A Simplified Protocol for the Stereospecific Nickel-Catalyzed C-S Vinylation Using NiX 2 Salts and Alkyl Phosphites

Article abstract of DOI:10.1055/s-0039-1690717

A Ni-catalyzed C-S cross-coupling using only NiI ₂ (0.5-2.5 molpercent) and P(O i Pr) ₃ (2.0-10.0 molpercent) is reported. Using an air-stable Ni(II) precatalyst, and a cheap and commercially available ligand, a scalable and robust method was developed to cross-couple various thiophenols and styryl bromides, including some sterically encumbered thiols, an α-bromocinnamaldehyde as well as a thiolation-cyclization.

Full text of DOI:10.1055/s-0039-1690717

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–I
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A. D. Marchese et al.
Paper
Synthesis
A Simplified Protocol for the Stereospecific Nickel-Catalyzed C–S
Vinylation Using NiX2 Salts and Alkyl Phosphites
Austin D. Marchese
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0-0
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2-
3
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0-2
7
4
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R1
R1
NiI2 (0.5–2.5 mol%)
P(OiPr)3 (2–10 mol%)
R
SH
S
Bijan Mirabi
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0
0-
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2-3
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Br
Ar
+
R
Ar
Egor M. Larin
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3
7
3
DIPEA (2.5 equiv), DMF (0.4 M)
120 °C, 18 h
SR'
Br
Mark Lautens*
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21 examples
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low catalyst load
22–92% yield
O
Davenport Research Laboratories, Department of Chemistry,
University of Toronto, 80 St. George Street, Toronto, ON, M5S
3H6, Canada
Ph
H
SPh
Ph
mark.lautens@utoronto.ca
S
SPh
Received: 22.08.2019
A) Takeda's Ni[P(OEt)3]4 C–S coupling (2006)
Accepted after revision: 28.09.2019
Published online: 24.10.2019
DOI: 10.1055/s-0039-1690717; Art ID: ss-2019-n473-op
Ni[P(OEt)3]4, Et3N
DMF, 120 °C
S
Br
C(sp2)
R
SH
+
C(sp2)
or
R
Abstract A Ni-catalyzed C–S cross-coupling using only NiI2 (0.5–2.5
mol%) and P(OiPr)3 (2.0–10.0 mol%) is reported. Using an air-stable
Ni(II) precatalyst, and a cheap and commercially available ligand, a scal-
able and robust method was developed to cross-couple various thio-
phenols and styryl bromides, including some sterically encumbered thi-
ols, an -bromocinnamaldehyde as well as a thiolation-cyclization.
Ni[P(OEt)3]4, NaH
DMF/THF, reflux
R = Alkyl, Aryl
B) Stewart's nickel phosphine/phosphite C–S coupling (2018)
Ni[P(OPh)3]4, Zn, Xantphos
SH
Cl
S
+
Ar2
Ar2
Ar1
Ar1
base, toluene, 110 °C
Key words nickel, cross-coupling, scalable, heterocycles
C) Lautens' Ni-catalyzed carboiodination employing NiI2 + P(OR)3 (2018/2019)
Utilizing base metals as catalysts in cross-coupling reac-
tions have garnered increasing interest in the last few
years.1 Nickel has emerged as a popular choice, as it offers
similar reactivity to its 4d relative, palladium, but is more
economical and occasionally allows for novel chemistry.
Amongst the various Ni-catalyzed cross-coupling reac-
tions reported, C–S couplings are relatively uncommon.2
The vast majority of Ni-catalyzed C–S cross-couplings em-
ploy the use of sensitive Ni(0) precatalysts, require the prior
synthesis of a Ni-complex (Scheme 1a,b),2a,d and/or need to
introduce a metal reducing agent.2a,b
Recently, our group reported Ni-catalyzed carboiodina-
tion reactions utilizing NiI2 and alkyl phosphites, without
the need for a metallic reducing agent such as zinc or man-
ganese (Scheme 1c).3 We sought to explore if this method
could be broadly applied to other types of cross-coupling
reactions.
Ni-phosphite catalysts have been shown to achieve C–S
cross-coupling reactions with aryl and vinyl halides.2a,d In
2006, Takeda reported the use of Ni[P(OEt)3]4 as a catalyst
for the vinylation of thiols (Scheme 1a),2d which was ex-
panded upon in their report of a Ni-catalyzed allylic thiola-
tion of allyl acetates.4 More recently, Stewart reported a
phosphine/phosphite C–S arylation of thiols using
I
I
R
NiI2 + P(OEt)3 or P(OiPr)3
Y
X
Y
X,Y = NR', CO or CO, N or NAc, CR"
R
X
Scheme 1 Relevant Ni-catalyzed coupling reactions employing phos-
phites as the ligand
Ni[P(OPh)3]4 and xantphos as a ligand, as well as Zn as a re-
ducing agent (Scheme 1b).2a These reports both share the
same requirement, namely the necessity to prepare the
Ni(0) precatalyst prior to the reaction. Ni(II) precatalysts for
C–S cross coupling with vinyl halides are rare, and still re-
quire formation of the Ni(II) complex.2e,f The synthesis of a
NiBr2(bipy) complex was accomplished prior to Ni(II) C–S
cross coupling, which has demonstrated a limited scope
and has shown inconsistencies with respect to the stereo-
selectivity of the reaction.2e
Herein we report a simple, robust, and scalable Ni-cata-
lyzed C–S vinylation employing an air-stable Ni(II) precata-
lyst, and a cheap phosphite ligand. Beyond the use of the
Ni(II) salt, this method improves upon the known Ni-phos-
phite C–S coupling protocols, as the reported catalyst load-
ing is less than one-half of the corresponding Ni(0)-
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–I
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
A. D. Marchese et al.
Paper
Synthesis
phosphite methodology. We have also broadened the sub-
strate scope to incorporate hindered ortho-substituted thio-
phenols (ortho-substituted thiophenols were not explored
in the previous vinylation methodology), as well as no lon-
ger requiring the distillation and degassing of the solvent;
something that was necessary in both of the previous Ni-
phosphite C–S cross coupling reactions. In addition, we re-
port a method to achieve a one-pot, two-step synthesis of
useful vinyl sulfones in moderate yield and excellent selec-
tivity, as well as a method to obtain sulfur-containing het-
erocycles via a thiolation-cyclization cascade reaction.
Initial success was obtained using conditions analogous
to Takeda’s, while employing the variation we had reported
using NiI2 (10 mol%) and triethyl phosphite (40 mol%) that
proved successful in our previously reported Ni-catalyzed
carboiodination (Table 1).
Changing the solvent to dimethylacetamide (DMA) gave
the product in only 44% yield. Changing to an inorganic base
such as K2CO3 gave 2a in 61% yield whereas 2.5 equivalents
of DIPEA provided 2a in 90% yield. Lowering the tempera-
ture to 100 °C led to incomplete conversion of starting ma-
terial and a yield of 80%. Fortunately, when using non-dried,
non-distilled, non-degassed DMF, the efficiency was un-
changed. This result is noteworthy, as both previous Ni-
phosphite C–S cross-coupling reports required dried and
degassed solvent, further illustrating the robust nature of
this method.
When the reaction was run under air, product 2a was
formed in a 50% yield. Changing the ligand to P(OiPr)3 with
DIPEA as the base further improved the reaction, generating
the product in a 93% yield. Reducing the catalyst load to 2.5
mol% while using P(OiPr)3 as the ligand and DIPEA as the
base showed little impact on the reaction. Changing the
catalyst to NiBr2 or NiCl2DME gave reduced yields of 87%
and 75%, respectively. We opted to continue using NiI2 as
the catalyst based on its superior reactivity and the higher
molecular weight of the NiI2 makes it a more practical op-
tion to use on small-scale. Lowering the amount of ligand to
7.5 mol% with 2.5 mol% catalyst did show a slight decrease
in yield (86%). Optimal conditions were achieved by dou-
bling the amount of substrate in the reaction, while reduc-
ing the amount of catalyst to 1.25 mol% with 5 mol%
P(OiPr)3, in DMF (0.42 M) at 120 °C for 18 hours, giving the
product 2a in 88% isolated yield.
Table 1 Optimization of Ni-Phosphite-Catalyzed C–S Cross Coupling
Br
SPh
NiI2 (10 mol%)
SH
P(OEt)3 (40 mol%)
+
Et3N (2.5 equiv), DMF (1 mL)
120 °C, 18 h
2a: 86%
90:10 E/Z
1a: 90:10 E/Z
(0.21 mmol)
(0.24 mmol)
Entry
Variation
Yield (%)a
1
2
3
4
DMA instead of DMF
K2CO3 instead of Et3N
DIPEA instead of Et3N
44
61
90
80
We then ran control reactions in order to further probe
the reaction. In the absence of NiI2 there remained a slow
background reaction, providing the product in 25% yield
and a 94:6 E/Z ratio. Non-catalyzed coupling has been pre-
viously reported,2f and is known to be extremely non-selec-
tive with significant decomposition observed, but the
mechanism is unknown. This background reaction was not
observed with all substrates, for example, 2s was observed
in only trace amount in the absence of NiI2 when starting
from the gem-dibromo olefin 1s.
100 °C instead of
120 °C
5
6
DMF out of the bottle
89
50
93
90
87
75
86
without use of inert atmosphere
P(OiPr)3 with DIPEA
7
8
P(OiPr)3, DIPEA, 2.5% catalyst load
P(OiPr)3, DIPEA, 2.5% NiBr2
P(OiPr)3, DIPEA, 2.5% NiCl2DME
9
10b
11
P(OiPr)3 (7.5 mol% instead of 10 mol%),
In the absence of P(OiPr)3, 1a reacted and gave product
2a in 77% isolated yield after 18 hours. Monitoring by NMR
spectroscopy showed 2a is formed in only 64% yield in the
absence of phosphite after 6 hours, as opposed to 84% yield
with the phosphite. This result indicates that the phosphite
plays a positive role in the catalytic reaction but is not es-
sential.
DIPEA, 2.5% catalyst load
12
P(OiPr)3, DIPEA, 1.25% catalyst load, 0.42 M 93 (88)
concentration
a All yields were determined by 1H NMR analysis of the crude reaction mix-
ture using 1,3,5-trimethoxybenzene as the internal standard. Concentra-
tion is with respect to the styryl bromide. The value in parentheses
corresponds to isolated yield.
b E/Z ratio was 93:7.
‘Ligand-free’ Ni-catalyzed C–S cross-coupling is known,
but only using aryl halides as the coupling partner.2c We
speculate that in the absence of the phosphite, excess thio-
phenol can act as a reducing agent, as thiols are known to
reduce various metal salts.5 In Stewart’s 2018 report, the
authors cite using Zn as a reducing agent to reduce in situ
generated disulfides. Phosphorus has also been known to
perform this reduction;6 however, as we only add 2–5 mol%
phosphite this path seems unlikely. We are currently un-
sure of the exact role the phosphite plays in the reaction as
It is important to note that the optimization reactions
maintained the 90:10 E/Z ratio from starting materials in
the products, suggesting the reaction is highly stereospecif-
ic. We subjected a 50:50 E/Z mixture of 1a to the reaction
conditions, which gave a mixture of 2a (70% NMR yield)
with a 1.4:1 E/Z ratio, as well as had 10% of unreacted (Z)-
1a. This result suggests that the reaction is stereospecific
for each isomer, and the rate of reaction of the Z-isomer is
slower, most likely due to the increased steric hindrance.
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–I

C
A. D. Marchese et al.
Paper
Synthesis
it may take part in the reduction of the NiI2 and/or act as a
ligand for the metal, but its presence is essential to achieve
high yields in this process.
addition at this site. Surprisingly the 3-nitro moiety was
well tolerated giving the product 2n in 91% yield. Introduc-
tion of a methyl group at the 2-position inhibited the reac-
tion, and 2o was isolated in only 22% yield. Increased steric
hindrance of the olefin, could impact complexation to the
olefin or oxidative addition into the vinyl bromide. Incorpo-
ration of a thiophene moiety led to the formation of prod-
uct 2p. Product 2p was only obtained in 56% isolated yield,
as the reaction and purification led to substantial decompo-
sition into unknown by-products. There was a slight degra-
dation in the stereospecificity of the reaction, as the prod-
uct was obtained in a 92:8 E/Z ratio.
Employing (Z)--bromocinnamaldehyde as the olefin
coupling partner gave the Z-product 2q in 78% yield with a
>95:5 Z/E ratio. This example demonstrates the excellent
chemoselectivity of the reaction and represents a conve-
nient method to perform an -functionalization of an enal,
as this system is particularly susceptible to 1,2 and 1,4-ad-
ditions in the presence of nucleophiles. Using (E)-(1-bro-
moprop-1-en-2-yl)benzene in the cross-coupling reaction
required 10 mol% catalyst to achieve complete conversion,
which afforded the E-thiolated product 2r in a 92% yield
with a >95:5 E/Z ratio.
We varied the stereoelectronic nature of the thiophenol
coupling partner (Scheme 2). Para-halogens on the aromat-
ic ring were tolerated, as the 4-Cl and 4-F substrates react to
give 91% and 77% yield, respectively, while maintaining
high stereospecificity (2b and 2c). An electron-withdrawing
4-CF3 group was also tolerated, providing the product 2d in
76% yield. A highly nucleophilic 4-OMe benzenethiol was
employed in the reaction, giving the product 2e in 88% yield
with a 91:9 E/Z ratio. Introduction of a 3-OMe group was
also possible, giving product 2f in 90% yield. Even ortho-
substitution on the thiophenol moiety was tolerated, as the
2-F, 2-Me, and even 2-iPr coupled products 2g–i were all
obtained in good to excellent yields. Interestingly, the yield
increased as the steric hindrance at the 2-position in-
creased. Nickel C–S coupling reactions are thought to termi-
nate via a reductive elimination.2b–d This trend may suggest
that increased steric hindrance at the ortho-position may
facilitate a more facile reductive elimination. These results
are noteworthy, as the previous Ni(0)-phosphite catalyzed
C–S vinylation report did not include any ortho-substituted
thiophenol coupling partners.
After examining the scope of vinyl sulfides, the ability
to generate dithiolated compounds was explored. Success
was found when employing the gem-dibromo olefin 1s as
the thioketene acetal 2s was obtained in 43% yield via a
double thiolation (Scheme 4). Expanding on this idea, we
attempted to perform an intra- and intermolecular C–S
coupling reaction.
We then focused our attention to the vinyl bromide cou-
pling partner (Scheme 3). Both para electron-donating and
-withdrawing groups were tolerated, giving products 2j and
2k in excellent yields. A substrate bearing a para-methyl
group also reacted, giving product 2l in 87% yield. A sub-
strate containing a chloride moiety at the 3-position im-
pacted the reaction, perhaps due to competitive oxidative
Br
NiI2 (1.25 mol%)
SH
R
S
P(OiPr)3 (5 mol%)
R
+
DIPEA (2.5 equiv), DMF (1 mL)
120 °C, 18 h
90:10 E/Z
(0.42 mmol)
(0.48 mmol)
S
S
S
Cl
F
2a: 88%
90:10 E/Z
2b: 91%
90:10 E/Z
2c: 77%
91:9 E/Z
S
S
S
CF3
OMe
OMe
2d: 76%
92:8 E/Z
2e: 88%
91:9 E/Z
2f: 90%
91:9 E/Z
S
F
S
S
iPr
Me
2h: 70%
95:5 E/Z
2i: 88%
90:10 E/Z
2g: 61%
92:8 E/Z
Scheme 2 Investigation of the stereoelectronic variability of the thiophenol component in the Ni-phosphite-catalyzed C–S cross-coupling reaction
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–I

D
A. D. Marchese et al.
Paper
Synthesis
R2
R2
NiI2 (1.25 mol%)
P(OiPr)3 (5 mol%)
SH
Br
R1
S
+
R1
R3
DIPEA (2.5 equiv), DMF (1 mL)
120 °C, 18 h
R3
(0.48 mmol)
>95:5 E/Z
(0.42 mmol)
S
S
S
MeO
F3C
Me
2j: 90%
2k: 87%
2l: 87%
>95:5 E/Z
>95:5 E/Z
>95:5 E/Z
S
S
S
Me
NO2
Cl
S
2n: 91%
>95:5 E/Z
2o: 22%
>95:5 E/Z
2m: 48%
>95:5 E/Z
Me
S
CHO
S
S
2p: 56%
92:8 E/Z
2q: 78%
>95:5 E/Z
2r: 92%
>95:5 E/Z
Scheme 3 Investigation of the stereoelectronic variability of the vinyl bromide component in the Ni-phosphite-catalyzed C–S cross-coupling reaction
Ni-catalyzed intramolecular C–S cross-couplings were
reported by Peng, using alkyl thiols tethered to an aryl io-
A) Double-thiolation using NiI2 and P(OiPr)3
Br
SPh
SPh
dide, to generate the cyclized products in moderate to ex-
cellent yields.2b Moreover, cyclizations using gem-dibromo
olefins are well established using Pd,7 but virtually un-
known with Ni. Double-thiolation has not been achieved
using simple thiols. We determined that benzothiophene 2t
could be isolated in 44% yield, arising from inter- and intra-
molecular C–S bond formation.
We also developed a one-pot, two-step method to ob-
tain vinyl sulfones via addition of mCPBA after the reaction,
as sulfone 2u was obtained in 50% yield, exclusively as the
E-isomer, a phenomenon also observed by Takeda in 2006
when they reported the mono-oxidation of the vinyl sulfide
to the sulfoxide.2d We observed 20% (NMR) yield of the cor-
responding sulfoxide in the reaction but were still unable to
push the reaction to full conversion by lengthening the re-
action time.
NiI2 (1.25 mol%)
SH
P(OiPr)3 (5 mol%)
Br
+
DIPEA (2.5 equiv), DMF (1 mL)
120 °C, 18 h
(0.88 mmol)
2s: 43%
1s: (0.4 mmol)
Br
NiI2 (2.5 mol%)
SH
SPh
P(OiPr)3 (10 mol%)
Br
S
SH
+
DIPEA (2.5 equiv), DMF (1 mL)
120 °C, 18 h
(0.44 mmol)
2t: 44%
1t: (0.4 mmol)
B) One-pot, two-step C–S cross-coupling/oxidation protocol
O
S
O
1) NiI2 (1.25 mol%)
P(OiPr)3 (5 mol%)
Br
SH
Ph
+
DIPEA (2.5 equiv), DMF (1 mL)
120 °C, 18 h
2) mCPBA (10 equiv)
DCM (3 mL), 1 h
1a: 90:10 E/Z
(0.4 mmol)
(0.42 mmol)
2u: 50%
>95:5 E/Z
We sought to showcase the scalability of this reaction.
The reaction was run on a 5.6 mmol scale (1.03 g) using
only 0.5 mol% catalyst, which gave product 2a in 90% yield.
We view these results as supporting the utility of this
methodology to generate vinyl sulfides, as it does not re-
quire any external metallic reducing agent, synthesis or uti-
lization of a Ni(0) precatalyst or any drying or deoxygen-
ation of solvents or reagents prior to the reaction.
C) Gram-scale Ni-phosphite catalyzed C-S cross-coupling reaction
Br
SPh
NiI2 (0.5 mol%)
SH
P(OiPr)3 (2 mol%)
+
DIPEA (2.5 equiv), DMF (0.4 M)
120 °C, 18 h
(6.16 mmol)
2a: 90%
90:10 E/Z
1a: 90:10 E/Z
(5.6 mmol)
Scheme 4 A) Ni-phosphite-catalyzed double thiolation of vinyl bro-
In conclusion, we have demonstrated a convenient, ro-
bust, and scalable method to perform stereospecific Ni-cat-
alyzed C–S vinylation reactions utilizing NiI2 and an alkyl
phosphite. This method builds upon the current literature
of Ni-phosphite cross-coupling reactions, as the ability to
mides. B) One-pot, two-step C–S cross-coupling/oxidation protocol. C)
Gram-scale Ni-phosphite-catalyzed C–S cross-coupling reaction.
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–I

E
A. D. Marchese et al.
Paper
Synthesis
start with air-stable Ni(II) salts and commercially available
phosphites negates the need for synthesis of Ni(0) precata-
lysts or metal reducing agents. This work reports a more ro-
bust version of Ni-catalyzed C–S vinylation reactions, as we
have had success with catalyst loads as low as 0.5 mol%,
while using an untreated hygroscopic solvent. Future work
includes further development of the double-thiolation cy-
clization reaction as seen in compound 2t, as to the best of
our knowledge, Ni-catalyzed cross-coupling cyclization re-
actions of gem-dibromo olefins are unexplored.
lon cap and Teflon tape. The reaction was heated between 120 °C for
18 h. The reaction mixture was cooled to r.t. and purified via silica gel
column flash chromatography with a mobile phase of 20:1 pen-
tane/DCM.
Ni-Catalyzed Thiolation-Cyclization; General Procedure 3
Reactions were run in 2-dram vials and stir bars that were oven-dried
overnight. The vial was charged with NiI2 (2.5 mol%), ligand P(OiPr)3
(10 mol%) under a flow of argon. DMF (1 mL) was added. The gem-
dibromide (0.42 mmol), DIPEA (4.4 equiv), and thiophenol (0.48
mmol) were added subsequently in that order. The vial was fitted
with a Teflon cap and Teflon tape. The reaction was heated between
120 °C for 18 h. The reaction mixture was cooled to r.t. and purified
via silica gel column flash chromatography with a mobile phase of
10:1 pentane/DCM.
All reactions were performed under an inert atmosphere of argon,
unless otherwise stated. Reactions were monitored by TLC and visu-
alized under UV light or by I2 staining. Flash column chromatography
was performed with Silicycle 46–60 m silica gel. Catalytic reactions
were performed in 2-dram vials equipped with a Teflon cap. THF was
distilled over Na/benzophenone. Toluene and DCM were distilled over
CaH2. 1,3,5-Trimethoxybenzene was dried overnight under vacuum
and stored in a desiccator.
One-Pot, Two-Step C–S Cross-Coupling Oxidation; General Proce-
dure 4
Reactions were run in 2-dram vials and stir bars that were oven-dried
overnight. The vial was charged with NiI2 (1.25 mol%), ligand P(OiPr)3
(5 mol%) under a flow of argon. DMF (1 mL) was added. Stytyl bro-
mide (0.42 mmol), DIPEA (2.5 equiv), and thiophenol (0.48mmol)
were added subsequently in that order. The vial was fitted with a Tef-
lon cap and Teflon tape. The reaction was heated between 120 °C for
18 h. The reaction was cooled to 0 °C, where a solution of mCPBA (10
equiv) in DCM (3 mL) was added dropwise. The reaction mixture was
let stir for 1 h and extracted with sat. aq NaHCO3 (5 ×). The crude was
concentrated in vacuo and purified via silica gel column flash chro-
matography with a mobile phase of 3:1 pentane/EtOAc.
All reagents and organic building blocks were purchased from com-
mercial suppliers (Sigma-Aldrich, Alfa Aesar, TCI, Combi-Blocks, Oak-
wood Chemical, AK Scientific) and used as received. NMR characteri-
zation data was collected at 296 K on aVarian Mercury 400 or an Agi-
lent DD2 500 equipped with a 5 mm Xses Cold Probe. Spectra were
internally referenced to the residual solvent signal (1H NMR: CDCl3 =
7.26 ppm, 13C NMR: CDCl3 = 77.0 ppm). Data for 1HNMR is reported as
follows: chemical shift ( ppm), multiplicity (standard abbreviations),
coupling constant (Hz), integration. Coupling constants were rounded
to the nearest 0.5 Hz. High-resolution mass spectra (HRMS) were ob-
tained on a Micromass 70S-250 spectrometer (EI) or an ABI/Sciex
QStar Mass Spectrometer (ESI) or a JEOL AccuTOF model JMS-T1000LC
mass spectrometer equipped with and IONICS® Direct Analysis in
Real Time (DART) ion source at Advanced Instrumentation for Molec-
ular Structure (AIMS) in the Department of Chemistry at the Universi-
ty of Toronto.
General Procedure 5 for 1i8
The corresponding carboxylic acid was stirred in a mixture of 1.5:1
MeCN/H2O (0.06 M). NaBr (3.0 equiv) and Na2CO3 (1.0 equiv) were
subsequently charged. Following this, a solution of Oxone (1.0 equiv)
in H2O (0.15 M) was added dropwise and the reaction mixture was
stirred overnight at r.t. Upon completion, the reaction was quenched
with Na2S2O3 and extracted thrice with EtOAc (3 ×) and subsequently
dried (MgSO4), concentrated and purified via silica gel column using
20:1 pentane/EtOAc.
Ni-Catalyzed C–S Cross-Coupling Reaction; General Procedure 1
Reactions were run in 2-dram vials and stir bars that were oven-dried
overnight. The vial was charged with NiI2 (1.25 mol%), ligand P(OiPr)3
(5 mol%) under a flow of argon. DMF (1 mL) was added. Styryl bro-
mide (0.42 mmol), DIPEA (2.5 equiv), and thiophenol (0.48 mmol)
were added subsequently in that order. The vial was fitted with a Tef-
lon cap and Teflon tape. The reaction was heated between 120 °C for
18 h. All NMR spectra were collected in CDCl3. Compounds were air-
stable at r.t. but were stored in the freezer for precaution. E/Z ratios
were obtained via 1H NMR from the crude reaction mixture to avoid
the possibility of artificial changes during the purification process.
For the reaction run on a 5.6 mmol scale, all procedures were the
same using a 9.5-dram vial and all reagents were scaled accordingly.
General Procedure 6 for 1j–m9
To a flame dried round-bottomed flask, were added aldehyde (1.0
equiv) and CBr4 (1.5 equiv) dissolved in DCM (0.15 M), and cooled to 0
°C. Ph3P (3 equiv) was added in three portions and the reaction was
stirred for 1 h. Upon reaction completion, the reaction mixture was
concentrated to about half of its initial volume, and roughly twice as
much pentane as DCM were added. The suspension was filtered over
a pad of silica gel, eluting with 30% EtOAc in pentanes to remove
triphenylphosphine oxide and concentrated. The crude was then re-
dissolved in DMF (0.7 M), and diethyl phosphite (3 equiv) and Et3N (3
equiv) were added. The reaction mixture was stirred overnight. Upon
reaction completion, H2O was added and the crude was extracted
thrice with pentane (3 ×). The combined organic phases were washed
once with 1 M HCl and concentrated. The crude was now dissolved in
iPrOH (0.66 M) and powdered NaOH (0.85 equiv) was added, and the
reaction was refluxed for 2 h. Upon reaction completion, it was dilut-
ed with pentane and washed with H2O and aq 1 M HCl. The organic
layers were concentrated and were purified via a silica gel column
eluting with pentanes.
Ni-Catalyzed Double C–S Cross-Coupling Reaction; General Proce-
dure 2
Reactions were run in 2-dram vials and stir bars that were oven-dried
overnight. The vial was charged with NiI2 (1.25 mol%), ligand P(OiPr)3
(5 mol%) under a flow of argon. DMF (1 mL) was added. The gem-di-
bromide (0.42 mmol), DIPEA (4.4 equiv) and thiophenol (0.95 mmol)
were added subsequently in that order. The vial was fitted with a Tef-
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–I

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A. D. Marchese et al.
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Synthesis
(E)-1-(2-Bromovinyl)-4-methoxybenzene (1j)
(E)-(4-Fluorophenyl)(styryl)sulfane (2c)
Vinyl bromide 1j was synthesized according to General Procedure 5
on a 5 mmol scale;8 yield: 594 mg (56%, 2.80 mmol); E/Z ratio = >95:5.
The known compound 2c was prepared according to General Proce-
dure 1 on a 0.42 mmol scale. Compound 2c was isolated via silica gel
flash column chromatography with a mobile phase of 100% pentane
as a white solid; yield: 75.8 mg (77%, 0.323 mmol, 91:9 E/Z); mp 31–
33 °C. Characterization was consistent with the literature reported
values.10
1H NMR (500 MHz, CDCl3):  = 6.42 (minor, d, J = 10.7 Hz, 0.09 H), 6.58
(d, J = 10.8 Hz, 0.09 H), 6.67 (major, d, J = 15.4 Hz, 1 H), 6.83 (major, d,
J = 15.4 Hz, 1 H), 7.07 (t, J = 8.7 Hz, 2 H), 7.25 (m, 1 H), 7.29–7.37 (m, 2
H), 7.43 (minor, dd, J = 8.9, 5.2 Hz, 0.25 H), 7.52–7.55 (minor, m, 0.1
H), 7.59 (minor, dd, J = 8.9, 5.2 Hz, 0.1 H).
(E)-1-(2-Bromovinyl)-4-(trifluoromethyl)benzene (1k)
Vinyl bromide 1k was synthesized according to General Procedure 6
on a 7 mmol scale;9 yield: 735 mg (42%, 2.94 mmol); E/Z ratio = >95:5.
(E)-1-(2-Bromovinyl)-4-methylbenzene (1l)
Vinyl bromide 1l was synthesized according to General Procedure 6
on a 3 mmol scale;9 yield: 447 mg (68%, 2.04 mmol); E/Z ratio = >95:5.
13C NMR (126 MHz, CDCl3):  (E-isomer) = 116.37 (d, J = 22.0 Hz),
123.89, 126.00, 127.62, 128.72, 131.21, 132.59, 132.65, 136.43,
162.31 (d, J = 247.3 Hz).
(E)-1-(2-Bromovinyl)-3-chlorobenzene (1m)
Vinyl bromide 1m was synthesized according to General Procedure 6
on a 7 mmol scale;9 yield: 953 mg (63%, 4.41 mmol); E/Z ratio = >95:5.
(E)-Styryl[4-(trifluoromethyl)phenyl]sulfane (2d)
(E)-1-(2-Bromovinyl)-3-nitrobenzene (1n)
The known compound 2d was prepared according to General Proce-
dure 1 on a 0.42 mmol scale. Compound 2d was isolated via silica gel
flash column chromatography with a mobile phase of 100% pentane
as a white solid; yield: 89.4 mg (76%, 0.319 mmol, 92:8 E/Z); mp 71–
74 °C. Characterization was consistent with the literature reported
values.11
1H NMR (500 MHz, CDCl3):  = 6.50 (minor, d, J = 10.6 Hz, 0.11 H), 6.75
(minor, d, J = 10.6 Hz, 0.1 H), 6.87 (major, d, J = 15.4 Hz, 1 H), 6.93
(major, d, J = 15.4 Hz, 1 H), 7.27–7.33 (m, 1 H), 7.35–7.38 (m, 2 H),
7.40–7.43 (m, 2 H), 7.46 (d, J = 7.8 Hz, 2 H), 7.57 (d, J = 8.3 Hz, 3 H).
Vinyl bromide 1n was synthesized according to General Procedure 6
on a 3 mmol scale;9 yield: 449 mg (66%, 2.01 mmol); E/Z ratio = >95:5.
(E)-1-(2-Bromovinyl)-2-methylbenzene (1o)
Vinyl bromide 1o was synthesized according to General Procedure 6
on a 7 mmol scale;9 yield: 645 mg (47%, 3.29 mmol); E/Z ratio = >95:5.
(E)-2-(2-Bromovinyl)thiophene (1p)
Vinyl bromide 1p was synthesized according to General Procedure 6
on a 5 mmol scale;9 yield: 423 mg (45%, 2.25 mmol); E/Z ratio = 90:10.
13C NMR (126 MHz, CDCl3):  (E-isomer) = 125.88 (q, J = 3.8 Hz), 126.3
(q, J = 272.5 Hz), 126.32, 128.19, 128.26, 128.47 (d, J = 18.0 Hz),
128.88, 128.92, 135.36, 136.01, 141.29 (d, J = 1.5 Hz).
(E)-Phenyl(styryl)sulfane (2a)
The known compound 2a was prepared according to General Proce-
dure 1 on a 0.42 mmol scale. Compound 2a was isolated via silica gel
flash column chromatography with a mobile phase of 5:1 pen-
tane/DCM as a colorless oil; yield: 78.4 mg (88%, 0.371 mmol). The re-
action was also run on a 1.03 g scale, using 0.5 mol% NiI2 and 2%
P(OiPr)3 in a 9.5-dram vial for 18 h at 120 °C; yield: 1.07 g (90%, 5.04
mmol, 90:10 E/Z). Characterization was consistent with the literature
reported values.10
(E)-(4-Methoxyphenyl)(styryl)sulfane (2e)
The known compound 2e was prepared according to General Proce-
dure 1 on a 0.42 mmol scale. Compound 2e was isolated via silica gel
flash column chromatography with a mobile phase of 20:1 pen-
tane/EtOAc as a white powder; yield: 91.8 mg (88%, 0.386 mmol, 91:9
E/Z); mp 48–51 °C. Characterization was consistent with the litera-
ture reported values.12
1H NMR (500 MHz, CDCl3):  = 6.51 (minor, d, J = 10.7 Hz, 0.08 H), 6.60
(minor, d, J = 10.7 Hz, 0.08 H), 6.75 (major, d, J = 15.5 Hz, 1 H), 6.90
(major, d, J = 15.5 Hz, 1 H), 7.17–7.28 (m, 2 H), 7.29–7.38 (m, 6 H),
7.39–7.46 (m, 2 H), 7.46–7.58 (m, 0.08 H).
1H NMR (500 MHz, CDCl3):  = 3.81 (minor, s, 0.3 H), 3.83 (major, s, 3
H), 6.42 (minor, d, J = 10.8 Hz, 0.1 H), 6.50 (minor, d, J = 10.8 Hz, 0.1
H), 6.53 (major, d, J = 15.4 Hz, 1 H), 6.85 (major, d, J = 15.5 Hz, 1 H),
6.90–6.96 (m, 2 H), 7.19–7.25 (m, 1 H), 7.25–7.35 (m, 4 H), 7.39–7.47
(m, 2 H), 7.52–7.56 (minor, m, 0.3 H).
13C NMR (126 MHz, CDCl3):  (E-isomer) = 123.39, 126.02, 126.95,
13C NMR (126 MHz, CDCl3):  (E-isomer) = 55.40, 114.91, 124.50,
127.59, 128.69, 129.16, 129.83, 131.81, 135.22, 136.53.
125.73, 125.82, 127.20, 128.64, 128.98, 133.49, 136.75, 159.59.
(E)-(4-Chlorophenyl)(styryl)sulfane (2b)
The known compound 2b was prepared according to General Proce-
dure 1 on a 0.42 mmol scale. Compound 2b was isolated via silica gel
flash column chromatography with a mobile phase of 5:1 pen-
tane/DCM as a white solid; yield: 94.2 mg (91%, 0.382 mmol, 90:10
E/Z); mp 52–56 °C. Characterization was consistent with the litera-
ture reported values.10
(E)-(3-Methoxyphenyl)(styryl)sulfane (2f)
The known compound 2f was prepared according to General Proce-
dure 1 on a 0.42 mmol scale. Compound 2f was isolated via silica gel
flash column chromatography with a mobile phase of 100% pentane
as a colorless oil; yield: 91.8 mg (90%, 0.386 mmol, 91:9 E/Z). Charac-
terization was consistent with the literature reported values.13
1H NMR (500 MHz, CDCl3):  = 6.45 (minor, d, J = 10.6 Hz, 0.11 H), 6.66
(minor, d, J = 10.7 Hz, 0.12 H), 6.78 (major, d, J = 15.5 Hz, 1 H), 6.85
(major, d, J = 15.5 Hz, 1 H), 7.25–7.30 (m, 1 H), 7.32–7.45 (m, 9 H),
7.52–7.58 (minor, m, 0.24 H).
1H NMR (500 MHz, CDCl3):  = 3.79 (minor, s, 0.3 H), 3.80 (major, s, 3
H), 6.52 (minor, d, J = 10.7 Hz, 0.1 H), 6.60 (minor, d, J = 10.8 Hz, 0.1
H), 6.76 (major, d, J = 15.5 Hz, 1 H), 6.80 (major, ddd, J = 8.3, 2.5, 0.9
Hz, 1 H), 6.82 (minor, dd, J = 2.5, 0.9 Hz, 0.1 H), 6.89 (major, d, J = 15.5
Hz, 1 H), 6.96 (major, dd, J = 2.5, 1.7 Hz, 1 H), 7.00 (major, ddd, J = 7.7,
13C NMR (126 MHz, CDCl3):  (E-isomer) = 122.50, 126.10, 127.84,
128.74, 129.30, 130.97, 132.76, 132.99, 133.85, 136.27.
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–I

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A. D. Marchese et al.
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Synthesis
1.7, 0.9 Hz, 1 H), 7.05 (minor, ddd, J = 7.7, 1.7, 0.9 Hz, 0.1 H), 7.21–7.28
(m, 2 H), 7.29–7.37 (m, 4 H), 7.37–7.41 (minor, m, 0.3 H), 7.53 (minor,
ddd, J = 8.4, 1.2, 0.6 Hz, 0.2 H).
as a white solid; yield: 91.0 mg (90%, 0.372 mmol, >95:5 E/Z); mp 47–
49 °C. Characterization was consistent with the literature reported
values.12
13C NMR (126 MHz, CDCl3):  (E-isomer) = 55.35, 112.73, 114.91,
121.85, 123.00, 126.09, 127.67, 128.71, 129.99, 132.18, 136.50,
136.62, 160.05.
1H NMR (500 MHz, CDCl3):  = 3.82 (major, s, 3 H), 3.84 (minor, s, 0.3
H), 6.39 (minor, d, J = 10.6 Hz, 0.1 H), 6.58 (minor, d, J = 10.6 Hz, 0.1
H), 6.73 (major, d, J = 15.4 Hz, 1 H), 6.78 (d, J = 15.4 Hz, 1 H), 6.88 (d,
J = 8.8 Hz, 2 H), 6.95 (d, J = 8.8 Hz, 0.1 H), 7.21–7.28 (m, 1 H), 7.29–
7.36 (m, 4 H), 7.38–7.44 (m, 2 H), 7.46–7.49 (m, 0.1 H), 7.50–7.53 (m,
0.1 H).
(E)-(2-Fluorophenyl)(styryl)sulfane (2g)
The known compound 2g was prepared according to General Proce-
dure 1 on a 0.42 mmol scale. Compound 2g was isolated via silica gel
flash column chromatography with a mobile phase of 100% pentane
as a colorless oil; yield: 58.9 mg (61%, 0.256 mmol, 92:8 E/Z). Charac-
terization was consistent with the literature reported values.10
13C NMR (126 MHz, CDCl3):  (E-isomer) = 55.33, 114.15, 120.07,
126.60, 127.39, 129.10, 129.26, 129.39, 132.76, 135.96, 159.39.
(E)-(4-Trifluoromethylstyryl)(phenyl)sulfane (2k)
1H NMR (500 MHz, CDCl3):  = 6.42 (minor, dd, J = 10.7, 0.6 Hz, 0.1 H),
6.67 (minor, d, J = 10.7 Hz, 0.1 H), 6.77 (major, d, J = 15.4 Hz, 1 H), 6.83
(major, d, J = 15.4 Hz, 1 H), 7.08–7.20 (m, 2 H), 7.25–7.32 (m, 7 H),
7.32–7.40 (m, 1 H), 7.48–7.82 (minor, m, 0.5 H).
13C NMR (126 MHz, CDCl3):  (E-isomer) = 115.88 (d, J = 21.9 Hz),
121.56, 122.14 (d, J = 17.3 Hz), 124.75 (d, J = 3.7 Hz), 126.10, 127.76,
128.70, 129.06 (d, J = 7.8 Hz), 132.07, 132.64, 136.32, 160.78 (d, J =
246.7 Hz).
The known compound 2k was prepared according to General Proce-
dure 1 on a 0.42 mmol scale. Compound 2k was isolated via silica gel
flash column chromatography with a mobile phase of 100% pentane
as a white solid; yield: 101.5 mg (87%, 0.365 mmol, >95:5 E/Z); mp
58–60 °C. Characterization was consistent with the literature report-
ed values.11
1H NMR (500 MHz, CDCl3):  = 6.59 (minor, d, J = 10.8 Hz, 0.05 H), 6.65
(major, d, J = 15.6 Hz, 1 H), 7.03 (major, d, J = 15.5 Hz, 1 H), 7.21–7.26
(m, 0.17 H), 7.28–7.35 (m, 1 H), 7.37–7.43 (m, 4 H), 7.45–7.49 (m, 2
H), 7.52 (dd, J = 8.3, 1.2 Hz, 0.35 H), 7.56 (d, J = 8.0 Hz, 2 H), 7.64 (d, J =
1.3 Hz, 0.1 H).
(E)-(2-Methylphenyl)(styryl)sulfane (2h)
The known compound 2h was prepared according to General Proce-
dure 1 on a 0.42 mmol scale. Compound 2h was isolated via silica gel
flash column chromatography with a mobile phase of 100% pentane
as a white solid yield: 66.5 mg (70%, 0.294 mmol, 95:5 E/Z); mp 34–36
°C. Characterization was consistent with the literature reported val-
ues.10
13C NMR (126 MHz, CDCl3):  (E-isomer) = 125.64 (q, J = 3.9 Hz),
125.94, 126.21 (q, J = 271.2Hz), 127.64, 127.69, 128.39, 129.11 (d, J =
10.0 Hz), 129.36, 130.77, 133.99, 139.96 (d, J = 1.4 Hz).
(E)-(4-Methylstyryl)(phenyl)sulfane (2l)
1H NMR (500 MHz, CDCl3):  = 2.44 (s, 3 H), 2.46 (s, 0.15 H), 6.39 (mi-
nor, dd, J = 10.8, 1.0 Hz, 0.05 H), 6.61 (major, d, J = 15.4 Hz, 1 H), 6.84
(major, d, J = 15.4 Hz, 1 H), 7.15–7.26 (m, 4 H), 7.28–7.37 (m, 4 H),
7.43 (ddd, J = 5.3, 3.2, 1.0 Hz, 1 H), 7.46–7.62 (minor, m, 0.3 H).
13C NMR (126 MHz, CDCl3):  (E-isomer) = 20.43, 123.32, 125.93,
126.74, 127.43, 128.67, 130.44, 130.90, 130.95, 133.73, 136.66,
138.71.
The known compound 2l was prepared according to General Proce-
dure 1 on a 0.42 mmol scale. Compound 2l was isolated via silica gel
flash column chromatography with a mobile phase of 100% pentane
as a white solid; yield: 82.2 mg (87%, 0.365 mmol, >95:5 E/Z); mp 40–
44 °C. Characterization was consistent with the literature reported
values.10
1H NMR (500 MHz, CDCl3):  = 2.36 (major, s, 3 H), 2.37 (minor, s, 0.14
H), 6.47 (minor, d, J = 10.6 Hz, 0.04 H), 6.60 (minor, d, J = 10.6 Hz, 0.04
H), 6.77 (major, d, J = 15.5 Hz, 1 H), 6.85 (major, d, J = 15.4 Hz, 1 H),
7.11–7.18 (major, m, 2 H), 7.21–7.24 (minor, m, 0.16 H), 7.28 (major,
d, J = 7.9 Hz, 3 H), 7.35 (major, t, J = 7.6 Hz, 2 H), 7.41–7.47 (m, 2 H),
7.45–7.51 (minor, m, 0.2 H).
(E)-(2-Isopropylphenyl)(styryl)sulfane (2i)
The known compound 2i was prepared according to General Proce-
dure 1 on a 0.42 mmol scale. Compound 2i was isolated via silica gel
flash column chromatography with a mobile phase of 100% pentane
as a colorless oil; yield: 93.4 mg (88%, 0.372 mmol, 90:10 E/Z). Charac-
terization was consistent with the literature reported values.14
13C NMR (126 MHz, CDCl3):  (E-isomer) = 21.25, 121.86, 126.02,
126.77, 129.13, 129.42, 129.55, 132.44, 133.79, 135.64, 137.60.
1H NMR (500 MHz, CDCl3):  = 1.23 (minor, d, J = 6.9 Hz, 0.4 H), 1.26
(major, d, J = 0.9 Hz, 3 H), 1.28 (major, d, J = 0.9 Hz, 3 H), 1.30 (minor,
d, J = 6.6 Hz, 0.4 H), 3.50 (major, ddd, J = 12.2, 7.7, 5.9 Hz, 1 H), 3.55–
3.68 (minor, m, 0.1 H), 6.40 (minor, dd, J = 10.8, 0.8 Hz, 0.1 H), 6.57
(minor, d, J = 10.8 Hz, 0.1 H) 6.59 (major, d, J = 15.5 Hz, 5 H), 6.85 (ma-
jor, d, J = 15.4 Hz, 2 H), 7.17–7.24 (m, 2 H), 7.28–7.36 (m, 6 H), 7.39–
7.47 (m, 1 H), 7.47–7.62 (minor, m, 0.14 H).
(E)-(3-Chlorostyryl)(phenyl)sulfane (2m)
The known compound 2m was prepared according to General Proce-
dure 1 on a 0.42 mmol scale. Compound 2m was isolated via silica gel
flash column chromatography with a mobile phase of 100% pentane
as a light-yellow oil; yield: 49.1 mg (48%, 0.202 mmol, >95:5 E/Z).
Characterization was consistent with the literature reported values.10
13C NMR (126 MHz, CDCl3):  (E-isomer) = 23.46, 30.58, 124.34,
125.84, 125.88, 126.59, 127.35, 127.94, 128.66, 130.62, 131.71,
132.62, 136.71, 149.18.
1H NMR (500 MHz, CDCl3):  = 6.50 (minor, d, J = 10.8 Hz, 0.5 H), 6.57
(minor, d, J = 10.8 Hz, 0.5 H), 6.60 (major, d, J = 15.5 Hz, 1 H), 6.92
(major, d, J = 15.5 Hz, 1 H), 7.16–7.20 (m, 2 H), 7.21–7.25 (m, 1 H),
7.28 (minor, t, J = 1.3 Hz, 0.2 H), 7.29–7.32 (m, 2 H), 7.33–7.39 (m, 2
H), 7.39–7.50 (m, 2 H), 7.46–7.54 (minor, m, 0.2 H).
(E)-(4-Methoxystyryl)(phenyl)sulfane (2j)
13C NMR (126 MHz, CDCl3):  (E-isomer) = 124.12, 125.75, 125.98,
127.31, 127.40, 129.05, 129.27, 129.87, 130.45, 134.36, 134.64,
138.38.
The known compound 2j was prepared according to General Proce-
dure 1 on a 0.42 mmol scale. Compound 2j was isolated via silica gel
flash column chromatography with a mobile phase of 100% pentane
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–I

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Synthesis
(E)-(3-Nitrostyryl)(phenyl)sulfane (2n)
13C NMR (126 MHz, CDCl3):  = 126.74, 128.67, 129.04, 129.17,
131.16, 131.37, 133.13, 133.69, 133.76, 151.10, 190.86.
The known compound 2n was prepared according to General Proce-
dure 1 on a 0.42 mmol scale. Compound 2n was isolated via silica gel
flash column chromatography with a mobile phase of 15:5:1 pen-
tane/DCM/EtOAc as a yellow oil; yield: 99.0 mg (91%, 0.382 mmol,
>95:5 E/Z).
1H NMR (400 MHz, CDCl3):  = 6.61 (major, d, J = 15.5 Hz, 1 H), 6.61
(minor, d, J = 10.8 Hz, 0.02 H), 6.71 (minor, d, J = 10.8 Hz, 0.02 H), 7.08
(major, d, J = 15.5 Hz, 1 H), 7.29–7.42 (major, m, 3 H), 7.43–7.52 (ma-
jor, m, 3 H), 7.55 (minor, d, J = 8.0 Hz, 0.09 H), 7.59 (major, d, J = 7.8
Hz, 1 H), 7.81–7.89 (minor, m, 0.05 H), 8.04 (major, ddd, J = 8.1, 2.3,
1.1 Hz, 1 H), 8.08–8.12 (minor, m, 0.03 H), 8.14 (major, t, J = 2.0 Hz, 1
H), 8.39 (minor, q, J = 2.3 Hz, 0.04 H).
(E)-Phenyl(2-phenylprop-1-en-1-yl)sulfane (2r)
The known compound 2r was prepared according to General Proce-
dure 2 on a 0.42 mmol scale. Compound 2r was isolated via silica gel
flash column chromatography with a mobile phase of 1:20 EtO-
Ac/pentane as a white oil; yield: 87.3 mg (92%, 0.386 mmol, >95:5
E/Z). Characterization was consistent with the literature reported val-
ues.10
1H NMR (400 MHz, CDCl3):  = 2.29 (s, 3 H), 6.61 (s, 1 H), 7.27 (dtt, J =
9.3, 7.3, 3.3 Hz, 2 H), 7.35 (dt, J = 7.9, 6.8 Hz, 4 H), 7.41–7.47 (m, 4 H).
13C NMR (126 MHz, CDCl3):  = 17.82, 121.39, 125.45, 126.47, 127.22,
13C NMR (126 MHz, CDCl3):  (E-isomer) = 120.24, 121.68, 126.73,
127.93, 128.82, 129.44, 129.56, 131.17, 131.53, 133.39, 138.32,
148.67.
128.43, 129.10, 129.13, 136.42, 137.25, 141.74.
(2-Phenylethene-1,1-diyl)bis(phenylsulfane) (2s)
HRMS (DART, M + NH4): m/z calcd for C14H15N2O2S: 275.08487; found:
275.08524.
The known compound 2s was prepared according to General Proce-
dure 2 on a 0.42 mmol scale using 10 mol% NiI2. Compound 2s was
isolated via silica gel flash column chromatography with a mobile
phase of 100% pentane as a white solid; yield: 57.8 mg (43%, 0.181
mmol); mp 65–67 °C. Characterization was consistent with the litera-
ture reported values.17
1H NMR (500 MHz, CDCl3):  = 7.16 (s, 1 H), 7.22–7.45 (m, 13 H), 7.64
(d, J = 7.1 Hz, 2 H).
13C NMR (126 MHz, CDCl3):  = 127.13, 127.78, 128.00, 128.21,
128.67, 128.95, 129.25, 130.96, 131.24, 132.17, 133.76, 133.86,
135.86, 137.69.
(E)-(2-Methylstyryl)(phenyl)sulfane (2o)
The known compound 2o was prepared according to General Proce-
dure 1 on a 0.42 mmol scale. Compound 2o was isolated via silica gel
flash column chromatography with a mobile phase of 100% pentane
as a clear oil; yield: 21.5 mg (22%, 0.093 mmol, >95:5 E/Z). Characteri-
zation was consistent with the literature reported values.10
1H NMR (500 MHz, CDCl3):  = 2.35 (s, 3 H), 6.80 (d, J = 15.4 Hz, 1 H),
6.99 (d, J = 15.3 Hz, 1 H), 7.10–7.20 (m, 3 H), 7.24–7.30 (m, 1 H), 7.35
(t, J = 7.9 Hz, 2 H), 7.43 (ddd, J = 7.0, 1.8, 1.0 Hz, 3 H).
13C NMR (126 MHz, CDCl3):  (E-isomer) = 19.84, 124.25, 125.33,
126.19, 126.85, 127.63, 129.15, 129.58, 130.03, 130.44, 135.17,
135.49, 135.57.
2-(Phenylthio)benzo[b]thiophene (2t)
The known compound 2t was prepared according to General Proce-
dure 3 on a 0.42 mmol scale. Compound 2t was isolated via silica gel
flash column chromatography with a mobile phase of 100% pentane
as a white solid; yield: 44.8 mg (44%, 0.185 mmol); mp 52–55 °C. 1H
NMR spectrum was consistent with the literature reported values.18
1H NMR (400 MHz, CDCl3):  = 7.14–7.33 (m, 3 H), 7.35–7.43 (m, 4 H),
7.51 (s, 1 H), 7.76 (d, J = 9.2 Hz, 1 H).
(E)-2-[2-(Phenylthio)vinyl]thiophene (2p)
The known compound 2p was prepared according to General Proce-
dure 1 on a 0.42 mmol scale. Compound 2p was isolated via silica gel
flash column chromatography with a mobile phase of 100% pentane
as a yellow oil; yield: 54.1 mg (56%, 0.235 mmol, 92:8 E/Z). Character-
ization was consistent with the literature reported values.15
1H NMR (500 MHz, CDCl3):  = 6.41 (minor, d, J = 10.3 Hz, 0.11 H), 6.71
(major, d, J = 15.2 Hz, 1 H), 6.84 (minor, d, J = 10.3 Hz, 0.11 H), 6.86
(major, d, J = 10.3 Hz, 1 H), 6.92–6.95 (m, 1 H), 6.97 (dd, J = 5.1, 3.6 Hz,
1 H), 7.07 (minor, dd, J = 5.1, 3.6 Hz, 0.15 H), 7.16 (dt, J = 5.1, 1.0 Hz, 1
H), 7.18 (minor, dd, J = 3.5, 1.0 Hz, 0.15 H), 7.21–7.25 (minor, m, 0.4
H), 7.25–7.31 (m, 1 H), 7.35 (t, J = 7.6 Hz, 2 H), 7.41 (dd, J = 8.4, 1.3 Hz,
2 H), 7.49 (minor, ddd, J = 18.6, 8.3, 1.2 Hz, 0.5 H).
13C NMR (126 MHz, CDCl3):  = 122.07, 123.55, 124.53, 124.93,
126.94, 128.98, 129.13, 130.83, 134.71, 136.64, 139.64, 142.68.
HRMS (DART M + H): m/z calcd for C14H11S2: 243.0297; found:
243.0292.
(E)-[2-(Phenylsulfonyl)vinyl]benzene (2u)
The known compound 2u was prepared according to General Proce-
dure 4 on a 0.42 mmol scale. Compound 2u was isolated via silica gel
flash column chromatography with a mobile phase of 100% pentane
as a yellow solid; yield: 51.3 mg (50%, 0.210 mmol, >95:5 E/Z); mp
60–64 °C. Characterization was consistent with the literature report-
ed values.19
1H NMR (500 MHz, CDCl3):  = 6.86 (d, J = 15.4 Hz, 1 H), 7.34–7.43 (m,
3 H), 7.49 (dd, J = 7.8, 1.9 Hz, 2 H), 7.52–7.58 (m, 2 H), 7.58–7.65 (m, 1
H), 7.69 (d, J = 15.4 Hz, 1 H), 7.95 (d, J = 7.1 Hz, 2 H).
13C NMR (126 MHz, CDCl3):  (E-isomer) = 122.44, 124.36, 125.25,
125.47, 127.01, 127.51, 129.19, 129.81, 135.02, 141.39.
(Z)-3-Phenyl-2-(phenylthio)acrylaldehyde (2q)
The known compound 2q was prepared according to General Proce-
dure 2 on a 0.42 mmol scale. Compound 2q was isolated via silica gel
flash column chromatography with a mobile phase of 1:1 pen-
tane/DCM as a yellow oil; yield: 78.2 mg (78%, 0.326 mmol, >95:5
Z/E). Characterization was consistent with the literature reported val-
ues.16
13C NMR (126 MHz, CDCl3):  (E-isomer) = 127.28, 127.65, 128.58,
129.09, 129.34, 131.23, 132.35, 133.38, 140.71, 142.50.
1H NMR (400 MHz, CDCl3):  = 7.12–7.22 (m, 1 H), 7.23–7.36 (m, 4 H),
7.39–7.60 (m, 3 H), 7.90 (s, 1 H), 7.98 (dd, J = 6.6, 3.0 Hz, 2 H), 9.57 (s,
1 H).
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–I

I
A. D. Marchese et al.
Paper
Synthesis
Funding Information
(4) Yatsumonji, Y.; Ishida, Y.; Tsubouchi, A.; Takeda, T. Org. Lett.
2007, 9, 4603.
We thank the University of Toronto (UofT), the Natural Science and
Engineering Research Council (NSERC), Alphora Research Inc. and
Kennarshore Inc. for financial support.()
(5) Metal-catalyzed oxidative coupling of thiols to disulfides, thus
reducing the metal, may be a potential method. For a review of
metal-catalyzed oxidative coupling of thiols using metals, see:
(a) Mandal, B.; Basu, B. RSC Adv. 2014, 4, 13854. For a specific
example pertaining to Ni, see: (b) Saxena, A.; Kumar, A.;
Mozumdar, S. J. Mol. Catal. A: Chem. 2007, 269, 35.
(6) For an example of disulfide reduction using phosphines or
phosphites, see: (a) Burns, J. A.; Butler, J. C.; Moran, J.;
Whitesides, G. M. J. Org. Chem. 1991, 56, 2648. (b) Schäfer, K.;
Asmus, A.-D. J. Phys. Chem. 1980, 84, 2156.
(7) For intra-inter molecular cyclizations with Pd generating ben-
zothiophenes, see: (a) Zhang, M.; Weng, Z. Org. Lett. 2019, 21,
5838. (b) Bryan, C. S.; Braunger, J. A.; Lautens, M. Angew. Chem.
Int. Ed. 2009, 48, 7064. (c) Newman, S. G.; Aureggi, V.; Bryan, C.
S.; Lautens, M. Chem. Commun. 2009, 5236. (d) Fang, Y. Q.;
Lautens, M. Org. Lett. 2005, 7, 3549. For recent examples of Pd
cyclizations of gem-dibromo olefins generating indoles, see:
(e) Zeidan, N.; Bognar, S.; Lee, S.; Lautens, M. Org. Lett. 2017, 19,
5058. (f) Newman, S. G.; Lautens, M. J. Am. Chem. Soc. 2010, 132,
11416.
Acknowledgment
A.D.M thanks OGS and NSERC for an NSERC Vanier fellowship. B.M.
thanks OGS for funding. E.M.L. thanks NSERC for a CGS D fellowship.
We thank Dr. Darcy Burns and Dr. Jack Sheng (University of Toronto)
for their assistance with NMR experiments.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1690717.
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© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–I