Catalysis of the Suzuki reaction by acyclic diaminocarbene palladium complexes generated in situ

Article abstract of DOI:10.1134/S1070363216090085

Acyclic diaminocarbene palladium complexes generated in situ by nucleophilic attack of morpholine, 4-nitrophenylhydrazine, or benzhydrazide on bis(isocyanide) palladium(II) complexes catalyzed the Suzuki reaction of 4-iodo- or 4-bromoanisole with phenylboronic acid. Morpholine turned out to be the best catalyst modifier. The cross coupling reaction under fairly mild conditions (reflux in ethanol in the presence of potassium carbonate) in 2 h afforded 4-methoxybiphenyl whose yield was insignificantly lower than in the presence of preliminarily prepared catalyst. Neither preliminary degassing nor protection from atmospheric moisture and oxygen was necessary.

Full text of DOI:10.1134/S1070363216090085

ISSN 1070-3632, Russian Journal of General Chemistry, 2016, Vol. 86, No. 9, pp. 2033–2036. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © D.V. Boyarskaya, V.P. Boyarskii, 2016, published in Zhurnal Obshchei Khimii, 2016, Vol. 86, No. 9, pp. 1466–1470.
Catalysis of the Suzuki Reaction by Acyclic Diaminocarbene
Palladium Complexes Generated In Situ
D. V. Boyarskaya and V. P. Boyarskii*
St. Petersburg State University, Universitetskaya nab. 7–9, St. Petersburg, 199034 Russia
*e-mail: v.boiarskii@spbu.ru
Received July 21, 2016
Abstract—Acyclic diaminocarbene palladium complexes generated in situ by nucleophilic attack of
morpholine, 4-nitrophenylhydrazine, or benzhydrazide on bis(isocyanide) palladium(II) complexes catalyzed
the Suzuki reaction of 4-iodo- or 4-bromoanisole with phenylboronic acid. Morpholine turned out to be the best
catalyst modifier. The cross coupling reaction under fairly mild conditions (reflux in ethanol in the presence of
potassium carbonate) in 2 h afforded 4-methoxybiphenyl whose yield was insignificantly lower than in the
presence of preliminarily prepared catalyst. Neither preliminary degassing nor protection from atmospheric
moisture and oxygen was necessary.
Keywords: acyclic diaminocarbenes, Suzuki reaction, bis(isocyanide) palladium complexes, in situ catalysis
DOI: 10.1134/S1070363216090085
Transition metal complexes are extensively used as
catalysts in organic reactions. Their catalytic activity
can be controlled by variation of the ligand structure,
and the complex added to the reaction mixture is often
referred to as precatalyst rather than catalyst [1, 2].
Many ligands are capable of reacting with organic and
inorganic compounds present in the reaction mixture,
thus changing their structure and hence the properties
of catalytic center which becomes “true catalyst.” Such
modifications extend the potential of metal complex
catalysis and make it possible to use relatively simple
transition metal complexes as precatalysts, so that
practical implementation of catalytic reactions is
facilitated.
the corresponding nitrogen nucleophile in boiling
chloroform or methylene chloride.
Taking into account mild conditions of the forma-
tion of these catalysts, we presumed that they can be
generated in situ in cross coupling reactions. In the
present work we checked this possibility in the Suzuki
reaction. As model reaction we selected cross-coupling
of 4-haloanisoles 1 and 2 with phenylboronic acid (3)
(Scheme 2). Our choice was determined by the fact
that the synthesis of methoxybiphenyls is an important
field of application of Suzuki reactions [21, 22]; the
products are used to monitor decomposition of per-
sistent organic pollutants, polychlorinated biphenyls,
in natural environment [23].
In this connection, of considerable interest are acyclic
diaminocarbene palladium(II) complexes (Pd-ADC)
that are now among the most efficient cross-coupling
catalysts [3, 4]. These complexes are generally syn-
thesized by reaction of various nitrogen nucleophiles
with bis(isocyanide) palladium complexes (Scheme 1;
R = Alk, Ar) [5–11]. We previously prepared a number
of Pd-ADCs which turned out to act as excellent
catalysts in Suzuki reactions with haloarenes [12, 13],
haloalkenes [14], and benzyl halides [15] and copper-
free Sonogashira reactions [16–20]. In all these
reactions, the catalyst was synthesized preliminarily by
reaction of bis(isocyanide) palladium complexes with
The cross coupling reactions were carried out in the
presence of different catalytic systems, specifically
Scheme 1.
R
R
HN
N
N
Cl
Cl
Cl
C
C
'
NR2
+ HNR'
Pd
Pd
2
C
Cl
N
R
R
Pd-ADC
2033

2034
BOYARSKAYA, BOYARSKII
Scheme 2.
[Pd]
+
+ Ph2
MeO
[Pd]:
X
(HO)2B
MeO
K2CO3
EtOH
80oC
1, 2
10
3
4
Cl
C
Cl
C
C6H4−4-NO2
HN
NH
Pd
(5); (CyNC)2PdCl2 (6) + 4-NO2−C6H4NHNH2 (7);
N
NH
Cy
Cy
(CyNC)2PdCl2 (6) + (CH2CH2OCH2CH2)NH (9);
(CyNC)2PdCl2 (6) + PhCONHNH2 (8);
X = Br (1), I (2).
acyclic diaminocarbene palladium complex 5 pre-
liminarily prepared as described in [14], dichlorobis
(cyclohexyl isocyanide)palladium (6), and mixtures of
6 with nitrogen nucleophiles 7–9. As we showed
previously, Pd-ADCs containing fragments of 7 and 8
[13, 14] efficiently catalyzed cross coupling reactions.
On the other hand, our attempts to obtain a carbene
complex by reaction of morpholine (9) with bis
(isocyanide) palladium complexes were unsuccessful,
and we failed to isolate the desired complex in the pure
state. Therefore, it was interesting to generate the cor-
responding catalyst in situ. The results of cross coupling
of 4-haloanisoles 1 and 2 with phenylboronic acid (3)
in the presence of different catalysts are given in table.
In all cases, the cross coupling was selective with
respect to 4-haloanizole, and the major product was 4-
methoxybiphenyl (4); unsubstituted biphenyl (10) was
formed as the only by-product. Unreacted phenyl-
boronic acid was partially converted to cyclic trimer
(PhBO)3 during the process. 4-Methoxybiphenyl (4)
was isolated and characterized by H NMR and mass
spectra. The spectral data of 4 coincided with those
reported in [24].
1
As might be expected, 4-iodoanisole (2) was more
reactive than 4-bromoanizole (1) in the Suzuki reac-
tion, though the difference in their reactivities tended
to decrease in the presence of active catalytic systems
Suzuki cross-coupling reaction of 4-haloanisoles 1 and 2 with phenylboronic acid (3) in the presence of different catalystsa
Yield,b %
Catalyst, 0.001 mol
per mole of ArX
Nitrogen nucleophile 7–9, mol per mole
Run no.
ArX
of ArX
4
10
1
2
1
1
1
1
1
1
1
2
2
2
2
2
2
5
–
>99
73
5
5
6
–
3
6 + 7
6 + 8
6 + 9
6 + 9
6 + 9
5
0.05
0.05
0.001
0.05
0.5
47
26
5
4
58
5
76
5
6
71
7
7
89
99 (98c)
6
8
–
4
9
6 + 7
6 + 7
6 + 8
6 + 9
6 + 9
0.05
0.5
87
6
10
11
12
13
7
–
0.05
0.05
0.5
53
1
87
3
95
2
a EtOH, 80°C, 2 h. b GC data. c Isolated yield.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 9 2016

CATALYSIS OF THE SUZUKI REACTION BY ACYCLIC DIAMINOCARBENE
2035
Scheme 3.
−
R
R
R
HN
N
N
N
+ H+
Cl
Cl
Cl
Cl
Cl
C
C
OEt
OEt
+ EtO−
Pd
Pd
Pd
C
C
Cl
N
N
R
R
R
11
[complex 5, system 6 + 9)]. The obtained data indi-
cated that cross-coupling catalysts can be formed in
situ from all nucleophiles 7–9; however, their catalytic
activity was lower than the activity of preliminarily
synthesized carbene complex 5. Bis(isocyanide)
complex 6 is capable of catalyzing the Suzuki reaction
in the absence of nucleophile. This may be due to
generation in situ of aminooxycarbene complex 11
(Scheme 3). The formation of such complexes via nucleo-
philic addition of alkoxide to coordinated isocyanide
was described in [25, 26], but these complexes were
poorly studied.
lower than the yield in the reaction catalyzed by
preliminarily prepared catalyst. The reaction requires
neither preliminary degassing nor protection from
atmospheric moisture and oxygen.
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded at
room temperature on a Bruker Avance II+ spectro-
meter at 400.13 and 100.61 MHz, respectively, using
CDCl3 as solvent. Gas chromatographic–mass spectro-
metric analyses were obtained on a Shimadzu GCMS
QP-2010 SE instrument [electron impact, 70 eV;
a.m.u. range 35–500; detector temperature 200°C; Rtx-
5MS column, 30 m×0.32 mm×0.25 μm; carrier gas
argon, flow rate 0.8 mL/min; oven temperature
programming from 50°C (2 min) to 250°C at a rate of
25 deg/min, 20 min at 250°C].
On the whole, among the catalysts generated in situ,
those based on morpholine showed the best catalytic
activity (see table; run nos. 7, 13).
The dependence of the catalytic activity on the
nucleophile concentration was interesting. Raising the
amount of 4-nitrophenylhydrazine (7) was accom-
panied by sharp reduction of the catalytic activity
instead of expected increase. These findings suggest
some inhibitory effect of 4-nitrophenylhydrazine on
the generated catalyst. No analogous inhibitory effect
was observed with morpholine (9). By contrast, the
best results were obtained using a large excess of mor-
pholine with respect to bis(isocyanide) palladium complex.
GC analysis was performed on a Khromatek
Kristall 5000.2 instrument equipped with a flame ioniza-
tion detector and an Optima 1 capillary column,
25 m×0.32 mm×0.35 μm.
Suzuki reaction catalyzed by preliminarily prepared
complex 5. A screw-cap ampule equipped with a mag-
netic stirrer was charged with 2 mL of ethanol, 0.2 mmol
of 4-haloanisole 1 or 2, 1.1 equiv of phenylboronic
acid (3), and 1.5 equiv of K2CO3. The mixture was
heated to 80°C with stirring, and 0.1 mL of a 2×10–3 M
solution of complex 5 [12] (2×10–7 mol) in ethanol
was added. The mixture was heated for 2 h at 80°C on
an oil bath, cooled to room temperature, and diluted
with 2 mL of water. The product was extracted into
hexane–methylene chloride (1:1, 2×5 mL), and the
combined extracts were dried over anhydrous Na2SO4
and analyzed by GC ad GC/MS. The solvent was
removed, and the residue was weighted and analyzed
by 1H NMR.
Thus, we have demonstrated the possibility for
carrying out Suzuki reaction in the presence of acyclic
diaminocarbene palladium complexes generated in situ
by nucleophilic attack of 4-nitrophenylhydrazine, benz-
hydrazide, or morpholine on a bis(isocyanide) palla-
dium(II) complex. The latter was shown to catalyze the
Suzuki reaction in alcoholic solution in the absence of
a nitrogen nucleophile. Among the examined nucleo-
philes, morpholine taken in a large excess turned out to
be the best modifier. The cross coupling reaction is
complete in 2 h under mild conditions (reflux in ethanol
in the presence of potassium carbonate) with formation
of 4-methoxybiphenyl. The yield is insignificantly
Suzuki reaction in the presence of catalysts
generated in situ (general procedure). A screw-cap
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 9 2016

2036
BOYARSKAYA, BOYARSKII
Dalton Trans., 2014, vol. 43, p. 15861. doi 10.1039/
C4DT01917B
ampule equipped with a magnetic stirrer was charged
with 2 mL of ethanol, 0.2 mmol of 4-haloanisole 1 or
2, 1.1 equiv of phenylboronic acid (3), 1.5 equiv of
K2CO3, and a required amount of nucleophile 7–9. The
mixture was heated to 80°C with stirring, and 0.1 mL
of a 2× 10–3 M solution of complex 6 (2×10–7 mol) in
ethanol was added. The mixture was then heated for
2 h at 80°C on an oil bath (80°C) and treated as
described above.
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ACKNOWLEDGMENTS
This study was performed under financial support
by the Russian Science Foundation (project no. 14-43-
00017) using the equipment of the Resource Center for
Magnetic Resonance and Educational Resource Center
of Chemistry at the St. Petersburg State University.
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