Oxime palladacycles: Stable and efficient catalysts for carbon-carbon coupling reactions

Article abstract of DOI:10.1021/ol0058644

(Formula presented) Oxime palladacycles are thermally stable complexes not sensitive to air or moisture, easily prepared from very cheap materials, which can be used as versatile and very efficient catalysts for different carbon-carbon bond-forming reactions.

Full text of DOI:10.1021/ol0058644

ORGANIC
LETTERS
2
000
Vol. 2, No. 13
823-1826
Oxime Palladacycles: Stable and
Efficient Catalysts for Carbon−Carbon
Coupling Reactions
1
a
Diego A. Alonso, Carmen N a´ jera,* and M Carmen Pacheco
Departamento de Qu ´ı mica Org a´ nica, UniVersidad de Alicante, Apartado 99,
03080 Alicante, Spain
cnajera@ua.es
Received March 27, 2000
ABSTRACT
Oxime palladacycles are thermally stable complexes not sensitive to air or moisture, easily prepared from very cheap materials, which can be
used as versatile and very efficient catalysts for different carbon−carbon bond-forming reactions.
II
Transition metal-catalyzed coupling reactions are one of the
most important processes in organic chemistry and have been
extensively studied since they represent a powerful and
popular method for the formation of carbon-carbon bonds.
This strategy has been applied to the synthesis of many
organic compounds, especially the complex natural products,
and to increase their efficiency. Carbometalated Pd com-
2
plexes, especially palladacycles, have emerged as very
promising catalysts for C-C bond-forming reactions.
Phospha-palladacycles 1, 2, 3, 4, 5, and 6 as well
as phosphine-free heterocyclic carbenes 7 and 8 and also
3
,4
5
6
7
8
9
3,10
11
1
2
cyclometalated imines 9 have been used in vinylation
1
in supramolecular chemistry and in materials science.
Organopalladium compounds play an important role in
homogeneous catalysis due to their versatility and nontox-
icity. They are used in numerous useful transformations for
laboratory and industrial chemistry. In particular, carbon-
carbon forming reactions represent particularly potent ap-
plications of palladium complexes as catalysts. During the
past few years, very active systems have been developed in
order to improve the stability of palladium-based catalysts
(2) Dyker, G. Chem. Ber./Recueil 1997, 130, 1567-1578.
(
3) For an excellent review, see: Herrmann, W. A.; B o¨ hm, V. P. W.;
Reisinger, C.-P. J. Organomet. Chem. 1999, 576, 23-41.
(4) (a) Herrmann, W. A.; Brossmer, C.; O¨ fele, K.; Reisinger, C.-P.;
Priermeier, T.; Beller, M.; Fischer, H. Angew. Chem., Int. Ed. Engl. 1995,
3
4, 1844-1848. (b) Beller, M.; Fischer, H.; Herrmann, W. A.; O¨ fele, K.;
Brossmer, C. Angew. Chem., Int. Ed. Engl. 1995, 34, 1848-1849.
(5) (a) Ohff, M.; Ohff, A.; Van der Boom, M. E.; Milstein, D. J. Am.
Chem. Soc. 1997, 119, 11687-11688. (b) Kiewel, K.; Liu, Y.; Bergbreiter,
D. E.; Sulikowski, G. A. Tetrahedron Lett. 1999, 40, 8945-8948.
(6) Shaw, B. L.; Perera, S. D.; Staley, E. A. Chem. Commun. 1998,
1
361-1362.
(7) Albisson, D. A.; Bedford, R. B.; Lawrence, S. E.; Scully, P. N. Chem.
(
1) For recent revisions, see: (a) Tsuji, J. In Palladium Reagents and
Commun. 1998, 2095-2096.
Catalysts: InnoVations in Organic Synthesis; Wiley: Chichester, 1995. (b)
Applied Homogeneous Catalysis with Organometallic Compounds, Volumes
and 2; Cornils, B., Herrmann, W. A., Eds.; VCH: Weinheim, 1996. (c)
Malleron, J.-L.; Fiaud, J.-C.; Legros, J.-Y. Handbook of Palladium-
Catalyzed Organic Reactions; Academic Press: San Diego, 1997. (d) Metal-
catalyzed Cross-coupling Reactions; Diederich, F., Stang, P. J., Eds.; Wiley-
VCH: Weinheim, 1998. (e) Transition Metals for Organic Synthesis,
Volumes 1 and 2; Beller, M., Bolm, C., Eds.; Willey-VCH: Weinheim,
998. (f) Stanforth, S. P. Tetrahedron 1998, 54, 263-303. (g) Recent
Advances in Organopalladium Chemistry. J. Organomet. Chem. 1999, 576,
(8) Miyazaki, F.; Yamaguchi, K.; Shibasaki, M. Tetrahedron Lett. 1999,
40, 7379-7383.
1
(9) Beletskaya, I. P.; Chuchurjukin, A. V.; Dijkstra, H. P.; Van Klink,
G. P. M.; Van Koten, G. Tetrahedron Lett. 2000, 41, 1075-1079.
(10) (a) Herrmann, W. A.; Elison, M.; Fischer, J.; K o¨ cher, C.; Artus, G.
R. J. Angew. Chem., Int. Ed. Engl. 1995, 34, 2371-2373. (b) Herrmann,
W. A.; Reisinger, C.-P.; Splieger, M. J. J. Organomet. Chem. 1998, 557,
93-96.
(11) Zhang, Ch.; Trudell, M. L. Tetrahedron Lett. 2000, 41, 595-598.
(12) (a) Ohff, M.; Ohff, A.; Milstein, D. Chem. Commun. 1999, 357-
358. (b) Weissman, H.; Milstein, D. Chem. Commun. 1999, 1901-1902.
1
1
.
1
0.1021/ol0058644 CCC: $19.00 © 2000 American Chemical Society
Published on Web 05/26/2000

“
Heck reaction”,13 with TONs (turnover number ) mol
5
6
product/mol Pd) of 10 -10 . Similarly, the alkynylation of
aryl bromides, the so-called “Sonogashira reaction”, has
been carried out with Herrmann’s catalyst 1 with more than
1
Scheme 1. Synthesis of Palladacycles 1118a
1
4
3
2
0 TON. In the case of the cross-coupling process between
aryl halides and aryltrialkyltin reagents, the “Stille reac-
1
5
3
7
tion”, complexes 1 and 4 are excellent catalysts, especially
5
the latter one with more than 10 TON. For the coupling of
aryl halides with organoboronic acids, the “Suzuki reac-
1
6
3,4b
7
3,10b
12b
tion”, compounds 1,
4, 7,
and 9 are adequate
2
6
catalysts with TONs between 10 and 10 . These pallada-
cycles exhibit higher air and thermal stability than palladium-
0) complexes and can operate through a Pd -Pd cycle
II
IV
(
0
II
17
instead of by the traditional Pd -Pd mechanism.
were synthesized and carbopalladated with lithium tetra-
chloropalladate and NaOAc in methanol at room temperature1
to provide chloro bridge complexes 11 in high yields
8a
(Scheme 1, Table 1).
Table 1. Synthesis of Palladacycles 11
entry
no.
R1
R2
yield (%)a
mp (°C)
1
2
3
4
5
11a
11b
11c
11d
11e
Ph
H
Cl
MeO
H
64
98
92
92
90
139-141b
208-210
135-137
209-212
>320
p-ClC6H4
p-MeOC6H4
Me
c
fluorenone
a
Isolated yield. b Lit. 150-152 °C.18a
c
Lit. 210 °C.18a
The arylation of olefins with aryl halidessgenerally
13
referred to as the “Heck reaction” swas first evaluated with
the palladium complexes 11. To determine the optimum
reaction conditions for the catalysts, we chose as a model
reaction the coupling between methyl acrylate and PhI in
the presence of catalyst 11a and TEA (triethylamine) (Table
The purpose of our study was to find a suitable, robust,
and easily prepared catalyst valid in a wide range of C-C
bond-forming processes. Therefore, the initial step was the
selection of a potential catalytic system amenable to sys-
tematic structural and electronic variation. One of the
appealing features of oxime-based palladacycles is that the
ligands may be tuned both sterically and electronically in a
synthetically straightforward manner by variation of the
corresponding ketone precursors. The fact that the aromatic
ketoxime-derived palladacycles are extraordinary thermally
2
). The reaction provided quantitative conversions with either
1
9
-2
DMF or NMP as solvents at 110 °C under air using 10
mol % of Pd in 2 or 1.5 h, respectively. When using other
different solvents such us CH CN, THF, dioxane, toluene,
or DME, lower conversions were always obtained (23-72%).
Reducing the catalyst loading to 10 mol % of Pd led to
longer reaction times but did not influence the reaction
conversion (compare entries 1 and 2, Table 1). As bases,
3
-
3
stable and not sensitive to oxygen or moisture, as well as
their ready and economical synthetic access,18 prompted us
2 3
TEA, K CO , and CsF can be used, with the reaction
to study their activity as catalysts in C-C bond-forming
reactions.
For the preparation of the complexes, different oximes 10,
derived from acetophenone, benzophenone, 4,4′-dichloroben-
zophenone, 4,4′-dimethoxybenzophenone, and fluorenone,
occuring faster with TEA (Table 2, entries 1, 4, and 5).
Similar results were obtained with complexes 11a, 11b, 11d,
and 11e; however, the reaction with the p-methoxy-
substituted benzophenone complex 11c was rather slower
under the reaction conditions identical to those used for 11a
or 11b (compare entries 3, 6, and 7, Table 2). p-Bromo-
acetophenone was chosen as a model aryl bromide for the
coupling with methyl acrylate to afford very good conver-
sions (Table 2, entries 11 and 12), although Jeffery’s
(
13) Heck, R. F. J. Am. Chem. Soc. 1968, 110, 5518-5526.
(14) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975,
4
467-4470.
(
(
(
(
15) Milstein, D.; Stille, J. K. J. Am. Chem. Soc. 1979, 101, 4992-4998.
16) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457-2483.
17) Shaw, B. L. New J. Chem. 1998, 77-79.
20
conditions, i.e., higher catalyst loadings and higher tem-
18) (a) Onoue, H.; Minami, K.; Nakagawa, K. Bull. Chem. Soc. Jpn.
1
970, 43, 3480-3485. (b) Nielson, A. J. J. Chem. Soc., Dalton Trans. 1981,
2
05-211. (c) Ryabov, A. D.; Kazaukov, G. M.; Yatsimirsky, A. K.;
(19) Commercially available solvents were used without further purifica-
Ku’zmina, L. G.; Burtseva, O. Y.; Dvortsova, M. V.; Polyakov, V. A. Inorg.
Chem. 1992, 31, 3083-3090.
tion.
(20) Jeffery, T. Tetrahedron Lett. 1985, 26, 2667-2670.
1824
Org. Lett., Vol. 2, No. 13, 2000

absence of the cocatalyst, cuprous iodide, resulted in the
formation of increased amounts of 1,4-diphenylbuta-1,3-
diyne and always led to lower reaction conversions.
In the case of the Stille reaction, trimethyl(phenyl)tin
was coupled with p-bromoacetophenone at 110 °C in toluene
as solvent under neutral conditions. The yields of product
were moderate to excellent when catalysts 11a-e were used
Table 2. Heck Coupling Reactions Catalyzed by Complexes
a
1
1
1
5
(
Table 4, entries 1-5). Of all the catalysts used, fluorenone-
catalyst
mol %
of Pd)
derived palladacycle 11e gave the best result.
(
t
yield
b
entry
R
Hal
solvent
base
TEA
TEA
TEA
(h)
(%)
TON
1.5 >99 (92)c 10
12
2
4.5 97
3.5 >99
1.5 >99
4
1
2
3
4
5
6
7
8
9
H
H
H
H
H
H
H
H
H
H
I
I
I
I
I
I
I
I
I
I
11a (0.01) NMP
11a (0.001) NMP
11a (0.01) DMF
11a (0.01) NMP
11a (0.01) NMP
11b (0.01) DMF
11c (0.01) DMF
11d (0.01) DMF
11e (0.01) DMF
11e (0.01) NMP
5
>99
98
10
9800
9700
a
b
Table 4. Stille and Suzuki Couplings Catalyzed by 11
K
2
CO
3
4
CsF
10
10
4
TEA
TEA
TEA
TEA
TEA
6
2
85
98
8500
9800
9500
1.5 95
yield (%)c
TON
4
entry
M
catalyst
t (h)
1
1
1
0
1
2
2
5
3
>99
10
d
d
>99 (97)c 199
Ac Br 11a (0.5)
Ac Br 11e (0.5)
DMF
DMF
NaOAC
NaOAC
1
2
3
4
5
6
7
8
9
-SnMe3
-SnMe3
-SnMe3
-SnMe3
-SnMe3
-B(OH)2
-B(OH)2
-B(OH)2
-B(OH)2
-B(OH)2
11a
11b
11c
11d
11e
11a
11b
11c
11d
11e
5
8
8
8
62
58
47
63
95 (95)d
93e
97e
94e
95e
21
19
16
21
32
930
970
940
950
970
>99
199
a
Reaction conditions: 1.0 equiv of ArX, 1.2 equiv of olefine, 1.4 equiv
of base. Determined by GC, based on the ArX using decane as internal
standard. Isolated yield after flash chromatography. The reaction was
carried out at 135 °C in the presence of 20 mol % of Bu4NCl.
b
c
d
5
0.5
0.5
0.5
0.5
0.5
peratures [Bu
of 11, and 135 °C] had to be used in this case.
The Sonogashira reaction14 has been investigated using
4
NCl, (20 mol %), NaOAc as base, 0.25 mol
%
e
f
1
0
97 (95)
a
Experimental details: 1.0 equiv of aryl bromide, 1.5 equiv of Me3SnPh,
phenylacetylene and phenyl iodide in the presence of
catalysts 11 (0.5 mol % of Pd), CuI (5 mol of %), and an
amine at 90 °C (Table 3). The influence of the amine was
catalyst (3 mol % of Pd). b Experimental details: 1.0 equiv of aryl bromide,
1
.5 equiv of PhB(OH)2, 2.0 equiv of K2CO3, catalyst (0.1 mol % of Pd).
c
d
Determined by GC, based on the aryl bromide. Isolated yield after flash
e
chromatography. A 2-4% yield of homocoupled product is obtained.
f
Isolated yield after recrystallization.
Table 3. Sonogashira Couplings Catalyzed by Complexes 11a
The coupling of aryl bromides and phenylboronic acid,
1
6
the “Suzuki reaction”, catalyzed by 11 was investigated,
and representative results are summarized in Table 4 (entries
6
-10). Under standard conditions, these catalysts are very
active, and the coupling between p-bromoacetophenone and
PhB(OH) in toluene at 110 °C took place with shorter times
(30 min), better yields, and higher TONs than for the Stille
reaction.
Finally, encouraged by the results obtained in the previous
cross-coupling processes using complexes 11, we examined
their application in other recently described catalytic process
for both inter- and intramolecular homocoupling of aryl
halides, the “Ullmann reaction”. In this methodology,
entry
catalyst
t (h)
yield (%)b,c
TON
1
2
3
4
5
11e
11a
11b
11c
11d
2
2
3
5.5
5.5
71 (68)d
67 [2]
71
75 [1]
66
142
134
142
150
132
2
a
Experimental details: 1.0 equiv of PhI, 1.2 equiv of phenylacetylene,
b
catalyst (0.5 mol % of Pd), CuI (5 mol %), 90 °C. Determined by GC,
based on PhI using decane as internal standard. The reaction stops at the
indicated time; in brackets yield of PhCtCCtCPh. Isolated yield after
flash chromatography.
c
d
catalytic Pd(OAc)
quinone (HQ) (50 mol %), CsCO
tolylphosphine or arsine as ligands (2-5 mol %) at temper-
2
(2-5 mol %) in the presence of hydro-
3
(100 mol %), and tri-o-
first determined with catalyst 11e since the choice of the
solvent has previously been shown to be critical for the
success of the reaction. Thus, when the reaction was
performed in the presence of TEA, piperidine, or H u¨ nig’s
base (diisopropylethylamine), low yields of cross-coupling
product (33-52%) and significant amounts of dimeric 1,4-
diphenylbuta-1,3-diyne were obtained. However, by using
pyrrolidine, and regardless of the catalyst used, the yields
were increased up to 75% in 2-5 h with formation of only
traces of the undesired diyne (Table 3, entries 1-5). The
21
atures between 75 and 125 °C in DMA are used. Our goal
in this case has been to use complex 11e as catalyst in the
intermolecular homocoupling of aryl halides in the absence
of phosphine or arsine ligands (Scheme 2). By using 1 mol
%
of 11e in the case of phenyl iodide at 110 °C in DMF
with HQ (50 mol %) and K CO as base (100 mol %), an
almost quantitative yield of biphenyl was obtained after 2 h
2
3
(
21) Hennings, D. D.; Iwama, T. Rawal, V. H. Org. Lett. 1999, 1, 1205-
1208.
Org. Lett., Vol. 2, No. 13, 2000
1825

temperatures and shorter reaction times, especially in Heck
and Suzuki processes. Their easy synthetic accessibility and
structural versatility make these complexes very promising
catalysts, and further studies in their applicability to other
organic transformations are currently under investigation.
Scheme 2. Ullmann-Type Coupling of Aryl Halides
Acknowledgment. This work has been supported by the
DGES of the Spanish Ministerio de Educaci o´ n y Cultura
(
85% isolated yield). In the case of p-bromoacetophenone,
(MEC) (PB97-0123). D.A.A. thanks MEC for a contract
a quantitative yield was obtained by just increasing the
catalyst loading to 2.5 mol % under the same reaction
conditions.
under the program Acciones para la Incorporaci o´ n a Espa n˜ a
de Doctores y Tecn o´ logos.
In summary, this preliminary study has demonstrated that
phosphine-free cyclopalladated oxime complexes 11 are very
efficient catalysts for a wide range of C-C coupling
reactions. The versatility of these catalysts, especially in the
case of the fluorenone derived 11e, is comparable to that of
the best systems reported so far. They usually require lower
Supporting Information Available: Experimental pro-
cedures for the synthesis of palladium complexes 11 and
catalytic processes. This material is available free of charge
via the Internet at http://pubs.acs.org.
OL0058644
1826
Org. Lett., Vol. 2, No. 13, 2000