Copper(II) thioxanthone carboxylate as a photoswitchable photocatalyst for photoinduced click chemistry

Article abstract of DOI:10.1016/j.tetlet.2015.09.155

A new efficient copper photocatalyst to photochemically induce the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction without the need for additional ligands is reported. The thioxanthone carboxylate moiety was combined with copper(II) ions b

Full text of DOI:10.1016/j.tetlet.2015.09.155

Accepted Manuscript
Copper(II) thioxanthone carboxylate as a photoswitchable photocatalyst for
photoinduced click chemistry
Sajjad Dadashi-Silab, Yusuf Yagci
PII:
S0040-4039(15)30196-9
DOI:
http://dx.doi.org/10.1016/j.tetlet.2015.09.155
TETL 46827
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
2 March 2015
2 September 2015
30 September 2015
Please cite this article as: Dadashi-Silab, S., Yagci, Y., Copper(II) thioxanthone carboxylate as a photoswitchable
photocatalyst for photoinduced click chemistry, Tetrahedron Letters (2015), doi: http://dx.doi.org/10.1016/j.tetlet.
2
015.09.155
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

1
Tetrahedron Letters
Copper(II) thioxanthone carboxylate as a photoswitchable photocatalyst for
photoinduced click chemistry
a
a,b
Sajjad Dadashi-Silab and Yusuf Yagci 
a
Department of Chemistry, Istanbul Technical University, Maslak 34469, Istanbul, Turkey
b
Center of Excellence for Advanced Materials Research (CEAMR) and Department of Chemistry, Faculty of Science King Abdulaziz University, Jeddah, 21589,
Saudi Arabia
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A new efficient copper photocatalyst to photochemically induce the copper(I)-catalyzed azide-
alkyne cycloaddition (CuAAC) reaction without the need for additional ligands is reported. The
thioxanthone carboxylate moiety was combined with copper(II) ions by a simple ion exchange
reaction to form a copper(II) thioxanthone carboxylate photocatalyst. In the catalytic process,
intramolecular photoinduced electron transfer was stimulated to reduce copper(II) ions giving
rise to a copper(I) species capable of catalyzing the CuAAC reaction. Temporal control over the
click reaction was demonstrated by intermittent light on/off experiments.
Available online
Keywords:
Copper(II)
2
009 Elsevier Ltd. All rights reserved.
Thioxanthone carboxylate
Photoinduced Click Chemistry
Cycloaddition
—
——

Corresponding author. Tel.: +90-212-285-3241; fax: +90-212-285-6386; e-mail: yusuf@itu.edu.tr

2
Tetrahedron
Light is an ubiquitous and abundant supply of energy and
Independently, Bowman and Vincent have contributed to the
field, reporting elegant, novel photoinitiator-based copper
catalytic systems involving the combination of a photoinitiator
can be used in photochemical processes as a traceless and
environmentally benign driving force for chemical reactions, for
which they are perceived as a “green” class of reactions
compared to thermally driven systems. In order for reactions to
be photochemically initiated, appropriate light sensitive species
II
with Cu ions to form a one-component photocatalyst. Such a
combination eliminates the problems associated with the poor
solubility of either Cu or the photoinitiator in different reaction
1,2
II
(
i.e. photocatalysts or photosensitizers) are required so that the
media with the aim of enhancing the efficiency of the
photocatalytic process. Bowman and co-workers reported that
photogenerated radicals derived from an acylphosphine oxide
energy of light can be easily converted into its chemical form.
Most research has focused on mechanistically understanding
photochemical processes and developing novel photocatalysts
with the aim of extending the scope of well-established light-
induced processes to new areas of chemistry, as well as reducing
the energy requirements for the initiation of the processes by
II
photoinitiator coordinated with Cu ions as the counteranion part
II 25
efficiently reduced Cu . Acylphosphine oxide photoinitiators
are cleavage type photoinitiators (Type I) and form two radicals
from bond dissociation by absorbing light. This system requires
the presence of an amine ligand which solubilizes the
photocatalyst. In an alternative to Type I photoinitiation, Vincent
and co-workers took advantage of a hydrogen abstraction-type,
3
using visible light photocatalysis. Conventional photochemical
reactions are mostly efficient in the UV region, requiring high-
energy input; thus novel photoinitiating systems active in the
visible range are of great importance.
26,27
benzophenone-based initiator.
They proposed an initiation
mechanism based on the formation of free radicals as a result of
hydrogen abstraction of the triplet state benzophenone moieties
from the amine ligand.
Light has recently begun to find its place in one of the most
powerful tools of modern synthetic chemistry, that is, the so-
called “click chemistry.” Copper(I)-catalyzed azide-alkyne
4
cycloaddition (CuAAC) being a premier example of click
reactions was discovered in 2001 by Sharpless and co-workers
Inspired by these works, herein, we report a photoswitchable
copper(II) thioxanthone carboxylate catalyst for the
photoinitiation of CuAAC. Sodium thioxanthone carboxylate
5,6
and has since been the central topic of a wide range of research in
7
+
–
the fields of organic chemistry, materials science and
(Na TX-CH
carboxylic acid (TX-CH
sodium hydroxide following a previously reported procedure.
Addition of copper(II) trifluoromethanesulfonate (Cu(OTf) ) to
the solution gave copper(II) thioxanthone carboxylate (Cu(TX)
2
COO ) was formed by treatment of thioxanthone
8,9
10
11
polymers, drug discovery and bioconjugation. The concept
of the photoinduced CuAAC relies on photochemical formation
of the active form of the copper catalyst, by
2
COOH) with an aqueous solution of
28
2
2
)
II
photoreduction of air-stable copper(II) (Cu ) species to active
which precipitated as a solid green while the NaOTf by-product
remained in the aqueous media (Scheme 1).
I
4
copper(I) (Cu ) by various photochemical processes. Protocols
II
for CuAAC reactions based on the reduction of Cu have been
reported which include the use of reducing agents or
electrochemical methods.
6
12,13
II
Copper complexes in combination with amine ligands (Cu /L)
have been proven to undergo a ligand-to-metal-charge-transferI
process under UV light illumination and are reduced to Cu
14
species. With this in mind, our group reported the first example
of the photoinduced CuAAC without the use of a conventional
I
photoinitiator, in which the required Cu catalyst for CuAAC was
15
formed in situ under UV light irradiation. In contrast, most
work on the photoinduced CuAAC has involved the indirect
II
reduction of Cu , using photoinitiators or photosensitizers to
II
promote the reduction of the Cu species. For instance,
photogenerated free radicals stemming from various
photoinitiators or photoinduced electron transfer reactions have
Scheme 1. Synthesis of copper(II) thioxanthone carboxylate
photocatalyst.
II
been reported as efficient protocols to reduce Cu , giving rise to
16-21
successful CuAAC transformations.
The use of
photoinitiators or photosensitizers brings the advantage of
extending the spectral sensitivity to higher wavelengths in
accordance with the optical behavior of the initiator, thus giving
reactions which proceed with low energetic requirements and
mild conditions. Photoinduced CuAAC also offers the
opportunity of providing spatiotemporal control over the reaction
which is rarely the case with its thermal counterparts. In this
regard, Bowman and co-workers reported the spatial control of
CuAAC in patterning hydrogels using a radical photoinitiator
Thioxanthone (TX) and its derivatives are well-known Type II
photoinitiators, extensively utilized in photopolymerization
29-32
systems,
which generate initiating free radicals or cationic
species by either hydrogen abstraction or photoinduced electron
transfer in conjunction with suitable co-initiators. TX based
photoinitiating systems are efficient photoinitiators with
absorption characteristics in the near UV and visible range which
compare favorably with benzophenones.
2
2
Remarkably, owing to the TX carboxylate moiety, the
resulting Cu(TX) photocatalyst was soluble in organic solvents
2
such as dimethylformamide (DMF), 1,4-dioxane, and dimethyl
sulfoxide; although other solvents such as acetonitrile or
2
methanol failed to dissolve it. The resulting Cu(TX) exhibited a
system.
Recently, we explored the potential of semiconducting
materials as heterogeneous photocatalysts in photoinduced
CuAAC reactions upon visible light irradiation. Mesoporous
2
3
24
graphitic carbon nitride or zinc oxide nanoparticles were able
strong absorption band in the near UV and visible range, with a
maxima at 385 nm, as well as a peak above 550 nm
II
to release electron-hole charge carriers by which Cu was
II
reduced to successfully catalyze the cycloaddition reaction.
corresponding to the Cu ions (Figure S1). Therefore, we first
attempted to evaluate the optical behavior of the Cu(TX)
2

3
2
photocatalyst under light. Irradiation of a solution of Cu(TX) in
DMF using a 23W household lamp, resulted in rapid
II
disappearance of the characteristic peak for Cu ions in the range
of 550-1000 nm within 20 min, indicating the successful
II
reduction of Cu . This was accompanied by a new peak arising
0
around 575 nm which could be attributed to the formation of Cu
27
nanoparticles (Figure 1-a, and Figure S2). Visually, the initial
green solution containing Cu(TX) species turned brown upon
irradiation due to the reduction of Cu ions, and then turned back
to bright green upon exposure to air, signifying a reversible
photoredox process (Figure 1-b).
2
II
Figure 2. Kinetics of the photoinduced CuAAC using Cu(TX)
2
: a)
model reaction with benzyl azide and phenylacetylene utilizing
Cu(TX) catalyst and irradiation by a 23W household lamp, b) real-
Figure 1. Photoreduction of Cu(TX)
spectra of a degassed solution of Cu(TX)
using a household lamp ([Cu(TX) ] = 1.66 × 10 M); b) visual
observation of a solution of Cu(TX)
further to Cu under irradiation as its color turned from green to
brown and then back to bright green by exposure to air.
2
: a) changes in the UV-vis
2
2
in DMF upon irradiation
time conversion as measured by FTIR spectroscopy through
-3
-1
2
integration of the azide peak around 2100 cm . c) Evidence of
I
2
and its reduction to Cu and
temporal control of the photoinduced CuAAC with the Cu(TX)
2
0
photocatalyst by alternating light “On/Off” experiments.
As previously stated, such photomediated processes bear the
advantage of providing temporal and spatial control over the
process. To prove this, we subjected the model click reaction to
alternating light and dark experiments. Keeping a degassed
solution of the model reaction in the dark, resulted in no
conversion; however shining a light from a household lamp
initiated the reaction and gave approximately 40% conversion
within 20 min. Removing the light source and bubbling air into
the system immediately stopped the reaction and again no
significant change in conversion was observed after 20 min in the
dark. Interestingly, degassing the solution and exposing to light
reinitiated the process with the reaction proceeding to completion
after another 20 min of irradiation. These results clearly
confirmed successful temporal control of the reaction by
With regard to the reduction mechanism, since no amines
were utilized as a ligand and other hydrogen donor compounds
were not present in the system, the possibility of quenching the
triplet state of TX by hydrogen abstraction could be discarded.
The photoinduced electron transfer reaction between the
II
photoexcited TX and Cu ions can be assumed as a conceivable
mechanism for the reduction process. Ligand-to-metal-charge-
II
transfer in Cu /L complexes has already been shown to be
II
responsible for reduction of the Cu in the presence of amine
14
ligands. In this case, a similar phenomenon of intramolecular
photoinduced electron transfer takes place between the TX
II
II
moiety and Cu resulting in the reduction of Cu species.
Although at present, the fate of the TX carboxylate moieties after
intramolecular electron transfer is not clear; future studies will
focus on the evaluation of the mechanistic details of the
photocatalytic process.
Cu(TX)
2
.
The click reaction was also attempted in the presence of amine
hydrogen donor compounds. N,N,N′,N′′,N′′-
Pentamethyldiethylenetriamine (PMDETA) and triethylamine
TEA) were chosen with the latter being known as an efficient
hydrogen donor and the former, being a commonly used ligand
for copper complexes (Table 1). Using Cu(TX) without any
additional compound, the reaction between benzyl azide and
phenylacetylene was complete after 40 min, whereas by addition
of an equimolar amount of PMDETA the reaction rate increased
twofold (Table 1, Runs 1 and 2). This rate enhancement could be
After confirming the occurrence of the photoredox process,
we applied TX(Cu) to the photochemically catalyzed CuAAC
2
(
reaction using benzyl azide and phenylacetylene as click
components in DMF. Experimentally, the degassed solution was
irradiated with a 23W household lamp without the use of an
additional ligand (Figure 2-a). The reaction was monitored by
real-time FTIR spectroscopy and a rapid reduction in the
2
-1
intensity of the azide peak at around 2100 cm was observed.
1
The reaction was complete within 40 min (Figure 2-b). The H
2
attributed to the fact that the solubility of Cu(TX) was further
NMR spectrum of the resulting compound confirmed the
successful reaction (Figure S3).
II
improved by the coordination of Cu ions with PMDETA, as
well as the probability of quenching the triplet state of TX by
PMDETA and subsequent formation of radicals capable of
It should be noted that during the CuAAC catalytic process,
II
II
0
reducing Cu . A significant rate enhancement was also observed
over-reduction of Cu ions leading to the formation of Cu
I
in the case of TEA reaching completion within 12 min (Table 1,
nanoparticles is highly unlikely as the Cu species thus formed
are rapidly trapped by the alkyne group functionality.
II
Run 3). Since TEA is not believed to coordinate with Cu , its
influence could be exclusively ascribed to the formation of free
radicals upon hydrogen abstraction leading to fast reduction of
II
Cu .

4
Tetrahedron
In order to develop a better picture of this new photocatalyst
with conventional copper systems, we used copper(II) chloride
CuCl ) in conjunction with TX-CH COOH. Irradiation of a
solution of benzyl azide and phenylacetylene in DMF containing
CuCl without any ligand resulted in no conversion after 180 min
Table 1, Run 4). However, addition of PMDETA to the system,
which enabled dissolution of CuCl , initiated the click reaction,
which proceeded to completion in 150 min (Table 1, Run 5 and
Figure S4). When TEA was used with CuCl in the absence of
4. Tasdelen, M. A.; Yagci, Y. Angew. Chem. Int. Ed. 2013, 52,
5930.
5
6
7
.
.
.
Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem. Int.
Ed. 2001, 40, 2004.
Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K.
B. Angew. Chem. Int. Ed. 2002, 41, 2596.
(
2
2
2
(
Moses, J. E.; Moorhouse, A. D. Chem. Soc. Rev. 2007, 36,
2
1249.
8
9
.
.
Lutz, J.-F. Angew. Chem. Int. Ed. 2007, 46, 1018.
Xi, W. X.; Scott, T. F.; Kloxin, C. J.; Bowman, C. N. Adv.
Funct. Mater. 2014, 24, 2572.
2
PMDETA, after 180 min the reaction reached only 54%
conversion (Table 1, Run 6).
1
0. Kolb, H. C.; Sharpless, K. B. Drug Discovery Today 2003, 8,
128.
11. Lutz, J.-F.; Borner, H. G. Prog. Polym. Sci. 2008, 33, 1.
1
Table 1. Effect of ligand and hydrogen-donor co-compounds
on the photocatalytic activity of Cu(TX)
a
2
12. Devaraj, N. K.; Dinolfo, P. H.; Chidsey, C. E. D.; Collman, J.
Co-compound
P. J. Am. Chem. Soc. 2006, 128, 1794.
Time Conv.
min) (%)
Run
Copper(II)
b
TX-
13. Hong, V.; Udit, A. K.; Evans, R. A.; Finn, M. G.
(
Amine
CH
2
COOH
ChemBioChem 2008, 9, 1481.
1
4. Hayase, K.; Zepp, R. G. Environ. Sci. Technol. 1991, 25,
273.
15. Tasdelen, M. A.; Yagci, Y. Tetrahedron Lett. 2010, 51, 6945.
1
2
3
4
5
Cu(TX)
Cu(TX)
Cu(TX)
2
2
2
–
–
40
100
100
100
<5
1
PMDETA
TEA
–
20
1
1
6. Ritter, S. C.; Koenig, B. Chem. Commun. 2006, 45, 4694.
7. Tasdelen, M. A.; Yilmaz, G.; Iskin, B.; Yagci, Y.
Macromolecules 2012, 45, 56.
–
12
CuCl
CuCl
CuCl
2
2
2
–
+
180
150
180
PMDETA
TEA
+
100
54
18. Alzahrani, A. A.; Erbse, A. H.; Bowman, C. N. Polym. Chem.
2014, 5, 1874.
6
+
19. Yilmaz, G.; Iskin, B.; Yagci, Y. Macromol. Chem. Phys.
a
Experimental conditions: benzyl azide (1 mmol),
2014, 215, 662.
phenylacetylene (1 mmol), Cu(TX)
2
(0.05 mmol), and DMF (4 mL).
20. Doran, S.; Murtezi, E.; Barlas, F. B.; Timur, S.; Yagci, Y.
Macromolecules 2014, 47, 3608.
b
Conversions determined by FTIR spectroscopy
2
2
1. Yagci, Y.; Tasdelen, M. A.; Jockusch, S. Polymer 2014, 55,
468.
3
In light of these results, it was reasonable to conclude that the
intramolecular photoinduced electron transfer of the triplet state
TX and Cu to form Cu was the dominant mechanism which
exhibited high efficiency when combined with Cu ions as the
counteranion. This was supported by the fact that no reaction
took place with CuCl and TX-CH COOH alone in the absence
2 2
of PMDETA. In the presence of either PMDETA or TEA,
prolonged irradiation times were needed to initiate the process,
which was accomplished by the reduction of Cu using
photogenerated free radicals through hydrogen abstraction
processes.
2. Adzima, B. J.; Tao, Y. H.; Kloxin, C. J.; DeForest, C. A.;
II
I
Anseth, K. S.; Bowman, C. N. Nat. Chem. 2011, 3, 256.
23. Dadashi-Silab, S.; Kiskan, B.; Antonietti, M.; Yagci, Y. RSC
Adv. 2014, 4, 52170.
4. Yetiskin, O.; Dadashi-Silab, S.; Khan, S. B.; Asiri, A. M.;
Yagci, Y. Asian J. Org. Chem. 2015, 4, 442.
5. Gong, T.; Adzima, B. J.; Bowman, C. N. Chem. Commun.
II
2
2
2
2013, 49, 7950.
II
6. Harmand, L.; Cadet, S.; Kauffmann, B.; Scarpantonio, L.;
Batat, P.; Jonusauskas, G.; McClenaghan, N. D.;
Lastecoueres, D.; Vincent, J.-M. Angew. Chem. Int. Ed. 2012,
5
1, 7137.
In conclusion, we have demonstrated a new photocatalyst
based on the combination of a TX carboxylate moiety with Cu
2
2
7. Harmand, L.; Lambert, R.; Scarpantonio, L.; McClenaghan,
II
N. D.; Lastecoueres, D.; Vincent, J.-M. Chem. Eur. J. 2013,
ions to photochemically initiate the CuAAC click reaction. The
process was realized in a ligand-free mode by the photogenerated
intramolecular electron transfer reaction between the triplet state
1
9, 16231.
8. Yilmaz, G.; Acik, G.; Yagci, Y. Macromolecules 2012, 45,
219.
2
II
I
TX and Cu leading to the in situ formation of Cu species. The
system offered temporal control over the click reaction as
evidenced by alternating light and dark experiments, and the
system may be adapted to light induced controlled/living radical
29. Balta, D. K.; Arsu, N.; Yagci, Y.; Jockusch, S.; Turro, N. J.
Macromolecules 2007, 40, 4138.
30. Yilmaz, G.; Aydogan, B.; Temel, G.; Arsu, N.; Moszner, N.;
Yagci, Y. Macromolecules 2010, 43, 4520.
3
3-35
polymerization processes,
specifically to Atom Transfer
31. Yagci, Y.; Jockusch, S.; Turro, N. J. Macromolecules 2010,
I
4
3, 6245.
2. Dadashi-Silab, S.; Aydogan, C.; Yagci, Y. Polym. Chem.
015, 10.1039/C5PY01004G.
Radical Polymerization where initiating species and catalyst Cu
ions can be generated simultaneously. Further studies along these
lines are now in progress.
3
3
3
3
2
3. Tasdelen, M. A.; Uygun, M.; Yagci, Y. Macromol. Rapid
Commun. 2011, 32, 58.
4. Ciftci, M.; Tasdelen, M. A.; Yagci, Y. Polym. Chem. 2014, 5,
Acknowledgments
600.
The authors acknowledge financial support from Istanbul
Technical University Research Fund.
5. Dadashi-Silab, S.; Tasdelen, M. A.; Yagci, Y. J. Polym. Sci.,
Part A: Polym. Chem. 2014, 52, 2878.
References and notes
Supplementary Material
1
2
.
.
Albini, A.; Fagnoni, M. Green Chem. 2004, 6, 1.
Protti, S.; Fagnoni, M. Photochem. Photobiol. Sci. 2009, 8,
Details of experimental procedures and additional UV-vis and
1499.
1
H NMR spectra are provided in the Supporting Information.
3
.
Yoon, T. P.; Ischay, M. A.; Du, J. Nat. Chem. 2010, 2, 527.

5

6
Tetrahedron
Graphical Abstract
Copper(II) thioxanthone carboxylate as a
photoswitchable photocatalyst for
photoinduced click chemistry
Leave this area blank for abstract info.
Sajjad Dadashi-Silab and Yusuf Yagci