Metal-free, visible-light-mediated transformation of aryl diazonium salts and (hetero)arenes: An efficient route to aryl ketones

Article abstract of DOI:10.1039/c5gc00644a

A visible-light-catalyzed synthesis of aryl ketones from aryldiazonium salts, CO and (hetero)arenes at room temperature is discovered. This transformation represents an efficient and attractive synthetic utilization of aryl diazonium salts.

Full text of DOI:10.1039/c5gc00644a

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Metal-free, visible-light-mediated transformation
of aryl diazonium salts and (hetero)arenes:
an efficient route to aryl ketones†
Cite this: DOI: 10.1039/c5gc00644a
Received 25th March 2015,
Accepted 8th May 2015
Lijun Gu,*a,c Cheng Jinb and Jiyan Liua
DOI: 10.1039/c5gc00644a
www.rsc.org/greenchem
A visible-light-catalyzed synthesis of aryl ketones from aryldiazo- ing conditions. Many visible-light photoredox catalysts such as
nium salts, CO and (hetero)arenes at room temperature is discov- metal or non-metal complexes have been used to solve the
ered. This transformation represents an efficient and attractive problem of visible light absorption efficiency.5 By using these
synthetic utilization of aryl diazonium salts.
methods, readily available, reactive aryl diazonium salts have
been widely utilized as a convenient aryl radical source.6 As a
result, many unusual transformations of these reagents have
been carried out by photocatalysis. It has been reported that in
the presence of a certain amount of CO aryl radicals can be
easily and efficiently converted into acyl radicals which will be
further oxidized to benzylidyneoxoniums by the oxidized dye
radical cation. Recently, the group of Xiao reported an intra-
molecular carboxylation reaction for the formation of
9H-fluoren-9-one.6c However, the intermolecular carboxylation
reactions for the synthesis of aryl ketones from aryl diazonium
salts, CO and (hetero)arenes using visible-light-induced photo-
redox catalysis have not been reported. Inspired by the pio-
neering work from the groups of Xiao and Wangelin, we
envisioned that (hetero)arenes might serve as a platform to
trap benzylidyneoxoniums. In connection with our broader
interest in visible-light-induced photocatalysis,7 herein we dis-
close our preliminary results on visible-light promoted trans-
formation of aryldiazonium salts and (hetero)arenes for the
synthesis of aryl ketones under base-free and transition-metal-
free conditions under a carbon monoxide atmosphere.8 The
method involves a redox reaction driven by visible light and
catalyzed by Eosin Y (Scheme 1).
Aryl ketones are common structural motifs in natural products
and are versatile building blocks in the synthesis of more
complex natural products, pharmaceuticals, agricultural
chemicals, dyes, and other commercially important materials.1
Owing to their structural diversity and remarkable biological
functions, the synthesis and transformation of aryl ketones
has been and continues to be a topic of research interest for
synthetic organic chemists.2 One approach towards efficient
aryl ketone synthesis is carbonylation of aromatic C–H bonds
with CO and aromatic boronic acids.3 This method has pro-
vided a straightforward route to versatile unsymmetric diaryl
ketones. The approach relies on the development of a wide
range of robust metal catalysts which elegantly combine many
central transition metals (i.e., Ru, Pd, Co, etc.) and diverse
organic ligands. The use of transition-metal catalysts is often
expensive and is required to be completely removed from pro-
ducts, especially in the synthesis of pharmaceutical com-
pounds. To overcome the drawbacks of the above-mentioned
transformation methods, photocatalysis may provide a valu-
able alternative that avoids the use of transition metals,
ligands, bases, or elevated temperatures.4
Visible light photoredox catalyst initiated organic trans-
formations are emerging as uniquely powerful tools for con-
structing new chemical bonds in organic synthesis due to their
more environmentally benign sustainability and mild operat-
aKey Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs
Commission & Ministry of Education, Yunnan Minzu University, Kunming,
Yunnan 650500, China
bNew United Group Company Limited, Changzhou, Jiangsu 213166, China
cKey Laboratory of Comprehensive Utilization of Mineral Resources in Ethnic
Regions, Yunnan Minzu University, Kunming, Yunnan 650500, China.
E-mail: gulijun2005@126.com
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
c5gc00644a
Scheme 1 Synthesis of aryl ketones via redox carbonylation.
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Table 2 Scope of aryldiazonium salts 1a
The effort was initiated by using phenyl diazonium tetra-
fluoroborate 1a with benzene 2a as a model reaction in the
presence of Eosin Y (1 mol%) under irradiation with 5 W white
LED light and a CO pressure of 70 atm in MeCN at room tem-
perature. The desired benzophenone 3aa was formed in 74%
yield after 16 h (Table 1, entry 1). Interestingly, the yield of 3aa
dramatically enhanced to 82% when the reaction was per-
formed with 5 W green LED light (Table 1, entry 2). Extensive
screening of solvents revealed that MeCN provided the best
results (Table 1, entries 2–5). In addition to Eosin Y, other
organic dyes such as Fluorescein, Rhodamine B and Rose
Bengal (RB) were less active in this acylation process (Table 1,
entries 6–8). Lower pressures of CO resulted in low conversion
(Table 1, entry 9). However, the reaction did not take place in
the absence of either the visible-light photoredox catalysts
(Table 1, entry 10) or additional visible light (Table 1, entry 11).
With the optimal reaction conditions established, we
applied the above visible-light photocatalysis protocol to a
range of both aryl diazonium salts 1 and (hetero)arenes 2 to
investigate the scope. The scope of aryldiazonium salts 1 was
initially explored in the presence of benzene 2a, Eosin Y
(1 mol%) under irradiation with 5 W green LED light and a CO
pressure of 70 atm in MeCN at room temperature. As summar-
ized in Table 2, this visible-light-induced acylation process dis-
played high functional-group tolerance and proved to be a
general method for the preparation of aryl ketones. Aryl diazo-
nium salts bearing electron-donating groups at the para posi-
tion of the phenyl ring, such as methyl and methoxyl,
proceeded smoothly in the reaction to give the corresponding
aryl ketones 3ab–3ac in good yields (Table 2, entries 1 and 2).
However, a substituent at the ortho position of the phenyl ring
gave the corresponding product 3ad with a decreasing yield
(Table 2, entry 3). These results indicated that the steric effects
affected the efficiency of the reactions. When using the meta-
Entry
1
Aryldiazonium salts 1
Aryl ketone 3
Yieldb (%)
71
2
3
68
56
4
70
5
6
7
77
64
75
8
9
59
62
a Reaction conditions: 1 (0.3 mmol), 2a (0.3 mmol), Eosin Y (1 mol%),
MeCN (2.0 mL), room temperature, CO (70 atm), 5 W green LED light
for 16 h. b Isolated yield.
Table 1 Optimization of the reaction conditionsa
substituted aryl diazonium salts as the substrate, the corres-
ponding aryl ketone 3ae was formed in 70% yield (Table 2,
entry 4). Electron-withdrawing-group-substituted aryl diazo-
nium salts, such as 1f–1i, were also well tolerated in the reac-
tion to afford the corresponding aryl ketones 3af–3ai in
59–77% yields (Table 2, entries 5–8). These results indicate
that the electronic nature of the aryl diazonium salts has little
influence on the acylation process. Aryl diazonium salt with a
naphthyl group (1j) also participated in this visible-light-
induced acylation process, affording the desired product in
62% yield (Table 2, entry 9).
Entry
Catalyst
Solvent
Yieldb(%)
1
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Fluorescein
Rhodamine B
RB
CH3CN
CH3CN
DMSO
THF
74
82
63
21
16
56
31
22
73
0
2c
3
4
5
6
7
EtOAc
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
8
9d
10
11e
Eosin Y
None
Eosin Y
0
a Reaction conditions: 1a (0.3 mmol), 2a (0.3 mmol), catalyst (1 mol%),
solvent (2.0 mL), room temperature, CO (70 atm), 5 W white LED light
for 16 h. b Isolated yield. c 5 W green LED light. d CO (60 atm). e In the
dark.
The visible-light-induced acylation was also tested on
several other (hetero)arenes. The reaction was particularly
effective with electron-rich aromatic rings. Heteroaromatic
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substrates 2b–2e underwent this reaction to furnish the corres- This visible-light-induced acylation protocol could also be
ponding products in 63%–84% yields (Table 3, entries 1–4). To applied to substrates 2i–2j (Table 3, entries 8 and 9). Impor-
highlight the utility of this transformation, the electron- tantly, the polysubstituted benzene derivative 2k gave the
deficient heteroarenes 2f–2g were subjected to the standard desired product 3ka in good yield (Table 3, entry 10). Unfortu-
reaction conditions. The desired products were obtained in nately, nitrobenzene did not deliver the corresponding ketone
moderate yields (Table 3, entries 5 and 6). When toluene 2h under the same reaction conditions (Table 3, entry 11).
was employed, the reaction afforded the two regioisomers 3ab
To gain an insight into the course of the reaction, we con-
and 3ad in 61% and 14% yield, respectively (Table 3, entry 7). ducted a series of control experiments.6b,6c When a radical-
trapping reagent, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)
(1.0 equiv.), was added to the model reaction, no aryl ketone
was obtained (Scheme 2, eqn (1)). These results suggest that
the photoreaction proceeds via a radical pathway. Further-
Table 3 Scope of (hetero)arenes 2a
more, the product yields severely dropped when no photo-
catalyst was present in the reaction and/or under dark
conditions. Reactions in the dark and at increased tempera-
tures (up to 80 °C) gave no desired product (Scheme 2,
eqn (2)), which excludes homolytic bond cleavage of the start-
ing material to an aryl radical under these conditions.
Entry
1
(Hetero)arenes 2
Aryl ketone 3
Yieldb (%)
84
On the basis of these preliminary results, and those of pre-
vious studies,6,9–11 we propose the mechanism shown in
Scheme 3. Initially, photoexcitation of Eosin Y by visible light
generates excited [Eosin Y*]. Then the electron-deficient
phenyl diazonium tetrafluoroborate 1a accepts one electron
from the excited [Eosin Y*]. This single-electron transfer (SET)
results in the generation of a phenyl radical (Ph•) and the oxi-
dized dye radical cation [Eosin Y+•]. The resulting phenyl
radical (Ph•) is rapidly trapped by CO to give a benzoyl radical
A. Further oxidation of A by [Eosin Y+•] results in the benzylidy-
neoxonium B. Finally, electronic trapping of B by benzene
gives the desired aryl ketone 3aa.
2
3
4
77
63
82
5
66
6
54
75
67
7c
8c
Scheme 2 Control experiment.
9c
69
51
10
11
0
a Reaction conditions: 1a (0.3 mmol), 2 (0.3 mmol), Eosin Y (1 mol%),
MeCN (2.0 mL), room temperature, CO (70 atm), 5 W green LED light
for 16 h. b Isolated yield. c GC yield.
Scheme 3 Plausible mechanism.
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In summary, we have developed a metal-free and base-free
carbonylation reaction by photoredox catalysis with green
light. Mechanistic studies support the sequential operation of
SET reduction, carbonylation, and back electron transfer to
give acylium cations. Aryl ketones can be prepared from arene
diazonium salts, CO, and (hetero)arenes at room temperature
under irradiation with visible light. Most importantly, simple
and readily available Eosin Y emerges as an efficient catalyst,
rather than a metal catalyst, which is often expensive and is
required to be completely removed from products, especially
in the synthesis of pharmaceutical compounds. Further inves-
tigations of the mechanism of the reaction and its application
are ongoing in our laboratory.
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