Visible-Light-Induced Organocatalytic Borylation of Aryl Chlorides

Article abstract of DOI:10.1021/jacs.9b00917

The preparation of arylboronates from unactivated aryl chlorides in a transition-metal-free manner is rather challenging. There are only few examples to achieve this goal by using ultraviolet irradiation. Based on the mechanistic understanding of the diboron/methoxide/pyridine reaction system, we achieved photoactivation of the in situ generated super electron donor and developed a visible-light-induced organocatalytic method for efficient borylation of unactivated aryl chlorides.

Full text of DOI:10.1021/jacs.9b00917

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Communication
Visible-Light-Induced Organocatalytic Borylation of Aryl Chlorides
Li Zhang, and Lei Jiao
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b00917 • Publication Date (Web): 29 May 2019
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Visible-Light-Induced Organocatalytic Borylation of Aryl
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Li Zhang and Lei Jiao*
Center of Basic Molecular Science (CBMS), Department of Chemistry, Tsinghua University, Beijing 10084, China
Supporting Information Placeholder
photoinduced borylation of aryl chlorides in the presence of
ABSTRACT: The preparation of arylboronates from
unactivated aryl chlorides in a transition-metal-free manner
is rather challenging. There are only few examples to
achieve this goal by using ultraviolet irradiation. Based on
3−
a rare-earth metal photocatalyst, CeCl
6
(Scheme 1b).
Despite these achievements, more efficient solutions to
chloroarene borylation are still in a high demand, and it
would be valuable to develop a new mode for chloroarene
borylation avoiding the use of expensive quartz reactor and
rare-earth metal photocatalyst. Herein, we report an
efficient visible-light-induced organocatalytic borylation
reaction of aryl chlorides developed based on mechanistic
study, which features broad substrate scope and operational
convenience (Scheme 1c).
the
mechanistic
understanding
of
the
diboron/methoxide/pyridine reaction system, we achieved
photoactivation of the in situ generated super electron
donor,
and
developed
a
visible-light-induced
organocatalytic method for efficient borylation of
unactivated aryl chlorides.
Recently, we have developed a radical borylation reaction
of aryl iodides and bromides employing diboron(4) as the
Arylboronates are widely utilized in organic synthesis,
materials science, and drug discovery as key building
17a
boron source and 4-phenylpyridine (1) as the catalyst.
17b
Further mechanistic study showed that,
the reaction
1-2
blocks. There is a constant quest for efficient synthetic
methods to access arylboronates from simple and readily
between B
produces
2
pin
2
and pyridine 1 in the presence of base
a
mixture of super electron donors (SEDs)
3-5
available starting materials.
Haloarenes are most
consisting of complexes 2 and 3 (Figure 1A). The SED
mixture activates haloarenes via single electron transfer (SET)
to form aryl radical as a key intermediate, which undergoes
borylation with the diboron(4) compound. With this
mechanistic information in mind, we hoped to realize the
commonly employed precursors to arylboronates. Over the
3
past decades, transition metal catalysis (e.g., Pd, Cu, Ni, Co,
4
and Zn ) enabled an efficient approach to arylboronates
employing iodo-, bromo-, and more challenging
chloroarenes as substrates, which featured broad substrate
scope and good functional group compatibility (Scheme 1a).
activation
of
chloroarenes
utilizing
the
B
2
pin /methoxide/pyridine reaction system by studying the
2
6-12
More recently, transition-metal-free borylation methods,
substituent effect of the SEDs. However, attempts to
improve the reduction ability of the SED mixture by tuning
the electronic nature of the substituents on pyridine 1
proved unsuccessful.
in
particular
photochemical
have attracted great research
borylation
8
-9,10f-g,11b-d,13-14
reactions,
interests and opened a new avenue to arylboronates.
However, most of these methods exhibit limited reactivities
compared with transition-metal-catalyzed reactions, which
often require the use of more reactive aryl iodides and
bromides as substrates. The use of unactivated chloroarenes
as substrates in transition-metal-free borylation reactions
remains a major challenge.
Considering the nature of aryl chlorides [e.g., for PhCl,
•
-
+/0 15
E
red(PhCl/PhCl ) = -3.28 V vs Fc
;
BDE(C-Cl) = 97.1
16
kcal/mol ], the cleavage of the C—Cl bond in a transition-
metal-free manner is rather difficult. As a breakthrough,
8a,d
8b,c
Li
and Larionov
independently reported the borylation
of aryl chlorides with a diboron(4) reagent under 254 nm
UV-irradiation; and most recently, Schelter1 realized a
4
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Ph
Ph
Ph
Scheme 1. Borylation of Aryl Chlorides
(A)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
B2pin2
H
(
a) Transition-metal-catalyzed borylation of aryl halides:
+
MeOK
+
N
H N
B
O
1
8-C-6
N
B
O
Me
+
OR
OR
K
O
O
Various transition-metal catalyst
THF, rt, 2 h
O
Ar
X = I, Br, Cl
(b) Photoinduced borylation of aryl chlorides:
X
Ar
B
(refs. 3-4)
K
HB(OR)2 or B2(OR)4
Ph
N
2
3
1
Mixture of super electron donors (SEDs)
cat. CeCl63-
UV light (365 nm)
glass reactor
Catalyst free
UV light (254 nm)
quartz reactor
OR
B
OR
Ar
Cl
or
Ar
B2(OR)4
B2(OR)4
(ref. 14)
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(ref. 8)
(c) Transition-metal-free borylation of aryl chlorides under visible light
(this work):
cat. 4-PhPy (1)
visible light (400 nm)
OR
B
OR
glass reactor
Ar
Cl
Ar
base, B2(OR)4
(
D)
Ph
Ph
Inspired by the principle that photoexcitation of an
electron donor (or acceptor) could enhance its reduction (or
oxidation) ability significantly,
investigate the photochemical properties of these SED
complexes, which remains unexplored and may lead to a
solution for chloroarene activation. The UV-vis spectrum
showed that ate complex 2 has an absorption band in the
H
4
00 nm LED
(10 W)
N
H N
B
18-20
MeO
4a (2 equiv.)
Cl
+
MeO
H
we intended to
O
K
THF, rt, 3 h
O
O
O
 = 9.3%
@ 24% conversion)
82% yield (GC)
(
2
·DME (1 equiv.)
Figure 1. Study on the reactivity of diboron-derived super
electron donors (SEDs). (A) The formation of SEDs from
diboron, methoxide, and 4-phenylpyridine (1); (B) The UV-
vis spectra of pure ate complex 2 and the SED mixture of
complexes 2 and 3; (C) Reactivity of the SED mixture for
3
00-500 nm region, while radical anion complex 3 exhibits a
characteristic absorption band in the 500-600 nm region
Figure 1B). Fluorescence spectroscopic study revealed that
(
the emission maximums of complexes 2 and 3 are at 547
and 621 nm, respectively. The observed absorption allows
for visible-light photoactivation of these SED complexes,
and the redox potentials of their excited states should be
significantly decreased as estimated by the Rehm-Weller
formalism (e.g., Eox(2 /2) = -1.11 V and Eox*(2 /2*) = -
3
photoexcitation, is able to undergo SET with more difficult
substrates, such as chloroarenes. Gratifyingly, this proposal
was proved feasible by a series of control experiments
haloarene
activation
under
photoexcitation;
(D)
Photoinduced activation of chloroarene by ate complex 2.
In order to figure out how the excited state of SED reacts
with chloroarenes, we performed fluorescence lifetime
measurement and luminance quenching experiment of ate
complex 2. The time-correlated single photon counting
21
•+
•+
+/0
.87 V vs Fc ). In principle, the SED mixture, after
(TCSPC) experiment showed that complex
2 has a
fluorescence lifetime (τ) of 6.1 ± 0.2 ns (Figure 2B). The
luminance quenching experiment with 1,4-dichlorobenzene
(4w) as the quencher revealed a linear relationship defined
by the Stern-Volmer equation, with a Stern-Volmer constant,
sv, of 8.6 M (Figure 2C). Thus the quenching rate
coefficient (k
and chloroarene 4w was calculated to be 1.4 ×10 M ·s ,
indicating a diffusion-controlled process. Given that the
formation of a donor-acceptor complex between 2 and the
chloroarene has not been observed, and the possibility of
the triplet excited state (T
process has been excluded (see the Supporting Information
for details), it is most likely that the S state of 2 is the
(
Figure 1C): without photoirradiation, the SED mixture was
able to slowly reduce 4-bromoanisole but not 4-
chloroanisole at room temperature; when a 520 nm LED was
applied as the light source (to excite complex 3), the
reduction of 4-bromoanisole took place more efficiently and
the reduction of 4-chloroanisole became observable; when
a 400 nm LED was used (to excite complex 2), both bromo-
and chloroarenes could be reduced efficiently. These
observations indicated that, the reduction abilities of both
-
1
K
q
) between the singlet excited state (S
1
) of 2
9
-1 -1
complexes
have
indeed
been
enhanced
after
1
) of 2 participating in the SET
photoexcitation, and complex 2 exhibits a superior reactivity.
A further experiment with independently prepared complex
2
important role of complex 2 in the activation of chloroarene
by photoinduced SET (Figure 1D). The reduction of 4-
chloroanisole to anisole was confirmed to proceed via the
aryl radical intermediate, since the reaction performed in
1
·DME under 400 nm photoirradiation emphasized the
reactive species that undergoes SET with the chloroarene
substrate (Figure 2A).
THF-d
8
as the solvent resulted in significant deuterium
incorporation in the 4-position of the anisole product (see
the Supporting Information).
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(
A)
Complex 2
Ground state)
borylation reaction of chloroarenes utilizing this reaction
(
1
2
3
4
5
6
7
8
9
Eox(2•+ /2) = -1.11 V
Eox*(2•+ /2*) = -3.87 V
m
o
d
e
.
T
h
e
r
e
f
o
r
e
Quench of 2* by
chloroarene via SET
hv (400 nm)
Table 2. Borylation of Aryl Chlorides
Fluorescence
emission
max  547 nm)
Complex 2*
(Singlet excited state)
ArCl
SET
[ArCl]
Ar
cat. 4-PhPy (1)
(
Cl
Ar
Cl
+
B2pin2
MeO
Ar
Bpin
CH3
MeONa, CH3CN
4
400 nm LED, rt, 12 h
5
MeO
H3C
Bpin
Bpin
Bpin
5c (90%)
Bpin
5
a (89%)
5b (83%)
(80%b for 1.88 g scale)
5d (90%)
(68%b for 1.37 g scale)
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
H3C
tBu
Bpin
Bpin H C
Bpin
5f (90%)
Bpin
5g (88%)
3
H3C
F
5e (92%)
5h (86%)
5l (72%)
Me
N
Me
Figure 2. Reaction of excited state ate complex with aryl
chloride. (A) Proposed reaction mechanism; (B)
Determination of the fluorescence lifetime of complex 2 by
time-correlated single photon counting (TCSPC); (C) Stern-
Volmer plot of the luminance quenching experiment with
Bpin
Bpin
O
Bpin
Bpin AcHN
5k (85%)
Bpin
5
i (74%)
5j (40%)
(78%b for 1.73 g scale)
O
O
Bpin
Bpin
NC
Bpin
MeO
EtO
5n (82%c)
NC
5o (80%)
5p (80%)
1,4-dichlorobenzene (1,4-DCB).
5m (90%)
Bpin
Table 1. Optimization of Reaction Conditionsa
N
Bpin
Bpin
Bpin
Bpin
5q (80%)
5r (78%)
5s (80%)
5t (63%)
Ph
N (1)
pinB
OR
OR
pinB
MeO
Cl
+
2
B pin
MeO
B
pinB
2
MeONa, CH3CN
00 nm LED, rt, Ar, 12 h
pinB
Bpin
4
N
4a
5a/5a'
S
Bn
5v (72%)
5u (61%)
5w (79%d)
5x (62%d)
Conv. (%)b
Yield (%)b
Entry Change from standard condtions
Bpin
1
2
3
4
5
6
7
8
9
None
99
96
33
91
99
40
66
92 (89)c
89
O
N
MeOK instead of MeONa
MTBE instead of CH3CN
DMSO instead of CH3CN
DMAc instead of CH3CN
365 nm LED instead of 400 nm LED
450 nm LED instead of 400 nm LED
5
y (80%)
5z (40%)
26
pinB
N
H
42
Application in sequencial diborylation:
52
I
Bpin
Bpin
1
(20 mol%)
1 (20 mol%)
B2hex2 (2.0 eq.)
B2pin2 (1.3 eq.)
35
MeOK (1.3 eq.)
MTBE, 85 °C, 12 h
Without light
MeONa (1.3 eq.)
MeCN, rt, 12 h
400 nm LED
53
5
Cl
Cl
Bhex
254 nm Hg lamp (28 W) instead of 400 nm LEDd
6
4aa
4ab (67%)
5ab (79%)
Without light
<1
<1
<1
<1
88
78
81
a
Reaction conditions: 4 (0.5 mmol, 1 equiv.), 1 (20 mol%),
MeONa (1.3 equiv.), and B pin (2.0 equiv.) in 1 mL of
CH CN, 10 W 400 nm LED, Ar atmosphere, rt, 12 h. Yields of
isolated products are reported in parentheses.
reaction was performed at 5 mmol scale and irradiated by a
0 W 400 nm LED at rt for 24 h. 1.3 equiv. of EtONa was
10
Without 4-phenylpyridine (1)
Reaction set up under aire
2
2
11
12
13
94
97
99
3
f
b
B2hex2 instead of B2pin2
The
Complex 2•DME (10 mol%) instead of 1
c
5
a
Reaction conditions: 4a (0.5 mmol, 1 equiv.), 1 (20 mol%),
MeONa (1.3 equiv.), diboron reagent (2.0 equiv.) in 1 mL of
d
used. 2.6 equiv. of MeONa and 4.0 equiv. of B
used.
2 2
pin were
b
solvent, 10 W LED, Ar atmosphere, rt, 12 h. Determined by
c
d
GC. Isolated yield. The reaction was performed in a quartz
we optimized the reaction conditions for the borylation of
chloroarene 4a using a mixture of B pin , methoxide, and
e
vessel.
The reaction was set up under air and then
2
2
f
performed in a sealed vessel.
glycolato)diboron.
B
2
hex
2
= bis(hexylene
pyridine 1 to generate complex 2 in situ under visible-light
irradiation (Table 1). Here only a catalytic amount of 1 was
used, since 1 could be regenerated after SET and thus acts
The above experimental findings served as a proof-of-
concept of the visible-light-induced electron transfer of SED
c o m p l e x 2 , w h i c h e n a b l e d t h e a c t i v a t i o n a n d
functionalization of chloroarenes via a radical pathway. In
this line, we hope to develop a synthetically useful
17b
as an organocatalyst.
It was found that, the optimal
reaction conditions include the use of a 10 W 400 nm LED
as the light source, MeCN as the solvent, and performing
the reaction at room temperature. MeOK and MeONa as the
methoxide source resulted in similar yields of the desired
borylation product 5a (entries 1 and 2), thus the inexpensive
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MeONa was employed in the synthetic reactions. Other
Scheme 2. Enabling Difficult Borylation Reactions
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
solvents, such as MTBE, DMSO, and DMAc, were proved
inferior (entries 3-5). Both UV (365 nm) and blue light (450
nm) could promote the reaction, albeit with decreased
yields (entries 6 and 7). The use of 254 nm irradiation (low-
Thermal method
1
(20 mol%), B pin2 (2.0 eq.)
2
MeOK (2.0 eq.), MTBE
85 °C, 12 h
Ar
X
or
Ar
Bpin
pressure Hg lamp) led to
a dramatically decreased
Photoinduced method
conversion (entry 8), probably due to various species
exhibiting intense absorption within this region, which
interfere with the efficient excitation of complex 2. Control
experiments revealed the essential role of both
photoirradiation and pyridine 1 on the observed reactivity
6
1 (20 mol%), B pin2 (2.0 eq.)
7
2
MeONa (1.3 eq.), MeCN
400 nm LED (10 W), rt, 12 h
Br
Br
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Aryl halide
substrates
H2N
Br
N
N
6
H
(
entries 9 and 10). Of special note, the reaction afforded a
a
6b
6c
0% yield
78% yield
similarly good yield when set up under air (entry 11), which
renders this method rather practical, because it avoids the
rigorous deoxygenation procedure. When bis(hexylene
Thermal method
10% yield
48% yield
0% yield
Photoinduced method
56% yield
glycolato)diboron
was
utilized
instead
of
The advantage of this visible-light-induced protocol lies
not only in the ability to borylate inert chloroarenes, but
also in greatly enhanced functional group tolerance
compared with the previously developed thermal conditions.
For instances (Scheme 2), 3-bromopyridine (6a), 6-
bromoindole (6b), and 4-bromoaniline (6c) produced very
poor yields of products under thermal borylation
bis(pinacolato)diboron, the corresponding borylation
product 5a’ could be obtained in a good yield as well (entry
12). Intriguingly, when a catalytic amount of complex 2·DME
was used in place of 1, the borylation reaction also
proceeded well (entry 13), indicating efficient regeneration
of the working SED under catalytic conditions.
17a
The reaction exhibited a broad substrate scope under the
optimized reaction conditions (Table 2). Chloroarenes with
either electron-donating or electron-withdrawing groups
reacted smoothly to afford arylboronates in good to
excellent yields (5a-p). Biphenyl, naphthyl, together with
some heteroaryl chlorides are also compatible substrates
and produced the borylation product in good yields (5q-v).
Diborylation products (5w and 5x) were obtained in good
yields when dichloroarenes are employed. The present
reaction showed excellent functional group tolerance, as
demonstrated by successful borylation of two drug
synthetic intermediates with chloroarene motifs (5y and 5z).
Notably, the reaction worked well with the substrates
bearing an NH group, enabling convenient borylation of
such substrates in a protecting-group-free manner (5l and
conditions,
while under photoinduced conditions
arylboronates were obtained in moderate to good yields.
We attribute this enhancement to the more favorable SET
process under photoexcitation, together with the mild
reaction conditions (room temperature).
In addition to chloroarenes, the present photoinduced
reaction system is competent for the activation of more
challenging substrate by SET. Fluorobenzene, with a C—F
16
bond dissociation energy of 127 kcal/mol, is a much more
inert substrate compared with chlorobenzene. The
borylation of fluoroarenes is also an important topic in
22
organic synthesis, and only one example of transition-
metal-free defluoroborylation promoted by UV-irradiation
9
was reported. We found that the present visible-light-
induced reaction system was able to realize the
defluoroborylation of fluorobenzene (8), with a satisfactory
yield (Scheme 3). This result indicates that, the
photoinduced reaction system with the in situ generation of
SED complex 2 serves as a general and practical single
electron reductant, where the excited state of complex 2
exhibits superior reactivity.
5z). Interestingly, sequential diborylation could be achieved
for dihaloarene 4aa by combined use of thermal and
photoinduced 4-phenylpyridine catalyzed borylation
reactions to afford differently substituted aryldiboronate
5ab. The borylation reaction could be performed at gram
scale in a glass Erlenmeyer flask by using a 50 W 400 nm
LED, affording comparable good yields of the borylation
products (5b, 5d, and 5k).
Scheme 3. Borylation of Fluorobenzene
1
(40 mol%)
B2pin2 (4.0 eq.)
MeONa (2.6 eq.)
F
Bpin
400 nm LED (10 W)
8
CH3CN, rt, 72 h
5c (67% yield)
In conclusion, based on the mechanistic understanding of
the pin /methoxide/pyridine reaction system, we
B
2
2
developed a highly efficient and practical organocatalytic
method for the borylation of unactivated aryl chlorides by
photoactivation of the in situ generated super electron
donor complex 2. The present method represents the first
example of organocatalytic activation of aryl chlorides (and
even fluorides) under visible-light irradiation, which
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highlights the power of photochemistry when merged with
super electron donor chemistry.
C–H bond functionalizations. Acc. Chem. Res. 2012, 45, 864. (d)
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Stahl, T.; Muether, K.; Ohki, Y.; Tatsumi, K.; Oestreich, M. Catalytic
generation of borenium ions by cooperative B–H cond activation:
the elusive direct electrophilic borylation of nitrogen heterocycles
with pinacolborane. J. Am. Chem. Soc. 2013, 135, 10978.
ASSOCIATED CONTENT
Supporting
Information.
Experimental
procedures,
(6) (a) Yamamoto, E.; Izumi, K.; Horita, Y.; Ito, H. Anomalous
reactivity of silylborane: transition-metal-free boryl substitution of
aryl, alkenyl, and alkyl halides with silylborane/alkoxy base systems.
J. Am. Chem. Soc. 2012, 134, 19997. (b) Uematsu, R.; Yamamoto, E.;
Maeda, S.; Ito, H.; Taketsugu, T. Reaction mechanism of the
anomalous formal nucleophilic borylation of organic halides with
silylborane: combined theoretical and experimental studies. J. Am.
Chem. Soc. 2015, 137, 4090. (c) Yamamoto, E.; Ukigai, S.; Ito, H.
Boryl substitution of functionalized aryl-, heteroaryl-and alkenyl
halides with silylborane and an alkoxy base: expanded scope and
mechanistic studies. Chem. Sci. 2015, 6, 2943.
(7) Zhang, J.; Wu, H.-H.; Zhang, J. Cesium carbonate mediated
borylation of aryl iodides with diboron in methanol. Eur. J. Org.
Chem. 2013, 2013, 6263.
(8) (a) Chen, K.; Zhang, S.; He, P.; Li, P. Efficient metal-free
photochemical borylation of aryl halides under batch and
continuous-flow conditions. Chem. Sci. 2016, 7, 3676. (b) Mfuh, A.
M.; Doyle, J. D.; Chhetri, B.; Arman, H. D. Larionov, O.V. Scalable,
metal-and additive-free, photoinduced borylation of haloarenes
and quaternary arylammonium salts. J. Am. Chem. Soc. 2016, 138,
additional information, and characterization data. This
material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
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Leijiao@mail.tsinghua.edu.cn
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We acknowledge the financial support from the National
Key Research and Development Plan (No. 2017YFA0505200)
and the National Natural Science Foundation of China (Nos.
21772110 and 21822304). We thank Prof. Ming-Tian Zhang
for helpful discussions and Ms. Han Li for assistance in the
time-resolved spectroscopic study. The technology platform
of CBMS is acknowledged for providing instrumentation.
2985. (c) Mfuh, A. M.; Nguyen, V. T. Chhetri, B.; Burch, J. E.; Doyle, J.
D.; Nesterov, V. N.; Arman, H. D.; Larionov, O. V. Additive-and metal-
free, predictably 1, 2- and 1, 3-regioselective, photoinduced dual C–
H/C–X borylation of haloarenes. J. Am. Chem. Soc. 2016, 138, 8408.
REFERENCE
(
d) Chen, K.; Cheung, M. S.; Lin, Z.; Li, P. Metal-free borylation of
electron-rich aryl (pseudo) halides under continuous-flow
photolytic conditions. Org. Chem. Front. 2016, 3, 875.
(
1) Boronic Acids: Preparation and Applications in Organic
Synthesis, Medicine and Materials, 2nd ed.; Hall, D. G., Ed.; Wiley-
VCH: Weinheim, Germany, 2011.
(
9) (a) Cheng, Y.; Mück-Lichtenfeld, C.; Studer, A. Transition
metal-free 1, 2-carboboration of unactivated alkenes. J. Am. Chem.
Soc. 2018, 140, 6221. (b) Cheng, Y.; Mück-Lichtenfeld, C.; Studer, A.
Metal-free radical borylation of alkyl and aryl iodides. Angew.
Chem., Int. Ed. 2018, 57, 16832.
(10) For transition-metal-free borylation reactions employing
nitrogen-containing aromatic compounds as starting materials, see:
(
2) (a) Suzuki, A. Organoborates in new synthetic reactions. Acc.
Chem. Res. 1982, 15, 178. (b) Miyaura, N.; Suzuki, A. Palladium-
catalyzed cross-coupling reactions of organoboron compounds.
Chem. Rev. 1995, 95, 2457. (c) Metal-Catalyzed Cross-Coupling
Reactions, 2nd ed.; Meijere, A. D., Ed.; Wiley-VCH: Weinheim,
Germany, 2004.
(3) For a review of transition-metal-catalyzed borylation of
haloarenes, see: Chow, W. K.; Yuen, O. Y.; Choy, P. Y.; So, C. M.; Lau,
C. P.; Wong, W. T.; Kwong, F. Y. A decade advancement of transition
metal-catalyzed borylation of aryl halides and sulfonates. RSC Adv.
(
a) Mo, F.; Jiang, Y.; Qiu, D.; Zhang, Y.; Wang, J. Direct conversion of
arylamines to pinacol boronates: a metal-free borylation process.
Angew. Chem., Int. Ed. 2010, 49, 1846. (b) Yu, J.; Zhang, L.; Yan, G.
Metal-free, visible light-induced borylation of aryldiazonium salts: a
simple and green synthetic route to arylboronates. Adv. Synth.
Catal. 2012, 354, 2625. (c) Zhu, C.; Yamane, M. Transition-metal-free
2013, 3, 12518.
(
4) For zinc-catalyzed borylation of haloarenes, see: (a)
3 2
borylation of aryltriazene mediated by BF ·OEt . Org. Lett. 2012, 14,
Nagashima, Y.; Takita, R.; Yoshida, K.; Hirano, K.; Uchiyama, M.
Design, generation, and synthetic application of borylzincate:
borylation of aryl halides and borylzincation of benzynes/terminal
alkyne. J. Am. Chem. Soc. 2013, 135, 18730. (b) Bose, S. K.; Fucke, K.;
Liu, L.; Steel, P. G.; Marder, T. B. Zinc-catalyzed borylation of primary,
secondary and tertiary alkyl halides with alkoxy diboron reagents at
room temperature. Angew. Chem. Int. Ed. 2014, 53, 1799. (c) Bose, S.
K.; Marder, T. B. Efficient synthesis of aryl boronates via zinc-
catalyzed cross-coupling of alkoxy diboron reagents with aryl
halides at room temperature. Org. Lett. 2014, 16, 4562. (d)Bose, S.
K.; Deißenberger, A.; Eichhorn, A.; Steel, P. G.; Lin, Z.; Marder, T. B.
Zinc-catalyzed dual C-X and C-H borylation of aryl halides. Angew.
Chem., Int. Ed. 2015, 54, 11843.
(5) For transition-metal-catalyzed C—H borylations, see: (a) Cho,
J.-Y.; Tse, M. K.; Holmes, D.; Maleczka, R. E.; Smith, M. R. Remarkably
selective iridium catalysts for the elaboration of aromatic C–H
bonds. Science 2002, 295, 305. (b) Mkhalid, I. A. I.; Barnard, J. H.;
Marder. T. B.; Murphy, J. M.; Hartwig, J. F. C–H activation for the
construction of C–B bonds. Chem. Rev. 2010, 110, 890. (c) Hartwig,
J. F. Borylation and silylation of C–H bonds: a platform for diverse
4560. (d) Qiu, D.; Jin, L.; Zheng, Z.; Meng, H.; Mo, F.; Wang, X.;
Zhang, Y.; Wang, J. Synthesis of pinacol arylboronates from
aromatic amines: a metal-free transformation. J. Org. Chem. 2013,
7
8, 1923. (e) Hu, J.; Wang, G.; Li, S.; Shi, Z. Selective C−N borylation
of alkyl amines promoted by Lewis base. Angew. Chem., Int. Ed.
018, 57, 15227. (f) Wu, J.; He, L.; Noble, A.; Aggarwal, V. K.
2
Photoinduced deaminative borylation of alkylamines. J. Am. Chem.
Soc. 2018, 140, 10700. (g) Xu, Y.; Yang, X.; Fang, H. Additive- and
photocatalyst-free borylation of arylazo sulfones under visible light.
J. Org. Chem. 2018, 83, 12831.
(
11) For transition-metal-free borylation reactions employing
activated ester compounds as starting materials, see: (a) Cheng, W.
M.; Shang, R.; Zhao, B.; Xing, W. L.; Fu, Y. Isonicotinate ester
catalyzed decarboxylative borylation of (hetero)aryl and alkenyl
carboxylic acids through N-hydroxyphthalimide esters. Org. Lett.
2017, 19, 4291. (b) Candish, L.; Teders, M.; Glorius, F. Transition-
metal-free, visible-light-enabled decarboxylative borylation of aryl
N-hydroxyphthalimide esters. J. Am. Chem. Soc. 2017, 139, 7440. (c)
Fawcett, A.; Pradeilles, J.; Wang, Y.; Mutsuga, T.; Myers, E. L.;
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Page 6 of 7
Aggarwal, V. K. Photoinduced decarboxylative borylation of
Melchiorre, P. Enhancing the potential of enantioselective
organocatalysis with light. Nature 2018, 554, 41. (i) Sideri, I. K.;
Voutyritsa, E.; Kokotos, C. G. Photoorganocatalysis, small organic
molecules and light in the service of organic synthesis: the
awakening of a sleeping giant. Org. Biomol. Chem. 2018, 16, 4596.
(20) For examples of photocatalysts that could reduce activated
aryl chlorides, see: (a) Ghosh, I.; Ghosh, T.; Bardagi, J. I.; König, B.
Reduction of aryl halides by consecutive visible light-induced
electron transfer processes. Science, 2014, 346, 725. (b) Discekici, E.
H.; Treat, N. J.; Poelma, S. O.; Mattson, K. M.; Hudson, Z. M.; Luo, Y.;
1
2
3
4
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6
7
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5
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5
6
carboxylic acids. Science, 2017, 357, 283. (d) Liu, W.; Yang, X.; Gao,
Y.; Li, C. J. Simple and efficient generation of aryl radicals from aryl
triflates: synthesis of aryl boronates and aryl iodides at room
temperature. J. Am. Chem. Soc. 2017, 139, 8621.
(
12) For transition-metal-free borylation reactions employing
miscellaneous substrates, see: (a) Ingleson, M. J. A Perspective on
direct electrophilic arene borylation. Synlett 2012, 23, 1411. (b)
Ingleson, M. J. Fundamental and applied properties of borocations.
Top. Organomet. Chem. 2015, 49, 39. (c) Warner, A. J.; Lawson, J. R.;
2
Fasano, V.; Ingleson, M. J. Formation of C(sp )-boronate esters by
Hawker, C. J.; de Alaniz, J. R. A highly reducing metal-free
0
1
2
3
4
5
6
7
8
9
0
1
2
3
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9
0
borylative cyclization of alkynes using BCl
3
. Angew. Chem., Int. Ed.
photoredox catalyst: design and application in radical
dehalogenations. Chem. Commun. 2015, 51, 11705. (c) Neumeier,
M.; Sampedro, D.; Majek, M.; de la Pena O'Shea, V. A.; Jacobi von
Wangelin, A.; Pérez-Ruiz, R. Dichromatic photocatalytic
substitutions of aryl halides with a small organic dye. Chem. - Eur. J.
2018, 24, 105. For example of photocatalyst that could reduce
unactivated aryl chlorides, see: (d) Yin, H.; Jin, Y.; Hertzog, J. E.;
Mullane, K. C.; Carroll, P. J.; Manor, B. C.; Anna, J. M.; Schelter, E. J.
The hexachlorocerate (III) anion: a potent, benchtop stable, and
readily available ultraviolet a photosensitizer for aryl chlorides. J.
Am. Chem. Soc. 2016, 138, 16266.
2015, 54, 11245. (d) Légaré, M.-A.; Courtemanche, M.-A.; Rochette,
É.; Fontaine, F.-G. Metal-free catalytic C–H bond activation and
borylation of heteroarenes. Science 2015, 349, 513.
(
13) (a) Jiang, M.; Yang, H.; Fu, H. Visible-light photoredox
borylation of aryl halides and subsequent aerobic oxidative
hydroxylation. Org. Lett. 2016, 18, 5248. (b) Hu, D.; Wang, L.; Li, P.
Decarboxylative borylation of aliphatic esters under visible-light
photoredox conditions. Org. Lett. 2017, 19, 2770.
(14) Qiao, Y.; Yang, Q.; Schelter, E. Photoinduced miyaura
borylation by a rare earth photoreductant: the hexachlorocerate (III)
anion. Angew. Chem., Int. Ed. 2018, 57, 10999.
(21) Rehm, D.; Weller, A. Kinetics of fluorescence quenching by
electron and H-atom transfer. Isr. J. Chem. 1970, 8, 259.
(
15) Pause, L.; Robert, M.; Savéant, J.-M. Can single-electron
transfer break an aromatic carbon−heteroatom bond in one step? A
novel example of transition between stepwise and concerted
mechanisms in the reduction of aromatic iodides. J. Am. Chem. Soc.
1999, 121, 7158.
(22) For recent examples on borylation reactions of aryl fluorides,
see: (a) Liu, X. W.; Echavarren, J.; Zarate, C.; Martin, R. Ni-catalyzed
borylation of aryl fluorides via C–F cleavage. J. Am. Chem. Soc. 2015,
137, 12470. (b) Niwa, T.; Ochiai, H.; Watanabe, Y.; Hosoya, T. Ni/Cu-
catalyzed defluoroborylation of fluoroarenes for diverse C–F bond
functionalizations. J. Am. Chem. Soc. 2015, 137, 14313. (c) Zhou, J.;
Kuntze-Fechner, M. W.; Bertermann, R.; Paul, U. S.; Berthel, J. H.;
Friedrich, A.; Du, Z.; Marder, T. B.; Radius, U. Preparing (multi)
fluoroarenes as building blocks for synthesis: nickel-catalyzed
borylation of polyfluoroarenes via C–F bond cleavage. J. Am. Chem.
Soc. 2016, 138, 5250. (d) Niwa, T.; Ochiai, H.; Hosoya, T. Copper-
catalyzed ipso-borylation of fluoroarenes. ACS Catal. 2017, 7, 4535.
(e) Lim, S.; Song, D.; Jeon, S.; Kim, Y.; Kim, H.; Lee, S.; Cho, H.; Lee, B.
C.; Kim, S. E.; Kim, K.; Lee, E. Cobalt-catalyzed C–F bond borylation
of aryl fluorides. Org. Lett. 2018, 20, 7249.
(16) The bond dissociation energy (BDE) data were taken from
the
http://ibond.chem.tsinghua.edu.cn or http://ibond.naikai.edu.cn.
17) Zhang, L.; Jiao, L. Pyridine-catalyzed radical borylation of aryl
Internet
Bond-energy
Databank
(iBond),
see:
(
halides. J. Am. Chem. Soc. 2017, 139, 607. (b) Zhang, L.; Jiao, L.
Super electron donors derived from diboron. Chem. Sci. 2018, 9,
2711.
(
18) (a) Turro, N. J.; Ramamurthy, V.; Scaiano, J. C. Modern
molecular photochemistry of organic molecules; Wiley Online Library:
New York, 2012. (b) CRC Handbook of Organic Photochemistry and
Photobiology, 3rd ed.; Griesbeck, A., Ghetti, F., Oelgemöller, M., Eds.;
CRC Press: Boca Raton, FL, 2012.
(
19) For selected examples of photoactivated super electron
donors as reducing agents, see: (a) Cahard, E.; Schoenebeck, F.;
Garnier, J.; Cutulic, S. P. Y.; Zhou, S.; Murphy, J. A. Electron transfer
to benzenes by photoactivated neutral organic electron donor
molecules. Angew. Chem., Int. Ed. 2012, 51, 3673. (b) Doni, E.;
O’Sullivan, S.; Murphy, J. A. Metal-free reductive cleavage of
benzylic esters and ethers: fragmentations result from single and
double electron transfers. Angew. Chem., Int. Ed. 2013, 52, 2239. (c)
O’Sullivan, S.; Doni, E.; Tuttle, T.; Murphy, J. A. Metal-free reductive
cleavage of C-N and S-N bonds by photoactivated electron transfer
from a neutral organic donor. Angew. Chem., Int. Ed. 2014, 53, 474.
For an example of photoactive charge transfer complexes
containing pyridine-boron structure, see: (d) Lima, F.; Kabeshov, M.
A.; Tran, D. N.; Battilocchio, C.; Sedelmeier, J.; Sedelmeier, G.;
Schenkel, B.; Ley, S. V. Visible light activation of boronic esters
enables efficient photoredox C(sp2)—C(sp3) cross-couplings in
flow. Angew. Chem., Int. Ed. 2016, 55, 14085. For reviews
emphasizing
the
combination
of
photochemistry
with
organocatalysis, see: (e) Narayanam, J. M.; Stephenson, C. R. Visible
light photoredox catalysis: applications in organic synthesis. Chem.
Soc. Rev. 2011, 40, 102. (f) Prier, C. K.; Rankic, D. A.; MacMillan, D. W.
Visible light photoredox catalysis with transition metal complexes:
applications in organic synthesis. Chem. Rev. 2013, 113, 5322. (g)
Skubi, K. L.; Blum, T. R.; Yoon, T. P. Dual catalysis strategies in
photochemical synthesis. Chem. Rev. 2016, 116, 10035. (h) Silvi, M.;
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