Metal-free, visible-light-mediated direct C-H arylation of heteroarenes with aryl diazonium salts

Article abstract of DOI:10.1021/ja212099r

Visible light along with 1 mol % eosin Y catalyzes the direct C-H bond arylation of heteroarenes with aryl diazonium salts by a photoredox process. We have investigated the scope of the reaction for several aryl diazonium salts and heteroarenes. The general and easy procedure provides a transition-metal-free alternative for the formation of aryl-heteroaryl bonds.

Full text of DOI:10.1021/ja212099r

Communication
pubs.acs.org/JACS
Metal-Free, Visible-Light-Mediated Direct C−H Arylation of
Heteroarenes with Aryl Diazonium Salts
Durga Prasad Hari, Peter Schroll, and Burkhard Konig*
̈
Institut fur Organische Chemie, Universitat Regensburg, Universitatsstraße 31, D-93053 Regensburg, Germany
̈
̈
̈
S
* Supporting Information
Aryl diazonium salts are an excellent source of aryl radicals
because of their relatively high reduction potentials.8 The
long-known Meerwein arylation uses this in a copper-
mediated redox process for the coupling of aryl diazonium
salts to alkenes or heteroarenes. However, the reaction
suffers from low yields (typically in the 20−40% range), high
catalyst loadings, and restriction to aqueous reaction media.
The Meerwein arylation has therefore not widely been used
in synthesis.9 Heinrich and co-workers10 reported the direct
arylation of phenols, anilines, and furans with aryl diazonium
salts using TiCl3 catalysis; the reaction possibly proceeds
through a radical mechanism. Recently, Sanford and co-
workers11 merged palladium catalysis with photocatalysis for
C−H arylation. Aryl diazonium salts are well-known oxida-
tive quenchers in photoredox chemistry,5k,12 which was first
applied by Cano-Yelo and Deronzier13 in the visible-light-
mediated Pschorr cyclization to convert stilbene diazonium
salts into the corresponding phenanthrene derivatives using
ABSTRACT: Visible light along with 1 mol % eosin Y
catalyzes the direct C−H bond arylation of heteroarenes
with aryl diazonium salts by a photoredox process. We
have investigated the scope of the reaction for several aryl
diazonium salts and heteroarenes. The general and easy
procedure provides a transition-metal-free alternative for
the formation of aryl−heteroaryl bonds.
rylated heteroarenes are widely used in materials science
A
because of their interesting optical and electronic
properties,1 but they also find biomedical applications as
peptide mimetics2 or drugs.3 The most efficient synthesis of
aryl−heteroaryl bonds is the direct arylation of heteroarenes by
C−H bond activation. In contrast to the well-known cross-
coupling reactions, such C−H activation methods do not require
preactivation of the heteroarene, and a variety of transition-
metal-catalyzed processes using aryl halides, arylboronic acids,
aryltin reagents, and diazonium salts as coupling partners
(Figure 1) have been developed.4 However, photocatalysis may
2+
Ru(bpy)3 as a photoredox catalyst. The same authors also
used a ruthenium complex in an oxidative quenching cycle for
the transformation of benzyl alcohol to aldehyde with aryl
diazonium salts as oxidative quenchers.14 We report now a
photocatalyzed single-electron transfer (SET)-mediated direct
C−H bond arylation of heteroarenes with aryl diazonium salts
that requires only green light and the organic dye eosin Y as a
catalyst.
First, the reaction conditions were optimized for the direct
arylation of furan (2a) with diazonium salt 1a, 530 nm light-
emitting diode (LED) irradiation, and 1 mol % eosin Y as a
photoredox catalyst. Various solvents, additives, and amounts
of 2a were examined at room temperature, and the desired
product was obtained in all cases. Dimethyl sulfoxide (DMSO)
was found to be a good solvent for the photoreaction. The
arylated product was obtained in good yield using an excess
of 10 equiv of 2a (Table 1, entry 2). Excess base decreased
the product yield (Table 1, entries 10−12), which was
attributed to direct reaction of the base with 1a. Control
reactions confirmed that both light and eosin Y are required
for significant conversion to the product (Table 1, entries 13
and 14).
Figure 1. Metal-catalyzed and photocatalytic approaches for direct
C−H arylation of heteroarenes.
Having optimized the reaction conditions, we examined the
scope of the reaction of 2a with different aryl diazonium salts 1.
Among the aryl diazonium salts used for direct arylation of
furan, electron-acceptor- (Table 2, entries 2−6) and neutral-
substituted (Table 2, entries 1 and 7) diazonium salts were
provide a valuable alternative that avoids the use of transition
metals, ligands, bases, or elevated temperatures. Recent reports
have demonstrated the formation of C−C,5 C−P,5m,6 and C−N7
bonds using visible light and ruthenium or iridium complexes or
organic dyes as photoredox catalysts.
Received: December 27, 2011
Published: January 30, 2012
© 2012 American Chemical Society
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Communication
a
Table 1. Optimization of the Reaction Conditions
Table 2. Scope of Aryl Diazonium Salts
a
entry
conditions
2a (5 equiv), DMSO
yield [%]
1
2
73
80
80
48
55
12
17
10
73
66
54
45
14
19
2a (10 equiv), DMSO
3
2a (15 equiv), DMSO
4
2a (10 equiv), DMF
5
2a (10 equiv), MeOH
6
2a (10 equiv), CH3CN
7
2a (10 equiv), EtOAc
8
2a (10 equiv), THF
9
2a (10 equiv), DMSO/H2O (3:1)
2a (10 equiv), DMSO, pyridine (2 equiv)
2a (10 equiv), DMSO, NaOAc (2 equiv)
10
11
12
13
14
t
2a (10 equiv), DMSO, BuOK (2 equiv)
2a (10 equiv), DMSO, no light, 72 h
2a (10 equiv), DMSO, no catalyst, 72 h
a
1
Yieds were determined by H NMR analysis.
found to be more efficient for product formation than electron-
donor-substituted ones (Table 2, entries 8−10). Moreover, a
range of functional groups, such as nitro, ester, cyano, and
hydroxyl groups were tolerated in this photoreaction. Notably,
halogen-substituted aryl diazonium salts successfully underwent
C−H bond arylation leaving the C−halogen bond intact, which
is useful for further synthetic elaboration.
The metal-free, photocatalyzed C−H arylation was also
effective for other heteroarenes, such as thiophene and pyrrole,
and the corresponding products were obtained in moderate to
good yields (Table 3).
Thienyl diazonium salt 6 led to heterobiaryls 7 and 8,
which are typical structural motifs of organic semiconductors
(Scheme 1a). In addition to heteroarenes, nitrobenzene
was converted in 50% yield into compound 10 and other
regioisomers (10%) after 20 h of irradiation with green light
(Scheme 1b).
The C−H arylation of heteroarenes with aryl diazonium
salts using eosin Y was expected to proceed through a radical
mechanism, and preliminary mechanistic investigations sup-
ported this assumption. When the reaction of aryl diazonium
salts was conducted in the absence of furan but with added
2,2,6,6-tetramethylpiperidinoxyl (TEMPO), compound 11
(Figure 2) was obtained. Furthermore, addition of TEMPO
to the reaction mixture of aryl diazonium salts, furan, and
eosin Y stopped the arylation process, and the TEMPO-
trapped intermediate 12 (Figure 2) was detected. The identified
compounds suggest that the photoreaction proceeds via a
radical pathway (see the Supporting Information for more
details).
On the basis of the above observations and literature
reports,10,11,13,15 a plausible mechanism for this photo-
reaction is proposed (Scheme 2). Initially, aryl radical 13 is
formed by SET from the excited state of eosin Y to aryl
diazonium salt 1. Addition of aryl radical 13 to heteroarene 2
gives radical intermediate 14, which is further transformed
to carbocation intermediate 15 by two possible pathways:
(a) oxidation of the radical intermediate 14 by the eosin
a
The reaction was performed with 1 (0.23 mmol), 2a (10 equiv), and
b
eosin Y (0.01 equiv) in 1.0 mL of DMSO. Isolated yields after
purification on SiO2.
Y radical cation to give 15 and (b) the oxidation of 14 by
aryl diazonium salt 1 in a radical chain transfer mecha-
nism. Finally, intermediate 15 is deprotonated, regenerating
the aromatic system and leading to the desired coupling
product 16.
In summary, we have reported a metal-free, direct inter-
molecular C−H arylation of heteroarenes by photoredox
catalysis with green light. The reaction proceeds smoothly at
room temperature, does not require transition-metal catalysts
or bases, and displays a broad scope toward diazonium salts
and heterocycles with a wide range of functional group
tolerance. This SET cross-coupling represents an efficient
alternative to the known transition-metal-catalyzed (Pd, Ru,
t
Ir, Rh, and Ti) and BuOK-promoted strategies for C−H
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a
Table 3. Scope of Heteroarenes
Scheme 1. C−H Photoarylation of (a) Heteroarenes with a
Thienyl Diazonium Salt and (b) Nitrobenzene with an Aryl
Diazonium Salt
Figure 2. TEMPO-trapped reaction intermediates.
Scheme 2. Suggested Mechanism for Photocatalytic Direct
C−H Arylation of Heteroarenes
ASSOCIATED CONTENT
■
S
* Supporting Information
Experimental procedures and characterization data for all
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
a
Reactions were carried out using 1 (0.23 mmol), heteroarene
(5 equiv in the case of thiophene derivatives, 2 equiv in the case of
pyrrole derivatives), and eosin Y (0.01 equiv) in 1.0 mL of DMSO.
AUTHOR INFORMATION
b
■
Isolated yields after purification on SiO2.
Corresponding Author
Burkhard.Koenig@chemie.uni-regensburg.de
arylation, and it overcomes the significant drawbacks of the
Meerwein arylation that have prevented its broader applica-
tion in organic synthesis. The induction of the reaction by
visible light may find applications beyond synthesis, such as in
the chemical patterning of surfaces. Further investigations of
the mechanism of the reaction and its application are ongoing
in our laboratory.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the GRK 1626 (Chemical Photo-
catalysis) of the German Science Foundation (DFG).
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