Visible light-induced aerobic oxidation of diarylalkynes to α-diketones catalyzed by copper-superoxo at room temperature

Article abstract of DOI:10.1039/d0gc00975j

We have developed the visible light induced simple copper(ii) chloride catalyzed oxidation of diarylacetylenes to α-diketones by molecular oxygen at room temperature. The in situ generated copper(ii)-superoxo complex is a light-absorbing species that oxidizes inert diarylacetylenes to α-diketones. In contrast to reported photochemical processes, the current oxidation protocol does not require any exogenous photocatalyst or radical initiator. The green chemistry metrics evaluation signifies that the E-factor for the current oxidation process is ～2.3 times better than that of reported photochemical processes. The current reaction scores 63 on the EcoScale of 0-100, indicating an adequate synthesis process. Thus, the overall oxidation process is simple, environmentally benign, and economically feasible. This journal is

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DOI: 10.1039/D0GC00975J
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Visible Light-Induced Aerobic Oxidation of Diarylalkynes to -
Diketones Catalyzed by Copper-superoxo at Room Temperature
Vaibhav Pramod Charpe†, Arunachalam Sagadevan†, and Kuo Chu Hwang*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
We have developed the visible light induced simple copper(II)
chloride catalyzed the oxidation of diarylacetylenes to -
diketones by molecular oxygen at room temperature. The in-situ
alkynes is one of the unique oxidation processes as internal alkynes
can be easily obtained from the Sonogashira coupling reaction7. In
this context, various thermal-mediated transition metal-catalyzed
oxidation processes have been developed for the synthesis of 1,2-
diketones, which includes the metals, such as Pd8a-d, Ru8e-h, Au8i,
Hg8j, Cu8k in combination with various oxidants, such as DMSO,
Ph2SO, oxone, K2S2O8 and Na2S2O8 (Scheme 1, eqn a). Although
these oxidation processes are highly efficient, these methods still
suffer from various drawbacks, such as a) harsh reaction conditions;
b) use of expensive metal catalysts; c) use of organic oxidants which
may generate unwanted wastes; d) instability of 1,2-diketones at
harsh conditions which may lead to the formation of by-products,
and e) high toxicity of reagents used in the processes.
generated copper(II)-superoxo complex is
a light-absorbing
species that oxidizes inert diarylacetylenes to -diketones. In
contrast to reported photochemical processes, the current
oxidation protocol does not require any exogenous photocatalyst
or radical initiator. The green chemistry metrics evaluation
signifies that the E-factor for the current oxidation process is ~2.3
times better than that of reported photochemical processes. The
current reaction scores 63 on the EcoScale of 0-100, indicates an
adequate synthesis process. Thus, the overall oxidation process is
simple, environmentally benign, and economically feasible.
From a green and sustainable point of view, the utilization of
molecular oxygen as a terminal oxidant as well as a reagent for
oxidative functionalization of CC triple bonds1a,b under mild
conditions (room temperature) has recently emerged as an efficient
and straightforward approach for the construction of value-added
oxygen-containing compounds1.
Scheme 1. Comparison of literature processes and the current
photochemical process.
Previous work
a) Transition metal catalyzed oxidation of diarylacetylenes
O
[Pd], [Ru],[Au][Hg]
Ph
Ph
Ph
Ph
external organic oxidants
RT to140oC
In this regard, -diketones are vital frameworks in organic
synthesis and pharmaceutical chemistry2. For instance, it acts as
precursors for the synthesis of a) N-heterocyclic carbenes (NHC), an
essential class of ligands in organometallic chemistry3; b) a variety
of organic chemicals or intermediates, importantly the synthesis of
bioactive heterocyclic molecules, such as indolone-N-oxide,
quinoxalines, and imidazoles4; c) antimicrobial and anticonvulsant
drugs5a, moreover, benzil derivatives also show the bioactivities in
-Requires high temperature
-expensive catalyst and ligands
O
b) Metal free oxidation of diarylacetylenes to -diketones

EosinY,air,
4-Chlorobenzenethiol,
blueLEDs,RT
O
-Produces high amount of
wastes(high E-factor)
-requires external organic
compounds
Ph
Ph
Ph
Ph
OR
ArSSAr(15mol%),ACN, O2,
RT,blue LEDs(450-455nm)
O
-need photosenitizers
c) Visible Light-Mediated Copper(I)-Catalysed Aerobic Oxidation of Ynamides/ Ynamines
R
N
O
antitumor application5b-d
.
R
5 mol% CuCl
N
Ph
(activated alkynes)
Ph
Ph
visible light
Due to their usefulness, several oxidation protocols have been
reported for the synthesis of 1,2-diketones from various substrates,
such as olefins, -hydroxy ketones, methylene ketones, terminal
alkynes, and internal alkynes6. Among which, oxidation of internal
Ph
O
ACN, O2, RT.
R= EDG/EWG
Present work: Visible light reaction
d)
O
10mol% CuCl2
5 mol% CuCl
Ph
Ar
Ph
Ph
I Ar
+
Ar
base
visible light
ACN, O2
visible light, RT
inactive
internal
alkynes
O
Ref: 9a
(i) Use of inexpensive CuCl2 as catalyst and O2 as oxidant. (ii) Low E-factor and high
reaction mass efficiency(RME) (iii) Internal alkynes substrates is prepared from our
previous work . (iv) Mild reaction conditions. (v) Works well with electron donating and
withdrawing groups.
Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan, ROC.
E-mail: kchwang@mx.nthu.edu.tw; Fax: (+886) 35711082.
†V. P. C and A. S contributed equally to this work.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
To conquer such challenges involved in any thermal chemical
reactions for the formation of the new chemical bond, visible light
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
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photo redox catalysis has recently been developed as a novel eco-friendly and sustainable process with low E-factor, high
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activation modality for various organic transformation1a-b,9,10. In this reaction mass efficiency (RME) and a good EDcoOSI:c1a0le.10v3a9lu/De0. GC00975J
context, visible light-mediated photooxidation of internal alkynes to
Inspired by our previous work that oxidation of
1,2-diketones have recently been reported11; however, these ynamides/ynamines 10h, we further optimized the condition for
processes still suffered usage of stoichiometric metal-salts also oxidation of diphenylacetylene (a model substrate) for the
.
.
indeed toxic bromine radical (Br )11a and nitrate radical (NO 3)11b
formation of benzil using copper salt and molecular oxygen under
visible light irradiation for 12 h (Table 1). In the screening of copper
catalysts (CuCl2, CuBr, CuCl), CuCl2 can catalyse oxidation of
diphenylacetylene to benzil in highest yield (76%) (Table 1, entries
1-3). No product was observed when other non-halide copper salts
such as Cu(OAc)2 and Cu(OTf)2 (Table 1, entries 4-5) was used as
catalysts. Next, we examined effects of solvents, such as ACN,
MeOH, ACN-MeOH (1:1) on the product yield, and among which
ACN gives the product 2a in good yield (entries 1-6). Further,
optimization experiments revealed that addition of 30 L (3.3
equiv.) of water surprisingly improves the product yield to 85%
(Table 1, entries 9-12); however, an excess amount of water (0.5
mL) lowers the product yield from 85% to 70% (entry 9). which
might be due to water-accelerated decomposition of the 1,2-
dioxete ring. The use of air balloon, instead of pure O2, slightly
diminished the yield to 72% (entry 13). When 1a was irradiated for
30 h under low light density (white bulb), only 52% of the product
was obtained (entry 14). Under a thermal+dark condition (at 80 oC),
only a trace amount of product was obtained (entry 15). Further
optimization studies indicate that the CuCl2, O2, and visible light are
essential for the formation of product (2a) in good yields.
were the reactive species.
Subsequently, Sun et al. reported the synthesis of diketones by
aerobic photooxidation of internal alkynes in the presence of eosin
Y as a photocatalyst and the 4-chlorobenzenethiol as a source of
thiophenyl radical12a
.
Similarly, Wang et. al.12b depicted
photoinduced thiyl radical catalyzed aerobic oxidation of
diarylacetylenes to -diketones by using diphenyldisulfide as a thiyl
radical source (Scheme 1, eqn b). Although these metal-free
strategies have been developed, these methods still have various
disadvantages, such as a) use of significant excess of radical
initiators (4-chlorobenzenethiol, and diphenyldisulfide); b) use of
organic photosensitizer, which may involve photo-bleaching
pathways; c) narrow substrate scope, and d) generation of high
amount of wastes which leads to a higher E-factor.
In light of the importance of the 1,2-diketones, the
development of efficient and environmentally friendly method for
the preparation of α-diketones via direct aerobic oxidation of inert
CC triple bond of internal alkynes by using inexpensive simple base
metal catalyst (i.e. Cu) especially under low energy visible light
irradiation, which would be of great importance in organic
synthesis. To this end, our group recently reported the visible-light-
induced, copper(I)-catalyzed various cross-coupling reactions10,
including aerobic oxidation of ynamides/ynamines to form α-
ketoimides/α-ketoamides9h (Scheme 1, eq c). In connection to our
previous work10h, herein, we report the first visible light-induced
copper catalyzed the oxidation of stable diarylacetylenes to -
diketones by molecular oxygen at room temperature (Scheme 1, d).
In contrast to our previous work10h, the oxidation of stable CC
triple bond of diarylacetylenes were more challenging and
promising than oxidation of reactive ynamides/ynamines (N-lone
pair delocalized with CC triple bond and thereby easily chelated by
Cu(I)-salt). In the current strategy, we envision that in-situ
generated copper(II) superoxo complex might be the light-
absorbing species, which upon photoexcitation allows for oxidation
of stable internal alkynes to -diketones (see details in mechanism
Scheme). Notably, internal alkynes substrates for this oxidation
method were synthesized by using our previously reported green
and highly efficient protocol of photoinduced copper(I) catalyzed
Sonogashira coupling reaction10a (scheme 1, eq d). Thus, by using
these methods, one can synthesize -diketones from the readily
available starting materials, such as aryl iodides and terminal
alkynes, which makes the overall synthesis of -diketones
economically and environmentally feasible. The importance of the
current aerobic oxidations process includes; a) the first report of
visible-light-driven aerobic oxidation of stable diarylacetylenes to
form -diketones at room temperature; b) use of molecular oxygen
as an oxidant; c) use of inexpensive CuCl2; d) no by-product
formation; e) broad substrates scope; f) an eco-friendly
photoinduced Sonogashira coupling reaction can efficiently
synthesize various internal alkynes substrates; g) signifies a green,
Table 1. Optimization of reaction conditionsa
O
10 mol% [Cu]-cat
Ph
Ph
Ph
Ph
2a
solvent, 12 h, O2
blue-LEDs, RT
O
1a
yield (%)b
76
Entry
[Cu] Catalyst
Solvent
CH3CN
CuCl2
CuBr
CuCl
Cu(OAc)2
Cu(OTf)2
1
2
CH3CN
CH3CN
68
73
3
4
5
n.r
n.r
CH3CN
CH3CN
CH3CN-MeOH
MeOH
55
48
18
70
72
6
7
8
9
10
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
THF
CH3CN(0.5mL H2O)
CH3CN(0.1mL H2O)
CH3CN(60L H2O)
CuCl2
81
11
12
CuCl2
CH CN(30 L H O)

3 2
85
13c
14d
15e
CuCl2
CH3CN
CH3CN
CH3CN
72
52
trace
n.r
CuCl2
CuCl2
none
16f
CH3CN
CH3CN
17g
CuCl2
trace
a) Unless otherwise mentioned, the reaction condition is as follows; 1a (0.5
mmol), 10 mol% of [Cu] catalyst, solvent (5 mL). The mixture was irradiated
with blue LEDs (power density: 40 mW/cm2 at 460 nm) for 12 h in an O2
atmosphere (1 atm). b) Yield of the isolated product. c) 1 atm. air (in
balloon) was used in the reaction. d) Irradiation with an ambient white light
bulb for 30 h (power density: 8 mW/cm2 at 460 nm). e) Reaction was
conducted in the dark at 80 oC. f) In the absence of CuCl2 catalyst. g) In the
absence of O2.
2 | J. Name., 2012, 00, 1-3
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aIsolated yield after purification by column chromatography on SiO2.
With the optimized condition in hand, we next systematically
investigated the substrate scope of mono and di-substituted
diarylacetylenes bearing electron donating, neutral, and
withdrawing groups (Table 2).
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bYield was calculated from the crude NMR.
DOI: 10.1039/D0GC00975J
In the case of heteroaryl acetylenes, only thiophene aryl
acetylene substrate (1q) works well to form an -diketone product
(2q) in good yield (72%). Whereas, the pyridine aryl acetylene
substrate did not work with the current oxidation process. It is
important to note that oxidation of 1r accomplished a mixture of 2r
(66% yield) and 2r‘ (10% yield). Formation of side product 2r‘ is
because the photoexcited copper(II) superoxo complex C can also
oxidize the benzylic carbon of the product 2r to form a ketone
product 2r‘. Our results indicate that oxidation of the CC triple
bond is more favourable and occurs earlier than oxidation of the
benzylic carbon. The other substrate, 1,4-diphenylbuta-1,3-diyne
(1s) undergoes similar oxidation to form product (2s) in 52% yield.
We did not observe further oxidation of the product 2s at its second
CC triple bond.
First, oxidation of electron-neutral compound 1-(phenylethynyl)
naphthalene forms the product (2b) in a good yield of 83%. Next,
diarylacetylenes bearing electron-donating groups (-Me, -tBu, -OMe,
-OH ) were oxidized smoothly to form products (2c-2g). The product
2g bearing hydroxyl functionality can be used for later synthetic
modifications7c. Further, the halogen (F, Cl, Br, I)-substituted
diarylacetylenes perform well in this transformation (2h-2l, 68-81%
yield). Diarylacetylenes with moderate and strong electron-
withdrawing groups (-CF3, -CN, -NO2,-COMe) also work well with the
current oxidation method to form corresponding products (2m-2p)
in moderate to good yield (61-71%).
Table 2. Substrate scope of mono-substituted diphenyl acetylenesa
To our disappointment, alkylarylalkynes such as but-1-
ynylbenzene (1t) gave only 16% of the oxidized product (2t) and
56% of benzoic acid (2t‘) upon 2 h short time photoirradiation. We
observe that the benzoic acid formation is due to the over oxidation
of product (2t). Moreover, dialkylalkynes substrates such as oct-4-
yne (1u) and hex-1-ynylcyclohexane (1v) upon oxidation forms
various unidentified products due to over-oxidation of the primary
oxidised diketone products (2u and 2v). Control experiments
showed that over-oxidation occurs in the case of dialkylinternal
alkynes (see Scheme S10 in SI for details).
O
R'
10 mol% CuCl2
R
R'
ACN, O2,
3.3equiv. H2O
Visible light, rt
O
R
2
1
R, R' = H/ EWG/ EDG
O
O
O
O
2a, 85% (12h)
2b, 83% (12h)
OMe
Me
tBu
O
O
O
Next, we examined the substrate scope of unsymmetrical di-
substituted diaryl acetylenes with electron-donating and
withdrawing groups on two aromatic units (Table 3).
Me
O
O
O
2c, 83% (12h)
2d, 81% (12h)
O
2e, 86% (12h)
O
Table 3. Substrate scope of di-substituted diarylacetylenesa
OH
Cl
F
O
OMe
R'
O
O
O
O
R'
10 mol% CuCl2
2f, 87% (12h)
F
2g, 81% (14h)
2h,81% (12h)
ACN, O2,
3.3equiv. H2O
Visible light, rt
R
O
Br
R
O
O
1
2
O
R, R' = EWG/ EDG
F
I
O
O
OMe
OMe
tBu
CF3
O
O
O
O
2i, 79% (12h)
2j, 76% (12h)
O
2k, 68% (12h)
O
CF3
CN
O
O
O
O
tBu
tBu
nBu
2w, 86% (12h)
2x, 82% (12h)
2y, 71% (15h)
O
Cl
Cl
O
O
O
O
O
O
2l, 74% (12h)
2m, 68% (15h)
O
2n, 71% (15h)
O
O
O
S
O
MeO
O
2ab, 70% (15h)
O
NO2
2z, 75% (14h)
2aa, 78% (14h)
O
O
O
O
2o, 61% (16h)
2p, 69% (15h)
2q, 72% (12h)
Ph
O
O
O
Ph
O
1s
O
tBu
MeO
O
O
O
2ad, 77% (16h)
2ac, 64% (12h)
O
Ph
O
O
Ph
aIsolated yield after purification by column chromatography on SiO2.
2r', 10% (12h)
2r, 66% (12h)
O
2s, 52% (16h)
First, the unsymmetrical diarylacetylenes with two different
electron-donating groups on two respective aromatic units were
subjected to the current aerobic oxidation process and
furnishing the corresponding products (2w & 2x) in good yields
of 86% and 82%, respectively. Furthermore, the unsymmetrical
O
O
O
COOH
nBu
O
O
O
2t, 16%b (2h)
2t', 56%b (2h)
2u, 0%
2v, 0%
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
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COMMUNICATION
diarylacetylenes with different combinations of electron-
Journal Name
Moreover, this aerobic oxidation reaction was carried out at
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donating (-tBu, -OMe, -ethyl) and withdrawing groups (-CF3, -Cl, - a gram scale. The reaction of 1a (0.9DgO,I: 150.0.103m9m/Do0lG)Ci0n09t7h5eJ
COCH3) were well tolerated in this oxidation protocol. presence of CuCl2 and O2 (1 atm) under blue LEDs irradiation at
Gratifyingly, these substrates with different combinations of room temperature for 21 h produces 0.76 g of 2a (72% yield).
electron-donating and withdrawing groups formed the desired Also, we have evaluated the green chemistry metrics10c for the
products (2y-2ad) in moderate to good yields (64-78%). In case current aerobic oxidation reaction in a preparative scale (Table
of substrates with strong electron-withdrawing groups, trace 4). The current green process for the synthesis of benzil (2a) has
amount benzoic acid of respective aromatic units was observed. an E-factor of 7.07, 100% atom economy, 72 % atom efficiency,
This is because the C-C bond of diketones bearing electron- 100% carbon efficiency and 84.4% reaction mass efficiency. In
withdrawing groups is weak and is susceptible to cleavage. The
structures of products 2a and 2ad were confirmed by single-
crystal X-ray diffraction13.
Table 4. Evaluation of green chemistry metrics for synthesis of 2a
Molecular mass of desired product
Atom economy (%) =
x 100
x 100
(AE)
Molecular mass of all reactants
Mass of desired product
To demonstrate the applications of the oxidized product
benzil (2a), some important reactions were carried out and
presented in the Scheme 2. First, well-known benzilic acid
rearrangement14a was demonstrated in which benzil (2a) in the
presence of strong base rearranged to form benzilic acid (3) in
89% yield. The benzilic acid derivatives are important precursors
used in organic synthesis.14b,c The second reaction demonstrated
is a two steps synthesis of trifenagrel (4’) (79% total yield) which
is a potent platelet aggregation inhibitor (see experimental
details in S.I).14e,f The third reaction is the synthesis of 2,3-
diphenylquinoxaline via condensation of benzene-1,2-diamine
with benzil. This condensation reaction forms the product 2,3-
diphenylquinoxaline (5) in 96% yield, and the derivatives of 2,3-
diphenylquinoxalines are good antibacterial agents (especially
against Mycobacterium smegmatis)14d. In addition, we have also
demonstrated the synthesis of 2,4,5-triphenyloxazole (6)14g, 1,2-
diphenylethane-1,2-diol (7) and 2,2-dimethyl-4,5-diphenyl-2H-
imidazole (8)14h (see experimental details in S.I). These
compounds and its derivatives are highly important in chemical
and pharmaceutical industries14. The structures of products 4, 5
and 6 were confirmed by single-crystal X-ray diffraction13.
Reaction mass efficiency (%) =
Mass of all reactants
(RME)
Reactant
1,2-diphenylethyne
0.9g
5.0 mmol FW 178.23
19.65 g
(25mL)
----
12.72 g
(16.2mL)
----
----
----
----
----
----
Solvent
ACN
----
Auxiliary
Recycled
Solvent
ACN
Product
Benzil
0.76g 3.6 mmol FW 210.22
Product yield = 72%
0.9g + 19.65g - 0.76g - 12.72g
E-factor
= 7.07 Kg waste/ 1 Kg product
=
0.86g
210
210
= 100%
x 100
=
Atom economy
=
Atom efficiency
72% x 100% /100 = 72%
14
=
Carbon efficiency
x 100
= 100%
14
0.76g
0.9g
=
Reaction mass efficiency
x 100
= 84.4%
Table 5. EcoScale15 calculation for the synthesis of 2a
EcoScale = 100 - Sum of individual penalties
Score on EcoScale: >75, Excellent; >50, Acceptable; <50, Inadequate
OH
A) Calculation of penalty points:
Parameters
Penalty points
14
OH
7
1. Yield
(100-%yield)/2 = (100-72)/2 = 14
88%
2. Price of reaction components
(To obtain 10 mmol of end product)
a. Diphenylacetylene = 2.48g = $8.4
Acetone,
NH4OAc,
N
SnCl2.2H2O,
NaBH4,
MeOH,
0o to rt
N
N
NH4OAc,
EtOH, reflux,
4h
AcOH,
reflux
b. CuCl2
c. ACN
= 0.18g = $0.2
= 40mL = $1.1
8
O
6
78%
Total price (USD) = $9.7
Thus, inexpensive (<$10)
73%
NH2
0
HO COOH
O
3. Safety
N
N
1.KOH, EtOH, reflux
2. HCl, H2O workup
NH2
ACN Solvent
EtOH, 60oC, 5h
O
Toxic (T)
5
5
2a
3
5
96%
Highly flammable (F)
4. Technical Setup
89%
NH4OH, Glycine,
EtOH, 80oC, 3h
N
Inconventional activation technique
(Photochemical activation)
2
1
OH
H
N
Br
N
O
5. Temperature and time
Room temperature and <24h
H
N
N
K2CO3,
MeOH, 60oC
N
6. Workup and purification
4
4'
93%
Removal of solvent with bp <150oC
Classical Chromatography
0
85%
Trifenagrel
10
Total Penalty Points
37
Scheme 2. Some important further reactions of benzil (2a).
4 | J. Name., 2012, 00, 1-3
B) EcoScale calculation:
EcoScale = 100- 37 = 63 (an acceptable synthesis)
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dark condition). In the next step, the π-alkyne coordinated
View Article Online
DOI: 10.1039/D0GC00975J
copper(II) peroxo complex C can undergo intramolecular radical
the green metrics evaluation, we have also included the amount
of recycled acetonitrile.
cyclization with the CC triple bond to furnish five-membered Cu(III)
complex D. Reductive elimination of Cu(III) complex D concurrently
regenerates the copper(I) species and 3,4-diphenyl-1,2-dioxete
intermediate E 10c,h,19. Further, cleavage of the O-O bond of the
intermediate E leads to formation of the desired product (2a). We
hypothesized that the presence of water might be able to
accelerate the cleavage of the O-O bond in the intermediate E, and
therefore promotes the product yield slightly from 76 to 85 %. The
proposed mechanism is supported by the experimental results
given in Tables 2 & 3, the UV-visible absorption spectra (see Fig. 1),
EPR measurements, and our previous work of mechanistic
studies.10c,h
The E-factor for the current oxidation reaction is ~2.3 times
better than a reported photochemical reaction for the formation
of -diketones12b. Next, we have also calculated the EcoScale15
value for the reaction based on six parameters (yield, price of
the reaction components, safety, technical setup,
temperature/time and workup and purification) (Table 5). The
EcoScale value for the current reaction is 63, which indicates
that the current method is an acceptable green synthesis
protocol from the safety, economic, and ecological features
point of view. In addition, the current photochemical oxidation
process does not produce any by-products; also, the reaction does
not require harsh reaction conditions, organic bases, and an
expensive metal catalyst. Furthermore, the current reaction
requires only simple reaction setup, a room temperature reaction,
inexpensive CuCl2, and molecular oxygen. Therefore, all these
specifications make this process eco-friendly and an excellent
green process.
Scheme 3. Proposed mechanism for the visible light-mediated
Cu(II)-superoxo catalysed oxidation of stable diarylacetylenes.
h

LMCT
*
CuCl2
(Cl2
)
+
CuCl
Cl
CuCl2
1a
O2
CuII
CuII
A
*
Ph
Ph
CuCl
O O
O O
CuII
0.4
C
O
B
CuCl in ACN before irr.
2
O
(
abs : 430-510 nm)

CuCl + 1a in ACN before irr.
2
blue-LEDs
0.3
0.2
0.1
0.0
CuCl in ACN before irr.
CuCl + 1a in ACN before irr.
O
CuCl + O in ACN 20 min irr.
reductive
Ph
CuIII
Ph
2
Ph
Ph
Ph
elimination
Ph
CuCl + O in ACN 40 min irr.
2
2
O
O
O O
E
O
CuI
2a (benzil)
D

= 486 (430-510 nm)
max
Conclusions
We have developed a quintessential method for the synthesis of
-diketones from stable diarylalkynes. This is the first report of
visible-light-induced copper-superoxo catalysed oxidation of
inactive diarylacetylenes to form -diketones by molecular oxygen
at room temperature. The oxidation method includes the use of
simple inexpensive Cu(II)Cl2 as a catalyst, O2 as oxidant and
tolerates a wide range of electron-donating and withdrawing
substrates (28 examples). We also demonstrated a few further
application reactions of benzil for the synthesis of benzillic acid, 2,3-
400
450
500
550
Wavelength (nm)
Figure 1. UV-visible absorption spectra of CuCl2 and CuCl in CH3CN.
Based on the experimental studies (see SI for details), UV-visible
spectra, and our previous works10c, h, a possible reaction mechanism
for the current process is proposed in Scheme 3. Upon
photoirradiation (blue LEDs, λmax = 460 nm) photoexcited CuCl2
undergoes an intramolecular LMCT (Ligand-Metal Charge Transfer)
process to generate CuCl16. Then, CuCl could readily react with
molecular oxygen to form copper(II) superoxo complex A (see
Figure 1 and Scheme 3)10c,h,17. EPR measurements show signals
corresponding to DMPO-OO(CuII) (see details in SI), indicating the
formation of superoxide free radical in the reaction solution. As
evidenced by UV-visible absorption spectra that the complex A has
an absorption band located in-between 430-510 nm (see Figure 1,
UV spectra). Photoexcitation of copper(II)-superoxo complex A
generates excited-state complex B and then readily interacts
(coordinated) with diarylacetylenes to form a complex C18. Indeed,
the photoexcited copper(II)-superoxo complex B could have strong
propensity to induce/oxidize the stable diarylacetylenes rather than
under thermal condition (i.e., relatively unattainable at the thermal
diphenylquinoxaline,
a trifenagrel drug (a potent platelet
aggregation inhibitor) and various other pharmaceutically active
compounds. The internal alkynes substrates can be readily
prepared by photoinduced Sonogashira coupling reaction. The
green metrics and EcoScale evaluation of the current process
indicate that this oxidation reaction is simple, green and highly
effective.
Acknowledgements
We are grateful to the Ministry of Science and Technology,
Taiwan for financial support. We also thank Dr. Hsin-Ru Wu of
the Instrumentation Center of National Tsing Hua University for
HRMS measurements.
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Green Chemistry
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Journal Name
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Graphical Abstract
Visible Light-induced Aerobic Oxidation of Diarylalkynes to -Diketones Catalyzed
by Copper-superoxo at Room Temperature
Vaibhav Pramod Charpe, Arunachalam Sagadevan, and Kuo Chu Hwang*
Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan.
E-mail: kchwang@mx.nthu.edu.tw; Fax: (+886) 35711082.
We demonstrate an environmentally benign and economically feasible method for oxidation of stable
diarylalkynes to diketones at room temperature using inexpensive copper(II) chloride salt, molecular oxygen
under low energy visible light irradiation.
O2
O
R
CuCl2
(1 atm)
blue LEDs, R.T.
O
R
R= EDG/ EWG
upto 85% (28 examples)
1. O2 as oxidant as well as reagent
2. Mild reaction conditions (Green process)
3. H2O accelerates the formation of product
4. Easily scale up to a gram scale
5. Low E-factor and high reaction mass efficiency (RME)
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