Metal- and chemical-oxidant-free c-h/c-h cross-coupling of aromatic compounds: The use of radical-cation pools

Article abstract of DOI:10.1002/anie.201202788

Pool and couple: A method for oxidative C-H/C-H cross-coupling has been developed using "radical-cation pools". Aromatic compounds react with aryl radical cations, which are generated and accumulated by low-temperature electrolysis (see scheme). This method avoids both the nonselective oxidation of substrates and oxidation of products and effects the C-H/C-H cross-coupling of aromatic compounds without metal complexes and chemical oxidants. Copyright

Full text of DOI:10.1002/anie.201202788

Angewandte
Chemie
DOI: 10.1002/anie.201202788
Radical-Cation Reactions
À
À
Metal- and Chemical-Oxidant-Free C H/C H Cross-Coupling of
Aromatic Compounds: The Use of Radical-Cation Pools**
Tatsuya Morofuji, Akihiro Shimizu, and Jun-ichi Yoshida*
À
À
The direct oxidative C H/C H cross-coupling, also known as
the dehydrogenative cross-coupling,[1] of unactivated aro-
matic compounds has fascinated many chemists because it
does not require prefunctionalization of starting aromatic
compounds and it serves as a straightforward, atom-,[2] and
step-economical[3] method for connecting two aromatic rings
[4,5]
À
À
by a single C C bond.
In 2007, a metal-catalyzed C C
À
cross-coupling reaction involving two C H activations and
employing a stoichiometric amount of oxidant was achieved
[4a–d]
and, since then, the method has been studied exten-
sively.[4e–n] In 2008, a metal-free biaryl compound synthesis
that uses a stoichiometric amount of an organoiodine(III)
oxidant was developed.[5] A new synthetic method that
À
À
enables metal- and chemical-oxidant-free C H/C H cross-
coupling of two aromatic compounds is needed. Electro-
chemical oxidation[6,7] serves as an efficient method that does
not use metal catalysts and chemical oxidants for activating
aromatic compounds. In fact, the subjection of a mixture of
two unactivated aromatic compounds to electrochemical
oxidation can give the cross-coupling products, although
yields are usually low.[8] Recently, Waldvogel and co-workers
reported a selective electrochemical phenol–arene cross-
coupling reaction using boron-doped diamond electrodes.[9]
This method, however, cannot be applied to aromatic
compounds that do not have a hydroxy group because the
phenoxyl radical intermediate plays a crucial role.
À
À
Scheme 1. Oxidative C H/C H cross-coupling of aromatic com-
pounds. a) A conventional approach. b) An approach based on the
“radical-cation pool” method.
the development of methods for direct anodic cross-coupling
is very challenging.
To avoid nonselective oxidation of starting materials and
the oxidation of products we have developed a method using
“radical-cation pools” (Scheme 1b). Thus, an aromatic com-
pound is allowed to react with a radical cation of another
aromatic compound, a species, which is generated and
accumulated by low-temperature electrolysis. In 1999, we
developed the cation-pool method, which involves generation
and accumulation of an unstable organic cation in the absence
of a nucleophile by low-temperature electrochemical oxida-
tion and a subsequent reaction of the cation with a nucleophile
under nonelectrolytic conditions. The method has been
successfully applied to N-acyliminium ions,[10] alkoxycarbe-
nium ions,[11] and diarylcarbenium ions.[12] The present
radical-cation-pool method has been developed by analogy
with the cation-pool method. This new method serves as
a powerful and selective method for synthesizing unsym-
metrical biaryl compounds from unactivated electron-rich
aromatic compounds in a straightforward and efficient way.
First, we chose to use pentamethylbenzene (1) as a sub-
strate because of simplicity of product selectivity (see
Table 1). As a coupling partner, we chose to use naphthalene
(2) because oxidation of 2 to give the corresponding radical
cation 3 is known in the literature.[5a,8a,b,13] The electrochem-
ical oxidation of 2 (0.44 mmol) was carried out in a 0.1m
solution of Bu4NB(C6F5)4 in CH2Cl2 in a H-type divided cell
equipped with a graphite felt anode and a platinum plate
cathode at À788C in the absence of 1. After 0.20 mF of
electricity was consumed, 1 (0.10 mmol) was added. The
reaction mixture was stirred at À788C for 3 hours. The
desired cross-coupling product 4 was obtained in 33% yield
À
À
In general, the oxidative C H/C H cross-coupling of two
aromatic compounds suffers from the formation of homo-
coupling products derived from the nonselective oxidation of
the starting materials (Scheme 1a). Based on statistics, the
yield of the cross-coupling product will be, at most, moderate
because of the formation of products derived from homo-
coupling. Overoxidation is also unavoidable because the
biaryl products have lower oxidation potentials than those of
the corresponding starting materials owing to the extended
p conjugation of the biaryl products (see below). Therefore,
[*] T. Morofuji, Dr. A. Shimizu, Prof. J. Yoshida
Department of Synthetic Chemistry and Biological Chemistry
Graduate School of Engineering, Kyoto University
Nishikyo-ku, Kyoto 615-8510 (Japan)
E-mail: yoshida@sbchem.kyoto-u.ac.jp
[**] We thank the Ministry of Education, Culture, Sports, Science &
Technology (Japan) for a Grant-in-Aid for Scientific Research on
Innovative Areas, Organic Synthesis Based on Reaction Integration
Development of New Methods and Creation of New Substances
(2105). We also thank Prof. Benoꢀt Champagne in Facultꢁs
Universitaires Notre-Dame de la Paix (FUNDP), Belgium for the use
of computers and the program for the theoretical calculations.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201202788.
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Table 1: Optimization of the reaction conditions.
Entry
T [8C]
Additive
Yield of 4 [%][a]
Recovered 1 [%][a]
Figure 1. Spin densities of radical cations and HOMOs of nucleophilic
aromatic coupling partners obtained by DFT calculations (B3LYP/6-
31G*). a–d) Spin densities of radical cations of 2, 18, 21, and 23,
respectively. e–j) HOMO of 5, 7, 9, 11, 13, and 15, respectively (the 3-
21G* basis set was used for iodine-containing compounds 11 and 15).
1
2
3
À40
À78
À90
À90
À90
À90
À90
–
–
–
THF
diethyl ether
DME
DME
11
33
27
46
66
73
91
40
55
52
32
25
23
–
4[b]
5[c]
6[d]
7[d,e]
the cross-coupling product 4 in 87% yield upon isolation
(Table 2, entry 1). Electron-rich benzenes such as 5 and 7
reacted with 3 to give the corresponding cross-coupling
products in good yields (Table 2, entries 2 and 3). The
regioselectivity observed for 5 and 7 was excellent, in that
other isomers were not detected. The HOMO coefficients
obtained by DFT calculations are consistent with the
observed regioselectivity (Figure 1e and f). Heteroaromatic
compounds, such as indoles 9 and 11, also gave the corre-
sponding cross-coupling products in good yields (Table 2,
entries 4 and 5), although the reactivity of electron-deficient
indole 13 was low (Table 2, entry 6). The energy of the
HOMO of 13 was lower than that of other substrates; this
finding is consistent with the lower reactivity of 13 (see the
Supporting Information for details). Benzothiophene 15 was
also effective in this reaction (Table 2, entry 7). The regiose-
lectivity of these reactions was also consistent with the
HOMO coefficients obtained by DFT calculations (Fig-
ure 1 g–j). Notably, iodine-containing compounds 12 and 16
were obtained in very good yields. Usually the oxidative
coupling of iodine-containing compounds under electrophilic
conditions leads to proto-deiodination[14] and only molybde-
num pentachloride is capable of mediating an oxidative
coupling of iodoarenes without loss of the iodine substitu-
ent.[15]
[a] Yields were determined by GC analysis using hexadecane as an
internal standard. [b] Tetrahydrofuran (THF; 0.5 mL) was added.
[c] Diethyl ether (0.5 mL) was added. [d] 1,2-Dimethoxyethane (DME;
0.5 mL) was added. [e] The reactions were carried out using 2
(0.66 mmol) with 0.30 mF of electricity.
(Table 1, entry 2). Four moles of 2 is necessary to produce one
mole of 4 because 3 is accumulated as a complex with 2 (the
radical cation of the naphthalene dimer)[13a] and 4 is produced
by the reaction of 1 and 3 followed by one-electron oxidation,
wherein the radical-cation naphthalene dimer is the oxidant.
To optimize the reaction conditions the reactions were
carried out at a variety of temperatures for the second step.
When the second step was carried out at À408C (Table 1,
entry 1) the yield of 4 was lower than when the step was
carried out at À788C (Table 1, entry 2) presumably because
the decomposition of 3 was competing with the cross-coupling
reaction. The reaction at À908C (Table 1, entry 3) also gave
a lower yield, presumably because of precipitation of 3 at this
temperature. To solve this solubility problem, we examined
the effect of additives that may enhance the solubility of 3 at
low temperatures (Table 1, entries 4–6), and found that 1,2-
dimethoxyethane (DME) was quite effective (Table 1,
entry 6). Moreover, the use of 0.3 mF of electricity and
0.66 mmol of 2 improved the yield of 4 to 91% (Table 1,
entry 7). It should be noted that the present method does not
suffer from oxidation of the products, although the oxidation
potential of 4 (1.48 V versus SCE in a 0.1m solution of
Bu4NB(C6F5)4 in CH2Cl2) is lower than those of 1 (1.57 V) and
2 (1.60 V).
The present method could also be applied to other radical
cations. The reaction of 2-bromonaphthalene (18) is interest-
ing: the radical-cation pool derived from 18 was generated in
an effective manner by anodic oxidation and the subsequent
coupling reaction took place preferentially on the benzene
ring not bearing the bromine atom to give 19. The product
À
derived from C C bond formation at the position ortho to the
The regioselectivity of the reaction is notable, because
only the 1-substituted naphthalene derivative 4 was obtained.
The corresponding 2-substituted product was not detected.
This is consistent with the high regioselectivity reported for
the reaction of naphthalene radical cations with other
bromine atom (20) was also obtained as a minor product. The
regioselectivity is consistent with the spin density values
obtained by DFT calculations (Figure 1b). The anodic
oxidation of pyrene (21), and fluoranthene (23) gave the
corresponding radical-cation pools, which reacted with 9 to
give the corresponding cross-coupling products in good yields
with high regioselectivity, a result, which is consistent with the
DFT calculations (Figure 1c and d). It should be noted that
the cheaper electrolyte, Bu4NPF6, could be used in these
reactions.
nucleophiles such as CNÀ and CH3CO2
analysis using the DFT calculation also suggests that reaction
at the 1-position is favored (Figure 1a).
Under the optimized reaction conditions, the reaction of
several aromatic compounds were examined (Table 2). The
reaction of radical cation 3 with pentamethylbenzene (1) gave
.
Spin density
À
[13c]
2
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[a]
À
À
Table 2: C H/C H cross-coupling of aromatic compounds.
Notably, the regioselectivity of the cross-coupling is
Entry Ar1H Ar2H
Product
Yield [%][b]
87
generally very high and is predictable based on the
spin density of the radical cation and the HOMO coef-
ficients of the nucleophilic aromatic partner obtained by
DFT calculations. The high regioselectivity of this method
contrasts with the lower regioselectivity of homolytic
aromatic substitutions that are used for biaryl compound
synthesis.[16] This difference in regioselectivity is probably
due to the different reactivity of the reactive intermedi-
ates: in homolytic aromatic substitutions, a highly reactive
s radical (aryl radical) reacts with the arene, whereas in the
approach herein, a less reactive p radical (aryl radical
cation) reacts with the arene. Notably, halogen-substituted
aromatic compounds are effective as both substrates
(Table 2, entries 2, 3, 5, and 7) and precursors of a radical
cation (Table 2, entry 8) and the halogen functionality in
the cross-coupling products can be used for further trans-
formations, such as halogen/metal exchange and transition
metal catalyzed coupling reactions. Therefore, we antici-
pate that this new method will form the basis of a wide
range of synthetic strategies for making organic com-
pounds containing aromatic rings.
1
2[c]
73
67
3
4
92
86
36
84
5
In conclusion, we have developed an efficient method
À
À
for the C H/C H cross-coupling of two unactivated
aromatic compounds using “radical-cation pools”. Because
this method consists of two sequential steps, namely the
generation and accumulation of a radical cation of an
aromatic compounds under oxidative conditions and then
the coupling of the radical cation with another aromatic
substrate under nonoxidative conditions, nonselective
oxidation of the starting materials and oxidation of the
products are avoided. Thus, the method serves as a selec-
6[d,e]
7[f]
À
À
tive technique for effecting a C H/C H cross-coupling of
aromatic compounds. The absence of metal complexes and
chemical oxidants in the reaction conditions is also
advantageous. Exploration of the full range of reactivity
of various aromatic compounds and radical-cation pools,
and applications to the synthesis of biaryl and heterobiaryl
compounds with interesting functions and biological
activity is currently in progress.
84
(19/
20=1.7:1)
8[g]
9[d,h,i]
71
70
Experimental Section
General procedure for oxidative cross-coupling: The anodic
oxidation was carried out using a H-type divided cell (4G glass
filter) equipped with a carbon felt anode (Nippon Carbon JF-20-
P7, ca. 160 mg, dried at 3008C/1 mmHg for 4 h before use) and
a platinum plate cathode (10 mm ꢀ 10 mm). In the anodic chamber
was placed a solution of an aromatic compound (0.66 mmol) in
a 0.1m solution of Bu4NB(C6F5)4 in CH2Cl2 (10.0 mL). In the
cathodic chamber were placed trifluoromethanesulfonic acid
10[d,h,i]
[a] The radical-cation pool was generated with 0.66 mmol of Ar1H using
3.0 mF of electricity in a 0.1m solution of Bu4NB(C6F5)4 in CH2Cl2 (10 mL) at
À788C; then, 0.10 mmol of Ar2H and DME (0.5 mL) were added at À908C
and the reaction mixture was stirred at À908C for 3 h. [b] Yields of isolated
product based on Ar2H. [c] 5.5 mmol of Ar1H and 5.0 mF of electricity were
used. [d] 8.8 mmol of Ar1H and 8.0 mF of electricity were used. [e] Additional
stirring of the reaction mixture at À308C for 5 h. [f] Additional stirring of the
reaction mixture at À208C for 2 h. [g] 0.1 mL of DME was used. [h] Bu4NPF6
was used instead of Bu4NB(C6F5)4. [i] 0.05 mmol of Ar2H was used and the
mixture was stirred at À408C for 3 h and then at À158C for 1.5 h.
(150 mL) and
a 0.1m solution of Bu4NB(C6F5)4 in CH2Cl2
(10.0 mL). The constant current electrolysis (8.0 mA) was carried
out at À788C with magnetic stirring of the reaction mixture for
60 min. An aromatic substrate (0.10 mmol) and 1,2-dimethoxy-
ethane (0.5 mL) were added to the anodic chamber at À908C. The
resulting mixture was stirred at À908C for 3 h. Then, Et3N
(0.2 mL) was added and the resulting mixture was warmed to
room temperature. After removal of the solvent under reduced
pressure, the residue was quickly filtered through a short column
(2 ꢀ 4 cm) of silica gel to remove electrolyte using n-hexane/
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EtOAc. The solvent was removed from the filtrate under reduced
pressure, and the crude product was purified with flash chromatog-
raphy on silica gel or GPC to obtain the cross-coupling product.
[7] a) H. J. Schꢂfer, Angew. Chem. 1981, 93, 978 – 1000; Angew.
Chem. Int. Ed. Engl. 1981, 20, 911 – 934; b) T. Shono, Tetrahe-
dron 1984, 40, 811 – 850; c) J. Utley, Chem. Soc. Rev. 1997, 26,
157 – 167; d) K. D. Moeller, Tetrahedron 2000, 56, 9527 – 9554;
e) H. Lund, J. Electrochem. Soc. 2002, 149, S21-S33; f) J. B.
Sperry, D. L. Wright, Chem. Soc. Rev. 2006, 35, 605 – 621; g) J.
Yoshida, K. Kataoka, R. Horcajada, A. Nagaki, Chem. Rev.
2008, 108, 2265 – 2299.
[8] a) K. Nyberg, Acta Chem. Scand. 1971, 25, 3770 – 3776; b) K.
Nyberg, Acta Chem. Scand. 1973, 27, 503 – 509; c) S. Yamaura, S.
Nishiyama, Synlett 2002, 4, 0533 – 0543.
[9] a) A. Kirste, G. Schnakenburg, F. Stecker, A. Fischer, S. R.
Waldvogel, Angew. Chem. 2010, 122, 983 – 987; Angew. Chem.
Int. Ed. 2010, 49, 971 – 975; b) A. Kirste, G. Schnakenburg, F.
Stecker, S. R. Waldvogel, Org. Lett. 2011, 13, 3126 – 3129; c) A.
Kirste, B. Elsler, G. Schnakenburg, S. R. Waldvogel, J. Am.
Chem. Soc. 2012, 134, 3571 – 3576.
[10] a) J. Yoshida, S. Suga, S. Suzuki, N. Kinomura, A. Yamamoto, K.
Fujiwara, J. Am. Chem. Soc. 1999, 121, 9546 – 9549; b) S. Suga,
M. Okajima, K. Fujiwara, J. Yoshida, J. Am. Chem. Soc. 2001,
123, 7941 – 7942; c) S. Suga, M. Watanabe, J. Yoshida, J. Am.
Chem. Soc. 2002, 124, 14824 – 14825; d) J. Yoshida, S. Suga,
Chem. Eur. J. 2002, 8, 2650 – 2658; e) T. Maruyama, Y. Mizuno, I.
Shimizu, S. Suga, J. Yoshida, J. Am. Chem. Soc. 2007, 129, 1902 –
1903.
[11] a) S. Suga, S. Suzuki, A. Yamamoto, J. Yoshida, J. Am. Chem.
Soc. 2000, 122, 10244 – 10245; b) M. Okajima, S. Suga, K. Itami,
J. Yoshida, J. Am. Chem. Soc. 2005, 127, 6930 – 6931; c) S. Suga,
K. Matsumoto, K. Ueoka, J. Yoshida, J. Am. Chem. Soc. 2006,
128, 7710 – 7711.
[12] a) T. Nokami, K. Ohata, M. Inoue, H. Tsuyama, A. Shibuya, K.
Soga, M. Okajima, S. Suga, J. Yoshida, J. Am. Chem. Soc. 2008,
130, 10864 – 10865; b) K. Terao, T. Watanabe, T. Suehiro, T.
Nokami, J. Yoshida, Tetrahedron Lett. 2010, 51, 4107 – 4109; c) T.
Nokami, T. Watanabe, N. Musya, T. Morofuji, K. Tahara, Y.
Tobe, J. Yoshida, Chem. Commun. 2011, 47, 5575 – 5577; d) T.
Nokami, T. Watanabe, N. Musya, T. Suehiro, T. Morofuji, J.
Yoshida, Tetrahedron 2011, 67, 4664 – 4671.
[13] a) H. P. Fritz, H. Gebauer, P. Friedrich, U. Schubert, Angew.
Chem. 1978, 90, 305 – 306; Angew. Chem. Int. Ed. Engl. 1978, 17,
275 – 276; b) C. Krçhnke, V. Enkelmann, G. Wegner, Angew.
Chem. 1980, 92, 941 – 942; Angew. Chem. Int. Ed. Engl. 1980, 19,
912 – 919; c) H. P. Fritz, P. Ecker, Chem. Ber. 1981, 114, 3643 –
3654; d) M. Tanaka, H. Nakashima, M. Fujiwara, H. Ando, Y.
Souma, J. Org. Chem. 1996, 61, 788 – 792.
Received: April 11, 2012
Published online: && &&, &&&&
À
À
Keywords: C C coupling · C H activation · electrochemistry ·
oxidation · radical ions
.
[1] C.-J. Li, Acc. Chem. Res. 2009, 42, 335 – 344.
[2] a) R. Noyori, Nat. Chem. 2009, 1, 5 – 6; b) T. Gaich, P. S. Baran, J.
Org. Chem. 2010, 75, 4657 – 4673; c) B. M. Trost, Science 1991,
254, 1471 – 1477.
[3] P. A. Wender, V. A. Verma, T. J. Paxton, T. H. Pillow, Acc.
Chem. Res. 2008, 41, 40 – 49.
[4] a) D. R. Stuart, K. Fagnou, Science 2007, 316, 1172 – 1175;
b) D. R. Stuart, E. Villemure, K. Fagnou, J. Am. Chem. Soc.
2007, 129, 12072 – 12073; c) K. L. Hull, M. S. Sanford, J. Am.
Chem. Soc. 2007, 129, 11904 – 11905; d) T. A. Dwight, N. R. Rue,
D. Charyk, R. Josselyn, B. DeBoef, Org. Lett. 2007, 9, 3137 –
3139; e) S. H. Cho, S. J. Hwang, S. J. Chang, J. Am. Chem. Soc.
2008, 130, 9254 – 9256; f) B.-J. Li, S.-L. Tian, Z. Fang, Z.-J. Shi,
Angew. Chem. 2008, 120, 1131 – 1134; Angew. Chem. Int. Ed.
2008, 47, 1115 – 1118; g) G. Brasche, J. Garcꢁa-Fortanet, S. L.
Buchwald, Org. Lett. 2008, 10, 2207 – 2210; h) P. Xi, F. Yang, S.
Qin, D. Zhao, J. Lan, G. Gao, C. Hu, J. You, J. Am. Chem. Soc.
2010, 132, 1822 – 1824; i) X. Zhao, C. S. Yeung, V. M. Dong, J.
Am. Chem. Soc. 2010, 132, 5837 – 5844; j) C.-Y. He, S. Fan, X.
Zhang, J. Am. Chem. Soc. 2010, 132, 12850 – 12852; k) Z. Wang,
K. Li, D. Zhao, J. Lan, J. You, Angew. Chem. 2011, 123, 5477 –
5481; Angew. Chem. Int. Ed. 2011, 50, 5365 – 5369; l) C. S. Yeung,
V. M. Dong, Chem. Rev. 2011, 111, 1215 – 1292; m) W. Han, P.
Mayer, A. R. Ofial, Angew. Chem. 2011, 123, 2226 – 2230;
Angew. Chem. Int. Ed. 2011, 50, 2178 – 2182; n) M. Kitahara,
N. Umeda, K. Hirano, T. Satoh, M. Miura, J. Am. Chem. Soc.
2011, 133, 2160 – 2162.
[5] a) T. Dohi, M. Ito, K. Morimoto, M. Iwata, Y. Kita, Angew.
Chem. 2008, 120, 1321 – 1324; Angew. Chem. Int. Ed. 2008, 47,
1301 – 1304; b) Y. Kita, K. Morimoto, M. Ito, C. Ogawa, A. Goto,
T. Dohi, J. Am. Chem. Soc. 2009, 131, 1668 – 1669; c) K.
Morimoto, N. Yamaoka, C. Ogawa, T. Nakae, H. Fujioka, T.
Dohi, Y. Kita, Org. Lett. 2010, 12, 3804 – 3807.
[6] a) H. Lund, O. Hammerich, Organic Electrochemistry, 4th ed.,
Marcel Dekker, New York, 2001; b) T. Shono, Electroorganic
Chemistry as a New Tool in Organic Synthesis, Springer, Berlin,
1984; c) Electroorganic Synthesis (Eds.: R. D. Little, N. L.
Weinberg), Marcel Dekker, New York, 1991; d) J. Grimshaw,
Electrochemical Reactions and Mechanisms in Organic Chemis-
try, Elsevier, Amsterdam, 2000; e) A. J. Fry, Electroorganic
Chemistry, 2nd ed., Wiley, New York, 2001; f) Roddꢀs Chemistry
of Carbon Compounds (Ed.: M. Sainsbury), Elsevier, Amster-
dam, 2002; g) S. Torii, Electroorganic Reduction Synthesis,
Vol. 1 – 2, Kodansha, Tokyo, 2006.
[14] N. Boden, R. J. Bushby, Z. Lu, G. Headdock, Tetrahedron Lett.
2000, 41, 10117 – 10120.
[15] a) S. R. Waldvogel, E. Aits, C. Holst, R. Frçhlich, Chem.
Commun. 2002, 1278 – 1279; b) B. Kramer, S. R. Waldvogel,
Angew. Chem. 2004, 116, 2501 – 2503; Angew. Chem. Int. Ed.
2004, 43, 2446 – 2449.
[16] A. Studer, D. P. Curran, Angew. Chem. 2011, 123, 5122 – 5127;
Angew. Chem. Int. Ed. 2011, 50, 5018 – 5022, and references
therein.
4
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Radical-Cation Reactions
Pool and couple: A method for oxidative
À
À
C H/C H cross-coupling has been
developed using “radical-cation pools”.
Aromatic compounds react with aryl
radical cations, which are generated and
accumulated by low-temperature elec-
trolysis (see scheme). This method
avoids both the nonselective oxidation of
substrates and oxidation of products and
T. Morofuji, A. Shimizu,
J. Yoshida*
&&&& — &&&&
À
Metal- and Chemical-Oxidant-Free C H/
À
C H Cross-Coupling of Aromatic
Compounds: The Use of Radical-Cation
Pools
À
À
effects the C H/C H cross-coupling of
aromatic compounds without metal
complexes and chemical oxidants.
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!