Heteroleptic copper(I) complexes as energy transfer photocatalysts for the intermolecular [2 + 2] photodimerization of chalcones, cinnamates and cinnamamides

Article abstract of DOI:10.1016/j.tetlet.2021.153091

The [2 + 2] photodimerization of chalcones, cinnamates and cinnamamides can be effectively catalyzed by heteroleptic copper(I) complexes. The reactions were carried out under mild reaction conditions and the products were obtained in 20–72% yield under visible light irradiation. The copper-based photocatalyst comprised of the rigid phenanthroline ligand with substituents at the 2,9-positions and the 4,7-positions showed high activity in the photodimerization via an energy transfer pathway.

Full text of DOI:10.1016/j.tetlet.2021.153091

Tetrahedron Letters 72 (2021) 153091
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Heteroleptic copper(I) complexes as energy transfer photocatalysts for
the intermolecular [2 + 2] photodimerization of chalcones, cinnamates
and cinnamamides
Qing-An Wu a, Chen-Chao Ren a, Feng Chen a, Tian-Qi Wang a, Yu Zhang a, Xue-Fen Liu b, Jian-Bin Chen c,
Shu-Ping Luo a,
⇑
a State Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, Zhejiang University of Technology, Chaowang Road 18, Hangzhou 310014, China
b Qianjiang College, Hangzhou Normal University, Hangzhou 310006, China
c Shandong Provincial Key Laboratory of Molecular Engineering, School of Chemistry and Chemical Engineering, Qilu University of Technology (Shandong Academy of Sciences),
Jinan 250353, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 18 January 2021
Revised 1 April 2021
Accepted 13 April 2021
Available online 16 April 2021
The [2 + 2] photodimerization of chalcones, cinnamates and cinnamamides can be effectively catalyzed
by heteroleptic copper(I) complexes. The reactions were carried out under mild reaction conditions
and the products were obtained in 20–72% yield under visible light irradiation. The copper-based photo-
catalyst comprised of the rigid phenanthroline ligand with substituents at the 2,9-positions and the 4,7-
positions showed high activity in the photodimerization via an energy transfer pathway.
Ó 2021 Elsevier Ltd. All rights reserved.
Keywords:
Copper-based photocatalysts
Visible light irradiation
Energy transfer
Introduction
fluorescence (TADF) properties. However, the applications of cop-
per-based photocatalysts mainly focus on single electron transfer
Visible-light-driven photocatalytic reactions have emerged over
the past decades as powerful tools in organic synthesis [1]. The
cyclobutane motif plays an important role in natural products
and bioactive compounds [2]. Intermolecular [2 + 2] photocycliza-
tion has become an important and commonly used method to
obtain cyclobutane-containing structures [3]. Generally, the
[2 + 2] cycloaddition of olefins requires UV irradiation [4] or visible
light irradiation in the presence of iridium [5] or ruthenium [6]
complexes with high quantum yields, good stability, and long flu-
orescence lifetimes. However, the use of high-energy ultraviolet
light can result in side-reactions and the rarity and toxicity of irid-
ium and ruthenium complexes limit their applications in produc-
tion. Therefore, the use of inexpensive, readily available
photocatalysts to replace noble-metal photocatalysts is an area of
considerable interest.
(SET) type photoreactions, and there are few reports on energy
transfer photocatalytic reactions [9]. Recently, Wu and co-workers
[10] and Reiser and co-workers [11] independently described the
use of noble-metal Ir photocatalysts to obtain a range of chalcone
and cinnamate dimers. Beeler and co-workers [12] reported the
application of flow chemistry using thiourea derived catalysts to
obtain cinnamate dimers under UV irradiation. Su and co-workers
[13] described the self-photodimerization of chalcone and cinna-
mate using a cage-shaped ruthenium photocatalyst, which mainly
resulted in the product of syn-HH products. Moreover, our group
[14] has found that donor–acceptor fluorophores are valuable
energy transfer catalysts, which can replace noble-metal photocat-
alysts for the photodimerization of chalcone-based substrates.
Therefore, we hoped to explore whether copper-based photocata-
lysts could also be used in photodimerization reactions.
Various noble-metal-free, copper-based photocatalysts have
been developed in the past decades [7]. Heteroleptic copper com-
plexes show excellent performance in photo-redox reactions and
water splitting [8], due to their novel thermally activated delayed
Results and discussion
A series of copper-based photocatalysts (Table 1) were synthe-
sized and their photophysical and electronic chemical properties
were determined (Figs. S1-S2, S5-S6, Table S6). The copper-based
⇑
Corresponding author.
E-mail address: luoshuping@zjut.edu.cn (S.-P. Luo).
https://doi.org/10.1016/j.tetlet.2021.153091
0040-4039/Ó 2021 Elsevier Ltd. All rights reserved.

Qing-An Wu, Chen-Chao Ren, F. Chen et al.
Tetrahedron Letters 72 (2021) 153091
Table 1
Table 2
Screening of copper-based photocatalysts.a
Optimization of the reaction conditions.a.
Entry
Photocatalyst
Solvent
Wavelength
Yieldb 2a (%)
1
2
PC1
PC1
PC1
PC1
PC1
PC1
PC1
PC1
PC1
EtOAc
CH3OH
DMC
Acetone
Toluene
CH3CN
CH2Cl2
1,4-dioxane
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
425 nm LED
425 nm LED
425 nm LED
425 nm LED
425 nm LED
425 nm LED
425 nm LED
425 nm LED
365 nm LED
375 nm LED
395 nm LED
450 nm LED
425 nm LED
425 nm LED
425 nm LED
425 nm LED
68
54
55
49
46
15
33
60
8
11
56
20
12
60
20
60
3c
4
5
6
7
8
9
10
11
12
13d
14e
15f
16g
PC1
PC1
PC1
PC1 (0.5%)
PC1 (5%)
/
EtOAc
EtOAc
EtOAc
PC1
a
Reagents and conditions: chalcone 1a (0.5 mmol), PC1 (1 mol%), solvent (5 mL),
hv, argon atmosphere, room temperature, RT, 24 h.
b
Determined by HPLC using diethyl phthalate as the internal standard.
c
DMC (dimethyl carbonate)
d
e
f
g
PC1 (0.5 mol%). PC1 (5 mol%). Without PC1 (1 mol%). Nitrogen atmosphere
was obtained in 68% yield (Table 1, entry 1), which demonstrated
the feasibility of PC1 as a photocatalyst. When the irradiation time
was extended to 36 h, the photodimerization yield did not increase
significantly (Table 1, entry 1). The screening of other copper-based
photocatalysts showed that PC5 gave the best yield for the pho-
todimerization of chalcone 1a (Table 1, entries 1–8).
Analysis of the structure–activity relationship of the copper-
based photocatalysts provided the following observations. When
the 4,7-positions are substituted with phenyl groups, the excited
photocatalyst is easily quenched by environmental factors. There-
fore, the PC2 catalyzed photodimerization yield is low (Table 1,
entry 2). If the copper-based photocatalyst contains a flexible P
ligand (DPEphos) instead of the rigid P ligand (xanthogen), the
nonradiative quenching of the excited state photocatalyst will
increase and the lifetime will be shortened [8a]. The excited state
of PC3 with a flexible phosphine ligand is easily quenched, which
leads to a low photodimerization yield (Table 1, entry 3). The
a
Reagents and conditions: chalcone 1a (0.5 mmol), photocatalyst (1 mol%), EtOAc
(5 mL), 20 W 425 nm LED (light intensity 127.8 mW/cm2), argon atmosphere, room
temperature, RT, 24 h.
2,9-positioned isopropyl group has a greater fluorescence
quenching slope than PC1 (Figs. S7-S8), indicating that PC5
transfers energy to the chalcone faster than PC1. The
photodimerization yield catalyzed by PC5 is therefore the highest
(Table 1, entry 5). The 2,9-positioned methyl group of
phenanthroline not only prevent the excited state of the
photocatalyst from being quenched, but also help maintain the
tetrahedral configuration of copper, thereby slowing nonradiative
decay [8a]. Therefore, the dimerization yield is low with PC8
(Table 1, entry 8). According to Wu and co-workers [10], the triplet
excited state potential of chalcone is 2.13 eV. The excited state
potential of the homogeneous copper-based photocatalyst PC7
(E0,0 = 2.05 eV) is lower than the substrate potential. Therefore,
PC7 absorbs most of the irradiated energy. The irradiated energy
cannot be transferred to the substrate, which makes the pho-
todimerization poor (Table 1, entry 7).
b
Determined by HPLC using diethyl phthalate as the internal standard.
Irradiation for 36 h.
c
d
E0,0=*E1/2 ox- E1/2 red- =E1/2ox -*E1/2
(E0,0 is roughly estimated by simple UV/Vis
red
and emission spectra, and are not accurate values.)
photocatalysts have similar spectral curves to iridium and ruthe-
nium photocatalysts.
To test the feasibility of copper-based photocatalysts in olefin
photodimerization, we initially investigated the [2 + 2] pho-
todimerization of chalcone 1a with various heteroleptic copper(I)
complexes (Table 1, entries 1–8). A solution of degassed ethyl acet-
ate (EtOAc) containing 0.1 M of chalcone and 1 mol% of PC1 was
irradiated with a 20 W LED (k = 425 nm) at room temperature.
After 24 h irradiation, the anti-HH photodimerization product 2a
2

Qing-An Wu, Chen-Chao Ren, F. Chen et al.
Tetrahedron Letters 72 (2021) 153091
Scheme 2. Scope of the dimerization with various cinnamates and cinnamamides. a
Reagents and conditions: cinnamates (0.5 mmol), PC1 (1 mol%), EtOAc (5 mL),
425 nm LED (light intensity 127.8 mW/cm2), argon atmosphere, room temperature,
RT, 24 h. b Reagents and conditions: cinnamamide (0.5 mmol), PC1 (1 mol%), EtOAc
(5 mL), 425 nm LED (light intensity 127.8 mW/cm2), argon atmosphere, room
temperature, RT, 36 h. d.r. (major/minor) determined by 1H NMR analysis of the
unpurified reaction mixture.
(Scheme 1, 2b-f). When the aryl substituent was an electron-with-
drawing group, the expected products were obtained in 30–59%
yield (Scheme 1, 2g-k, 2m, 2o-p). Additionally, the thiophene sub-
stituted benzene ring was a poor substrate, affording the corre-
sponding product in only 25% yield (Scheme 1, 2q).
In order to further expand the applications of the copper-based
photocatalyst, we shifted our attention to cinnamates and cinna-
mamides (Scheme 2). Cinnamic acid derivatives also dimerized
with high diastereoselectivity. Cinnamamides had lower reactivity,
and the photodimerization products were obtained in 20–35%
yield when the irradiation was extended to 36 h (Scheme 2, 2r-
s). Cinnamates showed similar reactivity to chalcones, and the
photodimerization products were obtained in 40–60% yield
(Scheme 2, 2u-x).
Scheme 1. Scope of the dimerization with various substituted chalcone derivatives.
a
Reagents and conditions: chalcone derivatives (0.5 mmol), PC1 (1 mol%), EtOAc
(5 mL), 425 nm LED (light intensity 127.8 mW/cm2), argon atmosphere, room
temperature, RT, 24 h. d.r. (major/minor) determined by 1H NMR analysis of the
unpurified reaction mixture.
Considering the ease of preparation and price of the photocata-
lysts, PC1 was used instead of PC5 to further optimize the reaction
conditions. The results of the solvent screening showed that EtOAc
gave the best yield (Table 2, entries 1–8). A survey of LED sources
with different wavelengths illustrated that 425 nm was the best
choice, which afforded 2a in 68% yield (Table 2, entry 1, entries
9–12). Although the absorption of the copper-based photocatalyst
at 395 nm is stronger than that at 425 nm, the yield was lower
(Table 2, entries 1 and 11). This may be due to increased side reac-
tions because of its high energy irradiation. Finally, we screened
the amount of the photocatalyst. Lowering the amount of PC1 or
increasing the amount of PC1 resulted in lower yields (Table 2,
entry 1, entries 13–14).
With the optimized conditions in hand, we then investigated
the scope of chalcone derivatives substituted with different func-
tional groups. Both electron-withdrawing and electron-donating
group substituted chalcones gave the desired photodimerization
products (Scheme 1). Electron-donating group substituted chal-
cones showed better reactivity. For example, methyl- and meth-
oxy-substituted photodimerization products were obtained in
69–70% yield (Scheme 1, 2b, 2f). Steric effects have a greater influ-
ence on the yield. The order of reactivity was ortho < meta < para,
and the expected products were obtained in 20–70% yield
Scheme 3. Mechanistic insights. Reagents and conditions: chalcone 1a (0.5 mmol),
PC1(1 mol%), EtOAc (5 mL), 425 nm LED (light intensity 127.8 mW/cm2), argon
atmosphere, room temperature, RT, 24 h. Determined by HPLC using diethyl
phthalate as the internal standard. Without PC1. With Et3N (1 mmol). With
TEMPO (1 mmol).
a
b
c
3

Qing-An Wu, Chen-Chao Ren, F. Chen et al.
Tetrahedron Letters 72 (2021) 153091
Declaration of Competing Interest
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
Acknowledgments
We greatly appreciate financial support from the National Nat-
ural Science Foundation of China (No. 21376222), the Natural
Science Foundation of Zhejiang Province (No. LY18B060011) and
the Youth Innovative Talents Recruitment and Cultivation Program
of Shandong Higher Education.
Appendix A. Supplementary data
Fig. 1. Plausible reaction mechanism.
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tetlet.2021.153091.
Next, we used chalcone 1a as a model substrate for control
experiments. The photodimerization product 2a was obtained in
only 20% yield without the copper-based photocatalyst under
20 W LED (k = 425 nm) irradiation (Scheme 3a). This was presum-
ably due to chalcone being directly excited at 425 nm to participate
in the photodimerization (Fig. S3). When Et3N was added to the
system, the yield dropped sharply, which illustrated that electron
transfer had a negative effect on the reaction (Scheme 3b). Upon
analysis of the electron paramagnetic resonance (EPR) spectrum,
we found that the copper-based photocatalyst promotes the pho-
todimerization of chalcone through an energy transfer pathway
rather than an electron transfer pathway (Fig. S9). The addition
of the free radical scavenger TEMPO significantly reduced the yield
(Scheme 3c). The above experiments indicated that the pho-
todimerization of chalcone forms a double radical intermediate
through energy transfer.
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