Oxime-Derived Palladium Complexes as Very Efficient Catalysts for the Heck-Mizoroki Reaction

Article abstract of DOI:10.1002/1615-4169(200202)344:2<172::AID-ADSC172>3.0.CO;2-9

Oxime-derived, chloro-bridged palladacycles 16 are efficient complexes for the Heck vinylation of aryl halides. The isolated catalysts are thermally stable, not sensitive to air or moisture and easily accessible from inexpensive starting materials. The reaction can be performed under aerobic conditions, with aryl iodides, bromides and chlorides with acrylic esters and olefins displaying turnover numbers (TON) of up to 10¹⁰ for phenyl iodide and turnover frequencies (TOF) of 1.4 × 10⁸ h^-1. Deactivated aryl bromides undergo the Heck reaction with styrene with TON and TOF values up to 97,000 and 6063 h^-1, respectively. Even aryl chlorides undergo the coupling reaction with olefins with TON up to 920. Complexes 16 catalyze the synthesis of 2,3-disubstituted indenones and indoles in good yields via annulation reaction of internal alkynes with o-bromoor o-chlorobenzaldehyde and o-iodoaniline, respectively.

Full text of DOI:10.1002/1615-4169(200202)344:2<172::AID-ADSC172>3.0.CO;2-9

FULL PAPERS
Oxime-Derived Palladium Complexes as Very Efficient Catalysts
for the Heck Mizoroki Reaction
a
¬
Diego A. Alonso, Carmen Najera,* M Carmen Pacheco
¬
Departamento de QuÌmica Organica, Universidad de Alicante, Apartado 99, 03080 Alicante, Spain
Fax: ( ‡ 34)-965-903-549, e-mail: cnajera@ua.es
Received: October 15, 2001; Accepted: December 27, 2001
Abstract: Oxime-derived, chloro-bridged palladacy- with TON and TOF values up to 97,000 and 6063 hÀ1,
cles 16 are efficient complexes for the Heck vinyl- respectively. Even aryl chlorides undergo the cou-
ation of aryl halides. The isolated catalysts are pling reaction with olefins with TON up to 920.
thermally stable, not sensitive to air or moisture and Complexes 16 catalyze the synthesis of 2,3-disubsti-
easily accessible from inexpensive starting materials. tuted indenones and indoles in good yields via
The reaction can be performed under aerobic con- annulation reaction of internal alkynes with o-bromo-
ditions, with aryl iodides, bromides and chlorides with or o-chlorobenzaldehyde and o-iodoaniline, respec-
acrylic esters and olefins displaying turnover numbers tively.
(TON) of up to 1010 for phenyl iodide and turnover
frequencies (TOF) of 1.4Â108 hÀ1. Deactivated aryl Keywords: catalysts; C-C coupling; metallacycles; N
bromides undergo the Heck reaction with styrene ligands, palladium.
Introduction
15[20] have been found to be stable but still very active
catalysts in Heck reactions with TONs (turnover
The palladium-catalyzed reaction of organic halides numberˆ mol product mol PdÀ1) up to 105 106. All
with alkenes (the Heck Mizoroki reaction[1]) has be- these cyclometallated compounds exhibit higher ther-
come one of the best methods for carbon-carbon bond mal stability compared with conventional Pd(0) cata-
formation in organic synthesis.[2]. During the last few lysts and can operate through a PdII-PdIV or Pd0-PdII
years, very active systems have been developed in order mechanism.[21]
to improve both stability and efficiency of palladium-
Very recently, as part of our studies to find robust and
based catalysts. These new systems are capable of easily prepared systems to catalyze C-C bond-forming
achieving extremely high catalytic activities even with reactions, we found that oxime-based palladacycles 16
fairly unreactive aryl bromides and chlorides. For are very efficient and versatile catalysts for a wide range
example, noteworthy advances have been described by of useful and well known C-C coupling processes[22] such
using sterically hindered, electron-rich phosphanes,[3] as Heck, Suzuki, Stille, Sonogashira and Ullmann
tetraphenylphosphonium salts in combination with N, reactions. These catalysts are very thermally and air
N-dimethylglycine (DMG),[4] and even under phos- stable and showed TONs up to 104 for the Heck coupling
phine-free conditions.[5] However, lately, palladacycles of aryl iodides with methyl acrylate. In this paper, we
have been by far the most developed and studied Heck- report on the evaluation and optimization of the Heck
type catalysts as they are presently the most successful coupling of aryl halides such as iodides, bromides and
and, because of their structural versatility and easy chlorides and different olefins with oxime-derived
synthetic accessibility, most promising catalysts in C-C palladacycles as catalysts[23,24] and also in cycloannula-
bond forming reactions.[6] Among them, phospha-palla- tion reactions with internal alkynes.
dacycles 1,[6c,7] 2,[8] [9] developed by Herrmann, Milstein
3
and Shaw, respectively, have been demonstrated to be
excellent catalysts for these types of processes (Fig-
ure 1). ortho-Palladated triaryl phosphites 4[10] and 5[11]
and phosphinite 6,[12] where ligand strength has been
Results and Discussion
decreased, have markedly higher activity than their Synthesis of Oxime-Derived Palladium Complexes
phosphino analogues. Finally, phosphine-free heterocy-
clic carbenes 7,[6c,13] 8,[14] 9,[15] and 10,[16] ortho-metallated For the preparation of the metallated complexes 16a d,
benzyl thioethers 11[17] and 12,[17b] benzyl ethers 13,[18] 17 and 18 different aliphatic and aromatic oximes 19
and cyclometallated imine-type derivatives 14[19] and derived from acetophenone, benzophenone, 4,4'-dime-
172
¹ VCH Verlagsgesellschaft mbH, D-69451 Weinheim, 1615-4150/02/34402-172 183 $ 17.50-.50/0
Adv. Synth. Catal. 2002, 344, No. 2

Oxime-Derived Palladium Catalyst for Heck Mizoroki Reaction
FULL PAPERS
R1
R1
Nph
P
Nph
OH
Li2PdCl4, NaOAc
MeOH, rt, 3 d
PR2
o-Tol
N
Tol-o
N
OH
P
R2
Pd
O
R2
OAc
Pd TFA
PR2
Pd
O
n
)
Pd
R
2
Cl
)
2
16a-d
19
OH
(
N
R
2
OH
Pd
N
Pd
)
2
2, n = 1,2
1
3
Cl
Cl
Fe
R
N
O
PR2
Pd
PR2
N
PdX2
X
18
17
)
2
N
R
Pd
Scheme 1.
Cl
P(OAr)2
O
N
O
5, R = OAr, X = I
6, R = i-Pr, X = Cl
4
7
OH
N
OH
N
N
Pd
N
(PhCN)2PdCl2
CH3CN, rt
X
I
N
S
N
N
N
N
Pd
Cl
+
N
+
N
N
Pd
Br
N
S
OH
I
Pd
N
Cl
OH
)
2
8
9
10
16e
SPh
L
Scheme 2.
O
SR
Pd
Pd
R
Pd Cl
SPh
Pd
O
L
)
2
Cl
12
Searching for tridentate NCN pincer-type catalysts,
the palladation of 1,3-diacetylbenzene dioxime (Ta-
ble 1, entry 5), had to be performed with bis(benzoni-
trile)dichloropalladium(II) [(PhCN)2PdCl2] in acetoni-
trile at room temperature and in the absence of base.
However, it was found to lead exclusively to the
formation of the monopalladated dimeric complex 16e
in a 40% isolated yield[27] (Scheme 2).
11, R = H, AcNH
13, L = PPh3, AsPh3
R
R1
R
N
N
OAc
N
Pd
)
Pd
N OH
)
Pd
2
R2
2
TFA
)
2
Cl
R
R
15
14
16
Figure 1.
All these palladacycles have been fully characterized
1
and have shown satisfactory IR, H, and 13C NMR
thoxybenzophenone, 4,4'-dichlorobenzophenone, pina- spectra (see Experimental Section). Their reduction
colone and acetylferrocene, were synthesized and with deuterated sodium cyanoborohydride (NaBD3
carbopalladated[25,26] with lithium tetrachloropalladate CN),[26] led to the expected Pd-D exchange affording
(Li2PdCl4) in MeOH in the presence of NaOAc as base the deuterated oximes 20a e, 21, and 22 in high yields
at room temperature to provide chloro-bridge com- (Scheme 3).
plexes 16a d, 17, and 18 in high yields (Scheme 1,
Table 1).
However, metallation of fluorenone oxime, with
Li2PdCl4 did not led to the corresponding cyclopalla-
Table 1. Synthesis of palladacycles 16 18.
Entry
No.
R1
R2
Yield [%][a]
mp [8C]
1
2
3
4
5
6
7
16a
16b
16c
16d
16e
17
Me
Ph
H
H
MeO
Cl
92
64
92
95
40
60
75
209 212[b]
139 141[c]
135 137
208 210
>320
p-MeOC6H4
p-ClC6H4
Me
pinacolone
acetylferrocene
4-C(CH3) ˆ NOH
152[d]
18
>320
[a]
Isolated yields.
[b]
[c]
[d]
Lit. 210 8C.[25a]
Lit.150 152 8C.[25a]
Lit. 156 160 8C.[25b,26]
Adv. Synth. Catal. 2002, 344, 172 183
173

Diego A. Alonso, et al.
FULL PAPERS
R1
R1
D
+
CO2Me
OH
NaBD3CN
N
I
N
OH
R2
Pd
THF/MeOH
0 °C to rt
R2
)
Cl
2
Pd catalyst (0.01 mol % Pd)
16a-d
20a-d
OH
DMF, TEA, 110 °C
CO2Me
OH
N
D
N
Scheme 4.
OH
D
N
Fe
N
OH
of triethylamine (TEA) as base and with a catalyst
loading of 10À2 mol % in Pd (Scheme 4, Table 2). The
reaction provided very similar results and quantitative
conversions under air for nearly all the dimeric com-
plexes with reaction periods within 1.5 h (for the 4,4'-
dichlorobenzophenone oxime derivative 16d) and 24 h
D
21[26]
22
20e
Scheme 3.
dated oxime as we initially assumed.[22] Instead, it was for monometallated dioxime complex 16e. Complexes
obtained a mixture of compounds the structures of 16a, b, and d, gave similar conversions and rates,
which are now under investigation in our laboratory. however, the reaction with the p-methoxy-substituted
Preliminary results have shown that carbopalladation benzophenone complex 16c was rather slower under the
did not take place in this case. The fact that fluorenone same reaction conditions (compare entries 1, 2, 3, and 4,
oxime was not cyclopalladated {not even under ligand- Table 2). This result clearly shows that, with respect to
exchange conditions[25d,28] with [Pd(dmba)Cl]2, (dmba ˆ catalyst efficiency, complexes containing electron-do-
N,N-dimethylbenzylamine)}, could be a consequence of nating groups in the aryl ring are inferior to precursors
the rigidity conferred to the system by the two linked substituted with neutral or electron-withdrawing
aromatic rings, which was not the situation in similar di- groups. A catalyst system prepared in situ from Li2
and polycyclic systems that have been easily palladated PdCl4 (0.01 mol % of Pd) and 4,4'-dichlorobenzophe-
and where only one aromatic ring was present in the none oxime (0.01 mol %) in the presence of base (excess
molecule.[29]
of K2CO3), was tested as well (Table 2, entry 8). In this
case, the yield was significantly lower (62% after 6 h)
than that obtained from the straight use of 16d (full
conversion after 1.5 h). This result is obvious as the
formation of the complex takes longer reaction periods
Heck Coupling of Aryl Halides with Olefins
The arylation of olefins with aryl halides was first and Li2PdCl4 itself catalyzes the reaction with lower
evaluated with palladium complexes 16 18 in order to rates (90% yield after 3.5 h) (Table 2, entry 9).
study their catalytic activity. We chose as a model
The optimum reaction conditions for the palladacycle
reaction the coupling between methyl acrylate and catalysts were studied for the coupling reaction of
phenyl iodide (PhI)[30] in DMFat 110 8C, in the presence phenyl iodide and methyl acrylate in the presence of
Table 2. Heck coupling: catalyst study.
Entry
Catalyst
t [h]
Yield [%][a],[b]
TON[c]
TOF [hÀ1][d]
1
2
3
4
5
6
7
8
9
16a
16b
16c
16d
16e
17
2
2
6
1.5
24
4
6
6
3.5
98
98
85
> 99
93
98
94
62
90
9800
9800
8500
10000
9300
9800
9400
6200
9000
4900
4900
1417
6667
388
2450
1567
1033
2571
18
16d[e]
Li2PdCl4
[a]
Determined by GLC, based on PhI using decane as internal standard.
[b]
[c]
[d]
[e]
Reaction conditions: PhI (2 mmol), methyl acrylate (2.4 mmol), TEA (2.8 mmol), catalyst, DMF (4 mL).
TON ˆ turnover number (mol product mol PdÀ1).
TOF ˆ turnover frequency (TON hÀ1).
16d was generated in situ in the reaction medium.
174
Adv. Synth. Catal. 2002, 344, 172 183

Oxime-Derived Palladium Catalyst for Heck Mizoroki Reaction
FULL PAPERS
impressive TON numbers were obtained (108) with very
good isolated yields. These results are the average of
3 runs (the reactions were run under similar conditions
in a Carousel Reaction StationTM, see Experimental
Section). In the case of employing lower catalyst loading
such us 10À8 mol % of Pd (Table 3, entry 17), conver-
sions ranging from 80 to 98% could be reached (average
of 6 runs) after 3 d affording turnover numbers of 1010
and turnover frequencies of 1.4Â108 hÀ1 which is, to the
CO2R
+
I
16
Solvent, Base, T
CO2R
Scheme 5.
catalysts 16b or 16d (Scheme 5, Table 3).[30] The reaction best of our knowledge, the highest catalytic activity of all
afforded quantitative conversions with either DMF or Heck reactions reported to date.[32] As mentioned
NMP as solvents at 110 8C under air[31] using 10À2 mol % above, the isolated yields of n-butyl cinnamate after
of Pd in 2 or 1.5 h, respectively (Table 3, entries 1 and 2). flash chromatography were in complete agreement with
When using other different solvents, CH3CN, dioxane, the conversions. Even under these very low catalyst
and DME, the reaction became slower, while experi- loading limits, the reactions can be carried out in air
ments run in THF, DMSO, and toluene gave very low without any previous purifications of phenyl iodide, the
conversions. During the course of our studies, we olefin, or the solvent. However, it is very important to
examined several different bases: TEA, K2CO3, and eliminate possible traces of catalyst from the reaction
CsF can be used, the reaction being faster with TEA vessel and the stirring bar in order to avoid what Dupont
(Table 3, entries 1, 9 and 10). At 110 8C, reducing the has called ™reaction vessel catalytic activity∫.[33] Then,
catalyst loading to 10À3 mol % Pd led to longer reaction under these very low catalyst loadings, the reaction
times, but did not influence the reaction conversion vessels and the stirring bar were always washed with
(Table 3, compare entries 1 and 11). When the catalyst concentrated nitric acid prior to run a new catalytic cycle
loading was brought down to 10À4 mol % of Pd (Table 3, with them.[34]
entry 13), the activity of the complex dropped signifi-
The pronounced thermal stability of palladacycles 16
cantly to give a 35% yield of methyl cinnamate after two was demonstrated by the absence of Pd-black precip-
days. However, this problem could be overcome by just itation after heating catalyst 16d in a DMF solution for
increasing the reaction temperature to 160 8C (bath 5 h. Only trace amounts were found after longer
temperature). Under these conditions, the reaction was reactions periods. Additionally, no deactivation of the
completed within 9 h (Table 3, entry 14) and it was catalyst was observed in subsequent catalytic runs when
possible to decrease the amount of Pd down to coupling phenyl iodide and methyl acrylate under
10À6 mol % with reproducible results for methyl and n- typical conditions (16d, 0.1 mol % of Pd), and GLC
butyl acrylate (Table 3, entries 15 and 16). In both cases analysis of 4 cycles yielded a constant rate of conversion
Table 3. Heck coupling: reaction conditions study.
Entry
16 [% mol Pd]
R
Solvent
Base
T [8C]
t [h]
Yield [%][a],[b]
TON
TOF [hÀ1]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
16b (10À2)
16b (10À2)
16b (10À2)
16b (10À2)
16b (10À2)
16b (10À2)
16b (10À2)
16b (10À2)
16b (10À2)
16b (10À2)
16b (10À3)
16d (10À2)
16d (10À4)
16d (10À4)
16d (10À6)
16d (10À6)
16d (10À8)
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
n-Bu
n-Bu
NMP
TEA
TEA
TEA
TEA
TEA
TEA
TEA
TEA
K2CO3
CsF
TEA
TEA
TEA
TEA
TEA
TEA
TEA
110
110
110
110
110
110
110
110
110
110
110
110
110
160
160
160
160
1.5
2
5
7
1
4.5
4.5
4.5
4.5
3.5
12
1.5
48
9
99 (92)
98
58
23
2
72
31
52
97
> 99
> 99
> 99
35
> 99
> 99(94)
> 99(98)
> 99(98)
9900
9800
5800
2300
200
7200
3100
5200
9700
10000
105
6600
4900
1160
329
200
1600
689
1156
2156
2857
8300
6667
73000
110000
107
DMF
CH3CN
THF
DMSO
dioxane
toluene
DME
NMP
NMP
NMP
DMF
DMF
DMF
DMF
DMF
DMF
10000
3.5 Â 105
106
108
108
1010
10
24
72
4.2Â106
1.4Â108
[a]
Determined by GLC, based on PhI using decane as internal standard. In parenthesis isolated yield after flash
chromatography.
Reaction conditions: PhI (2 mmol), alkyl acrylate (2.4 mmol), base (2.8 mmol), 16, solvent (4 mL).
[b]
Adv. Synth. Catal. 2002, 344, 172 183
175

Diego A. Alonso, et al.
FULL PAPERS
activation∫ of the oxime-derived palladacycle was
carried out (55% conversion versus no conversion after
20 min and 99% conversion versus 35% conversion after
35 min). The activation of the catalyst only took place in
this particular case. No activation was observed when
16d was previously heated for 3.5 h with phenyl iodide,
TEA, or methyl acrylate in DMF, where lower con-
versions were always obtained when compared with the
standard reaction. A heavy precipitation of Pd black was
16d (0.1 mol % Pd)
DMF, TEA, 110 °C
+
CO2Me
CO2Me
I
First cycle: 99%, 1.2 h
Second cycle: 97%, 1.5 h
Third cycle: 98%, 2 h
Fourth cycle: 96%, 2 h
Scheme 6.
of phenyl iodide after adding fresh reagents to the observed when complex 16d was heated in the presence
solution (Scheme 6). After the coupling, the reaction of methyl acrylate probably due to Pd-C bond cleavage
mixture usually exhibited the typical yellow-orange with C-C bond-forming reductive elimination.[6a]
colour of palladium in the divalent oxidation state or
We next investigated the reaction of various aryl
colourless when very low catalyst concentrations were halides with methyl acrylate (Scheme 7, Table 4). In the
used. In fact, only Pd(II) could be detected by XPS case of substituted aryl iodides, C-C coupling in the
experiments in the crude reaction mixture after the presence of TEA and catalytic amounts of 16d led
coupling was finished once the DMF and the methyl quantitatively to the corresponding methyl cinnamates.
cinnamate were evaporated under high vacuum con- Table 4 entries 1 5 summarize the results of the
ditions.
It is interesting to note that the catalyst in the first run
catalyzed reactions showing high reactivity for sterically
exhibited an induction period of about 20 min, signify-
ing that the catalytically active species, probably Pd(0)
nanoparticles,[4] was formed during the course of the
reaction.[35,36] This induction stage disappeared in suc-
cessive runs and when the catalyst, previously heated in
DMF, was used for the first run of the Heck coupling. In
this latter case higher conversions in shorter reaction
times were always obtained if compared when no ™pre
+
CO2Me
X
R
16d
DMF, base
CO2Me
R
Scheme 7.
Table 4. Heck coupling of aryl halides with methyl acrylate catalyzed by 16d.
Entry
16d [mol % Pd]
R
X
Base
T [8C]
t [h]
Yield [%][a],[b]
TON
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
0.01
0.01
0.01
0.01
0.01
0.5
0.5
2
0.5
0.5
1-iodonaphthalene
o-CH3
p-CH3O
p-CH3CO
p-Cl
p-CH3CO
p-NO2
p-NO2
TEA
TEA
TEA
TEA
110
110
110
110
110
130
130
130
130
130
130
130
130
130
130
130
130
160
160
24
3
5
6
5
5.5
2
2
24
4
6
24
24
9
5
3
5
4.5
24
>99
>99 (99)
94
97
>99
90
> 99
58
49
91
10000
10000
9400
9700
10000
180
200
29
I
I
I
I
Br
Br
Br
Br
TEA
[c]
[c]
[c]
[c]
[c]
[c]
[c]
[c]
[c]
[c]
[c]
[c]
[c]
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
H
98
1-bromonaphthalene
p-CH3
p-Ph
o-CH3
p-CH3O
o-Br
3,5-dibromo
p-NO2
p-NO2
182
108
160
49
113
185
200
154
920
115
0.5
0.5
0.5
0.5
Br
Br
Br
Br
Br
Br
Cl
Cl
Cl
54
80
24
57
0.5
92
0.5
100
77 (65)
92
0.5[d]
0.1[d]
0.2
[e]
p-OMe
Cs2CO3
23
[a]
Determined by GLC, based on ArX using decane as internal standard. In parenthesis, isolated yield after flash
chromatography.
Reaction conditions: ArX (2 mmol), methyl acrylate (2.4 mmol), base (2.8 mmol), DMF (4 mL), 16d.
The reaction was performed in the presence of TBAB (20 mol %).
n-Butyl acrylate was used as the olefin.
[b]
[c]
[d]
[e]
The reaction was performed in 1,4-dioxane and using LiBr (20 mol %) and n-butyl acrylate as the olefin.
176
Adv. Synth. Catal. 2002, 344, 172 183

Oxime-Derived Palladium Catalyst for Heck Mizoroki Reaction
FULL PAPERS
hindered ortho-substituted aryl iodides (entry 2). TOF times, employing, in this case, n-butyl acrylate as the
numbers generally ranged from 415 to 6700. Less olefin to give the corresponding cinnamate in a 92%
reactive electron-rich aryl iodides (Table 4, entries 2 yield. In the case of using p-chloroacetophenone,
and 3), did not require either higher catalyst concen- Michael addition to the alkene was a competing side
trations or longer reaction times.
reaction which predominated at these high temper-
The catalytic activity with aryl bromides[37] depends atures. When a deactivated aryl chloride such us p-
on the substitution of the aryl moiety (Table 4, en- chloroanisole was coupled with n-butyl acrylate, TBAB
tries 6 16). When the reaction was performed under was replaced by LiBr as cocatalyst and the reaction was
Jeffery×s conditions,[38] electron-withdrawing groups on carried out in the presence of Cs2CO3 and dioxane at
the aryl ring such as p-NO2 and p-CH3CO increased the 160 8C to give the substituted product in a low yield
reaction rate (Table 4, entries 6 and 7). When increasing (23%).
the catalyst loading from 0.5 to 2 mol % in the coupling
In order to study the effect of the olefin in the Heck
of p-bromonitrobenzene with methyl acrylate, the coupling, the reaction of aryl halides with styrene, p-
reaction rate diminished noticeably probably due to methoxystyrene, p-chlorostyrene, acrylonitrile, 2,3-di-
palladium metal aggregation (58% conversion after 2 h, hydrofuran and ethyl vinyl ether, was investigated in the
85% after 6 h). The coupling of 1-bromonaphthalene presence of palladacycles 16. The results are summar-
and methyl acrylate was finished in 4 h affording the ized in Tables 5 7. In the case of aryl iodides (Scheme 9,
corresponding product in an excellent 91% yield. On the Table 5), styrene gave very good conversions, with non-
contrary, bromobenzene, a relatively inactive halide, activated and activated substrates employing catalyst
gave a 49% yield of (E)-methyl cinnamate after 24 h. loadings between 0.1 and 0.01 mol % of Pd. With phenyl
Bromobenzenes substituted with electron-donating iodide (Table 5, entry 2) it was possible to reduce the
groups (Table 4, entries 11 14) required longer reac- catalyst loading to 10À2 mol % of Pd to produce a
tion times, especially when increasing the steric hin- mixture of a- and b-arylated products (a/b ˆ 1/7) in 87%
drance via ortho-substitution (Table 4, entry 13). Ex- total yield (TON ˆ 8700, TOF ˆ 100 hÀ1). The reaction
cellent yields were obtained when polybromobenzenes
such us 1,2-dibromobenzene and 1,3,5-tribromoben-
zene reacted with an excess of olefin affording the
Table 5. Heck coupling of aryl iodides with olefins catalyzed by 16.
Yield[b] [%]
Entry
t [h]
Aryl Iodide
I
16[a] [mol % Pd]
R
TON
980
corresponding aromatic di- and triacrylic methyl es-
ters.[39] ortho-Diethenylarenes have been used in the
synthesis of annulenes[40] and furans[41] as well as for the
preparation of enantiomerically pure cis-pentacin de-
rivatives[42] and antitumor antibiotics.[43] On the other
hand, 1,3,5-triethenylarenes could be used as a three-
directional core for a divergent dendrimer synthesis[44]
(Scheme 8 and Table 4, entries 15 and 16).
98[c]
16b (0.1)
Ph
1
4
I
87[c]
40
16b (0.01)
Ph
2
29
8700
I
I
p-MeOC6H4
p-ClC6H4
CN
16d (0.1)
16d (0.1)
16d (0.1)
3
4
5
6
6
9
400
350
530
O2N
35
We were pleased to observe that aryl chlorides[37] can
also be used (Table 4, entries 17 19). For example, the
coupling reaction of p-nitrochlorobenzene with methyl
acrylate mediated by 16d under Jeffery×s conditions
gave the desired cinnamate in a 65% yield (entry 17).
When lower catalyst loadings were used (0.1 mol % of
Pd, Table 4, entry 18) it was necessary to increase the
reaction temperature to 160 8C for similar reaction
O2N
I
53[d]
O2N
[a] Reaction conditions: ArI (2 mmol), alkene (2.4 mmol), TEA (2.8 mmol), 16, DMF (4
mL), 110 °C (bath temperature).
[b] Determined by GLC, based on ArI using decane as internal standard.
[c] α-Arylation product was also detected by GLC and 1H NMR analysis of the crude
reaction mixture in a 11% yield.
[d] E/Z = 6/1, determined by 1H NMR of the crude reaction mixture.
CO2Me
Br
Br
CO2Me
16d (0.5 mol % Pd), K2CO3
CO2Me
Bu4NBr, DMF, 130 °C
Br
CO2Me
Br
Br
MeO2C
CO2Me
Scheme 8.
Adv. Synth. Catal. 2002, 344, 172 183
177

Diego A. Alonso, et al.
FULL PAPERS
Table 6. Heck coupling of aryl bromides with olefins catalyzed by 16d.
I
[a] T [°C]
Yield [%][b]
+
R
Aryl Bromide
Entry
X
[mol % Pd]
t [h]
R
TON
174
Br
87(65)
1
0.5
2
Ph
130
R
16
O2N
O2N
O2N
Br
Br
X
>99(99)[c]
>99(97)
72[d]
DMF, TEA, 110 °C
p-MeOC6H4
p-ClC6H4
CN
2
0.5
130
4
200
Scheme 9.
3
4
0.5
0.5
130
130
4
4
200
144
Br
Br
Br
R
16d, TBAB
O2N
O2N
+
R
X
X
Solvent, K2CO3
OEt
130
130
40[e],[f]
83[h]
5
6
0.5
0.5
5
2
80
Br
Scheme 10.
[g]
166
-
MeCO
Ph
Br
83(45)
Ph
Ph
7
8
0.5
130
160
6
2
166
500
of p-iodonitrobenzene with other olefins led to the
resultant coupled products in moderate to good yields
(Table 5, entries 3 5).
Br
Br
Br
>99(98)[j]
0.2[i]
96[j]
88[j]
0.2[i],[k]
0.001[i]
160 3.5
480
9
Ph
Ph
The reaction of activated aryl bromides, such as p-
bromoacetophenone and p-bromonitrobenzene with
different olefins under PTC conditions, consistently
resulted in reasonable yields of 40 99% with
0.25 mol % of 16d (Scheme 10, Table 6, entries 1 6).
The coupling of 4-substituted styrenes with p-bromoni-
trobenzene (Table 6, entries 1 3), led to the corre-
sponding stilbenes with very good yields in all cases,
providing evidence that the efficiency of the catalyst in
this particular case is not so sensible towards electronic
factors. The reaction of p-bromonitrobenzene with enol
ethers, such us ethyl vinyl ether, showed a strong
preference for the b-arylation as reported by Herrmann
et al.[7a] In fact, no a-arylation product was detected by
GLC analysis (Table 6, entry 5). In the case of acryloni-
trile, a mixture of (E)- and (Z)-4-nitrocinnamonitrile in
74% yield (58/14) (Table 6, entry 4) was obtained. The
reaction with 2,3-dihydrofuran afforded a mixture of
regioisomers in a 74/7 ratio (Table 6, entry 6). Bromo-
benzene, a relatively deactivated halide, gave 92%
isolated yield of trans-stilbene after 2 h using only
0.2 mol % of Pd at 160 8C (Table 6, entry 8). The
reaction also worked (Table 6, entry 9) in the absence
160
24
10
88000
Br
Br
>99(78)[l]
97(85)[l]
Ph
Ph
0.2[i]
11
12
160
2
500
MeO
MeO
0.001[i]
97000
160 16
[a] Reaction conditions: ArBr (2 mmol), alkene (2.4 mmol), K2CO3 (2.8 mmol), TBAB (20
mol %), 16d, DMF (4 mL).
[b] Determined by GLC, based on ArBr using decane as internal standard. In
parenthesis, isolated yield after flash chromatography.
[c] α-Arylation product was obtained in a 3% yield, determined by GLC analysis of the
crude reaction mixture.
[d] E/Z = 4/1, determined by 1H NMR of the crude reaction mixture.
[e] E/Z = 5/3, determined by 1H NMR of the crude reaction mixture.
[f] Significant amounts of bis-p-nitrophenyl ether were also obtained.
[g] 2,3-Dihydrofuran.
[h]10/1 Mixture of regioisomers: 5-(4-acetophenyl)-2,3-dihydrofuran (74%) and
2-(4-acetophenyl)-2,3-dihydrofuran (7%).
[i] The reaction was carried out in NMP (4 mL).
[j] α-Arylation product was detected by GLC and 1H NMR analysis of the crude reaction
mixture in ca. 6% yield.
[k] The reaction was carried out in the absence of TBAB.
[l] E/Z = 9/1, determined by GLC analysis of the crude reaction mixture.
Cl
R
16d
+
R
X
X
Solvent, K2CO3
of TBAB, affording nearly the same yield but with lower Scheme 11.
turnover rates (3.5 h) and with a higher amount of a-
arylated product (1,1-diphenylethene, 10%). To test the
activity of the palladacycle 16d with bromobenzene, the (E)-4-nitrostilbene in high yield (93% conversion, 70%
reaction was performed using only 10À3 mol % of Pd isolated yield, TON ˆ 186, Table 7, entry 1). As illus-
(Table 6, entry 10), achieving at 160 8C in NMP as trated in entries 2 4, Heck couplings of p-chloroaceto-
solvent, very good activity (TON ˆ 88000, TOF ˆ phenone with styrene proceeded with low conversions
3667 hÀ1). Prompted by this very promising result, the under standard conditions (0.5 mol % of Pd, 130 8C)
activity of the oxime-derived catalyst was tested with and no progress was made when a higher concentration
deactivated substrates such as p-bromoanisole which, of TBAB (50 mol %) was used (entry 3), probably due
after only 16 h and using 10À3 mol % of Pd under air, to the blocking of free coordination sites of low-ligated
gave the corresponding stilbene with excellent conver- palladium(0) complexes by the excess of halide concen-
sions (97% conversion, 85% yield) and with record tration.[46] Once more, just by increasing the reaction
figures with respect to catalyst activity (TON ˆ 97000, temperature to 160 8C and in the presence of 20 mol %
TOF ˆ 6063 hÀ1).[45]
of TBAB, the desired (E)-4-acetylstilbene was obtained
With regard to aryl chlorides (Scheme 11, Table 7), p- in a very good yield in only 2 h. Only in the case of the
chloronitrobenzene, an activated substrate, afforded Heck coupling with p-chloronitrobenzene did the elec-
178
Adv. Synth. Catal. 2002, 344, 172 183

Oxime-Derived Palladium Catalyst for Heck Mizoroki Reaction
FULL PAPERS
Table 7. Heck coupling of aryl chlorides with styrenes catalyzed by 16d.
O
X
Yield[b] [%]
Entry
T [°C]
Aryl Chloride
[mol% Pd][a]
t [h]
R
TON
186
H
Ph
Ph
+
Cl
93(70)
Ph
1
0.5
130
8
O2N
Cl
O
Ph
130
130
2
3
0.5
4
4
40
80
70
16d (1 mol % Pd), K2CO3
MeCO
Ph
Cl
Cl
DMF, Bu4NBr, 130 or 160 °C
Ph
Ph
0.5
0.5
35[c]
Ph
MeCO
MeCO
X = Br, 2 h, 98%
160
160
4
5
2
6
100
200
180
X = Cl, 6 h, 94% (60%)
Cl
90(80)[d]
p-MeOC6H4
p-ClC6H4
0.5
0.5
O2N
O2N
NH2
I
Cl
R
R
+
>99(95)
6
160
4
200
Cl
Cl
7
8
Ph
Ph
0.5[e]
0.5[e]
160 24
60[f]
120
140
H
N
16d (1 mol % Pd), K2CO3
DMF, Bu4NBr, 130 °C
R
30
70[g]
160
N
Cl
R
9
0.2[e],[h]
24
160
110
Ph
22
R = C3H7, 9 h, 93% (55%)
R = Ph, 10 h, 98% (50%)
R = TMS, 4 h, 47%
MeO
[a] Reaction conditions: ArCl (2 mmol), alkene (2.4 mmol), K2CO3 (2.8 mmol), TBAB
(20 mol %), DMF (4 mL).
Scheme 12.
[b] Determined by GLC, based on ArCl using decane as internal standard. In
parenthesis isolated yield after flash chromatography.
[c] 50 mol % of TBAB was used.
[d] α-Arylation product was also detected by GLC and 1H NMR analysis of the crude
aldehyde reacted with tolane to produce 2,3-diphenyl-
indenone in a 98 and 94% conversion, respectively.
However 2-iodoaniline reacted with both hindered and
unhindered alkyl-, silyl-, and aryl-substituted alkynes
such as 4-octyne, bis(trimethylsilyl)acetylene, and tol-
ane with the conversions showed in Scheme 12.[50] This
annulation chemistry clearly demonstrates the versatil-
ity of oxime-derived palladacycles, as indenones and
reaction mixture in a 8% yield.
[e] The reaction was performed in NMP.
[f] α-Arylation product was also detected by GLC and 1H NMR analysis of the crude
reaction mixture in a 6% yield.
[g] α-Arylation product was also detected by GLC and 1H NMR analysis of the crude
reaction mixture in a 13% yield.
[h] LiBr (20 mol %) was used instead of TBAB.
tronic nature of the olefin come up as an important indoles are important features of a variety of natural and
feature. p-Chlorostyrene showed higher reaction rate medicinal products.
and better regioselectivity than p-methoxystyrene (Ta-
ble 7, entries 5 and 6). Non-activated aryl chlorides, such
as chlorobenzene and 2-chloropyridine took longer Conclusion
reaction times in the Heck coupling reaction with
styrene but still the substitution products were obtained In conclusion, oxime-derived palladacycles represent
in good yields (60% and 70%, respectively). In the case very efficient catalyst precursors for the Heck olefina-
of deactivated aryl chlorides (p-chloroanisole), a dra- tion of haloarenes. Extraordinary turnover numbers and
matic salt effect appeared as TBAB (no conversion after rates have been obtained under aerobic conditions for
48 h) had to be replaced by LiBr to afford the aryl iodides (TON up to 1010 and TOF up to 1.4Â108 hÀ1)
corresponding stilbene in 22% yield, showing that small and deactivated aryl bromides (TON up to 97000, TOF
changes in the co-catalyst really improve the catalyst up to 6063 hÀ1). Aryl chlorides presented turnover
productivity.
numbers up to 920 in the Heck coupling with olefins,
showing an important salt effect in the reaction per-
formance, in the case of deactivated substrates. More-
over, we have shown these systems as competent
catalysts for the palladium-catalyzed annulation of
internal alkynes by o-iodoaniline, o-bromo-, and o-
Annulation Reactions of Internal Alkynes Catalyzed
by Palladacycles 16
The synthesis of 2,3-disubstituted indenones[47] and chlorobenzaldehyde to afford indoles and indenones in
indoles[48] via annulation of internal alkynes[49] with 2- good to excellent yields. These catalysts are thermally
bromobenzaldehyde, 2-chlorobenzaldehyde, and 2-io- stable complexes not sensitive to air or moisture and can
doaniline, respectively, was achieved with 0.5 mol % of be synthesized from readily cheap and available starting
palladacycle 16d with yields ranging from 47 to 98% materials using a straightforward procedure. Their easy
(Scheme 12). 2-Bromobenzaldehyde and 2-chlorobenz- synthetic accessibility and structural versatility make
Adv. Synth. Catal. 2002, 344, 172 183
179

Diego A. Alonso, et al.
FULL PAPERS
Catalyst 16c: IR (KBr): n ˆ 3389 (OH), 1607 (C ˆ N), 1253
(C-O) cmÀ1; 1H NMR (DMSO-d6): d ˆ 3.72 (s, 6H, 2ÂOCH3),
3.83 (s, 6H, 2ÂOCH3), 6.73 (m, 4H, ArH), 7.09-7.44 (m with 2d,
J ˆ 8.6 Hz, 10H, ArH), 9.88, 10.30 (2m, 2H, NOH); 13C NMR
(125 MHz, CDCl3): d ˆ 55.2, 55.3, 110.5, 113.3, 113.5, 118.8,
120.7, 128.8, 130.9, 131.2, 134.3, 152.6, 158.3, 160.8, 165.8.
Catalyst 16d: IR (KBr): n ˆ 3691 3100 (OH) cmÀ1;
1H NMR (DMF-d7): d ˆ 6.76 (d, 2H, J ˆ 7.93 Hz, ArH), 7.11
(dd, 2H, J ˆ 7.93, 1.83 Hz, ArH), 7.64 7.71 (m, 8H, ArH), 7.78
(m, 2H, ArH), 10.83 10.86 (m, 2H, NOH); 13C NMR (DMF-d7
): d ˆ 124.9, 128.8, 129.0, 129.5 131.5, 133.0, 135.4, 136.0, 142.2,
152.0, 166.6.
these complexes very promising catalysts and further
studies in their applicability in other organic trans-
formations are currently under investigation.
Experimental Section
General
The reagents and solvents were obtained from commercial
sources and were generally used without further purification.
Gas chromatographic analyses were performed on an HP-5890
instrument equipped with a WCOT HP-1 fused silica capillary
Catalyst 17: IR (KBr): n ˆ 3080 3590 (OH), 1655 (C ˆ N)
cmÀ1; 1H NMR (500 MHz, DMSO-d6): dH ˆ 1.17 (s, 12H,
4ÂCH3C), 1.91 (s, 6H, 2ÂCH3C ˆ N), 2.36 (s, 4H, 2ÂCH2
Pd), 9.82 (s, 2H, 2ÂNOH); 13C NMR (125 MHz, DMSO-d6):
d ˆ 12.1, 27.6, 48.2, 48.7, 178.8.
1
column. H NMR spectra were recorded on Bruker AC-300
Catalyst 18: IR (KBr): n ˆ 3404 (OH), 1622 (C ˆ N) cmÀ1;
1H NMR (500 MHz, DMSO-d6): d ˆ 2.19 (s, 6H, 2ÂCH3), 4.14-
4.29 (m, 12H, 2ÂArH), 4.58 (s, 2H, 2ÂArH), 4.78 (s, 2H, ArH),
9.41 (s, 2H, 2ÂNOH).
MHz (300 MHz) and Bruker Avance (500 MHz). Chemical
shifts are reported in ppm using either tetramethylsilane (TMS,
0.00 ppm) or DMSO as internal standards. 13C NMR spectra
were recorded at 75 MHz with CDCl3, DMSO-d6 or DMF-d7 as
the internal reference. The catalysts were weighed up in an
electronic microscale (Sartorius, XM1000P) with precision of
1 mg. IR data were collected on a Nicolet Impact 400D of FT.
The XPS spectra have been obtained with a VG-Microtech
Multilab electron spectrometer, by using the Mg Ka
(1253.6 eV) radiation of twin anode in the constant analyser
energy mode with pass energy of 50 eV. Pressure of the analysis
chamber was maintained at 5 ¥ 10À10 mB. The binding energy
and the Auger kinetic energy scale were regulated by setting
the C1s transition at 284.6 eV. The accuracy of BE and KE
values was Æ 0.2 and Æ 0.3 eV, respectively. The BE and KE
values were obtained by using the Peak-fit Program imple-
mented in the control software of the spectrometer. The
reactions were set up in parallel with the aid of an RR98030
12 place Carousel Reaction StationTM equipped with gas tight
threaded caps with valve, cooling reflux head system and
digital temperature controller from Radleys Discovery Tech-
nologies.
Synthesis of Palladacycle 16e
A solution of PdCl2(PhCN)2 (188 mg, 0.49 mmol) and the
oxime (94 mg, 0.49 mmol) in acetonitrile (20 mL) was refluxed
at 85 8C for 4 h. Then, the precipitate was filtered and dried
(15 mm Hg) to afford catalyst 16e; yield: 40%. IR (KBr): n ˆ
1
3454 (OH), 1615, 1604 (C ˆ N) cmÀ1; H NMR (DMSO-d6):
d ˆ 2.27, 2.30 (2s, 12H, 4ÂCH3), 7.03 (s, 2H, ArH), 7.24 (m, 4H,
ArH), 10.15 (s, 2H, 2ÂNOH), 11.84 (s, 2H, 2ÂNOH);
13C NMR (DMSO-d6): d ˆ 11.2, 22.2, 118.7, 123.3, 125.9,
130.8, 136.7, 143.0, 165.6, 166.8.
Reduction of Complexes 16 with Sodium
Cyanoborodeuteride
To a mixture of the complex to be reduced (0.125 mmol) in
THF (2.5 mL) and MeOH (1.25 mL), sodium cyanoborodeu-
teride (0.25 mmol, 168 mg) was added portionwise at 0 8C and
the mixture was stirred for 1 h allowing to warm to room
temperature. The black precipitate was filtered off, the
solvents were evaporated (15 mm Hg) and the residue hydro-
lyzed with water, extracted with dichloromethane, the organic
layer dried (Na2SO4), and evaporated (15 mm Hg). The differ-
ent deuterated oximes were obtained with yields between 90
99%.
Synthesis of Palladacycles 16a 16d and 17 18
To a solution of Li2PdCl4 (2.62 g, 10 mmol) in methanol
(20 mL), a methanolic solution (10 mL) of the corresponding
oxime (10 mmol) and sodium acetate (0.82 g, 10 mmol) was
added. Then, the solution was stirred for 2 to 3 d at room
temperature, the mixture was filtered and after adding water
(10 mL), the corresponding cyclopalladated complexes pre-
cipitated. The different catalysts 16 were obtained with yields
between 60 98%. Yields and physical data are given in
Table 1, spectral data follow:
Deuterated oxime 20a: Rf: 0.63 (hexane/EtOAc, 3/2); mp
52 53 8C; IR (KBr): n ˆ 3239 (OH), 1645 (C ˆ N) cmÀ1;
1H NMR (DMSO-d6): d ˆ 2.14 (s, 3H, CH3), 7.36 7.65 (2m,
4H, ArH), 11.17 (s, 1H, NOH); 13C NMR (DMSO-d6): d ˆ 11.5,
125.5, 128.2, 128.3, 128.6, 136.9, 137.0 and 152.9; MS: m/z (rel.
Catalyst 16a: IR (KBr): n ˆ 3430 (OH), 1638 (C ˆ N) cmÀ1;
1H NMR (DMF-d7): d ˆ 2.31 (s, 6H, 2ÂCH3C ˆ N), 6.94 6.99
(m, 2H, ArH), 7.04 7.09 (m, 2H, ArH), 7.23 7.26 (m, 2H
ArH), 7.62 7.64 (m, 2H, ArH), 10.30 (m, 2H, NOH);
13C NMR (DMF-d7): d ˆ 11.05, 124.8, 126.2, 128.4, 135.6,
143.4, 150.6, 167.9.
‡
int.) ˆ 136 (M , 39), 135 (49), 107 (13), 106 (12), 104 (20), 103
(21), 95 (18), 94 (17), 79 (29), 78 (100), 77 (95), 76 (18), 67 (16),
66 (25), 65 (13), 63 (11), 52 (43), 51 (82), 50 (42), 42 (26), 40 (22).
Deuterated oxime 20b: Rf: 0.74 (hexane/EtOAc, 3/2); mp
143 144 8C; IR (KBr): n ˆ 3243 (OH), 1660 (C ˆ N) cmÀ1;
1H NMR (DMSO-d6): d ˆ 7.87 8.04 (2m, 9H, ArH), 9.35
9.52 (m, 1H, NOH); 13C NMR (DMSO-d6): d ˆ 126.9, 127.0,
128.1, 128.2, 128.3, 128.4, 128.8, 128.9, 135.5, 136.65, 136.74,
Catalyst 16b: IR (KBr): n ˆ 3373 (OH), 1645 (C ˆ N) cmÀ1;
1H NMR (DMF-d7): d ˆ 6.73 (m, 2H, ArH), 7.00 (m, 4H, ArH),
7.59 (m, 10H, 2ÂPhH), 7.76 (m, 2H, ArH), 10.47 (m, 2H,
NOH); 13C NMR (DMF-d7): dC ˆ 124.8, 127.9, 128.4, 129.2,
129.5, 130.2, 130.6, 136.1, 143.7, 151.1, 167.6.
180
Adv. Synth. Catal. 2002, 344, 172 183

Oxime-Derived Palladium Catalyst for Heck Mizoroki Reaction
FULL PAPERS
‡
‡
155.1; MS: m/z (rel. int.) ˆ 198 (M , 44), 197 (M 1, 28), 181
(45), 180 (28), 166 (14), 165 (12), 104 (11), 94 (12), 90 (14), 83
(20), 78 (43), 77 (100), 52 (26), 51 (79), 50 (29).
were always washed with concentrated HNO3 overnight prior
to use in a new catalytic reaction.
Deuterated oxime 20c: Rf: 0.46 (hexane/EtOAc, 3/2); mp
134 136 8C; IR (KBr): n ˆ 3227 (OH), 1609 (C ˆ N), 1252 (C-
O) cmÀ1; 1H NMR (CDCl3): d ˆ 3.82, 3.87 (2s, 6H, 2ÂOCH3),
6.84 6.87 (m, 2H, ArH), 6.99 (d, J ˆ 8.6 Hz, 2H, ArH), 7.40
7.44 (m, 3H, ArH), 11.00 (s, 1H, NOH); 13C NMR (CDCl3): d ˆ
55.2, 55.3, 113.5, 113.6, 113.7, 124.9, 129.1, 129.2, 129.4, 131.1,
Typical Experimental Procedure for Heck Coupling of
Aryl Bromides with Olefins
A 25-mL, round-bottom flask was charged with p-bromoni-
trobenzene (412 mg, 2 mmol), styrene (268 mL, 2.4 mmol),
potassium carbonate (387 mg, 2.8 mmol), tetrabutylamonium
bromide (129 mg, 0.4 mmol), catalyst 16d (4.079 mg,
0.005 mmol, 0.5 mol % Pd) and DMF (4 mL). The mixture
was stirred at 130 8C in air and the reaction progress was
analyzed by GLC. The reaction mixture was poured into excess
water and extracted several times with ethyl acetate. The
organic extract was dried and evaporated to afford (E)-4-
nitrostilbene; yield: 65% (pure on GLC and 1H NMR).
‡
157.0, 160.0, 160.6; MS: m/z (rel. int.) ˆ 243 (M 1, 26), 242
(11), 212 (13), 136 (67), 135 (100), 107 (12), 93 (11), 92 (16), 78
(19), 77 (33), 64 (15).
Deuterated oxime 20d: Rf: 0.68 (hexane/EtOAc, 3/2); mp
136 137 8C; IR (KBr): n ˆ 3617 3093 (OH), 1630 (C ˆ N)
cmÀ1; 1H NMR (DMSO-d6): d ˆ 7.30 7.46 (m, 5H, ArH), 7.53
(d, J ˆ 8.6 Hz, 2H, ArH), 11.58 (s, 1H, NOH); 13C NMR
(DMSO-d6): d ˆ 128.3, 128.4, 128.5, 128.59, 128.60, 130.9,
131.7, 133.3, 133.7, 135.1, 135.2, 153.2; MS: m/z (rel. int.) ˆ
‡
‡
268 (M ‡ 2, 28), 266 (M , 49), 251 (25), 250 (25), 249 (35), 248
(21), 215 (18), 154 (24), 153 (39), 139 (17), 138 (20), 114 (15),
113 (27), 112 (46), 111 (58), 100 (19), 82 (34), 75 (100), 52 (15),
51 (46), 54 (59), 40 (17).
Typical Experimental Procedure for Heck Coupling of
Aryl Chloride with Olefins
A 25-mL, round-bottom flask was charged with p-chloroni-
trobenzene (318 mg, 2 mmol), methyl acrylate (216 mL,
2.4 mmol), potassium carbonate (387 mg, 2.8 mmol), tetrabu-
tylamonium bromide (129 mg, 0.4 mmol), catalyst 16d
(4.079 mg, 0.005 mmol, 0.5 mol % Pd) and DMF (4 mL). The
mixture was stirred at 130 8C in air and the reaction progress
was analyzed by GLC. The product was isolated by pouring the
reaction mixture into excess water and extracting the aqueous
phase several times with ethyl acetate. The organic phases were
dried, evaporated (15 mm Hg) and the resulting crude product
was purified by flash chromatography (hexane/EtOAc) af-
fording methyl 3-(4-nitrophenyl)-2-propenoate; yield: 267 mg
(65%).
Deuterated oxime 20e: Rf: 0.53 (EtOAc); IR (KBr): n ˆ 3299
1
(OH), 1663, 1608 (C ˆ N) cmÀ1; H NMR (DMSO-d6): d ˆ
7.27 7.29 (m, 2H, ArH), 7.55 7.57 (m, 1H, ArH), 7.90 [s,
0.4H, ArH (partially deuterated)], 9.96 (s, 1H, NOH), 11.18 (s,
‡
‡
1H, NOH); MS: m/z (rel. int.) ˆ 193 (M , 22%), 192 (M 1,
14), 151 (19), 150 (14), 134 (18), 133 (15), 119 (14), 109 (17), 93
(14), 92 (16), 81 (14), 66 (16), 65 (14), 64 (11), 44 (31), 43 (100).
Deuterated oxime 22: Rf: 0.68 (hexane/EtOAc, 3/2); IR
(KBr): n ˆ 3631 3174 (OH), 1647 (C ˆ N) cmÀ1; 1H NMR
(DMSO-d6): d ˆ 2.04 (s, 3H, CH3CNOH), 4.16 (s, 5H, ArH),
4.30, 4.51 (2s, 3H, ArH), 10.57 (s, 1H, NOH); 13C NMR
(DMSO-d6): d ˆ 12.6, 66.08, 66.11, 68.9, 69.0, 82.6, 82.7, 152.9;
‡
MS: m/z (rel. int.) ˆ 244 (M , 100), 243 (20), 228 (10), 138 (24),
130 (11), 129 (10), 121 (29), 106 (12), 105 (12), 95 (11), 82 (11),
81 (16), 73 (38), 66 (12), 65 (19), 63 (13), 57 (11), 56 (100), 44
(53), 43 (22), 42 (15), 41 (12), 40 (62).
Typical Experimental Procedure for Annulation of
Alkynes
A 25-mL, round-bottom flask was charged with o-iodoaniline
(224 mg, 1 mmol), diphenylacetylene (267 mg, 1.5 mmol),
potassium carbonate (277 mg, 2 mmol), TBAB (65 mg,
0.2 mmol), catalyst 16d (4.079 mg, 0.005 mmol) and DMF
(4 mL). The mixture was stirred at 130 8C in air and the
reaction progress was analyzed by GLC. The product was
isolated by pouring the reaction mixture into excess water and
extracting the aqueous phase several times with ethyl acetate.
The organic phases were dried, evaporated (15 mm Hg) and
the resulting crude product was purified by flash chromatog-
raphy (hexane/EtOAc) affording 2,3-diphenylindole; yield:
116 mg (43%).
Typical Experimental Procedure for Heck Coupling of
Aryl Iodides with Olefins
A 25-mL, round-bottom flask was charged with iodobenzene
(570 mL, 5 mmol), methyl acrylate (540 mL, 6 mmol), triethyl-
amine (978 mL, 7 mmol), catalyst 16d (204 mg, 0.00025 mmol,
0.01 mol % Pd) and DMF (8 mL). The mixture was stirred at
110 8C in air and the reaction progress was analyzed by GLC.
The crude reaction mixture was extracted with water and
EtOAc (3Â15 mL). The organic phases were dried, evapo-
rated (15 mm Hg) and the resulting crude product was purified
by flash chromatography (hexane/EtOAc) affording methyl
cinnamate; yield: 749 mg (92%, 98% pure by GLC analysis).
In order to set up reactions under very highly diluted
conditions (10À3 mol % Pd) the different catalyst concentra-
tions were obtained by successive dilution of an initial catalyst
solution prepared by dissolving catalyst 16d in toluene
(maximum concentration, 3 mg of 16d/10 mL of toluene to
get the catalyst completely dissolved). The catalyst solution
was then introduced in the reaction mixture once all the
reactants and solvent had been added. In order to avoid
undesired ™reaction vessel or stirrer catalytic activity∫ they
Acknowledgements
This work has been supported by the DGES of the Spanish
¬
Ministerio de Educacion y Cultura (MEC) (PB97-0123). D. A.
A thanks MEC for a contract under the program Acciones para
¬
¬
la Incorporacion a Espanƒa de Doctores y Tecnologos. M. C. P.
thanks Generalitat Valenciana for a predoctoral fellowship.
Adv. Synth. Catal. 2002, 344, 172 183
181

Diego A. Alonso, et al.
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Adv. Synth. Catal. 2002, 344, 172 183

Oxime-Derived Palladium Catalyst for Heck Mizoroki Reaction
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.
Adv. Synth. Catal. 2002, 344, 172 183
183