Biaryl Ketones by Suzuki–Miyaura Cross-Coupling of Organotrifluoroborates and Acyl Chlorides

Article abstract of DOI:10.1002/ejoc.201600199

A procedure for the synthesis of biaryl ketones by a palladium-catalyzed Suzuki–Miyaura cross-coupling reaction between phenyltrifluoroborates and benzoyl chlorides is described. Organotrifluoroborates are unique to other cross-coupling reagents as they have a high functional-group tolerance and are moisture-stable. Moderate to excellent yields were obtained for all substrates tested.

Full text of DOI:10.1002/ejoc.201600199

DOI: 10.1002/ejoc.201600199
Full Paper
Ketones by Cross-Coupling
Biaryl Ketones by Suzuki–Miyaura Cross-Coupling of
Organotrifluoroborates and Acyl Chlorides
[a]
[b]
[a]
[a]
Alaina M. Forbes* G. Patrick Meier, Ebenezer Jones-Mensah, and Jakob Magolan
Abstract: A procedure for the synthesis of biaryl ketones by pling reagents as they have a high functional-group tolerance
a palladium-catalyzed Suzuki–Miyaura cross-coupling reaction and are moisture-stable. Moderate to excellent yields were ob-
between phenyltrifluoroborates and benzoyl chlorides is de- tained for all substrates tested.
scribed. Organotrifluoroborates are unique to other cross-cou-
Introduction
pling reactions (Table 1, Entries 1–8). We observed no ketone
formation at room temperature after 12 h under the conditions
reported by Bumagin and Korolev for the coupling of boronic
acids with acyl chlorides, PdCl and Na CO in an acetone/water
mixture (Entry 1). When this reaction was conducted at 65 °C
for 12 h, the desired biaryl ketone 3 was isolated in 15 % yield
In 1998, Suzuki, Miyaura and co-workers prepared biaryl ket-
ones by carbonylative cross-coupling between arylboronic acids
2
2
3
[
1]
and aryl halides in the presence of carbon monoxide. While
such carbonylative cross-couplings are valuable synthetic
[3a]
[
2]
tools, Pd-catalyzed cross-couplings between arylboronic acids
and acyl chlorides can also offer biaryl ketones without the
need for carbon monoxide as first demonstrated independently
(
Entry 2). Treatment of 1 and 2 with PdCl (PPh ) and K PO in
2 3 2 3 4
toluene at 110 °C, according to the method of Urawa and
[4]
Ogura, also resulted in no product formation (Entry 3). A 15 %
[
3]
by Bumagin et al. and Haddach et al. in 1999. Alternative
procedures for this cross-coupling have also been reported by
yield was observed when water was added as a co-solvent (En-
try 4). Water is important to cross-coupling reactions of tri-
fluoroborate salts, which proceed by in-situ hydration to bor-
[
4]
[5]
Urawa and Ogura, as well as by Zhang and co-workers. The
ubiquity of aryl ketones as pharmaceutically relevant targets
and synthetic intermediates warrants the continued develop-
ment of ever more versatile and robust methods toward their
access.
[
8]
onic acids. Hence, we investigated the aqueous conditions
reported by Zhang and co-workers in 2006 for coupling of aryl-
boronic acids with acyl chlorides. The authors used Pd(OAc) in
2
the presence of Na CO and poly(ethylene glycol) (PEG2000) or
2
3
In the past two decades, organotrifluoroborates have
1
-butyl-3-methylimidazolium hexafluorophosphate ([bmim]-
[
6]
emerged as versatile and useful organoboron reagents. In the
context of Suzuki–Miyaura cross-coupling chemistry, the advan-
tages of organotrifluoroborates over boronic acids and other
organoboron species are stability to air and moisture as well as
excellent functional-group tolerance. Given these advantages,
we sought to develop a new procedure for the synthesis of
ketones by Suzuki–Miyaura cross-coupling between organotri-
fluoroborates and acyl chlorides.
[
PF ]) in water. Unfortunately, these reaction conditions were
6
not effective with phenyltrifluoroborate, and only trace product
formation was observed (Entries 5, 6). Molander and co-work-
[
9]
ers readily coupled phenyltrifluoroborates with aryl halides
using Pd(PPh ) and 3 equiv. of K CO in toluene/water (10:1).
[
7]
3
4
2
3
We used a 1:3 ratio of trifluoroborate salt 1/acyl chloride 2 to
achieve a 77 % yield of the desired ketone 3 (Entry 7). Under
the same conditions we screened three alternative palladium
catalysts (Entries 8–10). Tris(dibenzylideneacetone)dipalladium
[
Pd (dba) ] resulted in a decreased product yield of 61 %, while
2 3
Results and Discussion
PdCl and Pd(OAc) yielded only trace amounts of the desired
2
2
ketone.
We began the development of this reaction by subjecting a 1:1
mixture of potassium phenyltrifluoroborate (1)/4-toluoyl chlor-
Having selected our catalyst, base, and solvent system, we
ide (2) to a series of reaction conditions previously reported by conducted a more thorough analysis of the remaining reaction
authors to be effective for various Suzuki–Miyaura cross-cou- parameters as summarized in Table 2. Adjustments to the
amount of Pd(PPh ) from 1.8 mol-% to 0.18 mol-% (Entry 2)
3
4
[
a] Department of Chemistry, University of Idaho,
Moscow, ID, 83844-2343, USA
E-mail: alaina@uidaho.edu
b] Department of Chemistry, Washington State University,
Pullman, WA 99164-4630, USA
and 18 mol-% (Entry 3), the reaction time from 12 h to 6 h
(Entry 4) and 19 h (Entry 5), and the temperature from 90 °C to
6
5 °C (Entry 6) all resulted in reduced yields. We varied the ratio
[
of substrates 1/2 (Entries 7–10) and found an optimal ratio to
be 1.5:1, which resulted in a 95 % isolated yield of ketone 3
(Entry 9). A 1:2 ratio of organotrifluoroborate/base (Entry 8) was
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under http://dx.doi.org/10.1002/ejoc.201600199.
Eur. J. Org. Chem. 2016, 2983–2987
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Table 1. Initial reaction development.
Entry
Substrate ratio
Catalyst
[mol-%]
Base
[equiv.]
Solvent
Temp.
[°C]
Time
[h]
Isolated yield
(
1/2)
[%]
1
2
3
4
5
6
7
8
9
1:1
1:1
1:1
1:1
1:1.2
1:1.2
1:3
1:3
1:3
1:3
PdCl
PdCl
2
1.0
1.0
2.0
2.0
0.5
1.8
1.8
1.8
1.8
1.8
Na
Na
2
2
CO
CO
3
1.6
1.6
1.5
1.5
1.6
1.6
3.0
3.0
3.0
3.0
acetone/H
acetone/H
2
2
O (6:1)
O (6:1)
r.t.
65
110
110
60
60
90
90
90
12
12
12
12
12
12
12
12
12
12
0
15
0
15
0
trace
77
61
trace
trace
2
3
PdCl
PdCl
2
(PPh
(PPh
3
3
2
2
)
)
2
K
K
3
PO
PO
4
toluene
2
2
3
4
toluene/H
2
O (50:1)
O (1:1)
O (1.2:1)
Pd(OAc)
Pd(OAc)
Na
Na
2
2
CO
CO
3
PEG2000/H
2
3
[bmim][PF
6
]/H
2
Pd(PPh
Pd (dba)
PdCl
Pd(OAc)
3
)
4
K
K
K
K
2
2
2
2
CO
CO
CO
CO
3
toluene/H
toluene/H
toluene/H
toluene/H
2
2
2
2
O (10:1)
O (10:1)
O (10:1)
O (10:1)
2
3
3
3
3
2
10
2
90
also found to be important in maintaining maximal yields, pre- conditions. We had envisaged that our tetrabutylammonium
sumably because variations from this ratio (Entries 11–13) result salts would have superior solubility in comparison to potassium
in the increased presence of unreactive “ate” complexes salts in our 10:1 toluene/water solvent system and would lead
–
[7a,10]
[
RB(OH)3 and RBF K].
to improved yields. However, only a trace amount of the ketone
was produced, and only after the water content had been
3
3
Table 2. Optimization of reaction parameters.
increased from 10:1 to 2.6:1 toluene/water reinforcing the criti-
cal role of water in the conversion of the organotrifluoroborate
into the reactive organoboron species in these reactions.
Potassium phenyltrifluoroborate (1) was prepared from
[
6a]
phenylboronic acid as illustrated in Scheme 1.
Tetrabutyl-
ammonium phenyltrifluoroborate (5) was prepared from the
potassium salt by cation exchange as reported by Batey and
Entry
1
2
Pd(PPh
3
)
4
K
2
CO
3
Temp. Time
Isolated
yield
[%]
[
8b]
co-workers (Scheme 1), but with a modification to the proce-
dure, whereby tetrabutylammonium hydrogen sulfate was used
rather than tetrabutylammonium hydroxide, which resulted in
a superior yield with fewer byproducts as observed by 19F NMR
spectroscopy.
[
equiv.] [equiv.] [mol-%] [equiv.]
[°C]
[h]
1
2
3
4
5
6
7
8
9
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.5
3
3.0
3.0
3.0
3.0
3.0
1.5
6.0
1.5
1
1
1
1
1
1.8
0.18
18
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
9.0
1.5
4.5
9
90
90
90
90
90
65
90
90
90
90
90
90
90
12
12
12
6
19
12
12
12
12
12
12
12
12
77
70
73
53
68
78
72
84
95
85
68
88
51
1.8
1.8
1.8
1.8
1.8
1.8
1.8
1.8
1.8
1.8
1
0
1
1
1.5
1.5
1.5
1
2
Scheme 1. Synthesis of trifluoroborate salts.
13
To investigate the scope of this reaction, the cross-couplings
The end results of our optimization was a set of preferred of four phenyltrifluoroborates with nine acyl chlorides were per-
reaction conditions summarized as follows: potassium organo- formed to yield twelve biaryl ketones as illustrated in Table 3.
trifluoroborate (1.5 equiv.), acyl chloride (1.0 equiv.), Pd(PPh3)4 Our optimal reaction conditions worked well for most sub-
(
1.8 mol-%), K CO (3 equiv.), in a solvent mixture of toluene/ strates. Minor modifications were needed in cases where the
2 3
water (10:1) at 90 °C for 12 h. Notably, we found it was best to organotrifluoroborate or acyl chloride was sterically hindered
use freshly oven-dried (140 °C) or flame-dried (see Experimental and/or had low solubility in the optimal solvent system as indi-
Section) K CO for this reaction. When K CO was used without cated in Table 3. In these cases, we found that doubling the
2
3
2
3
drying, the yields were reduced. This observation was unex- amount of organotrifluoroborate and base in general improved
pected and puzzling given the fact that the reaction solvent yields. Solubility was improved by adding a small amount of
includes water. Another interesting, but not completely under- acetone to the solvent system, 10:1:1 toluene/acetone/H O.
2
stood observation was the lack of reactivity of the tetrabutyl- Maximal yields and optimal reaction conditions are reported in
ammonium phenyltrifluoroborate salts in comparison to the po- Table 3 and analyzed below. First, we treated phenyl trifluoro-
tassium phenyltrifluoroborate salts under our optimal reaction borate (1) with seven different acyl chlorides to yield ketones
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Table 3. Substrate scope.[a]
of ketones 18 and 19 (29 % and 23 %, respectively; Scheme 2A).
The reaction between the aliphatic n-butyryl trifluoroborate
and toluyl chloride was not effective with no observed forma-
tion of the desired ketone (21; Scheme 2B).
Scheme 2. Attempted cross-couplings with aliphatic substrates. Reaction con-
ditions: acyl chloride (1.0 equiv.), potassium organotrifluoroborate
(
9
1.5 equiv.), Pd(PPh
0 °C, 12 h. Isolated yields are reported. [a] The amounts of organotrifluorob-
orate and K CO were doubled to 3.0 and 6.0 equiv., respectively.
3 4 2 3 2
) (1.8 mol-%), K CO (3.0 equiv.), toluene/H O (10:1),
2
3
Conclusions
We have demonstrated the effective cross-coupling of potas-
sium phenyltrifluoroborates with a variety of aromatic acyl
chlorides. The reaction tolerates a range of functional groups on
both coupling partners with observed yields largely substrate-
dependent. This work expands the utility of organo-
trifluoroborates and offers a promising new approach to the
preparation of aromatic ketones.
[
a] Reaction conditions: acyl chloride (1.0 equiv.), potassium organotrifluorob-
orate (1.5 equiv.), Pd(PPh (1.8 mol-%), K CO (3.0 equiv), toluene/H O (10:1),
0 °C, 12 h. Isolated yields are reported. [b] The amounts of organotrifluorob-
orate and K CO were doubled to 3.0 and 6.0 equiv., respectively. [c] The
solvent system was modified to toluene/acetone/H O (10:1:1).
3
)
4
2
3
2
9
2
3
2
8
–14. Two of the three electron-rich anisoyl chlorides were ef-
fective substrates yielding the para- and meta-methoxy-substi-
tuted benzophenones 8 and 9 in 92 % and 77 % yield, respec- Experimental Section
tively. The ortho-anisolyl chloride was an inferior substrate
General Information: All substrates, reagents, and solvents were
obtained from commercial suppliers and used as purchased without
further purification. NMR experiments were performed with a
yielding benzophenone 10 in just 44 %. Electron-poor para-
and meta-nitro-substituted benzoyl chlorides were suitable sub-
strates offering the corresponding benzophenones 11 and 12
in 83 % and 65 % yield, respectively. High chemoselectivity of
the organotrifluoroborate to the acyl chloride relative to a ring
Bruker AVANCE 300 MHz instrument, and samples were obtained in
1
CDCl (referenced to δ = 7.26 ppm for H and δ = 76.16 ppm for
3
13
C). Coupling constants [J] are in Hz. The multiplicities of the sig-
halide was observed with 3-chlorobenzoyl chloride resulting in nals are described using the following abbreviations: s = singlet,
a 74 % yield of ketone 13. Phenyl 2-thiophenyl ketone (14) was d = doublet, t = triplet, dd = doublet of doublets, m = multiplet.
Reaction progress was monitored by thin-layer chromatography
obtained in 73 % yield upon reaction with 2-thiophenyl chlor-
ide.
Next we treated 4-toluoyl chloride with three different
phenyltrifluoroborates to prepare benzophenones 15–17. The
electron-rich (para-methoxyphenyl)trifluoroborate and the elec-
tron-poor (meta-methoxycarbonylphenyl)trifluoroborate were
effective substrates in yielding benzophenones 15 and 16 in
(
TLC; Silica Gel 60 F254, EMD Chemicals Inc.), visualized under UV
light, and plates were developed using p-anisaldehyde. Flash chro-
matography was performed using silica gel (particle size 40–63 μm;
Sorbent Technologies). All potassium phenyltrifluoroborates were
[6a]
synthesized according to the methods reported by Vedejs et al.,
and Molander et al.
[11]
Synthesis of Tetrabutylammonium Phenyltrifluoroborate: Tetra-
70 % and 82 % yield, respectively, while the sterically encum-
butylammonium phenyltrifluoroborate was prepared using a modi-
bered (2,4,6-trimethylphenyl)trifluoroborate was a poor sub-
strate with 17 isolated in just 38 % yield.
[8b]
fication of the procedure of Batey et al.,
as follows. Potassium
phenyltrifluoroborate (50 mg, 0.270 mmol) was placed in a round-
The cross-coupling of phenyltrifluoroborate with 4-chloro- bottomed flask and dissolved in water (2 mL). Tetrabutylammonium
butyryl chloride and octanoyl chloride resulted in poor yields hydrogen sulfate (102 mg, 0.299 mmol) was then added, followed
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by dichloromethane (CH Cl ; 2 mL). The mixture was stirred at room 3-Nitrobenzophenone (12): The general procedure with Modifica-
2
2
temperature for 5 min. The biphasic mixture was then diluted with
tion 1 was applied to yield 12 as a yellow solid (60 mg, 65 % yield).
1
CH Cl (5 mL), allowed to separate, and the CH Cl layer was col-
H NMR (300 MHz, CDCl ): δ = 8.66–8.59 (m, 1 H), 8.44 (ddd, J =
2
2
2
2
3
lected. The aqueous layer was then rinsed with additional CH Cl2
8.2, 2.3, 1.2 Hz, 1 H), 8.14 (dt, J = 7.7, 1.4 Hz, 1 H), 7.85–7.77 (m, 2
2
(
2 × 5 mL), and the CH Cl layer was collected each time. The CH Cl
H), 7.75–7.62 (m, 2 H), 7.58–7.49 (m, 2 H) ppm. 13C NMR (75 MHz,
2
2
2
2
was evaporated under vacuum to give the product, a white crystal-
line precipitate (103 mg, 97 % yield). Spectral data was consistent
with that of previous reports.
CDCl ): δ = 193.25, 147.28, 138.24, 135.43, 134.53, 132.47, 129.13,
3
128.76, 127.86, 125.82, 123.83 ppm. NMR spectra are consistent
[
13]
with previously reported data.
General Procedure for the Synthesis of Biaryl Ketones: A round-
bottomed flask containing potassium carbonate (169 mg,
3-Chlorobenzophenone (13): The general procedure was applied
to yield 13 as a white solid (78 mg, 73 % yield). H NMR (300 MHz,
1
1
.220 mmol) was flame-dried and cooled under vacuum. A solution
of the potassium organotrifluoroborate (0.612 mmol) and tet-
rakis(triphenylphosphine)palladium (8.5 mg, 0.007 mmol, 1.8 mol- CDCl
) in toluene (5 mL) and H O (0.5 mL) was added to the flask and
129.03, 128.76, 127.59, 127.22 ppm. NMR spectra are consistent
CDCl
H), 7.57–7.50 (m, 2 H), 7.50–7.40 (m, 1 H) ppm. C NMR (75 MHz,
): δ = 194.33, 138.45, 136.14, 133.73, 131.94, 131.47, 129.14,
3
): δ = 7.85–7.78 (m, 3 H), 7.71–7.64 (m, 1 H), 7.64–7.57 (m, 2
13
3
%
2
[
5]
the mixture stirred at room temperature under nitrogen for 5 min.
The acyl chloride (0.408 mmol) was added by syringe, and the reac-
tion mixture was heated to 90 °C for 12 h. The reaction mixture was
filtered through a pipette packed with glass wool and rinsed with
toluene (2 mL). The filtrate was then washed with saturated sodium
hydrogen carbonatesolution (2 × 20 mL) and brine (2 × 20 mL). The
solvent was removed in vacuo and the crude product further puri-
fied by flash chromatography on silica gel (gradient elution with
EtOAc/hexanes) to yield the biaryl ketone products. Modification
with previously reported data.
2-Benzoylthiophene (14): The general procedure with Modifica-
tion 1 was applied to yield 14 as a white solid (86 mg, 74 % yield).
1
H NMR (300 MHz, CDCl ): δ = 7.87 (d, J = 6.9 Hz, 2 H), 7.72 (d, J =
3
3
.9 Hz, 1 H), 7.65 (d, J = 3.9 Hz, 1 H), 7.63–7.55 (m, 1 H), 7.52–7.43
13
(m, 2 H), 7.16 (dd, J = 5.0, 3.7 Hz, 1 H) ppm. C NMR (75 MHz,
CDCl ): δ = 187.29, 142.78, 137.31, 133.91, 133.27, 131.36, 128.27,
3
1
27.52, 127.06 ppm. NMR spectra are consistent with previously
[14]
reported data.
1
: The amounts of organotrifluoroborate and K CO were doubled
2 3
4
-Methoxy-4′-methylbenzophenone (15): The general procedure
to 3.0 and 6.0 equiv. respectively. Modification 2: The solvent sys-
tem was modified to toluene/acetone/H O (10:1:1).
1
was applied to yield 15 as a white solid (23 mg, 70 % yield).
H
2
NMR (300 MHz, CDCl ): δ = 7.83 (d, J = 8.8 Hz, 2 H), 7.70 (d, J =
3
4
-Methylbenzophenone (3): The general procedure was applied
8
.2 Hz, 2 H), 7.29 (d, J = 8.0 Hz, 2 H), 6.97 (d, J = 8.9 Hz, 2 H), 3.89
1
to yield 3 as a white solid (76 mg, 95 % yield). H NMR (300 MHz,
CDCl ): δ = 7.85–7.79 (m, 2 H), 7.75 (dd, J = 8.1, 1.5 Hz, 2 H), 7.64–
13
(s, 3 H), 2.45 (s, 3 H) ppm. C NMR (75 MHz, CDCl ): δ = 194.36,
3
3
162.15, 141.66, 134.66, 131.48, 129.61, 129.06, 127.96, 112.59, 54.55,
0.68 ppm. NMR spectra are consistent with previously reported
7
2
.55 (m, 1 H), 7.54–7.45 (m, 2 H), 7.37–7.24 (d, J = 9.6, 2.7 Hz, 2 H),
2
.49 (s, 1 H) ppm. 1 C NMR (75 MHz, CDCl ): δ = 197.29, 144.06,
3
[15]
3
data.
1
38.86, 135.79, 132.98, 131.14, 130.77, 129.82, 129.05. 22.49 ppm.
[
12]
2,4,4′,6-Tetramethylbenzophenone (16): The general procedure
NMR spectra are consistent with previously reported data.
with Modification 1 was applied to yield 16 as a colorless oil (37 mg,
4
-Methoxybenzophenone (8): The general procedure was applied
1
3
8 % yield). H NMR (300 MHz, CDCl ): δ = 7.70 (d, J = 8.3 Hz, 2 H),
3
1
to yield 8 as a white solid (79 mg, 92 % yield). H NMR (300 MHz,
CDCl ): δ = 7.87–7.79 (m, 2 H), 7.75 (dd, J = 8.1, 1.5 Hz, 2 H), 7.60–
7
.24 (d, J = 7.7 Hz, 2 H), 6.89 (s, 2 H), 2.44 (s, 3 H), 2.33 (s, 3 H), 2.09
13
3
(s, 6 H) ppm. C NMR (75 MHz, CDCl ): δ = 199.48, 143.60, 137.45,
3
7
(
.51 (m, 1 H), 7.51–7.41 (m, 2 H), 6.96 (d, J = 9.6, 2.7 Hz, 2 H), 3.87
136.30, 134.13, 133.29, 128.72, 128.64, 127.41, 20.87, 20.28,
s, 1 H) ppm. 13C NMR (75 MHz, CDCl ): δ = 194.58, 162.34, 137.42,
3
18.46 ppm. NMR spectra are consistent with previously reported
1
31.62, 130.95, 129.28, 128.79, 127.27, 112.67, 54.57 ppm. NMR
[15]
data.
[13]
spectra are consistent with previously reported data.
3-(Methoxycarbonyl)-4′-methylbenzophenone (17): The general
3
-Methoxybenzophenone (9): The general procedure was applied
procedure with Modifications 1 and 2 was applied to yield 17 as a
1
1
to yield 9 as a white solid (66 mg, 77 %). H NMR (300 MHz, CDCl ):
white solid (85 mg, 82 % yield). H NMR (300 MHz, CDCl ): δ = 8.44
3
3
δ = 7.85–7.77 (m, 2 H), 7.60–7.53 (m, 1 H), 7.46 (t, J = 8.3, 6.9 Hz, 2
(s, 1 H), 8.26 (d, J = 6.4 Hz, 1 H), 8.00 (d, J = 7.9 Hz, 1 H), 7.73 (d,
J = 8.3 Hz, 2 H), 7.59 (t, J = 7.7 Hz, 1 H), 7.32 (d, J = 8.0 Hz, 2 H),
H), 7.41–7.31 (m, 3 H), 7.16–7.09 (m, 1 H), 3.83 (s, 3 H) ppm. 13
C
NMR (75 MHz, CDCl ): δ = 195.41, 158.64, 137.97, 136.68, 131.43, 3.95 (s, 2 H), 2.47 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl ): δ = 194.36,
3
3
1
29.03, 128.24, 127.28, 121.83, 117.81, 113.45, 54.46 ppm. NMR 162.15, 141.66, 134.66, 131.48, 129.61, 129.06, 127.96, 112.59, 54.55,
[12]
spectra are consistent with previously reported data.
20.68 ppm. NMR spectra are consistent with previously reported
[
16]
data.
2
-Methoxybenzophenone (10): The general procedure with Modi-
1
fication 1 was applied to yield 10 as a clear oil (38 mg, 44 %). H
NMR (300 MHz, CDCl ): δ = 7.88–7.79 (m, 2 H), 7.62–7.52 (m, 1 H),
4-Chlorobutyrophenone (18): The general procedure with Modifi-
3
cation 1 was applied to yield 18 as a pale yellow oil (22 mg, 29 %
1
7
.51–7.43 (m, 3 H), 7.36 (m, 1 H), 7.11–6.95 (m, 2 H), 3.73 (s, 3 H)
yield). H NMR (300 MHz, CDCl ): δ = 8.05–7.91 (m, 2 H), 7.63–7.52
3
13
ppm. C NMR (75 MHz, CDCl ): δ = 197.25, 158.24, 138.74, 133.71, (m, 1 H), 7.54–7.41 (m, 2 H), 3.69 (t, J = 6.6 Hz, 2 H), 3.28–3.04 (m,
3
1
32.69, 130.65, 130.43, 129.82, 129.04, 121.36, 112.37, 55.61 ppm. 2 H), 2.24 (t, J = 6.7 Hz, 2 H) ppm. 13C NMR (75 MHz, CDCl ): δ =
3
[
5]
NMR spectra are consistent with previously reported data.
198.08, 135.97, 132.35, 127.80, 127.17, 43.81, 34.47, 25.97 ppm. NMR
[
13]
spectra are consistent with previously reported data.
n-Octanophenone (19): The general procedure was applied to
4
-Nitrobenzophenone (11): The general procedure was applied to
1
yield 11 as a yellow solid (82 mg, 83 % yield). H NMR (300 MHz,
CDCl ): δ = 8.33 (d, J = 8.8 Hz, 2 H), 7.93 (d, J = 8.7 Hz, 2 H), 7.80 yield 19 as a colorless oil (20 mg, 23 % yield). H NMR (300 MHz,
1
3
13
(d, J = 7.8 Hz, 2 H), 7.71–7.59 (m, 1 H), 7.58–7.46 (m, 2 H) ppm.
C
CDCl ): δ = 7.96 (d, J = 7.5 Hz, 2 H), 7.60–7.52 (m, 1 H), 7.51–7.42
3
NMR (75 MHz, CDCl ): δ = 193.86, 149.00, 142.04, 135.46, 132.57, (m, 2 H), 2.96 (t, J = 7.3 Hz, 2 H), 1.74 (t, J = 7.2 Hz, 2 H), 1.43–1.20
3
1
29.80, 129.21, 127.81, 122.66 ppm. NMR spectra are consistent (m, 8 H), 0.89 (t, J = 6.7 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3):
[13]
with previously reported data.
δ = 199.74, 136.33, 131.97, 127.69, 127.21, 37.80, 30.88, 28.51, 28.30,
Eur. J. Org. Chem. 2016, 2983–2987
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2986 © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
2
3.58, 21.78, 13.21 ppm. NMR spectra are consistent with previously
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Acknowledgments
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Keywords: Cross-coupling · Ketones · Borates · Palladium
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Published Online: ■
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