Base free Suzuki acylation reactions of sodium (aryl trihydroxyborate) salts: A novel synthesis of substituted aryl ketones

Article abstract of DOI:10.1016/j.jorganchem.2017.07.001

The first simple and efficient base free Pd(PPh₃)₄ catalysed synthesis of substituted aryl ketones from acyl chlorides and easily accessible sodium aryl trihydroxyborate salts in aqueous toluene is reported. The reaction conditions appeared versatile and tolerable to a variety of functional groups including, CF₃, OMe, SMe, Br, NO₂, F, OH and NH₂ furnishing 25 examples of substituted aryl ketones in isolated yields of up to 96% in 24 h. Beside the high purity, the ease and convenience of the isolation compared to boronic acids, sodium aryl trihydroxyborate salts could be used subsequently without the addition of excess amount of an activator and are more user-friendly in terms of the use of accurate reaction stoichiometry.

Full text of DOI:10.1016/j.jorganchem.2017.07.001

Accepted Manuscript
Base free Suzuki acylation reactions of sodium (aryl trihydroxyborate) salts: A novel
synthesis of substituted aryl ketones
Siphamandla Sithebe, Patience Molefe
PII:
S0022-328X(17)30423-0
10.1016/j.jorganchem.2017.07.001
JOM 20015
DOI:
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 30 March 2017
Revised Date: 23 June 2017
Accepted Date: 2 July 2017
Please cite this article as: S. Sithebe, P. Molefe, Base free Suzuki acylation reactions of sodium
(aryl trihydroxyborate) salts: A novel synthesis of substituted aryl ketones, Journal of Organometallic
Chemistry (2017), doi: 10.1016/j.jorganchem.2017.07.001.
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ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
BASE FREE SUZUKI ACYLATION REACTIONS OF SODIUM
(
ARYL TRIHYDROXYBORATE) SALTS: A NOVEL
SYNTHESIS OF SUBSTITUTED ARYL KETONES.
1
Siphamandla Sithebe* and Patience Molefe.
1
Address: Warren Laboratory, School of Chemistry and Physics, University of
KwaZulu-Natal, Private Bag X01, Scottsville, Pietermaritzburg, 3209, South Africa.
Email: sithebes@ukzn.ac.za
*
Siphamandla Sithebe
The first simple and efficient base free Pd(PPh ) catalysed synthesis of substituted
3
4
aryl ketones from acyl chlorides and easily accessible sodium aryl trihydroxyborate
salts in aqueous toluene is reported. The reaction conditions appeared versatile and
tolerable to a variety of functional groups including, CF , OMe, SMe, Br, NO , F, OH
3
2
and NH furnishing 25 examples of substituted aryl ketones in isolated yields of up to
2
9
6% in 24 hours. Beside the high purity, the ease and convenience of the isolation
compared to boronic acids, sodium aryl trihydroxyborate salts could be used
subsequently without the addition of excess amount of an activator and are more
user-friendly in terms of the use of accurate reaction stoichiometry.
Keywords
Base free, Suzuki-Miyaura acylation, substituted ketones, sodium aryl
trihydroxyborate salts, aromatic acyl chlorides.

ACCEPTED MANUSCRIPT
Introduction
The development of synthetic procedures capable of introducing acyl functionalities
have proven fruitful and are of great tool to construct a number of carbonyl organic
compounds including carboxylic esters, thioesters, amides, ketones to name but a
few [1]. Substituted aromatic ketones are particularly important building blocks
present in many natural products and biologically active pharmaceutical compounds
such as sulisobenzone [2a], (S)-ketoprofen [1c] and Safalcone [2b] and are also
important reaction intermediate in organic synthesis [3]. Traditional approaches to
aromatic ketones including, various oxidation processes [4], Friedel-Crafts acylation
[
5] and the use of organometallic reagents as nucleophiles [6]. These methods,
however, entails limitations and drawbacks such as harsh reaction conditions, poor
regioselectivity and functional group compatibility [7]. Alternative methods, such as
carbonylative cross-coupling reaction of aryl halides with aryl boronic acids, under
carbon monoxide atmosphere, have appeared with improved regioselectivity and
functional group compatibility and have emerged as attractive protocols for the
preparation of aromatic ketones [8]. On the other hand, palladium-catalysed
acylative Suzuki cross-coupling of carboxylic acids derivatives with boronic acids and
boronate esters, in the presence of at least two equivalence of a base, have become
a method of choice for the synthesis of ketones particularly because the starting
materials are readily available, non-toxic, stable towards moisture and easy to handle
[
9]. Great advancements have been witnessed in acylative Suzuki coupling reaction
in terms of acyl sources since the use of acyl chlorides as acylating agents pioneered
by Bumagin et al [10]. A variety of acyl donors have been wildly explored including
carboxylic anhydrides [11a], carboxylic acids [9], thiol esters [11b], and very recently
amides [11c, 11d]. Even though there is a great progress/development in acyl
sources, aryl boronic acids are still overwhelmingly dominating as aryl sources in

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acylative Suzuki coupling reactions. Only a few other aryl sources have been
reported in acylative Suzuki coupling of carboxylic acid derivatives including aryl
boronate [12], diarylborinic acids and sodium tetraarylboronates [9, 11d]. Thus, the
necessity to develop other aryl sources is evident. Cammidge et al. established that
aryltrihydroxyborate salts could be coupled smoothly with aryl halides in the Suzuki-
Miyaura cross-coupling reaction thus expanding the scope of aryl sources [13a]. The
suitability of aryltrihydroxyborate salts as efficient nucleophiles was further supported
by Molander et al [13b]. Given that these activated boron species, sodium
(aryltrihydroxyborate) salts, could be used directly without the need of additional base
and are more stable and more reactive than aryl boronic acids [13], we rationalise
that it should be more logic to couple sodium (aryltrihydroxyborate) salts with acyl
chlorides thus enriching acylative Suzuki cross-coupling reactions with respect to
arylating agents. To the best of our knowledge, there are no reports describing base
free Suzuki acylation reaction of sodium (aryltrihydroxyborate) salts with acyl
chlorides to synthesise substituted diaryl ketones. Herein, we report on the first
practical and efficient base free Pd(PPh ) catalysed acylative Suzuki coupling
3
4
reactions of sodium (aryltrihydroxyborate) salts with acyl chlorides in aqueous
toluene.
Results and Discussion
To begin our investigation, we first synthesised different sodium (aryl
trihydroxyborates) from cheap and easily accessible aryl halides following previously
[
13]
reported methods.
The corresponding aryl halide was reacted with magnesium
turnings to produce Grignard reagents which were subsequently quenched with
trimethoxyborate solution followed by the addition of concentrated NaOH(aq)
[
13]
(Scheme 1).

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1
. Mg
. B(OMe)3
. Normal workup
B(OH)2
B(OH) Na
3
Br
1
. Conc. NaOH(aq.)
2
R
R
R
3
2. Filtration
B(OH) Na
B(OH) Na
3
B(OH)
3
Na
B(OH) Na
3
B(OH) Na
3
3
H3C
H CS
H CO
F C
3
3
3
1
a (95%)
1b (98%)
1c (94%)
1d (97%)
1e (98%)
Scheme 1. Preparation of sodium aryl trihydroxyborate salts.
To investigate the suitability of our method in the synthesis of ketones, we initially
studied the reaction between sodium (phenyltrihydroxyborate) (1a) with toluoyl
chloride (2a) under different reaction conditions as a model reaction (Scheme 2). The
results of this investigation into determining the optimal reaction conditions for the
palladium-catalysed base free Suzuki acylation reactions are summarised in Table 1.
The cross-coupling reaction of 1a with 2a, in the absence of a catalyst, resulted in no
product formation and only the starting materials were detected (Table 1, entry 1).
The combination of palladium chloride with monodentate as well as bindentate
phosphine ligands, for example, PdCl /PPh and PdCl /dppf gave 3a in low yields
2
3
2
(
Table 1, entry 2 and 3). The addition of water slightly improved the yield of 3a to
8% (Table 1, entry 4) probably because of the solubility of 1a in aqueous toluene.
Other palladium (II) species afforded the desired product 3a with unsatisfactory yields
Table 1, entries 5-8). A sharp increase in the yield (79%) of product 3a was
observed when Pd(PPh ) was used as a catalyst in aqueous acetone (Table 1, entry
4
(
3
4
9
).

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a
Table 1: Initial optimisation of reaction conditions.
O
Pd catalyst
Solvent
O
PhB(OH) Na
3
+
MePh
Cl
MePh
Ph
1a
2a
3a
b
Entry
Catalyst
Solvent
Yield (%)
1
2
3
4
5
6
7
8
9
—
Toluene (r.t.)
Toluene (r.t)
Toluene (r.t)
0
27
PdCl /PPh3
2
PdCl /dppf
19
2
PdCl /dppf
Toluene/H O (r.t)
48
2
2
Pd(PPh ) Cl / PPh
Toluene/H O (r.t)
51
3
2
2
3
2
Pd(OAc) /dppf
Toluene/H O (r.t)
31
2
2
Pd(COD) Cl / PPh
Toluene/H O (r.t.)
Trace
55
2
2
3
2
Pd(PPh ) Cl /dppf
Toluene/H O (60 °C)
3
2
2
2
Pd(PPh3)4
Acetone/H O (60 °C)
79
2
10
11
12
13
14
15
Ni(dppf) /dppf
Toluene/H O (60 °C)
23
2
2
Ni(acac) /PPh3
Toluene/H O (60 °C)
Trace
71
2
2
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Toluene/H O (r.t.)
2
Toluene/H O (60 °C)
88
2
THF/ H O (60)
67
2
C
Toluene/H O (100 °C)
52
2
a
Reaction conditions: 1a (1 mmol), 2a (1.1 mmol), Pd catalyst (0.01 mmol), ligand (0.02
b
mmol), toluene (2 mL), 0.5 mL (water), 24 hours. Isolated yields after column and radial
C
chromatography. Microwave reactor was used, 100 W, 100Psi, Closed vessel, 10 minutes.
Given that nickel-based catalysts are increasingly becoming popular in cross-
coupling reactions [14], we performed the optimisation experiments in the presence
of Ni(dppf) /dppf and Ni(acac) /PPh catalysts. Unfortunately, both catalysts afforded
2
2
3

ACCEPTED MANUSCRIPT
3
a in poor yields (Table 1, entries 10 and 11). The best result was observed using
Pd(PPh ) catalyst in aqueous toluene at 60 °C (Table 1, entry 13). Increasing
3
4
temperature above 60°C only furnished 3a in a yield of 52% and promoted the
formation of homo-coupling by-products (Table 1, entry 15).
With the optimised reaction conditions in hand (Table 1, entry 13), the scope and
limitations of the current investigation was explored using a diverse range of acyl
chlorides and sodium (aryl trihydroxyborate) salts bearing electron-donating and/or
electron-withdrawing substituents and the results are summarised in Table 2.
Table 2: Base free Palladium-Catalysed acylation reactions of sodium
a
(aryltrihydroxyborate) salts with acyl chlorides.
O
O
B(OH) Na
3
Toluene/H O
Cl
2
+
Pd(PPh3)4
24 hrs
R
R'
R
R'
O
O
O
O
H
3
C
CH
3
CH
OCH
3
3
Br
3
d (94%)
3
3
a (88%)
3b (74%)
3c (79%)
O
O
O
O
F
H
3
C
OCH
3
H CS
H
3
C
NO
2
H
3
CS
CH
3
3
e (86%)
3
f (67%)
3g (74%)
3
h (86%)
O
O
O
O
H CS
F
H CS
NO
3
H CS
OCH3
3
3
2
H CS
3
3
l (51%)
3
i (69%)
3j (94%)
3
k (89%)

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O
O
O
O
F
H CO
3
NO2
H CO
OCH3
H CO
3
3
3
H CO
Cl
3
m (64%)
3n (93%)
3
o (90%)
3p (73%)
O
O
O
O
F3C
OCH3
F
3
C
NO
2
F C
3
F C
Br
3
3
q (82%)
3s (70%)
3t (86%)
3
r (91%)
O
O
O
O
F
F C
3
F
3
C
Cl
F3C
3
3
aa (0%)
3
u (81%)
3v (89%)
3w (94%)
O
O
O
O
3
H CS
3
H C
H CO
F3C
3
ee (0%)
3
dd (0%)
3
bb (0%)
3cc (0%)
a
Reaction conditions: Acyl chloride (1.1 mmol), sodium aryl trihydrxyboronate (1.0 mmol), Pd(PPh3)4
(
0.01 mmol), toluene (2.0 mL) and water (0.5 mL). All reaction were conducted under an argon
atmosphere to avoid premature oxidation of Pd(PPh ) at 60 °C, 24 hours. All yields were isolated
3
4
using column and/or radial chromatography.
Sodium (phenyltrihydroxyborate) (1a) reacted efficiently with acyl chlorides bearing
electron-donating as well as electron-withdrawing substituents, giving substituted
ketones 3a-3c in moderate to good yields (Table 2). Similar, the acylation reactions
of sodium (4-methylphenyltrihydroxyborate) (1b) with different acyl chlorides
proceeded smoothly affording ketones 3d and 3e in 94% and 86%, respectively. In
general, the acylative cross-coupling reactions of all sodium (aryl trihydroxyborate
salts) with 4-nitrobenzoyl chloride provides the desired ketones (3f, 3i, 3m and 3s) in
lower yields compared to other acyl chlorides probably due to competitive hydrolysis

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reactions. Sodium (4-(methylthio)phenyltrihydroxyborate) (1c) underwent efficient
acylation reactions with several acid chlorides leading to functionalised ketones
3
g-3k in 74-94%. As expectedly, the cross-coupling reaction of sodium
(4-(methythio)phenyltrihydroxyborate) (1c) with 2-substituted acyl chloride gave a
poor 51% yield (Table 1, 3l), presumably because of ortho-steric hindrance. The
trihydroxyborate reagent bearing an electron rich methoxy group (1d) also reacted
smoothly with the acyl chlorides to afford the corresponding products (3m-3p) in
good to excellent yields (64-93%). The acylation reactions of sodium
(4-(trifluoromethyl)phenylborate) (1e) with different nucleophiles were mostly
favoured giving the coupled-products in yields greater than 70% (Table 2). For
example, substrate 1e coupled favourably with electrophiles bearing moderate
electron-withdrawing substituents (Br, F and Cl) generating the expected diaryl
ketones 3r, 3v and 3w in 91%, 89% and 94% isolated yields, respectively. To further
investigate the scope and limitations of this reaction, we examined the reaction of
cinnamoyl chloride with trihydroxyboronate nucleophiles (1a-1e), however, there
were no products formed (Table 2, 3aa, 3bb, 3cc and 3dd) and only the starting
materials were detected along with the hydrolysis product (cinnamic acid). Further
investigations into finding optimal reaction conditions for alkyl and alkenyl acyl
chlorides with trihydroxyborate reagents are currently underway in our laboratory.
To demonstrate the true benefit of the base free acylative Suzuki-Miyaura cross
coupling protocol, we synthesised aryl ketones bearing base sensitive hydroxyl and
amino functionalities which are rather difficult to synthesis following the traditional
Suzuki-Miyaura cross-coupling reaction (Table 3).[26,27].

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a
Table 3: Synthesis of base senstivite diaryl ketones.
O
O
X
Toluene/H O
2
Cl
Base
+
Pd(PPh 3)4
2
4 hrs
R'
R'
R' = p-OH, p-NH
2
X = B(OH) , B(OH) Na
2
3
Entry
R
’
nucleophile
Base
Yield (%)
1
2
3
4
5
6
OH
NH2
OH
PhB(OH)2
PhB(OH)2
PhB(OH)2
PhB(OH)2
NaOH
NaOH
K CO
trace
trace
8
2
3
NH2
OH
K CO
trace
64
2
3
PhB(OH) Na
̶
̶
3
NH2
PhB(OH) Na
57
3
a
Reaction conditions: Acyl chloride (1.1 mmol), nucleophile (1.0 mmol), Pd(PPh ) (0.01 mmol),
3
4
toluene (2.0 mL) and water (0.5 mL). All reaction were conducted under an argon atmosphere to avoid
premature oxidation of Pd(PPh ) at 60 °C, 24 hours. All yields were isolated using column and/or
3
4
radial chromatography.
The cross coupling reaction of phenyl boronic acid with either
-aminobenzoylchloride or 4-hydroxybenzoylchloride, in the presence of a base
NaOH or K CO ), afforded the desired products (4-aminobenzophenone or
4
(
2
3
4
-hydroxybenzophenone) in only trace amounts (Table 3, entries 1-4). The poor
yields might be attributed to a base catalysed formation of the side products due to
the competative side reaction between an amino or the hydroxyl functionality with the
acyl chloride. The application of a base free acylation using trihydroxyborate salt as a
nucleophile afforded the desired products with improved yields of 64 and 57 % (Table
3
, entries 5 and 6).

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The main motivation behind the isolation and subsequent application of sodium
(aryltrihydroxyborate) salts was to investigate whether these pure, free-flowing
powder can be coupled with acyl chlorides in the Suzuki acylation reactions without
the addition of excess amount of a base. Gratifyingly, it became apparent that these
salts are excellent coupling partners in the Suzuki acylation reactions with aromatic
acyl chlorides. As anticipated, the nucleophiles do not require base activation step as
evident with no requirement of a base which is a great advantage for the synthesis of
ketones bearing base sensitive functional groups. In addition, sodium (aryl
trihydroxyborate salts) are pure thus eliminating the formation of inseparable mixtures
of boronic acids and boronic acid anhydrides making it convenient to calculate the
correct reaction stoichiometry [13].
Conclusion
We have developed the first base-free Suzuki acylation reactions of easily isolated
free flowing sodium (aryl trihydroxyborate salts) with different aromatic acyl chlorides
in aqueous toluene. The catalytic system appeared versatile and general, tolerating a
variety of functional groups such as OH, NH , NO , OMe, SMe CF , F, Cl and Br
2
2
3
whilst furnishing the coupled-products with isolated yields of up to 96% isolated yields
in 24 hours. Sodium (aryltrihydroxyborate) salts are therefore excellent coupling
partners for the synthesis of ketones under neutral Suzuki-acylative reaction
conditions developed.
Experimental
General consideration:
1
Commercially available reagents were used without further purification. H NMR (400
13
19
MHz), C NMR (100 MHz) and F (376.2 MHz) spectra were recorded as solution in
the specified deuterated solvents and are reported in parts per million (ppm)
11
downfield from tetramethylsilane (TMS) as an internal standard. B NMR spectra

ACCEPTED MANUSCRIPT
were referenced to BF ·OEt (external, neat, with capillary tube of acetone-d6 for the
3
2
deuterium lock). Purifications of the products were performed by flash-column
chromatography and centrifugal preparative thin-layer chromatography
chromatotron) on Fluka silica gel 60 cat No. 70–230 mesh (0.063–0.2 mm) and Merk
silica gel cat. No. 1.07749, respectively.
(
General procedure for the synthesis of sodium aryl trihydroxyborate salts.
Aryl halide (8.20 mmol), Mg (398.0 mg, 16.40 mmol) and dry THF (50.0 mL) were
placed in a 100 mL round-bottomed flask equipped with a Dean and Stark Apparatus,
magnetic stirrer bar and reflux condenser. The mixture was stirred at room
temperature until Grignard reagent has formed completely (minimum 30 minutes) and
eventually cooled to –78 °C. Trimethyl borate solution (1.83 mL, 16.40 mmol) was
added dropwise at –78 °C and the mixture was stirred overnight. THF was removed
under reduced pressure leaving a white precipitate which was dissolved in refluxing
toluene (30.0 mL) followed by the addition of concentrated NaOH solution until no
further precipitation occurred. The precipitate was filtered under vacuum, dried in an
oven and used without further purification[13a].
Sodium (phenyltrihydroxyborate) (1a): Following the general procedure [13a],
1
compound 1a was obtained as cream white powder (95%): H NMR (400 MHz, D O)
2
13
δH: 7.16-7.21 (m, 1H), 7.25-7.30 (m, 2H), 7.53 (d, J = 6.79 Hz, 2H) . C{1H} NMR
11
(
100 MHz, D O) δ : (C-B is not observed) 125.7, 127.3, 131.3, 167.7. B NMR (128
2 C
MHz, D O) δ : 3.1 ppm (s). Anal. calcd. for C H NaBO : C, 44.50, H, 4.98 Found C,
2
B
6
8
3
4
4.45, H, 4.92.
Sodium (4-methylphenyltrihydroxyborate) (1b): Following the general
1
procedure[13a], compound 1b was obtained as cream white powder (98%): H
NMR (400 MHz, D O) δ : 2.28 (s, 3H), 7.14 (d, J= 7.44 Hz, 2H), 7.45 (d, J = 7.73
2
H
13
Hz, 2H). C{1H} NMR (100 MHz, D O) δ : (C-B is not observed) 20.2, 127.9, 131.5,
2
C

ACCEPTED MANUSCRIPT
1
1
1
:
35.4, 168.0. B NMR (128 MHz, D O) δ : 3.2 ppm (s). Anal. calcd. for C H NaBO
2 B 7 10 3
C,47.78, H, 5.72 Found C, 44.71, H, 5.68.
Sodium (4-methylthiophenyltrihydroxyborate) (1c): Following the general
1
procedure[13a], compound 1c was obtained as white powder (94%): H NMR (400
MHz, D O) δ : 2.47 (s, 3H), 7.25 (d, J = 8.20 Hz, 2H), 7.52 (d, J = 8.27 Hz, 2H) .
2
H
13
C{1H} NMR (100 MHz, D O) δ : (C-B is not observed) 15.1, 125.9, 132.2, 133.7,
2
C
11
1
65.0. B NMR (128 MHz, D O) δ : 3.8 ppm (s). Anal. calcd. for C H NaBO S :
2 B 7 10 3
C,40.42, H, 4.84, S, 7.69 Found C, 40.39, H, 4.80, S, 7.79.
Sodium (4-methoxyphenyltrihydroxyborate) (1d): Following the general
1
procedure[13a], compound 1d was obtained as white powder (97%): H NMR (400
13
MHz, D O) δ : 3.80 (s, 3H), 6.91 (d, J = 8.56 Hz, 2H), 7.49 (d, J = 8.56 Hz, 2H). C
2
H
{
1H} NMR (100 MHz, D O) δ : (C-B is not observed) 55.2, 112.8, 132.6, 157.0,
2 C
1
1
1
4
67.6. B NMR (128 MHz, D O) δ : 3.4 ppm (s). Anal. calcd. for C H NaBO : C,
2 B 7 10 4
3.79, H, 5.25 Found C, 43.71, H, 5.22.
Sodium (4-trifluoromethylphenyltrihydroxyborate) (1e): Following the general
1
procedure[13a], compound 1e was obtained as white powder (98%): H NMR (400
13
MHz, D O) δ :7.56 (d, J = 7.99 Hz, 2H), 7.68 (d, J = 7.67 Hz, 2H). C{1H} NMR
2
H
1
(
100 MHz, D O) δ : (C-B is not observed) 126.3, 126.4, 126.9 (q, J = 33 Hz),
2 C CF
1
11
1
68.0. F{ H} NMR (376.2 MHz, D O): δ -63.6 (s). B NMR (128 MHz, D O) δ : 2.5
2 F 2 B
ppm (s). Anal. calcd. for C H NaBO : C, 36.53, H, 3.07 Found C, 36.46, H, 3.03.
7
7
3
General procedure for the Suzuki-Miyaura acylation reactions.
The corresponding borate salt (1 mmol), Pd(PPh ) (0.01 mmol, 11.56 mg), degassed
3
4
toluene (2.0 mL), degassed water (0.50 mL) were place in a 50 mL round-bottomed
flask with a magnetic stirrer bar and a rubber septum. The content of the flask was
kept under argon while acyl chloride (1.10 mmol), dissolved in degassed toluene (1.0
mL), was added dropwise via a syringe and the flask was heated to 60 °C on the oil
bath. After 24 hours, the reaction mixture was filtered and solvent removed under
vacue. The resulting residue was dissolved in DCM and was purified using flash-

ACCEPTED MANUSCRIPT
column chromatography or centrifugal preparative thin-layer chromatography
(chromatotron) using Hexane: Ethyl acetate (9:1) as an eluent.
Phenyl(p-tolyl)methanone(3a) [9]: Following the general procedure, compound 3a
was obtained as white crystalline solid (88%): (400 MHz, CDCl ) δ : 7.45–7.51 (m,
3
H
1
3
2
1
H), 7.56–7.61 (m, 1H), 7.78–7.82 (m, 2H). C {1H} NMR (100. MHz, CDCl ) δ :
3 C
28.3, 130.1, 132.4, 137.6, and 196.75. MS (EI), m/z (%): 39 (5), 51 (10), 65 (11), 77
+
(
22), 91 (30), 105 (30), 119 (100), 196 [M ] (60).
(4-Bromophenyl)(phenyl)methanone (3b)[16]: Following the general procedure,
1
compound 3b was obtained as crystalline solid (74%): H NMR (400 MHz, CDCl ):
3
13
7
.48-754 (m, 2 H), 7.60-7.73 (m, 5H), 7.78-7.82 (m, 2 H). C{1H} NMR (100 MHz,
CDCl ) δ : 127.5, 128.4, 129.9, 131.5, 131.6, 132.6, 136.3, 137.2 and 195.6. MS
3
C
+
(
EI), m/z (%): 51 (12), 77 (42), 105 (100), 152 (10), 183 (25), 260 [M ] (50).
(4-Methoxyphenyl)(phenyl) methanone (3c)[11d]:
Following the general
procedure, compound 3c was obtained as white crystalline solid (79%): (400 MHz,
CDCl ) δ : 3.87 (s, 3H), 6.95–6.98 (m, 2H), 7.46 (t, 7.6 Hz, 2H), 7.56 (t, J = 7.2 Hz,
3
H
1
3
1
5
H), 7.74–7.76 (m, 2H), 7.81–7.84 (m, 2H). C {1H} NMR (100 MHz, CDCl ) δ :
3 C
5.5, 113.5, 128.1, 129.7, 130.2, 131.8, 132.5, 138.3, 163.2 and 195.5 MS (EI), m/z
+
(
%): 50 (8), 77 (25), 105 (25), 151 (100), 228 [M ] (58).
Bis(p-tolyl)methanone (3d)[11d]: Following the general procedure, compound 3d
was obtained as white powder (94%) : (400 MHz, CDCl ) δ : 2.46 (s, 3H), 7.30 (d, J
3
H
13
=
8.01 Hz, 4H), 7.73 (d, J = 8.05 Hz, 4H). C {1H} NMR (100 MHz, CDCl ) δ : 21.6,
3 C
1
28.9, 130.1, 135.2, 142.9 and 196.2. MS (EI), m/z (%): 39 (4), 65 (15), 91 (31), 119
+
(
100), 195 (10), 210 [M ] (31).
(4-Methoxyphenyl)(p-tolyl)methanone (3e)[11c]: Following the general procedure,
1
compound 3e was obtained as white solid (86%): H NMR (400 MHz, CDCl ) δ : 2.44
3
H
(s, 3H), 3.94 (s, 3H), 7.00 (d, J = 7.6 Hz, 2H), 7.30 (d, J = 7.6 Hz, 2H), 7.71 (d, J =
1
3
8
5
.0 Hz, 2H), 7.84 (d, J = 8.4 Hz, 2H). C {1H} NMR (100. MHz, CDCl ) δ : 21.6,
3 C
5.4, 113.5, 128.8, 130.0, 130.5, 132.4, 135.5, 142.6, 163.0 and 195.3. MS (EI), m/z
+
(
%): 65 (8), 77 (15), 91 (21), 107 (9), 119 (25), 135 (100), 211 (13), 226 [M ] (50).

ACCEPTED MANUSCRIPT
(4-Nitrophenyl)(p-tolyl)methanone (3f) [17]: Following the general procedure,
1
compound 3f was obtained as white solid (67%): H NMR (400 MHz, CDCl ) δ : 2.51
3
H
13
(
s, 3H), 7.35 (d, J = 7.6 Hz, 2H), 7.95 (d, J = 7.6 Hz, 2H), 8.46 (d, J = 8.0 Hz, 2H). C
1H} NMR (100 MHz, CDCl ) δ : 21.7, 123.4, 129.3, 130.3, 130.5, 133.6, 143.3,
{
3
C
1
1
44.5, 149.7 and 194.5. MS (EI), m/z (%): 39 (9), 50 (9), 65 (17), 76 (10), 91 (39),
+
04 (5), 119 (100), 241 [M ] (20).
(4-Methylthiophenyl)(p-tolyl)methanone (3g)[18]: Following the general procedure,
compound 3g was obtained as pale yellow product (74%) : (400 MHz, CDCl ) δ :
3
H
2
8
1
.46 (s, 3H), 2.55 (s, 3H), 7.29-7.35 (m, 4H), 7.71 (d, J = 8.13 Hz, 2H), 7.75 (d, J =
13
.18 Hz, 2H). C{1H} NMR (100. MHz, CDCl ) δ : 14.9, 21.6, 124.8, 126.2, 128.9,
3
C
29.5, 130.0, 130.5, 130.6, 134.0, 135.1, 142.9, 144.9, 145.5, 162.5 and 195.5. MS
+
(
EI), m/z (%): 65 (18), 91 (33), 119 (63), 151 (100), 195 (12), 242 [M ] (80).
(4-Methythiophenyl)(3-fluorophenyl)methanone (3h) [19]: Following the general
procedure, compound 3h was obtained as white powder (86%) : (400 MHz, CDCl3)
δH: 2.57 (s, 3H), 7.27-7.36 (m, 3H), 7.44-7.54 (m, 2H), 7.53-7.58 (m, 1H), 7.76 (d, J =
13
8
.5 Hz, 2H). C {1H} NMR (100 MHz, CDCl ) δ : 14.8, 116.5 (d, J = 22 Hz), 119.1 (d,
3 C
J = 22 Hz), 124.9, 125.5, 127.1 (d, J = 8 Hz), 129.9 (d, J = 8 Hz), 130.5, 133.0, 139.9
19
1
(
d, J = 6.6 Hz), 145.9, 161.1 (d, J = 250 Hz), and 194.2. F { H} NMR (376.2 MHz,
+
CDCl ): δ -111.4 (s).MS (EI), m/z (%): 95 (20), 123 (30), 151 (2), 151 (100), 246 [M
3
F
]
(68).
(4-Methythiophenyl)(4-nitrophenyl)methanone (3i)[17]: Following the general
procedure, compound 3i was obtained as yellow crystals (69%) : (400 MHz, CDCl3)
δH: 2.58 (s, 3H), 7.34 (d, J = 8.50 Hz, 2H), 7.75 (d, J = 8.7 Hz, 2H), 7.92 (d, J = 8.8
13
Hz, 2H), 8.36 (d, J = 8.8 Hz, 2H). C {1H} NMR (100 MHz, CDCl ,) δ : 14.7, 123.5,
3
C
1
25.0, 130.4, 132.2, 143.3, 147.0, 149.7 and 193.7. MS (EI), m/z (%): 77 (67), 122
+
(
12), 123 (45), 151 (100), 150 (45), 227 (89), 273 [M ] (24).
(4-Methylthiophenyl)(4-methoxyphenyl)methanone (3j)[18]: Following the general
procedure, compound 3i was obtained as colourless crystals (94%) :(400 MHz,
CDCl ) δ : 2.56 (s, 3H), 3.91 (s, 3H), 6.99 (d, J = 8.8 Hz, 2H), 7.32 (d, J = 8.2 Hz, 2
3
H
13
H), 7.73 (d, J = 8.2 Hz, 2H), 7.82 (d, J = 8.7 Hz, 2H). C {1H} NMR (100 MHz,

ACCEPTED MANUSCRIPT
CDCl ) δ : 14.9, 55.4, 113.5, 124.9, 130.3, 132.3, 134.4, 144.4, 163.0, 194.6. MS
3
C
(EI), m/z (%): MS (EI), m/z (%): 65 (18), 91 (33), 119 (63), 151 (100), 195 (12), 258
+
[
M ] (80).
(4-Methylthiophenyl)(phenyl)methanone
(3k)[18]:
Following
the
general
procedure, compound 3k was obtained as yellow crystalline solid (89%) : (400 MHz,
CDCl ) δ : 2.56 (s, 3H), 7.28–7.36 (m, 2H), 7.47–7.54 (m, 2H), 7.57-7.63 (m, 1H),
3
H
1
3
7
1
1
.75-7.82 (m, 4H). C {1H} NMR (100 MHz, CDCl ) δ : 14.8, 124.8, 127.1, 128.2,
3 C
29.8, 130.6, 132.1, 133.7, 137.9, 145.3 and 195.7. MS (EI), m/z (%): 50 (8), 77 (25),
+
05 (25), 151 (100), 228 [M ] (58).
(4-Methylthiophenyl)(2-fluorophenyl)methanone (3l)[20]: Following the general
procedure, compound 3l was obtained as colourless crystals (51%) :(400 MHz,
CDCl ) δ : 2.54 (s, 3H), 7.14-7.21 (m, 1H), 7.25-7.34 (m, 3H), 7.50-7.58 (m, 2H),
3
H
1
3
7
1
.74-7.81 (m, 2H). C {1H} NMR (100 MHz, CDCl ) δ : 14.7, 116.2 (d, J = 22 Hz),
3 C
24.2, 124.8, 127.2, 130.6 (d, J = 3 Hz), 132, 133.5, 146.6, 158.6, 161.1 (d, J = 250
19
1
Hz) and 192.3. F{ H} NMR (376.2 MHz, CDCl ): δ -63.6 (s).MS (EI), m/z (%): 95
3
F
+
(
20), 123 (25), 151 (25), 151 (100), 246 [M ] (60).
(4-Methoxyphenyl)(4-nitrophenyl)methanone (3m)[18]: Following the general
procedure, compound 3m was obtained as colourless solid (64%) : (400 MHz,
CDCl ) δ : 3.93 (s, 3H), 7.02 (d, J = 8.76 Hz, 2H), 7.84 (d, J = 8.77 Hz, 2H), 7.90 (d,
3
H
13
J = 8.50 Hz, 2H), 8.35 (d, J = 8.45 Hz, 2H). C {1H} NMR (100 MHz, CDCl ) δ :
3
C
5
5.6, 114.0, 123.4, 128.9, 130.3, 132.6, 143.8, 149.5, 164.0, and 193.4 MS (EI), m/z
+
(
%): 77 (67), 122 (12), 92 (14), 123 (45), 151 (100), 150 (45), 227 (89), 257.2 [M ]
45).
(
Bis(4-methoxyphenyl)methanone (3n)[18]: Following the general procedure,
compound 3n was obtained as colourless needles (93%) : (400 MHz, CDCl ) δ : 3.91
3
H
13
(
s, 6H), 6.99 (d, J = 8.77 Hz, 4H), 7.81 (d, J = 8.75 Hz, 4H). C {1H} NMR (100
MHz, CDCl ) δ : 55.4, 113.4, 130.8, 132.2, 162.8, and 194.4. MS (EI), m/z (%): 77
3
C
+
(
13), 122 (12), 92 (10), 107 (10), 135 (100), 211 (15), 242 [M ] (30).

ACCEPTED MANUSCRIPT
(4-Methoxyphenyl)(4-chlorophenyl)methanone (3o)[18]: Following the general
procedure, compound 3o was obtained as colourless solid (90%) : (400 MHz, CDCl3)
δH: 3.91 (s, 3H), 6.99 (d, J = 8.7 Hz, 2H), 7.47 (d, J = 8.4 Hz, 2H), 7.73 (d, J = 8.5
13
Hz, 2H), 7.82 (d, J = 8.7 Hz, 2H). C {1H} NMR (100 MHz, CDCl ) δ : 55.2, 113.7,
3
C
1
28.5, 129.8, 131.1, 132.4, 136.4, 138.2, 163.4, and 194.2. MS (EI), m/z (%): 77
+
(
15), 92 (10),111 (15), 135 (100), 246 [M ] (30).
(4-Methoxyphenyl)(3-fluorophenyl)methanone (3p)[21]: Following the general
procedure, compound 3p was obtained as colourless solid (73%) : (400 MHz, CDCl3)
δH: 3.92 (s, 3H), 7.00 (d, J = 8.7 Hz, 2H), 7.25-7.32 (m, 1H), 7.45-7.50 (m, 2H), 7.53-
1
3
7
1
=
.58 (m, 1H), 7.84 (d, J = 8.9 Hz, 2H). C{1H} NMR (100 MHz, CDCl ,) δ : 55.5,
3 C
13.7, 116.5 (d, J = 22.3 Hz), 118.8 (d, J = 22.0 Hz), 125.4 (d, J = 3.7 Hz), 129.9 (d, J
19
1
8.8 Hz), 132.5, 140.4, 161.2, 163.5 and 194.0. F { H} NMR (376.2 MHz, CDCl ):
3
δF -111.9 (s). MS (EI), m/z (%): 64 (2), 77 (12), 95 (10), 107 (9), 123 (5), 135 (100),
+
2
30 [M ] (44).
(4-Methoxyphenyl)(4-(trifluoromethyl)phenyl)methanone (3q)[22]: Following the
general procedure, compound 3q was obtained as white needle-like crystals (82%):
(
400 MHz, CDCl ) δ : 3.93 (s, 3H), 7.01 (d, J = 8.7 Hz, 2H), 7.77 (d, J = 8.1 Hz, 2H),
3 H
13
7
.82-7.90 (m, 4H). C {1H} NMR (100 MHz, CDCl ) δ : 55.5, 123.6 (d, J = 271.0
3 C CF
2
Hz), 125.2 (q, J = 3,7 Hz), 129.4, 129.7, 133.6 (q, J = 33.2 Hz), 141.5, 163.7 and
CF
19
1
1
94.2. F{ H} NMR (376.2 MHz, CDCl ): δ -63.6 (s). MS (EI), m/z (%): 77 (11), 92
3 F
+
(
12), 107 (12), 135 (100), 145 (9), 280 [M ] (33).
(4-Bromophenyl)(4-(trifluoromethyl)phenyl)methanone (3r)[23]: Following the
general procedure, compound 3r was obtained as light brown powder (91%) : (400
MHz, CDCl ) δ : 7.65-7.72 (m, 4H), 7.79 (d, J = 8.1 Hz, 2H), 7.89 (d, J = 8.2 Hz, 2H).
3
H
13
2
C {1H} NMR (100. MHz, CDCl ) δ : 123.7 (d, J = 271.0 Hz), 125.4 (q, J = 3.0
3
C
CF
Hz), 128.3, 130.0, 131.5, 131.9, 133.8, 134.1 (q, JCF = 33.5 Hz), 135.4, 140.3 and
19
1
1
94.4. F { H} NMR (376.2 MHz, CDCl ): δ -63.0 (s). MS (EI), m/z (%): 50 (40), 75
3 F
+
(
49), 95 (13), 125 (15), 155 (29), 173 (62), 183 (100), 330 [M +1] (15).
(4-nitrophenyl)(4-(-trifluoromethyl)phenyl)methanone (3s)[24]: Following the
general procedure, compound 3s was obtained as light yellow solid (70%) : (400

ACCEPTED MANUSCRIPT
MHz, CDCl ) δ : 7.83 (d, J = 8.1 Hz, 2H), 7.93 (d, J = 8.1 Hz, 2H), 7.98 (d, J = 8.76
3
H
13
Hz, 2H), 8.39 (d, J = 8.77 Hz, 2H). C {1H} NMR (100 MHz, CDCl ) δ : 123.8 (d, J =
3
C
2
1
74. Hz) 125.7 (q, JCF = 3.2 Hz), 130.5 (d, J = 57.0 Hz), 134.7 (q, JCF = 33.2 Hz)
19
1
39.3, 141.8, 150.2 and 193.6.
F{ H} NMR (376.2 MHz, CDCl ): δ -63.1 (s).MS
3 F
+
(
EI), m/z (%): 50 (40), 76 (13), 95 (7), 120 (5), 173 (100), 295 [M ] (55).
(4-(trifluoromethyl)phenyl)methanone (3t)[11d]: Following the general procedure,
compound 3t was obtained as white powder (86%) : (400 MHz, CDCl ) δ : 7.50-7.57
3
H
(m, 2H), 7.63-7.69 (m, 1H), 7.78 (d, J = 8.20 Hz, 2H), 7.83 (d, J = 8.6 Hz, 2H), 7.92
13
(
d, J = 7.91 Hz, 2H). C{1H} NMR (100 MHz, CDCl ) δ : 123.8 (d, J = 271.7 Hz),
3
C
2
1
25.3 (dd, J = 7.2 Hz), 125.7 (q, J = 3.0 Hz), 128.5, 130.1, 133.2, 133.5, 133.9 (d,
CF
1
19
1
JCF = 33 Hz), 136.7, 140.7 and 195.5. F{ H} NMR (376.2 MHz, CDCl ): δ -63.6
3
F
+
(
s). MS (EI), m/z (%): 51 (10), 77 (38), 105 (100), 145 (29), 173 (31), 250 [M ] (38).
(p-tolyl)(4-(trifluoromethyl)phenyl)methanone (3u)[9]: Following the general
procedure, compound 3u was obtained as colourless crystals (81%) : (400 MHz,
CDCl ) δ : 2.48 (s, 3H), 7.33 (d, J = 7.8 Hz, 2H), 7.72-7.80 (m, 4H), 7.90 (d, J = 8.2
3
H
13
1
Hz, 2H). C {1H} NMR (100 MHz, CDCl ) δ : 21.6, 123.8 (d, J = 271.0 Hz), 125.4
3
C
CF
2
1
(
q, J = 3.2 Hz), 129.2, 130.2 (d, J = 33.5 Hz), 130.3, 133.7 (d, JCF = 33.0 Hz),
CF
1
9
1
1
6
34.1, 141.1, 144.0 and 195.2. F{ H} NMR (376.2 MHz, CDCl ,):MS (EI), m/z (%):
3
+
5 (10), 91 (38), 119 (100), 145 (19), 264 [M ] (38).
(4-Chlorophenyl)(4-(trifluoromethyl)phenyl)methanone (3v)[25]: Following the
general procedure, compound 3v was obtained as white needle-like crystals (89%) :
(
400 MHz, CDCl ) δ : 7.31-7.39 (m, 1H), 7.44-7.50 (m, 1H), 7.71-7.77 (m, 1H), 7.79
3 H
13
(
d, J = 8.1 Hz, 2H), 7.92 (d, J = 8.1 Hz, 2H). C{1H} NMR (100 MHz, CDCl ) δ :
3 C
5
3.4, 116.7 (d, JCF = 22.0 Hz), 120.1 (d, JCF = 22 Hz), 123.9 (d, JCF = 270.0 Hz) 125.4
(q, JCF = 3.0 Hz), 125.8 (d, JCF = 3.0 Hz), 128.4, 128.5, 130.2 (d, JCF = 8.0 Hz), 132.3,
19
1
1
32.5, 134 (q, JCF = 33.0 Hz), 140.1 and 194.1. F{ H} NMR (376.2 MHz, CDCl ):
3
δF -62.9 (s) and -111.8 (s). MS (EI), m/z (%): 77 (11), 92 (12), 107 (12), 135 (100),
+
1
45 (9), 280 [M ] (33).

ACCEPTED MANUSCRIPT
(3-Fluorophenyl)(4-(trifluoromethyl)phenyl)methanone (3w)[25]: Following the
general procedure, compound 3w was obtained as white needle-like crystals (94%) :
(
400 MHz, CDCl ) δ : 7.51 (d, J = 8.5 Hz, 2H), 7.76-7.81 (m, 4H), 7.89 (m, 2H).
3 H
13
C{1H} NMR (100 MHz, CDCl ) δ : 116.7 (d, J = 22.9 Hz), 120.1 (d, J = 21.3 Hz)
3
C
CF
1
25.4 (q, J = 11.8, 3.7 Hz) 125.8 (d, J = 2.9 Hz), 128.5, (d, J = 12.5 Hz), 130.1, 130.2
(d, J = 8.3 Hz), 131.5 (d, J = 3 Hz), 132.2 (d, J = 10.3 Hz), 138.8 (d, J = 7 Hz), 140.1,
1
1
62.2 (d, J = 248 Hz) and 194.2. MS (EI), m/z (%): 43 (11), 75 (21), 95 (8), 111
CF
+
(
25), 113 (9), 139 (100), 141 (40), 173 (30), 284 [M ] (30).
(4-aminophenyl)phenyl-methanone:[26] Following the general procedure, the titled
compound was obtained as yellow crystals (57%) :(400 MHz, CDCl ) δ : 4.16 (br s,
3
H
NH ), 6.68 (d, J = 8.7 Hz, 2H), 7.44-7.51 (m, 2H), 7.52-7.58 (m, 1H), 7.70-7.78 (m,
2
1
3
4
1
H). C{1H} NMR (100 MHz, CDCl ) δ : 113.6, 127.3, 128.1, 129.5, 131.4, 132.9,
3 C
38.9, 151.1 and 195.3. MS (EI), m/z (%): 39 (16), 50 (8), 51 (30), 63 (9), 65 (40), 79
+
(
38), 92 (30), 105 (8), 120 (100), 197 [M ] (55).
(4-hydroxyphenyl)phenyl-methanone: [27] Following the general procedure, the
titled compound was obtained as cream white powder (64%) : (400 MHz, CDCl ) δ :
3
H
4
.16 (br s, NH ), 6.98 (d, J = 8.7 Hz, 2H), 7.47-7.53 (m, 2H), 7.57-7.63 (m, 1H), 7.66
2
13
(
s, 1H), 7.76-7.84 (m. 4H). C{1H} NMR (100 MHz, CDCl ) δ : 115.4, 128.3,
3 C
1
6
29.4,129.8, 132.2, 133.2, 138.0, 161.0 and 197.1. MS (EI), m/z (%): 39 (6), 41 (8),
+
3 (11), 77 (20), 85 (5), 93 (38), 92 (11), 105 (20), 121 (100), 198 [M ] (55).
Acknowledgements
The authors thank the University of KwaZulu-Natal and National Research
Foundation for financial assistance.
Appendix. Supporting Information
Supporting Information File 1
1
13
11
Copies of H, C and B NMR of synthesised compounds are available.

ACCEPTED MANUSCRIPT
References
[
1] Zhang, Y. D.; Rovis, T. J. Am. Chem. Soc. 2004, 126, 15964–15965.
doi:10.1021/ja044113k (b) Ong, A. L.; Kamaruddin, A. H.; Bhatia, S. Process
Biochem. 2005, 40, 3526–3535. doi.org/10.1016/j.procbio.2005.03.054
2] Baughman, B. M. Stennett, E.; Lipner, R. E.; Rudawski, A. C.; Schidtke, S. J.
J. Phys. Chem. A 2009, 113, 8011–8019.doi: 10.1021/jp810256x (b) Wen, A.;
Wang, Z.; Hang, T.; Jia, Y.; Zhang, T.; Wu, Y., Gao, X.; Yang, Z. Chromatogr.
B 2007, 856, 348–352. doi.org/10.1016/j.jchromb.2007.05.014
[
[
[
3] (a). Corey, E. J.; Helal, C.J. Tetrahedron Lett. 1996, 37, 4837–4840.
doi.org/10.1016/0040-4039(96)00964-1 (b) Brunet, J.J.; Chauvin, R. Chem.
Soc. Rev. 1995, 24, 89–95.doi:10.1039/CS9952400089
4] Wu, J.; Lui, Y.; Ma, X.; Lui, P.; Gu, C.; Dia, B. Synth. Commun. 2016, 46,
1
741–1758. doi.org/10.1080/00397911.2016.1223314 (b) Mallat, T.; Baiker, A.
Chem. Rev. 2004, 104, 3037–3058.doi: 10.1021/cr0200116 (c) Tidwell, T.T.
Synthesis 1990, 10, 857–870. doi: 10.1055/s-1990-27036 (d) De Nooy, A. E.;
Besemer, A. C.; Van Bekkum, H. Synthesis 1996, 10, 1153–1176. doi: 1
0
.1055/s-1996-4369
[
5] Furstner, A.; Voigtlander, D.; Schrader, W.; Giebel, D.; Reetz, M.T. A Org.
Lett. 2001, 3, 417–420.doi: 10.1021/ol0069251 (b) Gmouth, S.; Yang, H.L.;
Vaultier, M. Org. Lett. 2003, 5, 2219–2222. doi: 10.1021/ol034529n (c) Fillion,
E.; Fishlock, D.; Wilsily, A.; Goll, J.M. J. Org. Chem. 2005, 70, 1316–1327.
doi: 10.1021/jo0483724
[
6] Labadie, J.W.; Stille, J.K. J. Am. Chem. Soc. 1983, 105, 669–670. doi:
1
0.1021/ja00341a083 (b) Reddy, C.K.; Knochel, P. Angew. Chem. Int. Ed.
Engl. 1996, 35, 1700–1701. doi:10.1002/anie.199617001 (c) Wu, T.C.; Xiong,

ACCEPTED MANUSCRIPT
H.P.;
doi:10.1021/jo00304a016
7] Wu, X.-F.; Neumann, H.; Beller, M. Angew. Chem., Int. Ed. 2010, 49, 5284–
288. doi:10.1002/anie.201002155 (b) Wu, X.-F.; Neumann, H.; Spannenberg,
A.; Schulz, T.; Jiao, H.; Beller, M. J. Am. Chem. Soc. 2010, 132, 14596–
Rieke,
R.D.
J.
Org.
Chem.
1990,
55,
5045–5051.
[
5
1
1
4602. Doi: 10.1021/ja1059922 (c) Ross, J.; Xiao, J.L.Green Chem. 2002, 4,
29–133.doi: 10.1039/B109847K
[
8] (a) Echavarren, A.M.; Stille, J.K. J. Am. Chem. Soc. 1988, 110, 1557–
565.doi: 10.1021/ja00213a032 (b) Kang, S.-K.; Yamaguchi, T.; Kim, T.-H.;
1
Ho, P.-S. J. Org. Chem. 1996, 61, 9082–9083.doi: 10.1021/jo962033w (c)
Ceccarelli, S.; Piarulli, U.; Gennari, C. J. Org. Chem. 2000, 65, 6254–6256.
doi: 10.1021/jo0004310
[
[
[
9] Si, S.; Wang, C.; Zhang, N., Zou, G. J. Org. Chem. 2016, 81, 4364–4370.doi:
1
0.1021/acs.joc.6b00421
10]
Bykov, V.V.; Korolev, D. N.; Bumagin, N.A. Russ. Chem. Bull. 1997, 46,
632–1632. doi: 10.1007/BF02502960
1
11]
(a) Yu, A.; Shen, L.; Cui, X.; Peng, D.; Wu, Y. Tetrahedron 2012, 68,
283–2288. doi.org/10.1016/j.tet.2012.01.053 (b) Villalobos, J. M.; Srogl, J.;
2
Liebeskind, L. S. J. Am. Chem. Soc. 2007, 129, 15734–1515735.doi:
0.1021/ja074931n (c) Li, X.; Zou, G. Chem. Commun. 2015, 51, 5089–5092.
doi: 10.1039/C5CC00430F (d) Li, X.; Zou, G. J. Organomet. Chem. 2015, 794,
1
1
36–145. doi.org/10.1016/j.jorganchem.2015.07.009
[
[
12]
Uruwa, Y.; Ogura, K. Tetrahedron Lett. 2003, 44, 271–273.
doi.org/10.1016/S0040-4039(02)02501-7
13]
(a) Cammidge, N. A.; Goddard, M. H. V.; Gopee, H.; Harrison, L. N.;
Hughes, L. D.; Schubert, J. C.; Sutton, M. B., Watts, L. G.; Whitehead, J. A.

ACCEPTED MANUSCRIPT
Org. Lett. 2006, 18, 4071–4074.doi: 10.1021/ol061564w. (b) Molander, G. A.;
Skrydstrup, T.; Bjerglund, K. M. Org. Lett. 2014, 16, 1888–1891.doi:
1
0.1021/ol5003362
[
[
[
[
[
14] Dander, J. E.; Garg, N. E. ACS Catal. 2017, 7, 1413–1423. doi:
1
0.1021/acscatal.6b03277
15]
Maseras, F.; Ujaqua, G.; Morgen, N. H.; Braga, A. A. C. J. Am. Chem.
Soc. 2005, 127, 9298–.9307. doi: 10.1021/ja050583i.
16]
Xu.; Yubing, H.; Yanli X.; Xiaodong T.; Wanqing W.; Huanfeng J. J.
Org. Chem. 2017, 82, 2211–2218. 10.1021/acs.joc.6b02697
17]
Zarei, A.; Hajipour, A. R.; Khazdooz, L. Tetrahedron Lett. 2008, 49,
715–6719. doi.org/10.1016/j.tetlet.2008.09.062
6
18]
Parella, R.; Kumar, A.; Babu, A. Tetrahedron Lett. 2003, 54, 1738–
742. doi.org/10.1016/j.tetlet.2013.01.081
1
[
[
19]
20]
Kulp, S. S.; McGee, M. J. J. Org. Chem. 1983, 48, 4097–4098.
Nicolia, E., Teulon, J-M. PTC Int. appl. 1997, WO 9737984 A1
9971016.
1
[
[
[
[
[
21]
Sharma, P.; Roshilla, S.; Jain, N. J. Org. Chem. 2017, 82, 1105–1113.
doi: 10.1021/acs.joc.6b02711
22]
Benischke, A. D.: Leroux, M.; Knoll, I.; Knochel, P. Org. Lett. 2016, 18,
626–3629.doi: 10.1021/acs.orglett.6b01677
3
23]
Kim, S-H.; Rieke, D. R. Synth. Commun. 1998, 28, 1065–1072.
doi.org/10.1080/00397919808003074
24]
Zhong, Y.; Gong, X.; Zhu, X.; Ni, Z.; Wang, J.; Han, W. RSC. Adv.
012, 4, 63216–63220. doi: 10.1039/C4RA10739J
2
25]
Dohi, S.; Moriyama, K.; Togo, H. Tetrahedron 2012, 68, 6557–6564.
doi.org/10.1016/j.tet.2012.05.059.

ACCEPTED MANUSCRIPT
[
[
26]
Porta, R.; Puglisi, A.; Colombo, G.; Rossi, S.; Benaglia, M. Beilstein J
Org Chem. 2016, 12, 2614–2619. doi: 10.3762/bjoc.12.257
27]
Hao, C.Y.; Wang, D.; Lin, Y. W.; Dong, L.; Jin, Y.; Zhang, X. R.; Zhu, H,
Y.; Chang, S. RSC Adv., 2016, 6, 86502–86509. doi: 10.1039/C6RA14678C

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Base-free palladium-catalysed Suzuki acylation transformation of sodium
(aryltrihydroxyborate) salts and aromatic acyl chlorides to substituted ketones.
The desired substituted diarylketones were produced in isolated yields of up to
9
6% at 60 °C in aqueous toluene.
Electrophiles bearing base sensitive functional groups were also accommodated
in the developed procedure.
The first acylation procedure to cross-couple ultra-stabilised sodium
(aryltrihydroxyborate) salts as activated nucleophiles with aromatic acyl chlorides
to prepare ketones.
.