Biaryl Cross-Coupling Enabled by Photo-Induced Electron Transfer

Article abstract of DOI:10.1002/adsc.201901601

We report a protocol for aryl cross-coupling of electron-deficient aryl halides with electron-rich (hetero)arenes that is driven solely by violet light. This process takes advantage of formation of photo-excited state of electron-deficient aryl halides, that are reduced by electron-rich (hetero)arenes to form a pair of aryl anion and cation radicals. The resulting aryl anion radicals of aryl halides undergo mesolysis of the carbon-halogen bond to generate aryl radicals, that are coupled most likely with aryl cation radicals to afford functionalized biaryls. (Figure presented.).

Full text of DOI:10.1002/adsc.201901601

Title: Biaryl cross-coupling enabled by photo-induced electron transfer
Authors: Hirohito Hayashi, Bin Wang, Xiangyang Wu, Shi Jie Teo,
Atsushi Kaga, Kohei Watanabe, Ryo Takita, Edwin K. L.
Yeow, and Shunsuke Chiba
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201901601
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10.1002/adsc.201901601
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Biaryl cross-coupling enabled by photo-induced electron
transfer
Hirohito Hayashi,a Bin Wang,a Xiangyang Wu,a Shi Jie Teo,a Atsushi Kaga,a Kohei
Watanabe,b Ryo Takita,b Edwin K. L. Yeow,a* and Shunsuke Chibaa*
a
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang
Technological University, Singapore 637371, Singapore.
[shunsuke@ntu.edu.sg (for S.C.); edwinyeow@ntu.edu.sg (for E. K. L. Y.)]
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033,
b
Japan.
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. We report a protocol for aryl cross-coupling of The resulting aryl anion radicals of aryl halides undergo
electron-deficient
aryl
halides
with
electron-rich mesolysis of the carbon-halogen bond to generate aryl
(hetero)arenes that is driven solely by violet light. This radicals, that are coupled most likely with aryl cation
process takes advantage of formation of photo-excited state radicals to afford functionalized biaryls.
of electron-deficient aryl halides, that are reduced by
electron-rich (hetero)arenes to form a pair of aryl anion and
cation radicals.
Keywords: Aryl radicals; Anion radicals; Visible light;
Cross-coupling; Single-electron-transfer
Wickens independently disclosed an elegant
combination of electricity and visible light to
generate highly reducing excited radical anions of
Introduction
The cross-coupling reaction is a central subject in
synthetic chemistry and catalysis, enabling carbon-
carbon and carbon-heteroatom bonds from various
sets of feedstock chemicals. Conventional methods
for the aryl cross-coupling to incorporate aromatic
motifs into the products use transition-metal catalysts
to mediate coupling of aryl (pseudo)halides as an
electrophile with organometallic or heteroatom
nucleophiles (Scheme. 1A).[1] Alternatively, aryl
cross-coupling can be mediated with open-shell aryl
radicals, which are typically generated from aryl
(pseudo)halides by a classical tin radical-mediated
dicyanoanthracene
(DCA)
and
naphthalene
monoimide (NpMI) derivatives, that can mediate
single-electron-reduction of aryl halides to afford aryl
radicals for the subsequent cross-coupling.[7]
Electron-donors activated by photo-irradiation or
generated by photo-induced electron-transfer are
found capable in inducing single-electron-reduction
of aryl halides to initiate biaryl-coupling under BHAS
radical chain mechanism.[8] The electron-donor-
acceptor (EDA) interaction, which induces electron
transfer within the resulting charge-transfer
complexes by photo-irradiation,[9] could also facilitate
method, single-electron-reduction (via anion radicals), generation of aryl radicals and their cross coupling
or photo-excitation (typically by irradiation of UV
light) (Scheme 1B).
reactions.[10-13]
On the other hand, leveraging of photo-induced
Recently, photo-induced radical chemistry has
proven complementary for aryl cross-coupling
reactions.[2] For example, it was demonstrated that
photo-excited highly reducing fac-Ir(ppy)3 can
undergo reduction of aryl halides[3] to form aryl
radicals, that can mediate base-promoted homolytic
aromatic substitution (BHAS)-type radical chain
biaryl coupling with unactivated arenes.[4,5]
Generation of highly reducing photo-excited anion
radicals of several -conjugate organic dyes has also
been utilized in reductive formation of aryl radicals
from aryl (pseudo)halides and subsequent biaryl
cross-coupling.[6] Very recently, Lambert/Lin and
electron
transfer
to
photo-excited
aryl
(pseudo)halides halides would be an attractive
alternative to facilitate aryl cross-coupling (Scheme
2). In this regard, Li has recently developed a
protocol for photo-induced generation of aryl radicals
from aryl (pseudo)halides through single-electron-
reduction of their photo-excited state by an iodide
ion.[14] The resulting aryl radicals undergo coupling
reactions with molecular iodine (I2) (Scheme 2A) or
bis(pinacolato)diborane (B2pin2) (Scheme 2B), and 5-
exo cyclization with a pendant alkene followed by
iodination of the resulting alkyl radicals. The same
1
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10.1002/adsc.201901601
Advanced Synthesis & Catalysis
A. Transition-metal catalyzed aryl cross coupling
electron to photo-excited aryl halides, promoting
subsequent C-C bond formation for construction of
biaryl motifs. Herein, we report a protocol for biaryl-
cross coupling between electron-deficient aryl halides
and electron-rich (hetero)arenes, that is enabled
solely by irradiation of violet light. The reaction
design, reaction optimization, and substrate scope as
well as mechanistic investigation are described.
transition metal
catalyst [Mn]
Ar
X
Ar
Nu
“Nu”
(nucleophile)
X = Cl, Br, I,
OSO2R
typically via
[Mn+2
Ar
]
B. Generation of aryl radicals for aryl cross coupling
Ar
X
Results and Discussion
via
electron
donor
To realize photo-induced biaryl cross-coupling
reactions via the photo-induced electron-transfer, we
first became interested in a pair of aryl halides having
an electron-withdrawing group such as 4’-
bromoacetophenone (1-Br) as the electron-acceptor
and N-methylpyrrole (2) as an electron donor,
possessing a lower ionization potential (Ip = 7.94
ev)[16] compared with other 5-membered ring
heteroaromatics such as furan (Ip = 8.88 ev) and
thiophene (Ip = 8.87 ev). Their cross-coupling was
recently demonstrated by highly reducing photo-
excited anion radicals generated under photoredox-[6]
or electrophoto-catalytic[7] reaction conditions as
depicted in Scheme 3.[17]
Ar
X
+e–
radical
Bu3SnH
AIBN
acceptor
Ar
R
X
Ar
X
Ar
R
radical
chain
aryl
radicals
via
*
h
n
Ar
X
Ar
X
Scheme 1. Aryl cross-coupling
Scheme 2. Photo-induced aryl cross-coupling.
group also reported photo-induced synthesis of aryl
phosphonates from aryl halides and H-phosphonates
in the presence of NaOt-Bu, in which single-electron-
reduction of photo-excited aryl halides by in-situ
generated sodium phosphite/phosphinite may operate
to initiate the ensuing radical coupling process
(Scheme 2C).[15] These methods commonly require
irradiation of energy intensive UV light to excite aryl
halides except for more reactive aryl iodides. We
reasoned that electron-rich arenes having a lower
ionization potential are capable in transferring an
Scheme 3. Biaryl cross-coupling catalyzed by highly
reducing photo-excited anion radicals.
2
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10.1002/adsc.201901601
Advanced Synthesis & Catalysis
A
D
E
F
B
–
T1
Ac
C
Ac
T1
S1
Ac
Ac
Ac
h
n
ISC
Br
+
1-Br
Br
[1-Br]•–
1•
electron
transfer
Br
1-Br
[1-Br]T1
+
Br
h
n
+
[1-Br]S1
[1-Br]T1
+
+
–Br–
2
[2]•+
Ac
[2]•+
N
N
2
Me
–Br•
Me
1•
N
Me
Ac
–H+
3
Figure 1. Transient absorption spectra. (A) ns-TA spectra of 1-Br (0.1 M) and (B) the corresponding transient kinetic
profile probed at 360 nm. (C) The reaction pathway by photo-excitation of 1-Br. (D) ns-TA spectra of a mixture of 1-Br
(0.1 M) and 2 (2 M). (E) The corresponding transient kinetic profile probed at 370 nm. (F) The reaction pathway by photo-
irradiation of 1-Br in the presence of 2. The mono-exponential decay/rise fits are also given in red. All samples were
prepared in DMSO under an Ar atmosphere. The pump wavelength is 355 nm. OD = optical density; ISC = intersystem
crossing; Ac = acetyl.
Photochemistry of substituted acetophenone
derivatives was studied previously and the absorption
profiles of the corresponding triplet states[18,19] and
anion radicals[20] were well characterized under
transient absorption spectroscopy. We recorded the
nanosecond-transient absorption (ns-TA) spectra of
1-Br in degassed DMSO using 355 nm pulsed
excitation at different delay times t (Figure 1A). At
short delay times (e.g., t = 44 ns), a broad band
centred at 430 nm is observed. This is attributed to
the triplet state [1-Br]T1 formed via rapid intersystem
crossing (ISC) from the excited S1(n,*) singlet state
[1-Br]S1 (Figure 1C).[18] It was also reported that the
absorption of triplet para-substituted acetophenones
containing electron-withdrawing groups falls in a
similar wavelength range.[19] At later times (e.g., t =
984 ns), a new peak at 360 nm and a featureless
broad band at wavelengths > 400 nm are seen, which
is likely due to the absorption of aryl radical [1]•
formed after C-Br bond cleavage of the triplet state
[1-Br]T1.[18a, 21] At delay time t ~ 3 s, the absorption
peak at 360 nm begins to decay mono-exponentially
with a rate constant krd = 7.2 × 104 s-1 (Figure 1B).
3
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10.1002/adsc.201901601
Advanced Synthesis & Catalysis
We next examined the ns-TA spectra of a mixture of
1-Br and N-methylpyrrole (2) in DMSO at different
delay times (Figure 1D). A band centred at 470 nm
was observed at early delay times (e.g., t = 48 ns),
which was assigned to the absorption of the anion
radical [1-Br]•–.[20] The anion radical [1-Br]•– decays
(e.g., t = 978 ns) as it undergoes back-electron-
transfer to [2]•+ or C-Br bond mesolysis to form aryl
radical [1]•. The lifetime of [1-Br]•– is 0.6 s,
obtained from the transient kinetic profile probed at
470 nm (Figure S1). After t ~ 1 s, a new peak at
370 nm and a broad featureless band appearing at >
400 nm are observed (e.g., t = 2.518 and 3.018 s).
In this case, the OD bands are attributed to aryl
radical [1]• formed after C-Br bond mesolysis of [1-
Br]•–. The bathochromic shift of the peak when
compared to aryl radical [1]• generated from 1-Br
itself (Figure 1A) is plausibly due to an
environmental effect on the absorption of aryl radical
[1]• in the presence of N-methylpyrrole (2). The rate
of formation of [1]• (krf = 6.8 × 105 s-1), obtained from
the rise of the 370 nm peak (Figure 1E), is slower
than the rate of [1-Br]•– decay (kad = 1.7 × 106 s-1);
indicating that back-electron-transfer is more efficient
than the C-Br bond mesolysis as the decay pathway
of [1-Br]•–. The aryl radical [1]• decays mono-
exponentially after t ~ 3 s with a rate constant krd =
1.3 ×106 s-1 (Figure 1E). This implicates that the
radical coupling between [1]• and [2]•+ within the
solvent cage to produce biaryl 3 (Figure 1F) could
contribute to the faster decay of [1]• as compared to
the solution of sole [1]• (Figure 1B).
Figure 2. (A) UV-vis absorption spectra of 1-Br (0.1 mM
in DMSO). (B) UV-vis absorption spectra of 1-Br (100
mM in DMSO) with 0 to 20 equiv of 2.
UV-vis absorption spectrum on 1-Br in DMSO
showed strong absorbance at 260 nm derived from
the -* transition (Figure 2A) and much weaker one
around at 352 nm from the n-* transition (Figure
2B). However, addition of pyrrole 2 to 1-Br did not
show clear enhancement and red-shifted tailing of the
absorbance, indicating that the EDA interaction
between 1-Br and 2 in their ground state is less likely
present.[22] Therefore, we assumed that photo-
induced electron-transfer to the photo-excited triplet
state [1-Br]T1 from N-methylpyrrole 2 is most likely
responsible for the formation of the anion radical [1-
Br]•–.[23]
Based on the above observations and mechanistic
hypothesis for biaryl-coupling between 1-Br and 2,
optimization of the reaction conditions was
implemented (Table 1). We observed that irradiation
of violet light (max = 390 nm) in DMSO as a solvent
promotes the expected cross-coupling to provide
biaryl 3 in 67% yield after stirring for 20 h (run 1).
The reaction could be accelerated by adding
inorganic carbonate bases (M2CO3: M = K, Na, or
Cs), completing the process within 6-7 h to give 3 in
good yields (runs 2-4).[24] However, use of other
inorganic salts such as KOAc (run 5) and KF (run 6)
as well as organic amines such as N,N-
diisopropylethylamine (i-Pr2NEt) (run 7) and 1,4-
diazabicyclo[2.2.2]octane (DABCO) (run 8) did not
improve the process efficiency. We next examined
the effect of the wavelength of the light sources. The
cross-coupling under shorter wavelength of the light
(max = 370 nm) proceeded to give 3 in 83% yield,
while the reaction progress became slower (run 9). In
this case, we speculated that the absorption of the
light by the coupling product 3 rendered the reaction
progress sluggish. On the other hand, light of longer
wavelength (max = 427 or 440 nm) was unable to
promote this process (runs 10 and 11). Under
irradiation of violet light (max = 390 nm), the
reaction in acetonitrile gave a comparable yield of 3,
while longer reaction time was required (run 12).
Use of other solvents such as methanol and
4
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10.1002/adsc.201901601
Advanced Synthesis & Catalysis
dichloroethane was found detrimental (runs 13 and
14).
Table 1. Optimization of the reaction conditionsa)
max
Time
(h)
Yield
(%)c)
Run
Solvent
Base
(nm)b)
1
2
3
4
5
6
7
8
9
10
11
12
13
390
390
390
390
390
390
390
390
370
427
440
390
390
390
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
–
20
6
6.5
7
67 (6)d)
73 (76)e)
68
K2CO3
Na2CO3
Cs2CO3
KOAc
KF
72
62
73
16
16
20
20
14
14
14
25
14
14
iPr2NEt
43 (5)d)
64 (6)d)
83
DMSO DABCO
Scheme 4. The reactions of 1-Br and 1-Cl.
DMSO
DMSO
DMSO
CH3CN
MeOH
DCE
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
8 (88)d)
0 (90)d)
72
We found that this protocol is applicable to aryl
bromides having -polar electron-withdrawing
groups such as acyl, formyl, cyano, and methoxy
carbonyl regardless of their position (i.e. para, meta,
or ortho to the dissociative C-Br bond) (4-7, 10-16),
whereas those with 4-bromoanisole and 4-
bromotrifluorotoluene were detrimental under the
reaction conditions (8 and 9) (Scheme 5A). It should
be noted that the coupling reactions of 4-
bromobenzophenone (for 4) and 2-acetyl-6-
bromonaphthalene (for 15) occur even under
irradiation of light of longer wavelength (max = 427
nm) with similar performance probably because their
-extended structures lend red-shifted absorption to
the corresponding aryl bromides. Chemoselective
coupling with bromide over fluoride or chloride was
observed in the reaction of 4-bromo-2-
fluorobenzonitrile, 2-bromo-3-fluorobenzaldehyde,
and 2-bromo-4-chlorobenzaldehyde to afford the
corresponding coupling products (17, 18, and 19,
respectively) in good yields as a sole product.
Polysubstituted biaryls 20 and 21 could be accessed
efficiently by the current protocol. Furthermore, the
present cross-coupling method is amenable to various
heteroaromatic bromides, allowing for a rapid access
to a series of unique heterobiaryls of medicinal
interests (22-31) (Scheme 5B). Of worthy to note is
the late stage functionalization of a drug compound,
nicergoline (for 31), demonstrating wide functional
group compatibility of the present protocol (Scheme
5B).
36 (47)d)
9 (91)d)
14
a)
All the reactions were conducted using 0.5 mmol of 1 in
b)
degassed DMSO (5 mL) under an Ar atmosphere. The
Kessil PR160 series (at max = 440, 427, 390, and 370 nm)
were used as the LED light source for the reactions
(https://www.kessil.com/photoredox/Products.php).
The
radiated energies of the light per area measured at a
distance of 3.5 cm are 41.3 mW/cm2 (440 nm), 49.4
mW/cm2 (427 nm), 50.4 mW/cm2 (390 nm), and 42.5
mW/cm2 (370 nm). See the Supporting Information for the
detailed reaction settings. c) 1H NMR yields based on the
d)
e)
internal standard.
yield.
Recovery yield of 1-Br. Isolated
The coupling reaction of 1-Br with 10 equiv of N-
methylpyrrole (2) afforded coupling product 3 in
comparable yield (69%), while longer reaction time
(11 h) was required (Scheme 4A). Further reduction
of the amount of 2 to 5 equiv lowered the yield of
coupling product 3 (57%). This protocol could be
implemented in a gram scale of 1-Br (6 mmol)
without loss of the process efficiency (Scheme 4B).
The coupling reaction of 4’-chloroacetophenone (1-
Cl) also proceeded to give 3 in 70% yield, but
required three times the reaction time presumably due
to the higher of bond dissociation energies of an aryl-
chloride bond (C6H5-Br, 80 kcal/mol; C6H5-Cl, 95
kcal/mol) (Scheme 4C).[25]
5
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10.1002/adsc.201901601
Advanced Synthesis & Catalysis
14%, respectively (Scheme 6A). This outcome
indicated that aryl radical A is formed and
subsequently undergoes rapid 5-exo cyclization[26] to
form alkyl radical B. Hydrogen atom abstraction of
alkyl radical B affords 33, whereas it also reacts with
pyrrole 2 and substrate 32 to form 34 and 35 (through
homolytic allylic substition), respectively.
The
reaction in the presence of 1,4-cyclohexadiene as a
hydrogen atom donor rendered the process more
selective and efficient, affording 33 in 80% yield as a
sole product (Scheme 6B). The cyclization of 36
with a 3,3-dimethylallyloxy tether similarly worked
well to afford dihydrobenzofuran 37 in 92% yield
(Scheme 6C).
a)
Scheme 5. Substrate scope.
All the reactions were
conducted using 0.5 mmol of aryl bromides (or chlorides)
Scheme 6. Radical clock experiments.
b)
in degassed DMSO (5 mL) under an Ar atmosphere.
c)
The yields from the reactions under 427 nm (max). The
yields from the reactions using the corresponding aryl
We next investigated other arenes as an alternative
coupling partner to N-methylpyrrole (2) (Scheme 7).
As for electron-rich arenes, we found that N-H
pyrrole (Ip = 8.2 eV) and 1,4-dimethoxybenzene (Ip =
7.9 eV) promote the cross-coupling to afford 38 and
39, respectively, in good yields.[27] On the other hand,
the reaction with benzene (Ip = 9.24 ev) was sluggish,
resulting in formation of biaryl 40 only in 31% yield
with incomplete conversion even by using larger
excess amounts (56 equiv) of benzene. Interestingly,
the reactions with 6-membered ring nitrogen-
heteroaromatic compounds, pyridine (Ip = 9.32 ev)
and pyrazine (Ip = 9.29 ev) proceeded slowly but
reached to the full conversion to afford 41 (as a
mixture of C2-, C3-, and C4 coupling adducts) and 42
in 77% and 54% yields, respectively.[28]
chlorides. d) 1H NMR yield based on the internal standard.
e)
f)
Recovery yields of the aryl bromides.
Due to
instability of the coupling product 10, the formyl group
was subsequently reduced by NaBH4 to convert it to the
corresponding alcohol. The isolated yield of the alcohol
was noted.
To capture transient aryl radical species, we
prepared radical clock substrate 32 having an alkoxy
tether ortho to the C-Br bond. The reaction of 32 in
the presence of N-methylpyrrole (2) under the present
optimized reaction conditions resulted in full
conversion within 21 h, affording three different
dihydrobenzofurans 33, 34, and 35 in 19%, 10%, and
6
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10.1002/adsc.201901601
Advanced Synthesis & Catalysis
a)
Scheme 7. Screening of arene coupling partners. All the
reactions were conducted using 0.5 mmol of 1-Br with 20
equiv of arenes (H-Ar) in degassed DMSO (5 mL) under
an Ar atmosphere. Isolated yields of the products were
b)
noted unless otherwise stated.
The reaction was
conducted in DMSO (2.5 mL) and benzene (2.5 mL). The
yield of 40 was measured by 1H NMR based on the
internal standard.
Finally, the reactivity of 3,5-dibromobenzonitrile
(43) toward photo-induced double arylation was
investigated (Scheme 8). The reaction of 43 in the
presence of N-methylpyrrole (2) could be controlled
by the reaction time: photo-irradiation of the mixtures
for 3 h provided mono-coupling product 44 in 63%
yield along with di-coupling adduct 45 in 10% yield,
whereas the reaction for 20 h allowed for formation
of di-coupling product 45 as a sole product in 63%
yield (Scheme 8A). Iterative coupling of 43 was also
achieved under the current protocol (Scheme 8B).[29]
Namely, treatment of 43 with 1,4-dimethoxybenzene
afforded mono-coupling adduct 46 in 40% yield.[30]
Subsequent photo-irradiation to the mixture of 46 and
N-methylpyrrole (2) gave 47 in 83% yield.
Scheme 8. Arylation of 3,5-dibromobenzonitrile (43).
Conclusion
This work demonstrated an operationally simple
protocol for aryl cross-coupling of electron-deficient
aryl bromides or chlorides with electron-rich
(hetero)arenes such as pyrroles and 1,4-
dimethoxybenzene, which is driven solely by violet
light. Photo-induced electron transfer to the transient
photo-excited aryl halides from electron-rich
(hetero)arenes is the key to enable the process, that
was supported by the nanosecond-transient
absorption spectroscopy.[31] It is our strong belief that
the leveraging of photo-induced electron-transfer to
drive light-induced bond-forging processes continues
to be exploited further in various synthetic
endeavours.
Experimental Section
A typical procedure (Table 1, entry 2): To a 25 mL
sealed tube was added 4’-bromoacetophenone (1-Br)
(0.498 mmol, 99.1 mg), K2CO3 (0.747 mmol, 103
mg) and N-methyl pyrrole (2) (9.96 mmol, 0.88 mL).
Degassed anhydrous DMSO (5 mL) was added and
the reaction was sparged with Ar. The tube was
sealed and irradiated by LED lamp (max = 390 nm)
for 6 h. The reaction mixture was then diluted with
Et2O and water. The aqueous layer was separated and
7
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10.1002/adsc.201901601
Advanced Synthesis & Catalysis
2017, 56, 8544; g) J. I. Bardagi, I. Ghosh, M.
Schmalzbauer, T. Ghosh, B. König, Eur. J. Org. Chem.
2018, 34; h) M. Neumeier, D. Sampedro, M. Májek, V.
A. de la Peña O’Shea, A. Jacobi von Wangelin, R.
Pérez-Ruiz, Chem. Eur. J. 2018, 24, 105.
extracted thrice with Et2O. The combined organic
layers were washed with brine, dried over MgSO4,
filtered and concentrated in vacuo. H NMR yield of
3 was recorded based on 1-Br using 1,1,2,2-
tetrachloroethane (0.19 mmol, 20 L) as an internal
standard. The resulting crude material was purified
by flash column chromatography (silica gel;
Hexane/EtOAc 95:5–90:10) to give 3 (0.378 mmol,
75.4 mg) in 76% yield as a white solid.
1
[7] a) H. Kim, H. Kim, T. H. Lambert, S. Lin, J. Am.
Chem. Soc. 2020, 142, 2087; b) .N. G. W. Cowper, C.
P. Chernowsky, O. P. Williams, Z. K. Wickens, J. Am.
Chem. Soc. 2020, 142, 2093.
[8] a) G. Nocera, A. Young, F. Palumbo, K. J. Emery, G.
Coulthard, T. McGuire, T. Tuttle, J. A. Murphy, J. Am.
Chem. Soc. 2018, 140, 9751; b) M. E. Budén, J. I.
Bardagí, M. Puiatti, R. A. Rossi, J. Org. Chem. 2017,
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Acknowledgements
This work was supported by funding from Nanyang
Technological University (for S.C. and E.K.L.Y), the Singapore
Ministry of Education (Academic Research Fund Tier 1: RG2/18
for S.C. and RG6/18 for E.K.L.Y), JSPS Grant-in-Aid for
Scientific Research (C) (19K0662) (for R.T.) and Uehara
Memorial Foundation (for R.T.).
performed using Research Center for Computational Science at
Okazaki, Japan.
[9] For reviews, see: a) Y. Wei, Q.-Q. Zhou, F. Tan, L.-Q.
Lu, W.-J. Xiao, Synthesis 2019, 51, 3021; b) C. G. S.
Lima, T. d. M. Lima, M. Duarte, I. D. Jurberg, M. W.
Paixão, ACS Catal. 2016, 6, 1389.
The computations were
[10] M. Tobisu, T. Furukawa, N. Chatani, Chem. Lett.
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8
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10.1002/adsc.201901601
Advanced Synthesis & Catalysis
[22] The slight enhancement of absorbance in the presence
of 5 and 20 equiv of 2 observed in Figure 2C is derived
simply from absorbance of 2.
[27] The reactions with furan and thiophene were sluggish,
providing the corresponding cross-coupling products in
very low yields (4% and 12% yields, respectively). See
the SI for details.
[23] The emission spectra of the mixture of 1a and 2
showed formation of a new peak around at 467 nm and
its intensity is enhanced with increase of the
concentration of 2 (see Figure S14). Since the ground
state absorption spectra of 1a do not shift in the
presence of 2 (Figure 2), we ascribe the newly formed
peak at 467 nm to the emission from an exciplex
formed between triplet state [1a]T1 and 2. Then, rapid
electron-transfer process might occur to form anion
radical [1a]•– as observed in Figure 1D, while direct
electron-transfer from 2 to [1a]T1 cannot be ruled out.
For details, see the Supporting Information. Further
investigation is underway to fully characterize the
dynamics of electron-transfer occurring after formation
of the exciplex.
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arenes of higher ionization potential (benzene, pyridine,
and pyrazine) proceed not via the electron-transfer
pathway, but probably via C-Br bond homolysis of
triplet state [1-Br]T1, that slowly forms aryl radical 1• .
ns-TA spectra of the mixture of 1-Br and benzene
displays a band clearly arising from the absorption of
the triplet state of 1-Br. See Figure S5 in the SI for
more details.
[29] Acetonitrile was better solvent than DMSO for this
iterative coupling (see the SI for details).
[30] Double coupling product was formed in 17% yield.
See the SI for details.
[24] No significant change of the profiles was observed on
the ns-TA spectra of 1-Br in the presence of K2CO3
and the mixture of 1-Br and 2 in the presence of K2CO3.
Both 2 and 3 did not display any ns-TA spectra when
excited at 355 nm. See Figures S2-S4 in the SI for
details.
[31] During the revision of this manuscript, it was
reported by Zheng that the coupling reactions of aryl
halides and N-methylpyrrole (and their derivatives) are
mediated by irradiation of blue LED light (455 nm)
even under aerobic conditions. The process is likely
triggered by photo-induced disproportionation of
polypyrroles to form a highly reducing anion radical of
N-methylpyrrole, which reduces aryl halides to
generate aryl radicals for ensuing biaryl coupling, see:
Z.-J. Li, S. Li, E. Hofman, A. H. Davis, G. Leem, W.
Zheng, Green. Chem. DOI: 10.1039/c9gc04248b.
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9
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Advanced Synthesis & Catalysis
FULL PAPER
Biaryl cross-coupling enabled by photo-induced
electron transfer
Adv. Synth. Catal. Year, Volume, Page – Page
Hirohito Hayashi, Bin Wang, Xiangyang Wu, Shi
Jie Teo, Atsushi Kaga, Kohei Watanabe, Ryo
Takita, Edwin K. L. Yeow,* and Shunsuke Chiba*
10
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