Generation and reactions of thiirenium ions by the Cation Pool method

Article abstract of DOI:10.24820/ark.5550190.p010.302

Thiirenium ions generated and accumulated by low-temperature electrochemical oxidation of disulfides in the presence of alkynes were successfully observed by low-temperature NMR, Raman, and mass spectroscopies and were found to be stable at temperatures below -40 °C. The thiirenium ions showed ambident reactivity toward subsequently added nucleophiles to give either disubstituted alkenes or alkynes depending on the nature of the nucleophiles.

Full text of DOI:10.24820/ark.5550190.p010.302

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Arkivoc 2018, part ii, 97-113
Organic Chemistry
Generation and reactions of thiirenium ions by the Cation Pool method
Akihiro Shimizu,a Shun Horiuchi,a Ryutaro Hayashi,a Kouichi Matsumoto,b Yu Miyamoto,b
Yusuke Morisawa,b Tomonari Wakabayashi,b and Jun-ichi Yoshida*a
a Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering,
Kyoto University, Nishikyo-ku, Kyoto 615-8510, Japan
b Department of Chemistry, School of Science and Engineering, Kindai University, Kowakae 3-4-1,
Higashi-Osaka, Osaka 577-8502, Japan
Email: yoshida@sbchem.kyoto-u.ac.jp
Dedicated to Professor Kenneth Laali on the occasion of his 65th anniversary
Received 08-13-2017
Accepted 10-28-2017
Published on line 11-05-2017
Abstract
Thiirenium ions generated and accumulated by low-temperature electrochemical oxidation of disulfides in the
presence of alkynes were successfully observed by low-temperature NMR, Raman, and mass spectroscopies
and were found to be stable at temperatures below −40 °C. The thiirenium ions showed ambident reactivity
toward subsequently added nucleophiles to give either disubstituted alkenes or alkynes depending on the
nature of the nucleophiles.
attack on C
Thiirenium Ion Pool
Ph
PhS
R
Nu
anodic
oxidation
R
Nu
+
S
PhSSPh
R
R
PhS
R
Nu
R
R
R
Nu
+
attack on S
Keywords: Electrosynthesis, cations, thiirenium ions, reactive intermediates, ambident reactivity
DOI: https://doi.org/10.24820/ark.5550190.p010.302
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Introduction
Thiirenium ions1 are important reactive intermediates in difunctionalization of alkynes. Because of their
instability, thiirenium ions are conventionally generated by the reaction of alkynes with RS+ equivalents in
special solvents such as liquid SO2.2-5 Some thiirenium ions having bulky substituent groups can be isolated and
characterized by X-ray crystal structural analysis.6 Recently, Poleschner et al. reported the synthesis of
thiirenium ions in CH2Cl2 by the reaction of disulfides with alkynes having bulky substituent groups using XeF2
as an one-electron oxidant and silylcarborate salt Me3Si+ CHB11Cl11− as a F− acceptor.7 However, generation
and accumulation of the thiirenium ions which do not have bulky substituent groups in normal organic
solvents are still challenging8 because nucleophiles derived from the RS+ equivalents such as Cl− and MeSSMe
reacts with thiirenium ions even at low temperatures and even in highly acidic media.2-5 Also, their generation
in the presence of strong nucleophiles prevents studies on their reactivity towards various nucleophiles.
Therefore, there is still room for a method for generating and accumulating thiirenium ions in normal organic
solvents in the absence of strong nucleophiles.
Electrochemical oxidation9-15 serves as a powerful method for generating and accumulating highly reactive
cationic species. (For recent papers on organic electrosynthesis, see for example, refs 16-18) Electrochemical
oxidation in solvents normally used in organic syntheses can be carried out by the cation pool method.19-21 We
have reported that the electrochemical oxidation of diaryl disulfides (ArSSAr) leads to the formation of
ArS(ArSSAr)+, which can be accumulated in solution at low temperatures (Figure 1).22-26 This reaction
presumably proceeds by generation of “ArS+” followed by its reaction with ArSSAr. Therefore, we envisaged
that the anodic oxidation of ArSSAr in the presence of alkynes leads to the formation of thiirenium ions (Figure
1). The method would enable not only characterization of thiirenium ions but also a study of their reactivity
towards various nucleophiles which can be added after their generation. Herein, we report the generation of
thiirenium ions having no bulky substituent groups by the “cation pool” method, their spectroscopic
characterization, and their reactions with subsequently added nucleophiles.
Figure 1. Generation and accumulation of ArS(ArSSAr)+ and thiirenium ions.
Results and Discussion
To generate and accumulate thionium ion 1a (Ar = Ph, R = Pr), electrochemical oxidation of PhSSPh (2) in the
presence of 4-octyne was carried out under constant current conditions at −78 °C in an H-type divided cell
equipped with an anode consisting of fine carbon fibers and a platinum plate cathode in 0.3 M Bu4PBF4/CD2Cl2
1
13
(Figure S1).27 After 2.1 F of electricity was applied, the resulting anodic solution was analyzed by H and C
1
13
NMR spectroscopies at −78 °C (Figure 2). In the H and C NMR spectra no signal of the disulfide 2 was
observed. Only signals which can be attributed to 1a were observed. All signals were assigned as shown in
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Figure 2 by using HMQC and HMBC measurements (Figures S2 and S3). Correlation between Ha,a’ and Ho,m in
NOE spectrum (Figure S4) indicates the generation and accumulation of thiirenium ion 1a in the solution. The
chemical shift of the alkenyl carbons (106.8 ppm) is consistent with those of a thiirenium ion having tert-butyl
groups reported in the literature (114.526 and 113.177). Notably, two signals assigned to Ha and Ha’ and two
signals assigned to Hb and Hb’ were observed at around 3.0 and 1.7 ppm, respectively (Figure 2a, inset),
indicating that 1a has a pyramidal sulfur atom whose inversion is prohibited or slow compared to the NMR
time scale. The pyramidal structure of 1a is consistent with the reported X-ray structure of the thiirenium ions
bearing bulky tert-butyl groups.6,7
Figure 2. a) 1H NMR and b) 13C NMR spectra of 1a at −78 °C in Bu4PBF4/CD2Cl2.
Thiirenium ion 1a generated in Bu4NB(C6F5)4/CH2Cl2 instead of Bu4PBF4/CD2Cl2 was analyzed by cold-
spray-ionization mass spectroscopy (CSI-MS)28 at 0 °C.29 The signal assigned to 1a was successfully observed
(Figure S5).
Raman spectra were measured during the electrochemical oxidation at −78 °C (Figure 3a).30,31 The solution
of ArSSAr (Ar = 4-FC6H4) and 4-octyne in Bu4NBF4/CH2Cl2 was electrochemically oxidized to give 1b (Ar = 4-
FC6H4, R = Pr).32 Increase of the electricity applied strengthened the signal at 1874 cm−1, which is assigned to
the stretching of the C−C double bond of 1b by DFT calculations (1862 cm−1, scaling factor: 0.961433). The
vibration frequencies of the C−C triple bond of 4-octyne, the C-C double bond of 1b, and the C-C double bond
of cis-4-octene show linear correlation with the C−C bond lengths obtained by DFT calculaꢀons (Figure 3b),
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which is similar to the tendency of seleniranium ions reported in the literature.34 The higher frequency and the
shorter bond length of 1b than those of cis-4-octene is not because of the bond order of the C−C double bond
of 1b (1.91) and cis-4-octene (1.93) but because of the higher s-character of the carbon atoms of 1b (41.1%,
sp1·43) than that of cis-4-octene (39.5%, sp1·53).
Figure 3. (a) Raman spectra of the reaction mixture during anodic oxidation at −78 °C in Bu4NBF4/CH2Cl2.
(b) Relation between the observed C−C vibraꢀons and C−C bond lengths obtained by DFT calculaꢀons
of 4-octyne, 1b, and cis-4-octene.
The thermal stability of thiirenium ion 1a was investigated.35 After a solution of 1a was kept at the second
temperature for 30 min, the resulting solution was recooled to −78 °C. Then, Bu4NCl (10 equiv) was added and
the mixture was stirred at −78 °C for 30 min. Aꢁer work-up the yields of products, chloro-substituted alkene
2a and fluoro-substituted alkene 2b were determined by gas chromatography. Plots of the yield of 2a against
the temperature (Figure 4) indicates that 1a is stable at temperatures lower than −40 °C. At the temperatures
higher than −20 °C, the yield of 2a decreased and the yield of 2b increased with an increase in the
−
temperature. Presumably, alkene 2b was produced by the reaction of 1a with the supporting electrolyte BF4
(vide infra).
Reactions of thiirenium ion 1a with various nucleophiles were investigated (Table 1). After electrochemical
generation and accumulation of the thiirenium ion, a nucleophile was added to the solution. The resulting
solution was stirred at −78 °C for 30 min and then at 20 °C for 30 min. Cl- reacted with 1a to give 2a in a good
yield. When a nucleophile was not added intentionally, 2b was obtained in a good yield (entry 2). Presumably
−
F− derived BF4 reacted with 1a. Br−, I−, ArO− (Ar = 4-O2N-C6H4), AcO−, TfO−, and SCN−, reacted with 1a to give
the corresponding substituted alkenes 2c-2h (entries 3-8). Stereochemistry of the alkenes was determined to
be E by the NOE measurements. MeOH reacted with 1a to give ketone 4, which was probably formed via
methoxy alkene (entry 9). Lithium acetylide gave a mixture of 2i and 3a (entry 10). Enyne 2i was formed by the
nucleophilic attack of the acetylide on C, whereas phenylthio-substituted alkyne 3a was formed by the attack
of the acetylide on S. Dimethylketene methyl trimethylsilyl acetal and Et2NH attacked the sulfur atom of 1a to
give compounds 3b and 3c, respectively (entries 11 and 12). Recovery of the alkyne was confirmed by the
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reaction using 8-hexadecyne and Et2NH (entry 13). These results indicate that 1a acts as an ambident
electrophile.36
Figure 4. Thermal stability of the thiirenium ion 1a in Bu4NBF4/CH2Cl2. Yields of 2a (red line) and 2b (black
line).
Table 1. Reactions of thiirenium ion 1a with nucleophilesa
Entry
1
Nu–
product 2
Entry
7
Nu–
product 2
product 3
PhS
Pr
PhS
Pr
Bu4NCl
Bu4NOTf
Pr
OTf
Pr
Cl
2a, 87%b
2g, 45%
PhS
Pr
PhS
Pr
2
3
8
9
Bu4NBF4
Bu4NBr
Bu4NSCN
MeOH
Pr
F
2b, 92%
Pr
2h, 67%
SCN
PhS
Pr
PhS
Pr
Pr
Br
Pr
O
4, 66%
Pr
2c, 82%
PhS
Pr
PhS
Pr
PhS
Ph
4
10
Bu4NI
Li
Ph
Pr I
2d, 69%
3a, 60%
2i, 14%
Ph
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Table 1. Continue
Entry
product 2
Entry
11
Nu–
product 2
product 3
Nu–
O
PhS
Pr
OTMS
OMe
Bu4NOArc
PhS
OMe
5
Pr
OAr
Ar = C6H4NO2-4
2e, 40%
3b, 50%
PhS NEt2
PhS
Pr
12
Et2NH
3c, 58%
6
Bu4NOAc
Pr
OAc
PhS NEt2
13d
Et2NH
2f, 61%
3c, 82%
a PhSSPh (0.125 mmol) was electrochemically oxidized (2.1 F) in the presence of 4-octyne (0.25 mmol) in a 0.3 M solution
of Bu4NBF4 in CH2Cl2 at −78 °C. 10 equiv of nucleophile was added. Isolated yields are shown unless otherwise stated.
b The yields were determined by GC using an internal standard. c 7.1 eq of Bu4NOAr was added. d 8-Hexadecyne was used
instead of 4-octyne. 94% of 8-hexadecyne was recovered.
To obtain a deeper insight into the reactivity of the thiirenium ion we carried out DFT calculations. These
calculations show that the LUMO of 1a has large coefficients on the sulfur and the two carbon atoms of the
three-membered ring (Figure 5a), indicating that nucleophiles can attack both sulfur and carbon atoms. The
DFT calculation also shows that the carbon atom has higher positive potential than the sulfur atom although
the thiirenium ion formally has a positive charge on the sulfur atom (Figure 5b).
Figure 5. a) LUMO and b) electrostatic potential of 1a.
The following mechanistic arguments may be reasonable (Figure 6). The ketene silyl acetal and Et2NH
attack the sulfur atom, which has a formal positive charge, to give 3 and the acetylene (path a), whereas
halide, acetate, triflate, and SCN anions and methanol attack the carbon atom to give 2 (path b). The lithium
acetylide attacks both the carbon and sulfur atoms of 1. In the case of halide, acetate, and triflate ions as
nucleophiles the reverse reaction of path a might be possible, because such nucleophiles are also good leaving
groups. If such an equilibrium exists, 2 can be produced even if path a is preferable. To examine such a
possibility, the experiments using an externally added acetylene having different R groups were carried out.
The equilibrium would lead to the exchange of acetylenes and the formation of thiirenium ion 1 with different
R groups, which eventually gives 2 with different R groups.
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PhS Nu
3
path a
path b
+
Ph
path a
Nu–
R
R
+
S
R
R
PhS
R
R
1
path b
Nu
2
Figure 6. Plausible explanation for the product selectivity.
5-Decyne (1 equiv) was added to a solution of 1a and the mixture was reacted with Bu4NCl. 2a was
obtained as the major product (68%) in addition to 2j (14%) (Figure 7). The reaction via path a gives 3 and 4-
octyne, which might go out of the solvent cage. The reverse reaction of 3 with 5-decyne in the bulk solution
gives 1c, which react with Cl- via path b to give 2j. This means the equilibrium discussed above does exist,
although it does not play a major role. Another possibility to be considered is that an acetylene exchange
reaction took place between 1a and 5-decyne to give 1c prior to the reaction with Cl-.
In a second experiment, 4-octyne (1 equiv) was added to a solution of 1c which was electrochemically
generated from 5-decene and PhSSPh, and the mixture was reacted with Bu4NCl. 2j was obtained as the major
product (94%) in addition to a small amount of 2a (2%).
These experiments revealed that in the reaction of 1 with Cl- path b is faster than path a, although a small
amount of 2 might be produced via 3 through path a and its reverse reaction.
Figure 7. Reactions of 1 with Cl- in the presence of alkynes.
Conclusions
In conclusion, we show that thiirenium ions having no bulky substituent groups can be generated and
accumulated in CH2Cl2 by electrochemical oxidation of disulfide in the presence of alkynes at low
temperatures such as −78 °C. The thiirenium ions were successfully characterized by NMR, MS, and Raman
spectroscopic analyses and exhibited two types of reactivity depending on the nature of nucleophiles.
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Experimental Section
1
13
13
General. H and C NMR spectra were recorded in CDCl3 on Varian Mercury plus-400 (1H: 400 MHz, C: 100
MHz) spectrometer, or JEOL ECA-600P spectrometer (1H: 600 MHz, 13C: 150 MHz) with tetramethylsilane as an
internal standard unless otherwise noted. Mass spectra were obtained on JEOL JMS-SX102A mass
spectrometer (EI). GC analysis was performed on a Shimadzu GC-2014 gas chromatograph equipped with a
flame ionization detector using a fused silica capillary column (column, CBP1; 0.22 mm × 25 m). Merck
precoated silica gel F254 plates (thickness 0.25 mm) was used for thin-layer chromatography (TLC) analysis.
Flash chromatography was carried out on silica gel (Kanto Chem. Co., Silica Gel N, spherical, neutral, 40−100
μm) unless otherwise noted. All reactions were carried out under argon atmosphere unless otherwise noted.
The anodic oxidation was carried out using an H-type divided cell (4G glass filter) equipped with a carbon felt
anode (Nippon Carbon GF-20-P21E, ca. 160 mg for 0.25 mmol scale, dried at 300 °C/1 mmHg for 3 h before
use) and a platinum plate cathode (10 mm × 10 mm) (Figure S1). Although we used a cell of our original
design, similar electrochemical cells are commercially available at Adams & Chittenden Scientific Glass
(http://adamschittenden.com/gallery.html?category=4) and EC Frontier.,Inc. (http://www.ec-frontier.co.jp/VB-
9.html ). A Kikusui PMC350-0.2A was used as DC power supply for the electrolysis.
Bu4NBF4 was purchased from TCI and dried at 25 °C/1 mmHg for 12 h. Dichloromethane was washed with
water, distilled from P2O5, redistilled from dried K2CO3 to remove a trace amount of acid, and stored over 4Å
molecular sieves. Dichloromethane-d2 (CD2Cl2 D-99.80%) was purchased and stored over molecular sieves 4A.
Unless otherwise noted, all materials were obtained from commercial suppliers and used without further
purification. Bis(4-fluorophenyl)disulfide was prepared according to a reported procedure.37,38 Compounds
1
2a,39 2b,40 2c,39 2d,39 2f,41 2h,39 and 3c42 were oil, and were characterized by comparison of their H NMR
spectra with those reported in the literature.
platinum lead wire
platinum lead wire
rubber septum
rubber septum
60 mm
platinum plate cathode
carbon felt anode
4G glass filter
20 mm
70 mm
Figure 8. An H-type divided cell for electrolysis.
Generation and accumulation of thiirenium ion. The anodic oxidation was carried out in an H-type divided
cell equipped with a carbon felt anode and a platinum plate cathode. In the anodic chamber was placed a
solution of PhSSPh (0.5 equiv) and 4-octyne (1 equiv) in 0.3 M Bu4PBF4, Bu4NB(C6F5)4, or Bu4NBF4 in CH2Cl2 (10
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mL). In the cathodic chamber were placed 0.3 M Bu4PBF4, Bu4NB(C6F5)4, or Bu4NBF4 in CH2Cl2 (10 mL) and
trifluoromethanesulfonic acid (60 μl). The constant current electrolysis (8.0 mA) was carried out at −78 °C with
magnetic stirring until 2.1 F of electricity was applied.
Reactions of thiirenium ion with nucleophiles. The electrolysis of PhSSPh (27.3 mg, 0.125 mmol) in the
presence of 4-octyne (28.6 mg, 0.250 mmol) was carried out as described above. To a solution of the
thiirenium ion thus generated in the anodic chamber was added a solution of nucleophile (2.50 mmol) in
CH2Cl2 at −78 °C and the reacꢀon mixture was sꢀrred at −78 °C for 30 min, and then at 20 °C for 30 min. The
solution in the anodic chamber was collected and the solvent was removed under reduced pressure and the
residue was quickly filtered through a short column (2 x 3 cm) of silica gel to remove Bu4NBF4. After removal of
the solvent under reduced pressure, the crude product was purified by flash chromatography and GPC to
obtain the products.
Reactions of thiirenium ion with nucleophiles
(E)-4-Chloro-5-phenylthio-4-octene (2a)
The electrolysis (2.1 F) of PhSSPh (27.6 mg, 0.126 mmol) in the presence of 4-octyne (27.7 mg, 0.251 mmol),
and subsequent treatment with 2.5 M Bu4NCl/CH2Cl2 (1 mL) gave the title compound (87% yield). The yield
was determined by GC analysis using hexadecane as internal standard.
(E)-4-Fluoro-5-phenylthio-4-octene (2b)
The electrolysis (2.1 F) of PhSSPh (76.0 mg, 0.348 mmol) in the presence of 4-octyne (74.5 mg, 0.676 mmol)
followed by flash chromatography (hexane/EtOAc 100:0, then 10:3) gave the title compound (148.3 mg, 92%
yield).
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(E)-4-Bromo-5-phenylthio-4-octene (2c)
The electrolysis (2.1 F) of PhSSPh (31.6 mg, 0.145 mmol) in the presence of 4-octyne (31.2 mg, 0.283 mmol),
and the subsequent treatment with 2.5 M Bu4NBr/CH2Cl2 (1 mL) followed by a short column of silica gel
(hexane/EtOAc 1:1) and GPC gave the title compound (61.5 mg, 82%).
(E)-4-Iodo-5-phenylthio-4-octene (2d)
The electrolysis (2.1 F) of PhSSPh (31.5 mg, 0.144 mmol) in the presence of 4-octyne (31.7 mg, 0.288 mmol),
and the subsequent treatment with a solution of Bu4NI (923 mg, 2.50 mmol) in CH2Cl2 (1.0 mL) followed by a
short column of silica gel (hexane/EtOAc 1:1) and GPC gave the title compound (55.7 mg, 69%).
(E)-4-(4-Nitrophenoxy)-5-phenylthio-4-octene (2e)
The electrolysis (2.1 F) of PhSSPh (27.8 mg, 0.127 mmol) in the presence of 4-octyne (26.9 mg, 0.244 mmol),
and the subsequent treatment with a solution of Bu4NO(C6H4-p-NO2) (660 mg, 1.74 mmol) in CH2Cl2 (4.0 mL)
followed by a short column of silica gel (hexane/EtOAc 1:1) and GPC gave the title compound (34.7 mg, 40%).
1H NMR (400 MHz, CDCl3) δ 8.24 (d, J 9.3 Hz, 2H), 7.35−7.20 (m, 4H), 7.02 (d, J 9.3 Hz, 2H), 2.63 (t, J 7.8 Hz, 2H),
2.13 (t, J 7.7 Hz, 2H), 1.58−1.42 (m, 4H), 0.92 (t, J 7.4 Hz, 3H), 0.78 (t, J 7.5 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
161.7, 154.7, 142.4, 135.0, 129.08, 129.07, 126.4, 126.1, 124.5, 116.0, 32.0, 31.8, 21.3, 20.9, 13.67, 13.63;
LRMS (EI) m/z 357 (M+); HRMS (EI) calcd for C20H23NO3S (M+): 357.1399, found: 357.1391.
(E)-4-Acetoxy-5-phenylthio-4-octene (2f)
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The electrolysis (2.1 F) of PhSSPh (27.2 mg, 0.125 mmol) in the presence of 4-octyne (25.6 mg, 0.232 mmol),
and the subsequent treatment with a solution of Bu4NOAc (754 mg, 2.50 mmol) in CH2Cl2 (1.0 mL) followed by
a short column of silica gel (hexane/EtOAc 1:1) and GPC gave the title compound (39.2 mg, 61%).
(E)-4-Trifluoromethanesulfonyloxy-5-phenylthio-4-octene (2g)
The electrolysis (2.1 F) of PhSSPh (27.4 mg, 0.126 mmol) in the presence of 4-octyne (27.6 mg, 0.250 mmol),
and the subsequent treatment with a solution of Bu4NOTf (979 mg, 2.50 mmol) in CH2Cl2 (1.0 mL) followed by
a short column of silica gel (hexane/EtOAc 1:1) and GPC gave the title compound (41.5 mg, 45%). 1H NMR (400
MHz, CDCl3) δ 7.33−7.21 (m, 5H), 2.78 (t, J 7.5 Hz, 2H), 2.27 (t, J 7.5 Hz, 2H), 1.67−1.49 (m, 4H), 0.96 (t, J 7.5 Hz,
3H), 0.84 (t, J 7.5 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 151.4, 133.4, 129.9, 129.5, 129.2, 126.9, 118.4 (q, JC−F
=
36.1 Hz), 33.6, 32.5, 21.1, 20.3, 13.4, 13.2; LRMS (EI) m/z 368 (M+); HRMS (EI) calcd for C15H19F3O3S2 (M+):
368.0728, found: 368.0730.
(E)-4-Thiocyanato-5-phenylthio-4-octene (2h)
The electrolysis (2.1 F) of PhSSPh (27.4 mg, 0.126 mmol) in the presence of 4-octyne (27.6 mg, 0.250 mmol),
and the subsequent treatment with the solution of Bu4NSCN (752 mg, 2.50 mmol) in CH2Cl2 (1.0 mL) followed
by a short column of silica gel (hexane/EtOAc 1:1) and GPC gave the title compound (46.3 mg, 67%).
5-(Phenylthio)octan-4-one (4)
The electrolysis (2.1 F) of PhSSPh (24.3 mg, 0.111 mmol) in the presence of 4-octyne (23.2 mg, 0.27 mmol),
and the subsequent treatment with CH3OH (81.2 mg, 2.53 mmol) followed by flash chromatography
(hexane/EtOAc 100:0, then 5:1) to the title compound (32.7 mg, 66 %). 1H NMR (400 MHz, CDCl3) δ 7.37−7.33
(m, 2H), 7.31−7.22 (m, 3H), 3.64 (t, J 7.5 Hz, 1H), 2.55 (t, J 7.7 Hz, 2H), 1.85−1.75 (m, 1H), 1.72−1.62 (m, 1H),
13
1.60−1.53 (m, 2H), 1.51−1.44 (m, 1H), 1.42−1.31 (m, 1H), 0.92 (t, J 7.5 Hz, 3H), 0.88 (t, J 7.5 Hz, 3H); C NMR
(100 MHz, CDCl3) δ 207.5, 133.3, 132.3, 129.0, 127.7, 56.7, 41.2, 32.5, 20.6, 17.3, 13.77, 13.72; LRMS (EI) m/z
236 (M+); HRMS (EI) calcd for C14H20OS (M+): 236.1235, found: 236.1231.
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(E)-4-Phenylthio-5-phenylethynyl-4-octene (2i)
The electrolysis (2.1 F) of PhSSPh (27.5 mg, 0.126 mmol) in the presence of 4-octyne (27.6 mg, 0.25 mmol),
and the subsequent treatment with the solution of 1.0 M lithium phenylacetylide/THF (2.5 mL) followed by a
short column of silica gel (hexane/EtOAc 1:1) and GPC gave 2i (10.8 mg, 14 %) and 3a (31.8 mg, 60 %). 1H NMR
(400 MHz, CDCl3) δ 7.46−7.42 (m, 2H), 7.35−7.26 (m, 7H), 7.24−7.19 (m, 1H), 2.58 (t, J 7.5 Hz, 2H), 2.52 (t, J 7.5
13
Hz, 2H), 1.71−1.62 (m, 2H), 1.61−1.52 (m, 2H), 0.98 (t, J 7.5 Hz, 3H), 0.88 (t, J 7.5 Hz, 3H); C NMR (100 MHz,
CDCl3) δ 142.5, 134.9, 131.3, 130.6, 128.9, 128.3, 128.0, 126.9, 126.6, 123.7, 94.4, 89.3, 37.0, 36.2, 22.1, 22.0,
13.69, 13.62; LRMS (EI) m/z 320 (M+); HRMS (EI) calcd for C22H24S (M+): 320.1599, found: 320.1598.
We could not determine the stereochemistry of 2i by NOE measurement because the chemical shift of the
protons of two methylene groups next to the alkene moiety are very close (2.52 and 2.58 ppm).
Phenyl(phenylethynyl)sulfane (3a)
13
1H NMR (400 MHz, CDCl3) δ 7.53−7.47 (m, 4H), 7.37−7.33 (m, 5H), 7.25−7.21 (m, 1H); C NMR (100 MHz,
CDCl3) δ 132.9, 131.7, 129.2, 128.6, 128.4, 126.5, 126.2, 122.9, 97.9, 75.4; LRMS (EI) m/z 210 (M+); HRMS (EI)
calcd for C14H10S (M+):210.0503, found: 210.0494.
Methyl 2-methyl-2-(phenylthio)propionate (3b)
The electrolysis (2.1 F) of PhSSPh (27.5 mg, 0.126 mmol) in the presence of 4-octyne (27.6 mg, 0.250 mmol),
and subsequent treatment with dimethylketene methyl trimethylsilyl acetal (436 mg, 2.50 mmol) followed by
a short column of silica gel (hexane/EtOAc 1:1) and GPC gave the title compound (26.6 mg, 50%). 1H NMR (400
13
MHz, CDCl3) δ 7.47−7.44 (m, 2H), 7.40−7.30 (m, 3H), 3.66 (s, 3H), 1.49 (s, 6H); C NMR (100 MHz, CDCl3) δ
174.4, 136.7, 131.4, 129.4, 128.6, 52.2, 51.0, 25.8; LRMS (EI) m/z 210 (M+); HRMS (EI) calcd for C11H14O2S
(M+):210.0715, found: 210.0714.
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Diethyl(phenylthio)amine (3c)
The electrolysis (2.1 F) of PhSSPh (27.6 mg, 0.126 mmol) in the presence of 8-hexadecyne (56.1 mg, 0.252
mmol), and subsequent treatment with diethylamine (185 mg, 2.53 mmol) followed by a short column of silica
gel (hexane/EtOAc 1:1) and GPC gave the title compound (37.3 mg, 82%) and 8-hexadecyne (52.9 mg, 94%).
Thermal stability. After generating thionium ion from PhSSPh (27.3 mg, 0.125 mmol) and 4-octyne (28.6 mg,
0.25 mmol) at −78 °C as described above, the solution was stirred at T °C (T = −78, −60, −40, −20, and 0) for 30
min. The solution was recooled to −78 °C, added Bu4NCl (2.5 mmol) in CH2Cl2 and stirred at −78 °C for 30 min
and then at 20 °C for 30 min. The solvent was removed under reduced pressure and the residue was quickly
filtered through a short column (2 x 3 cm) of silica gel to remove Bu4NBF4. The silica gel was washed with
hexane/EtOAc 1:1. After removal of the solvent under reduced pressure, the crude product was analyzed by
gas chromatography.
Reference reaction. In the anodic chamber were placed 4-octyne or 5-decyne (0.25 mmol), and PhSSPh (0.125
mmol), Bu4NBF4 (3.0 mmol), and CH2Cl2 (10 mL). In the cathodic chamber were placed
trifluoromethanesulfonic acid (60 μL), Bu4NBF4 (3.0 mmol) and CH2Cl2 (10 mL). The constant current
electrolysis (8.0 mA) was carried out at −78 °C with magneꢀc sꢀrring unꢀl 2.1 F of electricity was passed. To
the anodic chamber was added another alkyne (0.25 mmol). The solution was stirred for 10 min at −78 °C. To
the anodic chamber was added 2.5 M Bu4NCl/CH2Cl2 (1 mL), and to the cathodic chamber CH2Cl2 (1 mL) was
added at −78 °C. The soluꢀon was sꢀrred for 30 min at −78 °C, and then 30 min at 20 °C. The solution in the
anodic chambers was collected and the solvent was removed under reduced pressure. The residue was
filtered through a short column (2 x 4 cm) of silica gel to remove Bu4NBF4 by using hexane/EtOAc (1:1 v/v) as
an eluent. After removal of the solvent under reduced pressure the crude product was analyzed by GC using
tetradecane as an internal standard.
(E)-5-Chloro-6-phenylthio-5-hexene (2j)
In the anodic chamber were placed 5-decyne (34.6 mg, 0.25 mmol) and diphenyl disulfide (27.5 mg, 0.126
mmol). Electrochemical oxidation (2.1 F) and subsequent addition of the solution of 2.5 M Bu4NCl/CH2Cl2 (1
mL) followed by a short column of silica gel (hexane/EtOAc 1:1) gave the crude of the title compound. After
removal of the solvent under reduced pressure the crude product was analyzed by GC using tetradecane as an
1
internal standard (99% yield). H NMR (400 MHz, CDCl3) δ 7.27−7.19 (m, 4H), 7.17−7.12 (m, 1H), 2.80 (t, J 7.5
Hz, 2H), 2.37 (t, J 7.9 Hz, 2H), 1.62−1.54 (m, 4H), 1.53−1.45 (m, 4H), 0.91 (t, J 7.2 Hz, 3H), 0.84 (t, J 7.3 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 139.8, 135.5, 129.5, 128.9, 128.8, 126.1, 37.0, 33.8, 30.1, 29.9, 22.2, 21.8, 13.90,
13.89; LRMS (EI) m/z 282 (M+); HRMS (EI) calcd for C16H27ClS (M+): 282.1209, found: 282.1208.
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NMR analyses. A solution of thiirenium ion 1a generated and accumulated from PhSSPh (49.4 mg, 0.226
mmol) and 4-octyne (48.5 mg, 0.440 mmol) in 0.3 M Bu4PBF4 in CD2Cl2 (6.0 mL) was transferred to Ar-flushed
NMR tubes at −78 °C by Ar-flushed 1 mL syringe cooled with dry ice. NMR measurements were carried out
13
using JEOL ECA-600P spectrometer (1H: 600 MHz, C: 150 MHz). Spectra so obtained are presented in the
Supplementary File.
MS analyses; typical procedure. In the anodic chamber were placed 4-octyne (118.6 mg, 1.08 mmol), PhSSPh
(114.6 mg, 0.525 mmol), Bu4NB(C6F5)4 (923.9 mg, 1.0 mmol), and CH2Cl2 (10 mL). In the cathodic chamber
were placed trifluoromethanesulfonic acid (120 μL, 1.37 mmol), Bu4NBF4 (926 mg, 1.0 mmol), and CH2Cl2 (10
mL). The constant current electrolysis (15.0 mA) was carried out at −78 °C with magneꢀc sꢀrring unꢀl 2.1 F of
electricity was passed. The reaction mixture of the anodic chamber was analyzed by CSI-MS (spray
temperature; 0 °C): HRMS (CSI) m/z calcd for C14H19S+ (M+): 219.1202, found: 219.1209.
Raman analyses. A laser beam from a fiber-coupled output of cw laser, Toptica XTRA, 250 mW at 785 nm, was
conducted through the solution in the anodic chamber of the electrochemical cell. Scattered light was
collected in the direction perpendicular to the axis of the laser beam by using a combination of quartz lenses
focusing the light on the surface of the entrance cross section of the bundle of forty optical fibers with a 100
μm diameter for each. The optical components were contained in a vacuum-tight glass tube sealed with
rubber o-rings and partly dipped into the reactant solution. The electrochemical cell was independently
purged with N2 gas to avoid humidity in air. For the measurement, the vacuum seal of the optical component
was crucial in avoiding frost, which scatters both the excitation and signal beams.
The collected light was conducted through the optical fibers to a spectrometer for dispersion, Acton 320 PI
(1200 G/mm blazed at 500 nm or 600 G/mm blazed at 1000 nm), and detected by using a liquid-nitrogen
cooled CCD array detector, PyLoN:256-OE 1024 x 256 pixels of 26 x 26 μm2. To minimize stray light, a sharp-
edge long-pass filter, Semrock RazorEdge 785R (o.d. <10−6 at 785 nm), was placed in front of the entrance slit
of the spectrometer, where the image of the exit cross section of the fiber bundle with vertically aligned forty
optical fibers was focused. Spectra were accumulated for 6 min 40 sec (a 4-sec exposure time by 100 times
accumulation) for each and redundantly stored one by one for 4 hours (400 sec by 60 spectra) during the
electrolysis. Spectral resolution was 0.2 nm, which corresponds to 3 cm−1 at 815 nm where a Raman band of
~
~
470 cm−1 was observed.
DFT calculations. DFT calculations were conducted with the Gaussian 09 program.43 All geometry
optimizations were carried out at the B3LYP level of density functional theory with the 6-31G(d) basis set. The
bond order and s-character were obtained by the natural bond orbital (NBO) analysis. See Supplementary file.
Acknowledgements
This work was supported by the JSPS (KAKENHI Grants JP26220804, and JP16K14057).
Supplementary Material
Experimental procedures and spectroscopic data for new compounds.
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