Cross-coupling hydrogen evolution reaction in homogeneous solution without noble metals

Article abstract of DOI:10.1021/ol500534w

A highly efficient noble-metal-free homogeneous system for a cross-coupling hydrogen evolution (CCHE) reaction is developed. With cheap, earth-abundant eosin Y and molecular catalyst Co(dmgH)₂Cl₂, good to excellent yields for coupling reactions with a variety of isoquinolines and indole substrates and H₂ have been achieved without any sacrificial oxidants. Mechanistic insights provide rich information on the effective, clean, and economic CCHE reaction.

Full text of DOI:10.1021/ol500534w

Letter
pubs.acs.org/OrgLett
Cross-Coupling Hydrogen Evolution Reaction in Homogeneous
Solution without Noble Metals
Jian-Ji Zhong, Qing-Yuan Meng, Bin Liu, Xu-Bing Li, Xue-Wang Gao, Tao Lei, Cheng-Juan Wu,
Zhi-Jun Li, Chen-Ho Tung, and Li-Zhu Wu*
Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry &
University of Chinese Academy of Sciences, the Chinese Academy of Sciences, Beijing,100190, P. R. China
S
* Supporting Information
ABSTRACT: A highly efficient noble-metal-free homogeneous
system for a cross-coupling hydrogen evolution (CCHE) reaction
is developed. With cheap, earth-abundant eosin Y and molecular
catalyst Co(dmgH)2Cl2, good to excellent yields for coupling
reactions with a variety of isoquinolines and indole substrates and
H2 have been achieved without any sacrificial oxidants.
Mechanistic insights provide rich information on the effective, clean, and economic CCHE reaction.
Scheme 1. Cross-Coupling Hydrogen Evolution in
Homogeneous Solution without Noble Metals
eveloping efficient and atom-economic methods for C−C
Dbond formation is always an important concern in
synthetic chemistry.1,2 The cross-dehydrogenative coupling
reaction3 is a desirable synthetic approach toward C−C bond
formation, as it does not require additional functionalization of
subcomponents. Reactions of this type often involve the use of
stoichiometric sacrificial oxidants, which leads to low atom
economy and possible generation of toxic wastes. A new type of
reaction, cross-coupling hydrogen evolution (CCHE) reaction,4
has recently appeared, which avoids the use of any sacrificial
oxidants and yields hydrogen gas (H2) as the sole byproduct.
By combining eosin Y and a graphene-supported RuO2
nanocomposite (G-RuO2)5 as a photosensitizer and a catalyst,
the CCHE reaction proceeds smoothly to afford the desired
cross-coupling products and H2 in quantitative yields under
visible light irradiation. This novel reaction offers a potential
solution for highly efficient, clean, and economical C−C bond
formation.
In an effort to expand our knowledge and to develop a new
system of the CCHE reaction, we replaced the noble metal
heterogeneous catalyst G-RuO2 with inexpensive molecular
catalysts. In this contribution, we report an elegant new
catalytic system for the CCHE reaction in a homogeneous
solution. Here, an earth-abundant Co(dmgH)2Cl2 (dmgH =
dimethylglyoximate) complex is used as a catalyst to capture
the electrons and protons eliminated from the C−H bonds of
the substrates (Scheme 1). For a systematic comparison of the
G-RuO2 system, eosin Y is employed as a photosensitizer to
initiate the cross-coupling of N-phenyl-tetrahydroisoquinolines
and indoles, a typical cross-coupling reaction under visible-light
catalysis.6,7
the reaction mixture was deaerated by bubbling nitrogen and
then irradiated by green LEDs (λ = 525 10 nm) at room
temperature. Significantly, 55% and 63% yields of the desired
cross-coupling product and H2, respectively, could be obtained
with no use of any sacrificial oxidants (Table 1, entry 1). And
the cross-coupling product and H2 are the only products
detected. Increasing the amount of Co(dmg)2Cl2 and eosin Y
resulted in a large improvement in both conversion and yield of
the reaction (Table 1, entries 2−5). When 3 mol % of eosin Y
and 8 mol % of Co(dmgH)2Cl2 were used, the conversion
approached 100% and the yields of the cross-coupling product
and H2 were achieved in yields of 94% and 98%, respectively.
When the CCHE reaction proceeded in H2O, however, only a
12% yield of the cross-coupling product and a 16% yield of H2
were obtained (Table 1, entry 6). Addition of an organic
solvent greatly enhanced the performance of the reaction
(Table 1, entries 5, 7, 8). Among various organic solvents,
CH3CN was the best for the CCHE reaction. H2O is also of
significance in the reaction. When the CCHE reaction was
carried out in CH3CN, a negligible amount of desired cross-
Our initial study focused on the cross-coupling of N-phenyl-
tetrahydroisoquinolines and indoles for their prevalent skeleton
in natural products.8 After 1 mol % of eosin Y and 5 mol % of
Co(dmgH)2Cl2 were added into a mixture of CH3CN and H2O
containing N-phenyl-tetrahydroisoquinoline 1a and indole 2a,
Received: February 19, 2014
Published: March 14, 2014
© 2014 American Chemical Society
1988
dx.doi.org/10.1021/ol500534w | Org. Lett. 2014, 16, 1988−1991

Organic Letters
Letter
a
quenched by Co(dmgH)2Cl2 to generate [eosin Y]•+ for the
oxidation of 1a. The other is that the photoexcited eosin Y
could be reductively quenched by 1a to produce [eosin Y]•−,
which delivers an electron to the Co(dmgH)2Cl2 catalyst for
proton reduction to H2. To determine the dominant reaction
pathway in the system, a flash photolysis investigation was
undertaken in terms of the rich spectroscopic property of eosin
Y.9 As shown in Figure 1a, immediately after a laser excitation
Table 1. Optimization of the Reaction Conditions
b
c
d
e
entry
EY
cat.
solvent
convn
H2 (%)
3a (%)
1
2
3
4
5
6
7
8
1%
1%
1%
3%
5%
3%
3%
3%
3%
5%
8%
10%
8%
8%
8%
8%
8%
8%
H2O/CH3CN
H2O/CH3CN
H2O/CH3CN
H2O/CH3CN
H2O/CH3CN
H2O
65
80
82
100
100
18
45
55
6
63
76
79
98
97
16
43
54
3
55
69
71
94
91
12
39
50
5
H2O/DMF
H2O/CH3OH
CH3CN
f
9
a
Reaction conditions: 0.1 mmol of N-phenyl-tetrahydroisoquinoline
1a, 0.2 mmol of indole 2a, corresponding eosin Y, and cat.
(Co(dmgH)2Cl2) were added, and the solution was strictly deaerated
and irradiated for 16 h by 525 nm green LEDs, with methane as the
b
c
d
internal standard. H2O/CH3CN 4:1. Corresponding to 1a. Yields
detected by gas chromatography using pure methane as an internal
Figure 1. (a) Transient absorption spectra observed after laser
excitation (λex = 532 nm) of system containing (1) eosin Y (1.0 × 10−5
M); (2) eosin Y (1.0 × 10−5 M), 1a (3.3 × 10−4 M); (3) eosin Y (1.0
× 10−5 M), 1a (3.3 × 10−4 M), Co(dmgH)2Cl2 (2.7 × 10−5 M). The
concentration ratio of the substrate is identical to that in the reaction.
(b) Spectroelectrochemical absorption spectrum of 1a•+ in CH3CN/
H2O by oxidation of 1a (1.0 × 10−5 M) at 0.90 V voltage relative to
NHE. (c and d) UV−vis absorption spectra of system containing 1a
(4.0 × 10−4 M), 2a (8.0 × 10−4 M), eosin Y (1.2 × 10−5 M),
Co(dmgH)2Cl2 (3.2 × 10−5 M) in H2O/CH3CN 4:1 before and after
irradiation by green LEDs (525 10 nm).
e
standard based on 1a. Yields detected by NMR using 4-nitroaceto-
f
phenone as an internal standard based on 1a. Co(dmgH)2pyCl
instead of Co(dmgH)2Cl2.
coupling product and H2 were detected (Table 1, entry 9).
When D2O instead of H2O was used as the solvent, D2 was
obtained as the only byproduct with no alteration of the
reaction efficiency (Scheme S1), possibly a result of a quick
exchange of H2O with the released proton from the substrate.
And the best ratio of H2O to CH3CN was found to be 4:1
(Table S1). Further experiments indicated that the conversion
of 1a was negligible when eosin Y or Co(dmgH)2Cl2 was
absent from the reaction mixture, and no conversion of 1a
could be detected if the reaction was conducted in darkness.
by 532 nm light, a strong negative bleach of the ground state
absorption of eosin Y at approximately 520 nm and the
characteristic absorption assigned to the triplet excited state
(3[eosin Y]*) at 560 nm were observed. When N-phenyl-
tetrahydroisoquinoline 1a was introduced into the solution of
eosin Y, a new absorption band, which is in accordance with the
eosin Y radical anion ([eosin Y]•−), appeared at 410 nm at the
4
Given that noble-metal G-RuO2 was replaced by the
inexpensive Co(dmgH)2Cl2 molecular catalyst, we compared
the two systems and found that the amount of eosin Y was
decreased from 20 to 3 mol % for the CCHE reaction in the
homogeneous solution, and simultaneously 1a could be
completely converted to the desired cross-coupling product
and H2 in a shorter reaction time but with higher yields (Table
1, entry 4). For the indole with an ester group that showed the
lowest reactivity in the G-RuO2 heterogeneous system,4 the
reactivity of this noble-metal-free homogeneous reaction
system enhanced four times (Scheme 3). Moreover, the
homogeneous reaction can be carried out in a mixture of
organic solvent and water. Therefore, it is possible to expand
the scope of water-insoluble substrates for the CCHE reaction.
The catalyst changed from G-RuO2 to Co(dmgH)2Cl2,
which resulted in greatly improved catalytic performance,
prompting us to shed light on the mechanism of the CCHE
reaction. For consistency regarding reaction conditions, all
subsequent mechanistic studies were performed under the
optimal conditions. Although no obvious change could be
detected in the UV−vis absorption spectrum of each
component, eosin Y, 1a, Co(dmgH)2Cl2, and indoles as well
as their mixtures, these spectra suggested that only eosin Y in
the reaction mixture could be excited by green LED light (SI,
Figure S1). In this situation, two reaction pathways are possible.
One is that the photoexcited eosin Y might be oxidatively
3
expense of the [eosin Y]* absorption at 560 nm. The result
suggested that the electron transfer from 1a to 3[eosin Y]* took
place. In contrast, introduction of Co(dmgH)2Cl2 into the
eosin Y solution with 532 nm laser irradiation resulted in no
change of the 3[eosin Y]* absorption (SI, Figure S2c). Clearly,
3
the reductive quenching pathway of the photoexcited [eosin
Y]* dominates the homogeneous catalytic system.
Further addition of Co(dmgH)2Cl2 into a mixture of eosin Y
and 1a in a 4:1 H2O/CH3CN solution led to a distinct
quenching of [eosin Y]•− upon laser excitation at 532 nm. The
lifetime of [eosin Y]•− changed from 39.8 to 4.3 μs indicating
the electron transfer from [eosin Y]•− to Co(dmgH)2Cl2.
Simultaneously, a new absorption with a maximum appeared at
370 nm in the transient absorption spectra. The emerged
absorption band is similar to that of 1a under oxidation
potential at 0.90 V versus NHE in CH3CN/H2O (Figure 1b).
The result indicated that the 1a•+ at 370 nm is generated by
electron transfer from 1a to the excited eosin Y. This is, to the
best of knowledge, the first time the N-phenyl-tetrahydro-
isoquinoline radical cation was observed directly in the cross-
coupling reactions. Importantly, monitoring the absorption
spectral change before and after irradiation provided evidence
of the formation of the reduced intermediates of Co-
1989
dx.doi.org/10.1021/ol500534w | Org. Lett. 2014, 16, 1988−1991

Organic Letters
Letter
a
(dmgH)2Cl2. Before irradiation, the absorption spectrum was
simply the sum of the individual components and eosin Y
showed the absorption in the visible light region. Upon
irradiation by green LEDs for 2 min, a characteristic absorption
appeared at 450 nm consistent with the formation of CoII
species as reported in the literature (Figure 1c). Prolonged
irradiation within 4 min led to new lower energy absorptions at
550−650 nm, in addition to the one at 450 nm (Figure 1d).
The new lower energy bands are identical to CoI species
reported in the literature, which is a crucial intermediate for H2
evolution.10
Scheme 3. Scope of Indoles
On the basis of the above observations, we proposed a
plausible mechanism for the CCHE reaction (Scheme 2). Upon
Scheme 2. Proposed Mechanism
a
Reaction conditions: 0.1 mmol of 1a, 0.2 mmol of 2, 4 mL of H2O, 1
mL of CH3CN, 2.04 mg of eosinY, 2.9 mg of Co(dmgH)2Cl2; the
solution is strictly deaerated, with pure methane as the internal
standard, and irradiated for 16−22 h by 525 nm green LEDs. b Yields
detected by 1H NMR using 4-nitroacetophenone as an internal
visible light irradiation, eosin Y is immediately excited to its
singlet excited state 1[eosin Y]* followed by a quick intersystem
3
crossing (ISC) to its triplet excited state [eosin Y]* with a
lifetime of 98.8 μs (SI, Figure S3a). Subsequent electron
c
standard based on 1a; isolated yields are given in parentheses.
Corresponding to 1a.
3
transfer from 1a to [eosin Y]* results in the formation of the
eosin Y radical anion, [eosin Y]•−, and amine radical cation
1a•+; the electron transfer rate constant (k1) from 1a to the
3
excited [eosin Y]* was estimated to be 3.76 × 109 M−1 s−1
3
according to the lifetime of [eosin Y]* with (0.8 μs) and
system, the yield of the cross-coupling product and H2 is greatly
enhanced in the homogeneous solution when the substituted
group is Br or ester in the indole skeleton. When N-phenyl-
tetrahydroisoquinolines with various substituted groups were
examined, good to excellent yields were also obtained (Scheme
4). As tabulated in Scheme 4, the steric hindrance seems not to
have a big impact on the final results, while the yield of the
cross-coupling product and H2 decreased when R6 was F, Cl, or
Br, respectively.
without (98.8 μs) 1a (SI, Figure S3b). The generated amine
radical cation 1a•+ releases a proton and is further oxidized to
generate an iminium intermediate, which can effectively react
with nucleophiles to afford the desired cross-coupling product.
The formed eosin Y radical anion ([eosin Y]•−), on the other
hand, delivers an electron to Co(dmgH)2Cl2 to regenerate
eosin Y to its ground state. Based on the lifetime alternation of
[eosin Y]•− from 39.8 to 4.3 μs (SI, Figure S3c, d), the rate of
electron transfer (k2) from [eosin Y]•− to Co(dmgH)2Cl2 was
determined to be 7.78 × 109 M−1 s−1. The cascade electron
transfer from substrate 1a to the excited 3[eosin Y]* to produce
[eosin Y]•−, and then from the reduced radical anion [eosin
Y]•− to Co(dmgH)2Cl2, is believed to be responsible for the
efficient CCHE reaction in the homogeneous solution. It is
suggested that the formation of H2 is protonation of CoI to
form a CoIII−H hydrid.10 H2 is generated by either protonation
of the CoIII−H hydrid, H2 elimination and reduction of CoIII to
CoII, or reduction of the CoIII−H hydrid to the CoII−H hydrid
followed by protonation to give H2 and CoII. The alternative
involves a reaction between two CoIII−H hydrids to form H2
and 2 molecules of CoII.
In summary, we have developed a noble-metal-free
homogeneous strategy for the CCHE reaction with no use of
any sacrificial oxidants under visible light irradiation. Using low-
cost, earth-abundant eosin Y and Co(dmgH)2Cl2 as a
photosensitizer and a catalyst, good to excellent yields of
cross-coupling products and virtual equivalents of H2 evolution
have been achieved without any sacrificial oxidants. The
homogeneous CCHE reaction is attractive because it can be
performed in a mixture of organic solvent and water, which
greatly expands the scope of substrates not soluble in water.
Mechanistic insights revealed that the efficient CCHE reaction
relies on the cascade electron transfer from substrate 1a to the
3
excited [eosin Y]* to generate the [eosin Y]•− radical anion,
Under the optimized conditions, various indole derivatives
were examined to show the generality of the CCHE reaction in
a homogeneous solution (Scheme 3). When the electron-
withdrawing or -donating groups were introduced at different
positions of indoles, the desired cross-coupling product with
concomitant emission of H2 could also be obtained in good to
excellent yields. In contrast to the reported heterogeneous
which delivers an electron to Co(dmgH)2Cl2 for proton
reduction to H2. Importantly, direct evidence of the formation
of cation radical 1a•+ was obtained for the first time in the
cross-coupling reaction by visible light catalysis and reduced
CoII and CoI species as intermediates, which greatly enriches
our knowledge for the development of cleaner, safer, and more
atom-economic CCHE reactions.
1990
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Organic Letters
Letter
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Scheme 4. Scope of Tetrahydroisoquinolines
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a
Reaction conditions: 0.1 mmol of 1a, 0.2 mmol of 2, 4 mL of H2O, 1
mL of CH3CN, 2.04 mg of eosinY, 2.9 mg of Co(dmgH)2Cl2. The
solution is strictly deaerated, with pure methane as the internal
b
standard, and irradiated for 16−22 h by 525 nm green LEDs. Yields
detected by 1H NMR using 4-nitroacetophenone as an internal
standard based on 1a; isolated yields are given in parentheses.
cCorresponding to 1a.
ASSOCIATED CONTENT
■
S
* Supporting Information
Experimental details and characterization of all compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(9) (a) Joselevich, E.; Willner, I. J. Phys. Chem. 1995, 99, 6903.
(b) Islam, S. D. M.; Konishi, T.; Fujitsuka, M.; Ito, O.; Nakamura, Y.;
Usui, Y. Photochem. Photobiol. 2000, 71, 675.
AUTHOR INFORMATION
Corresponding Author
(10) (a) Dempsey, J. L.; Brunschwig, B. S.; Winkler, J. R.; Gray, H. B.
Acc. Chem. Res. 2009, 42, 1995. (b) Artero, V.; Chavarot-Kerlidou, M.;
Fontecave, M. Angew. Chem., Int. Ed. 2011, 50, 7238. (c) Eisenberg, R.;
Lazarides, T.; McCormick, T.; Du, P.; Luo, G.; Lindley, B. J. Am.
Chem. Soc. 2009, 131, 9192.
■
*E-mail: lzwu@mail.ipc.ac.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support for this research from the Ministry of Science
and Technology of China (2013CB834804, 2014CB239402,
and 2013CB834505), the National Natural Science Foundation
of China (21390404, 21090343, and 91027041), and the
Chinese Academy of Sciences is gratefully acknowledged.
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