Photo-nickel dual catalytic benzoylation of aryl bromides

Article abstract of DOI:10.1039/c9cc04726c

The dual catalytic arylation of aromatic aldehydes by aryl bromides using UV-irradiation and a nickel catalyst is reported. The reaction product serves as a photocatalyst and a hydrogen atom transfer agent for this transformation.

Full text of DOI:10.1039/c9cc04726c

View Article Online
View Journal
ChemComm
Chemical Communications
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: T. E. Schirmer, A.
Wimmer, F. Weinzierl and B. Koenig, Chem. Commun., 2019, DOI: 10.1039/C9CC04726C.
Volume 54
This is an Accepted Manuscript, which has been through the
Number
January 2018
Pages 1-112
1
4
Royal Society of Chemistry peer review process and has been
accepted for publication.
ChemComm
Chemical Communications
rsc.li/chemcomm
Accepted Manuscripts are published online shortly after acceptance,
before technical editing, formatting and proof reading. Using this free
service, authors can make their results available to the community, in
citable form, before we publish the edited article. We will replace this
Accepted Manuscript with the edited and formatted Advance Article as
soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes to the
text and/or graphics, which may alter content. The journal’s standard
Terms & Conditions and the Ethical guidelines still apply. In no event
shall the Royal Society of Chemistry be held responsible for any errors
or omissions in this Accepted Manuscript or any consequences arising
from the use of any information it contains.
ISSN 1359-7345
COMMUNICATION
S. J. Connon, M. O. Senge et al.
Conformational control of nonplanar free base porphyrins:
towards bifunctional catalysts of tunable basicity
rsc.li/chemcomm

Please do not adjust margins
Page 1 of 5
ChemComm
View Article Online
DOI: 10.1039/C9CC04726C
COMMUNICATION
Photo-Nickel Dual Catalytic Benzoylation of Aryl Bromides†
Tobias Emanuel Schirmer,a Alexander Wimmer, a Florian Wolfgang Clemens Weinzierl a and
Burkhard König *a
Received,
Accepted
DOI: 10.1039/x0xx00000x
The dual catalytic arylation of aromatic aldehydes by aryl bromides
using irradiation and a nickel catalyst is reported. The reaction
product serves as photocatalyst and hydrogen atom transfer agent
of this transformation.
A) Classical Approaches for Diarylketon Synthesis
O
Friedel-Crafts-Acylation
FG
Addition of carbon nucleophiles
to carbonyl compounds
Photo redox catalysis has emerged into a powerful tool for C−H
activation.1-4 Particularly, merging photo- and nickel-catalysis
enabled the functionalization of a wide range of C−H bonds.5-9
As the field of photocatalysis develops, expensive iridium
catalysts are successively replaced by novel organic dyes.10, 11 At
the same time, long known photocatalysts such as
benzophenones regain interests due to their ability to act as
efficient triplet sensitizer or photoinduced hydrogen atom
transfer catalysts. 10,12, 13
FG = CO2H, COCl,
[M]
CN, CONR2,CO2R
M = Li, MgX, ZnX, etc
B) Catalytic Approaches for Diarylketon Synthesis
O
O
Y
X
Y
[Pd], [Ni],
[Co], [Rh]
X
CO
+
+
[Pd]
X = H, Cl, CN, CO2H, NR2,OR
Y = Hal, BF3K, BR2, OTf, [M]
In his recent work on dual catalytic sp3 C−H functionalization,
Martin demonstrated the efficiency of a carefully designed
benzophenone in dual catalytic transformations.14 A similar
approach was later independently reported by Hashmi15 and
Rueping,16 employing benzaldehyde and benzophenones,
respectively, as combined HAT-photocatalyst and sensitizer for
nickel catalysed sp3 C−H arylations. Besides their utility in recent
synthetic applications as well as classical photochemistry, diaryl
ketones are an ubiquitous motive in pharmaceuticals, making
their synthesis an attractive target of ongoing research.17
As non-catalytic approaches such as the Friedel-Craft acylation
often lack regioselectivity and the addition of organometallic
reagents to carbonyls either require prefunctionalization or
reoxidation (Scheme 1a), catalytic methods have been
continuously developed over the years.18, 19 Both different acyl
surrogates and aldehydes have been employed together with
transition metals such as palladium20-29 rhodium30, 31 nickel32-35
and cobalt36 to furnish benzophenones. The use of CO as
carbonyl source is likewise well established (scheme 1b).37, 38
Recent developments in photoredox catalysis allow to access
the acyl radical in a mild and selective manner (Scheme 1c).
However, photochemical methods for the synthesis of ketones
by C−H activation focused mostly on the coupling of aliphatic
aldehydes.9
C) Photocatalytic Approach for Diarylketon Synthesis
O
CO2H
O
O
SET
[Ir]
Ar-X
[Ni]
O
hv
HAT
H
D) This Work
O
O
Br
[Ni]
H
+
395 nm LED
insitu generation of the photocatalyst
Scheme 1 (a) Classical and (b) catalytic methods for the synthesis of diaryl ketones as
well as novel dual catalytic approaches (c and d).
To extend the catalytic approach to aromatic aldehydes, we
envisioned a nickel-based dual-catalytic methodology, which
exploits the ability of diaryl ketones to act as sensitizer and HAT-
catalysts.
We started our investigation with the coupling of
4-chlorobenzaldehyde (1a) with 4-bromo-benzonitrile (2a).
Gratifyingly, the respective ketone 3a was observed under
various conditions, revealing acetone as the optimal solvent,
(4,4'-dimethyl-2,2'-bipyridyl)nickel(II) bromide as the most
efficient precatalyst and sodium carbonate as best base during
the initial screening (Table 1).
a. Institute of Organic Chemistry, Faculty of Chemistry and Pharmacy, University of
Regensburg, D-93040 Regensburg (Germany) E-mail: burkhard.koenig@ur.de.
†Electronic Supplementary Information (ESI) available: experimental details,
characterization data and spectra of all compounds. See DOI: 10.1039/x0xx00000x
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 2 of 5
COMMUNICATION
Journal Name
Table 1 Optimization and control reactions a
View Article Online
DOI: 10.1039/C9CC04726C
O
O
A)
Na2CO3 (2 equiv.)
Ni(dmbpy)Br2 (5 mol%)
acetone (0.25 M)
Br
H
O
O
R
R
+
Na2CO3 (2 equiv.)
Br
Cl
Cl
H
Ni(dmbpy)Br2 (5 mol%)
acetone (0.25 M)
395 nm LED, 8h, 25 °C
1a
O
2
3
+
Cl
CN
Cl
CN
395 nm LED, 8h, 25 °C
1a
2a
3a
O
O
N
Entry
1
2
3
4
5
6
7
8
Deviation from standard condition
Yieldb [%]
93% (86%)c
40%
0%
Cl
Cl
Cl
Cl
CN Cl
Cl
Cl
Cl
Cl
OCF3
None
Ni(dtbbpy)Br2
DMSO
3a, 86% yield
3b, 48% yield
3c, 65% yield
O
O
O
N
S
MeCN
PhH
Cs2CO3
K2CO3
50%
8%
61%
71%
2%
8%
0%
0%
0%
N
Cl
Cl
Cl
Cl
N
3d, 57% yield
3e, 60% yield
3f, 59% yield
O
O
O
K2HPO4
9
no base
NiBr2 as catalyst
4,4'-dimethyl-2,2'-bipyridne as catalyst
CF3
CF3
CF3
S
F
10
11
12
13
14
15
O
O
3g, 65% yield
3i, 64% yield
3h, 78% yield
O
O
O
no catalyst
in the dark
55°C in the dark
455 nm
N
0%
0%
0%
Cl
CO2tBu
3j, 96% yield
3k, 40% yield
3l, 79% yield
CF3
O
O
O
a Unless otherwise noted, the reactions were carried out with 4-bromobenzonitrile
(0.5 mmol), 4-chlorobenzaldehyde (0.75 mmol), Na2CO3 (1.0 mmol) and
Ni(dmbpy)Br2 (0.025 mmol) in dry acetone (0.25 M) under irradiation with UV-LEDs
(395 nm) and under N2-atmosphere for 8 h at 25 °C. b Yield determined by
calibrated GC-FID analysis with 1,3,5-trimethoxybenzene as internal
standard. c Isolated yield after purification by column chromatography in
parentheses.
O
4a, 81% yield
4b, 56% yield
4c, 72% yield
B)
Unsuccessful Aryl Bromides
Br Br
Br
N
Br
Br
S
N
Ph
CF3
After performing the control experiments and confirming the
essential contribution of all reaction components to the product
formation, we explored the scope of this transformation.
The reaction of electron deficient substrates gave cyano-,
ester-, sulfonyl- and trifluoromethyl-substituted benzophenons
(3a, 3g, 3i, 3j, 3l) in good to excellent yields. Dihalogenated
ketons (3d, 3h) were obtained in moderate to good yields. The
reaction is not limited to phenyl bromides. For example,
benzothiazoyl ketone 3f was obtained in 59% yield (Scheme 2).
Heteroaryl ketones (3b, 3e, 3k) were formed from
bromopyridines and -pyrimidine in moderate yield. However,
neither 2-bromo-4-(trifluoromethyl)pyridine nor 2-bromo-
benzothiazole furnished significant amounts of product. The
same was observed for 4-bromobiphenyl, 2-bromotoluene and
9-bromophenanthrene.39 Using benzaldehyde as coupling
partner allowed benzoylation of bromobenzene and electron
rich aryl bromides in moderate to good yields (4a-c).
Scheme 2 (a) Aryl bromide scope. All reactions were carried out with aryl
bromide (0.5 mmol), 4-chlorobenzaldehyde or benzaldehyde (0.75 mmol),
Na2CO3 (1.0 mmol) and Ni(dmbpy)Br2 (0.025 mmol) in dry acetone (0.25 M) under
irradiation with UV-LEDs (395 nm) and under N2-atmosphere for 8 h at
25 °C. Isolated yield after purification by column chromatography. (b) Unsuccessful
aryl bromides under standard conditions.
After establishing the aryl bromide scope, we investigated the
aldehyde scope, using 4-bromobenzonitrile as the coupling
partner (Scheme 3).
Benzaldehyde reacted smoothly under the developed reaction
conditions and afforded 5a in very good yield. Fluorinated
benzaldehydes formed the respective ketones in good to
excellent yields (5e, 5i-k). Both very electron poor
benzophenons (5b-e, 5k) as well as “push-pull” systems (5f-i),
bearing an electron donating on one side, and one electron
withdrawing substituent on the other, were synthesized in good
to excellent yields (5f-i). Whilst benzoyl-protected
hydroxybenzaldehyde was transformed into ketone 5l in good
yield, neither 4-hydroxybenzaldehyde nor 4-amino-
benzaldehyde reacted to the ketone.40
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 3 of 5
ChemComm
Please do not adjust margins
Journal Name
COMMUNICATION
Scheme 4 Plausible mechanism.
View Article Online
O
O
A)
Na2CO3 (2 equiv.)
Ni(dmbpy)Br2 (5 mol%)
acetone (0.25 M)
DOI: 10.1039/C9CC04726C
Br
H
R
R
+
The photocatalytic cycle starts with benzophenone BP
absorbing a photon to reach its triplet-state BP* and hence
enabling it to abstract a hydrogen atom from aldehyde 1 to
form both the acyl radical 1· and radical BP-H. The oxidative
addition of the nickel(0)-complex A into the aryl bromide bond
furnishes nickel(II) species B, which serves as radical-trap for
acyl radical 1·. The formed nickel(III) species C is believed to
undergo reductive elimination to benzophenone BP and
complex D. Single electron transfer (SET) from BP-H to the
nickel(I) bromide D is closing the catalytic cycle, furnishing both
nickel(0) complex A and the ground state benzophenone BP.
However, the formation of the first photocatalytically active
species remains elusive. Attempted photoreduction of the
precatalyst with a mixture of benzaldehyde and sodium
carbonate allows the observation of an apparently air sensitive
species formed after already a few minutes of irradiation (see
supporting information). GC-MS analysis of the mixture
revealed traces of different products known to form upon
photolysis of benzaldehyde such as benzene, benzil and its
decarbonylation product benzophenone, of which we consider
the latter ones together with the aldehyde capable to initiate
the reaction.44
CN
CN
395 nm LED, 8h, 25 °C
1
2a
5
O
O
O
O
CN
NC
CN
CN
CN
CN
5a, 81% yield
CN
5b, 63% yield
5c, 71% yield
O
O
O
O
O
CN F3C
CN
5d, 85% yield
5e, 61% yield
5f, 98% yield
O
O
O
CN
CN
F3CO
5g, 63% yield
5h, 73% yield
5i, 67% yield
O
O
O
F
F3C
CN
CN
BzO
CN
5j, 97% yield
5k, 70% yield
5l, 79% yield
Unsuccessful Aldehydes
O
B)
O
O
O
O
O
HO
H2N
Ph
In conclusion, we have developed a photochemical nickel-
catalyzed benzoylation of aryl bromides with a variety of
aldehydes. The reaction does not need the initial addition of a
O
Scheme
3 (a) Aldehyde scope. All reactions were carried out with
4-bromobenzonitrile (0.5 mmol), aldehyde (0.75 mmol), Na2CO3 (1.0 mmol) and photocatalyst, since the products of the reaction serve as
Ni(dmbpy)Br2 (0.025 mmol) in dry acetone (0.25 M) under irradiation with UV-LEDs
(395 nm) and under N2-atmosphere for 8 h at 25 °C. Isolated yield after purification
by column chromatography. (b) Unsuccessful aldehydes under standard conditions
photocatalysts after the reaction was initiated by photolysis of
the respective benzaldehyde. Financial support from the
German Science Foundation (DFG; KO 1537/18-1) is
acknowledged. Shun Wang, Qing-Yuan Meng and Indrajit Gosh
The mechanism of different nickel-based metalla-
are acknowledged for helpful discussions. We thank Julia Zach
photocatalyzed reactions have been investigated in
for her technical support and Ranit Lahmy for her help on the
computations and experimental studies.14, 40, 41 Different modes
manuscript.
of C-H activation are discussed, including σ-bond metathesis by
a sensitized nickel(II)-aryl bromide complex (complex B, Scheme
4) and HAT by bromine radicals that form upon homolytic
Conflicts of interest
There is no conflict to declare.
fragmentation of the same excited complex. The use of
benzophenones (BP*) as photocatalyst, however, opens a new
potential reaction pathway, as triplet excited BP* can serve as
sensitizer to facilitate energy transfer based pathways, but
Notes and references
43
additionally can act as HAT catalyst itself.42,
A plausible
mechanism based on the latter property is shown below.
1
2
3
4
5
6
7
8
J. Twilton, C. Le, P. Zhang, M. H. Shaw, R. W. Evans and D. W.
C. MacMillan, Nat. Rev. Chem., 2017, 1, 0052.
M. D. Levin, S. Kim and F. D. Toste, ACS Cent. Sci., 2016, 2,
293-301.
M. N. Hopkinson, B. Sahoo, J. L. Li and F. Glorius, Chem. Eur.
J., 2014, 20, 3874-3886.
K. L. Skubi, T. R. Blum and T. P. Yoon, Chem. Rev., 2016, 116,
10035-10074.
D. R. Heitz, J. C. Tellis and G. A. Molander, J. Am. Chem. Soc.,
2016, 138, 12715-12718.
B. J. Shields and A. G. Doyle, J. Am. Chem. Soc., 2016, 138,
12719-12722.
M. K. Nielsen, B. J. Shields, J. Liu, M. J. Williams, M. J. Zacuto
and A. G. Doyle, Angew. Chem. Int. Ed., 2017, 56, 7191-7194.
L. K. G. Ackerman, J. I. Martinez Alvarado and A. G. Doyle, J.
Am. Chem. Soc., 2018, 140, 14059-14063.
SET
N
N
Ni0
NiI
N
N
Br
A
D
O
Ar
ArBr
OH
Ar'
Ar'
BP
Ar
BP-H
O
hv
H
Ar'
1
O
HAT
Ar
BP*
Ar'
O
N
O
Ar
Br
Ar'
Ar
NiII
N
Ar'
N
1
NiIII
B
N
C
Br
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 4 of 5
COMMUNICATION
Journal Name
9
X. Zhang and D. W. C. MacMillan, J. Am. Chem. Soc., 2017,
139, 11353-11356.
42 Y. L. Chow, G. E. Buono-Core, C. W. Lee and J. C.VSiecwaAiartnicloe,OJn.line
Am. Chem. Soc., 1986, 108, 7620-7627.
DOI: 10.1039/C9CC04726C
10 N. A. Romero and D. A. Nicewicz, Chem. Rev., 2016, 116,
10075-10166.
11 L. Marzo, S. K. Pagire, O. Reiser and B. König, Angew. Chem.
Int. Ed., 2018, 57, 10034-10072.
43 P. J. Wagner, R. J. Truman and J. C. Scaiano, J. Am. Chem.
Soc., 1985, 107, 7093-7097.
44 M. Berger, I. L. Goldblatt and C. Steel, J. Am. Chem. Soc.,
1973, 95, 1717-1725.
12 D. Ravelli, M. Fagnoni and A. Albini, Chem. Soc. Rev., 2013,
42, 97-113.
13 M. Fagnoni, D. Dondi, D. Ravelli and A. Albini, Chem. Rev.,
2007, 107, 2725-2756.
14 Y. Shen, Y. Gu and R. Martin, J. Am. Chem. Soc., 2018, 140,
12200-12209.
15 L. Zhang, X. Si, Y. Yang, M. Zimmer, S. Witzel, K. Sekine, M.
Rudolph and A. S. K. Hashmi, Angew. Chem. Int. Ed., 2019,
58, 1823-1827.
16 A. Dewanji, P. E. Krach and M. Rueping, Angew. Chem. Int.
Ed., 2019, 58, 3566-3570.
17 K. Surana, B. Chaudhary, M. Diwaker and S. Sharma,
MedChemComm, 2018, 9, 1803-1817.
18 R. K. Dieter, Tetrahedron, 1999, 55, 4177-4236.
19 K. Demkiw, H. Araki, E. L. Elliott, C. L. Franklin, Y. Fukuzumi, F.
Hicks, K. Hosoi, T. Hukui, Y. Ishimaru, E. O'Brien, Y. Omori, M.
Mineno, H. Mizufune, N. Sawada, Y. Sawai and L. Zhu, J. Org.
Chem., 2016, 81, 3447-3456.
20 X. Wang, F. D. Liu, H. Y. Tu and A. D. Zhang, J. Org. Chem.,
2014, 79, 6554-6562.
21 K. Liu, S.-W. Tao, C. Qian and Y.-M. Zhu, Eur. J. Org. Chem.,
2018, 2018, 4769-4775.
22 H. Tatamidani, F. Kakiuchi and N. Chatani, Org. Lett., 2004, 6,
3597-3599.
23 S. Panja, P. Maity and B. C. Ranu, J. Org. Chem., 2018, 83,
12609-12618.
24 D. Lee, T. Ryu, Y. Park and P. H. Lee, Org. Lett., 2014, 16,
1144-1147.
25 J. Ruan, O. Saidi, J. A. Iggo and J. Xiao, J. Am. Chem. Soc.,
2008, 130, 10510-10511.
26 P. Alvarez-Bercedo, A. Flores-Gaspar, A. Correa and R.
Martin, J. Am. Chem. Soc., 2010, 132, 466-467.
27 A. Flores-Gaspar, A. Gutierrez-Bonet and R. Martin, Org.
Lett., 2012, 14, 5234-5237.
28 T. Wakaki, T. Togo, D. Yoshidome, Y. Kuninobu and M. Kanai,
ACS Catal., 2018, 3123-3128.
29 B. Suchand and G. Satyanarayana, J. Org. Chem., 2016, 81,
6409-6423.
30 T. Ishiyama and J. Hartwig, J. Am. Chem. Soc., 2000, 122,
12043-12044.
31 M. Pucheault, S. Darses and J. P. Genet, J. Am. Chem. Soc.,
2004, 126, 15356-15357.
32 L. Chu, J. M. Lipshultz and D. W. MacMillan, Angew. Chem.
Int. Ed., 2015, 54, 7929-7933.
33 Y.-C. Huang, K. K. Majumdar and C.-H. Cheng, J. Org. Chem.,
2002, 67, 1682-1684.
34 L. J. Gu, C. Jin and H. T. Zhang, Chem. Eur. J., 2015, 21, 8741-
8744.
35 J. K. Vandavasi, X. Hua, H. B. Halima and S. G. Newman,
Angew. Chem. Int. Ed., 2017, 56, 15441-15445.
36 J. Karthikeyan, K. Parthasarathy and C. H. Cheng, Chem.
Commun., 2011, 47, 10461-10463.
37 X. F. Wu, H. Neumann and M. Beller, Chem. Soc. Rev., 2011,
40, 4986-5009.
38 X. He, Y. Cao, X. D. Lang, N. Wang and L. N. He,
ChemSusChem, 2018, 11, 3382-3387.
39 Please refere to the supporting information for more
information.
40 R. Sun, Y. Qin, S. Ruccolo, C. Schnedermann, C. Costentin and
D. G. Nocera, J. Am. Chem. Soc., 2019, 141, 89-93.
41 O. Gutierrez, J. C. Tellis, D. N. Primer, G. A. Molander and M.
C. Kozlowski, J. Am. Chem. Soc., 2015, 137, 4896-4899.
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 5
ChemComm
View Article Online
DOI: 10.1039/C9CC04726C
O
O
395 nm LED
Ni PC
No extra photocatalyst required
H
R
R
R'
27 examples
up to 98% yield
TOC
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1