Cobalt-catalyzed cross-dehydrogenative coupling reaction in water by visible light

Article abstract of DOI:10.1021/ol503744a

By using catalytic amount of CoCl₂ with dmgH (dimethylglyoxime) as ligand to form a photosensitizer in situ, a highly selective, efficient, and environmentally benign visible light mediated cross-dehydrogenative coupling (CDC) reaction has been

Full text of DOI:10.1021/ol503744a

Letter
pubs.acs.org/OrgLett
Cobalt-Catalyzed Cross-Dehydrogenative Coupling Reaction in
Water by Visible Light
Cheng-Juan Wu, Jian-Ji Zhong, Qing-Yuan Meng, Tao Lei, Xue-Wang Gao, 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: By using catalytic amount of CoCl2 with dmgH
(dimethylglyoxime) as ligand to form a photosensitizer in situ, a
highly selective, efficient, and environmentally benign visible light
mediated cross-dehydrogenative coupling (CDC) reaction has been
developed in aqueous medium. The desired cross-coupling C−C bonds that involve Csp3 with Csp, Csp2, and Csp3, respectively,
were achieved exclusively in high yields without formation of any other byproduct.
there are no reports about visible light catalyzed CDC reactions
performed in water.
onstruction of C−C bonds has always been a research
Cfocus of organic chemists, and transition-metal-catalyzed
activation of C−H bonds is well-known to provide atom-
economic and efficient ways for such transformation.1 As one of
the most powerful C−H activation processes, cross-dehydro-
genative-coupling (CDC) reaction2 constructs C−C bonds
directly from two different C−H bonds under oxidative
conditions. The oxidation protocol involves metal catalysts
together with oxygen or organic oxidants. This straightforward
reaction avoids the prefunctionalization and defunctionalization
of substrates, which has been part of traditional synthetic
design, and has made considerable progress in the past
decades.3 In particular, the visible light4 catalyzed CDC
reaction5 has appeared at the forefront owing to its mild,
clean, and environmentally benign characteristics. Various
noble metal complexes based on Ir(III),5a Ru(II),5b Pt(II),5h
Au(III),5f,i and Pd(II)5j have been employed as photocatalysts
to initiate the cross-coupling reactions efficiently. However,
these catalysts were expensive and suffered complicated
synthesis. Developing inexpensive and easily available metal
complexes would be a superior choice and would meet the
requirements of green chemistry.
As an extension of our continuous research efforts to explore
greener and milder CDC reactions, we developed a new system
for the activation of C−H bonds mediated by visible light in
water in ambient conditions. During this reaction, one
cobaloxime complex generated in situ from earth-abundant
and cost-effective transition metal cobalt salts7 and dmgH
(dimethylglyoxime) was used as a photocatalyst instead of
traditional light-harnessing photocatalysts. Good to excellent
yields of the desired cross-coupling products of N-phenyl-
1,2,3,4-tetrahydroisoquinolines and indoles were obtained in
aqueous solution under visible light irradiation (Scheme 1).
Scheme 1. Cobalt-Catalyzed Cross-Dehydrogenative
Coupling Reaction in Water by Visible Light
On the other hand, it is noteworthy that most of the cross-
coupling reactions have been performed in organic solvents.
The use of water as a solvent for organic transformations has
attracted considerable attention because it not only offers
several “green chemistry” benefits but also accelerates the rate
and increases the selectivity of the reaction. To realize this type
of transformation in water featured with greenness, nontoxicity,
and low cost has yet to be explored. To date, only limited
examples utilizing water as the reaction medium have been
reported.6 Li et al. made use of copper bromide to catalyze a
cross-coupling reaction between two sp3 C−H bonds in
water.6b Our group3l realized an efficient aerobic CDC reaction
in water catalyzed by recyclable graphene-supported RuO2
nanoparticles. Despite advances, to the best of our knowledge,
Noticeably, the developed simple system herein could compete
with photocatalyzed CDC reactions based on traditional noble
metal complexes in yield as well as selectivity. On the other
hand, compared with traditional thermal CDC reactions that
were carried out in organic solvents, the established system still
maintained the efficiency in water, which satisfied the need of
modern organic chemistry.
Our preliminary studies focused on the cross-coupling of N-
phenyl-1,2,3,4-tetrahydroisoquinoline (1a) with indole (2a)
under the irradiation of blue LEDs (λmax = 450 nm) at room
temperature. To our delight, when the mixture containing
Received: December 29, 2014
© XXXX American Chemical Society
A
DOI: 10.1021/ol503744a
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Letter
catlytic amount of CoCl2 with dmgH (dimethylglyoxime) as
ligand and the substrates in CH3CN was irradiated under
visible light, the formation of the desired cross-coupling
product was observed in 40% yield (Table 1, entry 1). To
Information, Table S1, entry 4). Moreover, the yield would
achieve 95% if the reaction underwent under oxygen
atmosphere (Table S1, entry 5). In order to determine the
function of the molecular oxygen in the process, we studied the
active species of oxygen in the system by electron-spin
resonance (ESR)8 spectroscopy as shown in Figure 1. 2,2,6,6-
a
Table 1. Optimization of the Reaction Conditions
b
entry CoCl2 (mol %) dmgH (mol %)
solvent
CH3CN
yield (%)
1
2
3
4
5
6
7
8
9
16
16
16
16
16
16
16
8
32
32
32
32
32
32
32
16
8
40
DMF
none
trace
43
CH2Cl2
CH3OH
H2O/CH3CN
H2O/CH3CN
H2O
c
58
d
66
83
H2O
84
8
H2O
73
10
11
12
13
8
24
16
16
16
H2O
75
e
f
8
H2O
76
Figure 1. ESR measurements of (a) a solution in H2O/CH3CN of
CoCl2, dmgH without 1a in the presence of TEMP under the
irradiation of blue LEDs; (b) a solution in H2O/CH3CN of CoCl2,
dmgH with 1a in the presence of TEMP under the irradiation of blue
LEDs; (c) a solution in H2O/CH3CN of CoCl2, dmgH without 1a in
the presence of DMPO under the irradiation of blue LEDs; (d) a
solution in H2O/CH3CN of CoCl2, dmgH with 1a in the presence of
DMPO under the irradiation of blue LEDs.
8
H2O
95
g
8
H2O
96
a
Reaction conditions: 0.1 mmol of 1a, 0.3 mmol of 2a, corresponding
CoCl2, and dmgH were added in 1 mL of solvent, the solution was
b
irradiated under blue LEDs (λ = 450 nm) in air for 24 h. Yields
determined by 1H NMR using diphenylacetonitrile as an internal
c
d
standard. Volume ratio of H2O/CH3CN was 1:1. Volume ratio of
H2O/CH3CN was 1:0.5. 0.2 mmol of 2a was used. 0.4 mmol of 2a
was used. 0.5 mmol of 2a was used.
e
f
g
Tetramethylpiperidine (TEMP) was employed as a probe to
1
enhance the reaction efficiency, we tried to optimize the
reaction conditions. When the reaction was conducted in DMF
or CH2Cl2, negligible amount of the desired cross-coupling
product could be observed (Table 1, entries 2 and 3).
Compared with the reaction in CH3CN, a similar yield of
43% was obtained in CH3OH (Table 1, entry 4). Furthermore,
a different performance was shown when the reaction was
performed in different volume ratio of H2O/CH3CN mixture.
The increased ratio of H2O/CH3CN resulted in an improved
yield of the cross-coupling product (Table 1, entries 5−6). This
finding suggested the possibility of H2O as the green solvent.
Indeed, when the reaction was performed in H2O, the yield
achieved 83% (Table 1, entry 7). Afterward, we found that 8
mol % of CoCl2 and 16 mol % of dmgH were the optimal
amounts (Table 1, entries 8−10). Increasing the amount of
nucleophilic indole to 4 equiv resulted in the best yield of 95%
in the reaction (Table 1, entries 8 and 11−13). As a result, the
visible light mediated CDC reaction was able to efficiently
proceed in the optimized conditions, i.e., 8 mol % of CoCl2
with 16 mol % of dmgH in H2O, irradiated by blue LEDs for 24
h in aerobic conditions at room temperature. Control
experiments indicated that each component of the reaction is
critical to the reaction efficiency (Supporting Information,
Table S1, entries 1−4). Significantly, during the process, only
the desired cross-coupling product could be generated, and no
byproduct was detected.
trap O2, and 5,5-dimethyl-1-pyrroline N-oxide (DMPO) was
used to capture O2•−. No any signal was detected when the
mixture containing TEMP, CoCl2, and dmgH was irradiated by
blue LEDs, even if N-phenyl-1,2,3,4-tetrahydroisoquinoline
(1a) was present. There was no signal when DMPO was
added into the H2O/CH3CN solution containing CoCl2 and
•−
dmgH. However, a characteristic signal of O2 captured by
DMPO was clearly observed after addition of 1a. This finding
indicated that the addition of 1a resulted in photoinduced
electron transfer to generate O2•−, which was a crucial
intermediate in the reaction.
To understand the interaction, UV−vis absorption spectra of
the subcomponents and their mixture were monitored (Figure
2). After the mixture was stirred for 2 h in air, the absorption
spectra of the mixture of CoCl2 and dmgH in H2O/CH3CN
became similar to that of CoIII(dmgH)2Cl2, and the high-
resolution mass spectra have also proved the generation of
CoIII(dmgH)2Cl2 (Figure S1, Supporting Information). Based
on above results, we speculated that CoIII(dmgH)2Cl2
generated in situ was the catalyst in essence. To verify the
speculation, CoIII(dmgH)2Cl2 was used instead of CoCl2 and
dmgH in the reaction under the same condition and a yield of
98% could be achieved after 24 h (Supporting Information,
Table S1, entry 6). In addition, CoCl2 was found to be unable
to interact with dmgH to form CoIII(dmgH)2Cl2 in CH2Cl2 and
DMF (Figure S2, Supporting Information), leading to poor
reaction performance (Table 1, entries 2 and 3).
Molecular oxygen played an important role in this system.
None of the desired cross-coupling product was observed when
the reaction was carried out in N2 atmosphere (Supporting
On the basis of the above results, we proposed a plausible
mechanism shown in Scheme 2. CoCl2 together with dmgH in
B
DOI: 10.1021/ol503744a
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Letter
a
Scheme 3. Scope of Tetrahydroisoquinolines and Indoles
Figure 2. UV−vis absorption spectra of system: (a) CoCl2 (1.0 × 10−4
M) in H2O/CH3CN 1:1; (b) dmgH (2.0 × 10−4 M) in H2O/CH3CN
1:1; (c) mixture of CoCl2 (1.0 × 10−4 M) and dmgH (2.0 × 10−4 M)
in H2O/CH3CN 1:1; (d) mixture of CoCl2 (1.0 × 10−4 M) and dmgH
(2.0 × 10−4 M) in H2O/CH3CN 1:1 after irradiation under blue LEDs
in air for 2 h; (e) mixture of CoCl2 (1.0 × 10−4 M) and dmgH (2.0 ×
10−4 M) in H2O/CH3CN 1:1 after irradiation under blue LEDs in air
for 24 h; (f) CoIII(dmgH)2Cl2 (1.0 × 10−4 M) in H2O/CH3CN 1:1.
Scheme 2. Proposed Reaction Mechanism
air conditions resulted in the formation of CoIII(dmgH)2Cl2.
Upon irradiation by visible light, CoIII(dmgH)2Cl2 reached its
exicited state and then abstracted one electron from 1a to
generate 1a•+ and Co (II) intermediate.9 Subsequently, Co(II)
intermediate reacted with O2 to produce the superoxide radical
anion (O2•−) and regenerate CoIII(dmgH)2Cl2. O2•− abstracted
one proton from 1a•+ to create the HOO• radical, which
continued to capture a hydrogen atom to form H2O2.10 The
generated 1a• further lose one electron to afford iminium ion 2,
followed by nucleophile addition to give rise to the desired
product 3a.
With the understanding of the reaction mechanism, we
attempted to investigate the universality of the visible light
mediated cobalt-catalyzed CDC reaction in water. First, the
scope with respect to tetrahydroisoquinolines was examined
(Scheme 3, 3a−g,r). For both electron-withdrawing and
electron-donating groups, the desired coupling products could
be obtained in good to excellent yields. When tetrahydroiso-
quinoline was linked with electron-donating groups, the yield of
the product decreased slightly which may be due to the
electronic effect. The strong electron-withdrawing nitro group
would reduce the yield greatly (Scheme 3, 3r). Meanwhile, it
a
Reaction conditions: 0.1 mmol of 1, 0.4 mmol of 2, 0.008 mmol of
CoCl2, and 0.016 mmol of dmgH were added in 1 mL of water; the
solution was irradiated under blue LEDs (λ = 450 nm) in air for 24 h.
b
Yields determined by 1H NMR using diphenylacetonitrile as an
internal standard; isolated yields are given in parentheses.
can be seen that steric hindrance has no effect on the outcome
of this transformation. Furthermore, good to excellent yields
were also obtained by using a variety of substituted nucleophilic
indoles (Scheme 3, 3h−q). Note that indoles containing
electron-donating groups proceeded better than those with
electron-withdrawing groups which can be explained by the fact
that the electron-donating substituents could enhance the
nucleophilicity of the indoles. Significantly, the desired products
with halogen substituent on the rings were potential
intermediates for further functionalization. Other nucleophilic
substrates such as sp3 C−H of nitroalkane and dimethyl
malonate even sp C−H of phenylacetylene are also effective for
such transformation (Scheme S1, Supporting Information).
In summary, we have developed a highly selective, efficient,
and environmentally benign method for the visible light
C
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Letter
K.-T.; Vuorinen, A.; Pap
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ai, I.; Neuvonen, A. J.; Pihko, P. M. J. Am.
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By using earth-abundant and simple cobalt salt with dmgH as a
ligand to form a photosensitizer in situ, good to excellent yields
of the desired cross-coupling products could be achieved in
aerobic conditions at room temperature under visible light
irradiation. The catalytic process has no other byproduct
showing exclusive selectivity for the cross-coupling C−C bonds
formation of sp3 C−H with sp3 C−H, sp2 C−H, and sp C−H.
Moreover, the reaction is performed in water which is
environmentally benign. Such an approach enriches low cost
metal catalysis and represents a lower cost, milder, and greener
process for organic transformation.
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ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental details and characterization of all compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
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AUTHOR INFORMATION
Corresponding Author
■
*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, 91427303 and 21402217), the Key
Research Programme of the Chinese Academy of Sciences
(KGZD-EW-T05), and the Chinese Academy of Sciences is
gratefully acknowledged.
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