UVA- and Visible-Light-Mediated Generation of Carbon Radicals from Organochlorides Using Nonmetal Photocatalyst

Article abstract of DOI:10.1021/acs.joc.8b01306

Carbon radicals are reactive species useful in various organic transformations. The C-X bond cleavage of organohalides by photoirradiation is a common method to generate carbon radicals in a controlled fashion. The use of organochloride substrates is still a formidable challenge due to the low reduction potential and the high dissociation energy of the C-Cl bond. In this report, we address these issues by using a nonmetal organic molecule with a relatively simple structure as a photocatalyst. In this catalyst (bis(dimethylamino)carbazole), the amino groups increase both the HOMO and LUMO energy levels, especially in the former. As a result, compared to the parent molecule, the new catalyst shows experimentally red-shifted absorption in the visible region and forms an excited state with better reducing capability. This photocatalyst was used in the reduction of unactivated aryl chlorides and alkyl chlorides in the presence of hydrogen atom donor at room temperature. The catalytic system can also be applied to the coupling of aryl chlorides with electron-rich arene and heteroarenes to affect the C-C bond-forming reactions. Our mechanistic study results support the assumption that carbon radicals are formed from the organochlorides via a single-electron-transfer step.

Full text of DOI:10.1021/acs.joc.8b01306

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Article
UVA- and visible light-mediated generation of carbon
radicals from organochlorides using non-metal photocatalyst
Ryosuke Matsubara, Tatsushi Yabuta, Ubaidah Md Idros, Masahiko
Hayashi, Fumitoshi Ema, Yasuhiro Kobori, and Ken Sakata
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01306 • Publication Date (Web): 13 Jul 2018
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The Journal of Organic Chemistry
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UVA- and visible light-mediated generation of carbon radicals from
organochlorides using non-metal photocatalyst
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Ryosuke Matsubara,*,§ Tatsushi Yabuta,§ Ubaidah Md Idros,§ Masahiko Hayashi,§ Fumitoshi Ema,§
Yasuhiro Kobori,§ Ken Sakata¶
§ Department of Chemistry, Graduate School of Science, Kobe University, Nada, Kobe 657-8501, Japan
¶ Faculty of Pharmaceutical Sciences, Toho University, Miyama, Funabashi, Chiba 274-8510, Japan
ABSTRACT: Carbon radicals are reactive species useful in various organic transformations. The C–X bond cleavage of orga-
nohalides by photo-irradiation is a common method to generate carbon radicals in a controlled fashion. The use of organo-
chloride substrates is still a formidable challenge due to the low reduction potential and the high dissociation energy of the
C–Cl bond. In this report, we address these issues by using a non-metal organic molecule with a relatively simple structure as
a photocatalyst. In this catalyst (bis(dimethylamino)carbazole), the amino groups increase both the HOMO and LUMO energy
levels, especially in the former. As a result, compared to the parent molecule, the new catalyst shows experimentally red-
shifted absorption in the visible region and forms an excited state with better reducing capability. This photocatalyst was
used in the reduction of unactivated aryl chlorides and alkyl chlorides in the presence of hydrogen atom donor at room tem-
perature. The catalytic system can also be applied to the coupling of aryl chlorides with electron-rich arene and heteroarenes
to affect the C–C bond forming reactions. Our mechanistic study results support the assumption that carbon radicals are
formed from the organochlorides via a single-electron transfer step.
yields were only moderate.7b,9 In this report, we used UVA
and visible light to generate carbon radicals from organo-
INTRODUCTION
chlorides, including unactivated ones, through single elec-
tron transfer using N-ethyl-3,6-bis(dimethylamino)carba-
zole (CAR1), a non-metal PC with a simple structure.
Carbon radicals are short-lived reactive species that can
participate in the formation and cleavage of various bonds.
Therefore, their formation and utilization in a controlled
manner have been an important research topic in organic
chemistry.1 Since carbon–halogen (C–X) bonds are preva-
lent in organic compounds, and many organohalides are
commercially available or readily synthesized, the for-
mation of carbon radicals via the cleavage of C–X bonds is a
useful transformation. Whereas the conventional methods
to generate carbon radicals from C–X bonds relied on the
use of stoichiometric amount of metal-based reagents such
RESULTS AND DISCUSSION
Design and Property of Carbazole-Based Photocatalyst
Our lab has focused on photoredox reactions using PCs
with carbazole as a central framework. Previously, we re-
ported that a 3,6-dimethoxycarbazole derivative (CAR3,
Scheme 1), which has an electron-deficient aryl substituent
on the carbazole nitrogen, could catalyze the photochemical
dehalogenation of unactivated primary alkyl bromides.10
The fact that carbazole CAR3 showed higher reducing abil-
ity than CAR2 (Scheme 1) was rationalized by assuming
that the charge-transfer (CT) excited state of CAR3 effec-
tively suppresses back electron transfer. However, the
CAR3 could not reduce some of the more demanding sub-
strates, such as aryl bromides and organochlorides.
2
as SmI2 or SnBu3H/AIBN,3 the light-mediated alternative
process, in which the C–X bonds are cleaved in the presence
of photocatalysts (PCs) upon irradiation, has drawn much
attention due to its environmentally benign nature.4
Many research groups have reported light-mediated
electron-transfer systems that induce C–X bond cleavage.
However, most such studies employed substrates with C–I5
or activated C–Br bonds, such as those with halogens at the
benzylic position or -position to carbonyl groups (Figure
1A).6 In comparison, organochlorides tend to be cheaper
and more widely available. Therefore, methods to activate
the C–Cl bond for further transformation are highly desired.
In photocatalytic electron transfer reactions, however,7 a
limited examples of photochemical radical formation from
“unactivated” aryl chlorides (that is, those bearing no elec-
tron withdrawing group) have been reported, due to the
strongly negative reduction potential of aryl chlorides (e.g.
To design a better PC, we consider the following aspects.
(1) Based on the Rehm-Weller equation,11 a higher energy
level in the highest occupied molecular orbital (HOMO) of
the ground state PC (that is, a lower oxidation potential) and
a higher excitation energy lead to better reducing ability in
the excited PC species. (2) At the same time, the oxidation
potential of the ground state PC should not be too low, so
that the PC regeneration (PC+  PC) remains feasible. (3)
The ideal PC should absorb photons at wavelengths longer
than 350 nm, to avoid unwanted direct excitation of sub-
strates and allow the utilization of the UVA and visible light

–
Ered [PhCl/PhCl ] = –2.88 V vs SCE) (Figure 1B).8 Further,
they utilized metal-containing PCs and/or the product
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Page 2 of 12
(A)
cupied molecular orbital (LUMO) (Figure 2). This observa-
1
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5
6
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tion suggests that the introduction of electron-donating
groups at C3 and C6 would raise the HOMO energy with
minimal effect on the LUMO level, possibly leading to higher
reducing ability in the excited PC species (vide supra) and
redshifted light absorption. Therefore, we identified 3,6-di-
aminocarbazole (CAR1) as a promising PC with high reduc-
ing ability.
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reduction potential (absolute value)
(B)
Li et al (2013)
Ir(ppy)3 (2.5 mol%)
KOtBu (3 equiv)
h(CFL)
Figure 2. Frontier orbitals of carbazole calculated using
DFT at B3LYP level of theory employing 6-31G(d,p) basis
set. The C3 and C6 atoms are indicated by red arrows.
+
Cl
90 oC, 36 h
(112 equiv)
35% yield
only this example
CAR1 was previously tested by Jamison et al.13 as a can-
didate PC in the Saito deoxygenation reaction,14 where it
gave no product and was abandoned. CAR1 can be readily
synthesized from N-ethylcarbazole in two steps. Cyclic volt-
ammetric analysis of CAR1 revealed its oxidation potential
to be +0.27 V vs SCE, which is 0.57 V lower than that of the
dimethoxy-substituted variant CAR2 (+0.84 V vs SCE) (Fig-
ure S1A). This could be attributed to the raised HOMO level
of CAR1 caused by the strong electron-donating NMe2
groups, which was corroborated by the DFT calculation
(Figure 3A and Figure S2). Experimental absorption spectra
of CAR1 and CAR2 are compared in Figure 3B. The lowest
energy peak of CAR1, which is attributed to the HOMO →
LUMO transition, reaches visible light region with wave-
lengths as long as 430 nm, while that of CAR2 ends at only
390 nm. The bathochromic shift in the absorption spectrum
of CAR1 compared to CAR2 (Figure 3B) can be ascribed to
the increased HOMO energy level and the marginal change
of the LUMO energy level by changing –OMe (CAR2) to –
NMe2 (CAR1). From the onset value of the fluorescence
emission peak (  410 nm, Figure S3), the excited state of
CAR1 was estimated to be 3.02 eV above the ground state.
According to the above data, the excited-state oxidation po-
Anna and Schelter et al (2016)
[CeCl63] (10 mol%)
toluene (10 equiv)
Cl
H
h(black light)
MeO
46% yield
MeO
rt, 72 h
only this example
Konig et al (2017)
rhodamine 6G (10 mol%)
DyI2 (10 mol%)
iPr2NEt (2 equiv)
Cl
H
h(455 nm)
DMF, 25 oC, 72 h
R
R
Up to 82% yield
(R = Me, OMe or Ph)
Figure 1. (A) Photo-induced radical generation from organo-
halides via single electron transfer. (B) Previously reported
photocatalytic radical generation from unactivated aryl chlo-
rides.
CO2Me
CO2H

*
+
tential of CAR1 could be approximated by Eox [CAR1 /
CAR1*] = +0.27 – 3.02 = –2.75 V vs SCE, using the Rehm-
Weller equation.11 This value is comparable to the reduction
potential of chlorobenzene.
Et
N
CF3
CF3
N
N
X
X
Me2N
NMe2
MeO
OMe
The fluorescence emission spectrum of CAR1 is slightly
affected by the solvent polarity (Figure S3), becoming more
red-shifted and less well resolved when the solvent polarity
increases. According to the Lippert-Mataga equation,15 the
dipole moment change ( = e - g) between the ground
and excited states was estimated to be 4.83 D, which is
larger than that of CAR2 (3.46 D)(Table S1, Figure S4). The
calculation showed that the S1 excited state of CAR1 has a
much higher dipole moment than that of CAR2, in good
agreement with the experimental data (Figure S5). These
results indicate that the S1 state of CAR1 has a weak CT
character, which is probably derived from a charge transfer
CAR1
CAR3
CAR4
: X = NMe2
CAR2: X = OMe
Scheme 1 Structures of related non-metal PCs
region of sunlight. (4) Based on our previous finding,10 the
CT excited state helps to retard the unproductive back elec-
tron transfer.12
DFT calculation for the parent molecule (carbazole)
showed large orbital coefficients at C3 and C6 in the HOMO,
while nodes exist on these two carbons in the lowest unoc-
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catalyst loading did not have a significant effect on the reac-
(A)
1
tion rate (entries 13 vs 14), indicating that the reaction rate
was limited by the light irradiation intensity. Indeed, when
the irradiation power was doubled, the product yield
changed from 51% to 86% (entries 15 vs 10).18 No reaction
occurred without light irradiation (entry 16) or without PC
(entry 17).
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3
4
5
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7
8
9
Table 1. Optimization for the dehalogenation of unacti-
vated aryl chloride using different PCsa
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Reduction of primary alkyl chloride
Cl
H
12
12
LED (max = 365 nm)
catalyst (5 mol%)
1a
2a
CHD (2 equiv), base (2 equiv)
23 C, solvent, 48 h
(B)
Cl
H
4
3.5
3
7
7
Reduction of unactivated aryl chloride
3a
4a
entry
sub-
strate
PC
base
sol-
yield
(%)
CAR1
CAR2
vent
2.5
2
1
1a
1a
1a
1a
1a
1a
1a
1a
1a
3a
3a
3a
3a
3a
3a
3a
3a
CAR1
CAR2
CAR3
CAR4
CAR1
CAR2
CAR1
CAR1
–
Bu3N
THF
2
2
Bu3N
THF
0
1.5
1
3
Bu3N
THF
0
0.5
0
4
Bu3N
THF
0
5
Bu3N
DMF
DMF
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
21
1
200
250
300
350
400
450
500
6
Bu3N
Wavelength [nm]
7
Bu3N
45
63
0
8
iPr2NEt
iPr2NEt
iPr2NEt
iPr2NEt
K2CO3
iPr2NEt
iPr2NEt
iPr2NEt
iPr2NEt
iPr2NEt
Figure 3. (A) Comparison of the DFT-calculated frontier orbit-
als for CAR1 and CAR2. (B) Experimental absorption spectra of
CAR1 (orange line) and CAR2 (blue line). from the NMe2 lone-
pairs to the arene-based unoccupied orbital.16
9
10
11
12
13
14
15d
16e
17
CAR1
CAR2
CAR1
CAR1b
CAR1c
CAR1
CAR1
–
51
10
45
48
44
86
0
Carbazole-Catalyzed Generation of Carbon Radicals
from Organohalides by Photo-Irradiation
For the photochemical radical generation from unac-
tivated organochlorides, we first discuss the reduction of a
primary alkyl chloride 1a. The initial PC experiments con-
ducted for CAR1–CAR4 using UVA-LED irradiation (max
=
365 nm, 440 mW) with PC (5 mol%), 1,4-cyclohexadiene
(CHD, 2 equiv) and Bu3N (2 equiv) in THF revealed that only
CAR1 showed a catalytic activity (entries 1–4, Table 1). For-
tunately, the use of high-polarity solvents dramatically in-
creased the product yield (entries 5–7), with N,N-dime-
thylacetamide (DMA) being the optimal solvent (entry 7).
This trend can be attributed to the solvation-assisted facile
electron transfer from PC* to 1a.17 The yield further in-
0
a Conditions: substrate (0.18 mmol, 1 equiv), PC (5 mol%), CHD
(2 equiv), base (2 equiv), solvent (0.1 M), UVA-LED (max = 365
nm, 440 mW), argon atmosphere, 23 C, GC yield shown (inter-
b
c
d
nal standard method). 1 mol%. 10 mol%. UVA-LED (880
mW). e No light.
i
creased when the base was changed from Bu3N to Pr2NEt
Next, we examined the substrate scope for photochemi-
cal reductions of organohalides using CAR1, and the results
are summarized in Table 2. Aryl chlorides bearing no elec-
tron-withdrawing group (3a–f) afforded the reduced prod-
ucts in good-to-high yields regardless of the substitution po-
sitions, as seen in the results of 3c–e. The exclusive for-
mation of the cyclized product 5 from 3f with a pendant ole-
fin suggested that this reaction proceeded via aryl radical
formation. Unsurprisingly, aryl chlorides having electron-
withdrawing groups (3g–i) and -extended systems (3j and
3k) were better substrates for this reaction, giving corre-
sponding products in high yields after shorter reaction
(entry 8). It was confirmed that PC CAR1 is required for this
photocatalysis (entry 9). When these optimal reaction con-
ditions were applied to the photochemical reduction of an
unactivated aryl chloride 3a, the reduction product 4a was
formed at 51% yield (entry 10). CAR2 again gave lower
yield than CAR1 (entry 11 vs. 10). Tertiary amine could be
replaced by inorganic base K2CO3 without significant loss of
reactivity (entry 12 vs 10), suggesting that tertiary amine
does not play a key role in the catalyst regeneration but
works just as a base in this reaction. This result does not
contradict the fact that the oxidation potential of tertiary
amine is higher than that of CAR1 (vide supra). Varying the
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times. The reduction of 3g was also performed using a con-
Page 4 of 12
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2
3
4
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7
8
tinuous flow system equipped with a quartz cell (4 cm  1
cm  0.1 cm) and an HPLC pump. A 0.02 M DMA solution of
3g was passed through the cell (inner volume 0.4 mL) at a
rate 0.2 mL/min under UVA-LED irradiation, affording the
reduced product in 73% yield (residence time: 2 min). The
visible light absorption of CAR1 ( = 400–500 nm, Figure
S3) allowed the reduction of 3j and 3k under visible light
irradiation with high yields (83% and 91%, respectively).
Sunlight-mediated reaction using CAR1 was demonstrated
(Figure 4), in which the products were obtained in accepta-
ble yields. A fluoroarene 6 also underwent the photochemi-
cal reduction to give the reduced product in a good yield.
Figure 4. Sunlight-mediated reduction of chloronaphthalenes
using CAR1. The yields of product (naphthalene) were deter-
mined by GC analysis.
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Table 3. Photochemical coupling reactions of aryl chlo-
rides with (hetero)arenesa
Several alkyl halides were also examined. In addition to
the primary alkyl chloride 1a, secondary and tertiary alkyl
chlorides (1b and 1c, respectively) uneventfully gave the
desired alkanes in good yields. The primary alkyl fluoride 7
did not react under this condition.
Table 2. Photochemical reductions of organohalides using
CAR1a
a
Conditions: organohalides (0.18 mmol, 1 equiv), CAR1 (5
i
mol%), CHD (2 equiv), Pr2NEt (2 equiv), DMA (0.1 M), UVA-
a Conditions: aryl chloride (0.18 mmol, 1 equiv), (hetero)arene
(20 equiv), CAR1 (5 mol%), Pr2NEt (2 equiv), DMSO (0.1 M),
LED (880 mW), argon atmosphere, 23 C, GC yield shown (in-
ternal standard method). b Isolated yield. c UVA-LED (440 mW).
d Flow system (See Supporting Information). e Visible light ( =
400–500 nm).
i
UVA-LED (440 mW), argon atmosphere, 23 C, isolated yield
i
c
shown. b K2CO3 (2 equiv) instead of Pr2NEt. UVA-LED (880
d
mW). Aryl chloride (0.18 mmol, 1 equiv), (hetero)arene (0.9
mL), CAR1 (5 mol%), K2CO3 (2 equiv), DMSO (0.9 mL), UVA-
e
LED (880 mW), argon atmosphere, 90 C. Visible light
(400―500 nm). f NMR yield using durene as an internal stand-
ard.
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We then turned our attention to the C–C bond forming
2.2
2
1
2
3
4
5
6
7
8
reactions utilizing the developed catalytic system of CAR1
(Table 3). Judicious choice of coupling partner and reaction
condition was necessary to permit the addition reaction of
the aryl radical (which has a short lifetime) and suppress its
competitive hydrogen abstraction. Similar to the reactions
developed by König et al.,8a,8b the photochemical coupling
reaction of electron-deficient aryl chlorides with electron-
rich (hetero)arenes could be realized using 5 mol% of CAR1
(8a–d). The omission of CHD and the use of DMSO instead
of DMA were the keys to suppress the formation of reduc-
tion product, because both CHD and DMA are potential hy-
drogen atom donors. Chloropyridines could also serve as a
radical donor to form the pyridine adducts 8e–f in accepta-
ble yields. Unsurprisingly, unactivated (electronically neu-
tral) aryl chlorides gave adducts in low yields (<10%) under
the same reaction conditions. However, an increased tem-
perature (90 C) increased the yields from these challenging
substrates. In addition, the use of inorganic base instead of
organic base and excess amount of radical acceptors were
effective, probably due to the suppression of competitive
hydrogen abstraction of the aryl radicals. Under the opti-
mized conditions, electronically neutral arene adducts with
pyrroles (8g–k) were obtained. Visible light irradiation also
gave the C–C bond formation product (44% yield for 8i).
Benzene adduct and its deuterated variant 8l and 8m were
generated in moderate yields.19
2
1
1.8
1.6
1.4
1.2
1
3k
0
2
4
6
PhCl
iPr2NEt
9
0
200
[Quencher]/mM
400
10
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Figure 5. Fluorescence quenching of CAR1 in the presence of
varying concentrations of 3k, PhCl, or Pr2NEt as quenchers.
i
The quenching rate constants (kq) according to the Stern-
Volmer equation are 1.33×1010, 1.53×107, and 2.16×107 M–1 s–
1, respectively. The fluorescence lifetime of CAR1 in THF was
determined to be  = 17.1 ns by the photoluminescence decay
measurement (Figure S8) and used for the kq calculation. Meas-
urements were performed with 5 M of CAR1 in THF for 3k,
and in DMA for PhCl and iPr2NEt. Inset: magnification of the low
concentration region for 3k.
100
ON OFF ON OFF ON OFF ON OFF ON
80
60
40
20
0
Mechanistic Observations
The fluorescence quenching method has often been
used to gain insight into reaction mechanisms. Electron
transfer involving a photocatalyst in singlet excited state
leads to a reduction (i.e., quenching) of fluorescence from
the photocatalyst. The quenching rate constant (kq) can be
obtained by measuring fluorescence intensity in the pres-
ence of various concentrations of quenchers by means of
the Stern-Volmer equation:
0
50
100
150
200
퐼ꢀ
Time /min
(1)
= 1 + 푘ꢁꢂ[Q]
퐼
where I0 and I are the fluorescence intensities in the ab-
sence and presence of quencher, respectively; s is the life-
time of the singlet excited state; and [Q] is the quencher con-
centration. In this study, three different quenchers were
used: 1-chloronaphthalene (3k, an activated aryl chloride),
PhCl (an unactivated aryl chloride), and iPrNEt2 (a potential
reductant). From the results (Figure 5), 3k exhibits strong
quenching effects. The other two quenchers had weaker ef-
fects.
Figure 6. Progress of photochemical reduction of 3g using
CAR1 under intermittent irradiation. Reaction conditions are
identical to those in Table 2.
Based on the above experimental findings, a catalytic
mechanism of the photochemical reactions of organohalide
using CAR1 was proposed, as shown in Figure 7 (using aryl
chloride as a representative example). The excited singlet
CAR1 (1CAR*) with a highly negative oxidation potential
(E* = –2.75 V vs SCE) transfers one electron to aryl chloride
(oxidative quenching cycle) to form an aryl radical (Ar),21
which abstracts a hydrogen atom from CHD or other solvent
to afford the reduced product (Ar–H). In the absence of re-
active hydrogen atom donor, Ar can react with an electron-
rich (hetero)arene to generate the radical adduct 12, which
is converted to the coupling product 14. CAR1+ accepts an
electron from 10 or 13 to regenerate CAR1, thus the cata-
lytic cycle is completed. Results of the “light/dark” experi-
ment and the quantum yields less than unity infer that a rad-
ical-chain process is unlikely in this system. This experi-
mental conclusion against a radical-chain process is reason-
able because an electron transfer from 10 or 13 to an aryl
To test whether any radical-chain mechanism is opera-
tive in this reaction (meaning that the photosensitized
CAR1 merely works as an initiator), substrate 3g was sub-
jected to the “light/dark experiment”, i.e. photochemical re-
duction with intermittent irradiation with 30-min ON fol-
lowed by 10-min OFF in one cycle. Figure 6 shows no reac-
tion progress during the light-OFF periods. The quantum
yields of photochemical reductions of 3g and 3k (the same
reactions shown in Table 2) were determined to be 0.047
and 0.69, respectively. The results of the light/dark experi-
ment and the quantum yield of less than unity infer that a
radical-chain mechanism is unlikely in our system.20
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chloride, which is necessary for the radical-chain propaga- measured using a JEOL JMS=T100LP (DART method, ambi-
1
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4
5
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tion, is thermodynamically unfeasible.
ent ionization). GC analyses were performed using a Shi-
mazu GC-2025 gas chromatograph equipped with GL Sci-
ence Inertcap 5. Preparative column chromatography was
performed using Kanto Chemical silica gel 60 N (spherical,
neutral). Thin layer chromatography (TLC) was carried out
on Merk 25 TLC silica gel 60 F254 aluminium sheets. All start-
ing materials were obtained from commercial sources un-
less otherwise noted. Carbazole CAR1,23 CAR2,23 CAR310,
and aryl chloride 3f24 are known in the literature and syn-
thesized according to the reported method. Substrate 3f
was synthesized according to the reported method. All the
calculations were carried out using Gaussian 09.25
h
Reduction
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C-C bond formation
Spectral measurement Photoluminescence spectra
were recorded on a spectrofluorometer (Jasco FP-6500)
with a quartz absorption cuvette (light path: 1 cm). UV–
visible spectra were recorded on a Shimadzu UV-1800
spetrometer with a quartz absorption cuvette (light path: 1
cm).
Figure 7. Plausible catalytic mechanism of CAR1.
CONCLUSION
Redox property Cyclic voltammetric measurements
were performed at 298 K, using an ALS CHI606S electro-
chemical analyzer, by using a solvent deaerated by Ar bub-
bling for 30 min before each measurement. The supporting
electrolyte was 0.10 M TBAClO4. A conventional three-elec-
trode cell was used with a platinum working electrode and
a platinum wire as a counter electrode. The cyclic voltam-
mograms were recorded with respect to the Ag/AgNO3 (10
mM) reference electrode at a sweep rate of 100 mV/s. The
reduction or oxidation potentials (determined as the peak
potentials) were corrected to the SCE scale on the basis of
the measurement of the redox potential of the Fc/Fc+ cou-
ple as the standard (+0.43 V vs SCE)26.
A bis(dimethylamino)carbazole (CAR1) was found to
catalytically function as a photoreductant to generate car-
bon radicals from organochlorides. It is a structurally sim-
ple organic molecule with no metals, and can be readily and
cheaply synthesized. Due to its two strong electron-donat-
ing NMe2 groups, CAR1 has an exceptionally high reducing
ability upon irradiation. Spectroscopic and electrochemical
data showed that the oxidation potential of its excited state
reaches as low as –2.75 V vs SCE. Using CAR1 as a PC, vari-
ous types of organohalides could undergo photochemical
reduction, including unactivated (i.e. without electron-
withdrawing substituents adjacent to halides) alkyl chlo-
rides and aryl chlorides. C–C bond formation with electron-
rich (hetero)arenes was also possible. Another benefit of
the NMe2 groups is the redshift of absorption bands to reach
the visible region, allowing the employment of visible light
irradiation or even sunlight in place of UVA light. The exper-
imental results were consistent with the assumption that
the aryl radical is generated from the aryl chloride in this
reaction, and a plausible catalytic mechanism was pro-
posed.
3,6-Bis(dimethylamino)-9H-carbazole To a 500 mL
three-necked flask, 3,6-dibromocarbazole (6.0 g, 18.4
mmol, 1.0 equiv), dimethylamine hydrochloride (3.6 g, 44.4
mmol, 2.4 equiv), Pd2(dba)3 (0.17 g, 0.185 mmol, 1.0 mol%),
Ruphos (0.205 g, 0.440 mmol, 2.4 mol%), and a THF solu-
tion of LiHMDS (1.3 M, 82 mL, 107 mmol, 5.8 equiv) were
added in this order. The mixture was heated at 100 C for
21 h, then dimethylamine hydrochloride (0.90 g, 11.1 mmol,
0.6 equiv) and a THF solution of LiHMDS (1.3 M, 20 mL, 27
mmol, 1.45 equiv) were added. The mixture was heated at
100 C for 3 h. The resultant mixture was poured into 1 M
HCl aq. (130 mL), then sat. NaHCO3 aq. (130 mL) was added.
The mixture was concentrated by a rotary evaporator. The
residue was extracted with ethyl acetate thrice, dried over
anhydrous MgSO4, and filtered. The filtrate thus obtained
was concentrated in vacuo. The residual solid was slurried
in hexane/ethyl acetate mixed solvent (10 : 1) and filtered.
The solid was again slurried in hexane/ethyl acetate mixed
solvent (5 : 1) and filtered. The solid thus obtained was pu-
rified by chromatography on silica gel (hexane/ethyl ace-
tate/Et3N = 100/20/0.2) to give the product (3.33 g, 71%
yield). Green solid. Mp 134.4–134.6 C ; 1H NMR (400 MHz,
Acetone-d6):  = 9.56 (s, 1H), 7.49 (d, J = 2.4 Hz, 2H), 7.30 (d,
J = 8.8 Hz, 2H), 7.00 (dd, J = 8.8, 2.4 Hz, 2H), 2.93 (s, 12H);
13C NMR (100 MHz, Acetone-d6):  = 146.1, 135.6, 124.8,
115.9, 111.9, 105.3, 42.8; IR (neat): 3100, 3014, 2841, 1609,
1567, 1496, 1440, 1432, 1327, 1308, 1240, 1225, 1191,
1160, 1138, 1110, 938, 851, 822, 800, 789, 728, 678, 645
Despite the recent explosive development of photosen-
sitization reactions, PCs with high reducing ability are still
rare, let alone those that function under visible light.22 The
development of such reduction-based reactions for more
difficult substrates is underway in our laboratory.
EXPERIMENTAL SECTION
General All reactions were carried out in well cleaned
and oven-dried glassware with magnetic stirring. Opera-
tions were performed under an atmosphere of dry argon us-
ing Schlenk and vacuum techniques. Melting points were
1
measured on a Yanaco MP-500D and are not corrected. H
and 13C NMR spectra (400 and 100 MHz, respectively) were
recorded on a Bruker Avance III HD 400 using TMS (0 ppm)
and CDCl3 (77.0 ppm) in CDCl3 and residual acetone (2.05
ppm) and CD3COCD3 (29.84 ppm) in acetone-d6 as an inter-
nal standard, respectively. The following abbreviations are
used in connection with NMR; s = singlet, d = doublet, t =
triplet, q = quartet and m = multiplet. Mass spectra were
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The Journal of Organic Chemistry
cm–1; HRMS (DART): m/z calcd for C16H20N3: 254.1652
[M+H+]; found: 254.1657.
i
1,4-cyclohexadiene (33.7 L, 0.36 mmol, 2 equiv), Pr2NEt
(61.5 L, 0.36 mmol, 2 equiv), pentadecane (internal stand-
ard for GC analysis, 30 L) and DMA (1.8 mL). The mixture
was deaerated by bubbling of argon for 10 min. The mixture
was irradiated with 400–500 nm light (a 300W Xenon lamp,
Asahi Spectra MAX-303 equipped with a 300- to 600-nm ul-
traviolet-visible module, and a combination of a 400-nm
long-pass and 500-nm short-pass filters) at 23 C for the in-
dicated time (see the main text). Due to the volatility of the
products, the yield of the product was determined by GC
analysis based on the ratio of product to pentadecane.
1
2
3
4
5
6
7
8
Methyl
4-(3,6-bis(dimethylamino)-9H-carbazol-9-
yl)-3-trifluoromethylbenzoate (CAR4) K3PO4 (385.8 mg,
1.82 mmol, 3.0 equiv) was added to a sealed tube and flame-
dried under vacuum. CuI (23.1 mg, 0.12 mmol, 0.2 equiv),
N,N-dimethyl-1,2-ethandiamine (19.6 L、0.18 mmol, 0.3
equiv) and THF (2.2 mL) were added. The mixture was
stirred for 10 min at rt. Methyl 4-iodo-3-(trifluorome-
thyl)benzoate (200 mg, 0.61 mmol, 1.0 equiv) and 3,6-
bis(dimethylamino)carbazole (230.2 mg, 0.91 mmol, 1.5
equiv) were added and the mixture was heated at 80 ℃ for
18 h. The reaction mixture was cooled to rt, then ethyl ace-
tate was added. The resultant mixture was washed with
brine four times, dried over anhydrous Na2SO4, and filtered.
The filtrate was concentrated in vacuo and purified by chro-
matography on SiO2 to give the product (42 mg, 15% yield).
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Photochemical reduction of 3g under flow system The
flow-system equipment was manually assembled with a
HPLC double-plunger pump, fluorinated transparent plastic
tubes, a quartz flow-cell (0.1  1.0  4.0 cm), and four LED
lamps. The overview of the system is shown SI (Figure S6
and S7). A deaerated DMA solution of 3g (1.0 equiv, 20 mM),
CAR1 (5 mol%, 1 mM), 1,4-cyclohexadiene (2.0 equiv, 40
mM), iPr2NEt (2.0 equiv, 40 mM) and pentadecane (internal
standard, 0.5 v/v%) was passed through the quartz cell at
0.2 mL/min flow rate with irradiation. Because the inner
volume of the cell is 0.4 mL, the residence time is 2 min. Af-
ter the steady state was reached the aliquot of the output
solution was analyzed by GC, revealing that the yield of the
desired product was 73% yield.
1
Red oil. H NMR (400 MHz, CDCl3):  = 8.61 (d, J = 1.6 Hz,
1H), 8.34 (dd, J = 8.4, 2.0 Hz, 1H), 7.44 (d, J = 2.4 Hz, 2H),
7.39 (d, J = 8.0 Hz, 1H), 6.95 (dd, J = 9.0, 2.6 Hz, 2H), 6.71 (d,
J = 8.8 Hz, 2H), 4.02 (s, 3H), 3.01 (s, 12H); 13C NMR (100
MHz, CDCl3):  = 165.3, 146.0, 141.8, 137.3, 134.4, 132.7,
131.1 (q, JC-F = 31 Hz), 130.5, 129.0 (q, JC-F = 5 Hz), 124.6,
122.7 (q, JC-F = 273 Hz), 114.9, 110.4, 104.3, 52.8, 42.5; IR
(neat): 2954, 2872, 2834, 2786, 1726, 1614, 1576, 1496,
1475, 1436, 1322, 1253, 1227, 1164, 1131, 1054, 965, 945,
923, 831, 795, 751, 731, 702, 662, 655, 598 cm–1; HRMS
(DART): m/z calcd for C25H25F3N3O2: 456.1899 [M+H+];
found: 456.1930.
Sun light-mediated photochemical reductions (Fig-
ure 4) To a 100 mL two-necked round-bottomed flask were
added naphthalene chloride 3j or 3k (0.18 mmol, 1.0 equiv),
CAR1 (2.5 mg, 9 mol, 5 mol%), 1,4-cyclohexadiene (33.7
i
General procedure of photochemical reductions of or-
ganohalides using CAR1 (Table 2) To a pyrex glassware
were added alkyl or aryl halide (0.18 mmol, 1.0 equiv),
CAR1 (2.5 mg, 9 mol, 5 mol%), 1,4-cyclohexadiene (33.7
L, 0.36 mmol, 2 equiv), Pr2NEt (61.5 L, 0.36 mmol, 2
equiv), pentadecane (internal standard for GC analysis, 30
L) and DMA (1.8 mL). The mixture was deaerated by bub-
bling of argon for 10 min. The mixture was stood without
stirring on the roof of the building on May 13th, 2017 (the
outside temperature was 30 C) for the indicated time. The
reaction was monitored by GC analysis. The yield of the
product was determined by GC analysis based on the ratio
of product to pentadecane.
i
L, 0.36 mmol, 2 equiv), Pr2NEt (61.5 L, 0.36 mmol, 2
equiv), pentadecane (internal standard for GC analysis, 30
L) and DMA (1.8 mL). The mixture was deaerated by bub-
bling of argon for 10 min. The mixture was irradiated with
two or four LED lamps (total 440 or 880 mW, respectively)
at 23 C for the indicated time (see the main text). Due to
the volatility of the products, the yield of the product was
determined by GC analysis based on the ratio of product to
pentadecane except the reaction of 3f, in which compound
5 was isolated by chromatography.
Photochemical coupling reactions of aryl chlorides
with (hetero)arenes (Table 3) (Procedure A) To a pyrex
glassware were added aryl chloride (0.18 mmol, 1.0 equiv),
(hetero)arene (3.6 mmol, 20 equiv), CAR1 (2.5 mg, 9 mol,
i
5 mol%), Pr2NEt (61.5 L, 0.36 mmol, 2 equiv) and DMSO
2,3-Dihydroxy-3-methylbenzofurane (5)27 To a pyrex
glassware were added 1-alloxy-2-chlorobenzene (3f, 27.0
L, 0.18 mmol, 1.0 equiv), CAR1 (2.5 mg, 9 mol, 5 mol%),
(1.8 mL). The mixture was deaerated by bubbling of argon
for 10 min. The mixture was irradiated with two LED lamps
(total 440 mW) at 23 C for the indicated time (see the main
text). Then brine was added to the reaction mixture to
quench the reaction. The resultant mixture was extracted
with Et2O thrice, dried over anhydrous Na2SO4, and filtered.
The filtrate was concentrated in vacuo and purified by chro-
matography on SiO2 to afford the product.
i
1,4-cyclohexadiene (33.7 L, 0.36 mmol, 2 equiv), Pr2NEt
(61.5 L, 0.36 mmol, 2 equiv), pentadecane (internal stand-
ard for GC analysis, 30 L) and DMA (1.8 mL). The mixture
was deaerated by bubbling of argon for 10 min. The mixture
was irradiated with two or four LED lamps (total 440 or 880
mW, respectively) at 23 C for 44 h. The reaction mixture
was cooled to rt, then ethyl acetate was added. The resultant
mixture was washed with brine once and water thrice, dried
over anhydrous Na2SO4, and filtered. The filtrate was con-
centrated in vacuo and purified by chromatography on SiO2
to give 5 (11.4 mg, 49% yield).
(Procedure B) To a pyrex glassware were added aryl
chloride (0.18 mmol, 1.0 equiv), (hetero)arene (3.6 mmol,
20 equiv), CAR1 (2.5 mg, 9 mol, 5 mol%), iPr2NEt (61.5 L,
0.36 mmol, 2 equiv) and DMSO (1.8 mL). The mixture was
deaerated by bubbling of argon for 10 min. The mixture was
irradiated with two or four LED lamps (total 440 mW or 880
mW, respectively) at 23 C for the indicated time (see the
main text). Then brine was added to the reaction mixture to
quench the reaction. The resultant mixture was extracted
Photochemical reductions using visible light (for 3j
and 3k) To a pyrex glassware were added alkyl or aryl hal-
ide (0.18 mmol, 1.0 equiv), CAR1 (2.5 mg, 9 mol, 5 mol%),
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with EtOAc thrice, dried over anhydrous Na2SO4, and fil-
tered. The filtrate was concentrated in vacuo and purified
by chromatography on SiO2 to afford the product.
product yield was calculated by taking it into account), 48%
yield, colorless oil.
1
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3
4
5
6
7
8
1-Methyl -2-(3-methoxyphenyl)-1H-pyrrole (8j)32 Pro-
cedure C. 11.5 mg (after chromatographic isolation the
product included EtOAc (0.5 mg) because we avoided rigor-
ous evaporation considering the potential volatility. The
product yield was calculated by taking it into account), 34%
yield, colorless oil.
(Procedure C) To a pyrex glassware were added aryl
chloride (0.18 mmol, 1.0 equiv), (hetero)arene (0.9 mL, 56–
73 equiv), CAR1 (2.5 mg, 9 mol, 5 mol%), K2CO3 (49.8 mg,
0.36 mmol, 2 equiv) and DMSO (0.9 mL). The mixture was
deaerated by bubbling of argon for 10 min. The mixture was
irradiated with four LED lamps (total 880 mW) at 90 C for
the indicated time (see the main text). Then brine was
added to the reaction mixture to quench the reaction. The
resultant mixture was extracted with Et2O thrice, dried over
anhydrous Na2SO4, and filtered. The filtrate was concen-
trated in vacuo and purified by chromatography on SiO2 to
afford the product.
Methyl 4-(1H-pyrrol-2-yl)benzoate (8a)28 Procedure
A. 22.3 mg, 62% yield, white solid.
Methyl 4-(1-methyl-1H-pyrrol-2-yl)benzoate (8b)28
Procedure A. 25.5 mg, 66% yield, white solid.
Methyl 4-(2,4,6-trimethoxyphenyl)benzoate (8c)28
Procedure A. 32.9 mg, 60% yield, white solid.
2-(2-Naphthalenyl)-1H-pyrrole (8d)29 Procedure A.
18.0 mg, 52%, yellow solid.
2-(1-Methyl-1H-pyrrol-2-yl)pyridine (8e)30 Procedure
B. Irradiated with the LED lamps (total 440 mW). 13.2 mg
(after chromatographic isolation the product included
EtOAc (0.6 mg) because we avoided rigorous evaporation
considering the potential volatility. The product yield was
calculated by taking it into account), 46%, yellow oil.
3-(1-Methyl-1H-pyrrol-2-yl)pyridine (8f)31 Procedure
B. Irradiated with the LED lamps (total 880 mW). 13.2 mg,
46%, yellow oil.
1-Methyl-2-(2-methoxyphenyl)-1H-pyrrole
(8k)33
9
Procedure C. 9.0 mg, 27% yield, colorless oil.
4-Octyl-1,1’-biphenyl (8l)34 Procedure C. 10.4 mg, 22%
yield, white solid.
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4-Octyl(2’,3’,4’,5’,6’-2H5)-1,1’-biphenyl (8m) Proce-
dure C. 13.6 mg, 28% yield, white solid. Mp 38.5—39.2 oC; 1H
NMR (400 MHz, CDCl3):  = 7.51 (d, J = 8 Hz, 2H), 7.25 (d, J =
8.4 Hz, 2H), 2.64 (t, J = 7.6 Hz, 2H), 1.65 (m, 2H), 1.33-1.28
(m, 10H), 0.88 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
 = 142.1, 141.0, 138.5, 128.8, 128.7 (t, J = 18 Hz), 128.2 (t,
24 Hz), 126.9, 126.5 (t, J = 24 Hz), 35.6, 31.9, 31.5, 29.5, 29.4,
29.3, 22.7, 14.1; IR (neat): 2955, 2918, 2848, 1515, 1465,
1381, 1332, 1135, 1019, 992, 862, 834, 815, 762, 721, 635,
552 cm–1; HRMS (DART): m/z calcd C20H22D5: 272.2421
[M+H+]; found: 272.2427.
Visible light-mediated photochemical coupling reac-
tions of 3c with N-methylpyrrole (synthesis of 8i) To a py-
rex glassware were added 3c (0.18 mmol, 1.0 equiv), N-
methylpyrrole (0.9 mL, 56 equiv), CAR1 (2.5 mg, 9 mol, 5
mol%), K2CO3 (49.8 mg, 0.36 mmol, 2 equiv) and DMSO (0.9
mL). The mixture was deaerated by bubbling of argon for 10
min. The mixture was irradiated with 400–500 nm light (a
300W Xenon lamp, Asahi Spectra MAX-303 equipped with a
300- to 600-nm ultraviolet-visible module, and a combina-
tion of a 400-nm long-pass and 500-nm short-pass filters)
at 90 C for 72 h. Then brine was added to the reaction mix-
ture to quench the reaction. The resultant mixture was ex-
tracted with Et2O thrice, dried over anhydrous Na2SO4, and
filtered. The filtrate was concentrated in vacuo and purified
by chromatography on SiO2 to afford the product 8i (44%
yield).
2-(4-Octylphenyl)-1H-pyrrole (8g) Procedure C. 16.7
o
1
mg, 37% yield, white solid. Mp 69.5–70.0 C; H NMR (400
MHz, CDCl3):  = 8.39 (s, 1H), 7.39 (d, J = 8.4 Hz, 2H), 7.18 (d,
J = 8.4 Hz, 2H), 6.78 (m, 1H), 6.48 (m, 1H), 6.29 (q, J = 2.9 Hz,
1H), 2.59 (t, J = 7.8 Hz, 2H), 1.61 (m, 2H), 1.31–1.27 (m,
10H), 0.88 (t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3):  =
141.0, 132.3, 130.2, 128.9, 123.8, 118.4, 109.9, 105.4, 35.6,
31.9, 31.5, 29.5, 29.3, 29.3, 22.7, 14.1; IR (neat): 3395, 2950,
2918, 2848, 1507, 1463, 1126, 1108, 1031, 823, 796, 782,
732, 718, 559, 526 cm–1; HRMS (ESI): m/z calcd for C18H26N:
256.2065 [M+H+]; found: 256.2093.
Light/dark experiment (Figure 6) To a pyrex glass-
ware were added 3g (0.18 mmol, 1.0 equiv), CAR1 (2.5 mg,
9 mol, 5 mol%), 1,4-cyclohexadiene (35.0 mg, 0.36 mmol,
2 equiv), iPr2NEt (61.5 L, 0.36 mmol, 2 equiv), pentadecane
(internal standard for GC analysis, 30 L) and DMA (1.8
mL). The mixture was deaerated by bubbling of argon for 10
min. The mixture was subjected to ON/OFF rotations of ir-
radiation with two LED lamps (30 min-ON followed by 10
min-OFF for one cycle) at 23 C. The reaction progress was
monitored by GC analysis of the aliquots taken out of the re-
action at intervals. The yield was determined based on the
ratio of product to pentadecane.
1-Methyl-2-(4-octylphenyl)-1H-pyrrole (8h) Proce-
1
dure C. 27.2 mg, 56% yield, yellow oil. H NMR (400 MHz,
CDCl3):  = 7.31 (dt, J = 8.1, 1.9 Hz, 2H), 7.20 (d, J = 8.0 Hz,
2H), 6.70 (t, J = 2.2 Hz, 1H), 6.21–6.18 (m, 2H), 3.66 (s, 3H),
2.62 (t, J = 7.8 Hz, 2H), 1.64 (m, 2H), 1.33–1.28 (m, 10H),
0.88 (t, J = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3):  = 141.6,
134.7, 130.6, 128.5, 128.3, 123.3, 108.2, 107.6, 35.7, 35.0,
31.9, 31.5, 29.5, 29.4, 29.3, 22.7, 14.1; IR (neat): 2922, 2852,
1505, 1475, 1414, 1309, 1240, 1089, 1056, 1015, 982, 838,
777, 705, 606, 547 cm–1; HRMS (ESI): m/z calcd for C19H28N:
270.2222 [M+H+]; found: 270.2246.
1-Methyl-2-(4-methoxyphenyl)-1H-pyrrole (8i)32 Pro-
cedure C. 16.3 mg (after chromatographic isolation the
product included EtOAc (2.0 mg) because we avoided rigor-
ous evaporation considering the potential volatility. The
ASSOCIATED CONTENT
Supporting Information.
Cyclic voltammograms, dipole moment change determination,
experimental procedures (Table 1, flow system, fluorescence
lifetime, and quantum yield determination), theoretical calcu-
lation data and 1H and 13C NMR spectra (PDF)
This material is available free of charge via the Internet at
http://pubs.acs.org.
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The Journal of Organic Chemistry
Barriault, L. Photoredox Transformations with Dimeric Gold
AUTHOR INFORMATION
Complexes. Angew. Chem. Int. Ed. 2013, 52, 13342–13345.
[7] Other types of photochemical reactions using aryl chlorides.
Strong base-mediated reactions: (a) Budén, M. E.; Guastavino,
J. F.; Rossi, R. A. Room-Temperature Photoinduced Direct C-H-
Arylation via Base-Promoted Homolytic Aromatic Substitu-
tion. Org. Lett. 2013, 15, 1174–1177; (b) Cheng, Y.; Gu, X.; Li,
P. Visible-Light Photoredox in Homolytic Aromatic Substitu-
tion: Direct Arylation of Arenes with Aryl Halides. Org. Lett.
2013, 15, 2664–2667; homolytic cleavage of C–Cl bonds: (c)
Mfuh, A. M.; Doyle, J. D.; Chhetri, B.; Arman, H. D.; Larionov, O.
V. Scalable, Metal- and Additive-Free, Photoinduced Boryla-
tion of Haloarenes and Quaternary Arylammonium Salts. J.
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Corresponding Author
* matsubara.ryosuke@people.kobe-u.ac.jp
ACKNOWLEDGMENT
This work was carried out by the joint research program of Mo-
lecular Photoscience Research Center, Kobe University
(H29001). We thank Profs. Atsunori Mori and Kentaro Okano
in Kobe University for their help on mass analysis. Financial
supports from JSPS KAKENHI Grant Number JP16K18844,
Shorai Foundation for Science and Technology, and Research
Foundation for Opto-Science and Technology are greatly ap-
preciated. This work was also supported by the Ministry of Ed-
ucation, Culture, Sports, Science and Technology (MEXT), Ja-
pan, and by Special Coordination Funds for Promoting Science
and Technology, Creation of Innovation Centers for Advanced
Interdisciplinary Research Areas (Innovative Bioproduction
Kobe), MEXT, Japan.
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