Catalytic activity of palladium(II) diaminocarbene complexes in the Sonogashira and Suzuki reactions

Article abstract of DOI:10.1134/S107042801304009X

Palladium(II) complexes with chelating and non-chelating diaminocarbene ligands were assessed as catalysts in the cross-coupling reactions of haloarenes with oct-1-yne (Sonogashira reaction) and phenylboronic acid (Suzuki reaction). Both complexes exhibited a higher catalytic activity than traditional phosphine ligandbased systems in the Sonogashira reaction, and they ensured cross-coupling not only with iodoarenes but also with bromoarenes activated by electron-withdrawing substituents. The catalytic activities of the examined complexes in the Suzuki reaction were appreciably different: the palladium(II) complex with the chelating ligand turned out to be considerably less active than the complex with the non-chelating ligand.

Full text of DOI:10.1134/S107042801304009X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 4, pp. 551–554. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © V.N. Mikhailov, E.A. Savicheva, V.N. Sorokoumov, V.P. Boyarskii, 2013, published in Zhurnal Organicheskoi Khimii, 2013,
Vol. 49, No. 4, pp. 567–571.
Dedicated to the 100th Anniversary of Corresponding Member
of the Russian Academy of Sciences A.A. Petrov
Catalytic Activity of Palladium(II) Diaminocarbene Complexes
in the Sonogashira and Suzuki Reactions
V. N. Mikhailov, E. A. Savicheva, V. N. Sorokoumov, and V. P. Boyarskii
St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198504 Russia
e-mail: vadimpb@yahoo.com
Received November 14, 2012
Abstract—Palladium(II) complexes with chelating and non-chelating diaminocarbene ligands were assessed as
catalysts in the cross-coupling reactions of haloarenes with oct-1-yne (Sonogashira reaction) and phenylboronic
acid (Suzuki reaction). Both complexes exhibited a higher catalytic activity than traditional phosphine ligand-
based systems in the Sonogashira reaction, and they ensured cross-coupling not only with iodoarenes but also
with bromoarenes activated by electron-withdrawing substituents. The catalytic activities of the examined
complexes in the Suzuki reaction were appreciably different: the palladium(II) complex with the chelating
ligand turned out to be considerably less active than the complex with the non-chelating ligand.
DOI: 10.1134/S107042801304009X
Palladium complexes with cyclic (A) [1] and
acyclic (B) [2] diaminocarbene ligands are used as
homogeneous catalysts in cross-coupling reactions.
possible to obtain structurally diverse carbene com-
plexes, including chelates (e.g., complex I). Such
chelates could exhibit unusual catalytic activity in
cross-coupling reactions.
··
··
Bu-t
R
R
R1
R1
Ph
N
N
N
N
R2
N
R2
Cl
Cl
C
Cl
N
H
N
C
H
Pd
Pd
Ph
N
Ph
N
A
B
N
Bu-t
NH
Cy
Cy
Aminocarbene complexes are more stable to oxida-
tion than traditionally used phosphine complexes. In
addition, carbene palladium complexes exhibit very
high catalytic activity in oxidative addition reactions of
haloarenes due to donor properties of the ligands.
Therefore, such complexes are highly efficient as cata-
lysts in various cross-coupling reactions with halo-
arenes, such as Suzuki, Heck, Sonogashira, and other
reactions [3–7]. Most procedures for the synthesis of
palladium carbene complexes require preliminary pre-
paration of carbene ligand and its subsequent intro-
duction into the metal coordination sphere and are
multistep and laborious, which restricts the range of
variation of structural parameters of the catalysts. In
this connection, the synthesis of diaminocarbene com-
plexes via simple addition of nitrogen-containing nu-
cleophiles to isocyanide palladium complexes attracts
increased interest [8–12]. This approach makes it
Ph
I
II
Tskhovrebov et al. [13] recently demonstrated that
palladium(II) diaminocarbene chelates in the presence
of triphenylphosphine are capable of catalyzing the
Sonogashira reaction and compared their catalytic
activity with the activity of commercially available
PdCl2(PPh3)2 in the reaction of 1-iodo-2-nitrobenzene
(III) with oct-1-yne (VII) (Scheme 1).
The present study was aimed at comparing the
catalytic activities of palladium(II) complexes I and II
with chelating and non-chelating diaminocarbene
ligands in the synthesis of arylacetylenes according to
Sonogashira and in the Suzuki reaction leading to
biphenyl derivatives.
The Sonogashira cross-coupling was studied using
1-iodo-2-nitrobenzene (III), 1-bromo-2-nitrobenzene
551

MIKHAILOV et al.
552
Scheme 1.
[Pd], CuI
base, solvent
C6H13
R
R
+
HC
X
C6H13
III–VI
VII
VIII, IX
III, IV, VI, VIII, R = 2-NO2; V, IX, R = 4-CN; III, X = I; IV, V, X = Br; VI, X = Cl.
(IV), 4-bromobenzonitrile (V), and 1-chloro-2-nitro-
benzene (VI) as haloarene component and oct-1-yne
(VII) as terminal alkyne (Scheme 1). ortho-Substituted
haloarenes were selected mainly as substrates taking
into account strong interest in ortho-substituted aryl-
acetylenes which are widely used as intermediate prod-
ucts in the synthesis of pharmacologically important
substituted heterocycles such as indoles, quinolines,
isoquinolines, indolo[1,2-c]quinolines, furopyridines,
and dihydropyrazoles [14].
As shown in [13], the conversion in the Sono-
gashira reactions carried out in ethanol depends on the
presence of PPh3 in the reaction mixture. It was pre-
sumed that PPh3 is necessary to enhance the stability
of the catalytic system. On the other hand, the catalyst
may be stabilized via the use of a complexing solvent.
However, in the reaction of haloarene III with oct-1-
yne (VII) in acetonitrile with no PPh3 the substrate
conversion was as low as 20% in 24 h. Addition of
5 mol % of PPh3 increased the conversion to 100%.
Insofar as aminocarbene complexes are considerably
more active than classical phosphine catalysts [13], we
presumed that the role of PPh3 is to form a complex
with copper and ensure solubility of copper acetylide.
Using compounds IV and V as examples, we
showed that bromoarenes readily react with acetylene
VII under catalysis by complex I in the presence of
5 mol % of PPh3. After 24 h at room temperature, the
conversion of IV was 60%, the amount of the catalyst
being 0.07 mol %; raising the temperature and increas-
ing the reaction time resulted in more than 80% con-
version. The conversion of V in 24 h was 64%. Un-
fortunately, we failed to attain an appreciable conver-
sion of 1-chloro-4-nitrobenzene (VI) in the reaction
with VII in the presence of 0.07 mol % of complex I
even under prolonged (48 h) heating at 80°C.
Thus the use of 0.07 mol % of palladium complex I
with chelating aminocarbene ligand in the presence of
5 mol % of PPh3 ensures considerable conversion in
the Sonogashira cross-coupling with both iodo- and
bromoarenes.
Aminocarbene complex II showed a high efficiency
as catalyst in the Suzuki reaction [12]. The catalytic
activity of complex II in the Sonogashira reaction in
Table 1. Catalytic activity of complexes I and II in the Sonogashira reaction
ArX
Catalyst (mol %)
Solvent, base
Temperature, °C Reaction time, h Yield,a % TONb
TOFc
e
IIId
III
III
IV
IV
V
I (0.05) + PPh3
EtOH, K2CO3
MeCN, Et3N
MeCN, Et3N
THF, Et3N
60
60
60
20
60
80
80
60
60
18
24
24
24
38
24
48
13
72
100
020
100
060
081
064
–
2000
0290
1400
0850
1150
0900
–
111
012
058
035
030
018
–
I (0.07)
e
I (0.07) + PPh3
e
I (0.07) + PPh3
e
I (0.07) + PPh3
THF, Et3N
e
I (0.07) + PPh3
Dioxane, Et3N
Dioxane, Et3N
EtOH, K2CO3
EtOH, K2CO3
e
VI
III
III
I (0.07) + PPh3
e
II (0.07) + PPh3
100
070
1400
3890
108
054
e
II (0.018) + PPh3
a
b
c
d
e
According to the 1H NMR data.
Turnover number.
Turnover frequency, h–1.
Data of [13].
5 mol % with respect to ArX.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 4 2013

CATALYTIC ACTIVITY OF PALLADIUM(II) DIAMINOCARBENE COMPLEXES
Table 2. Catalytic activity of complexes I and II in the Suzuki reaction
553
Catalyst (mol %)
Reaction time, min
Yield,a %
TON
TOF, h–1
I (1×10–3)
I (1×10–3)
I (1×10–3)
I (3×10–3)
I (1×10–2)
IIb (1×10–5)
010
030
060
060
060
120
37
52
60
76
97
97
370
520
600
2220
1040
0600
250
0250
097
0097
9.7×104
4.8×104
According to the 1H NMR data.
Data of [12].
a
b
the presence of 5 mol % of PPh3 was comparable with
the activity of chelate I. The conversion of iodoarene
III in ethanol was complete in 13 h at 60°C.
sphere exhibit higher catalytic activity. From this view-
point, the chelating ligand in complex I should also
hinder Suzuki reaction.
The Sonogashira reaction mechanism does not
impose so severe constraints on mutual arrangement of
the ligands in the arylpalladium complex formed by
oxidative addition. Although in this case the trans-
metalation step remains more favorable for the com-
plexes with trans orientation of the ligands Ar and X,
this effect is compensated by the complexity of
cis/trans isomerization of the alkynylarylpalladium
intermediate generated in the transmetalation step [18].
Presumably, this factor eliminates advantages of the
trans orientation of the anionic ligands Ar and X, thus
reducing the catalytic activity of the non-chelate
complex to a level comparable with the activity of the
palladium chelate.
On the whole, the Sonogashira reaction catalyzed
by palladium(II) complex I with chelating diamino-
carbene ligand possessing an amidine fragment
requires a considerably smaller amount of the catalyst
as compared to the classical PdCl2(PPh3)2-based cata-
lytic system to ensure equally high yield. The reaction
in the presence of complex I readily occurs not only
with iodoarenes but also with bromoarenes having
electron-withdrawing substituents. Complex II with
non-chelating diaminocarbene ligand shows a com-
parable catalytic activity. On the other hand, the use of
chelate I to catalyze Suzuki reaction is unreasonable,
since its activity is appreciably lower than that of com-
plex II with non-chelating ligand. A probable reason is
specific features of the cis/trans isomerization of inter-
mediate arylpalladium complexes.
Having estimated the catalytic activities of com-
plexes I and II in the Sonogashira reaction, it was
interesting to compare their activities in the Suzuki
cross-coupling reaction. As model reaction for study-
ing the catalytic activity of palladium aminocarbene
chelate I, we selected the reaction of 4-bromoanisole
(X) with phenylboronic acid (XI) (Scheme 2). This
choice was determined by the fact that the catalytic
activity of complex II (which is the most efficient
among currently known catalyst for the Suzuki reac-
tion) was studied just in the above reaction [12]. The
data in Table 2 show that palladium(II) chelate I is
considerably less active than non-chelate complex II.
Scheme 2.
OMe
B(OH)2
+
Br
X
XI
[Pd], K2CO3, EtOH
OMe
XII
The observed effect of chelation on the catalytic
activity in cross-coupling reactions is likely to be
related to specific features of the reaction mechanisms.
The Suzuki reaction mechanism [15] requires the pres-
ence of a palladium complex with trans arrangement
of the ligands Ar and X at the transmetalation step of
the catalytic cycle [16]. Stronger binding of the
chelating ligand in complex I hampers formation of
such complexes during the reaction. This is consistent
with the results of calculations [17], according to
which phosphine complexes where the neutral ligand
occupies only one rather two sites in the coordination
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded on
a Bruker DPX 300 instrument at 300.13 and 75.5 MHz,
respectively, using CDCl3 as solvent. Commercial re-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 4 2013

MIKHAILOV et al.
554
agents of analytical grade were used without additional
purification. The solvents were purified according to
standard procedures.
REFERENCES
1. Arduengo, A.J., Harlow, R.L., and Kline, M., J. Am.
Chem. Soc., 1991, vol. 113, p. 361.
Typical procedure for the Sonogashira reaction
of haloarenes III–VI with oct-1-yne (VII). Haloarene
III–VI, 2.5 mol, and oct-1-yne (VII), 5.0 mmol
(55 mg), were dissolved in 10 ml of appropriate sol-
vent, 14.5 mol of the corresponding base was added,
palladium catalyst, 0.24 mol (45 mg) of CuI, and (if
necessary) 0.11 mol (30 mg) of PPh3 were added, and
the mixture was stirred under the conditions indicated
in Table 1. The mixture was then cooled to room
temperature, 2 ml of diethyl ether and 4 ml of water
were added, the organic layer was separated, washed
with water (2×5 ml), dried over Na2SO4, and evapo-
rated under reduced pressure, and the residue was
analyzed by 1H NMR.
2. Alder, R.W., Allen, P.R., Murray, M., and Orpen, A.G.,
Angew. Chem., Int. Ed. Engl., 1996, vol. 35, p. 1121.
3. Gushchin, P.V., Kuznetsov, M.L., Haukka, M.,
Wang, M.-J., Gribanov, A.V., and Kukushkin, V.Y.,
Inorg. Chem., 2009, vol. 48, p. 2583.
4. De Frémont, P., Marion, N., and Nolan, S.P., Coord.
Chem. Rev., 2009, vol. 253, p. 862.
5. Nolan, S.P. and Navarro, O., Comprehensive Organo-
metallic Chemistry III, Mingos, D.M.P. and Crab-
tree, R.H., Eds., Amsterdam: Elsevier, 2007, vol. 11, p. 1.
6. Fortman, G.C. and Nolan, S.P., Chem. Soc. Rev., 2011,
vol. 40, p. 5151.
7. Boyarskiy, V.P., Luzyanin, K.V., and Kukushkin, V.Y.,
Coord. Chem. Rev., 2012, vol. 256, p. 2029.
1-Nitro-2-(oct-1-yn-1-yl)benzene (VIII) [19].
1H NMR spectrum, δ, ppm: 0.92 t (3H, CH3, J = 6 Hz),
1.25–1.40 m [4H, (CH2)2], 1.41–1.58 m (2H, CH2),
1.63 m (2H, ≡CCH2CH2), 2.49 t (2H, ≡CCH2, J =
7 Hz), 7.39 t (1H, Harom, J = 7 Hz), 7.49–7.65 m (2H,
8. Chugaev, L.A. and Skanavi-Grigor’eva, M.S., Zh. Russ.
Fiz.-Khim. Ob–va., 1915, vol. 47, p. 776.
9. Crociani, B., Boschi, T., and Belluco, U., Inorg. Chem.,
1970, vol. 9, p. 2021.
10. Wanniarachchi, Y.A. and Slaughter, L.M., Chem.
H
arom), 7.96 d (1H, Harom, J = 7 Hz).
4-(Oct-1-yn-1-yl)benzonitrile (IX) [20]. H NMR
Commun., 2007, p. 3294.
1
11. Burke, A., Balch, A.L., and Enemark, J.H., J. Am.
Chem. Soc., 1970, vol. 92, p. 2555.
12. Luzyanin, K.V., Tskhovrebov, A.G., Carias, M.C.,
Guedes da Silva, M.F.C., Pombeiro, A.J.L., and
Kukushkin, V.Y., Organometallics, 2009, vol. 28,
p. 6559.
13. Tskhovrebov, A.G., Luzyanin, K.V., Kuznetsov, M.L.,
Sorokoumov, V.N., Balova, I.A., Haukka, M., and
Kukushkin, V.Y., Organometallics, 2011, vol. 30,
p. 863.
spectrum, δ, ppm: 0.89 t (3H, CH3, J = 6 Hz), 1.26–
1.48 m [4H, (CH2)2], 1.54 m (2H, ≡CCH2CH2), 2.42 t
(2H, ≡CCH2, J = 7 Hz), 7.44 d (2H, Harom, J = 7 Hz),
7.54 d (2H, Harom, J = 7 Hz).
Typical procedure for the Suzuki reaction of
4-bromoanisole (X) with phenylboronic acid (XI).
A mixture of 0.20 mol (39 mg) of 4-bromoanisole (X),
0.22 mol (27 mg) of phenylboronic acid (XI), 0.20 mol
(6.2 mg) of acenaphthene (internal standard for NMR),
0.72 mol (100 mg) of K2CO3, and 1 ml of ethanol was
heated to 80°C, a solution of a required amount of
complex I or II in 0.1 ml of ethanol was added, and the
mixture was stirred at 80°C for a time indicated in
Table 1. The mixture was then cooled to room tem-
perature, 2 ml of carbon tetrachloride and 4 ml of
water were added, and the organic layer was separated,
washed with water (2×5 ml), dried over Na2SO4, and
analyzed by 1H NMR.
14. Kirsch, G., Hesse, S., and Comel, A., Curr. Org. Synth.,
2004, vol. 1, p. 47.
15. Miyaura, N., Yamada, K., and Suzuki, A., Tetrahedron
Lett., 1979, vol. 20, p. 3437.
16. Echavarren, A.M. and Cárdenas, D.J., Metal-Catalyzed
Cross-Coupling Reactions, de Meijere, A. and
Diederich, F., Eds., Weinheim: Wiley-VCH, 2004,
2nd ed.
17. Kozuch, S. and Shaik, S., J. Mol. Catal. A: Chem.,
2010, vol. 324, p. 120.
1
4-Methoxybiphenyl (XII) [21]. H NMR spec-
18. Osakada, K. and Yamamoto, T., Coord. Chem. Rev.,
trum, δ, ppm: 3.88 s (3H, OCH3), 7.02 d (2H, Harom
,
2000, vol. 198, p. 379.
J = 8.6 Hz), 7.31–7.36 m (1H, Harom), 7.42–7.47 m
19. Anastasia, L. and Negishi, E., Org. Lett., 2001, vol. 3,
(2H, Harom), 7.60–7.65 m (4H, Harom).
p. 3111.
This study was performed under financial support
by the President of the Russian Federation (Program
for state support of young Russian scientists, project
no. MK-504.2011.3) and by the Russian Foundation
for Basic Research (project no. 11-03-00048-a).
20. Foss, F., Mathews, T., Macdonald, T., Yugesh, K.,
Kennedy, P., Snyder, A., Davis, M., and Lynch, K.,
Bioorg. Med. Chem., 2009, vol. 17, p. 6123.
21. Justik, M.W., Protasiewicz, J.D., and Updegraff, J.B.,
Tetrahedron Lett., 2009, vol. 50, p. 6072.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 4 2013