Cascade approach to trichloroalkyl phenyl ethers from benzyne, epoxides, and chloroform

Article abstract of DOI:10.1246/cl.2009.1030

The reaction of o-(trimethylsilyl)phenyl triflate with CsF and propene oxide in the presence of chloroform gave an isomeric mixture of trichloroalkyl phenyl ethers in 72% yield. The reaction of 1,2-epoxy-5-hexene with benzyne afforded 1,2-epoxy6-phenyl-3-

Full text of DOI:10.1246/cl.2009.1030

1030
Chemistry Letters Vol.38, No.11 (2009)
Cascade Approach to Trichloroalkyl Phenyl Ethers
from Benzyne, Epoxides, and Chloroform
Kentaro Okuma,ꢀ Haruna Hino, Ayumi Sou, Noriyoshi Nagahora, and Kosei Shioji
Department of Chemistry, Fukuoka University, Jonan-ku, Fukuoka 814-0180
(Received August 10, 2009; CL-090743; E-mail: kokuma@fukuoka-u.ac.jp)
O
The reaction of o-(trimethylsilyl)phenyl triflate with CsF
TMS
R
and propene oxide in the presence of chloroform gave an isomer-
ic mixture of trichloroalkyl phenyl ethers in 72% yield. The re-
action of 1,2-epoxy-5-hexene with benzyne afforded 1,2-epoxy-
6-phenyl-3-hexene in 66% yield. Thus, single bond insertion of
one of the C–O bonds of epoxides and ene reaction proceeded
chemoselectively.
O
R
2
CCl3
CCl3
OTf
+
rt
1
3
CH3CN
CsF
CHCl3
+
O
+
R
Arynes are very useful intermediates for their insertion abil-
ity to carbon–carbon and carbon–heteroatom double and single
bonds.1 Recently, many insertion reactions of benzyne with
Sn–Sn, Sn–C, N–C, and C–C single bonds using o-(trimethyl-
silyl)phenyl triflate (1) as a benzyne precursor have been report-
ed.2 However, there are very few reports on the reaction of ben-
zyne with epoxides 2. Ghosh et al. reported the formation of N-
(9-carbazoyl)-2-chloroaniline (1.3%) by the reaction of 2-car-
boxybenzene diazonium chloride with propene oxide (2a).3
Nakayama et al. also reported the reaction of benzyne with
1,3-benzodithiole-2-thione in the presence of propene oxide
(2a) to give tetracyclic sulfonium chloride.4 While 2a was only
used as a proton trapping reagent in these reactions, one true ex-
3'
2a: R= Me
2b: R= Et
3a: R= Me
3b: R= Et
2c: R= n-Bu
3c: R= n-Bu
2d: R= n-hexyl
3d: R= n-hexyl
Scheme 1.
Table 1. Reaction of 2 with benzyne and CHCl3
Products
(Yield/%)
30
2
equiv
Time/h
3
2a
2a
2b
2c
2d
10
5
10
10
10
16
24
24
16
24
48
43
39
37
19
24
21
26
25
6
ˇ
ample to react an epoxide with benzyne was reported by Pena
et al.5 Benzyne inserts into one of the C–O bonds of styrene
oxide to form 2,3-dihydrobenzofuran (32%) as the major
product together with five other reaction products. Very recently,
palladium-catalyzed three component coupling reaction of allyl-
ic epoxides with benzyne was reported.6 We have reported the
reaction of benzyne prepared from benzenediazonium carboxyl-
ate with THF in the presence of chloroform, which produced
novel phenyl ethers in moderate yields.7 These results prompted
us to investigate the reaction of benzyne with epoxides. Herein,
we report a simple cascade approach for the synthesis of chlori-
nated alkyl phenyl ethers from benzyne, epoxides, and chloro-
form.
and chloroform at rt resulted in the formation of 2-(trichloro-
methyl)butyl phenyl ether (3b) and 3,3,3-trichloro-1-ethylpropyl
phenyl ether (3b0) in 39 and 26% yields, respectively. Similarly,
1,2-hexene oxide (2c) or 1,2-octene oxide (2d) afforded 3c and
3c0 in 37 and 25% yields, or 3d and 3d0 in 19 and 6% yields,
respectively (Table 1).
We first investigated the reaction of 2a with benzyne. Treat-
ment of 2a with benzenediazonium carboxylate in refluxing
chloroform resulted in the formation of biphenylene in 12%
yield. No product relating to 2a was obtained. However, when
10 equivalents of 2a was treated with triflate 1, CsF, and chloro-
form in CH3CN at rt, an isomeric mixture of 3,3,3-trichloro-2-
methylpropyl phenyl ether (3a) and 3,3,3-trichloro-1-methyl-
propyl phenyl ether (3a0) was obtained in 48 and 24% yields, re-
spectively (Scheme 1). When tetrabutylammonium fluoride
(TBAF) was used as a fluoride source, phenyl ethers 3a and
3a0 were obtained in 2 and 1% yields, respectively.8 In the ab-
sence of chloroform, phenyl ethers 3 or products relating 2a
were not obtained.
When cyclopentene oxide (2e) was allowed to react with tri-
flate at rt in acetonitrile, trans-1-phenoxy-2-(trichloromethyl)-
cyclopentane (3e) was obtained in 32% yield (Scheme 2). Sim-
ilarly, cyclohexene oxide (2f) was allowed to react with benzyne
and chloroform to afford trans-1-phenoxy-2-(trichloromethyl)-
cyclohexane (3f) and trans-1-chloro-2-phenoxycyclohexane
(4) in 28 and 6% yields, respectively. These results suggested
that the intermediate for this reaction would be not carbocation
but oxonium ion. Thus, tandem reaction of benzyne, epoxides
2, and chloroform to give phenyl ethers 3 was achieved.
When deuteriochloroform was used instead of chloroform,
ortho deuterated 3a and 3a0 were obtained. Thus, the reaction
might proceed as follows: Epoxide 2 reacts with benzyne to give
the corresponding betaines a, which abstract a proton of chloro-
form to give oxonium ions b. Trichloromethyl anion attacks the
ꢀ-carbon of oxygen to afford final ethers 3 (Scheme 3).
Since CsF was found to be a good fluoride source, we then
investigated the other epoxides under these conditions. Treat-
ment of 1,2-butene oxide (2b) (10 equiv) with triflate 1, CsF,
Copyright Ó 2009 The Chemical Society of Japan

Chemistry Letters Vol.38, No.11 (2009)
1031
References and Notes
O
CCl3
1
a) H. Yoshida, M. Watanabe, H. Fukushima, J. Ohshita, A.
Kunai, Org. Lett. 2004, 6, 4049. b) K. Okuma, K. Shiki, K.
Shioji, Chem. Lett. 1998, 79. c) K. Okuma, A. Okada, Y.
Koga, Y. Yokomori, J. Am. Chem. Soc. 2001, 123, 7166;
O
1
2e: n = 0
2f: n = 1
+
CsF
n
n
rt
CH3CN
3e: n = 0
3f: n = 1
ˇ
´
´
For a recent review: D. Pena, D. Perez, E. Guitian, Angew.
Chem., Int. Ed. 2006, 45, 3579.
+
CHCl3
Cl
2
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) H. Yoshida, M. Watanabe, T.
Morishita, J. Ohshita, A. Kunai, Chem. Commun. 2007,
1505. f) Y.-Y. Yang, W.-G. Shou, Y.-G. Wang, Tetrahedron
Lett. 2007, 48, 8163. g) I. Larrosa, M. I. Da Silva, P. M.
Gomez, 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.
O
+
4
Scheme 2.
O
O
R
a
R
2
3
4
5
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.
CHCl3
O
R
´
ˇ
´
S. Beltran-Rodil, D. Pena, E. Guitian, Synlett 2007, 1308;
also see: R. W. Hoffmann, Dehydrobenzene and Cyclo-
alynes, Academic Press, New York, 1967, p. 178.
3
H
b
CCl3
6
7
8
M. Jeganmohan, S. Bhuvaneswari, C.-H. Cheng, Angew.
Chem., Int. Ed. 2009, 48, 391.
K. Okuma, K. Fukuzaki, A. Nojima, K. Shioji, Y. Yokomori,
Tetrahedron Lett. 2008, 49, 3063.
Scheme 3.
O
Typical reaction: To a dried mixture of triflate 1 (1.0 mmol)
and CsF (3.0 mmol) was added a solution of propene oxide
(2a) (10 mmol) and chloroform (10 mmol) in acetonitrile
(3.0 mL). After stirring for 16 h at rt, the reaction mixture
was evaporated and added water (15 mL). The reaction mix-
ture was extracted with ether (5 mL ꢁ 3). The combined ex-
tract was dried over sodium sulfate, filtered, and evaporated
to give a pale brown oil, which was chromatographed over
silica gel by elution with hexane:ethyl acetate (5:1) to give
phenyl ether 3a (0.48 mmol) and 3a0 (0.24 mmol). Com-
+
1
1
CsF
O
2g
+ CHCl3
rt
5a
CH3CN
O
O
+
CsF
2h
O
O
rt
1
+
CHCl3
pound 3a: colorless oil. H NMR (CDCl3): ꢁ 1.53 (d, 3H,
5b
CH3CN
J ¼ 5:6 Hz, CH3), 3.06 (m, 1H, CH), 3.94 (dd, 1H, J ¼ 9:2
and 8.8 Hz, OCHH), 4.58 (dd, 1H, J ¼ 9:2 and 3.2 Hz,
OCHH), 6.85–6.99 (m, 3H, Ph), 7.30 (t, 2H, J ¼ 7:6 Hz,
Ph). 13C NMR (CDCl3): ꢁ 15.33 (CH3), 54.50 (CH), 69.39
(OCH2), 103.20 (CCl3), 114.85, 121.48, 129.81, 158.56 (Ph).
HRMS: (m=z): Calcd for C10H11Cl3O; 251.9875. Found
251.9867 (Mþ). Compound 3a0: colorless oil. 1H NMR
(CDCl3): ꢁ 1.46 (d, 3H, J ¼ 5:6 Hz, CH3), 2.93 (dd, 1H,
J ¼ 15:2 and 3.6 Hz, CHH), 3.30 (dd, 1H, J ¼ 15:2 and
6.0 Hz, CHH), 4.80 (m, 1H, OCH), 6.88–7.02 (m, 3H, Ph),
7.32 (dd, 2H, J ¼ 8:0 and 7.6 Hz, Ph). 13C NMR (CDCl3):
ꢁ 20.87 (CH3), 60.95 (CH2), 71.78 (OCH), 97.60 (CCl3),
116.32, 121.53, 129.84, 157.35 (Ph). HRMS: (m=z): Calcd
for C10H11Cl3O; 251.9875. Found 251.9840 (Mþ).
Scheme 4.
Interestingly, when 1,2-epoxy-5-hexene (2g) was used as
a substrate, a mixture of (E)- and (Z)-1,2-epoxyy-6-phenyl-4-
hexene (5a) was obtained in 68% yield (E:Z = 65:35). Similar-
ly, allyl glycidyl ether (2h) reacted with triflate to give 3-phenyl-
prop-1-enyl glycidyl ether (5b) in 65% yield (E:Z = 60:40),
suggesting that the ene reaction proceeded predominantly
(Scheme 4). Previously, many authors reported the ene reaction
of benzyne with alkenes, however many gave [2 þ 2] or [4 þ 2]
adducts as side products.9 The present reaction provided ene re-
action products exclusively.
Thus, a cascade approach to trichloroalkyl phenyl ethers
from epoxides, benzyne, and chloroform was achieved. The
presents result opened a door to the reaction of benzyne with ep-
oxides.
9
a) G. Friedrichs, E. Goos, J. Gripp, H. Nicken, J.-B.
Schonborn, H. Vogel, F. Temps, Z. Phys. Chem. 2009,
223, 387. b) L. Lombardo, D. Wege, Tetrahedron 1974,
30, 3945.
Published on the web (Advance View) October 3, 2009; doi:10.1246/cl.2009.1030