry 2). When 6a was treated with triflate 1a (2.2 equiv) and
CsF (6.6 equiv) in acetonitrile at 60 °C, 10a and 11a was
However, there is no report on the reaction of quinoline N-
oxides (6) with arynes. If we choose 6 as a substrate, initially
formed 1,3-dipolar cycloadduct 7 would rearrange to give
O
N
N
F
H
O
TMS
6a
1a
O
N
O
O
2
CsF
H
N
N
O
TMS
OTf
OTf
7
8
N
+
5
1a
or
N2
H
CO2
N
N
N
OH
O
N
OH
HO
10
N
HO
4
3
11
9
Scheme 1.
Scheme 2.
Published on the web March 23, 2013; doi:10.1246/bcsj.20120325

616
Bull. Chem. Soc. Jpn. Vol. 86, No. 5 (2013)
Novel Formation of Oxazepino[4,5-a]quinolines
Table 2. Reaction of 1 with Substituted 6
Table 1. Reaction of Triflate 1a with Quinoline N-Oxide
(6a) in CH3CN
R
R
R'
TMS
CsF
TMS
OTf
CsF
R'
R'
N
+
+
N
O
CH3CN
N
CH3CN
R'
N
HO
OTf
60 °C
HO
10a
O
6a
1a: R' = H
10b: R = 2-Me, R' = H
10c: R = 3-Me, R' = H
10d: R = 6-Cl, R' = H
10e: R = 3-Me, R' = Me
6b: R = 2-Me
6c: R = 3-Me
6d: R = 6-Cl
1b: R' = Me
1a
1c: R' = MeO
1d: R' = -CH2OCH2-
10f : R = 3-Me, R' = MeO
10g: R = 3-Me, R' = -OCH2O-
H
R
N
+
R'
H
O
O
N
R'
+
11a
Products/%
R'
R'
1a
/equiv
Temp Time
Entry
Fluoride
/°C
/h
11b: R = 2-Me, R' = H
11c: R = 3-Me, R' = H
11d: R = 6-Cl, R' = H
11e: R = 3-Me, R' = Me
11f : R = 3-Me, R' = MeO
11g: R = 3-Me, R' = -OCH2O-
10a
11a
1
2
3
4
5
1.2
2.2
2.2
2.4
2.2
CsF
CsF
CsF
CsF
TBAF
rt
rt
60
reflux
60
16
18
7
8
2
54
19
21
20
13
9
33
50
37
®
Time
/h
10
11
Entry
6
1
Yield/%
Yield/%
1
2
3
4
5
6
6b
6c
6d
6c
6c
6c
1a
1a
1a
1b
1c
1d
6
6
6
8
8
8
10b
®
15
12
5
®
®
11b
®
39
18
64
55
48
isolated in 21% and 50% yields, respectively (Entry 3). When
2.2 equiv of 1a and 2.4 equiv of tetrabutylammonium fluoride
(TBAF) were used, only 10a was obtained in 13% yield
(Entry 5).
10c
10d
10e
10f
10g
11c
11d
11e
11f
11g
In contrast to the reaction of pyridine N-oxide 2 with
benzyne, proton transfer occurred at the 2-position of the
quinoline ring, indicating that our initial prediction (prefer-
ential formation of 10) would be correct. When two equivalents
of 1a were used at 60 °C, additional benzyne further reacted
with 1,3-adduct to afford novel dibenzo[1,4]oxazepine 11a.
The structure of 11a was confirmed by spectroscopic data.
1H NMR of 11a shows a doublet at 5.70 ppm along with three
A2B2 ortho-substituted aromatic protons and two olefinic
protons. 13C NMR of 11a shows a methine carbon signal at
59.7 ppm along with 20 aromatic and olefinic carbons.
Since the optimum conditions were determined (2.2 equiv of
1 and 6.6 equiv of CsF in acetonitrile at 60 °C), we then tried
the reaction of substituted quinoline N-oxides 6 with 1 to deter-
mine whether more oxazepines 11 would be formed (Table 2).
When 2-methylquinoline N-oxide (6b) was treated with 1a, an
inseparable mixture was obtained (Entry 1). Similarly, treat-
ment of 2-phenyquinoline N-oxide with triflate 1a and CsF
gave no cycloadduct, indicating that 2-substitution at the quino-
line ring may retard 1,3-dipolar addition. When 3-methylquino-
line N-oxide (6c) was treated with triflate 1a, 2-(2-hydroxy-
phenyl)-3-methylquinoline (10c) and dibenzo[1,4]oxazepine
11c were obtained in 15% and 39% yields, respectively
(Entry 2). When 6-chloroquinoline N-oxide (6d) was treated
with 1a, 2-(2-hydroxyphenyl)-6-chloroquionline (10d) and di-
benzo[1,4]oxazepine 11d were obtained in 12 and 18% yields,
respectively (Entry 3).
Figure 1. ORTEP drawing of compound 11c.
tively (Entry 4). Reaction of 4,5-methylenedioxy-2-(trimethyl-
silyl)phenyl triflate (1c) with 6c afforded [1,4]oxazepine 11f in
55% yield (Entry 5). When 4,5-methylenedioxy-2-(trimethyl-
silyl)phenyl triflate (1e) was treated with 6c, the corresponding
11g was obtained in 48% yield. Fortunately, as single crystals
of 11c were obtained, X-ray crystallographic analysis was
performed. The result is shown in Figure 1.
Reaction of 6c with 4,5-dimethyl-2-(trimethylsilyl)phenyl
triflate (1b) gave 2-(2-hydroxy-4,5-dimethylphenyl)quinoline
(10e) and [1,4]oxazepine 11e in 5% and 64% yields, respec-

K. Okuma et al.
Bull. Chem. Soc. Jpn. Vol. 86, No. 5 (2013)
617
slow
N
CsF
10
11
H
+
1a
+
12
13
N
O
N
O
CH3CN
OH
14
7
Ph
N
Scheme 3.
Ph
O
+
N2
CsF
CH3CN
+
OH
N
N
O
CO2
O
12
15
13
Scheme 5.
Scheme 4.
The reaction might proceed as follows: initially formed
[3 + 2] adduct 7 slowly rearranges to give 2-(2-hydroxylphen-
yl)quinoline 10. Another molar equivalent of benzyne reacts
with adduct 7 to afford N-O bond insertion product, oxazepine
11 (Scheme 3). Although tandem reactions of benzyne have
been recently reported, many of which were double-cyclo-
addition or three components reaction,8 this is the first example
of tandem 1,3-dipolar cycloaddition and N-O single bond
insertion.
It is well known that reaction of nitrones with benzyne gives
2,1-benzisoxazoline derivatives. For example, Huisgen et al.
reported that the reaction of benzyne with 3,4-dihydroisoquino-
line N-oxide (12) gave 92% of 5,6-dihydronaphtho[2,3-a]-
benzisoxazoline (13).2 Other researchers also reported this type
of reaction, which resulted in the formation of benzisoxazolines
in good yields (Scheme 4).4a
However, there is no report on the formation of N-O bond
insertion products from these benzisoxazolines. Thus, we then
tried the reaction of nitrone 12 with benzyne derived from 1a
and CsF in the hope of obtaining N-O bond insertion product.
Treatment of nitrone 12 with triflate 1a and CsF resulted in
the formation of 5,6-dihydronaphtho[2,3-a]benzisoxazoline
(13) in 78% yield, the result of which is similar to that of
Huisgen et al.2 However, when 2 equiv of triflate 1a was
used, 2-(2-hydroxyphenyl)-3,4-dihydroisoquinoline (14) (19%)
and 2-[(2-diphenylamino)ethyl]-2¤-hydroxybenzophenone (15)
(11%) were obtained along with benzisoxazoline 13 (41%)
(Scheme 5).
Ring-opened product 14 would be formed from 13 in the
presence of a small amount of water and CsF, which was
confirmed by the independent reaction of adduct 13 with CsF
(1 equiv) and water (2 equiv) in acetonitrile. Although the
reason that pentacyclic oxazepines were obtained only by use
of quinoline N-oxides 6 is not clear at present, one can
postulate the difference in the N-O single bond energy of 1,3-
dipolar adducts between 7 and 13. Actually, when isoquinoline
N-oxide, which would be another candidate of aromatic amine
N-oxides, was treated with triflate 1a in the presence of CsF, an
inseparable mixture was formed, suggesting that the difference
in the N-position between quinoline and isoquinoline N-oxide
plays an important role for this reaction.
Conclusion
An efficient one-pot synthesis of novel nitrogen- and
oxygen-containing heterocycles (dibenzo[1,4]oxazepines) was
accomplished by the reaction of quinoline N-oxides with
arynes. This is the first example of the synthesis of seven-
membered cyclic oxazepino[4,5-a]quinolines. Notable advan-
tages of the present method are: i) simplicity of the procedure,
ii) mild reaction conditions, and iii) easy availability of the
starting materials.
Experimental
General. All chemicals were obtained from commercial
suppliers and were used without further purification. Analytical
TLC was carried out on precoated plates (Merck silica gel
60, F254) and flash column chromatography was performed
with silica gel (Merck, 70-230 mesh). NMR spectra (1H at 400
MHz; 13C at 100 MHz) were recorded in CDCl3, and chemical
shifts are expressed in ppm relative to internal TMS for 1H- and
13C NMR. Melting points are uncorrected.
Reaction of 1a with Quinoline N-Oxide (6a) in the
Presence of CsF. To a suspension of 6a (0.073 g, 0.50 mmol)
and CsF (0.50 g, 3.3 mmol) in acetonitrile (6 mL) was added 1a
(0.179 g, 0.60 mmol) dropwise at rt. After stirring for 16 h, the
reaction mixture was washed with brine, extracted with ethyl
acetate (5 mL © 3), dried over magnesium sulfate, filtered, and
evaporated to give pale brown solid, which was chromato-
graphed over silica gel by elution with dichloromethane to
afford 10a (0.059 g, 0.27 mmol) and 11a (0.013 g, 0.045 mmol).
2-(2-Hydroxyphenyl)quinoline (10a): yellow plates, mp 113-
115 °C (lit,9 115-117 °C). 1H NMR (CDCl3): ¤ 6.97 (t, J =
7.5 Hz, 1H, Ar), 7.09 (d, J = 8.0 Hz, 1H, Ar), 7.37 (t, J = 7.7
Hz, 1H, Ar), 7.56 (dd, J = 8.0 and 7.5 Hz, 1H, Ar), 7.75 (t,
J = 7.8 Hz, 1H, Ar), 7.83 (d, J = 8.3 Hz, 1H, Ar), 7.96 (d, J =
8.0 Hz, 1H, Ar), 8.05-8.07 (m, 2H, Ar), 8.28 (d, J = 8.9 Hz,
1H, Ar). 13C NMR (CDCl3): ¤ 117.26, 118.66, 118.74, 119.00,
126.55, 126.69, 126.94, 127.54, 127.60, 130.49, 132.06,

618
Bull. Chem. Soc. Jpn. Vol. 86, No. 5 (2013)
Novel Formation of Oxazepino[4,5-a]quinolines
137.63, 144.77, 158.03, 161.04 (Ar). Dibenzo[1,4]oxazepino-
[4,5-a]quinoline 11a: pale brown oil. 1H NMR (CDCl3): ¤ 5.86
(d, J = 6.2 Hz, 1H), 6.00 (dd, J = 6.2, 9.5 Hz, 1H), 6.65-6.73
(m, 2H, Ar), 6.82 (d, J = 9.7 Hz, 1H), 6.86-6.99 (m, 3H, Ar),
7.04 (d, J = 7.5 Hz, 1H, Ar), 7.06-7.19 (m, 4H, Ar), 7.25 (d,
J = 8.0 Hz, 1H, Ar), 7.28 (d, J = 8.0 Hz, 1H, Ar). 13C NMR
(CDCl3): ¤ 55.91, 114.72, 119.23, 120.68, 121.14, 122.19,
122.75, 123.52, 123.55 (q), 125.80, 127.17, 127.38, 127.44,
128.40, 128.84, 129.03, 133.01 (q), 133.61 (q), 142.03 (q),
152.35 (q), 156.05 (q). MS (m/z): Calcd for C21H15NO; 297.10.
Found; (M+ ¹ 1) 296.03. Anal. Calcd for C21H15NO: C, 84.82;
H, 5.08; N, 4.71%. Found: C, 84.83; H, 5.19; N, 4.63%.
Reaction of 1a (2.2 equiv) with Quinoline N-Oxide (6a) in
the Presence of CsF. To a suspension of 6a (0.073 g, 0.50
mmol) and CsF (0.50 g, 3.3 mmol) in acetonitrile (6 mL)
was added 1a (0.328 g, 1.10 mmol) at 60 °C. After stirring
for 7 h, the reaction mixture was washed with brine, extracted
with ethyl acetate (5 mL © 3), dried over magnesium sulfate,
filtered, and evaporated to give pale brown solid, which was
chromatographed over silica gel by elution with dichloro-
methane to afford 10a (0.023 g, 0.11 mmol) and 11a (0.074 g,
0.25 mmol).
J = 8.8 Hz, 1H, =CH), 6.77 (d, J = 9.7 Hz, 1H, Ar), 6.84 (d,
J = 8.8 Hz, 1H, Ar), 6.90-6.99 (m, 2H, Ar), 7.01 (s, 1H, Ar),
7.10-7.28 (m, 6H, Ar). 13C NMR (CDCl3): ¤ 55.91 (CH),
115.99, 120.77, 122.26, 122.59, 122.88, 123.61, 123.79 (q),
124.83 (q), 126.12, 126.94, 127.30, 127.46, 128.45, 129.21,
132.56 (q), 133.61 (q), 140.59 (q), 152.28 (q), 155.88 (q). Anal.
Calcd for C21H14ClNO¢H2O: C, 72.10; H, 4.61; N, 4.00%.
Found: C, 72.15; H, 4.78; N, 3.79%.
Reaction of 6c with Triflate 1b in the Presence of CsF. To
a suspension of 6c (0.080 g, 0.50 mmol) and CsF (3.3 mmol) in
acetonitrile (10 mL) was added triflate 1b (0.358 g, 1.1 mmol)
dropwise at 60 °C. After stirring for 8 h, the reaction mixture
was washed with brine, extracted with ethyl acetate (5 mL © 3),
dried over magnesium sulfate, filtered, and evaporated to give
pale brown solid, which was chromatographed over silica
gel by elution with dichloromethane to afford 10e (0.007 g,
0.027 mmol) and 11e (0.119 g, 0.324 mmol). 2-(2-Hydroxy-4,5-
dimethylphenyl)-3-methylquinoline (10e) colorless plates. mp
1
152-154 °C. H NMR (CDCl3): ¤ 2.26 (s, 3H, Me), 2.29 (s,
3H, Me), 2.72 (s, 3H, Me), 6.93 (s, 1H, Ar), 7.46 (s, 1H, Ar),
7.51 (t, J = 6.8 Hz, 1H, Ar), 7.67 (t, J = 7.2 Hz, 1H, Ar), 7.76
(d, J = 8.0 Hz, 1H, Ar), 7.99 (d, J = 8.0 Hz, 1H, Ar), 8.10
(s, 1H, Ar). 13C NMR (CDCl3): ¤ 19.38 (Me), 20.17 (Me),
22.67 (Me), 119.16, 119.45, 126.41, 126.81, 126.86, 126.93,
127.67, 129.59, 129.79, 130.70, 139.64, 140.17, 144.39,
156.53, 158.46 (Ar). HRMS (m/z): Calcd for C18H17NO;
263.1310. Found; 263.1315 (M+). 1,9,10,14,15-Pentamethyl-
dibenzo[1,4]oxazepino[4,5-a]quinoline (11e): colorless plates,
mp 72-74 °C. 1H NMR (CDCl3): ¤ 1.97 (s, 3H, Me), 2.09
(s, 3H, Me), 2.13 (s, 6H, 2Me), 2.23 (s, 3H, Me), 5.58 (s, 1H,
CH), 6.58 (s, 1H, Ar), 6.62-6.69 (m, 2H, Ar), 6.73 (d, J =
8.0 Hz, 1H, Ar), 6.86 (t, J = 8.0 Hz, 1H, Ar), 6.90 (s, 1H,
Ar), 6.95-7.03 (m, 3H, Ar). 13C NMR (CDCl3): ¤ 18.97 (Me),
19.36 (Me), 19.43 (Me), 19.64 (Me), 21.82 (Me), 60.14 (CH),
114.29, 118.79, 121.64, 122.59, 124.02, 124.45, 126.47,
127.45, 127.52, 127.65, 128.55, 129.96, 130.39, 130.54,
131.20, 133.92, 137.28, 140.75, 149.46, 154.66 (Ar). HRMS
(m/z): Found: M+: 367.1925. Calcd for C26H25NO: M+:
367.1936.
Compound 11f: pale yellow fine plates, mp 78-80 °C.
1H NMR (CDCl3): ¤ 2.02 (s, 3H, Me), 3.70 (s, 3H, OMe), 3.73
(s, 3H, OMe), 3.81 (s, 3H, OMe), 3.91 (s, 3H, OMe), 5.60
(s, 1H, CH), 6.49 (s, 1H, Ar), 6.62 (s, 1H, Ar), 6.67 (s, 1H, Ar),
6.72 (s, 1H, Ar), 6.75 (s, 1H, Ar), 6.66-6.74 (m, 2H, Ar),
6.88 (t, J = 7.6 Hz, 1H, Ar), 7.02 (d, J = 7.6 Hz, 1H, Ar).
13C NMR (CDCl3): ¤ 21.47 (Me), 56.00 (OMe), 56.11 (OMe),
56.30 (OMe), 56.31 (OMe), 59.82 (CH), 104.87, 104.99,
109.55, 109.70, 113.94, 118.93, 123.00, 123.93, 124.28,
124.29, 126.19, 127.70, 130.71, 140.76, 143.93, 144.43,
145.13, 146.46, 148.75, 150.04. MS (m/z): Calcd for
C25H23NO5: 417.16. Found: 417.01 (M+). Anal. Calcd for
C26H25NO5: C, 72.37; H, 5.84; N, 3.25. Found: C, 72.48; H,
5.83; N, 3.34.
Other reactions were carried out in a similar manner.
2-(2-Hydroxyphenyl)-3-methylquinoline (10c): colorless
1
needles, mp 117-119 °C (lit.10 mp 119 °C). H NMR (CDCl3):
¤ 2.72 (s, 3H, Me), 6.94 (t, J = 8.0 Hz, 1H, Ar), 7.13 (d,
J = 7.6 Hz, 1H, Ar), 7.34 (t, J = 7.6 Hz, 1H, Ar), 7.55 (t, J =
7.6 Hz, 1H, Ar), 7.68-7.71 (m, 2H, Ar), 7.78 (d, J = 8.0
Hz, 1H, Ar), 8.03 (d, J = 8.8 Hz, 1H, Ar), 8.14 (s, 1H, OH).
1-Methyldibenzo[1,4]oxazepino[4,5-a]quinoline (11c): color-
less needles, mp 188-189 °C. 1H NMR (CDCl3): ¤ 1.99 (s,
3H, Me), 5.71 (s, 1H, CH), 6.61 (s, 1H, =CH), 6.69 (t, J =
8.0 Hz, 1H, Ar), 6.74 (d, J = 8.0 Hz, 1H, Ar), 6.86 (t, J =
6.8 Hz, 1H, Ar), 6.91 (t, J = 8.0 Hz, 1H, Ar), 6.93 (d, J =
7.6 Hz, 1H, Ar), 6.98 (t, J = 7.6 Hz, 1H, Ar), 7.07 (t, J =
8.0 Hz, 1H, Ar), 7.12-7.18 (m, 2H, Ar), 7.22-7.26 (m, 2H, Ar).
13C NMR (CDCl3): ¤ 21.46, 59.79, 114.15, 119.24, 120.59,
122.19, 123.48, 124.09 (q), 124.37 (q), 125.02, 126.17, 126.25,
126.79, 127.53, 128.86, 130.19, 131.44, 132.86 (q), 140.08 (q),
151.32 (q), 156.68 (q). HRMS (m/z): Calcd for C22H17NO;
311.1310. Found; (M+) 311.1303. X-ray crystallographic data:
Space group P212121. a = 9.767(3) ¡, b = 10.497(3) ¡, c =
¹3
15.894(5) ¡. V = 1629.7(9) ¡3. Z = 4. Dcalcd = 1.269 Mg m
.
R1 = 0.0699, wR2 = 0.0914. GOF = 1.003. Crystal graphic
data of 11c was deposited with Cambridge Crystallographic
Centre. Deposition No. CCDC 901565 for compound 11c.
Copies of the data can be obtained free of charge via http://
www.ccdc.cam.ac.uk/conts/retrieving.html.
2-(2-Hydroxyphenyl)-6-chloroquinoline
(10d):
yellow
plates, mp 149-151 °C (lit.11), H NMR (CDCl3): ¤ 6.97 (dd,
J = 8.0, 7.6 Hz, 1H, Ar), 7.10 (d, J = 8.4 Hz, 1H, Ar), 7.38 (dd,
J = 8.4, 8.0 Hz, 1H, Ar), 7.69 (d, J = 8.8 Hz, 1H, Ar), 7.82
(s, 1H, Ar), 7.94 (d, J = 8.0 Hz, 1H, Ar), 7.99 (d, J = 8.8 Hz,
1H, Ar), 8.07 (d, J = 8.8 Hz, 1H, Ar), 8.20 (d, J = 8.8 Hz,
1H, Ar). Anal. Calcd for C15H10ClNO¢H2O: C, 65.82; H, 4.42;
N, 5.12%. Found: C, 65.61; H, 4.18; N, 4.78%.
1
Compound 11g: yellow plates, mp 265-268 °C. 1H NMR
(CDCl3): ¤ 1.96 (s, 3H, Me), 5.57 (s, 1H, CH), 5.81 (s, 1H,
OCH2O), 5.87 (s, 1H, OCH2O), 5.91 (s, 1H, OCH2O), 5.94
(s, 1H, OCH2O), 6.44 (s, 1H, Ar), 6.58 (s, 1H, Ar), 6.63-6.76
(m, 5H, Ar), 6.89 (t, J = 7.2 Hz, 1H, Ar), 7.00 (d, J = 7.2 Hz,
1H, Ar). 13C NMR (CDCl3): ¤ 21.56 (Me), 59.63 (CH), 101.55
4-Chlorodibenzo[1,4]oxazepino[4,5-a]quinoline (11d): pale
1
brown plates, mp 59-61 °C, H NMR (CDCl3): ¤ 5.85 (d, J =
5.2 Hz, 1H, CH), 6.05 (dd, J = 3.2, 2.8 Hz, 1H, =CH), 6.63 (d,

K. Okuma et al.
Bull. Chem. Soc. Jpn. Vol. 86, No. 5 (2013)
619
(OCH2O), 101.77 (OCH2O), 102.60, 103.09, 106.06, 106.32,
114.46, 119.37, 124.20, 124.69, 125.29, 126.00, 126.53,
127.81, 130.84, 140.51, 142.86, 143.55, 144.79, 146.05,
147.27, 151.11 (Ar). HRMS (m/z): Found: M+: 399.1102.
Calcd for C24H17NO5: M+: 399.1107.
(15:1) to afford 14 (0.030 g, 0.13 mmol). Starting 13 was also
recovered (0.011 g, 0.05 mmol).
This work was partially supported by the Collaborative
Research Program of Institute for Chemical Research, Kyoto
University (grant Nos. 2011-69 and 2012-67).
Reaction of 3,4-Dihydroisoquinoline N-Oxide (12) with
Triflate 1a and CsF. To a suspension of 12 (0.075 g, 0.51
mmol) and CsF (0.274 g, 1.8 mmol) in acetonitrile (10 mL) was
added 1a (0.358 g, 0.11 mmol) at rt. After stirring for 16 h,
the reaction mixture was washed with brine, extracted with
ethyl acetate (10 mL © 3), dried over sodium sulfate, filtered,
and evaporated to give pale brown solid, which was chromato-
graphed over silica gel by elution with dichloromethane-ethyl
acetate (15:1) to afford 13 (0.046 g, 0.21 mmol), 14 (0.022 g,
0.097 mmol), and 15 (0.022 g, 0.055 mmol).
References
1
For reviews, see: R. W. Hoffmann, Dehydrobenzene and
Cycloalkynes, Academic Press, New York, 1967; A. Padwa, 1,3-
Dipolar Cycloaddition Chemistry, John Wiley & Sons, New York,
1984; C. Wentrup, Aust. J. Chem. 2010, 63, 979; T. Kitamura,
Aust. J. Chem. 2010, 63, 987; K. Okuma, Heterocycles 2012,
85, 515.
Compound 13: pale yellow crystals, mp 82-84 °C, (lit.2 mp
2
3
R. Huisgen, R. Knorr, Naturwissenschaften 1961, 48, 716.
T. Sasaki, T. Yoshioka, Bull. Chem. Soc. Jpn. 1969, 42,
1
84 °C). H NMR (CDCl3): ¤ 2.88 (m, 1H, CHH), 2.98 (m, 1H,
826; A. Abiko, Chem. Lett. 1995, 357; M. A. Bigdeli, A. E.
Tipping, J. Fluorine Chem. 1992, 58, 101; A. W. Rautr, A. G.
Doshi, R. B. Raghuwanshi, Orient. J. Chem. 1998, 14, 363; T.
Kitamura, M. Todaka, I. Shin-machi, Y. Fujiwara, Heterocycl.
Commun. 1998, 4, 205; I. Nagy, G. Hajós, Z. Riedl, Heterocycles
2004, 63, 2287.
CHH), 3.36 (m, 2H, CH2), 5.83 (s, 1H, CH), 6.86 (d, J = 7.6
Hz, 1H, Ar), 6.91 (t, J = 7.2 Hz, 1H, Ar), 7.14 (d, J = 7.6 Hz,
1H, Ar), 7.18 (t, J = 7.6 Hz, 1H, Ar), 7.21 (d, J = 7.2 Hz, 1H,
Ar), 7.22 (d, J = 7.2 Hz, 1H, Ar), 7.32 (t, J = 7.2 Hz, 1H,
Ar), 7.41 (d, J = 7.6 Hz, 1H, Ar). 13C NMR (CDCl3): ¤ 26.96
(CH2), 50.03 (CH2), 65.77 (CH), 108.83, 121.73, 123.72,
123.73, 126.98, 127.14, 127.34, 128.73, 128.88, 129.18,
133.64, 134.24, 156.74.
Compound 14: yellow plates, mp 68-70 °C, 1H NMR
(CDCl3): ¤ 2.77 (t, J = 7.2 Hz, 2H, CH2), 3.78 (t, J = 6.8 Hz,
2H, CH2), 6.83 (t, J = 8.0 Hz, 1H, Ar), 7.05 (d, J = 8.0 Hz, 1H,
Ar), 7.30-7.37 (m, 3H, Ar), 7.45 (t, J = 7.6 Hz, 1H, Ar), 7.58
(d, J = 8.0 Hz, 1H, Ar), 7.61 (d, J = 8.0 Hz, 1H, Ar). 13C NMR
(CDCl3): ¤ 26.67 (CH2), 45.21 (CH2), 117.34, 118.03, 118.20,
126.44, 127.50, 127.68, 128.54, 130.52, 130.96, 131.69,
139.34, 162.07, 169.02. HRMS (m/z): Calcd for C15H13NO:
M+: 223.0997. Found: M+: 223.0990.
Compound 15: yellow oil. 1H NMR (CDCl3): ¤ 2.96
(t, J = 7.6 Hz, 2H, CH2), 3.88 (t, J = 7.6 Hz, 2H, CH2), 6.77
(t, J = 7.6 Hz, 1H, Ar), 6.80-6.95 (m, 6H, Ar), 7.07 (d, J =
7.6 Hz, 1H, Ar), 7.16-7.31 (m, 8H, Ar), 7.43-7.54 (m, 2H, Ar),
12.23 (s, 1H, OH). 13C NMR (CDCl3): ¤ 31.60 (CH2), 54.21
(CH2), 118.65, 119.13, 120.12, 120.91, 121.49, 126.13, 128.02,
129.50, 130.56, 131.17, 133.95, 137.28, 137.28, 137.51,
138.20, 147.64, 163.76 (Ar), 204.34 (C=O). HRMS (m/z):
Found: M+: 393.1720. Calcd for C27H23NO2: M+: 393.1729.
Reaction of Benzisoxazoline 13 with CsF. To a suspen-
sion of CsF (0.090 g, 0.60 mmol) and water (0.008 g, 0.44
mmol) in acetonitrile (5 mL) was added benzisoxazoline 13
(0.045 g, 0.20 mmol) at rt. After stirring for 16 h, the reaction
mixture was washed with brine, extracted with ethyl acetate
(5 mL © 3), dried over sodium sulfate, filtered, and evapo-
rated to give pale brown solid, which was chromatographed
over silica gel by elution with dichloromethane-ethyl acetate
4
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