Convenient and Inexpensive Route to Sulfonylated Pyridines via S N Ar Reaction of Electron-Rich Pyridines by Iron Catalysis

Article abstract of DOI:10.1055/s-0036-1591541

Sulfonylated pyridines were synthesized in moderate to excellent yields, with a wide scope of substituted pyridines and sulfinate salts as starting materials, by an iron-catalyzed S _N Ar reaction. This new methodology exhibits advantages for the synthesis of these useful substrates, such as the use of a readily available, inexpensive catalyst, prevention of the disproportionation of the sulfinate salts, and, more importantly, providing access to electron-rich pyridine substrates.

Full text of DOI:10.1055/s-0036-1591541

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–G
paper
A
en
F. Chen et al.
Paper
Synthesis
Convenient and Inexpensive Route to Sulfonylated Pyridines via
SNAr Reaction of Electron-Rich Pyridines by Iron Catalysis
Fei Chena
X
Franklin Chacón-Huetea
Hassan El-Husseini1,a
Pat Forgione*a,b
R
O
S
N
O
O
S
SNAr "inactive" pyridines
ONa
R
R
R
N
cat. FeCl3
a Department of Chemistry & Biochemistry, Concordia
University, 7141 rue Sherbrooke O. H4B 1R6, Montréal,
QC, Canada
b Centre for Green Chemistry and Catalysis, Montréal,
QC, Canada
X = Br, I, Cl
limiting reagent
26 examples 26~89%
pat.forgione@concordia.ca
Received: 27.11.2017
Accepted after revision: 12.01.2017
Published online: 20.02.2018
of Guo reported a copper(I)-catalyzed reaction between
several chloropyridines and sodium sulfinate salts by using
a
household microwave reflux apparatus, with good
DOI: 10.1055/s-0036-1591541; Art ID: ss-2017-m0768-op
yields.21 In the same year, Maloney’s group reported a met-
al-free nucleophilic SNAr reaction to access sulfonylated
pyridines mostly with activated, electron-poor chloropyri-
dines by employing a stoichiometric amounts of HCl. Pyr-
idyl bromides, iodides, and triflates have only been report-
ed once for the synthesis of these sulfones, and their use
was limited to activated, electron-deficient pyridines.24 One
major limitation of these reported methodologies is that
they require an excess of the potentially valuable sulfinate
salt. Recently Sreedhar and co-workers expanded sulfone
formation by using copper ferric nanoparticles; however,
the 2-bromopyridines remained the limiting reagents
(Scheme 1).22
Abstract Sulfonylated pyridines were synthesized in moderate to ex-
cellent yields, with a wide scope of substituted pyridines and sulfinate
salts as starting materials, by an iron-catalyzed SNAr reaction. This new
methodology exhibits advantages for the synthesis of these useful sub-
strates, such as the use of a readily available, inexpensive catalyst, pre-
vention of the disproportionation of the sulfinate salts, and, more im-
portantly, providing access to electron-rich pyridine substrates.
Key words sulfinate salts, sulfones, iron catalysis, pyridines, coupling
Aryl sulfones are interesting moieties in various fields,
including the pharmaceutical industry, agrochemicals, and
polymer synthesis.2–8 Among these, aryl sulfones and sulfo-
nylated pyridines are highlighted as an important class of
versatile and useful compounds.9,10 Additionally, these pyri-
dines play an important role as directing groups for further
functionalization as applied to complex molecule synthe-
sis.11–17
General methods to access sulfonylated pyridines in-
clude the oxidation of thiol ethers,18–20 coupling reac-
tions,21,22 and SNAr chemistry.23,24 The most common oxida-
tion method involves the use of odoriferous thiols that re-
sult in the production of a large quantity of hazardous
waste.18 Metal-catalyzed cross-coupling of sulfinate salts
with halopyridines25,26 and pyridylboronic acids27,28 have
also been reported, but yields are generally low for the for-
mation of the corresponding sulfonylated pyridines. Sulfone
formation through an SNAr reaction was reported in 1989
by Ulman and co-workers.29 Employing this method re-
quires electron-poor arene substrates, which limits the
scope of the reaction. The synthesis of sulfonylated pyri-
dines through an SNAr reaction by using a modified house-
hold microwave was reported in 2009.30 In 2011, the group
In this work, we explore the use of sulfinate salts as the
limiting reagent through an SNAr reaction with inactivated
pyridines (electron-rich and neutral). The starting point for
the optimization route were the conditions reported by
Maloney’s group;24 the reaction with 2-chloropyridine (2a)
resulted in a dramatic drop from the 89% reported yield to
37% when sulfinate 1a was used as the limiting reagent (Ta-
ble 1, entry 1). To expand the scope and robustness of the
reactions, we evaluated the use of FeCl3 as Lewis acid to re-
place HCl, which would be useful for substrates that are
Brønsted acid sensitive. Initially, replacing the HCl (1 equiv)
with FeCl3 (1 equiv) resulted in complete decomposition of
the starting materials (entry 2). Formation of the desired
sulfonylated pyridine was observed when catalytic
amounts of FeCl3 and an increased temperature were em-
ployed (entries 3 and 4). Modification of the solvent system
to DMSO–H2O (3:1) dramatically increased the formation of
the desired product (entry 5). Further lowering of the cata-
lyst loading and adjusting the additive equivalents and
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–G

B
F. Chen et al.
Paper
Synthesis
price in bulk for this catalyst. We evaluated a variety of
halopyridines with a focus on challenging SNAr substrates
including inactive bromo- or iodopyridines (Table 2). Im-
pressively, bromo- (entry 3) and iodopyridine (entry 4)
provided the corresponding product in equal or better
yields than the more electron-poor chloropyridine (entry
1), used during our initial optimization. Further increasing
the electronegativity by employing 2-fluoropyridine result-
ed in a dramatic decrease in yield (entry 2). Our hypothesis
is that as the electronegativity of the halogen atom decreas-
es, there is an increased coordination of pyridine to the iron
catalyst that facilitates the addition of the sulfinate, while
simultaneously avoiding disproportionation reactions in
comparison to using HCl.
previous work:
a) Maloney (2010)
O
TBACl (0.3 equiv)
HCl (1 equiv)
DMA, 100 °C, 24 h
O
O
Cl
S
S
ONa
+
R
R
N
22 examples
75–98%
N
1.5 equiv
limiting reagent
one example of active pyridyl bromides, iodides and triflates
b) Others
O
O
O
X
S
+
R
R
S
R
N
R
ONa
N
limiting reagent
Guo 2011: X = Cl
sulfinate salts (1.0 equiv)
Sreedhar 2014: X = Br
sulfinate salts (1.2 equiv)
CuCl (10 mol%), quinoline (10 mol%)
10 examples with pyridine 55–82%
CuFe2O4,1,10-phenanthroline (10 mol%)
one example with pyridine 87%
this work:
O
Table 1 Optimization of the Conditions for the Formation of Sulfo-
nylated Pyridine 3aa
O
O
S
X
cat.
Fe(III)
S
ONa
O
O
O
R
Cl
R'
+
R
R'
FeCl3
N
S
S
N
ONa
+
N
limiting reagent
X = Br, I
nBu4NCl, solvent
temperature, time
air
N
inactive pyridines
Scheme 1 Reported methods for the synthesis of sulfonylated pyri-
1a
2a
3a
dines and the present work
Entry Cat.
nBu4NCl Solvent
(equiv) (2 M)
Temp,
time
Yield
(%)
(equiv)
concentration of the reaction further improved the yields
(entries 6–12). A 66% yield of the desired product 3a was
obtained on a 2 mmol reaction scale (entry 12); however,
larger reaction scales (10–30 mmol) employing the same
conditions resulted in an increase in the yield to 78% (entry
15). Fe(acac)3 was also evaluated as the catalytic iron source
and provided similar yields (entry 16). The absence of the
additive has a negligible effect when FeCl3 is employed (en-
try 13), but reduces the yield by 10% with Fe(acac)3 as the
catalyst (entry 17). With these newly optimized conditions,
we revisited the use of stoichiometric HCl (entry 18), but
only a 38% yield of the corresponding product was ob-
tained. The known disproportionation of the sulfinic acids
under acidic conditions31 is the likely cause of these re-
duced yields, highlighting the value of employing Lewis
acids such as FeCl3 in these reactions.
With the concern that our optimized conditions of using
FeCl3 in DMSO/H2O could act as an HCl source, we replaced
the water portion of the solvent with buffer solution (phos-
phate buffer, pH 7.2, 7.8, and 8.3) and obtained similar
yields (62%, 71%, and 70%, respectively, compared with 66%
when using just water, Table 1, entry 12). Furthermore,
when Et3N (0.03 equiv) was added to neutralize the possi-
ble acid generated, a 77% yield was obtained that again is in
agreement with the iron catalyst not acting as an acid
source. FeCl3 was selected over Fe(acac)3 to proceed with
the investigation, on the basis of the broad availability and
1
2
3
4
5
6
7
8
9
HCl (1)
0.15
0.15
0.15
0.15
0.15
0.15
0.15
0.15
1.0
DMA
100 °C, 24 h 37
100 °C, 24 h
FeCl3 (1)
FeCl3 (0.3)
FeCl3 (0.1)
FeCl3 (0.1)
FeCl3 (0.2)
FeCl3 (0.3)
–
DMA
–
DMA
120 °C, 24 h 8b
140 °C, 24 h 12
140 °C, 20 h 44
140 °C, 20 h 40
140 °C, 20 h 38
140 °C, 20 h trace
140 °C, 20 h 44
140 °C, 20 h 57
DMSO
DMSO–H2O (3:1)
DMSO–H2O (3:1)
DMSO–H2O (3:1)
DMSO–H2O (3:1)
DMSO–H2O (3:1)
DMSO–H2O (3:1)
FeCl3 (0.01)
10 FeCl3 (0.01)
11 FeCl3 (0.01)
12 FeCl3 (0.01)
13 FeCl3 (0.01)
14 FeCl3 (0.01)
15c FeCl3 (0.01)
0.3
0.15
0.15
–
DMSO–H2O (3:1, 0.5 M) 140 °C, 20 h 35
DMSO–H2O (3:1)
DMSO–H2O (3:1)
140 °C, 20 h 66
140 °C, 20 h 60
0.15
0.15
DMSO–H2O (3:1, 4 M) 140 °C, 20 h 52
DMSO–H2O (3:1)
DMSO–H2O (3:1)
DMSO–H2O (3:1)
DMSO–H2O (3:1)
140 °C, 20 h 78
140 °C, 20 h 64
140 °C, 20 h 45
140 °C, 20 h 38
16 Fe(acac)3 (0.01) 0.15
17 Fe(acac)3 (0.01)
18 HCl (1)
–
0.15
a Reaction conditions: 1a (2 mmol, 1.0 equiv), 2a (1.1 equiv), FeCl3, nBu4NCl,
in air.
b Yield determined by 1H NMR.
c Reaction carried out on 10–30 mmol scale.
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F. Chen et al.
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Synthesis
Table 2 Halopyridine Scopea
Table 3 Scope of Electron-Rich Pyridinesa
O
X
S
O
O
O
O
O
X
FeCl3 (1 mol%)
S
FeCl3 (1 mol%)
S
S
+
ONa
ONa
+
R
R
N
N
nBu4NCl
R
N
N
nBu4NCl
(0.15 equiv)
DMSO/H2O (3:1)
140 °C, 20 h
2 M
(0.15 equiv)
R
DMSO/H2O (3:1)
140 °C, 20 h
2 M
1a
2
3
1a
2
3
Entry
1
Substrate 2
Product 3
Isolated yield
(%)
Entry
Substrate 2
Product 3
Isolated yield
(%)
O
O
O
O
O
Cl
O
O
O
O
O
S
S
S
S
Br
S
S
S
S
66
12
69
85
N
1
78
77
68
N
N
N
2a
3a
3a
3a
3a
3b
3c
3d
2e
O
F
O
Br
2
3
4
N
2
3
N
N
N
2b
2f
O
Br
O
Br
N
N
N
N
2c
2g
O
I
O
Br
N
N
N
4
5
72
48
N
2d
2h
a Reaction conditions: 1 (2 mmol, 1.0 equiv), 2 (1.2 equiv), FeCl3 (1 mol%),
nBu4NCl (0.15 equiv), DMSO–H2O (3:1, 2 M), 140 °C, 20 h.
3e
3f
OMe
O
O
O
S
Br
We evaluated this methodology employing a range of
electron-rich pyridine substrates. Since the identified main
side product is the sulfonic acid of the corresponding sulfi-
nate salt, we initiated investigations under an argon atmo-
sphere and degassed the solvent to avoid oxygen in the re-
action medium.32–34 Methyl substituents on 2-bromo-
pyridines in various positions have no significant steric
influence on the yield (68–78%, Table 3, entries 1–4). How-
ever, when a methoxy group is at the 3-position of 2-
bromopyridine, the yield is reduced to 48% (entry 5). 2-
Iodo-3-methylpyridine provides the corresponding product
in a higher yield than that resulting from the equivalent
brominated analogue, which is in agreement with the coor-
dination hypothesis (85% vs 78%, entry 6 vs entry 1). Addi-
tionally, the 4-iodopyridine analogue also participates in
the reaction under these conditions and produces the cor-
responding sulfonylated pyridine in 61% yield (entry 7).
Overall, generally inactive electron-rich pyridines are well
suited to iron catalysis and small substituents have limited
steric effect.
N
O
N
2i
O
O
I
S
S
6
7
85
61
N
N
3b
3g
2j
O
I
N
N
2k
a Reaction conditions: 1 (1.0 equiv), 2 (1.2 equiv), FeCl3 (1 mol%), nBu4NCl
(0.15 equiv), DMSO–H2O (3:1, 2 M), 140 °C, 20 h.
bromopyridines, and various electron-rich to electron-defi-
cient sulfinates are well tolerated in the reaction. This reac-
tion provided higher yields with electron-neutral sulfinate
substrates, such as benzenesulfonylated pyridine 3h, which
is obtained in a yield of 71% starting from 2-bromopyridine
in comparison to 82% from 2-iodopyridine (entry 1), and p-
toluenesulfinate salt which yielded 79% and 89% of product
3a (entry 2). To evaluate the effect of the position of the
substituent, p-, m-, and o-toluenesulfinates were examined.
Various sulfinate salts 1 were studied in the reactions
with both 2-bromopyridine and 2-iodopyridine (Table 4).
The results demonstrate that 2-iodopyridines provide the
corresponding products in better yields compared with 2-
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F. Chen et al.
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Synthesis
o-Toluenesulfinate resulted in a lower yield (entry 4) when
compared to its para isomer (entry 2), presumably due to
higher steric hindrance, while m-toluenesulfinate has a
slightly lower yield (70% and 78%,entry 3). Both electron-
rich and electron-deficient sulfinate substrates are well tol-
erated in this reaction. With 2-bromopyridine, the elec-
tron-rich anisolesulfinate has a lower yield (62%, entry 5)
than the electron-deficient 4-(trifluoromethyl)benzenesul-
finate (77%, entry 6). However, with 2-iodopyridine, the 4-
(trifluoromethyl)benzenesulfinate has a lower yield than
the anisolesulfinate (78% and 88% respectively, entries 5
and 6). Modest results were obtained with naphthalenesul-
finates (entries 7 and 8), with a higher yield for the 1-naph-
thalene isomer. Overall, this reaction tolerates a range of
sulfinate substrates, including electron-rich, electron-neu-
tral, and electron-deficient, as well as sterically hindered
sulfinates.
Table 4 Scope of Sodium Sulfinate Salts
O
O
O
S
X
S
FeCl3 (1 mol%)
ONa
+
R
R
N
N
nBu4NCl
(0.3 equiv)
DMSO/H2O (3:1)
140 °C, 20 h
2 M
X = Br, I
2
1
3
Entry Substrate 1
Product 3
Yield (%) Yield (%)
X = Br X = I
O
O
SO2Na
S
1
2
3
4
5
71
82
N
1b
1a
1c
3h
3a
3i
O
O
SO2Na
S
S
79
89
N
In conclusion, we have developed an iron-catalyzed re-
action for the synthesis of sulfonylated pyridines in good to
excellent yields. In this method, inexpensive and readily
available FeCl3 has been used to replace HCl, which increas-
es the robustness of the reaction towards acid-sensitive
substrates. With this in mind, this methodology uses sulfi-
nate salts as the limiting reagents, since its acid-catalyzed
disproportionation is avoided. An examination on the effect
of small substituents on the pyridine ring led to the conclu-
sion that little to no steric effect was reflected in the yields.
Moreover, it was also demonstrated that electron-rich, elec-
tron-neutral, and electron-deficient sulfinate substrates
can be employed with this methodology with good to ex-
cellent yields. Finally, this new methodology allows access
to the challenging electron-rich sulfonylated pyridines,
which have proven to be versatile building blocks in mod-
ern organic synthesis.
O
O
SO2Na
70b
42b
62b
78b
46b
88b
N
O
O
N
SO2Na
S
1d
3j
O
O
SO2Na
S
N
MeO
1e
MeO
3k
O
O
SO2Na
S
6
77b
78b
N
F3C
F3C
1g
3l
All reactions were performed in a round-bottom flask containing a
Teflon-coated stir bar, unless more specific conditions are stated.
Chemicals were purchased from Aldrich, Alfa Aesar, or AK Scientific
and used without further purification. All solvents were purchased as
ACS grade from Fisher Scientific or JT Baker and distilled water was
obtained from an in-house water distillery prior to use. Flash chro-
matography was carried out using 40–63 μm silica gel (Silicycle).
Melting points were obtained using a Stuart SMP30 bench apparatus.
NMR spectra were recorded with a Varian Inova 500 MHz spectrome-
ter and were referenced to the residual solvent signal or TMS signal.
High-resolution mass spectra (HRMS) were obtained using a LC-TOF
ESI positive mode mass spectrometer.
O
O
SO2Na
S
7
8
41
59
27
N
1h
1i
3m
3n
O
O
SO2Na
S
26b
N
a Reaction conditions: 1 (2 mmol, 1.0 equiv), 2 (1.2 equiv), FeCl3 (1 mol%),
nBu4NCl (0.3 equiv), DMSO–H2O (3:1, 2 M), 140 °C, 20 h.
b FeCl3 (10 mol%) used.
Sulfonylated Pyridines 3; General Procedure
degassed for 30 min in a sonicator under argon atmosphere, and then
heated to 140 °C and stirred for 20 h. The resulting mixture was
cooled to r.t. and neutralized with 2 M aq NaOH solution, and then
extracted with EtOAc (3×). The combined organic phase was washed
with distilled H2O, followed by a brine solution, and then was dried
The sulfinate salt 1 (2 mmol, 1.0 equiv) and halopyridine 2 (1.2 equiv)
in DMSO–H2O (3:1, 2 M) were added to a round-bottom flask con-
taining nBu4NCl (0.3 equiv) and FeCl3 (0.01 equiv). The mixture was
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E
F. Chen et al.
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Synthesis
over Na2SO4 and filtered. The solvent was then removed under re-
duced pressure. The residue was purified by column chromatography
(silica gel, EtOAc–hexanes–CH2Cl2, 5:45:55) to give the desired sulfo-
nylated pyridine product 3.
Colorless solid; mp 143–145 °C.
1H NMR (500 MHz, CDCl3): δ = 8.49 (d, J = 1.7 Hz, 1 H), 8.08 (d, J = 8.0
Hz, 1 H), 7.94 (d, J = 8.0 Hz, 2 H), 7.69 (dd, J = 8.0, 1.7 Hz, 1 H), 7.32 (d,
J = 8.0 Hz, 2 H), 2.41, 2.39 (2s, 6 H).
13C NMR (125 MHz, CDCl3): δ = 156.41, 150.92, 144.57, 138.08,
137.41, 136.36, 129.73 (2 C), 128.78 (2 C), 121.79, 21.63, 18.50.
HRMS (EI): m/z [M + H]+ calcd for C13H13NO2S: 248.0740; found:
248.0740.
2-Tosylpyridine (3a) CAS: 51954-53-1
Prepared following the general procedure unless specified otherwise.
Synthesized from sulfinate salt 1a with different halopyridines 2a–d.
Yield: 308.4 mg, 1.32 mmol (66%) (from 2a with no degassed solvent).
Yield: 56.1 mg, 0.24 mmol (12%) (from 2b with no degassed solvent).
Yield: 368.6 mg, 1.58 mmol (79%) (from 2c).
6-Methyl-2-tosylpyridine (3e)
Synthesized following the general procedure from sulfinate salt 1a
with halopyridine 2h.
Yield: 415.2 mg, 1.78 mmol (89%) (from 2d).
Yield: 357.1 mg, 1.44 mmol (72%).
Colorless solid; mp 112–113 °C.
Pale pink solid; mp 126–128 °C.
1H NMR (500 MHz, CDCl3): δ = 8.67 (ddd, J = 4.7, 1.7, 0.8 Hz, 1 H), 8.19
(dt, J = 7.9, 1.0 Hz, 1 H), 7.95 (d, J = 8.5 Hz, 2 H), 7.92 (td, J = 7.9, 1.7 Hz,
1 H), 7.45 (ddd, J = 7.9, 4.7, 1.0 Hz, 1 H), 7.33 (dd, J = 8.5, 0.8 Hz, 2 H),
2.42 (s, 3 H).
1H NMR (500 MHz, CDCl3): δ = 7.98 (d, J = 8.0 Hz, 2 H), 7.96 (d, J = 7.4
Hz, 1 H), 7.76 (t, J = 7.4 Hz, 1 H), 7.32 (d, J = 8.0 Hz, 2 H), 7.28 (d, J = 7.4
Hz, 1 H), 2.56 (s, 3 H), 2.41 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 159.13, 150.40, 144.82, 138.04,
13C NMR (125 MHz, CDCl3): δ = 160.21, 158.29, 144.52, 137.83,
135.93, 129.78 (2 C), 128.96 (2 C), 126.74, 122.01, 21.65.
136.27, 129.62 (2 C), 128.97 (2 C), 126.63, 119.13, 24.39, 21.64.
HRMS (EI): m/z [M + H]+ calcd for C12H11NO2S: 234.0583; found:
HRMS (EI): m/z [M + H]+ calcd for C13H13NO2S: 248.0740; found:
243.0583.
248.0740.
3-Methyl-2-tosylpyridine (3b) CAS: 1258786-30-9
3-Methoxy-2-tosylpyridine (3f) CAS: 1258786-31-0
Synthesized following the general procedure from sulfinate salt 1a
with halopyridine 2e or 2j.
Synthesized following the general procedure from sulfinate salt 1a
with halopyridine 2i.
Yield: 387.9 mg, 1.57 mmol (78%) (from 2e).
Yield: 421.9 mg, 1.71 mmol (85%) (from 2j).
Colorless solid; mp 123–125 °C.
1H NMR (500 MHz, CDCl3): δ = 8.39 (dd, J = 4.6, 1.5 Hz, 1 H), 7.89 (d, J =
8.3 Hz, 2 H), 7.63 (d, J = 7.3 Hz, 1 H), 7.34–7.28 (m, 3 H), 2.74 (s, 3 H),
2.44 (s, 3 H).
Yield: 255.1 mg, 0.97 mmol (48%).
Light yellow solid; mp 123–125 °C.
1H NMR (500 MHz, CDCl3): δ = 8.23 (dd, J = 4.5, 1.3 Hz, 1 H), 7.89 (d, J =
8.2 Hz, 2 H), 7.43 (dd, J = 8.4, 4.5 Hz, 1 H), 7.33 (dd, J = 8.4, 1.3 Hz, 1 H),
7.29 (d, J = 8.2 Hz, 2 H), 3.87 (s, 3 H), 2.42 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 154.02, 146.08, 144.49, 140.50,
136.75, 129.31 (2 C), 129.08 (2 C), 128.79, 121.14, 56.13, 21.65.
HRMS (EI): m/z [M – H]– calcd for C13H13NO3S: 262.05433; found:
13C NMR (125 MHz, CDCl3): δ = 156.76, 146.43, 144.50, 141.31,
136.32, 133.36, 129.50 (2 C), 129.02 (2 C), 126.53, 21.68, 18.86.
262.0545.
HRMS (EI): m/z [M + H]+ calcd for C13H13NO2S: 248.0740; found:
248.0740.
4-Tosylpyridine (3g) CAS: 66154-65-2
Synthesized following the general procedure from sulfinate salt 1a
with halopyridine 2k.
4-Methyl-2-tosylpyridine (3c) CAS: 51954-51-9
Synthesized following the general procedure from sulfinate salt 1a
with halopyridine 2f.
Yield: 286.8 mg, 1.23 mmol (61%).
Yield: 381.8 mg, 1.54 mmol (77%).
Pale brown solid; mp 134–135 °C.
Colorless solid; mp 138–139 °C.
1H NMR (500 MHz, CDCl3): δ = 8.81 (d, J = 6.0 Hz, 1 H), 7.84 (d, J = 8.2
Hz, 1 H), 7.75 (d, J = 6.0 Hz, 1 H), 7.35 (d, J = 8.2 Hz, 1 H), 2.42 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 151.13 (2 C), 150.12, 145.40, 136.68,
1H NMR (500 MHz, CDCl3): δ = 8.51 (d, J = 4.6 Hz, 1 H), 8.02 (s, 1 H),
7.94 (d, J = 8.3 Hz, 2 H), 7.33 (d, J = 8.3 Hz, 2 H), 7.24 (d, J = 4.6 Hz, 1 H),
2.46 (s, 3 H), 2.42 (s, 3 H).
130.26 (2 C), 128.18 (2 C), 120.47 (2 C), 21.65.
13C NMR (125 MHz, CDCl3): δ = 158.93, 150.14, 149.94, 144.69,
HRMS (EI): m/z [M + H]+ calcd for C12H11NO2S: 234.0583; found:
136.10, 129.74 (2 C), 128.90 (2 C), 127.49, 122.76, 21.65, 21.25.
234.0583.
HRMS (EI): m/z [M + H]+ calcd for C13H13NO2S: 248.0740; found:
248.0735.
2-(Phenylsulfonyl)pyridine (3h) CAS: 24244-60-8
Synthesized following the general procedure from sulfinate salt 1b
with bromopyridine 2c or iodopyridine 2d.
5-Methyl-2-tosylpyridine (3d) CAS: 51954-52-0
Synthesized following the general procedure from sulfinate salt 1a
with halopyridine 2g.
Yield: 311.5 mg, 1.42 mmol (71%) (from 2c).
Yield: 360.0 mg, 1.64 mmol (82%) (from 2d).
Colorless solid; mp 88–90 °C.
Yield: 334.1 mg, 1.35 mmol (68%).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–G

F
F. Chen et al.
Paper
Synthesis
1H NMR (500 MHz, CDCl3): δ = 8.67 (ddd, J = 4.7, 1.7, 1.0 Hz, 1 H), 8.21
(dt, J = 7.9, 1.0 Hz, 1 H), 8.10–8.04 (m, 2 H), 7.93 (td, J = 7.9, 1.7 Hz, 1
H), 7.65–7.59 (m, 1 H), 7.57–7.51 (m, 2 H), 7.46 (ddd, J = 7.7, 4.7, 1.0
Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 158.84, 150.46, 138.95, 138.09,
133.74, 129.10 (2 C), 128.92 (2 C), 126.90, 122.19.
2-{[4-(Trifluoromethyl)phenyl]sulfonyl}pyridine (3l) CAS:
2139244-99-6
Synthesized following the general procedure from sulfinate salt 1g
with bromopyridine 2c or iodopyridine 2d.
Yield: 442.4 mg, 1.54 mmol (77%) (from 2c).
Yield: 452.9 mg, 1.58 mmol (78%) (from 2d).
Colorless solid; mp 131–132 °C.
1H NMR (500 MHz, CDCl3): δ = 8.69 (ddd, J = 4.7, 1.7, 1.0 Hz, 1 H),
8.27–8.18 (m, 3 H), 7.97 (td, J = 7.7, 1.7 Hz, 1 H), 7.85–7.78 (m, 2 H),
7.51 (ddd, J = 7.7, 4.7, 1.0 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 158.13, 150.63, 142.47, 138.25, 135.35
(q, J = 33.1 Hz), 129.61 (2 C), 127.28, 126.18 (q, J = 3.8 Hz, 2 C), 123.13
(q, J = 272.68 Hz), 122.36.
HRMS (EI): m/z [M + H]+ calcd for C11H9NO2S: 220.0427; found:
220.0427.
2-(m-Tolylsulfonyl)pyridine (3i) CAS: 2139245-00-2
Synthesized following the general procedure from sulfinate salt 1c
with bromopyridine 2c or iodopyridine 2d.
Yield: 323.6 mg, 1.39 mmol (70%) (from 2c).
Yield: 360.5 mg, 1.55 mmol (78%) (from 2d).
Colorless solid; mp 104–105 °C.
HRMS (EI): m/z [M + H]+ calcd for C12H8F3NO2S: 288.0301; found:
288.0299.
1H NMR (500 MHz, CDCl3): δ = 8.67 (ddd, J = 4.7, 1.7, 1.0 Hz, 1 H), 8.20
(dt, J = 7.9, 1.0 Hz, 1 H), 7.93 (td, J = 7.9, 1.7 Hz, 1 H), 7.89–7.82 (m, 2
H), 7.46 (ddd, J = 7.9, 4.7, 1.0 Hz, 1 H), 7.43–7.39 (m, 2 H), 2.41 (s, 3 H).
2-(Naphthalen-1-ylsulfonyl)pyridine (3m)
Synthesized following the general procedure from sulfinate salt 1h
with bromopyridine 2c or iodopyridine 2d.
13C NMR (125 MHz, CDCl3): δ = 158.92, 150.45, 139.38, 138.79,
138.08, 134.58, 129.15, 128.98, 126.86, 126.04, 122.20, 21.30.
HRMS (EI): m/z [M + H]+ calcd for C12H11NO2S: 234.0583; found:
234.0585.
Yield: 220.6 mg, 0.82 mmol (41%) (from 2c).
Yield: 318.7 mg, 1.18 mmol (59%) (from 2d).
Colorless solid; mp 139–140 °C.
1H NMR (500 MHz, CDCl3): δ = 8.72–8.67 (m, 1 H), 8.62 (dd, J = 7.4, 1.3
Hz, 1 H), 8.60 (ddd, J = 4.7, 1.7, 1.0 Hz, 1 H), 8.33 (dt, J = 7.9, 1.0 Hz, 1
H), 8.13 (d, J = 8.2 Hz, 1 H), 7.99–7.90 (m, 2 H), 7.67 (dd, J = 8.2, 7.4 Hz,
1 H), 7.62–7.50 (m, 2 H), 7.43 (ddd, J = 7.7, 4.7, 1.0 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 159.10, 150.18, 138.05, 135.51,
134.11, 133.98, 131.39, 128.97, 128.94, 128.30, 126.89, 126.81,
124.70, 124.48, 122.32.
2-(o-Tolylsulfonyl)pyridine (3j) CAS: 2139245-01-3
Synthesized following the general procedure from sulfinate salt 1d
with bromopyridine 2c or iodopyridine 2d.
Yield: 197.2 mg, 0.85 mmol (42%) (from 2c).
Yield: 216.8 mg, 0.93 mmol (46%) (from 2d).
Colorless solid; mp 77–78 °C.
1H NMR (500 MHz, CDCl3): δ = 8.64 (ddd, J = 4.7, 1.7, 1.0 Hz, 1 H), 8.27
(dd, J = 7.9, 1.5 Hz, 1 H), 8.21 (dt, J = 7.9, 1.0 Hz, 1 H), 7.96 (td, J = 7.9,
1.7 Hz, 1 H), 7.50 (dd, J = 7.6, 1.5 Hz, 1 H), 7.48 (ddd, J = 7.6, 4.7, 1.0 Hz,
1 H), 7.42 (dddd, J = 7.9, 7.6, 1.3, 0.7 Hz, 1 H), 7.26 (ddt, J = 7.6, 1.3, 0.7
Hz, 1 H), 2.48 (s, 3 H).
HRMS (EI): m/z [M + H]+ calcd for C15H11NO2S: 270.0583; found:
270.0584.
2-(Naphthalen-2-ylsulfonyl)pyridine (3n)
Synthesized following the general procedure from sulfinate salt 1i
with bromopyridine 2c or iodopyridine 2d.
13C NMR (125 MHz, CDCl3): δ = 158.99, 150.25, 138.68, 137.96,
136.82, 133.96, 132.46, 130.68, 126.90, 126.50, 122.27, 20.43.
HRMS (EI): m/z [M + H]+ calcd for C12H11NO2S: 234.0583; found:
234.0584.
Yield: 140.1 mg, 0.52 mmol (26%) (from 2c).
Yield: 144.9 mg, 0.54 mmol (27%) (from 2d).
Colorless solid; mp 138–139 °C.
1H NMR (500 MHz, CDCl3): δ = 8.70 (s, 1 H), 8.67 (d, J = 4.7 Hz, 1 H),
8.28 (d, J = 7.9 Hz, 1 H), 8.05–7.84 (m, 5 H), 7.64 (m, 2 H), 7.45 (ddd, J =
7.7, 4.7, 1.2 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 158.95, 150.48, 138.08, 135.84,
135.36, 132.17, 130.82, 129.55, 129.33, 129.31, 127.92, 127.54,
126.84, 123.55, 122.26.
2-[(4-Methoxyphenyl)sulfonyl]pyridine (3k) CAS: 121346-51-8
Synthesized following the general procedure from sulfinate salt 1e
with bromopyridine 2c or iodopyridine 2d.
Yield: 310.4 mg, 1.25 mmol (62%) (from 2c).
Yield: 438.4 mg, 1.76 mmol (88%) (from 2d).
Colorless solid; mp 111–112 °C.
HRMS (EI): m/z [M + H]+ calcd for C15H11NO2S: 270.0583; found:
1H NMR (500 MHz, CDCl3): δ = 8.67 (ddd, J = 4.7, 1.7, 1.0 Hz, 1 H), 8.18
(d, J = 7.9 Hz, 1 H), 8.00 (d, J = 9.0 Hz, 2 H), 7.91 (td, J = 7.9, 1.7 Hz, 1 H),
7.44 (ddd, J = 7.9, 4.7, 1.0 Hz, 1 H), 7.00 (d, J = 9.0 Hz, 2 H), 3.86 (s, 3 H).
270.0582.
Funding Information
13C NMR (125 MHz, CDCl3): δ = 163.89, 159.41, 150.36, 138.00, 131.19
(2 C), 130.28, 126.60, 121.79, 114.40 (2 C), 55.64.
HRMS (EI): m/z [M + H]+ calcd for C12H11NO3S: 250.0532; found:
250.0533.
This work was funded by the Natural Sciences and Engineering Re-
search Council (NSERC) of Canada and Le Fonds de Recherche Nature
et technologies du Québec (FQRNT). Support was also kindly provided
by Centre for Green Chemistry and Catalysis (CGCC), and Concordia
University.
)(
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–G

G
F. Chen et al.
Paper
Synthesis
Supporting Information
(11) Hull, K. L.; Anani, W. Q.; Sanford, M. S. J. Am. Chem. Soc. 2006,
128, 7134.
(12) Kalyani, D.; Dick, A. R.; Anani, W. Q.; Sanford, M. S. Org. Lett.
2006, 8, 2523.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1591541.
S
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p
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ortiInfogrmoaitn
S
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–G