An efficient procedure for the synthesis of ortho-trialkylsilylaryl triflates: Easy access to precursors of functionalized arynes

Article abstract of DOI:10.1055/s-2002-33110

o-Trialkylsilylaryl triflates which are useful aryne precursors are prepared from o-bromophenols by an efficient, one-pot procedure involving O-silylation, metal-halogen exchange, O- to C-silyl migration, and entrapment of the phenoxide with triflic anhydride.

Full text of DOI:10.1055/s-2002-33110

1454
PRACTICAL SYNTHETIC PROCEDURES
An Efficient Procedure for the Synthesis of ortho-Trialkylsilylaryl Triflates:
Easy Access to Precursors of Functionalized Arynes
S
ynthesis of ortho
-
i
Trialky
e
lsilylaryl
T
g
riflates o Peña, Agustín Cobas, Dolores Pérez,* Enrique Guitián*
Departamento de Química Orgánica, Universidad de Santiago de Compostela
and Unidad Asociada al CSIC, 15706 Santiago de Compostela, Spain
Fax +34(981)591014; E-mail: goenrgui@usc.es
PSP
Received 3 April 2002
Dedicated to Prof. Ekkehard Winterfeldt on the occasion of his 70th birthday
No
3
Abstract: o-Trialkylsilylaryl triflates, which are useful aryne precursors, are prepared from o-bromophenols by an efficient, one-pot pro-
cedure involving O-silylation, metal–halogen exchange, O- to C-silyl migration, and entrapment of the phenoxide with triflic anhydride.
Key words: silylation, triflates, arynes, metalations
Scheme 1
Arynes,1 once considered as mere chemical curiosities, The use of 2-trimethylsilylphenyl triflate (2a)5 as a ben-
are now currently common reaction partners in organic zyne precursor was first reported in 1983 by Himeshima
synthesis. Their rich chemistry, in particular their highly et al.,4a who obtained 2a in 86% yield from (o-trimethyl-
electrophilic character and their reactivity as dienophiles silylphenoxy)trimethylsilane (preparation of the latter in
in Diels–Alder reactions, has been exploited in the synthe- two steps from an o-halophenol had been described
sis of natural products and in the construction of complex previously6). Our modified procedure for the synthesis of
unnatural organic molecules.1b Our group2 and others3 2a involves quantitative silylation of 2-bromophenol (1a)
have described the use of arynes in metal-catalyzed cy- by treatment with hexamethyldisilazane (HMDS) at 80 °C
cloadditions, which is a convenient route to polycyclic ar- (with or without solvent),7 and reaction of a solution of the
omatic systems.
crude product in THF with one equivalent of BuLi at –100
°C, followed by addition of one equivalent of Tf2O and
quenching at low temperature (Scheme 1). After column
chromatography, triflate 2a is isolated in 92% yield from
1a (Table 1, entry 1). This transformation is extremely
simple from the experimental point of view since the first
step, silylation, does not require aqueous work up or puri-
fication of the product, and in the second step a relatively
complex transformation is achieved in a single operation.
One of the limitations of the use of arynes in synthesis is
the scarcity of convenient methods for their generation
under mild reaction conditions, although this problem has
been partially overcome with the development of novel
generation procedures.4 A hitherto more intractable prob-
lem has been the limited availability of precursors for sub-
stituted benzynes or polycyclic arynes, which have often
had to be prepared by multistep procedures affording very
moderate overall yields. In this article we describe a The mechanism of the process, shown in Scheme 2, in-
straightforward general method for the synthesis of func- volves conversion of (o-bromophenoxy)trimethylsilane
tionalized o-trimethylsilylaryl triflates, from which the (3) to the carbanion 4 by metal–halogen exchange, migra-
corresponding arynes can be generated by fluoride-in- tion of the trimethylsilyl group from oxygen to carbon,
duced 1,2-elimination under mild conditions. Further- and trapping of the resulting lithium phenoxide 5 with tri-
more, these highly functionalized arenes can be useful in flic anhydride.6,8,9 Careful control of the reaction temper-
other kinds of transformations, such as palladium-cata- ature is crucial for the success of this transformation, as a
lyzed cross-coupling reactions.
higher temperature favors nucleophilic attack by the base
on the silicon atom of 3 and also promotes polymerization
of THF in the presence of trace amounts of triflic acid.
Synthesis 2002, No. 10, 30 07 2002. Article Identifier:
1437-210X,E;2002,0,10,1454,1458,ftx,en;Z06002SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

PRACTICAL SYNTHETIC PROCEDURES
Synthesis of ortho-Trialkylsilylaryl Triflates
1455
Scheme 3
Similarly the use of o-bromohydroxyarenes 9a–d2d,11
(Table 2) as substrates gave good to excellent yields of tri-
flates 10–13 (Figure and Table 2), which have been used
by our group as precursors of the corresponding polycy-
clic arynes.2d
Scheme 2
Table 1 Synthesis of o-Trimethylsilylphenyl Triflates 2a
Entry Bromo- R3 R4
phenol
R5 R6
Methodb Product Yield
(%)c
1
2
3
4
5
6
1a
1b
1c
1d
1e
1f
H
H
H
H
H
H
H
H
H
H
H
F
H
A
A
A
B
B
B
2a
2b
2c
2d
2e
2f
92
81
66
69
78
80
H
OMe
H
Figure The structures of polycyclic o-trimethylsilylaryl triflates
10–13 prepared
Me
Me
F
Br
H
Table 2 Synthesis of Polycyclic o-Trimethylsilylaryl Triflatesa,b
Entry o-Bromohydroxyarene (9)
Product Yield (%)c
Cl
H
H
a See Scheme 1.
1
2
3
4
1-bromo-2-naphthol (9a)
10
11
12
13
87
82
79
65
b Method A: 1. HMDS (0.6 equiv); 80 °C, 45 min. 2. i) BuLi (1.1
equiv)/THF; –100 to –80 °C, 20 min. ii) Tf2O (1.2 equiv); –100 to
–80 °C, 20 min.Method B: 1. HMDS (1.1 equiv)/THF; reflux, 90 min.
2. as in Method A.
2-bromo-1-phenanthrol (9b)
3-bromo-4-phenanthrol (9c)
10-bromo-9-phenanthrol (9d)
c Yield of isolated products.
a See Scheme 3.
b Reaction conditions: 1. HMDS (1.1 equiv)/THF, reflux, 90 min. 2. i)
BuLi (1.1 equiv)/THF, –100 to –80 °C, 20 min. ii) Tf2O (1.2 equiv);
–100 to –80 °C, 20 min.
The same experimental procedure was successfully em-
ployed for the synthesis of triflates 2b–f (Table 1), which
as previously reported,2,3are precursors of the correspond-
ing functionalized arynes 6. We found that our one-pot
transformation of o-bromophenols 1 to o-trimethylsilylar-
yl triflates 2 was compatible with a variety of substitution
patterns and with the presence of either electron-donating
groups (entries 2 and 3) or electron-withdrawing groups
(entries 5 and 6) on the benzene ring. Note that the selec-
tivity of the metal–halogen exchange step allows prepara-
tion of the halogenated benzyne precursors 2d–f.
Bromophenols 1a and 1c–f are commercially available,
while 2-bromo-6-methoxyphenol (1b) is easily prepared
by regioselective bromination of 2-methoxyphenol.10
c Yield of isolated products.
We have also employed a similar strategy for the prepara-
tion of a novel benzyne precursor, 2-(tert-butyldimethyls-
ilyl)phenyl triflate (15). In this case, formation of the
intermediate silyl ether 14 was achieved in quantitative
yield by reaction of 1 with tert-butyldimethylsilyl chlor-
ide and imidazole. Sequential treatment of 14 with BuLi
and Tf2O under the reaction conditions previously de-
scribed then resulted in metal–halogen exchange, migra-
tion of the trialkylsilyl group and trapping of the resulting
phenoxide, giving 15 in 85% yield (Scheme 4).
In the course of one of our research projects we have also
found that o-trimethylsilylaryl triflates containing more
complex functional groups, such as 8 (Scheme 3), can
likewise be efficiently obtained from the corresponding
bromophenols (in this case 7) under the same reaction
conditions as above.
Scheme 4
Synthesis 2002, No. 10, 1454–1458 ISSN 0039-7881 © Thieme Stuttgart · New York

1456
D. Peña et al.
PRACTICAL SYNTHETIC PROCEDURES
stirring was continued for 20 min while the temperature reached to
–80 °C. Cold sat. aq NaHCO3 was added, the phases were separated
and the aqueous layer was extracted with Et2O. The combined or-
ganic layers were dried (Na2SO4), filtered, and concentrated under
reduced pressure. Purification of the residue by column chromatog-
raphy (SiO2) afforded the corresponding triflate.
To prove that this new compound can be used as a ben-
zyne precursor, we reacted a solution of 15 in acetonitrile
with Bu4NF in the presence of furan, obtaining the Diels–
Alder aduct 16 in 56% yield after stirring at room temper-
ature for 14 hours. Reaction of triflate 15 under the typical
conditions previously established by our group for the cy-
clotrimerization of benzyne [2 equiv CsF, 0.1 equiv
Pd(PPh3)4, MeCN]2a resulted in very slow reaction rates,
with a 60% recovery of the starting material 15 after stir-
ring at room temperature for four days; however the use
of Bu4NF as a source of fluoride ion afforded, after 14
hours, a 45% yield of triphenylene 17 (Scheme 5). Com-
parison of these results with those previously reported for
similar experiments using 2-trimethylsilylphenyl triflate
(2a)2a,4a suggests that benzyne can be generated with sim-
ilar efficiency from both precursors, although triflate 15 is
less reactive. Compound 15 thus provides a novel alterna-
tive for processes in which slow generation of benzyne is
desirable.
Method B: A mixture of o-bromohydroxyarene (1.0 equiv) and
HMDS (2.2–2.4) in THF (0.3 M) was stirred under reflux for 90 min
in a flask provided with a condenser and a CaCl2 tube. The solvent
was evaporated under reduced pressure and the residue was subject-
ed to vacuum to remove excess NH3 and unreacted HMDS. After 1H
NMR confirmation of the quantitative formation of the correspond-
ing silyl ether, the preparation of the triflate was continued as in
Method A.
2-Trimethylsilylphenyl Trifluoromethanesulfonate (2a)4a
Method A was followed using 2-bromophenol (1a; 4.0 mL, 34.5
mmol), HMDS (4.3 mL, 20.7 mmol), BuLi (15.2 mL, 2.38 M, 36.2
mmol), Tf2O (7.0 mL, 41.4 mmol) and THF (230 mL). Column
chromatography (SiO2, Et2O–hexane, 1:99) afforded 2a (9.5 g,
92%) as a colorless oil.
2-Methoxy-6-trimethylsilylphenyl Trifluoromethanesulfonate
(2b)
Method A was followed using 2-bromo-6-methoxyphenol10 (1b;
0.60 g, 2.95 mmol), HMDS (0.5 mL, 2.36 mmol), BuLi (1.7 mL, 1.9
M, 3.23 mmol), Tf2O (0.62 mL, 3.68 mmol) and THF (15 mL). Col-
umn chromatography (SiO2, EtOAc/hexane, 1:4) afforded 2b
(0.773 g, 81%) as a colorless oil.
1H NMR (CDCl3): = 7.32 (t, J = 7.7 Hz, 1 H), 7.12 (dd, J = 7.4,
1.5 Hz, 1 H), 7.05 (dd, J = 8.1, 1.5 Hz, 1 H), 3.87 (s, 3 H), 0.42 (s,
9 H).
13C NMR (CDCl3): = 150.1, 143.2, 135.1, 128.7, 126.7, 119.0 (q,
J = 320 Hz, CF3), 114.0, 55.5, –0.6.
Scheme 5
To sum up, we have developed a straightforward general
method for the efficient preparation of o-trialkylsilylaryl
triflates from readily available o-bromophenols. The
transformation is extremely simple from the experimental
point of view, requiring only one aqueous workup and one
purification step, and is of wide applicability to the syn-
thesis of precursors of substituted and polycyclic arynes.
MS: m/z (%) = 313 (M+ – 15, 5), 180 (41), 58 (100).
4-Methyl-2-trimethylsilylphenyl Trifluoromethanesulfonate
(2c)3c
Method A was followed using 2-bromo-4-methylphenol (1c; 1.21
mL, 10 mmol), HMDS (1.24 mL, 6.0 mmol), BuLi (5.39 mL, 2.04
M, 11 mmol), Tf2O (2.1 mL, 12.5 mmol) and THF (70 mL). Column
chromatography (SiO2, hexane) afforded 2c (2.06 g, 66%) as a col-
orless oil.
All reactions were performed under argon, unless otherwise noted.
Solvents were dried by distillation from a drying agent: THF from
Na/benzophenone; toluene from Na; MeCN from CaH2. 1H and 13
C
NMR spectra were recorded at 250.13 and 62.83 MHz, respectively.
LR and HR mass spectra were recorded using EI (70 eV) or FAB.
TLC was performed on Merck silica gel 60 F254; chromatograms
were visualized with UV light (254 and 360 nm), phosphomolybdic
acid, and/or p-anisaldehyde. Column chromatography was per-
formed on Merck silica gel 60 (ASTM 230–400 mesh). Hexameth-
2-Bromo-4-methyl-6-trimethylsilylphenyl Trifluoromethane-
sulfonate (2d)
Method B was followed using 2,6-dibromo-6-methylphenol (1d;
2.66 g, 10 mmol) and HMDS (2.27 mL, 11 mmol) in THF (33 mL);
and then BuLi (4.27 mL, 2.46 M, 10.5 mmol) and Tf2O (2.0 mL, 12
mmol) in THF (60 mL). Column chromatography (SiO2, hexane)
afforded 2d (2.69 g, 69%) as a colorless oil.
1H NMR (CDCl3): = 7.50 (br s, 1 H), 7.31 (br s, 1 H), 2.37 (s, 3
H), 0.42 (s, 9 H).
yldisilazane
(HMDS)
was
purchased
from
Merck;
trifluoromethanesulfonic anhydride from Strem, and other commer-
cially available reagents from Aldrich Chemical Co. All purchased
reagents were used without further purification.
13C NMR (CDCl3): = 146.7, 139.4, 137.0, 136.3, 136.1, 118.7 (q,
J = 320 Hz, CF3), 116.0, 20.5, 0.0.
ortho-Trialkylsilylaryl Triflates; General Procedures
Method A: A mixture of o-bromohydroxyarene (1.0 equiv) and
HMDS (1.2–1.6 equiv) was stirred at 80 °C for 45 min in a flask
protected with a CaCl2 tube. Excess NH3 and unreacted HMDS
were then removed under vacuum, and after 1H NMR confirmation
of the quantitative formation of the corresponding silyl ether, the
crude product was dissolved in THF (0.15 M), the solution was
cooled to –100 °C (external temperature, liquid N2/Et2O bath) and
BuLi (1.1 equiv) was added dropwise. The mixture was stirred for
20 min while the temperature reached –80 °C. Then the mixture was
again cooled to –100 °C, Tf2O (1.2 equiv) was added dropwise, and
MS: m/z (%) = 377 (42), 244 (60), 242 (58), 58 (100).
4,5-Difluoro-2-trimethylsilylphenylTrifluoromethanesulfonate
(2e)2b
Method B was followed using 2-bromo-4,5-difluorophenol (1e;
0.34 mL, 3 mmol) and HMDS (0.68 mL, 3.3 mmol) in THF (10
mL); and then BuLi (1.62 mL, 2.04 M, 3.3 mmol) and Tf2O (0.66
mL, 3.9 mmol) in THF (20 mL). Column chromatography (SiO2,
hexane) afforded 2e (0.782 g, 78%) as a colorless oil.
Synthesis 2002, No. 10, 1454–1458 ISSN 0039-7881 © Thieme Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
Synthesis of ortho-Trialkylsilylaryl Triflates
1457
4-Chloro-2-trimethylsilylphenyl Trifluoromethanesulfonate
(2f)3d
tracted with CH2Cl2 (2 30 mL). The combined organic layers
were dried (Na2SO4), filtered, and concentrated under reduced pres-
sure. The residue was purified by column chromatography (SiO2,
Et2O–hexane, 1:9) to afford 14 (2.60 g, 100%) as a colorless oil.
1H NMR (CDCl3): = 7.51 (dd, J = 7.9, 1.6 Hz, 1 H), 7.17 (m, 1 H),
6.89–6.79 (m, 2 H), 1.04 (s, 9 H), 0.25 (s, 6 H).
Method B was followed using 2-bromo-4-chlorophenol (1f; 0.64 g,
3.08 mmol) and HMDS (0.7 mL, 3.39 mmol) in THF (10 mL); and
then BuLi (1.66 mL, 2.04 M, 3.39 mmol) and Tf2O (0.67 mL, 4.0
mmol) in THF (20 mL). Column chromatography (SiO2, hexane)
afforded 2f (0.798 g, 80%) as a colorless oil.
1H NMR (CDCl3): = 7.52 (d, J = 2.5 Hz, 1 H), 7.36 (m, 1 H), 7.25
(d, J = 7.2 Hz, 1 H), 1.52 (s, 9 H).
13C NMR (CDCl3): = 152.6, 133.4, 128.2, 122.3, 120.3, 115.4,
25.7, 18.3, –4.2.
MS: m/z (%) = 288 (1), 286 (1), 231 (100), 229 (98).
13C NMR (CDCl3): = 153.1, 135.9, 135.3, 133.5, 131.0, 121.0,
118.6 (q, J = 320 Hz, CF3), –1.1.
2-(tert-Butyldimethylsilyl)phenyl Trifluoromethanesulfonate
(15)
MS: m/z (%) = 332 (0.5), 317 (100), 184 (53), 58 (100).
To a stirred solution of 14 (2.60 g, 9 mmol) in THF (30 mL) cooled
to –100 °C, was added dropwise BuLi (4.67 mL, 2.12 M, 9.9 mmol).
The stirring was continued for 30 min while the temperature
reached –80 °C. Then the mixture was again cooled to –100 °C,
Tf2O (1.90 mL, 11.25 mmol) was added dropwise, and the stirring
continued for 20 min while the temperature returned to –80 °C.
Cold sat. aq NaHCO3 (30 mL) was added, the phases were separated
and the aqueous layer was extracted with Et2O (2 50 mL). The
combined organic layers were dried (Na2SO4), filtered, and concen-
trated under reduced pressure. The residue was purified by column
chromatography (SiO2, hexane) to afford 15 (2.61 g, 85%) as a col-
orless oil.
3-(Pent-3-ynyloxy)-2-trimethylsilylphenyl Trifluoromethane-
sulfonate (8)
Method B was followed using 2-bromo-3-(pent-3-ynyloxy)phenol12
(7; 0.168 g, 1.39 mmol) and HMDS (0.29 mL, 1.39 mmol) in THF
(5 mL); and then BuLi (0.356 mL, 2.04 M, 0.726 mmol) and Tf2O
(0.14 mL, 0.825 mmol) in THF (5 mL). Column chromatography
(SiO2, Et2O–hexane, 2:98) afforded 8 (0.180 g, 72%) as a colorless
oil.
1H NMR (CDCl3): = 7.35 (t, J = 8.3 Hz, 1 H), 6.94 (d, J = 8.3 Hz,
1 H), 6.80 (d, J = 8.4 Hz, 1 H), 4.05 (t, J = 6.8 Hz, 2 H), 2.69–2.61
(m, 2 H), 1.79 (t, J = 2.5 Hz, 3 H), 0.40 (s, 9 H).
13C NMR (CDCl3): = 164.3, 154.7, 131.6, 120.8, 119.0 (q, J = 320
Hz, CF3), 112.8, 109.7, 77.7, 75.0, 67.0, 19.6, 1.2.
1H NMR (CDCl3): = 7.53 (dd, J = 7.2, 1.8 Hz, 1 H), 7.48–7.29 (m,
3 H), 0.89 (s, 9 H), 0.38 (s, 6 H).
13C NMR (CDCl3): = 155.7, 137.6, 131.2, 129.5, 126.8, 119.0,
118.6, (q, J = 320 Hz), 26.5, 17.6, –4.7.
MS: m/z (%) = 365 (M+ – 15, 11), 217 (12), 67 (100).
1-Trimethylsilylnaphthyl 2-Trifluoromethanesulfonate (10)2d
Method B was followed using 1-bromo-2-naphthol (9a; 2.23 g, 10
mmol) and HMDS (2.06 mL, 10 mmol) in THF (40 mL); and then
BuLi (4.46 mL, 2.41 M, 11 mmol) and Tf2O (2.1 mL, 12.5 mmol)
in THF (40 mL). Column chromatography (SiO2, Et2O–hexane,
5:95) afforded 10 (3.032 g, 87%) as a colorless oil.
MS: m/z (%) = 283 (M+ – 57, 100).
Reaction of 15 with NBu4F in the Presence of Furan
To a solution of 15 (170 mg, 0.5 mmol) and furan (0.181 mL, 2.5
mmol) in MeCN (2 mL) cooled at 0 °C was added dropwise a 0.1 M
solution of NBu4F in THF (0.75 mL, 0.75 mmol). After stirring at
r.t. for 14 h, a mixture of CH2Cl2 and H2O (1:1, 30 mL) was added
and the phases were separated. The aqueous layer was extracted
with CH2Cl2 (2 10 mL), and the combined organic layers were
dried (Na2SO4) filtered, and concentrated under reduced pressure.
The residue was purified by column chromatography (SiO2, hex-
ane–CH2Cl2, 95:5) to afford 1,4-dihydro-1,4-epoxynaphthalene4c
(16; 40 mg, 56%) as a white solid; mp 51 °C (Lit.13 51–56).
2-Trimethylsilylphenanthryl 1-Trifluoromethanesulfonate
(11)2d
Method B was followed using 2-bromo-1-phenanthrol2d (9b; 0.221
g, 0.81 mmol) and HMDS (0.165 mL, 0.81 mmol) in THF (5 mL);
and then BuLi (0.385 mL, 2.41 M, 0.93 mmol) and Tf2O (0.170 mL,
1.01 mmol) in THF (5 mL). Column chromatography (SiO2, hex-
ane) afforded 11 (0.263 g, 82%) as a white solid; mp 68 °C.
1H NMR (CDCl3): = 7.24–7.22 (m, 2 H), 7.00 (s, 2 H), 6.96–6.94
(m, 2 H), 5.69 (s, 2 H).
3-Trimethylsilylphenanthryl 4-Trifluoromethanesulfonate
(12)2d
Reaction of 15 with NBu4F in the Presence of Pd(PPh3)4
To a suspension of 15 (170 mg, 0.5 mmol) and Pd(PPh3)4 (58 mg,
0.05 mmol) in THF (2 mL) cooled to 0 °C was added dropwise a 0.1
M solution of NBu4F in THF (0.75 mL, 0.75 mmol). After stirring
at r.t. for 14 h, a mixture of CH2Cl2 and H2O (1:1, 30 mL) was added
and the phases were separated. The aqueous layer was extracted
with CH2Cl2 (2 10 mL), and the combined organic layers were
dried (Na2SO4), filtered, and concentrated under reduced pressure.
The residue was purified by column chromatography (SiO2, hex-
ane–CH2Cl2, 95:5) to afford triphenylene (17; 17 mg, 45%) as a
white solid; mp 194–196 °C (Lit.14 mp 198 °C).
Method B was followed using 3-bromo-4-phenanthrol2d (9c; 0.650
g, 2.38 mmol) and HMDS (0.490 mL, 2.83 mmol) in THF (10 mL);
and then BuLi (1.09 mL, 2.41 M, 2.62 mmol) and Tf2O (0.50 mL,
3.0 mmol) in THF (16 mL). Column chromatography (SiO2, hex-
ane) afforded 12 (0.747 g, 79%) as a white solid; mp 49 °C.
10-Trimethylsilylphenanthryl 9-Trifluoromethanesulfonate
(13)2d
Method B was followed using 10-bromo-9-phenanthrol2d (9d;
0.476 g, 1.74 mmol) and HMDS (0.4 mL, 1.92 mmol) in THF (6
mL); and then BuLi (1.83 mL, 2.46 M, 1.83 mmol) and Tf2O (0.37
mL, 2.18 mmol) in THF (12 mL). Column chromatography (SiO2,
Et2O–hexane, 2:98) afforded 13 (0.454 g, 65%) as a white solid; mp
94 °C.
1H NMR (CDCl3): = 8.67 (m, 6 H), 7.67 (m, 6 H).
Acknowledgments
(2-Bromophenoxy)-tert-butyldimethylsilane (14)
Financial supports from the DGES (BQU2000-0464) and PGIDT
(01PXI20902PN) are gratefully acknowledged. We also thank the
Spanish Ministry of Education and Culture for the award of a fel-
lowship to D. Peña.
To a solution of 2-bromophenol (1a; 1.050 mL, 9 mmol) and imida-
zole (1.150 g, 16.9 mmol) in CH2Cl2 (50 mL) was added TBDMSCl
(2.450 g, 16.2 mmol). After stirring at r.t. for 2 h, H2O (50 mL) was
added, the phases were separated and the aqueous phase was ex-
Synthesis 2002, No. 10, 1454–1458 ISSN 0039-7881 © Thieme Stuttgart · New York

1458
D. Peña et al.
PRACTICAL SYNTHETIC PROCEDURES
(8) For similar migrations induced by meta-halogen exchange
with RLi, see: (a) Heinicke, J.; Nietzschmann, E.; Tzschach,
A. J. Organomet. Chem. 1983, 243, 1. (b) Maruoka, K.;
Itoh, T.; Araki, Y.; Shirasaka, T.; Yamamoto, H. Bull. Chem.
Soc. Jpn. 1988, 61, 2975. (c) Simchen, G.; Pletschinger, J.
Angew. Chem., Int. Ed. Engl. 1976, 15, 428.
(9) For migrations induced by metalation with s-BuLi/TMEDA,
see: Billedeau, R. J.; Sibi, M. P.; Snieckus, V. Tetrahedron
Lett. 1983, 24, 4515.
References
(1) General reviews on aryne chemistry: (a) Hoffmann, R. W.
Dehydrobenzene and Cycloalkynes; Academic Press: New
York, 1967. (b) Hart, H. In The Chemistry of Functional
Groups, The Chemistry of Triple-Bonded Functional
Groups, Suppl.C2; Patai, S., Ed.; Wiley: Chichester, 1994,
1017–1134.
(2) (a) Peña, D.; Escudero, S.; Pérez, D.; Guitián, E.; Castedo,
L. Angew. Chem. Int. Ed. 1998, 37, 2659. (b) Peña, D.;
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(5) Now commercially available from Sigma-Aldrich.
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Synthesis 2002, No. 10, 1454–1458 ISSN 0039-7881 © Thieme Stuttgart · New York