Palladium-catalyzed coupling of benzoyl halides with aryltrifluorosilanes leading to diaryl ketones

Article abstract of DOI:10.1246/cl.160223

Acyl-aryl Hiyama coupling of acyl halides with arylsilanes has been achieved by employing a palladium/phosphine catalyst system. A variety of acyl chlorides and fluorides can be applied for coupling with arylsilicon reagents, and unsymmetrical benzophenone derivatives can be prepared using this protocol.

Full text of DOI:10.1246/cl.160223

CL-160223
Received: March 7, 2016 | Accepted: March 30, 2016 | Web Released: April 6, 2016
Palladium-catalyzed Coupling of Benzoyl Halides with Aryltrifluorosilanes
Leading to Diaryl Ketones
Yohei Ogiwara, Yuki Maegawa, Daisuke Sakino, and Norio Sakai*
Department of Pure and Applied Chemistry, Faculty of Science and Technology,
Tokyo University of Science (RIKADAI), Noda, Chiba 278-8510
(E-mail: sakachem@rs.noda.tus.ac.jp)
Acyl-aryl Hiyama coupling of acyl halides with arylsilanes
atom was essential for the coupling; in the case of tetraorgano-
silanes, the major formation of an acyl fluoride is considered a
demerit (Scheme 1A).2 Another approach was the coupling of
aryl halides with acylsilanes, such as in 2011, when Krska and
co-workers developed a coupling of aryl bromides with aryl
trimethylsilyl ketone as an acyl anion equivalent in the presence
of a palladium catalyst (Scheme 1B).3 Numerous efficient cross-
coupling reactions of acid halides with a variety of organo-
metallic reagents, which is classified as a (C)-type coupling,
have been reported, such as B,5 Mg,6 Al,7 Zn,8 In,9 Sn,10 Hg,11
and Bi,12 are also available for coupling with carboxylic acid
derivatives.13 In contrast, as far as we could ascertain, there has
been no report of the direct preparation of diaryl ketones via
coupling with organosilicon compounds, with one notable
exception: coupling of phenylbenzothioates with ArSi(OMe)3
in the presence of CuI, TBAF, and Pd(PPh3)4 as the catalyst
(Scheme 1C).4
However, the acyl derivative used in that procedure was
limited to a thioester, and the use of other acyl electrophiles as a
counter partner for a similar cross-coupling with organosilicon
compounds remains unexplored.14 Hence, the development of
a transition-metal-catalyzed coupling reaction of organosilicon
compounds with typical acyl halides leading to the preparation
of diaryl ketones is considered one of the most effective and
attractive routes, and both these substrates are extremely
economical and widely available. In this communication, we
describe a novel (C)-type coupling preparation of diaryl ketones,
which is a palladium-catalyzed acyl-aryl Hiyama cross-coupling
using an acid halide, or a pseudohalide, such as an acid chloride
and an acyl fluoride, as the acyl electrophiles.
has been achieved by employing a palladium/phosphine catalyst
system. A variety of acyl chlorides and fluorides can be applied
for coupling with arylsilicon reagents, and unsymmetrical
benzophenone derivatives can be prepared using this protocol.
Keywords: Palladium catalyst
| Acyl halide |
Organosilicon compound
In modern synthetic chemistry, the transition-metal-cata-
lyzed cross-coupling reaction is a powerful tool for the
formation of a carbon-carbon bond. Organosilicon compounds
are among the most attractive coupling reagents because of their
chemical stability, high availability, and low toxicity. Hence, a
cross-coupling using organosilicon compounds (Hiyama cou-
pling) ranks high on the list of the most important carbon-
carbon bond formation strategies.1 Numerous researchers have
developed a variety of useful and straightforward methodologies
for the transition-metal-catalyzed coupling for the construction
of diaryl ketones, which function as important building blocks in
organic and pharmaceutical chemistry. The three most recent
approaches to silicon-based cross-coupling for diaryl ketone
synthesis are summarized in Scheme 1: (A) carbonylative
coupling of aryl halides with arylsilanes;2 (B) coupling of aryl
halides with acylsilanes;3 and (C) coupling of acyl electrophiles
with arylsilanes.4
Hiyama and co-workers reported the palladium-catalyzed
carbonylative coupling of aryl iodides with arylfluorosilanes.
The striking features of this reaction were that carbon monoxide
was embedded in the diary ketone framework under only 1 atm,
and the use of an organosilane containing more than one fluorine
Initially, we investigated the reaction conditions caused by
the coupling of 3,5-dimethylbenzoyl chloride (1a) with a
phenylsilicon reagent in the presence of 3.5 equiv of CsF in
xylene at 140 °C for 24 h (Table 1).15 When the reaction was
performed using phenyltrifluorosilane (2a) with a catalytic
amount of Pd(OAc)2/PPh3, 23% of the desired diaryl ketone 3aa
was detected by GC analysis (Entry 1). Ligand screening was
then conducted to improve the chemical yield. The electron-
withdrawing triarylphosphine, P(4-CF3C6H4)3, showed a similar
effect as PPh3 (Entry 2). By contrast, the use of a more electron-
donating methoxy-substituted triarylphosphine improved the
yield of the ketone (Entry 3). Although the use of PCy3 did
not give the product (Entry 4), the use of PtBu3 as a ligand
effectively promoted the coupling to give diaryl ketone 3aa in
75% isolated yield (Entry 5). It is well known that a Pd/PtBu3-
based catalyst system often exhibits high reactivity for a variety
of cross-couplings because of its steric bulkiness and electron
richness.16 However, other bulky and electron-rich phosphines
or carbenes, such as XPhos and IMes, were ineffective for this
coupling (Entries 6 and 7). The effect of a silyl substituent on the
(A) carbonylative coupling of arylhalides with arylsilanes
O
[Pd]
Ar1–I
Ar2–Si
+
Ar1
Ar2
CO
(Si: SiFnMe3–n
)
(B) cross-coupling of arylhalides with acylsilanes
O
O
O
O
[Pd]
Ar1–Br
+
Ar2
Si
Ar1
Ar1
Ar1
Ar2
Ar2
Ar2
(Si: SiMe3)
(C) cross-coupling of thioesters with arylsilanes
O
Pd(PPh3)4
Ar2–Si
+
Ar1
SPh
CuI, TBAF
(Si: Si(OMe)3)
cross-coupling of acylhalides with arylsilanes (this work)
O
Pd(OAc)2/PtBu3
Ar2–Si
+
Ar1
X
CsF
(Si: SiF3)
X: Cl, Br, F, OCOPh
Scheme 1. Palladium-catalyzed silicon-based coupling for
diaryl ketone.
790 | Chem. Lett. 2016, 45, 790–792 | doi:10.1246/cl.160223
© 2016 The Chemical Society of Japan

Table 1. Optimization of the reaction conditionsa
Table 3. Palladium-catalyzed Hiyama coupling of various acyl
electrophiles with phenylsilane 2aa
Pd(OAc)2 (5 mol %)
O
O
Pd(OAc)2 (5 mol %)
ligand (20 mol %)
Cl
Ph
O
O
+
PhSiX3
PtBu3 (20 mol %)
CsF, xylene
140 °C, 24 h
+
PhSiF3
Ar
X
CsF, xylene
140 °C, 24 h
Ar
Ph
1a
2
3aa
4–6
2a
3
Product Yield/%b
Entry
PhSiX3
Ligand
Yield/%b
Entry Substrate Ar
X
1
2
3
4
5
6
7
8
PhSiF3 (2a)
2a
2a
2a
2a
2a
2a
PPh3
23
25
41
ndc
75d
37
31
3f
1
2
3
4
5
6
7
8
9
4a
4b
4c
4d
4e
4f
4h
4k
4m
5
3,5-Me2C6H3
Ph
F
F
F
F
F
F
F
F
F
Br
3aa
3ba
3ca
3da
3ea
3fa
3ha
3ka
3ma
3ba
3ea
54c
63c
50
59
47
33
55
55
P(4-CF3C6H4)3
P(4-MeOC6H4)3
PCy3
PtBu3
2-MeC6H4
3-MeC6H4
4-MeC6H4
4-MeOC6H4
4-CF3C6H4
2-naphthyl
cynnamyl
Ph
XPhos
IMese
PhSi(OEt)3
PtBu3
10
37c
23c
aReaction conditions: 1a (0.4 mmol), PhSiX3 (1.2 mmol),
Pd(OAc)2 (0.02 mmol), ligand (0.08 mmol), and CsF (1.4
mmol) in xylene (0.4 mL) at 140 °C for 24 h. GC yield. Not
detected. dIsolated yield. eIMes was generated in situ from
IMes¢HCl with tBuOK (1:1). fEthyl 3,5-dimethylbenzoate was
determined in an 80% NMR yield.
10
11
6
(4-MeC6H4CO)2O
b
c
aReaction conditions: acyl halides, or pseudohalides, 4-6
(1 mmol), 2a (3 mmol), Pd(OAc)2 (0.05 mmol), PtBu3
(0.2 mmol), and CsF (3.5 mmol) in xylene (1 mL) at 140 °C
b
c
for 24 h. GC yield. 0.4 mmol scale.
Table 2. Pd/PtBu3-catalyzed coupling of benzoyl chlorides 1
with aryltrifluorosilane 2a
or 4-positions, were applied to the coupling with phenylsilane 2a
to give asymmetric diaryl ketones 3ca-3ea in 58-64% isolated
yields. The coupling of various benzoyl chlorides 1f-1j bearing
either electron-donating or electron-withdrawing groups, such as
a methoxy, fluoro, trifluoromethyl, nitro, and cyano group, at the
4-position with phenylsilane 2a formed diaryl ketones 3fa-3ja
in moderate to good yields. Substrates bearing 2-naphthyl,
2-thienyl, and cinnamyl moieties can be also applicable to the
coupling with 2a, though the yields were decreased, to afford
the coupling products 3ka, 3la, and 3ma. Methyl-substituted
unsymmetrical- and symmetrical diaryl ketones 3ab-3ad were
prepared from a combination of 3,5-dimethylbenzoyl chloride
(1a) and the corresponding arylsilanes 2b-2d. Further, 3-
methylbenzophenone (3da) was obtained from benzoyl chloride
(1b) and 3-methylated arylsilane 2c, as well as the reaction of
benzoyl chloride 1d with 2a.
Pd(OAc)2 (5 mol %)
O
O
PtBu3 (20 mol %)
Ar2SiF3
+
Ar1
Cl
CsF, xylene
140 °C, 24 h
Ar1
Ar2
1
2
3
O
O
O
O
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
3ba, 70%
3ca, 58%
3da, 64%
3ea, 63%
O
O
O
O
Ph
Ph
MeO
NC
F
F3C
O2N
3fa, 61%
3ga, 54%
3ha, 55%
3ia, 47%
O
O
O
O
S
Ph
3ja, 35%b
3ka, 55%b
3la, 40%b
3ma, 21%b
This protocol was then expanded to other acid derivatives
(Table 3). Compared with a typical acid chloride, acyl fluorides
generally behave as more stable electrophiles toward a nucle-
ophile, such as water, and they can be easily prepared from the
corresponding carboxylic acids or acyl chlorides.17 Hence, the
utility of acyl fluorides as an electrophile is considered to be
significant for this type of a coupling. Moreover, the catalytic
conversion of acyl fluorides to diaryl ketones has been rare,
except for one example with a nickel catalyst reported by Rovis
and co-workers.8e When the reaction of acyl fluoride 4a with
arylsilane 2a was conducted using a catalytic system composed
of Pd(OAc)2/PtBu3 and CsF at 140 °C for 24 h, the desired
coupling product 3aa, which would have been formed via
an acyl C-F bond cleavage, was produced in 54% GC yield,
(Entry 1). Several acyl fluorides 4b-4f, 4h, 4k, and 4m can also
be used in the coupling to give benzophenone derivatives 3ba-
3ma, respectively (Entries 2-9). When both acyl bromide 5 and
acid anhydride 6 were applied to the substrate, the corresponding
benzophenone derivatives 3ba and 3ea were obtained in
moderate yields (Entries 10 and 11).
O
O
O
O
Ph
3ab, 60%
3ac, 45%
3ad, 62%
3da, 51%
aReaction conditions: 1 (0.4 mmol), 2 (1.2 mmol), Pd(OAc)2
(0.02 mmol), PtBu3 (0.08 mmol), and CsF (1.4 mmol) in xylene
(0.4 mL) at 140 °C for 24 h. Isolated yields are shown. b1 mmol
scale.
employed phenylsilane was critical to this transformation; when
using a trialkoxylsilane, PhSi(OEt)3, acid chloride 1a was
converted into the corresponding ethyl ester in 80% yield, and
only 3% of the desired ketone 3aa was detected (Entry 8).
The formation of various diaryl ketones was then performed
using benzoyl chlorides 1 with aryltrifluorosilanes 2 under the
optimal conditions described for Entry 5 in Table 1 (Table 2).
The reaction of benzoyl chloride (1b) with phenyltrifluorosilane
(2a) afforded benzophenone (3ba) in good yield. Acid chlorides
1c-1e bearing a methyl group on the aromatic ring, at the 2-, 3-,
Chem. Lett. 2016, 45, 790–792 | doi:10.1246/cl.160223
© 2016 The Chemical Society of Japan | 791

Although the mechanistic investigations of this coupling are
yet to be conducted, it is assumed that the reaction would
proceed in a manner similar to a typical Hiyama cross-coupling
process: (i) oxidative addition of an acyl halide to palladium(0);
(ii) transmetalation of the aryl group on the pentacoordinate
silicate, which is generated from an arylsilane with CsF, to
the acyl palladium complex; and (iii) reductive elimination to
produce a diaryl ketone, with the regeneration of palladium(0).
In summary, we have demonstrated the first Hiyama cross-
coupling of acyl halides, or pseudohalides, with aryltrifluorosi-
lanes, leading to the preparation of diaryl ketones, using a
Pd(OAc)2/PtBu3 catalyst system. Noteworthy features of this
method include the applicability of the transformation to highly
versatile acyl chlorides and to an inactive acyl fluoride, and the
achievement of this conversion by a combination of commer-
cially and readily available catalysts and substrates. A key factor
in our success was the utilization of a bulky and electron-rich
trialkylphosphine ligand and a fluoride-substituted organosilicon
transmetalating reagent. Efforts are underway to further optimize
and mechanistically study this coupling, along with other
applications for this catalyst system.
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Supporting Information is available on http://dx.doi.org/
10.1246/cl.160223.
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792 | Chem. Lett. 2016, 45, 790–792 | doi:10.1246/cl.160223
© 2016 The Chemical Society of Japan