Nickel-Catalyzed Oxidative Coupling Reaction of Phenyl Benzyl Sulfoxides

Article abstract of DOI:10.1021/acs.organomet.8b00476

A novel method to produce disulfoxides diastereoselectively from phenyl benzyl sulfoxides is reported. The Ni(PⁿBu₃)₂Cl₂]/NIXANTPHOS catalyst system successfully promotes an oxidative coupling reaction of aryl benzylic sulfoxides to disulfoxides. An intermediate aldehyde, produced from the elimination of α-hydroxy sulfoxides, is proposed to generate the key sulfenate anion, enabling the formation of the disulfoxide product. A range of disulfoxides was produced in moderate to high yields (30-83%) and diastereoselectivity (rac/meso ranging from 3:1 to >20:1).

Full text of DOI:10.1021/acs.organomet.8b00476

Article
pubs.acs.org/Organometallics
Cite This: Organometallics XXXX, XXX, XXX−XXX
Nickel-Catalyzed Oxidative Coupling Reaction of Phenyl Benzyl
Sulfoxides
,†,‡
‡
‡
,‡
Xiaoxia Liang,*
Chen Wu, Zhipeng Zheng, and Patrick J. Walsh*
†
Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China
Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia,
‡
Pennsylvania 19104-6323, United States
*
S Supporting Information
ABSTRACT: A novel method to produce disulfoxides diaster-
eoselectively from phenyl benzyl sulfoxides is reported. The
n
Ni(P Bu ) Cl ]/NIXANTPHOS catalyst system successfully pro-
3
2
2
motes an oxidative coupling reaction of aryl benzylic sulfoxides to
disulfoxides. An intermediate aldehyde, produced from the
elimination of α-hydroxy sulfoxides, is proposed to generate the
key sulfenate anion, enabling the formation of the disulfoxide
product. A range of disulfoxides was produced in moderate to high
yields (30−83%) and diastereoselectivity (rac/meso ranging from
3
:1 to >20:1).
INTRODUCTION
■
Sulfoxides have attracted considerable interest from researchers
in different fields for a variety of applications. They have been
1
−3
found in natural products,
synthetic intermediates (Figure 1A−C),
drug discovery and as medications, including armodafinil
successfully employed as
4
−15
and used in
16
1
7
and nexium (Figure 1D−F). They have been gaining
attention as ligands in transition-metal catalysis (Figure 1G−
1
8−29
I).
Particular attention has been paid to the coordination
chemistry of bis(sulfoxides), which are useful as ligands for
1
8−31
metal-catalyzed transformations
extractions of lanthanide and actinide ions (Figure 1J).
Sulfoxides are generally prepared by selective oxidation of
and for liquid−liquid
32
3
3−36
sulfides,
nucleophilic displacements on R′S(O)XR (XR
37
=
NR or OR) with Grignard or organolithium complexes,
2
3
8
cross-coupling with α-halo sulfoxides or direct C−H
3
9
functionalization, and arylation of sulfenate anions [RS−
−
40−51
O] using transition metal catalysts.
Bis(phenylsulfinyl)
methanes are typically accessed by either selective oxidation of
1
1,52−54
bis(phenylsulfides)
sulfonate esters.
leads to low yields.
or nucleophilic substitution of
5
2,55
In some cases, the oxidative approach
53
Oxidative cross-coupling methods have recently undergone
rapid development, owing to their potential for green and
economic synthesis. This area of intense research activity
56
includes classical couplings, C−H functionalizations, and
radical chemistry for chemical, materials, and biological
Figure 1. Representative sulfoxides and their uses.
5
7−62
synthesis.
During the past several years, palladium
complexes have dominated the catalytic systems; however,
the expense and greater toxicity of palladium have prompted
significant interest in developing nickel-catalyzed oxidative
coupling reactions for the construction of carbon−carbon and
Received: July 7, 2018
63,64
carbon−heteroatom bonds.
Novel methods for oxidative
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.organomet.8b00476
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
coupling to form C−C, C−N, C−O, C−S, and C−halogen
Table 1. Optimization of the Oxidative Coupling of Phenyl
Benzyl Sulfoxide 1a
6
5−67
a
bonds have been reported.
Despite these advances,
diastereoselective oxidative coupling reactions to generate
bis(sulfoxides) with formation of the C−S bond remains
challenging.
Herein, we present a novel nickel-catalyzed diastereoselec-
tive oxidative coupling reaction to produce disulfoxides
(
Scheme 1). We hypothesize that the reaction proceeds via a
b
,
c
d
entry
nickel source
Ni(COD)2
base
solvent AY (%)
dr
Scheme 1. Synthetic Approach to Bis(phenylsulfinyl)
Methanes Outlined Herein
t
1
2
3
4
5
6
7
8
9
NaO- Bu
CPME
Tol
THF
32
20
12
8
16
48
25
20
56
68
70
82
0
6:1
6:1
6:1
6:1
6:1
8.5:1
6:1
5:1
8.5:1
8.5:1
8.5:1
8.5:1
0
a
t
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
NaO- Bu
t
NaO- Bu
t
KO- Bu
CPME
CPME
CPME
CPME
CPME
CPME
CPME
CPME
CPME
CPME
CPME
CPME
t
LiO- Bu
n
t
Ni(P Bu ) Cl
NaO- Bu
3
2
2
t
Ni(dppp)Cl2
Ni(OAc)2
NaO- Bu
t
NaO- Bu
n
t
e
e
e
e
i
Ni(P Bu ) Cl
NaO- Bu
3
2
2
2
2
2
2
a
DTBP: di-tert-butyl peroxide; CPME: cyclopentyl methyl ether.
n
t
,
f
,
f
,
f
1
1
0
1
Ni(P Bu ) Cl
NaO- Bu
3
2
n
t
,
,
g
Ni(P Bu ) Cl
NaO- Bu
3
2
−
n
t
h
sulfenate anion [ArSO] , which is cross-coupled by the nickel
catalyst. Disulfoxides are produced in moderate to good yields
with fair to excellent diastereoselectivities.
12
13
14
Ni(P Bu ) Cl
NaO- Bu
3
2
n
t
Ni(P Bu ) Cl
NaO- Bu
3
2
t
i
without nickel source
without nickel source
NaO- Bu
0
0
0
0
t
1
5
NaO- Bu
RESULTS AND DISCUSSION
a
■
Assay yields (AY) of the mixtures of diastereomers were determined
with H NMR spectroscopy by integration of the worked up but
unpurified reaction mixtures using toluene as internal standard.
Reactions were conducted on a 0.1 mmol scale of 1a in 2 mL of
solvent. Reactions were conducted with [Ni]/NIXANTPHOS
loading 10/10 mol %. Diastereomeric ratios were determined by
H NMR spectroscopy of crude reaction mixtures. Reactions were
conducted with [Ni]/NIXANTPHOS loading 20/20 mol %.
Reactions were conducted with di-tert-butyl peroxide (DTBP).
Reactions were conducted on a 0.5 mmol scale of 1a in 10 mL of
solvent. Reactions were conducted on a 0.5 mmol scale of 1a in 25
mL of solvent. Reactions were conducted without NIXANTPHOS.
1
Initial studies began with phenyl benzyl sulfoxide (1a),
Ni(COD) (10 mol %), and van Leeuwen’s NIXANTPHOS
2
68,69
b
(
L1, 10 mol %) as the ligand.
Given the important role
c
that solvents and bases play in coupling reactions, we first
d
screened a variety of solvents [cyclopentyl methyl ether
1
e
(
(
CPME), toluene, tetrahydrofuran (THF), dimethoxyethane
DME), 1,4-dioxane, 2-methyltetrahydrofuran (2-Me-THF),
f
t
dichloromethane (DCM)] with NaO- Bu as the base. After 16
h at room temperature, only three of the reactions led to
products (Table 1, entries 1−3). Among the solvents tested,
g
h
i
t
the coupling of 1a with NaO- Bu in CPME afforded the best
1
assay yield (AY, determined by H NMR spectroscopy of
worked up, unpurified reaction mixtures by integration against
characterized by X-ray crystallography (see the Supporting
Information for details). Note that there are two possible meso
diastereomers, but only the anti-anti is observed throughout
this work and not the syn-syn diastereomer. The background
reactions in the absence of the Ni source and NIXANTPHOS
also were tested, and the results indicated that the disulfoxide
a toluene internal standard; 32%, entry 1). Under otherwise
t
identical reaction conditions, substitution of KO- Bu and
t
t
LiO- Bu for NaO- Bu afforded lower AY (8 and 16%, entries 4
and 5), and no product was obtained using other bases
[
LiN(SiMe ) , NaN(SiMe ) , KN(SiMe ) , LiOSiMe , or
3 2 3 2 3 2 3
n
KOSiMe3].
was only produced when both Ni(P Bu ) Cl and NIXANT-
3 2
2
We next screened several nickel sources (for more details,
PHOS were present (entries 13−15).
see Table S1). The yield increased to 48% when Ni-
Using the optimized reaction conditions (Table 1, entry 12),
the scope of substituted aryl benzyl sulfoxides was explored.
The diastereoselectivity (rac to meso) ranged from 3:1 to 8.7:1
(Table 2). Reactions with substituted phenyl benzyl sulfoxides
bearing electron-withdrawing groups, like 4-F (1b), 4-CF3
(1c), and 4-Cl (1d), gave 2b, 2c, and 2d in 82% (6:1 dr),
70% (4:1 dr), and 83% yields (8.7:1 dr), respectively.
Compound rac-2c was characterized by X-ray crystallography
(see the Supporting Information for details). Substituted
phenyl benzyl sulfoxides with electron-donating 4-Me (1e) and
n
(
P Bu ) Cl was used in place of Ni(COD) (entry 6), but
3
2
2
2
did not improve with Ni(dppp)Cl or Ni(OAc) (entries 7 and
2
2
8
). A series of 12 phosphine ligands and 6 nitrogen-based
ligands were compared with NIXANTPHOS (L1) but only
NIXANTPHOS provided the disulfoxide product (see Table
S2 for details). Increasing the [Ni]/NIXANTPHOS loading
from 10:10 to 20:20 mol % improved the AY to 56% (entry 9).
Lastly, different oxidants were examined (see Table S3), and
the highest yield was observed when the reaction was
conducted in the presence of di-tert-butyl peroxide (DTBP,
t
4- Bu (1f) groups produced products 2e and 2f in 61% (4.5:1
2
.2 equiv) and dry air (entry 10, 68% AY).
Having established suitable conditions, we examined the
dr) and 69% yield (4:1 dr). Sterically hindered 1-naphthyl
benzyl sulfoxide provided the corresponding product (2g) in
60% yield (3:1 dr). Due to the importance of heterocycles in
medicinal chemistry, heterocyclic substrates were examined. 2-
(Benzylsulfinyl) thiophene 1h furnished the coupling product
2h in 60% yield (4:1 dr). Under the conditions outlined above,
1-(benzylsulfinyl)-4-methoxybenzene led to very low yield
effect of increasing the reaction scale from 0.1 to 0.5 mmol of
sulfoxide 1a (entry 11, 70% AY) and decreasing the
concentration of 1a (entry 12, 82% AY and 76% isolated
yield of 2a after column chromatography). It is noteworthy
that the minor diastereomer, meso-2a (anti-anti), was
B
DOI: 10.1021/acs.organomet.8b00476
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Article
Table 2. Diastereoselective Oxidative Coupling of Various
Substituted Phenyl Benzyl Sulfoxides
Table 3. Diastereoselective Oxidative Coupling of Various
Phenyl Substituted Benzyl Sulfoxides
,
a b
,
a b
a
Isolated yields for mixtures of diastereomers after chromatographic
b
1
purification. Diastereomeric ratios were determined by H NMR
spectroscopy of the crude reaction mixtures.
(
<10%), most likely due to the higher pK value of the benzylic
a
hydrogens. We were unsuccessful at increasing the yield
through optimization. Attempts to carry out the coupling of N-
heterocyclic substrates, such as 3-(benzylsulfinyl)pyridine and
a
3
-(benzylsulfinyl)-quinoline, resulted in recovery of starting
Isolated yields for mixtures of diastereomers after chromatographic
b
1
material and decomposition, respectively.
purification. Diastereomeric ratios were determined by H NMR
spectroscopy of the crude reaction mixtures.
After demonstrating the scope of substituted aryl benzyl
sulfoxides in the coupling reactions, we next turned our
attention to the substrate scope with respect to substitution on
the benzyl group (Table 3). Overall, substrates with electron-
withdrawing groups gave better yields than those with
electron-donating groups, and the diastereoselectivity (rac to
meso) ranged from 3:1 to >20:1. Electron-withdrawing 4-F
to couple N-heterocyclic substrates, 3-(phenylsulfinyl-methyl)-
pyridine, and 3-(phenyl-sulfinylmethyl) quinoline, led to
recovery of starting material and decomposition, respectively.
To gain insight into the pathway for this novel nickel-
catalyzed diastereoselective oxidative coupling reaction, several
experiments were carried out, as shown in Scheme 2. Both
benzaldehyde (17% yield by GC) and benzoic acid (22%
isolated yield), the product from oxidation of benzaldehyde,
were identified as byproducts of the reaction (Scheme 2A).
Observation of the isolated byproduct diphenyl disulfide (8%,
(
1i), 4-CF (1j), 3-CF (1k), and 4-Cl (1l) groups were well-
3 3
tolerated, giving 2i, 2j, 2k, and 2l in 62% (3:1 dr), 63% (7:1
dr), 76% (>20:1 dr), and 72% yields (9.8:1 dr), respectively.
Substrates bearing electron-donating groups, such as 4-Me
t
(
1m), 4- Bu (1n), and 4-OMe (1o), furnished the products
70
2
m−2o in 30−50% yield and 4:1−7.3:1 dr. Analogues with
sterically hindered groups, such as 2-tolyl (1p) and 1-naphthyl
1q), yielded the corresponding products in 76% (4.7:1 dr)
Scheme 2A) suggests that the sulfenate anion may be an
intermediate, because sulfenate anions are known to undergo
disproportionation to generate disulfides and benzenesulfinate
(
70−72
and 36% yields (6:1 dr), respectively. The heterocyclic
salts.
To explore the possibility of a sulfenate anion
substrates, 3-(phenylsulfinylmethyl) thiophene (1r) and 2-
intermediate, we next employed phenethyl-sulfinylbenzene in
the reaction (Scheme 2B). It is known that under basic
conditions phenethyl-sulfinylbenzene undergoes elimination to
generate styrene and the sulfenate anion. In the reaction,
both disulfoxide 2e (15%) and 2t (9%) were found, supporting
the intermediacy of the sulfenate anion. We were curious if the
benzyl group of 1a could be cleaved in a pathway that did not
involve the nickel catalyst. Thus, sulfoxide 1a was subjected to
(
phenylsulfinylmethyl) thiophene (1s), provided 41% (6:1 dr)
and 39% yields (6:1 dr), respectively. No products derived
73
from oxidation of the thiophene sulfur were identified.
n
Increasing the catalyst loading to 40 mol % Ni(P Bu ) Cl
3
2
2
and 40 mol % NIXANTPHOS and increasing the reaction
time to 24 h did not increase the yield with heterocyclic
substrates. Furthermore, under the same conditions, attempts
C
DOI: 10.1021/acs.organomet.8b00476
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Article
a
Scheme 2. Experiments to Probe the Reaction Mechanism
(A) by base generates a nucleophile (B) that can undergo
transmetalation with Ni(II) complex F via path a to form a
Ni−C bond. Deprotonated sulfoxide B, with an electron-rich
carbanion, can be oxidized through path b to form an α-
hydroxy sulfoxide (C). In the presence of base, C is
deprotonated to expel the sulfenate anion (D), and form the
aromatic aldehyde (E). Oxidation of the liberated benzalde-
hyde (E) to benzoic acid can explain its formation in Scheme
2
A. Sulfenate anions are known to undergo transmetalation
40,41,43,50
with transition metals.
Attack by the sulfenate anion
(
D) on Ni(II) intermediate G provides the transmetalation
product (H), which undergoes reductive elimination to
generate the C−S bond of the disulfoxide (I). The resulting
Ni(0) intermediate (J) can be oxidized to a Ni(II) species,
such as F or a related Ni(II) compound to close the catalytic
cycle.
The oxidation processes in the proposed reaction pathway
can be envisioned to occur with either dioxygen or di-tert-butyl
peroxide. One might imagine that the diastereoselectivity can
be set in either the transmetalation or reductive elimination
steps. We recently disclosed computational evidence that in
the case of the palladium catalyzed enantioselective arylation of
sulfenate anions, the palladium sulfenate is O-bound after
transmetalation. It was also discovered that the isomerization
of the Pd−O−SPh to Pd−S(O)Ph has a higher barrier than
the reductive elimination to form the sulfoxide, Ar−S(
a
n
Reaction conditions (a): 20 mol % Ni(P Bu ) Cl , 20 mol %
3
2
2
t
NIXANTPHOS, 3 equiv NaO- Bu, 2.2 equiv DTBP, and dry air, in 25
mL CPME at room temperature for 16 h; (b): 3 equiv NaO- Bu, 2.2
equiv DTBP, and dry air, in 25 mL CPME at room temperature for 16
h.
t
50
O)Ph. Thus, in the Ni-catalyzed process outlined herein, it is
also possible that the diastereoselectivity determining step is
isomerization to S-bound sulfenate anion [Ni]−S(O)Ph.
t
base (NaO- Bu), dry air, and DTBP at rt for 16 h. Although
conversion was low (Scheme 2C) benzoic acid (4% isolated
yield), derived from air oxidation of benzaldehyde, and starting
sulfoxide 1a (65%) were observed when the reaction was
conducted without nickel and ligand (Scheme 2C). This result
suggests that there is a transition metal free route to cleave the
S-benzyl group, likely generating sulfenate anions. Given the
low conversion in Scheme 2C, however, under the disulfoxide
forming reaction conditions it may be possible that there is a
nickel catalyzed oxidation of 1a under basic conditions that
leads to the sulfenate anions and benzaldehyde. Alternatively,
there may be an in situ generated intermediate that is more
efficient at benzylic oxidation.
CONCLUSION
■
In summary, we have reported a unique oxidative coupling
process to generate disulfoxides directly from phenyl benzyl
sulfoxides in a diastereoselective fashion. A [Ni(P Bu ) ]Cl /
n
3
2
2
NIXANTPHOS-based catalyst promotes the reaction, and a
variety of disulfoxides were produced in moderate yields and
diastereoselectivities. Mechanistic studies indicate the sulfenate
anion formation through C−S bond cleavage and a core
catalytic cycle involving C−S bond formation. The proposed
mechanism highlights the possible reasons for the moderate
yields in these reactions. To achieve high yields, the fate of the
deprotonated sulfoxide must be equally divided between
On the basis of the results of these experiments, a catalytic
cycle is proposed in Figure 2. Deprotonation of the sulfoxide
Figure 2. Proposed mechanism highlighting key intermediates in the nickel-catalyzed oxidative coupling process.
D
DOI: 10.1021/acs.organomet.8b00476
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Organometallics
Article
formation of the sulfenate anion and transmetalation to
nickel(II). Excess conversion to the sulfenate anion, for
example, would result in less deprotonated sulfoxide for the
transmetalation and reduce the yield. Additionally, the
sensitivity of sulfenate anions to oxidation may also reduce
the yields observed in these reactions.
acetate. The solvent was removed under reduced pressure to yield a
brown solid. The residue was purified by flash chromatography on
silica gel to give the product.
Bis(phenylsulfinyl)phenylmethane (2a). The reaction was per-
formed following General Procedure A with 1a (108 mg, 0.5 mmol,
t
1
.0 equiv), NaO- Bu (144 mg, 1.5 mmol, 3.0 equiv), and di-tert-butyl
peroxide (200 μL, 1.1 mmol, 2.2 equiv). The crude product was
isolated by flash chromatography on silica gel (eluted with EtOAc/
EXPERIMENTAL SECTION
CH
.5:1) as a white solid. Compound rac-2a was purified by silica gel
column (eluted with EtOAc/CH Cl = 3:97) to give white solid (55.3
2 2
Cl = 5:95) to give the product (64.6 mg, 76% yield, rac/meso =
■
8
General Methods. All reactions were carried out under dry air.
Anhydrous CPME, Toluene, THF, DME, 1,4-dioxane, 2-Me-THF,
and DCM were purchased from Sigma-Aldrich and directly used
without further purification. Unless otherwise stated, reagents were
commercially available and used as purchased without further
purification. Chemicals were purchased from Sigma-Aldrich, Acros,
Alfa Aesar Matrix Scientific, or Frontier Scientific, and solvents were
purchased from Fisher Scientific and Sigma-Aldrich. The progress of
the reactions was monitored by thin-layer chromatography using
Whatman precoated silica gel 60 F-254 plates and visualized by short-
2
2
mg, 65% yield). The spectroscopic data of rac-2a are as follows: R =
f
1
0
.2 (EtOAc/CH Cl = 1:9). Mp = 170−171 °C. H NMR (500 MHz,
2
2
3
CDCl ): δ 7.46−7.26 (m, 9H), 7.18−7.11 (m, 3H), 6.80 (d, J
=
H−H
3
1
3
1
7
1
1
1
.6 Hz, 2H), 4.30 (s, 1H) ppm. C{ H} NMR (125 MHz, CDCl ): δ
42.2, 140.7, 131.9, 131.4, 130.8, 129.8, 129.2, 129.0, 128.4, 125.0,
24.9, 124.7, 95.4 ppm. IR (thin film): 3057, 2921, 1492, 1418, 1214,
174, 1118, 1098, 998, 786, 612 cm . HRMS calculated for
3
−
1
+
C H O S Na 363.0489, found 363.0477 [M + Na] .
1
9
16
2 2
Bis(4-fluorophenylsulfinyl)phenylmethane (2b). The reaction was
wave ultraviolet light as well as by treatment with I . Flash
2
performed following General Procedure B with 1b (117 mg, 0.5
chromatography was performed with silica gel (230−400 mesh,
t
mmol, 1.0 equiv), NaO- Bu (144 mg, 1.5 mmol, 3.0 equiv), and di-
Silicycle). The NMR spectra were obtained using a Bruker 500 MHz
̈
tert-butyl peroxide (200 μL, 1.1 mmol, 2.2 equiv). The crude product
was isolated by flash chromatography on silica gel (eluted with
EtOAc/CH Cl = 5:95) to give the product (77.3 mg, 82% yield, rac/
Fourier transform NMR spectrometer. Chemical shifts are reported in
units of parts per million (ppm) downfield from tetramethylsilane
2
2
(
TMS), and all coupling constants are reported in hertz. The infrared
spectra were taken with KBr plates with a PerkinElmer Spectrum
600 Series spectrometer. High-resolution mass spectrometry
HRMS) data were obtained on a Waters LC-TOF mass
spectrometer (model LCT-XE Premier) using electrospray ionization
ESI) in positive or negative mode, depending on the analytes.
Melting points were determined on a Mel-Temp melting point
apparatus and were uncorrected. Phenyl benzyl sulfoxide and its
derivatives were prepared according to the literature procedures.
meso = 6:1) as a yellow solid. The product was dissolved in
chloroform and layered with ethanol (ethanol/CHCl (20:1)), which
3
1
(
was left open to the air at room temperature. After slow evaporation,
crystalline rac-2b (white solid, 65.1 mg, 69% yield) was obtained. The
spectroscopic data of rac-2b are as follows: R = 0.3 (EtOAc/CH Cl
2
f
2
(
1
=
1:9). Mp = 150−151 °C. H NMR (500 MHz, CDCl ): δ 7.51−
.46 (m, 4H), 7.38 (m, 1H), 7.27 (m, 2H), 7.16 (m, 4H), 7.08 (d,
JH−H = 8.0 Hz, 2H), 4.25 (s, 1H) ppm. C{ H} NMR (125 MHz,
3
7
3
13
1
74,75
CDCl ): δ 164.9 (d, J = 253.7 Hz), 136.2, 130.8, 129.8, 128.4,
Procedure and Characterization for Formation of Bis-
3
C−F
1
27.5, 127.4, 125.2, 116.7, 116.5, 92.4 ppm [two carbon signals are
(
phenylsulfinyl)-phenylmethane Derivatives by Nickel-Cata-
lyzed Oxidative Coupling Reactions. General Procedure A. To
missing due to overlapping]. IR (thin film): 3060, 2903, 1587, 1489,
1455, 1402, 1294, 1226, 1155, 1083, 1012, 751, 635 cm . HRMS
calculated for C19H F O S 377.0482, found 377.0490 [M + H] .
−
1
an oven-dried vial (20 mL) equipped with a stir bar were added
n
+
Ni(P Bu ) Cl (53.4 mg, 0.1 mmol) and NIXANTPHOS (55.2 mg,
15 2 2 2
3
2
2
0
.1 mmol) inside a nitrogen filled glovebox, followed by 5.0 mL of dry
Bis[4-(trifluoromethyl)phenylsulfinyl]phenylmethane (2c). The
reaction was performed following General Procedure B with 1c
t
CPME; meanwhile, NaO- Bu (144 mg, 1.5 mmol, 3.0 equiv) and
sulfoxide (1, 0.5 mmol, 1.0 equiv) were mixed in the oven-dried flask,
followed by 20.0 mL dry CPME. After the catalyst/ligand solution
and the starting material/base solution were stirred for 2 h at 24 °C
separately, they were mixed in an oven-dried round-bottomed flask
t
(142 mg, 0.5 mmol, 1.0 equiv), NaO- Bu (144 mg, 1 mmol, 3.0 equiv)
and di-tert-butyl peroxide (200 μL, 1.1 mmol, 2.2 equiv). The crude
product was isolated by flash chromatography on silica gel (eluted
with EtOAc/CH
rac/meso = 4:1) as a yellow solid. The product was dissolved in
chloroform and layered with ethanol (ethanol/CHCl (20:1)), which
Cl = 5:95) to give the product (83.4 mg, 70% yield,
2
2
(
100 mL). The flask was sealed with a rubber septum and sealing tap
and moved out of glovebox. Di-tert-butyl peroxide (200 μL, 1.1 mmol,
.2 equiv) was added by syringe into the flask. Then, dry air was
3
2
was left open to the air at room temperature. After slow evaporation,
crystalline rac-2c (yellow solid, 65.0 mg, 56% yield) was obtained.
added through a syringe opened to the air, loaded with cotton and
anhydrous CaCl on the top. The reaction mixture was stirred at
The spectroscopic data of rac-2c are as follows: R
f
= 0.4 (EtOAc/
): δ
2
1
room temperature for 16 h. Afterward, the sealed flask was opened to
air, and the reaction mixture was passed through a short pad of silica
gel packed in a syringe. The pad was then rinsed with 25 mL of ethyl
acetate. The solvent was removed under reduced pressure to yield a
brown solid. The residue was purified byflash chromatography on
silica gel to give the product.
CH
2
Cl
2
= 1:9). Mp = 152−153 °C. H NMR (500 MHz, CDCl
3
3
3
7.57 (d, JH−H = 8.4 Hz, 2H), 7.53 (d, JH−H = 8.4 Hz, 2H), 7.38−
7.30 (m, 5H), 7.20 (t, JH−H = 7.8 Hz, 2H), 6.80 (s, 2H), 4.31 (s, 1H)
3
1
3
1
ppm. C{ H} NMR (125 MHz, CDCl
C−F = 33.2 Hz), 130.4, 130.3, 129.6 (q, JC−F = 270.0 Hz), 128.8,
125.9 (q, JC−F = 7.5 Hz), 125.8 (q, JC−F = 7.5 Hz), 125.6, 125.3 (q,
C−F = 270.0 Hz), 125.0, 124.9, 123.8, 95.1 ppm. IR (thin film): 3018,
): δ 146.1, 144.8, 133.6 (q,
3
J
General Procedure B. To an oven-dried vial (20 mL) equipped
J
n
−1
with a stir bar were added Ni(P Bu ) Cl (53.4 mg, 0.1 mmol) and
2962, 1323, 1260, 1215, 1093, 1061, 1015, 757, 668 cm . HRMS
3
2
2
+
NIXANTPHOS (55.2 mg, 0.1 mmol) inside a nitrogen-filled
glovebox, followed by 5.0 mL of dry CPME. After the catalyst/ligand
solution was stirred for 2 h at 24 °C, it was added to the mixture
calculated for C21H F O S 477.0418, found 477.0417 [M + H] .
15 6 2 2
Bis(4-clorophenylsulfinyl)phenylmethane (2d). The reaction was
performed following General Procedure B with 1d (145 mg, 0.5
t
t
solution of NaO- Bu (144 mg, 1.5 mmol, 3.0 equiv) and sulfoxide (1,
mmol, 1.0 equiv), NaO- Bu (144 mg, 1.5 mmol, 3.0 equiv), and di-
0
.5 mmol, 1.0 equiv) with CPME (20 mL) in an oven-dried round-
tert-butyl peroxide (200 μL, 1.1 mmol, 2.2 equiv). The crude product
was isolated by flash chromatography on silica gel (eluted with
EtOAc/CH Cl = 5:95) to give the product (83.9 mg, 83% yield, rac/
bottomed flask (100 mL). The flask was sealed with a rubber septum
and sealing tap, then moved out of glovebox. Di-tert-butyl peroxide
2
2
(200 μL, 1.1 mmol, 2.2 equiv) was added by syringe. Then, dry air
meso = 8.7:1) as a white solid. The product was dissolved in
was added through a syringe opened to the air, loaded with cotton
chloroform and layered with ethanol (ethanol/CHCl (20:1)), which
3
and anhydrous CaCl on top. The reaction mixture was stirred at
was left open to the air at room temperature. After slow evaporation,
crystalline rac-2d (white solid, 68.1 mg, 67% yield) was obtained. The
spectroscopic data of rac-2d are as follows: R = 0.3 (EtOAc/CH Cl
2
2
room temperature for 16 h. The sealed flask was opened to air, and
the reaction mixture was passed through a short pad of silica gel
packed in a syringe. The pad was then rinsed with 25 mL of ethyl
f
2
1
= 1:9). Mp = 158−159 °C. H NMR (500 MHz, CDCl ): δ 7.40−
3
E
DOI: 10.1021/acs.organomet.8b00476
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
3
4
= 4.0 Hz, 1H), 7.46 (d, 4J
7
(
1
1
1
.30 (m, 2H), 7.26−7.16 (m, 7H), 7.09 (d, J
= 8.4 Hz, 2H), 6.80
MHz, CDCl ): δ 7.52 (d, J
= 4.0
H−H
H−H
3
H−H
1
3
1
3
3
s, 2H), 4.24 (s, 1H) ppm. C{ H} NMR (125 MHz, CDCl ): δ
40.2, 138.7, 138.0, 137.6, 130.4, 129.9, 129.2, 129.1, 128.4, 125.9,
25.8, 124.1, 95.0 ppm. IR (thin film): 3059, 2912, 1572, 1493, 1452,
294, 1277, 1171, 1082, 1011, 784, 697 cm . HRMS calculated for
C H Cl O S Na 430.9710, found 430.9732 [M + Na] .
Bis(4-methylphenylsulfinyl)phenylmethane (2e). The reaction
was performed following General Procedure A with 1e (115 mg,
Hz, 1H), 7.36 (t, J
= 7.5 Hz, 1H), 7.24 (m, 3H), 7.04 (d, J
7.0 Hz, 2H), 6.97 (s, 2H), 6.87 (s, 1H), 4.75 (s, 1H) ppm. C{ H}
NMR (125 MHz, CDCl ): δ 143.1, 141.6, 132.2, 131.9, 130.6, 130.5,
129.9, 129.6, 128.5, 127.2, 127.0, 125.1, 96.3 ppm. IR (thin film):
3080, 2922, 1493, 1452, 1437, 1400, 1338, 1267, 1223, 1159, 1089,
1000, 852, 783, 615 cm . HRMS calculated for C H O S
352.9798, found 352.9822 [M + H] .
Bis(phenylsulfinyl)(4-fluorophenyl)methane (2i). The reaction
was performed following General Procedure B with 1i (117 mg, 0.5
=
3
H−H
H−H
1
3
1
3
−
1
+
19
14
2
2 2
−
1
15 13 2 4
+
t
0
.5 mmol, 1.0 equiv), NaO- Bu (144 mg, 1.5 mmol, 3.0 equiv) and di-
tert-butyl peroxide (200 μL, 1.1 mmol, 2.2 equiv). The crude product
was isolated by flash chromatography on silica gel (eluted with
EtOAc/CH Cl = 5:95) to give the product (56.2 mg, 61% yield, rac/
meso = 4.5:1) as a yellow solid. Compound rac-2e was purified by
silica gel column (eluted with EtOAc/CH Cl = 3:97) to give yellow
t
mmol, 1.0 equiv), NaO- Bu (144 mg, 1.5 mmol, 3.0 equiv) and di-tert-
butyl peroxide (200 μL, 1.1 mmol, 2.2 equiv). The crude product was
isolated by flash chromatography on silica gel (eluted with EtOAc/
CH Cl = 5:95) to give the product (55.5 mg, 62% yield, rac/meso =
2
2
2
2
2
2
solid (42 mg, 46% yield). The spectroscopic data of rac-2e are as
3:1) as a yellow solid. Compound rac-2i was purified by silica gel
1
follows: R = 0.2 (EtOAc/CH Cl = 1:9). Mp = 150−151 °C. H
column (eluted with EtOAc/CH Cl = 3:97) to give yellow solid
f
2
2
2
2
3
NMR (500 MHz, CDCl ): δ 7.26 (m, 2H), 7.18 (d, J
H), 7.13 (t, J
7.2 Hz, 2H), 4.28 (s, 1H), 2.29 (s. 3H), 2.28 (s, 3H) ppm. C{ H}
= 8.0 Hz,
(38.0 mg, 42% yield). The spectroscopic data of rac-2i are as follows:
3
H−H
3
3
1
2
=
= 8.0 Hz, 2H), 7.09−7.05 (m, 5H), 6.81 (d, J
R = 0.2 (EtOAc/CH Cl = 1:9). Mp = 124−125 °C. H NMR (500
H−H
H−H
f
2
2
1
3
1
MHz, CDCl ): δ 7.38 (m, 1H), 7.34−7.28 (m, 5H), 7.25−7.28 (m,
3
3
3
NMR (125 MHz, CDCl ): δ 142.1, 141.6, 138.5, 137.0, 130.5, 129.5,
2H), 7.15 (d, J
= 8.0 Hz, 2H), 6.83 (t, J
= 8.6 Hz, 2H), 6.77
3
H−H
H−H
1
3
1
1
29.4, 129.3, 128.0, 124.8, 124.5, 124.4, 94.9, 21.3, 21.2 ppm. IR (thin
(m, 2H), 4.27 (s, 1H) ppm. C{ H} NMR (125 MHz, CDCl ): δ
3
−
1
film): 3019, 1445, 1374, 1260, 1215, 1096, 1046, 755, 668 cm .
162.5 (JC−F = 233.7 Hz), 141.7, 140.1, 132.2, 132.1, 131.7, 131.2,
128.9, 128.8, 124.5, 124.2, 120.6, 115.4 (d, JC−F = 21.2 Hz), 94.2 ppm
[one carbon signal is missing due to overlapping]. IR (thin film):
HRMS calculated for C H O S 369.0983, found 369.0980 [M +
2
1
21
2 2
+
H] .
−
1
Bis(4-(tert-butyl)phenylsulfinyl)phenylmethane (2f). The reaction
3018, 1215, 1106, 757, 668 cm . HRMS calculated for C H FO S
19 16 2 2
+
was performed following General Procedure A with 1f (136 mg, 0.5
359.0576, found 359.0590 [M + H] .
t
mmol, 1.0 equiv), NaO- Bu (144 mg, 1.5 mmol, 3.0 equiv), and di-
Bis(phenylsulfinyl)(4-(trifluoromethyl)phenyl)methane (2j). The
reaction was performed following General Procedure B with 1j (142
tert-butyl peroxide (200 μL, 1.1 mmol, 2.2 equiv). The crude product
was isolated by flash chromatography on silica gel (eluted with
EtOAc/CH Cl = 5:95) to give the product (78.2 mg, 69% yield, rac/
t
mg, 0.5 mmol, 1.0 equiv), NaO- Bu (144 mg, 1.5 mmol, 3.0 equiv),
and di-tert-butyl peroxide (200 μL, 1.1 mmol, 2.2 equiv). The crude
product was isolated by flash chromatography on silica gel (eluted
with EtOAc/CH Cl = 5:95) to give the product (64.3 mg, 63% yield,
2
2
meso = 4:1) as a yellow solid. Compound rac-2f was purified by silica
gel column (eluted with EtOAc/CH Cl = 3:97) to give yellow solid
2
2
2
2
(
60.2 mg, 53% yield). The spectroscopic data of rac-2f are as follows:
rac/meso = 7:1) as brown a solid. Compound rac-2j was purified by
1
R = 0.2 (EtOAc/CH Cl = 1:9). Mp = 141−142 °C. H NMR (500
silica gel column (eluted with EtOAc/CH Cl = 3:97) to give brown
f
2
2
2
2
3
MHz, CDCl ): δ 7.28 (m, 1H), 7.27−7.19 (m, 6H), 7.11 (t, J
=
solid (55.3 mg, 54% yield). The spectroscopic data of rac-2j are as
3
H−H
3
3
1
7
2
(
.8 Hz, 2H), 7.05 (d, J
H), 4.28 (s, 1H), 1.21(s, 9H), 1.20 (s, 9H) ppm. C{ H} NMR
= 8.4 Hz, 2H), 6.80 (d, J
= 7.3 Hz,
follows: R = 0.3 (EtOAc/CH Cl = 1:9). Mp = 141−142 °C. H
H−H
H−H
f
2
2
1
3
1
3
NMR (500 MHz, CDCl ): δ 7.40 (m, 1H), 7.38 (d, J
= 8.2 Hz,
= 8.2 Hz, 2H),
= 7.7 Hz, 2H), 4.35 (s, 1H) ppm. C{ H} NMR (125
3
H−H
3
125 MHz, CDCl ): δ 155.2, 154.9, 138.7, 137.1, 130.7, 129.3, 127.9,
3H), 7.32−7.26 (m, 4H), 7.24 (m, 2H), 7.13 (d, J
3
H−H
3
13
1
1
25.9, 125.7, 124.9, 124.4, 124.2, 95.0, 34.9, 34.8, 31.1, 31.0 ppm. IR
6.91 (d, J
H−H
(
thin film): 2961, 1474, 1461, 1443, 1416, 1269, 1107, 1070, 1021,
MHz, CDCl ): δ 141.4, 139.9, 132.0, 131.4, 130.5, 129.2, 129.1,
128.9, 127.1 (q, JC−F = 278.9 Hz), 124.8 (q, JC−F = 5.0 Hz), 124.5,
3
−
1
9
90. 842, 745, 688 cm . HRMS calculated for C H O S 453.1922,
2
7
33
2 2
+
found 453.1935 [M + H] .
124.1, 94.4 ppm [one carbon signal is missing due to overlapping]. IR
−
1
Bis(1-naphthylsulfinyl)phenylmethane (2g). The reaction was
performed following General Procedure B with 1g (133 mg, 0.5
mmol, 1.0 equiv), NaO- Bu (144 mg, 1.5 mmol, 3.0 equiv), and di-
(thin film): 3018, 1215, 1050, 757, 669 cm . HRMS calculated for
+
C H F O S 409.0544, found 409.0522 [M + H] .
2
0
16
3
2 2
t
Bis(phenylsulfinyl)(3-(trifluoromethyl)phenyl)methane (2k). The
tert-butyl peroxide (200 μL, 1.1 mmol, 2.2 equiv). The crude product
was isolated by flash chromatography on silica gel (eluted with
EtOAc/CH Cl = 3:97) to give the product (66.0 mg, 60% yield, rac/
reaction was performed following General Procedure B with 1k (142
mg, 0.5 mmol, 1.0 equiv), NaO- Bu (144 mg, 1.5 mmol, 3.0 equiv),
t
and di-tert-butyl peroxide (200 μL, 1.1 mmol, 2.2 equiv). The crude
product was isolated by flash chromatography on silica gel (eluted
with EtOAc/CH Cl = 5:95) to give the product (77.2 mg, 76% yield,
2
2
meso = 3:1) as a yellow solid. Compound rac-2g was purified by silica
gel column (eluted with EtOAc/CH Cl = 2:98) to give white solid
2
2
2
2
(
44.8 mg, 41% yield). The spectroscopic data of rac-2g are as follows:
rac/meso > 20:1) as a yellow solid. Compound rac-2k was purified by
1
R = 0.4 (EtOAc/CH Cl = 1:9). Mp = 140−141 °C. H NMR (500
MHz, CDCl ): δ 8.40 (s, 1H), 8.01 (s, 1H), 7.89−7.67 (m, 5H),
silica gel column (eluted with EtOAc/CH Cl = 3:97) to give yellow
f
2
2
2
2
solid (72.1 mg, 71% yield). The spectroscopic data of rac-2k are as
3
1
7
4
1
1
1
1
.46−7.31 (m, 3H), 7.25−7.15 (m, 3H), 7.05 (m, 4H), 6.73 (s, 2H),
follows: R = 0.3 (EtOAc/CH Cl = 1:9). Mp = 131−132 °C. H
f
2
2
.83 (s, 1H) ppm. 1 C{ H} NMR (125 MHz, CDCl ): δ 138.2, 136.0,
3
1
NMR (500 MHz, CDCl ): δ 7.54 (d, J = 7.5 Hz, 1H), 7.42−7.33
H−H
3
3
3
3
33.5, 132.9, 132.2, 131.0, 130.7, 129.4, 129.2, 128.9, 128.7, 127.7,
27.6, 127.3, 127.1, 126.7, 126.3, 125.5, 125.3, 125.1, 125.0, 124.7,
21.7, 120.3, 88.1 ppm. IR (thin film): 3021, 2984, 2941, 1478, 1465,
(m, 7H), 7.23−7.28 (m, 3H), 7.13 (d, J
= 7.5 Hz, 2H), 6.73 (s,
H−H
1
3
1
1H), 4.36 (s, 1H) ppm. C{ H} NMR (125 MHz, CDCl ): δ 141.4,
3
139.9, 133.4, 131.9, 131.4, 130.7, 129.1, 128.9, 128.5, 127.1 (q, JC−F
=
−
1
445, 1374, 1248, 1216, 1096, 1046, 939, 847, 757, 668 cm . HRMS
275.0 Hz), 127.0 (q, JC−F = 7.25 Hz), 126.0, 125.9 (q, JC−F = 7.25
Hz), 124.4, 124.0, 94.5 ppm. IR (thin film): 3018, 1331, 1215, 1135,
+
calculated for C H O S 441.0983, found 441.0992 [M + H] .
27
21
2 2
−
1
Bis(2-thienylsulfinyl)phenylmethane (2h). The reaction was
1050, 758, 669 cm . HRMS calculated for C H F O S 409.0544,
20 16 3 2 2
+
performed following General Procedure A with 1h (111 mg, 0.5
mmol, 1.0 equiv), NaO- Bu (144 mg, 1.5 mmol, 3.0 equiv), and di-
found 409.0557 [M + H] .
t
Bis(phenylsulfinyl)(4-chlorophenyl)methane (2l). The reaction
tert-butyl peroxide (200 μL, 1.1 mmol, 2.2 equiv). The crude product
was isolated by flash chromatography on silica gel (eluted with
EtOAc/CH Cl = 5:95) to give the product (52.6 mg, 60% yield, rac/
was performed following General Procedure B with 1l (145 mg, 0.5
mmol, 1.0 equiv), NaO- Bu (144 mg, 1.5 mmol, 3.0 equiv), and di-
t
tert-butyl peroxide (200 μL, 1.1 mmol, 2.2 equiv). The crude product
was isolated by flash chromatography on silica gel (eluted with
EtOAc/CH Cl = 5:95) to give the product (67.4 mg, 72% yield, rac/
2
2
meso = 4:1) as a yellow solid. Compound rac-2h was purified by silica
gel column (eluted with EtOAc/CH Cl = 3:97) to give yellow solid
2
2
2
2
(
40.2 mg, 46% yield). The spectroscopic data of rac-2h are as follows:
meso = 9.8:1) as a yellow solid. Compound rac-2l was purified by
1
R = 0.2 (EtOAc/CH Cl = 1:9). Mp = 131−132 °C. H NMR (500
silica gel column (eluted with EtOAc/CH Cl = 3:97) to give yellow
f
2
2
2
2
F
DOI: 10.1021/acs.organomet.8b00476
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
3
solid (58.2 mg, 62% yield). The spectroscopic data of rac-2l are as
MHz, CDCl ): δ 7.81 (d, J
= 7.5 Hz, 1H), 7.36−7.31 (m, 4H),
H−H
H−H
3
1
3
follows: R = 0.2 (EtOAc/CH Cl = 1:9). Mp = 138−139 °C. H
7.26−7.19 (m, 8H), 6.73 (d, J = 7.5 Hz, 1H), 4.66 (s, 1H), 0.81
(s, 3H) ppm. C{ H} NMR (125 MHz, CDCl ): δ 141.8, 138.1,
131.6, 131.5, 131.2, 129.9, 129.6, 128.8, 128.7, 125.6, 124.7, 124.5,
123.0, 90.4, 17.8 ppm [one carbon signal is missing due to
overlapping]. IR (thin film): 3056, 2924, 2854, 1452, 1437, 1419,
1383, 1274, 1197, 1159, 1132, 1119, 786, 697 cm . HRMS calculated
for C H O S 355.0826, found 355.0832 [M + H] .
Bis(phenylsulfinyl)(1-naphthyl)methane (2q). The reaction was
performed following General Procedure B with 1q (145 mg, 0.5
mmol, 1.0 equiv), NaO- Bu (144 mg, 1.5 mmol, 3.0 equiv), and di-
f
2
2
1
3
1
NMR (500 MHz, CDCl ): δ 7.38 (m, 2H), 7.32−7.24 (m, 6H), 7.14
3
3
3
3
3
(
=
d, J
= 7.7 Hz, 2H), 7.09 (d, J
7.5 Hz, 2H), 4.27 (s, 1H) ppm. C{ H} NMR (125 MHz, CDCl ):
= 7.7 Hz, 2H), 6.73 (d, J
H−H
H−H
H−H
1
3
1
3
δ 141.6, 140.3, 135.9, 131.8, 131.5, 131.2, 129.0, 128.8, 128.3, 124.5,
−
1
1
1
24.2, 123.2, 94.4 ppm. IR (thin film): 3018, 1490, 1444, 1215, 1088,
−
1
+
050, 755, 690 cm . HRMS calculated for C H ClO S 375.0280,
1
9
16
2
2
20 19
2 2
+
found 375.0298 [M + H] .
Bis(phenylsulfinyl)(4-methylphenyl)methane (2m). The reaction
was performed following General Procedure A with 1m (115 mg, 0.5
t
t
mmol, 1.0 equiv), NaO- Bu (144 mg, 1.5 mmol, 3.0 equiv), and di-
tert-butyl peroxide (200 μL, 1.1 mmol, 2.2 equiv). The crude product
was isolated by flash chromatography on silica gel (eluted with
tert-butyl peroxide (200 μL, 1.1 mmol, 2.2 equiv). The crude product
was isolated by flash chromatography on silica gel (eluted with
EtOAc/CH Cl = 5:95) to give the product (40.1 mg, 45% yield, rac/
EtOAc/CH
meso = 6:1) as a yellow solid. Compound rac-2q was purified by silica
gel column (eluted with EtOAc/CH Cl = 2:98) to give yellow solid
(27.8 mg, 29% yield). The spectroscopic data of rac-2q are as follows:
Cl = 3:97) to give the product (34.7 mg, 36% yield, rac/
2
2
2
2
meso = 7.25:1) as a yellow solid. Compound rac-2m was purified by
2
2
silica gel column (eluted with EtOAc/CH Cl = 3:97) to give yellow
2
2
1
solid (35.0 mg, 40% yield). The spectroscopic data of rac-2m are as
R
f
= 0.2 (EtOAc/CH
MHz, CDCl ): δ 8.00 (d, JH−H = 7.5 Hz, 1H), 7.78 (d, JH−H = 8.0
Hz, 1H), 7.58 (t, JH−H = 7.5 Hz, 2H), 7.26 (m, 3H), 7.15−7.01 (m,
Cl = 1:9). Mp = 130−131 °C. H NMR (500
2 2
3 3
1
follows: R = 0.2 (EtOAc/CH Cl = 1:9). Mp = 123−124 °C. H
3
f
2
2
3
3
NMR (500 MHz, CDCl ): δ 7.44−7.35 (m, 8H), 7.16 (d, J
= 8.1
= 7.2 Hz, 2H),
3
H−H
3
3
3
3
Hz, 2H), 6.93 (d, J
= 7.8 Hz, 2H), 6.67 (d, J
6H), 6.95 (t, JH−H = 7.5 Hz, 2H), 6.83 (t, JH−H = 7.5 Hz, 1H), 6.45
H−H
H−H
1
3
1
3
13
1
4
1
1
1
.26 (s, 1H), 2.27 (s, 3H) ppm. C{ H} NMR (125 MHz, CDCl ): δ
42.0, 140.5, 139.6, 131.4, 131.0, 130.4, 128.8, 128.8, 128.6, 125.3,
24.5, 124.4, 121.4, 95.1, 21.2 ppm. IR (thin film): 3055, 2922, 2854,
511, 1476, 1443, 1112, 1076, 1022, 998, 826, 719, 688 cm . HRMS
(t, JH−H = 8.6 Hz, 1H), 5.29 (s, 1H) ppm. C{ H} NMR (125 MHz,
CDCl ): δ 141.7, 140.3, 132.9, 131.8, 131.4, 131.1, 130.2, 129.8,
128.7, 128.4, 128.3, 126.2, 125.3, 124.4, 124.3, 120.4, 120.0, 89.0 ppm
[one carbon signal is missing due to overlapping]. IR (thin film):
3056, 2966, 2928, 1464, 1418, 1160, 1129, 1070, 998, 804, 780, 688
3
3
−
1
+
calculated for C H O S Na 377.0646, found 377.0638 [M + Na] .
20
18
2 2
−
1
Bis(phenylsulfinyl)(4-(tert-butyl)phenyl))methane (2n). The re-
action was performed following General Procedure A with 1n (136
cm . HRMS calculated for C23
H
18
O
2
S
2
Na 413.0646, found 413.0647
+
[M + Na] .
t
mg, 0.5 mmol, 1.0 equiv), NaO- Bu (144 mg, 1.5 mmol, 3.0 equiv),
Bis(phenylsulfinyl)(3-thienyl)methane (2r). The reaction was
performed following General Procedure A with 1r (111 mg, 0.5
mmol, 1.0 equiv), NaO- Bu (144 mg, 1.5 mmol, 3.0 equiv), and di-
tert-butyl peroxide (200 μL, 1.1 mmol, 2.2 equiv). The crude product
was isolated by flash chromatography on silica gel (eluted with
and di-tert-butyl peroxide (200 μL, 1.1 mmol, 2.2 equiv). The crude
product was isolated by flash chromatography on silica gel (eluted
with EtOAc/CH Cl = 5:95) to give the product (49.7 mg, 50% yield,
t
2
2
rac/meso = 4:1) as a yellow solid. Compound rac-2n was purified by
silica gel column (eluted with EtOAc/CH Cl = 3:97,) to give yellow
EtOAc/CH
meso = 6:1) as a yellow solid. The rac-2r was purified by silica gel
column (eluted with EtOAc/CH Cl = 3:97) to give yellow solid
28.5 mg, 33% yield). The spectroscopic data of rac-2r are as follows:
2 2
Cl = 5:95) to give the product (35.6 mg, 41% yield, rac/
2
2
solid (37.1 mg, 37% yield). The spectroscopic data of rac-2n are as
1
follows: R = 0.2 (EtOAc/CH Cl = 1:9). Mp = 118−119 °C. H
2
2
f
2
2
3
(
NMR (500 MHz, CDCl ): δ 7.37−7.22 (m, 8H), 7.14 (d, J
= 7.5
3
H−H
1
3
R = 0.2 (EtOAc/CH Cl = 1:9). Mp = 132−133 °C. H NMR (500
Hz, 4H), 6.72 (d, J
= 7.5 Hz, 2H), 4.29 (s, 1H), 1.25 (s, 9H)
f
2
2
H−H
ppm. 13C{ H} NMR (125 MHz, CDCl ): δ 153.0, 142.1, 140.6,
1
MHz, CDCl ): δ 7.45−7.39 (m, 2H), 7.35−7.26 (m, 7H), 7.21 (s,
3
3
4
1
(
H), 7.20 (t, J
= 1.7 Hz, 1H), 7.14 (m, 1H), 7.10 (m, 1H), 4.51
1
3
31.5, 131.1, 130.2, 128.8, 128.6, 125.0, 124.6, 124.6, 121.5, 95.0,
4.6, 31.1 ppm. IR (thin film): 3018, 1215, 1050, 746, 669 cm .
H−H
1
3
1
−
1
s, 1H) ppm. C{ H} NMR (125 MHz, CDCl ): δ 142.0, 140.4,
31.6, 131.2, 128.9, 128.8, 128.5, 127.3, 125.6, 124.5, 124.3, 123.8,
3
1
9
8
3
HRMS calculated for C H O S 397.1296, found 397.1318 [M +
2
3
25
2 2
+
0.9 ppm. IR (thin film): 3057, 2920, 1474, 1418, 1173, 1069, 1021,
H] .
−
1
74, 836, 798, 688 cm . HRMS calculated for C H O S Na
Bis(phenylsulfinyl)(4-(methoxyl)phenyl)methane (2o). The reac-
17 14
2 3
+
69.0054. found 369.0063 [M + Na] .
Bis(phenylsulfinyl)(2-thienyl)methane (2s). The reaction was
performed following General Procedure A with 1s (111 mg, 0.5
mmol, 1.0 equiv), NaO- Bu (144 mg, 1.5 mmol, 3.0 equiv), and di-
tert-butyl peroxide (200 μL, 1.1 mmol, 2.2 equiv). The crude product
was isolated by flash chromatography on silica gel (eluted with
EtOAc/CH Cl = 5:95) to give the product (33.3 mg, 39% yield, rac/
meso = 6:1) as a yellow solid. Compound rac-2s was purified by silica
gel column (eluted with EtOAc/CH Cl = 3:97) to give yellow solid
(26.8 mg, 31% yield). The spectroscopic data of rac-2s are as follows:
tion was performed following General Procedure A with 1o (123 mg,
t
0
.5 mmol, 1.0 equiv), NaO- Bu (144 mg, 1.5 mmol, 3.0 equiv), and
di-tert-butyl peroxide (200 μL, 1.1 mmol, 2.2 equiv). The crude
product was isolated by flash chromatography on silica gel (eluted
with EtOAc/CH Cl = 7:93) to give the product (27.4 mg, 30% yield,
t
2
2
rac/meso = 6.4:1) as a yellow solid. Compound rac-2o was purified by
silica gel column (eluted with EtOAc/CH Cl = 5:95) to give yellow
2
2
2
2
solid (20.0 mg, 22% yield). The spectroscopic data of rac-2o are as
1
follows: R = 0.2 (EtOAc/CH Cl = 1:9). Mp = 104−105 °C. H
2
2
f
2
2
3
NMR (500 MHz, CDCl ): δ 7.44−7.24 (m, 8H), 7.15 (d, J
= 7.5
= 8.0 Hz, 2H),
3
H−H
1
3
3
R = 0.2 (EtOAc/CH Cl = 1:9). Mp = 112−113 °C. H NMR (500
MHz, CDCl ): δ 7.54 (m, 1H), 7.47 (m, 1H), 7.35 (m, 2H), 7.28−
Hz, 2H), 6.71 (d, J
= 7.5 Hz, 2H), 6.65 (d, J
f
2
2
H−H
H−H
1
3
1
4
1
1
1
.24 (s, 1H), 3.74 (s, 3H) ppm. C{ H} NMR (125 MHz, CDCl ): δ
60.7, 142.1, 140.5, 131.8, 131.4, 131.0, 128.8, 128.6, 124.5, 124.4,
16.3, 113.5, 94.8, 55.1 ppm. IR (thin film): 3018, 1510, 1441, 1254,
215, 1179, 1086, 1046, 754, 668 cm . HRMS calculated for
3
3
3
7
1
.21 (m, 4H), 7.04 (d, J
= 7.0 Hz, 2H), 6.98 (m, 2H), 6.87 (m,
H−H
1
3
1
H), 4.76 (s, 1H) ppm. C{ H} NMR (125 MHz, CDCl ): δ 143.1,
141.6, 132.8, 132.4, 132.0, 130.7, 130.5, 130.0, 129.7, 128.7, 128.6,
127.3, 127.1, 125.2, 96.3 ppm. IR (thin film): 3082, 2922, 2854, 1579,
493, 1451, 1400, 1338, 1223, 1089, 1000, 918, 852, 783, 615 cm .
3
−
1
+
C H O S Na 393.0595, found 393.0599 [M + Na] .
20
18
3 2
−
1
1
Bis(phenylsulfinyl)(2-methylphenyl)methane (2p). The reaction
HRMS calculated for C H O S 347.0234, found 347.0227 [M +
was performed following General Procedure A with 1p (115 mg, 0.5
17 15
2 3
+
t
H] .
mmol, 1.0 equiv), NaO- Bu (144 mg, 1.5 mmol, 3.0 equiv) and di-tert-
butyl peroxide (200 μL, 1.1 mmol, 2.2 equiv). The crude product was
isolated by flash chromatography on silica gel (eluted with EtOAc/
CH Cl = 5:95) to give the product (67.0 mg, 76% yield, rac/meso =
ASSOCIATED CONTENT
Supporting Information
■
2
2
*
S
4.73:1) as a yellow solid. Compound rac-2p was purified by silica gel
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.8b00476.
column (eluted with EtOAc/CH Cl = 3:97) to give yellow solid
2
2
(
50.3 mg, 57% yield). The spectroscopic data of rac-2p are as follows:
R = 0.2 (EtOAc/CH Cl = 1:9). Mp = 150−151 °C. H NMR (500
1
f
2
2
G
DOI: 10.1021/acs.organomet.8b00476
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Synthetic procedures, NMR spectra, and X-ray data
Article
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(PDF)
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Cartesian coordinates (XYZ)
(
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Chem., Int. Ed. 2014, 53, 6533−6537.
CCDC 1831929−1831930 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
(
15) Nguyen, M. H.; Imanishi, M.; Kurogi, T.; Smith, A. B. Total
Synthesis of (−)-Mandelalide A Exploiting Anion Relay Chemistry
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(
(
AUTHOR INFORMATION
Corresponding Authors
E-mail: liangxiaoxia@sicau.edu.cn.
E-mail: pwalsh@sas.upenn.edu.
■
Contreras, P. C.; Bhat, R. V. Differential patterns of regional c-Fos
induction in the rat brain by amphetamine and the novel wakefulness-
promoting agent modafinil. Neurosci. Lett. 1998, 241, 95−98.
(17) Aktiebolag, A. Method for the treatment of gastric acid-related
diseases and production of medication using (−) enantiomer of
omeprazole. U.S. Patent US5877192A, 1999.
*
*
ORCID
Xiaoxia Liang: 0000-0001-5002-5327
Patrick J. Walsh: 0000-0001-8392-4150
Notes
(
18) Mellah, M.; Voituriez, A.; Schulz, E. Chiral Sulfur Ligands for
Asymmetric Catalysis. Chem. Rev. 2007, 107, 5133−5209.
19) Sipos, G.; Drinkel, E. E.; Dorta, R. The emergence of sulfoxides
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20) Trost, B. M.; Rao, M. Development of Chiral Sulfoxide Ligands
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21) Otocka, S.; Kwiatkowska, M.; Madalinska, L.; Kiełbasinski, P.
́ ́
(
The authors declare no competing financial interest.
4
(
ACKNOWLEDGMENTS
P.J.W. thanks the National Science Foundation (CHE-
464744) for financial support. X.L. thanks the Program for
■
1
5
(
China Scholarship Council (201606915017) and NSFC
81703387).
Chiral Organosulfur Ligands/Catalysts with a Stereogenic Sulfur
Atom: Applications in Asymmetric Synthesis. Chem. Rev. 2017, 117,
(
4
147−4181.
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DOI: 10.1021/acs.organomet.8b00476
Organometallics XXXX, XXX, XXX−XXX

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