Integrated electrochemical-chemical oxidation mediated by alkoxysulfonium Ions

Article abstract of DOI:10.1021/ja202880n

Generation of carbocations by the "cation pool" method followed by reaction with dimethyl sulfoxide (DMSO) gave the corresponding alkoxysulfonium ions. Alkoxysulfonium ions could also be generated by in situ DMSO trapping of electrochemically generated carbocations. The resulting alkoxysulfonium ions were transformed into carbonyl compounds by treatment with triethylamine. The present integrated electrochemical-chemical oxidation can be applied to the oxidation of diarylmethanes to diaryl ketones, toluenes to benzaldehydes, and aryl-substituted alkenes to 1,2-diketones. Moreover, the oxidation of unsaturated compounds bearing a nucleophilic group in an appropriate position gives cyclized carbonyl compounds.

Full text of DOI:10.1021/ja202880n

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pubs.acs.org/JACS
Integrated ElectrochemicalꢀChemical Oxidation Mediated by
Alkoxysulfonium Ions
Yosuke Ashikari, Toshiki Nokami, and Jun-ichi Yoshida*
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku,
Kyoto 615-8510, Japan
S Supporting Information
b
Scheme 1. Chemical Oxidation Mediated by Alkoxysulfo-
nium Ions
ABSTRACT: Generation of carbocations by the “cation
pool” method followed by reaction with dimethyl sulfoxide
(DMSO) gave the corresponding alkoxysulfonium ions.
Alkoxysulfonium ions could also be generated by in situ
DMSO trapping of electrochemically generated carboca-
tions. The resulting alkoxysulfonium ions were transformed
into carbonyl compounds by treatment with triethylamine.
The present integrated electrochemicalꢀchemical oxida-
tion can be applied to the oxidation of diarylmethanes to
diaryl ketones, toluenes to benzaldehydes, and aryl-substi-
tuted alkenes to 1,2-diketones. Moreover, the oxidation of
unsaturated compounds bearing a nucleophilic group in an
appropriate position gives cyclized carbonyl compounds.
reaction to give RR0CdO is a two-electron oxidation. If
substrates of lower oxidation state, for example RR0CH2,
could be used to generate alkoxysulfonium ions, the overall
reaction would be a four-electron oxidation, and the method
would serve as a highly useful way of oxidizing organic
compounds.
rganic synthesis has been developed mainly on the basis of
It is well-known that electrochemical oxidation serves as a
powerful method for generating carbocations and onium ions
under mild conditions.4 In fact, various types of electrochemical
oxidation reactions proceed by a mechanism involving carboca-
tions, though carbocations are usually trapped spontaneously by
nucleophiles that are present in the reaction medium. However,
we have developed an effective method for generating and
accumulating carbocations or onium ions by low-temperature
electrochemical oxidation. The method, which is called the
“cation pool” method, has been successfully applied to N-
acyliminium ions,9 alkoxycarbenium ions,10 and diarylcarbenium
ions.11 On the basis of these backgrounds, we envisaged that
carbocations generated by the cation pool method could be used
for a subsequent reaction with DMSO to generate alkoxysulfo-
nium ions, which would then react with an amine base to give the
corresponding carbonyl compounds (Scheme 2). In fact, Mayr
and co-workers observed in their mechanistic studies that
diarylcarbenium ions generated by chemical SN1 reaction reacted
with DMSO and that subsequent treatment with triethylamine
gave the diaryl ketones.12 It should be noted that unlike the
chemical methods, the oxidation state of the precursor in the
electrochemical method is lower than that of the resulting
alkoxysulfonium ion. Therefore, we initiated our studies of the
integration of the electrochemical method and the chemical
method mediated by alkoxysulfonium ions.
O
step-by-step synthesis. However, combining multiple steps
without isolating intermediates is strongly needed to enhance the
power and efficiency of organic synthesis.1,2 To this end,
chemists have been interested in the integration of chemical
reactions to develop synthetic transformations that would be
otherwise impossible, such as the generation of unstable highly
reactive species that are swiftly utilized for a further reaction
before they decompose.3
In addition to chemical reactions using chemical reagents and/
or catalysts, electrochemical reactions4,5 using electron transfer
on the surface of the electrode serve as a powerful means of
generating highly reactive species. Electrochemistry allows for
the selective introduction and removal of electrons under mild
conditions, whereas this process usually requires harsh condi-
tions when the chemical method is employed.
Among a variety of reactions used in organic synthesis,
selective oxidation of organic compounds still remains as a major
challenge.6 We envisaged that integration of electrochemical
oxidation and chemical oxidation would be a nice approach to
this challenge, and we report here an example of such integration
that is mediated by an unstable reactive intermediate.
We chose to use alkoxysulfonium ions as key intermediates
because treatment of an alkoxysulfonium ion with a base such as
triethylamine eventually gives the corresponding carbonyl com-
pound; this serves as one of the mildest methods for oxidation of
organic compounds [dimethyl sulfoxide (DMSO) oxidation]
(Scheme 1).7,8 Although alkoxysulfonium ions can be generated
by several chemical methods, the oxidation state of the precur-
sors (RR0CHX; X = heteroatom) and the resulting alkoxysulfo-
nium ions (RR0CHꢀOS+Me2) are the same, and the overall
To test the feasibility of the present concept, we first examined
the reaction of an electrochemically generated diarylcarbenium
ion with DMSO. Thus, diarylcarbenium ion 2 was generated and
Received: March 30, 2011
Published: July 11, 2011
r
2011 American Chemical Society
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|

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Scheme 2. Integrated ElectrochemicalꢀChemical Oxidation
Mediated by Alkoxysulfonium Ions
accumulated by the electrochemical oxidation of diarylmethane 1
in CD2Cl2 using Bu4NBF4 as a supporting electrolyte at ꢀ78 °C
according to the “cation pool” method (Figure 1, method A).11
The addition of DMSO to 2 gave alkoxysulfonium ion 3, which
was well-characterized by NMR analysis at ꢀ78 °C. Treatment of
the solution of 3 with triethylamine gave the corresponding diaryl
ketone 4 in 91% yield. This proof-of-principle experiment
revealed that the electrochemical reaction and the chemical
reaction could be integrated effectively through the intermediacy
of a carbocation and an alkoxysulfonium ion. The method was
also applicable to diarylmethane 5 to produce the corresponding
diaryl ketone 6 (Table 1).
In-situ trapping of carbocations by DMSO is also effective
when the substrate oxidation potential is lower than that of
DMSO (1.76 V vs SCE). For example, the electrochemical
oxidation of 4-methoxytoluene (7) (1.38 V vs SCE) in 1:2
DMSO-d6/CD2Cl2 (Figure 1, method B) gave alkoxysulfonium
ion 8, which was characterized by NMR analysis. In this case, the
electrolysis could be carried out at 24 °C because the alkoxy-
sulfoniuim ion is more stable than the corresponding carboca-
tion. Treatment of 8 with triethylamine gave aldehyde 9 in 86%
yield. It is noteworthy that the cation pool method cannot be
used in this case because 4-methoxybenzyl cation is not stable
enough to accumulate in the solution even at ꢀ78 °C. It is also
noteworthy that the success of the in situ method is attributed to
the fact that 7 is more easily oxidized than DMSO. In contrast,
the oxidation potential of diarylmethane 1 (1.96 V vs SCE) is
higher than that of DMSO, and therefore, the electrochemical
oxidation of 1 should be carried out in the absence of DMSO.
However, a wide range of organic compounds can serve as substrates
for the in situ method. For example, xanthene (10) was oxidized
effectively by method B to give 9-xanthenone (11) (Table 1).
The present method could be extended to the oxidation of
aryl-substituted alkenes. For example, 4,40-dichloro-trans-stil-
bene (12) was electrochemically oxidized in the presence of
DMSO-d6 at 0 °C (Figure 2). The NMR study indicated the
formation of dialkoxysulfonium ion 13 in the solution. Treat-
ment of 13 with triethylamine gave the corresponding 1,2-
diketone 14 in 83% yield. In contrast, chemical oxidation of
trans-stilbene using RuCl3/NaIO4 gives the corresponding 1,2-
diketone (benzil) in only 5% yield and the carbonꢀcarbon bond
cleavage product (benzoic acid) as the major product.13 In
addition, the electrochemical method also often suffers from
overoxidation. For example, anodic oxidation of alkenes14 and of
1,2-diols15 and their derivatives often leads to carbonꢀcarbon
bond cleavage. The present method solves this otherwise
formidable problem by integration with an extremely mild
chemical method such as DMSO oxidation. Therefore, the
present method serves as a powerful and highly selective
method for the conversion of alkenes to 1,2-dicarbonyl com-
pounds (Table 1).
Figure 1. Typical examples of the integrated electrochemicalꢀchemica-
loxidation and 1H NMR spectra of the cationic intermediates 2, 3, and 8.
appropriate position that can perticipate in the electrochemical
oxidation were examined.16,17 The electrochemical oxidation of 23
took place in the presence of DMSO-d6 at 0 °C (Figure 3). The
formation of cyclized alkoxysulfonium ion 24 was confirmed by
NMR analysis. Treatment of 24 with triethylamine gave the
corresponding cyclized carbonyl compound 25.
The alkene substrate scope was also investigated (Table 2).
Alkenes bearing a nucleophilic moiety such as a tosylamide
(23 and 26), a hydroxyl group (28), or an aromatic ring (30)
gave the corresponsingcyclized ketonesinmoderateto high yields.
Moreover, the electrolysis of 1,6-dienes 32, 34, 36, and 38 gave the
corresponding cyclized products 33, 35, 37, and 39, respectively.
In order to gain deeper insight into the mechanism, we
measured the oxidation potentials of the substrates (Table 2)
and compared them with those of olefinic compounds without
nucleophilic functional groups. The oxidation potentials of 23,
26, 28, and 30 were less positive than that of β-methylstyrene
(1.42 V vs SCE), indicating that the radical cation generated by
one-electron oxidation undergoes rapid cyclization. Also, the
oxidation potential of 32 (1.16 V vs SCE) was less postive than
that of 40 (1.54 V vs SCE), suggesting that the radical cation
rapidly reacts with the other carbonꢀcarbon double bond,18 as
shown in Figure 4.
Todemonstrate theutility andversatilityof thepresentmethod,
oxidation reactions of alkenes bearing a nucleophilic group in an
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Table 1. Integrated ElectrochemicalꢀChemical Oxidation of
Organic Compoundsa
Figure 3. Integrated electrochemicalꢀchemical oxidation of alkene 23
and the 1H NMR spectrum of the cyclized cationic intermediate 24.
Figure 4. Comparison of oxidation potentials and a proposed mechan-
ism involving the rapid cation radical cyclization.
Table 2. Integrated ElectrochemicalꢀChemical Oxidation
Involving Cyclizationa
a The reactions were carried out on a 0.25 mmol scale. b Determined by
rotating disk electrode (RDE) voltammetry in 0.1 M LiClO4/CH3CN
c
using SCE as a reference electrode. Isolated yields are given, unless
otherwise stated. d GC yield. e The reaction was carried out on a 1.3
mmol scale. f NMR yield.
a The reactions were carried out on a 0.25 or 0.13 mmol scale.
b Determined by RDE voltammetry in 0.1 M LiClO4/CH3CN using
SCE as a reference electrode. c Isolated yields. d 1:2 DMSO/CH2Cl2
was used. e Bu4NB(C6F5)4 was used as a supporting electrolyte.
Figure 2. Integrated electrochemicalꢀchemical oxidation of 4,40-di-
1
chloro-trans-stilbene and the H NMR spectrum of the cationic inter-
transformations under mild conditions without the use of
hazardous strong chemical reagents.19 The present method
based on integration of the electrochemical method with an
extremely mild, environmentally benign chemical method opens
a new aspect of the chemistry of oxidation reactions. Further
mediate 13.
The electrochemical method is often cited as being envi-
ronmentally favorable because it enables straightforward
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work to explore the full range of the scope of the present
approach and its application to the synthesis of molecules with
interesting biological activities and functions is in progress.
J. Am. Chem. Soc. 2007, 129, 11692. (g) Park, Y. S.; Little, R. D.
Electrochim. Acta 2009, 54, 5077. (h) Kakiuchi, F.; Kochi, T.; Mutsutani,
H.; Kobayashi, N.; Urano, S.; Sato, M.; Nishiyama, S.; Tanabe, T. J. Am.
Chem. Soc. 2009, 131, 11310. (i) Kirste, A.; Schnakenburg, G.; Stecker,
F.; Fischer, A.; Waldvogel, S. R. Angew. Chem., Int. Ed. 2010, 49, 971.
(6) For example, see: Lenoir, D. Angew. Chem., Int. Ed. 2006,
45, 3206.
’ ASSOCIATED CONTENT
S
Supporting Information. Experimental procedures,
b
(7) For SwernꢀMoffatt-type oxidation, see: Mancuso, A. J.; Swern,
spectroscopic data for new compounds, and crystallographic
data (CIF). This material is available free of charge via the
Internet at http://pubs.acs.org.
D. Synthesis 1981, 165.
(8) For Kornblum oxidation, see: Kornblum, N.; Powers, J. W.;
Anderson, G. J.; Jones, W. J.; Larson, H. O.; Levand, O.; Weaver, W. M.
J. Am. Chem. Soc. 1957, 79, 6562.
(9) For N-acyliminium ion pools, see: (a) Yoshida, J.; Suga, S.;
Suzuki, S.; Kinomura, N.; Yamamoto, A.; Fujiwara, K. J. Am. Chem. Soc.
1999, 121, 9546. (b) Suga, S.; Okajima, M.; Fujiwara, K.; Yoshida, J.
J. Am. Chem. Soc. 2001, 123, 7941. (c) Suga, S.; Watanabe, M.; Yoshida, J.
J. Am. Chem. Soc. 2002, 124, 14824. (d) Yoshida, J.; Suga, S. Chem.—Eur.
J. 2002, 8, 2651. (e) Maruyama, T.; Mizuno, Y.; Shimizu, I.; Suga, S.;
Yoshida, J. J. Am. Chem. Soc. 2007, 129, 1902.
’ AUTHOR INFORMATION
Corresponding Author
yoshida@sbchem.kyoto-u.ac.jp
’ ACKNOWLEDGMENT
(10) For alkoxycarbenium ion pools, see: (a) Suga, S.; Suzuki, S.;
Yamamoto, A.; Yoshida, J. J. Am. Chem. Soc. 2000, 122, 10244. (b)
Okajima, M.; Suga, S.; Itami, K.; Yoshida, J. J. Am. Chem. Soc. 2005,
127, 6930. (c) Suga, S.; Matsumoto, K.; Ueoka, K.; Yoshida, J. J. Am.
Chem. Soc. 2006, 128, 7710.
(11) For diarylcarbenium ion pools, see: (a) Okajima, M.; Soga, K.;
Nokami, T.; Suga, S.; Yoshida, J. Org. Lett. 2006, 8, 5005. (b) Nokami,
T.; Ohata, K.; Inoue, M.; Tsuyama, H.; Shibuya, A.; Soga, K.; Okajima,
M.; Suga, S.; Yoshida, J. J. Am. Chem. Soc. 2008, 130, 10864. (c) Okajima,
M.; Soga, K.; Watanabe, T.; Terao, K.; Nokami, T.; Suga, S.; Yoshida, J.
Bull. Chem. Soc. Jpn. 2009, 82, 594. (d) Terao, K.; Watanabe, T.; Suehiro,
T.; Nokami, T.; Yoshida, J. Tetrahedron Lett. 2010, 51, 4107. (e)
Nokami, T.; Watanabe, T.; Musya, N.; Morofuji, T.; Tahara, K.; Tobe,
Y.; Yoshida, J. Chem. Commun. 2011, 47, 5575. (f) Nokami, T.;
Watanabe, T.; Musya, N.; Suehiro, T.; Morofuji, T.; Yoshida, J. Tetra-
hedron 2011, 67, 4464.
This work was supported by a Grant-in-Aid for Scientific
Research and a Grant-in-Aid for the Global COE program from
MEXT, Japan.
’ REFERENCES
(1) For reviews, see: (a) Tietze, L. F. Chem. Rev. 1996, 96, 115. (b)
Ryu, I.; Sonoda, N.; Curran, D. P. Chem. Rev. 1996, 96, 177. (c) Parsons,
P. J.; Penkett, C. S.; Shell, A. J. Chem. Rev. 1996, 96, 195. (d) Louie, J.;
Bielawski, C. W.; Grubbs, R. H. J. Am. Chem. Soc. 2001, 123, 11312. (e)
Ugi, I. Pure Appl. Chem. 2001, 73, 187. (f) Fogg, D. E.; dos Santos, E. N.
Coord. Chem. Rev. 2004, 248, 2365. (g) de Meijere, A.; von Zezschwitz,
P.; Br€ase, S. Acc. Chem. Res. 2005, 38, 413. (h) Wasilke, J.-C.; Obrey, S. J.;
Baker, R. T.; Bazan, G. C. Chem. Rev. 2005, 105, 1001. (i) Schmidt, B.
Pure Appl. Chem. 2006, 78, 469. (j) Enders, D.; H€uttl, M. R. M.; Grondal,
C.; Raabe, G. Nature 2006, 441, 861.
(2) For recent examples, see: (a) Orita, A.; Yaruva, J.; Otera, J.
Angew. Chem., Int. Ed. 1999, 38, 2267. (b) Orita, A.; Yoshioka, N.;
Struwe, P.; Braier, A.; Beckmann, A.; Otera, J. Chem.—Eur. J. 1999,
5, 1355. (c) D€omling, A.; Ugi, I. Angew. Chem., Int. Ed. 2000, 39, 3168.
(d) Bienaymꢀe, H.; Hulme, C.; Oddon, O.; Schmitt, P. Chem.—Eur. J.
2000, 6, 3321. (e) Balme, G.; Bossharth, E.; Monteiro, N. Eur. J. Org.
Chem. 2003, 4101. (f) Ajamian, A.; Gleason, J. L. Angew. Chem., Int. Ed.
2004, 43, 3754. (g) Shimizu, M.; Shimono, K.; Hiyama, T. Chem. Lett.
2006, 35, 838. (h) Clarke, P. A.; Santos, S.; Martin, W. H. C. Green Chem.
2007, 9, 438. (i) Bremner, W. S.; Organ, M. G. J. Comb. Chem. 2007,
9, 14. (j) Fuwa, H.; Tako, T.; Ebine, M.; Sasaki, M. Chem. Lett. 2008,
37, 904. (k) Nokami, T.; Tsuyama, H.; Shibuya, A.; Nakatsutsumi, T.;
Yoshida, J. Chem. Lett. 2008, 37, 942. (l) Ikeda, S.; Shibuya, M.; Kanoh,
N.; Iwabuchi, Y. Chem. Lett. 2008, 37, 962. (m) Numata, Y.; Kawashima,
J.; Hara, T.; Tajima, Y. Chem. Lett. 2008, 37, 1018. (n) Yamaguchi, K.;
Kotani, M.; Kamata, K.; Mizuno, N. Chem. Lett. 2008, 37, 1258. (o)
Babu, G.; Orita, A.; Otera, J. Chem. Lett. 2008, 37, 1296. (p) Cernak,
T. A.; Lambert, T. H. J. Am. Chem. Soc. 2009, 131, 3124. (q) Hardee,
D. J.; Lambert, T. H. J. Am. Chem. Soc. 2009, 131, 7536.
(3) (a) Suga, S.; Yamada, D.; Yoshida, J. Chem. Lett. 2010, 39, 404.
(b) Yoshida, J.; Saito, K.; Nokami, T.; Nagaki, A. Synlett 2011, 1189.
(4) For recent reviews of organic electrochemistry, see: (a) Moeller,
K. D. Tetrahedron 2000, 56, 9527. (b) Lund, H. J. Electrochem. Soc. 2002,
149, S21. (c) Sperry, J. B.; Wright, D. L. Chem. Soc. Rev. 2006, 35, 605.
(d) Yoshida, J.; Kataoka, K.; Horcajada, R.; Nagaki, A. Chem. Rev. 2008,
108, 2265.
(5) For some recent examples, see: (a) Hasegawa, M.; Ishii, H.; Cao,
Y.; Fuchigami, T. J. Electrochem. Soc. 2006, 153, D162. (b) Hayashi, K.;
Kim, S.; Chiba, K. Electrochemistry 2006, 74, 621. (c) Wu, X.; Dube,
M. A.; Fry, A. J. Tetrahedron Lett. 2006, 47, 7667. (d) Tajima, T.;
Kurihara, H.; Fuchigami, T. J. Am. Chem. Soc. 2007, 129, 6680. (e)
Mitsudo, K.; Kaide, T.; Nakamoto, E.; Yoshida, K.; Tanaka, H. J. Am.
Chem. Soc. 2007, 129, 2246. (f) Horii, D.; Fuchigami, T.; Atobe, M.
(12) (a) Phan, T. B.; Nolte, C.; Kobayashi, S.; Ofial, A. R.; Mayr, H.
J. Am. Chem. Soc. 2009, 131, 11392. A reaction of benzyl cations with
DMSO has also been reported in the literature. See:(b) Scheit, K. H.;
Kampe, W. Angew. Chem., Int. Ed. Engl. 1965, 4, 787.
(13) Tabatabaeian, K.; Mamaghani, M.; Mahmoodi, N. O.; Khorshidi,
A. Catal. Commun. 2008, 9, 416. For other methods of oxidizing alkenes to
1,2-diketones, see:Manandhar, S.; Singh, R. P.; Eggers, G. V.; Shreeve, J. M.
J. Org. Chem. 2002, 67, 6415.
(14) (a) Halas, S. M.; Okyne, K.; Fry, A. J. Electrochim. Acta 2003,
48, 1837. (b) B€aumer, U.-St.; Sch€afer, H. J. J. Appl. Electrochem. 2005,
35, 1283.
(15) Shono, T.; Matsumura, Y.; Hashimoto, T.; Hibino, K.; Hama-
guchi, H.; Aoki, T. J. Am. Chem. Soc. 1975, 97, 2546.
(16) Electrochemical dimethoxylation of styrenes and related com-
pounds has been reported. See: (a) Raoult, E.; Sarrazin, J.; Tallec, A.
J. Appl. Electrochem. 1984, 14, 639. (b) Ogibin, Y. N.; Ilovaiskii, A. I.;
Nikishin, G. I. Russ. Chem. Bull. 1994, 43, 1536.
(17) For electron-transfer-mediated cyclization reactions, see: (a)
Tokuda, M.; Miyamoto, T.; Fujita, H.; Suginome, H. Tetrahedron 1991,
47, 747. (b) Tokuda, M.; Fujita, H.; Miyamoto, T.; Suginome, H.
Tetrahedron 1993, 49, 2413. (c) New, D. G.; Tesfai, Z.; Moeller, K. D.
J. Org. Chem. 1996, 61, 1578. (d) Xu, H.-C.; Moeller, K. D. J. Am. Chem.
Soc. 2008, 130, 13542. (e) Liu, L.; Floreancig, P. E. Angew. Chem., Int. Ed.
2010, 49, 3069. (f) Xu, H.-C.; Moeller, K. D. Angew. Chem., Int. Ed. 2010,
49, 8004.
(18) (a) Moeller, K. D.; Tinao, L. V. J. Am. Chem. Soc. 1992,
114, 1033. (b) Reddy, S. H. K.; Chiba, K.; Sun, Y.; Moeller, K. D.
Tetrahedron 2001, 57, 5183. (c) Huang, K. D.; Moeller, K. D. Tetrahedron
2006, 62, 6536.
(19) (a) Matthews, M. A. Pure Appl. Chem. 2001, 73, 1305. (b)
Rusling, J. F. Pure Appl. Chem. 2001, 73, 1895. (c) Mentel, M.; Beier,
M. J.; Breinbauer, R. Synthesis 2009, 1463 and references cited therein.
11843
dx.doi.org/10.1021/ja202880n |J. Am. Chem. Soc. 2011, 133, 11840–11843