Pd-catalysed conjugate addition of arylboronic acids to α,β-unsaturated ketones under microwave irradiation

Article abstract of DOI:10.2478/s11696-011-0016-3

The Pd-catalysed conjugate addition of arylboronic acids to α,β-unsaturated cyclic ketones was studied under controlled microwave irradiation conditions. A variety of catalysts, bases and solvents was explored in order to achieve optimum yields in the sho

Full text of DOI:10.2478/s11696-011-0016-3

Chemical Papers 65 (3) 338–344 (2011)
DOI: 10.2478/s11696-011-0016-3
ORIGINAL PAPER
Pd-catalysed conjugate addition of arylboronic acids
to α,β-unsaturated ketones under microwave irradiation
Viera Poláčková, Vladimír Bariak, Radovan Šebesta*, Štefan Toma
Department of Organic Chemistry, Faculty of Natural Sciences, Comenius University,
Mlynská dolina CH-2, 842 15 Bratislava, Slovakia
Received 1 October 2010; Revised 16 December 2010; Accepted 20 December 2010
The Pd-catalysed conjugate addition of arylboronic acids to α,β-unsaturated cyclic ketones was
studied under controlled microwave irradiation conditions. A variety of catalysts, bases and solvents
was explored in order to achieve optimum yields in the shortest possible reaction time. Under
optimised conditions (Pd(OAc)2/2,2ꢀ-bipyridine and KF in a mixture of toluene, water, and acetic
acid and 10 min microwave irradiation), a range of arylboronic acids was successfully added to
several cyclic enones. With chiral phosphane ligands, a promising enantioselectivity was obtained
(85 % ee).
c
ꢀ 2011 Institute of Chemistry, Slovak Academy of Sciences
Keywords: palladium, catalysis, Michael addition, arylboronic acid, microwave irradiation
Introduction
Pd-catalysed Suzuki-Miyaura reaction (Poláčková et
al., 2006; Poláčková & Toma, 2007), Pd-catalysed al-
lylic substitution with arylboronic acids (Poláčková
et al., 2007), and CuI-catalysed aromatic amination
(Veverková & Toma, 2008). Elevated reaction tem-
peratures often result in lower enantioselectivity. Mi-
crowave heating, however, has been successfully ap-
plied to accelerate asymmetric reactions without a
decrease in their enantioslectivities (Almansa et al.,
2008; Genov et al., 2007, 2008).
The conjugate addition of organometallic reagents
to enones is a widely used method for the formation
of β-substituted carbonyl compounds, which are ver-
satile synthons for further structural transformations.
Rhodium complexes are the catalysts most frequently
used for the addition of arylboronic acids to enones.
Some Pd-based catalysts have also been described for
this reaction (Bedford et al., 2007; Gutnov, 2008; He
et al., 2007; Cho et al., 1995; Nishikata et al., 2004;
Suzuma et al., 2007; Yamamoto et al., 2006). The first
enantioselective Pd-catalysed conjugate addition of
arylboronic acids to a variety of α,β-unsaturated com-
pounds was reported by Minnaard (Gini et al., 2005).
Product yields and enantioselectivities were high, but
Microwave irradiation (MWI) is now an estab-
lished technique in organic synthesis (Kappe, 2004;
Kappe et al., 2009; Kappe & Stadler, 2005; Tierney &
Lidstro¨m, 2005). It is often applied as a substitute for
conventional heating in order to accelerate reactions or
suppress the decomposition or formation of unwanted
by-products. Microwave irradiation is also very use-
ful in the synthesis of biologically active compounds
(Gavande et al., 2010; Helan et al., 2010; Kováčová
et al., 2010). Moreover, applying a closed-vessel tech-
nique enables the heating of solvents far above their
boiling point. The higher reaction temperatures at el-
evated pressures lead to impressive results in respect
of reducing reaction times and improving chemical
yields (Kappe & Dallinger, 2009). Microwave heating
is also beneficial to many transition metal-catalysed
carbon-carbon bond forming reactions (Alonso et al.,
2008; Barge et al., 2008; Larhed et al., 2002; Singh
et al., 2008). Researchers from our laboratory also
contributed to the development of microwave-assisted
metal-catalysed reactions. We demonstrated that mi-
crowave heating was effective in a certain type of
*Corresponding author, e-mail: radovan.sebesta@fns.uniba.sk

V. Poláčková et al./Chemical Papers 65 (3) 338–344 (2011)
Table 1. Spectral data of the compounds prepared
339
Compound
Spectral data
Reference
II
1H NMR (CDCl3), δ: 1.68–1.94 (m, 2H), 2.02–2.25 (m, 2H), 2.30–2.73 (m, 4H), 2.94–3.10 (Gini et al., 2005)
(m, 1H), 7.09–7.49 (m, 5H)
HPLC (hexane/propan-2-ol (ϕr = 98 : 2), 0.8 mL min−1), tR/min: 18.3 (major), 20.0
(minor)
V
1H NMR (CDCl3), δ: 1.91–2.05 (m, 1H), 2.24–2.56 (m, 4H), 2.64–2.73 (m, 1H), 3.35–3.50 (Gini et al., 2005)
(m, 1H), 7.20–7.38 (m, 5H)
VI
1H NMR (CDCl3), δ: 1.92–2.03 (m, 1H), 2.26–2.36 (m, 2H), 2.41–2.51 (m, 2H), 2.64–2.71 (Itooka et al., 2003)
(m, 1H), 3.40 (m, 1H), 7.13 (dtd, J = 0.6 Hz, J = 1.8 Hz, J = 7.2 Hz, 1H), 7.22–7.30 (m,
3H)
VII
VIII
IX
1H NMR (CDCl3), δ: 1.88–2.02 (m, 1H), 2.24–2.52 (m, 4H), 2.62–2.71 (m, 1H), 3.34–3.46 (Kantam et al., 2008)
(m, 1H), 7.19 (d, J = 8.1 Hz, 2H), 7.33 (d, J = 8.1 Hz, 2H)
13C NMR (CDCl3), δ: 31.1, 38.8, 41.6, 45.6, 128.1, 128.7, 132.3, 141.5, 217.8
1H NMR (CDCl3), δ: 1.96–2.04 (m, 1H), 2.30–2.37 (m, 2H), 2.46–2.52 (m, 2H), 2.70 (dd, (Takaya et al., 1999)
J = 18.3 Hz, J = 7.2 Hz, 1H), 3.49 (m, 1H), 7.38 (d, J = 8.1 Hz, 2H), 7.60 (d, J = 8.1 Hz,
2H)
1H NMR (CDCl3), δ: 2.17–2.27 (m, 1H), 2.34–2.61 (m, 4H), 2.82 (dd, J = 7.2 Hz, J = 18.0 (Fujio et al., 1998)
Hz, 1H), 4.18–4.28 (m, 1H), 7.36–7.61 (m, 4H), 7.75 (d, J = 8.1 Hz, 1H), 7.88–7.91 (m, 1H),
8.10 (d, J = 8.1 Hz, 1H)
X
1H NMR (CDCl3), δ: 1.72–1.89 (m, 2H), 2.05–2.19 (m, 2H), 2.34–2.61 (m, 4H), 2.95–3.03 (Itooka et al., 2003)
(m, 1H), 7.09 (td, J = 8.4 Hz, J = 1.8 Hz, 1H), 7.21–7.28 (m, 3H)
XI
1H NMR (CDCl3), δ: 1.67–1.90 (m, 2H), 2.02–2.22 (m, 2H), 2.29–2.63 (m, 4H), 2.91–3.06 (Cho et al., 1995)
(m, 1H), 7.14 (d, J = 8.1 Hz, 2H), 7.30 (d, J = 8.1 Hz, 2H)
XII
XIII
XIV
1H NMR (CDCl3), δ: 1.69–1.90 (m, 2H), 2.01–2.20 (m, 2H), 2.29–2.63 (m, 4H), 2.92–3.07 (Mariz et al., 2008)
(m, 1H), 7.13–7.24 (m, 2H), 6.96–7.08 (m, 2H)
1H NMR (CDCl3), δ: 1.77–1.92 (m, 2H), 2.09–2.21 (m, 2H), 2.38–2.62 (m, 4H), 3.09 (m, (Takaya et al., 1998)
1H), 7.34 (d, J = 8.3 Hz, 2H), 7.59 (d, J = 8.3 Hz, 2H)
1H NMR (CDCl3), δ: 1.80–2.04 (m, 2H), 2.11–2.28 (m, 2H), 2.36–2.81 (m, 4H), 3.78–3.87 (Cho et al., 1995)
(m, 1H), 7.36–7.54 (m, 4H), 7.73 (d, J = 7.7 Hz, 1H), 7.83–7.87 (m, 1H), 8.02 (d, J = 8.1
Hz, 1H)
XV
1H NMR (CDCl3), δ: 1.45–1.56 (m, 1H), 1.65–1.79 (m, 2H), 1.93–2.10 (m, 3H), 2.53–2.62 (Gini et al., 2005)
(m, 3H), 2.82–2.92 (m, 2H), 7.16–7.22 (m, 3H), 7.28–7.34 (m, 2H)
XVI
1H NMR (CDCl3), δ: 1.59–1.71 (m, 1H), 1.73–1.95 (m, 2H), 2.02–2.15 (m, 2H), 2.21–2.33 (Vandyck et al., 2006)
(m, 1H), 2.68–2.74 (m, 2H), 2.79 (td, J = 2.1 Hz, J = 14.2 Hz, 1H), 3.05 (dd, J = 11.7 Hz,
14.2 Hz, 1H), 3.73 (tt, J = 11.4 Hz, J = 2.4 Hz, 1H), 7.35 (d, J = 7,2 Hz, 1H), 7.44–7.55
(m, 3H), 7.73 (d, J = 8.1 Hz, 1H), 7.85–7.88 (m, 1H), 8.06 (d, J = 8.7 Hz, 1H)
XVII
1H NMR (CDCl3), δ: 1.46–1.55 (m, 1H), 1.63–1.77 (m, 2H), 1.96–2.10 (m, 3H), 2.52–2.66 (Gutsche et al., 1958)
(m, 3H), 2.87–2.95 (m, 2H), 7.11 (d, J = 8.4 Hz, 2H), 7.26 (d, J = 8.4 Hz, 2H)
13C NMR (CDCl3), δ: 24.0, 29.1, 39.1, 42.1, 43.9, 51.1, 127.8, 128.7, 131.9, 145.3, 213.1
XIX
XXI
1H NMR (CDCl3), δ: 2.43–2.51 (m, 1H), 2.61–2.72 (m, 1H), 2.94–3.10 (m, 2H), 3.29–3.39 (Comins et al., 2001)
(m, 1H), 4.36–4.44 (m, 1H), 5.93–5.96 (m, 1H), 7.27–7.40 (m, 10H)
1H NMR (CDCl3), δ: 1.97–2.10 (m, 1H), 2.59–2.68 (dd, J = 17.6 Hz, 10.7 Hz, 1H), 2.88– (Shintani et al., 2005)
2.96 (ddd, J = 17.6 Hz, J = 5.9 Hz, J = 1.6 Hz, 1H), 3.19–3.29 (m, 1H), 4.35–4.43 (m, 1H),
4.48–4.54 (m, 1H), 7.20–7.23 (m, 2H), 7.27–7.30 (m, 1H), 7.34–7.39 (m, 2H)
reactions were rather slow.
tage Initiator reactor (maximum power setting of 300
W). All reactions were performed in an argon atmo-
sphere. The H NMR spectra of the compounds dis-
Conjugate addition of arylboronic acids to enones
is often, even at higher temperatures, a rather slow re-
action. We therefore argued that MWI could be a use-
ful alternative source of energy for this kind of trans-
formation. This paper shows that microwave heating
is indeed effective in promoting Pd-catalysed addition
of arylboronic acids to cyclic enones. Furthermore, we
show that chiral ligands may also be used.
1
solved in CDCl3 with tetramethylsilane as an internal
standard were measured using a Varian Gemini spec-
trometer (300 MHz). Enantiomeric excess (ee) was de-
termined by HPLC on Chiralcel OD-H column (Dai-
cel Chemical Industries) with hexane/propan-2-ol as
a mobile phase and UV detection at 208 nm. Assign-
ment of the absolute configuration of product II was
made by comparison of HPLC data with literature
values (Mariz et al., 2008). Ligands XXII (Hayashi et
al., 1980), XXIII (Togni et al., 1994), XXIV (Almássy
Experimental
Microwave experiments were carried out in the Bio-

340
V. Poláčková et al./Chemical Papers 65 (3) 338–344 (2011)
Table 2. Effect of Pd compounds and bases on the Pd-catalysed 1,4-addition of PhB(OH)2 to enone I with PPh3 as the liganda
Entry
Catalyst
Base
Temperature/◦C
Additive
Yieldb/%
1
2
3
4
5
6
7
8
9
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
–
Cs2CO3
Cs2CO3
KF
KF
K3PO4
–
K3PO4
KF
KF
130
130
170
170
170
170
130
170
170
170
–
0
20
34
< 5
< 5
0
CHCl3
CHCl3
–
AcOH
Pd(OAc)2
–
–
–
–
–
Pd2dba3 · CHCl3
Pd2dba3 · CHCl3
Pd2dba3 · CHCl3
Pd(PPh3)4
0
58
40
0
10
a) Reaction conditions: Pd catalyst (5 mole %), PPh3 (10 mole %), PhB(OH)2 (3 eq), base (3 eq), MWI, 10 min; b) isolated pure
product II.
O
O
et al., 2007), XXV, and XXVI (Arnold et al., 2000)
were prepared according to literature procedures.
i
PhB(OH)2
+
Typical procedure for Pd-catalysed conjugate
addition of ArB(OH)2 under MWI
Ph
I
II
Fig. 1. Conjugate addition of phenylboronic acid to cyclohex-
2-enone (I). Reaction conditions: i) [Pd]/L, toluene/
H2O, MWI.
Pd(OAc)2 (5 mole %, 5.6 mg, 0.025 mmol) and
2,2ꢀ-bipyridine (bpy) (20 mole %, 15.6 mg, 0.1 mmol)
were added to a solution of cyclohex-2-enone (I) (48.0
mg, 0.5 mmol), arylboronic acid (1.5 mmol), and KF
(1.5 mmol, 87.1 mg) in toluene (1 mL), water (0.3
mL), and AcOH (1 mL) under argon. The reaction
junction with K3PO4 gave product II in the highest
yield (58 %) (Table 2, entry 8).
◦
mixture in a sealed vessel was heated to 170 C by
microwave irradiation in the reactor for 10 min. The
reaction mixture was then cooled and neutralised with
saturated NaHCO3 (20 mL). The organic layer was ex-
tracted with Et2O (3 × 15 mL). The combined organic
extracts were washed with brine, dried (Na2SO4), and
concentrated under diminished pressure. Flash chro-
matography (SiO2, hexane/EtOAc (ϕr = 9 : 1)) of the
crude reaction mixture afforded the product, which
was identified by comparison of its 1H NMR spectrum
with literature data.
It was shown that 2,2ꢀ-bipyridine (bpy) as the lig-
and had a beneficial effect on the conjugate addition
of arylboronic acids to α,β-unsaturated carbonyl com-
pounds by inhibiting β-hydride elimination (Lin &
Lu, 2006). We therefore decided to evaluate Pd-bpy
complex as the catalyst in the test reaction. However,
Pd(OAc)2 and bpy under MWI (130◦C, 10 min) af-
forded only the starting material. A paper by Lin and
Lu inspired us to examine the effect of acetic acid as
an additive (Lu & Lin, 2005). The addition of acetic
acid to the reaction mixture in the solvent/H2O did
lead to higher yields of 3-phenylcyclohexanone (II)
(32 % yield in toluene/H2O, 55 % in THF/H2O).
In anhydrous THF, the results were less remarkable
(46 % yield). Interestingly, the addition of acetic acid
had no effect on the catalytic system with PPh3 (Ta-
ble 2, entry 5). Subsequently, we tested bases using the
Pd(OAc)2/bpy catalytic system in the solvent mixture
of toluene, water, and acetic acid. Cesium carbonate
only afforded a 10 % yield of 3-phenylcyclohexanone
(Table 3, entry 8). Chloroform was also documented
as a useful additive in the conjugate addition of aryl-
boronic acids (Suzuma et al., 2007). However, in our
system, CHCl3 only led to a low yield of product II
both in Pd (OAc)2, and PPh3 as well as Pd(OAc)2
and bpy (Table 2, entries 2 and 3; Table 3, entries
5 and 9). On the other hand, the catalytic system
Pd(OAc)2/bpy with K3PO4 as a base in the presence
of acetic acid gave 73 % yield under MWI (170◦C, 10
Results and discussion
Our preliminary studies focused on optimisation
of the reaction conditions, which included the effect of
reaction temperature, time, solvent, palladium precur-
sors, and ligands. The conjugate addition of phenyl-
boronic acid to cyclohex-2-enone (I ) was chosen as a
model reaction (Fig. 1). The aim was to find a simple
catalytic system affording high chemical yields in the
shortest possible time.
The initial studies were conducted with PPh3 as
ligand. The addition of phenylboronic acid to I carried
out in the presence of Pd(OAc)2 and PPh3 gave com-
plicated reaction mixtures, which consisted mostly of
the starting materials and biphenyl (homocoupling
product of phenylboronic acid) (Table 2, entries 1–6).
Of the three simple Pd sources and typical bases used
in additions of arylboronic acids, Pd2(dba)3 in con-

V. Poláčková et al./Chemical Papers 65 (3) 338–344 (2011)
341
Table 3. Effect of Pd compounds and bases on the Pd-catalysed 1,4-addition of PhB(OH)2 to enone I with bpy as the liganda
Entry
Catalyst
Base
Temperature/◦C
Additive
Yieldb/%
1
2
3
4
5
6
7
8
9
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
–
–
–
KF
KF
130
130
130
170
170
170
170
170
170
130
170
–
AcOH
THF, H2O, AcOH
–
0
32
55
35
39
74
73
10
5
CHCl3
AcOH
AcOH
AcOH
AcOH
–
KF
K3PO4
Cs2CO3
–
–
KF
Pd2dba3 · CHCl3
Pd2dba3 · CHCl3
Pd(OAc)2
10
11
0
18c
AcOH
a) Reaction conditions: Pd catalyst (5 mole %), bpy (10 mole %), PhB(OH)2 (3 eq), base (3 eq), MWI, 10 min; b) isolated pure
products after flash chromatography; c) control experiment performed by conventional heating (170◦C, oil bath, 10 min).
Table 4. Conjugate addition of arylboronic acids to cyclic
O
N
O
N
enones
i
+
PhB(OH)2
O
n
O
n
Pd(OAc)2, bpy, KF
toluene/H2O/AcOH
Ph
OPh
+ RB(OH)2
O
O
O
OPh
MWI (170 °C, 10 min)
R
I, n = 2
III, n = 1
IV , n = 3
X VIII
X IX
O
V–XV II
O
i
O
Compound
n
R
Yield/%
PhB(OH)2
+
Ph
V
VI
VII
VIII
IX
1
1
1
phenyl
3-chlorophenyl
4-chlorophenyl
71
62
73
44
14
71
83
48
57
16
34
18
38
XX
XXI
Fig. 2. Conjugate addition of phenylboronic acid to func-
tionalised enones. Optimised reaction conditions:
i) Pd(OAc)2, bpy, KF, AcOH/toluene/H2O, MWI
(170◦C, 10 min).
1
1
2
2
2
2
2
3
3
3
4-trifluoromethylphenyl
1-naphthyl
X
XI
3-chlorophenyl
4-chlorophenyl
4-fluorophenyl
4-trifluoromethylphenyl
1-naphthyl
XII
XIII
XIV
XV
XVI
XVII
while the reactivity of cyclohept-2-enone (IV ) was
lower. Only traces of the addition product with 4-
methoxyphenylboronic acid were observed by NMR.
Similarly, 1-naphthylboronic acid was less reactive
with all enones, and the corresponding products IX,
XIV, and XVI were isolated in low yields. A possible
reason for the lower reactivity could be a more pro-
nounced steric effect of 1-naphthylboronic acid. This
effect was already noted in Pd-catalysed coupling re-
actions of sterically hindered arylboronic acids (Cam-
midge & Crépy, 2004; Genov et al., 2006). In this case,
we also examined CsF as a base, but the yield of XIV
was even lower (13 %).
Functionalised substrates, XVIII and XX, were
also submitted to the conjugate addition under op-
timised conditions (Fig. 2). The resulting products,
XIX and XXI, were isolated in rather low yields (10
% and 18 %, respectively). Compounds such as XVIII
and XX are generally less reactive in conjugate addi-
tions; therefore, more energetic conditions would be
required to achieve higher product yields.
phenyl
1-naphthyl
4-chlorophenyl
min). The control experiment (conjugate addition of
phenylboronic acid to I ) performed by conventional
heating in an oil bath (170◦C, 10 min) mimicking the
microwave conditions gave only an 18 % yield of prod-
uct II (Table 3, entry 11).
Having established good experimental conditions
for the addition of phenylboronic acid to I, we then
investigated the conjugate addition of several aryl-
boronic acids to cyclic enones (Table 4). The reac-
tions of phenylboronic acid substituted with electron-
withdrawing substituents, such as chloro-, fluoro-, and
trifluoromethyl, resulted in moderate to good yields
(39–83 %) of the corresponding addition products
(VI–VIII, X–XIII, XVII ). Cyclopent-2-enone (III )
and I gave comparable yields of addition products,
We also inquired whether a chiral ligand rather

342
V. Poláčková et al./Chemical Papers 65 (3) 338–344 (2011)
Conclusions
O
I
O
i
In conclusion, we report the first microwave-
assisted Pd-catalysed conjugate addition of aryl-
boronic acids to α,β-unsaturated cyclic ketones. The
employment of a commercially available and inexpen-
sive catalytic system consisting of Pd(OAc)2/bpy in
combination with KF as the base in a mixture of
toluene/water/acetic acid led to good yields of addi-
tion products. A range of arylboronic acids may be
added to α,β-unsaturated ketones. Compared with
conventional heating, the microwave-assisted reac-
tions proceed with good yields in dramatically shorter
reaction times (10 min). Less reactive functionalised
substrates may also be used, although product yields
were lower under comparable conditions. Catalysts
with chiral ferrocene diphosphane ligands afford an in-
teresting level of enantiomeric purity of the addition
product (up to 85 % ee).
PhB(OH)2
+
Ph
II
PCy2
NMe2
PCy2
PPh2
PPh2
PPh2
Fe
Fe
Fe
PPh2
PPh2
XXIII
XXIV
XXII
Ph
Me
N
O
O
O
Me
Me
Me
Me
P
N
P
O
Ph
Me
XXVI
XXV
Acknowledgements. Part of this work was funded by the
Slovak Scientific Grant Agency, VEGA grant No. 1/0265/09.
NMR measurements were provided within the frame of Slovak
State Programme, Project No. 2003SP200280203.
Fig. 3. Conjugate addition of phenylboronic acid to enone
I
i)
using chiral ligands. Reaction conditions:
ligand (XXII–XXVI),
K3PO4 · H2O, toluene/H2O, MWI, 10 min.
Pd2(dba)2 · CHCl3,
References
Table 5. Screening of selected chiral ligands in the addition of
PhB(OH)2 to enone Ia
Almansa, R., Guijarro, D., & Yus, M. (2008). Microwave-
accelerated enantioselective addition of dialkylzinc reagents
to N-(diphenylphosphinoyl)imines catalysed by β-aminoalco-
hols with the prolinol skeleton. Tetrahedron: Asymmetry, 19,
1376–1380. DOI: 10.1016/j.tetasy.2008.05.005.
Entry
Ligand
Yieldb/%
eec/%
1
2
3
4
5
XXII
XXIII
XXIV
XXV
12
21
37
21
37
49 (S)
46 (S)
85 (S)
19 (R)
12 (R)
Almássy, A., Barta, K., Franci`o, G., Šebesta, R., Leitner, W., &
Toma, Š. (2007). [5]Ferrocenophane based ligands for stere-
oselective Rh-catalyzed hydrogenation and Cu-catalyzed
Michael addition. Tetrahedron: Asymmetry, 18, 1893–1898.
DOI: 10.1016/j.tetasy.2007.08.011.
XXVI
Alonso, F., Beletskaya, I. P., & Yus, M. (2008). Non-conventio-
nal methodologies for transition-metal catalysed carbon–
carbon coupling: a critical overview. Part 2: The Suzuki re-
action. Tetrahedron, 64, 3047–3101. DOI: 10.1016/j.tet.2007.
12.036.
a) Reaction conditions: Pd(OAc)2 (5 mole %), chiral ligand (10
mole %), PhB(OH)2 (3 eq), K3PO4 (3 eq), MWI; b) isolated
pure product II; c) determined by HPLC.
Arnold, L. A., Imbos, R., Mandoli, A., de Vries, A. H. M.,
Naasz, R., & Feringa, B. L. (2000). Enantioselective catalytic
conjugate addition of dialkylzinc reagents using copper–
phosphoramidite complexes; ligand variation and non-linear
effects. Tetrahedron, 56, 2865–2878. DOI: 10.1016/s0040-
4020(00)00142-3.
Barge, A., Tagliapietra, S., Tei, L., Cintas, P., & Cravotto,
G. (2008). Pd-catalyzed reactions promoted by ultrasound
and/or microwave irradiation. Current Organic Chemistry,
12, 1588–1612. DOI: 10.2174/138527208786786327.
Bedford, R. B., Betham, M., Charmant, J. P. H., Haddow, M.
F., Orpen, A. G., Pilarski, L. T., Coles, S. J., & Hursthouse,
M. B. (2007). Simple palladacyclic and platinacyclic catalysts
for the 1,4-conjugate addition of arylboronic acids and aryl-
siloxanes to enones. Organometallics, 26, 6346–6353. DOI:
10.1021/om700724c.
Cammidge, A. N., & Crépy, K. V. L. (2004). Synthesis of chiral
binaphthalenes using the asymmetric Suzuki reaction. Tetra-
hedron, 60, 4377–4386. DOI: 10.1016/j.tet.2003.11.095.
Cho, C. S., Motofusa, S.-i., Ohe, K., Uemura, S., & Shim, S.
C. (1995). A new catalytic activity of antimony(III) chlo-
ride in palladium(0)-catalyzed conjugate addition of aromat-
ics to α,β-unsaturated ketones and aldehydes with sodium
than bpy would induce a reasonable level of enantios-
electivity under MWI conditions. Five representative
chiral ligands XXII–XXVI were tested in the addition
of phenylboronic acid to I (Fig. 3). With ferrocenyl
diphosphane ligands XXII–XXIV, the product (S)-II
was isolated with promising enantioselectivities (up
to 85 % ee). Under anhydrous conditions, using CsF
as the base, yields as well as enantioselectivity were
lower (10 % yield, 50 % ee). Although higher enantios-
electivities have been reported in several cases under
conventional conditions (Gini et al., 2005; Xu et al.,
2010), the result obtained with ligand XXIV under
MWI conditions is interesting and potentially useful.
The use of phosphoramidite ligands XXV and XXVI
led to only 19 % and 12 % ee, respectively. However, it
should be noted that the reaction conditions using the
above ligands were not optimised. Table 5 summarises
the results of the screening of chiral ligands.

V. Poláčková et al./Chemical Papers 65 (3) 338–344 (2011)
343
tetraphenylborate and arylboronic acids. The Journal of Or-
ganic Chemistry, 60, 883–888. DOI: 10.1021/jo00109a019.
Comins, D. L., Brooks, C. A., & Ingalls, C. L. (2001). Reduction
of N-acyl-2,3-dihydro-4-pyridones to N-acyl-4-piperidones
using zinc/acetic acid. The Journal Organic Chemistry, 66,
2181–2182. DOI: 10.1021/jo001609l.
Fujio, M., Tanaka, M., Wu, X.-M., Funakoshi, K., Sakai,
K., & Suemune, H. (1998). ortho-Halogeno substituents ef-
fect in asymmetric cyclization of 4-aryl-4-pentenals using
a rhodium catalyst. Chemistry Letters, 27, 881–882. DOI:
10.1246/cl.1998.881.
to α,β-unsaturated carbonyl compounds. Helvetica Chimica
Acta, 91, 1947–1953. DOI: 10.1002/hlca.200890208.
Kappe, C. O. (2004). Controlled microwave heating in modern
organic synthesis. Angewandte Chemie International Edi-
tion, 43, 6250–6284. DOI: 10.1002/anie.200400655.
Kappe, C. O., & Dallinger, D. (2009). Controlled microwave
heating in modern organic synthesis: highlights from the
2004–2008 literature. Molecular Diversity, 13, 71–193. DOI:
10.1007/s11030-009-9138-8.
Kappe, C. O., Dallinger, D., & Murphree, S. S. (2009). Practical
microwave synthesis for organic chemists: Strategies, instru-
ments, and protocols. Weinheim, Germany: Wiley–VCH.
Kappe, C. O., & Stadler, A. (2005). Microwaves in organic
and medicinal chemistry (Series: Methods and principles in
medicinal chemistry, Vol. 25). Weinheim, Germany: Wiley–
VCH.
Gavande, N., Johnston, G. A. R., Hanrahan, J. R.,
&
Chebib, M. (2010). Microwave-enhanced synthesis of 2,3,6-
trisubstituted pyridazines: application to four-step synthesis
of gabazine (SR-95531). Organic and Biomolecular Chem-
istry, 8, 4131–4136. DOI: 10.1039/C0OB00004C.
Genov, M., Almorín, A., & Espinet, P. (2007). Microwave
assisted asymmetric Suzuki-Miyaura and Negishi cross-
coupling reactions: synthesis of chiral binaphthalenes. Tetra-
hedron: Asymmetry, 18, 625–627. DOI: 10.1016/j.tetasy.
2007.03.001.
Kováčová, S., Kováčiková, L., Lácová, M., Boháč, A., & Sal-
išová, M. (2010). Microwave assisted one pot synthesis of
7-substituted 2-(2-oxo-2H-chromen-3-yl)acetic acids as pre-
cursors of new anti-tumour compounds. Chemical Papers,
64, 806–811. DOI: 10.2478/s11696-010-0059-x.
Genov, M., Almorín, A., & Espinet, P. (2006). Efficient synthe-
sis of chiral 1,1ꢀ-binaphthalenes by the asymmetric Suzuki–
Miyaura reaction: Dramatic synthetic improvement by sim-
ple purification of naphthylboronic acids. Chemistry – A Eu-
ropean Journal, 12, 9346–9352. DOI: 10.1002/chem.200600
616.
Genov, M., Salas, G., & Espinet, P. (2008). Effect of microwave
heating in the asymmetric addition of dimethylzinc to alde-
hydes. Journal of Organometallic Chemistry, 693, 2017–
2020. DOI: 10.1016/j.jorganchem.2008.03.003.
Larhed, M., Moberg, C., & Hallberg, A. (2002). Microwave-
accelerated homogeneous catalysis in organic chemistry. Ac-
counts of Chemical Research, 35, 717–727. DOI: 10.1021/
ar010074v.
Lin, S., & Lu, X. (2006). Palladium–bipyridine catalyzed con-
jugate addition of arylboronic acids to α,β-unsaturated car-
bonyl compounds in aqueous media. Tetrahedron Letters, 47,
7167–7170. DOI: 10.1016/j.tetlet.2006.07.154.
Lu, X., & Lin, S. (2005). Pd(II)-bipyridine catalyzed conju-
gate addition of arylboronic acid to α,β-unsaturated car-
bonyl compounds. The Journal of Organic Chemistry, 70,
9651–9653. DOI: 10.1021/jo051561h.
Mariz, R., Luan, X., Gatti, M., Linden, A., & Dorta, R. (2008).
A chiral bis-sulfoxide ligand in late-transition metal catal-
ysis; rhodium-catalyzed asymmetric addition of arylboronic
acids to electron-deficient olefins. Journal of the American
Chemical Society, 130, 2172–2173. DOI: 10.1021/ja710665q.
Nishikata, T., Yamamoto, Y., & Miyaura, N. (2004). 1,4-
Addition of arylboronic acids and arylsiloxanes to α,β-
unsaturated carbonyl compounds via transmetalation to di-
cationic palladium(II) complexes. Organometallics, 23, 4317–
4324. DOI: 10.1021/om0498044.
Poláčková, V., & Toma, Š. (2007). Effect of microwave irradi-
ation on the reactivity of chloroarenes in Suzuki—Miyaura
reaction. Chemical Papers, 61, 41–45. DOI: 10.2478/s11696-
006-0093-x.
Poláčková, V., Toma, Š., & Augustínová, I. (2006). Microwave-
promoted cross-coupling of acid chlorides with arylboronic
acids: a convenient method for preparing aromatic ketones.
Tetrahedron, 62, 11675–11678. DOI: 10.1016/j.tet.2006.09.
055.
Poláčková, V., Toma, Š., & Kappe, C. O. (2007). Microwave-
assisted arylation of rac-(E)-3-acetoxy-1,3-diphenylprop-1-
ene with arylboronic acids. Tetrahedron, 63, 8742–8745. DOI:
10.1016/j.tet.2007.06.045.
Shintani, R., Duan, W.-L., Nagano, T., Okada, A., & Hayashi,
T. (2005). Chiral phosphine–olefin bidentate ligands in
asymmetric catalysis: Rhodium-catalyzed asymmetric 1,4-
addition of aryl boronic acids to maleimides. Angewandte
Chemie International Edition, 44, 4611–4614. DOI: 10.1002/
anie.200501305.
Singh, B. K., Kaval, N., Tomar, S., van der Eycken, E., & Par-
mar, V. S. (2008). Transition metal-catalyzed carbon–carbon
bond formation Suzuki, Heck, and Sonogashira reactions us-
ing microwave and microtechnology. Organic Process Re-
search & Development, 12, 468–474. DOI: 10.1021/op800047f.
Gini, F., Hessen, B., & Minnaard, A. J. (2005). Palladium-
catalyzed enantioselective conjugate addition of arylboronic
acids. Organic Letters, 7, 5309–5312. DOI: 10.1021/ol05222
2d.
Gutnov, A. (2008). Palladium-catalyzed asymmetric conjugate
addition of aryl–metal species. European Journal of Organic
Chemistry, 2008, 4547–4554. DOI: 10.1002/ejoc.200800541.
Gutsche, C. D., Strohmayer, H. F., & Chang, J. M. (1958).
Ring enlargements VI. The diazomethane-carbonyl reaction:
Product ratios from the reactions of diazomethane with var-
ious substituted 2-phenylcyclohexanons. The Journal Or-
ganic Chemistry, 23, 1–5. DOI: 10.1021/jo01095a001.
Hayashi, T., Mise, T., Fukushima, M., Kagotani, M., Na-
gashima, N., Hamada, Y., Matsumoto, A., Kawakami, S.,
Konishi, M., Yamamoto, K., & Kumada, M. (1980). Asym-
metric synthesis catalyzed by chiral ferrocenylphosphine–
transition metal complexes. I. Preparation of chiral ferro-
cenylphosphines. Bulletin of the Chemical Society of Japan,
53, 1138–1151. DOI: 10.1246/bcsj.53.1138.
He, P., Lu, Y., Dong, C.-G., & Hu, Q.-S. (2007). Anionic four-
electron donor-based palladacycles as catalysts for addition
reactions of arylboronic acids with α,β-unsaturated ketones,
aldehydes, and α-ketoesters. Organic Letters, 9, 343–346.
DOI: 10.1021/ol062814b.
Helan, V., Mills, A., Drewry, D., & Grant, D. (2010). A rapid
three-component MgI2-mediated synthesis of 3,3-pyrollidinyl
spirooxindoles. The Journal of Organic Chemistry, 75, 6693–
6695. DOI: 10.1021/jo101077g.
Itooka, R., Iguchi, Y.,
& Miyaura, N. (2003). Rhodium-
catalyzed 1,4-addition of arylboronic acids to α,β-unsatura-
ted carbonyl compounds: Large accelerating effects of bases
and ligands. The Journal of Organic Chemistry, 68, 6000–
6004. DOI: 10.1021/jo0207067.
Kantam, M. L., Subrahmanyam, V. B., Kumar, K. B. S.,
Venkanna, G. T., & Sreedhar, B. (2008). Rhodium fluo-
roapatite catalyzed conjugate addition of arylboronic acids

344
V. Poláčková et al./Chemical Papers 65 (3) 338–344 (2011)
Suzuma, Y., Yamamoto, T., Ohta, T., & Ito, Y. (2007). Asym-
metric 1,4-addition reaction of arylboronic acid to enone cat-
alyzed by palladium with ferrocene-based phosphine ligand.
Chemistry Letters, 36, 470–471. DOI: 10.1246/cl.2007.470.
Takaya, Y., Ogasawara, M., & Hayashi, T. (1999). Rhodium-
catalyzed asymmetric 1,4-addition of arylboron compounds
generated in situ from aryl bromides. Tetrahedron Letters,
40, 6957–6961. DOI: 10.1016/s0040-4039(99)01412-4.
Takaya, Y., Ogasawara, M., Hayashi, T., Sakai, M., & Miyaura,
N. (1998). Rhodium-catalyzed asymmetric 1,4-addition of
aryl- and alkenylboronic acids to enones. Journal of the
American Chemical Society, 120, 5579–5580. DOI: 10.1021/
ja980666h.
Vandyck, K., Matthys, B., Willen, M., Robeyns, K., Van
Meervelt, L., Van der Eycken, J. (2006). Rhodium-
&
catalyzed asymmetric conjugate additions of boronic acids
to enones using DIPHONANE: A novel chiral bisphosphine
ligand. Organic Letters, 8, 363–366. DOI: 10.1021/ol0522788.
Veverková, E., & Toma, Š. (2008). Study of CuI catalyzed cou-
pling reactions of aryl bromides with imidazole and aliphatic
amines under microwave dielectric heating. Chemical Papers,
62, 334–338. DOI: 10.2478/s11696-008-0033-z.
Xu, Q., Zhang, R., Zhang, T., & Shi, M. (2010). Asym-
metric 1,4-addition of arylboronic acids to 2,3-dihydro-4-
pyridones catalyzed by axially chiral NHC–Pd(II) complexes.
The Journal of Organic Chemistry, 75, 3935–3937. DOI:
10.1021/jo1006224.
Tierney, J. P., & Lidstr¨om, P. (Eds.) (2005). Microwave assisted
organic synthesis. Oxford, UK: Wiley–Blackwell.
Yamamoto, T., Iizuka, M., Ohta, T., & Ito, Y. (2006). Palla-
dium catalyzed conjugate 1,4-addition of organoboronic acids
to α,β-unsaturated ketones. Chemistry Letters, 35, 198–199.
DOI: 10.1246/cl.2006.198.
Togni, A., Breutel, C., Schnyder, A., Spindler, F., Landert,
H., & Tijani, A. (1994). A novel easily accessible chiral
ferrocenyldiphosphine for highly enantioselective hydrogena-
tion, allylic alkylation, and hydroboration reactions. Jour-
nal of the American Chemical Society, 116, 4062–4066. DOI:
10.1021/ja00088a047.