Nucleophilic disulfurating reagents for unsymmetrical disulfides construction via copper-catalyzed oxidative cross coupling

Article abstract of DOI:10.1016/j.tet.2017.05.010

Novel disulfuration was established via cross coupling between nucleophilic disulfurating reagent and arylsilane introducing two sulfur atoms in one step. This methodology was applied to synthesize various unsymmetrical disulfides under mild conditions via copper-catalyzed oxidative Hiyama-type cross coupling, providing a new pathway for disulfide synthesis. In addition, pH value of system displayed a key role in alcoholysis process.

Full text of DOI:10.1016/j.tet.2017.05.010

Tetrahedron 73 (2017) 3702e3706
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Nucleophilic disulfurating reagents for unsymmetrical disulfides
construction via copper-catalyzed oxidative cross coupling
,
,
, b, *
Zhihong Dai a 1, Xiao Xiao a 1, Xuefeng Jiang a
a Shanghai Key Laboratory of Green Chemistry and Chemical Process, Department of Chemistry, East China Normal University, 3663 North Zhongshan Road,
Shanghai 200062, PR China
b State Key Laboratory of Elemento-organic Chemistry, Nankai University, Tianjin 300071, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Novel disulfuration was established via cross coupling between nucleophilic disulfurating reagent and
arylsilane introducing two sulfur atoms in one step. This methodology was applied to synthesize various
unsymmetrical disulfides under mild conditions via copper-catalyzed oxidative Hiyama-type cross
coupling, providing a new pathway for disulfide synthesis. In addition, pH value of system displayed a
key role in alcoholysis process.
Received 23 January 2017
Received in revised form
17 April 2017
Accepted 2 May 2017
Available online 4 May 2017
© 2017 Elsevier Ltd. All rights reserved.
Keywords:
Nucleophilic disulfurating reagents
Unsymmetrical disulfides
Copper
Synthetic methods
1. Introduction
molysite/manganese dioxide have to be utilized, and pH value of
the system regulated by sodium carbonate plays a key role in the
Disulfide extensively exists in numerous significant molecules
with biological and pharmaceutical activity (Scheme 1).1 Therefore,
development of highly efficient synthetic methods to access sulfur-
sulfur bond has been intensively pursued by synthetic commu-
nity.2,3 Symmetrical disulfide can be facilely synthesized via
oxidation of thiol,2a while efficient examples have been scarcely
reported for the unsymmetrical disulfide synthesis.2b,3 Continuous
with our concept of sulfur atom transfer study,4 a strategy of con-
structing unsymmetrical disulfides with two different valent inor-
ganic sulfur source via a comproportionation process had been
reported.5a On the basis of masked strategy, a new type of nucle-
ophilic disulfurating reagent had been designed and synthesized,
which was utilized to construct unsymmetrical disulfide with
arylboronic acid under mild copper-catalyzed oxidative cross-
coupling conditions through a highly selective CeS bond cleavage
and reformation (Scheme 2a).5b
disulfuration. Compared to organoboron reagents and other metal
reagents employed in cross coupling processes, silicon-based nu-
cleophiles possess the characteristic of neutrality, easy handling,
high chemical stability, low toxicity, and relatively low cost.6,7 In
this manuscript, we report a novel and facile methodology for
Hiyama-type cross-coupling of disulfurating reagent with oxygen
as sole oxidant under mild conditions.
2. Result and discussion
We commenced our study with trimethoxy(phenyl)silane 1a
and BnSSAc 2a as the disulfur coupling partner in the presence of
copper sulfate pentahydrate (10 mol %) and 2,2'-bipyridine (12 mol
%) in MeOH at room temperature. When one equivalent of TBAF as
the activator of inert CeSi bond was added, the desired unsym-
metrical disulfide 4a was obtained in 12% yield (Table 1, entry 1).
Ligand screening shown that 4,4'-dimethoxy-2,2'-bipyridine was
the best ligand in this disulfurtion (Table 1, entries 1e3). Further
investigation revealed the yields were improved when phenolic
derivatives were utilized as additive (Table 1, entries 4e7).8 How-
ever, decreasing the amount of fluoride source did not affected the
yield of desired product 4a (Table 1, entry 8). A better result was
achieved when TsOH$H2O (0.3 equiv.) as pH value conditioner was
In our previous Suzuki-type cross-coupling, prooxidant of
* Corresponding author. Shanghai Key Laboratory of Green Chemistry and
Chemical Process, Department of Chemistry, East China Normal University, 3663
North Zhongshan Road, Shanghai 200062, PR China.
E-mail address: xfjiang@chem.ecnu.edu.cn (X. Jiang).
Z. D. and X. X. contributed equally to this work.
1
http://dx.doi.org/10.1016/j.tet.2017.05.010
0040-4020/© 2017 Elsevier Ltd. All rights reserved.

Z. Dai et al. / Tetrahedron 73 (2017) 3702e3706
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donating functional groups are compatible with the cross-
coupling conditions (Scheme 3; 3a-h). Arylsilane with amide con-
taining active hydrogen was successfully used to afford the corre-
sponding disulfane (Scheme 3; 3d). Notably, the halogen-
substituted arylsilane, proceed favourably in the transformation,
which was arduously compatible in traditional cross-coupling re-
actions (Scheme 3; 3e, f). Thiophenylsilane leads to formation of
the desired product in more modest yield as well (Scheme 3; 3i).
Significantly, vinylsilane performed efficiently in this trans-
formation (Scheme 3; 3j). The scope with respect to the disulfu-
rating reagents was further studied. For most cases, the reaction of
disulfurating reagent was found to tolerate both benzyl and alkyl
groups with various substituents in moderate to excellent yields
(Scheme 3; 4aei). For example, reaction of trimethoxy(phenyl)
silane 1a and disulfurating reagents 2b or 2c gave rise to the cor-
responding products 4b or 4c in 85% or 89 yields (Scheme 3; 4b, c),
respectively. Disulfurating reagents with halide groups were also
found to be suitable substrates for coupling with trimethox-
y(phenyl)silane 1a (Scheme 3; 4d-h), and the desired products
were generated in moderate to high yields. Propargyl substituted
reagent was also tolerant in this transformation (Scheme 3; 4l).
Secondary disulfurating reagents were well compatible in this
cross-coupling (Scheme 3; 4m, n). A host of disulfide reagents with
heterocycles, indolyl and benzofuranyl, were suitable partners in
this process and the desired products were isolated in good yields
(Scheme 3; 4o-q). When 6 mmol of 2a was carried out in the re-
action, the unsymmetrical disulfide 4a was afforded in 61% yield.
A plausible mechanism for the Hiyama-type cross-coupling re-
Scheme 1. Representative significant disulfides.
Scheme 2. Strategies for disulfide construction.
Table 1
Optimization of disulfuration.a
Entry
TBAF (equiv.)
Ligand (mol%)
Additive 1 (equiv.)
Additive 2 (equiv.)
Yieldb (%)
1
1
Bipy (12)
e
e
12
2
3
4
5
6
7
8
9
1
1
1
1
1
1
0.5
0.5
0.5
0.5
0.5
4,4'-diMe-Bipy (12)
4,4'-diMeO-Bipy (12)
4,4'-diMeO-Bipy (12)
4,4'-diMeO-Bipy (12)
4,4'-diMeO-Bipy (12)
4,4'-diMeO-Bipy (12)
4,4'-diMeO-Bipy (12)
4,4'-diMeO-Bipy (12)
4,4'-diMeO-Bipy (20)
4,4'-diMeO-Bipy (20)
4,4'-diMeO-Bipy (20)
e
e
14
33
45
46
37
48
47
57
e
e
PhOH (1.0)
C6F6OH (1.0)
p-CF3C6H4OH (1.0)
p-FC6H4OH (1.0)
p-FC6H4OH (1.0)
p-FC6H4OH (1.0)
p-FC6H4OH (1.0)
PhOH (1.0)
PhOH (0.5)
e
e
e
e
e
TsOH$H2O (0.3)
TsOH$H2O (0.3)
TsOH$H2O (0.3)
TsOH·H2O (0.3)
10
11
12
92
92 (85)c
92 (84)c
a
Trimethoxy(phenyl)silane (0.6 mmol, 3 equiv.), 2a (0.2 mmol, 1 equiv.), CuSO4$5H2O (0.02 mmol, 10 mol%), 4,4'-dimethoxy-2,2'-bipyridine (0.04 mmol, 20 mol%), TBAF
(0.1 mmol, 0.5 equiv.), PhOH (0.1 mmol, 0.5 equiv.) and TsOH$H2O (0.06 mmol, 0.3 equiv.) were added to MeOH (2 mL) stirring at r.t. for 10 h under O2 atmosphere.
b
Yield was determined by 1H NMR of the crude reaction mixture using an internal standard.
Isolated yield.
c
employed in the reaction (Table 1, entry 9). The optimized condi-
tions were obtained by enhancing the loading of ligand to afford
92% yield of benzyl(phenyl)disulfane (Table 1, entry 10). Finally, we
were pleased to observe that cross-coupling was also efficient with
phenol as additive (Table 1, entries 11 and 12).
With this preliminary result in hand, the scope of these copper-
catalyzed Hiyama-type coupling reactions of silane reagents was
investigated under the optimized conditions, and the results are
shown in Scheme 3. A spectrum of functional groups furnished on
silane substrates, bearing electron-withdrawing and electron-
action of disulfurating reagents with arylsilanes is shown in
Scheme 4.6,9 Disulfur anion 510 was tardily released in-situ through
alcoholysis of disulfane reagent 2 under the appropriate pH value
conditions. Ligand-exchange of Cu(II) 6 with intermediate 5 pro-
ceeded to complex 7. The complex 8 was generated via trans-
metalation with arylsilane. The resulting aryl Cu(II) 8 specie was
furtherly oxidized through single electron transfer process under
the assistance of another Cu(II) 6 to afford aryl Cu(III) 10 interme-
diate and Cu(I) 9.9a-c Product 3 was subsequently formed through
reductive elimination, releasing Cu(I) 9 simultaneously.9d Rapid

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Z. Dai et al. / Tetrahedron 73 (2017) 3702e3706
4. Experimental section
4.1. General experimental
NMR spectra were recorded on BRUKERDRX 400 spectrometers.
Chemical shifts were recorded in parts per million (ppm, d) relative
to chloroform (
d
¼ 7.26, singlet). 1H NMR splitting patterns are
designated as singlet (s), doublet (d), triplet (t), quartet (q), dd
(doublet of doublets), m (multiplets), and etc. Splitting patterns
that could not be easily interpreted are designated as multiplet (m)
or broad (br). Carbon nuclear magnetic resonance (13C NMR)
spectra were recorded on a Bruker (100 MHz) spectrometer.
4.2. Preparation of 3a-3j
To a tube were added RSSAc 2a-2q (0.2 mmol, 1 equiv.),
CuSO4·5H2O (0.02 mmol, 10 mol%), 4,4’-diMeObipy (0.04 mmol,
20 mol%), TsOH$H2O (0.06 mmol, 0.3 equiv.), PhOH (0.1 mmol, 0.5
equiv.), aryltriethoxylsilane (0.6 mmol, 3 equiv.), TBAF solution
1.0 M in THF (0.1 mmol, 0.5 equiv.) and MeOH (2 mL), the mixture
was stirred at 25 ꢀC for 10 h under O2 atmosphere before it was
concentrated under vacuum. Purification by column chromatog-
raphy afforded the desired product 3.
4.2.1. 1-Benzyl-2-(p-tolyl)disulfane (3a)
73% yield, colorless oil; 1H NMR (400 MHz, CDCl3)
d
7.39 (d,
J ¼ 8.2 Hz, 2H), 7.35e7.26 (m, 5H), 7.14 (d, J ¼ 8.0 Hz, 2H), 3.97 (s,
2H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 137.1, 136.7, 133.6,
129.7, 129.4, 128.6, 128.5, 127.4, 43.3, 21.0; MS (EI) m/z 246 (Mþ).
4.2.2. 1-Benzyl-2-(4-methoxyphenyl)disulfane (3b)
73% yield, colorless oil; 1H NMR (400 MHz, CDCl3)
d
7.35e7.29
Scheme 3. The scope of disulfuration.
(m, 2H), 7.27e7.16 (m, 5H), 6.79e6.74 (m, 2H), 3.88 (s, 2H), 3.74 (s,
3H); 13C NMR (100 MHz, CDCl3)
d 159.5, 136.8, 131.9, 129.4, 128.5,
127.9, 127.4, 114.6, 55.4, 43.3; MS (EI) m/z 262 (Mþ).
4.2.3. 4-(benzyldisulfanyl)phenyl acetate (3c)
67% yield, colorless oil; 1H NMR (400 MHz, CDCl3)
d7.43e7.38
(m, 2H), 7.28e7.21 (m, 5H), 7.02e6.93 (m, 2H), 3.92 (s, 2H), 2.27 (s,
3H); 13C NMR (100 MHz, CDCl3)
d169.2, 149.7, 136.5, 134.3, 129.4,
129.2, 128.5, 127.6, 122.1, 43.4, 21.1; HRMS (EI) Calcd for C15H14O2S2
290.0435, Found 290.0434.
4.2.4. N-(4-(benzyldisulfanyl)phenyl)acetamide (3d)
90% yield, white solid; 1H NMR (400 MHz, CDCl3)
d
7.66 (s, 1H),
7.42 (d, J ¼ 8.5 Hz, 2H), 7.38e7.33 (m, 2H), 7.29e7.20 (m, 5H), 3.91
(s, 2H), 2.14 (s, 3H); 13C NMR (100 MHz, CDCl3)
168.5, 137.2, 136.5,
d
132.2, 129.5, 129.3, 128.5, 127.5, 120.4, 43.3, 24.5; HRMS (EI) Calcd
for C15H15NOS2 289.0595, Found 285.0596.
Scheme 4. Plausible mechanistic cycle.
4.2.5. 1-Benzyl-2-(4-chlorophenyl)disulfane (3e)
67% yield, white solid; 1H NMR (400 MHz, CDCl3)
d
7.38e7.33
(m, 2H), 7.32e7.27 (m, 5H), 7.27e7.23 (m, 2H), 3.96 (s, 2H); 13C NMR
aerobic oxidation from Cu(I) 9 to Cu(II) 6 was realized with the help
of oxygen, which regenerated the catalytic cycle.
(100 MHz, CDCl3)
d 136.4, 135.7, 132.8, 129.4, 129.0, 128.9, 128.5,
127.6, 43.4; MS (EI) m/z 266 (Mþ).
3. Conclusion
4.2.6. 1-Benzyl-2-(4-bromophenyl)disulfane (3f)
84% yield, white solid; 1H NMR (400 MHz, CDCl3)
In summary, we have developed the first example of achieving
Hiyama-type oxidative cross-coupling reaction for unsymmetrical
disulfide catalyzed by copper complex under mild conditions. Both
electron-rich and electron-deficient arylsilanes are found to be
compatible with this new transformation. The matching pH value
of system provided by the additives was shown key role in alco-
holysis process. Our current efforts are directed at further
expanding new disulfurating reagents to unsymmetrical disulfides.
d 7.43e7.37
(m, 2H), 7.34e7.25 (m, 7H), 3.96 (s, 2H); 13C NMR (100 MHz, CDCl3)
d
136.3(4), 136.3(2), 131.8, 129.3, 129.2, 128.5, 127.6, 120.6, 43.4; MS
(EI) m/z 310 (Mþ).
4.2.7. 1-Benzyl-2-(m-tolyl)disulfane (3g)
60% yield, colorless oil; 1H NMR (400 MHz, CDCl3)
d 7.33e7.24
(m, 6H), 7.23 (s, 1H), 7.19 (t, J ¼ 7.6 Hz, 1H), 7.02 (d, J ¼ 7.4 Hz, 1H),

Z. Dai et al. / Tetrahedron 73 (2017) 3702e3706
3705
3.96 (s, 2H), 2.33 (s, 3H); 13C NMR (100 MHz, CDCl3)
d
138.8, 136.7,
(100 MHz, CDCl3)
d
162.2 (d, 1JC-F ¼ 246.1 Hz), 136.75 (s), 132.3 (d,
3
129.4, 128.7, 128.5, 128.2, 127.7, 127.5, 124.8, 43.5, 21.3; MS (EI) m/z
4JC-F ¼ 3.3 Hz), 131.0 (d, JC-F ¼ 8.1 Hz), 128.9, 127.6 (s), 126.8 (s),
246 (Mþ).
115.3 (d, JC-F ¼ 21.3 Hz), 42.32 (s); HRMS (EI) Calcd for C13H11FS2
2
250.0285, Found 250.0282.
4.2.8. 1-Benzyl-2-(3-methoxyphenyl)disulfane (3h)
79% yield, colorless oil; 1H NMR (400 MHz, CDCl3)
d
7.31e7.22
4.3.6. 1-(2,6-dichlorobenzyl)-2-phenyldisulfane (4f)
(m, 5H), 7.22e7.17 (m, 1H), 7.07e7.00 (m, 2H), 6.74 (ddd, J ¼ 8.3, 2.4,
81% yield, colorless oil; 1H NMR (400 MHz, CDCl3)
d
7.54e7.49
1.1 Hz, 1H), 3.94 (s, 2H), 3.78 (s, 3H); 13C NMR (100 MHz, CDCl3)
(m, 2H), 7.32e7.25 (m, 2H), 7.24 (s, 1H), 7.22e7.17 (m, 1H), 7.13e7.06
d
160.0, 138.3, 136.6, 129.7, 129.3, 128.5, 127.5, 119.6, 112.8, 112.3,
(m,1H), 4.34 (s, 2H); 13C NMR (100 MHz, CDCl3)
d 137.1,136.0,132.9,
55.3, 43.4; MS (EI) m/z 262 (Mþ).
129.0, 128.7, 128.2, 127.2, 126.7, 38.6; MS (EI) m/z 300 (Mþ).
4.2.9. 2-(benzyldisulfanyl)thiophene (3i)
4.3.7. 1-(4-bromobenzyl)-2-phenyldisulfane (4g)
33% yield, colorless oil; 1H NMR (400 MHz, CDCl3)
d
7.33 (dd,
76% yield, colorless oil;1H NMR (400 MHz, CDCl3)
d
7.47e7.36
(m, 4H), 7.31e7.26 (m, 2H), 7.23 (ddd, J ¼ 7.4, 3.7, 1.3 Hz, 1H),
7.15e7.11 (m, 2H), 3.88 (s, 2H); 13C NMR (100 MHz, CDCl3)
136.7,
J ¼ 5.3, 1.3 Hz, 1H), 7.28e7.19 (m, 5H), 7.06 (dd, J ¼ 3.6, 1.2 Hz, 1H),
6.89 (dd, J ¼ 5.3, 3.6 Hz,1H), 3.99 (s, 2H); 13C NMR (100 MHz, CDCl3)
d
d
136.5, 133.9, 130.6, 129.5, 128.6, 127.5, 43.5; HRMS (EI) Calcd for
135.7, 131.6, 131.0, 128.9, 127.9, 126.9, 121.5, 42.5; MS (EI) m/z 310
C
11H10S3 237.9945, Found 237.9947.
(Mþ).
4.2.10. 1-Benzyl-2-vinyldisulfane (3j)
4.3.8. 1-(4-iodobenzyl)-2-phenyldisulfane (4h)
68% yield, colorless oil; 1H NMR (400 MHz, CDCl3)
d
7.38e7.27
75% yield, white solid; 1H NMR (400 MHz, CDCl3)
d 7.61e7.55 (m,
(m, 5H), 6.25 (dd, J ¼ 16.3, 9.5 Hz, 1H), 5.50 (d, J ¼ 16.3 Hz, 1H), 5.31
2H), 7.45e7.39 (m, 2H), 7.32e7.26 (m, 2H), 7.26e7.20 (m, 1H), 7.00
(d, J ¼ 9.5 Hz, 1H), 3.93 (s, 2H); 13C NMR (100 MHz, CDCl3)
d
136.8,
(d, J ¼ 8.3 Hz, 2H), 3.86 (s, 2H); 13C NMR (100 MHz, CDCl3)
d 137.5,
133.2, 129.3, 128.5, 127.5, 113.7, 42.5; HRMS (EI) Calcd for C9H10S2
136.6,136.2,131.2, 128.9,127.7,126.9, 93.1, 42.5; HRMS (EI) Calcd for
182.0224, Found 182.0223.
C13H11IS2 357.9347, Found 357.9349.
4.3. Preparation of 4a-4q
4.3.9. 1-(4-nitrobenzyl)-2-phenyldisulfane (4i)
73% yield, white solid; 1H NMR (400 MHz, CDCl3)
d 8.12e8.06
To a tube were added RSSAc 2a-2q (0.2 mmol, 1 equiv.),
CuSO4·5H2O (0.02 mmol, 10 mol%), 4,4’-diMeObipy (0.04 mmol,
20 mol%), TsOH$H2O (0.06 mmol, 0.3 equiv.), PhOH (0.1 mmol, 0.5
equiv.), phenyltrimethoxylsilane (0.6 mmol, 3 equiv.), TBAF solution
1.0 M in THF (0.1 mmol, 0.5 equiv.) and MeOH (2 mL), the mixture
was stirred at 25 ꢀC for 10 h under O2 atmosphere before it was
concentrated under vacuum. Purification by column chromatog-
raphy afforded the desired product 4.
(m, 2H), 7.40 (d, J ¼ 8.4 Hz, 4H), 7.29e7.24 (m, 2H), 7.23e7.18 (m,
1H), 3.98 (s, 2H); 13C NMR (100 MHz, CDCl3)
147.2, 144.3, 136.2,
130.2, 128.9, 128.0, 127.2, 123.6, 42.2; HRMS (EI) Calcd for
13H11NO2S2 277.0231, Found 277.0229.
d
C
4.3.10. Ethyl 4-(phenyldisulfanyl)butanoate (4j)
69% yield, colorless oil; 1H NMR (400 MHz, CDCl3)
d 7.56e7.50
(m, 2H), 7.35e7.29 (m, 2H), 7.25e7.19 (m, 1H), 4.11 (q, J ¼ 7.2 Hz,
2H), 2.76 (t, J ¼ 7.1 Hz, 2H), 2.40 (t, J ¼ 7.3 Hz, 2H), 2.01 (p, J ¼ 7.2 Hz,
4.3.1. 1-Benzyl-2-phenyldisulfane (4a)
2H), 1.24 (t, J ¼ 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 172.8, 137.1,
84% yield, colorless oil; 1H NMR (400 MHz, CDCl3)
d
7.46e7.41
128.9, 127.6, 126.8, 60.4, 37.6, 32.5, 23.8, 14.2; MS (EI) m/z 256 (Mþ).
(m, 2H), 7.30e7.16 (m, 8H), 3.92 (s, 2H); 13C NMR (100 MHz, CDCl3)
d
136.9, 136.5129.3, 128.9, 128.5, 127.5(4), 127.5(0), 126.7, 43.2; MS
4.3.11. 1-Phenethyl-2-phenyldisulfane (4k)
(EI) m/z 232 (Mþ).
76% yield, colorless oil; 1H NMR (400 MHz, CDCl3)
d 7.56 (d,
J ¼ 7.7 Hz, 2H), 7.38e7.28 (m, 4H), 7.25 (t, J ¼ 6.5 Hz, 2H), 7.18 (d,
4.3.2. 1-(4-methoxybenzyl)-2-phenyldisulfane (4b)
85% yield, white solid; 1H NMR (400 MHz, CDCl3)
J ¼ 7.3 Hz, 2H), 3.00 (s, 4H); 13C NMR (100 MHz, CDCl3)
d 139.8,
d
7.47 (dt,
137.3, 129.0, 128.6, 128.5, 127.5, 126.8, 126.4, 39.9, 35.2; MS (EI) m/z
J ¼ 3.1, 1.9 Hz, 2H), 7.33e7.28 (m, 2H), 7.24e7.18 (m, 3H), 6.85e6.79
246 (Mþ).
(m, 2H), 3.92 (s, 2H), 3.79 (s, 3H); 13C NMR (100 MHz, CDCl3)
d
159.0, 137.1, 130.5, 128.9, 128.4, 127.5, 126.7, 113.9, 55.2, 42.7; MS
4.3.12. 1-Phenyl-2-(3-phenylprop-2-yn-1-yl)disulfane (4l)
(EI) m/z 262 (Mþ).
71% yield, yellow oil; 1H NMR (400 MHz, CDCl3)
d
7.64e7.59 (m,
2H), 7.33e7.24 (m, 7H), 7.24e7.19 (m, 1H), 3.74 (s, 2H); 13C NMR
(100 MHz, CDCl3) 136.7, 131.7, 129.0, 128.3, 128.1, 127.9, 127.1,
4.3.3. 1-(4-(methylthio)benzyl)-2-phenyldisulfane (4c)
89% yield, white solid; 1H NMR (400 MHz, CDCl3)
d
d
7.49e7.43
122.6, 84.8, 84.2, 28.4; HRMS (EI) Calcd for C15H12S2 256.0380,
(m, 2H), 7.33e7.27 (m, 2H), 7.24e7.14 (m, 5H), 3.91 (s, 2H), 2.47 (s,
Found 256.0383.
3H); 13C NMR (100 MHz, CDCl3)
d 137.8, 136.9, 133.2, 129.8, 128.8,
127.6, 126.7, 126.5, 42.8, 15.7; MS (EI) m/z 278 (Mþ).
4.3.13. 1-Phenyl-2-(1-phenylethyl)disulfane (4m)
73% yield, colorless oil; 1H NMR (400 MHz, CDCl3)
d 7.49e7.43
4.3.4. 1-(3-(chloromethyl)benzyl)-2-phenyldisulfane (4d)
(m, 2H), 7.36e7.25 (m, 7H), 7.23e7.18 (m, 1H), 4.13 (q, J ¼ 7.0 Hz,
76% yield, white solid; 1H NMR (400 MHz, CDCl3)
d
7.46e7.41
1H), 1.71 (d, J ¼ 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 141.3,
(m, 2H), 7.31e7.18 (m, 7H), 4.52 (s, 2H), 3.95 (s, 2H); 13C NMR
137.5, 128.8, 128.5, 127.6, 127.3, 126.5, 50.1, 20.5, MS (EI) m/z 246
(100 MHz, CDCl3)
d
137.6, 137.2, 136.8, 129.5, 129.4, 128.9, 127.6(7),
(Mþ).
127.6(5), 126.8, 45.9, 43.0; MS (EI) m/z 280 (Mþ).
4.3.14. 1-Benzhydryl-2-phenyldisulfane (4n)
4.3.5. 1-(4-fluorobenzyl)-2-phenyldisulfane (4e)
80% yield, colorless oil; 1H NMR (400 MHz, CDCl3)
88% yield, colorless oil; 1H NMR (400 MHz, CDCl3)
d
7.48e7.42
(m, 6H), 7.38e7.32 (m, 4H), 7.32e7.23 (m, 5H), 5.35 (s,1H); 13C NMR
(100 MHz, CDCl3) 139.6, 136.9, 128.7(9), 128.8(3), 128.5, 128.4,
127.5, 126.9, 60.3; MS (EI) m/z 308 (Mþ).
d
7.48e7.42
(m, 2H), 7.33e7.27 (m, 2H), 7.27e7.20 (m, 3H), 7.00e6.93 (m, 2H),
d
3.92 (s, 2H); 19F NMR (282 MHz, CDCl3)
d
ꢁ114.67; 13C NMR

3706
Z. Dai et al. / Tetrahedron 73 (2017) 3702e3706
(i) Conway TT, DeMaster EG, Goon DJW, Shirota FN, Nagasawa HT. J Med Chem.
4.3.15. 1-(2-(phenyldisulfanyl)ethyl)-1H-indole (4o)
76% yield, yellow oil; 1H NMR (400 MHz, CDCl3)
1999;42:4016;
d
7.65 (d,
(j) Nicolaou KC, Hughes R, Pfefferkorn JA, Barluenga S, Roecker AJ. Chem Eur J.
2001;7:4280;
J ¼ 7.9 Hz, 1H), 7.61e7.56 (m, 2H), 7.39e7.31 (m, 3H), 7.30e7.25 (m,
1H), 7.25e7.20 (m, 1H), 7.16e7.11 (m, 1H), 7.06 (d, J ¼ 3.1 Hz, 1H),
6.51 (d, J ¼ 3.1 Hz,1H), 4.44 (t, J ¼ 8.0 Hz, 2H), 3.09 (t, J ¼ 8.0 Hz 2H);
(k) Trabi M, Craik DJ. Trends Biochem Sci. 2002;27:132;
(l) Tan RX, Jensen PR, Williams PG, Fenical W. J Nat Prod. 2004;67:1374;
ꢀ
(m) A.-Cebollada J, Kosuri P, R.-Pardo JA, Fernandez JM. Nat Chem. 2011;3:882;
13C NMR (100 MHz, CDCl3)
d 136.7, 135.7, 129.2, 128.7, 128.2, 127.8,
(n) Caldarelli SA, Hamel M, Duckert J-F, et al. J Med Chem. 2012;55:4619;
(o) Nicolaou KC, Lu M, Totokotsopoulos S, et al. J Am Chem Soc. 2012;134:
17320;
127.4, 121.7, 121.1, 119.6, 109.0, 101.7, 45.2, 37.8; HRMS (EI) Calcd for
16H15NS2 285.0646, Found 285.0641.
C
(p) Ilani T, Alon A, Grossman I, et al. Science. 2013;341:74;
(q) Hanschen FS, Lamy E, Schreiner M, Rohn S. Angew Chem Int Ed. 2014;53:
11430;
4.3.16. Tert-butyl 4-((phenyldisulfanyl)methyl)-1H-indole-1-
(r) Scharf DH, Habel A, Heinekamp T, Brakhage AA, Hertweck C. J Am Chem Soc.
2014;136:11674;
(s) Chankhamjon P, B.-Schmidt D, Scherlach K, et al. Angew Chem Int Ed.
2014;53:13409;
carboxylate (4p)
84% yield, colorless oil; 1H NMR (400 MHz, CDCl3)
d 8.10 (d,
J ¼ 8.2 Hz, 1H), 7.64 (d, J ¼ 3.6 Hz, 1H), 7.52e7.45 (m, 2H), 7.34e7.20
(t) Song M, Kim J-S, Liu L, Husain M, V.-Torres A. Cell Rep. 2016;14:2901;
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(m, 4H), 7.15 (d, J ¼ 7.3 Hz, 1H), 6.65 (d, J ¼ 3.8 Hz, 1H), 4.25 (s, 2H),
1.71 (s, 9H); 13C NMR (100 MHz, CDCl3)
d 149.6, 137.0, 135.3, 129.9,
128.8, 128.3, 127.7, 126.7, 125.9, 124.1, 123.9, 114.8, 105.3, 83.7, 41.1,
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(c) Heimer NE. J Org Chem. 1985;50:4164;
28.2; HRMS (EI) Calcd for C20H21NO2S2 371.1014, Found 371.1010.
4.3.17. 2-((phenyldisulfanyl)methyl)benzofuran (4q)
77% yield, colorless oil; 1H NMR (400 MHz, CDCl3)
d 7.49e7.42
(d) Barton DHR, Hesse RH, O'Sullivan AC, Pechet MM. J Org Chem. 1991;56:
6697;
(m, 3H), 7.41e7.37 (m, 1H), 7.29e7.23 (m, 1H), 7.22e7.17 (m, 3H),
7.16e7.10 (m, 1H), 6.60 (s, 1H), 4.07 (s, 2H); 13C NMR (100 MHz,
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CDCl3)
d 155.1, 152.5, 136.5, 128.7, 128.3, 127.8, 126.8, 124.2, 122.7,
120.7, 111.1, 106.1, 36.1; HRMS (EI) Calcd for C15H12OS2 272.0330,
Found 272.0331.
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4.4. Gram-scale operation
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10.1039/C6CC09201B.
To a tube were added BnSSAc 2a (6 mmol, 1.19 g, 1 equiv.),
CuSO4·5H2O (0.6 mmol, 150 mg, 10 mol%), 4,4’-diMeObipy
(1.2 mmol, 259.5 mg, 20 mol%), TsOH$H2O (1.8 mmol, 342.4 mg, 0.3
equiv.), PhOH (3 mmol, 282.4 mg, 0.5 equiv.), phenyl-
trimethoxylsilane (18 mmol, 3.57 g, 3 equiv.), TBAF solution 1.0 M in
THF (3 mmol, 3 mL, 0.5 equiv.) and MeOH (60 mL), the mixture was
stirred at 25 ꢀC for 10 h under O2 atmosphere before it was
concentrated under vacuum. Purification by column chromatog-
raphy afforded the desired product 4a (850 mg, 61%).
5. (a) Xiao X, Feng M, Jiang X. Chem Commun. 2015;51:4208;
(b) Xiao X, Feng M, Jiang X. Angew Chem, Int Ed. 2016;55:14121.
6. For reviews, see: (a) Nakao Y, Hiyama T. Chem Soc Rev. 2011;40:4893;
(b) Sore HF, Galloway WRJD, Spring DR. Chem Soc Rev. 2012;41:1845.
7. Selected examples, see: (a) Lee J-Y, Fu GC. J Am Chem Soc. 2003;125:5616;
(b) Zhang L, Wu J. J Am Chem Soc. 2008;130:12250;
(c) Dai X, Strotman NA, Fu GC. J Am Chem Soc. 2008;130:3302;
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Toxicol Environ Mutagen. 2011;724:1;
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(h) Hansen MM, Jolly RA, Linder RJ. Org Process Res Dev. 2015;19:1507;
(i) Tymonko SA, Smith RC, Ambrosi A, Denmark SE. J Am Chem Soc. 2015;137:
6192;
Acknowledgments
We are grateful for financial support provided by NSFC
(21672069, 21472050, 21272075), DFMEC (20130076110023), Fok
Ying Tung Education Foundation (141011), Program for Shanghai
Rising Star (15QA1401800), Professor of Special Appointment
(Eastern Scholar) at Shanghai Institutions of Higher Learning, and
National Program for Support of Top-notch Young Professionals.
Appendix ASupplementary data
(j) Melvin PR, Hazari N, Beromi MM, Shah HP, Williams MJ. Org Lett. 2016;18:
5784;
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2017.05.010.
(k) Wu Y, Zhang H-R, Cao Y-X, Lan Q, Wang X-S. Org Lett. 2016;18:5564.
8. Ito Hajime, Sensui Hiro-omi, Arimoto Kikuo, Miura Katsukiyo, Hosomi Akira.
New access to cross-coupling reaction between arylsilanes or heteroarylsilanes
and aryl halides mediated by a Copper(I) salt. Chem Lett. 1997;26(7):639e640.
9. For reviews, see: (a) McCann SD, Stahl SS. Acc Chem Res. 2015;48:1756
(Selected examples, see);
(b) King AE, Brunold TC, Stahl SS. J Am Chem Soc. 2009;131:5044;
(c) King AE, Huffman LM, Casitas A, Costas M, Ribas X, Stahl SS. J Am Chem Soc.
2010;132:12068;
(d) He C, Zhang G, Ke J, et al. J Am Chem Soc. 2013;135:488;
(e) Wang F, Wang D, Mu X, Chen P, Liu G. J Am Chem Soc. 2014;136:10202.
10. Selected examples, see: (a) Davidson BS, Molinski TF, Barrows LR, Ireland CM.
J Am Chem Soc. 1991;113:4709;
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