Reaction of benzyne with styrene oxide: Insertion of arynes into a C-O bond of epoxides

Article abstract of DOI:10.1055/s-2007-977460

Benzyne inserts into one of the C-O bonds of styrene oxide to form a dihydrobenzofuran as the major product together with five other reaction products. A detailed study of the reaction mixture clarified an intriguing forty-year-old personal communication from Stiles and Haag. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-977460

1308
LETTER
Reaction of Benzyne with Styrene Oxide: Insertion of Arynes into a C–O Bond
of Epoxides
R
eactionof Be
a
nzyne
w
ith
n
Styrene
O
x
d
ide ra Beltrán-Rodil,1 Diego Peña,* Enrique Guitián
Departamento de Química Orgánica, Facultad de Química, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain
Fax +34(98)1591014; E-mail: qodpena@usc.es
Received 28 December 2006
Dedicated to Professor Reinhard W. Hoffmann for his comprehensive and fascinating monograph on aryne chemistry
O
O
Abstract: Benzyne inserts into one of the C–O bonds of styrene
R
+
oxide to form a dihydrobenzofuran as the major product together
with five other reaction products. A detailed study of the reaction
mixture clarified an intriguing forty-year-old personal communica-
tion from Stiles and Haag.
R
1
3
4
Scheme 2
Key words: arynes, epoxides, furans, insertions, ring expansion
The reaction of triflate 5 with styrene oxide (6, 2 equiv) in
the presence of CsF (2 equiv) in acetonitrile at room tem-
perature led to the formation of 2,3-dihydro-3-phenyl-
benzofuran (7) in 32% yield (Scheme 3).9,10 As expected,
this compound is the major product isolated by Stiles and
Haag on using a different benzyne precursor.8
In recent years, the discovery of a method for the genera-
tion of arynes under mild reaction conditions2 has stimu-
lated the development of formal insertions of arynes into
element–element sigma bonds (Scheme 1).3 This method-
ology has a promising future as a means of preparing
complex ortho-disubstituted arenes.4
OTf
O
O
O
CsF
Ph
Ph
+
X
MeCN
r.t., 24 h
X
+
TMS
6
8
7
5
Ph
Y
Y
32% yield
not detected
1
2
Scheme 3
Scheme 1
Although regioisomeric dihydrobenzofuran 8 was not
detected in the reaction mixture, it was possible to isolate
compounds 9–12 in varying yields (Figures 1 and 2).
Interestingly, the mixture (E/Z)-9 was also obtained by
Stiles et al.8
In 1962, Stiles and coworkers reported the first insertion
of benzyne into a C–O bond. The reaction of ethoxyacet-
ylene with benzyne, generated by thermal decomposition
of benzenediazonium-2-carboxylate, led to a 37% yield of
2-ethoxyphenylacetylene.5 Although this is the first and
only paper published to date on the formal insertion of an
aryne into a C–O sigma bond,6 a personal communication
by the same group, cited in Hoffmann’s seminal mono-
graph on aryne chemistry,7 disclosed the reaction of
benzyne with styrene oxide leading to the formation of a
dihydrobenzofuran in 9% yield.8 This ring-expansion
reaction involved the formal insertion of an aryne into a
C–O sigma bond of an epoxide (Scheme 2). Intriguingly,
in the last forty years no further reference has been made
to this reaction. Herein we report our findings related to
this transformation, using o-(trimethylsilyl)phenyl triflate
(5) as the benzyne precursor. Our results confirm the
personal communication by Stiles and Haag.
O
Ph
Product
Yield (%)
(E/Z)-9 13 (3.3:1)
(E/Z)-9
10
10
11
12
15
O
17
5
11
12
Figure 1
The formation of compound 7 and (E/Z)-9 can be
explained in terms of nucleophilic attack by the epoxide
on benzyne (Scheme 4). Subsequent ring opening of the
epoxide would give the zwitterion 14 which could evolve
in two ways either by collapsing to afford dihydrobenzo-
furan 7 or by intramolecular proton transfer to form the
mixture of olefins (E/Z)-9.11 The regioselective formation
of dihydrobenzofuran 7 as opposed to 8 could be due to
SYNLETT 2007, No. 8, pp 1308–1310
1
6.
0
5.
2
0
0
7
Advanced online publication: 08.05.2007
DOI: 10.1055/s-2007-977460; Art ID: D40206ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Reaction of Benzyne with Styrene Oxide
1309
As expected, analysis of this reaction by GC/MS
(Figure 3) and subsequent comparison with the reaction
using triflate 5 (Figure 2), suggested the formation of the
two possible isomeric dihydrobenzofurans 17a,b in a 1:1
ratio. In addition, the presence of two peaks (1:1 ratio)
corresponding to two isomeric methylphenanthrenes
(18a,b), and three peaks (1:2:1 ratio) corresponding to
three isomeric ditolyl ethers (19a–c), suggested that these
products incorporate one and two molecules of aryne,
respectively.
Figure 2 GC/MS analysis of the reaction of triflate 5 with epoxide 6
the selective ring opening of intermediate 13 to afford
zwitterion 14, in which the positive charge is in the more
stable benzylic position.12
O
O
7
Ph
Ph
1
6
+
(E/Z)-9
13
14
Figure 3 GC/MS analysis of the reaction of triflate 16 with
epoxide 6
Scheme 4
The isolation of byproducts 10–12 can be explained on the
basis of classical aryne chemistry. Biphenylene (12) could
be obtained by benzyne dimerization7 and its isolation is
considered as an indication of the presence of this inter-
mediate. The Diels–Alder reaction of phenoxystyrenes
(E/Z)-9 with benzyne could give rise to intermediate 15,
which could evolve by elimination to afford phenanthrene
(10) together with phenoxide (Scheme 5). The reaction of
benzyne with phenoxide would subsequently lead to the
formation of diphenyl ether (11).
To further support the mechanism depicted in Scheme 5,
we performed the reaction of triflate 16 with olefin (E)-9
(Scheme 7). As expected, analysis of this reaction by GC/
MS indicated the presence of two isomeric methylphenan-
threnes (18a,b, 1:1 ratio) and two isomeric phenyl tolyl
ethers (21a,b, 1:1 ratio).
X
X
Y
O
CsF
+
16 + (E)-9
Y
OPh
OPh
18a, X = H, Y = Me
18b, X = Me, Y = H
21a, X = H, Y = Me
21b, X = Me, Y = H
PhO–
+
10
Scheme 7
1
H
1
In conclusion, the insertion of benzyne into a C–O sigma
bond of styrene oxide has been studied in detail and the re-
sults support the statement of a forty-year-old personal
communication.8 Although this reaction has not yet been
optimized from a synthetic point of view, it is the first
example of the insertion of arynes into a sigma bond of
strained cyclic molecules.13
F–
11
9
15
Scheme 5
In order to confirm a mechanism in which benzyne is an
intermediate, we performed the reaction using triflate 16
(Scheme 6), which is a precursor of the asymmetric aryne
4-methylbenzyne.2b
Acknowledgment
X
O
Financial support from the Spanish Ministry of Education and
Science (MEC, CTQ2004-05752) and from FEDER and the Xunta
de Galicia (DXID, 05PXIC20904PN) is gratefully acknowledged.
Dr. D. Peña also thanks the MEC for the award of a Ramón y Cajal
research contract. We thank Prof. Dolores Pérez for helpful discus-
sions.
OTf
O
CsF
+
Ph
Y
MeCN
r.t., 24 h
TMS
Ph
16
6
17a, X = H, Y = Me
17b, X = Me, Y = H
Scheme 6
Synlett 2007, No. 8, 1308–1310 © Thieme Stuttgart · New York

1310
S. Beltrán-Rodil et al.
LETTER
mmol), styrene oxide (6, 228 mL, 2.00 mmol) and CsF (304
mg, 2.00 mmol) was stirred in MeCN (15 mL) for 24 h. The
resulting mixture was concentrated under reduced pressure
and the residue was purifed by column chromatography
(SiO2; CH2Cl2–hexane, 1:99 to 50:50) to afford compounds
7 and 9–12. All of the products gave satisfactory NMR (1H,
13C) and MS. Selected data for 7:10 1H NMR (250 MHz,
CDCl3): d = 7.36–7.14 (m, 6 H), 7.02 (m, 1 H), 6.90–6.82
(m, 2 H), 4.90 (dd, J = 9.4, 8.7 Hz, 1 H), 4.67 (dd, J = 9.2,
7.3 Hz, 1 H), 4.42 (dd, J = 8.6, 7.3 Hz, 1 H); 13C NMR (62.8
MHz, CDCl3): d = 160.2 (C), 142.8 (C), 130.5 (C), 128.8
(2CH), 128.5 (CH), 127.8 (2CH), 127.0 (CH), 125.2 (CH),
120.8 (CH), 109.6 (CH), 79.1 (CH2), 48.5 (CH); MS (EI):
m/z (%): 196 (100). GC/MS were performed on an Agilent
6890N/5973 inert instrument with a HP–5MS capillary
column (25 mm × 30 m × 25 mm; 70 to 300 °C, 30 °C/min).
(10) Arnold, D. R.; Fahie, B. J.; Lamont, L. J.; Wierzchowski, J.;
Young, K. M. Can. J. Chem. 1987, 65, 2734.
(11) This mechanism is the same as that proposed in reference 8.
(12) The use of other epoxides such us cyclohexene oxide or
propylene oxide did not afford the corresponding insertion
products.
(13) There is only one example of the insertion of arynes into
element–element sigma bonds of cyclic molecules, in
particular five- and six-membered-ring disilanes, see:
Yoshida, H.; Ikadai, J.; Shudo, M.; Ohshita, J.; Kunai, A.
Organometallics 2005, 24, 156.
References and Notes
(1) Current address: Department of Chemistry, University of
York, Heslington, York YO10 5DD, UK.
(2) (a) Himeshima, Y.; Sonoda, T.; Kobayashi, H. Chem. Lett.
1983, 1211. (b) Peña, D.; Cobas, A.; Pérez, D.; Guitián, E.
Synthesis 2002, 1454.
(3) For some recent representative examples, see: (a) Yoshida,
H.; Tanino, K.; Ohshita, J.; Kunai, A. Angew. Chem. Int. Ed.
2004, 43, 5052. (b) Tambar, U. K.; Stoltz, B. M. J. Am.
Chem. Soc. 2005, 127, 5340. (c) Liu, Z.; Larock, R. C. J.
Am. Chem. Soc. 2005, 127, 13112. (d) Lin, W.; Sapountzis,
I.; Knochel, P. Angew. Chem. Int. Ed. 2005, 44, 4258.
(4) For a recent highlight, see: Peña, D.; Pérez, D.; Guitián, E.
Angew. Chem. Int. Ed. 2006, 45, 3579.
(5) Stiles, M.; Burckhardt, U.; Haag, A. J. Org. Chem. 1962, 27,
4715.
(6) Recently Yoshida et al. reported the insertion of arynes into
the C=O double bond of aldehydes: Yoshida, H.; Watanabe,
M.; Fukushima, H.; Ohshita, J.; Kunai, A. Org. Lett. 2004,
6, 4049.
(7) Hoffmann, R. W. Dehydrobenzene and Cycloalkynes;
Academic Press: New York, 1967.
(8) Stiles, M.; Haag, A. personal communication in reference 7
(page 178).
(9) General procedure for the reaction of triflate 5 with styrene
oxide (6): In a Schlenk tube equipped with a septum and a
magnetic stirring bar, a mixture of triflate 5 (242 mL, 1.00
Synlett 2007, No. 8, 1308–1310 © Thieme Stuttgart · New York

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