Nickel-Catalyzed Decarbonylative Thioetherification of Acyl Fluorides via C-F Bond Activation

Article abstract of DOI:10.1055/a-1484-6216

Nickel-catalyzed decarbonylative thioetherification of acyl fluorides has been developed. This transformation allows an array of acyl fluorides to react with thiophenols. A wide range of functional groups are well tolerated and the corresponding sulfides can be obtained in good to excellent yields. This protocol provides the formation of diverse carbon-sulfur bonds via a highly efficient decarbonylative process.

Full text of DOI:10.1055/a-1484-6216

Submission Date:
Accepted Date:
Publication Date:
2021-03-13
2021-04-16
2021-04-16
Accepted Manuscript
Synthesis
Nickel-Catalyzed Decarbonylative Thioetherification of Acyl Fluorides via C-F
Bond Activation
Jingwen You, Qiang Chen, Yasushi Nishihara.
Affiliations below.
DOI: 10.1055/a-1484-6216
Please cite this article as: You J, Chen Q, Nishihara Y. Nickel-Catalyzed Decarbonylative Thioetherification of Acyl Fluorides via C-F Bond
Activation. Synthesis 2021. doi: 10.1055/a-1484-6216
Conflict of Interest: The authors declare that they have no conflict of interest.
Abstract:
Nickel-catalyzed decarbonylative thioetherification of acyl fluorides has been developed. This transformation allows an array
of acyl fluorides to react with thiophenols. A wide range of functional groups are well tolerated and the corresponding sulfides
can be obtained in good to excellent yields. This protocol provides the formation of diverse carbon-sulfur bonds via a highly
efficient decarbonylative process.
Corresponding Author:
Yasushi Nishihara, Okayama University, Research Institute for Interdisciplinary Science, 3-1-1 Tsushimanaka, Kita-ku,, 700-8530 Okaya-
ma, Japan, ynishiha@okayama-u.ac.jp
Affiliations:
Jingwen You, Okayama University, Graduate School of Natural Science and Technology, Okayama, Japan
Qiang Chen, Okayama University, Graduate School of Natural Science and Technology, Okayama, Japan
Yasushi Nishihara, Okayama University, Research Institute for Interdisciplinary Science, Okayama, Japan
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Synthesis
Paper / PSP / Special Topic
Nickel-Catalyzed Decarbonylative Thioetherification of Acyl Fluorides via
C-F Bond Activation
,a
Jingwen You
Qiang Chen
a
b
Yasushi Nishihara *
a
Graduate School of Natural Science and Technology,
Okayama University, 3-1-1 Tsushimanaka, Kita-ku, Okayama
700-8530, Japan
b
Research Institute for Interdisciplinary Science, Okayama
University, 3-1-1 Tsushimanaka, Kita-ku, Okayama 700-8530,
Japan
*
indicates the main/corresponding author.
ynishiha@okayama-u.ac.jp
Click here to insert a dedication.
Received:
Accepted:
Published online:
DOI:
bonds with transition metal catalysts.6 Moreover, acyl fluorides
have been widely applied in various transition-metal-catalyzed
transformations via the decarbonylative pathway to form C-C
Abstract Nickel-catalyzed decarbonylative thioetherification of acyl fluorides
has been developed. This transformation allows an array of acyl fluorides to
react with thiophenols. A wide range of functional groups are well tolerated
and the corresponding sulfides can be obtained in good to excellent yields.
This protocol provides the formation of diverse carbon-sulfur bonds via a
highly efficient decarbonylative process.
bonds, such as palladium-catalyzed trifluoromethylation, nickel-
9
catalyzed Suzuki-Miyaura coupling,10 iridium-catalyzed arylation
via C-H bond activation11 nickel or palladium-catalyzed
alkylation,12 and nickel or palladium-catalyzed alkynylation.13 In
addition, acyl fluorides not only can form divers C-C bonds also
have constructed various carbon-heteroatom C-X (X = H,14 B,15 Si,
Key words C-F bond activation, decarbonylation, thioetherification, acyl
fluorides, sulfides
1
6
17
and Sn ) bonds by new transition-metal-catalyzed
decarbonylative transformations via C-F bond cleavage. Herein,
we report the nickel-catalyzed cross-coupling for C-S bond
formation by decarbonylative thioetherification via activation of
carbon-fluorine bonds of acyl fluorides.
Sulfur-containing molecules, especially diaryl sulfides, are
important structural scaffolds in a large number of natural
products.1 The traditional synthetic method for the formation of
C–S bonds is Stadler–Ziegler reaction, in which aryldiazonium
salts react with thiolates to form diaryl sulfides.2 However, this
method is faced with the complication of preparing and isolating
the unstable diazonium salts and thiolates.3 Therefore, an
efficient method of the synthesis of sulfides still needs to be
We started our research by optimizing the reaction
conditions using benzoyl fluoride (1a) and 4-methylthiophenol
(
2a) (2.0 equiv) as coupling partners and NiCl ·DME (10 mol %)
2
as the catalyst and the results are listed in Table 1. Various
bidentate phosphine ligands such as DPPE (1,2-
bis(diphenylphosphino)ethane),
bis(diphenylphosphino)propane),
DPPP
DPPF
(1,3-
(1,1’-
explored.
Nevertheless, some challenges still remain in
and
transition-metal-catalyzed cross-coupling reactions to form
carbon-sulfur bonds. For example, the thioetherification of aryl
halides with thiols and thiophenols are often conducted with the
most commonly used being the expensive palladium.4 In recent
years, carboxylic acids and their derivatives have attracted much
attention in synthetic organic chemistry.5,6 Along this line, recent
studies have revealed that nickel catalysts are effective for
decarbonylative cross-coupling reactions to construct carbon-
carbon and carbon-heteroatom bonds using less reactive
bis(diphenylphosphino)ferrocene) were investigated to afford
the corresponding decarbonylative product 3aa in 44%, 84%,
and 50% yields, respectively (entries 1-3). When the reaction
was conducted using K
2
CO , K
3 3
PO
4
, or NaOAc instead of Na
2
CO ,
3
3aa was obtained in lower yields (entries 4-6). To our delight,
when the amount of 2a was reduced to 1.5 equiv, the desired
product 3aa was obtained in 90% yield (entry 7). However,
further decrease in the amount of 2a to 1.2 equiv resulted in
lower yield (Table S3 in the Supporting Information). When the
7
7g,8
electrophiles such as esters and amides as alternatives to aryl
halides.
reaction was conducted without Na
2
CO , the yield of 3a was
3
dramatically decreased to 45% (entry 8). In the absence of the
nickel catalyst, the desired product 3a was not obtained at all,
and the thioester 4a was obtained in 68% yield (entry 9).
On the other hand, the development of novel reactions using
acyl fluorides has become one of the focus areas in organic
synthesis due to their high stability, ease of preparation from the
corresponding carboxylic acids, and moderate reactivity of C-F
Template for SYNTHESIS © Thieme Stuttgart · New York
2021-04-16
page 1 of 6

Synthesis
Paper / PSP / Special Topic
Table 1 Optimization of Reaction Conditionsa
yield of 3a
%)b
yield of 4a
(%)b
entry
ligand
base
(
1
2
3
4
5
DPPE
DPPP
DPPF
DPPP
DPPP
DPPP
DPPP
DPPP
DPPP
-
Na
Na
Na
2
2
2
CO
CO
CO
3
3
3
44
84
50
57
63
60
15
0
16
1
K
K
2
CO
PO
3
3
4
1
6
NaOAc
trace
0
14
24
68
7c
8c,d
9c
Na
Na
-
90 (90)
2
CO
3
2
CO
3
68
45
0
1
0c,e
Na
2
CO
3
aReaction conditions: 1a (0.2 mmol), 2a (2.0 equiv), NiCl
·DME (10 mol %), 1,3-
(1.5 equiv), toluene (1
2
bis(diphenylphosphino)propane (DPPP) (30 mol %), Na
2
CO
3
b
mL), 140 °C, 24 h. GC yields using n-dodecane as an internal standard and an
c
d
isolated yield is shown in parentheses. 2a (1.5 equiv). NiCl
2
·DME (5 mol%).
e
2
Without NiCl ·DME and DPPP.
With the optimized reaction conditions in hand, the
substrate scope of acyl fluorides was investigated. As shown in
Scheme 1, a series of acyl fluorides bearing electron-donating
groups such as alkyl (1b) and aryl (1c) gave the corresponding
products 3b and 3c in good to excellent yields. Furthermore,
various acyl fluorides bearing electron-withdrawing groups such
as cyano (1d), ketone (1e), and ester (1f) well tolerated in the
reaction conditions and afforded the target products 3d-3f in 72-
Scheme 1 Scope with respect to acyl fluorides. Reagents and conditions: 1 (0.2
mmol),
2a
(0.3
mmol),
NiCl
2
·DME
(10
mol
CO
%),
(1.5 equiv),
1,3-
bis(diphenylphosphino)propane (DPPP) (30 mol %), Na
2
3
8
0% yields. Notably, acyl fluorides bearing fluorine (1g) and
toluene (1 mL), 140 °C, 24 h under N
Reaction performed in 8 mmol scale for 24 h.
2
. Isolated yields.
a
chlorine (1h) atoms also afforded the desired products in good
yields. Moreover, naphthyl-derived substrates (1i and 1j) were
also compatible to give 3i and 3j in 94% and 81% yields,
Besides, the aliphatic thiol 2b also can be tolerated in this
reaction, afforded the desired product 3q in 83% yield (Scheme
respectively.
Acyl fluorides with heterocycles including
benzofuran, benzothiophene, and quinoline yielded 3k-3m in
good yields. To our delight, cinnamoyl fluoride (1n) and C(sp )-
2).
3
containing acyl fluoride 1o tolerated the reaction conditions and
afforded the desired products 3n and 3o in 68% and 55% yields,
respectively. Besides, acyl fluoride 1p derived from probenecid
could also afford 82% of 3p. More practically, the reaction was
applicable to large-scale synthesis, yielding up to 1.19 g of 3a in
74% yield.
Scheme 2 Reagents and conditions: 1a (0.2 mmol), 2b (0.3 mmol), NiCl
2
·DME
10 mol %), 1,3-bis(diphenylphosphino)propane (DPPP) (30 mol %), Na CO
1.5 equiv), toluene (1 mL), 140 °C, 24 h under N . Isolated yields.
(
(
2
3
2
Next, acyl fluorides 1 and thiols 2 with substituents in the para-
position were employed to investigate the electronic effects in this
reaction and to verify whether the same desired products could be
obtained (Scheme 3). As a result, the combination of both
substrates with electron-donating groups gave 3r in good yields.
Interestingly, however, acyl fluoride 1r bearing an electron-
donating methyl group and thiol 2d having an electron-
withdrawing trifluoromethyl group afforded 3s in 93% yield,
whereas the reverse combination gave the desired product in
only 52% isolated yield. Notably, this result is contrary to the
usual trend where the carbon-fluorine bond of acyl fluorides 1
bearing electron-withdrawing groups is more readily cleaved
and thiophenols 2 having electron-donating groups is more
nucleophilic.
Template for SYNTHESIS © Thieme Stuttgart · New York
2021-04-16
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Synthesis
Paper / PSP / Special Topic
as shown in Scheme 5. First, acyl fluorides 1 are oxidatively
added to Ni(0) to generate the acylnickel(II) intermediate A.
Subsequently, the acylnickel(II) complex B is generated through
ligand exchange with thiophenols and thiol 2.
Then,
decarbonylation and a sequential CO extrusion occur to give the
intermediate C, from which reductive elimination provides
thioethers 3, regenerating the Ni(0) catalyst. On the other hand,
intermediate B can also be generated by direct oxidation addition
of the C(acyl)-S bond of thioesters 4, which is formed by the
reaction of acyl fluorides 1 with thiophenols 2 in the presence of
base. However, considering the effect of the halogen as shown in
Scheme 4, the reaction route via intermediate A seems to be more
dominant.
Scheme 3 Verification of electronic effects. Reagents and conditions: 1 (0.2
mmol),
bis(diphenylphosphino)propane (DPPP) (30 mol %), Na
toluene (1 mL), 140 °C, 24 h under N . Isolated yields.
2
(0.3
mmol),
NiCl
2
·DME
(10
mol
2
CO
%),
(1.5 equiv),
1,3-
3
2
In general, compared to acyl chlorides, acyl fluorides are less
reactive, or in other words, more stable due to their strong
carbon-fluorine bonds, but interestingly, many examples of
reactions with acyl fluorides have been reported in which the
product yields are higher than those with acyl
chlorides.11,12b,13,15a,16,17a Therefore, we next investigated the
effect of the halogen atoms in acyl halides 1 on this reaction. The
reaction of 2-naphthoyl fluoride (1h) or 2-naphthoyl chloride
(1h-Cl) with 4-methylthiophenol (2a) was conducted under
standard conditions where the nickel catalyst, ligand, and base
were added at approximately the same time. Surprisingly, the
desired product 3h was obtained in 81% GC yield, without the
remaining 4h, whereas only 6% of 3h was formed when 2-
naphthoyl chloride was employed (Scheme 4a). As a control
experiment, when acyl chloride 1h-Cl reacted with thiol 2a
Scheme 5 Proposed mechanism.
In summary, we have developed the nickel-catalyzed de-
carbonylative thioetherification of various acyl fluorides with
thiophenols. The process tolerated a wide range of functional
groups, even at the high temperatures required for
decarbonylation, and afforded unsymmetrical diaryl sulfides in
good to excellent yields. This protocol provided for the formation
of a diverse range of C-S bonds through a highly efficient
decarbonylative process. Further applications to the synthesis of
natural product compounds and detailed mechanistic studies to
clarify the effects of halogens are currently underway in our
laboratory.
without nickel catalyst in the presence of Na
2
CO , 3h was not
3
observed at all, and only thioester 4h was obtained in 78% yield.
Besides, once 4h was isolated and subjected to the standard
reaction conditions of this study, the target product 3h was
obtained in 81% yield (Scheme 4b). This result is consistent with
the report by Rueping on the synthesis of sulfides from
thioesters18 by
a
similar nickel-catalyzed decarbonylation
reaction.7g
The experimental section has no title; please leave this line here.
Unless otherwise noted, all the reactions were carried out under an argon
or a nitrogen atmosphere using standard Schlenk techniques. Solvents
were employed as eluents for all other routine operation, as well as
dehydrated solvent were purchased from commercial suppliers and
employed without any further purification. Glassware was dried in an
oven (130 °C) and heated under reduced pressure before use. For thin
layer chromatography (TLC) analyses throughout this work, Merck
precoated TLC plates (silica gel 60 GF254, 0.25 mm) were used. Silica gel
column chromatography was carried out using Silica gel 60 N (spherical,
1
neutral, 40–100 μm) from Kanto Chemicals Co., Inc. The NMR spectra ( H,
1
3
1
19
1
C{ H}, and F{ H}) were recorded on Mercury-400 (400 MHz)
spectrometers. Chemical shifts (δ) are in parts per million relatives to
1
13
1
3
CDCl at 7.26 ppm for H and at 77.16 ppm for C{ H}, respectively. The
19
1
3
F{ H} NMR spectra were measured by using CCl F (δ = 0.00 ppm) as an
external standard. The GC yields were determined by GC analysis of the
crude mixture, using n-dodecane as an internal standard. GC analyses
were performed on a Shimadzu GC-14A equipped with a flame ionization
detector using Shimadzu Capillary Column (CBP1-M25-025) and
Scheme 4 Effect of halogen atoms in acyl halides.
Based on the results of the relevant mechanistic studies
obtained above, the catalytic cycle for this reaction is proposed
Shimadzu C-R6A-Chromatopac integrator.
Infrared spectra were
recorded on a Shimadzu IR Prestige-21 spectrophotometer. Elemental
Template for SYNTHESIS © Thieme Stuttgart · New York
2021-04-16
page 3 of 6

Synthesis
Paper / PSP / Special Topic
analyses were carried out with a Perkin-Elmer 2400 CHN elemental
analyzer at Okayama University.
(4-Fluorophenyl)(p-tolyl)sulfane (3g)7g
Colorless oil. R = 0.44 (hexane). Isolated yield is 78% (34.2 mg).
1H NMR (400 MHz, CDCl
): δ 7.33-7.29 (m, 2H), 7.25-7.22 (m, 2H), 7.14-
.12 (m, 2H), 7.02-6.98 (m, 2H), 2.34 (s, 3H).
f
Chemicals
3
Unless otherwise noted, materials obtained from commercial suppliers
were used without further purification. Nickel(II) chloride ethylene glycol
dimethyl ether complex was purchased from Sigma-Aldrich Co. LLC. 1,3-
Bis(diphenylphosphino)propane and benzoyl fluoride (1a) (purity >
7
13
1
C{ H} NMR (101 MHz, CDCl
C-F = 8 Hz), 132.4, 131.3, 130.7 (d, JC-F = 132 Hz), 130.2, 116.4 (d, JC-F = 22
Hz), 21.2.
3
): δ 162.1 (d, JC-F = 248 Hz), 137.4, 132.9 (d,
J
9
8%) were purchased from Tokyo Chemical Industry Co., Ltd. Acyl
19
1
3
F{ H} NMR (376 MHz, CDCl , rt): δ -62.7.
fluorides 1b-1u12-17,19 were prepared according to the literatures and
showed the identical spectra reported.
4-Chlorophenyl)(p-tolyl)sulfane (3h)3
(
Colorless solid. R
f
= 0.59 (hexane). Isolated yield is 70% (33.0 mg).
): δ 7.31-7.29 (m, 2H), 7.24-7.21 (m, 2H), 7.19-
Synthesis of 3: General Procedure
1H NMR (400 MHz, CDCl
3
An oven-dried 20 mL of Schlenk tube containing a magnetic stirring bar
was charged with NiCl ·DME (4.39 mg, 0.02 mmol, 10 mol %), DPPP (24.8
2
mg, 0.06 mmol, 30 mol %), and toluene (1 mL) under nitrogen, which was
stirred for 30 seconds at room temperature. Then, acyl fluorides 1 (0.2
7
.14 (m, 4H), 2.36 (s, 3H).
C{ H} NMR (101 MHz, CDCl
30.3, 129.3, 21.3.
1
3
1
3
): δ 138.2, 136.1, 132.6, 132.4, 130.9, 130.8,
1
2 3
mmol), thiophenols 2 (0.3 mmol) and Na CO (31.8 mg, 0.3 mmol) were
added. The mixture was heated at 140 ºC in a heating block with stirring
for 24 h. After being at room temperature, the mixture was quenched with
Naphthalen-1-yl(p-tolyl)sulfane (3i)22
Colorless solid. Rf = 0.32 (hexane). Isolated yield is 94% (47.0 mg).
1H NMR (400 MHz, CDCl
3
): δ 8.41-8.38 (m, 1H), 7.89-7.86 (m, 1H), 7.83-
saturated NH
4
Cl and then aqueous solution was extracted with diethyl
7
7
.80 (m, 1H), 7.56-7.51 (m, 3H), 7.42-7.38 (m, 1H), 7.19-7.17 (m, 2H),
ether. The combined organic phase was dried over anhydrous MgSO
4
, and
.09-7.07 (m, 2H), 2.32 (s, 3H).
evaporated under vacuum to remove the volatiles. The residue was
purified by column chromatography (EtOAc/hexane) on silica gel to
afford the corresponding products 3.
1
3
1
C{ H} NMR (101 MHz, CDCl
3
): δ 136.7, 134.2, 133.2, 132.7, 132.5, 131.1,
1
30.4, 130.1, 128.6
4
, 128.5
7
, 126.9, 126.5, 125.9, 125.5, 21.2.
Phenyl(p-tolyl)sulfane (3a)3
Naphthalen-2-yl(p-tolyl)sulfane (3j)7g
Colorless solid. R = 0.40 (hexane). Isolated yield is 81% (40.5 mg).
1H NMR (400 MHz, CDCl
): δ 7.81-7.71 (m, 4H), 7.48-7.45 (m, 2H), 7.39-
7.35 (m, 3H), 7.19-7.16 (m, 2H), 2.38 (s, 3H).
Colorless oil. R
f
= 0.36 (hexane). Isolated yield is 90% (36.0 mg).
): δ 7.35-7.32 (m, 2H), 7.32-7.27 (m, 4H), 7.24-
f
1H NMR (400 MHz, CDCl
3
3
7
.20 (m, 1H), 7.18-7.15 (m, 2H), 2.37 (s, 3H).
1
3
1
13
1
C{ H} NMR (101 MHz, CDCl
3
): δ 137.7, 137.2, 132.4, 131.4, 130.2, 129.9,
3
C{ H} NMR (101 MHz, CDCl ): δ 137.7, 134.5, 133.9, 132.2, 132.1, 131.5,
1
29.2, 126.5, 21.3.
130.2, 128.8, 128.5, 128.0, 127.8, 127.4, 126.7, 126.0, 21.3.
(
4-(tert-Butyl)phenyl)(p -tolyl)sulfane (3b)20
Colorless oil. R = 0.36 (hexane). Isolated yield is 79% (40.0 mg).
1H NMR (400 MHz, CDCl
): δ 7.32-7.22 (m, 6H), 7.12 (d, J = 8 Hz, 2H), 2.34
2-(p-Tolylthio)benzofuran (3k)7g
f
Colorless oil. R
1H NMR (400 MHz, CDCl
7.22 (m, 4H), 7.13-7.11 (m, 2H), 6.98 (s, 1H), 2.33 (s, 3H).
f
= 0.28 (hexane). Isolated yield is 81% (39.0 mg).
3
3
): δ 7.56-7.54 (m, 1H), 7.46-7.44 (m, 1H), 7.32-
(
s, 3H), 1.30 (s, 9H).
1
3
1
13
1
C{ H} NMR (101 MHz, CDCl
30.1, 126.3, 34.6, 31.4, 21.3.
3
): δ 150.0, 137.3, 133.2, 132.2, 131.7, 130.3,
3
C{ H} NMR (101 MHz, CDCl ): δ 156.8, 149.0, 137.6, 130.3, 130.2, 130.0,
1
128.5, 125.1, 123.1, 120.9, 113.5, 114.4, 21.2.
[
1,1'-Biphenyl]-4-yl(p-tolyl)sulfane (3c)7g
Colorless solid. R = 0.32 (hexane). Isolated yield is 90% (34.5 mg).
1H NMR (400 MHz, CDCl
): δ 7.58-7.55 (m, 2H), 7.52-7.49 (m, 2H), 7.46-
.41 (m, 2H), 7.37-7.31 (m, 5H), 7.19-7.16 (m, 2H), 2.37 (s, 3H).
2-(p-Tolylthio)benzo[b]thiophene (3l)22
f
Colorless solid. R
1H NMR (400 MHz, CDCl
4H), 7.15-7.11 (m, 2H), 2.35 (s, 3H).
f
= 0.33 (hexane). Isolated yield is 72% (37.0 mg).
3
3
): δ 7.75-7.72 (m, 2H), 7.44 (s, 1H), 7.38-7.25 (m,
7
1
3
1
13
1
C{ H} NMR (101 MHz, CDCl
3
): δ 140.8, 139.8, 138.2, 136.7, 132.8, 131.6,
3
C{ H} NMR (101 MHz, CDCl ): δ 142.4, 139.8, 137.6, 136.3, 132.7, 130.2,
1
30.6, 130.5, 129.3, 128.2, 127.8, 127.4, 21.6.
130.1, 130.0, 124.8, 124.6, 123.5, 122.1, 21.2.
4
-(p-Tolylthio)benzonitrile (3d)21
Colorless solid. R = 0.09 (EA/hexane = 1/20). Isolated yield is 76% (39.0
mg).
1H NMR (400 MHz, CDCl
6-(p-Tolylthio)quinoline (3m)23
f
Colorless solid. R
mg).
1H NMR (400 MHz, CDCl
): δ 8.84-8.83 (m, 1H), 7.99-7.96 (m, 2H), 7.59 (d,
3
f
= 0.4 (hexane/EA =1/1). Isolated yield is 78% (39.0
3
): δ 7.45-7.40 (m, 4H), 7.27-7.24 (m, 2H), 7.13-
7
.10 (m, 2H), 2.41 (s, 1H).
C{ H} NMR (101 MHz, CDCl
26.8, 190.4, 108.4, 21.4.
J = 2.0 Hz, 1H), 7.55-7.52 (m, 1H), 7.40-7.33 (m, 3H), 7.20-7.18 (m, 2H),
1
3
1
3
): δ 146.7, 140.1, 135.1, 132.4, 130.9, 126.9,
2.37 (s, 3H).
13
1
1
C{ H} NMR (101 MHz, CDCl
3
): δ 150.1, 147.0, 138.5, 136.6, 135.3, 133.2,
1
30.7, 130.5, 130.1 , 130.0 , 128.7, 126.6, 121.7, 21.3.
3
7
Phenyl(4-(p-tolylthio)phenyl)methanone (3e)7g
Styryl(p-tolyl)sulfane (3n)7g
Colorless solid. E/Z = 10/1. R
mg).
Colorless solid. Rf = 0.08 (hexane/EA = 5/1). Isolated yield is 80% (44.0
mg).
f
= 0.21 (hexane). Isolated yield is 68% (31.0
1H NMR (400 MHz, CDCl
7
): δ 7.77-7.75 (m, 2H), 7.69-7.67 (m, 2H), 7.59-
.54 (m, 1H), 7.48-7.43 (m, 4H), 7.25-7.22 (m, 2H), 7.20-7.17 (m, 2H), 2.40
s, 3H).
3
(E)-isomer.
1H NMR (400 MHz, CDCl
(
3
): δ 7.41-7.23 (m, 6H), 7.26-7.21 (m, 1H), 7.19-
1
3
1
C{ H} NMR (101 MHz, CDCl
3
): δ 195.9, 145.4, 139.4, 137.8, 134.6, 134.4,
7.17 (m, 2H), 6.88 (d, J = 15.2 Hz, 1H), 6.67 (d, J = 15.2 Hz, 1H), 2.34 (s, 3H).
13
1
1
32.3, 130.8, 130.6, 129.9, 128.3, 128.0, 126.5, 21.4.
C{ H} NMR (101 MHz, CDCl
3
): δ 137.4, 136.8, 131.3, 130.7, 130.6, 130.1,
1
28.8, 127.5, 126.0, 124.6, 21.2.
Methyl 4-(p-tolylthio)benzoate (3f)7g
(Z)-isomer.
1H NMR (400 MHz, CDCl
Colorless oil. R
f
= 0.24 (hexane/EA = 20/1). Isolated yield is 72% (40.0
3
): δ 7.56-7.54 (m, 2H), 7.41-7.23 (m, 3H), 7.26-
mg).
7.21 (m, 2H), 7.13-7.11 (m, 2H), 6.56 (d, J = 10.4 Hz, 1H), 6.48 (d, J = 10.4
Hz, 1H), 2.37 (s, 3H).
1H NMR (400 MHz, CDCl
): δ 7.89-7.85 (m, 2H), 7.42-7.39 (m, 2H), 7.23-
.20 (m, 2H), 7.16-7.13 (m, 2H), 3.88 (s, 3H), 2.39 (s, 3H).
3
7
1
3
1
(Naphthalen-2-ylmethyl)(p-tolyl)sulfane (3o)7g
C{ H} NMR (101 MHz, CDCl
3
): δ 166.9, 145.6, 139.3, 134.5, 130.6, 130.1,
1
28.2, 127.1, 126.8, 52.2, 21.4.
Colorless solid. R
f
= 0.17 (hexane). Isolated yield is 55% (29.1 mg).
Template for SYNTHESIS © Thieme Stuttgart · New York
2021-04-16
page 4 of 6

Synthesis
Paper / PSP / Special Topic
1H NMR (400 MHz, CDCl
): δ 7.83-7.84 (m, 3H), 7.66 (s, 1H), 7.48-7.45 (m,
3
A.; Hertweck, C. Chem. Rev. 2017, 117, 5521. (c) Pan, F.; Shi, Z.-J.
ACS Catal. 2014, 4, 280.
(2) (a) Hilbert, G. E.; Johnson, T. B. J. Am. Chem. Soc. 1929, 51, 1526. (b)
Petrillo, G.; Novi, M.; Garbarino, G.; Dell’Erba, C. Tetrahedron Lett.
3
H), 7.26-7.23 (m, 2H), 7.06 (d, J = 7.6 Hz, 2H), 4.24 (s, 2H), 2.31 (s, 3H).
C{ H} NMR (101 MHz, CDCl
1
3
1
3
): δ 136.8, 135.3, 133.4, 132.7, 132.4, 131.0,
1
29.8, 128.4, 127.8 , 127.7 , 127.5, 127.2, 126.2, 125.9, 40.3, 21.2.
2
6
1
985, 26, 6365.
3) Bhowmik, A.; Yadav M.; Fernandes, R. A. Org. Biomol. Chem.
020,18, 2447.
N,N-Dipropyl-4-(p-tolylthio)benzenesulfonamide (3p)
Colorless solid. R = 0.18 (hexane/EA = 5/1). Isolated yield is 82% (60.0
f
mg).
(
(
2
4) (a) Itoh, T.; Mase, T. Org. Lett. 2004, 6, 4587. (b) Fernandez-
Rodriguez, M. A.; Shen, Q.; Hartwig, J. F. J. Am. Chem. Soc. 2006, 128,
1H NMR (400 MHz, CDCl
7
): δ 7.63-7.60 (m, 2H), 7.41-7.39 (m, 2H), 7.24-
.22 (m, 2H), 7.17-7.14 (m, 2H), 3.05-3.01 (m, 4H), 2.34 (s, 3H), 1.59-1.49
m, 4H), 0.86 (t, J = 7.4 Hz, 6H).
3
2
180. (c) Fernandez Rodriguez, M. A.; Shen, Q.; Hartwig, J. F. Chem.
Eur. J. 2006, 12, 7782. (d) Lee, J.-Y.; Lee, P. H. J. Org. Chem. 2008,
3, 7413. (e) Alvaro, E.; Hartwig, J. F. J. Am. Chem. Soc. 2009, 131,
858. (f) Fernandez-Rodriguez, M. A.; Hartwig, J. F. J. Org. Chem.
009, 74, 1663. (g) Saravanan, P.; Anbarasan, P. Org. Lett. 2014,
6, 848. (h) Mao, J.; Jia, T.; Frensch, G. and Walsh, P. J. Org. Lett.
014, 16, 5304. (i) Xu, J.; Liu, Y. R. Y.; Yeung, C. S.; Buchwald, S. L.
(
1
3
1
C{ H} NMR (101 MHz, CDCl
3
): δ 145.2, 139.7, 136.7, 134.7, 130.7, 127.6,
7
7
2
1
1
26.9, 50.2, 22.2, 21.4, 11.3. One carbon was not observed.
-1
FT-IR (cm ): 2959 (s), 2931 (s), 2874 (s), 1493 (s), 1470 (s), 1454 (s),
387 (s), 1337 (s), 1310 (s), 1190 (s), 1155 (s), 1151 (s), 1097 (s), 1074
s), 1014 (s), 995 (s), 837(s).
1
(
2
2 2
Anal. Calcd for C19H25NO S : C, 62.78; H, 6.93; N, 3.85%. Found: C, 62.39;
ACS Catal. 2019, 9, 6461.
H, 6.67; N, 3.80%.
(
5) For selected reviews on carboxylic acids, see: (a) Gooßen, L. J.;
Rodriguez, N.; Gooßen, K. Angew. Chem., Int. Ed. 2008, 47, 3100. (b)
Rodriguez, N.; Gooßen, L. J. Chem. Soc. Rev. 2011, 40, 5030.
6) For selected reviews on carboxylic acids derivatives, see: (a) Guo,
L.; Rueping, M. Chem. Eur. J. 2018, 24,7794. (b) Blanchard, N.; Bizet,
V. Angew. Chem. Int. Ed. 2019, 58, 6814. (c) Zhao, Q.; Szostak, M.
ChemSusChem 2019, 12, 2983. (d) Ogiwara, Y.; Sakai, N. Angew.
Chem. Int. Ed. 2020, 59, 574. (e) Wang, Z.; Wang, X.; Nishihara, Y.
Chem Asian J. 2020, 15, 1234. (f) Lu, H.; Yu, T.; Xu, P.; Wei, H. Chem.
Rev. 2021, 121, 365.
Dodecyl(phenyl)sulfane (3q)24
Colorless solid. R = 0.48 (hexane). Isolated yield is 68% (31.0 mg).
1H NMR (400 MHz, CDCl
): δ 7.34-7.26 (m, 4H), 7.18-7.14 (m, 1H), 2.92 (t,
f
(
3
J = 7.4 Hz, 2H), 1.69-1.61 (m, 2H), 1.44-1.38 (m, 2H), 1.26 (s, 16H), 0.89 (t,
J = 6.8 Hz, 3H).
13
1
C{ H} NMR (101 MHz, CDCl
3 3 2
): δ 137.2, 128.9 , 128.9 , 125.7, 33.7, 32.1,
2
9.7 , 29.7 , 29.7 , 29.6, 29.5, 29.31, 29.27, 29.0, 22.8, 14.3.
9
7
3
(
4-Methoxyphenyl)(p-tolyl)sulfane (3r)3
Colorless solid. R = 0.22 (EA/hexane = 1/30). Isolated yield is 84% (38.8
mg).
1H NMR (400 MHz, CDCl
(
7) (a) Correa, A.; Cornella, J.; Martin, R. Angew. Chem. Int. Ed. 2013, 52,
f
1
878. (b) Meng, L.; Kamada, Y.; Muto, K.; Yamaguchi, J.; Itami, K.
Angew. Chem. Int. Ed. 2013, 52, 10048. (c) Hong, X.; Liang, Y.; Houk,
K. N. J. Am. Chem. Soc. 2014, 136, 2017. (d) Lu, Q.; Yu, H.; Fu, Y. J.
Am. Chem. Soc. 2014, 136, 8252. (e) Pu, X.; Hu, J.; Zhao, Y.; Shi, Z.
ACS Catal. 2016, 6, 6692. (f) Yue, H.; Guo, L.; Liao, H.-H.; Cai, Y.; Zhu,
C. Rueping, M. Angew. Chem. Int. Ed. 2017, 56, 4282. (g) Lee, S-C.;
Liao, H-H.; Chatupheeraphat, A.; Rueping, M. Chem. Eur. J. 2018, 24,
3
): δ 7.38-7.36 (m, 2H), 7.15-7.13 (m, 2H), 7.08-
7
.06 (m, 2H), 6.89-6.86 (m, 2H), 3.81 (s, 3H), 2.31 (s, 3H).
1
3
1
C{ H} NMR (101 MHz, CDCl
3
): δ 159.6, 136.2, 134.50, 134.46, 129.9,
1
29.5, 125.7, 115.0, 55.5, 21.1.
p-Tolyl(4-(trifluoromethyl)phenyl)sulfane (3s)7g
Colorless solid. R = 0.38 (hexane). Isolated yield is 93% (49.9 mg).
1H NMR (400 MHz, CDCl
): δ 7.49-7.42 (m, 4H), 7.26-7.22 (m, 4H), 2.42 (s,
3
608.
8) (a) Shi, S.; Meng, G.; Szostak, M. Angew. Chem. Int. Ed. 2016, 55,
959. (b) Hu, J.; Zhao, Y.; Liu, J.; Zhang, Y.; Shi, Z. Angew. Chem. Int.
f
(
3
6
3
H).
Ed. 2016, 55, 8718. (c) Dey, A.; Sasmal, S.; Seth, K.; Lahiri, G. K.;
Maiti, D. ACS Catal. 2017, 7, 433.
1
3
1
3
C{ H} NMR (101 MHz, CDCl ): δ 144.0, 139.4, 134.4, 130.7, 128.3, 127.6
(
q, JC-F = 33 Hz), 127.4, 127.0 (q, JC-F = 272 Hz), 125.8 (q, JC-F = 4 Hz), 21.3.
F{ H} NMR (376 MHz, CDCl , rt): δ -62.7.
3
(
9) Keaveney, S. T.; Schoenebeck, F. Angew. Chem. Int. Ed. 2018, 57,
1
9
1
4
073.
10) Malapit, C. A.; Bour, J. R.; Brigham, C. E.; Sanford, M. S. Nature 2018,
63, 100.
(
5
Funding Information
(
11) Sakurai, S.; Yoshida, T.; Tobisu, M. Chem. Lett. 2019, 48, 94.
(
12) (a) Okuda, Y.; Xu, J.; Ishida, T.; Wang, C.-A.; Nishihara, Y. ACS Omega.
None.
2
2
018, 3, 13129. (b) Fu, L.; Chen, Q.; Wang, Z; Nishihara, Y. Org. Lett.
020, 22, 2350.
Acknowledgment
(
13) (a) Chen, Q.; Fu, L.; Nishihara, Y. Chem. Commun. 2020, 56,7977. (b)
Chen, Q.; Fu, L.; You, J.; Nishihara, Y. Synlett 2020, 10.1055/s-0040-
1705954.
The authors gratefully thank Ms. Megumi Kosaka and Mr. Motonari
Kobayashi (Department of Instrumental Analysis, Advanced Science
Research Center, Okayama University) for performing elemental analyses,
and the SC-NMR Laboratory (Okayama University) for the NMR spectral
measurements.
(14) Ogiwara, Y.; Sakurai, Y.; Hattori, H.; Sakai, N. Org. Lett. 2018, 20,
4
204.
15) (a) Wang, Z.; Wang, X.; Nishihara, Y. Chem. Commun. 2018, 54,
3969. (b) Malapit, C. A.; Bour, J. R.; Laursen, S. R.; Sanford, M. S. J.
(
1
Supporting Information
Am. Chem. Soc. 2019, 141, 17322.
(
(
16) Wang, X.; Wang, Z.; Nishihara, Y. Chem. Commun. 2019, 55, 10507.
17) (a) Wang, X.; Wang, Z.; Liu, L.; Asanuma, Y.; Nishihara, Y. Molecules
Supporting information for this article is available online at
http://dx.doi.org
2019, 24, 1671. (b) Kayumov, M.; Zhao, J.-N.; Mirzaakhmedov, S.;
YES (this text will be updated with links prior to publication)
Wang, D.-Y.; Zhang, A. Adv. Synth. Catal. 2019, 362, 776.
18) Chen, T.; Tan, Q.; Liu, X.; Liu, L.; Huang, T.; Han, L.-B. Synthesis 2021,
95.
19) Munoz, S. B.; Dang, H.; Ispizua-Rodriguez, X.; Mathew, T.; Prakash,
G. K. S. Org. Lett. 2019, 21, 1659.
(
(
(
Primary Data
This text will be updated with links prior to publication.
20) Xu, H.; Liang, Y.; Zhou, X.; Feng, Y.-S. Org. Biomol. Chem., 2012, 10,
2562.
References
(21) Li, J.; Bao, W.; Zhang, Y.; Rao, Y. Eur. J. Org. Chem. 2019, 7175.
(22) Liu, D.; Ma, H.; Fang, P.; Mei, T. Angew. Chem. Int. Ed. 2019, 58, 5033.
(23) Liu, B.; Lim, C.; Miyake, G. M. J. Am. Chem. Soc. 2017, 139, 13616.
(
1) (a) Nakazawa, T.; Xu, J.; Nishikawa, T.; Oda, T.; Fujita, A.; Ukai, K.;
Mangindaan, R. E. P.; Rotinsulu, H.; Kobayashi, H.; Namikoshi, M. J.
Nat. Prod. 2007, 70, 439. (b) Dunbar, K. L.; Scharf, D. H.; Litomska,
Template for SYNTHESIS © Thieme Stuttgart · New York
2021-04-16
page 5 of 6

Synthesis
Paper / PSP / Special Topic
(24) Delcaillau, T.; Bismuto, A.; Lian, Z.; Morandi, B. Angew. Chem. Int.
Ed. 2020, 59, 2110.
Template for SYNTHESIS © Thieme Stuttgart · New York
2021-04-16
page 6 of 6

Supporting Information
for
Nickel-Catalyzed Decarbonylative Thioetherification of Acyl Fluorides
via C-F Bond Activation
a
a
*b
Jingwen You, Qiang Chen, and Yasushi Nishihara
a
Graduate School of Natural Science and Technology, Okayama University,
-1-1 Tsushimanaka, Kita-ku, Okayama 700-8530, Japan
Research Institute for Interdisciplinary Science, Okayama University,
3
b
3
-1-1 Tsushimanaka, Kita-ku, Okayama 700-8530, Japan
Phone: +81-86-251-7855
Fax: +81-86-251-7855
Email: ynishiha@okayama-u.ac.jp
Table of Contents
1
2
. Optimization of Reaction Conditions
S2–S5
1
13
1
19
1
. Copies of H, C{ H}, and F{ H} NMR Charts for the Products
S6–S26

1
. Optimization of Reaction Conditions
Table S1. Screening of the Liganda
yield (%)b
entry
ligand (x mol %)
3
a
4a
15
5
4
4
4
0
0
1
1
26
24
26
27
37
43
57
8
1
2
3
4
DPPE (30 mol %)
DPPP (30 mol %)
DPPF (30 mol %)
DCYPE (30 mol %)
8
0
5
16
52
60
5
3
PPh (30 mol %)
6c
DPPP (15 mol %)
DPPP (15 mol %)
DPPP (40 mol %)
0
32
35
7
8d
8
4
trace
aReactions were carried out with 1a (0.2 mmol, 1.0 equiv), 2a (0.4 mmol, 2.0 equiv) and NiCl2`DME
0.02 mmol, 10 mol %), Na CO
(0.3 mmol, 1.5 equiv). bGC yields, using n-dodecane as an
internal standard. cPd(OAc)
(
2
3
(10 mol %). d2a (0.3 mmol, 1.5 equiv).
2
S2

Table S2. Screening of the Basea
yield (%)b
entry
base (1.5 equiv)
3
a
4a
0
5
8
4
24
1
2
Na
2
CO
3
5
8
6
6
7
1
0
3
1
15
18
31
23
K
2
CO
3
3c
4
Na
CO
3
trace
trace
1
2
NaOAc
PO
5
K
3
4
aReactions were carried out with 1a (0.2 mmol, 1.0 equiv), 2a (0.4 mmol, 2.0 equiv) and
NiCl2`DME (0.02 mmol, 10 mol %), DPPP (0.06 mmol, 30 mol %), base (0.3 mmol, 1.5 equiv) in
toluene at 140 °C for 24 h. bGC yields, using n-dodecane as an internal standard. cBase (3.0
equiv).
S3

Table S3. Screening of the Amount of Compound 2aa
Me
O
S
+
S
NiCl ·DME (10 mol %)
2
O
Me
SH
DPPP (30 mol %)
Na CO3 (1.5 equiv)
3a
+
2
4a
F
toluene
Me
2a (x equiv)
Me
1
40 oC, 24 h
1
a (0.2 mmol)
S
S
Me
5
yield (%)b
entry
2a (x equiv)
3
a
4a
0
5
8
4
24
1
2
2.0
1.5
1.2
1.5
1.5
9
6
3
8
0
9
0
3
0
8
0
trace
20
3
4c
5d
39
3
6
aReactions were carried out with 1a (0.2 mmol, 1.0 equiv), NiCl2`DME (0.02 mmol, 10 mol %),
DPPP (0.06 mmol, 30 mol %), Na CO
(0.3 mmol, 1.5 equiv) in toluene at 140 °C for 24 h. bGC
yields, using n-dodecane as an internal standard. 120 C. d12 h.
2
3
c
o
S4

Table S4. Control Experimentsa
yield (%)b
entry
Deviations from standard condition
3
a
4a
0
5
none
90
45
0
8
1
2
3
4
Without Na
2
CO
3
24
68
67
8
24
Without NiCl2`DME and DPPP
Benzoyl chloride instead of 1a
0
trace
aReactions were carried out with 1a (0.2 mmol, 1.0 equiv), 2a (0.3 mmol, 1.5 equiv), NiCl2`DME
0.02 mmol, 10 mol %), DPPP (0.06 mmol, 30 mol %), Na CO (0.3 mmol, 1.5 equiv) in toluene at
40 °C for 24 h. bGC yields, using n-dodecane as an internal standard.
(
2
3
1
S5

1
13
1
19
1
2
. Copies of H, C{ H}, and F{ H} NMR Charts for the Products
1
13
1
3
H NMR (400 MHz) and C{ H} NMR (101 MHz) spectra of 3a (rt, CDCl ).
S6

1
13
1
3
H NMR (400 MHz) and C{ H} NMR (101 MHz) spectra of 3b (rt, CDCl ).
S7

1
13
1
3
H NMR (400 MHz) and C{ H} NMR (101 MHz) spectra of 3c (rt, CDCl ).
S8

1
13
1
3
H NMR (400 MHz) and C{ H} NMR (101 MHz) spectra of 3d (rt, CDCl ).
S9

1
13
1
3
H NMR (400 MHz) and C{ H} NMR (101 MHz) spectra of 3e (rt, CDCl ).
S10

1
13
1
3
H NMR (400 MHz) and C{ H} NMR (101 MHz) spectra of 3f (rt, CDCl ).
S11

1
13
1
3
H NMR (400 MHz) and C{ H} NMR (101 MHz) spectra of 3g (rt, CDCl ).
S12

1
9
1
F{ H} NMR (376 MHz) spectrum of 3g (rt, CDCl
3
).
S13

1
13
1
3
H NMR (400 MHz) and C{ H} NMR (101 MHz) spectra of 3h (rt, CDCl ).
S14

1
13
1
3
H NMR (400 MHz) and C{ H} NMR (101 MHz) spectra of 3i (rt, CDCl ).
S15

1
13
1
3
H NMR (400 MHz) and C{ H} NMR (101 MHz) spectra of 3j (rt, CDCl ).
S16

1
13
1
3
H NMR (400 MHz) and C{ H} NMR (101 MHz) spectra of 3k (rt, CDCl ).
S17

1
13
1
3
H NMR (400 MHz) and C{ H} NMR (101 MHz) spectra of 3l (rt, CDCl ).
S18

1
13
1
3
H NMR (400 MHz) and C{ H} NMR (101 MHz) spectra of 3m (rt, CDCl ).
S19

1
13
1
3
H NMR (400 MHz) and C{ H} NMR (101 MHz) spectra of 3n (rt, CDCl ).
S20

1
13
1
3
H NMR (400 MHz) and C{ H} NMR (101 MHz) spectra of 3o (rt, CDCl ).
S21

1
13
1
3
H NMR (400 MHz) and C{ H} NMR (101 MHz) spectra of 3p (rt, CDCl ).
S22

1
13
1
3
H NMR (400 MHz) and C{ H} NMR (101 MHz) spectra of 3q (rt, CDCl ).
S23