Carbonylative Hiyama coupling of aryl halides with arylsilanes under balloon pressure of CO

Article abstract of DOI:10.1016/j.tetlet.2016.02.058

An efficient protocol has been developed for the carbonylative Hiyama coupling of aryl halides using the cesium fluoride as a promoter by palladium-catalyzed in NMP. This protocol was applied to a wide variety of functionalized and hindered aryl iodides and bromides with arylsilanes, to afford the desired biaryl ketones in good to excellent yields.

Full text of DOI:10.1016/j.tetlet.2016.02.058

Accepted Manuscript
Carbonylative Hiyama Coupling of Aryl Halides with Arylsilanes under Balloon
Pressure of CO
Sheng Chang, Ying Jin, Xiu Rong Zhang, Yong Bing Sun
PII:
S0040-4039(16)30167-8
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.02.058
TETL 47333
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
1 December 2015
5 February 2016
16 February 2016
Please cite this article as: Chang, S., Jin, Y., Zhang, X.R., Sun, Y.B., Carbonylative Hiyama Coupling of Aryl
Halides with Arylsilanes under Balloon Pressure of CO, Tetrahedron Letters (2016), doi: http://dx.doi.org/10.1016/
j.tetlet.2016.02.058
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Carbonylative Hiyama Coupling of Aryl Halides with
Arylsilanes under Balloon Pressure of CO
a,
a
a
b
Sheng Chang *, Ying Jin , Xiu Rong Zhang , Yong Bing Sun
a
College of Pharmacy, JiLin Medical University, JiLin 132013, JiLin, PR China. Tel.:
+
86 432 6645 5032. E-mail address: jmu_changsheng @126.com (S. Chang)
College of Pharmacy, Jiang Xi University of Traditional Chinese Medicine, Nan
b
Chang 3300043, Jiang Xi, PR China
Abstract
An efficient protocol has been developed for the carbonylative Hiyama coupling of
aryl halides using the cesium fluoride as a promoter by palladium-catalyzed in NMP.
This protocol was applied to a wide variety of functionalized and hindered aryl
iodides and bromides with arylsilanes, to afford the desired biaryl ketones in good to
excellent yields.
Keywords
carbonylation, Hiyama coupling, Pd-catalyzed, arylsilanes
Introduction
Palladium-catalyzed coupling reactions represent an important toolbox for the
1
functionalization of arene derivatives. Among the various types of coupling
processes, the catalytic cross-coupling reaction between aryl electrophiles and
organometallic nucleophiles accompanied by insertion of carbon monoxide allow for
the straightforward preparation of symmetrical or unsymmetrical diaryl ketones,
2
which represents a powerful tool in organic synthesis. Such structures are key
3
4
components in a variety of important pharmaceuticals including Tricor, Evistor and

5
Sector in addition to being numerous photosensitizers and advanced organic
6
materials. The Pd-catalyzed carbonylative Suzuki−Miyaura reaction represents a
viable three-component coupling protocol for rapid access to biaryl ketones and
became the most popular protocol among Pd-catalyzed carbonylation method with
7
CO. This is attributed in a large degree to unique properties of organoboron reagents,
8
such as ready availabilities, high stabilities and low toxicities. Otherwise, the
carbonylative Negishi, Stille and Hiyama reactions are classical examples of
9
transition metal-catalyzed carbonylation with CO to deliver biaryl ketones. Among
them, the Hiyama cross-coupling reaction have attracted much attention and have
1
0
made great progress in the construction of new C–C bonds. In comparison with
Stille coupling using toxic tin reagents and Suzuki coupling with problems in
purifying the boron reagents, organosilanes in Hiyama coupling are low toxicity, low
cost, ready availability, high chemical stability, and the leaving silicon group can be
converted to harmless SiO by incineration, making this method attractive from
2
1
1
environmental-friendly points of view. Recently, the cross-coupling of arylsiloxanes
with various coupling partners have drawn much attentions, such as
1
2
13
14
15
tosylates/mesylates, aryldiazonium salts, arylsulfinates, arylsulfonyl chlorides,
1
6
17
arylsulfonyl hydrazides, and arylhydrazines. The first carbonylative Hiyama
1
8
coupling have been reported by Hiyama over twenty years ago, diaryl ketones were
produced in good yields via the palladium-catalyzed carbonylative coupling of
arylfluorosilanes with aryl iodides in the presence of KF. However, the related
Hiyama-type carbonylations has been scarcely studied since then.
Although there is now considerable literature precedence for carbonylative
transformation, the majority of the work has been carried out with iodides. Only a
1
9
handful of reports focus on the use of aryl bromides as viable substrates, and in all
cases these transformations were carried out with organoboron reagents as the
nucleophilic coupling partner. No doubt that aryl bromides were low cost and ready
available reagents, in the meantime the more challenging coupling partner. Herein, we
report that the Pd-catalyzed carbonylative Hiyama coupling of aryl bromides using
the cesium fluoride as a promoter. This protocol was also applied to a wide variety of

functionalized and hindered aryl iodides.
Results and Discussion
Our study commenced with the decarboxylative Hiyama coupling of bromobenzene
with triethoxy(phenyl)silane using KF as the promoter and Pd(OAc) as the catalyst
2
under balloon pressure of CO. The reaction could only afford the desired product in
o
very low yield at 80 C in NMP. It was found, however, that the desired product could
be obtained in 50% yield when iodobenzene and triethoxy(phenyl)silane were mixed
o
and heated at 80 C for 12 h (Table 1, entry 1). To explore a more efficient catalytic
system for this decarboxylative Hiyama coupling, a model reaction was investigated
in detail by varying different parameters such as catalyst, promoter, and solvent to
develop appropriate reaction conditions for this transformation (Table 1).
At the outset, different transition metal catalysts, viz. Cu(OAc)
2
, Co(OAc)
2
, RhCl ,
3
RuCl , and Ni(OAc) , were screened using CsF as a promoter in NMP to determine
3
2
their catalytic efficacy (Table 1, entries 2-6). We were astonished to see that only the
palladium salt could bring about the desired conversion, and therefore the studies
were directed to look at the prospective of other palladium salts too. All the palladium
salts tried, viz. Pd(PPh
3
)
4
, Pd
2
(dba)
3
, Pd (dba)
2
, PdCl
2
, PdCl
2
(PPh
3
)
3
, PdCl (dppf) and
2
PdCl
2
(MeCN)
2
, invariably worked well (Table 1, entries 7-13), but the performance
of PdCl
2
(MeCN)
2
was maximum, providing the carbonylative Hiyama coupling
o
product in 79% yield at 80 C (Table 1, entry 13). The experiment under identical
conditions without the aid of a catalyst ended with no conversion (Table 1, entry 14).
.
The additive TBAF3H
2
O was also found to promote the reaction, allowing a good
yield (Table 1, entry 15). As the nature of the promoter is assumed to have a marked
impact on the removal of silicon group, different fluorine sources such as NH F, NaF
4
and AgF were also examined (Table 1, entries 16-18). Subsequent investigation on the
role of promoters for the aforementioned reaction revealed CsF as the most favored
one to push the reaction forward (Table 1, entry 19). In the absence of a promoter

under the same set of conditions, no conversion was observed (Table 1, entry 20). In
addition, the solvent effects were tested for this reaction in the presence of CO.
Whereas toluene did not afford any product (Table 1, entry 21), the other solvents, viz.
1
,4-dioxane, CH CN, DMSO and DMF, gave rise to 74%, 78%, 88% and 82%
3
product yields respectively (Table 1, entries 22-25). Finally as concluded above, the
optimal reaction conditions for the reaction turned out to be triethoxy(phenyl)silane
o
(
(
0.5 mmol) and iodobenzene (0.5 mmol), at 80 C with PdCl
2
(MeCN) /CsF in NMP
2
Table 1, entry 19). Then, we optimized the reaction conditions on the basis of
triethoxy(phenyl)silane and bromobenzene. The reaction gave a moderate yield in the
presence of PdCl
2
(MeCN)
2
and CsF (Table 1, entry 26). To our delight, the yield was
o
dramatically increased when the reaction temperature was increased to 100 C (Table
1
, entry 27). In addition, no better results were obtained when the reaction was carried
out under higher temperature (Table 1, entry 28). After extensive optimization, it was
o
found that the reaction could perform at 100 C with the additive CsF in the presence
of an PdCl
2
(MeCN) catalyst in NMP.
2
Table 1 Influence of the reaction conditions in carbonylative Hiyama cross-coupling
of iodobenzene with triethoxy(phenyl)silane
b
Entry
Promoter
KF
Catalyst
Solvent
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
Yield(%)
1
2
3
4
5
6
7
8
Pd(OAc)
2
50
-
KF
Cu(OAc)
2
2
KF
Co(OAc)
-
KF
RhCl
RuCl
Ni(OAc)
Pd(PPh
Pd (dba)
3
-
KF
3
-
KF
2
-
KF
3
)
4
57
54
KF
2
3

9
KF
KF
KF
KF
KF
KF
Pd (dba)
PdCl
PdCl (PPh
PdCl (dppf)
PdCl (MeCN)
2
NMP
NMP
59
53
67
72
79
-
1
0
2
1
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
2
3
)
3
NMP
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
NMP
2
2
NMP
-
NMP
.
TBAF3H
2
O
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
2
(MeCN)
(MeCN)
(MeCN)
(MeCN)
(MeCN)
(MeCN)
(MeCN)
(MeCN)
(MeCN)
(MeCN)
(MeCN)
(MeCN)
(MeCN)
(MeCN)
2
2
2
2
2
2
2
2
2
2
2
2
2
2
NMP
84
59
68
82
95
-
NH
4
F
2
NMP
AgF
NaF
CsF
-
2
NMP
2
NMP
2
NMP
2
NMP
CsF
CsF
CsF
CsF
CsF
CsF
CsF
CsF
2
toluene
1,4-dioxane
-
2
74
78
88
82
69
91
90
2
CH CN
3
2
DMSO
DMF
NMP
NMP
NMP
2
c
2
6
7
8
2
d
e
2
2
2
2
a
Reaction conditions: triethoxy(phenyl)silane (0.5 mmol), iodobenzene (0.5 mmol)
o
(
0.5 mmol), promoter (0.5 mmol), catalyst (5 mol%), solvent (5.0 ml) at 80 C for 6
b
c
hours under CO (1 atm) unless otherwise indicated. Isolated yield. Iodobenzene
o
d
was replaced by bromobenzene (0.5 mmol) at 80 C. Iodobenzene was replaced by
o
e
bromobenzene (0.5 mmol) at 100 C. Iodobenzene was replaced by bromobenzene
o
(
0.5 mmol) at 120 C.
With the optimal conditions in hand, the scope of the transformation was
investigated, and the results were summarized in Table 2. As shown in Table 2, both
electron-donating and -withdrawing groups attached to triethoxy(phenyl)silane were

all suitable for this protocol. Aryl silanes with different substituents, such as Me, F,
NO , and CF , could all provide the corresponding products with 88-95% yields
Table 2, column A, entries 1-5). In addition, 3,4-methyl and 2-methyl substituted aryl
2
3
(
silanes also reacted with iodobenzene to obtain the desired products in 87% and 84%
yields (Table 2, column A, entries 6-7). This indicated that the electronic and steric
nature of the aryl silanes had little influence on the reaction efficiency. Notably,
chloro-substituent could also tolerant with this method to afford the corresponding
products in good to excellent yields (Table 2, column A, entries 8-10). Encouraged by
the results obtained with iodobenzene, we focused our attention on the reaction of
bromobenzene and aryl silanes with the same functionalized groups for comparison.
Delightfully, the results in Table 2 (column B) demonstrated a good functional-group
tolerance for different functionalized aryl silanes. The results demonstrated that the
electronic nature of the aryl silanes had little influence on the reaction efficiency, as
all the desired products were obtained in good yields (Table 2, column B, entries 1-5).
The substrate scope of various steric hindrance aryl silanes with bromobenzene was
explored (Table 2, column B, entries 6-7), only with slightly decrease of efficiency.
Aryl silanes bearing
a
chloro- group afforded the corresponding
4
-chlorobenzophenone, 3-chlorobenzophenone and 2-chlorobenzophenone in 90%, 85%
and 81% yields, respectively (Table 2, column B, entries 8-10).
Table 2 Pd-catalyzed carbonylative Hiyama coupling of aryl silanes with
a
iodobenzene or bromobenzene
b
c
Entry
1
R
4-CH
H
Yield (%)
93
Yield (%)
89
3
2
3
95
89
91
92
4
-F

4
-NO
-CF
,4-CH
2-CH
2
4
5
92
88
88
84
4
3
3
3
6
7
8
87
84
93
83
78
90
3
4
3
2
-Cl
-Cl
-Cl
9
87
88
85
81
1
0
a
Reaction conditions: aryl silanes (0.5 mmol), CsF (0.5 mmol),
PdCl
2
(MeCN)
2
(5 mol%), NMP (5.0 ml) for 6 hours under CO
b
(
1 atm) unless otherwise indicated. Iodobenzene (0.5 mmol) at
o
c
o
8
0 C with isolated yield. Bromobenzene (0.5 mmol) at 100 C
with isolated yield.
We next explored the substrate scope of the palladium-catalyzed carbonylative
Hiyama coupling reactions. The substrate scope of various aryl iodines with
triethoxy(phenyl)silane was explored (Table 3). Delightfully, the results in Table 3
demonstrated a good functional-group tolerance for different aryl iodines, such as
methyl, trifluoromethyl, nitro, fluoro, and chloro were suitable for this transformation
(
Table 3, entries 1-5). Bromo-contained substrate, such as 1-bromo-4-iodobenzene
and 1-bromo-2-iodobenzene, which is sensitive in many coupling reactions, survived
well under this carbonylative Hiyama conditions, giving the corresponding
bromobenzophenones in good to excellent yields (Table 3, entries 6-7). We did not
observe the by-products of the coupling with bromated arenes in these reactions.
3
-chloro-substituted were converted to the corresponding products in good yield
Table 3, entry 8). Ortho-position substituted aryl iodines such as
-methyl-iodobenzene and 2-chloro-iodobenzene proceeded smoothly to generate
corresponding ketones in good yields (Table 3, entries 9-10). When a highly steric
(
2

hindrance halides such as pentamethyl-iodobenzene and pentafluoro-iodobenzene was
used as substrates, 73% and 75% yield of products were obtained (Table 3, entries
1
1-12). It is noteworthy that 2-iodopyridine was also proved to be reactive (Table 3,
entry 13).
Table 3 Pd-catalyzed carbonylative Hiyama coupling of triethoxy(phenyl)silane with
a
various aryl iodines
b
Entry
R
Yield (%)
92
1
2
3
4
5
6
7
8
9
4-CH
3
-C
-C
-C
6
H
5
4-CF
3
6
H
5
85
89
93
91
94
87
86
80
83
73
75
72
4-NO
2
6
H
5
4-F-C
6
H
5
4-Cl-C
6
H
5
4-Br-C
6
6
H
5
5
2-Br-C
H
3-Cl-C
6
H
5
2-CH
3
-C
6
H
5
1
0
2-Cl-C
6
H
5
11
2,3,4,5,6-CH
2,3,4,5,6-F-C
2-pyridinyl
3
-C
6
H
5
1
2
3
6
H
5
1
a
Reaction conditions: triethoxy(phenyl)silane (0.5
mmol), aryl iodine (0.5 mmol), CsF (0.5 mmol),
o
PdCl
2
(MeCN)
2
(5 mol%), NMP (5.0 ml) at 80 C for 6
b
hours under CO (1 atm) unless otherwise indicated.
Isolated yield.

To further expand the scope of the substrates, aryl bromides were also investigated.
To our delight, aryl bromides could easily be reacted with triethoxy(phenyl)silane, to
afford the corresponding products (Table 4). The results indicated that aryl bromides,
bearing either an electron-donating or -withdrawing group on the aromatic ring,
o
performed smoothly with triethoxy(phenyl)silane at 100 C, and all the desired
products were obtained in good yields (82-90%)(Table 4, entries 1-6). To our delight,
cyano was also compatible for the transformation and the corresponding product was
afforded in moderate to good yields (77-90%, Table 4, entries 6-7). Meanwhile, aryl
bromide bearing a sterically hindered group, such as chloro at their
ortho-/meta-positions, also underwent the reaction with triethoxy(phenyl)silane
smoothly, providing the corresponding products in slightly lower yields (78–80%)
compared with their corresponding para-substituted ones (Table 4, entries 8-9).
However, a weak ortho position effect was observed in the reaction of
2
-methyl-bromobenzene (Table 4, entry 10). When pentamethyl-bromobenzene and
pentafluoro-bromobenzene were used, the desired product was obtained in 76% and
9% yield, upon isolation (Table 4, entries 11-12). This poor yield may be due to
7
steric hindrance. The thienyl and pyridinyl group survived well under the standard
conditions, giving the corresponding products in moderate yields (Table 4, entries
1
3-14). Importantly, structurally challenging nitrogen heterocyclic moiety in a
number of bioactive natural products, such as oxazole and pyrimidine derivatives,
were also coped with this conditions (Table 4, entries 15-16).
Table 4 Pd-catalyzed carbonylative Hiyama coupling of triethoxy(phenyl)silane with
a
various aryl bromides
b
Entry
R
Yield (%)
87
84
1
2
4-CH
3
-C
6
H
5
4-CF
3
-C
6
H
5

3
4
5
6
7
8
9
1
4-NO
2
-C
6
H
5
82
88
86
90
77
80
78
85
76
79
70
75
68
71
4-F-C
6
H
5
4-Cl-C
6
H
5
4-CN-C
6
6
H
5
5
2-CN-C
H
3-Cl-C
6
6
H
5
5
2-Cl-C
H
0
2-CH
3
-C
6
H
5
11
2,3,4,5,6-CH
3
-C
6
H
5
1
1
1
1
2
3
4
5
6
2,3,4,5,6-F-C
6
H
5
2-thienyl
3-pyridinyl
oxazol-2-yl
1
3,5-pyrimidinyl
a
Reaction conditions: triethoxy(phenyl)silane (0.5 mmol),
(MeCN)
aryl bromide (0.5 mmol), CsF (0.5 mmol), PdCl
2
2
o
(
(
5 mol%), NMP (5.0 ml) at 100 C for 6 hours under CO
b
1 atm) unless otherwise indicated. Isolated yield.
Mechanism
A possible mechanism for the carbonylative Hiyama coupling is proposed in Scheme
. It is suggested that the Pd(II) pre-catalyst is first reduced by the generated CO to
1
[20]
Pd(0). Oxidative addition of the carbon-halide bond (C-Br or C-I) to the generated
Pd(0) generates the corresponding acyl palladium species (I) which followed by CO
coordination and insertion to generate the intermediate (II). Attack of fluoride ion to
arylsilanes followed by migration of a aryl group generates the intermediate (III) , and
the terminal unsymmetrical diaryl ketones are produced after the reductive
elimination with the concomitant generation of Pd(0), which finishes the catalytic

cycle. In addition, a base such as Cesium fluoride reacts with PhSi(OR)
transmetalation step (Scheme 1).
3
to facilitate
Scheme 1. The plausible mechanism for the carbonylative Hiyama coupling of aryl
halides
Conclusion
In conclusion, a new procedure for the preparation of biaryl ketone compounds
through the Pd-catalyzed carbonylative Hiyama cross-coupling of aryl iodines or aryl
bromides with various organosilicon reagents was developed. This novel method
provides easy access to biaryl ketone compounds by using commercially available
and inexpensive aryl halides. The reaction did not require too much time, harsh
reaction conditions, an high-pressure carbon monoxide atmosphere, or the exclusion
of air. This cost-effective methodology will be very attractive for both academia and
industry because commercially available aryl halides are used as the coupling partners.
This new reaction may be used in the future as a complement to the classical
carbonylative Hiyama cross-coupling reaction.

Acknowledgements
This work was financially supported by the Education Department of JiLin Province
Natural Science Research Program (2015404) and the Science Technology
Department of JiLin Province(20140311110YY).
Supplementary data
Supplementary data associated with this article can be found, in the online version
Reference and notes
1.
(a) Hassan, J.; Sévignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem. Rev. 2002, 102, 1359;
b) Bringmann, G.; Price Mortimer, A. J.; Keller, P. A.; Gresser, M. J.; Garner, J.; Breuning,
M. Angew. Chem. Int. Ed. 2005, 44, 5384; (c) Corbet, J.-P.; Mignani, G. Chem. Rev. 2006,
06, 2651; (d) Grimsdale, A. C.; Leok Chan, K.; Martin, R. E.; Jokisz, P. G.; Holmes, A. B.
(
1
Chem. Rev. 2009, 109, 897; (e) Metal-Catalyzed Cross-Coupling Reactions, 2nd ed.; de
Meijere, A., Diederich, F., Eds.; Wiley-VCH: Weinheim, Germany, 2004; (f) Jana, R.; Pathak,
T. P.; Sigman, M. S. Chem. Rev. 2011, 111, 1417; (g) Metal-Catalyzed Cross-Coupling
Reactions and More. de Meijere, A. Bräse, S. and Oestreich, M. Eds.; Wiley-VCH: Weinheim,
Germany, 2014; (h) New Trends in Cross-Coupling Theory and Applications. Colacot, T. J.
Eds.; The Royal Society of Chemistry, Cambridge, 2015.
2
3
.
.
Brennfuhrer, A.; Neumann, H.; Beller, M. Angew. Chem. Int. Ed. 2009, 48, 4114.
Lindhardt, A. T.; Simmonsen, R.; Taaning, R. H.; Gøgsig, T. M.; Nilsson, G. N.; Stenhagen,
G.; Elmore, C. S.; Skrydstrup, T. J. Labelled. Compd. Radiopharm. 2012, 55, 411.
Jeong, E. J.; Liu, Y.; Lin, H.; Hu, M. Drug Metab. Dispos. 2005, 33, 785.
4
5
6
.
.
.
Kantor, T. G. Pharmacotherapy 1986, 6, 93.
(a) Surry, D. S.; Buchwald, S. L. Angew. Chem., Int. Ed. 2008, 47, 6338; (b) Zapf, A.; Beller,
M. Chem. Commun. 2005, 431; (c) Jana, R.; Pathak, T. P.; Sigman, M. S. Chem. Rev. 2011,
111, 1417.

7.
(a) Wakita, Y.; Yasunaga, T.; Akita, M.; Kojima, M. J. Organomet. Chem. 1986, 301, C17; (b)
Ishiyama, T.; Kizaki, H.; Miyaura, N.; Suzuki, A. Tetrahedron Lett. 1993, 34, 1595; (c) Wu,
X.-F.; Neumann, H.; Beller, M. Chem. Soc. Rev. 2011, 40, 4986; (d) Blangetti, M.; Rosso, H.;
Prandi, C.; Deagostino, A.; Venturello, P. Molecules 2013, 18, 1188.
8
9
.
.
Boronic Acids-Preparation and Applications in Organic Synthesis, Medicine and Materials,
Hall, D. G. Ed.; Wiley-VCH, Weinheim, 2011, vol. 2.
For some recent reviews on Pd-catalyzed carbonylations of aryl halides with CO, see: (a)
Gadge, S. T.; Bhanage, B. M. RSC Adv. 2014, 4, 10367; (b) Fang, W. W.; Zhu, H. B.; Deng,
Q. Y.; Liu, S. L.; Liu, Y. X.; Shen, Y. J.; Tu, T. Synthesis, 2014, 46, 1689; (c) Wu, X.- F.;
Neumann, H.; Beller, M. Chem. Rev. 2013, 113, 1; (d) Transition Metal Catalyzed
Carbonylation Reactions-Carbonylative Activation of C–X Bonds, Wu, X.-F.; Beller, M. Eds.;
Springer-Verlag Berlin,Heidelberg, 2013; (e) Wu, X.- F.; Neumann, H.; Beller, M. Chem. Soc.
Rev. 2011, 40, 4986; (f) Magano, J.; Dunetz, J. R. Chem. Rev. 2011, 111, 2177; (g) Grigg, R.;
Mutton, S. P. Tetrahedron, 2010, 66, 5515; (h) Brennfuhrer, A.; Neumann, H.; Beller, M.
Angew. Chem. Int. Ed. 2009, 48, 4114.
1
1
1
0. (a) Denmark, S. E.; Ober, M. H. Aldrichim. Acta 2003, 36, 76; (b) Denmark, S. E.; Liu, J.
H.-C. Angew. Chem., Int. Ed. 2010, 49, 2978; (c) Denmark, S. E.; Regens, C. S. Acc. Chem.
Res. 2008, 41, 1486; (d) Nakao, Y.; Hiyama, T. Chem. Soc. Rev. 2011, 40, 4893; (e) Sore, H.
F.; Galloway, W. R. J. D.; Spring, D. R. Chem. Soc. Rev. 2012, 41, 1845.
1. (a) Zhang, H.-J.; Priebbenow, D. L.; Bolm, C. Chem. Soc. Rev. 2013, 42, 8540; (b) Franzen, R.
G. Tetrahedron 2000, 56, 685; (c) Ashby, E. C.; Laemmle, J.; Neumann, H. M. Acc. Chem.
Res. 1974, 7, 272; (d) Elsayed-Ali, H. E.; Waldbusser, E. U.S. Pat. 200400767552004; (e)
Boller, E. R. U. S. Pat. 35089131970.
2. (a) So, C. M.; Lee, H. W.; Lau, C. P.; Kwong, F. Y. Org. Lett. 2009, 11, 317; (b) Zhang, L.;
Wu, J. J. Am. Chem. Soc. 2008, 130, 12250.
1
1
1
1
1
3. Cheng, K.; Wang, C.; Ding, Y.; Song, Q.; Qi, C.; Zhang, X.-M. J. Org. Chem. 2011, 76, 9261.
4. Cheng, K.; Hu, S.; Zhao, B.; Zhang, X.-M.; Qi, C. J. Org. Chem. 2013, 78, 5022.
5. Zhang, W.; Liu, F.; Li, K.; Zhao, B. Appl. Organometal. Chem. 2014, 28, 379.
6. Miao, H.; Wang, F.; Zhou, S.; Zhang, G.; Li, Y. Org. Biomol. Chem. 2015, 13, 4647.
7. Zhang, H.; Wang, C.; Li, Z.; Wang, Z. Tetrahedron Lett. 2015, 56, 5371.

1
1
8. (a) Natanaka, Y.; Hiyama, T. Chem. Lett. 1989, 2049. (b) Hatanaka, Y.; Fukushima, S.;
Hiyama, T. Tetrahedron 1992, 48, 2113.
9. (a) Ishiyama, T.; Kizaki, H.; Hayashi, T.; Suzuki, A.; Miyaura, N. J. Org. Chem. 1998, 63,
4726; (b) Couve-Bonnaire, S.; Carpentier, J.-F.; Mortreux, A.; Castanet, Y. Tetrahedron Lett.
2001, 42, 3689; ꢀcꢁ ꢂeuꢃannꢄ ꢅꢆꢇ ꢈrennꢉꢊhrer, A.; Beller, M. Chem. Eur. J. 2008, 14, 3645;
(
d) Kaganovsky, L.; Gelman, D.; Rueck-Braun, K. J. Organomet. Chem. 2010, 695, 260.
20. (a) Mohamed Ahmed, M. S.; Mori, A. Org. Lett. 2003, 5, 3057. (b) Liang, B.; Huang, M.;
You, Z.; Xiong, Z.; Lu, K.; Fathi, R.; Chen, J.; Yang, Z. J. Org. Chem. 2005, 70, 6097.
Graphical Abstract
An efficient protocol has been developed for the carbonylative Hiyama coupling of
aryl halides using the cesium fluoride as a promoter by palladium-catalyzed in NMP.
This protocol was applied to a wide variety of functionalized and hindered aryl
iodides and bromides with arylsilanes, to afford the desired biaryl ketones in good to
excellent yields.