Electrophilic Triflyl-arylation and Triflyl-pyridylation by Unsymmetrical Aryl/Pyridyl-λ3-iodonium Salts: Synthesis of Aryl and Pyridyl Triflones

Article abstract of DOI:10.1021/acs.joc.7b01690

Unsymmetrical diaryl-λ³-iodonium salts containing aryl triflone (Ar-SO₂CF₃) were designed and synthesized. X-ray crystal structure analysis of the salt indicated a T-shaped geometry at the iodine atom. The salts were found to be powerful electrophilic reagents for triflyl-arylation of C-, N-, and O-centered nucleophiles under mild conditions. Electrophilic transfer of pyridine triflone (Py-SO₂CF₃) to nucleophiles was also realized by the use of corresponding triflylpyridyl-aryl-λ³-iodonium salts. Selection of auxiliaries (dummy ligands) of unsymmetrical diaryl-λ³-iodonium salts is crucial for this transformation.

Full text of DOI:10.1021/acs.joc.7b01690

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Note
Electrophilic Triflyl-arylation and Triflyl-pyridylation by Unsymmetrical
Aryl/Pyridyl-#3-iodonium Salts: Synthesis of Aryl and Pyridyl Triflones
PRAJWALITA DAS, and Norio Shibata
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b01690 • Publication Date (Web): 25 Aug 2017
Downloaded from http://pubs.acs.org on August 26, 2017
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prompting chemists to develop new methodologies for the
synthesis of aryl triflones.
Electrophilic Triflyl-arylation and Triflyl-
pyridylation by Unsymmetrical Aryl/Pyridyl-λ3-
iodonium Salts: Synthesis of Aryl and Pyridyl
Triflones
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Prajwalita Das and Norio Shibata*
Department of Nanopharmaceutical Sciences, Department of
Life Science and Applied Chemistry, Nagoya Institute of
Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555, Japan
nozshiba@nitech.ac.jp
RECEIVED DATE (will be automatically inserted after
manuscript is accepted).
Figure 1: Bioactive compounds consisting of an aryl triflone moiety.
Several
methods
such
as
the
use
of
trifluoromethanesulfonylating (triflylating) reagents, oxidation
of corresponding trifluoromethylthio aromatic compounds,
transformation from SO2CF3-containing building blocks, and
intramolecular rearrangements have been developed over the
years.9 Despite of all, methods for nucleophilic substitution on
an Ar-SO2CF3 motif, SNAr reaction, remain challenging due to
the electrophilic nature of sulfone, giving rise to
regioselectivity issues. Not many reports are available for
nucleophilic substitution on Ar-SO2CF3 and a SciFinder®
search for the same reveals that a powerful electron-
withdrawing group such as nitro (NO2) on the aryl ring is
recommended with a suitable leaving group Y for rendering
the required regioselectivity for substitution via the SNAr
reaction.10a,b In the case of Ar(F)-SO2CF3, both SNAr and SN2
reactions are reported depending on the hetero-
nucleophiles.10c-f The SN2 substitution reaction by carbon
nucleophiles on the sulfonyl center is also anticipated in the
absence of a suitable functional group on the aryl ring (Ar)11
(Scheme 1a). Thus, herein we present a methodology for the
direct electrophilic introduction of the Ar-SO2CF3 group into
C, N and O-centered nucleophiles, i.e., electrophilic triflyl-
arylation using unsymmetrical diaryl-λ3-iodonium salts 1,
providing the corresponding triflyl-arylated products 2—4 in
good to excellent yields. Moreover, this idea can be extended
to another reagent for the direct electrophilic introduction of
the pyridine triflone (Py-SO2CF3) moiety into nucleophiles by
corresponding triflyl-pyridylaryl-λ3-iodonium salts (Scheme
1b).
Abstract: Unsymmetrical diaryl-λ3-iodonium salts
containing aryl triflone (Ar-SO2CF3) were designed and
synthesized. X-ray crystal structure analysis of the salt
indicated a T-shaped geometry at the iodine atom. The salts
were found to be powerful electrophilic reagents for triflyl-
arylation of C, N, and O-centered nucleophiles under mild
conditions. Electrophilic transfer of pyridine triflone (Py-
SO2CF3) to nucleophiles was also realized by the use of
corresponding
triflylpyridylaryl-λ3-iodonium
salts.
Selection of auxiliaries (dummy ligands) of unsymmetrical
diaryl-λ3-iodonium salts is crucial for this transformation.
In the quest for the development of new chemical compounds,
the field of fluorine chemistry has always maintained a strong
foothold. The powerful influence of fluorine is owed to its
unique properties, including its ability to physically and
chemically alter a molecule’s properties.1 Fluorinated aromatic
compounds such as arylfluorides (Ar-F) and trifluoromethyl
aromatics (Ar-CF3) are two of the most popular fluorinated
aromatic motifs as bioactive compounds of pharmaceuticals
and agrochemicals,2 high energy materials,3 liquid crystals4
and also as medical diagnostic tools via PET scans.5 Of the
many fluorinated aromatics, we are currently interested in the
aryl trifluoromethanesulfonyl compounds (aryl triflones, Ar-
SO2CF3), which are used as structural units in bioactive
compounds,6 chiral catalysts,7 and functional materials8
(Figure 1). The SO2CF3 group is highly electronegative
(SO2CF3, σm = 0.79, σp = 0.93; CF3, σm = 0.43, σp = 0.54) and
mildly lipophilic (SO2CF3, π = 0.55; CF3, π = 0.88)9a making it
an attractive candidate for the aforesaid categories and
Scheme 1. a) Nucleophilic substitution on SO2CF3-aromatics with or
without a NO2 group. b) Triflyl-arylation and triflyl-pyridylation of carbon
and hetero-centered nucleophiles with diaryl-λ3-iodonium salts 1.
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Figure 2: X-ray crystallographic analysis of 1b (CCDC1560414) drawn at
50% probability.
With the iodonium salts 1 in hand, electrophilic triflyl-
arylation was first investigated by the reactions with cyclic β-
keto esters 6a—e in the presence of NaH in DMF at room
temperature (Scheme 3).14 Iodonium salts 1a,b proved to be
good triflyl-arylating reagents resulting in products having a
quaternary carbon center; while 1c was not reactive. The lack
of reactivity of 1c is presumably due to steric repulsion of the
ortho-SO2CF3 and iodide, which made attack of the
nucleophile difficult. The reaction of iodonium salts 1a,b
proceeded well for all ester groups providing good yields and
was not affected by increasing the size of the esters (Me, tBu,
Ad) 2aa—2bc. Substrate 6d, which has two electron-donating
OMe groups on the benzene ring, also provided triflyl-arylated
products 2ad and 2bd in good yields, but the presence of an
electron-withdrawing Br group in 6e reduced yield to around
30% for 2ae and 2be. As an add-on, the triflyl-arylation of an
acyclic β-keto ester 6f with reagent 1a was also attempted in
the presence of tBuOK14a and it provided the product 2af in
moderate yield.
Diaryl-λ3-iodonium salts have been investigated for their
various synthetic utilities.12–16 An extremely electrophilic
iodine center induces the attack by the nucleophiles providing
the arylation products. With the use of unsymmetrical diaryl-
λ3-iodonium salts, the selective aryl transfer of one of the two
aromatic moieties to the nucleophile is of critical importance.
This is highly dependent on the electronical and steric
properties of each aryl group, and high aryl-selectivity can be
achieved by the careful design of each aryl group.12 Previous
investigations showed that electron-rich and sterically
demanding aromatics are suitable as auxiliaries, i.e., dummy
aryl groups, while electron-deficient aromatics tend to
predominately transfer to the nucleophiles. From the
viewpoint of electronegativity, fluorinated aromatic groups are
ideal for the selective transfer-arylation to nucleophiles from
unsymmetrical diaryl-λ3-iodonium salts.17 We thus designed
trifluoromethylsulfonyl-aryl-λ3-aryliodonium salts 1a—c and
1d—f which account for the para-, meta- and ortho-SO2CF3
on the phenyl ring, respectively (Scheme 2).
Scheme 3: Triflyl-arylation of β-keto esters 6 by iodonium salts 1a,b.a
Scheme 2: Synthesis of diaryliodonium salts 1 from the corresponding
iodides 5.a
Two dummy aromatics, mesitylene 1a—c and anisole
1d—f, were selected due to their steric and/or electronic
richness, thereby achieving selective transfer-arylation.
Reagents 1 were synthesized from iodides 5a—c18 by the
treatment of mesitylene or anisole with m-CPBA and
trifluoromethanesulfonic acid at room temperature.13 All the
unsymmetrical diaryl-λ3-iodonium salts were obtained in
moderate to high yields (30—91%) and confirmed by
spectroscopic analyses. An X-ray crystallographic analysis of
1b revealed a T-shaped geometry at the iodine atom (Figure
2).
Next, we investigated the triflyl-arylation reaction of
aniline derivatives 7 with 1a,b.15 Aniline 7a provided the
desired products 3aa and 3ba in good yields in the presence of
Cu under 80 °C in N-Methyl-2-pyrrolidone (NMP).17b The
presence of a halogen atom (Br, Cl) and an electron-donating
group (OMe) on the benzene ring were all effectively
sustained to provide the corresponding products 3ab, 3bb, 3ac
and 3ad in good yields. The presence of the electron-
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withdrawing NO2 group on the sterically demanding ortho-
position of aniline 7e also underwent a reaction to provide the
triflyl-phenylated product 3ae in 71% yield (Scheme 4).
Considering our approach of electrophilic triflyl-arylation,
we finally decided to further extend the design of reagents for
the triflyl-pyridylation reaction. It is well known that pyridine
is the most commonly occurring heterocycle in bioactive
compounds.19a Keeping in mind the importance of fluorine for
rendering bioactivity, the development of methodologies for
the introduction of fluoro-functionalized pyridines is very
crucial. Indeed, CF3-pyridines are one of the most widely
occurring fluorinated heterocycles in pharmaceuticals and
agrochemicals.19b The recent big commercial success of CF3-
pyridines led us to develop pyridine triflones (CF3SO2-
Scheme 4: Triflyl-arylation of anilines 7 with iodonium salts 1a,b.a
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pyridines).
Thus,
we
designed
iodonium
salts,
trifluoromethylsulfonyl-pyridine-λ3-aryliodonium salts 1,
which can lead to the introduction of pyridine triflone into
various organic compounds. Two types of salts 1 were
prepared in the same manner as their aryl counterparts, from
the corresponding pyridine iodide 5d with mesitylene or
anisole as a dummy ligand to yield iodonium salts 1g (96%)
and 1h (65%), respectively (Scheme 6a). We next investigated
the reaction for carbon and hetero-centered nucleophiles
(Scheme 6b). The reaction of β-keto esters 6a, 6e and 6f with
reagent 1g provided the triflyl-pyridylated products 2ga, 2ge
and 2gf in 89%, 70% and 30% yield, respectively. The use of
aniline 7a as an N-nucleophile for iodonium salt 1g provided
product 3ga in 53% yield. For the reaction with phenol 8a,
iodonium salt 1h was chosen and the desired product 4ha was
obtained in excellent yield (99%).
We further examined O-nucleophiles such as phenols and
alcohols 8 in the triflyl-arylation reaction (Scheme 5).16
Proceeding with this investigation, we found that the iodonium
salts 1d,e having an anisole dummy ligand reacted with 8 in
the presence of NaOH in H2O at 50°C, to provide better
yields than 1a,b with
a mesitylene auxiliary. Anisole
decreases steric hindrance for the incoming nucleophile while
the electronic status on the benzene ring of 1 is not that
different from mesitylene, allowing it to attack the
electrophilic iodine center more easily in this case.12a A wide
variety of substrates 8a—f including two electron-rich OMe
groups and an electron-withdrawing NO2 group were found to
withstand the reaction to provide the triflyl-arylation products
4da—dc and 4ea in good to excellent yields. Naphthyl- and
benzyl alcohol-derived products 4dd—4df were also obtained
in good to excellent yield by iodonium salt 1d. It should be
noted that sterically demanding ortho-triflylphenyl-
aryliodonium salt 1f also provided the desired arylation
product 4fa in 88% yield.
Scheme 6: a) Synthesis of CF3SO2-pyridylaryl-λ3-iodonium salts 1g,h
from pyridine iodide 5d. b) Triflyl-pyridylation of β-keto esters (6a,e,f),
aniline (7a) and phenol (8a).
Scheme 5: Triflyl-arylation of phenols and alcohols 8 by iodonium salts
1d—f.a
In conclusion, we have developed triflyl-aryl/pyridyl-aryl-
λ3-iodonium salts 1, which are excellent reagents for triflyl-
arylation and triflyl-pyridylation reactions for C- and hetero-
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centered nucleophiles. These iodonium salts are stable, easy-
to-handle, and useful to synthesize aryl and pyridyl triflones in
good to high yields under mild conditions. This methodology
13C{1H}NMR (CDCl3, 175 MHz) δ = 119.9 (q, J = 325.5 Hz), 123.7,
128.6, 131.7, 135.29, 137.0, 137.3.
5-Bromo-2-((trifluoromethyl)sulfonyl)pyridine
9d:
Following
paves
a
way to achieve
a
variety of SO2CF3-
General Procedure A, 5-bromo-2-((trifluoromethyl)thio)pyridine
(1.85 g, 7.1 mmol), RuCl3·xH2O (73.7 mg, 0.35 mmol) and NaIO4
(4.5 g, 21.3 mmol) in H2O (3.7 mL): MeCN (1.9 mL): CCl4 (1.9 mL)
were used at rt for 14 h. Isolated by column chromatography on silica
gel (n-hexane/EtOAc, 9/1) to give the desired product 9d as a white
solid (1.8 g) in 87% yield. Mp: 67–70 °C; HRMS (EI-TOF) m/z: [M]+
Calcd for C6H3NO2F3SBr 288.9020; Found 288.9008; 1H NMR
(CDCl3, 300 MHz) δ = 8.10—8.12 (m, 1H), 8.23—8.26 (m, 1H), 8.95
arylated/heteroarylated derivatives which can act as building
blocks for the synthesis of bioactive compounds and catalysts.
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EXPERIMENTAL SECTION
General information: All reactions were performed in oven-dried
glassware under positive pressure of nitrogen or argon unless
mentioned otherwise. Solvents were transferred via syringe and were
introduced into reaction vessels though a rubber septum. All reactions
were monitored by thin-layer chromatography (TLC) carried out on
0.25 mm Merck silica gel (60-F254). The TLC plates were visualized
with UV light and KMnO4 in water/heat. Column chromatography
was carried out on columns packed with silica gel (60N spherical
neutral size 63-210 µm). The 1H NMR (300 MHz), 19F NMR (282
MHz), and 13C NMR (175 MHz or 125 MHz) spectra for solution in
CDCl3 or (CD3)2CO were recorded on Varian Mercury 300, Bruker
Avance 500 and Joel 700 NMR spectrometers. Chemical shifts (δ) are
expressed in ppm downfield from TMS (δ = 0.00) or C6F6 [δ = −162.2
(CDCl3) or −163.5 ((CD3)2CO)] as an internal standard. Mass spectra
were recorded on a SHIMADZU GCMS-QP5050A (EI-MS) and
SHIMAZU LCMS-2020 (ESI-MS). Solvents CH3CN, CH2Cl2, DMF,
THF and NMP were dried and distilled before use.
(s, 1H); 19F NMR (CDCl3, 282 MHz)
δ = –75.92 (s, 3F);
13C{1H}NMR (CDCl3, 175 MHz) δ = 119.8 (q, J = 323.75 Hz), 127.4,
128.6, 141.5, 149.6, 152.9.
General
Procedure
B:
Preparation
of
iodo-
((trifluoromethyl)sulfonyl)benzene/pyridine 521: To a flame-dried
Schlenk-tube, CuI (10 mol %), NaI (2.0 equiv) and aryl bromide 9
(1.0 equiv) were added and evacuated and backfilled with Argon. n-
pentanol (1.0 mL/mmol ArBr) and N,N'-dimethylethylenediamine
(DMEDA) (20 mol %) were then added and the mixture was stirred at
rt for 3 min, followed by 110 °C for 49—72 h. The resulting
suspension was cooled to rt, diluted in aqueous NH3 solution (28
wt%) and H2O, and extracted with CH2Cl2 three times. The combined
organic layer was washed with brine, dried over anhydrous Na2SO4
and concentrated under reduced pressure. The crude product was
purified by column chromatography on silica gel to give the desired
product 5.
General
Procedure
A:
Preparation
of
bromo-
stirred
((trifluoromethyl)sulfonyl)benzene/pyridine 920: To
a
solution of phenyl(pyridyl)trifluoromethylsulfide (1.0 eq.) in H2O:
MeCN: CCl4 (2:1:1) at rt, RuCl3·xH2O (5 mol%) was added in one
portion followed by sodium periodate (3.0 eq.) portion wise. The
reaction mixture was monitored by TLC and upon completion of the
reaction, it was filtered through a celite pad and washed with Et2O.
The organic layer was washed with brine three times and the
combined organic layer was concentrated in vacuo. The crude was
then purified using column chromatography on silica gel to give the
desired bromo-((trifluoromethyl)sulfonyl)benzene/pyridine 9.
1-Iodo-4-((trifluoromethyl)sulfonyl)benzene 5a: Following General
Procedure B, 1-bromo-4-((trifluoromethyl)sulfonyl)benzene 9a (1.9 g,
6.6 mmol), CuI (125 mg, 0.66 mmol), NaI (1.9 g, 13.2 mmol) and
DMEDA ( .14 mL, 1.32 mmol) in n-pentanol (2.5 mL) were used at
130 °C for 72 h. Isolated by a short column chromatography on silica
gel (n-hexane) to give the desired product 5a as a white solid (2.0 g)
in 88% yield. Mp: 76–79 °C; HRMS (EI-TOF) m/z: [M]+ Calcd for
C7H4O2F3SI 335.8929; Found 335.8954; 1H NMR (CDCl3, 300 MHz)
δ = 7.71—7.84 (m, 2H), 7.88—8.07 (m, 2H); 19F NMR (CDCl3, 282
MHz) δ = –78.72 (s, 3F); 13C{1H}NMR (CDCl3, 175 MHz) δ = 106.0,
119.7 (q, J = 325.5 Hz), 131.8, 132.2, 133.0, 133.5, 139.5.
1-Iodo-3-((trifluoromethyl)sulfonyl)benzene 5b: Following General
Procedure B, 1-bromo-3-((trifluoromethyl)sulfonyl)benzene 9b (1.56
g, 5.4 mmol), CuI (103 mg, 0.54 mmol), NaI (1.6 g, 10.8 mmol) and
DMEDA ( 0.12 mL, 1.08 mmol) in n-pentanol (2 mL) were used at
130 °C for 72 h. Isolated by a short column chromatography on silica
gel (n-hexane) to give 1.8 g yellow oil which was an inseparable
mixture of the 9b and 5b (Check SI). HRMS (EI-TOF) m/z: [M]+
Calcd for C7H4O2F3SI 335.8929; Found 335.8923.
1-Iodo-2-((trifluoromethyl)sulfonyl)benzene 5c: Following General
Procedure B, 1-bromo-2-((trifluoromethyl)sulfonyl)benzene 9c (1.5 g,
5.2 mmol), CuI (99 mg, 0.52 mmol), NaI (1.54 g, 10.4 mmol) and
DMEDA ( 0.1 mL, 1.0 mmol) in n-pentanol (2 mL) were used at 130
°C for 72 h. Isolated by a short column chromatography on silica gel
(n-hexane) to give 1.5 g yellow oil which was an inseparable mixture
of the 9c and 5c (Check SI). HRMS (EI-TOF) m/z: [M]+ Calcd for
C7H4O2F3SI 335.8929; Found 335.8940.
1-Bromo-3-((trifluoromethyl)sulfonyl)benzene
9b:
Following
General Procedure A, (3-bromophenyl)(trifluoromethyl)sulfane (1.54
g, 6.0 mmol), RuCl3·xH2O (62 mg, 0.3 mmol) and NaIO4 (3.9 g, 18
mmol) in H2O (3.4 mL): MeCN (1.7 mL): CCl4 (1.7 mL) were used at
rt for 1 h. Isolated by column chromatography on silica gel (n-
hexane/EtOAc, 9/1) to give the desired product 9b as a colorless oil
(1.56 g) in 90% yield. HRMS (EI-TOF) m/z: [M]+ Calcd for
C7H4O2F3SBr 287.9067; Found 287.9085; 1H NMR (CDCl3, 300
MHz) δ = 7.57 (t, J = 9 Hz, 1H), 7.95—8.00 (m, 2H), 8.17 (s, 1H);
19F NMR (CDCl3, 282 MHz) δ = –78.44 (s, 3F); 13C{1H}NMR
(CDCl3, 175 MHz) δ = 119.8 (q, J = 323.75 Hz), 124.0, 129.4, 131.5,
133.4, 133.5, 139.8.
1-Bromo-2-((trifluoromethyl)sulfonyl)benzene
9c:
Following
General Procedure A, (2-bromophenyl)(trifluoromethyl)sulfane (1.56
g, 6.0 mmol), RuCl3·xH2O (62 mg, 0.3 mmol) and NaIO4 (3.9 g, 18
mmol) in H2O (3.4 mL): MeCN (1.7 mL): CCl4 (1.7 mL) were used at
rt for 1 h. Isolated by column chromatography on silica gel (n-
hexane/EtOAc, 9/1) to give the desired product 9c as a white solid
(1.5 g) in 86% yield. Mp: 42–44 °C; HRMS (EI-TOF) m/z: [M]+
Calcd for C7H4O2F3SBr 287.9067; Found 287.9079; 1H NMR
(CDCl3, 300 MHz) δ = 7.62—7.65 (m, 2H), 7.88—7.91 (m, 1H),
8.21—8.24 (m, 1H); 19F NMR (CDCl3, 282 MHz) δ = –76.18(s, 3F);
5-Iodo-2-((trifluoromethyl)sulfonyl)pyridine
5d:
Following
General Procedure B, 5-iodo-2-((trifluoromethyl)sulfonyl)pyridine 9d
(1.5 g, 5.2 mmol), CuI (95.2 mg, 0.5 mmol), NaI (1.53 g, 10.3 mmol)
and DMEDA ( 0.1 mL, 1.0 mmol) in n-pentanol (2. mL) were used at
130 °C for 72 h. Isolated by a column chromatography on silica gel
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(n-hexane/EtOAc 9/1) to give the desired product 5d as a white solid
δ = 21.3, 26.9, 112.0, 119.53, 120.6 (q, J = 323.75 Hz), 121.9 (q, J =
320 Hz), 129.9, 131.8, 133.2, 134.3, 137.5, 142.2, 144.9, 147.3.
Anisole(4-((trifluoromethyl)sulfonyl)phenyl)-λ6-iodane
(1.03 g) in 59% yield. Mp: 72–75 °C; HRMS (EI-TOF) m/z: [M]+
Calcd for C6H3NO2F3SI 336.8881; Found 336.8903; 1H NMR
(CDCl3, 300 MHz) δ = 7.97 (d, J = 9 Hz, 1H), 8.44 (dd, J = 6 Hz, 3
Hz, 1H), 9.10 (s, 1H); 19F NMR (CDCl3, 282 MHz) δ = –75.94 (s,
3F); 13C{1H}NMR (CDCl3, 175 MHz) δ = 102.3, 119.8 (q, J = 327.25
Hz), 127.3, 147.3, 150.2, 157.8.
trifluoromethanesulfonate 1d: Following General Procedure C, 5a
(505 mg, 1.5 mmol), mCPBA (406 mg, 1.65 mmol), TfOH (0.3 mL,
2.6 mmol) and anisole (0.2 mL, 1.7 mmol) in CH2Cl2 (15 mL) were
used from 0 °C to rt for 15 h to give 1d as a dark grey solid (669 mg)
in 75% yield. Mp: 133–136 °C; HRMS (ESI-TOF) m/z: [M–OTf]+
Calcd. for C14H11O3F3SI 442.9426; Found 442.9416; 1H NMR
((CD3)2CO), 300 MHz) δ = 3.90 (s, 3H), 7.14—7.19 (m, 2H), 8.27 (d,
J = 9 Hz, 2H), 8.34—8.39 (m, 2H), 8.67—8.71 (m, 2H); 19F NMR
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General Procedure C: Preparation of diaryliodonium salts 113:
mCPBA (assume 69 wt%, 1.1 equiv) was dried in vacuo at rt for 1 h
before
the
addition
of
iodo-
((trifluoromethyl)sulfonyl)benzene/pyridine 5 (1.0 equiv) and CH2Cl2
in a round bottomed flask. The solution was cooled to 0 °C followed
by the dropwise addition of TfOH (1.7 equiv), and the resulting
mixture was stirred at rt for 2 h. It was then cooled to 0 °C and arene
(1.1 equiv) was added dropwise. The mixture was warmed to rt and
stirred for 15–20 h. The solvent was then removed under reduced
pressure. The resulting crude product was precipitated by adding
Et2O. For reagent 1g and 1h the Et2O solution had to be stored at –20
°C for 12 h for complete precipitation to take place. The precipitate
was filtered and dried in vacuo to give 1 as a white to grey solid.
Mesityl(4-((trifluoromethyl)sulfonyl)phenyl)-λ6-iodane
((CD3)2CO), 282 MHz)
δ = –80.16 (s, 3F), –79.86 (s, 3F);
13C{1H}NMR ((CD3)2CO), 126 MHz) δ = 56.4, 103.3, 119.0, 120.5
(q, J = 323.75 Hz), 121.8 (q, J = 320 Hz), 124.8, 134.2, 135.0, 137.5,
139.5, 164.4.
Anisole(3-((trifluoromethyl)sulfonyl)phenyl)-λ6-iodane
trifluoromethanesulfonate 1e: Following General Procedure C, 5b18
(505 mg, 1.5 mmol), mCPBA (406 mg, 1.65 mmol), TfOH (0.3 mL,
2.6 mmol) and anisole (0.2 mL, 1.7 mmol) in CH2Cl2 (15 mL) were
used from 0 °C to rt for 15 h to give 1e as a dark grey solid (703 mg)
in 79% yield for overall two steps starting from 9b (1.5 mmol). Mp:
178–180 °C; HRMS (ESI-TOF) m/z: [M–OTf]+ Calcd for
trifluoromethanesulfonate 1a: Following General Procedure C, 5a
(710 mg, 2.1 mmol), mCPBA (515.4 mg, 2.3 mmol), TfOH (0.4 mL,
3.6 mmol) and mesitylene (0.3 mL, 2.3 mmol) in CH2Cl2 (6 mL) were
used from 0 °C to rt for 15 h to give 1a as a white solid (1.15 g) in
91% yield. Mp: 193–196 °C; HRMS (ESI-TOF) m/z: [M–OTf]+
Calcd for C16H15O2F3SI 454.9790; Found 454.9789; 1H NMR
((CD3)2CO), 300 MHz) δ = 2.39 (s, 3H), 2.72 (s, 6H), 7.34 (s, 2H),
8.26 (d, J = 9 Hz, 2H), 8.45 (d, J = 9 Hz, 2H); 19F NMR ((CD3)2CO),
282 MHz) δ = –80.16 (s, 3F), –79.84 (s, 3F); 13C{1H}NMR
((CD3)2CO), 126 MHz) δ = 21.0, 27.1, 120.5 (q, J = 323.75 Hz),
121.8, 122 (q, J = 320 Hz), 122.6, 131.4, 134.4, 134.9, 136.5, 143.9,
146.0.
1
C14H11O3F3SI 442.9426; Found 442.9425; H NMR ((CD3)2CO), 300
MHz) δ = 3.88 (s, 3H), 7.15 (d, J = 9 Hz, 2H), 8.04 (t, J = 9 Hz, 1H),
8.37—8.43 (m, 3H), 8.89 (d, J = 9 Hz, 1H), 8.99 (s, 1H); 19F NMR
((CD3)2CO), 282 MHz)
δ = –80.10 (s, 3F), –79.90 (s, 3F);
13C{1H}NMR ((CD3)2CO), 126 MHz) δ = 56.3, 104.0, 116.7, 118.8,
120.4 (q, J = 322.5 Hz), 121.8 (q, J = 318.75 Hz), 134.1, 134.6,
134.9, 137.4, 139.1, 144.3, 164.2.
Anisole(2-((trifluoromethyl)sulfonyl)phenyl)-λ6-iodane
trifluoromethanesulfonate 1f: Following General Procedure C, 5c18
(505 mg, 1.5 mmol), mCPBA (406 mg, 1.65 mmol), TfOH (0.3 mL,
2.6 mmol) and anisole (0.2 mL, 1.7 mmol) in CH2Cl2 (15 mL) were
used from 0 °C to rt for 15 h to give 1f as a dark grey solid (256 mg)
in 30% yield for overall two steps starting from 9c (1.44 mmol). Mp:
125–128 °C; HRMS (ESI-TOF) m/z: [M–OTf]+ Calcd for
Mesityl(3-((trifluoromethyl)sulfonyl)phenyl)-λ6-iodane
trifluoromethanesulfonate 1b: Following General Procedure C, 5b18
(710 mg, 2.1 mmol), mCPBA (515.4 mg, 2.3 mmol), TfOH (0.4 mL,
3.6 mmol) and mesitylene (0.3 mL, 2.3 mmol) in CH2Cl2 (6 mL) were
used from 0 °C to rt for 15 h to give 1b as a white solid (1.15 g) in
91% yield for overall two steps starting from 9b (2.1 mmol). Mp:
165–168 °C; HRMS (ESI-TOF) m/z: [M–OTf]+ Calcd for
1
C14H11O3F3SI 442.9426; Found 442.9423; H NMR ((CD3)2CO), 300
MHz) δ = 3.96 (s, 3H), 7.27 (d, J = 9 Hz, 2H), 8.18—8.20 (m, 3H),
8.34 (d, J = 9 Hz, 2H), 8.55 (d, J = 6 Hz, 1H); 19F NMR ((CD3)2CO),
282 MHz) δ = –79.82 (s, 3F), –78.85 (s, 3F); 13C{1H}NMR
((CD3)2CO), 126 MHz) δ = 56.5, 101.5, 114.3, 119.4, 240.5 (q, J =
323.75 Hz), 121.8 (q, J = 318.75 Hz), 123.9, 129.8, 134.69, 136. 7,
137.7, 140.6, 141.6, 165.0.
1
C16H15O2F3SI 454.9790; found 454.9792; H NMR ((CD3)2CO), 300
MHz) δ = 2.37 (s, 3H), 2.73 (s, 6H), 7.32 (s, 2H), 8.02 (t, J = 9 Hz,
1H), 8.40 (d, J = 6 Hz, 1H), 8.51 (d, J = 9 Hz, 1H), 8.76 (s, 1H); 19F
NMR ((CD3)2CO), 282 MHz) δ = –80.09 (s, 3F), –79.89 (s, 3F);
13C{1H}NMR ((CD3)2CO), 126 MHz) δ = 21.0, 27.0, 114.2, 120.4 (q,
J = 323.75 Hz), 121.8 (q, J = 318.75 Hz), 122.3, 131.3, 134.3, 134.7,
135.0, 136.4, 142.8, 143.7, 145.8.
5-(Mesityl-
λ6-iodaneyl)-2-((trifluoromethyl)sulfonyl)pyridine
trifluoromethanesulfonate 1g: Following General Procedure C, 5d
(505 mg, 1.5 mmol), mCPBA (406 mg, 1.65 mmol), TfOH (0.3 mL,
2.6 mmol) and mesitylene (0.2 mL, 1.7 mmol) in CH2Cl2 (9 mL) were
used from 0 °C to rt for 18 h to give 1g as a white solid (874 mg) in
96% yield. Mp: 132–135 °C; HRMS (ESI-TOF) m/z: [M–OTf]+
Calcd for C15H14NO2F3SI 455.9742; Found 455.9749; 1H NMR
((CD3)2CO), 300 MHz) δ = 2.39 (s, 3H), 2.75 (s, 6H), 7.33 (s, 2H),
8.48 (d, J = 9 Hz, 1H), 8.93 (d, J = 9 Hz, 1H) 8.40 (d, J = 3 Hz, 1H);
19F NMR ((CD3)2CO), 282 MHz) δ = –80.16 (s, 3F), –79.86 (s, 3F);
13C{1H}NMR ((CD3)2CO), 126 MHz) δ = 21.0, 27.2, 119.1, 120.6 (q,
J = 325 Hz), 121.7 (q, J = 378.75 Hz), 121.8, 129.9, 131.4, 143.9,
146.1, 146.1, 153. 5, 154.9.
Mesityl(2-((trifluoromethyl)sulfonyl)phenyl)-λ6-iodane
trifluoromethanesulfonate 1c: Following General Procedure C, 5c18
(710 mg, 2.1 mmol), mCPBA (515.4 mg, 2.3 mmol), TfOH (0.4 mL,
3.6 mmol) and mesitylene (0.3 mL, 2.3 mmol) in CH2Cl2 (6 mL) were
used from 0 °C to rt for 15 h to give 1c as a white solid (720 mg) in
57% yield for overall two steps starting from 9c (2.1 mmol). Mp:
145–147 °C; HRMS (ESI-TOF) m/z: [M–OTf]+ Calcd for
1
C16H15O2F3SI 454.9790; Found 454.9782; H NMR ((CD3)2CO), 300
MHz) δ = 2.47 (s, 3H), 2.66 (s, 6H), 7.40—7.51 (m, 3H), 8.07—8.20
(m, 2H), 8.57 (d, J = 6 Hz, 1H); 19F NMR ((CD3)2CO), 282 MHz) δ =
–79.87 (s, 3F), –79.10 (s, 3F); 13C{1H}NMR ((CD3)2CO), 126 MHz)
5-(Anisyl-λ6-iodaneyl)-2-((trifluoromethyl)sulfonyl)pyridine
trifluoromethanesulfonate 1h: Following General Procedure C, 5d
(337 mg, 1.0 mmol), mCPBA (271 mg, 1.1 mmol), TfOH (0.2 mL,
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1.7 mmol) and anisole (0.1 mL, 1.1 mmol) in CH2Cl2 (6 mL) were
1H), 8.12 (s, 1H); 19F NMR (CDCl3, 282 MHz) δ = –78.76 (s, 3F);
used from 0 °C to rt for 18 h to give 1h as a dark green solid (384 mg)
in 65% yield. Mp: 166–170 °C; HRMS (ESI-TOF) m/z: [M–OTf]+
Calcd for C13H10NO3F3SI 443.9378; Found 443.9379; 1H NMR
((CD3)2CO), 300 MHz) δ = 3.91 (s, 3H), 7.17 (d, J = 9 Hz, 2H), 8.40
(d, J = 9 Hz, 2H), 8.52 (d, J = 9 Hz, 1H), 9.19 (dd, J = 6 Hz, 3 Hz,
1H), 9.63 (d, J = 3 Hz, 1H); 19F NMR ((CD3)2CO), 282 MHz) δ = –
79.90 (s, 3F), –77.36 (s, 3F); 13C{1H}NMR ((CD3)2CO), 126 MHz) δ
= 55.4, 102.3, 118.1, 119.6 (q, J = 325 Hz), 120.2 (q, J = 318.75 Hz),
120.2, 128.7, 138.5, 145.9, 152.5, 154.7, 163.5.
General Procedure D: Triflyl-arylation/pyridylation of β-keto
esters: Method 117c: To a suspension of NaH (60% suspension in oil,
1.2 equiv) in DMF (10 mL/mmol β-keto ester), cyclic β-keto ester 6a-
e (1.0 equiv) was added, and the mixture was stirred at rt for 10 min.
Diaryliodonium salt 1 (1.1 equiv) was then added to the mixture in
one portion at rt. After completion of the reaction, H2O was slowly
added to the reaction mixture and extracted three times with Et2O.
The combined organic layer was washed with brine, dried over
anhydrous Na2SO4 and concentrated under reduced pressure. The
crude product was purified by column chromatography on silica gel to
give α-SO2CF3-phenyl/pyridine-β-keto ester 2.
13C{1H}NMR (CDCl3, 126 MHz) δ = 40.2, 53.8, 64.6, 119.8 (q, J =
326.34 Hz), 125.6, 126.5, 128.6, 130.1 (d, J = 13.86 Hz), 130.2,
131.8, 134.6, 136.3 (d, J = 22.68 Hz), 140.7, 151.8, 170.1, 198.9.
Tert-Butyl
1-oxo-2-(4-((trifluoromethyl)sulfonyl)phenyl)-2,3-
dihydro-1H-indene-2-carboxylate 2ab: Following General Procedure
D Method 1, cyclic β-ketoester 6b, (23.2 mg, 0.1 mmol), NaH (60%
suspension in oil, 4.8 mg, 0.12 mmol) and reagent 1a (66.5 mg, 0.11
mmol) in DMF (1 mL) were used at room temperature for 3 h.
Isolated by column chromatography on silica gel (n-hexane/EtOAc,
8/2) to give the desired product 2ab as white solid (31 mg) in 71%
yield. Mp: 76–79 °C; HRMS (ESI-TOF) m/z: [M+Na]+ calcd for
C21H19O5F3NaS 463.0803; Found 463.0809; 1H NMR (CDCl3, 300
MHz) δ = 1.38 (s, 9H), 3.58 (d, J = 15 Hz, 1H), 4.17 (d, J = 18 Hz,
1H), 7.46 (t, J = 6 Hz, 1H), 7.54 (d, J = 9 Hz, 1H), 7.69 (t, J = 6 Hz,
1H), 7.81 (d, J = 9 Hz, 2H), 7.86 (d, J = 9 Hz, 1H), 8.01 (d, J = 9 Hz,
2H); 19F NMR (CDCl3, 282 MHz) δ = –78.86 (s, 3F); 13C{1H}NMR
(CDCl3, 126 MHz) δ = 27.8, 40.2, 66.1, 83.8, 119.9 (q, J = 326.34
Hz), 125.4, 126.3, 128.5, 129.5, 130.2, 130.9, 134.9, 136.1, 148.1,
151.8, 168.4, 199.2.
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Tert-butyl
1-oxo-2-(3-((trifluoromethyl)sulfonyl)phenyl)-2,3-
Method 214a: To a suspension of tBuOK (1.2 equiv) in THF (10
mL/mmol β-keto ester), acyclic β-keto ester 6f (1.0 equiv) was added,
and the mixture was stirred at rt for 1 h. Diaryliodonium salt 1 (1.5
equiv) was then added to the mixture in one portion at rt. After
completion of the reaction, H2O was slowly added to the reaction
mixture and extracted three times with EtOAC. The combined organic
layer was washed with brine, dried over anhydrous Na2SO4 and
concentrated under reduced pressure. The crude product was purified
by column chromatography on silica gel to give α-SO2CF3-
phenyl/pyridine-β-keto ester 2.
dihydro-1H-indene-2-carboxylate 2bb: Following General Procedure
D Method 1, cyclic β-ketoester 6b, (23.2 mg, 0.1 mmol), NaH (60%
suspension in oil, 4.8 mg, 0.12 mmol) and reagent 1b (66.5 mg, 0.11
mmol) in DMF (1 mL) were used at room temperature for 3 h.
Isolated by column chromatography on silica gel (n-hexane/EtOAc,
8/2) to give the desired product 2bb as yellow oil (28 mg) in 65%
yield. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C21H19O5F3NaS
1
463.0803; Found 463.0808; H NMR (CDCl3, 300 MHz) δ = 1.37 (s,
9H), 3.58 (d, J = 18 Hz, 1H), 4.18 (d, J = 18 Hz, 1H), 7.45 (t, J = 6
Hz, 1H), 7.55 (d, J = 9 Hz, 1H), 7.68 (q, J = 6 Hz, 2H), 7.85 (d, J = 9
Hz, 1H), 7.97 (d, J = 6 Hz, 1H), 8.05 (d, J = 6 Hz, 1H), 8.18 (s, 1H);
19F NMR (CDCl3, 282 MHz) δ = –78.79 (s, 3F); 13C{1H}NMR
(CDCl3, 126 MHz) δ = 27.7, 39.9, 65.5, 83.8, 119.9 (q, J = 327.6 Hz),
125.4, 126.5, 128.4, 130.0 (t, J = 31.5 Hz), 131.5, 134.8, 136.15 (d, J
= 15.12), 141.2, 151.8, 168.4, 199.4.
(3r)-Adamantan-1-yl-1-oxo-2-(4-((trifluoromethyl)sulfonyl)phenyl)
-2,3-dihydro-1H-indene-2-carboxylate 2ac: Following General
Procedure D Method 1, cyclic β-ketoester 6c, (31 mg, 0.1 mmol),
NaH (60% suspension in oil, 4.8 mg, 0.12 mmol) and reagent 1a
(66.5 mg, 0.11 mmol) in DMF (1 mL) were used at room temperature
for 3 h. Isolated by column chromatography on silica gel (n-
hexane/EtOAc, 8/2) to give the desired product 2ac as viscous oil (45
mg) in 87% yield. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for
C27H25O5F3NaS 541.1272; Found 541.1278; 1H NMR (CDCl3, 300
MHz) δ = 1.61 (s, 7H), 2.00 (s, 6H), 2.13 (s, 3H), 3.57 (d, J = 18 Hz,
1H), 4.15 (d, J = 18 Hz, 1H), 7.45 (t, J = 6 Hz, 1H), 7.54 (d, J = 9 Hz,
1H), 7.69 (d, J = 9 Hz, 2H), 7.80—7.86 (m, 3H), 8.01 (d, J = 9 Hz,
1H), 19F NMR (CDCl3, 282 MHz) δ = –78.81 (s, 3F); 13C{1H}NMR
(CDCl3, 126 MHz) δ = 30.9, 36.0, 40.3, 40.9, 66.1, 83.9, 119.9 (q, J =
326.34 Hz), 125.4, 126.3, 128.4, 129.5, 130.1, 130.8, 134.9, 136.1,
148.1, 151.9, 167.9, 199.2.
Methyl 1-oxo-2-(4-((trifluoromethyl)sulfonyl)phenyl)-2,3-dihydro-
1H-indene-2-carboxylate 2aa: Following General Procedure
D
Method 1, cyclic β-ketoester 6a, (19 mg, 0.1 mmol), NaH (60%
suspension in oil, 4.8 mg, 0.12 mmol) and reagent 1a (66.5 mg, 0.11
mmol) in DMF (1 mL) were used at room temperature for 3 h.
Isolated by column chromatography on silica gel (n-hexane/EtOAc,
8/2) to give the desired product 2aa as white solid (34 mg) in 86%
yield. Mp: 127–130 °C; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for
C18H13O5F3NaS 421.0333; Found 421.0336; 1H NMR (CDCl3, 300
MHz) δ = 3.58 (d, J = 18 Hz, 1H), 3.76 (s, 3H), 4.27 (d, J = 18 Hz,
1H), 7.48 (t, J = 9 Hz, 1H), 7.55 (d, J = 9 Hz, 1H), 7.71 (t, J = 6 Hz,
1H), 7.76 (d, J = 9 Hz, 2H), 7.87 (d, J = 6 Hz, 1H), 8.02 (d, J = 9 Hz,
2H); 19F NMR (CDCl3, 282 MHz) δ = –78.74 (s, 3F); 13C{1H}NMR
(CDCl3, 126 MHz) δ = 40.5, 53.9, 65.3, 119.9 (q, J = 326.34 Hz),
125.6, 126.5, 128.7, 129.4, 130.5, 131.1, 134.6, 136.5, 147.7, 151.8,
169.9, 198.8.
Methyl 1-oxo-2-(3-((trifluoromethyl)sulfonyl)phenyl)-2,3-dihydro-
1H-indene-2-carboxylate 2ba: Following General Procedure
D
Method 1, cyclic β-ketoester 6a, (19 mg, 0.1 mmol), NaH (60%
suspension in oil, 4.8 mg, 0.12 mmol) and reagent 1b (66.5 mg, 0.11
mmol) in DMF (1 mL) were used at room temperature for 3 h.
Isolated by column chromatography on silica gel (n-hexane/EtOAc,
8/2) to give the desired product 2ba as white solid (37 mg) in 93%
yield. Mp: 75–77 °C; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for
C18H13O5F3NaS 421.0333; Found 421.0322; 1H NMR (CDCl3, 300
MHz) δ = 3.61 (d, J = 18 Hz, 1H), 3.74 (s, 3H), 4.25 (d, J = 18 Hz,
1H), 7.47 (t, J = 9 Hz, 1H), 7.56 (d, J = 9 Hz, 1H), 7.70 (q, J = 6 Hz,
1H), 7.87 (d, J = 9 Hz, 2H), 7.99 (d, J = 9 Hz, 1H), 8.02—8.06 (m,
(3r)-Adamantan-1-yl-1-oxo-2-(3-((trifluoromethyl)sulfonyl)phenyl)
-2,3-dihydro-1H-indene-2-carboxylate 2bc: Following General
Procedure D Method 1, cyclic β-ketoester 6c, (31 mg, 0.1 mmol),
NaH (60% suspension in oil, 4.8 mg, 0.12 mmol) and reagent 1b
(66.5 mg, 0.11 mmol) in DMF (1 mL) were used at room temperature
for 3 h. Isolated by column chromatography on silica gel (n-
hexane/EtOAc, 8/2) to give the desired product 2bc as white solid (42
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mg) in 81% yield. Mp: 107–110 °C; HRMS (ESI-TOF) m/z: [M+Na]+
D Method 1, cyclic β-ketoester 6e, (27 mg, 0.1 mmol), NaH (60%
Calcd for C27H25O5F3NaS 541.1272; Found 541.1267; 1H NMR
(CDCl3, 300 MHz) δ = 1.60 (s, 7H), 1.99 (s, 6H), 2.12 (s, 3H), 3.57
(d, J = 18 Hz, 1H), 4.18 (d, J = 15 Hz, 1H), 7.45 (t, J = 9 Hz, 1H),
7.54 (d, J = 6 Hz, 1H), 7.67 (q, J = 9 Hz, 6 Hz, 2H), 7.84 (d, J = 6 Hz,
1H), 7.97 (d, J = 9 Hz, 1H), 8.04—8.07 (m, 1H), 8.19 (s, 1H); 19F
NMR (CDCl3, 282 MHz) δ = –78.71 (s, 3F); 13C{1H}NMR (CDCl3,
126 MHz) δ = 30.9, 36.0, 40.0, 40.9, 65.6, 83.8, 119.9 (q, J = 326.34
Hz), 125.4, 126.3, 128.4, 129.9 (t, J = 32.76 Hz), 131.5, 134.8, 136.0,
136.3, 141.2, 151.9, 168.0, 199.3.
suspension in oil, 4.8 mg, 0.12 mmol) and reagent 1b (66.5 mg, 0.11
mmol) in DMF (1 mL) were used at room temperature for 12 h.
Isolated by column chromatography on silica gel (n-hexane/EtOAc,
7/3) to give the desired product 2be as white solid (15 mg) in 30%
yield. Mp: 97–100 °C; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for
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C18H12O5F3NaSBr 498.9439; Found 498.9434; H NMR (CDCl3, 300
MHz) δ = 3.58 (d, J = 15 Hz, 1H), 3.74 (s, 3H), 4.23 (d, J = 18 Hz,
1H), 7.60—7.63 (m, 1H), 7.65—7.71 (m, 2H), 7.73 (s, 1H), 7.99—
8.03 (m, 2H), 8.11 (s, 1H); 19F NMR (CDCl3, 282 MHz) δ = –78.70
(s, 3F); 13C{1H}NMR (CDCl3, 126 MHz) δ = 39.7, 53.9, 64.6, 119.8
(q, J = 326.34 Hz), 126.7, 129.8, 130.1, 130.2, 130.3, 131.9, 132.1,
132.4, 133.4, 136.1, 140.3, 153.2, 169.7, 197.7.
Methyl-5,6-dimethoxy-1-oxo-2-(4-
((trifluoromethyl)sulfonyl)phenyl)-2,3-dihydro-1H-indene-2-
carboxylate 2ad: Following General Procedure D Method 1, cyclic β-
ketoester 6d, (25 mg, 0.1 mmol), NaH (60% suspension in oil, 4.8
mg, 0.12 mmol) and reagent 1a (66.5 mg, 0.11 mmol) in DMF (1 mL)
were used at room temperature for 3 h. Isolated by column
chromatography on silica gel (n-hexane/EtOAc, 5/5) to give the
desired product 2ad as white solid (36 mg) in 78% yield. Mp: 178–
181 °C; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C20H17O7F3NaS
Ethyl-3-(4-fluorophenyl)-3-oxo-2-(4-
((trifluoromethyl)sulfonyl)phenyl)propanoate 2af: Following General
Procedure D Method 2, acyclic β-ketoester 6f, (21 mg, 0.1 mmol),
tBuOK (13 mg, 0.12 mmol) and reagent 1a (90 mg, 0.15 mmol) in
THF (1 mL) were used at room temperature for 24 h. Isolated by
column chromatography on silica gel (n-hexane/EtOAc, 9/1) to give
the desired product 2af as colorless oil (15 mg) in 36% yield. HRMS
(EI-TOF) m/z: [M]+ Calcd for C18H14O5F4S 418.0498; Found
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481.0545; Found 481.0540; H NMR (CDCl3, 300 MHz) δ = 3.42 (d,
J = 18 Hz, 1H), 3.77 (s, 3H), 3.94 (s, 3H), 4.00 (s, 3H), 4.18 (d, J = 18
Hz, 1H), 6.90 (s, 1H), 7.26 (d, J = 6 Hz, 1H), 7.73 (d, J = 6 Hz, 2H),
8.01 (d, J = 6 Hz, 2H); 19F NMR (CDCl3, 282 MHz) δ = –78.75 (s,
3F); 13C{1H}NMR (CDCl3, 126 MHz) δ = 40.5, 53.9, 56.5 (d, J =
31.5 Hz), 65.7, 105.4, 107.1, 119.9 (q, J = 326.34 Hz), 127.3, 129.3,
130.4, 131.1, 147.7, 148.4, 150.4, 157.1, 170.2, 197.2.
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418.0492; H NMR (CDCl3, 300 MHz) δ = 1.15 (t, J = 9 Hz, 3H),
4.11 (q, J = 6 Hz, 2H), 6.28 (s, 1H), 7.07–7.15 (m, 2H), 7.17–7.22 (m,
2H), 7.58–7.63 (m, 2H), 7.95 (d, J = 9 Hz, 2H); 19F NMR (CDCl3,
282 MHz)
δ = –107.75– –107.65 (m, 1F), –79.06 (s, 3F);
13C{1H}NMR (CDCl3, 126 MHz) δ = 14.1, 60.8, 107.3 (d, J = 2.5
Hz), 116.7 (d, J = 22.5 Hz), 117.0, 119.9 (q, J = 323.75 Hz), 124.2,
128.7 (d, J = 3.75 Hz), 128.9 (d, J = 8.75 Hz), 133.5, 158.9, 163.70
(d, J = 8.75 Hz), 163.71, 165.7.
Methyl-5,6-dimethoxy-1-oxo-2-(3-
((trifluoromethyl)sulfonyl)phenyl)-2,3-dihydro-1H-indene-2-
carboxylate 2bd: Following General Procedure D Method 1, cyclic β-
ketoester 6d, (25 mg, 0.1 mmol), NaH (60% suspension in oil, 4.8
mg, 0.12 mmol) and reagent 1b (66.5 mg, 0.11 mmol) in DMF (1 mL)
were used at room temperature for 3 h. Isolated by column
chromatography on silica gel (n-hexane/EtOAc, 5/5) to give the
desired product 2bd as white solid (43 mg) in 94% yield. Mp: 168–
170 °C; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C20H17O7F3NaS
Methyl
1-oxo-2-(6-((trifluoromethyl)sulfonyl)pyridin-3-yl)-2,3-
dihydro-1H-indene-2-carboxylate 2ga: Following General Procedure
D Method 1, cyclic β-ketoester 6a, (19 mg, 0.1 mmol), NaH (60%
suspension in oil, 4.8 mg, 0.12 mmol) and reagent 1g (66 mg, 0.11
mmol) in DMF (1 mL) were used at room temperature for 3 h.
Isolated by column chromatography on silica gel (n-hexane/EtOAc,
8/2) to give the desired product 2ga as white solid (31 mg) in 89%
yield. Mp: 136–138 °C; HRMS (ESI-TOF) m/z: [M]+ Calcd for
C17H13NO5F3S 400.0467; Found 400.0449; 1H NMR (CDCl3, 300
MHz) δ = 3.67 (d, J = 18 Hz, 1H), 3.77 (s, 3H), 4.27 (d, J = 15 Hz,
1H), 7.50 (t, J = 6 Hz, 1H), 7.58 (d, J = 6 Hz, 1H), 7.71—7.77(m,
1H), 7.88 (d, J = 9 Hz, 1H), 8.21 (d, J = 9 Hz, 1H), 8.33 (dd, J = 3
Hz, 6 Hz, 1H), 8.96 (d, J = 3 Hz, 1H); 19F NMR (CDCl3, 282 MHz) δ
= –76.03 (s, 3F); 13C{1H}NMR (CDCl3, 126 MHz) δ = 39.6, 54.1,
63.2, 119.9 (q, J = 327.6 Hz), 125.7, 125.9, 126.5, 128.9, 134.2,
136.2, 136.8, 138.2, 140.7, 149.9, 151.1, 151.7, 169.4, 198.1.
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481.0545; Found 481.0555; H NMR (CDCl3, 300 MHz) δ = 3.48 (d,
J = 15 Hz, 1H), 3.75 (s, 3H), 3.94 (s, 3H), 4.01 (s, 3H), 4.15 (d, J = 15
Hz, 1H), 6.94 (s, 1H), 7.25 (s, 1H), 7.67 (t, J = 9 Hz, 1H), 7.99 (t, J =
9 Hz, 2H), 8.09 (s, 1H); 19F NMR (CDCl3, 282 MHz) δ = –78.73 (s,
3F); 13C{1H}NMR (CDCl3, 126 MHz) δ = 40.2, 53.8, 56.6 (d, J =
34.02 Hz), 64.9, 105.4, 107.1, 119.9 (q, J = 326.34 Hz), 127.3, 129.9,
130.1, 130.2, 131.7, 136.2, 141.3, 147.7, 150.4, 156.9, 170.4, 197.4.
Methyl 5-bromo-1-oxo-2-(4-((trifluoromethyl)sulfonyl)phenyl)-2,3-
dihydro-1H-indene-2-carboxylate 2ae: Following General Procedure
D Method 1, cyclic β-ketoester 6e, (27 mg, 0.1 mmol), NaH (60%
suspension in oil, 4.8 mg, 0.12 mmol) and reagent 1a (66.5 mg, 0.11
mmol) in DMF (1 mL) were used at room temperature for 12 h.
Isolated by column chromatography on silica gel (n-hexane/EtOAc,
7/3) to give the desired product 2ae as white solid (16 mg) in 33%
yield. Mp: 109–101 °C; HRMS (ESI-TOF) m/z: [M–H]– Calcd for
C18H11O5F3SBr 474.9463; Found 474.9456; 1H NMR (CDCl3, 300
MHz) δ = 3.55 (d, J = 15 Hz, 1H), 3.77 (s, 3H), 4.26 (d, J = 18 Hz,
1H), 7.62 (d, J = 6 Hz, 1H), 7.73 (t, J = 9 Hz, 4H), 8.03 (d, J = 9 Hz,
2H); 19F NMR (CDCl3, 282 MHz) δ = –78.73 (s, 3F); 13C{1H}NMR
(CDCl3, 126 MHz) δ = 39.9, 54.1, 65.3, 119.1(q, J = 326.34 Hz),
126.7, 129.3, 129.8, 130.7, 131.2, 132.2, 132.4, 133.4, 147.2, 153.2,
169.5, 197.6.
Methyl-5-bromo-1-oxo-2-(6-((trifluoromethyl)sulfonyl)pyridin-3-
yl)-2,3-dihydro-1H-indene-2-carboxylate 2ge: Following General
Procedure D Method 1, cyclic β-ketoester 6e, (27 mg, 0.1 mmol),
NaH (60% suspension in oil, 4.8 mg, 0.12 mmol) and reagent 1g
(66.5 mg, 0.11 mmol) in DMF (1 mL) were used at room temperature
for 12 h. Isolated by column chromatography on silica gel (n-
hexane/EtOAc, 7/3) to give the desired product 2ge as yellow solid
(34 mg) in 70% yield. Mp: 133–135 °C; HRMS (ESI-TOF) m/z: [M–
1
H]– Calcd for C17H10NO5F3SBr 475.9415; Found 475.9412; H NMR
(CDCl3, 300 MHz) δ = 3.63 (d, J = 18 Hz, 1H), 3.77 (s, 3H), 4.26 (d,
J = 18 Hz, 1H),7.64 (d, J = 9 Hz 1H), 7.72—7.76 (m, 2H), 8.21 (d, J
= 6 Hz, 1H), 8.29—8.33 (m, 1H), 8.94 (d, J = 1.5 Hz, 1H); 19F NMR
(CDCl3, 282 MHz) δ = –75.95 (s, 3F); 13C{1H}NMR (CDCl3, 126
MHz) δ = 39.1, 54.3, 63.3, 119.8 (q, J = 326.34 Hz), 125.9, 126.8,
Methyl 5-bromo-1-oxo-2-(3-((trifluoromethyl)sulfonyl)phenyl)-2,3-
dihydro-1H-indene-2-carboxylate 2be: Following General Procedure
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129.9, 132.5, 132.6, 133.0, 138.1, 140.3, 150.2, 151.0, 153.1, 168.9,
196.9.
Ethyl-3-(4-fluorophenyl)-3-oxo-2-(6-
Found 303.0412; 1H NMR (CDCl3, 300 MHz) δ = 6.49 (s, 1H),
7.23—7.29 (m, 3H), 7.37—7.47 (m, 3H), 7.99 (d, J = 9 Hz, 1H), 7.41
(d, J = 3 Hz, 1H); 19F NMR (CDCl3, 282 MHz) δ = –77.32 (s, 3F);
13C{1H}NMR (CDCl3, 126 MHz) δ = 118.8, 120.1 (q, J = 327.6 Hz),
122.8, 126.2, 128.8, 130.2, 137.9, 138.1, 139.0, 146.3.
((trifluoromethyl)sulfonyl)pyridin-3-yl)propanoate 2gf: Following
General Procedure D Method 2, acyclic β-ketoester 6f, (21 mg, 0.1
mmol), tBuOK (13 mg, 0.12 mmol) and reagent 1g (91 mg, 0.15
mmol) in THF (1 mL) were used at room temperature for 24 h.
Isolated by column chromatography on silica gel (n-hexane/EtOAc,
8/2) to give the desired product 2gf as colorless oil (12 mg) in 30%
yield. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C17H13NO5F4NaS
442.0348; Found 442.0345; 1H NMR (CDCl3, 300 MHz) δ = 1.18 (t, J
= 9 Hz, 3H), 4.12 (q, J = 6 Hz, 2H), 6.31 (s, 1H), 7.10–7.16 (m, 2H),
7.47 (dd, J = 3 Hz, 6 Hz, 1H), 7.60–7.64 (m, 2H), 8.14 (d, J = 9 Hz,
1H), 8.61 (d, J = 3 Hz, 1H); 19F NMR (CDCl3, 282 MHz) δ = –
106.98– –106.88 (m, 1F), –76.47 (s, 3F); 13C{1H}NMR (CDCl3, 126
MHz) δ = 14.1, 60.9, 107.4 (d, J = 1.25 Hz), 116.9 (d, J = 22.5 Hz),
119.9 (q, J = 325 Hz), 123.4, 128.1 (d, J = 2.5 Hz), 128.5, 128.9 (d, J
= 8.75 Hz), 140.8, 143.5, 158.3 (d, J = 52.5 Hz), 163.4, 163.9, 165.9.
General Procedure E: Triflyl-arylation/pyridylation of
Anilines17b: To a flame-dried test tube, Cu (0) powder (10 mol %),
NMP (2.0 mL/mmol aniline) and aniline 7a–e (1.0 equiv) were added
and the resulting mixture was stirred at rt for 10 min under nitrogen.
To the mixture, diaryliodonium salt 1 (1.1 equiv) was added in one
portion and the mixture was then stirred at 80 °C. After completion of
the reaction, the mixture was cooled to rt, filtered through a pad of
silica and the residue was rinsed with Et2O. The filtrate was
concentrated under reduced pressure. The crude product was purified
by column chromatography on silica gel to give diarylamine 3.
4-Bromo-N-(4-((trifluoromethyl)sulfonyl)phenyl)aniline
3ab:
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Prepared according to the General Procedure E, using aniline 7b (34.4
mg, 0.2 mmol), Cu (0) powder (1.2 mg, 0.02 mmol) and reagent 1a
(132 mg, 0.22 mmol) in NMP (0.4 mL) at 80 °C for 12 h. Isolated by
column chromatography (n-hexane/EtOAc, 8/2) to give the desired
product 3ab as white solid (37 mg) in 48% yield. Mp: 131–133 °C;
HRMS (ESI-TOF) m/z: [M–H]– calcd for C13H8NO2F3SBr 377.9411;
Found 377.9410; 1H NMR (CDCl3, 300 MHz) δ = 6.37 (s, 1H),
7.00—7.04 (m, 2H), 7.09—7.13 (m, 2H), 7.49—7.53 (m, 2H), 7.81
(d, J = 9 Hz, 2H); 19F NMR (CDCl3, 282 MHz) δ = –79.52 (s, 3F);
13C{1H}NMR (CDCl3, 126 MHz) δ = 114.6, 118.1, 118.9, 120.1 (q, J
= 326.34 Hz), 124.2, 133.1 (d, J = 30.24 Hz), 138.1, 151.5.
N-(4-Bromophenyl)-3-((trifluoromethyl)sulfonyl)aniline
3bb:
Prepared according to the General Procedure E, using aniline 7b (34.4
mg, 0.2 mmol), Cu (0) powder (1.2 mg, 0.02 mmol) and reagent 1b
(132 mg, 0.22 mmol) in NMP (0.4 mL) at 80 °C for 12 h. Isolated by
column chromatography (n-hexane/EtOAc, 8/2) to give the desired
product 3bb as white solid (55 mg) in 73% yield. Mp: 96–99 °C;
HRMS (ESI-TOF) m/z: [M–H]– calcd for C13H8NO2F3SBr 377.9411;
Found 377.9408; 1H NMR (CDCl3, 300 MHz) δ = 6.01 (bs, 1H),
6.98—7.04 (m, 2H), 7.37—7.42 (m, 1H), 7.43—7.48 (m, 2H), 7.51
(d, J = 6 Hz, 2H), 7.57 (s, 1H); 19F NMR (CDCl3, 282 MHz) δ = –
78.86 (s, 3F); 13C{1H}NMR (CDCl3, 126 MHz) δ = 115.9, 117.2,
119.9 (q, J = 326.34 Hz), 121.6, 122.1, 123.7, 131.1, 132.5, 132.9,
139.8, 145.1.
N-phenyl-4-((trifluoromethyl)sulfonyl)aniline
3aa:
Prepared
according to the General Procedure E, using aniline 7a (18.2 µL, 0.2
mmol), Cu (0) powder (1.2 mg, 0.02 mmol) and reagent 1a (132 mg,
0.22 mmol) in NMP (0.4 mL) at 80 °C for 12 h. Isolated by column
chromatography (n-hexane/EtOAc, 9/1) to give the desired product
3aa as yellow solid (45 mg) in 74% yield. Mp: 89–92 °C; HRMS
(ESI-TOF) m/z: [M+Na]+ Calcd for C13H10NO2F3NaS 324.0282;
Found 324.0289; 1H NMR (CDCl3, 300 MHz) δ = 6.39 (s, 1H),
7.01—7.05 (m, 2H), 7.19—7.26 (m, 3H), 7.39—7.44 (m, 2H), 7.80
(d, J = 9 Hz, 2H); 19F NMR (CDCl3, 282 MHz) δ = –79.58 (s, 3F);
13C{1H}NMR (CDCl3, 126 MHz) δ = 114.4, 118.3, 120.2 (q, J =
326.34 Hz), 122.9, 125.5, 129.9, 133.2, 138.9, 152.0.
4-Chloro-N-(4-((trifluoromethyl)sulfonyl)phenyl)aniline
3ac:
Prepared according to the General Procedure E, using aniline 7c (36
mL, 0.2 mmol), Cu (0) powder (1.2 mg, 0.02 mmol) and reagent 1a
(132 mg, 0.22 mmol) in NMP (0.4 mL) at 80 °C for 12 h. Isolated by
column chromatography (n-hexane/EtOAc, 7/3) to give the desired
product 3ac as white solid (50 mg) in 67% yield. Mp: 125–128 °C;
HRMS (ESI-TOF) m/z: [M–H]– calcd for C13H8NO2F3SCl 333.9916;
Found 333.9917; 1H NMR (CDCl3, 300 MHz) δ = 6.35 (bs, 1H),
7.00—7.04 (m, 2H), 7.16—7.19 (m, 2H), 7.34—7.38 (m, 2H), 7.81
(d, J = 9 Hz, 2H); 19F NMR (CDCl3, 282 MHz) δ = –79.51 (s, 3F);
13C{1H}NMR (CDCl3, 126 MHz) δ = 114.5, 118.9, 120.1 (q, J =
326.34 Hz), 124.1, 130.08, 130.6, 133.3, 137.5, 151.6.
N-Phenyl-3-((trifluoromethyl)sulfonyl)aniline
3ba:
Prepared
according to the General Procedure E, using aniline 7a (18.2 µL, 0.2
mmol), Cu (0) powder (1.2 mg, 0.02 mmol) and reagent 1b (132 mg,
0.22 mmol) in NMP (0.4 mL) at 80 °C for 12 h. Isolated by column
chromatography (n-hexane/EtOAc, 9/1) to give the desired product
3ba as green oil (46 mg) in 77% yield. HRMS (ESI-TOF) m/z:
4-Methoxy-N-(4-((trifluoromethyl)sulfonyl)phenyl)aniline
3ad:
Prepared according to the General Procedure E, using aniline 7d (24
mg, 0.2 mmol), Cu (0) powder (1.2 mg, 0.02 mmol) and reagent 1a
(132 mg, 0.22 mmol) in NMP (0.4 mL) at 80 °C for 12 h. Isolated by
column chromatography (n-hexane/EtOAc, 8/2) to give the desired
product 3ad as white solid (30 mg) in 45% yield. Mp: 84–86 °C;
HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C14H12NO3F3NaS
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[M+Na]+ Calcd for C13H10NO2F3NaS 324.0282; Found 324.0284; H
NMR (CDCl3, 300 MHz) δ = 6.02 (bs, 1H), 7.08—7.15 (m, 3H),
7.33—7.42 (m, 3H), 7.42—7.49 (m, 2H), 7.58 (s, 1H); 19F NMR
(CDCl3, 282 MHz) δ = –78.90 (s, 3F); 13C{1H}NMR (CDCl3, 126
MHz) δ = 116.8, 119.9 (q, J = 326.34 Hz), 120.3, 121.2, 121.5, 123.3,
123.8, 129.9, 130.9, 132.3, 140.5, 145.7.
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354.0388; Found 354.0381; H NMR (CDCl3, 300 MHz) δ = 6.22 (s,
1H), 6.84—6.88 (m, 2H), 6.93—6.96 (m, 2H), 7.17 (d, J = 9 Hz, 2H),
7.75 (d, J = 6 Hz, 2H); 19F NMR (CDCl3, 282 MHz) δ = –79.66 (s,
3F); 13C{1H}NMR (CDCl3, 126 MHz) δ = 55.7, 113.5, 115.2, 117.3,
120.2 (q, J = 326.34 Hz), 126.2, 131.4, 133.2, 153.4, 157.9.
N-Phenyl-6-((trifluoromethyl)sulfonyl)pyridin-3-amine
3ga:
Prepared according to the General Procedure E, using aniline 7a (18.2
µL, 0.2 mmol), Cu (0) powder (1.2 mg, 0.02 mmol) and reagent 1g
(132 mg, 0.22 mmol) in NMP (0.4 mL) at 80 °C for 12 h. Isolated by
column chromatography (n-hexane/EtOAc, 7/3) to give the desired
product 3ga as yellow solid (32 mg) in 53% yield. Mp: 120–122 °C;
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C12H10N2O2F3S 303.0415;
2-Nitro-N-(4-((trifluoromethyl)sulfonyl)phenyl)aniline
3ae:
Prepared according to the General Procedure E, using aniline 7e (28
mg, 0.2 mmol), Cu (0) powder (1.2 mg, 0.02 mmol) and reagent 1a
(132 mg, 0.22 mmol) in NMP (0.4 mL) at 80 °C for 12 h. Isolated by
column chromatography (n-hexane/EtOAc, 7/3) to give the desired
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product 3ae as white solid (49 mg) in 71% yield. Mp: 128–130 °C;
(ESI-TOF) m/z: [M+Na]+ Calcd for C13H9O3F3SNa 325.0122; Found
325.0116; H NMR (CDCl3, 300 MHz) δ = 6.94 (d, J = 9 Hz, 1H),
7.11 (d, J = 9 Hz, 2H), 7.24—7.29 (m, 2H), 7.43 (t, J = 9 Hz, 2H),
7.65 (t, J = 9 Hz, 1H), 8.09 (d, J = 6 Hz, 1H); 19F NMR (CDCl3, 282
MHz) δ = –77.19 (s, 3F); 13C{1H}NMR (CDCl3, 126 MHz) δ = 118.2,
120.2 (q, J = 327.6 Hz), 120.6, 121.5, 122.9, 125.7, 130.4, 130.6,
138.3, 154.6, 158.8.
HRMS (ESI-TOF) m/z: [M–H]– Calcd for C13H8N2O4F3S 345.0157;
Found 345.0152; 1H NMR (CDCl3, 300 MHz) δ = 7.09—7.14 (m,
1H), 7.42—7.45 (m, 2H), 7.57—7.65 (m, 2H), 7.99 (d, J = 9 Hz, 2H),
8.25 (d, J = 6 Hz, 1H), 9.43 (s, 1H); 19F NMR (CDCl3, 282 MHz) δ =
–79.15 (s, 3F); 13C{1H}NMR (CDCl3, 126 MHz) δ = 118.8, 119.6,
121.3, 121.9, 123.7, 127.1, 133.1, 135.7, 137.2, 137.8, 148.0.
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General Procedure F: SO2CF3-arylation/pyridylation of
Alcohols: Method 116b: To a solution of NaOH (2.0 equiv) in H2O
(5.0 mL/mmol alcohol) alcohol 8a–f (1.0 equiv) was added at rt and
the mixture was stirred at rt for 5 min. Diaryliodonium salt 1 (1.2
equiv) was then added to the mixture, which was stirred at 50 °C.
After completion of the reaction, the resulting mixture was cooled to
rt, H2O was added and extracted three times with EtOAc. The
combined organic layer was washed with brine, dried over anhydrous
Na2SO4 and concentrated under reduced pressure. The crude product
was purified by column chromatography on silica gel to give SO2CF3
phenyl ether 4.
5-Phenoxy-2-((trifluoromethyl)sulfonyl)pyridine 4ha: Prepared
according to the General Procedure F, Method 2, using tBuOK (13.5
mg, 0.12 mmol), phenol 8a (22 mg, 0.1 mmol) and reagent 1h (72
mg, 0.12 mmol) in THF (0.3 mL) at 40 °C for 4 h. Isolated using
column chromatography over silica gel (n-hexane/EtOAc, 8/2) to give
the desired product 4ha as white solid (30 mg) in 99% yield. Mp:
151–154 °C; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for
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C12H8NO3F3SNa 326.0075; Found 326.0077; H NMR (CDCl3, 300
MHz) δ = 7.13—7.16 (m, 2H), 7.32—7.41 (m, 2H), 7.47—7.53 (m,
2H), 8.15 (d, J = 9 Hz, 1H), 8.60 (d, J = 3 Hz, 1H); 19F NMR (CDCl3,
282 MHz) δ = –76.62 (s, 3F); 13C{1H}NMR (CDCl3, 126 MHz) δ =
119.9 (q, J = 327.6 Hz), 120.7, 123.7, 126.7, 128.5, 130.9, 142.0,
143.1, 153.5, 159.6.
Method 216d: To a suspension of tBuOK (1.2 equiv) in THF (0.5
mL/mmol), phenol 8 (1.0 equiv) was added at 0 °C and the reaction
mixture was stirred at this temperature for 10 min. The reagent 1h
(1.2 equiv) was added in one portion and the reaction was stirred in a
preheated oil bath at 40 °C until completion. The reaction was
quenched by water at 0 °C. The organic phase was separated and the
aqueous phase was extracted with dichloromethane three times. The
combined organic phases were dried over anhydrous Na2SO4, filtered
and the solvent was concentrated under reduced pressure. The crude
product was isolated by column chromatography over silica gel (n-
hexane/EtOAc) to give the desired product 4.
1,3-Dimethoxy-5-(4-((trifluoromethyl)sulfonyl)phenoxy)benzene
4db: Prepared according to the General Procedure F, Method 1, using
NaOH (8 mg, 0.2 mmol), phenol 8b (15.4 mg, 0.1 mmol) and reagent
1d (72.5 mg, 0.12 mmol) in H2O (0.5 mL) at 50 °C for 3 h. Isolated
using column chromatography over silica gel (n-hexane/EtOAc, 9/1)
to give the desired product 4db as yellow solid (25 mg) in 68% yield.
Mp: 59–62 °C; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for
C15H13O5F3SNa 385.0333; Found 385.0329; 1H NMR (CDCl3, 300
MHz) δ = 3.79 (s, 6H), 6.26 (d, J = 1.5 Hz, 2H), 6.38 (t, J = 3 Hz,
1H), 7.14—7.19 (m, 2H), 7.97 (d, J = 9 Hz, 2H); 19F NMR (CDCl3,
282 MHz) δ = –79.17 (s, 3F); 13C{1H}NMR (CDCl3, 126 MHz) δ =
55.7, 98.0, 99.4, 117.9, 119.9 (q, J = 326.34 Hz), 123.8, 133.4, 155.8,
162.2, 165.1.
1-Phenoxy-4-((trifluoromethyl)sulfonyl)benzene 4da: Prepared
according to the General Procedure F, Method 1, using NaOH (8 mg,
0.2 mmol), phenol 8a (9.4 mg, 0.1 mmol) and reagent 1d (71 mg,
0.12 mmol) in H2O (0.5 mL) at 50 °C for 3 h. Isolated using column
chromatography over silica gel (n-hexane/EtOAc, 9/1) to give the
desired product 4da as colorless oil (30 mg) in 98% yield. HRMS
(ESI-TOF) m/z: [M–H]– Calcd for C13H8O3F3S 301.0146; Found
1-Nitro-3-(4-((trifluoromethyl)sulfonyl)phenoxy)benzene
4dc:
Prepared according to the General Procedure F, Method 1, using
NaOH (8 mg, 0.2 mmol), phenol 8c (13.9 mg, 0.1 mmol) and reagent
1d (72.5 mg, 0.12 mmol) in H2O (0.5 mL) at 50 °C for 3 h. Isolated
using column chromatography over silica gel (n-hexane/EtOAc, 9/1)
to give the desired product 4dc as white solid (31 mg) in 90% yield.
Mp: 83–85 °C; HRMS (EI-TOF) m/z: [M]+ calcd for C13H8NO5F3S
1
301.0151; H NMR (CDCl3, 300 MHz) δ = 7.10—7.14 (m, 4H), 7.29
(t, J = 9 Hz, 1H), 7.46 (t, J = 9 Hz, 2H), 7.96 (d, J = 9 Hz, 2H); 19F
NMR (CDCl3, 282 MHz) δ = –79.14 (s, 3F); 13C{1H}NMR (CDCl3,
126 MHz) δ = 117.8, 119.9 (q, J = 326.34 Hz), 120.9, 123.7, 126.1,
130.6, 133.5, 154.1, 165.4.
1
347.0075; Found 347.0080; H NMR (CDCl3, 300 MHz) δ =7.20—
1-Phenoxy-3-((trifluoromethyl)sulfonyl)benzene 4ea: Prepared
according to the General Procedure F, Method 1, using NaOH (8 mg,
0.2 mmol), phenol 8a (9.4 mg, 0.1 mmol) and reagent 1e (71 mg, 0.12
mmol) in H2O (0.5 mL) at 50 °C for 3 h. Isolated using column
chromatography over silica gel (n-hexane/EtOAc, 9/1) to give the
desired product 4ea as colorless oil (18 mg) in 60% yield. HRMS (EI-
TOF) m/z: [M]+ Calcd for C13H9O3F3S 302.0225; Found 302.0221;
1H NMR (CDCl3, 300 MHz) δ = 7.05—7.08 (m, 2H), 7.21—7.26 (m,
1H), 7.40—7.45 (m, 3H), 7.59—7.64 (m, 2H), 7.74 (d, J = 9 Hz, 1H);
19F NMR (CDCl3, 282 MHz) δ = –78.74 (s, 3F); 13C{1H}NMR
(CDCl3, 126 MHz) δ = 119.5, 119.9 (q, J = 326.34 Hz), 119.9, 124.8,
125.3, 126.0, 130.5, 131.4, 132.8, 155.3, 159.1.
1-Phenoxy-2-((trifluoromethyl)sulfonyl)benzene 4fa: Prepared
according to the General Procedure F, Method 1, using NaOH (8 mg,
0.2 mmol), phenol 8a (9.4 mg, 0.1 mmol) and reagent 1f (71 mg, 0.12
mmol) in H2O (0.5 mL) at 50 °C for 3 h. Isolated using column
chromatography over silica gel (n-hexane/EtOAc, 9/1) to give the
desired product 4fa as colorless oil (27 mg) in 88% yield. HRMS
7.23 (m, 2H), 7.49 (d, J = 9 Hz, 1H), 7.67 (t, J = 9 Hz, 1H), 7.99 (d, J
= 3 Hz, 1H), 8.05 (d, J = 9 Hz, 2H), 8.17 (d, J = 9 Hz, 1H); 19F NMR
(CDCl3, 282 MHz) δ = –78.94 (s, 3F); 13C{1H}NMR (CDCl3, 126
MHz) δ = 115.9, 118.6, 120.6, 121.2, 123.8, 125.6, 126.8, 131.4,
133.8, 149.6, 155.0, 163.7.
2-Nitro-1-(4-((trifluoromethyl)sulfonyl)phenoxy)naphthalene 4dd:
Prepared according to the General Procedure F, Method 1, using
NaOH (8 mg, 0.2 mmol), phenol 8d (19 mg, 0.1 mmol) and reagent
1d (72.5 mg, 0.12 mmol) in H2O (0.5 mL) at 50 °C for 3 h. Isolated
using column chromatography over silica gel (n-hexane/EtOAc, 9/1)
to give the desired product 4dd as yellow solid (34 mg) in 92% yield.
Mp: 125–127 °C; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for
1
C17H10NO5F3SNa 420.0129; Found 420.0118; H NMR (CDCl3, 300
MHz) δ =7.07—7.11 (m, 2H), 7.62—7.67 (m, 1H), 7.73—7.78 (m,
1H), 7.94—8.04 (m, 5H), 8.12 (d, J = 9 Hz, 1H); 19F NMR (CDCl3,
282 MHz) δ = –78.94 (s, 3F); 13C{1H}NMR (CDCl3, 126 MHz) δ =
116.9, 119.9 (q, J = 325.08 Hz), 121.0, 123.8, 124.9, 127.3, 127.5,
128.7, 129.1, 130.4, 133.7, 136.8, 138.9, 143.6, 164.9.
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Int. Ed. 2011, 123, 3051–3054. d) Amatucci, G. G.; Pereira, N. J.
Fluorine Chem. 2007, 128, 243–262.
4. a) Hird, M. Chem. Soc. Rev. 2007, 36, 2070-2095. b) Kirsch, P.;
Bremer, M. Angew. Chem. Int. Ed. 2000, 39, 4216–4235. c) Kirsch,
P.; Bremer, M.; Heckmeier, M.; Tarumi K. Angew. Chem. Int. Ed.
1999, 38, 1989–1992.
1-(Benzyloxy)-4-((trifluoromethyl)sulfonyl)benzene 4de: Prepared
according to the General Procedure F, Method 1, using NaOH (8 mg,
0.2 mmol), phenol 8e (10.3 µL, 0.1 mmol) and reagent 1d (72.5 mg,
0.12 mmol) in H2O (0.5 mL) at 50 °C for 3 h. Isolated using column
chromatography over silica gel (n-hexane/EtOAc, 9/1) to give the
desired product 4de as white solid (31 mg) in 98% yield. Mp: 77–80
°C; HRMS (EI-TOF) m/z: [M]+ Calcd For C14H11O3F3S 316.0381;
Found 316.0385; 1H NMR (CDCl3, 300 MHz) δ =5.18 (s, 2H), 7.16—
7.19 (m, 2H), 7.38—7.43 (m, 5H), 7.94—7.97 (m, 2H); 19F NMR
(CDCl3, 282 MHz) δ = –79.27 (s, 3F); 13C{1H}NMR (CDCl3, 126
MHz) δ = 70.9, 116.1, 120.0 (q, J = 325.08 Hz), 122.3, 127.7, 128.8,
129.0, 133.4, 135.2, 165.4.
1-Bromo-4-((4-((trifluoromethyl)sulfonyl)phenoxy)methyl)benzene
4df: Prepared according to the General Procedure F, Method 1, using
NaOH (8 mg, 0.2 mmol), phenol 8f (19 mg, 0.1 mmol) and reagent 1d
(72.5 mg, 0.12 mmol) in H2O (0.5 mL) at 50 °C for 3 h. Isolated
using column chromatography over silica gel (n-hexane/EtOAc, 9/1)
to give the desired product 4df as white solid (36 mg) in 92% yield.
Mp: 101–103 °C; HRMS (ESI-TOF) m/z: [M–H]– Calcd for
C14H9O3F3SBr 392.9408; Found 392.9406; 1H NMR (CDCl3, 300
MHz) δ =5.13 (s, 2H), 7.15—7.19 (m, 2H), 7.31 (d, J = 6 Hz, 2H),
7.56 (d, J = 9 Hz, 2H), 7.97 (d, J = 9 Hz, 2H); 19F NMR (CDCl3, 282
MHz) δ = –79.29 (s, 3F); 13C{1H}NMR (CDCl3, 126 MHz) δ = 70.1,
116.1, 119.9 (q, J = 326.34 Hz), 122.6, 122.8, 129.3, 132.2, 133.4,
134.2, 165.1.
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ASSOCIATED CONTENT
Supporting Information.
ORTEP diagram of 1b and 1H NMR, 19F NMR and 13C NMR spectra
for all new compounds.
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ACKNOWLEDGMENT
This research was partially supported by the Advanced Catalytic
Transformation (ACT-C) from the JST Agency and JSPS KAKENHI
Grant Number JP16H01017 in Precisely Designed Catalysts with
Customized Scaffolding. Trifluoromethanesulfonic acid is a gift from
Central Glass Inc.
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731−764 and references cited therein. b) Billard, T.; Langlois, B. R.
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