Two efficient pathways for the synthesis of aryl ketones catalyzed by phosphorus-free palladium catalysts

Article abstract of DOI:10.1016/j.mcat.2017.10.021

Allylic alcohols, 1-buten-3-ol, 1-penten-3-ol and 1-octen-3-ol, reacted with aryl iodides (iodotoluene, 4-iodotoluene, 4-iodophenol and 4-iodanisole) under Heck reaction conditions to form corresponding saturated aryl ketones in one step. The same products were obtained in a two-step tandem reaction consisted of the Heck coupling of allylic alcohols with aryl iodides, followed by hydrogenation. Reactions were catalyzed by phosphorus-free palladium precursors modified with the menthol-substituted imidazolium chlorides. Formation of crystalline palladium nanoparticles, of the diameter up to 65 nm, in the reaction mixture was evidenced by TEM.

Full text of DOI:10.1016/j.mcat.2017.10.021

Molecular Catalysis 445 (2018) 61–72
Contents lists available at ScienceDirect
Molecular Catalysis
journal homepage: www.elsevier.com/locate/mcat
Research Paper
Two efficient pathways for the synthesis of aryl ketones catalyzed by
phosphorus-free palladium catalysts
A. Wirwisa, J. Feder-Kubisb, A.M. Trzeciaka,∗
a University of Wrocław, Faculty of Chemistry, 14 F. Joliot-Curie, 50-383 Wrocław, Poland
b Wrocław University of Science and Technology, Faculty of Chemistry, Wybrzez˙ e Wyspian´skiego 27, 50-370 Wrocław, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
Allylic alcohols, 1-buten-3-ol, 1-penten-3-ol and 1-octen-3-ol, reacted with aryl iodides (iodotoluene,
4-iodotoluene, 4-iodophenol and 4-iodanisole) under Heck reaction conditions to form corresponding
saturated aryl ketones in one step. The same products were obtained in a two-step tandem reaction con-
sisted of the Heck coupling of allylic alcohols with aryl iodides, followed by hydrogenation. Reactions
were catalyzed by phosphorus-free palladium precursors modified with the menthol-substituted imida-
zolium chlorides. Formation of crystalline palladium nanoparticles, of the diameter up to 65 nm, in the
reaction mixture was evidenced by TEM.
Received 28 August 2017
Received in revised form 10 October 2017
Accepted 17 October 2017
Keywords:
Heck coupling
Allylic alcohols
Palladium
© 2017 Elsevier B.V. All rights reserved.
Ionic liquid
Aryl ketone
Isomerization
Nanoparticles
1. Introduction
synthesis methods for aryl ketones is obvious. Among them, the
palladium-catalyzed Heck arylation of unsaturated ketones could
Aryl carbonyl compounds, aldehydes and ketones, have
attracted considerable attention from synthetic chemists for many
years. This is due to their properties, allowing them to be
used as building blocks in the industrial production of phar-
maceuticals, cosmetics, or agrochemicals [1–9]. In this context,
particular attention has been paid to one group of aryl car-
bonyl compounds, 4-aryl-2-butanones. For example, raspberry
ketone, 4-(4-hydroxyphenyl)-2-butanone, is a component of anti-
cancer medicine and a dietary supplement [2–6]; nabumetone,
be considered. Thus, the Heck arylation of 3-buten-2-on with
iodoanisole and iodophenol has been performed with homoge-
neous and heterogeneous palladium catalysts [13,18]. Palladium
nanoparticles in ionic liquid media have been employed with good
results in the arylation of 3-buten-2-on with iodobenzene, followed
by the hydrogenation of 4-phenyl-3-buten-2-one to 4-phenyl-3-
butan-2-one [19–21].
The Heck arylation of unsaturated allyl alcohols presents an
alternative synthetic strategy leading to aryl ketones. In this
very challenging process, high chemo- and regioselectivity can
be achieved due to the efficiency of double bond isomerization
[23–26]. The Heck arylation of different allylic substrates has been
performed with PdCl2 [27] and Pd(OAc)2 [28–31] under homoge-
neous conditions or after the impregnation of palladium on the
polymer [32]. Good results have been obtained employing palla-
dium systems with phosphorus ligands [28,33–35] or palladacyclic
compounds [36].
4-(6-methoxy-2-naphthalenyl)-2-butanone, is
a non-steroidal
anti-inflammatory drug, insecticide ingredient, and component in
detergent preparation [22].
Aryl carbonyl compounds can be prepared by commonly known
organic methods, such as Friedel–Crafts alkylation [10], Wittig
olefination [11–13], or aldol condensation [14–17]. The main dis-
advantages of these procedures consist in the generation of large
amounts of by-products and the need for expensive organophos-
phorus starting materials eventually forming environmentally
unfriendly phosphorus waste. Therefore, the need to develop new
The unique reactivity of allylic alcohols has also been exploited
in the preparation of aryl-substituted dicarbonyl compounds
[37,38]. Carbonylative coupling between allylic alcohols and aryl
iodides has resulted in the formation of 1,4-diketones in high yield
[37]. Dicarbonyl compounds have been prepared by the palladium-
∗
corresponding author.
E-mail address: anna.trzeciak@chem.uni.wroc.pl (A.M. Trzeciak).
http://dx.doi.org/10.1016/j.mcat.2017.10.021
2468-8231/© 2017 Elsevier B.V. All rights reserved.

62
A. Wirwis et al. / Molecular Catalysis 445 (2018) 61–72
Scheme 1. Hydrogen transfer in an ␣-alkyl-palladium intermediate.
catalyzed Heck coupling of ␤-bromocarbonyl compounds with
allylic alcohols [38].
2. Results and discussion
In most cases, ␤-aryl ketone has been obtained as the main
product of the Heck arylation of allylic alcohols. Although the inter-
pretation of the selectivity of this reaction is still under debate
[23–26], it can be assumed that ␤-hydride transfer (␤-hydride elim-
ination) is decisive for ketone formation. The rearrangement of
an ␣-alkyl-palladium intermediate, formed by migratory insertion,
has led to an unsaturated alcohol or an saturated ketone. Thus, the
selective catalyst should favor the transfer (elimination) of Hb over
Ha (Scheme 1).
Interestingly, tetraalkylammonium salts and ionic liquids sig-
nificantly influence the reaction course [22,39,40]. For example,
the application of TBAA (tetrabutylammonium acetate) in reactions
of 1-octen-3-ol have resulted in the selective formation of ␣-aryl
alcohol, without isomerization to aryl ketone [40]. In contrast,
TBAB (tetrabutylammonium bromide) has facilitated the forma-
tion of ␤-aryl ketone under similar conditions [40]. Aryl ketones
have mainly been formed in the presence of TBAC (tetrabutylam-
monium chloride) [34,41], while alcohol has been obtained in the
[bmim][BF4]/DMSO solution.
Our research aimed at the evaluation and comparison of two
protocols leading to arylated ketones. In both procedures, a pal-
ladium catalyst was employed in a two-step tandem reaction. In
the first method, unsaturated allylic alcohols were used as sub-
strates, while in an alternative method, unsaturated ketones were
employed. In both cases, the first step consisted of the Heck cou-
pling, followed by hydrogen transfer (isomerization of unsaturated
alcohol) or the hydrogenation of unsaturated ketone.
Considering literature examples that report the improvement
of allylic alcohol reactions by ionic liquids, we decided to study the
effect of menthol-modified imidazolium chlorides on the reaction
course. Till now, these ionic liquids have not been used in catalytic
reactions [42,43].
2.1. Arylation of allylic alcohols
Our investigations started from the studies of the arylation of 1-
buten-3-ol with iodobenzene and its substituted derivatives. The
formation of arylated ketone in this system was possible in two
steps. First, the formation of unsaturated arylated alcohol was
expected as a result of the Heck arylation at ␤ (products 1a–d) and
␣ carbons (products 2a–d). According to the literature, in most sys-
tems arylation at the ␤ position has been preferred [23–26]. The
second step, involving the isomerization of unsaturated arylated
allylic alcohol, leads to saturated ketone (Fig. 1). Thus, the palladium
catalyst should be active in both steps, namely the Heck coupling
and isomerization. As mentioned in the introduction, ketones 1a–d
could be formed by the rearrangement of the ␴-alkyl palladium
intermediate without the isolation of unsaturated arylated alcohol.
Different palladium precursors were tested in this reac-
tion, including simple PdCl2 or Pd(OAc)2 and anionic complexes
[CA]2[PdCl4] containing an imidazolium cation with menthyl sub-
stituents (Table 1). These complexes were prepared in the reaction
of PdCl2(cod) with imidazolium chlorides of the type [CA]Cl.(Fig. 2)
In all reactions, the saturated ketone 1a was obtained as the main
product. The yield of the second product, 2a, did not exceed 10%.
It is worth noting that the isomerization reaction to 1a was very
efficient under the applied conditions and, as a result, unsaturated
alcohol was not found in the reaction mixture.
The highest conversion to 1a, 90%, was obtained for PdCl2(cod)
in the DMF/H2O solvent mixture, while 82% of 1a was formed in
DMF. The pre-treatment of the catalyst precursor with H2 (1 atm)
before the introduction of the substrates, in order to form Pd(0)
in situ, only slightly changed the product composition, and 86% of
1a was formed. It can, therefore, be assumed that the Pd(II) pre-
cursor undergoes fast reduction in situ forming catalytically active
Pd(0), similarly as was observed in other C C bond forming reac-
tions [46–49]. The in situ reduction is so efficient under the reaction
conditions that the presence of H2 has in fact no significant influ-
ence on the reaction course. Consequently, the pre-treatment of the
catalyst is not needed to get high conversion. Interestingly, when
a Pd(0) complex, Pd2dba3, was used, the yield of 1a was lower,
It was also expected that these ionic liquids would form
in situ anionic palladates of the type [CA]2[PdX4] (CA = imidazolium
cation) with attractive catalytic activity. In fact, the high cat-
alytic activity of similar palladates has been evidenced in oxidative
Heck reaction and in the functionalization of olefins by arylsilanes
[44,45].
Fig. 1. Arylation of 1-buten-3-ol.

A. Wirwis et al. / Molecular Catalysis 445 (2018) 61–72
63
Table 1
Reactions of 1-buten-3-ol with PhI catalyzed by different palladium catalysts.
Table 2
The effect of the palladium amount in reaction of 1-buten-3-ol with PhI.
entry
catalyst
Pd/[CAIII]Cl
1a%
2a%
Solvent
mol% Pd
1a%
2a%
TON (for 1a)
a
1
2
3
4
5
6
7
8
PdCl2
PdCl2
–
1/2
–
–
1/2
–
62
62
73
40
50
82
86
90
80
66
88
85
67
62
56
27
28
21
6
6
7
3
5
8
9
9
9
8
8
10
7
7
7
2
2
2
DMF
DMF
DMF
DMF
DMF
DMF
DMF/H2O
DMF/H2O
DMF
2
1
0.5
0.3
90 (85)*
87 (86)*
(86)*
9 (10)
9 (10)
(10)
9 (10)
(10)
(7)
(3)
3 (3)
45 (43)
87
172
296
870
1220
4600
22000
a
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
a
a
89 (87)*
(87)*
0.1
PdCl2(cod)
PdCl2(cod)a
PdCl2(cod)
PdCl2(cod)
PdCl2(cod)a
PdCl2(cod)a
PdCl2(cod)
Pd2dba3
0.05
0.005
0.001
(61)*
–
–
(23)*
22 (23)*
9
1/2
1/2
1/1
1/1
–
Reaction conditions: 2.68 mmol PhI; 2.68 mmol 1-buten-3-ol; 2.5 mmol NaHCO3;
catalyst: PdCl2(cod); 80 ◦C; 24 h; DMF/H2O 3/2 (5 cm3),
10
11
12
13
14
15
16
17
18
DMF
DMF/H2O
DMF/H2O
DMF
DMF
DMF
DMF
DMF
DMF
*
data in parentheses were obtained using PdCl2(cod) and [CAIII]Cl, Pd/IL = 1/1.
Pd2dba3
Pd2dba3
1/1
be achieved, characteristic for the high efficiency of the catalytic
system (Table 2).
1/2
–
[CAI]2[PdCl4]b
[CAII]2[PdCl4]b
[CAIV]2[PdCl4]b
The further optimization of the reaction conditions was
performed for the PdCl2(cod)/[CAIII]Cl catalytic system (Table
S1–supplementary data). It was found that a reaction time of 6 h
was quite sufficient to get high conversion to 1a, in particular apply-
ing temperature 90 ◦C.
Reaction conditions: 2.68 mmol 1-buten-3-ol; 2.68 mmol of PhI; 2 mol% Pd; 80 ◦C;
24 h, 2.5 mmol NaHCO3; 5 cm3 DMF or DMF/H2O = 3/2 (5 cm3); IL = [CAIII]Cl; a pre-
treatment of Pd precursor with H2 (30 min); b anionic palladates obtained in reaction
of [CAI]Cl; [CAII]Cl or [CAIV]Cl with PdCl2(cod).
Interestingly, the reaction appeared insensitive to reactant con-
centration changes as illustrated by the results presented in Table
S2 (supplementary data). In the first experiment, when 5 cm3 of the
DMF/H2O mixture was used, 86% of 1a was obtained after 6 h. Only
slightly lower yield was obtained when the same amounts of sub-
strates reacted in a volume of 2.5 cm3. Doubling the concentration
by using double the substrate amount in a volume of 2.5 cm3 gave
practically the same result. Thus, up-scaling the process is possi-
ble without changing the product composition. From the practical
point of view, this can be considered an advantage of this system.
Having optimized the reaction conditions in hand, we tested
different iodobenzenes as arylating agents in the synthesis of satu-
rated ketones (Fig. 3). In all reactions, the desired product, ketone
1, was formed as the main one. The effect of the [CA]Cl co-catalyst
was the weakest for PhI, and the addition of [CA]Cl practically did
not influence the yield of products. Conversion to 1a was at the
level of 80%.
namely 67%. With Pd(OAc)2 used as the catalyst precursor, con-
version to 1a was 73%. It decreased significantly (to 40%) when the
reaction solution was pre-treated with H2. Anionic palladium com-
plexes, [CA]2[PdCl4], appeared less active, forming only 21–28% of
1a.
The modification of the catalytic system by the introduction of
imidazolium chlorides [CA]Cl (Fig. 1) did not change reaction selec-
tivity, and 1a was mainly formed. The conversion and yield were
similar to those obtained without [CA]Cl salts. It is also seen that
pre-made [CA]2[PdCl4] anionic complexes were less active than
systems containing palladium complexes and [CA]Cl, in which pal-
ladates could be formed in situ.
In further experiments, the effect of the palladium amount on
the reaction course was studied. In both series of experiments,
performed in the absence and in the presence of [CAIII]Cl, very
similar results were obtained. In the range of concentrations from
2 to 0.1 mol%, ca. 90% of 1a was formed. When the palladium
amount decreased to 0.05 mol%, the yield of 3a also decreased to
61%. At 0.005 and 0.001 mol% of palladium, only 22–23% of 1a was
formed. Nevertheless, TON values as high as 22 000, could easily
In reactions of 4-iodotoluene, 4-iodophenol, and 4-iodoanisole,
the presence of [CA]Cl caused the increase of substrate conversion
by 10–20%. The negative effect of the OH group on the substrate was
clearly seen for 4-iodophenol, which gave the lowest conversion.
However, selectivity was excellent at the same time because only
one product was formed.
Fig. 2. Ionic liquids and palladium anionic complexes used in these studies.

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A. Wirwis et al. / Molecular Catalysis 445 (2018) 61–72
Fig. 3. Heck arylation of 1-buten-3-ol with ArI in the presence of different ionic liquids ([CA]Cl).
Reaction conditions: 1.34 mmol 1-buten-3-ol; 1.34 mmol ArI; 0.5 mol% PdCl2(cod); 1.25 mmol NaHCO3; Pd/IL = 1/1; DMF/H2O 1.5/1 (2.5 cm3); 6 h; 90 ◦C.
Table 3
The arylation of 1-octen-3-ol, another allyl alcohol tested, pro-
Heck arylation of 3-buten-2-one with PhI in the presence of PdCl2(cod) and [CA]Cl.
ceeded similarly and mainly produced saturated ketones 3a–d
(Fig. 4). 1-Octen-3-ol reacted smoothly with PhI and 4-iodoanisole,
while lower conversions were noted for 4-iodotoluene. More-
over, only one product was formed in the 4-iodophenol reaction.
The effect of the presence of [CA]Cl salts was not spectacular,
although some conversion increase in the presence of [CAI]Cl and
[CAII]Cl was noted for 4-iodotoluene (Fig. 5). Reaction conditions:
1.34 mmol 1-octen-3-ol; 1.34 mmol ArI; 0.5 mol% PdCl2(cod);
1.25 mmol NaHCO3; Pd/IL = 1/1; DMF/H2O 1.5/1 (2.5 cm3); 6 h;
90 ◦C.
ArI
PhI
IL
7a%
8a%
Conversion[%]
–
70
82
71
78
79
1
3
–
–
2
71
85
71
78
81
[CAI]Cl
[CAII]Cl
[CAIII]Cl
[CAIV]Cl
Reaction conditions: 1.34 mmol 3-buten-2-one; 1.34 mmol PhI; 0.5 mol% PdCl2(cod);
1.25 mmol NaHCO3; Pd/IL = 1/1; DMF = 2.5 cm3; 24 h; 100 ◦C.
The reaction of 1-penten-3-ol with aryl iodides occurs with the
formation of 1-aryl-3-pentanone (5a–d) (Fig. 6).
84–88%, was obtained for the longest chain alcohol, 1-octen-3-ol.
Conversely, only 60–70% of the desired product was formed in reac-
tion of 1-penten-3-ol. In all cases, the ionic liquid [CAII]Cl was the
most effective increasing the reaction yield.
Unexpectedly, definitely lower conversions were noted for this
alcohol, in the range from 50 to 72%. Ionic liquids, [CA]Cl, positively
modified the reaction course for iodobenzene and 4-iodophenol,
while only a small effect was noted for 4-iodoanisole (Fig. 7).
The coupling of 1-penten-3-ol with 4-iodophenol proceeded with
moderate yield of 5c, ca. 50%. On the other hand, selectivity to
this product was close to 100%, and only traces of 6c (below 3%)
were found. In one reaction, with 4-iodoanisole in the presence
of [CAII]Cl, small amount of aryl alcohol, 4-(4-methoxyphenyl)-1-
penten-3-ol (4%) was found.
Reaction conditions: 1.34 mmol 1-penten-3-ol; 1.34 mmol
ArI; 0.5 mol% PdCl2(cod); 1.25 mmol NaHCO3; Pd/IL = 1/1;
DMF/H2O = 1.5/1 = 2.5 cm3; 6 h; 90 ◦C.
The influence of the allylic alcohol structure on the reaction
course is illustrated in Fig. 8. The highest yield of the ketone,
2.2. Synthesis of raspberry ketone
As has already been mentioned, 4-aryl-2-butanones exhibit
biological activity, and therefore their efficient synthesis is of prac-
tical importance. For example, 4-(4-hydroxyphenyl)-2-butanone,
raspberry ketone, is a precursor of an anticancer drug and a
dietary supplement ingredient. Using experience in the studies of
the coupling reaction of 1-buten-3-ol with iodobenzene, the effi-
cient synthesis of raspberry ketone was developed (Fig. 9). In this
method, 0.1 mol% of Pd(OAc)2 was sufficient to form the ketone
with 100% yield.
Fig. 4. Heck arylation of 1-octen-3-ol.

A. Wirwis et al. / Molecular Catalysis 445 (2018) 61–72
65
Fig. 5. Heck arylation of 1-octen-3-ol with ArI in the presence of different ionic liquids ([CA]Cl).
Fig. 6. Heck arylation of 1-penten-3-ol.
Fig. 7. Heck arylation of 1-penten-3-ol with ArI in the presence of different ionic liquids ([CA]Cl).

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A. Wirwis et al. / Molecular Catalysis 445 (2018) 61–72
Fig. 8. Efficiency of ketone formation in reactions of allylic alcohols with PhI.
Fig. 9. Synthesis of raspberry ketone.
Table 4
Table 5
Results after the second step, hydrogenation of the unsaturated aryl ketone.
Heck arylation of 3-buten-2-one with 4-iodophenol.
ArI
PhI
IL
8a%
9a%
1a%
Conversion[%]
ArI
IL
7c%
Conversion
–
2
3
–
5
3
14
6
4
11
7
77
83
74
78
82
93
92
78
94
92
–
29
14
16
29
12
29
14
16
29
12
4-iodophenol
[CAI]Cl
[CAII]Cl
[CAIII]Cl
[CAIV]Cl
[CAI]Cl
[CAII]Cl
[CAIII]Cl
[CAIV]Cl
Reaction conditions: the mixtures obtained under conditions reported in Table 5 were
Reaction conditions: 1.34 mmol 3-buten-2-one; 1.34 mmol ArI; 0.5 mol% PdCl2(cod);
treated with H2 (1 atm); 6 h; 100 ◦C.
1.25 mmol NaHCO3; Pd/IL = 1/1; DMF = 2.5 cm3; 24 h; 100 ◦C.
2.3. Arylation of unsaturated ketones
iodobenzene conversion and high selectivity to 1a formed with a
yield of 77–83%. The presence of H2 also facilitated the hydrogena-
tion of 8a to 9a; however, the final yield of 9a remained below 14%.
The best selectivity to 1a was obtained in the presence of [CAI]Cl.
The Heck coupling of 3-buten-2-one with 4-iodophenol was less
efficient under the same conditions. Product 7c was obtained selec-
tively; however, its highest yield was only 29% in reaction with
PdCl2(cod) alone and in the presence of [CAIII]Cl (Table 5).
Interestingly, the conversion of 4-iodophenol significantly
increased in an H2 atmosphere (Table 6). The results presented in
Table 6 were obtained after 6 h of stirring solutions prepared under
conditions reported in Table 5 in an H2 atmosphere. Conversion
increase up to 81–100% was noted in all systems; however, prod-
uct mixtures were formed depending on the kind of IL. The highest
yield of the expected product (1c), 98%, was obtained without IL. A
good result, the yield of 70%, was achieved in reaction with [CAIII]Cl.
The presence of [CAI]Cl and [CAIV]Cl facilitated the formation of
unsaturated ketone, 7c; however, its reduction is rather slow in
the presence of these co-catalysts (Table 6).
The second method leading to saturated ketones employed 3-
buten-2-one and aryl iodides (iodobenzene or 4-iodophenol) as
substrates. In this two-step procedure, the hydrogenation of the
unsaturated aryl ketone should be performed after the Heck cou-
pling (Fig. 10). The studies aimed at the development of conditions
enabling the performance of this tandem process in one vessel,
without the separation of unsaturated ketones, the first reaction
products.
The arylation of 3-buten-2-one by PhI produced 7a with high
selectivity and a yield of 70–82%. The product of diarylation, 8a, was
found in trace amounts, up to 3% (Table 3). A significant improve-
ment of conversion, by 14%, was achieved after the addition of
[CAI]Cl as a co-catalyst.
Next, H2 (1 atm) was introduced into the same reaction ves-
sel, and the reaction mixture was heated for 6 h at 100 ◦C. After
that time, product 1a was formed as the main one with a yield of
74–83%. The results presented in Table 4 confirmed the increase of

A. Wirwis et al. / Molecular Catalysis 445 (2018) 61–72
67
Fig. 10. Synthesis of saturated ketones in a tandem reaction.
Fig. 11. TEM picture of [CAI]2[PdCl4]+DMF+H2 (atm) (30 min).
Table 7
Heck coupling of 3-buten-2-one with PhI in the presence of [CA]2[PdCl4] complexes.
Complex
H2
7a%
8a%
9a%
1a%
Biphenyl
Time/Temp. [h/◦C]
Conversion[%]
[CAI]2[PdCl4]
–
–
–
+
+
+
+
43
45
47
–
68
–
–
–
–
13
6
–
–
–
26
9
–
–
–
52
4
–
–
–
–
2
–
3
24/100
24/100
24/100
5/100
5/100
5/100
5/100
43
45
47
91
90
91
85
[CAII]2[PdCl4]
[CAIV]2[PdCl4]
[CAI]2[PdCl4]
[CAII]2[PdCl4]
[CAIV]2[PdCl4]
PdCl2(cod) + [CAIII]Cl
7
11
28
28
55
33
10
Reaction conditions: 1.34 mmol 3-buten-2-one; 1.34 mmol ArI; 0.5 mol% Pd; 1.25 mmol NaHCO3; DMF = 2.5 cm3.
This protocol worked quite well for the synthesis of raspberry
ketone but only in the absence of IL.
plexes was investigated. First, the coupling of 3-buten-2-one with
PhI was performed for 24 h. After that time, 7a was identified as the
only product, with a yield of 43–47% (Table 7).
When the same reaction was performed in an H2 atmosphere
(1 atm), conversion increased significantly, to 85–91%, already after
5 h. However, the regioselectivity was not satisfactory because,
besides the desired monoarylated products, 7a and 1a, diarylated
2.4. Catalytic activity of anionic palladates
In order to get a deeper understanding of the role of ionic liquids
in the systems studied, the catalytic activity of [CA]2[PdCl4] com-

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A. Wirwis et al. / Molecular Catalysis 445 (2018) 61–72
Table 6
Results after the second step, hydrogenation of the unsaturated aryl ketone.
ArI
IL
7c%
8c%
9c%
1c%
Conversion[%]
–
–
–
6
–
5
–
–
5
14
6
–
98
19
51
70
–
98
91
100
81
98
4-iodophenol
[CAI]Cl
[CAII]Cl
[CAIII]Cl
[CAIV]Cl
61
35
–
98
Reaction conditions: the mixtures obtained under conditions reported in Table 7 were
treated with H2 (1 atm); 6 h; 100 ◦C.
Fig. 14. Pd(0) nanoparticle size distribution after 2 months.
ogy was not changed significantly, indicating good stabilization by
[CAI]Cl recovered during the decomposition of [CAI]2[PdCl4].
In the second experiment, a similar reaction of [CAI]2[PdCl4]
with H2 was performed in the presence of the base NaHCO3. The
obtained Pd NPs were slightly smaller, ca. 7 nm in diameter, and
mostly round in shape (Figs. 15 and 16).
Interestingly, the TEM analysis of the post-reaction mixture con-
taining [CAI]2[PdCl4] and all the reactants (3-buten-2-on, PhI, and
H2) showed significantly bigger Pd NPs with well-defined shapes,
for example triangular (Fig. 17). The size distribution was rather
broad (Fig. 18), and some agglomerates were also observed.
Nevertheless, it was interesting to find that the post-reaction
sample analyzed after 2 months also contained well-defined crys-
talline Pd NPs (Fig. 19).
Pd NPs found in the post-reaction mixtures were significantly
larger than those observed in our previous studies [46–49]. The
crystalline shapes of nanoparticles were also only rarely noted. One
can assume that the ionic liquid formed during the decomposition
of the [CAI]2[PdCl4] complex, in this case [CAI]Cl, contributed to the
crystallization process.
Fig. 12. Pd(0) nanoparticle size distribution after the reaction of [CAI]2[PdCl4] with
H2.
ketones, 8a and 9a, were also formed. Complexes [CAI]2[PdCl4] and
[CAIV]2[PdCl4] formed the highest amounts of 1a, 52 and 55%. Using
[CAII]2[PdCl4], only 4% of 1a was found. The most characteristic for
these systems was the tendency to form diarylated products, both
saturated and unsaturated. The diarylation of 7a competed with
its hydrogenation to 1a leading to a decrease in regioselectivity.
The same feature was also observed for the two-component sys-
tem containing PdCl2(cod) and [CAIII]Cl, in which [CAIII]2[PdCl4]
could be formed in situ. In this reaction, 33% of 1a was obtained.
The yield of the diarylated product 9a was slightly lower, 28%.
2.5. TEM studies
2.6. The role of Pd NPs in the catalytic reaction: the mercury test
Palladates, [CA]2[PdCl4], demonstrated increased catalytic
activity in the presence of H2. Under these conditions, the formation
of palladium nanoparticles, Pd NPs, was very likely. To verify that
hypothesis, TEM studies of the reaction mixtures were undertaken.
The first sample was obtained by the treatment of [CAI]2[PdCl4]
in DMF with H2 for 30 min. TEM analysis showed the presence of
Pd NPs with diameters of 8–12 nm, with the maximum at 10 nm
(Figs. 11 and 12).
The mercury test is one of the simplest methods used for the
diagnosis of the catalytic reaction pathway [50,51]. It is expected
that palladium nanoparticles or underligated palladium species
will form amalgams with Hg(0), inactive in the catalytic reaction.
Consequently, the inhibition of the reaction course in the presence
of Hg(0) could indicate an important role of Pd NPs in the catalytic
process. This is the case of our system (Table 8). The reaction of
3-buten-2-on with PhI under an H2 atmosphere produced 23% of
7a in 1 h. The yield increased to 58% when the reaction time was
extended to 2 h. When Hg(0) was added after 1 h to the same reac-
tion, and heating continued for the next 1 h, the final yield of 7a was
The same sample analyzed after two months contained
slightly bigger Pd NPs, with the average diameter of ca. 15 nm
(Figs. 13 and 14). Although Pd NPs were stored in air, their morphol-
Fig. 13. TEM picture of [CAI]2[PdCl4] + DMF + H2 (30 min) after 2 months.

A. Wirwis et al. / Molecular Catalysis 445 (2018) 61–72
69
Fig. 15. TEM picture of the sample of [CAI]2[PdCl4] + DMF + NaHCO3 + H2 (30 min) after 2 months.
Table 8
Hg(0) poisoning test.
Hg(0)
Time [h]
7a[%]
–
–
+
1
2
2
23
58
28
Reaction conditions: 1.34 mmol 3-buten-2-one; 1.34 mmol PhI; 0.5 mol% Pd;
[CAI]2[PdCl4]; 1.25 mmol NaHCO3; DMF = 2.5 cm3; H2 from the beginning of the
reaction.
Fig. 18. Pd(0) nanoparticle size distribution after the reaction.
2.7. Isomerization and hydrogenation of allylic alcohols
The reaction employing allylic alcohols and aryl halides to form
arylated saturated ketones was found highly efficient for different
substrates. This is due to the high ability of the applied catalysts
to carry out the isomerization of arylated alcohols formed in the
first step. It should be pointed out here that the isomerization of
the allylic substrate before the Heck coupling could generate unde-
sirable side products [52,53]. In order to estimate the reactivity
of the studied catalysts towards allylic alcohols, the test reactions
were performed using the complexes [CAI]2[PdCl4] and PdCl2(cod)
+ [CAIV]Cl and 3-buten-2-ol as substrates. Interestingly, no prod-
ucts were found after 4 h at 90 ◦C. However, the application of an H2
atmosphere resulted in the conversion of alcohol into two products,
a hydrogenation product, 2-butanol, and an isomerization prod-
Fig. 16. Pd(0) nanoparticle size distribution after 2 months.
only 28%. It could, therefore, be assumed that the formation of the
amalgam eliminated catalytically active Pd NPs from the catalytic
cycle, and, consequently, the formation of the product significantly
slowed down.
Fig. 17. TEM picture of [CAI]2[PdCl4] + DMF + NaHCO3 + 3-buten-2-on + PhI + H2 (30 min).

70
A. Wirwis et al. / Molecular Catalysis 445 (2018) 61–72
Fig. 19. TEM picture of [CAI]2[PdCl4] + DMF + NaHCO3 + 3-buten-2-on + PhI + H2 (30 min) after 2 months.
Fig. 20. Heck arylation of 3-buten-2-ol in the presence of H2.
uct, 2-butanone. The pre-made anionic complex, [CAI]2[PdCl4], was
more active than the in situ formed one, [CAI]2[PdCl4] (Fig. 20).
In conclusion, the studied complexes catalyze the isomerization
and hydrogenation of allylic alcohols under mild conditions well,
but only in the presence of H2. In agreement with the TEM studies,
this activity could be assigned to Pd NPs, while Pd(II) complexes
did not react with allylic alcohols.
formed on a 2400 CHNS Vario EL III apparatus. TEM measurements
were carried out using a FEI Tecnai G2 20 X-TWIN electron
microscope operating at 200 kV. Catalytic reaction products were
identified and analyzed with a HP 5890 Series II gas chromatograph
connected to HP 5971A mass selective detector. Separation was
achieved on a capillary HP-5 column coated with a diphenyl (5%)
dimethylsiloxane (95%) copolymer film. Helium was used as the
carrier gas.
3. Experimental
3.2. Arylation of 1-alken-3-ols
3.1. Instrumental methods
The reactions were carried out in a 50 cm3 Schlenk tube with
magnetic stirring. The reagents, iodobenzene (1.34 mmol), NaHCO3
(1.25 mmol; 0.1050 g), PdCl2(cod) (0.5 mol%; 6.7 × 10−6 mol;
0.001913 g), and IL (6.7 × 10−6 mol), were introduced to the Schlenk
1H NMR and 13C NMR were recorded on a Bruker Avance
500 MHz spectrometer (1H NMR 500 MHz, 13C NMR 125 MHz)
using TMS as internal reference. Elemental analyses were per-

A. Wirwis et al. / Molecular Catalysis 445 (2018) 61–72
71
tube under an N2 atmosphere. Next, 1-alken-3-ol (1.34 mmol) and
the solvent, DMF or DMF/H2O = 1.5/1, were added with a pipette.
The Schlenk tube was closed with a rubber plug, and the reaction
mixture was stirred at 90 ◦C for 6 h. After the given reaction time,
the Schlenk tube was cooled down, and the organic products were
separated by extraction with diethyl ether (three times with 4, 3,
and 3 cm3). The products were GC–MS analyzed (Hewlett Packard
8454A) with mesitylene (75 ␮l) as the internal standard.
down, and the organic products were separated by extraction with
diethyl ether (three times with 4, 3, and 3 cm3). The products were
GC–MS analyzed (Hewlett Packard 8454A) with mesitylene (75
␮l) as the internal standard.
4. Conclusions
In these studies, two highly efficient methods leading to aryl
ketones were developed. Allylic alcohols were used as substrates,
and phosphorus-free palladium compounds were employed as cat-
alyst precursors. In the second method, unsaturated ketones were
first arylated according to the Heck protocol, and the resulting aryl
ketone was hydrogenated to the final product. Under the stud-
ied conditions, the efficiency of this strategy was satisfactory for
iodobenzene but not for 4-iodophenol.
3.3. Arylation of 3-buten-2-one followed by hydrogenation
The reactions were carried out in a 50 cm3 Schlenk tube with
magnetic stirring. The reagents, iodobenzene (1.34 mmol), NaHCO3
(1.25 mmol; 0.1050 g), PdCl2(cod) (0.5 mol%; 6.7 × 10−6 mol;
0.001913 g), and IL (6.7 × 10−6 mol) or [CA]2[PdCl4] [0.5 mol%;
6.7 × 10−6 mol], were introduced to the Schlenk tube under an N2
atmosphere. Next, 3-buten-2-on (1.34 mmol, 0.109 cm3) and DMF
(2.5 cm3) were added with a pipette. The Schlenk tube was closed
During the reactions, Pd(II) was reduced to Pd(0) nanoparti-
cles, which participated in the catalytic process, most probably
as a catalytically active form of palladium. The surface of Pd(0)
nanoparticles was modified by ionic liquids which formed a layer
preventing agglomeration to the less active palladium forms. How-
ever, ionic liquids had only moderate influence on the reaction
course, although, in the reaction of 1- penten-3-ol, the yield of
ketone increased by 20% in the presence of IL. It could be therefore
concluded that ionic liquids did not restrict access of substrates
to the catalytically active centers. On the other hand, a negative
effect of ionic liquids in the Heck coupling of 3-buten-2-one with
4-iodophenol can indicate on the competition between substrates
and ionic liquid for a place in the palladium environment. Further-
more, IL influenced the morphology of the palladium nanoparticles
that formed big crystals of well-defined shape. The catalytic activity
of anionic palladates, [CA]2[PdCl4], in the Heck coupling of unsatu-
rated alcohols and ketones was rather low. This could be explained
by the slow transformation of these complexes to Pd(0) nanoparti-
cles which was however significantly facilitated by the introduction
of an H2 atmosphere. Consequently the reactivity increased, but
the selectivity of the reaction changed, and di-aryl ketones were
formed.
The comparison of the two protocols studied indicated the
advantages of the one using allylic alcohols as substrates. In com-
parison to the procedure employing unsaturated ketones, the
reactions of allylic alcohols could be performed in one step under
mild conditions in a relatively short time.
The possibility to perform efficiently the synthesis of aryl
ketones from allylic alcohols in the studied system could be ratio-
nalized from the mechanistic point of view. Because of the low
ability of palladium to isomerize the allylic alcohol substrate, iso-
merization did not compete with Heck arylation. Advantageously,
Heck coupling proceeded mainly in ␤-position and the resulting ␴-
alkyl palladium intermediate could undergo isomerization to the
final ketone. At this stage, the studied catalysts demonstrated high
ability to activate C H bonds in the alkyl group coordinated to
palladium.
with a rubber plug, and the reaction mixture was stirred at 100 ◦
C
for 24 h. After that time, the Schlenk tube was filled with H2 from
a balloon (1 atm), and heating continued for 6 h. Next, the Schlenk
tube was cooled down, and the organic products were separated
by extraction with diethyl ether (three times with 4, 3, and 3 cm3).
The products were GC–MS analyzed (Hewlett Packard 8454A) with
mesitylene (75 ␮l) as the internal standard.
3.4. Arylation of 3-buten-2-ol in H2 atmosphere
The reactions were carried out according to the procedure
described above, applying an H2 atmosphere (1 atm) instead of an
N2 one.
3.5. Preparation of samples for TEM
a)[CAI]2[PdCl4] + DMF + H2(30min)
The complex [CAI]2[PdCl4] (0.5 mol%; 6.7 × 10−6 mol; 0.0056 g)
and DMF (2.5 cm3) were introduced into a 50 cm3 Schlenk tube.
The Schlenk tube was closed with a rubber plug, frozen in liquid
nitrogen, and air was evacuated using a pump. The evacuation was
repeated three times, and next the Schlenk tube was connected to
a balloon with H2 (1 atm). The solution was heated at 100 ◦C for
30 min, cooled down, and analyzed by TEM.
b)[CAI]2[PdCl4] + DMF + NaHCO3 + H2(30min)
The sample was prepared according to the procedure described
above with the addition of NaHCO3 (1.25 mmol; 0.1050 g).
c)[CAI]2[PdCl4] + DMF + NaHCO3
+ 3-buten-2-on + PhI + H2(30 min)
The sample was prepared according to the procedure described
above with the addition of NaHCO3 (1.25 mmol; 0.1050 g), 3-buten-
2-on (1.34 mmol; 0.109 cm3), and PhI (1.34 mmol; 0.15 cm3).
Acknowledgements
3.6. Hg(0) test
The reactions were carried out in a 50 cm3 Schlenk tube
with magnetic stirring. The reagents, iodobenzene (1.34 mmol,
0.150 cm3), NaHCO3 (1.25 mmol; 0.1050 g), [CAI]2[PdCl4] (0.5
mol%; 6.7 × 10−6 mol; 0.0056 g), 3-buten-2-on (1.34 mmol,
0.109 cm3), PhI (1.34 mmol, 0.150 cm3), and DMF (2.5 cm3), were
added in an N2 atmosphere. The Schlenk tube was closed with a
rubber plug, and the reaction mixture was stirred at 100 ◦C for
1 h. After that time, Hg(0) was added (3.35 × 10−3 mmol; 50 ␮l],
and heating continued for 1 h. Next, the Schlenk tube was cooled
Financial support of National Science Centre (NCN, Poland) with
grant 2014/15/B/ST5/02101 is gratefully acknowledged.
Appendix A. Supplementary data
Supplementary data associated with this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.mcat.2017.10.
021.

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A. Wirwis et al. / Molecular Catalysis 445 (2018) 61–72
[26] L. Xu, M.J. Hilton, X. Zhang, P.-O. Norrby, Y.-D. Wu, M.S. Sigman, O. Wiest, J.
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