Three component reaction of arynes with cyclic ethers and active methines: Synthesis of ω-trichloroalkyl phenyl ethers

Article abstract of DOI:10.1246/bcsj.20100062

Synthesis of ω-chlorinated alkyl phenyl ethers by tandem reaction of arynes with cyclic ethers and active methines was achieved. Reaction of benzenediazonium 2-carboxylate with tetrahydropyran or tetrahydrofuran in refluxing chloroform afforded 6,6,6-trichlorohexyl phenyl ether or 5,5,5-trichloropentyl phenyl ether in 40% and 61% yields, respectively. When dichloroacetonitrile was used as a reactant, 5,5-dichloro-5-cyanopentyl phenyl ether was obtained in 61% yield. While benzenediazonium carboxylate did not react with epoxides, reaction of benzyne derived from 2-(trimethylsilyl)phenyl triflate with epoxides afforded 3,3,3-trichloropropyl phenyl ethers in good yields as isomeric mixtures. The reaction of oxetanes with benzyne was also reported.

Full text of DOI:10.1246/bcsj.20100062

1238 Bull. Chem. Soc. Jpn. Vol. 83, No. 10, 1238–1247 (2010)
© 2010 The Chemical Society of Japan
Three Component Reaction of Arynes with Cyclic Ethers and Active
Methines: Synthesis of ½-Trichloroalkyl Phenyl Ethers
Kentaro Okuma,*1 Yuta Fukuzaki,1 Akiko Nojima,1 Ayumi Sou,1 Haruna Hino,1 Nahoko Matsunaga,1
Noriyoshi Nagahora,1 Kosei Shioji,1 and Yoshinobu Yokomori2
1Department of Chemistry, Faculty of Science, Fukuoka University, Jonan-ku, Fukuoka 814-0180
2National Defense Academy, Hashirimizu, Yokosuka 239-8686
Received March 4, 2010; E-mail: kokuma@fukuoka-u.ac.jp
Synthesis of ½-chlorinated alkyl phenyl ethers by tandem reaction of arynes with cyclic ethers and active methines
was achieved. Reaction of benzenediazonium 2-carboxylate with tetrahydropyran or tetrahydrofuran in refluxing
chloroform afforded 6,6,6-trichlorohexyl phenyl ether or 5,5,5-trichloropentyl phenyl ether in 40% and 61% yields,
respectively. When dichloroacetonitrile was used as a reactant, 5,5-dichloro-5-cyanopentyl phenyl ether was obtained
in 61% yield. While benzenediazonium carboxylate did not react with epoxides, reaction of benzyne derived from
2-(trimethylsilyl)phenyl triflate with epoxides afforded 3,3,3-trichloropropyl phenyl ethers in good yields as isomeric
mixtures. The reaction of oxetanes with benzyne was also reported.
Arynes are widely used as reactive intermediates, which
are clearly evident from an elegant array of work that
Results and Discussion
has appeared in the recent literature covering a number of
different synthetic transformation.1 We have reported the
synthesis of benzothietes, benzothianes, and 1,3-benzo-
dithioles by using 2-(trimethylsilyl)phenyl triflate (1), ben-
zenediazonium carboxylate (2), or phenyl[2-(trimethylsilyl)-
phenyl]iodonium triflate as benzyne precursors.2 Recently,
many insertion reactions of benzyne with single bonds
containing Sn-Sn, Sn-C, N-C, and C-C using triflate 1 as a
benzyne precursor have been reported.3 Although C-O bond
insertion of arynes with ethers was reported more than 4
decades ago,4 there are very few reports on the reaction of
benzyne with cyclic ethers. Cyclic ethers such as tetrahydro-
furan (THF) reacted with benzyne prepared from 2 to afford
N-4-phenoxybutyl-N-phenylanthranilic acid (17%) and 1,4-
diphenoxybutane (4%).5 The reaction of 1,2-epoxypropane
(3a) with benzyne prepared from 2 afforded N-(9-carbazolyl)-
2-chloroaniline (1.3%).6 Nakayama et al. also reported that the
reaction of benzyne with 1,3-benzodithiole-2-thione in the
presence of 3a gave tetracyclic sulfonium chloride.7 While 3a
was only used as a proton trapping reagent in these reactions,
benzyne inserts into one of the C-O bonds of (1,2-epoxyl-
ethyl)benzene to form 2,3-dihydrobenzofuran (32%) as the
major product together with five other reaction products.8
1,2-Epoxycyclohexane was allowed to react with benzyne to
afford 3-phenoxycyclohexene in 23% yield.9 Palladium-
catalyzed three component coupling reaction of allylic
epoxides with benzyne was also reported.10 Recently, we have
communicated the three component reaction of cyclic ethers
with arynes.11 In this paper, we would like to describe the full
details of novel tandem reaction of benzyne with active
methines and ethers such as tetrahydropyran (THP), THF,
oxetanes 4, and epoxides 3.
Reaction of Tetrahydropyran with Benzyne. We first
chose THP as a cyclic ether. Treatment of 2, prepared from
anthranilic acid and isoamyl nitrite, with THP (10 equiv) in
refluxing chloroform resulted in the formation of 6,6,6-
trichlorohexyl phenyl ether (5a) in 40% yield along with a
small amount of benzoic acid (7%) (Scheme 1). The structure
1
of 5a was confirmed by H- and 13C NMR, and finally X-ray
crystallographic analysis.11 In the absence of chloroform, the
reaction provided a complex mixture of unidentified products.
Since triflate 1 is a commercially available and stable reagent to
generate benzyne under very mild reaction conditions,3,12 we
then tried the reaction of triflate 1 with THP and chloroform
at rt. Treatment of 1 with THP (10 equiv) and chloroform
(10 equiv) in the presence of CsF (4 equiv) resulted in the
formation of ether 5a in 52% yield (Scheme 1).
To investigate the scope and limitation of this novel tandem
reaction, we then tried the reaction of benzyne with other
active methylenes and methines. The reaction of triflate 1 with
acetylacetone or methyl acetoacetate was already reported by
Yoshida et al., which led to C-C bond insertion products.13 The
reaction of triflate 1 with methyl acetoacetate was also reported
O
N2
CO2
O
CCl3
+ CHCl3
2
TMS
OTf
CsF
5a
1
Scheme 1.
Published on the web October 5, 2010; doi:10.1246/bcsj.20100062

K. Okuma et al.
Bull. Chem. Soc. Jpn. Vol. 83, No. 10 (2010) 1239
O
CsF
THF
1
2
O
O
O
O
CsF
CH3CN
THF
+ CHCl3
1 +
+
CCl3
O
CH3CN
rt, 5 h
+ CHCl3
Scheme 2.
6
8a
Scheme 4.
R
H
7a: R=CN
7b: R=COOMe
C
R'
H
R
O
7a: R=CN
Cl
Cl
C
7b: R=COOMe
2
7c: R=COCH
Cl
Cl
3
THP, reflux, 5 h
R'
2
O
THF, reflux, 5 h
5b: R'= C(Cl)2CN
26%
5c: R'= C(Cl)2COOMe 34%
8b: R'= C(Cl)2CN
65%
8c: R'= C(Cl)2COOMe 34%
Scheme 3.
8d: R'=
27%
O
Cl
by Tambar and Stoltz.3c Thus, we have tried these reactions in
the presence of THP. When triflate 1 was added to a suspension
of THP (20 equiv), chloroform (20 equiv), CsF (3 equiv), and
acetylacetone (2 equiv) at rt, 1-(2-acetylphenyl)-2-propanone
(6) was obtained in 52% yield. No product relating to THP was
obtained, suggesting that acetylacetone is more reactive than
THP toward benzyne (Scheme 2).
Cl
H3C
Scheme 5.
refluxing solution of dichloroacetone (7c) (3 equiv) in THF, the
corresponding O-attacked ether 8d was obtained in 27% yield
(Scheme 5).
The reaction of 2 with THP and dichloroacetonitrile (7a) or
methyl dichloroacetate (7b) gave 6,6-dichloro-6-cyanohexyl
phenyl ether (5b) or methyl 2,2-dichloro-7-phenoxyheptanoate
(5c) in 26% and 34% yields, respectively (Scheme 3).
Unfortunately, when triflate 1 was treated with 7a and
chloroform in the presence of CsF, starting triflate 1 was
recovered unchanged due to the lability of active methines
toward CsF. When 7a was mixed with CsF in acetonitrile, the
color of the solution immediately turned black, which led to a
polymeric tar.
When 2-diazonio-3-methylbenzoate (2¤) was treated with 7a
in refluxing THF, 5,5-dichloro-5-cyanopentyl 2-methylphenyl
ether (8e) and 5,5-dichloro-5-cyanopentyl 3-methylphenyl
ether (8f) were obtained in 25% and 17% yields, respectively.
Thus, the reaction might proceed as follows. Carboxylate 2¤
initially extruded molecular nitrogen and carbon dioxide to
afford benzyne, which reacted with THF to give THF-stabilized
dipole intermediates (a and a¤). These dipoles abstracted
protons of dichloroacetonitrile to afford oxonium ions (b and
b¤) and dichlorocyanomethyl anion. When cations b and b¤
were finally attacked by the methyl anion, the corresponding
ethers 8e and 8f were formed (Scheme 6).
Since Nakayama et al. have reported that the reaction of
cyclic thioethers with benzyne prepared from 2-carboxyben-
zenediazonium chloride gave the corresponding ½-chloroalkyl
phenyl thioethers in moderate yields,16 we have tried the
reaction of tetrahydrothiophene (9) with triflate 1 in the
presence of chloroform to determine whether trichloroalkyl
phenyl thioether would be obtained. Treatment of thiophene 9
with triflate 1 in the presence of chloroform and CsF resulted in
the formation of 4-phenylsulfanylbut-1-ene (10) and 4-chloro-
butyl phenyl thioether (11) in 18% and 12% yields, respec-
tively. Sulfonium ion intermediate was isolated as an tetra-
phenylborate in a separate experiment (Scheme 7).
Singal et al. reported the formation of 1,2-diarylbenzazeti-
dines by the reaction of azomethines with benzyne derived
from 2,17 whereas Shou et al. have recently reported the
formation of 6-arylphenanthridines by the reaction of aromatic
aldehydes with anilines and carboxylate 2,18 suggesting that
in situ formed benzylideneanilines 12 further reacted with
benzyne to give cycloadducts. Aly et al. also reported that the
reaction of diarylazines with benzyne gave acridines.19 These
different results prompted us to compare the reactivity between
imines and cyclic ethers. Thus, we have tried the competitive
reaction of carboxylate 2 with THF and benzylideneanilines 12.
Reaction of THF with Benzyne. Recently, Feltenberger
et al. have reported the reaction of benzyne with THF at
110 °C, which led to the formation of C-O insertion product
(2,3,4,5-tetrahydrobenzo[b]oxepine).14 We have tried the reac-
tion of benzyne with THF in refluxing chloroform to inves-
tigate whether the ring expansion product would be formed as
Feltenberger stated. Treatment of carboxylate 2 with 20 equiv
of chloroform in refluxing THF resulted in the formation of
5,5,5-trichloropentyl phenyl ether (8a) and benzoic acid in
61% and 8% yields, respectively. When 2 was treated with
THF (10 equiv) in refluxing chloroform, 8a was afforded in
48% yield. When a mixture of 2 and chloroform (3 equiv) was
refluxed in THF, 8a was obtained in 32% yield along with
benzoic acid (10%). In all cases, no ring expansion product
was obtained. When triflate 1 was treated with CsF, THF, and
chloroform in acetonitrile, ether 8a was obtained in 61% yield
(Scheme 4). When tetrabutylammonium fluoride (TBAF) was
used as a fluoride source, the yield of 8a was decreased to 17%.
When carboxylate 2 was used as a benzyne precursor, active
methylenes such as dichloromethane, malononitrile, and
methyl acetoacetate did not afford the corresponding tandem
reaction products.15 When 2 was added to a refluxing solution
of 7a (5 equiv) in THF, the corresponding ether 8b was
obtained in 61% yield along with benzoic acid (8%). Similarly,
7b gave 8c in 34% yield. Interestingly, when 2 was added to a

1240 Bull. Chem. Soc. Jpn. Vol. 83, No. 10 (2010)
Reaction of Cyclic Ethers with Arynes
CH3
CH3
CH3
O
CH3
N2
-N2, -CO2
O
+
CO2
O
2'
a
a'
CH3
CH3
CH3
Cl
H
O
H
O
H
H
CCl2(CN)
CCl2(CN)
C Cl
+
O
CN
8e
CH3
b
b'
+
H
O
Cl
Cl
C
CN
8f
Scheme 6.
CCl3
R
O
S
O
CsF
rt
CH3CN
S
2
+
+ CHCl3
1 +
CHCl3
reflux, 2 h
4a
13a: 46%
9
R
CCl3
O
S
O
CsF
1
CHCl3
+
+
S
rt, 15 h
CH3CN
R
TfO
R
10 18%
13a: R = H:
86%
4a: R= H
4b: R= CH3
13b: R = CH3: 89%
+
Cl
Scheme 9.
S
11 12%
refluxing chloroform resulted in the formation of 4,4,4-
trichlorobutyl phenyl ether (13a) in 46% yield, whereas when
a solution of 4a (10 equiv) and chloroform (10 equiv) in
acetonitrile was added to a mixture of triflate 1 and CsF, ether
13a was obtained in 86% yield. Similarly, by using 3,3-
dimethyloxetane (4b) as a substrate, phenyl ether 13b was
obtained in 89% yield (Scheme 9).
Scheme 7.
R'
2
N
+
THF
CCl3
A notable difference in the reactivity toward 4a between 1
and 2 might be the difference in the formation rate of benzyne.
When carboxylate 2 was treated with refluxing chloroform,
benzyne immediately formed within a few seconds, which
reacted with oxetane to afford phenyl ether 13a in 46% yield.
Similarly, Friedman et al. reported that careful thermolysis
of 2 in hot dichloroethane resulted in the formation of
biphenylene in 30% yield, due to the relatively high rate of
benzyne formation under similar conditions.20 On the other
hand, when triflate 1 was used as a benzyne precursor, the
solubility of CsF toward acetonitrile was low, indicating that
small amount of fluoride reacted with 1 to afford benzyne
gradually. In this case, oxetane can react with benzyne more
efficiently to afford betaine intermediate, which resulted in the
formation of phenyl ether 13a in good yield. Partial complex-
ation of Cs+ with oxetane might also play an important role
for improvement of the yield of 13a.21 When a suspension
of 4b (10 equiv), THF (10 equiv), CHCl3 (10 equiv), and CsF
(3 equiv) in acetonitrile was treated with 1 at rt for 15 h, only
CHCl3
O
reflux
8a
R
12a: R = H, R' = H
12b: R = CH3, R' = Cl
Scheme 8.
When a solution of benzylideneaniline (12a) and THF
(20 equiv) in refluxing chloroform was added to carboxylate
2, phenyl ether 8a was obtained in 28% yield. Starting 12a was
recovered unchanged. When p-chlorobenzylidene-p-toluidine
(12b) was used as an imine, 8a was obtained in 21% yield
(Scheme 8). These results clearly showed that cyclic ether is
more reactive than azomethines.
Reaction of Benzyne with Oxetanes. Since 5- and 6-
membered cyclic ethers provided moderate yields of ring-
opened products, we then tried the reaction of benzyne with
oxetanes 4. Treatment of carboxylate 2 with oxetane (4a) in

K. Okuma et al.
Bull. Chem. Soc. Jpn. Vol. 83, No. 10 (2010) 1241
+
N2
O
+
O
O
CHCl3
reflux
-
CH3
CsF
CO2
+
1 + 4b
3a
2
12%
O
rt, 15 h
CH3CN
CHCl3
+
CH3
CCl3
TMS
CCl3
O
CHCl3
CsF
rt
17a
OTf
13b: 80%
1
O
CH3CN
Scheme 10.
CCl3
+ 3a +
CHCl3
+
CH3
17a'
O
CsF
1
+
+
Ph
Scheme 12.
rt
O
Ph
CH3CN
3b
14: 18%
O
TMS
CHCl3
R
O
O
R
+
3
Ph
CCl3
OTf
+
rt
1
17
15: 8%
CH3CN
CsF
+
CHCl3
O
CCl3
+
+
R
17'
3a: R= CH3
17a: R= CH3
17b: R= Et
16: 3%
3c: R= Et
3d: R= n-Bu
3e: R= n-hexyl
3f: R= CH2OPh
3g: R= CH2Cl
17c: R= n-Bu
Scheme 11.
17d: R= n-hexyl
13b was obtained in 80% yield, indicating that oxetane 4b is
more reactive than THF (Scheme 10).
Scheme 13.
Reaction of Benzyne with Epoxides. Peña et al. have
reported that the reaction of benzyne with (1,2-epoxyethyl)-
benzene (3b) gave ring expansion product, 2-phenyl-2,3-
dihydrobenzofuran (14) (32%), and other products.8 Thus, we
have tried the reaction of benzyne with epoxides to determine
whether the corresponding ring expansion products would
be formed. Treatment of 3b with carboxylate 2 in refluxing
chloroform gave a complex mixture of unidentified products.
When the reaction was carried out by using triflate 1 as a
benzyne precursor, benzofuran 14 (18%), phenyl styryl ether
(15) (8%), and phenanthrene (16) (3%) were obtained, the
result of which was quite similar to that of Peña et al. These
results suggested that intramolecular cyclization (ring expan-
sion) occurred more easily than intermolecular reaction with
chloroform by the use of 3b (Scheme 11).
We then investigated the reaction of 3a with benzyne.
Reaction of 3a with carboxylate 2 in refluxing chloroform
afforded biphenylene in 12% yield. No ring expansion product
was obtained. However, when triflate 1 was used as a benzyne
precursor, an isomeric mixture of 3,3,3-trichloro-2-methyl-
propyl phenyl ether (17a) and 3,3,3-trichloro-1-methylpropyl
phenyl ether (17a¤) was obtained (Scheme 12). When TBAF
was used as a fluoride source, phenyl ethers 17a and 17a¤ were
obtained in 26% and 10% yields, respectively. By using CsF
as a fluoride source, the yields were increased to 48 and 24%
yields, respectively. In the absence of chloroform, products
relating to 3a were not obtained.
Since CsF found to be a good fluoride source, we then
investigated the other epoxides under these conditions
(Scheme 13). Treatment of 1,2-epoxylbutane (3c) (10 equiv)
with triflate 1, CsF, and chloroform at rt resulted in the
formation of 2-trichloromethylbutyl phenyl ether (17b) and
3,3,3-trichloro-1-ethylpropyl phenyl ether (17b¤) in 39 and
26% yields, respectively (Entry 3, Table 1). Similarly, 1,2-
epoxyhexane (3d) afforded 17c and 17c¤ in 37 and 25% yields,
respectively (Entry 4). However, when 2,3-epoxypropyl phenyl
ether (3f) and 3-chloro-1,2-epoxypropane (3g) were used
as substrates, starting epoxides were recovered unchanged
(Entries 6 and 7). Thus, tandem reaction of benzyne, epoxides
3, and chloroform to give phenyl ethers 17 was achieved.
Interestingly, when 5,6-epoxy-1-hexene (3h) was used as a
substrate, a mixture of (E)- and (Z)-5,6-epoxy-1-phenyl-2-
hexene (18a) was obtained in 68% yield (E:Z = 2:1). Similarly,
allyl 2,3-epoxypropyl ether (3i) reacted with triflate 1 to give 3-
phenylprop-1-enyl 2,3-epoxylpropyl ether (18b) in 55% yield
(E:Z = 1:1), suggesting that ene reaction proceeded predom-
inantly (Scheme 14). Although a variety of ene-type reactions
of benzyne with alkenes and thiones appeared, many of them
gave [2 + 2] or [4 + 2] cycloadducts as side products.2b,22

1242 Bull. Chem. Soc. Jpn. Vol. 83, No. 10 (2010)
Reaction of Cyclic Ethers with Arynes
Table 1. Reaction of Epoxide
Chloroform
3
with Benzyne and
Products (Yield/%)
O
H3CH2C
CH2CH3
O
CH2CH3
1 + CsF
+ CHCl3
CH3CN
rt, 15 h
Entry
3
equiv
Time/h
19a: 26%
17
17¤
1
2
3
4
5
6
7
3a
3a
3c
3d
3e
3f
10
5
10
10
10
5
16
24
24
16
24
24
24
17a 48
17a 43
17b 39
17c 37
17d 19
®
17a¤ 24
17a¤ 21
17b¤ 26
17c¤ 25
Bu
O
O
CH2
CH CH2
1 + CsF
+ CHCl3
Bu
Bu
CH3CN
rt, 15 h
17d¤
6
H
CH3
®
®
3g
5
®
O
Bu
21%
O
O
19b
1 + CsF
3h
Scheme 15.
+ CHCl3
rt, 15h
18a: 68%
CH3CN
Experimental
O
O
3i
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 (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 (¤ 0.00) and
CDCl3 (¤ 77.00) for 1H- and 13C NMR. Melting points are
uncorrected.
1 + CsF
O
O
+ CHCl3
rt, 15h
CH3CN
18b: 55%
Scheme 14.
Reaction of Benzyne with Acyclic Ethers. Finally, we
have investigated the reaction of benzyne prepared from 1
and CsF with acyclic ethers. The reaction of 2 with diethyl
ether in refluxing chloroform was already reported by
Richmond and Spendel more than 4 decades ago,9 which
resulted in the formation of ethyl phenyl ether (19a) in 40%
yield, indicating that intramolecular proton abstraction of
betaine intermediate is faster. This result prompted us to
investigate the reaction of 1 with ether and chloroform to
see whether intermolecular proton abstraction of chloroform
would proceed. Treatment of 1 with diethyl ether, chloroform,
and CsF in acetonitrile at rt for 15 h resulted in the formation of
19a in 26% yield. Similarly, the reaction of 1 with dibutyl
ether, chloroform, and CsF gave butyl phenyl ether (19b) in
21% yield. No products relating to chloroform were obtained.
These results clearly showed that intramolecular hydrogen
abstraction is faster than proton abstraction of chloroform
(Scheme 15).
Materials. Benzenediazonium 2-carboxylate was synthe-
sized by the reaction of anthranilic acid with isoamylnitrite in
THF.20,23 2-(Trimethylsilyl)phenyl triflate (1) was synthesized
by a method described by Sonoda et al.24
Reaction of Triflate 1 with THP, Chloroform, and CsF in
Acetonitrile. A solution of triflate 1 (0.30 g, 1.0 mmol) in
acetonitrile (3.0 mL) was added to a suspension of CsF (0.61 g,
4.0 mmol), THP (0.86 g, 10 mmol), and chloroform (1.19 g,
10 mmol) in acetonitrile (5.0 mL). After stirring for 15 h at
rt, the reaction mixture was evaporated and water (15 mL)
was added. The reaction mixture was extracted with ether
(5 mL © 3). The combined extract was dried over sodium
sulfate, filtered, and evaporated to give pale brown oil, which
was chromatographed over silica gel by elution with hexane-
EtOAc (10:1) to give phenyl ether 5a (0.145 g, 0.52 mmol).
6,6,6-Trichlorohexyl phenyl ether (5a): colorless crystals, mp
1
50-51 °C. H NMR (CDCl3): ¤ 1.58-1.62 (m, 2H, CH2), 1.83-
1.91 (m, 4H, CH2), 2.72 (dd, 2H, J = 7.0 Hz and 7.2 Hz, CH2),
3.99 (t, 2H, J = 5.6 Hz, OCH2), 6.90 (d, 2H, J = 8.0 Hz, o-Ph),
6.95 (t, 1H, J = 7.2 Hz, p-Ph), 7.28 (dd, 2H, J = 7.2 Hz and
8.0 Hz, m-Ph). 13C NMR (CDCl3): ¤ 25.27 (CH2), 26.50 (CH2),
29.29 (CH2), 55.33 (CH2), 67.62 (OCH2), 100.30 (q-C), 114.72
(Ph), 120.91 (Ph), 129.74 (Ph), 159.22 (Ph). Anal. Found: C,
50.82; H, 4.97%. Calcd for C12H15Cl3O: C, 51.18; H, 5.37%.
Reaction of Benzenediazonium 2-Carboxylate (2) with
Conclusion
Reaction of THP, THF, and oxetanes with benzyne in the
presence of chloroform gave the corresponding ½-trichlori-
nated alkyl phenyl ethers in moderate yields. Reaction of
benzyne prepared from 1 and CsF with epoxides and chloro-
form gave phenyl ethers or ene reaction products. Thus, a
cascade approach to trichloroalkyl phenyl ethers was achieved
by using triflate 1, diazonium carboxylate 2, and cyclic ethers
in the presence of chloroform. On the other hand, reaction of
diethyl ether or dibutyl ether gave intramolecular reaction
products. This method provides a new route to ½-chlorinated
alkyl phenyl ethers.
THP and Chloroform.
To a solution of THP (0.860 g,
10.0 mmol) in chloroform (10 mL) was added carboxylate 2
(0.148 g, 1.0 mmol) in one portion. After refluxing for 2 h, the
reaction mixture was evaporated and chromatographed over
silica gel by elution with hexane-EtOAc (5:1) to afford 5a

K. Okuma et al.
Bull. Chem. Soc. Jpn. Vol. 83, No. 10 (2010) 1243
(0.112 g, 0.40 mmol). Further elution with hexane-EtOAc (1:1)
gave benzoic acid (0.009 g, 0.07 mmol), which was shown to
be identical to an authentic sample (mp 110-112 °C).
5,5,5-Trichloropentyl phenyl ether (8a): colorless oil.
1H NMR (CDCl3): ¤ 1.84-2.10 (m, 4H, CH2), 2.77 (dd, 2H,
J = 7.0 Hz and 7.2 Hz, CH2), 4.01 (t, 2H, J = 5.6 Hz, OCH2),
6.90 (d, 2H, J = 7.6 Hz, o-Ph), 6.95 (t, 1H, J = 7.2 Hz, p-Ph),
7.24-7.32 (m, 2H, m-Ph). 13C NMR (CDCl3): ¤ 24.05 (CH2),
28.65 (CH2), 55.37 (CH2), 67.64 (OCH2), 100.28 (q-C), 114.84
(Ph), 121.11 (Ph), 129.76 (Ph), 159.02 (Ph). Anal. Found: C,
49.71; H, 4.76%. Calcd for C11H13Cl3O: C, 49.38; H, 4.90%.
HRMS (EI): m/z 265.9928. Calcd for C11H1335Cl3O, 266.0032
(M+).
Reaction of Benzenediazonium 2-Carboxylate (2) with
THP and Methyl Dichloroacetate (7b). To a solution of THP
(0.860 g, 10.0 mmol) and methyl dichloroacetate (7b) (1.42 g,
10.0 mmol) in dichloromethane (10 mL) was added carboxylate
2 (0.148 g, 1.0 mmol) in one portion. After refluxing for 3 h, the
reaction mixture was evaporated and chromatographed over
silica gel by elution with hexane-EtOAc (5:1) to afford methyl
2,2-dichloro-7-phenoxyheptanoate (5c) (0.071 g, 0.34 mmol).
When a mixture of 2 (0.148 g, 1.0 mmol) and THF (0.72 g,
10.0 mmol) was refluxed in chloroform (6.0 mL), ether 8a
(0.155 g, 0.58 mmol) was isolated along with benzoic acid
(0.010 g, 0.080 mmol).
1
Compound 5c: colorless oil. H NMR (CDCl3): ¤ 1.54-1.60
(m, 2H, CH2), 1.63-1.69 (m, 2H, CH2), 1.79-1.86 (m, 2H,
CH2), 2.46 (dd, 2H, J = 7.0 Hz and 7.2 Hz, CH2), 3.89 (s, 3H,
CH3), 3.97 (t, 2H, J = 5.6 Hz, OCH2), 6.90 (d, 2H, J = 8.0 Hz,
o-Ph), 6.94 (t, 1H, J = 7.2 Hz, p-Ph), 7.28 (dd, 2H, J = 7.2 Hz
and 8.0 Hz, m-Ph). 13C NMR (CDCl3): ¤ 25.12 (CH2), 25.70
(CH2), 29.22 (CH2), 45.29 (CH2), 54.62 (OCH3), 67.64
(OCH2), 84.69 (q-C), 114.69 (Ph), 120.83 (Ph), 129.67 (Ph),
159.20 (Ph), 166.86 (C=O). Anal. Found: C, 55.14; H, 5.96%.
Calcd for C14H18Cl2O3: C, 55.10; H, 5.94%.
Reaction of Triflate 1 with THF, Chloroform, and CsF in
Acetonitrile. A solution of triflate 1 (0.298 g, 1.0 mmol) in
acetonitrile (3.0 mL) was added to a suspension of CsF
(0.304 g, 2.0 mmol), THF (0.72 g, 10 mmol), and chloroform
(1.19 g, 10 mmol) in acetonitrile (6.0 mL). After stirring for
15 h at rt, the reaction mixture was evaporated and water
(15 mL) was added. The reaction mixture was extracted with
ether (5 mL © 3). The combined extract was dried over sodium
sulfate, filtered, and evaporated to give pale brown oil, which
was chromatographed over silica gel by elution with hexane-
EtOAc (10:1) to give phenyl ether 8a (0.163 g, 0.61 mmol).
Reaction of Triflate 1 with THF, Chloroform, and Bu4NF
Phenyl ethers 5a and 5b were synthesized in a similar
manner: Compound 5a (0.113 g, 0.40 mmol).
6,6-Dichloro-6-cyanohexyl phenyl ether (5b) (0.070 g,
1
0.26 mmol): colorless oil. H NMR (CDCl3): ¤ 1.60-1.66 (m,
2H, CH2), 1.78-1.89 (m, 4H, CH2), 2.52 (dd, 2H, J = 7.0 Hz
and 7.2 Hz, CH2), 3.99 (t, 2H, J = 5.6 Hz, OCH2), 6.88 (d, 2H,
J = 8.0 Hz, o-Ph), 6.96 (t, 1H, J = 7.2 Hz, p-Ph), 7.28 (t, 2H,
J = 7.6 Hz, m-Ph). 13C NMR (CDCl3): ¤ 25.33 (CH2), 25.64
(CH2), 29.13 (CH2), 48.22 (CH2), 67.45 (OCH2), 69.09 (q-C),
114.67 (Ph), 115.77 (CN), 120.95 (Ph), 129.72 (Ph), 159.11
(Ph). Anal. Found: C, 57.30; H, 5.54; N, 5.12%. Calcd for
C13H15Cl2NO: C, 57.37; H, 5.56; N, 5.15%. MS (EI): m/z
271.2. Calcd for C13H15Cl2NO, 271.0 (M+).
Reaction of Triflate 1 with THP, Chloroform, Acetyl-
acetone, and CsF. To a suspension of acetylacetone (0.100 g,
1.0 mmol), THP (0.860 g, 10.0 mmol), chloroform (1.19 g,
10.0 mmol), and CsF (0.226 g, 1.5 mmol) in acetonitrile
(3.0 mL) was added triflate 1 (0.149 g, 0.50 mmol) in aceto-
nitrile (2.0 mL) in one portion. After stirring for 5 h at rt, the
reaction mixture was evaporated and extracted with hexane
(7 mL © 3) and CH2Cl2 (6 mL © 3). The combined extract was
chromatographed over silica gel by elution with hexane-
CH2Cl2 (1:1) to afford 1-(2-acetylphenyl)propan-2-one (6)
(0.046 g, 0.026 mmol). Compound 6: colorless oil.13 1H NMR
(CDCl3): ¤ 2.28 (s, 3H, CH3), 2.58 (s, 3H, CH3), 4.02 (s, 2H,
CH2), 7.17 (dd, 1H, J = 8.0 Hz and 1.2 Hz, Ar), 7.38 (ddd, 1H,
J = 8.0 Hz, 8.0 Hz, and 1.2 Hz, Ar), 7.47 (ddd, 1H, J = 8.0 Hz,
8.0 Hz, and 1.2 Hz, Ar), 7.84 (dd, 1H, J = 8.0 Hz and 1.2 Hz,
Ar).
in Acetonitrile.
To a solution of triflate 1 (0.149 g,
0.50 mmol), THF (2.0 mL, 24 mmol), and chloroform (1.19 g,
10 mmol) in acetonitrile (5.0 mL) was added a solution of
Bu4NF (1.0 M in THF, 1.0 mL, 1.0 mmol). After stirring for
15 h at rt, the reaction mixture was evaporated and water
(15 mL) was added. The reaction mixture was extracted with
ether (5 mL © 3). The combined extract was dried over sodium
sulfate, filtered, and evaporated to give pale brown oil, which
was chromatographed over silica gel by elution with hexane-
dichloromethane (5:1) to afford ether 8a (0.023 g, 0.086 mmol).
Reaction of Carboxylate 2 with THF and Dichloroaceto-
nitrile (7a). A suspension of carboxylate 2 (0.148 g, 1.0
mmol) in THF (3.0 mL) was added to a refluxing suspension of
dichloroacetonitrile (7a) (0.55 g, 5.0 mmol), molecular sieves
3A (0.2 g) in THF (8 mL). After refluxing for 5 h, the reaction
mixture was evaporated and the residue was chromatographed
over silica gel by elution with hexane-EtOAc (10:1 to 2:1) to
give 5,5-dichloro-5-cyanopentyl phenyl ether (8b) (0.158 g,
0.61 mmol) and benzoic acid (0.08 mmol).
5,5-Dichloro-5-cyanopentyl phenyl ether (8b) (0.167 g,
1
0.67 mmol): colorless oil. H NMR (CDCl3): ¤ 1.90-1.94 (m,
4H, CH2), 2.59 (dd, 2H, J = 7.0 Hz and 7.2 Hz, CH2), 4.02 (t,
2H, J = 5.6 Hz, OCH2), 6.89 (d, 2H, J = 7.6 Hz, o-Ph), 6.96
(t, 1H, J = 7.2 Hz, p-Ph), 7.30 (t, 2H, J = 7.6 Hz, m-Ph).
13C NMR (CDCl3): ¤ 22.66 (CH2), 28.02 (CH2), 47.80 (CH2),
66.89 (OCH2), 68.79 (q-C), 114.46 (Ph), 115.50 (CN), 120.91
(Ph), 129.52 (Ph), 158.68 (Ph). Anal. Found: C, 56.05; H, 5.07;
N, 5.43%. Calcd for C12H13Cl2NO: C, 55.83; H, 5.08; N,
5.43%. MS (EI): m/z 257.0. Calcd for C12H1335Cl2NO, 257.0
(M+).
Reaction of Carboxylate 2 with THF and Chloroform.
A mixture of carboxylate 2 (0.148 g, 1.0 mmol), chloroform
(2.38 g, 20 mmol), and molecular sieves 3A (0.2 g) in THF
(6.0 mL) was stirred for 1 h then refluxed for 2 h. The reaction
mixture was evaporated and the residue was chromatographed
over silica gel by elution with hexane-EtOAc (10:1) to give
5,5,5-trichloropentyl phenyl ether (8a) (0.163 g, 0.61 mmol).
Further elution with hexane-EtOAc (3:1) gave benzoic acid
(0.010 g, 0.080 mmol).
Methyl 2,2-dichloro-6-phenoxyhexanoate (8c) (0.099 g,
1
0.34 mmol): colorless oil. H NMR (CDCl3): ¤ 1.77-1.89 (m,
4H, CH2), 2.51 (dd, 2H, J = 7.0 Hz and 7.2 Hz, CH2), 3.89 (s,

1244 Bull. Chem. Soc. Jpn. Vol. 83, No. 10 (2010)
Reaction of Cyclic Ethers with Arynes
3H, CH3), 3.99 (t, 2H, J = 5.6 Hz, OCH2), 6.90 (d, 2H, J =
7.6 Hz, o-Ph), 6.94 (t, 1H, J = 7.2 Hz, p-Ph), 7.28 (t, 2H,
J = 7.2 Hz, m-Ph). 13C NMR (CDCl3): ¤ 22.22 (CH2), 28.77
(CH2), 45.07 (CH2), 57.64 (OCH3), 67.38 (OCH2), 84.56
(q-C), 114.72 (Ph), 120.96 (Ph), 129.69 (Ph), 159.09 (Ph),
166.81 (C=O). Anal. Found: C, 53.65; H, 5.54%. Calcd for
C13H16Cl2O3: C, 53.62; H, 5.54%. MS (EI): m/z 290.0. Calcd
for C13H1635Cl2O3, 290.0 (M+).
4-Phenoxybutyl 2,2-dichloro-1-methylethenyl ether (8d)
(0.074 g, 0.27 mmol): colorless oil. 1H NMR (CDCl3): ¤
1.83-1.96 (m, 4H, CH2), 2.03 (s, 3H, CH3), 3.88 (dd, 2H,
J = 7.0 Hz and 7.2 Hz, OCH2), 4.01 (t, 2H, J = 5.6 Hz, OCH2),
6.88 (d, 2H, J = 7.6 Hz, o-Ph), 6.94 (t, 1H, J = 7.2 Hz, p-Ph),
7.28 (t, 2H, J = 7.6 Hz, m-Ph). 13C NMR (CDCl3): ¤ 15.45
(CH3), 26.09 (CH2), 26.72 (CH2), 67.47 (OCH2), 69.38
(OCH2), 106.68 (CCl2), 114.70 (Ph), 120.87 (Ph), 129.68
(Ph), 149.27 (=C), 159.16 (Ph). Anal. Found: C, 56.77; H,
5.76%. Calcd for C13H16Cl2O2: C, 56.74; H, 5.86%.
(m, 1H, =CH), 7.05-7.40 (m, 5H, Ph). MS: Calcd for C10H12S;
164.0660. Found (M+): 164.0648. Compound 11: colorless
oil.26 1H NMR (CDCl3): ¤ 1.78 (m, 2H, CH2), 1.90 (m, 2H,
CH2), 2.92 (t, 2H, J = 7.2 Hz, CH2), 3.54 (t, 2H, J = 7.2 Hz,
CH2), 7.10-7.40 (m, 5H, Ph). MS: Calcd for C10H13ClS;
200.0426. Found: (M+) 200.0435.
Reaction of Triflate 1 with Tetrahydrothiophene (9) and
CsF: Isolation of S-Phenylthiolanium Tetraphenylborate.
To a mixture of CsF (270 mg, 1.8 mmol) and tetrahydrothio-
phene (9) (83 mg, 0.6 mmol) in acetonitrile (4 mL) was added
triflate 1 (91 mg, 0.3 mmol). After stirring for 5 h, the mixture
was evaporated to give pale yellow oil, which was filtered
through short silica gel column by elution with ethyl acetate
to give colorless oil of S-phenylthiolanium triflate (0.068 g,
1
0.21 mmol). H NMR (CDCl3): ¤ 2.35 (m, 4H, CH2), 3.70 (m,
2H, CH2), 4.18 (m, 2H, CH2), 7.58-7.70 (m, 3H, Ph), 7.81 (d,
2H, J = 7.2 Hz, Ph). 13C NMR (CDCl3): ¤ 29.36 (CH2), 48.83
(CH2), 120.92 (q, JCF = 318 Hz, CF3), 126.25, 129.99, 131.57,
134.31 (Ph). The resulting oil was dissolved in acetonitrile
(5 mL) and added to a solution of sodium tetraphenylborate
(342 mg, 1.0 mmol) in acetonitrile (6 mL). Immediately, color-
less crystals were precipitated, which were filtered and washed
with water. The residue was recrystallized from methanol-ether
to afford colorless crystals (51 mg, 0.16 mmol). Mp 199-
201 °C. Anal. Found: C, 84.07; H, 6.78%. Calcd for C34H33BS:
C, 84.29; H, 6.87%.27
Reaction of 2-Diazonio-3-methylbenzoate (2¤) with THF
and Dichloroacetonitrile (7a). A mixture of 2-diazonio-3-
methylbenzoate (2¤) (0.162 g, 1.0 mmol), dichloroacetonitrile
(7a) (1.10 g, 10 mmol), molecular sieves 3A (0.2 g) in THF
(8 mL) was stirred for 1 h then refluxed for 2 h. The reaction
mixture was evaporated and the residue was chromatographed
over silica gel by elution with hexane-EtOAc (10:1) to give
5,5-dichloro-5-cyanopentyl 2-methylphenyl ether (8e) (0.068 g,
0.25 mmol) and 5,5-dichloro-5-cyanopentyl 3-methylphenyl
ether (8f) (0.046 g, 0.17 mmol).
Reaction of Benzylideneaniline (12a) with Carboxylate 2
and THF in Refluxing Chloroform. A mixture of carbox-
ylate 2 (1.48 g, 1.0 mmol, molecular sieves 3A (0.2 g), benzyl-
ideneaniline (12a) (181 mg, 1.0 mmol), and THF (720 mg,
10 mmol) in chloroform (6 mL) was stirred for 1 h then refluxed
for 2 h. The reaction mixture was evaporated and the residue
was chromatographed over silica gel by elution with hexane-
EtOAc (10:1) to give phenyl ether 8a (74 mg, 0.28 mmol).
Reaction of Carboxylate 2 with Oxetane (4a) in Refluxing
Chloroform. A mixture of carboxylate 2 (1.48 g, 1.0 mmol),
molecular sieves 3A (0.2 g), and oxetane (4a) (0.58 g, 10 mmol)
in chloroform (6 mL) was stirred for 1 h then refluxed for 2 h.
The reaction mixture was evaporated and the residue was
chromatographed over silica gel by elution with hexane-EtOAc
(10:1) to give 4,4,4-trichlorobutyl phenyl ether (13a) (0.116 g,
1
Compound 8e: colorless oil. H NMR (CDCl3): ¤ 1.94-2.00
(m, 4H, CH2), 2.23 (s, 3H, CH3), 2.62 (dd, 2H, J = 7.0 Hz and
7.2 Hz, CH2), 4.03 (t, 2H, J = 5.6 Hz, OCH2), 6.80 (d, 1H, J =
7.6 Hz, Ar), 6.87 (t, 1H, J = 7.2 Hz, Ar), 7.14 (t, 1H, J =
7.6 Hz, Ar), 7.16 (t, 1H, J = 7.2 Hz, Ar). 13C NMR (CDCl3): ¤
16.53 (CH3), 22.98 (CH2), 28.28 (CH2), 48.04 (CH2), 67.05
(OCH2), 69.10 (q-C), 110.97 (Ph), 115.74 (CN), 120.75 (Ph),
127.00 (q-C), 127.04 (Ph), 157.02 (Ph). Anal. Found: C, 57.62;
H, 5.48; N, 5.11%. Calcd for C13H15Cl2NO: C, 57.37; H, 5.56;
N, 5.15%. MS (EI): m/z 271.1. Calcd for C13H1535Cl2NO,
271.0 (M+).
1
Compound 8f: colorless oil. H NMR (CDCl3): ¤ 1.89-1.96
(m, 4H, CH2), 2.33 (s, 3H, CH3), 2.58 (dd, 2H, J = 7.0 Hz
and 7.2 Hz, CH2), 4.00 (t, 2H, J = 5.6 Hz, OCH2), 6.69-6.79
(m, 3H, Ar), 7.17 (t, 1H, J = 7.2 Hz, Ar). 13C NMR (CDCl3): ¤
21.75 (CH3), 22.90 (CH2), 28.26 (CH2), 48.02 (CH2), 67.07
(OCH2), 69.03 (q-C), 111.51 (Ph), 115.59 (Ph), 115.73 (CN),
121.97 (Ph), 129.47 (Ph), 139.81 (Ph), 158.94 (Ph). HRMS
(EI): m/z 271.0516. Calcd for C13H1535Cl2NO, 271.0531 (M+).
Reaction of Triflate 1 with Tetrahydrothiophene (9),
Chloroform, and CsF. To a mixture of CsF (460 mg, 3.0
mmol), chloroform (241 mg, 2.0 mmol), and tetrahydrothio-
phene (9) (176 mg, 2.0 mmol) in acetonitrile (10 mL) was
added triflate 1 (303 mg, 1.0 mmol). After stirring for 6 h, the
mixture was evaporated to give colorless oily crystals, which
were chromatographed over silica gel by elution with hexane-
EtOAc (10:1) to afford 4-phenylsulfanylbut-1-ene (10) (30 mg,
0.18 mmol) and 4-chlorobutyl phenyl thioether (11) (24 mg,
0.12 mmol). Compound 10: colorless oil.25 1H NMR (CDCl3):
¤ 2.38 (m, 2H, CH2), 3.00 (t, 2H, J = 7.6 Hz, SCH2), 5.01 (d,
1H, J = 6.8 Hz, =CH), 5.06 (d, 1H, J = 14.0 Hz, =CH), 5.78
1
0.46 mmol). 13a: colorless oil. H NMR (CDCl3): ¤ 2.24-2.31
(m, 2H, CH2), 2.89-2.95 (m, 2H, CH2), 4.07 (t, 2H, J = 6.4 Hz,
OCH2), 6.89 (d, 2H, J = 7.6 Hz, o-Ph), 6.94 (t, 1H, J = 7.6 Hz,
p-Ph), 7.29 (t, 2H, J = 7.6 Hz, m-Ph). 13C NMR (CDCl3): ¤
26.92 (CH2), 52.45 (CH2), 66.24 (OCH2), 99.97 (q-C), 114.69
(Ph), 121.24 (Ph), 129.77 (Ph), 158.85 (Ph). HRMS (EI): m/z
251.9859. Calcd for C10H1135Cl3O, 251.9875 (M+).
Reaction of Triflate 1 with Oxetane (4a), Chloroform,
and CsF. To a dried mixture of triflate 1 (0.149 g, 0.50 mmol)
and CsF (0.46 g, 3.0 mmol) in acetonitrile (2.0 mL) was added a
solution of oxetane (4a) (0.580 g, 10 mmol) and chloroform
(1.19 g, 10 mmol) in acetonitrile (3.0 mL). After stirring for
15 h at rt, the reaction mixture was evaporated to give pale
brown oil, which was chromatographed over silica gel by
elution with hexane-EtOAc (10:1) to give phenyl ether 13a
(0.109 g, 0.43 mmol).
The reaction of 3,3-dimethyloxetane (4b) with triflate 1 was
carried out in a similar manner.

K. Okuma et al.
Bull. Chem. Soc. Jpn. Vol. 83, No. 10 (2010) 1245
Compound 13b (0.125 g, 0.45 mmol): pale yellow oil.
1H NMR (CDCl3): ¤ 1.31 (s, 6H, CH3), 3.06 (s, 2H, CH2),
3.82 (s, 2H, OCH2), 6.90 (d, 2H, J = 7.6 Hz, Ph), 6.95 (t, 1H,
J = 7.2 Hz, Ph), 7.29 (dd, 2H, J = 7.2 Hz and 7.6 Hz, Ph).
13C NMR (CDCl3): ¤ 25.55 (CH3), 37.30 (CH2), 60.55 (CH2),
75.53 (OCH2), 98.38 (CCl3), 114.53, 120.82, 129.42, 158.82
(Ph). HRMS (EI): m/z 280.0183. Calcd for C12H1535Cl3O,
280.0183 (M+).
Reaction of Triflate 1 with 3,3-Dimethyloxetane (4b),
THF, Chloroform, and CsF. To a dried mixture of triflate 1
(0.059 g, 0.20 mmol), 3,3-dimethyloxetane (4b) (0.172 g, 2.0
mmol), THF (0.144 g, 2.0 mmol), and CsF (0.092 g, 0.60 mmol)
in acetonitrile (3.0 mL) was added a solution of chloroform
(0.60 g, 5.0 mmol) in acetonitrile (2.0 mL). After stirring for
15 h at rt, the reaction mixture was evaporated to give pale
brown oil, which was chromatographed over silica gel by
elution with hexane-EtOAc (10:1) to give phenyl ether 13b
(0.045 g, 0.16 mmol).
Other reactions were carried out in a similar manner
(0.5 mmol of 1 was used).
Compound 17b (39%): pale yellow oil. 1H NMR (CDCl3): ¤
1.17 (t, 3H, J = 7.6 Hz, CH3), 1.80-1.95 (m, 1H, CHH), 2.10-
2.20 (m, 1H, CHH), 2.75-2.81 (m, 1H, CH), 4.15 (dd, 1H,
J = 6.4 Hz and 10.0 Hz, CHH), 4.47 (dd, 1H, J = 4.0 Hz
and 10.0 Hz, OCHH), 6.91-7.01 (m, 3H, Ph), 7.29 (t, 2H,
J = 7.6 Hz, Ph). 13C NMR (CDCl3): ¤ 12.49 (CH3), 23.94
(CH2), 60.65 (CH2), 68.25 (OCH2), 97.88 (CCl3), 114.63,
121.17, 129.53, 158.34 (Ph). HRMS (EI): m/z 266.0036. Calcd
for C11H1335Cl3O, 266.0032 (M+).
1
Compound 17b¤ (26%): pale yellow oil. H NMR (CDCl3):
¤ 1.03 (t, 3H, J = 7.2 Hz, CH3), 1.80-1.95 (m, 2H, CH2), 3.00
(dd, 1H, J = 15.2 Hz and 2.4 Hz, CHH), 3.22 (dd, 1H,
J = 15.2 Hz and 4.8 Hz, CHH), 4.68 (dd, 1H, J = 4.8 Hz
and 2.4 Hz, OCH), 6.91-6.99 (m, 3H, Ph), 7.27 (t, 2H,
J = 7.2 Hz, Ph). 13C NMR (CDCl3): ¤ 9.00 (CH3), 27.24 (CH2),
58.64 (CH2), 76.31 (OCH), 97.88 (CCl3), 116.32, 121.41,
129.79, 157.73 (Ph). HRMS (EI): m/z 266.0079. Calcd for
C11H1335Cl3O, 266.0032 (M+).
Compound 17c (37%): pale yellow oil. 1H NMR (CDCl3): ¤
0.93 (t, 3H, J = 7.6 Hz, CH3), 1.24-1.61 (m, 4H, CH2), 1.65-
1.82 (m, 1H, CHH), 2.05-2.13 (m, 1H, CHH), 2.80-2.84 (m,
1H, CH), 4.13 (dd, 1H, J = 10.0 Hz and 5.6 Hz, OCHH), 4.46
(dd, 1H, J = 10.0 Hz and 3.6 Hz, OCHH), 6.90-7.00 (m, 3H,
Ph), 7.29 (t, 2H, J = 7.6 Hz, Ph). 13C NMR (CDCl3): ¤ 14.13
(CH3), 22.89 (CH2), 30.25 (CH2), 30.76 (CH2), 59.39 (CH),
68.92 (OCH2), 103.32 (CCl3), 114.87, 121.39, 129.77, 158.59
(Ph). HRMS (EI): m/z 294.0358. Calcd for C13H1735Cl3O,
294.0345 (M+).
Compound 17c¤ (25%): pale yellow oil. 1H NMR (CDCl3): ¤
0.90 (t, 3H, J = 6.8 Hz, CH3), 1.80-1.95 (m, 4H, CH2), 1.73-
1.79 (m, 2H, CH2), 2.97 (dd, 1H, J = 15.2 Hz and 2.8 Hz,
CHH), 3.22 (dd, 1H, J = 15.2 Hz and 6.4 Hz, CHH), 4.66-4.70
(m, 1H, OCH), 6.91-6.99 (m, 3H, Ph), 7.27 (t, 2H, J = 7.6 Hz,
Ph). 13C NMR (CDCl3): ¤ 14.83 (CH3), 23.47 (CH2), 27.55
(CH2), 34.83 (CH2), 59.68 (CH2), 75.98 (OCH), 98.47 (CCl3),
116.84, 121.97, 130.40, 158.34 (Ph). HRMS (EI): m/z
294.0348. Calcd for C13H1735Cl3O, 294.0345 (M+).
Reaction of Triflate 1 with (1,2-Epoxyethyl)benzene (3b).
To a dried mixture of triflate 1 (0.298 g, 1.0 mmol) and CsF
(0.46 g, 3.0 mmol) was added a solution of epoxide 3b (1.20 g,
10 mmol) and chloroform (1.19 g, 10 mmol) in acetonitrile
(5.0 mL). After stirring for 16 h at rt, the reaction mixture was
evaporated and to it was added water (15 mL). The reaction
mixture was extracted with ether (5 mL © 3). The combined
extract was dried over sodium sulfate, filtered, and evaporated
to give a pale brown oil, which was chromatographed
over silica gel by elution with hexane-EtOAc (5:1) to give
2-phenyl-2,3-dihydrobenzofuran (14) (0.035 g, 0.18 mmol),
phenyl styryl ether (15) (0.016 g, 0.080 mmol), and phenan-
threne (16) (0.005 g, 0.03 mmol). Benzofuran 14: colorless oil.
1H NMR spectral data of 14 and 15 were identical with that
reported.8 (E) and (Z) mixture of styryl ether 15: colorless oil.28
1
Phenanthrene (16): colorless crystals, mp 98-100 °C. H NMR
spectral data of 16 were identical with an authentic sample.
Reaction of Triflate 1 with 1,2-Epoxypropane (3a),
Chloroform, and CsF.
To a dried mixture of triflate 1
(0.149 g, 0.50 mmol) and CsF (0.46 g, 3.0 mmol) was added
a solution of epoxide 3a (0.58 g, 10 mmol) and chloroform
(1.19 g, 10 mmol) in acetonitrile (3.0 mL). After stirring for
16 h at rt, the reaction mixture was evaporated to give pale
brown oily solid, which was chromatographed over silica gel
by elution with hexane-EtOAc (5:1) to give phenyl ether 17a
(0.061 g, 0.24 mmol) and 17a¤ (0.030 g, 0.12 mmol). Com-
Compound 17d (19%): pale yellow oil. 1H NMR (CDCl3): ¤
0.93 (t, 3H, J = 7.2 Hz, CH3), 1.30-1.62 (m, 8H, CH2), 1.75-
1.83 (m, 1H, CHH), 2.04-2.11 (m, 1H, CHH), 2.80-2.88 (m,
1H, CH), 4.13 (dd, 1H, J = 4.2 Hz and 10.0 Hz, OCHH), 4.46
(dd, 1H, J = 4.4 Hz and 10.0 Hz, OCHH), 6.92 (d, 2H, J =
7.6 Hz, Ph), 6.98 (t, 1H, J = 7.6 Hz, Ph), 7.30 (t, 2H, J = 7.6
Hz, Ph). HRMS (EI): m/z 322.0662. Calcd for C15H2135Cl3O,
322.0658 (M+).
1
pound 17a: colorless oil. H NMR (CDCl3): ¤ 1.66 (d, 3H,
J = 7.6 Hz, CH3), 3.00 (m, 1H, CH), 3.89 (dd, 1H, J = 7.2 Hz
and 7.6 Hz, OCHH), 4.40 (dd, 1H, J = 7.2 Hz and 6.0 Hz,
OCHH), 6.75-6.90 (m, 3H, Ph), 7.30 (dd, 2H, J = 7.2 Hz and
7.6 Hz, Ph). 13C NMR (CDCl3): ¤ 18.00 (CH3), 52.00 (CH),
69.00 (OCH2), 103.00 (CCl3), 113.00, 121.00, 129.00, 158.50
(Ph). HRMS (EI): m/z 251.9867. Calcd for C10H1135Cl3O,
251.9875 (M+). Compound 17a¤: colorless oil. 1H NMR
(CDCl3): ¤ 1.49 (d, 3H, J = 7.2 Hz, CH3), 2.95 (dd, 1H,
J = 10.5 Hz and 3.2 Hz, CHH), 3.28 (dd, 1H, J = 10.5 Hz and
3.6 Hz, CHH), 4.80 (m, 1H, OCH), 6.88-7.02 (m, 3H, Ph), 7.32
(dd, 2H, J = 7.2 Hz and 7.6 Hz, Ph). 13C NMR (CDCl3): ¤
20.05 (CH3), 61.00 (CH2), 71.00 (OCH), 96.00 (CCl3), 116.00,
121.00, 127.50, 157.00 (Ph). HRMS (EI): m/z 251.9840. Calcd
for C10H1135Cl3O, 251.9875 (M+).
1
Compound 17d¤ (6%): pale yellow oil. H NMR (CDCl3): ¤
0.88 (t, 3H, J = 7.2 Hz, CH3), 1.20-1.80 (m, 10H, CH2), 2.98
(dd, 1H, J = 3.2 Hz and 15.2 Hz, OCHH), 3.21 (dd, 1H,
J = 6.4 Hz and 15.2 Hz, OCHH), 4.72 (m, 1H, OCH), 6.89-
7.00 (m, 3H, Ph), 7.28 (t, 2H, J = 7.6 Hz, Ph). HRMS (EI): m/z
322.0668. Calcd for C12H2135Cl3O, 322.0658 (M+).
Reaction of Carboxylate 2 with 1,2-Epoxypropane (3a),
and Chloroform.
To a solution of epoxide 3a (0.58 g,
10.0 mmol) in chloroform (1.19 g, 10 mmol) was added car-
boxylate 2 (0.148 g, 1.0 mmol). After refluxing for 3 h, the reac-
tion mixture was evaporated and chromatographed over silica
gel by elution with hexane to afford biphenylene (0.018 g,

1246 Bull. Chem. Soc. Jpn. Vol. 83, No. 10 (2010)
Reaction of Cyclic Ethers with Arynes
Hard, The Chemistry of Triple-Bonded Functional Groups, Supple-
ment C2, ed by S. Patai, Wiley, Chichester, 1994, Chap. 18. d) D.
Peña, D. Pérez, E. Guitián, Angew. Chem., Int. Ed. 2006, 45, 3579.
e) H. Pellissier, M. Santelli, Tetrahedron 2003, 59, 701.
0.12 mmol), which was identical with an authentic sample. Mp
112-113 °C.
Reaction of 1 with 5,6-Epoxy-1-hexene, Chloroform, and
CsF. To a dried mixture of triflate 1 (0.149 g, 0.50 mmol) and
CsF (3.0 mmol) was added a solution of 5,6-epoxy-1-hexene
(3h) (0.49 g, 5.0 mmol) and chloroform (1.19 g, 10 mmol) in
acetonitrile (3.0 mL). After stirring for 15 h at rt, the reaction
mixture was evaporated and to it was added water (15 mL). The
reaction mixture was extracted with ether (5 mL © 3). The
combined extract was dried over sodium sulfate, filtered, and
evaporated to give pale brown oil, which was chromatographed
over silica gel by elution with hexane-EtOAc (5:1) to give
epoxide 18a (0.059 g, 0.34 mmol).
2
a) K. Okuma, T. Yamamoto, T. Shirokawa, T. Kitamura, Y.
Fujiwara, Tetrahedron Lett. 1996, 37, 8883; K. Okuma, K. Shiki,
K. Shioji, Chem. Lett. 1998, 79. b) K. Okuma, S. Sonoda, Y. Koga,
K. Shioji, J. Chem. Soc., Perkin Trans. 1 1999, 2997. c) K. Okuma,
K. Shiki, S. Sonoda, Y. Koga, K. Shioji, T. Kitamura, Y. Fujiwara,
Y. Yokomori, Bull. Chem. Soc. Jpn. 2000, 73, 155. d) T.
Shigetomi, H. Soejima, Y. Nibu, K. Shioji, K. Okuma, Y.
Yokomori, Chem.®Eur. J. 2006, 12, 7742.
3
a) H. Yoshida, Y. Honda, T. Hiyama, E. Shirakawa, Chem.
Commun. 2001, 1880. b) H. Yoshida, K. Tanino, J. Ohshita, A.
Kunai, Angew. Chem., Int. Ed. 2004, 43, 5052. c) U. K. Tambar,
B. M. Stoltz, J. Am. Chem. Soc. 2005, 127, 5340. d) W. Lin, I.
Sapountzis, P. Knochel, Angew. Chem., Int. Ed. 2005, 44, 4258.
e) Y.-Y. Yang, W.-G. Shou, Y.-G. Wang, Tetrahedron Lett. 2007,
48, 8163. f) I. Larrosa, M. I. Da Silva, P. M. Gómez, P. Hannen, E.
Ko, S. R. Lenger, S. R. Linke, A. J. P. White, D. Wilton, A. G. M.
Barrett, J. Am. Chem. Soc. 2006, 128, 14042. g) K. M. Allan, B. D.
Hong, B. M. Stoltz, Org. Biomol. Chem. 2009, 7, 4960.
1
Mixture of (E)- and (Z)-18a (2:1): pale yellow oil. H NMR
(CDCl3): ¤ 2.20-2.45 (m, 2H, CH2), 2.45-2.55 (m, 1H,
OCHH), 2.72-2.76 (m, 1H, OCHH), 2.96-2.99 (m, 1H, OCH),
3.35-3.49 (m, 2H, PhCH2), 5.40-5.62 (m, 1H, =CH), 5.68-
5.81 (m, 1H, =CH), 7.15-7.23 (m, 2H, Ph), 7.25-7.32 (m, 3H,
Ph). 13C NMR (CDCl3): ¤ 30.35 (CH2), 33.77 (PhCH2), 35.50
(CH2), 39.26 (PhCH2), 46.79 (OCH2), 46.81 (OCH2), 51.74
(OCH), 51.80 (OCH), 124.45 (=CH), 125.92 (=CH), 126.21,
126.22, 128.50, 128.61, 128.68, 128.69, 131.41, 132.47 (Ph),
140.60 (=CH), 140.70 (=CH). HRMS (EI): m/z 174.1049.
Calcd for C12H14O, 174.1045 (M+).
4
a) M. Stiles, U. Burckhardt, A. Haag, J. Org. Chem.
1962, 27, 4715. b) J. P. N. Brewer, H. Heaney, J. M. Jablonski,
Tetrahedron Lett. 1968, 9, 4455. c) H. Wasserman, J. M.
Fernandez, J. Am. Chem. Soc. 1968, 90, 5322.
1
Mixture of (E)- and (Z)-18b (1:1): colorless oil. H NMR
5
a) E. Wolthuis, B. Bouma, J. Modderman, L. Sytsma,
(CDCl3): ¤ 2.60-2.68 (m, 2H, E- and Z-OCHH), 2.81-2.84 (m,
2H, E- and Z-OCHH), 3.20 (br, 2H, E- and Z-OCH), 3.24 (d,
1H, J = 6.0 Hz, E-PhCH2), 3.45 (d, 1H, J = 6.0 Hz, Z-PhCH2),
3.65 (dd, 1H, J = 5.6 Hz and 12.0 Hz, E-CHH), 3.75 (dd,
J = 5.6 Hz and 12.0 Hz, Z-OCHH), 3.95 (dd, 1H, J = 2.8 Hz
and 12.0 Hz, E-OCHH), 4.04 (dd, 1H, J = 12.0 Hz and 2.8 Hz,
Z-OCHH), 4.61 (dt, 1H, J = 6.0 Hz and 7.2 Hz, Z-=CH), 4.98
(dt, J = 7.6 Hz and 12.8 Hz, E-=CH), 6.10 (d, 1H, J = 6.0 Hz,
Z-=CH), 6.37 (d, 1H, J = 12.8 Hz, E-=CH), 7.00-7.33
(m, 10H, 2Ph). 13C NMR (CDCl3): ¤ 31.05 (Z-PhCH2), 34.78
(E-PhCH2), 44.99 (E-CH2), 45.19 (Z-CH2), 51.01 (E-CH),
51.53 (Z-CH), 70.49 (E-OCH2), 71.67 (Z-OCH2), 104.74
(E-=CH), 107.17 (Z-=CH), 126.63, 126.91, 129.16, 129.18,
129.22, 129.27, 142.22, 142.42 (Ph), 146.24 (Z-=CH), 147.74
(E-=CH). HRMS (EI): m/z 190.0989 and 190.0988. Calcd for
C12H14O, 190.0994 (M+).
Reaction of Triflate 1 with Dibutyl Ether and Chloro-
form. To a mixture of CsF (465 mg, 3.0 mmol), chloroform
(598 mg, 5.0 mmol), and dibutyl ether (642 mg, 5.0 mmol) in
acetonitrile (10 mL) was added triflate 1 (150 mg, 0.5 mmol) in
one portion. After stirring for 15 h, the reaction mixture was
concentrated, taken up in brine (10 mL), and extracted with
ethyl acetate (7 mL © 3). The combined extract was dried over
sodium sulfate, filtered, and evaporated to give pale yellow oil,
which was chromatographed over silica gel by elution with
hexane-EtOAc (10:1) to afford butyl phenyl ether (19b)
(16 mg, 0.10 mmol), the spectral data of which was identical
with an authentic sample.
Tetrahedron Lett. 1970, 11, 407. b) S. Hayashi, N. Ishikawa, Bull.
Chem. Soc. Jpn. 1972, 45, 642.
6
R. Ghosh, E. B. Sheinin, C. L. Bell, L. Bauer, J.
Heterocycl. Chem. 1975, 12, 203.
J. Nakayama, A. Kimata, H. Taniguchi, F. Takahashi, Bull.
Chem. Soc. Jpn. 1996, 69, 2349.
S. Beltrán-Rodil, D. Peña, E. Guitián, Synlett 2007, 1308;
7
8
Also see: R. W. Hoffmann, Dehydrobenzene and Cycloalkynes,
Academic Press, New York, 1967, p. 178.
9
G. D. Richmond, W. Spendel, Tetrahedron Lett. 1973, 14,
4557.
10 M. Jaganmohan, S. Bhuvaneswari, C.-H. Cheng, Angew.
Chem., Int. Ed. 2009, 48, 391.
11 a) K. Okuma, Y. Fukuzaki, A. Nojima, K. Shioji, Y.
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Hino, A. Sou, N. Nagahora, K. Shioji, Chem. Lett. 2009, 38, 1030.
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13 H. Yoshida, M. Watanabe, J. Ohshita, A. Kunai, Chem.
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formation of acyl-acylation product as stated by Tambar and
Stoltz.3c
14 J. B. Feltenberger, R. Hayashi, Y. Tang, E. S. C. Babiash,
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15 CuBr-catalyzed C-H insertion reaction of benzyne with
acetylacetone was recently reported. See Ref. 3e.
16 J. Nakayama, K. Hoshino, M. Hoshino, Chem. Lett. 1985,
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