Porphyrin-Catalyzed Photochemical C–H Arylation of Heteroarenes

Article abstract of DOI:10.1002/ejoc.201601518

Organic dyes are a promising class of photoredox catalysts and offer a meaningful alternative to broadly applied Ru and Ir complexes. We found that porphyrins with tuned physicochemical properties, by tailoring various substituents at the periphery of the

Full text of DOI:10.1002/ejoc.201601518

A Journal of
Accepted Article
Title: Porphyrin-catalyzed photochemical C-H arylation of heteroarenes
Authors: Dorota Gryko, Katarzyna Rybicka-Jasińska, and Burkhard
König König
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European Journal of Organic Chemistry
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COMMUNICATION
Porphyrin-catalyzed photochemical C-H arylation of heteroarenes
[a]
[b]
[a]
Katarzyna Rybicka-Jasińska, Burkhard König, and Dorota Gryko*
In memory of professor Teodor Silviu Balaban
Abstract: Organic dyes are a promising class of photoredox
catalysts and offer a meaningful alternative to broadly applied Ru-
and Ir-complexes. We have found that porphyrins with tuned
physicochemical properties, via tailoring various substituents at the
periphery of the macrocycle, are effective in catalyzing light-induced
direct arylation of heteroarenes and coumarins with diazonium salts.
Mechanistic studies confirmed that the reaction operates by an
oxidative quenching pathway of the porphyrin.
photocatalyst. This example represents a reductive quenching
pathway of porphyrins.
We wondered, whether free-base porphyrins are also able to
promote
a direct arylation of heteroarenes by C-H bond
activation via an oxidative quenching? Under light irradiation this
reaction is effectively promoted by a ruthenium complex and
8
eosin Y. On the other hand, Kanai and co-workers found that
porphyrins catalyze C(3)-H arylation of coumarins with aryl
9
diazonium salts. Intriguingly, the reaction was not affected by
the presence or absence of light. However, only very electron
rich porphyrins, namely tetra(4-diethylaminophenyl)porphyrin,
catalyzed the reaction and less electron–rich tetra(4-
methoxyphenyl)- or tetraphenylporphyrins were not effective. It
was proposed that the porphyrin reduces the aryl diazonium
tetrafluoroborate affording an aryl radical and nitrogen.
Introduction
Photoredox catalysis is strongly associated with the use of Ru-
and Ir-complexes. Surprisingly, organic dyes, though interesting,
have attracted much less attention. The list of compounds used
1
2
as metal-free photocatalysts collected by Romero and Nicewicz
comprise of only 33 compounds. But the structural diversity of
The thermodynamic driving force of a redox process is
determined by the difference in redox potentials of the half
reactions. As aryl diazonium salts’ reduction potentials vary
3
organic chromophores, and their different redox and
photochemical properties, may provide access to new and more
efficient photocatalysts. To this end porphyrinoids, represented
in nature by chlorophyll - the most efficient photocatalyst, offer
unique opportunities. Due to stability issues, it is rarely applied
as a catalyst in synthetic organic chemistry. However, fully
aromatic porphyrins with well-established photophysical
properties have already been used to harvest light energy for
around 0.0-0.2 V vs. SCE, weak reductants should promote this
8c,10
reaction.
Under light irradiation porphyrin reducing properties
are altered, and based on the Eox even tetraphenylporphyrin
should facilitate the formation of the phenyl radical (Table 1,
entry 1). Herein, we report that porphyrins in the excited state
can indeed act as a reductant.
4
artificial photosynthesis, phototherapy, imaging etc. Moreover,
their metal complexes proved efficient in catalyzing various
reactions, for example: C-H hydroxylation, cyclopropanation,
Results and Discussion
alkylation, amination, epoxidation, olefination, oxidative Mannich
In the initial experiment, furan (1) was reacted with diazonium
5
reaction and oxidative amine coupling.
However, in
2
salt 2 in the presence of H TPP (4) under light irradiation
photochemistry they are mainly associated with the generation
(
Scheme 1).
6
of singlet oxygen or other oxygen reactive species. Only
recently, we have reported their use as photoredox catalysts in a
7
C-C bond forming reaction. Light induced -alkylation of
aldehydes with diazo reagents in the presence of morpholine
afforded the desired products in satisfactory yield. Mechanistic
studies revealed that once in the excited state, a porphyrin
oxidizes an enamine to the cation radical that subsequently
reacts with a carbene generated via a photo synthetic pathway.
The resulting intermediate is reduced by back electron transfer
from the porphyrin’s anion radical thus regenerating the
Scheme 1. Model reaction of furan with diazonium salts.
After 3 h the reaction furnished the desired product 3 in 80%
yield (Table 1, entry 1). Background reactions clearly showed
that both the porphyrin and light are required for effective
production of arylated furan 3 (entries 2-4). In the absence of
porphyrin, but under light irradiation product 3 formed in only 8%
yield; this could be attributed to the direct, light-triggered
heterolysis of starting material 2 followed by the reaction with
furan (1) (entry 3). Surprisingly, tetra(4-diethylaminophenyl)-
porphyrin (5), though a better electron donor, was less effective
than porphyrin 4 (compare entries 1 and 6).
[
[
a]
b]
K. Rybicka-Jasińska and D. Gryko
Institute of Organic Chemistry Polish Academy of Sciences
Kasprzaka 44/52, 01-224 Warsaw, Poland
E-mail: dorota.gryko@icho.edu.pl
B. König
Department of Chemistry and Pharmacy
University of Regensburg
Universitätsstr. 31, 93053 Regensburg, Germany
Supporting information for this article is given via a link at the end of
the document.
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European Journal of Organic Chemistry
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COMMUNICATION
Substituents, present at the periphery of the macrocycle, have a
determinant role on redox properties of porphyrins. Accordingly, With the best photoredox catalyst selected, we optimized the
properties of a catalyst for reactions involving PET processes.
1
1
various porphyrins were tested as catalysts in the model
reaction (Chart 1, Table 2).
reaction conditions with respect to solvent and catalyst loading.
Various solvents, suitable for dissolving porphyrins, were
studied: DMSO, DMF, DCM, and MeOH (see SI). DMSO
assured product formation with the highest yield.
[
a]
Table 1. Control experiments.
[
b]
Entry
Porphyrin
Light
Time
Yield of 3 (%)
(h)
[a]
Table 2. Screening of photoredox catalysts.
1
2
3
4
5
6
H
2
TPP (4)
yes
no
3
80
5
No
16
3
•+
*
Entry
Porphyrin
E
ox*[Por /Por ]
mV)
k
1 -1
q
Yield
-
(
(M s )
of 3
No
yes
yes
no
8
[b]
(%)
No
16
16
3
23
6
10
1
2
3
4
5
H
2
TPP (4)
-0.91(S)
0.42(T)
1.5x10
80
12a
-
H
2
TPP (4)
9
[c]
H
2
T(4-OMeP)P (6)
-0.99(S)
12b
2.9x10
41
H
2
(4- Et
2
NP)P (5)
yes
23
-
0.54(T)
12c
[e]
H
2
T(4-CO
2
MeP)P (7)
-0.81(S)
0.31(T)
-
74
[
a] Reaction conditions: diazonium salt (2, 0.25 mmol), furan (1, 2.5
mmol, 10 equiv.), DMSO (2 mL), porphyrin (1 mol%), blue LED (455
nm). [b] Yield determined by GC.
-
9
H
2 5
T(F P)P (8)
-1.04(S)
0.78(T)
7.2x10
86
[d]
12d
-
(81)
[
e]
[d]
H
2
OEtP (9)
-1.52(S)
1.15(T)
-
72
12e
-
[
a] Reaction conditions: diazonium salt (2, 0.25 mmol), furan (1, 10
equiv.), DMSO (2 mL), porphyrin (1 mol%), blue LED (455 nm), 3 h. [b]
Yield determined by GC. [c] Catalyst loading was lower due to solubility
issues. [d] Isolated yield. [e] k
q
not provided due to solubility issues,
2,45
1,95
1,45
0,95
y = 158,31x + 0,9602
R² = 0,9875
y = 67,235x + 0,9658
R² = 0,9769
y = 30,668x + 0,9934
Figure 1. Porphyrins tested as photoredox catalysts.
R² = 0,9955
0
0,002
0,004
Porphyrin 8
0,006
Porphyrin 6
0,008
0,01
[
c]
Porphyrin 4
Substituents, present at the periphery of the macrocycle, have a
1
1
determinant role on redox properties of porphyrins. Accordingly,
various porphyrins were tested as catalysts in the model
reaction (Chart 1, Table 2). Interestingly, the best result, was
obtained from electron-poor tetra(pentafluorophenyl)porphyrin
Figure 2. Stern-Volmer experiments for diazonium salt 2 and porphyrins 4, 8,
and 6.
(
8) (entry 4). Stern-Volmer quenching experiments showed that
diazonium salt 2 quenches the luminescence of all porphyrins
tested, though with different quenching rates (Figure 2). The
highest quenching rate was observed for H TPP (4) that gave
2
slightly lower yield than the best catalyst 8. Notwithstanding, its
oxidation potential in the excited states is 0.13 V higher than the
potential of porphyrin 8 (compare entry 1 and 4). On the other
hand porphyrin 9 with the lowest oxidation potential gave the
product in 72% (entry 5). Plots of yields vs both quenching rates
8
6
4
0
0
0
Porphyrin (8)
Porphyrin (4)
Porphyrin (6)
20
0
2
4
6
8
10
12
14
-1
16
-
1
9
kq [M s *10 ]
Figure 3. The correlation between kq and yield for porphyrins 4, 6, and 8.
q
(k ) and oxidation potentials in the exited state (Eox*) clearly
shows that for the arylation of heteroarenes with diazonium salts
there is an optimal quenching rate and catalyst redox properties
in the excited state (Figure 3 and 4). This highlights the
importance of fine tuning of both electro- and photochemical
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European Journal of Organic Chemistry
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COMMUNICATION
8
8
7
7
6
8
3
8
3
8
If so, the porphyrin in its excited state reduces the diazonium
salt while forming a cation radical. Indeed, the Stern-Volmer
experiment confirmed that diazonium salt 2 quenches the
luminescence of the porphyrin contrary to furan (1) (Figure 1).
We were also able to trap radical A as adduct with TEMPO and
detect it by ESI MS (See SI). In the next step, radical B is
oxidized to intermediate C that after proton elimination furnishes
arylated product 3. For this step two pathways were proposed:
oxidation by a porphyrin cation radical or by another molecule of
the starting material 2 in a radical chain reaction. In our case,
oxidation by the porphyrin cation radical predominates as the
reaction quantum yield was calculated to be  = 1.4 ± 0.8 (for
details see SI). This is in contrast to the eosin Y-catalyzed
reaction (4.7 ± 0.6).
Porphyrin (8)
Porphyrin (4)
Porphyrin (7)
Porphyrin (9)
-1,5 -1,7
-
0,7
-0,9
-1,1
E [mV]
-1,3
Figure 4. The correlation between Eox*(S) and yield for porphyrins 4, 7, 8, 9.
Gratifyingly, the best catalyst loading was as low as 1 mol%
Table 3, entry 2). Furthermore, we have also examined the
amount of furan (1) used. As the concentration was diminished
the yield gradually decreased with a 5-fold excess giving a
satisfactory yield (Table 3, entries 2, 5-7).
(
[
a]
Table 3. Optimization of the catalyst loading and furan equiv.
Finally, the optimized conditions [diazonium salt (2, 0.25
mmol), furan (1, 10 equiv.), DMSO (2 mL), porphyrin 8 (1 mol%),
blue LED (455 nm), 3 h,] were used exploring the scope and
limitations of the reaction (Scheme 3). In general, the reaction
gave moderate to good yields in arylation of furan (1) with
diazonium salts with different functional groups being well
[
b]
Entry
Catalyst loading
Furan (1) (equiv.)
Yield of 3 (%)
(
mol%)
1.5
1.0
0.8
0.1
1
1
2
3
4
5
6
7
10
10
10
10
15
5
78
86
71
42
71
76
2
tolerated (-Br, - Cl, - NO , -OMe). Notwithstanding, electron-
donor substituted diazonium salts were found to be less efficient
for arylation of furan (10) than electron-acceptor substituted
ones.
1
[
c]
1
2.5
41
[
a] Reaction conditions: diazonium salt (2, 0.25 mmol), furan (1, 10 equiv.),
DMSO (2 mL), porphyrin (1 mol%), blue LED (455 nm), 3 h. [b] Yield
determined by GC. [c] Isolated yield.
The mechanism of the photocatalytic, direct C-H arylation of
heteroarenes with aryl diazonium salts catalyzed by eosin Y has
8
b
been proposed by König and co-workers and studied in detail
8
c
by Wangelin and Majek. The crucial step involves generation
of an aryl radical via SET from the excited state eosin Y to the
aryl diazonium salt and its subsequent addition to a heteroarene
furnishing an aryl radical intermediate. We reasoned that in our
case a similar mechanism should operate (Scheme 2).
Scheme 3. Arylation of heteroarenes with diazonium salts.
Porphyrin-catalyzed photochemical arylation was also
effective for other compounds such as thiophene (10) and
coumarin (25) (Scheme 2 and 3), but arylation of pyrrole
derivatives (11) and (12) proved to be difficult under porphyrin
catalysis. Supposably, porphyrin 8 reacts in the exited state
faster with pyrrole or indole derivatives than with the diazonium
Scheme 2. Plausible mechanism for photochemical arylation of heteroarenes
with diazonium salts in the presence of porphyrin (ineffective chain
propagation steps omitted for clarity).
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European Journal of Organic Chemistry
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COMMUNICATION
salt 2 thus precluding the formation of the phenyl radical. Indeed, importance of the proper tuning of the photocatalyst redox
Stern-Volmer experiments showed that both N-methylpyrrole
11) and N-methylindole (12) effectively quenched the
luminescence of the porphyrin contrary to furan and thiophene,
likely via a reductive quenching (Figure 4).
behavior and photophysical properties for an efficient
photocatalytic reaction. The porphyrins’ electro- and
photochemical properties can be easily changed by the proper
substituent selection at the periphery of the macrocycle. Hence,
this class of compounds represents a unique case as their
photocatalytic properties can be adjusted to the reaction’s need.
(
Acknowledgements
Financial support of the National Science Centre (grant
PRELUDIUM) and the Deutsche Forschungsgemeinschaft (GRK
1626) is acknowledged. KRJ thanks the Deutsche Akademische
Austauschdienst (iPUR program) for a short term fellowship.
Scheme 4. Arylation of coumarins with diazonium salts.
Keywords: photocatalysis • porphyrins • C-H arylation • aryl
diazonium salts • heteroarenes
y = 12,766x + 0,9786
1,9
1,7
1,5
1,3
1,1
0,9
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1
y = 5,4426x + 0,9791
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R² = 0,9872
y = 0,5418x + 1,0002
y = 0,2896x + 0,9995 y = 0,0795x + 0,9999
R² = 0,9872
R² = 0,9982
R² = 0,9912
[
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0,1
0,15
0,2
0,25
0,3
furan
[
M]
[
[
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thiophene
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1
Figure 5. Stern-Volmer experiments for different heteroarenes and porphyrin 8.
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The obtained yields are in inverse proportion to the arene
quenching rates. Hence, the prerequisite for an effective
reaction is the lack of a reaction between an arene and a
porphyrin in the excited state. To confirm our hypothesis, we
performed the reaction of diazonium salt 2 with electron-poor N-
Boc-pyrrole (13) for which the calculated quenching rate was
similar to that of thiophene (10). Indeed, in this case the reaction
afforded arylated product (24) in 29% yield.
[
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Summing up, we have shown that porphyrins are suitable
photoredox catalysts for the direct C-H arylation of heteroarenes.
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photoinduced electron transfer from a porphyrin in its exited
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3
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European Journal of Organic Chemistry
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COMMUNICATION
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Entry for the Table of Contents (Please choose one layout)
Layout 2:
COMMUNICATION
Photocatalysis*
Katarzyna Rybicka-Jasińska, Burkhard
König and Dorota Gryko*
Page No. – Page No.
Porphyrin-catalyzed photochemical
C-H arylation of heteroarenes
Porphyrins are suitable photoredox catalysts for direct C-H arylation of
heteroarenes with aryl diazonium salts. The reaction involves PET from a porphyrin
in its exited state to a diazonium salt.
*one or two words that highlight the emphasis of the paper or the field of the study
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