Facile preparation of 2-iodophenyl trifluoromethanesulfonates: Superior aryne precursors

Article abstract of DOI:10.1055/s-2007-985565

A comparative study of 3-methoxyaryne precursors revealed 2-iodo-3-methoxyphenyl triflate as the most effective in nonpolar solvent. Use of Hoppe's N-isopropyl carbamate allows for the systematic preparation of a variety of 2-iodophenyl triflates via a directed ortho-lithiation-iodination- decarbamation sequence. These steps are possible without isolation of the intermediate iodophenyl carbamates. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-985565

LETTER
2227
Facile Preparation of 2-Iodophenyl Trifluoromethanesulfonates: Superior
Aryne Precursors
P
reparation of 2-Io
s
dophenyl
h
Trifluorome
o
thanesulfona
k
tes Ganta, Timothy S. Snowden*
Department of Chemistry, The University of Alabama, Box 870336, Tuscaloosa, AL 35487-0336, USA
Fax +1(205)3489104; E-mail: snowden@bama.ua.edu
Received 18 December 2006
Table 1 Comparison of ortho-Methoxybenzyne Precursors
Abstract: A comparative study of 3-methoxyaryne precursors
revealed 2-iodo-3-methoxyphenyl triflate as the most effective in
nonpolar solvent. Use of Hoppe’s N-isopropyl carbamate allows for
the systematic preparation of a variety of 2-iodophenyl triflates via
a directed ortho-lithiation–iodination–decarbamation sequence.
These steps are possible without isolation of the intermediate
iodophenyl carbamates.
Entry Benzyne
precursor
Temp
(°C)
Solvent
THF
Reagent Isolated
yield (%)
1
2
3
4
5
6
7
8
9
Reflux
Reflux
–78
20% CsF <10
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
TMS
F
Key words: arynes, carbamate, halogenation, iodophenyl triflate,
metalations
THF
THF
THF
THF
THF
CsF
73a
TMS
OTf
b
Recently, we required a series of methoxyarynes as inter-
mediates toward polysubstituted aromatic products. A
benzyne trapping study with various precursors to meth-
oxyarynes (Scheme 1) revealed 2-iodo-3-methoxyphenyl
triflate1 as the most suitable under our constraint of a non-
polar solvent system (Table 1). Although benzyne gener-
ation via treatment of aryl silanes with fluoride is effective
in polar acetonitrile at ambient temperature,2 many nu-
cleophiles are not compatible with the reflux conditions
required to generate the aryne in tetrahydrofuran (entries
1 and 2). Meanwhile, the use of LiTMP-zincate proved in-
effective in our hands (entry 3).3 Ortho-lithiation–LiCl
elimination of 3-chloroanisole resulted in unsatisfactory
mixtures of bi- and polyaryl products along with the ex-
pected cycloadduct (entries 4 and 5).4 Lithium–halogen
exchange with 3-fluoro-2-iodoanisole afforded a 77%
yield of the desired cycloadduct in toluene.5,6 The reaction
also produced ca. 15% of 3-fluoro-2-(3-methoxyphenyl)
anisole, presumably due to incomplete lithium fluoride
elimination and subsequent addition to methoxybenzyne
(entry 7). The biaryl formation was even more pro-
nounced when this reaction was conducted in tetrahydro-
furan at temperatures ranging from –78 °C to 0 °C (e.g.,
entry 6).6 Aryne generation via the iodophenyl tosylate
(entry 8) improved upon the lithium fluoride elimination
LTMP,
ZnMe2
–
Br
Cl
–78
n-BuLi
n-BuLi
n-BuLi
22c
0
Complex
mixture
Cl
–78
55
77
72
90
I
F
–42
Toluene n-BuLi
I
F
–78
THF
THF
n-BuLi
n-BuLi
I
OTs
I
–78
reagent, temp,
solvent
OMe
O
OMe
OMe
Y
X
(10 equiv)
OTf
O
a Reaction required 12 h at reflux using 2.0 equiv CsF.
b Only 1-(3-methoxyphenyl)-2,2,6,6-tetramethylpiperidine was
obtained.
Scheme 1 Comparative 3-methoxybenzyne trapping study
c Produced a mixture of polyaryl products and the cycloadduct.
SYNLETT 2007, No. 14, pp 2227–2231
0
3
.0
9
.2
0
0
7
Advanced online publication: 13.08.2007
DOI: 10.1055/s-2007-985565; Art ID: S19606ST
© Georg Thieme Verlag Stuttgart · New York

2228
A. Ganta, T. S. Snowden
LETTER
CbH
1) TMSOTf, TMEDA,
Et2O, 0–25 °C, 30 min
2) TMEDA, n-BuLi,
–78 °C, 1 h
O
i-PrNCO,
cat. DMAP,
THF, ∆
OH
O
N
H
OTf
OH
Tf2O, DIPEA, CH2Cl2,
–78 °C to 25 °C
I
I
3) I2, THF, –78 °C, 2 h
then NaOH, EtOH,
25 °C, 2 h
X
X
X
X
Scheme 2 Preparation of various 2-iodophenyl trifluoromethanesulfonates
in tetrahydrofuran.7 However, this experiment spawned to the 2-iodophenyl triflate at –78 °C garnered the desired
several minor byproducts along with the cycloadduct. aryne, which was trapped by furan with negligible side-
Conducting the reaction at –42 °C offered comparable product formation (entry 9) thereby proving superior to
yields.8 We ultimately found that introduction of n-BuLi the other examined precursors.
Table 2 Products and Yields Connected with the 2-Iodophenyl Triflate Preparation Outlined in Scheme 2
Entry Carbamate
1
Compd Yield
(%)a
2-Iodophenol
Compd Yield
(%)a
2-Iodophenyl triflate
Compd Yield
(%)a
1
9710
11
8410
21
9431
OH
OCbH
OTf
I
I
MeO
OMe
MeO
MeO
OMe
MeO
MeO
OMe
OTf
2
3
2
3
9617
9818
12
13
7413
7725
22
23
921b
9232
OCbH
OH
I
MeO
I
I
I
OCbH
OTf
OH
OMe
OMe
OTf
OMe
OH
4
5
4
5
9411a
9619
9820
9821
9622
9823
9224
14
15
16
17
18
19
20
7526
8726
8527
7628
7714
6229
5830
24
25
26
27
28
29
30
9333
9834
9335
9236
9037
9138
9139
OCbH
I
I
Ph
Cl
F
OCbH
Ph
Cl
F
OTf
OTf
Ph
Cl
F
OH
OH
I
I
I
I
6
6
OCbH
OCbH
7
7
OH
OTf
I
I
8
8
OCbH
OH
OTf
F
F
I
F
I
9
9
F3C
OH
F3C
OCbH
F3C
OTf
I
I
10
10
I
I
OCbH
OH
OTf
F3C
F3C
F3C
a Isolated yield of purified product. Characterization data is provided under the indicated reference number.
Synlett 2007, No. 14, 2227–2231 © Thieme Stuttgart · New York

LETTER
Preparation of 2-Iodophenyl Trifluoromethanesulfonates
2229
Because of the relative efficiency with which the 2-iodo- stituent.12 This is contrasted by the regioselectivity exhib-
phenyl triflate served as a benzyne precursor, we were ited by 2, where the methoxy and CbH substituents share
surprised that there exists no general procedure for the a synergistic directing effect toward lithiation–iodination
systematic preparation of such compounds. While direct to give 12 after decarbamation.13 An analogous regio-
iodination of substituted phenols has been used en route to chemical result was encountered in the iodination of 8.14
2-iodophenyl triflates, the protocols do not allow for
We have identified 2-iodophenyl triflates as privileged
reliable regioselective introduction of the halogen when
aryne precursors in nonpolar solvents. The regioselective
regioisomeric products are possible or when deactivated
preparation of both activated and select deactivated
iodophenyl triflates is possible using Hoppe’s directed
substrates are employed.9
Hoppe and Kauch reported the preparation of two 2-iodo- ortho-lithiation approach.15,16 Compounds 21–30, which
phenols using a directed ortho-metalation–iodination include eight new 2-iodoaryl triflates, likely will find util-
approach.10 The method involves in situ generated N-sily- ity in the preparation of disparate polysubstituted aromat-
lated N-isopropyl carbamates to direct the aryl lithiation ics via the popular use of benzynes in organic synthesis.
step. The advantage of the O-aryl N-isopropyl carbamate These compounds should also prove useful in transition-
(CbH) versus alternative dialkyl carbamates as the direct- metal-catalyzed processes.
ing group is the simple installation and removal of the
monoalkylcarbamate under mildly basic conditions.
Acknowledgment
The N-isopropyl carbamates of a variety of phenols were
We are grateful to The University of Alabama for start-up research
prepared in excellent yields following the method of
funds.
Hoppe and purified via flash chromatography
(Scheme 2).11 The 3- and 4-trifluoromethylphenols re-
References and Notes
quired a minor modification to the reported procedure in
that heating at reflux for 72 hours in the presence of 30%
DMAP was necessary for complete carbamation. The aryl
carbamates were then treated with TMEDA and TMSOTf
at 0 °C followed by TMEDA and n-BuLi at –78 °C for
1 hour. A solution of I2 dissolved in THF was then added
and stirred for 2 hours at –78 °C. The solution was gradu-
ally warmed and the solvent removed by rotary evapora-
tion. After concentrating, the addition of 95% EtOH and
powdered NaOH allowed for release of the CbH group
without isolation of the 2-iodophenyl isopropylcarbam-
ate. Following purification of the prepared ortho-iodo-
phenols, the compounds were smoothly transformed into
the desired 2-iodophenyl triflates by standard treatment
with triflic anhydride.1d
(1) (a) Matsumoto, T.; Hosoya, T.; Katsuki, M.; Suzuki, K.
Tetrahedron Lett. 1991, 32, 6735. (b) Matsumoto, T.;
Hosoya, T.; Suzuki, K. J. Am. Chem. Soc. 1992, 114, 3568.
(c) Hosoya, T.; Takashiro, E.; Matsumoto, T.; Suzuki, K. J.
Am. Chem. Soc. 1994, 116, 1004. (d) Hamura, T.; Hosoya,
T.; Yamaguchi, H.; Kuriyama, Y.; Tanabe, M.; Miyamoto,
M.; Yasui, Y.; Matsumoto, T.; Suzuki, K. Helv. Chim. Acta
2002, 85, 3589.
(2) (a) Himeshima, Y.; Sonoda, T.; Kobayashi, H. Chem. Lett.
1983, 12, 1211. (b) Peña, D.; Escudero, S.; Pérez, D.;
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Chem. Soc. 1999, 121, 5827.
(3) Uchiyama, M.; Miyoshi, T.; Kajihara, Y.; Sakamoto, T.;
Otani, Y.; Ohwada, T.; Kondo, Y. J. Am. Chem. Soc. 2002,
124, 8514.
(4) The successful formation of 2-methoxybenzyne by dehydro-
halogenation of 3-chloroanisole at temperatures < –95 °C
has been reported: (a) Iwao, M. J. Org. Chem. 1990, 55,
3622. (b) Kaelin, D. E. Jr.; Lopez, O. D.; Martin, S. F. J. Am.
Chem. Soc. 2001, 123, 6937.
(5) For a seminal study of benzyne generation from ortho-
dihalobenzenes using organolithium reagents, see: Gilman,
H.; Gorsich, R. D. J. Am. Chem. Soc. 1957, 79, 2625.
(6) (a) Adejare, A.; Miller, D. D. Tetrahedron Lett. 1984, 25,
5597. (b) Grunewald, G. L.; Kolar, A. J.; Palanki, M. S. S.;
Paradkar, V. M.; Reitz, T. J.; Sall, D. J. Org. Prep. Proced.
Int. 1990, 22, 747.
The workup of activated aromatic compounds 11 and 12
(Table 2) required special care to avoid generation of
regioisomeric and polyiodinated products. The pH was
carefully adjusted to pH 6–8 with 2 N HCl after decar-
bamation to afford the desired monoiodinated isomers. If
the workup was conducted at pH <5, reversible electro-
philic iodination ensued, eroding the yields.9c Despite the
activated nature of 13, no loss of regioisomeric purity was
exhibited when the crude material was treated under acid-
ic conditions.
Competitive dehydrohalogenation did not occur when 6,
7, or 8 were subjected to the halogenation protocol. Ben-
zylic deprotonation was also absent with 3 under these
conditions. This serves as a testament to the powerful di-
recting effect of the CbH group. The yields of deactivated
2-iodophenols 19 and 20 were improved by using tert-bu-
tyllithium in place of n-BuLi. The regioselective iodina-
tion para to the trifluoromethyl group in 10 might result
from the significant field effect of the trifluoromethyl sub-
(7) (a) Giles, R. G. F.; Sargent, M. V.; Sianipar, H. J. Chem.
Soc., Perkin Trans. 1 1991, 1571. (b) Giles, R. G. F.;
Hughes, A. B.; Sargent, M. V. J. Chem. Soc., Perkin Trans. 1
1991, 1581. (c) Baker, R. W.; Baker, T. M.; Birkbeck, A. A.;
Giles, R. G. F.; Sargent, M. V.; Skelton, B. W.; White, A. H.
J. Chem. Soc., Perkin Trans. 1 1991, 1589.
(8) The 2-iodophenyl tosylate reportedly serves as an efficient
aryne precursor upon treatment with isopropylmagnesium
chloride and warming in the presence of a nucleophile: Lin,
W.; Ilgen, F.; Knochel, P. Tetrahedron Lett. 2006, 47, 1941.
Synlett 2007, No. 14, 2227–2231 © Thieme Stuttgart · New York

2230
A. Ganta, T. S. Snowden
LETTER
(9) (a) Srebnik, M.; Mechoulam, R.; Yona, I. J. Chem. Soc.,
Perkin Trans. 1 1987, 1423. (b) Doad, G. J. S.; Barltrop, J.
A.; Petty, C. M.; Owen, T. C. Tetrahedron Lett. 1989, 30,
1597. (c) Thomsen, I.; Torssell, K. B. G. Acta Chem. Scand.
1991, 45, 539. (d) Barluenga, J.; Gonzàlez, J. M.; García-
Martín, M. A.; Campos, P. J.; Asensio, G. J. Org. Chem.
1993, 58, 2058. (e) Yonezawa, S.; Komurasaki, T.; Kawada,
K.; Tsuri, T.; Fuji, M.; Kugimiya, A.; Haga, N.; Mitsumori,
S.; Inagaki, M.; Nakatani, T.; Tamura, Y.; Takechi, S.;
Taishi, T.; Ohtani, M. J. Org. Chem. 1998, 63, 5831.
(f) Yang, S. G.; Kim, Y. H. Tetrahedron Lett. 1999, 40,
6051. (g) Denieul, M. R.; Laursen, B.; Hazell, R.; Skrydstup,
T. J. Org. Chem. 2000, 65, 6052. (h) Mukaiyama, T.;
Kitagawa, H.; Matsuo, J. Tetrahedron Lett. 2000, 41, 9383.
(i) Narender, N.; Srinivasu, P.; Kulakarni, S. J.; Raghavan,
K. V. Synth. Commun. 2002, 32, 2319. (j) Jereb, M.; Zupan,
M.; Stavber, S. Chem. Commun. 2004, 2614. (k) Krishna
Mohan, K. V. V.; Narender, N.; Kulkarni, S. J. Tetrahedron
Lett. 2004, 45, 8015. (l) Patil, B. R.; Bhusare, S. R.; Pawar,
R. P.; Vibhute, Y. B. Tetrahedron Lett. 2005, 46, 7179.
(10) Kauch, M.; Hoppe, D. Synthesis 2006, 1578.
(11) (a) Kauch, M.; Hoppe, D. Can. J. Chem. 2001, 79, 1736.
(b) Kauch, M.; Snieckus, V.; Hoppe, D. J. Org. Chem. 2005,
70, 7149.
MHz, CDCl3): d = 7.16 (t, J = 8.2 Hz, 1 H), 6.66 (dt, J = 5.0,
2.0 Hz, 2 H), 6.62 (t, J = 2.0 Hz, 1 H), 4.79 (d, J = 0.7 Hz, 1
H), 3.82 (dt, J = 13.2, 6.4 Hz, 1 H), 3.72 (s, 3 H), 1.16 (d,
J = 6.5 Hz, 6 H). 13C NMR (125 MHz, CDCl3): d = 160.3,
153.5, 152.0, 129.5, 113.8, 111.1, 107.5, 55.3, 43.4, 22.8.
HRMS (EI): m/z [M]+ calcd for C11H15NO3: 209.1052;
found: 209.1056.
(18) Compound 3: white solid, mp 105–106 °C. IR (neat): 3343
(m), 1739 (s), 1608 (m), 739 (m) cm–1. 1H NMR (500 MHz,
CDCl3): d = 6.96 (d, J = 8.0 Hz, 1 H), 6.75 (s, 1 H), 6.71 (d,
J = 8.0 Hz, 1 H), 4.97 (d, J = 4.0 Hz, 1 H,), 3.86 (td, J = 6.7,
13.1 Hz, 1 H), 3.81 (s, 3 H), 2.32 (s, 3 H), 1.20 (d, J = 6.5 Hz,
6 H). 13C NMR (125 MHz, CDCl3): d = 153.5, 151.1, 137.6,
136.0, 122.7, 120.9, 113.1, 55.7, 43.3, 22.7, 21.2. HRMS
(EI): m/z [M]+ calcd for C12H17NO3: 223.1208; found:
223.1210.
(19) Compound 5: white solid, mp 151–152 °C. IR (neat): 3391
(m), 1738 (s), 1502 (s), 847 (w), 746 (s) cm–1. 1H NMR (500
MHz, CDCl3): d = 7.55 (d, J = 7.5 Hz, 4 H), 7.42 (t, J = 7.4
Hz, 2 H), 7.33 (t, J = 7.1 Hz, 1 H), 7.20 (d, J = 8.0 Hz, 2 H),
4.89 (d, J = 4.9 Hz, 1 H), 3.91 (dd, J = 12.8, 6.3 Hz, 1 H),
1.24 (d, J = 6.3 Hz, 6 H). 13C NMR (125 MHz, CDCl3):
d = 153.6, 150.4, 140.5, 138.3, 128.7, 127.9, 127.1, 127.0,
121.8, 43.4, 22.8. HRMS (EI): m/z [M]+ calcd for
(12) MacPhee, J. A.; Panaye, A.; Dubois, J. E. Tetrahedron 1978,
34, 3553.
(13) Sloan, C. P.; Cuevas, J. C.; Quesnelle, C.; Snieckus, V.
Tetrahedron Lett. 1988, 29, 4685.
C16H17NO2: 255.1259; found: 255.1259.
(20) Patonay, T.; Patonay-Peli, E.; Mogyorodi, F. Synth.
Commun. 1990, 20, 2865.
(21) Compound 7: white solid, mp 123–124 °C. IR (neat): 3326
(br), 1739 (s), 1495 (s), 845 (s), 746 (s) cm–1. 1H NMR (500
MHz, CDCl3): d = 7.04 (td, J = 8.6, 16.7 Hz, 4 H), 4.98 (s, 1
H), 3.87 (dd, J = 6.5, 13.1 Hz, 1 H), 1.20 (d, J = 6.4 Hz, 6 H).
13C NMR (125 MHz, CDCl3): d = 159.7 [d, J(CF) = 243.2
Hz], 153.6, 146.8 [d, J(CF) = 2.6 Hz], 122.9 [d, J(CF) = 8.4
Hz], 115.6 [d, J(CF) = 23.4 Hz], 43.4, 22.7. HRMS (EI):
m/z [M]+ calcd for C10H12FNO2: 197.0852; found: 197.0853.
(22) Compound 8: white solid, mp 85–86 °C. IR (neat): 3433 (m),
1601 (s), 1508 (m), 748 (s) cm–1. 1H NMR (500 MHz,
CDCl3): d = 7.29 (dd, J = 8.3, 15.3 Hz, 1 H), 6.91 (ddd,
J = 6.0, 8.1, 6.6 Hz, 3 H), 4.84 (d, J = 0.9 Hz, 1 H), 3.89 (qd,
J = 6.6, 13.4 Hz, 1 H), 1.24 (d, J = 6.6 Hz, 6 H). 13C NMR
(125 MHz, CDCl3): d = 162.7 [d, J(CF) = 246.6 Hz], 153.0,
151.9 [d, J(CF) = 11.0 Hz], 129.8 [d, J(CF) = 9.4 Hz], 117.2
[d, J(CF) = 2.0 Hz], 112.0 [d, J(CF) = 21.1 Hz], 109.5 [d,
J(CF) = 24.3 Hz], 43.4, 22.7. HRMS (EI): m/z [M]+ calcd for
C10H12FNO2: 197.0852; found: 197.0850.
(23) Compound 9: white solid, mp 119–120 °C. IR (neat): 3316
(br), 1739 (s), 1535 (s), 814 (m), 700 (s) cm–1. 1H NMR (500
MHz, CDCl3): d = 7.36 (m, 3 H), 7.25 (d, J = 7.0 Hz, 1 H),
4.93 (d, J = 3.9 Hz, 1 H), 3.81 (qd, J = 13.5, 6.6 Hz, 1 H),
1.15 (d, J = 6.6 Hz, 6 H). 13C NMR (125 MHz, CDCl3):
d = 153.0, 151.1, 131.6 [q, J(CF) = 32.8 Hz], 129.6, 125.1,
125.1, 123.6 [q, J(CF) = 272.3 Hz], 121.7 [d, J(CF) = 3.7
Hz], 118.7 [dd, J(CF) = 3.6 Hz, J = 7.4 Hz], 43.5, 22.6.
HRMS (EI): m/z [M]+ calcd for C11H12F3NO2: 247.0820;
found: 247.0824.
(14) Sanz, R.; Castroviejo, M. P.; Fernández, Y.; Fañanás, F. J.
J. Org. Chem. 2005, 70, 6548.
(15) General Procedure for the Preparation of 2-Iodophenols
11–20
To a solution of the carbamate (2.5 mmol) dissolved in dry
Et2O (25 mL) under argon was added TMEDA (1.1 equiv,
2.75 mmol) at 0 °C. Then TMSOTf (1.1 equiv, 2.75 mmol)
was slowly added to the solution and the reaction mixture
was allowed to warm to r.t. over a period of 30 min. After
cooling the solution to –78 °C, TMEDA (2.0 equiv, 5.0
mmol) was added followed by the dropwise addition of n-
BuLi or t-BuLi (2.0–2.5 equiv, 5.0–6.2 mmol). The reaction
mixture was stirred for 1 h and was then treated with I2 (1.0
equiv, 2.5 mmol) dissolved in THF (3 mL). After reacting
for 2 h, EtOH (0.25 mL) was added and the solvent was
removed by rotary evaporation. The resultant residue was
dissolved in EtOH (25 mL) and treated with 5 mL of aq 2 N
NaOH (4 equiv, 10 mmol). The reaction proceeded for 2 h,
after which the pH was adjusted to 6–8 with 2 N HCl. The
aqueous layer was extracted with Et2O (3 ꢀ 25 mL) and the
combined organic layers were washed with a 1 M solution of
Na2S2O3 (25 mL), then dried and filtered. Upon concen-
tration, the resulting residue was purified using flash
chromatography (hexane–EtOAc, 95:5 to 9:1) affording the
desired 2-iodophenol.
(16) General Procedure for the Preparation of 2-Iodophenyl
Triflates 21–30
To a –78 °C solution of 2-iodophenol (1.0 mmol) in CH2Cl2
(3 mL) was added anhydrous i-Pr2NEt (1.25 mmol) and
Tf2O (1.25 mmol). After 10 min, the cooling bath was
removed and the reaction mixture was allowed to warm to
r.t. The reaction was quenched with H2O (5 mL) after 1–2 h,
and the aqueous phase was extracted with Et2O (3 ꢀ 5 mL).
The combined organic layers were dried and concentrated.
The crude material was then purified by flash chromatog-
raphy (100% hexane to hexane–EtOAc, 98:2) or recrystal-
lized from hexane to afford the desired 2-iodophenyl triflate.
(17) Compound 2: white solid, mp 54–55 °C. IR (neat): 3441 (m),
1734 (s), 1507 (m), 908 (m), 732 (m) cm–1. 1H NMR (500
(24) Compound 10: white solid, mp 88–89 °C. IR (neat): 3339
(br), 1743 (s), 1490 (s), 804 (m), 743 (s) cm–1. 1H NMR (500
MHz, CDCl3): d = 7.46 (m, 2 H), 7.41 (s, 1 H), 7.36 (d,
J = 7.3 Hz, 1 H), 4.89 (d, J = 4.6 Hz, 1 H), 3.90 (qd, J = 6.7,
13.4 Hz, 1 H), 1.25 (d, J = 6.5 Hz, 6 H). 13C NMR (125 MHz,
CDCl3): d = 153.05, 151.1, 131.6 [q, J(CF) = 32.7 Hz],
129.6, 125.1, 123.6 [q, J(CF) = 272.3 Hz], 121.79 [d,
J(CF) = 3.6 Hz], 118.7 [dd, J(CF) = 7.3, 3.5 Hz], 43.5, 22.6.
HRMS (EI): m/z [M]+ calcd for C11H12F3NO2: 247.0820;
found: 247.0822.
(25) Weeratunga, G.; Jaworskasobiesiak, A.; Horne, S.; Rodrigo,
R. Can. J. Chem. 1987, 65, 2019.
Synlett 2007, No. 14, 2227–2231 © Thieme Stuttgart · New York

LETTER
Preparation of 2-Iodophenyl Trifluoromethanesulfonates
2231
(26) Compound is commercially available.
(27) Varma, P. S.; Yasodhoda, K. M. J. Indian Chem. Soc. 1939,
16, 477.
(28) Finger, G. C.; Gortatowski, M. J.; Shiley, R. H.; White, R.
H. J. Am. Chem. Soc. 1959, 81, 94.
(29) Mylari, B. L.; Armento, S. J.; Beebe, D. A.; Conn, E. L.;
Coutcher, J. B.; Dina, M. S.; O’Gorman, M. T.; Linhares, M.
C.; Martin, W. H.; Oates, P. J.; Tess, D. A.; Withbroe, G. J.;
Zembrowski, W. J. J. Med. Chem. 2005, 48, 6326.
(30) Selliah, R.; Dantanarayana, A.; Haggard, K.; Egan, J.; Do, E.
U.; May, J. A. J. Labelled Compd. Radiopharm. 2001, 44,
173.
(31) Compound 21: recrystallization from hexane, white solid,
mp 79–80 °C. IR (neat): 3053 (m), 2987 (w), 1600 (m), 1573
(w), 1456 (m), 1423 (m), 1326 (m), 1265 (s), 1245 (m), 1218
(s), 1160 (m), 1139 (m), 1083 (m), 1059 (m), 1020 (w), 968
(m), 895 (m), 826 (m), 810 (m), 740 (s) cm–1. 1H NMR (500
MHz, CDCl3): d = 6.54 (d, J = 2.45 Hz, 1 H), 6.42 (d,
J = 2.47 Hz, 1 H), 3.88 (s, 3 H), 3.82 (s, 3 H). 13C NMR (125
MHz, CDCl3): d = 161.8, 160.4, 151.4, 118.6 [q, J(CF) =
318.5 Hz], 99.8, 98.1, 71.4, 56.8, 55.8. HRMS (EI): m/z [M]+
calcd for C9H8F3IO5S: 411.9089; found: 411.9106.
(32) Compound 23: viscous liquid. IR (neat): 2946 (w), 1590 (s),
1504 (s), 1461 (s), 1421 (m), 1301 (m), 1211 (m), 1133 (m),
1041 (m), 946 (m), 873 (m), 836 (m), 798 (m), 769 (m) cm–1.
1H NMR (360 MHz, CDCl3): d = 7.23 (dd, J = 0.6, 1.8 Hz,
1 H), 6.77 (d, J = 1.3 Hz, 1 H), 3.84 (s, 3 H), 2.30 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 151.1, 140.7, 138.1,
131.6, 122.5, 118.7 [q, J(CF) = 321.0 Hz], 89.5, 56.1, 20.9.
HRMS (EI): m/z [M]+ calcd for C9H8F3IO4S: 395.9140;
found: 395.9142.
(dd, J = 2.5, 8.8 Hz, 1 H), 7.25 (d, J = 8.9 Hz, 1 H). 13C NMR
(125 MHz, CDCl3): d = 148.9, 140.0, 134.6, 130.1, 122.6,
118.6 [q, J(CF) = 320.7 Hz], 89.6. HRMS (EI): m/z [M]+
calcd for C7H3ClF3IO3S: 385.8488; found: 385.8497.
(36) Compound 27: liquid. IR (neat): 2985 (w), 1588 (s), 1474
(s), 1428 (s), 1250 (m), 1226 (m), 1139 (m), 1029 (m), 907
(m), 856 (m), 817 (m), 734 (m) cm–1. 1H NMR (500 MHz,
CDCl3): d = 7.61 (dd, J = 3.0, 7.3 Hz, 1 H), 7.29 (dd, J = 4.6,
9.1 Hz, 1 H), 7.14 (ddd, J = 3.0, 7.3, 9.1 Hz, 1 H). 13C NMR
(125 MHz, CDCl3): d = 160.8 [d, J(CF) = 254.0 Hz], 146.5
[d, J(CF) = 3.4 Hz], 127.5 [d, J(CF) = 25.6 Hz], 122.9 [d,
J(CF) = 9.2 Hz], 118.7 [q, J(CF) = 320.6 Hz], 116.9 [d,
J(CF) = 23.7 Hz], 89.4 [d, J(CF) = 8.8 Hz]. HRMS (EI):
m/z [M]+ calcd for C7H3F4IO3S: 369.8772; found: 369.8778.
(37) Compound 28: viscous liquid. IR (neat): 3154 (w), 1577 (m),
1457 (s), 1428 (s), 1281 (w), 1248 (m), 1220 (s), 1139 (s),
1096 (w), 1035 (w), 975 (s), 906 (s), 835 (m), 787 (m), 725
(s) cm–1. 1H NMR (500 MHz, CDCl3): d = 7.43 (dt, J = 8.4,
6.1 Hz, 1 H), 7.16 (d, J = 8.4 Hz, 1 H), 7.11 (ddd, J = 8.3,
7.2, 1.2 Hz, 1 H). 13C NMR (125 MHz, CDCl3): d = 163.0 [d,
J(CF) = 252.6 Hz], 151.0 [d, J(CF) = 4.5 Hz], 130.7 [d,
J(CF) = 9.0 Hz], 118.7 [q, J(CF) = 320.7 Hz], 117.7 [d,
J(CF) = 2.8 Hz], 115.3 [d, J(CF) = 24.2 Hz], 79.2 [d,
J(CF) = 29.5 Hz]. HRMS (EI): m/z [M]+ calcd for
C7H3F4IO3S: 369.8784; found: 369.8783.
(38) Compound 29: recrystallization from hexane, white needles,
mp 37–38 °C. IR (neat): 3154 (w), 1606 (s), 1479 (s), 1430
(s), 1398 (m), 1323 (m), 1246 (m), 1221 (m), 1140 (m), 1181
(m), 1080 (m), 1023 (m), 906 (m), 829 (m), 808 (m), 735 (m)
cm–1. 1H NMR (500 MHz, CDCl3): d = 8.08 (d, J = 8.3 Hz,
1 H), 7.54 (d, J = 1.3 Hz, 1 H), 7.38 (dd, J = 8.3, 1.7 Hz, 1
H). 13C NMR (125 MHz, CDCl3): d = 150.3, 141.6, 132.9 [q,
J(CF) = 34.2 Hz], 126.1 [q, J(CF) = 3.5 Hz], 122.7 [q,
J(CF) = 272.9 Hz], 119.1 [q, J(CF) = 3.6 Hz], 118.7 [q,
J(CF) = 320.8 Hz], 94.1 [d, J(CF) = 0.9 Hz]. HRMS (EI):
m/z [M – Tf]+ calcd for C7H3F3IO: 286.9181; found:
286.9175.
(39) Compound 30: recrystallization from hexane, white needles,
mp 39–40 °C. IR (neat): 2985 (w), 1430 (s), 1399 (m), 1323
(m), 1265 (m), 1246 (m), 1221 (m), 1180 (m), 1139 (m),
1080 (m), 1023 (m), 906 (m), 808 (m), 729 (m) cm–1. 1H
NMR (500 MHz, CDCl3): d = 8.08 (dd, J = 8.3, 0.5, Hz, 1
H), 7.54 (d, J = 1.4 Hz, 1 H), 7.38 (dd, J = 8.3, 1.3 Hz, 1 H).
13C NMR (125 MHz, CDCl3): d = 150.3, 141.6, 132.8 [q,
J(CF) = 34.2 Hz], 126.1 [q, J(CF) = 3.5 Hz], 122.7 [q,
J(CF) = 272.7 Hz], 119.1 [q, J(CF) = 3.3 Hz], 118.6 [q,
J(CF) = 320.7 Hz], 94.1. HRMS (EI): m/z [M – Tf]+ calcd
for C7H3F3IO: 286.9181; found: 286.9192.
(33) Qing, F. L.; Fan, J.; Sun, H. B.; Yue, X. J. J. Chem. Soc.,
Perkin Trans. 1 1997, 3053.
(34) Compound 25: recrystallization from hexane, white needles,
mp 41–42 °C. IR (neat): 2925 (w), 1583 (s), 1469 (s), 1425
(s), 1375 (m), 1247 (m), 1213 (s), 1172 (m), 1137 (m), 1031
(m), 885 (m), 833 (m), 798 (m), 761 (m) cm–1. 1H NMR (500
MHz, CDCl3): d = 8.10 (d, J = 2.2 Hz, 1 H), 7.60 (dd,
J = 2.2, 8.6 Hz, 1 H), 7.53 (td, J = 1.8, 3.3 Hz, 1 H), 7.46 (td,
J = 1.6, 15.0 Hz, 2 H), 7.46 (d, J = 1.6, 4.8 Hz, 1 H), 7.42 (td,
J = 1.9, 4.8 Hz, 1 H), 7.38 (d, J = 8.6 Hz, 1 H). 13C NMR
(125 MHz, CDCl3): d = 149.5, 143.0, 139.1, 137.9, 129.1,
128.6, 128.5, 127.2, 122.0, 118.7 [q, J(CF) = 321.0 Hz],
89.4. HRMS (EI): m/z [M]+ calcd for C13H8F3IO3S:
427.9191; found: 427.9190.
(35) Compound 26: liquid. IR (neat): 2960 (w), 1569 (s), 1461
(s), 1428 (s), 1371 (m), 1214 (m), 1174 (m), 1137 (m), 1101
(m), 1031 (m), 883 (m), 821 (m), 790 (m), 763 (m) cm–1. 1H
NMR (500 MHz, CDCl3): d = 7.90 (d, J = 2.5 Hz, 1 H), 7.40
Synlett 2007, No. 14, 2227–2231 © Thieme Stuttgart · New York

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