Highly efficient aerobic oxidative hydroxylation of arylboronic acids: Photoredox catalysis using visible light

Article abstract of DOI:10.1002/anie.201107028

To shed light on: The title reaction allows the generation of a variety of functionalized phenols and analogues using [Ru(bpy)₃Cl ₂]·6 H₂O as the photocatalyst under very mild reaction conditions. This reaction not only incorporates an oxygen atom from molecular oxygen directly into the product, but also expands the application of visible-light photocatalysis. bpy=bipyridine. Copyright

Full text of DOI:10.1002/anie.201107028

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DOI: 10.1002/anie.201107028
Photochemistry
Highly Efficient Aerobic Oxidative Hydroxylation of Arylboronic
Acids: Photoredox Catalysis Using Visible Light**
You-Quan Zou, Jia-Rong Chen, Xiao-Peng Liu, Liang-Qiu Lu, Rebecca L. Davis,
Karl Anker Jørgensen,* and Wen-Jing Xiao*
The development of green and sustainable methods for
effective synthesis of fine chemicals is an important goal in
our society. During the last decade, visible-light photoredox
catalysis has shown great promise as a method to advance
these goals. As a result of its high natural abundance, benign
environmental impact, cleanliness, and sustainability,[1] pho-
tocatalysis using visible light is a reliable and powerful tool.[2]
In this context, there are several examples of its usefulness,
including asymmetric alkylation of aldehydes,[3] [2+2] cyclo-
addition of enones,[4] [3+2] cycloaddition of aryl cyclopropyl
ketones,[5] reductive dehalogenation,[3d,6] radical addition to
unsaturated bonds,[7] and coupling reactions.[8,9] Despite these
advances, oxidative reactions initiated by visible light are
largely unexplored. In 2003, Zen et al. reported a visible-light
photocatalytic reaction for the oxidation of sulfides into
sulfoxides.[10] Later, Zhao et al. oxidized alcohols to aldehydes
using visible light and dye-sensitized TiO2.[11] Recently, the
groups of Blechert and Wang[12] developed a metal-free
photooxidative system to achieve the oxidation of amines and
alcohols, and Jiao et al. described the use of a RuII polypyr-
idine complex and 4-methoxypyridine to promote the con-
version of a-aryl halogen derivatives into a-aryl carbonyl
compounds.[13]
which was generated from molecular oxygen, plays a key role
throughout the process. Based on the investigation of the
mechanism, we envisioned that this kind of highly active
species might have Lewis basicity and therefore react with the
appropriate acidic components. We report herein the realiza-
tion of this strategy for the direct aerobic oxidative hydrox-
ylation of arylboronic acids to aryl alcohols using visible-light
irradiation and air as the source of the terminal oxidant.
In this reaction, we envisioned that the superoxide radical
anion generated from the photoredox cycle could react with
arylboronic acids because of its Lewis acidity, which arises
from the vacant p orbital on the boron atom, followed by a
series of rearrangements to provide aryl alcohols (Scheme 1).
The molecular oxygen in air has been widely used as a
green oxidant in synthesis.[14] Consequently, the development
of visible-light photooxidative reactions using air as the
oxidant is highly desirable. We recently developed a visible-
light-induced oxidation/[3+2] cycloaddition/oxidative aroma-
tization sequence for dihydroisoquinoline esters and electron-
deficient alkenes or alkynes to construct pyrrolo[2,1-a] iso-
quinolines.[15,16] In this sequence, a superoxide radical anion,
Scheme 1. Concept of the visible-light-induced aerobic oxidative
hydroxylation of arylboronic acids.
It is well known that phenols serve as versatile intermediates
and building blocks in the chemical and pharmaceutical
industries, and many efficient and straightforward methods
have been established to successfully convert arylboronic
acids into phenols.[17] To the best of our knowledge, this is the
first example of oxidative hydroxylation of arylboronic acids
using a visible-light photocatalytic strategy.
The reaction of 4-methoxyphenylboronic acid (1a) with
[Ru(bpy)3Cl2]·6H2O (2 mol%; bpy = bipyridine) in the pres-
ence of Et3N (2.0 equiv) and air (open to air, without bubbling
air) in DMF under irradiation with visible light was used for
the screening process. To our delight, the reaction occurred to
give the desired 4-methoxyphenol (2a) in 90% yield after
48 hours (Table 1, entry 1). Encouraged by these results, a
series of control experiments was performed. In the absence
of any one of the reaction parameters/reagents, little or no
conversion was observed (Table 1, entries 2–8). These results
show that the photocatalyst, amine, air, and visible light are all
essential for the reaction and support the photocatalytic
model for this reaction.
[*] Y.-Q. Zou, Dr. J.-R. Chen, X.-P. Liu, Dr. L.-Q. Lu, Prof. Dr. W.-J. Xiao
Key Laboratory of Pesticide & Chemical Biology, Ministry of
Education, College of Chemistry, Central China Normal University
152 Luoyu Road, Wuhan, Hubei 430079 (China)
E-mail: wxiao@mail.ccnu.edu.cn
Prof. Dr. W.-J. Xiao
State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences
Shanghai 200032 (China)
Dr. R. L. Davis, Prof. Dr. K. A. Jørgensen
Center for Catalysis, Department of Chemistry, Aarhus University
8000 Aarhus C (Denmark)
E-mail: kaj@chem.au.dk
[**] We are grateful to the National Science Foundation of China (NO.
21072069 and 21002036) and the National Basic Research Program
of China (2011CB808600) for support of this research.
Next, we focused our attention on optimization of the
reaction conditions. A survey of solvents showed that the
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201107028.
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Table 1: Screening and control experiments.[a]
were also examined in DMF. Notably, it was found that the
redox reagents had a significant effect on this reaction. When
N,N-diisopropylethylamine was used, the reaction was com-
pleted within 28 hours and gave 2a in 93% yield (Table 2,
entry 7). In sharp contrast, the 4-methoxy-N,N-diphenylani-
line, which is often used in photoredox catalysis, proved
ineffective in this system (Table 2, entry 8). Finally, the effect
of different photocatalysts was explored; tris[2-phenylpyridi-
nato-C2,N]iridium(III) was shown to require longer reaction
times than [Ru(bpy)3Cl2]·6H2O (Table 2, entries 9 and 10
versus entries 2 and 7).
The scope of the light-induced photoredox catalytic
aerobic oxidative hydroxylation of arylboronic acids is
summarized in Table 3. Under the optimized reaction con-
ditions, a wide range of arylboronic acids were smoothly
oxidized to the corresponding aryl alcohols in good to
excellent yields. As shown in Table 3, arylboronic acids 1a–r
bearing electron-neutral, electron-donating, and electron-
withdrawing substituents were effectively converted into the
desired phenols and analogues. We found that the electron-
deficeint arylboronic acids reacted slightly faster than the
electron-rich ones (Table 3, entries 10–15 versus 3–9). More
importantly, the electron-rich phenols, which are difficult to
obtain from the traditional nucleophilic substitution of
arylhalides, can be easily generated using this photocatalytic
method (Table 3, entries 1, and 3–9).
Entry
Visible
light
Photo-
catalyst
Air
Et3N
Yield [%][b]
1
2
3
4
5
6
7
+
À
+
À
+
+
+
+
À
À
+
À
+
+
+
+
+
+
+
À
+
+
+
À
+
+
+
À
90
n.r.
n.r.
n.r.
trace
trace
trace
[a] Reaction conditions: 1a (0.50 mmol), [Ru(bpy)3Cl2]·6H2O (2 mol%),
Et3N (2.0 equiv), DMF (5 mL), 36 W fluorescence lamp irradiation, and
air for 48h. [b] Yield of isolated product. DMF=N,N’-dimethylform-
amide, n.r.=no reaction.
transformation was not very sensitive to the reaction media;
DMSO, DMF, CH3CN, MeOH, and EtOH were all suitable
for this reaction, and 2a was obtained in good to excellent
yield (Table 2, entries 1–5). DMF was found to be the most
efficient solvent, thus providing the highest yields in the
shortest time, whereas with H2O the yield of 2a decreased to
60% (Table 2, entry 6). The quenching reagents of amines
Perhaps more significantly, 1,4-phenylenediboronic acid
(1s) also proved to be a good substrate, thus generating
hydroquinone (2s) without loss in reaction efficiency. Using
photocatalytic reaction conditions similar to those described
above, 2s was obtained in 82% yield after 50 hours when
using an increased catalyst loading (4 mol%) and redox
reagent loading (4.0 equiv) [Eq. (1)].
Table 2: Optimization of reaction conditions.[a]
The substrate scope of this methodology has been
extended to the use of phenylboronic pinacol ester 1t,
which is a derivative of phenylboronic acid. To our delight,
the desired product 2b was isolated in 94% yield after
19 hours [Eq. (2)].
Entry
Photo-
Solvent
Amine
t [h]
Yield [%][b]
catalyst
1
2
3
4
5
6
7
8
9
C1
C1
C1
C1
C1
C1
C1
C1
C2
C2
DMSO
DMF
CH3CN
MeOH
EtOH
H2O
DMF
DMF
DMF
DMF
A1
A1
A1
A1
A1
A1
A2
A3
A1
A2
60
48
96
72
72
96
28
96
96
84
86
90
77
90
89
60
93
trace
89
To develop the metal-free version of this reaction, we
started to examined the feasibility of using organic
dyes.[3d,8d,11] Application of Acid Red 87 in the reaction of
1a under irradiation by visible light provided the hydroxy-
lated product 2a in 90% yield after 96 hours [Eq. (3)].
10
90
[a] Reaction conditions: 1a (0.50 mmol), photocatalyst (2 mol%), amine
(2.0 equiv), DMF (5 mL), 36 W fluorescence lamp irradiation, and air.
[b] Yield of isolated product. DMSO=dimethylsulfoxide.
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To obtain some insight into the mechanism of this
reaction, we carried out two 18O-labeling experiments
[Eqs. (4) and (5)] and some computational studies. The
HRMS analysis of the product shows that the hydroxy
oxygen atom of the product originates from molecular
oxygen rather than from water.[18,19]
Table 3: Visible-light-induced aerobic oxidative hydroxylation of aryl
boronic acids.[a]
Entry
Ar
t [h]
28
Yield [%][b]
93 (2a)
1
2
While a precise reaction mechanism awaits further study,
a plausible catalytic cycle is depicted in Scheme 2.[20] It is
proposed that molecular oxygen is first reduced to the
superoxide radical anion by the RuI/tripyridine complex.
The radical anion then reacts with boronic acid to generate
the intermediate A. The radical anion A then abstracts a
hydrogen atom from the triethyl ammonium radial cation to
form intermediate B.[21,8a] The formation of the hydroxylated
product occurs by rearrangement of B into C with subsequent
hydrolysis. However, the oxidative quenching cycle cannot be
excluded in this reaction system.[18,23]
28
81 (2b)
3
4
5
28
32
24
72 (2c)
72 (2d)
91 (2e)
6
7
8
24
28
24
94 (2 f)
77 (2g)
94 (2h)
To shed some light on the mechanism, a computational
study was undertaken. Quantum chemical computations were
applied to examine the mechanism of the conversion of the
intermediate B into C (Figure 1).[24] The rearrangement of B
9
48
69 (2i)
10
11
16
24
95 (2j)
71 (2k)
12
24
92 (2l)
13
14
16
24
95 (2m)
96 (2n)
Figure 1. Species involved in the conversion of B into C. All energies
are zero-point corrected electronic energies in kcalmolÀ1 and are
relative to B. Bond distances reported in ꢀngstroms.
15
16
17
24
72
72
94 (2o)
83 (2p)
87 (2q)
to C was found to be a concerted process with a barrier of
17.5 kcalmolÀ1 for phenyl boronic acid (1b). Substituent
effects were also examined computationally using models
containing p-nitrile (1m) or p-methoxy (1a) groups. In both
models, the substituent was shown to have only a small effect
on the barrier for rearrangement, as the transition-state
energies for 1m and 1a were calculated to be 16.7 and
18.9 kcalmolÀ1, respectively.
18
72
86 (2r)
To better understand the reactivity of the intermediate B
and explain why the reaction occurs through this tetrahedral
boron intermediate, we examined the molecular orbitals
involved in the transformation. In studying the HOMO-1 and
[a] Reaction conditions: 1 (0.50 mmol), [Ru(bpy)3Cl2]·6H2O (2 mol%),
iPr2NEt (2.0 equiv), DMF (5 mL), 36 W fluorescence lamp irradiation,
and air. [b] Yield of isolated product.
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antibonding orbital of the peroxide in the LUMO + 1. This
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the peroxygen atom and not the carbon–boron s bond. On
the basis of orbital interactions in B, it is clear that boron must
have a tetrahedral geometry for the rearrangement to occur.
In conclusion, we have developed a visible-light initiated
aerobic oxidative hydroxylation of arylboronic acids using air
as the oxidant. This new reaction protocol combines visible
light with air in a single reaction system and shows great
substrate tolerance providing rapid and efficient access to a
variety of functionalized phenols and analogues in a highly
concise fashion. Computational and experimental investiga-
tions indicate that the active intermediate is a boron peroxo
complex and that the aromatic fragment is transferred in a
concerted manner to one of the peroxygen atoms.
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Received: October 5, 2011
Published online: December 7, 2011
Keywords: boron · oxidation · photooxidation · ruthenium ·
.
synthetic methods
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[24] Calculations were performed with GAUSSIAN09. Geometries
were optimized without symmetry constraints at the B3LYP/6-
311G + (d,p)[25] level of theory in a solvent cavity (PCM) using
solvent parameters for DMF. See the Supporting Information for
the complete references on theoretical methods.
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[18] Please see the Supporting Information for details.
[19] During the preparation of this manuscript, Fukuzumi et al.
reported elegant work on the photooxygenation of benzene to
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[20] Another mechanism involving the formation and rearrangement
of an anionic bridged peroxy boron species was also explored
computationally. However, the barriers for rearrangement of
this intermediate proved to be too large (> 40 kcalmolÀ1) to be
considered reasonable for a reaction occurring at room temper-
ature. (See the Supporting Information for details.).
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