Visible light-mediated direct arylation of arenes and heteroarenes using diaryliodonium salts in the presence and absence of a photocatalyst

Article abstract of DOI:10.1246/cl.130547

Diaryliodonium salts have been used as aryl radical sources under visible light-mediated photoredox catalysis. Benzene and a range of heteroarenes are arylated with Ar₂I+ in the presence of [Ir(ppy)₂(bpy)] PF₆ upon irradiation with visible light. When pyrroles are used, the arylation proceeds in the absence of a photoredox catalyst. Both processes are initiated by photoinduced single-electron-transfer to Ar₂I+, generating aryl radicals.

Full text of DOI:10.1246/cl.130547

doi:10.1246/cl.130547
Published on the web June 29, 2013
1203
Visible Light-mediated Direct Arylation of Arenes and Heteroarenes
Using Diaryliodonium Salts in the Presence and Absence of a Photocatalyst
Mamoru Tobisu,*1,2 Takayuki Furukawa,3 and Naoto Chatani*3
1Center for Atomic and Molecular Technologies, Graduate School of Engineering, Osaka University, Suita, Osaka 565-0871
2Unit of Elements Strategy Initiative for Catalysts and Batteries, Kyoto University, Katsura, Kyoto 615-8510
3Department of Applied Chemistry, Faculty of Engineering, Osaka University, Suita, Osaka 565-0871
(Received June 12, 2013; CL-130547; E-mail: tobisu@chem.eng.osaka-u.ac.jp, chatani@chem.eng.osaka-u.ac.jp)
Diaryliodonium salts have been used as aryl radical sources
under visible light-mediated photoredox catalysis. Benzene and
a range of heteroarenes are arylated with Ar2I+ in the presence
of [Ir(ppy)2(bpy)]PF6 upon irradiation with visible light. When
pyrroles are used, the arylation proceeds in the absence of a
photoredox catalyst. Both processes are initiated by photo-
induced single-electron-transfer to Ar2I+, generating aryl
radicals.
radicals via an oxidative quenching pathway under visible light
irradiation.9 It was envisaged that diaryliodonium salts (Ar2I+)10
could be used as aryl sources in terms of their reduction
potentials, stability, and availability. Indeed, it has been
proposed that a phenyl radical could be involved in visible
light-induced polymerization initiated by Ph2I+ and a photo-
catalyst.11 Sanford recently reported the use of an aryl radical
generated from Ar2I+ by visible light photocatalysis as an
effective arylating agent in a palladium-catalyzed C-H bond
arylation.12 These reports highlight the need for further inves-
tigation into more fundamental reaction systems to fully explore
the potential utility of Ar2I+ as an aryl source in visible light-
induced photoredox reactions. Herein, we describe several
different visible light-mediated transformations of Ar2I+ in the
presence and absence of a photoredox catalyst.
After several optimization studies (see SI for details), we
found that the aryl radicals could be generated from Ar2I+ under
irradiation with white LED light (- = 400-750 nm) in the
presence of [Ir(ppy)2(bpy)]PF6 (1, ppy: 2-phenylpyridine, bpy:
2,2¤-bipyridine) and were applicable to homolytic aromatic
substitution processes1,5 (Table 1). When the photolysis of
diphenyliodonium 2 was conducted in benzene, biphenyl was
obtained in 54% yield (Entry 1). Pyridine was also phenylated
under these conditions to give a mixture of regioisomers,
suggesting the involvement of a radical substitution process
rather than the occurrence of ionic or metal-mediated arylation
mechanism (Entry 2).13 Other electron-deficient N-heteroarenes,
including pyrazine (Entry 3)14 and pyrimidine (Entry 4),13 also
participated in this visible light-mediated direct arylation
reaction. The phenyl radical generated from 2 was also
intercepted by several different five-membered heteroarenes. A
particularly successful result was obtained with pyrrole, which
delivered the 2-phenylated product exclusively (Entry 5).15 The
application to imidazole and thiophene also resulted in a
regioselective phenylation, although the yields were modest
(Entries 6 and 7).
The aryl radical is well known as a highly reactive
intermediate capable of participating in a variety of different
arylation reactions, including homolytic aromatic substitution.1
Classically, aryl radicals have been generated according to
several different procedures, including thermal decomposition of
diaroyl peroxide, the treatment of suitable aromatic precursors
with stoichiometric oxidants, reductants, or radical mediators,
and the irradiation of suitable precursors with high-energy UV
light.2 Visible light photocatalysis3,4 has recently emerged as a
mild method for the generation of aryl radicals, and therefore
represents a powerful strategy for the development of new
arylation processes. This approach uses photoexcitation with
visible light to initiate a single-electron-transfer (SET) process
between a metal catalyst, such as [Ru(bpy)3]2+ or an organic
dye, and an aromatic substrate. The most successful acceptor
substrates are aryl diazonium salts, which can readily generate
aryl radicals via the loss of nitrogen through a photoinduced
reductive SET process (Scheme 1).5 Aryl sulfonyl chlorides6
and aryl halides,7 which are both more stable and readily
available, have also been shown to be viable precursors,
although the application of these precursors is currently limited,
partly because of their relatively low reduction potentials.8
Koike and Akita reported that arylboronates can generate aryl
X
X
+ e
During the course of our investigation into the scope of
heteroarene acceptors, we noticed that pyrrole behaved differ-
ently from other heteroarenes. For example, the arylation of
pyridine with iodonium salt 2, required the presence of the
photocatalyst and LED irradiation to efficiently afford the
desired product (Table 2). In contrast, pyrrole could be arylated
to an appreciable extent under LED irradiation in the absence of
a photocatalyst, although no arylation occurred in the absence
of the LED irradiation. These results appeared to be unusual
because pyrrole and iodonium salt 2 do not absorb light in the
visible region (400-750 nm). Although several examples of the
metal-free direct arylation of (hetero)arenes using Ar2I+ salts
have been reported in the literature, these reactions usually
X
E1/2red vs. SCE =
I
N2
I
SO2Cl
- 2.2 to - 1.6V
- 1.0 V
- 0.36 to - 0.26 V
this work
+ 0.3 V
Scheme 1. Generation of an aryl radical via single-electron-
transfer and typical reductive quenchers.
Chem. Lett. 2013, 42, 1203-1205
© 2013 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

1204
Table 1. Photocatalyzed arylation of (hetero)arenes using 2a
1 mol%
[Ir(ppy)2(bpy)]PF6 (1)
N
Y
Y
PhI
Me
H
Z
PF6
Ph
Z
Ph
3
I
Ph
I
+
N
Ph
Ph
Ph
Ph
Me
rt, 16 h
X
X
2
4
2
solvent
(ca. 40 equiv)
white LED
*Ir(III) Ir(IV)
Entry (Hetero)arene
1c
Product(s) Yield/%b
Ir(III)
N
hν
Me
Ph
hν
54
NMe
H
Ph
PhI
N
N
Me
Me
4
I
7
+
Ph
5
3
55
Ph
Ph
2
H+
Ph
(2-:3-:4- = 56:31:12)
CT complex 6
N
3
2
N
N
product
N
Ph
3d
33
Scheme 2. Two pathways for visible light-mediated arylation
of pyrrole with 2.
N
N
N
5
N
N
75
Ph
4
4
SET from photoexcited *Ir(III) species to 2 would lead to the
formation of the phenyl radical 3 and an Ir(IV) complex. Indeed,
iodonium 2 decreased the emission intensity of *Ir(III) with a
Stern-Volmer constant of 32 M¹1, whereas pyrrole did not have
any discernible impact on the emission intensity (see SI for
details). The subsequent addition of radical 3 to pyrrole forms
the dearomatized radical 4, which is prone to oxidation by
Ir(IV), leading to the cationic intermediate 5 and regeneration of
the Ir(III) photocatalyst.18 The second pathway could be initiated
by a SET via excitation of the CT complex 6,19 which would
generate the pyrrole radical cation 7 and phenyl radical 3. The
recombination of 7 and 3 would provide the common cationic
intermediate 5, which leads to a 2-arylated product upon
deprotonation. In a separate experiment, we confirmed that when
the reaction mixture was placed in the dark following 25 min of
irradiation with an LED, it stalled (see SI for details). This
observation suggests that the involvement of a radical chain
pathway, in which photoirradiation is required only for the
initial generation of a radical, is negligible under our catalytic
conditions.
2
(2-:4-:5- = 31:57:12)
N
5
88
Ph
N
N
Me
N
Me
N
6
36
42
Ph
Ph
N
N
Me
Me
7
S
S
aReaction conditions:
2 (0.30 mmol), 1 (3.0 ¯mol), and
degassed (hetero)arene (1.0 mL) in a 10-mL round-bottom
flask under irradiation with white LED for 16 h, unless
otherwise noted. bIsolated yield based on 2. cIn degassed
benzene (0.90 mL) and EtOH (0.10 mL). d2 (0.30 mmol), 1
(3.0 ¯mol), pyrazine (12 mmol) in degassed CH3CN (0.30 mL).
Table 2. Control experiments for photocatalyzed arylation of
pyridine and pyrrole using 2
1
1 mol%
4
The scope of iodonium salts was next investigated in the
arylation of pyrroles (Table 3). Several different substituents,
including halides (Entries 1 and 2), CF3 (Entry 3), and alkyl
groups (Entries 4 and 5) were found to be well-tolerated and
gave the corresponding 2-arylated pyrroles in the presence of
photocatalyst 1. The electron-rich diaryliodonium did not
undergo the photoarylation of pyrrole, and this result is
consistent with our proposal that the reductive quenching of
Ar2I+ would initiate the reaction (Entry 6). The electronic effect
of the aryl group had a more profound impact on the non-
catalyzed pathway. The CF3-substituted diaryliodonium afforded
the corresponding arylated product in 74% yield in the absence
of photocatalyst 1, likely because of the effective formation of a
CT complex. It is noteworthy that the unprotected NH-free
pyrroles also underwent the photoarylation reaction (Entries 7
and 8).
In summary, we have shown that diaryliodonium salts can
be used as aryl radical precursors in the context of visible light-
mediated photoredox catalysis. It was demonstrated that an aryl
radical generated by the reductive quenching of Ar2I+ with an
excited *Ir(III) species can participate in a homolytic aromatic
substitution reaction with benzene and several heteroarenes at
ambient temperature. It is noteworthy that visible light irradi-
Ph2IPF6 (2)
3
2
Ph or
or
(ca. 40 equiv)
Ph
N
N
rt, 16-23 h
white LED
N
N
Me
Me
Variation from
Yield with
pyridinea/%
Yield with
pyrrole/%
Entry
the “standard conditions”
1
2
3
4
None
Without 1
57 (54:30:16)
9 (56:44:0)
0
88
54
trace
75
Without LED (in dark)
Under an atmosphere of air 57 (59:27:14)
aRatio of regioisomers in product is shown in parenthesis.
2-:3-:4-position.
require elevated temperatures (100 °C)16a,16b or the addition of an
acid16c,16d or base16e to promote the reaction. UV-vis spectro-
scopic analysis of the reaction mixture revealed the formation of
a new absorption band in a visible region when pyrrole and
diphenyliodonium 2 were mixed. This new band is attributed to
the formation of a colored charge-transfer (CT) complex.17
These observations led us to propose that two photo-
chemical pathways are involved in the reaction of iodonium 2
with pyrrole (Scheme 2). One is photoredox catalysis, where a
Chem. Lett. 2013, 42, 1203-1205
© 2013 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

1205
Table 3. Photocatalyzed arylation using various Ar2I+ a
Isolated yield/%
3
4
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Entry Ar2I+
Product
With 1 Without 1
1
2
3
4
5
6
7
(4-ClC6H4)2IOTf
75
68
53
41
N
Me
Cl
(4-BrC6H4)2IOTf
(4-CF3C6H4)2IBF4
(4-MeC6H4)2IOTf
(4-t-BuC6H4)2IOTf
(4-MeOC6H4)2IOTf
Ph2IPF6
N
Me
Br
76
74
N
5
6
Me
CF3
Me
60
18
N
Me
7
8
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61
13
N
Me
t-Bu
OMe
trace
63
trace
32
N
PhI: a) A. J. Fry, R. L. Krieger, J. Org. Chem. 1976, 41, 54. b) L.
Pause, M. Robert, J.-M. Savéant, J. Am. Chem. Soc. 1999, 121, 7158.
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Me
¹
2012, 14, 113. Ph2I+X : d) M. S. Mbarak, D. G. Peters, J.
Ph
N
H
+
Electroanal. Chem. Interfacial Electrochem. 1983, 152, 183. PhN2
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Y. Yasu, T. Koike, M. Akita, Adv. Synth. Catal. 2012, 354, 3414.
:
Et
Me
9
8
Ph2IPF6
48
47
10 E. A. Merritt, B. Olofsson, Angew. Chem., Int. Ed. 2009, 48, 9052.
11 A recent example: J. Lalevée, F. Dumur, C. R. Mayer, D. Gigmes,
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Fouassier, Macromolecules 2012, 45, 4134.
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Ueda, T. Taniguchi, K. Itami, Org. Lett. 2008, 10, 4673.
14 Because pyrazine is solid at rt, the reaction was conducted in
CH3CN, which may be one of the reasons for the relatively low
yield.
Me
Ph
N
H
aReaction conditions: iodonium salt (0.30 mmol) and pyrrole
derivative (1.0 mL) in a 10-mL round-bottom flask under
irradiation with white LED for 16 h, in the presence or absence
of 1 (3.0 ¯mol).
15 The regioselectivities observed with 5-membered heteroarenes are
identical to those observed in other radical arylation. For example,
see: D. P. Hari, P. Schroll, B. König, J. Am. Chem. Soc. 2012, 134,
2958.
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ation can effectively promote the 2-arylation of pyrroles with
Ar2I+ in the absence of a photoredox catalyst via a CT complex
6. These results imply that similar noncatalytic pathways could
be involved in other known arylation reactions of electron-rich
species using Ar2I+, in addition to photocatalytic and ionic
mechanisms. Further studies toward developing visible light-
mediated synthetic methods are currently underway in our
laboratory.20,21
This work was supported by “Molecular Activation Directed
toward Straightforward Synthesis,” “Organic Synthesis Based
on Reaction Integration,” and “Elements Strategy Initiative to
Form Core Research Center” from MEXT, Japan. We thank
Professors Gaku Fukuhara, Tadashi Mori, and Yoshihisa Inoue
(Osaka University) for providing access to facilities for
spectroscopic studies and many fruitful discussions. We also
thank the Instrumental Analysis Center, Faculty of Engineering,
Osaka University, for HRMS.
17 CT complexes using Ar2I+: H. Hennig, O. Brede, R. Billing, J.
Schönewerk, Chem.®Eur. J. 2001, 7, 2114. See also ref 16d.
18 Involvement of an energy-transfer pathway from *Ir(III) to 2 cannot
be excluded. In such a pathway, the formation of iodobiphenyls is
often observed. However, it was not observed in the present study.
J. L. Dektar, N. P. Hacker, J. Org. Chem. 1990, 55, 639.
19 N. J. Turro, V. Ramamurthy, J. C. Scaiano, Modern Molecular
Photochemistry of Organic Molecules, University Science Books,
California, 2010, pp. 454-461.
20 a) During the preparation of this manuscript, Xue and Xiao reported
a similar photocatalytic arylation using Ar2I+, although noncatalytic
arylation did not occur under their conditions. Y.-X. Liu, D. Xue,
J.-D. Wang, C.-J. Zhao, Q.-Z. Zou, C. Wang, J. Xiao, Synlett 2013,
24, 507. b) Quite recently, generation of aryl radicals from sulfonium
salts under photoredox catalysis has been reported: S. Donck, A.
Baroudi, L. Fensterbank, J.-P. Goddard, C. Ollivier, Adv. Synth.
Catal. 2013, 355, 1477.
References and Notes
1
A representative review: a) S. E. Vaillard, B. Schulte, A. Studer, in
Modern Arylation Methods, ed. by L. Ackermann, Wiley-VCH,
Weinheim, 2009, pp. 475-511. doi:10.1002/9783527627325.ch13.
Our work in this area: b) M. Tobisu, K. Koh, T. Furukawa, N.
Chatani, Angew. Chem., Int. Ed. 2012, 51, 11363.
21 Supporting Information is available electronically on the CSJ-
Journal Web site, http://www.csj.jp/journals/chem-lett/index.html.
2
Radicals in Organic Synthesis, ed. by P. Renaud, M. P. Sibi, Wiley-
VCH, Weinheim, 2001, Vol. 1. doi:10.1002/9783527618293.
Chem. Lett. 2013, 42, 1203-1205
© 2013 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/