Photocatalytic Hydrogen-Evolution Cross-Couplings: Benzene C-H Amination and Hydroxylation

Article abstract of DOI:10.1021/jacs.6b05498

We present a blueprint for aromatic C-H functionalization via a combination of photocatalysis and cobalt catalysis and describe the utility of this strategy for benzene amination and hydroxylation. Without any sacrificial oxidant, we could use the dual catalyst system to produce aniline directly from benzene and ammonia, and phenol from benzene and water, both with evolution of hydrogen gas under unusually mild conditions in excellent yields and selectivities.

Full text of DOI:10.1021/jacs.6b05498

Subscriber access provided by UNIV OF NEW HAMPSHIRE
Communication
Photocatalytic Hydrogen-Evolution Cross-
Couplings: Benzene C-H Amination and Hydroxylation
Yi-Wen Zheng, Bin Chen, Pan Ye, Ke Feng, Wenguang
Wang, Qing-yuan Meng, Li-Zhu Wu, and Chen-Ho Tung
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.6b05498 • Publication Date (Web): 28 Jul 2016
Downloaded from http://pubs.acs.org on July 28, 2016
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
Journal of the American Chemical Society is published by the American Chemical
Society. 1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 5
Journal of the American Chemical Society
1
2
3
4
5
6
Photocatalytic Hydrogen-Evolution Cross-Couplings: Benzene C-H
Amination and Hydroxylation
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
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
1
,2†
1†
1,2
1
2
1
Yi-Wen Zheng , Bin Chen , Pan Ye , Ke Feng , Wenguang Wang , Qing-Yuan Meng , Li-Zhu
1
*
1,2*
Wu , Chen-Ho Tung
1
Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and
Chemistry & University of Chinese Academy of Sciences, Chinese Academy of Sciences. Beijing, 100190, P.R. China.
2
Key Lab of Colloid and Interface Chemistry of Ministry of Education, School of Chemistry and Chemical Engineer-
ing, Shandong University. Jinan, 250100, P.R. China.
Supporting Information Placeholder
ammonia (reaction 1) and phenol from the reaction of ben-
ABSTRACT: We present a blueprint for aromatic C-H func-
zene with water (reaction 2). An equivalent amount of hy-
drogen gas in both reactions was yielded as the sole byprod-
uct. These reactions were carried out at unusually mild con-
ditions, and aniline and phenol were produced in excellent
yields.
tionalization via combination of photocatalysis and cobalt
catalysis, and describe the utility of this strategy for benzene
amination and hydroxylation. Without any sacrificial oxidant,
we could use the dual catalyst system to produce aniline di-
rectly from benzene and ammonia, and phenol from benzene
and water with evolution of hydrogen gas under unusually
mild conditions in excellent yields and selectivities.
Scheme 1. Photocatalytic benzene C-H amination and
hydroxylation with hydrogen evolution
Aniline, phenol, and their derivatives are widely used in-
termediates for the manufacture of agrochemicals, pharma-
ceuticals, polymers, dyes and pigments, and optoelectronic
materials. Aniline is produced in industry by hydrogenation
of nitrobenzene that is prepared by nitration of benzene with
1
concentrated mixed acid . Reducing the nitro group use ei-
2
ther Béchamp (with Fe / HCl as a reducing system) or sul-
3
fide reduction (with H S or NaHS as a reducing agent) tech-
2
nology. These processes use stoichiometric reducing agents
and create large amounts of environmentally toxic waste.
Currently phenol is produced in industry by the cumene pro-
cess that involves three steps: propylation of benzene, autox-
The above synthetic reactions show significant atom-
economy and step-economy. These reactions can be regarded
as improved dehydrogenative cross-coupling reactions with
benzene as one partner and ammonia or water as another
partner. During the past decade the catalytic dehydrogena-
tive cross-couplings between two carbon-hydrogen (C-H)
bonds and between one C-H bond and one heteroatom-
hydrogen (X-H) bond, that build a carbon-carbon (C-C) and
a carbon-heteroatom (C-X) linkage, respectively, have be-
come a potential synthetic strategy to synthesize various
4
idation to cumene hydroperoxide, and Hock rearrangement .
These reactions are carried out under high temperature, high
pressure, and very-acidic conditions. The overall yield of
phenol from benzene is below 5%. In recent years, one-step
5
amination of benzene with ammonia producing aniline and
6,7
one-step oxygenation of benzene to phenol by using vari-
ous kinds of catalysts have been extensively studied. Howev-
er, such processes are often carried out under severe condi-
tions, and afford very low yields and poor selectivities of ani-
line and phenol. Evidently, it is highly desirable to develop
methods for amination and hydroxylation of benzene into
aniline and phenol respectively that are economically feasible
without toxic waste production, and are performed with high
chemoselectivity under mild conditions.
8
kinds of functional arenes . Compared with the conventional
cross-couplings where aryl halides are usually used as one
partner, such coupling reactions allow use of less functional-
ized reagents, thus reduce the number of steps to the target
9
molecule and minimize waste production . However, alt-
Herein we wish to report two dream chemical reactions:
one-step amination of benzene to aniline and one-step hy-
droxylation of benzene to phenol. As shown in Scheme 1,
aniline was produced from the reaction of benzene with
hough these reactions are termed as “dehydrogenative cross-
coupling”, hydrogen gas is not usually the byproduct. Such
reactions often involve the use of stoichiometric amount of
sacrificial oxidants such as peroxides, high-valent metals (Cu
1
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 2 of 5
9
salts, Ag salts), and iodine (III) oxidants . This leads to low
We began our investigation with the amination of benzene
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
atom-economy and possible generation of toxic wastes. Our
approach, namely hydrogen-evolution cross-couplings, com-
bines a photocatalyst with a metal cocatalyst to create a dual
by using a Boc-protected ammonia (Boc-NH , 2a, Boc: t-
2
butoxycarbonyl), an activated ammonia, as the amination
reagent (Scheme 3a). The reaction conditions were opti-
mized by irradiating the solution of benzene (1a, 40 mM), 2a
1
0
catalyst system . The former catalyst uses light energy as the
driving force for the cross-coupling, while the later catalyst
may capture electrons from the substrates and/or reaction
intermediates to reduce the protons eliminated from the C-H
+
–
(2 equiv), QuCN ClO (5 mol%) and Co(dmgBF ) (CH CN)
2
4
2
2
3
(3 mol%) in dry and degassed acetonitrile with a light of
wavelength longer than 300 nm at room temperature. The
1
1
1
and X-H bonds into molecular hydrogen . Thus, without use
of any sacrificial oxidant, the dual catalyst system may afford
progress of the reaction was followed by H NMR spectrosco-
py (fig. S1), and the reaction time profiles was shown in fig-
ure S2. The amount of produced hydrogen was measured by
GC analysis. Generally, after 5 h irradiation the conversion of
benzene was ca. 80%. The yield both of Boc-protected ani-
line (3a) and hydrogen gas based on the consumption of
benzene was close to 100%. Control experiments confirmed
that the photocatalyst, cobalt catalyst and light irradiation
are necessary for the amination to occur. It was noted that
solvent is critical for the amination reaction (table S1). Use of
methanol or N,N-dimethylformamide as solvent resulted in
no product formation. In contrast, use of the mixture of ace-
tonitrile and dichloromethane as solvent gave comparable
product yields as in acetonitrile in the same irradiation time.
We suggest that in the solvents able to coordinate to the
cross-coupling products and equivalent amount of H as sole
2
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
byproduct. This kind of cross-couplings are particularly use-
ful for the reactions that involve species sensitive to oxida-
tion.
Scheme 2. Proposed pathway for functionalization of
benzene
cobalt
catalyst,
the
acetonitrile
molecule(s)
in
Co(dmgBF ) (CH CN) complex might be replaced by the
2
2
3
2
solvents (fig. S3), and the generated complexes are inactive
for the catalysis of the proton reduction. Another possibility
for the inhibition of the amination in methanol or N,N-
dimethylformamide is that the excited state of the photo-
catalyst is quenched by the large amount of such solvents.
The substrate scope of the amination with 2a was also exam-
ined. Carbonyl-substituted benzenes and phenyl halides
could be smoothly aminated with high selectivities under the
above conditions (fig. S4).
Our design is outlined in Scheme 2. Here, an onium is
+
used as the photocatalyst (PC ). Upon excitation, the gener-
+
ated excited state(s) of photocatalyst (PC *) may undergo
single electron transfer from benzene to produce benzene
•
radical cation and photocatalyst radical (PC ). The later spe-
cies may give an electron to the metal cocatalyst (for exam-
III
II
ple, Co ) to produce Co and ground state photocatalyst
+
a
(
PC ), thus completing the photocatalysis cycle. The former
species reacts with an anionic nucleophile (X ) to give a
dienyl radical. This adduct may transfer an electron to Co
producing Co and dienyl cation, which upon deprotonating
Scheme 3. Photocatalytic amination of benzene .
–
II
I
I
affords the desired substituted benzene. The Co may use the
received two electrons in each catalyst turnover to reduce
the two protons eliminated from X-H and benzene C-H into
III
a molecule H and returns to Co , thus, completing the co-
2
balt catalysis cycle. The synergistic combination of photoca-
talysis and metal catalysis enables the direct installment of a
functional group (X) in the place of a C-H bond of benzene
and production of equivalent amount of H2.
The crucial step for the initiation of the hydrogen-
evolution cross-couplings is the electron transfer oxidation of
benzene. The one-electron oxidation potential of benzene is
1
2
high (Eox = 2.48 V vs. SCE in acetonitrile) , thus, the photo-
catalyst must have extremely strong oxidizing ability upon
excitation. Several photocatalysts able to oxidize benzene
have been reported, and we found that among them com-
a
λ > 300 nm, in CH3CN, ambinent conditions. Selectivity =
+
mercial available 1-methylquinolinum ion (QuH ) and 3-
yield / conversion.
+
cyano-1-methylquinolinum ion (QuCN ) [E = 2.46 and 2.72
red
7a
In the above photocatalytic reaction 3a is the sole amina-
tion product. Even at high conversion no further amination
products (multiaminobenzene) were detected. When 3a in-
stead of benzene was used as the starting material the photo-
catalytic reaction under the identical conditions could not
occur after prolonged irradiation. One can expect that the
V vs. SCE at excited state respectively , Scheme 1] performed
well. On the other hand, Co(dmgBF ) (CH CN) (dmg = di-
2
2
3
2
methylglyoximate, Scheme 1) was established to be an effi-
13
cient catalyst for reduction of protons to H . Thus, in this
2
+
–
+
–
work we select QuH ClO4 or QuCN ClO4 as the photocata-
lyst and Co(dmgBF ) (CH CN) as the metal cocatalyst for the
2
2
3
2
+
photoinduced electron transfer from 3a to QuCN excited
amination and hydroxylation of benzene.
state should occur, because the oxidation peak potential of
2
ACS Paragon Plus Environment

Page 3 of 5
Journal of the American Chemical Society
3
a is smaller than that of benzene (fig. S5). Indeed, 3a can
sumption of benzene (fig. S6). To evaluate whether this cata-
lyst system could be applied to large scale production of
phenol, a preparative gram-scale photocatalytic reaction was
also performed (see supplementary materials). After irradia-
tion for 26 h, the isolated yield of phenol was 41% and equiv-
+
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
quench the luminescence of QuCN . Possibly, the pair of 3a
cation radical and QuCN generated by the photoinduced
electron transfer undergoes rapid back electron transfer to
return the starting material. Such a mechanism has been well
precedented .
•
7
alent amount of H was obtained. The remainder of the mass
2
balance was attributed to unreacted benzene.
Boc-NH serves as the amination reagent in the above re-
2
action. Accordingly, an additional synthetic step was re-
quired to liberate the desired aniline, although such depro-
tection of the amine group can be easily pursued. Subse-
quently we carried out the amination of benzene directly
using either ammonia or an ammonium salt as the amination
reagents. We found that under the above optimized condi-
tions direct use of ammonia as the amination reagent does
not lead to the production of aniline. It has been well estab-
lished that coordination of ammonia to a transition metal
The origin of the hydroxyl group in phenol and molecular
hydrogen was confirmed by the experiments using benzene-
1
8
d and D O or H O as the starting materials (fig. S7). The
6
2
2
+
–
solution of benzene-d , water, QuCN ClO and the cobalt
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
6
4
catalyst in acetonitrile was irradiated. After the irradiation
was completed, the sample was analyzed by GC-MS and a
mass peak at m/z = 99 (phenol-d ) in the crude solution was
5
observed, and H / DH / D in the gas phase was detected by
2
2
GC. Similarly, H / DH / D was also detected in the reaction
2
2
14
15
ion or to BF3 would decrease the strength of the N-H
bonds of ammonia and cause a higher acidity of the protons.
Therefore such ammine-metal or ammine-BF3 complexes
might be able to aminate benzene. Thus, we first use hex-
aamminecobalt(III) chloride (2b) as an amination reagent
of benzene and D O. On the other hand, after irradiation of
2
18
the solution containing benzene, H2 O and the catalysts, the
18
produced phenol showed a mass peak at m/z = 96 (Ph OH).
These observations unambiguously indicate that water serves
as the source of oxygen atom in the produced phenol, and
one proton in the hydrogen molecule comes from benzene,
another proton from water. Fukuzumi and coworkers report-
ed their excellent results on photocatalytic oxygenation of
(
(
Scheme 3b, table S2). Irradiation of the solution of benzene
+
–
10 mM), 2b (0.2 equiv), QuH ClO4 (10 mol%) and
Co(dmgBF ) (CH CN) (3 mol%) in 10 mL acetonitrile for 10 h
2
2
3
2
7
resulted in ca. 16% conversion of benzene, and the yield of
aniline was ca. 89% based on the consumption of benzene.
The unreacted benzene could be quantitatively recovered.
Then, we explored whether a catalytic amount of cobaltous
acetate can activate ammonia (2c) for the amination reaction
benzene to phenol in the presence of an oxidant . The oxy-
gen atom in the product originates from the oxidant. Use
water as the source of oxygen atom to oxidize alcohols to
carboxylate salts and amines to amides by employing Ru
pincer complexes as catalyst has also been recently report-
1
6
(
Scheme 3c). We prepared the solution of benzene (10 mM),
ed . However, these reactions do not concern with arene
hydroxylation and amination, and are not photocatalytic
reactions. To our knowledge, our above work is the first re-
port for the reaction of benzene with water producing phe-
nol and hydrogen gas under mild conditions.
+
ammonia (0.6 equiv), QuH (10 mol%), Co(AcO) (10 mol%),
2
dmgH (5 mol%) and BF ·Et O (5 mol%) in 10 mL of dry ace-
2
3
2
tonitrile. We believe that the later three components can
produce Co(dmgBF ) (CH CN) with the solvent (see sup-
2
2
3
2
plementary materials), and the excess of Co(AcO) can form
2
a
complex
with
ammonia.
The
as-generated
14
Table 1. Scope of photocatalytic hydroxylation of
arenes.
Co(dmgBF ) (CH CN) and the cobalt-ammonia complex
2
2
3
2
can serve as the cocatalyst and amination reagent respective-
ly (table S3). Irradiation of the above prepared solution for 10
h led to 30% conversion of benzene. The yield of aniline was
ca. 90%, and that of hydrogen was quantitative. We found
that use of excess of ammonia led to low conversion, possibly
H
mol% QuCN+
OH
5
3
mol% Co(dmgBF2)2(CH3CN)2
R + H O
R
+ H2
2
> 300 nm, CH3CN, ambient conditions
1
1
a - 1i
.0 equiv 10 equiv
4
5a - 5i
+
due to the quenching of the excited QuH by ammonia. In-
O
O
deed, addition of ammonia to the solution with six portions
each of 0.2 equiv could improve the conversion of benzene to
over 40% under identical conditions and the yield of aniline
and hydrogen remained no changes. Subsequently we use
OH
5
a
HO
5b
HO
5c
9
0% conv., 100% select. 58% conv., 100% select. 34% conv., 99% select.
(o : m : p = 65 : 11 : 24) (o : m : p = 57 : 14 : 28)
catalytic amount of BF to activate ammonia (Scheme 3d).
3
Irradiation of the solution of benzene (10 mM), ammonia
O
O
O
+
(
0.6 equiv), QuH (10 mol%), Co(dmgBF ) (CH CN) (3
2
2
3
2
OH
O
NH2
mol%) and BF ·Et O (5 mol%) in 10 mL acetonitrile for 5h led
3
2
HO
5d
HO
5e
HO
5f
to ca. 20% conversion of benzene, and the yield of aniline
based on the consumption of benzene was ca 80%. The un-
reacted benzene was quantitatively recovered. Evidently,
BF ·Et O with ammonia formed complex BF ·NH , thus am-
53% conv., 78% select.
49% conv., 97% select. 63% conv., 84% select.
(
o : m : p = 55 : 4 : 19)
(o : m : p = 57 : 17 : 23) (o : m : p = 55 : 12 : 17)
Cl
3
2
3
3
Cl
Cl
Cl
Cl
monia was activated.
2
HO
HO
The dual catalyst system was successfully extended to the
hydroxylation of benzene. Irradiation of the degassed solu-
tion of benzene (40 mM) and water (10 equiv) in acetonitrile
HO
1
5
g
5h
5i
6
5% conv., 97% select.
(o : p = 11 : 86)
53%conv., 99% select.
C1-OH : C2-OH = 92 : 7)
77% conv., 98% select.
(
+
–
with 5 mol% QuCN ClO4 as photocatalyst and 3 mol%
Co(dmgBF ) (CH CN) as proton reduction catalyst for 5 h
2
2
3
2
The data in parentheses denote the ratio of the yield of or-
tho-, meta- to para- isomers of hydroxylation products.
gave ca. 90% conversion of benzene, and the yields of phenol
(5a) and hydrogen were greater than 95% based on the con-
3
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 5
Corresponding Author
As in the photocatalytic amination, the produced phenol
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
can not undergo further photocatalytic reaction to yield di-
hydroxy-benzene even at high conversion. This is in contrast
to the cases of one-step oxygenation of benzene to phenol
where over-oxygenation occurs and the selectivity of phenol
production is low. To confirm this observation we carried out
the photocatalytic hydroxylation of phenol under the same
conditions. Indeed, after prolonged irradiation the starting
material was quantitatively recovered. Again, this selectivity
*lzwu@mail.ipc.ac.cn; chtung@mail.ipc.ac.cn
Author Contributions
†These authors contributed equally.
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
might originate from the fact that the photoinduced pair of
•
5
a cation radical and QuCN undergoes fast recombination to
We are grateful for financial supports from the Ministry of
Science and Technology of China (2013CB834505,
2013CB834804, and 2014CB239402), the National Natural
Science Foundation of China (21390404, 91427303 and
21402217), the Strategic Priority Research Program of the
Chinese Academy of Sciences (XDB17030200) and the Chi-
nese Academy of Sciences.
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
7
return to the starting material .
Since 2-hydroxy aromatic ketones and halides are useful
synthetic intermediates for the preparation of various oxy-
gen-containing and halogen-containing heterocycles and key
1
7
building blocks for certain drugs , we subsequently studied
the photocatalytic hydroxylation of several carbonyl-
substituted benzenes and phenyl halides by use of the above
optimized reaction conditions. A variety of substituted ben-
zenes such as phenyl ketones, benzoic acid, benzoate, ben-
zamide and halides (1b-1i) were transformed into the corre-
sponding phenol products (Table 1). Generally after 5 h irra-
diation the conversion of substituted benzenes could reach
to ca. 60%, and the yields of the substituted phenols and
molecular hydrogen were excellent based on the consump-
tion of the starting material. The hydroxylation products
involve ortho-, meta- and para- isomers, and among them
the ortho-hydroxylation products are dominated (55 ~ 65%)
for phenyl ketones, benzoic acid, benzoate and benzamide,
while for phenyl halides the para-hydroxylation products are
preferably formed. For benzamide (1f), in addition to hy-
droxylation product 5f, the amidation product (5f´, 14% yield,
see suporting infromation) was also isolated. We have pre-
REFERENCES
(
1) Downing, R. S.; Kunkeler, P. J.; van Bekkum, H. Catal. Today
997, 37, 121.
2) Liu, Y.; Lu, Y.; Prashad, M.; Repič, O.; Blacklock, T. J. Adv.
1
(
Synth. Catal. 2005, 347, 217.
(3) Ratcliffe, C. T.; Soled, S. L.; Singnorelli, A. J.; Mador, I. L. U.S.
patent. 4,326,081, Apr. 20, 1982.
(
(
4) Schmidt, R. J. Appl. Catal., A 2005, 280, 89.
5) (a) Del Pesco, T. W. U.S. Patent 4,001,260, Jan 04, 1977; (b) Del
Pesco, T. W. U.S. Patent 4,031,106, Jun 21, 1977; (c) Romero, N. A.;
Margrey, K. A.; Tay, N. E.; Nicewicz, D. A. Science 2015, 349, 1326; (d)
Yuzawa, H.; Yoshida, H. Chem. Commun. 2010, 46, 8854.
(6) (a) Niwa, S.-i.; Eswaramoorthy, M.; Nair, J.; Raj, A.; Itoh, N.;
Shoji, H.; Namba, T.; Mizukami, F. Science 2002, 295, 105; (b)
Morimoto, Y.; Bunno, S.; Fujieda, N.; Sugimoto, H.; Itoh, S. J. Am.
Chem. Soc. 2015, 137, 5867.
+
(
7) (a) Ohkubo, K.; Kobayashi, T.; Fukuzumi, S. Angew. Chem. Int.
pared the above samples but without photocatalyst QuCN .
Ed. 2011, 50, 8652; (b) Ohkubo, K.; Fujimoto, A.; Fukuzumi, S. J. Am.
Chem. Soc. 2013, 135, 5368.
Irradiation of such samples led to no conversion of the start-
ing materials. This expelled the possibility that the above
reactions are initiated by direct excitation of the substrates.
As aromatic ketones, acids, esters, amides and halides are
common scaffolds in drugs and natural products, this photo-
catalytic reaction can potentially open a facile route to rapid
access of hydroxylated analogues of a broad range of sub-
strates.
(
8) (a) Li, C.-J. Acc. Chem. Res. 2009, 42, 335; (b) Yeung, C. S.;
Dong, V. M. Chem. Rev. 2011, 111, 1215; (c) Chen, X.; Hao, X.-S.; Good-
hue, C. E.; Yu, J.-Q. J. Am. Chem. Soc. 2006, 128, 6790; (d) Thu, H.-Y.;
Yu, W.-Y.; Che, C.-M. J. Am. Chem. Soc. 2006, 128, 9048.
(9) Liu, C.; Zhang, H.; Shi, W.; Lei, A. Chem. Rev. 2011, 111, 1780.
(10) The successful merger of photocatalysis with metal catalysis
or organocatalysis in organic synthesis has been developed by Mac-
Millan, Doyle and coworkers, and Yoon and coworkers. See: (a)
Nicewicz, D. A.; MacMillan, D. W. C. Science 2008, 322, 77; (b) Zuo,
Z.; Ahneman, D. T.; Chu, L.; Terrett, J. A.; Doyle, A. G.; MacMillan,
D. W. C. Science 2014, 345, 437; (c) Du, J.; Skubi, K. L.; Schultz, D. M.;
Yoon, T. P. Science 2014, 344, 392.
To summarize, we have developed a new type of reactions,
namely hydrogen-evolution cross-coupling reactions, by
combination of a photocatalyst with a metal cocatalyst. By
this strategy in the absence of any oxidant we successfully
accomplish the amination and hydroxylation of benzene with
ammonia (or Boc-protected amine) and water as a partner of
the cross-couplings respectively. These reactions are accom-
panied by liberation of hydrogen gas. The yields and selectiv-
ities of anilines and phenols were excellent and the reactions
were carried out under unusually mild conditions. We hope
that this general method for the combination of activation of
arene C-H bonds with proton reduction will result in the
development of additional transformations.
(
11) Meng, Q.-Y.; Zhong, J.-J.; Liu, Q.; Gao, X.-W.; Zhang, H.-H.;
Lei, T.; Li, Z.-J.; Feng, K.; Chen, B.; Tung, C.-H.; Wu, L.-Z. J. Am.
Chem. Soc. 2013, 135, 19052.
(
12) Merkel, P. B.; Luo, P.; Dinnocenzo, J. P.; Farid, S. J. Org. Chem.
2009, 74, 5163.
(13) Xiang, M.; Meng, Q.-Y.; Li, J.-X.; Zheng, Y.-W.; Ye, C.; Li, Z.-J.;
Chen, B.; Tung, C.-H.; Wu, L.-Z. Chem. Eur. J. 2015, 21, 18080.
(14) Eßmann, R. J. Mol. Struct. 1995, 351, 91.
(15) (a) van der Vlugt, J. I. Chem. Soc. Rev. 2010, 39, 2302; (b)
Bauschlicher Jr, C. W.; Ricca, A. Chem. Phys. Lett. 1995, 237, 14.
(
16) (a) Gunanathan, C.; Milstein, D. Science 2013, 341; (b)
Khusnutdinova, J. R.; Ben-David, Y.; Milstein, D. J. Am. Chem. Soc.
ASSOCIATED CONTENT
2014, 136, 2998.
Supporting Information
(17) (a) Shan, G.; Yang, X.; Ma, L.; Rao, Y. Angew. Chem. Int. Ed.
012, 51, 13070; (b) Singh, P. P.; Thatikonda, T.; Kumar, K. A. A.;
2
Synthetic details and spectral data. This material is available
free of charge via the Internet at http://pubs.acs.org.
Sawant, S. D.; Singh, B.; Sharma, A. K.; Sharma, P. R.; Singh, D.;
Vishwakarma, R. A. J. Org. Chem. 2012, 77, 5823.
AUTHOR INFORMATION
4
ACS Paragon Plus Environment

Page 5 of 5
Journal of the American Chemical Society
1
TOC:
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
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
5
ACS Paragon Plus Environment