Aryl Ketones as Single-Electron-Transfer Photoredox Catalysts in the Nickel-Catalyzed Homocoupling of Aryl Halides

Article abstract of DOI:10.1002/ejoc.201601352

An intriguing photoredox system for the homocoupling of aryl halides is reported wherein thioxanthone catalyzes a single-electron transfer from an amine reductant to nickel.

Full text of DOI:10.1002/ejoc.201601352

A Journal of
Accepted Article
Title: Aryl Ketones as Single-Electron Transfer Photoredox Catalysts In Nickel Cata-
lyzed Homo-Couplings of Aryl Halides
Authors: Yusuke Masuda; Naoki Ishida; Masahiro Murakami
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201601352
Link to VoR: http://dx.doi.org/10.1002/ejoc.201601352
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European Journal of Organic Chemistry
10.1002/ejoc.201601352
COMMUNICATION
Aryl Ketones as Single-Electron Transfer Photoredox Catalysts In
Nickel Catalyzed Homo-Couplings of Aryl Halides
Yusuke Masuda, Naoki Ishida, and Masahiro Murakami*
Abstract: An intriguing photoredox system for homo-coupling of aryl
Light (CFL)
thioxanthone (10 mol %)
NiCl2(dtbbpy) (5 mol %)
i-Pr2NEt (0.40 mmol)
halides is reported wherein thioxanthone catalyzes single electron
transfer from an amine reductant to nickel.
MeO
OMe
MeO
Br
t-BuOH (5 mL),
ambient temp., 12 h
Photoredox catalysis emerged as a central theme of research in
synthetic chemistry[1] since the groups of MacMillan,[2] Yoon,[3]
Akita,[4] and Stephenson[5] each independently reported work on
1a
2a 87%
(0.20 mmol)
2+
the utility of Ru(bpy)3 in this context. Subsequent to these
seminal studies, transition metal complexes based on ruthenium
or iridium have been employed routinely as photoredox catalysts.
The use of more affordable earth-abundant metals such
copper,[6] chromium,[7] and iron[8] as photoredox catalysts would
be desirable. Utilization of organic dyes in place of transition
metal complexes also has been extensively explored.[9] However,
the cooperative use of such organic dyes in metal/photoredox
systems[1e,1g,1h,1i,9a,9h] remains significantly limited. If practical or
even industrial applications are to be considered, the
development of simple and effective low-molecular weight
organic photoredox catalysts should be addressed.
Aryl ketones possess an energetically low-lying * orbital.
Although a symmetric forbidden transition, upon absorption of a
photon, an electron in the n orbital can be transferred to the
vacant but energetically accessible * orbital (n → * excitation).
The initially formed singlet excited state undergoes rapid
intersystem crossing to the energetically lower triplet state,
which is relatively long-lived as relaxation to the ground state is
spin-forbidden. A fascinating property of the triplet excited state
resides in its ability to mediate single electron transfer or
hydrogen atom transfer to produce a highly reducing ketyl-type
intermediate.[10] Therefore, we expected aryl ketones might
serve as single-electron transfer photoredox catalysts,[11]
representing a simple and abundant alternative to transition
metal complexes and organic dyes. We now report that
inexpensive, commercially available thioxanthone acts as an
efficient photoredox catalyst for single-electron transfer in
cooperation with a nickel catalyst,[12] as illustrated in the
reductive homo-coupling reaction of aryl halides.
t-Bu
t-Bu
variation
yield of 2a / %
O
no light
0
0
0
0
N
N
no thioxanthone
no NiCl2(dtbbpy)
no i-Pr2NEt
S
Ni
Cl
Cl
thioxanthone
NiCl2(dtbbpy)
Scheme 1. Reductive Homo-Coupling of 1a with Ketone/Nickel Dual Catalysis.
promotes a reductive homo-coupling reaction of aryl halides. A
typical procedure is exemplified in Scheme 1. A mixture of 3-
bromoanisole (1a, 0.20 mmol), thioxanthone (0.02 mmol),
NiCl2(dtbbpy) (0.01 mmol), and i-Pr2NEt (0.40 mmol) in t-BuOH
(5.0 mL) was prepared in an ordinary Pyrex glass tube under a
nitrogen atmosphere. The tube was closed with a screw cap and
was irradiated with a household compact fluorescent lamp (CFL,
20 W) at ambient temperature for 12 h. A standard acid-base
extractive work-up followed by preparative thin-layer
chromatography furnished the biaryl 2a in 87% isolated yield. No
reaction took place under dark. Each of thioxanthone,
NiCl2(dtbbpy), and i-Pr2NEt was indispensable. The use of other
aryl ketones like acetophenone, benzophenone, and xanthone in
place of thioxanthone also furnished 2a albeit in lower yields.[15]
We propose a mechanism consisting of three redox cycles
for the cooperative system (Scheme 2). It initiates with Cycle I
for photoredox. The thioxanthone catalyst A (placed at the
bottom) absorbs a photon. The excited thioxanthone A* picks up
single electron from i-Pr2NEt to produce the ketyl radical B and
aminyl radical cation C.[16,17] The ketyl radical B reduces the
nickel(II) species (1/2 equiv) to the nickel(0) species (1/2
equiv)[18,19] and the thioxanthone catalyst A regenerates. Overall,
the thioxanthone play a role of a bridge to deliver single electron
from i-Pr2NEt to nickel(II).
When aryl halides or pseudohalides are treated with a
stoichiometric amount of a nickel(0) complex, a reductive homo-
coupling reaction occurs to give biaryls.[13] The use of
stoichiometric reductants such as zinc(0) and manganese(0)
enables corresponding nickel-catalyzed processes.[14] We found
that a cooperative system consisting of light, thioxanthone
(catalytic), nickel (catalytic), and i-Pr2NEt (stoichiometric)
Then, Cycle II for nickel redox follows. 3-Bromoanisole 1a
oxidatively adds onto the nickel(0) species to form the
arylnickel(II) complex D, which is located at the bisection of
Cycles II and III. The nickel(II) complex D dichotomizes into two
ways; one leading to nickel(II) dibromide (1/2 equiv) in Cycle II,
and the other leading to diarylnickel(II) E (1/2 equiv) in Cycle
III.[20] The nickel(II) dibromide is reduced by the ketyl radical B
back to nickel(0), completing Cycle II for nickel redox.
[a]
Y, Masuda, Dr. N. Ishida, Prof. M. Murakami*
Department of Synthetic Chemistry and Biological Chemistry
Kyoto University
The diarylnickel(II) species
E in Cycle III undergoes
Katsura, Kyoto 615-8510, Japan
reductive elimination. The coupling product 2a is thus produced
and simultaneously nickel(0) species is regenerated. It works on
another molecule of 3-bromoanisole 1a to reproduce the
arylnickel(II) species D, closing the Cycle III.
E-mail: murakami@sbchem.kyoto-u.ac.jp
Homepage: http://www.sbchem.kyoto-u.ac.jp/murakami-lab/
Supporting information for this article is given via a link at the end of
the document.
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European Journal of Organic Chemistry
10.1002/ejoc.201601352
COMMUNICATION
N
Et
i-Pr
i-Pr
C
O
[NiII]X2
Ar [NiII] Ar
1/2
(X = Cl or Br)
1/2
N
Et
i-Pr
E
i-Pr
S
B
O
*
Ar [NiII] Br
Cycle I
Cycle II
Cycle III
1/2
D
Ar Ar
S
2a
A*
O
1/2 [Ni0]
1/2 [Ni0]
S
Ar- = 3-MeO-C6H4-
1/2
1a
1/2
1a
Ar Br
Ar Br
Light
A
Photoredox Cycle
Nickel Redox Cycle
Homo-Coupling Cycle
Scheme 2. Proposed Mechanism Consisting of Three Catalytic Cycles.
A wide variety of aryl halides 1 were subjected to the
standard reaction conditions [1 (0.20 mmol), thioxanthone (0.02
mmol), NiCl2(dtbbpy) (0.01 mmol), i-Pr2NEt (0.40 mmol), t-BuOH
(5.0 mL), irradiation with a household CFL (20 W) at ambient
temperature for 12 h], and the results are listed in Table 1. p-
Tolyl and p-anisyl bromides gave the homo-coupling products
2b and 2c in 70 and 67% yield, respectively. Whereas the
reaction of 4-chlorotoluene was sluggish (14%), 4-iodotoluene
afforded the biaryl 2b in good yield. Aryl bromides having
electron-donating and -withdrawing substituents were both
suitable substrates (2d-2h). A potentially reactive boryl group on
the aromatic ring survived under the present reaction conditions
(2i). 2-Bromonaphthalene and 4-bromobiphenyl with extended
aromatic π-conjugation furnished the doubly extended biaryls 2j
(79%) and 2k (79%), respectively. 3-Bromothiophene also
coupled to furnish the 3,3'-bithiophene 2l (68%). Benzyl bromide
successfully participated in the reaction to afford 1,2-
diphenylethane 2m (84%), although alkyl bromides like
phenethyl bromide and n-octyl bromide failed to give the homo-
coupling products. Analogous reaction conditions were applied
to a cross-coupling reaction of 1a (0.20 mmol) with 1-iodooctane
(0.50 mmol). The desired cross-coupling product, 1-methoxy-3-
ocylbenzene was obtained in 17% yield and the major product
was the biaryl 2a (36%).
In conclusion, we report the reductive homo-coupling
reaction of aryl halides mediated by a cooperative catalytic
system consisting of light, thioxanthone, nickel, and i-Pr2NEt.
Very recently, A. Lei reported an analogous system for a
reductive cross-coupling reaction of aryl halides with alkyl
halides, in which an iridium complex cooperates with a nickel
catalyst as the single-electron transfer photoredox catalyst.[21]
Disclosed in our study is that even a simple and small organic
molecule can play the same role as an iridium complex vis-á-vis
single electron transfer from tertiary amines to nickel. This
finding has the potential to improve cost-effectiveness across
diverse photoredox-catalyzed processes.
Experimental Section
A photo-induced homo-coupling reaction of aryl bromide 1a: A
typical procedure: Inside a nitrogen-filled glove box, 3-bromoanisole 1a
(37.4 mg, 0.20 mmol), NiCl2(dtbbpy) (3.98 mg, 0.01 mmol, 5 mol%),
thioxanthone (4.3 mg, 0.02 mmol, 10 mol%) i-Pr2NEt (51.7 mg, 0.40
mmol, 2 equiv.), and t-BuOH (5 mL) were placed in a J-Young type
Schlenk tube. The tube was closed with a screw cap and was then taken
out of the glove box. The reaction mixture was irradiated with a CFL for
12 h at ambient temperature. After the irradiation, the reaction mixture
was quenched with sat. NH4Cl aq. and extracted with ethyl acetate (3
times). The organic layer was washed with water (3 times) and sat. NaCl
aq., and was dried over Na2SO4. The solvent was removed under the
reduced pressure. The residue was purified by preparative thin-layer
chromatography (hexane/dichloromethane = 1/1) to give biaryl 2a (18.6
mg, 0.18 mmol, 87% yield) as colorless oil.
Finally, we applied the coupling reaction to a flow system to
demonstrate the scalability. A suspension containing 1a (2.0
mmol), thioxanthone (0.10 mmol), NiCl2(dtbbpy) (0.20 mmol),
and i-Pr2NEt (4.0 mmol) in t-BuOH (50 mL) was pushed at the
rate of 3.0 mL/h into a FEP tube (internal diameter 1.0 mm,
length 3 m) wrapping around a cylindrical water-cooling jacket,
which was irradiated with three CFLs. After the standard
purification by column chromatography on silica gel, 2a was
obtained in 62% isolated yield.
Acknowledgements
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European Journal of Organic Chemistry
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COMMUNICATION
This work was supported in part by Grants-in-Aid for Scientific
Research (S) (15H05756) from MEXT and ACT-C program from
JST. Y.M. acknowledged JSPS fellowship for young scientists.
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European Journal of Organic Chemistry
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COMMUNICATION
Table 1. Scope.[a]
Light (CFL)
NiCl2(dtbbpy) (5 mol%)
thioxanthone (10 mol%)
i-Pr2NEt (0.40 mmol)
Ar
X
Ar Ar
t-BuOH (5 mL),
ambient temp., 12 h
1
2
(0.20 mmol)
MeO
OMe
OMe
Me
Me
MeO
OMe
t-Bu
t-Bu
2b
2c
MeO
2d
2e
67%
X = Cl 14%
X = Br 70%
X = I 72%
74%
84%
F3C
CF3
NC
CN
MeO2C
CO2Me
pinB
Bpin
2h
2i
2f
2g
62%
67%
84%[b]
52%
S
Ph
Ph
S
2m
84%
2l
68%
2k
2j
79%
79%
[a] Reaction conditions: aryl halide (0.20 mmol), NiCl2(dtbbpy) (0.010 mmol; 5.0 mol %), thioxanthone (0.020 mmol; 10 mol %), i-Pr2NEt (0.40 mmol; 2.0 equiv), t-
BuOH (5.0 mL), irradiated with a CFL (20W) at ambient temperature for 12 h. Aryl bromides are used otherwise noted. Isolated yields were shown. [b] i-Pr2NPh
was used instead of i-Pr2NEt, 24 h.
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European Journal of Organic Chemistry
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COMMUNICATION
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European Journal of Organic Chemistry
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Layout 2:
COMMUNICATION
Yusuke Masuda, Naoki Ishida, and
Masahiro Murakami*
Page No. – Page No.
Aromatic Ketone as Single-Electron
Transfer Photoredox Catalyst
Cooperating with Nickel Catalyst for
Homo-Coupling of Aryl Halides
An intriguing photoredox system for reductive homo-coupling of aryl halides is
developed. Thioxanthone is a key element carrying single electron from amine to
nickel.
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