Introduction of Aryl Fluorosulfates into the Realm of Catellani Reaction Substrates

Article abstract of DOI:10.1021/acs.joc.9b02352

Application of activated phenol fluorosulfates as substrates in a Pd/NBE mediated sequential alkylation-arylation, commonly known as a Catellani reaction, is presented. These substrates provide a level of complementarity to the commonly used aryl halides and, in combination with a plethora of existing Catellani reaction variations, enable even wider application of this powerful synthetic tool.

Full text of DOI:10.1021/acs.joc.9b02352

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Note
Introduction of Aryl Fluorosulfates into the
Realm of Catellani Reaction Substrates
Vidmantas Bieli#nas, and Wim M. De Borggraeve
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b02352 • Publication Date (Web): 30 Oct 2019
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The Journal of Organic Chemistry
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Introduction of Aryl Fluorosulfates into the Realm of Catellani
Reaction Substrates
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Vidmantas Bieliūnas and Wim M. De Borggraeve*
Molecular Design and Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, Box 2404, 3001 Leuven,
Belgium.
wim.deborggraeve@kuleuven.be
Supporting Information Placeholder
ABSTRACT: Application of activated phenol fluorosulfates as substrates in a Pd/NBE mediated sequential alkylation-arylation,
commonly known as a Catellani reaction, is presented. These substrates provide a level of complementarity to the commonly used
aryl halides and, in combination with a plethora of existing Catellani reaction variations, enable even wider application of this
powerful synthetic tool.
Two decades ago, Catellani et al for the first time described
the use of norbornene (NBE) as transient mediator to facilitate
aromatic C-H activation via palladacycle formation – a
discovery that enabled one-pot sequential ortho/ipso
functionalization of iodoarenes.1 Since then this catalytic
system has gathered significant interest and inspired researchers
to develop novel variations of the reaction.2 Even though the
range of compatible terminal reagents and introducible
functionalities expanded rapidly, the substrate scope remained
largely limited to aryl iodides. Indeed, only recent reports detail
the application of aryl bromides3 or arylboronic acids,4 while
only a few sparse accounts of aryl sulfonate application are
available to this day.5
by subjecting phenols to SO2F2 gas – a stable commodity
chemical available in pressurized cylinders for large scale
applications,11 or generated from solid reagents in a two-
chamber reactor for small scale experiments.12 When weak
bases are used for deprotonation, amino groups and aliphatic
hydroxy groups are spared, and the resulting aryl fluorosulfate
is endowed with reactivity of a triflate at the low overall cost of
a mesylate.13 Furthermore, low-molecular weight fluorosulfates
are thermally stable and more volatile than corresponding
phenols or triflates, facilitating purification by vacuum
distillation.
With these favorable chemical and physical properties in
mind, establishing the compatibility of phenol fluorosulfates
with a Catellani-type reaction becomes paramount for
advancing their use in organic synthesis. To elucidate the
general behavior of aryl fluorosulfates under Pd/NBE catalysis,
a phosphine ligand-independent variant of the Catellani
reaction was chosen (Scheme 1).14 It was also an opportunity to
expand on this particular transformation as it was explored
superficially in terms of tolerable substrate and reactant
combinations.
The introduction of aryl bromides was a tremendous
advancement towards broader application of the Catellani
reaction. Yet both bromides and iodides are related chemical
entities, often sharing common substitution patterns and formal
synthesis routes. Furthermore, terrestrial sources are scarce in
naturally occurring halogenated aromatic compounds.6
Phenols, however, are ubiquitous both in biomass and in fossil
materials,7 are susceptible to pre-functionalization owing to
their high reactivity, and can be uneventfully transformed into
corresponding sulfonates.8
Several 2-substituted fluorosulfates were initially tested and
we were pleased by the excellent reactivity of 1a, even though
the two other substrates were recovered nearly quantitatively
(Scheme 1). During separate experiments, 1b provided partial
conversion in the presence of X-phos, but a complex mixture
was produced. S-phos, PPh3, xantphos and dcype were even less
effective.3a In addition, substrate 1c was not transformed into
the desired material even in the presence of X-phos. With
Aryl triflates are regarded as the default sulfonates for
transition metal-catalyzed reactions, while recent work also
demonstrates the application of tosylates and mesylates in
combination with complex phosphine ligands.9 However, the
revived interest in aryl fluorosulfate chemistry offers an
attractive alternative.10 Fluorosulfates are efficiently prepared
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preliminary results at hand, it was decided to focus on activated also observed, confirming that its transformation can also be
1
2
3
4
5
6
7
8
fluorosulfates. An extensive optimization was performed on 1a
as the model substrate (SI Table S1) leading to the standard
conditions disclosed in the scheme of Table 1.
accomplished without phosphine ligands. A broad range of
activated bromides is expected to exhibit a similar reactivity.
Lastly, the iodide 8a largely favored the alternative reaction
path in agreement with literature,19 demonstrating
complementarity to fluorosulfates in the transformation
discussed herein. This side-reaction also occurred with the
bromide 7a, but to a much lesser extent.
Scheme 1. Alkyl halide scope.
R1
B(OH)2
R1
Pd(OAc)2
Br
+
+
3
OSO2F
Ph
Table 2. Comparison of leaving groups.
(NBE)
K2CO3, DMF
H
nBu
9
1a, R1 = CO2Me
2a
3a
4aaa (70%)
4baa (0%)
4caa (0%)
1.20 equiv 2a
1.25 equiv 3a
CO2Me
CO2Me
CO2Me
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1b, R1 = Me
1c, R1 = OMe
+
5 mol% Pd(OAc)2
50 mol% NBE
6 equiv K2CO3
DMF (0.50 M)
70 °C, 4h
Ph
Ph
LG
aReagents and conditions: BuBr (1.50 equiv), PhB(OH)2 (1.20
equiv), Pd(OAc)2 (5 mol%), NBE (100 mol%), K2CO3 (6 equiv),
DMF ([1a] = 0.20M), 80 °C, 5 hours. Isolated yield.
nBu
CO2Me
H
1a, 5a-8a
0.40 mmol
2aaa
9aa
Firstly, it was established that 70 °C offered the best balance
between the reaction rate, selectivity and robustness.15
Increasing the concentration of the fluorosulfate compared to
the initial conditions (described under entry 1 of Table 1)
further enhanced both the rate and the selectivity, and allowed
to reduce the number of equivalents of other reagents, therefore
reducing the overall environmental impact and cost of the
process. Variations of auxiliary reagents, additives and
solvents, however, were poorly tolerated. For example, PPh3
ligand coming from Pd(PPh3)4 suppressed the C-H activation
(entry 2), likely by outcompeting NBE before its migratory
insertion.16 X-phos allowed the desired reaction, but failed to
provide improvements (entry 3), while norbornene N2 led to
complex mixtures (entry 4).17 Greener solvents18 and soluble
bases suppressed the reactivity (entries 5-6). The
incompatibility of the latter precluded the implementation of
this protocol as a telescoped flow fluorosulfation-Catellani
process.
substrate
LG
2aaa/9aaa 2aaab
9aab
n/a
1a
5a
6a
7a
8a
-OSO2F
-OSO2CF3
-OSO2Me
-Br
100:0
100:0
n/a
82%
81%
0%
n/a
0%
—
94:6
62%
9%
-I
26:74
45%
aGC-MS data. bIsolated yield.
To further the substrate scope, several readily available
activated phenols were transformed into corresponding
fluorosulfates that were then applied in the Catellani reaction
(Table 3). We were pleased to observe, that most of the chosen
substrates provided the expected products (entries 2-11) and the
outcome was unaffected by a 10-fold scale-up (entry 1). Under
these conditions, the symmetrical bis(fluorosulfate) 1p reacted
once, while the second fluorosulfate moiety served as an
activating group and remained intact (entry 16). Naturally, in
absence of preinstalled ortho substituents (R1 = H), C-H
activation of both ortho positions occurred (entry 17). Presence
of aldehyde or nitrile moieties at the 2-position (entries 14, 15)
led to complex mixtures devoid of the target material, but
aldehyde functionality was well tolerated at the 4-position
(entry 13). Unfortunately, compounds bearing weakly electron-
withdrawing substituents were insufficiently reactive under the
standard conditions. In cases of poor reactivity (Scheme 1 and
Table 3, entry 12) rapid and irreversible precipitation of Pd-
black occurred within minutes and most of the substrate could
be recovered even after prolonged reaction time. These
observations suggest the ease of oxidative insertion of Pd0 into
the C-O bond to be the primary outcome-determining factor.
Table 1. Optimization of reaction conditions.
"Standard Conditions"
CO2Me
CO2Me
Pd(OAc)2
5 mol%
B(OH)2
Br
+
+
OSO2F
Ph
3
50 mol% NBE
6 equiv K2CO3
DMF (0.50 M)
70 °C, 4h
H
nBu
4aaa
82%
1a
0.40 mmol
2a
3a
1.20 equiv 1.25 equiv
iPr
N1
(NBE)
N2
Endo/exo
5:1
X-Phos
Cy2P
CO2K
iPr
iPr
entry main deviations from standard conditions
yielda
1
2
3
4
5
6
[1a] = 0.20M, 100 mol% NBE, 1.5 equiv 2a 74%
Table 3. Carbocyclic substrate scope.
Pd(PPh3)4 (5 mol%) as the catalyst
X-Phos as an additive (6 mol%)
N2 instead of N1
0%
R2
4
3
R2
Pd(OAc)2
5 mol%
75%
49%
<5%
<26%
R1
B(OH)2
R1
2
Br
+
+
1
3
50 mol% NBE
6 equiv K2CO3
DMF (0.50 M)
70 °C, 4h
OSO2F
Ph
MeCN or -valerolactone instead of DMF
KOAc, TEA or nBu4NOAc as base
H
nBu
1a-q
0.40 mmol
2a
3a
4aaa-oaa
4pab, 10qaa
1.20 equiv 1.25 equiv
aIsolated yield.
entry
1
R1
R2
4
time yielda
With the optimal conditions at hand, it was prudent to
1b
1a
1d
1e
1f
CO2Me
CO2Me
NO2
–
4aaa
4daa
4eaa
4faa
4 h
3 h
2 h
3 h
82%
77%
73%
78%
establish the difference between common leaving groups,
especially between halides and sulf(on)ates (Table 2). The
reactivity of fluorosulfate 1a and triflate 5a was essentially
indistinguishable,13 while most of the mesylate 6a was
recovered unchanged. Good reactivity of the bromide 7a was
2
4-Cl
–
3
4
NO2
4-OMe
2
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had an overall negative effect, marked by increased reaction
rate and deteriorated selectivity. 2d and 2e almost completely
shut down the reaction due to even greater steric demand
imposed by the rigidity and conformation preference of the
corresponding rings. General reactivity of unstrained secondary
alkyl halides is expected to lie between 2c and 2d.22 Benzyl
chloride (2f) provided comparable yield to primary alkyl
bromides, whereas benzyl bromide completely failed to provide
the target material.3a The primary alkyl chloride 2g also
displayed reactivity, but some re-optimization to improve the
selectivity towards the target material remains desired.
5
1g
1h
1i
CF3
CF3
F
–
4gaa
4haa
4iaa
4jaa
4jaa
4 h
4 h
5 h
5 h
5 h
5 h
5 h
4 h
3 h
4 h
4 h
70%
1
2
3
4
5
6
7
8
6
7c
5-F
–
30%
52%
8
1j
Me
Me
Me
Me
Me
OMe
CHO
CN
4-NO2
4-NO2
34%
9c
10
1j
69%
1k
4-COMe 4kaa
4-COMe 4kaa
63%
11c,e 1k
74%
[<5%]g
12
13
14
15
1l
4-Cl
4laa
9
1m
1n
1o
4-CHO
4maa
4naa
4oaa
74%
10
11
12
13
14
15
16
17
Scheme 3. Alkyl halide scope.a
–
–
[0%]g
[0%]g
Pd(OAc)2
5 mol%
CO2Me
B(OH)2
CO2Me
Hal
+
+
3-Me,
4-OSO2F
16c,f 1p
17d,h 1q
Me
4pab
6 h
55%
Alkyl
OSO2F
Ph
50 mol% NBE
6 equiv. K2CO3
DMF (0.50 M)
70 °C, 4h
H
Alkyl
1a
2b-g
3a
H
4-CO2Et 10qaa 3 h
74%
4aba-aga
0.40 mmol
1.20 equiv 1.25 equiv
aIsolated yield. 4.0 mmol scale. 1.4 equiv nBuBr. 2.25 equiv
b
c
d
Br
e
f
g
Br
Cl
5
nBuBr. 100 mol% NBE. Boronic acid 3b used. GC-MS yield.
Br
Cl
Ph
Br
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h2,6-dibutylated product is obtained.
2b, 78%
2c, 60%b,c,d 2d, [8%]b,c,e 2e, [2%]b,c,e 2f, 73% 2g, 44%b
Substrates 1i-k and 1p were insufficiently active to be fully
consumed in 5 hours under the standard conditions and/or
produced significant amounts of corresponding non-alkylated
Suzuki-Miyaura coupling products. Both issues were solved
either by increasing the nBuBr loading alone (entries 7, 9 and
16) or by concurrently increasing the amount of norbornene
(entry 11). It is worth noting that greater NBE loading reliably
suppresses the Suzuki-Miyaura side-reaction but inhibits the
migratory de-insertion, leading to increased amounts of NBE-
inclusion products (commonly described in literature) that
complicate chromatographic purification.20
b
aIsolated yields of the corresponding products. 2.0 equiv of 2,
12h. c100 mol% NBE. d10 mol% Pd(OAc)2. eGC-MS yield.
Typical electron-rich and electron-deficient boronic acids
3b-j were tested and sterically unhindered acids (Table 4,
entries 1-5, 7) displayed largely similar performance. 2-
substituted boronic acids 3i and 3j, however, failed to provide
the desired material in practical quantities even with fluorine as
the substituent. Brominated boronic acid 3g was incompatible
as well, largely due to its consumption in side-reactions not
involving the substrate.
Pleased by the results with the carbocyclic substrates we
switched to heterocyclic aromatic fluorosulfates 1r-u (Scheme
2). The pyridine-2-fluorosulfate (1t) was especially interesting
as the heterocyclic nitrogen could innately provide the needed
electron-withdrawal. Unfortunately, only the thiophene
derivative 1r was in line with the expectations. Fluorosulfate 1s
was susceptible to norbornene inclusion, leading to partial
conversion and poor yield, while pyridine-2-fluorosulfate (1t)
and quinoline-8-fluorosulfate (1u) were completely unreactive.
It is suspected, that in case of the latter, coordination of Pd to
Lewis-basic nitrogen inhibits the target reaction either before
the oxidative addition takes place or, more likely, after the
migratory insertion of norbornene.21 Attempts to prepare
quinoline-4-fluorosulfate from 4-quinolol were made, but the
instability of the obtained compound precluded further
investigation.
Table 4. Boronic acid scope.
Pd(OAc)2
5 mol%
CO2Me
CO2Me
OH
B
Br
+
+
3
Aryl
OH
OSO2F
Aryl
50 mol% NBE
6 equiv. K2CO3
DMF (0.50 M)
70 °C, 4h
H
nBu
1a
2a
3b-j
4aab-aaj
0.40 mmol
1.20 equiv 1.25 equiv
entry
boronic acid “Aryl”
product
yielda
87%
79%
85%
74%
70%
9%
1
2
3
4
5
6
7
8
9
3b
4-MeO-C6H4
4-F-C6H4
4aab
4aac
4aad
4aae
4aaf
4aag
4aah
4aai
4aaj
3c
3d
3e
3f
3-MeO-C6H4
3-F-C6H4
3-Cl-C6H4
3-Br-C6H4
2-Naphthyl
2-MeO-C6H4
2-F-C6H4
Scheme 2: Heterocyclic product scope.a
3g
3h
3i
N
CO2Me
CO2Me
Ph
78%
S
N
N
nBu
[<5%]b,c
[<5%]b,c
Ph
Ph
Ph
nBu
3j
nBu
nBu
aIsolated yields. b12-hour reaction time. cGC-MS yield.
4raa
74% yield
4saa
19% yield
4taa
0% yield
4uaa
0% yield
During the early stages of investigation, it was noticed that
the K2CO3/DMF system is excellent for the synthesis of the
fluorosulfates themselves. This observation prompted an
experiment to combine both steps and achieve rapid
functionalization of phenols without the isolation of the
fluorosulfate intermediate (Scheme 4).13 It was decided, that the
most straightforward way of introducing the remaining
aIsolated yields under standard conditions.
The following alkyl halide trial showed that both straight
chain and branched primary alkyl halides should be well
tolerated (Scheme 3). Secondary alkyl bromide 2c was
significantly less reactive and required more forcing conditions
for a comparable outcome. A switch to a corresponding iodide
3
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IR spectra were recorded on a Bruker ALPHA FT-IR spectrometer
with ALPHA-P sampling module.
Elemental analyses were performed on a Thermo Scientific Flash
2000 elemental analyzer.
Melting points were measured using Mettler Toledo DSC822e and
processed with STARe thermal analysis software.
GC-MS analysis was performed using a ThermoFinnigan Trace GC
oven with Restek Rxi-5MS (50 m, 0.20 mm ID, 0.33 μm) capillary
column (helium carrier gas, 17:1 split injection) coupled with a
Thermo Scientific ITQ900 EI-MS ion trap. A 50 °C (1 min.) – 20
°C/min – 300 °C (5 min.) program was used.
Analytical TLC was performed on pre-coated aluminum-supported
silica gel 60 F245 (250 m) TLC plates with the aid of UV (254
nm) visualization. Preparative liquid flash chromatography was
conducted on direct phase silica gel (40-60 m, average pore
diameter 60 Å) from Acros Organics.
Catellani reaction components while maintaining inert
atmosphere is to transfer the post-fluorosulfation reaction slurry
onto the solid reagents and add the alkyl bromide last. Different
approaches to reagent addition are feasible as long as Pd(OAc)2
is not in solution in the absence of the fluorosulfate substrate in
order to avoid premature Pd-black precipitation.
1
2
3
4
5
6
7
8
Scheme 4. Telescoped fluorosulfation-Catellani reaction.
R2
R2
R1
R1
I: SO2F2, 2 equiv. K2CO3,
DMF (0.50 M), rt, 2h
9
OH
1.20 equiv. nBuBr (2a),
II:
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nBu
1.25 equiv. PMP-B(OH)2 (3b),
11d
O
5 mol% Pd(OAc)2,
50 mol% NBE,
6 equiv K2CO3,
(R1 = CO2Me, R2 = Cl)
4dab, 78%
4eab, 67%
11e
(R1 = NO2, R2 = H)
DMF (0.50 M), 70 °C, 3h
Reagents were obtained from commercial sources (Sigma-Aldrich,
Acros Organics, Fluorochem) and were used directly without
purification. Petroleum ether (boiling range 40 – 65 °C, VWR) was
distilled prior to use. Other chromatography solvents were of
analytical grade (Fischer Scientific) and were used as received.
Anhydrous solvents over molecular sieves in Acroseal™ bottles
and Palladium (II) acetate (99.9% trace metals basis) were
purchased from Acros Organics. Deuterated chloroform (99.8% D,
0.1% v/v of TMS as internal standard) was purchased from Sigma-
Aldrich.
Despite the additional presence of KF and SO2F2 in the
reaction mixture arising from the fluorosulfation step and
possible transfer of TFA and H2O vapor from the gas-
generating chamber, only the rate of the Catellani reaction was
slightly reduced whereas the combined yield was in line with
expectations. Naturally, the setup could be further simplified
and made even more reliable by using pure SO2F2 from a
pressurized cylinder, enabling rapid library generation in multi-
well plates. Furthermore, the gaseous nature of the reagent
allows it to be flushed out of the fluorosulfation mixture with a
stream of inert gas if it hinders the following reaction in any
way, leaving only the formed KF as an additional compound,
which is known for its compatibility with Pd catalysis.23
1,1’-sulfonyldiimidazole (SDI)
The material was prepared following a modified literature
procedure.24 SO2Cl2 (24.7 mL, 98.5 wt%, 300 mmol, 1.0 equiv) in
DCM (210 mL) was added dropwise (5 mL/min) to a vigorously
stirred suspension of imidazole (92.8 g, 99 wt%, 1.35 mol, 4.5
equiv) in DCM (540 mL) maintained at 0 °C. Complete dissolution
if imidazole was observed prior to precipitation of imidazolium
chloride. Once the addition was completed, the cooling was
maintained for 3 hours and then the suspension was left at ambient
temperature for 18 hours. Imidazolium chloride was filtered off; the
filter cake was washed with DCM (3 × 100 mL) and the combined
filtrate was washed with H2O (150 mL), dried with Na2SO4 and
evaporated under reduced pressure. The crystalline residue was
recrystallized from boiling 2-PrOH (300 mL) to afford the
analytically pure target material (53.32 g, 90% yield) as thick
colorless plates.
In conclusion, the presented application of fluorosulfates in
a Catellani-type ortho-alkylation/ipso-arylation reaction paves
the way for rapid multi-functionalization of phenols bearing
electron-withdrawing groups. By offering an alternative
reaction outcome in comparison to corresponding aryl iodides
and marginally superior performance to corresponding
bromides, it empowers synthetic pathways that might have been
previously overlooked. Furthermore, both the Catellani reaction
and the preceding fluorosulfation of phenols are inherently
compatible, providing a technique for rapid generation of
compound libraries.
1H NMR (400 MHz, CDCl3) δ: 8.04 (dd, J = 1.4, 0.8 Hz, 1H), 7.31
(dd, J = 1.7, 1.4, 1H), 7.17 (dd, J = 1.7, 0.8 Hz, 1H). 13C{1H} NMR
(101 MHz, CDCl3): 136.5, 132.4, 117.3.
Experimental Section
General methods
1H NMR spectra were recorded in CDCl3 on a Bruker Avance™ III
HD 400 (400 MHz) spectrometer. Chemical shifts are reported in
parts per million using the solvent (7.26 ppm, singlet) as internal
reference. First-order multiplets are described as d (doublet), t
(triplet), q (quartet), p (pentet), h (hextuplet), hept (heptet) and as
combinations thereof, with “br.” indicating a broadened peak(s).
When possible, second-order multiplets are described according to
their spin system with the corresponding nuclei underlined.
Coupling constants were verified with WINDMNR 7.1.14 NMR
simulation software.
General procedure for synthesis of aryl fluorosulfates 1a-u
A 10 mL two-chamber reactor (total volume of 10–12 mL) was
used for reactions generating up to 2.5 mmol of SO2F2. The 100 mL
reactor was used for up to 15 mmol of SO2F2 and the 400 mL
reactor was used for up to 50 mmol of SO2F2 respectively (picture
of these reactors is provided as SI Figure S1-1). Running the
reaction significantly (two times and more) below these indicated
thresholds requires raising the excess of SO2F2 to up to 1.50 equiv
for reliable full conversion. The gas is highly soluble in organic
solvents therefore the actual pressure is lower than theoretical.12
Chamber A of a 10 mL two-chamber reactor was charged with 1,1’-
sulfonyldiimidazole (496 mg, 2.5 mmol, 1.25 equiv) and potassium
fluoride (349 mg, 6.0 mmol, 3.0 equiv). Next, chamber B was
charged with the corresponding phenol (2 mmol, 1.0 equiv) or diol
(1 mmol, 0.50 equiv), fine dry potassium carbonate (552 mg, 4
mmol, 2.0 equiv) and acetonitrile (4 mL). The reactor was capped
and trifluoroacetic acid/water mixture (2 mL, 50:50 v/v) was
injected into chamber A through the septa using a syringe. A 15 –
30 s delay followed by gradual gas evolution was observed over the
next 30 minutes. Contents of both chambers were vigorously stirred
at 20 °C ambient temperature for 18 hours.
Proton-decoupled 13C NMR and 13C APT spectra were recorded in
CDCl3 on Bruker Avance™ III HD 400 (101 MHz) and Bruker
Avance™ II+ 600 (126 MHz) spectrometers. Chemical shifts are
reported in parts per million using the solvent (77.00 ppm, triplet)
as internal reference. Number of attached protons were deduced by
APT experimental data and indicated in parenthesis.
19F NMR spectra (non-decoupled) were recorded in CDCl3 on a
Bruker Avance™ III HD 400 (376 MHz) spectrometer. Chemical
shifts are reported in parts per million using CFCl3 (0.00 ppm,
singlet) as internal reference. Coupling constants were verified with
WINDMNR 7.1.14 NMR simulation software.
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Both chambers were uncapped and the SO2F2 was allowed to
Anal. Calcd for C8H6ClFO5S: C, 35.77; H, 2.25; N, 0.00. Found:
C, 35.78; H, 2.24; N, 0.00. H NMR (400 MHz, CDCl3) δ: 8.08
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diffuse out of the reactor over 1 hour. Contents of the chamber B
were transferred into a separatory funnel containing EtOAc or PE
(20 mL) and water (60 mL). The target material was extracted into
the organic phase, which was then washed with water (2 × 20 mL)
and brine (20 mL), dried with Na2SO4 and evaporated under
reduced pressure. The residue was purified by flash
chromatography on silica gel, filtration trough a plug of silica gel
or vacuum distillation.
(dd, J = 2.7, 0.4 Hz, 1H), 7.62 (dd, J = 8.7, 2.7 Hz, 1H), 7.37 (ddd,
J = 8.7, 1.4, 0.4 Hz, 1H), 3.98 (s, 3H). 13C{1H} NMR (101 MHz,
CDCl3) δ: 162.7 (C=O), 146.8 (d, J = 1.2 Hz, C), 134.8 (C), 134.2
(CH), 132.8 (CH), 125.3 (d, J = 1.4 Hz, C), 123.9 (CH), 53.1 (CH3).
19F NMR (376 MHz, CDCl3) δ: 41.2 (d, J = 1.4 Hz). EI-MS m/z
(calc. 268.0): 268.0 (33%, M+∙), 270.0 (11%, M+∙), 237.0 (61%),
154 (100%). IR (neat) cm-1: 1730.8, 1451.9, 1436.0, 1170.9,
911.05.
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Methyl 2-((fluorosulfonyl)oxy)benzoate (1a)
General procedure was followed using 1.0 equiv of methyl 2-
hydroxybenzoate (1.83 g, 1.56 mL, 12 mmol). The crude material
was purified by flash chromatography on silica gel using PE/EtOAc
(9:1) to afford analytically pure title compound as a colorless oil
(5.265 g, 90%).
2-Nitrophenyl sulfurofluoridate (1e)
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General procedure was followed using 1.0 equiv of 2-nitrophenol
(1.39 g, 10 mmol). The crude material was purified by flash
chromatography on silica gel using PE/EtOAc (8:2) to afford
analytically pure title compound as a faintly yellow oil (1.69 g,
77%).
Anal. Calcd for C6H4FNO5S: C, 32.59; H, 1.82; N, 6.33. Found: C,
32.73; H, 1.80; N, 6.59. 1H NMR (400 MHz, CDCl3) δ: 8.20 (dd,
J = 8.2, 1.7 Hz, 1H), 7.79 (ddd, J = 8.2, 7.6, 1.7 Hz, 1H), 7.63 (ddd,
J = 8.2, 7.6, 1.4 Hz, 1H), 7.58 (dt, J = 8.2, 1.4 Hz, 1H). 13C{1H}
NMR (101 MHz, CDCl3) δ: 141.7 (d, J = 1.2 Hz, C), 141.3 (br. s,
C), 135.4 (CH), 129.6 (CH), 126.9 (CH), 123.8 (d, J = 0.7 Hz, CH).
19F NMR (376 MHz, CDCl3) δ: 42.1 (d, J = 1.4 Hz). EI-MS m/z
(calc. 221.0): 221.1 (100%, M+∙), 191.2 (46%), 108.3 (41%), 80.1
(63%), 63.1 (87%). IR (neat) cm-1: 1533.5, 1453.0, 1345.8, 1234.0,
910.2.
Alternatively, general procedure was followed using 1.0 equiv of
methyl salicylate (3.80 g, 3.24 mL, 25 mmol). Fractional vacuum
distillation of the crude material (110 °C at 1 mbar) provided the
analytically pure title compound as a colorless oil (4.100 g, 70%).
1H NMR (400 MHz, CDCl3) δ: 8.11 (ddd, J = 7.8, 1.8, 0.4 Hz, 1H),
7.66 (ddd, J = 8.2, 7.5, 1.8 Hz, 1H), 7.51 (ddd, J = 7.8, 7.5, 1.2 Hz,
1H), 7.42 (dddd, J = 8.2, 1.6, 1.2, 0.4 Hz, 1H), 3.98 (s, 3H). 13C{1H}
NMR (101 MHz, CDCl3) δ: 163.8 (C=O), 148.5 (d, J = 1.3 Hz, C),
134.4 (CH), 132.9 (CH), 128.8 (CH), 123.9 (d, J = 1.3 Hz, C), 122.4
(CH), 52.8 (CH3). 19F NMR (376 MHz, CDCl3) δ: 41.1 (d, J = 1.6
Hz). EI-MS m/z (calc. 234.0): 234.1 (23%, M+∙), 203.2 (100%),
120.1 (48%). IR (neat) cm-1: 1727.3, 1447.1, 1231.2, 911.8, 777.6.
The obtained analytical data is in agreement with literature.12
4-Methoxy-2-nitrophenyl sulfurofluoridate (1f)
General procedure was followed using 1.0 equiv of 4-methoxy-2-
nitrophenol (338 mg, 2.0 mmol). The crude material was purified
by flash chromatography on silica gel using PE/EtOAc (8:2) to
afford analytically pure title compound as a faintly yellow oil (406
mg, 81%).
Anal. Calcd for C7H6NFO6S: C, 33.47; H, 2.41; N, 5.58. Found: C,
33.82; H, 2.01; N, 6.07. 1H NMR (400 MHz, CDCl3) δ: 7.65 (d, J
= 3.1 Hz, 1H), 7.46 (dd, J = 9.1, 1.4 Hz, 1H), 7.23 (dd, J = 9.1, 3.1
Hz, 1H), 3.92 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ: 159.4
(C), 141.7 (br. s, C), 135.0 (d, J = 1.2 Hz, C), 124.7 (CH), 120.7
(CH), 111.3 (CH), 56.4 (CH3). 19F NMR (376 MHz, CDCl3) δ: 41.1
(d, J = 1.4 Hz). EI-MS m/z (calc. 251.0): 251.2 (99%, M+∙), 168.2
(87%), 110.2 (44%), 69.1 (100%). IR (neat) cm-1: 1616.5, 1451.2,
1232.7, 1173.5, 801.1.
2-Methylphenyl sulfurofluoridate (1b)
General procedure was followed using 1.0 equiv of 2-methylphenol
(2.70 g, 25 mmol). The crude material was purified by filtration
through a short pad of silica gel using PE/EtOAc (95:5) to afford
the title compound as a colorless volatile oil (4.51 g, 94%).
1H NMR (400 MHz, CDCl3) δ: 7.35 – 7.26 (m, 4H), 2.39 (s, 3H).
13C{1H} NMR (101 MHz, CDCl3) δ: 149.1 (d, J = 1.0 Hz, C), 132.3
(CH), 130.5 (d, J = 0.9 Hz, C), 128.5 (CH), 127.7 (CH), 120.9 (d,
J = 1.1 Hz, CH), 16.0 (d, J = 1.4 Hz, CH3). 19F NMR (376 MHz,
CDCl3) δ: 38.6 (p, J = 1.1 Hz). EI-MS m/z (calc. 190.0): 190.3
(64%, M+∙), 107.2 (36%), 89.2 (31%), 77.2 (100%). IR (neat) cm-
1: 1443.4, 1230.8, 915.12, 817.0, 764.4.
The obtained analytical data is in agreement with literature.10e
2-Methoxyphenyl sulfurofluoridate (1c)
2-(Trifluoromethyl)phenyl sulfurofluoridate (1g)
General procedure was followed using 1.0 equiv of 2-
methoxyphenol (248 mg, 2.0 mmol). The crude material was
purified by flash chromatography on silica gel using PE/EtOAc
(95:5) to afford analytically pure title compound as a colorless
volatile oil (357 mg, 87%).
General procedure was followed using 1.0 equiv of 2-
(trifluoromethyl)phenol (1.62 g, 10 mmol). The crude material was
filtered through a short pad of silica using PE/EtOAc (98:2) to
afford analytically pure title compound as a volatile colorless oil
(2.30 g, 94%).
Anal. Calcd for C7H4F4O3S: C, 34.44; H, 1.65; N, 0.00. Found: C,
34.27; H, 1.52; N, 0.00. 1 NMR (400 MHz, CDCl3) δ: 7.82 – 7.76
(m, 1H), 7.76 – 7.66 (m, 1H), 7.60 – 7.52 (m, 2H). 13C{1H} NMR
(101 MHz, CDCl3) δ: 146.9 (qd, J = 1.8, 1.1 Hz, C), 134.0 (d, J =
1.1 Hz, CH), 128.6 (CH), 128.1 (q, J = 4.8 Hz, CH), 123.0 (qd, J =
33.0, 1.4 Hz, C), 122.00 (q, J = 273.0 Hz, CF3), 121.95 (d, J = 1.3
Hz, CH). 19F NMR (376 MHz, CDCl3) δ: 41.7 (qd, J = 5.6, 1.9 Hz),
-61.5 (d, J = 5.5 Hz). EI-MS m/z (calc. 244.0): 244.0 (100%, M+∙),
161.0 (67%), 133.1 (86%), 113.1 (60%). IR (neat) cm-1: 1453.2,
1316.9, 1137.0, 1114.9, 906.3.
1H NMR (400 MHz, CDCl3) δ: 7.35 (ddd, J = 8.4, 7.5, 1.6 Hz 1H),
7.31 (dddd, J = 8.2, 1.6, 1.3, 0.3 Hz, 1H), 7.06 (ddp, J = 8.4, 1.5,
0.3 Hz, 1H), 6.99 (ddd, J = 8.2, 7.5, 1.5 Hz, 1H), 3.92 (d, J = 0.3
Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ: 151.2 (C), 139.0 (d,
J = 1.2 Hz, C), 129.6 (CH), 122.4 (d, J = 0.9 Hz, CH), 120.9 (CH),
113.5 (CH), 56.1 (CH3). 19F NMR (376 MHz, CDCl3) δ: 39.1 (d, J
= 1.3 Hz). EI-MS m/z (calc. 206.0): 206.0 (62%, M+∙), 123.0
(59%), 95.7 (55%), 77.1 (100%). IR (neat) cm-1: 1499.9, 1440.0,
1230.6, 1101.79, 910.4, 757.1
The obtained analytical data is in agreement with literature.10b
Methyl 5-chloro-2-((fluorosulfonyl)oxy)benzoate (1d)
General procedure was followed using 1.0 equiv of methyl 5-
chloro-2-hydroxybenzoate (1.87 g, 10 mmol). The crude material
was purified by flash chromatography on silica gel using PE/EtOAc
(9:1) to afford analytically pure title compound as a colorless oil
(2.61 g, 97%).
5-Fluoro-2-(trifluoromethyl)phenyl sulfurofluoridate (1h)
General procedure was followed using 1.0 equiv of 2-
(trifluoromethyl)phenol (1.08 g, 6 mmol). The crude material was
purified by flash chromatography on silica gel using PE/EtOAc
(95:5 – 80:20) to afford two equally sized fractions. The first
fraction provided the title compound as a highly volatile colorless
oil (690 mg, 44%).
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Evaporation more polar fraction and recrystallization of the residue
afford analytically pure title compound as a colorless oil (450 mg,
97%).
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from boiling heptane afforded the corresponding diaryl sulfate (1h-
2, vide infra) as a colorless crystalline solid (700 mg, 55%).
Anal. Calcd for C7H3F5O3S: C, 32.07; H, 1.15; N, 0.00. Found: C,
32.60; H, 1.30; N 0.00. 1H NMR (400 MHz, CDCl3) δ: 7.80 (ddqd,
J = 8.8, 5.7, 0.7, 0.3 Hz, 1H), 7.34 (dm, J = 8.1 Hz, 1H), 7.26 (dddq,
J = 8.8, 7.4, 2.4, 0.7 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ:
164.7 (dq, J = 258.5, 1.1 Hz, CF), 147.5 (dp, J = 11.0, 1.5 Hz, C),
129.7 (dq, J = 9.7, 4.8 Hz, CH), 121.7 (q, J = 272.7 Hz, CF3), 119.5
(qdd, J = 33.6, 4.2, 1.2 Hz, C), 115.9 (d, J = 21.7 Hz, CH), 110.7
(dd, J = 26.7, 1.3 Hz, CH). 19F NMR (376 MHz, CDCl3) δ: 41.9
(qd, J = 5.5, 1.4 Hz), -61.0 (ddq, J = 5.5, 1.6, 0.7 Hz), -101.4 (dddq,
J = 8.1, 7.4, 5.7, 1.6 Hz). EI-MS m/z (calc. 262.0): 262.0 (66%,
M+∙), 179.1 (79%), 151.1 (100%), 101.1 (53%). IR (neat) cm-1:
1458.7, 1312.3, 1135.1, 1107.2, 814.1.
Anal. Calcd for C9H9FO4S: C, 46.55; H, 3.91; N, 0.00. Found: C,
46.80; H, 3.49; N 0.00. 1H NMR (400 MHz, CDCl3) δ: 7.95 – 7.90
(m, 1H), 7.88 (ddq, J = 8.6, 2.3, 0.6 Hz, 1H), 7.42 (ddp, J = 8.6,
1.6, 0.4 Hz, 1H), 2.62 (s, 3H), 2.45 (br. s, 3H). 13C{1H} NMR (101
MHz, CDCl3) δ: 196.4 (C=O), 151.7 (d, J = 1.0 Hz, C), 136.9 (C),
132.3 (CH), 131.2 (d, J = 0.9 Hz, C), 128.0 (CH), 121.2 (d, J = 1.2
Hz, CH), 26.7 (CH3), 16.1 (d, J = 1.3 Hz, CH3). 19F NMR (376
MHz, CDCl3) δ: 39.6 (dq, J = 1.6, 0.8 Hz). EI-MS m/z (calc.
232.0): 232.0 (4%, M+∙), 217.0 (100%), 134.0 (25%). IR (neat) cm-
1: 1689.1, 1446.9, 1231.2, 1098.5, 806.2.
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4-Chloro-2-methylphenyl sulfurofluoridate (1l)
General procedure was followed using 1.0 equiv of 4-chloro-2-
methylphenol (285 mg, 2.0 mmol). The intermediate phenolate salt
hindered stirring, therefore full conversion was not reached. The
crude material was purified by flash chromatography on silica gel
using PE/EtOAc (98:2) to afford analytically pure title compound
as a colorless oil (256 mg, 57%).
Anal. Calcd for C7H6ClFO3S: C, 37.43; H, 2.69; N, 0.00. Found:
C, 37.85; H, 2.30; N, 0.00. 1H NMR (400 MHz, CDCl3) δ: 7.34 –
7.29 (m, 1H), 7.29 – 7.24 (m, 2H), 2.37 (s, 3H). 13C{1H} NMR (101
MHz, CDCl3) δ: 147.3 (d, J = 1.0 Hz, C), 134.1 (CH), 132.5 (d, J
= 0.9 Hz, C), 132.1 (CH), 127.8 (CH), 122.3 (d, J = 1.1 Hz, CH),
16.0 (d, J = 1.3 Hz, CH3). 19F NMR (376 MHz, CDCl3) δ: 38.7 (br.
s). EI-MS m/z (calc. 224.0): 224.0 (98%, M+∙), 226.0 (32%,
M+∙+2), 141.0 (100%), 143.0 (33%), 77.0 (96%). IR (neat) cm-1:
1446.6, 1232.2, 1099.4, 863.8, 805.2.
Bis(5-fluoro-2-(trifluoromethyl)phenyl) sulfate (1h-2):
Obtained during 1h synthesis in 55% yield (vide supra).
Anal. Calcd for C14H6F8O4S: C, 39.84; H, 1.43; N, 0.00. Found: C,
39.94; H, 1.34; N, 0.00. 1H NMR (400 MHz, CDCl3) δ: 7.76 (ddqd,
J = 8.8, 5.8, 0.6, 0.3 Hz, 2H), 7.46 (ddqd, J = 8.7, 2.4, 0.6, 0.3 Hz,
2H), 7.20 (dddq, J = 8.8, 7.4, 2.4, 0.7 Hz, 2H). 13C{1H} NMR (101
MHz, CDCl3) δ: 164.7 (dq, J = 257.4, 1.1 Hz, CF), 148.0 (dq, J =
11.2, 1.6 Hz, C), 129.4 (dq, J = 10.1, 4.9 Hz, CH), 121.9 (q, J =
272.7 Hz, CF3), 119.1 (qd, J = 33.3, 4.1 Hz, C), 114.9 (d, J = 21.8
Hz, CH), 110.3 (d, J = 26.8 Hz, CH). 19F NMR (376 MHz, CDCl3)
δ: -61.0 (dh, J = 1.7, 0.7 Hz), -102.1 (dddq, J = 8.7, 7.4, 5.8, 1.7
Hz). EI-MS m/z (calc. 422.0): 422.0 (100%, M+∙), 243.0 (78%),
179.1 (61%), 151.1 (66%), 101.1 (52%). IR (neat) cm-1:1128.3,
1109.0, 825.0.
4-Formyl-2-methoxyphenyl sulfurofluoridate (1m)
2-Fluorophenyl sulfurofluoridate (1i)
General procedure was followed using 1.0 equiv of 4-hydroxy-3-
methoxybenzaldehyde (304 mg, 2.0 mmol). The crude material was
purified by flash chromatography on silica gel using PE/EtOAc
(7:3) to afford analytically pure title compound as an oxygen-
sensitive colorless oil that solidified on standing (451 mg, 96%).
Melting point: 49 – 50 °C. 1H NMR (400 MHz, CDCl3) δ: 10.00
(s, 1H), 7.59 (br. d, J = 1.5 Hz, 1H), 7.55 – 7.49 (m, 2H), 4.01 (s,
3H). 13C{1H} NMR (101 MHz, CDCl3) δ: 190.3 (CHO), 152.0 (d,
J = 0.9 Hz, C), 142.8 (d, J = 1.3 Hz, C), 137.0 (C), 124.0 (CH),
123.1 (d, J = 0.9 Hz, CH), 112.1 (CH), 56.5 (CH3). 19F NMR (376
MHz, CDCl3) δ: 40.5 (d, J = 1.0 Hz). EI-MS m/z (calc. 234.0):
234.2 (100%, M+∙), 151.2 (44%), 95.2 (33%), 77.2 (44%). IR (neat)
cm-1: 1699.7, 1687.5, 1447.6, 1229.4, 904.8.
General procedure was followed using 1.0 equiv of 2-fluorophenol
(1.12 g, 0.893 mL, 10 mmol). The crude material was purified by
flash chromatography on silica gel using PE/EtOAc (95:5) to afford
analytically pure title compound as a highly volatile colorless oil
(1.64 g, 85%).
1H NMR (400 MHz, CDCl3) δ: 7.45 – 7.37 (m, 2H), 7.32 – 7.22
(m, 2H). 13C{1H} NMR (125 MHz, CDCl3) δ: 153.6 (dd, J = 254.6,
0.6 Hz, CF), 137.2 (dd, J = 13.1, 0.9 Hz, C), 130.1 (d, J = 7.1 Hz,
CH), 125.1 (d, J = 4.1 Hz, CH), 123.3 (t, J = 0.9 Hz, CH), 117.9 (d,
J = 17.9 Hz, CH). 19F NMR (376 MHz, CDCl3) δ: 38.6 (dd, J =
10.3, 1.2 Hz), -128.3 (ddddd, J = 10.3, 9.9, 7.3, 4.7, 1.3 Hz). EI-
MS m/z (calc. 194.0): 194.0 (80%, M+∙), 111.0 (47%), 83.0 (100%),
57.0 (44%). IR (neat) cm-1: 1499.3, 1450.8, 1232.6, 942.1, 761.2.
The obtained analytical data is in agreement with literature.10e
The obtained analytical data is in agreement with literature.11a
2-Formylphenyl sulfurofluoridate (1n)
2-Methyl-4-nitrophenyl sulfurofluoridate (1j)
Modified procedure was followed using 1.0 equiv of 2-
hydroxybenzaldehyde (244 mg, 212 L 2.0 mmol), DIPEA (775
mg, 1.05 mL, 6 mmol, 3.0 equiv) as base and neat TFA (2.0 mL)
as acid. The crude material was purified by flash chromatography
on silica gel using PE/EtOAc (8:2) to afford analytically pure title
compound as an oxygen sensitive colorless oil (315 mg, 77%).
1H NMR (400 MHz, CDCl3) δ: 10.32 (t, J = 0.6 Hz, 1H), 8.03 (ddd,
J = 7.7, 1.9, 0.4 Hz, 1H), 7.76 (ddd, J = 8.3, 7.5, 1.9 Hz, 1H), 7.60
(dddd, J = 7.7, 7.5, 1.1, 0.6 Hz, 1H), 7.50 (dddd, J = 8.3, 1.7, 1.1,
0.4 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ: 186.2 (d, J = 0.9
Hz, CHO), 150.6 (C), 135.9 (CH), 130.8 (CH), 129.3 (CH), 128.1
(C), 122.1 (d, J = 0.9 Hz, CH). 19F NMR (376 MHz, CDCl3) δ:
38.8 (dd, J = 1.7, 0.6 Hz). EI-MS m/z (calc. 204.0): 204.0 (2%,
M+∙), 203.0 (11%), 120.0 (100%), 92.2 (46%). IR (neat) cm-
1:1699.6, 1481.8, 1231.5, 911.0, 774.4.
General procedure was followed using 1.0 equiv of 2-methyl-4-
nitrophenol (306 mg, 2.0 mmol). The crude material was purified
by flash chromatography on silica gel using PE/EtOAc (85:15) to
afford analytically pure title compound as a faintly yellow oil (405
mg, 86%).
Anal. Calcd for C7H6FNO5S: C, 35.75; H, 2.57; N, 5.96. Found: C,
35.59; H, 2.39; N, 6.36. 1H NMR (400 MHz, CDCl3) δ: 8.27 – 8.21
(m, 1H), 8.19 (ddq, J = 9.0, 2.8, 0.6 Hz, 1H), 7.52 (ddp, J = 9.0,
1.5, 0.4 Hz, 1H), 2.51 (br. s, 3H). 13C{1H} NMR (101 MHz, CDCl3)
δ: 152.2 (d, J = 1.0 Hz, C), 147.0 (C), 132.9 (d, J = 1.0 Hz, C),
127.4 (CH), 123.3 (CH), 122.1 (d, J = 1.3 Hz, CH), 16.3 (d, J = 1.2
Hz, CH3). 19F NMR (376 MHz, CDCl3) δ: 40.3 (dq, J = 1.5, 0.7
Hz). EI-MS m/z (calc. 235.0): 235.0 (100%, M+∙), 219.0 (15%),
205.0 (49%), 177.0 (38%). IR (neat) cm-1: 1530.0, 1449.3, 1349.8,
1233.8, 1222.0, 800.4
The obtained analytical data is in agreement with literature.10b
4-Acetyl-2-methylphenyl sulfurofluoridate (1k)
2-Cyanophenyl sulfurofluoridate (1o)
General procedure was followed using 1.0 equiv of 4-acetyl-2-
methylphenol (300 mg, 2.0 mmol). The crude material was purified
by flash chromatography on silica gel using PE/EtOAc (85:15) to
General procedure was followed using 1.0 equiv of 2-
hydroxybenzonitrile (1.19 g, 10 mmol). The crude material was
purified by flash chromatography on silica gel using PE/EtOAc
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(8:2) to afford analytically pure title compound as a colorless oil
8.4, 4.6 Hz, 1H), 4.06 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3)
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(1.71 g, 85%).
δ: 162.5 (C=O), 149.4 (CH), 146.4 (d, J = 1.3 Hz, C), 141.4 (d, J =
0.9 Hz, C), 131.1 (CH), 128.2 (CH), 53.4 (CH3). 19F NMR (376
MHz, CDCl3) δ: 42.0 (d, J = 1.4 Hz). EI-MS m/z (calc. 235.0):
232.0 (0%, M+∙), 204.1 (21%), 177.2 (100%), 82.1 (54%). IR (neat)
cm-1: 1732.7, 1452.1, 1429.8, 1080.3, 906.3.
1H NMR (400 MHz, CDCl3) δ: 7.81 (ddd, J = 7.8, 1.7, 0.4 Hz, 1H),
7.77 (ddd, J = 8.5, 7.8, 1.7 Hz, 1H), 7.57 (td, J = 7.8, 1.1 Hz, 1H),
7.57 (dddd, J = 8.5, 1.3, 1.1 Hz, 0.4 Hz, 1H). 13C{1H} NMR (101
MHz, CDCl3) δ: 149.9 (d, J = 1.0 Hz, C), 135.0 (CH), 134.5 (CH),
129.2 (CH), 122.3 (d, J = 1.3 Hz, CH), 113.2 (C), 107.4 (d, J = 1.0
Hz, C). 19F NMR (376 MHz, CDCl3) δ: 40.2 (d, J = 1.3 Hz). EI-
MS m/z (calc. 201.0): 201.1 (88%, M+∙), 118.1 (57%), 90.1 (100%),
63.0 (53%). IR (neat) cm-1: 2239.4, 1448.4, 1235.0, 905.9, 819.1.
The obtained analytical data is in agreement with literature.10b
Pyridin-2-yl sulfurofluoridate (1t)
General procedure was followed using 1.0 equiv of 2-pyridone
(190 mg, 2.0 mmol). The crude material was purified by flash
chromatography on silica gel using pentane/DCM (50:50) to afford
analytically pure title compound as a highly volatile colorless oil
(265 mg, 75%).
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2,3-Dimethyl-1,4-phenylene bis(sulfurofluoridate) (1p)
General procedure was followed using 0.5 equiv of 2,3-
dimethylbenzene-1.4-diol (414 m, 3 mmol). The crude material
was purified by flash chromatography on silica gel using PE/MTBE
(7:3) to afford analytically pure title compound as a colorless oil
(907 mg, 94%).
Anal. Calcd for C8H8F2O6S2: C, 31.79; H, 2.67; N, 0.00. Found: C,
31.80; H, 2.70; N, 0.00. 1H NMR (400 MHz, CDCl3) δ: 7.31 (br. s,
2H), 2.36 (s, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ: 147.8 (d, J
= 0.8 Hz, C), 133.0 (d, J = 0.8 Hz, C), 120.0 (d, J = 1.3 Hz, CH),
13.4 (d, J = 1.3 Hz, CH3). 19F NMR (376 MHz, CDCl3) δ: 39.1
(dq, J = 1.4, 0.7 Hz). EI-MS m/z (calc. 302.0): 302.2 (73%, M+∙),
219.2 (100%), 136.2 (71%), 108.2 (54%). IR (neat) cm-1: 1445.8,
1235.0, 1171.4, 912.0, 797.4.
1H NMR (400 MHz, CDCl3) δ: 8.43 (ddd, J = 4.9, 2.0, 0.8 Hz, 1H),
7.93 (ddd, J = 8.3, 7.4, 2.0 Hz, 1H), 7.41 (ddd, J = 7.4, 4.9, 0.8 Hz,
1H), 7.20 (dt, J = 8.3, 0.8 Hz, 1H). 13C{1H} NMR (101 MHz,
CDCl3) δ: 156.3 (d, J = 1.5 Hz, C), 148.6 (CH), 141.2 (CH), 124.2
(CH), 114.2 (d, J = 2.6 Hz, CH). 19F NMR (376 MHz, CDCl3) δ:
43.9 (s). EI-MS m/z (calc. 177.0): 177.1 (36%, M+∙), 149.1 (100%).
IR (neat) cm-1: 1466.1, 1445.7, 1234.3, 1160.5, 910.7.
The obtained analytical data is in agreement with literature.25
Quinolin-8-yl sulfurofluoridate (1u)
General procedure was followed using 1.0 equiv of quinolin-8-ol
(290 mg, 2.0 mmol). The crude material was filtered through silica
using PE/EtOAc (6:4) and recrystallized from heptane/MTBE (9:1)
to afford analytically pure title compound as a white solid (348 mg,
77%).
Ethyl 4-((fluorosulfonyl)oxy)benzoate (1q)
1
General procedure was followed using 1.0 equiv of ethyl 4-
hydroxybenzoate (166 mg, 1.0 mmol). The crude material was
purified by flash chromatography on silica gel using PE/EtOAc
(9:1) to afford analytically pure title compound as a colorless oil
(234 mg, 94%).
Melting point: 64 – 65 °C. H NMR (400 MHz, CDCl3) δ: 9.07
(ddd, J = 4.3, 1.7, 0.3 Hz, 1H), 8.25 (ddd, J = 8.4, 1.7, 0.3 Hz, 1H),
7.90 (ddt, J = 8.3, 1.3, 0.3 Hz, 1H), 7.76 (dddd, J = 7.7, 1.3, 1.2,
0.3 Hz, 1H), 7.60 (ddd, J = 8.2, 7.7, 0.3 Hz, 1H), 7.56 (ddt, J = 8.4,
4.3 Hz, 0.3 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ: 151.8
(CH), 145.9 (d, J = 1.2 Hz, C), 140.4 (C), 135.9 (CH), 129.9 (C),
1H NMR (400 MHz, CDCl3) δ: 8.18 (AA’MM’X, JAM+AA’ = 9.0
Hz, JAX = 0 Hz, 2H), 7.42 (AA’MM’X, JAM+MM’ = 9.0 Hz, JMX
=
128.7 (CH), 125.9 (CH), 122.7 (CH), 121.3 (d, J = 0.9 Hz, CH). 19
F
1.0 Hz, 2H), 4.41 (q, J = 7.1 Hz, 2H), 1.41 (t, J = 7.1 Hz, 3H).
13C{1H} NMR (101 MHz, CDCl3) δ: 164.9 (C), 152.7 (d, J = 0.8
Hz, C), 132.0 (CH), 131.0 (C), 120.9 (d, J = 1.2 Hz, CH), 61.6
(CH2), 14.2 (CH3). 19F NMR (376 MHz, CDCl3) δ: 38.2 (t, J = 1.1
Hz). EI-MS m/z (calc. 248.0): 248.2 (4%, M+∙), 220.2 (57%), 203.2
(100%), 120.2 (19%). IR (neat) cm-1: 1719.8, 1450.2, 1273.6,
1232.3, 909.3.
NMR (376 MHz, CDCl3) δ: 40.1 (d, J = 1.2 Hz). EI-MS m/z (calc.
227.0): 227.2 (95%, M+∙), 144.2 (47%), 116.2 (100%), 89.16
(42%). IR (neat) cm-1: 1941.2, 1442.0, 1427.1, 846.9, 786.8.
The obtained analytical data is in agreement with literature.25
Methyl 2-(((trifluoromethyl)sulfonyl)oxy)benzoate (5a)
Neat Tf2O (1.693 g, 1.02 mL, 6.0 mmol, 1.2 equiv) was added
dropwise to a solution of methyl 2-hydroxybenzoate (761 mg, .650
L, 5 mmol) and pyridine (791 mg, 650 L, 10 mmol, 2.0 equiv)
in DCM (10 mL) at 0 °C and the resulting suspension was stirred
for 6 hours. It was then diluted with DCM (40 mL), washed with
1N HCl (2 × 50 mL), water (50 mL) and sat. aq NaHCO3 (50 mL),
dried with Na2SO4 and evaporated under reduced pressure. The
residue was purified by flash chromatography on silica gel using
PE/EtOAc (9:1) to afford the pure target material as a faintly straw-
colored oil (1.286 g, 91%).
The obtained analytical data is in agreement with literature.10b
Methyl 3-((fluorosulfonyl)oxy)thiophene-2-carboxylate (1r)
General procedure was followed using 1.0 equiv of methyl 3-
hydroxythiophene-2-carboxylate (316 mg, 2.0 mmol). The crude
material was purified by flash chromatography on silica gel using
PE/EtOAc (85:15) to afford analytically pure title compound as a
colorless oil (440 mg, 92%).
1H NMR (400 MHz, CDCl3) δ: 7.58 (d, J = 5.5 Hz, 1H), 7.12 (dd,
J = 5.5, 1.2 Hz, 1H), 3.94 (s, 3H). 13C{1H} NMR (101 MHz,
CDCl3) δ: 159.7 (C=O), 145.5 (d, J = 1.1 Hz, C), 130.7 (CH), 122.4
(d, J = 1.1 Hz, C), 121.9 (d, J = 0.7 Hz, CH), 52.7 (CH3). 19F NMR
(376 MHz, CDCl3) δ: 39.6 (d, J = 1.2 Hz). EI-MS m/z (calc.
234.0): 240.2 (100%, M+∙), 209.2 (74%), 126.2 (35%), 101.2
(35%). IR (neat) cm-1: 1719.3, 1438.0, 1234.0, 868.2, 773.6.
The obtained analytical data is in agreement with literature.25
1H NMR (400 MHz, CDCl3) δ: 8.10 (ddd, J = 7.8, 1.9, 0.4 Hz, 1H),
7.63 (ddd, J = 8.3, 7.5, 1.9 Hz, 1H), 7.48 (ddd, J = 7.8, 7.5, 1.1 Hz,
1H), 7.31 (dp, J = 8.3, 0.4 Hz, 1H), 3.97 (s, 3H). 13C{1H} NMR
(101 MHz, CDCl3) δ: 164.2 (C=O), 148.3 (C), 134.3 (CH), 132.8
(CH), 128.4 (CH), 124.4 (C, 122.7 (q, J = 1.3 Hz, CH), 118.7 (q, J
= 320.6 Hz, CF3), 52.6 (CH3). 19F NMR (376 MHz, CDCl3) δ: -
74.0 (s). EI-MS m/z (calc. 284.0): 284.2 (61%, M+∙), 253.2 (45%),
189.2 (100%), 95.2 (32%). IR (neat) cm-1: 1728.7, 1422.4, 1201.6,
1135.4, 888.8.
Methyl 3-((fluorosulfonyl)oxy)picolinate (1s)
The obtained analytical data is in agreement with literature.26
General procedure was followed using 1.0 equiv of methyl 3-
hydroxypicolinate (306 mg, 2.0 mmol). The crude material was
purified by flash chromatography on silica gel using PE/EtOAc
(6:4) to afford analytically pure title compound as a colorless oil
(379 mg, 81%).
Anal. Calcd for C7H6FNO5S: C, 35.75; H, 2.57; N, 5.96. Found: C,
36.03; H, 2.64; N, 6.30. 1H NMR (400 MHz, CDCl3) δ: 8.80 (dd,
J = 4.6, 1.4 Hz, 1H), 7.84 (dt, J = 8.4, 1.4 Hz, 1H), 7.66 (dd, J =
Methyl 2-((methylsulfonyl)oxy)benzoate (6a)
Neat MsCl (550 mg, 374 L, 4.8 mmol, 1.2 equiv) was added
dropwise to a solution of methyl 2-hydroxybenzoate (609 mg, .520
L, 4 mmol) and TEA (567 mg, 781 L, 6.4 mmol, 1.4 equiv) in
DCM (8 mL) at 0 °C and the resulting suspension was stirred for 6
hours. It was left to stir for 12 hours at ambient temperature and
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then diluted with DCM (40 mL), washed with 1N HCl (2 × 50 mL),
13C{1H} NMR (101 MHz, CDCl3) δ: 168.9 (C=O), 142.0 (C), 141.3
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water (50 mL) and sat. aq NaHCO3 (50 mL), dried with Na2SO4
and evaporated under reduced pressure. The residue was purified
by flash chromatography on silica gel using PE/EtOAc (6:4) to
afford the pure target material as a viscous colorless oil (850 mg,
92%).
(C), 139.8 (C), 132.2 (CH), 131.9 (C), 128.9 (CH), 127.6 (CH),
127.1 (CH), 126.8 (CH), 126.7 (CH), 51.7 (CH3), 33.4 (CH2), 32.8
(CH2), 22.4 (CH2), 13.7 (CH3). EI-MS m/z (calc. 268.1): 268.1
(77%, M+∙), 236.2 (84%), 207.2 (74%), 193.2 (60%), 165.3 (100%).
IR (neat) cm-1: 2954.3, 1729.6, 1286.7, 1136.8, 761.3.
1H NMR (400 MHz, CDCl3) δ: 7.98 (ddd, J = 7.8, 1.8, 0.4 Hz, 1H),
7.58 (ddd, J = 8.3, 7.4, 1.8 Hz, 1H), 7.44 (ddd, J = 8.3, 1.2, 0.4 Hz,
1H), 7.39 (ddd, J = 7.8, 7.4, 1.2 Hz, 1H), 3.93 (s, 4H), 3.28 (s, 3H).
13C{1H} NMR (101 MHz, CDCl3) δ: 164.7, 147.7, 133.8, 132.0,
127.2, 124.4, 124.1, 52.4, 38.4. EI-MS m/z (calc. 230.0): 230.1
(18%, M+∙), 199.1 (20%), 152.1 (100%), 120.1 (86%), 92.1 (49%).
IR (neat) cm-1: 1722.2, 1157.2, 1079.2, 867.5.
Typical telescoped fluorosulfation – Catellani procedure
Methyl
6-butyl-4-chloro-4'-methoxy-(1,1'-biphenyl)-2-
carboxylate (4dab)
Chamber A of a small two-chamber reactor was charged with 1,1’-
sulfonyldiimidazole (496 mg, 2.5 mmol, 1.25 equiv) and potassium
fluoride (349 mg, 6.0 mmol, 3.0 equiv). Next, chamber B was
charged with methyl 5-chloro-2-hydroxybenzoate (11d, 187mg, 1
mmol, 1.0 equiv) and fine dry potassium carbonate (276 mg, 2
mmol, 2.0 equiv). The reactor was capped and subjected to 5
vacuum – argon cycles. DMF (2 mL) was injected into chamber B
and trifluoroacetic acid/water mixture (2 mL, 50:50 v/v) was
injected into chamber A through the corresponding septa using a
syringe. A short delay followed by gradual gas evolution was
observed over the next 30 minutes. Contents of both chambers were
vigorously stirred at ambient temperature (20 °C) for 3 hours.
Palladium acetate (11.2 mg, 0.05 mmol, 5 mol%), fine dry
potassium carbonate (553 mg, 4.0 mmol, 4.0 equiv), norbornene
(47.1 mg, 0.50 mmol, 0.5 equiv) and 4-methoxyphenylboronic acid
(3b, 182 mg, 1.20 mmol, 1.20 equiv) were weighed into a 5 mL
screw-cap pressure vial and the vial was briefly flushed with argon.
The suspension from the chamber B of the actively stirred two-
chamber reactor was then transferred to this pressure vial via a 3
mL syringe, 1-bromobutane was added (2a, 164 mg, 130 L, 1.20
mmol, 1.20 equiv) and the vial was immersed into a pre-heated oil
bath (70 °C). The reaction was conducted for 3 hours under
vigorous stirring.
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The obtained analytical data is in agreement with literature.27
Typical small-scale Catellani procedure (0.4 mmol)
Methyl 6-butyl-(1,1'-biphenyl)-2-carboxylate (4aaa)
Palladium acetate (4.5 mg, 0.02 mmol, 5 mol%) and fine dry
potassium carbonate (332 mg, 2.4 mmol, 6.0 equiv) was weighed
into a 5 mL screw-cap pressure vial which was then capped and
subjected to 5 vacuum/argon cycles. Norbornene (18.8 mg, 0.20
mmol, 0.5 equiv), phenylboronic acid (3a, 61.0 mg, 0.50 mmol,
1.25 equiv) and methyl 2-((fluorosulfonyl)oxy)benzoate (1a, 93.7
mg, 0.40 mmol) were weighed into a 1.5 mL screw-cap vial and
briefly flushed with argon. 1-bromobutane (2a, 65.8 mg, 51.9 L
0.48 mmol, 1.20 equiv) and DMF (0.8 mL) were then added under
inert atmosphere. The obtained solution was transferred via 1mL
syringe to the 5 mL screw-cap pressure vial containing the catalyst
and the base. The pressure vial was immediately immersed into a
pre-heated oil bath (70 °C) and the reaction was conducted for 4
hours under vigorous stirring.
The blackened reaction mixture was poured into water (40 mL) and
extracted with PE (20 mL). The organic phase was then washed
with water (40 mL) and brine (10 mL), dried with Na2SO4 and
concentrated under reduced pressure. The black residue was
purified by flash chromatography on silica gel using PE/EtOAc
(95:5) as solvent to afford the title compound as a viscous colorless
oil (88 mg, 82%). Analytical information provided with the scaled-
up procedure (vide infra).
The blackened reaction mixture was poured into water (200 mL)
and extracted with PE (50 mL). The organic phase was then washed
with water (100 mL) and brine (20 mL), dried with Na2SO4 and
concentrated under reduced pressure. The black residue was
purified by flash chromatography on silica gel using PE/MTBE
(9:1) as solvent to afford the title compound as a viscous colorless
oil (261 mg, 78%).
Typical scaled-up Catellani procedure (4.0 mmol)
Methyl 6-butyl-(1,1'-biphenyl)-2-carboxylate (4aaa)
Anal. Calcd for C19H21ClO3: C, 68.57; H, 6.36; N, 0.00. Found: C,
68.63; H, 6.05; N, 0.00. 1H NMR (400 MHz, CDCl3) δ: 7.60 (d, J
Palladium acetate (45 mg, 0.20 mmol, 5 mol%) and fine dry
potassium carbonate (2.76 g, 20 mmol, 5.0 equiv) was weighed into
a 25 mL round-bottom flask, which was then capped with a septa
and subjected to 5 vacuum/argon cycles. Norbornene (188 mg, 2.0
mmol, 0.5 equiv), phenylboronic acid (3a, 610 mg, 5.0 mmol, 1.25
equiv) and methyl 2-((fluorosulfonyl)oxy)benzoate (1a, 937 mg,
673 L, 4.0 mmol) were weighed into a 10 mL flask and briefly
flushed with argon. 1-bromobutane (2a, 658 mg, 519 L, 4.8 mmol,
1.20 equiv) and DMF (8.0 mL) were then added under inert
atmosphere. The obtained solution was transferred via 10 mL
syringe to the 25 mL round-bottom flask containing the catalyst and
the base. The flask was immediately immersed into a pre-heated oil
bath (70 °C) and the reaction was conducted for 4 hours under
vigorous stirring.
The blackened reaction mixture was poured into water (200 mL)
and extracted with PE (60 mL). The organic phase was then washed
with water (100 mL) and brine (20 mL), dried with Na2SO4 and
concentrated under reduced pressure. The black residue was
purified by flash chromatography on silica gel using PE/EtOAc
(95:5) as solvent to afford the title compound as a viscous colorless
oil (879 mg, 82%).
= 2.3 Hz, 1H), 7.37 (d, J = 2.3 Hz, 1H), 7.05 (AA’XX’, JAX+AA’ =
8.7 Hz, 2H), 6.92 (AA’XX’, JAX+XX’ = 8.7 Hz, 2H), 3.85 (s, 3H),
3.56 (s, 3H), 2.43 – 2.34 (m, 2H), 1.43 – 1.32 (m, 3H), 1.17 (h, J =
7.3 Hz, 2H), 0.77 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (101 MHz,
CDCl3) δ: 167.8 (C=O), 158.7 (C), 144.5 (C), 139.5 (C), 133.6 (C),
132.7 (C), 131.7 (CH), 130.8 (C), 130.0 (CH), 126.5 (CH), 113.3
(CH), 55.2 (CH3), 52.1 (CH3), 33.1 (CH2), 32.8 (CH2), 22.3 (CH2),
13.7 (CH3). EI-MS m/z (calc. 332.1): 332.1 (100%, M+∙), 334.1
(33%, M+∙+2), 300.1 (48%), 272.1 (60%). IR (neat) cm-1: 2954.8,
1734.2, 1284.2, 1242.2, 1153.0, 830.7.
Methyl 6-butyl-4-chloro-(1,1'-biphenyl)-2-carboxylate (4daa)
Typical small-scale procedure was followed using methyl 5-chloro-
2-((fluorosulfonyl)oxy)benzoate (1d, 107 mg, 0.4 mmol). The
reaction was conducted for 3 hours. The crude product was purified
by flash chromatography using PE/EtOAc (96:4) as solvent to
afford the title compound as a viscous colorless oil (93 mg, 77%).
Anal. Calcd for C18H19ClO2: C, 71.40; H, 6.33; N, 0.00. Found: C,
71.36; H, 6.47; N, 0.00. 1H NMR (400 MHz, CDCl3) δ: 7.64 (d, J
= 2.3 Hz, 1H), 7.39 (d, J = 2.3 Hz, 1H), 7.37 (AA’BB’C, 3H), 7.13
(AA’BB’C, 2H), 3.53 (s, 3H), 2.42 – 2.34 (m, 2H), 1.42 – 1.33 (m,
2H), 1.16 (h, J = 7.3 Hz, 2H), 0.75 (t, J = 7.3 Hz, 3H). 13C{1H}
NMR (101 MHz, CDCl3) δ: 167.5 (C=O), 144.1 (C), 139.9 (C),
138.7 (C), 133.2 (C), 132.9 (C), 131.9 (CH), 128.9 (CH), 127.8
(CH), 127.2 (CH), 126.7 (CH), 52.0 (CH3), 33.1 (CH2), 32.8 (CH2),
22.3 (CH2), 13.8 (CH2), 13.7 (CH3). EI-MS m/z (calc. 302.1):
Anal. Calcd for C18H20O2: C, 80.56; H, 7.51; N, 0.00. Found: C,
80.56; H, 7.64; N, 0.00. 1H NMR (400 MHz, CDCl3) δ: 7.65 (dd,
J = 7.6, 1.5 Hz, 1H), 7.42 (dd, J = 7.7, 1.5 Hz, 1H), 7.41 – 7.39(m,
4H), 7.17 (AA’BB’C, 2H), 3.52 (s, 3H), 2.52 – 2.27 (m, 2H), 1.44
– 1.32 (m, 2H), 1.16 (h, J = 7.3 Hz, 2H), 0.75 (t, J = 7.3 Hz, 3H).
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The Journal of Organic Chemistry
302.3 (100%, M+∙), 304.3 (100%, M+∙+2), 270.2 (8%), 241.2 (96%),
dd, J = 8.8, 5.3 Hz, 1H), 7.45 – 7.35 (m, 3H), 7.22 – 7.14 (m, 2H),
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8
227.3 (70%), 199.3 (65%). IR (neat) cm-1: 2955.2, 1735.2, 1282.2,
7.11 (br. t, J = 8.9 Hz, 1H), 2.36 – 2.27 (m, 2H), 1.37 – 1.27 (m,
2H), 1.14 (h, J = 7.3 Hz, 2H), 0.72 (t, J = 7.3 Hz, 3H). 13C{1H}
NMR (101 MHz, CDCl3) δ: 163.0 (dq, J = 251.0, 1.2 Hz, CF),
143.0 (dq, J = 5.9, 1.7 Hz, C), 136.3 (d, J = 2.2 Hz, C), 131.1 (d, J
= 16.0 Hz, C), 129.5 (q, J = 1.3 Hz, CH), 127.8 (CH), 127.5 (CH),
125.3 (qd, J = 29.5, 3.3 Hz, C), 125.0 (dq, J = 10.0, 5.7 Hz, CH),
123.8 (q, J = 273.8 Hz, CF3), 114.1 (d, J = 24.0 Hz, CH), 32.1 (d,
J = 1.3 Hz, CH2), 26.1 (d, J = 2.4 Hz, CH2), 22.6 (CH2), 13.5 (CH3).
19F NMR (376 MHz, CDCl3) δ: -57.6 (dp, J = 2.2, 0.7 Hz), -111.7
(ddq, J = 9.2, 5.3, 2.2 Hz). EI-MS m/z (calc. 296.1): 296.1 (78%,
M+∙), 267.1 (30%), 253.1 (82%), 233.1 (100%), 183.2 (39%). IR
(neat) cm-1: 2960.2, 1314.7, 1126.0, 1099.1, 701.1.
1192.7, 700.3.
2-Butyl-6-nitro-1,1'-biphenyl (4eaa)
Typical small-scale procedure was followed using 2-nitrophenyl
sulfurofluoridate (1e, 59.0 L, 88.5 mg, 0.4 mmol). The reaction
was conducted for 2 hours. The crude product was purified by flash
chromatography using PE/EtOAc (95:5) as solvent to afford the
title compound as a viscous faintly yellow oil (74 mg, 73%).
Anal. Calcd for C16H17NO2: C, 75.27; H, 6.71; N, 5.49. Found: C,
75.49; H, 6.78; N, 5.93. 1H NMR (400 MHz, CDCl3) δ: 7.63 (dd,
J = 8.0, 1.4 Hz, 1H), 7.49 (dd, J = 7.7, 1.4 Hz, 1H), 7.45 – 7.35 (m,
4H), 7.20 (AA’BB’C, 2H), 2.49 – 2.39 (m, 2H), 1.45 – 1.33 (m,
2H), 1.17 (h, J = 7.3 Hz, 2H), 0.76 (t, J = 7.3 Hz, 3H). 13C{1H}
NMR (101 MHz, CDCl3) δ: 150.6 (C), 143.9 (C), 135.5 (C), 134.9
(C), 132.9 (CH), 128.8 (CH), 128.3 (CH), 127.88 (CH), 127.86
(CH), 120.8 (CH), 33.2 (CH2), 32.8 (CH2), 22.3 (CH2), 13.7 (CH3).
EI-MS m/z (calc. 255.1): 255.2 (13%, M+∙), 238.3 (100%), 210.3
(35%), 196.3 (59%), 165.3 (91%). IR (neat) cm-1: 2957.0, 1524.1,
1358.4, 744.9, 699.7.
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2-Butyl-6-fluoro-1,1'-biphenyl (4iaa)
Typical small-scale procedure was followed using 2-fluorophenyl
sulfurofluoridate (1i, 77.7 mg, 0.4 mmol) and 1.4 equiv of 1-
bromobutane (2a, 60.4 L, 76.7 mg, 0.56 mmol) The reaction was
conducted for 5 hours. The crude product was purified by flash
chromatography using PE/toluene (95:5) as solvent to afford the
title compound as a colorless oil (47 mg, 52%).
Anal. Calcd for C16H17F: C, 84.17; H, 7.51; N, 0.00. Found: C,
84.29; H, 7.65; N, 0.00. 1H NMR (400 MHz, CDCl3) δ: 7.47 – 7.40
(m, 2H), 7.40 – 7.34 (m, 1H), 7.30 – 7.24 (m, 2H), 7.25 (ddd, J =
8.2, 7.7, 5.8 Hz, 1H), 7.07 (ddd, J = 7.7, 1.2, 0.6 Hz, 1H), 6.96 (ddd,
J = 9.3, 8.2, 1.2 Hz, 1H), 2.51 – 2.40 (m, 2H), 1.46 – 1.34 (m, 2H),
1.18 (h, J = 7.3 Hz, 2H), 0.76 (t, J = 7.3 Hz, 3H). 13C{1H} NMR
(101 MHz, CDCl3) δ: 159.9 (d, J = 243.8 Hz, CF), 143.5 (d, J = 2.3
Hz, C), 134.7 (d, J = 1.2 Hz, C), 130.0 (d, J = 1.0 Hz, CH), 129.2
(d, J = 16.0 Hz, C), 128.3 (d, J = 8.9 Hz, CH), 128.1 (CH), 127.4
(CH), 124.5 (d, J = 3.1 Hz, CH), 112.6 (d, J = 23.2 Hz, CH), 33.3
(CH2), 32.5 (d, J = 2.6 Hz, CH2), 22.4 (CH2), 13.7 (CH3). 19F NMR
(376 MHz, CDCl3) δ: -115.2 (dd, J = 9.3, 5.8 Hz). EI-MS m/z
(calc. 228.1): 228.1 (90%, M+∙), 199.1 (21%), 186.1 (57%), 185.1
(90%), 183.1 (49%), 165.1 (100%). IR (neat) cm-1: 2956.4, 1456.8,
1241.4, 762.5, 736.6, 699.2.
2-Butyl-4-methoxy-6-nitro-1,1'-biphenyl (4faa)
Typical small-scale procedure was followed using 4-methoxy-2-
nitrophenyl sulfurofluoridate (1f, 100 mg, 0.4 mmol). The reaction
was conducted for 3 hours. The crude product was purified by flash
chromatography using PE/EtOAc (95:5) as solvent to afford the
title compound as a viscous yellow oil (89 mg, 78%).
Melting point: 68 – 70 °C. Anal. Calcd for C17H19NO3: C, 71.56;
H, 6.71; N, 4.91. Found: C, 71.25; H, 6.67; N, 5.26. 1H NMR (400
MHz, CDCl3) δ: 7.38 (AA’BB’C, 3H), 7.17 (AA’BB’C, 2H), 7.17
(d, J = 2.7 Hz, 1H), 7.03 (d, J = 2.7 Hz, 1H), 3.88 (s, 3H), 2.46 –
2.30 (m, 2H), 1.45 – 1.32 (m, 2H), 1.16 (h, J = 7.3 Hz, 2H), 0.75 (t,
J = 7.3 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ: 158.6 (C),
151.1 (C), 145.1 (C), 135.5 (C), 129.3 (CH), 128.2 (CH), 127.7
(CH), 127.6 (C), 119.2 (CH), 105.7 (CH), 55.7 (CH3), 33.08 (CH2),
33.07 (CH2), 22.3 (CH2), 13.7 (CH3). EI-MS m/z (calc. 285.1):
285.1 (100%, M+∙), 268.4 (47%), 266.4 (46%), 165.3 (33%), 152.3
(34%). IR (neat) cm-1: 2957.3, 1527.4, 1466.6, 766.6, 700.4.
2-Butyl-6-methyl-4-nitro-1,1'-biphenyl (4jaa)
Typical small-scale procedure was followed using 2-methyl-4-
nitrophenyl sulfurofluoridate (1j, 94.1 mg, 0.4 mmol) and 1-
bromobutane (2a, 60.4 L, 76.7 mg, 0.56 mmol, 1.4 equiv). The
reaction was conducted for 5 hours. The crude product was purified
by flash chromatography using heptane/DCM/EtOAc (80:19:1) as
solvent to afford the title compound as a colorless oil (74 mg, 69%).
Anal. Calcd for C17H19NO2: C, 75.81; H, 7.11; N, 5.20. Found: C,
75.88; H, 7.21; N, 5.59. 1H NMR (400 MHz, CDCl3) δ: 7.97 (ABq,
AB = 11.1 Hz, J = 2.4 Hz, 2H), 7.46 (AA’BB’C, 2H), 7.40
(AA’BB’C, 1H), 7.10 (AA’BB’C, 2H), 2.49 – 2.27 (m, 2H), 2.09
(t, J = 0.6 Hz, 3H), 1.48 – 1.36 (m, 2H), 1.18 (h, J = 7.3 Hz, 2H),
0.76 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ: 148.2
(C), 146.9 (C), 142.9 (C), 138.8 (C), 138.3 (C), 128.6 (CH), 128.4
(CH), 127.5 (CH), 121.8 (CH), 121.2 (CH), 33.3 (CH2), 33.0 (CH2),
22.3 (CH2), 21.2 (CH3), 13.7 (CH3). EI-MS m/z (calc. 269.1):
269.1 (92%, M+∙), 266.1 (39%), 210.1 (50%), 180.1 (100%), 165.2
(78%). IR (neat) cm-1: 2957.0, 1514.6, 1342.6, 745.1, 702.4.
2-Butyl-6-(trifluoromethyl)-1,1'-biphenyl (4gaa)
Typical small-scale procedure was followed using 2-
(trifluoromethyl)phenyl sulfurofluoridate (1g, 67.8 L, 97.7 mg,
0.4 mmol). The reaction was conducted for 4 hours. The crude
product was purified by flash chromatography using heptane as
solvent to afford the title compound as a colorless oil (78 mg, 70%).
Anal. Calcd for C17H17F3: C, 73.35; H, 6.16; N, 0.00. Found: C,
73.60; H, 6.34; N, 0.00. 1H NMR (400 MHz, CDCl3) δ: 7.58 (dd,
J = 7.7, 1.4 Hz, 1H), 7.45 (br. d, J = 7.2 Hz, 1H), 7.42 – 7.34 (m,
4H), 7.22 – 7.16 (m, 2H), 2.34 – 2.26 (m, 2H), 1.44 – 1.32 (m, 2H),
1.15 (h, J = 7.3 Hz, 2H), 0.75 (t, J = 7.3 Hz, 3H). 13C{1H} NMR
(101 MHz, CDCl3) δ: 143.3 (C), 140.1 (q, J = 1.6 Hz, C), 137.4
(C), 132.4 (q, J = 1.0 Hz, CH), 129.7 (q, J = 1.4 Hz, CH), 129.1 (q,
J = 28.8 Hz, CH), 127.44 (CH), 127.36 (CH), 127.2 (CH), 124.2
(q, J = 274.2 Hz, CF3), 123.2 (q, J = 5.5 Hz, CH), 33.4 (CH2), 32.8
(CH2), 22.4 (CH2), 13.7 (CH3). 19F NMR (376 MHz, CDCl3) δ: -
57.9 (q, J = 0.7 Hz). EI-MS m/z (calc. 278.1): 278.1 (89%, M+∙),
249.1 (26%), 235.1 (100%), 215.1 (87%), 165.1 (49%). IR (neat)
cm-1: 2958.7, 1314.3, 1123.2, 653.1.
2-Butyl-4-acetyl-6-methyl-1,1'-biphenyl (4kaa)
Modified typical small-scale procedure was followed using 4-
acetyl-2-methylphenyl sulfurofluoridate (1k, 92.9 mg, 0.4 mmol),
1.4 equiv of 1-bromobutane (2a, 60.4 L, 76.7 mg, 0.56 mmol) and
1 equiv of norbornene (37.7 mg, 0.4 mmol). The reaction was
conducted for 5 hours. The crude product was purified by flash
chromatography using PE/EtOAc (95:5) as solvent to afford the
title compound as a colorless oil (79 mg, 74%).
Anal. Calcd for C19H22O: C, 85.67; H, 8.32; N, 0.00. Found: C,
86.05; H, 8.35; N, 0.00. 1H NMR (400 MHz, CDCl3) δ: 7.72 (d, J
= 1.9 Hz, 1H), 7.69 (d, J = 1.9 Hz, 1H), 7.44 (AA’BB’C, 2H), 7.36
(AA’BB’C, 1H), 7.12 (AA’BB’C, 2H), 2.63 (s, 3H), 2.42 – 2.32
2-Butyl-3-fluoro-6-(trifluoromethyl)-1,1'-biphenyl (4haa)
Typical small-scale procedure was followed using 5-fluoro-2-
(trifluoromethyl)phenyl sulfurofluoridate (1h, 110 mg, 0.4 mmol).
The reaction was conducted for 4 hours. The crude product was
purified by flash chromatography using heptane as solvent to afford
the title compound as a colorless oil (36 mg, 30%).
Anal. Calcd for C17H16F4: C, 68.91; H, 5.44; N, 0.00. Found: C,
69.92; H, 5.82; N, 0.00. 1H NMR (400 MHz, CDCl3) δ: 7.57 (br.
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(m, 2H), 2.06 (s, 3H), 1.46 – 1.34 (m, 2H), 1.17 (h, J = 7.4 Hz, 2H),
Methyl 4-butyl-3-phenylpicolinate (4saa)
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0.75 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ: 198.4
(C=O), 146.6 (C), 141.5 (C), 139.8 (C), 136.8 (C), 136.0 (C), 128.7
(CH), 128.4 (CH), 127.12 (CH), 127.05 (CH), 126.4 (CH), 33.4
(CH2), 33.3 (CH2), 26.7 (CH3), 22.5 (CH2), 21.1 (CH3), 13.7 (CH3).
EI-MS m/z (calc. 266.2): 266.1 (38%, M+∙), 251.2 (100%), 181.1
(27%), 165.2 (16%). IR (neat) cm-1: 2955.6, 1680.7, 1197.8, 702.6.
Typical small-scale procedure was followed using methyl 3-
((fluorosulfonyl)oxy)picolinate (1s, 94.1 mg, 0.4 mmol). The
reaction was conducted for 6 hours. The crude product was purified
by flash chromatography using PE/EtOAc (7:3) as solvent to afford
the title compound as a colorless oil (20 mg, 19%).
Anal. Calcd for C17H19O2N: C, 75.81; H, 7.11; N, 5.20. Found: C,
75.69; H, 7.24; N, 5.66. 1H NMR (400 MHz, CDCl3) δ: 8.55 (d, J
= 5.0 Hz, 1H), 7.46 – 7.36 (AA’BB’C, 3H), 7.34 (d, J = 5.0 Hz,
1H), 7.20 (AA’BB’C, 2H), 3.66 (s, 3H), 2.55 – 2.37 (m, 2H), 1.48
– 1.37 (m, 2H), 1.19 (h, 7.3 Hz, 2H), 0.77 (t, J = 7.3 Hz, 4H).
13C{1H} NMR (101 MHz, CDCl3) δ: 167.0 (C=O), 151.7 (C), 149.0
(C), 148.0 (CH), 136.9 (C), 136.4 (C), 128.9 (CH), 128.1 (CH),
127.7 (CH), 125.8 (CH), 52.3 (CH3), 32.3 (CH2), 32.2 (CH2), 22.3
(CH2), 13.6 (CH3). EI-MS m/z (calc. 269.1): 269.3 (0.3%, M+∙),
239.2 (33%), 210.3 (20%), 182.3 (100%). IR (neat) cm-1: 2955.0,
1736.2, 1299.2, 1152.0, 700.9.
2-butyl-6-methoxy-[1,1'-biphenyl]-4-carbaldehyde (4maa)
Typical small-scale procedure was followed using 4-formyl-2-
methoxyphenyl sulfurofluoridate (1m, 93.6 mg, 0.4 mmol). The
reaction was conducted for 3 hours. The crude product was purified
by flash chromatography using PE/EtOAc (93:7) as solvent to
afford the title compound as a colorless oil (79 mg, 74%).
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Anal. Calcd for C18H20O2: C, 80.56; H, 7.51; N, 0.00. Found: C,
1
80.73; H, 7.38; N, 0.00. H NMR (400 MHz, CDCl3) δ: 9.99 (s,
1H), 7.44 (AA’BB’C, 2H), 7.43 (d, J = 1.6 Hz, 1H), 7.37
(AA’BB’C, 1H), 7.31 (d, J = 1.6 Hz, 1H), 7.19 (AA’BB’C, 2H),
3.77 (s, 3H), 2.47 – 2.39 (m, 2H), 1.49 – 1.36 (m, 2H), 1.18 (h, J =
7.3 Hz, 2H), 0.77 (t, J = 7.3 Hz, 1H). 13C{1H} NMR (101 MHz,
CDCl3) δ: 192.3 (CHO), 157.7 (C), 143.5 (C), 137.3 (C), 136.4 (C),
136.3 (C), 129.5 (CH), 128.0 (CH), 127.3 (CH), 125.3 (CH), 106.6
(CH), 55.9 (CH3), 33.1 (CH2), 32.7 (CH2), 22.4 (CH2), 13.7 (CH3).
EI-MS m/z (calc. 268.1): 268.1 (66%, M+∙), 226.1 (24%), 197.1
(100%), 165.2 (33%). IR (neat) cm-1: 2955.8, 1692.9, 1381.0,
1148.4, 699.9.
Methyl 6-(cyclopropylmethyl)-[1,1'-biphenyl]-2-carboxylate
(4aba)
Typical small-scale procedure was followed using methyl 2-
((fluorosulfonyl)oxy)benzoate (1a, 67.3 L, 93.7 mg, 0.4 mmol)
and (bromomethyl)cyclopropane (2b, 46.6 L, 64.8 mg, 0.48
mmol, 1.20 equiv). The reaction was conducted for 4 hours. The
crude product was purified by flash chromatography using
PE/EtOAc (94:6) as solvent to afford the title compound as a
viscous colorless oil (83 mg, 78%).
Anal. Calcd for C18H18O2: C, 81.17; H, 6.81; N, 0.00. Found: C,
81.10; H, 7.01; N, 0.00. 1H NMR (400 MHz, CDCl3) δ: 7.69 (ddt,
J = 7.7, 1.4, 0.5 Hz, 1H), 7.62 (ddt, J = 7.8, 1.4, 0.6 Hz, 1H), 7.42
– 7.30 (m, 4H), 7.16 (AA’BB’C, 2H), 3.52 (s, 3H), 2.32 (d, J = 6.9
Hz, 2H), 0.86 – 0.72 (m, 1H), 0.50 – 0.35 (m, 2H), 0.08 – -0.04 (m,
2H). 13C{1H} NMR (101 MHz, CDCl3) δ: 168.8 (C=O), 141.3 (C),
139.9 (C), 131.9 (CH), 131.7 (C), 128.9 (CH), 127.7 (CH), 127.2
(CH), 126.92 (CH), 126.87 (CH), 51.7 (CH3), 37.6 (CH2), 11.3
(CH), 4.8 (CH2). EI-MS m/z (calc. 266.1): 266.3 (6%, M+∙), 234.2
(54%), 206.2 (100%), 205.2 (95%), 178.3 (83%). IR (neat) cm-1:
3000.9, 1728.7, 1286.5, 1137.2, 759.5, 700.1.
6-butyl-4'-methoxy-2,3-dimethyl-[1,1'-biphenyl]-4-yl
sulfurofluoridate (4pab)
Modified typical small-scale procedure was followed using 2,3-
dimethyl-1,4-phenylene bis(sulfurofluoridate) (1p, 121 mg, 0.4
mmol), 1.4 equiv of 1-bromobutane (2a, 60.4 L, 76.7 mg, 0.56
mmol), 1 equiv of norbornene (37.7 mg, 0.4 mmol) and 4-
methoxyphenylboronic acid (3b, 76.0 mg, 0.5 mmol, 1.25 eqiuv.)
The reaction was conducted for 6 hours. The crude product was
purified by flash chromatography using heptane/EtOAc (96:4) as
solvent to afford the title compound as a colorless oil (81 mg, 55%).
Anal. Calcd for C19H23FO4S: C, 62.28; H, 6.33; N, 0.00. Found: C,
62.49; H, 6.28; N, 0.00. 1H NMR (400 MHz, CDCl3) δ: 7.07 (br. s,
1H), 7.00 (AA’BB’, JAB+AA’ = 8.9 Hz, 2H), 6.96 (AA’BB’, JAB+BB’
= 8.9 Hz, 2H), 3.87 (s, 3H), 2.34 – 2.24 (m, 2H), 2.27 (s, 3H) 1.96
(s, 3H), 1.41 – 1.30 (m, 2H), 1.16 (h, J = 7.3 Hz, 2H), 0.77 (t, J =
7.3 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ: 158.6 (C), 148.1
(d, J = 0.9 Hz, C), 141.7 (C), 141.0 (C), 138.5 (C), 132.2 (C), 130.2
(CH), 125.9 (d, J = 0.8 Hz, C), 118.0 (d, J = 1.0 Hz, CH), 113.8
(CH), 55.2 (CH3), 33.2 (CH2), 33.0 (CH2), 22.3 (CH2), 18.0 (CH3),
13.8 (CH3), 13.0 (d, J = 1.3 Hz, CH3). 19F NMR (376 MHz, CDCl3)
δ: 38.3 (dq, J = 1.7, 0.8 Hz). EI-MS m/z (calc. 366.1): 366.4 (100%,
M+∙), 283.4 (52%), 241.4 (79%), 224.4 (48%), 223.4 (48%). IR
(neat) cm-1: 2956.7, 1442.3, 1222.4, 1033.2, 792.0.
Methyl 6-isopropyl-(1,1'-biphenyl)-2-carboxylate (4aca)
Modified small-scale procedure was followed using methyl 2-
((fluorosulfonyl)oxy)benzoate (1a, 67.3 L, 93.7 mg, 0.4 mmol),
2-bromopropane (2c, 75.1 L, 98.4 mg, 0.80 mmol, 2.0 equiv), 1.0
equiv of norbornene (37.7 mg, 0.4 mmol) and 10 mol% of
Pd(OAc)2 (9.0 mg). The reaction was conducted for 12 hours. The
crude product was purified by flash chromatography using
PE/EtOAc (94:6) as solvent to afford the title compound as a
viscous colorless oil (61 mg, 60%).
Anal. Calcd for C17H18O2: C, 80.28; H, 7.13; N, 0.00. Found: C,
80.05; H, 6.90; N, 0.00. 1H NMR (400 MHz, CDCl3) δ: 7.63 (dd,
J = 7.6, 1.4 Hz, 1H), 7.52 (dd, J = 7.9, 1.4 Hz, 1H), 7.43 – 7.31 (m,
4H), 7.18 (AA’BB’C, 2H), 3.51 (s, 3H), 2.84 (hept, J = 7.0 Hz, 1H),
1.10 (d, J = 7.0 Hz, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ: 168.9
(C=O), 147.9 (C), 140.4 (C), 139.8 (C), 131.8 (C), 128.9 (CH),
128.6 (CH), 127.7 (CH), 127.5 (CH), 126.8 (CH), 126.5 (CH), 51.7
(CH3), 29.4 (CH), 24.0 (CH3). EI-MS m/z (calc. 254.1): 254.4
(37%, M+∙), 222.4 (57%), 207.4 (100%), 179.4 (58%). IR (neat)
cm-1: 2962.6, 1729.9, 1720.0, 1286.1, 700.5.
Methyl 4-butyl-3-phenylthiophene-2-carboxylate (4raa)
Typical small-scale procedure was followed using methyl 3-
((fluorosulfonyl)oxy)thiophene-2-carboxylate (1r, 93.6 mg, 0.4
mmol). The reaction was conducted for 4 hours. The crude product
was purified by flash chromatography using PE/EtOAc (95:5) as
solvent to afford the title compound as a colorless oil (82 mg, 74%).
Anal. Calcd for C16H18O2S: C, 70.04; H, 6.61; N, 0.00. Found: C,
69.95; H, 6.57; N, 0.00. 1H NMR (400 MHz, CDCl3) δ: 7.46 – 7.33
(AA’BB’C, 3H), 7.21 (AA’BB’C, 2H), 7.20 (s, 1H), 3.69 (s, 3H),
2.38 – 2.32 (m, 2H), 1.47 – 1.35 (m, 2H), 1.21 (h, J = 7.2 Hz, 2H),
0.80 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ: 162.4
(C=O), 148.7 (C), 144.3 (C), 136.1 (C), 129.0 (CH), 128.2 (C),
127.9 (CH), 127.5 (CH), 125.9 (CH), 51.7 (CH3), 31.9 (CH2), 28.8
(CH2), 22.2 (CH2), 13.8 (CH3). EI-MS m/z (calc. 274.1): 274.2
(31%, M+∙), 232.2 (100%), 200.15 (48%), 172.2 (80%). IR (neat)
cm-1: 2952.7, 1721.1, 1699.1, 1210.3, 697.8.
Methyl 6-benzyl-(1,1'-biphenyl)-2-carboxylate (4afa)
Small-scale procedure was followed using methyl 2-
((fluorosulfonyl)oxy)benzoate (1a, 67.3 L, 93.7 mg, 0.4 mmol),
benzyl chloride (2f, 55.2 L, 60.8 mg, 0.48 mmol, 1.2 equiv), The
reaction was conducted for 4 hours. The crude product was purified
by flash chromatography using PE/EtOAc (92:8) as solvent to
afford the title compound as a viscous colorless oil (88 mg, 73%).
HRMS (ESI-TOF) m/z: [M+Na] Calcd for C21H18O2Na: 325.1199;
found: 325.1199. 1H NMR (400 MHz, CDCl3) δ: 7.75 – 7.66 (m,
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1H), 7.40 – 7.28 (m, 5H), 7.23 – 7.11 (m, 3H), 7.13 – 7.06 (m, 2H),
(d, J = 7.9 Hz, CH), 127.4 (CH), 126.9 (CH), 114.7 (d, J = 21.3 Hz,
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6.94 – 6.86 (m, 2H), 3.80 (s, 2H), 3.53 (s, 3H). 13C{1H} NMR (101
MHz, CDCl3) δ: 168.7 (C=O), 141.8 (C), 140.7 (C), 140.1 (C),
139.5 (C), 133.2 (CH), 132.1 (C), 128.9 (CH), 128.9 (CH), 128.2
(CH), 127.8 (CH), 127.4 (CH), 127.3 (CH), 127.0 (CH), 125.9
(CH), 51.8 (CH3), 39.1 (CH2). EI-MS m/z (calc. 302.1): 302.3
(30%, M+∙), 270.3 (100%), 242.3 (67%), 241.3 (71%), 165.2 (92%).
CH), 51.8 (CH3), 33.4 (CH2), 32.8 (CH2), 22.4 (CH2), 13.7 (CH3).
19F NMR (376 MHz, CDCl3) δ: -116.3 (tt, J = 8.7, 5.5 Hz). EI-MS
m/z (calc. 286.1): 286.4 (100%, M+∙), 254.3 (65%), 225.3 (74%),
183.4 (85%). IR (neat) cm-1: 2955.3, 1729.1, 1219.8, 1137.1,
761.4.
Methyl
(4aad)
6-butyl-3'-methoxy-(1,1'-biphenyl)-2-carboxylate
Methyl 6-hexyl-(1,1'-biphenyl)-2-carboxylate (4aga)
Modified small-scale procedure was followed using methyl 2-
((fluorosulfonyl)oxy)benzoate (1a, 67.3 L, 93.7 mg, 0.4 mmol)
and 1-chlorohexane (2g, 110 L, 96.5 mg, 0.80 mmol, 2.0 equiv).
The reaction was conducted for 12 hours. The crude product was
purified by flash chromatography using PE/EtOAc (96:4) as
solvent to afford the title compound as a viscous colorless oil (52
mg, 44%).
Anal. Calcd for C20H24O2: C, 81.04; H, 8.16; N, 0.00. Found: C,
81.51; H, 8.29; N, 0.00. 1H NMR (400 MHz, CDCl3) δ: 7.65 (dd,
J = 7.6, 1.5 Hz, 1H), 7.41 (dd, J = 7.7, 1.5 Hz, 1H), 7.36 (t, J = 7.7
Hz, 1H), 7.40 – 7.29 (AA’BB’C, 3H), 7.17 (AA’BB’C, 2H), 3.52
(s, 3H), 2.44 – 2.36 (m, 2H), 1.44 – 1.32 (m, 2H), 1.24 – 1.04 (m,
6H), 0.81 (t, J = 7.0 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ:
168.9 (C=O), 142.0 (C), 141.3 (C), 139.8 (C), 132.2 (CH), 131.9
(C), 128.9 (CH), 127.6 (CH), 127.1 (CH), 126.8 (CH), 126.7 (CH),
51.7 (CH3), 33.1 (CH2), 31.4 (CH2), 31.1 (CH2), 29.0 (CH2), 22.4
(CH2), 14.0 (CH3). EI-MS m/z (calc. 296.2): 296.5 (58%, M+∙),
264.4 (60%), 207.4 (72%), 193.4 (67%), 165.4 (100%). IR (neat)
cm-1: 2926.5, 1730.2, 1287.8, 1136.4, 699.9.
Typical small-scale procedure was followed using methyl 2-
((fluorosulfonyl)oxy)benzoate (1a, 67.3 L, 93.7 mg, 0.4 mmol)
and 3-methoxyphenylboronic acid (3d, 76.0 mg, 0.5 mmol, 1.25
eqiuv.) The reaction was conducted for 4 hours. The crude product
was purified by flash chromatography using PE/EtOAc (93:7) as
solvent to afford the title compound as a viscous colorless oil (101
mg, 85%).
Anal. Calcd for C19H22O3: C, 76.48; H, 7.43; N, 0.00. Found: C,
76.70; H, 7.34; N, 0.00. 1H NMR (400 MHz, CDCl3) δ: 7.63 (dd,
J = 7.6, 1.5 Hz, 1H), 7.41 (dd, J = 7.7, 1.5 Hz, 1H), 7.33 (t, J = 7.7
Hz, 1H), 7.29 (ddd, J = 8.3, 7.5, 0.4 Hz, 1H), 6.88 (ddd, J = 8.3,
2.6, 1.0 Hz, 1H), 6.77 (ddd, J = 7.5, 1.5, 1.0 Hz, 1H), 6.73 (ddd, J
= 2.6, 1.5, 0.4 Hz, 1H), 3.81 (s, 3H), 3.55 (s, 3H), 2.50 – 2.36 (m,
2H), 1.46 – 1.35 (m, 2H), 1.18 (p, J = 7.3 Hz, 2H), 0.77 (t, J = 7.3
Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ: 168.9 (C=O), 159.0
(C), 141.9 (C), 141.2 (C), 141.0 (C), 132.2 (CH), 131.9 (C), 128.6
(CH), 127.2 (CH), 126.6 (CH), 121.6 (CH), 114.5 (CH), 112.5
(CH), 55.2 (CH3), 51.8 (CH3), 33.5 (CH2), 32.8 (CH2), 22.4 (CH2),
13.8 (CH3). EI-MS m/z (calc. 298.2): 298.3 (32%, M+∙), 266.3
(53%), 238.4 (100%), 209.4 (32%). IR (neat) cm-1:2953.7, 1730.0,
1285.5, 1136.4, 759.9.
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Methyl
(4aab)
6-butyl-4'-methoxy-(1,1'-biphenyl)-2-carboxylate
Methyl 6-butyl-3'-fluoro-(1,1'-biphenyl)-2-carboxylate (4aae)
Typical small-scale procedure was followed using methyl 2-
((fluorosulfonyl)oxy)benzoate (1a, 67.3 L, 93.7 mg, 0.4 mmol)
and 3-fluorophenylboronic acid (3e, 70.0 mg, 0.5 mmol, 1.25
eqiuv.) The reaction was conducted for 4 hours. The crude product
was purified by flash chromatography using PE/EtOAc (95:5) as
solvent to afford the title compound as a viscous colorless oil (85
mg, 74%).
Anal. Calcd for C18H19FO2: C, 75.50; H, 6.69; N, 0.00. Found: C,
75.40; H, 6.74; N, 0.00. 1H NMR (400 MHz, CDCl3) δ: 7.69 (dd,
J = 7.6, 1.5 Hz, 1H), 7.43 (dd, J = 7.7, 1.5 Hz, 1H), 7.36 (t, J = 7.7
Hz, 1H), 7.34 (dddd, J = 8.3, 7.6, 6.0, 0.4 Hz, 1H), 7.04 (dddd, J =
8.8, 8.3, 2.6, 1.0 Hz, 1H), 6.95 (ddd, J = 7.6, 1.5, 1.0 Hz, 1H), 6.91
(dddd, J = 9.6, 2.6, 1.5, 0.4 Hz, 1H), 3.56 (s, 3H), 2.43 – 2.36 (m,
2H), 1.44 – 1.33 (m, 2H), 1.17 (h, J = 7.3 Hz, 2H), 0.77 (t, J = 7.3
Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ: 168.4 (C=O), 162.3
(d, J = 245.9 Hz, CF), 142.1 (d, J = 7.9 Hz, C), 141.9 (C), 140.1 (d,
J = 1.9 Hz, C), 132.4 (CH), 131.5 (C), 129.1 (d, J = 8.4 Hz, CH),
127.5 (CH), 127.0 (CH), 124.8 (d, J = 2.9 Hz, CH), 116.1 (d, J =
21.6 Hz, CH), 113.8 (d, J = 21.0 Hz, CH), 51.8 (CH3), 33.4 (CH2),
32.7 (CH2), 22.4 (CH2), 13.7 (CH3). 19F NMR (376 MHz, CDCl3)
δ: -114.6 (ddd, J = 9.6, 8.8, 6.0 Hz). EI-MS m/z (calc. 286.1): 286.2
(32%, M+∙), 254.2 (100%), 225.3 (74%), 183.4 (93%). IR (neat)
cm-1: 2955.0, 1728.6, 1284.3, 1136.8, 759.7.
Typical small-scale procedure was followed using methyl 2-
((fluorosulfonyl)oxy)benzoate (1a, 67.3 L, 93.7 mg, 0.4 mmol)
and 4-methoxyphenylboronic acid (3b, 76.0 mg, 0.5 mmol, 1.25
eqiuv.) The reaction was conducted for 4 hours. The crude product
was purified by flash chromatography using PE/EtOAc (93:7) as
solvent to afford the title compound as a viscous colorless oil (104
mg, 87%).
Anal. Calcd for C19H22O3: C, 76.48; H, 7.43; N, 0.00. Found: C,
76.45; H, 7.63; N, 0.00. 1H NMR (400 MHz, CDCl3) δ: 7.61 (dd,
J = 7.6, 1.5 Hz, 1H), 7.40 (dd, J = 7.7, 1.5 Hz, 1H), 7.32 (t, J = 7.7
Hz, 1H), 7.09 (AA’XX’, JAX+AA’ = 8.8 Hz, 2H), 6.92 (AA’XX’,
JAX+XX’ = 8.8 Hz, 2H), 3.85 (s, 3H), 3.55 (s, 3H), 2.47 – 2.37 (m,
2H), 1.44 – 1.32 (m, 2H), 1.17 (p, J = 7.3 Hz, 2H), 0.77 (t, J = 7.3
Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ: 169.1 (C=O), 158.4
(C), 142.4 (C), 140.9 (C), 132.3 (C), 132.1 (CH), 132.0 (C), 130.0
(CH), 127.0 (CH), 126.5 (CH), 113.1 (CH), 55.1 (CH3), 51.8 (CH3),
33.4 (CH2), 32.8 (CH2), 22.4 (CH2), 13.8 (CH3). EI-MS m/z (calc.
298.2): 298.4 (100%, M+∙), 266.4 (39%), 238.4 (51%), 195.4
(42%). IR (neat) cm-1: 2954.1, 1729.5, 1285.7, 1241.5, 1135.7.
Methyl 6-butyl-4'-fluoro-(1,1'-biphenyl)-2-carboxylate (4aac)
Typical small-scale procedure was followed using methyl 2-
((fluorosulfonyl)oxy)benzoate (1a, 67.3 L, 93.7 mg, 0.4 mmol)
and 4-fluorophenylboronic acid (3c, 70.0 mg, 0.5 mmol, 1.25
eqiuv.) The reaction was conducted for 4 hours. The crude product
was purified by flash chromatography using PE/EtOAc (95:5) as
solvent to afford the title compound as a viscous colorless oil (91
mg, 79%).
Anal. Calcd for C18H19FO2: C, 75.50; H, 6.69; N, 0.00. Found: C,
75.50; H, 6.65; N, 0.00. 1H NMR (400 MHz, CDCl3) δ: 7.66 (dd,
J = 7.6, 1.5 Hz, 1H), 7.42 (dd, J = 7.7, 1.5 Hz, 1H), 7.35 (t, J = 7.7
Hz, 1H), 7.14 (AA’MM’X, JAM+AA’ = 8.8 Hz, JAX = 5.5 Hz, 2H),
7.08 (AA’MM’X, JAM+MM’ = 8.8 Hz, JMX = 8.8 Hz, 2H), 3.56 (s,
3H), 2.43 – 2.34 (m, 2H), 1.44 – 1.30 (m, 2H), 1.23 – 1.10 (h, J =
7.3 Hz, 2H), 0.76 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (101 MHz,
CDCl3) δ: 168.7 (C=O), 161.9 (d, J = 245.4 Hz, CF), 142.2 (C),
140.3 (C), 135.7 (d, J = 3.7 Hz, C), 132.4 (CH), 131.9 (C), 130.5
Methyl 6-butyl-3'-chloro-(1,1'-biphenyl)-2-carboxylate (4aaf)
Typical small-scale procedure was followed using methyl 2-
((fluorosulfonyl)oxy)benzoate (1a, 67.3 L, 93.7 mg, 0.4 mmol)
and 3-chlorophenylboronic acid (3f, 78.2 mg, 0.5 mmol, 1.25
eqiuv.) The reaction was conducted for 4 hours. The crude product
was purified by flash chromatography using PE/EtOAc (95:5) as
solvent to afford the title compound as a viscous colorless oil (85
mg, 70%).
Anal. Calcd for C18H19ClO2: C, 71.40; H, 6.33; N, 0.00. Found: C,
71.57; H, 6.50; N, 0.00. 1H NMR (400 MHz, CDCl3) δ: 7.69 (dd,
J = 7.6, 1.5 Hz, 1H), 7.42 (dd, J = 7.7, 1.5 Hz, 1H), 7.36 (t, J = 7.6
Hz, 1H), 7.34 – 7.29 (m, 2H), 7.19 – 7.17 (m, 1H), 7.10 – 7.03 (m,
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1H), 3.57 (s, 3H), 2.46 – 2.33 (m, 2H), 1.45 – 1.33 (m, 2H), 1.18
1.34 (m, 2H), 1.18 (h, J = 7.5 Hz, 2H), 0.77 (t, J = 7.3 Hz, 3H).
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7
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(h, J = 7.3 Hz, 2H), 0.77 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (101
MHz, CDCl3) δ: 168.4 (C=O), 141.9 (C), 141.8 (C), 140.0 (C),
133.6 (C), 132.5 (CH), 131.4 (C), 129.0 (CH), 128.9 (CH), 127.6
(CH), 127.3 (CH), 127.1 (CH), 127.0 (CH), 51.9 (CH3), 33.4 (CH2),
32.8 (CH2), 22.4 (CH2), 13.7 (CH3). EI-MS m/z (calc. 302.1):
302.0 (60%, M+∙), 304.2 (20%, M+∙+2), 270.0 (90%), 235.2 (100%),
199.1 (71%). IR (neat) cm-1: 2954.5, 1728.3, 1286.0, 1138.0,
758.4.
13C{1H} NMR (101 MHz, CDCl3) δ: 159.2 (C), 151.1 (C), 144.3
(C), 134.5 (C), 132.6 (CH), 130.0 (CH), 127.7 (CH), 127.4 (C),
120.6 (CH), 113.7 (CH), 55.2 (CH3), 33.2 (CH2), 32.8 (CH2), 22.3
(CH2), 13.7 (CH3). EI-MS m/z (calc. 285.1): 285.5 (100%, M+∙),
268.5 (43%), 226.5 (34%), 210.5 (43%). IR (neat) cm-1: 2956.7,
1524.9, 1514.3, 1244.2, 831.3.
Dimethyl (1,1':2',1''-terphenyl)-2,3'-dicarboxylate (9aa)
Typical small-scale procedure was followed using methyl 2-
iodobenzoate (8a, 58.8 L, 105 mg, 0.4 mmol). The reaction was
conducted for 4 hours. The crude product was purified by flash
chromatography using PE/EtOAc (8:2) as solvent to afford the title
compound as a viscous colorless oil (31 mg, 45%).
Methyl 3'-bromo-6-butyl- (1,1'-biphenyl)-2-carboxylate (4aag)
Typical small-scale procedure was followed using methyl 2-
((fluorosulfonyl)oxy)benzoate (1a, 67.3 L, 93.7 mg, 0.4 mmol)
and 3-bromophenylboronic acid (3g, 100 mg, 0.5 mmol, 1.25
eqiuv.) The reaction was conducted for 4 hours. The crude product
was purified by flash chromatography using PE/EtOAc (95:5) as
solvent to afford the partially purified title compound as a tan oil
(12 mg, 9%).
HRMS (ESI-TOF) m/z: [M+Na] C18H19BrO2Na: 369.0460; found:
369.0461. 1H NMR (400 MHz, CDCl3) δ: 7.69 (dd, J = 7.6, 1.5 Hz,
1H), 7.48 (ddd, J = 8.0, 2.0, 1.1 Hz, 1H), 7.42 (dd, J = 7.7, 1.5 Hz,
1H), 7.36 (t, J = 7.6 Hz, 1H), 7.34 (ddd, J = 2.0, 1.6, 0.4 Hz, 1H),
7.26 (ddd, J = 8.0, 7.6, 0.4 Hz, 1H), 7.11 (ddd, J = 7.6, 1.6, 1.1 Hz,
1H), 3.57 (s, 3H), 2.43 – 2.34 (m, 2H), 1.44 – 1.34 (m, 2H), 1.18
(h, J = 7.3 Hz, 2H), 0.77 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (101
MHz, CDCl3) δ: 168.3 (C=O), 142.0 (C), 141.9 (C), 139.9 (C),
132.5 (CH), 131.8 (CH), 131.4 (C), 129.9 (CH), 129.2 (CH), 127.8
(CH), 127.6 (CH), 127.1 (CH), 121.7 (C), 51.9 (CH3), 33.4 (CH2),
32.8 (CH2), 22.4 (CH2), 13.7 (CH3). EI-MS m/z (calc. 346.0):
346.2 (26%, M+∙), 348.2 (26%, M+∙+2), 314.3 (30%), 235.3 (100%),
165.3 (78%). IR (neat) cm-1: 2952.9, 1728.7, 1285.9, 1138.0,
758.6.
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1H NMR (400 MHz, CDCl3) δ: 7.83 (dd, J = 7.6, 1.5 Hz, 1H), 7.72
(ddd, J = 7.7, 1.5, 0.5 Hz, 1H), 7.45 (t, J = 7.6 Hz, 1H), 7.39 (dd, J
= 7.7, 1.5 Hz, 1H), 7.33 (td, J = 7.6, 1.5 Hz, 1H), 7.23 (td, J = 7.7,
1.4 Hz, 1H), 7.14 – 7.07 (m, 3H), 7.07 (ddd, J = 7.6, 1.4, 0.5 Hz,
1H), 6.97 (br. s, 2H), 3.61 (s, 3H), 3.55 (s, 3H). 13C{1H} NMR (101
MHz, CDCl3) δ: 169.1 (C=O), 167.4 (C=O), 142.2 (C), 141.9 (C),
140.0 (C), 139.2 (C), 132.0 (CH), 132.0 (CH), 131.8 (CH), 131.0
(CH), 130.4 (C), 129.7 (CH), 129.4 (CH), 128.5 (CH), 127.2 (br.,
CH), 126.9 (CH), 126.8 (CH), 126.6 (CH), 51.8 (CH3), 51.8 (CH3).
EI-MS m/z (calc. 346.1): 346.3 (4%, M+∙), 314.3 (100%), 383.3
(55%), 225.3 (95%). IR (neat) cm-1: 2949.7, 1721.1, 1286.3,
1256.1, 701.4.
The obtained analytical data is in agreement with literature.19a
Ethyl 2,6-dibutyl-(1,1'-biphenyl)-4-carboxylate (10qaa)
Modified small-scale procedure was followed using ethyl 4-
((fluorosulfonyl)oxy)benzoate (1q, 99.3 mg, 0.4 mmol) and 1-
bromobutane (2a, 97.3 L, 123 mg, 0.9 mmol, 2.25 equiv).
Reaction conducted for 3 hours. The crude product was purified by
flash chromatography using PE/MTBE (95:5) as solvent to afford
the title compound as a viscous colorless oil (100 mg, 74%).
Anal. Calcd for C23H30O2: C, 81.61; H, 8.93; N, 0.00. Found: C,
Methyl 3-butyl-2-(naphthalen-2-yl)benzoate (4aah)
Typical small-scale procedure was followed using methyl 2-
((fluorosulfonyl)oxy)benzoate (1a, 67.3 L, 93.7 mg, 0.4 mmol)
and naphthalen-2-ylboronic acid (3h, 86.0 mg, 0.5 mmol, 1.25
eqiuv.) The reaction was conducted for 4 hours. The crude product
was purified by flash chromatography using PE/EtOAc (95:5) as
solvent to afford the title compound as a viscous colorless oil (99
mg, 78%).
Anal. Calcd for C22H22O2: C, 82.99; H, 6.96; N, 0.00. Found: C,
83.01; H, 6.72; N, 0.00. 1H NMR (400 MHz, CDCl3) δ: 7.91 – 7.87
(m, 1H), 7.86 (d, J = 8.2 Hz, 1H), 7.84 – 7.78 (m, 1H), 7.69 (dd, J
= 7.6, 1.5 Hz, 1H), 7.60 (br. s, 1H), 7.53 – 7.46 (m, 2H), 7.45 (dd,
J = 7.7, 1.5 Hz, 1H), 7.38 (t, J = 7.7 Hz, 1H), 7.35 (dd, J = 8.4, 1.7
Hz, 1H), 3.44 (s, 3H), 2.42 (ABX2, AB = 11.2 Hz, JAB = 13.8 Hz,
JAX = JBX = 7.4 Hz, 2H), 1.46 – 1.34 (m, 2H), 1.12 (h, J = 7.3 Hz,
2H), 0.71 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ:
168.9 (C=O), 142.2 (C), 141.2 (C), 137.5 (C), 133.0 (C), 132.3 (C),
132.2 (CH), 132.1 (C), 128.0 (CH), 127.80 (CH), 127.75 (CH),
127.29 (CH), 127.25 (CH), 127.0 (CH), 126.8 (CH), 126.0 (CH),
125.7 (CH), 51.7 (CH3), 33.4 (CH2), 32.9 (CH2), 22.3 (CH2), 13.7
(CH3). EI-MS m/z (calc. 318.2): 318.5 (100%, M+∙), 286.5 (62%),
258.5 (65%), 215.5 (95%). IR (neat) cm-1: 2953.0, 1728.0, 1285.4,
1136.5, 757.6, 743.7.
1
81.60; H, 8.91; N, 0.00. H NMR (400 MHz, CDCl3) δ: 7.78 (s,
2H), 7.41 (AA’BB’C, 2H), 7.35 (AA’BB’C, 1H), 7.12 (AA’BB’C,
2H), 4.40 (q, J = 7.1 Hz, 2H), 2.36 – 2.29 (m, 4H), 1.42 (t, J = 7.1
Hz, 3H), 1.44 – 1.33 (m, 4H), 1.15 (h, J = 7.4 Hz, 4H), 0.74 (t, J =
7.3 Hz, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ: 167.0 (C=O),
145.8 (C), 141.4 (C), 139.6 (C), 129.18 (C), 129.15 (CH), 128.0
(CH), 127.4 (CH), 126.9 (CH), 60.8 (CH2), 33.39 (CH2), 33.35
(CH2), 22.5 (CH2), 14.4 (CH3), 13.7 (CH3). EI-MS m/z (calc.
338.2): 338.1 (45%, M+∙), 295.1 (25%), 223.2 (43%), 167.2
(100%). IR (neat) cm-1: 2955.9, 1716.5, 1202.6, 768.8, 703.6.
SUPPORTING INFORMATION
Picture of the two-chamber reactors, detailed optimization table,
and 1H, 13C{1H}, 13C{1H} APT and 19F NMR spectra of the
synthesized compounds (PDF).
Acknowledgements
This research has received funding from the European Union's EU
Framework Programme for Research and Innovation Horizon 2020
under Grant Agreement No 721290. The Hercules Foundation of
the Flemish Government is acknowledged for supporting the
purchase of a 400 MHz NMR spectrometer through project
AKUL1311 and providing high-resolution mass spectrometry
equipment through grant 20100225–7.
2-Butyl-4'-methoxy-6-nitro-1,1'-biphenyl (4eab)
Typical telescoped procedure was followed using 2-nitrophenol
(11e, 139 mg, 1.0 mmol). The Catellani reaction step was
conducted for 3 hours. The crude product was purified by flash
chromatography using PE/EtOAc (96:4) as solvent to afford the
title compound as a viscous yellow oil (191 mg, 67%).
Anal. Calcd for C17H19NO3: C, 71.56; H, 6.71; N, 4.91. Found: C,
71.25; H, 6.43; N, 5.32. 1H NMR (400 MHz, CDCl3) δ: 7.58 (dd,
J = 8.0, 1.4 Hz, 1H), 7.47 (dd, J = 7.8, 1.4 Hz, 1H), 7.38 (t, J = 7.9
Hz, 1H), 7.12 (AA’XX’, JAX+AA’ = 8.8 Hz, 2H), 6.94 (AA’XX’,
JAX+XX’ = 8.8 Hz, 2H), 3.85 (s, 3H), 2.49 – 2.41 (m, 2H), 1.45 –
The authors declare no competing financial interest.
REFERENCES
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2. (a) Ye, J.; Lautens, M. Palladium-Catalysed Norbornene-
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15. Higher temperatures promoted premature precipitation of
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