Regiospecific syntheses of functionalized diaryliodonium tosylates via [hydroxy(tosyloxy)iodo]arenes generated in situ from (diacetoxyiodo)arenes

Article abstract of DOI:10.1021/jo202517v

Ready access to ¹⁸F-labeled aryl synthons is required for preparing novel radiotracers for molecular imaging with positron emission tomography. Diaryliodonium salts react with cyclotron-produced no-carrier-added [¹⁸F]fluoride ion to

Full text of DOI:10.1021/jo202517v

Article
pubs.acs.org/joc
Regiospecific Syntheses of Functionalized Diaryliodonium Tosylates
via [Hydroxy(tosyloxy)iodo]arenes Generated in Situ from
(Diacetoxyiodo)arenes
Joong-Hyun Chun and Victor W. Pike*
Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Room B3 C346A, Building 10, 10
Center Drive, Bethesda, Maryland 20892-1003, United States
S
* Supporting Information
ABSTRACT: Ready access to 18F-labeled aryl synthons is
required for preparing novel radiotracers for molecular
imaging with positron emission tomography. Diaryliodonium
salts react with cyclotron-produced no-carrier-added [18F]-
fluoride ion to produce [18F]aryl fluorides. We aimed to
prepare functionalized diaryliodonium salts to serve as
potential precursors for producing useful 18F-labeled aryl
synthons, such as 18F-labeled halomethylbenzenes, benzaldehydes, and benzoic acid esters. Such salts were designed to have one
functionalized aryl ring, one relatively electron-rich ring, such as 4-methoxyphenyl or 2-thienyl, and a nonfluorine containing
weakly nucleophilic anion. Generation of a [hydroxy(tosyloxy)iodo]arene from a functionalized (diacetoxyiodo)arene in situ
followed by treatment with an electron-rich arene, such as anisole or thiophene, or with a functionalized arylstannane gave
expedient regiospecific access to a wide range of functionally diverse diaryliodonium tosylates in moderate to high yields (44−
98%). The described methodology broadens the scope for producing new functionalized diaryliodonium salts for diverse
applications.
labeled benzoic acid esters, benzyl halides, and benzaldehydes.
Several methods exist for the preparation of diaryliodonium
salts, and these have recently been categorized and reviewed.3
The vast majority of such methods are applicable to preparing
diaryliodonium salts bearing relatively unreactive substituents,
such as alkyl, alkoxy, or phenyl, and some of these are also
known to be suitable for preparing salts with more reactive
substituents, such as halo or nitro. However, diaryliodonium
salts bearing halomethyl functionality have not been reported.
In addition, literature precedent on the syntheses of diary-
liodonium salts with formyl substituents is sparse10−17 and in
some cases has entailed the use of undesirable reagents, such as
organomercury compounds10,11 or strong acids12,13
INTRODUCTION
■
Diaryliodonium salts are hypervalent compounds that are
classified as diaryl-λ3-iodanes.1 They are of increasing interest in
organic synthesis as effective arylating agents.2−4 Moreover,
diaryliodonium salts have gained particular value for introduc-
ing the short-lived positron-emitter fluorine-18 (t1/2 = 109.7
min) into radiotracers for molecular imaging in animal and
human subjects with positron emission tomography (PET).5
Uniquely, reactions of diaryliodonium salts with cyclotron-
produced [18F]fluoride ion can efficiently introduce fluorine-18
onto electron-rich or electron-deficient aromatic rings at any
desired carbon position in a rapid single step (Scheme 1).6−9
Here we report that variously functionalized diaryliodonium
tosylates were readily accessed as their tosylates in moderate to
high yields by generating a [hydroxy(tosyloxy)iodo]arene
(HTIA) from a prepared (diacetoxyiodo)arene in situ for
subsequent treatment with either an electron-rich arene or an
arylstannane. This convenient methodology, as well as meeting
our particular needs, will also be generally useful to others for
preparing functionalized diaryliodonium salts for use as
reagents or for their other potential applications (e.g., as
photoinitiators or bactericides).2,3
Scheme 1. General Utility of Diaryliodonium Salts for
Preparing [18F]Fluoroarenes from Cyclotron-Produced
[18F]Fluoride Ion
We particularly wished to prepare functionalized diary-
liodonium salts in which one aryl ring is especially electron-rich,
such as a 4-methoxyphenyl or 2-thienyl ring, because such a
We are further interested in exploiting the radiofluorination
of diaryliodonium salts for rapid access to functionalized
[18F]fluoroarenes that might serve as labeling synthons in the
preparation of PET radiotracers. These synthons include 18F-
Received: December 14, 2011
Published: January 26, 2012
© 2012 American Chemical Society
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ring confers high selectivity for radiofluorination at a
functionalized partner ring that is relatively less electron-
rich.6−9,18 Moreover, we wished to avoid salts with strongly
nucleophilic or fluorine-containing counterions because
nucleophilic anions might compete in subsequent radio-
fluorination reactions and fluorine-containing anions might
undesirably release nonradioactive fluoride ion to dilute the
specific radioactivity of the [18F]fluoride ion.5 Therefore,
tosylate was considered to be an acceptably benign counterion
for our specific purpose.
Scheme 2. Synthesis of Diaryliodonium Tosylates via the
Generation of HTIAs in Situ Followed by Treatment with an
Electron-Rich Arene
a
An attractive approach for the single-step syntheses of
diaryliodonium tosylates is treatment of an electron-rich
arene17 or an organometallic reagent, such as an arylsilane,19
arylboronic acid,20 or arylstannane,21 with the hypervalent-λ3-
iodane, [hydroxy(tosyloxy)iodo]benzene,22 especially as the
latter is commercially available as Koser’s reagent. We
considered that the synthetic scope of such useful methods
might be expanded for general access to unsymmetrical
diaryliodonium salts that would be useful precursors to
functionalized [18F]fluoroarenes as labeling synthons. The use
of Koser’s reagent restricts the synthesis of diaryliodonium salts
to those in which one ring is phenyl. Moreover, highly electron-
rich derivatives of Koser’s reagent, such as 4-[hydroxy-
(tosyloxy)iodo]anisole23,24 and 2-[hydroxy(tosyloxy)iodo]-
thiophene,25 are unstable, and sometimes violently so,23 when
isolated. Therefore, we aimed to explore whether such
derivatives might instead be prepared and used safely and
effectively in situ.
a
Reagents and conditions: (i) sodium perborate in MeCO2H or
peracetic acid in MeCO2H; (ii) p-TsOH·H2O, MeCN/CHCl3, reflux;
(iii) reflux.
RESULTS AND DISCUSSION
■
We were attracted to the use of congeneric (diacetoxyiodo)-
arenes (λ3-iodane diacetates) as starting materials to prepare
the required [hydroxy(tosyloxy)iodo]arenes (HTIAs) as
reactive intermediates, since these diacetates are generally
found to be stable microcrystalline solids.2,26 We envisaged a
synthetic approach in which an iodoarene would first be
oxidized to a (diacetoxyiodo)arene with peracetic acid in acetic
acid27,28 or sodium perborate tetrahydrate in acetic acid27 and
in which the isolated diacetate would then be treated with p-
TsOH·H2O plus an electron-rich arene or arylstannane. The
required (diacetoxyiodo)arenes (1−13) were readily obtained,
and the outlined approach was rapidly successful in producing a
wide range of the targeted functionalized diaryliodonium
tosylates, as we now describe.
In the use of this method with electron-rich anisole (Scheme
2), electrophilic substitution by the functionalized HTIA
intermediate occurred exclusively at the para position, and
gave the target diaryliodonium tosylates in moderate to very
high yields (46−90%), as exemplified in 12 examples (21−32;
Table 1). Thus, this method was effective for introducing
chloromethyl or bromomethyl groups into ortho, meta or para
position, methoxycarbonyl or ethoxycarbonyl into the meta
position, acetyl groups into the meta and/or para position, and
(diacetoxy)methyl into the ortho position. The regiospecificity
of the HTIA intermediates for electrophilic substitution at the
para position of anisole was remarkable but also fully consistent
with earlier findings. For example, the reagent formed between
PhI(OAc)2 and triflic acid is known to react exclusively at the 4-
position of anisole to produce (4-methoxyphenyl)-
phenyliodonium triflate.29 We further found that the use of
highly electron-rich 1,3,5-trimethoxybenzene with 4-
chloromethyl(diacetoxyiodo)benzene (Scheme 2) gave the
corresponding iodonium salt (33) in excellent yield (98%,
Table 1).
The halomethyl iodonium tosylates (21−26) are potential
precursors to [18F]fluorobenzyl halides. [18F]4-Fluorobenzyl
bromide has already proved to be a useful labeling synthon for
producing PET radiotracers,5 including radiotracers for imaging
cannabinoid subtype 1,30 histamine subtype 3,31 and delta
opioid receptors.32 However, the radiosynthesis of this synthon
has previously used three steps.30 [18F]3-Fluorobenzyl bromide
was recently used to label [18F]lapatinib, a potential radiotracer
of ERb81/ErbB2 tyrosine kinase.33 In this case, the [18F](3-
bromomethyl)fluorobenzene was prepared for the first time
from an iodonium salt in two radiosynthetic steps. The
syntheses of the diaryliodonium salts (21−26) allow us to
explore whether such [18F]fluorobenzyl halides can be prepared
more efficiently and simply in a single radiosynthetic step.
We further demonstrated that potential diaryliodonium
tosylate precursors to [18F]3-fluorobenzyl bromide that have
either 2-thienyl (34) or 5-methyl-2-thienyl (35) as the electron-
rich aryl ring could be prepared similarly from thiophene or 2-
methylthiophene (Scheme 2) in high and moderate yield (83%
and 57%, respectively; Table 1). When the more electron-rich
2-methoxythiophene was used as arene, the target diary-
liodonium salt (36) was formed in high yield (∼78%, preceding
drying attempt) (Table 1) but proved unstable to drying under
vacuum at room temperature. This salt was the only one arising
from this study showing instability.
Thiophene was also used as the electron-rich arene to
prepare diaryliodonium tosylates bearing a 3-methoxycarbonyl
(37) or 4-methoxycarbonyl (38) substituent on a phenyl ring
with a 2-thienyl partner ring in good yields (58% and 83%,
respectively; Table 1). The regioselectivity was as expected for
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Table 1. Yields of Substituted Diaryliodonium Tosylates (ArI+4-MeOC6H4OTs−) from (Diacetoxy)iodoarenes
(R1R2ArI(OAc)2) and Electron-Rich Arenes
attack of an electrophilic agent on thiophene and is in accord
with the report that HTIAs react with thiophene at the 2-
position.17 Although esters of [18F]4-fluorobenzoic acid may be
prepared in a single radiosynthetic step by aromatic
nucleophilic substitution with [18F]fluoride ion in p-nitro
precursors, radiochemical yields are low.34 Use of a 4-
trimethylammonium leaving group improves radiochemical
yield.35 However, such aromatic nucleophilic substitution
reactions are not expected to be applicable to preparing
[18F]3-fluorobenzoic acid esters in acceptable yields.5 Ready
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access to iodonium salts bearing alkoxycarbonyl groups such as
37 and 38 will allow us to explore whether they are superior
precursors for the radiosyntheses of [18F]3-fluoro- and [18F]4-
fluorobenzoic acid esters.
We were interested to see how well arylstannanes bearing a
less electron-withdrawing substituent might perform in our
method of diaryliodonium tosylate synthesis. We found that the
iodonium tosylate bearing a 3-acetoxy group (29) could be
prepared in 79% yield from 3-(tri-n-butylstannyl)phenyl acetate
and 4-methoxy(diacetoxyiodo)benzene (Table 2), which is very
comparable to the yield achieved from the treatment of 3-
acetoxy(diacetoxyiodo)benzene with anisole (83%, Table 1).
Similarly, the iodonium tosylate bearing a 3-methylamido group
(42) was obtained from the arylstannane in high yield (65%)
(Table 2).
In summary, diaryliodonium tosylates having one aryl ring
bearing chloromethyl, bromomethyl, ester, aldehyde, or amide
functionality and another relatively electron-rich ring can be
conveniently prepared in moderate to high yields (44−98%) by
treating HTIAs, generated in situ, with either electron-rich
arenes or organostannanes.
We wished to prepare (4-methoxyphenyl)aryliodonium
tosylates bearing electron-withdrawing functional groups, such
as formyl, since such salts might serve as useful precursors to
[18F]fluorobenzaldehydes, which have been demonstrated to be
useful labeling agents.36 Although (diacetoxyiodo)arenes and
HTIAs may react well and regioselectively with highly electron-
rich arenes and heteroarenes they generally show low reactivity
toward moderately electron-rich arenes. For example, Koser’s
reagent fails to react even with benzene or toluene in
acetonitrile.19 By contrast, Koser’s reagent reacts readily with
organometallic reagents, such as arylstannanes,21 to produce
the corresponding phenylaryliodonium tosylates. Stannylated
benzaldehydes proved readily accessible (Scheme 3). We were
EXPERIMENTAL SECTION
Scheme 3. Synthesis of Functionalized Diaryliodonium
Tosylates by Treating 4-[Hydroxy(tosyloxy)iodo]anisole,
Generated in Situ, With Arylstannanes
■
Methods. 1H (400 MHz) and 13C (100 MHz) NMR spectra were
recorded at room temperature. 1H and 13C chemical shifts are reported
in δ units (ppm) downfield relative to the signal for tetramethylsilane.
High resolution mass spectra (HRMS) were acquired under electron
ionization conditions using a double-focusing high-resolution mass
spectrometer. Melting points are uncorrected.
a
Preparation of (Diacetoxyiodo)arenes. (Diacetoxyiodo)arenes
(1−15) were prepared by oxidation of iodoarenes with either peracetic
acid in acetic acid26 or sodium perborate27 in acetic acid, as follows.
3-Chloromethyl(diacetoxyiodo)benzene (1). Peracetic acid in
acetic acid (32 wt %; 5 mL) was added dropwise to 3-iodobenzyl
chloride (2.8 mmol, 0.71 g) at −10 °C (ice−salt bath), and the
mixture was slowly warmed to rt and stirred overnight (ca. 14 h).
Consumption of 3-iodobenzyl chloride was monitored by TLC (silica
gel, hexane Rf = 0.38). Aqueous acetic acid (10% v/v) was added to
the yellow solution. The precipitate was recovered by filtration, washed
with water (10 mL) and then diethyl ether (10 mL × 3), and dried in
1
vacuo for 4 h to give 1 (0.62 g; 59%): mp =143−144 °C; H NMR
(CDCl3) δ 8.12 (t, J = 1.6 Hz, 1H), 8.04 (d, J = 8 Hz, 1H), 7.63 (d, J =
7.6 Hz, 1H), 7.50 (t, J = 8 Hz, 1H), 4.63 (s, 2H), 2.02 (s, 6H); 13C
NMR (CDCl3) δ 176.5, 140.5, 134.7, 134.6, 131.7, 131.1, 121.4, 44.7,
20.4.
a
Reagents and conditions: (i) sodium perborate in MeCO2H; (ii) p-
TsOH·H2O, MeCN, reflux; (iii) R6Sn2, Pd(PPh3)4, 1,4-dioxane, reflux;
(iv) CHCl3, reflux (R = Me for 29 and R= n-Bu for 39−42).
The following compounds 2−13 were prepared likewise. In
syntheses where addition of aqueous acetic acid gave no precipitate,
the yellow solution was extracted with dichloromethane. The organic
layers were then dried over MgSO4 and evaporated to give a yellow oil
which solidified when triturated with diethyl ether.
2-Chloromethyl(diacetoxyiodo)benzene (2): white solid (84%);
mp = 151−152 °C; 1H NMR (CDCl3) δ 8.25 (dd, J = 0.8, 8 Hz, 1H),
8.04 (dd, J = 1.6, 7.6 Hz, 1H), 7.66 (dt, J = 1.2, 7.6 Hz, 1H), 7.42 (dt, J
= 1.6, 7.6 Hz, 1H), 4.89 (s, 2H), 1.99 (s, 6H); 13C NMR (CDCl3) δ
176.5, 138.8, 137.7, 133.0, 130.9, 125.1, 47.8, 20.3.
4-Chloromethyl(diacetoxyiodo)benzene (3): white solid (52%);
mp = 142−145 °C; 1H NMR (CDCl3) δ 8.09 (d, J = 6.8 Hz, 2H), 7.52
(d, J = 8.4 Hz, 2H), 4.62 (s, 2H), 2.02 (s, 6H); 13C NMR (CDCl3) δ
176.5, 141.3, 135.3, 130.9, 120.9, 44.8, 20.4.
2-Bromomethyl-(diacetoxyiodo)benzene (4): white solid (45%);
mp = 113−115 °C; 1H NMR (CDCl3) δ 8.23 (d, J = 6.4 Hz, 1H), 7.75
(dd, J = 2, 8.4 Hz, 1H), 7.63 (dt, J = 2, 7.6 Hz, 1H), 7.39 (dt, J = 2.8,
8.8 Hz, 1H), 4.78 (s, 2H), 2.00 (s, 6H); 13C NMR (CDCl3) δ 175.9,
138.6, 137.3, 132.5, 132.4, 130.8, 130.3, 124.8, 33.8, 19.7.
therefore able to explore the synthesis of functionalized (4-
methoxyphenyl)aryliodonium tosylates through treatment of 4-
methoxy-(diacetoxyiodo)benzene with tosic acid followed by a
stannylated benzaldehyde. This approach (Scheme 3) gave 3-
formylphenyl(4′-methoxyphenyl)iodonium tosylate (39), the 4-
formyl analogue (40), and the 6-methoxy derivative of 39 (41)
in moderate yields (44−50%; Table 2). Similarly, use of 2-
(diacetoxyiodo)thiophene with a stannylated benzaldehyde
(Scheme 4) gave the 3-formylphenyl(2′-thienyl)iodonium
tosylate (43) and the 6-methoxy analogue (44) in moderate
yields (48%) (Table 2). Clearly, the formyl groups in the meta
or para position to the tin substituent resisted oxidation in
these syntheses. Curiously, in contrast to our success in
preparing diaryliodonium tosylates with meta or para formyl
groups, all attempts to prepare the o-formyl analogues of 39 or
43 failed. The reason is at present unclear but may be related to
the potential for an o-formyl group to form a stable five-
membered benzoiodoxole compound. No o-formyl diary-
liodonium salt has yet been reported. Nonetheless, we envisage
that the prepared (2-diacetoxymethyl)diaryliodonium tosylate
(32) can serve as a precursor to [18F]2-fluorobenzaldehyde in
two steps, namely radiofluorination to [18F](2-
diacetoxymethyl)fluorobenzene followed by hydrolysis.
3-Bromomethyl(diacetoxyiodo)benzene (5): white solid (73%);
mp = 130−132 °C; 1H NMR (CDCl3) δ 8.11 (t, J = 1.6 Hz, 1H), 8.01
(dt, J = 1.2, 8 Hz, 1H), 7.62 (dt, J = 1.2, 7.6 Hz, 1H), 7.48 (t, J = 7.6
Hz, 1H), 4.50 (s, 2H), 2.02 (s, 6H); 13C NMR (CDCl3) δ 176.5,
140.8, 135.1, 134.6, 132.3, 131.2, 121.3, 31.3, 20.4.
4-Bromomethyl(diacetoxyiodo)benzene (6): pale yellow solid
1
(42%); mp = 131−133 °C; H NMR (CDCl3) δ 8.06 (dd, J = 2,
6.4 Hz, 2H), 7.51 (d, J = 8.4 Hz, 2H), 4.49 (s, 2H), 2.02 (s, 6H); 13C
1934
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Table 2. Yields of Substituted Diaryliodonium Tosylates from a (Diacetoxyiodo)arene Treated with a Substituted Arylstannane
(s, 6H); 13C NMR (CDCl3) δ 176.5, 168.5, 151.3, 132.0, 131.3, 128.3,
125.3, 120.5, 21.0, 20.4.
4-Acetoxy(diacetoxyiodo)benzene (10): white solid (49%); mp =
153−155 °C; 1H NMR (CDCl3: δ 8.09 (dd, J = 2.4, 7.2 Hz, 2H), 7.23
(dd, J = 2, 8.8 Hz, 2H), 2.34 (s, 3H), 2.02 (s, 6H); 13C NMR (CDCl3)
δ 176.5, 168.6, 153.4, 136.5, 124.4, 117.3, 21.1, 20.4.
Scheme 4. Synthesis of 2-Thienylaryliodonium Salts Bearing
an Aldehyde Group on the Non-Thienyl Ring
a
3,4-Diacetoxy(diacetoxyiodo)benzene (11): pale yellow solid
(47%); mp = 140−142 °C; 1H NMR (CDCl3) δ 7.97−7.93 (m,
2H), 7.34 (d, J = 8.4 Hz, 1H), 2.33 (s, 6H), 2.02 (s, 6H); 13C NMR
(CDCl3) δ 176.6, 167.4, 167.3, 144.9, 143.1, 133.1, 130.4, 125.6, 116.2,
20.6, 20.5, 20.3.
4-Methoxycarbonyl(diacetoxyiodo)benzene (12): pale yellow
solid (19%); mp = 136−138 °C (lit.37 mp =150.0−153.3 °C); H
1
NMR (CDCl3) δ 8.17−8.12 (m, 4H), 3.97 (s, 3H), 2.02 (s, 6H); 13C
NMR (CDCl3) δ 176.5, 165.5, 134.9, 133.1, 131.8, 125.7, 52.7, 20.4.
2-(Diacetoxymethyl)(diacetoxyiodo)benzene (13): white solid
1
(43%); mp = 140−143 °C; H NMR (CDCl3) δ 8.32 (d, J = 7.6
Hz, 1H), 7.85 (s, 1H), 7.79 (dd, J = 1.2, 7.6 Hz, 1H), 7.70 (t, J = 7.6
Hz, 1H), 7.51 (dt, J = 1.6, 7.6 Hz, 1H), 2.13 (s, 6H), 1.98 (s, 6H); 13C
NMR (CDCl3) δ 176.5, 168.3, 168.1, 138.5, 136.4, 132.5, 132.3, 130.0,
a
121.5, 91.1, 20.6, 20.2.
2-(Diacetoxyiodo)thiophene (14). Sodium perborate tetrahydrate
(7.69 g, 50 mmol) was added portionwise over 30 min to a solution of
Reagents and conditions: (i) sodium perborate in MeCO2H, 50 °C;
overnight; (ii) p-TsOH·H2O, MeCN, reflux; (iii) CHCl3, reflux.
2-iodothiophene (1.05 g, 5 mmol) in acetic acid (50 mL). The
temperature was raised to 50 °C and the mixture stirred at this
temperature overnight (ca. 14 h). The resulting solid was filtered off,
NMR (CDCl3) δ 176.5, 141.7, 138.0, 135.4, 131.5, 130.8, 120.8, 31.4,
20.4.
3-Methoxycarbonyl(diacetoxyiodo)benzene (7): pale yellow solid
and the filtrate was concentrated in vacuo. The product was extracted
1
(30%); mp = 163−165 °C; H NMR (CDCl3) δ 8.75 (t, J = 1.6 Hz,
with dichloromethane (30 mL × 3) and washed with water (100 mL ×
1H), 8.28−8.25 (m, 2H), 7.59 (t, J = 8 Hz, 1H) 3.97 (s, 3H), 2.02 (s,
2). The organic layers were dried over MgSO4 and concentrated to a
6H); 13C NMR (CDCl3) δ 176.5, 165.0, 138.9, 136.1, 132.6, 130.8,
pale yellow oil. Trituration of this oil with Et2O gave solids that were
123.1, 121.2, 52.3, 20.3.
filtered off, washed with Et2O, and dried under vacuum to give 14 as a
white solid (0.58 g, 35%): mp = 115−118 °C (lit.38 mp = 120−122
3-Ethoxycarbonyl(diacetoxyiodo)benzene (8): white solid (19%);
mp = 113−115 °C; 1H NMR (CDCl3) δ 8.74 (t, J = 1.6 Hz, 1H), 8.26
(dd, J = 1.6, 8 Hz, 2H), 7.58 (t, J = 8 Hz, 1H), 4.42 (q, J = 7.2, 2H),
2.02 (s, 6H), 1.43 (t, J = 6.8 Hz, 3H); 13C NMR (CDCl3) δ 176.6,
164.5, 138.9, 136.0, 133.2, 132.6, 130.8, 121.1, 61.9, 20.4, 14.3.
3-Acetoxy(diacetoxyiodo)benzene (9): white solid (51%); mp
=121−123 °C; 1H NMR (CDCl3) δ 7.95−7.92 (m, 1H), 7.89 (t, J = 2
Hz, 1H), 7.52 (t, J = 8 Hz, 1H), 7.36−7.33 (m, 1H), 2.34 (s, 3H), 2.02
°C; lit.39 mp = 112−119 °C). H NMR (CDCl3) δ 7.78 (dd, J = 1.2,
3.6 Hz, 1H), 7.64 (dd, J = 1.2, 5.2 Hz, 1H), 7.15−7.13 (m, 1H), 2.02
(s, 6H); 13C NMR (CDCl3) δ 177.0, 139.1, 134.9, 128.7, 106.3, 20.4.
4-Methoxy(diacetoxyiodo)benzene (15).28 This compound was
prepared in the same manner as 14 and obtained as a white solid
(34%): mp = 85−88 °C (lit.40 mp =88−90 °C); 1H NMR (CDCl3) δ
8.01 (d, J = 9.2 Hz, 2H), 6.97 (d, J = 9.2 Hz, 2H), 3.87 (s, 3H), 2.00
1
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(s, 6H); 13C NMR (100 MHz, CDCl3) δ 176.34, 162.2, 137.1, 116.6,
111.7, 55.6, 20.4.
Preparation of Arylstannanes. Arylstannanes 16−20 were
prepared from iodoarenes by treatment with either hexamethylditin41
or hexa-n-butylditin42 over palladium catalyst, as follows.
4H), 7.45 (t, J = 8.4 Hz, 1H), 7.21 (d, J = 8.8 Hz, 2H), 7.05 (d,
J = 8.8 Hz, 2H), 4.98 (s, 2H), 3.84 (s, 3H), 2.36 (s, 3H); 13C
NMR (MeOD-d4) δ 164.7, 143.7, 141.8, 141.2, 139.1, 138.6,
134.9, 133.5, 133.4, 129.9, 127.1, 120.2, 119.0, 104.7, 56.5, 21.5;
HRMS [M − OTs]•+ calcd for C14H13OClI 358.9700, found
358.9697.
N-Methyl-3-(trimethylstannyl)benzamide (16). 3-Iodo-N-methyl-
benzamide (0.73 g, 2.8 mmol) bis(trimethylditin) (1.00 g, 3.1 mmol)
and Pd(PPh3)4 catalyst (0.068 g, 0.05 mmol) were added to toluene
(20 mL) under argon. This mixture was refluxed overnight and the
precipitate then filtered off. The filtrate was concentrated in vacuo, and
the remaining crude oil was purified with column chromatography
(silica gel, 50% EtOAc/hexane) to give 16 (Rf = 0.35) as a white solid
(0.39 g, 44%): mp = 91−92 °C; 1H NMR (CDCl3) δ 7.88 (d, J = 1.2
Hz, 1H), 7.67−7.65 (m, 1H), 7.62−7.60 (m, 1H), 7.38 (t, J = 7.2 Hz,
1H), 6.14 (s, br, 1H), 3.02 (d, J = 4.8 Hz, 3H), 0.31 (s, 9H); 13C NMR
(CDCl3) δ 168.8, 143.2, 138.8, 134.1, 128.0, 126.5, 26.9, −7.77.
4-Tri-n-butylstannylbenzaldehyde (17). Bis(tri-n-butylditin) (2.61
g, 4.5 mmol) and Pd(PPh3)4 (0.084 g, 0.07 mmol) were added to a
solution of 4-iodobenzaldehyde (1.03 g, 4.4 mmol) in 1,4-dioxane (20
mL) under argon. This mixture was refluxed for 8 h. The resulting
dark precipitate was filtered off on a Celite pad, and the filtrate was
concentrated in vacuo. Column chromatography (silica gel; 5%
EtOAc/hexane) of the crude oil gave 17 (Rf = 0.43) as a colorless oil
(1.10 g, 63%): 1H NMR (CDCl3) δ 9.99 (s, 1H), 7.81−7.77 (m, 2H),
7.67−7.60 (m, 2H), 1.57−1.51 (m, 6H), 1.36−1.31 (m, 6H), 1.13−
1.09 (m, 6H), 0.89 (t, J = 7.6 Hz, 9H); 13C NMR (CDCl3) δ 192.7,
152.5, 136.9, 135.9, 128.4, 29.0, 27.3, 13.6, 9.7. Spectroscopic data
correspond to reported data.43
The following compounds (22−38) were prepared likewise from
the appropriate functionalized HTIA and an electron-rich arene
(anisole, 1,3,5-trimethoxybenzene, thiophene, 2-methylthiophene, or
2-methoxythiophene).
3-Chloromethylphenyl(4′-methoxyphenyl)iodonium tosylate
1
(22): yield 84%; mp = 170−171 °C; H NMR (CDCl3) δ 8.00 (s,
1H), 7.89 (dd, J = 2, 7.2 Hz, 2H), 7.82 (d, J = 8 Hz, 1H), 7.51 (d, J = 8
Hz, 3H), 7.31 (t, J = 8 Hz, 1H), 7.04 (d, J = 8 Hz, 2H), 6.84 (dd, J = 2,
7.2 Hz, 2H), 4.46 (s, 2H), 3.80 (s, 3H), 2.32 (s, 3H); 13C NMR
(CDCl3) δ 162.5, 142.4, 141.2, 139.6, 137.5, 134.3, 134.1, 131.7, 131.5,
128.5, 126.0, 117.6, 115.7, 103.6, 55.6, 44.5, 21.3; HRMS [M −
OTs]•+ calcd for C14H13OClI 358.9700, found 358.9694.
4-Chloromethylphenyl(4′methoxyphenyl)iodonium tosylate (23):
1
yield 90%; mp = 191−193 °C; H NMR (MeOD-d4) δ 8.09 (t, J = 8
Hz, 4H), 7.69 (d, J = 8 Hz, 2H), 7.55 (d, J = 8.4 Hz, 2H), 7.22 (d, J =
7.6 Hz, 2H), 7.05 (d, J = 8.8 Hz, 2H), 4.67 (s, 2H), 3.84 (s, 3H), 2.36
(s, 3H); 13C NMR (MeOD-d4) δ 164.7, 144.3, 143.7, 141.8, 138.8,
136.5, 133.2, 130.0, 127.1, 119.0, 115.9, 104.8, 56.5, 45.5, 21.5; HRMS
[M − OTs]•+ calcd for C14H13OClI 358.9700, found 358.9700.
2-Bromomethylphenyl(4′-methoxyphenyl)iodonium tosylate
1
(24): yield 46%. mp = 135−137 °C; H NMR (MeOD-d4): δ 8.30
(d, J = 7.6 Hz, 1H), 8.15 (d, J = 8.8 Hz, 2H), 7.77 (dd, J = 2, 7.6 Hz,
1H), 7.70−7.65 (m, 3H), 7.42 (dt, J = 2.4, 7.6 Hz, 1H), 7.22 (d, J = 7.6
Hz, 2H), 7.06 (d, J = 8.8 Hz, 2H), 4.89 (s, 2H), 3.85 (s, 3H), 2.37 (s,
3H); 13C NMR (MeOD-d4): δ 164.8, 143.7, 141.8, 141.7, 139.1, 138.7,
134.9, 133.5, 133.4, 130.0, 127.1, 120.2, 119.0, 104.6, 56.5, 35.3, 21.5;
HRMS [M − OTs]•+ calcd for C14H13OBrI 402.9195, found 402.9195.
3-Bromomethylphenyl(4′-methoxyphenyl)iodonium tosylate
3-Tri-n-butylstannylbenzaldehyde (18). This was prepared as
1
described for 17: colorless oil (61%); H NMR (CDCl3): δ 10.02 (s,
1H), 8.02−7.92 (m, 1H), 7.81−7.77 (m, 1H), 7.74−7.72 (m, 1H),
7.51−7.75 (m, 1H), 1.57−1.51 (m, 6H), 1.37−1.31 (m, 6H), 1.13−
1.09 (m, 6H), 0.89 (t, J = 7.2 Hz, 9H); 13C NMR (CDCl3) δ 193.1,
143.5, 142.5, 137.6, 135.5, 129.4, 128.3, 29.0, 27.3, 13.6, 9.6.
Spectroscopic data correspond to reported data.44
1
(25): yield 78%; mp = 171−173 °C; H NMR (CDCl3) δ 8.00 (s,
1H), 7.89 (d, J = 8.8 Hz, 2H), 7.79 (d, J = 8 Hz, 1H), 7.51 (t, J = 8.4
Hz, 3H), 7.29 (t, J = 7.6 Hz, 1H), 7.04 (d, J = 8 Hz, 2H), 6.85 (d, J =
9.2 Hz, 2H), 4.35 (s, 2H), 3.81 (s, 3H), 2.32 (s, 3H); 13C NMR
(CDCl3) δ 162.5, 142.6, 141.5, 139.4, 137.5, 134.7, 134.0, 132.8, 131.7,
128.5, 126.0, 117.6, 115.8, 103.6, 55.6, 31.2, 21.3; HRMS [M −
OTs]•+ calcd for C14H13OBrI 402.9195, found 402.9192.
4-Methoxy-3-(tri-n-butylstannyl)benzaldehyde (19). Bis-
(tributylditin) (1.94 g, 3.3 mmol) and Pd(PPh3)4 (0.034 g, 0.03
mmol) were added to a solution of 3-iodo-4-methoxybenzaldehyde
(0.79 g, 3.0 mmol) in toluene (20 mL) at rt under argon. This mixture
was refluxed overnight. The resulting dark precipitate was removed by
filtration on Celite pad, and the filtrate toluene solution was
concentrated in vacuo. Column chromatography (silica gel; 20%
EtOAc/hexane) of the crude oil gave 19 (Rf = 0.5) as a pale yellow oil
4-Bromomethylphenyl(4′-methoxyphenyl)iodonium tosylate
1
(26): yield 81%; mp =139−141 °C; H NMR (CDCl3) δ 7.88 (t, J
1
= 7.2 Hz, 4H), 7.48 (d, J = 8 Hz, 2H), 7.31 (d, J = 8.4 Hz, 2H), 7.03
(d, J = 7.6 Hz, 2H), 6.82 (d, J = 9.2 Hz, 2H), 4.38 (s, 2H), 3.79 (s,
3H), 2.31 (s, 3H); 13C NMR (CDCl3) δ 162.4, 142.4, 141.4, 139.4,
137.5, 135.0, 131.9, 128.5, 126.0, 117.5, 115.2, 103.8, 55.6, 31.3, 21.3;
HRMS [M − OTs]•+ calcd for C14H13OBrI 402.9195, found 402.9199.
[3-(Methoxycarbonyl)phenyl](4′-methoxyphenyl)iodonium tosy-
late (27): yield 63%; mp = 155−157 °C; 1H NMR (MeOD-d4) δ 8.71
(s, 1H), 8.32 (d, J = 8.4 Hz, 1H), 8.25 (d, J = 7.2 Hz, 1H), 8.12 (d, J =
10 Hz, 2H), 7.68 (d, J = 5.6 Hz, 2H), 7.62 (t, J = 6 Hz, 1H), 7.21 (d, J
= 7.2 Hz, 2H), 7.06 (d, J = 7.2 Hz, 2H), 3.93 (s, 3H), 3.83 (s, 3H),
2.35 (s, 3H); 13C NMR (MeOD-d4) δ 166.2, 164.8, 143.7, 141.8,
140.2, 138.9, 136.7, 134.9, 134.1, 133.3, 129.9, 127.1, 119.1, 116.7,
104.8, 56.5, 53.4, 21.4; HRMS [M − OTs]•+ calcd for C15H14O3I
368.9988, found 368.9984.
(1.12 g, 87%): H NMR (CDCl3) δ 9.89 (s, 1H), 7.90 (d, J = 2 Hz,
1H), 7.83 (dd, J = 2.4, 8.8 Hz, 1H), 6.90 (dd, J = 6.8, 15.2 Hz, 1H),
3.86 (s, 3H), 1.55−1.50 (m, 6H), 1.36−1.30 (m, 6H), 1.11−1.07 (m,
6H), 0.89 (t, J = 7.2 Hz, 9H); 13C NMR (CDCl3) δ 191.1, 168.6,
138.8, 133.2, 131.7, 130.1, 108.7, 55.4, 29.0. 27.2, 13.4, 9.8.
3-(Tri-n-butylstannyl)phenyl Acetate (20). This was prepared as
described for 19: colorless oil (60%); 1H NMR (CDCl3) δ 7.35−7.29
(m, 2H), 7.14 (d, J = 2.4 Hz, 1H), 7.02−6.99 (m, 1H), 2.29 (s, 3H),
1.57−1.49 (m, 6H), 1.37−1.30 (m, 6H), 1.08−1.04 (m, 6H), 0.88 (t, J
= 7.6 Hz, 9H); 13C NMR (CDCl3) δ 169.5, 150.3, 143.9, 133.8, 128.7,
121.1, 28.9, 27.3, 21.2, 13.6, 9.6.
Synthesis of Functionalized Diaryliodonium Salts by
Treating HTIAs with Electron-Rich Arenes.
2-
Chloromethylphenyl(4′-methoxyphenyl)iodonium tosylate (21). p-
TsOH·H2O (0.15 g, 0.8 mmol) was added to a suspension of 2-
chloromethyl(diacetoxyiodo)benzene (0.31 g, 0.8 mmol) in
MeCN (2 mL), giving an intense yellow solution, which was
immediately diluted with chloroform (20 mL). Anisole (0.22 g,
2 mmol) was added, and the resultant pale yellow solution was
then refluxed for 4 h. The consumption of HTIA was
monitored with KI−starch paper. Solvent was then removed
under reduced pressure, and the yellow oily residue was
triturated with Et2O (30 mL). Precipitate was filtered off,
washed with Et2O, dried under vacuum for 4 h, and
recrystallized from MeOH/Et2O to give 21 as a white solid
(0.38 g, 83%): mp =172−174 °C; 1H NMR (MeOD-d4) δ 8.33
(d, J = 8.4 Hz, 1H), 8.11 (d, J = 8.8 Hz, 2H), 7.77−7.67 (m,
3-(Ethoxycarbonyl)phenyl(4′-methoxyphenyl)iodonium tosylate
(28): yield 69%; mp = 173−175 °C; 1H NMR (CDCl3) δ 8.44 (s, 1H),
8.22 (d, J = 8 Hz, 1H), 8.12 (d, J = 7.6 Hz, 1H), 7.88 (d, J = 8.8 Hz,
2H), 7.50 (d, J = 8 Hz, 2H), 7.42 (t, J = 8 Hz, 1H), 7.02 (d, J = 8 Hz,
2H), 6.85 (d, J = 8.8 Hz, 2H), 4.35 (q, J = 7.2 Hz, 2H), 3.80 (s, 3H),
2.31 (s, 3H), 1.36 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3) δ 164.3,
162.6, 142.4, 139.6, 138.8, 137.4, 135.1, 133.6, 132.3, 131.4, 128.5,
126.0, 117.6, 115.9, 104.0, 61.8, 55.6, 21.3, 14.2; HRMS [M − OTs]•+
calcd for C16H16O3I 383.0144, found 383.0133.
3-Acetoxyphenyl(4′-methoxyphenyl)iodonium tosylate (29):
1
yield 88%; mp = 149−150 °C; H NMR (MeOD-d4) δ 8.08 (dd, J
= 3.2, 9.2 Hz, 2H), 8.00−7.96 (m, 2H), 7.69 (dd, J = 0.8, 8 Hz, 2H),
7.54 (t, J = 8 Hz, 1H), 7.43−7.40 (m, 1H), 7.22 (d, J = 8.4 Hz, 2H),
1936
dx.doi.org/10.1021/jo202517v | J. Org. Chem. 2012, 77, 1931−1938

The Journal of Organic Chemistry
Article
7.08−7.05 (m, 2H), 3.85 (s, 3H), 2.36 (s, 3H), 2.29 (s, 3H); 13C NMR
(MeOD-d4) δ 170.4, 164.7, 153.5, 143.8, 141.8, 138.8, 133.7, 133.3,
130.0, 129.7, 127.3, 127.1, 119.4, 115.6, 104.8, 56.5, 21.5, 20.9; HRMS
[M − OTs]•+ calcd for C15H14O3I 368.9988, found 368.9986.
4-Acetoxyphenyl(4′-methoxyphenyl)iodonium tosylate (30):
127.1, 119.1, 99.3, 53.5, 21.5; HRMS [M − OTs]•+ calcd for
C12H10O2SI 344.9446, found 344.9447.
[4-(Methoxycarbonyl)phenyl](2′-thienyl)iodonium tosylate (38):
yield 83%; mp = 188−190 °C; 1H NMR (MeOD-d4) δ 8.26 (dd, J = 2,
7.2 Hz, 2H), 8.32 (dd, J = 1.6, 6.8 Hz, 2H), 8.05 (dd, J = 1.2, 3.6 Hz,
1H), 7.92 (dd, J = 1.2, 5.2 Hz, 1H), 7.69 (d, J = 5.6 Hz, 2H), 7.23−
7.18 (m, 3H), 3.92 (s, 3H), 2.36 (s, 3H); 13C NMR (MeOD-d4) δ
166.8, 143.7, 142.8, 141.8, 139.2, 136.0, 135.2, 133.7, 131.1, 130.0,
127.1, 123.4, 99.1, 53.4, 21.5; HRMS [M − OTs]•+ calcd for
C12H10O2SI 344.9446, found 344.9442.
1
yield 88%; mp 157−159 °C; H NMR (CDCl3) δ 7.94 (dd, J = 2,
7.2 Hz, 2H), 7.88 (dd, J = 2, 7.2 Hz, 2H), 7.94 (dd, J = 1.6, 4.8 Hz,
2H), 7.05−7.00 (m, 4H), 6.80 (dd, J = 2, 9.2 Hz, 2H), 3.78 (s, 3H),
2.30 (s, 3H), 2.28 (s, 3H); 13C NMR (CDCl3) δ 168.5, 162.3, 152.9,
142.5, 139.3, 137.5, 136.1, 128.5, 126.0, 124.8, 117.4, 111.4, 104.3,
55.5, 21.2, 21.1; HRMS [M − OTs]•+ calcd for C15H14O3I 368.9988,
found 368.9986.
Syntheses of Functionalized Diaryliodonium Salts through
Reaction of the HTIA from 4-Methoxy(diacetoxyiodo)benzene
with Functionalized Arylstannanes. 3-Formylphenyl(4′-
methoxyphenyl)iodonium Tosylate (39). p-TsOH·H2O (0.10 g,
0.53 mmol) was added to a suspension of 4-methoxy-
(diacetoxyiodo)benzene (0.19 g, 0.53 mmol) in MeCN (2
mL) while the mixture was cooled to 0 °C. The resultant yellow
solution was diluted with chloroform (15 mL). 3-Formyl-3-(tri-
n-butylstannyl)benzaldehyde (0.21 g, 0.52 mmol) in chloro-
form (5 mL) was added in portions and the mixture gradually
heated to reflux for 2 h. The consumption of organotin
compound was monitored by TLC (silica gel, 5% EtOAc/
hexane; Rf = 0.4), and disappearance of HTIA was confirmed
with KI−starch paper. The reaction mixture was then cooled to
rt, and solvent was removed in vacuo to give a pale yellow oil
which was triturated with Et2O. Solid was filtered off, washed
with Et2O, and dried under vacuum to give 39 as a white solid:
3, 4-Diacetoxyphenyl(4′-methoxyphenyl)iodonium tosylate (31):
yield 86%; mp 155−156 °C; 1H NMR (CDCl3) δ 7.91−7.88 (m, 3H),
7.83 (dd, J = 2, 8.8 Hz, 1H), 7.41 (d, J = 8 Hz, 2H), 7.11 (d, J = 8.8
Hz, 2H), 7.00 (d, J = 7.6 Hz, 2H), 6.76 (d, J = 8.8 Hz, 2H), 3.75 (s,
3H), 2.29 (s, 3H), 2.26 (s, 3H), 2.22 (s, 3H); 13C NMR (CDCl3) δ
167.5, 167.4, 162.4, 144.9, 143.3, 142.3, 139.4, 137.7, 133.1, 130.2,
128.5, 126.1, 126.0, 117.4, 110.6, 104.4, 55.6, 21.3, 20.6, 20.5; HRMS
[M − OTs]•+ calcd for C17H16O5I 427.0043, found 427.0044.
[2-(Diacetoxymethyl)phenyl](4′-methoxyphenyl)iodonium tosy-
1
late (32): yield 77%; mp 150−153 °C; H NMR (MeOD-d4) δ 8.28
(dd, J = 0.8, 8 Hz, 1H), 8.07 (dd, J = 2, 7.2 Hz, 2H), 7.86−7.84 (m,
2H), 7.77 (dt, J = 0.8, 7.6 Hz, 1H), 7.72 (d, J = 8.4 Hz, 2H), 7.56 (dt, J
= 1.6, 8 Hz, 1H), 7.22 (d, J = 7.6 Hz, 2H), 7.07 (d, J = 9.2 Hz, 2H),
3.84 (s, 3H), 2.36 (s, 3H), 2.12 (s, 6H); 13C NMR (MeOD-d4) δ
170.3, 164.8, 143.8, 141.8, 138.7, 138.6, 138.3, 135.9, 134.6, 131.9,
129.9, 127.1, 119.1, 116.7, 104.7, 92.7, 56.6, 21.5, 20.7; HRMS [M −
OTs]•+ calcd for C18H18O5I 441.0199, found 441.0192.
1
yield 44%; mp = 156−159 °C; H NMR (CDCl3) δ 9.81 (s,
1H), 8.41 (s, 1H), 8.22 (d, J = 8 Hz, 1H), 7.94−7.90 (m, 3H),
7.47−7.40 (m, 3H), 6.98 (d, J = 8 Hz, 2H), 6.81 (d, J = 9.2 Hz,
2H), 3.78 (s, 3H), 2.29 (s, 3H); 13C NMR (CDCl3) δ 189.9,
162.5, 142.2, 140.0, 139.7, 138.5, 137.7, 136.0, 131.8, 131.2,
128.5, 125.9, 117.51, 116.9, 104.1, 55.6, 21.2; HRMS [M −
OTs]•+ calcd for C14H12O2I 338.9882, found 338.9880.
The following compounds (40−44) were prepared similarly.
4-Formylphenyl(4′-methoxyphenyl)iodonium tosylate (40): yield
52%; mp = 184−187 °C; 1H NMR (CDCl3) δ 9.93 (s, 1H), 8.10 (d, J
= 8.4 Hz, 2H), 7.90 (d, J = 9.2 Hz, 2H), 7.71 (d, J = 8.4 Hz, 2H), 7.41
(d, J = 8 Hz, 2H), 6.99 (d, J = 8 Hz, 2H), 6.81 (d, J = 9.2 Hz, 2H),
3.78 (s, 3H), 2.29 (s, 3H); 13C NMR (CDCl3) δ 190.7, 162.5, 142.1,
139.7, 137.8, 137.6, 135.2, 131.6, 128.5, 125.9, 122.2, 117.5, 104.1,
55.6, 21.3; HRMS [M − OTs]•+ calcd for C14H12O2I 338.9882, found
338.9878.
4-Chloromethylphenyl(2′,4′,6′-trimethoxyphenyl)iodonium tosy-
late (33): yield 98%; mp = 185−187 °C; 1H NMR (MeOD-d4) δ 7.93
(d, J = 8.4 Hz, 2H), 7.68 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 8.4 Hz, 2H),
7.21 (d, J = 8 Hz, 2H), 6.41 (s, 2H), 4.65 (s, 2H), 3.97 (s, 6H), 3.89 (s,
3H), 2.36 (s, 3H); 13C NMR (MeOD-d4) δ 169.0, 161.6, 143.9, 143.8,
141.8, 136.3, 132.9, 129.9, 127.1, 115.3, 93.1, 86.4, 57.9, 56.8, 45.6,
21.5; HRMS [M − OTs]•+ calcd for C16H17O3ClI 418.9911, found
418.9906.
3-Bromomethylphenyl(2′-thienyl)iodonium tosylate (34): yield
1
83%; mp = 138−140 °C; H NMR (CDCl3) δ 8.01 (t, J = 1.6 Hz,
1H), 7.84 (d, J = 8.4 Hz, 1H), 7.81 (dd, J = 1.2, 4 Hz, 1H), 7.58 (dd, J
= 0.8, 5.2 Hz, 1H), 7.50−7.47 (m, 3H), 7.29 (t, J = 8 Hz, 1H), 7.07−
7.02 (m, 3H), 4.33 (s, 2H), 2.32 (s, 3H); 13C NMR (CDCl3) δ 142.1,
141.5, 140.7, 139.7, 136.2, 134.3, 133.6, 132.1, 131.7, 129.6, 128.6,
125.9, 118.7, 99.2, 31.2, 21.3; HRMS [M − OTs]•+ calcd for
C11H9SBrI 378.8653, found 378.8651.
3-Formyl-6-methoxyphenyl(4′-methoxyphenyl)iodonium tosy-
1
late (41): yield 50%; mp = 185−187 °C; H NMR (CDCl3) δ 9.77
(s, 1H), 8.16 (d, J = 2 Hz, 1H), 7.99 (dd, J = 1.6, 8.4 Hz, 1H), 7.91
(dd, J = 2, 6.8 Hz, 2H), 7.51 (d, J = 2 Hz, 2H), 7.10−7.03 (m, 3H),
6.87 (dd, J = 2, 6.8 Hz, 2H), 4.02 (s, 3H), 3.82 (s, 3H), 2.31 (s, 3H);
13C NMR (CDCl3) δ 188.4, 162.7, 160.8, 142.4, 139.6, 137.8, 136.8,
3-Bromomethylphenyl(5′-methyl-2′-thienyl)iodonium tosylate
1
(35): yield 57%; mp = 163−165 °C; H NMR (CDCl3) δ 8.00 (t, J
= 1.6 Hz, 1H), 7.82 (dq, J = 0.8, 8.4 Hz, 1H), 7.61 (d, J = 4 Hz, 1H),
7.53 (dd, J = 2, 6.4 Hz, 2H), 7.49 (d, J = 8 Hz, 1H), 7.30 (t, J = 8 Hz,
1H), 7.07 (dd, J = 0.4, 8 Hz, 2H), 6.71−6.70 (m, 1H), 4.34 (s, 2H),
2.57 (s, 3H), 2.33 (s, 3H); 13C NMR (CDCl3) δ 152.4, 142.2, 141.5,
141.4, 139.7, 134.0, 133.3, 132.1, 131.7, 128.6, 128.2, 126.0, 118.8,
94.6, 31.2, 21.3, 15.5; HRMS [M − OTs]•+ calcd for C12H11SBrI
392.8810, found 392.8807.
135.3, 132.2, 128.5, 126.0, 117.7, 112.2, 106.6, 102,1, 57.6, 55.6, 21.3;
HRMS [M − OTs]•+ calcd for C15H14O3I 368.9988, found 368.9982.
[3-(Methylcarbamoyl)phenyl](4′-methoxyphenyl)iodonium tosy-
late (42): yield 65%; mp =172−173 °C; 1H NMR (MeOD-d4) δ 8.53
(t, J = 1.6 Hz, 1H), 8.24 (dq, J = 0.8, 8 Hz, 1H), 8.10 (dd, J = 2, 7.6
Hz, 2H), 8.04 (dq, J = 1.2, 8 Hz, 1H), 7.68 (dd, J = 1.6, 8 Hz, 2H),
7.59 (t, J = 8 Hz, 1H), 7.21 (d, J = 8 Hz, 2H), 7.06 (dd, J = 3.2, 10.4
Hz, 2H), 3.84 (s, 3H), 2.91 (s, 3H), 2.36 (s, 3H); 13C NMR (MeOD-
d4) δ 167.9, 164.8, 143.7, 141.8, 139.2, 138.9, 138.6, 135.1, 133.2,
131.7, 130.0, 127.1, 119.1, 116.8, 104.7, 56.5, 27.2, 21.5; HRMS [M −
OTs]•+ calcd for C15H15NO2I 368.0148, found 368.0150.
3-Formylphenyl(2′-thienyl)iodonium tosylate (43): yield 48%; mp
= 153−156 °C; 1H NMR (CDCl3) δ 9.82 (s, 1H), 8.40 (t, J = 1.6 Hz,
1H), 8.25 (dq, J = 1.2, 8 Hz, 1H), 7.94 (dt, J = 1.2, 7.6, 1H), 7.86 (dd,
J = 1.2, 4 Hz, 1H), 7.58 (dd, J = 1.2, 5.2 Hz, 1H), 7.49 (t, J = 4.8 Hz,
1H), 7.43 (d, J = 8 Hz, 2H), 7.04−7.02 (m, 3H), 2.32 (s, 3H); 13C
NMR (CDCl3) δ 189.5, 141.1, 140.2, 139.4, 138.6, 136.5, 135.3, 132.0,
131.6, 131.5, 129.8, 128.7, 125.9, 119.5, 21.3; HRMS [M − OTs]•+
calcd for C11H8OSI 314.9341, found 314.9340.
3-Bromomethylphenyl(5′-methoxy-2′-thienyl)iodonium tosylate
1
(36): yield 78%; mp = 58−59 °C; H NMR (CDCl3) δ 7.97 (t, J = 2
Hz, 1H), 7.81 (dd, J = 1.2, 8 Hz, 1H), 7.64 (dd, J = 1.6, 8 Hz, 2H),
7.55−7.51 (m, 2H), 7.35 (t, J = 8 Hz, 1H), 7.12 (d, J = 8 Hz, 2H), 6.22
(d, J = 4.4 Hz, 1H), 4.37 (s, 2H), 3.95 (s, 3H), 2.34 (s, 3H); 13C NMR
(CDCl3) δ 176.0, 142.3, 141.8, 141.6, 139.8, 133.3, 132.5, 132.2, 131.9,
128.7, 126.0, 119.1, 107.2, 61.0, 31.1, 21.3. This compound
decomposed to a black tar during drying under vacuum at room
temperature.
[3-(Methoxycarbonyl)phenyl](2′-thienyl)iodonium tosylate (37):
1
yield 58%; mp = 140−141 °C; H NMR (MeOD-d4) δ 8.76 (s, 1H),
8.37 (d, J = 7.2 Hz, 1H), 8.26 (d, J = 7.6 Hz, 1H), 8.05 (d, J = 2.8 Hz,
1H), 7.90 (d, J = 5.6 Hz, 1H), 7.69−7.62 (m, 3H), 7.22−7.17 (m,
3H), 3.94 (s, 3H), 2.36 (s, 3H); 13C NMR (MeOD-d4) δ 166.1, 143.7,
142.7, 141.8, 139.9, 139.1, 136.5, 134.9, 134.3, 133.4, 131.1, 130.0,
3-Formyl-6-methoxyphenyl(2′-thienyl)iodonium tosylate (44):
1
yield 48%; mp = 178−179 °C; H NMR (CDCl3) δ 9.73 (s, 1H),
1937
dx.doi.org/10.1021/jo202517v | J. Org. Chem. 2012, 77, 1931−1938

The Journal of Organic Chemistry
Article
7.97 (dd, J = 2, 8.4 Hz, 1H), 7.76 (dd, J = 1.2, 4 Hz, 1H), 7.51 (dd, J =
1.2, 5.2 Hz, 1H), 7.41 (dd, J = 1.6, 8.4 Hz, 2H), 7.06−7.01 (m, 3H),
6.97 (dd, J = 3.6, 5.2 Hz, 1H), 4.02 (s, 3H), 2.31 (s, 3H); 13C NMR
(CDCl3) δ 188.4, 160.6, 142.1, 140.4, 139.7, 138.9, 135.5, 135.0, 131.8,
129.2, 128.5, 125.9, 112.2, 110.2, 98.5, 57.4, 21.3; HRMS [M −
OTs]•+ calcd for C12H10O2SI 344.9446, found 344.9441.
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ASSOCIATED CONTENT
■
S
* Supporting Information
1H NMR and 13C NMR spectra of synthesized compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(33) Basuli, F.; Wu, H.; Li, C.; Shi, Z.-D.; Sulima, A.; Griffiths, G. L. J.
Labelled Compd. Radiopharm. 2011, 54, 633−636.
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AUTHOR INFORMATION
■
Corresponding Author
*E-mail: pikev@mail.nih.gov.
Notes
(35) Jalilian, A. R.; Seyfi, P.; Afarideh, H.; Shafiee, A. Appl. Radiat.
Isot. 2001, 54, 407−411.
(36) Lemaire, C.; Damhaut, P.; Plenevaux, A.; Comar, D. J. Nucl.
Med. 1997, 35, 1996−2002.
The authors declare no competing financial interest.
(37) Leffler, J. E.; Story, L. J. J. Am. Chem. Soc. 1967, 89, 2333−2338.
(38) Togo, H.; Nabana, T.; Yamaguchi, K. J. Org. Chem. 2000, 65,
8391−8394.
ACKNOWLEDGMENTS
■
This research was supported by the Intramural Research
Program of the National Insitutes of Health (NIMH).
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