Published on the web December 5, 2011
1453
Diaryl Ketone Synthesis by [RuHCl(CO)(PPh ) ]-catalyzed Coupling Reaction
3
3
of Arylboronic Acids with Aryl Aldehydes
Takahide Fukuyama,* Hiromi Okamoto, and Ilhyong Ryu*
Department of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka 599-8531
(
Received September 22, 2011; CL-110774; E-mail: fukuyama@c.s.osakafu-u.ac.jp)
O
[RuHCl(CO)(PPh3)3]
O
[
RuHCl(CO)(PPh ) ] was found to be an efficient catalyst
3
3
Ar1 B(OH)2
+
for the coupling reaction of arylboronic acids with aryl
aldehydes. The reaction proceeded smoothly in the presence of
K CO and H O to give diaryl ketones in good yields. Diaryl
ketones were obtained from primarily formed alcohols via Ru-
catalyzed transfer hydrogenation reaction.
H
Ar2
Ar1
Ar2
2
3
2
Scheme 1. [RuHCl(CO)(PPh ) ]-catalyzed coupling reaction
of arylboronic acids with aldehydes.
3
3
Table 1. RuH-catalyzed coupling reaction of 1a with 2aa
Diaryl ketone frameworks are found in a variety of
biologically active compounds1 and organic materials with
potential use in optical, magnetic, and electronic applications.
2
Diaryl ketones are typically prepared by addition of organo-
metallic compounds, such as arylmagnesium or aryllithium
reagents, to aryl aldehydes, followed by oxidation. These
reactions require stoichiometric amounts of organometallic
reagents and oxidants. Cross-coupling reaction of aryl aldehydes
with aryl halide represents a straightforward approach to access
b
Entry
Ru-cat.
Base
Yield /%
1
2
3
4
5
6
[RuHCl(CO)(PPh3)3]
[RuHCl(CO)(PPh3)3]
[RuHCl(CO)(PPh ) ]
[RuHCl(CO)(PPh3)3]
[RuHCl(CO)(PPh3)3]
none
13
28
2
3
4
Cs2CO3
t-BuOK
K2CO3
K CO
diaryl ketones. It has been reported that palladium and nickel
3
3
can catalyze such coupling reactions. Recent work revealed that
arylboronic acids can also serve as a coupling partner of aryl
62
c
5
6
7
trace
aldehydes in Rh-, Pd-, and Pt-catalyzed reactions in diaryl
ketone synthesis.
2
3
d
e
[RuHCl(CO)(PPh3)3]
[RuH2(CO)(PPh3)3]
[RuH2(PPh3)4]
K2CO3
K2CO3
K2CO3
K2CO3
66
7
8
9
37
17
4
Recently, we reported that a ruthenium hydride complex,
[
¡
RuHCl(CO)(PPh ) ] catalyzed the reaction of aldehydes with
3 3
8
9,10
[RuHCl(PPh3)3]
,¢-unsaturated ketones or dienes
leading to 1,3-diketones
or ¢,£-unsaturated ketones, in which addition of ruthenium
carbon species to aldehydes followed by ¢-hydride elimina-
tion from a ruthenium alkoxide intermediate would be
involved as the key steps. Herein we report that [RuHCl-
aConditions: 1a (0.5 mmol), 2a (1 mmol), Ru-cat. (5 mol %),
base (1 mmol), H2O (1 mmol), toluene (2 mL), 110 °C, 13 h.
b
c
NMR yield using anisole as an internal standard. Reaction
d
e
without H2O. 0.5 M. Isolated yield by flash chromatography
on SiO2.
11
(
CO)(PPh3)3] can effectively catalyze the coupling reaction
of aldehydes with arylboronic acids, resulting in good yields
of diaryl ketones (Scheme 1).12 During the course of our
study, Wan and co-workers reported a similar [RuCl2(CO)3]2/
P(t-Bu) -catalyzed coupling reaction of aldehydes with arylbo-
3
ronic acids to give aryl ketones. In this case the RuH species
formed in situ was proposed to be the key catalytic
species.
With optimized reaction conditions in hand, we then
investigated the scope of [RuHCl(CO)(PPh3)3]-catalyzed
coupling reactions of a variety of arylboronic acids with aryl
1
3,14
1
5
The reaction of phenylboronic acid (1a) with o-tolualdehyde
2a) was investigated as a model reaction. Thus, when the
aldehydes. The results are shown in Table 2. The reaction of
1a with para substituted benzaldehydes 2b, 2c, and 2d gave
the corresponding diaryl ketones 3b, 3c, and 3d in moderate
to good yields (Entries 24). The reaction of p-tolylboronic
acid (1b) with 2b gave 4,4¤-dimethylbenzophenone (3e) in
49% yield (Entry 5). p-Methoxycarbonyl-substituted benzal-
dehyde 2e exhibited high reactivity, giving the corresponding
product 3f in quantitative yield (Entry 6). Several methoxy-
substituted phenylboronic acids 1c1e were examined, which
gave the corresponding diaryl ketones in good yields (Entries
710). The reactions of arylboronic acids with aliphatic
aldehydes, such as 1-heptanal and pivalaldehyde, were slug-
gish to give the corresponding alkyl aryl ketones in less than
20% yields. Alkylboronic acids and heteroaromatic boronic
(
reaction of 1a with 2a was carried out in the presence of a
catalytic amount of [RuHCl(CO)(PPh3)3] (5 mol %) and H2O
(
2
(
2 equiv) in toluene at 110 °C for 13 h, the coupling product,
-methylbenzophenone (3a), was obtained in 13% yield
Table 1, Entry 1). Addition of K CO was found to be effective
2
3
to give 3a in 62% yield (Entry 4). When the reaction was
conducted in the absence of H2O only a trace amount of 3a was
formed (Entry 5). Increasing the concentration of substrate
(
0.5 M of 1a) also improved the yield of 3a up to 66% (Entry 6).
Other ruthenium hydride complexes, such as [RuH2(CO)-
PPh ) ], [RuH (PPh ) ], and [RuHCl(PPh ) ] were less effective
(
3
3
2
3 4
3 3
for the present coupling reaction (Entries 79).
Chem. Lett. 2011, 40, 14531455
© 2011 The Chemical Society of Japan