Chemical photocatalysis with 1-(N, N-dimethylamino)pyrene

Article abstract of DOI:10.1055/s-0032-1317532

1-(N,N-Dimethylamino)pyrene was applied as chemical photocatalyst for two different organic reactions: Both the photocatalytically driven nucleophilic addition of methanol to 1,1-diphenylethylene and the photocatalytic deprotection of N-phenylsulfonylindole gave the corresponding products in good yields and in a highly sustainable way after short irradiation with high-power LED. This concept can potentially be transferred to other photochemical reactions. Copyright

Full text of DOI:10.1055/s-0032-1317532

LETTER
▌2803
lCetther emical Photocatalysis with 1-(N,N-Dimethylamino)pyrene
Chemical Photocatalysis with 1-(N,N-Dimethylamino)pyrene
Alexander Penner, Effi Bätzner, Hans-Achim Wagenknecht*
Karlsruhe Institute of Technology, Institute for Organic Chemistry, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
Fax +49(721)60844825; E-mail: wagenknecht@kit.edu
Received: 02.08.2012; Accepted after revision: 10.10.2012
MeOH
photocatalyst
Abstract: 1-(N,N-Dimethylamino)pyrene was applied as chemical
photocatalyst for two different organic reactions: Both the photocat-
alytically driven nucleophilic addition of methanol to 1,1-diphenyl-
MeO
hν
ethylene and the photocatalytic deprotection of N-phenylsulfonylindole
gave the corresponding products in good yields and in a highly sus-
tainable way after short irradiation with high-power LED. This con-
cept can potentially be transferred to other photochemical reactions.
MeCN
1
2
Scheme 1 Photocatalytic nucleophilic addition to 1 as test reaction
Key words: pyrene, chromophore, electron transfer, alkene, indole
First, we tested common aromatic chromophores as po-
tential photocatalysts based on naphthalene (as previously
published),12 and additionally anthracene and pyrene de-
rivatives (Table 1). For this screening, irradiation was per-
formed by a conventional 200 W Hg(Xe) lamp (ozone-
free) without monochromator. This, in the photochemical
sense rather unselective irradiation was to cover the broad
Chemical photocatalysis in the organic-chemical context
can be applied in such a way that a redox active chromo-
phore, upon irradiation with light, induces an electron
transfer to the substrate.1–7 This photophysical process
(charge separation) is coupled to a subsequent chemical
reaction. The absorbed light energy contributes to the
overall energy balance of the reaction and thereby increas-
es its sustainability. The photocatalysis should work in the
UV-A/Vis range in order to increase sustainability by ap-
plying high-power light-emitting diodes (LED) as a cheap
and reliable source for irradiation. This concept drives our
search for new photocatalytic methods which can be ac-
complished by rethinking photochemical reactions that
have been known for decades. Herein, we describe our ef-
forts to develop photocatalytic versions of two simple, but
synthetically important reactions. Both reactions have in
common that a photoinduced electron-transfer step is the
initial photochemical step.
Table 1 Chromophore Screening for the Nucleophilic Addition to 1
Yielding 2a
Entry
Photocatalyst
Yield (%)b
1
2
naphthalene
0
3
1-methylnaphthalene
3
1-methoxynaphthalene
1,4-dimethoxynaphthalene
2,6-dimethoxynaphthalene
2-(methylthio)naphthalene
1-(N,N-dimethylamino)naphthalene
1,5-di(N,N-dimethylamino)naphthalene
anthracene
12
56
37
49
17
63
2
4
5
6
Photochemical addition of amines to styrenes and stil-
benes were first reported by Cookson8 and Kawanishi.9
Lewis and co-workers elucidated exciplex states as key
intermediates for this kind of reactions.10 On the other
hand, photohydration of aromatic alkenes requires the di-
rect excitation of the alkene component by energy-rich
UV light.11 The first attempt to perform this type of reac-
tion by photosensitization was published by Arnold and
Maroulis.12 They applied naphthalene derivatives to
achieve the nucleophilic addition of methanol to alkenes.
However, this process is still not compatible with irradia-
tion by LED. Hence, we wanted to develop a new photo-
catalytic version of this reaction and used 1,1-
diphenylethylene (1) as test substrate to avoid a prochiral
center (Scheme 1).
7
8
9
10
11
12
14
15
16c
17c
9-methylanthracene
3
9,10-dimethylanthracene
9,10-dimethoxyanthracene
pyrene
9
24
4
1-(N,N-dimethylamino)pyrene
1-(N,N-dimethylamino)pyrene
1-(N,N-dimethylamino)pyrened
29
33
75
a Reaction conditions: 1 (2 mM), photocatalyst (2 mM), in MeCN–
MeOH (7:3; 4 mL), argon atmosphere, 15 h, r.t., 200 W Hg(Xe) arc
lamp, cut-off filter λ < 305 nm, reactants identified by GC–MS, quan-
tified by GC-FID.
SYNLETT 2012, 23, 2803–2807
Advanced online publication: 31.10.2012
DOI: 10.1055/s-0032-1317532; Art ID: ST-2012-B0654-L
© Georg Thieme Verlag Stuttgart · New York
b Averaged yield from at least two independent reactions.
c With LED illuminator λ = 365 nm.
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
d With 5% (v/v) Et3N.

2804
A. Penner et al.
LETTER
excitation range of all applied chromophores by one lamp,
and makes sense in the context of preparative organic
photocatalysis to compare yields under comparable reac-
tion conditions. The starting material 1 absorbs light in the
range below 300 nm; hence it was important to equip the
lamp with a 305 nm cut-off filter. The samples had to be
degassed very carefully in order to avoid the formation of
benzophenone as an undesired side product. The screen-
ing reactions were performed in an acetonitrile–methanol
mixture (7:3), stopped after 15 hours irradiation time, and
analyzed by GC–MS.
It is clear that the yields reflect the different extinction co-
efficients of the different chromophores above 305 nm to
a certain extent. Nevertheless, from these results it be-
came obvious that electron-donating groups are crucial
for successful photocatalysis. This indicates an electron-
transfer mechanism which will be further discussed be-
low. In fact, the best yields of 1,1-diphenyl-1-methoxy-
ethane (2) were obtained with those photocatalysts that
carry two methylated hydroxyl or amino groups (Table 1,
entries 4, 5, 8, 12, and 15). Among the most promising
photocatalysts in the test reactions, 1-(N,N-dimethylami-
no)pyrene (D) has the highest exctinction in the range
around 350–370 nm. High-power LED are available for
distinct excitation at these wavelengths. Beside this, D
represents also a powerful reductant with a reduction po-
tential of –2.16 V.13 Together with the reduction potential
of –2.08 V (vs. NHE)14 for 1, the Rehm–Weller equation
gives a small ΔG of approximately 100 meV for the initial
electron-transfer step. Hence, we further investigated this
photocatalytic reaction using a special illuminator that
contains 250 mW (optical output) high-power LED for ir-
radiation at 365 nm, a Peltier temperature control element
and a stirrer. Using this apparatus, the reaction in entry 15
(Table 1) could now reach completion in three hours. The
yield, however, was not significantly increased (Table 1,
entry 16). An important observation in the latter reaction
was found in the GC–MS analysis: The photocatalyst D
degrades during the photochemical reaction and thereby
limits the photocatalytic conversion from 1 into 2. Assum-
ing an electron transfer from D to the substrate 1 as the ini-
tial step for the photocatalysis it was reasonable to add
Et3N to get better recovery of the oxidized radical cation
of D (D+·) to ground state D. In fact, in the presence of 5%
(v/v) Et3N product 2 could be obtained in 75% yield. In
order to get more insight into the kinetic behavior of this
reaction, aliquots were taken every ten minutes during ir-
radiation and were analyzed by GC–FID. The data plot
(Figure 1, top) showed clear conversion from 1 into 2
which is finished after ca. three hours.
Figure 1 Top: Time-dependent analysis of the photocatalytic conver-
sion of 1 into 2 in the presence of 1.0 (straight line) and 0.1 equiv D
(dashed line); 1 (2 mM), in MeCN–MeOH (7:3, 4 mL), 5% (v/v)
Et3N, r.t., LED illuminator λ = 365 nm. Bottom: Yields obtained with
stoichiometric and substochiometric amounts of D; 1 (2 mM), in
MeCN–MeOH (7:3, 4 mL), 5% (v/v) Et3N, 3 h, 25 °C, LED illumina-
tor λ = 365 nm.
true chemical photocatalysis. After three hours irradiation
the yields decreased from 71% (with 1 equiv D) down to
45% of product 2 in the presence of 0.1 equivalent D. The
detailed kinetic analysis (Figure 1, top, dashed lines) re-
vealed that the latter reaction just needs more time (ca. 6
h) to reach completion with only slightly diminished yield
(65% vs. 71%). The control experiment without any pho-
tocatalyst D showed no conversion at all. It is important to
point out additionally that all reactions with the LED illu-
minator did not require degassing of the reaction samples.
Arnold and Maroulis proposed an electron-transfer mech-
anism for the nucleophilic addition. In fact, a Stern–Vol-
mer plot indicates fluorescence quenching of D in the
presence of 1 (data not shown). Hence, we assume a sim-
ilar electron-transfer mechanism for the conversion of 1
into 2 that is photocatalyzed by D in the absence of Et3N.
Based on the observed degradation of D during this reac-
tion, the most critical step of this mechanistic cycle seems
to be the back electron transfer from the protonated (neu-
tral) diphenylethyl radical to the photocatalyst D. Obvi-
ously, Et3N represents the electron donor better than the
substrate radical, since degradation of D is significantly
reduced. Moreover, addition of Et3N increases the yield of
2 significantly. This implies the idea that Et3N closes the
cycle and gets regenerated by oxidation of the diphenyle-
thyl radical. Thereby an additional electron shuttle is pro-
vided by Et3N for the improved back electron transfer. On
the other hand, this makes the formation of side product 2
very plausible, since the diphenylethyl radical cannot only
Careful analysis of the GC–MS/GC–FID data revealed,
however, a second product 3 which is formed concomi-
tantly with the main product 2, but only in the presence of
Et3N. It was identified to be 1,1-diphenylethane (3).The
addition of Et3N as an additional electron shuttle in this
photocatalytic reaction offers the possibility to use D in
substoichiometric amounts. These reactions were tested
down to 0.1 equivalents D (Figure 1, bottom) to achieve
Synlett 2012, 23, 2803–2807
© Georg Thieme Verlag Stuttgart · New York

LETTER
Chemical Photocatalysis with 1-(N,N-Dimethylamino)pyrene
2805
be oxidized by the Et3N radical cation but also reduced by Et3N give rise to the amount of side product 3. This obser-
Et3N itself; subsequent protonation of the diphenylethyl vation supports additionally the proposed mechanism
radical anion gives the saturated product 3.
(Scheme 2).
It is remarkable that in the absence of MeOH as nucleo-
phile for the photoocatalytic addition, product 4 is ob-
tained in yields of 62–67% (Scheme 3) by addition of
Et3N. No product 3 is obtained in these reactions. Based
on the proposed role of Et3N as described above it seems
to be very plausible that electron transfer to the substrate
1 and generation of the photocatalyst D (from D+·) by ox-
idation of Et3N yields a radical ion pair, that (upon proton
transfer) recombines simply to product 4.
Ph
–
Ph
Ph
Ph
1
MeOH
– MeO–
Ph
+
*
D
D
D
Ph
Ph
Ph OMe
MeOH
– H+
+
hν
Ph
Ph
Et2N
2
photocatalyst
hν
Ph
Ph OMe
+
MeOH
– H+
+
MeCN
Et3N
D
D
Et3N
Et3N
4
Ph
Ph
1
Ph
2
+
–
Ph
Ph
Ph
MeOH
Ph
Ph
Ph
Ph
–
+
Et3N
Et2N
+
+
– MeO–
Ph
Ph
+
3
Et3N
Et3N
Scheme 3 Top: Photocatalytic addition of Et3N to 1 in the absence
of MeOH; 1 (2 mM), D (2 mM), in MeCN (4 mL), 5% (v/v) Et3N, 3
h, 25 °C, LED illuminator 265 nm. Bottom: Proposed mechanism for
this reaction.
Scheme 2 Proposed mechanism for the photocatalytic nucleophilic
addition of MeOH to 1 in the absence of Et3N (top) and in the pres-
ence of Et3N (bottom)
To support the proposed role of Et3N as an electron shuttle
we performed additional photocatalytic experiments with
different amounts of Et3N (0–180 equiv) and three hours
irradiation time by LED (Figure 2). At low Et3N concen-
trations the photocatalyst D gets degraded, as already
mentioned above. Thus, product 2 is formed only in lower
yield (ca. 30%). Additionally, benzophenone is formed as
a significant and undesired side product. On the other
hand, 180 equivalents Et3N are enough to keep the photo-
catalyst D active until complete conversion of 1 takes
place. If the photocatalytic experiment with 40 equiva-
lents Et3N is compared to the reaction with 180 equiva-
lents it becomes obvious that higher concentrations of
The substrate scope of this photocatalytic addition was
elucidated with several α-phenylstyrenes and styrenes
(Table 2). It became obvious that electron-withdrawing
groups are required for this reaction (Table 2, entries 1–4
and 7); methoxy-substituted α-phenylstyrene (Table 2, en-
try 5) and unsubstituted styrene (Table 2, entry 6) showed
no significant amounts of products. This result is due to
the small driving force for the initial photoinduced elec-
tron-transfer step as already discussed above in the case of
1.
In a last set of experiments we wanted to extend the scope
of this photocatalytic concept and method to a completely
different reaction that is initiated by an photoinduced elec-
tron transfer which is the deprotection of sulfonylated in-
doles. The phenylsulfonyl protecting group is used very
often for amines, especially aromatic amines, such as in-
dole.15 The disadvantage of this group, however, is its
high stability which requires harsh basic or acidic condi-
tions to remove it.16,17 This limits the synthetic usefulness
of this kind of protecting group. Photodesulfonylation of
sulfonamides18 and amines19 was achieved by direct exci-
tation of the substrate. Excitation of indoles at 254 nm in-
duced an electron transfer to Et3N and gave deprotected
indoles in moderate yield and accompanied by a couple of
side products.20 We applied nearly the same reaction con-
ditions that were previously elucidated for the conversion
of 1 into 2 for the deprotection of N-phenylsulfonylindole
(5) to indole (6, Scheme 4).
In the absence of Et3N, degradation of the photocatalyst D
was so fast and efficient that no deprotection of 5 could be
achieved at all by excitation at 365 nm with LED (Table
Figure 2 Photocatalytic conversion of 1 into 2 with different amounts
of Et3N. Conditions: 1 (2 mM), D (2 mM), in MeCN–MeOH (7:3; 4
mL), 3 h, 25 °C, LED illuminator.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2012, 23, 2803–2807

2806
A. Penner et al.
LETTER
0.1 equivalents D gave only 30% yield (Table 3, entry 5),
but conversion was not complete in two hours, similar to
the corresponding photocatalytic nucleophilic addition
that was discussed above (Figure 1, bottom). These results
demonstrate that the photocatalytic reaction conditions
elucidated for the conversion of 1 into 2 can be transferred
to other photochemical problems, such as the deprotection
of 5 to 6.
Table 2 Photocatalytic Addition Reactions of α-Phenylstyrenes and
Styrenesa
D
hν
MeO
R2
R2
R2
5% Et3N
+
R1
MeCN–MeOH
(7:3)
R1
R1
Entry
R1
H
R2
Yield (%)
addition
Yield (%)
reduction
In order to test this methodology representatively in ‘real’
synthesis we used it for deprotection of N-sulfonylated in-
dole nucleoside 7 that was synthesized according to the
literature (Scheme 5).21 Without any workup after deprot-
ection of 7, the 5′-hydroxy group was protected with DMT
which is needed for later DNA building-block chemistry.
The reaction on a 100 mg scale (compound 7) yielded
49% of the desired indole nucleoside 8.
1
2
3
4
5
6
7
H
75b
68b
35b
34c
5d
23
31
65
2
CO2Me
CN
Ph
Ph
Ph
Ph
H
F
MeO
Ph
1
Ph
0e
0
O
S
O
H
N
CO2Me
H
58b
42
N
1. D, hν
MeCN, Et3N
20 °C, 2 h
a Conditions: substrate (2 mM), MeCN–MeOH (7:3, 4 mL), 5 % (v/v)
Et3N, r.t., LED illuminator λ = 365 nm, reactants identified and quan-
DMT
O
HO
O
O
2. DMTCl, Et3N
pyridine
tified by GC–MS.
b Nearly complete conversion.
c Conversion 36%.
d Conversion 6%.
40 °C, 2 d
OH
OH
8
7
49%
e No conversion.
Scheme 5 Photocatalytic deprotection of N-sulfonylated indole nu-
cleoside 7
Ph
O
S
H
O
D
Our results show clearly that it is worth to revisit known
photochemical reactions and develop photocatalytic ver-
sions. Better yields were obtained for both types of photo-
catalytic processes that are presented herein. The
irradiation in the UV-A/Vis range increases the sustain-
ability significantly by applying energy-efficient high-
power LED as a cheap and reliable source for light. The
mild and nonacidic and nonbasic conditions make this
type of photocatalysis a promising alternative for organic
synthesis including protecting-group chemistry. This
principal concept and type of methodology will certainly
be applicable for other organic reactions in the future.
N
N
hν
MeCN
6
5
Scheme 4 Photocatalytic deprotection of N-sulfonylated indole 4
3, entry 1). The situation changed completely after addi-
tion of Et3N; good yield (77%, Table 3, entry 2) was ob-
tained for the deprotected indole 6 in the presence of an
equimolar amount of D (Table 3, entry 2). An even better
yield (87%, Table 3, entry 4) was achieved in the presence
of only 0.5 equivalents photocatalyst. The reaction with
Table 3 Photocatalytic Deprotection of 5 to 6a
Synthesis of 8
In a cuvette with a stir bar, 719 (100 mg, 268 µmol, 1 equiv) was dis-
solved in MeCN (1.20 mL) and Et3N (1.80 mL, 20.1 mmol, 75
equiv). D (65.7 mg, 268 µmol, 1 equiv) was added and the solution
was irradiated for 2 h (365 nm, 20 °C). The deprotection was ob-
served by TLC [CH2Cl2–MeOH (10:1), Rf = 0.35]. The solvents
were removed under vacuum. The crude product was dissolved in
anhydrous pyridine (1.5 mL). Et3N (40 µL, 536 µmol, 1 equiv) and
DMTCl (118 mg, 349 µmol, 1.3 equiv) were added, and the mixture
was stirred over night at 40 °C. The reaction was observed by TLC
[CH2Cl2–MeOH (25:1), Rf = 0.60]. Et3N (40 µL, 536 µmol, 1 equiv)
and DMTCl (118 mg, 349 µmol, 1.3 equiv) were added again, and
the mixture was stirred for another night at 40 °C. The solvents were
removed under vacuum. The remaining pyridine was lyophilized
out of benzene. The dried crude product was purified by column
chromatography [silica gel, CH2Cl2–acetone (25:1), 1% Et3N]
yielding a brown solid (49%). The spectroscopic data was in agree-
ment with the literature.19
Entry
D (mM)
Et3N (equiv)
Yield (%)b
1
2
3
4
5
2
–
0
77c
0
2
200
200
200
200
–
1
87c
30
0.5
a Conditions: 5 (2 mM), D, Et3N, in MeCN (1 mL), 2 h, 25 °C, 250
mW LEDs output at 365 nm, reactants identified by GC–MS, quanti-
fied by GC–FID.
b Averaged yield from at least two independent reactions.
c Conversion 100%.
Synlett 2012, 23, 2803–2807
© Georg Thieme Verlag Stuttgart · New York

LETTER
Chemical Photocatalysis with 1-(N,N-Dimethylamino)pyrene
2807
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Acknowledgment
Financial support by GRK 1626 (Chemical Photocatalysis) and KIT
is gratefully acknowledged.
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