Biaryl diketone synthesis via palladium-catalyzed carbonylative coupling with carbon monoxide or various metal carbonyls

Article abstract of DOI:10.1002/bkcs.10904

Biaryl diketones were synthesized via palladium-catalyzed carbonylative coupling in the presence of a palladium N-heterocyclic carbene complex and CO or metal carbonyls. Different arylboronic acids along with various CO-releasing molecules were tested to

Full text of DOI:10.1002/bkcs.10904

Article
DOI: 10.1002/bkcs.10904
BULLETIN OF THE
S. K. Cho et al.
KOREAN CHEMICAL SOCIETY
Biaryl Diketone Synthesis via Palladium-catalyzed Carbonylative
Coupling with Carbon Monoxide or Various Metal Carbonyls
Soo Kyung Cho,† Ju Hyun Song,† Jung Tae Hahn,‡ and Dai il Jung†,
*
†Department of Chemistry, Dong-A University, Busan 604-714, South Korea. *E-mail: dijung@dau.ac.kr
‡Department of Beautycare, U1 University, Yeonamsan-lo, Eumbongmyeon, Chungcheonnam-do, 31415,
South Korea
Received May 21, 2016, Accepted July 26, 2016, Published online September 26, 2016
Biaryl diketones were synthesized via palladium-catalyzed carbonylative coupling in the presence of a pal-
ladium N-heterocyclic carbene complex and CO or metal carbonyls. Different arylboronic acids along with
various CO-releasing molecules were tested to study the influence of structure. Generally, steric hindrance
of arylboronic acids and CO-releasing ability of various metal carbonyls played significant roles. In most
cases, single ketone products were found as the side products rather than direct coupling products.
Keywords: Biaryl diketone, Palladium-catalyzed carbonylation, N-heterocyclic carbene, Carbon monox-
ide, Metal carbonyl
Introduction
published literature.20 All other chemicals were purchased
from Sigma-Aldrich Korea (Seoul, South Korea) and used
as received.
Biaryl ketones are useful building blocks for biologically
active molecules.1–3 Many studies have been dedicated to the
synthesis of carbonylative coupling of aryl compounds such
as the one pioneered by Heck.4–6 Carbonylative coupling has
since been further developed to synthesize a range of carbon
nucleophiles, including tin,7 copper,8–11 boron,12 zinc,13
aluminum,14 magnesium,15 and silicon.16 However, the syn-
thesis of unsymmetrical biaryl ketones using electron-
deficient aryl electrophiles is limited owing to the direct cou-
pling side reaction without carbonyl insertion. Much work
has been dedicated to overcome this limitation and to synthe-
size unsymmetrical biaryl ketones.17,18 Such efforts include
palladium-catalyzed cross-coupling reactions of arylboronic
acids with aryl iodides, bromides, or triflates by Ishiyama
et al.19 Metal iodide additives that were essential for aryl bro-
mides or triflates were unnecessary for aryl iodides.
In line with efforts to synthesize biologically active biaryl
ketones, our group previously reported the carbonylative
coupling of 4,40-diiodobiphenyl with phenylboronic acid to
synthesize a biaryl diketone product, biphenyl-4,40-diylbis
(phenylmethanone).20 In this study, we broaden the scope
by using various arylboronic acids, including 1,10-biphenyl-,
1-naphthalenyl-, and heterocyclic boronic acids. Effects of
CO-releasing molecules such as CO gas itself and various
metal carbonyls (molybdenum hexacarbonyl,21–23 dimanga-
nese decacarbonyl,24 dicobalt octacarbonyl,25,26 iron
pentacarbonyl,27 and triiron dodecacarbonyl28,29) were also
studied to elucidate the reaction mechanism.
General Procedure for Carbonylative Coupling Reac-
tion Under CO. The Pd(NHC) complex (3 μmol) was dis-
solved in 15 mL of anisole purged with N2 to form a pale
brown homogeneous solution. Then, 4,40-diiodobiphenyl
(0.5 mmol), arylboronic acid (1 mmol), and potassium car-
bonate (1.5 mmol) were added. The atmosphere was chan-
ged to CO (1 atm) and the reaction mixture was maintained
at 80ꢀC for 24 h. After elimination of the Pd(NHC) com-
plex by filtration, the reaction mixture was diluted with
10 mL water and extracted with methylene chloride three
times. The combined organic layer was dried with magne-
sium sulfate, filtered, and concentrated. The products were
purified by column chromatography (ethyl acetate/n-hex-
ane = 1/20 v/v) to give the corresponding compounds 1a,
3a, and 5a. (Analytical data provided in Appendix S1, Sup-
porting information.)
General Procedure for Carbonylative Coupling Reac-
tion with Metal Carbonyls.
4,40-Diiodobiphenyl
(0.5 mmol), arylboronic acid (1 mmol), potassium carbo-
nate (1.5 mmol), the Pd(NHC) complex (3 μmol), and the
metal carbonyl (0.7 mmol) were dissolved in 15 mL ani-
sole purged with N2. The reaction mixture was maintained
at 80ꢀC for 24 h. After elimination of the Pd(NHC) com-
plex by filtration, the reaction mixture was diluted with
10 mL water and extracted with methylene chloride three
times. The combined organic layer was dried with magne-
sium sulfate, filtered, and concentrated. The products were
purified by column chromatography (ethyl acetate/n-hex-
ane = 1/20 v/v) to give the corresponding compounds
1b–f, 3b–f, and 5b–f. (Analytical data provided in Appen-
dix S1, Supporting information.)
Experimental
Materials.
A palladium N-heterocyclic carbene [Pd
(NHC)] complex was prepared according to previously
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Article
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KOREAN CHEMICAL SOCIETY
Results and Discussion
Reaction Conditions. The carbonylative coupling reac-
tions of 4,40-diiodobiphenyl with various arylboronic acids
were carried out in anisole at 80ꢀC in the presence of a
Pd(NHC) complex [bis-(1,3-dihydro-1,3-dimethyl-2H-imi-
dazol-2-ylidene)diiodopalladium] and potassium carbonate,
with either CO gas or metal carbonyls (Figure 1). The reac-
tion afforded biaryl diketones 1, 3, and 5, and monocarbo-
nylated side products 2, 4, and 6 with lower yields in most
cases.
Reaction parameters were carefully chosen after a thor-
ough review of published results. For example, the use of
potassium carbonate as a base is known to avoid direct cou-
pling without carbonyl insertion, and aryl iodide affords
better results in shorter reaction times than aryl bromides or
triflates.19 Finally, 4,40-diiodobiphenyl was chosen to study
the effects of the arylboronic acid structure and CO-
releasing molecules on the reaction.
Figure 1. Synthesis of 4,40-diiodobiphenyl with different aryl-
boronic acids. Reactions were carried out in the presence of a
Pd(NHC) complex and potassium carbonate with CO-releasing
molecules in anisole at 80ꢀC.
Table 1. Summary of carbonylative coupling of 4,40-diiodobiphenyl and arylboronic acids with carbon monoxide gas or various metal
carbonyls.
Product yield (%)a
Product
Aryl halide
Arylboronic acid
CO-releasing molecule
Dicarbonylation
Monocarbonylation
1a
1b
1c
1d
1e
1f
3a
3b
3c
3d
3e
3f
COb
42.6
52.3
6.6
48.6
62.5
9.9
25.3
21.4
9.8
11.6
15.9
7.9
12.7
13.5
33.1
11.2
10.6
24.8
18.4
22.1
10.5
16.4
9.5
Mo(CO)6
Mn2(CO)10
Co2(CO)8
Fe(CO)5
Fe3(CO)12
CO
Mo(CO)6
Mn2(CO)10
Co2(CO)8
Fe(CO)5
Fe3(CO)12
15.7
5a
5b
5c
5d
5e
5f
7a
7b
7c
7d
7e
7f
CO
30.6
21.5
Mo(CO)6
Mn2(CO)10
Co2(CO)8
Fe(CO)5
Fe3(CO)12
CO
Mo(CO)6
Mn2(CO)10
Co2(CO)8
Fe(CO)5
Fe3(CO)12
24.6
5.7
28.6
11.1
18.2
12.7
3.2
20.9
N. R.
N. R.
N. R.
N. R.
N. R.
N. R.
N. R.
N. R.
N. R.
N. R.
N. R.
N. R.
a
Isolated yield.
b
Carbon monoxide gas at 1 atm.
N. R., no reaction.
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Article Biaryl Diketone Synthesis via Palladium-catalyzed Carbonylative Coupling
KOREAN CHEMICAL SOCIETY
Figure 2. Simplified catalytic cycles of biaryl diketone (Cycle A) and monocarbonylation product (Cycle B) syntheses.
Effect of Arylboronic Acid Structure. Different arylboro-
nic acids were used to study the effect of structure on the
reaction outcome. Phenylboronic acid, naphthalen-1-
ylboronic acid, 1,10-biphenyl-4-ylboronic acid, and
pyridine-4-ylboronic acid were tested. The reaction out-
comes are summarized in Table 1. Phenylboronic acid
afforded products (1a–f) with higher yields than those of
1,10-biphenyl-4-ylboronic acid (3a–f) and naphthalene-1-
ylboronic acid (5a–f), presumably owing to the steric hin-
drance of the biphenyl and naphthalenyl groups. There was
no significant difference between the reactions using
naphthalen-1-ylboronic acid and 1,10-biphenyl-4-ylboronic
acid, although the products of the reaction involving
naphthalene-1-ylboronic acid showed slightly higher yields.
In the case of pyridine-4-ylboronic acid, no reaction
occurred regardless of reaction conditions. This was inter-
esting because Ishiyama et al. demonstrated carbonylative
coupling of phenylboronic acid with heterocyclic halides
(2-bromothiophene, 3-bromoquinoline, 2-bromopyridine,
and 2-bromofurane), although the authors reported that 2-
bromopyridine and 2-bromofurane showed lower yields.19
Mo(CO)6 is a popular reagent in organometallic synthe-
sis, as CO ligands are readily displaced by other donor
ligands and are photo-activatable.30 Co2(CO)8 releases CO
upon decomposition.31 Fe(CO)5 is also sensitive to light,
and, when heated, converts to small amounts of metal clus-
ters of Fe3(CO)12 and releases CO.32 Mn2(CO)10 and
Fe3(CO)12, on the other hand, are relatively stable in air,
and high temperature is required for their decomposition to
yield CO.33,34 Therefore, it can be suggested that Mo(CO)6,
Co2(CO)8, and Fe(CO)5 are better CO-releasing molecules
than Mn2(CO)10 and Fe3(CO)12 by virtue of their higher
reactivity.
Reaction Mechanism. The carbonylative coupling of aryl
halide and arylboronic acid proceeds through the catalytic
cycle of the palladium catalyst (Figure 2, Cycle A). The
first step is the oxidative addition of palladium to the aryl
halide (i). The CO then coordinates to the palladium(II) cat-
alyst, followed by the migratory CO insertion into the Pd-
aryl bond (ii). The transmetalation step (iii) is normally the
rate-determining step, when the ligands are transferred from
the organoboron species to the palladium(II) complex.
Then, the reductive elimination (iv) of diketone products
regenerates the initial palladium(0) species.
Direct coupling without carbonyl groups giving biaryls is
often the side reaction, when the CO insertion (ii) is slower
than the transmetalation (iii). However, monocarbonylated
products (products 2a–f, 4a–f, and 6a–f) were found
instead in this study (Table 1). The catalytic cycle of the
monocarbonylated products are represented as Cycle B
(Figure 2).
Influence of CO-releasing Molecules. CO gas (1 atm)
and different metal carbonyls (molybdenum hexacarbonyl,
dimanganese decacarbonyl, dicobalt octacarbonyl, iron pen-
tacarbonyl, and triiron dodecacarbonyl) were studied for
CO insertion. The reaction results are summarized in
Table 1. CO gas afforded products with high yields for all
three groups (products 1a, 3a, and 5a). Mo(CO)6,
Co2(CO)8, and Fe(CO)5 also resulted in higher yields than
Mn2(CO)10 and Fe3(CO)12 did, with the exception of pro-
ducts 5c and 5d.
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BULLETIN OF THE
Article Biaryl Diketone Synthesis via Palladium-catalyzed Carbonylative Coupling
KOREAN CHEMICAL SOCIETY
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carbonylative
cross-coupling
of
4,40-
diiodobiphenyl with different arylboronic acids and various
CO-releasing molecules. The steric hindrance of arylboro-
nic acids played a significant role, with phenylboronic acid
resulting in generally higher yields than 1,10-biphenyl-4-
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Supporting Information. Additional supporting informa-
tion is available in the online version of this article.
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