An electroinitiated cation chain reaction: Intramolecular carbon-carbon bond formation between thioacetal and olefin groups

Article abstract of DOI:10.1002/anie.200705748

(Figure Presented) The treatment of an olefinic thioacetal with a catalytic amount of ArS(ArSSAr)-⁺B(C₆F⁵) ₄^-, or the electrolysis of a mixture of an olefinic thioacetal and ArSSAr, gives rise to effective intramolecular carbon-carbon bond formation (see scheme). This transformation opens up great potential for electroinitiated cation chain reactions in organic synthesis.

Full text of DOI:10.1002/anie.200705748

Communications
DOI: 10.1002/anie.200705748
Electroinitiated Reactions
An Electroinitiated Cation Chain Reaction: Intramolecular Carbon–
Carbon Bond Formation between Thioacetal and Olefin Groups**
Kouichi Matsumoto, Shunsuke Fujie, Koji Ueoka, Seiji Suga, and Jun-ichi Yoshida*
In memory of Yoshihiro Matsumura
In organic synthesis, radical chain reactions are widely
utilized for the synthesis of complex organic molecules.[1] In
contrast, cationic chain reactions[2] are not so widely used,
although carbocationic reactions[3] and cationic chain-growth
polymerization[4] are applied extensively in organic and
polymer synthesis, respectively. Herein we report an example
of a cationic chain reaction which is initiated by an electro-
chemically generated cationic species.
For the mechanism, there are several points to be
considered.[12] The conversion of 1 into 2 takes place
quantitatively, as we reported previously.[5] However, the
reaction of 2 and 3 might be unfavorable because 4 does not
have a neighboring cation-stabilizing group such as an oxygen
atom, and this step might be a bottleneck for the overall
reaction.[13] The last step to form a stable product 5 from
unstable cation 4, however, could be energetically favorable,
making the overall reaction successful. Another important
point to be considered is that the second step could be made
entropically favorable by intramolecularization of the reac-
tion.
This work stems from our earlier observation[5] that the
low-temperature electrochemical oxidation of ArSSAr[6]
leads to the formation of ArS(ArSSAr)+,[7] an equivalent of
ArS+ [8] that reacts with thioacetal 1[9] to give the correspond-
ing alkoxycarbenium ion 2[10] and ArSSAr (Scheme 1). We
envisaged that the reaction of the thus-obtained alkoxycar-
benium ion with an olefin 3 leads to the formation of a second
cation 4,[11] which might react with ArSSAr to give a
sulfenylated product 5 to regenerate “ArS+”. The “ArS+”
species would act as an activator of another molecule of 1.
Therefore, the overall reaction should take place with a
catalytic amount of “ArS+”.
On the basis of the above considerations, we started to
work on the cation chain reactions initiated by electrochemi-
cally generated “ArS+”. We decided to focus our research on
the intramolecular version of the reaction. Thus, thioacetal 6a
(Scheme 2, R = C7H15, Ar= p-FC6H4) bearing a carbon–
carbon double bond was allowed to react with ArS-
(ArSSAr)+BF4 (1 equiv), which was prepared by anodic
À
oxidation of ArSSAr using Bu4NBF4 as a supporting electro-
lyte in CH2Cl2 at À788C (0.67 FmolÀ1 based on ArSSAr).[14]
As shown in Scheme 2, the reaction at À788C led to the
formation of cyclized compound 7a[15] (81% yield) as a
mixture of two diastereomers (cis/trans 6.8:1). Fluoride,
instead of ArS, is introduced onto the olefinic carbon atom,
À
À
indicating that BF4 or a fluoride ion derived from BF4
serves as a nucleophile.
To avoid the fluoride attack, Bu4NB(C6F5)4 was used as a
supporting electrolyte for the initial electrolysis. The forma-
tion of ArS(ArSSAr)+B(C6F5)4 was confirmed by H NMR
spectroscopy and cold-spray ionization (CSI) mass spectrom-
etry.[16] The reaction with 6a at À788C led to effective
formation of 8a (72% yield). In this case ArSSAr attacks the
cyclized cation as a nucleophile. It is interesting to note that
only the cis isomer was obtained (see below).
À
1
Scheme 1. Concept of a “ArS+”-mediated chain reaction of thioacetal
and olefin.
If the concept shown in Scheme 1 is feasible, the reaction
should take place with a catalytic amount of ArS(ArSSAr)+.
Thus, the reaction using 20 mol% of ArS(ArSSAr)+ was
examined, but the yield of 8a was low (33%). However, the
presence of an excess amount of ArSSAr gave rise to effective
[*] K. Matsumoto, S. Fujie, K. Ueoka, Dr. S. Suga, Prof. J. Yoshida
Department of Synthetic and Biological Chemistry
Graduate School of Engineering
Kyoto University
Kyotodaigakukatsura, Nishikyo-ku, Kyoto, 615-8510 (Japan)
Fax: (+81)75-383-2727
E-mail: yoshida@sbchem.kyoto-u.ac.jp
[**] This work was financially supported in part by a Grant-in-Aid for
Scientific Research from the Japan Society for the Promotion of
Science. We are also grateful to Nippon Shokubai Co. and Nippoh
Chemicals Co. for providing sodium tetrakis(pentafluorophenyl)-
borate as a precursor of Bu4NB(C6F5)4.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
Scheme 2. Intramolecular reaction of thioacetal and olefin.
2506
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Chemie
formation of 8a in 82% yield. In this case, ArSSAr
(1.00 mmol) was electrolyzed with 0.04Fmol À1 of electricity
(initiation method A; see Table 1), and the thus-obtained
solution containing ArS(ArSSAr)+ (0.04mmol) and ArSSAr
(0.94mmol) was allowed to react with 6a (0.2 mmol). Further
decrease of the amount of ArS(ArSSAr)+ (0.02 mmol)
resulted in a decrease of the yield (47%), but the yield
could be increased by increasing the reaction temperature
(69% at À208C, 75% at 08C).
This reaction is generally applicable to various unsatu-
rated thioacetals (6a–g), and six-membered ring formation
takes place effectively as shown in Table 1. The tetrahydro-
pyran rings obtained in this reaction serve as common
structural units in a variety of biologically active molecules.[17]
It is also noteworthy that the ArS group can be used for
further transformations.
This intramolecular carbon–carbon bond-formation reac-
tion seems to proceed by a cation chain mechanism
(Scheme 3). The initial electrolysis generates “ArS+”, which
reacts with 6 to give alkoxycarbenium ion 9 and ArSSAr. The
cyclization[18,19] gives 10, which reacts with ArSSAr to give
product 8. In the last step “ArS+” is regenerated to initiate the
next sequence. A high stereoselectivity was observed (exclu-
sive formation of the cis isomers, except in 8b), which
Scheme 3. Mechanism of the electroinitiated cation chain reaction.
indicates that the carbon–carbon bond formation and the
subsequent reaction of thus-generated 10 with ArSSAr take
place in a somewhat concerted manner. The fact that the use
of an excess amount of ArSSAr accelerates the reaction is
consistent with this mechanism. At a higher concentration of
ArSSAr this step becomes more favorable, and hence, the
overall reaction is accelerated.
It is noteworthy that the direct (in-cell) electrolysis of a
mixture of 6 and ArSSAr was also effective in initiating the
reaction (Table 1, initiation method B). Thus, a catalytic
amount of electricity (0.20 FmolÀ1 based on 6a) was passed
through a solution of 6a (0.2 mmol) and ArSSAr (1.0 mmol)
in 0.1m Bu4NB(C6F5)4/CH2Cl2 under constant-current condi-
tions. After the electrolysis the reaction mixture was stirred
for 20 min to obtain 8a in 63% yield. This initiation method is
generally applicable to other substrates, as shown in Table 1.
In conclusion, we have developed a chain reaction
initiated by the electrochemically generated “ArS+” cation,
which involves intramolecular carbon–carbon bond forma-
tion. In-cell electrolysis was also effective for the initiation.
This electroinitiated cation chain reaction adds a new
dimension to organic cation chemistry[3] and organic electro-
chemistry.[20] Applications of this concept to other cation
chain reactions are in progress in our laboratory.
Table 1: Intramolecular carbon–carbon bond formation catalyzed by
“ArS+”.
Thioacetal
Initiation Product
method[a]
Yield
[%][b]
A
B
82[c]
63[c]
6a
6b
8a
8b
A
B
84[d,e]
73[d,f]
A
B
65
60
6c
8c
A
B
88
70
6d
6e
8d
8e
A
B
75
68
Experimental Section
Electrochemical generation and accumulation of ArS(ArSSAr)+-
B(C6F5)4À (Ar= p-FC6H4): The anodic oxidation was carried out in an
H-type divided cell (4G glass filter) equipped with a carbon felt anode
and a platinum plate cathode (40 ” 20 mm2). In the anodic chamber
was placed a solution of ArSSAr (Ar= p-FC6H4; 103 mg, 0.405 mmol)
in 0.1m Bu4NB(C6F5)4/CH2Cl2 (8.0 mL). In the cathodic chamber were
placed 0.1m Bu4NB(C6F5)4/CH2Cl2 (8.0 mL) and trifluoromethane-
sulfonic acid (44.2 mg, 0.295 mmol). The constant-current electrolysis
(8 mA) was carried out at À788C with magnetic stirring until
0.67 FmolÀ1 of electricity was consumed. The anodic solution thus
obtained was analyzed by CSI-MS (spray temperature 08C): HRMS
A
B
62
51
6 f
8 f
A
B
63
52
6g
8g
[a] Initiation method A: ArSSAr (Ar=p-FC6H4; 1.00 mmol) was electro-
lyzed in 0.1m Bu4NB(C6F5)4/CH2Cl2 (8 mL) at À788C by using
0.04 FmolÀ1 of electricity. The solution thus obtained was allowed to
react withthioacetal 6 (0.20 mmol) at À788C for 20 min. Then the
reaction was quenched with Et3N (1.0 mL). Initiation method B: A
solution containing thioacetal 6 (0.20 mmol) and ArSSAr (Ar=p-FC6H4;
1.00 mmol) in 0.1m Bu4NB(C6F5)4/CH2Cl2 (8 mL) was electrolyzed
(0.20 FmolÀ1 based on 6) under constant-current conditions at À788C.
[b] Yield of isolated product. [c] Yield determined by GC methods.
[d] 3 equiv of ArSSAr was used. [e] d.r. =9.9:1 cis/trans. [f] d.r.=9.7:1
cis/trans.
(CSI) calcd for C18H12F3S3 (ArS(ArSSAr)+ (Ar= p-FC6H4), [M+]):
+
381.0047; found: 381.0084. The NMR measurement was carried out at
À808C. Chemical shifts are reported using the methylene signal of
CH2Cl2 at d = 5.32 ppm (1H NMR) as a standard. The large signal
coming from CH2Cl2 was reduced by the usual pulse techniques:
1H NMR (600 MHz, 10:1 CH2Cl2/CD2Cl2): d = 7.22–7.30 (t, J =
8.6 Hz, 6H), 7.35–7.60 ppm (brs, 6H). The 1H NMR spectrum was
very similar to that of ArS(ArSSAr)+BF4À reported previously.[5]
Angew. Chem. Int. Ed. 2008, 47, 2506 –2508
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Communications
Typical procedure for initiation method A: The anodic oxidation
[5] S. Suga, K. Matsumoto, K. Ueoka, J. Yoshida, J. Am. Chem. Soc.
2006, 128, 7710.
was carried out in an H-type divided cell as described above. In the
anodic chamber was placed a solution of ArSSAr (Ar= p-FC6H4;
254mg, 1.00 mmol) in 0.1 m Bu4NB(C6F5)4/CH2Cl2 (8.0 mL). In the
cathodic chamber were placed 0.1m Bu4NB(C6F5)4/CH2Cl2 (8.0 mL)
and trifluoromethanesulfonic acid (6.8 mg, 0.0453 mmol). The con-
stant-current electrolysis (8 mA) was carried out at À788C with
magnetic stirring until 0.04Fmol À1 of electricity was consumed. To
the anodic chamber containing electrogenerated ArS(ArSSAr)+-
B(C6F5)4À was added 3-butenyl 1-(4-fluorophenylthio)octyl ether (6a;
60.5 mg, 0.195 mmol) and the mixture was stirred for 20 min at
À788C. The reaction was quenched with Et3N (1 mL). The solvent
was removed under reduced pressure and the residue was quickly
filtered through a short column (height 2 cm, diameter 3 cm) of silica
gel to remove Bu4NB(C6F5)4. The silica gel was washed with ether
(150 mL). The GC analysis of the combined filtrate indicated that 8a
was formed in 82% yield (GC retention time 17.5 min, CBP-1
column; diameter 0.22 mm, thickness 0.25 mm, length 25 m; initial
oven temperature 1008C; rate of temperature increase 108CminÀ1).
[6] a) A. Bewick, D. E. Coe, J. M. Mellor, D. J. Walton, J. Chem. Soc.
Chem. Commun. 1980, 51; b) Q. T. Do, D. Elothmani, J. Simonet,
G. Le Guillanton, Electrochim. Acta 2005, 50, 4792, and refer-
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[7] a) A. S. Gybin, W. A. Smit, V. S. Bogdanov, M. Z. Krimer, J. B.
Kalyan, Tetrahedron Lett. 1980, 21, 383; b) V. S. Bogdanov, A. S.
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[9] Electrochemical generation of alkoxycarbenium ion pools from
thioacetals: a) S. Suzuki, K. Matsumoto, K. Kawamura, S. Suga,
J. Yoshida, Org. Lett. 2004, 6, 3755; electrochemical oxidation of
thioacetals: b) J. Yoshida, M. Sugawara, N. Kise, Tetrahedron
Lett. 1996, 37, 3157; c) J. Yoshida, M. Sugawara, M. Tatsumi, N.
Kise, J. Org. Chem. 1998, 63, 5950.
[10] a) S. Suga, S. Suzuki, A. Yamamoto, J. Yoshida, J. Am. Chem.
Soc. 2000, 122, 10244; b) S. Suga, S. Suzuki, J. Yoshida, Org. Lett.
2005, 7, 4717.
[11] Addition of a cation to a carbon–carbon double bond: a) S. Suga,
T. Nishida, D. Yamada, A. Nagaki, J. Yoshida, J. Am. Chem. Soc.
2004, 126, 14338; b) H. Mayr, Angew. Chem. 1990, 102, 1415;
Angew. Chem. Int. Ed. Engl. 1990, 29, 1371.
[12] Reactivity of cations: a) H. Mayr, A. R. Ofial, Angew. Chem.
2006, 118, 1876; Angew. Chem. Int. Ed. 2006, 45, 1844; b) M.
Hofmann, N. Hampel, T. Kanzian, H. Mayr, Angew. Chem. 2004,
116, 5518; Angew. Chem. Int. Ed. 2004, 43, 5402.
[13] Since a rather stable a-methoxybenzyl cation has been reported
to add smoothly to propene, this process might not be problem-
atic; see, H. Mayr, W. Striepe, J. Org. Chem. 1983, 48, 1159.
[14] Theoretical amount of electricity to convert ArSSAr into
ArS(ArSSAr)+.
1
8a: H NMR (400 MHz, CDCl3): d = 0.87 (t, J = 6.8 Hz, 3H), 1.18–
1.62 (m, 14H), 1.76–1.90 (m, 2H), 3.08 (dddd, J = 12.0, 12.0, 4.0,
4.0 Hz, 1H), 3.16–3.25 (m, 1H), 3.37 (ddd, J = 12.0, 12.0, 2.0 Hz, 1H),
3.99 (ddd, J = 12.0, 6.4, 1.6 Hz, 1H), 6.96–7.03 (m, 2H), 7.38–7.44 ppm
(m, 2H); 13C NMR (150 MHz, CDCl3): d = 14.1, 22.6, 25.4, 29.2, 29.6,
31.8, 33.3, 36.2, 38.8, 44.7, 67.6, 77.6, 116.0 (d, J = 21.5 Hz), 128.3,
135.8 (d, J = 8.6 Hz), 162.6 ppm (d, J = 245.6 Hz); LRMS (EI): m/z:
310 [M+], 183 [M+ÀSC6H4F]; HRMS (EI) calcd for C18H27FOS [M+]:
310.1767; found 310.1767.
Typical procedure for initiation method B: The anodic oxidation
was carried out in an H-type divided cell as described above. In the
anodic chamber was placed a solution of 3-butenyl 1-(4-fluorophe-
nylthio)octyl ether (6a; 62.0 mg, 0.200 mmol) and ArSSAr (Ar= p-
FC6H4; 254.1 mg, 1.00 mmol) in 0.1m Bu4NB(C6F5)4/CH2Cl2 (8.0 mL).
In the cathodic chamber were placed 0.1m Bu4NB(C6F5)4/CH2Cl2
(8.0 mL) and trifluoromethanesulfonic acid (10.2 mg, 0.0680 mmol).
The constant-current electrolysis (8 mA) was carried out at À788C
with magnetic stirring until 0.20 FmolÀ1 of electricity (based on 6a)
was consumed. The mixture was stirred for 20 min at À788C, and then
the reaction was quenched with Et3N (1 mL). The solvent was
removed under reduced pressure and the residue was quickly filtered
through a short column (height 2 cm, diameter 3 cm) of silica gel to
remove Bu4NB(C6F5)4. The silica gel was washed with ether (150 mL).
The GC analysis of the combined filtrate indicated that 8a was
formed in 63% yield.
[15] a) J. Yoshida, Y. Ishichi, S. Isoe, J. Am. Chem. Soc. 1992, 114,
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[16] K. Yamaguchi, J. Mass Spectrom. 2003, 38, 473.
[17] S. Santos, P. A. Clarke, Eur. J. Org. Chem. 2006, 2045.
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Received: December 15, 2007
Published online: February 19, 2008
Keywords: carbocations · electrochemistry · oxidation · sulfur ·
.
synthetic methods
´
13640; h) A. P. Dobbs, L. Pivnevi, M. J. Penny, S. Martinovic,
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[19] The use of BF3·OEt2 instead of “ArS+” under similar conditions
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2508 www.angewandte.org
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