A simple and efficient copper-free catalytic system based on a palladacycle for the arylation of alkynes

Article abstract of DOI:10.1002/adsc.200505310

The palladacycle [Pd(k²-C,N-C=(C₆H ₅)C(Cl)CH₂NMe₂)(μ-Cl)]₂ (1) derived from the chloropalladation of 3-(dimethylamino)-1-phenyl-1-propyne and its phosphine adduct [Pd(k²-C,N-C=(C₆H₅)C(Cl) CH₂NMe₂)P(4-CF₃C₆H₄) ₃(Cl)] (3) promote the alkynylation of bromo- and iodoarenes under relatively mild reaction conditions. The coupling of iodoarenes and activated bromoarenes with terminal alkynes can be conducted at room temperature. Turnover numbers have been achieved up to 10⁵ with iodoarenes and up to 94 for deactivated bromoarenes but at higher temperatures (120°C). Selective poisoning experiments (Hg, Collman and Crabtree tests) suggest that soluble Pd(0) species are the most probable catalytically active species involved in this Csp²-Csp coupling reaction.

Full text of DOI:10.1002/adsc.200505310

FULL PAPERS
DOI: 10.1002/adsc.200505310
A Simple and Efficient Copper-Free Catalytic System Based on a
Palladacycle for the Arylation of Alkynes
Crestina S. Consorti,a Fabricio R. Flores,a Frank Rominger,b Jairton Duponta,*
a
Laboratory of Molecular Catalysis, Institute of Chemistry, Av. Bento GonÅalves, 9500 Porto Alegre 91501-970 RS, Brazil
Fax: (þ55)-51-3316-7304, e-mail: dupont@iq.ufrgs.br
b
Organisch-Chemisches Institut der Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg,
Germany
Fax: (þ49)-6221-487-672, e-mail: frank.rominger@uni-hd.de
Received: August 4, 2005; Accepted: November 21, 2005
2
¼
Abstract: The palladacycle [Pd(k -C,N-C (C6H5)- enes and up to 94 for deactivated bromoarenes but
C(Cl)CH2NMe2)(m-Cl)]2 (1) derived from the chloro- at higher temperatures (1208C). Selective poisoning
palladation of 3-(dimethylamino)-1-phenyl-1-propyne experiments (Hg, Collman and Crabtree tests) sug-
2
¼
and its phosphine adduct [Pd(k -C,N-C (C6H5)C(Cl)- gest that soluble Pd(0) species are the most probable
CH2NMe2)P(4-CF3C6H4)3(Cl)] (3) promote the alky- catalytically active species involved in this Csp2 –Csp
nylation of bromo- and iodoarenes under relatively coupling reaction.
mild reaction conditions. The coupling of iodoarenes
and activated bromoarenes with terminal alkynes
ꢀ
can be conducted at room temperature. Turnover Keywords: arylation; C C bond formation; cross-cou-
numbers have been achieved up to 105 with iodoar- pling; palladacycles; Sonogashira reaction
Introduction
[OP(i-Pr)2]2-2,6}] catalyzes the coupling of aryl chlor-
ides with phenylacetylene in the presence of ZnCl2 as
The arylation (employing aryl halides) of alkenes (Heck co-catalyst to give the products in modest to excellent
coupling), arylboronic acids (Suzuki coupling) and al- yields.[18] The use of relatively high amounts of Pd (typ-
kynes (Sonogashira coupling or Heck alkynylation) ically 5–10%) and copper or zinc salts (10–15%), and
are among the most investigated catalytic processes the use of amines as solvents render this method limited
mediated by transition-metal complexes. Palladium- for practical applications.
based complexes are by far the most used and effective
The alkynylation of aryl halides can be also performed
catalyst precursors for the promotion of such coupling in the absence of Cu salts – the Heck protocol is inher-
reactions.[1,2] Indeed, there is a legion of catalyst precur- ently simpler than the Sonogashira reaction. However,
sors and experimental protocols that allow the Heck and in these cases more drastic reaction conditions must be
Suzuki coupling to be performed with almost any aryl employed (usually temperatures >708C). Moreover,
halide, employing very low Pd loadings (down to ppbs) generally this protocol is limited to vinyl halides, iodoar-
and under mild reaction conditions such as at room tem- enes and bromoarenes substituted with electron-with-
perature.[3–8] In contrast, the current scope of the Pd-cat- drawing groups and relative large quantities of palladi-
alyzed alkynylations of aryl halides is still rather limit- um must be used (2–4%).[19] Relatively more efficient
ed.[9] The classical experimental protocol involves, in Pd catalytic systems can be formed by the use, for exam-
most of the cases, the use of a palladium source such as ple, of [Pd2dba3/P(t-Bu)3][20] or [Pd(h3-alyl)-m-Cl)2]/
[21]
[PdCl2(PPh3)2] or [Pd(PPh3)4] in the presence ofCu salts, P(t-Bu)3 and other Pd compounds associated with
known as the Sonogashira reaction.[10–15] More active phosphines.[22,23] However, large amounts of palladium
catalytic systems have been recently reported that and auxiliary ligands (5 mol % of Pd and 10% of the
employ in most of the cases the Pd complex associated phosphines) must be employed. The Hermann–Beller
with sterically hindered phosphines,[16,17] such as PC-palladacycle is quite active for the coupling of bro-
P(t-Bu)3, but many more persuasive developments and moarenes with phenylacetylene and turnover numbers
examples are certainly needed to fully justify the use up to 8000 in the case of 4-bromoacetophenone have
of structurally more elaborate and/or expensive been reported.[24] However, this system is not active
phosphines. The pincer-type palladacycle [PdCl{C6H3- for other alkynes such as 1-hexyne and trimethylsilyl-
Adv. Synth. Catal. 2006, 348, 133 – 141
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133

Crestina S. Consorti et al.
FULL PAPERS
Scheme 1.
acetylene. Apalladacycle derived from an oxime deriv-
ative is probably the most efficient Pd precursor to pro-
mote the arylation of various alkynes reported to date.
This system typically operates with 0.1 mol % of palladi-
um in the presence of stoichiometric amounts of base
without the addition of phosphine ligands but the reac-
tion has to be performed at 1108C.[25] It is, however, sur-
prisingly that little is known about the catalytically ac-
tive species and reaction paths involved in these Pd-cat-
alyzed alkynylation reactions if compared with the huge
efforts devoted to the Heck and Suzuki couplings.
It is evident that there is a need for more efficient and
simple palladium catalyst precursors that operate under
milder reaction conditions for the arylation of alkynes.
Figure 1. Molecular structure of 2. Selected bond distances
(A) and angles (8): Molecule A: Pd1 C1 2.050(3), Pd1 N1
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
2.186(3), Pd1 P1 2.2722(8), Pd1 Cl1 2.4013(9), C1 C2
ꢀ
ꢀ
ꢀ
ꢀ
1.331(5); C1 Pd1 N1 82.46(11), C1 Pd1 P1 93.55(9),
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
N1 Pd1 P1 173.61(7), P1 Pd1 Cl1 93.13(3), N1 Pd1 Cl1
90.79(8). Molecule B: Pd1 C1 2.057(3), Pd1 N1 2.189(3),
Pd1 P1 2.2613(8), Pd1 Cl1 2.4001(9), C1 C2 1.332(5),
C1 Pd1 N1 83.11(13), C1 Pd1 P1 93.06(10), N1 Pd1 P1
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
175.76(9), P1 Pd1 Cl1 92.71(3), N1 Pd1 Cl1 91.18(9).
We have recently reported that the palladacycle
2
¼
{Pd[k -C,N-C (C6H5)C(Cl)CH2NMe2](m-Cl)}2 (1) de-
rived from the chloropalladation of the 3-(dimethyl- blet for the NMe2 group with a 4JP, H ¼2.4 Hz and 4JP, H
¼
amino)-1-phenyl-1-propyne is amongst the most effec- 2.9 Hz, respectively. The methylene hydrogens also ap-
4
4
tive catalyst precursors for the coupling of haloarenes pear as doublet with JP, H ¼1.4 Hz and JP, H ¼1.9 Hz in
1
with alkenes and in some cases this reaction can be con- the H NMR spectra of 2 and 3, respectively. These
ducted at room temperature.[26] We now report that pal- 4JP, H coupling constants are typical for P-ligands located
ladacycle 1[27] is also an effective catalyst precursor for trans to the Pd-N moieties as observed in analogous
the alkynylation of iodo- and bromoarenes at room tem- monomeric palladacycles. Moreover, the molecular
perature. For comparative purposes we have also inves- structure of 2 has also been ascertained by means of
tigated the electron-rich and electron-poor phosphine X-ray studies. Two independent molecules were found
adducts 2 and 3 (Scheme 1).[28–30] Moreover, poisoning for complex 2 showing only small deviations in the
tests have been performed in order to get insight into phosphine conformation. The structure of 2, together
the nature of the catalytically active species involved with selected bond distances and angles is shown in Fig-
in this Csp2 –Csp coupling reaction.
ure 1.
Crystallographic data and details of the structure de-
termination are presented in Table 1 (see also Experi-
mental Section). In compound 2 the Pd(II) center is co-
ordinated in a distorted square-planar fashion by the N
and the P donor groups, a C(sp2) vinyl atom and a Cl
atom. The C(vinyl) Pd Cl bond angle is 173.58 and
the P and N donor groups are also in mutual trans posi-
tions with a bond angle of 174.68 showing an angular de-
Results and Discussion
Preparation and Characterization of Palladacycles 2
and 3
ꢀ
ꢀ
The phosphine adducts 2 and 3 were prepared in good viation of 5.48 from exact trans coordination. The loca-
yields by simple addition of di-t-butylphosphine or tion of the P-ligand trans to the NMe2 group is reflected
ꢀ
tris-p-trifluoromethane-phenylphosphine, respectively, on the Pd N bond distance of 2.187 Š in 2 that is larger
to a dichloromethane solution of palladacycle 1 at than that observed in the dimeric palladacycle 1
room temperature. The monomeric palladacycles 2 (2.064 Š).[31] The s Pd C(vinyl) single bond in 2
ꢀ
and 3 were isolated as light yellow powders and charac- (2.054 Š) is slightly larger than those observed in analo-
terized by C,H,N-analysis, 1H and 13C NMR. In particu- gous compounds, where the distances fall in the range
lar the 1H NMR spectra of 2 and 3 in CDCl3 show a dou- between 1.991 and 2.011 Š.
134
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Copper-Free Catalytic System for Arylation of Alkynes
FULL PAPERS
Table 1. Crystal data and structure refinement for 2.
Empirical formula
C19H32Cl2NPPd
Formula weight
Temperature
Wavelength
Crystal system
Space group
Z
482.73
230(2) K
0.71073 Š
Triclinic
P1u¯
4
Unit cell dimensions
a¼11.2665(1) Š
b¼11.6317(1) Š
c¼18.0339(1) Š
a¼87.573(1)8
b¼78.682(1)8
g¼87.020(1)8
3
Volume
2312.98(3) Š
Density (calculated)
Absorption coefficient
Crystal shape
Crystal size
Theta range for data collection
Index ranges
Reflections collected
Independent reflections
Observed reflections
Absorption correction
Max. and min. transmission
Refinement method
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices (I>2s(I))
Largest diff. peak and hole
1.39 g/cm3
1.10 mmꢀ1
polyhedron
0.27ꢁ0.25ꢁ0.25 mm3
1.1 to 27.6 deg.
ꢀ14ꢂhꢂ14, ꢀ15ꢂkꢂ15, ꢀ23ꢂlꢂ23
23933
10495 (R(int)¼0.0312)
7813 (I>2s(I))
Semi-empirical from equivalents
0.77 and 0.75
Full-matrix least-squares on F2
10495/0/447
1.02
R1¼0.037, wR2¼0.084
ꢀ3
0.98 and ꢀ0.66 e Š
Catalytic Performance of Palladacycles 1–3 in the
Alkynylation Reaction
extended to aryl bromides (Table 3) and other alkynes
(Table 4).
The experimental protocol using palladacycle 1 has
The potential of compounds 1–3 as catalyst precursors been thus successfully extended to aryl bromides con-
was initially probed in the coupling of phenylacetylene taining either electron-withdrawing of electron-donat-
with iodobenzene using various reaction conditions (sol- ing groups affording disubstituted alkynes in good
vent, base, temperature and Pd loadings). DMA(dime-
yields. Note the reaction involving bromoarenes substi-
thylacetamide) is the solvent of choice and among the tuted with electron-withdrawing groups can be per-
various bases [NaOAc/NBu4Br, Na2CO3, pyrrolidine, formed at room temperature (see entries 2, 7 and 12, Ta-
HMTA(hexamethylenetetramine) and NEt ] tested, ble 3) in contrast to the bromo substrates containing
3
NBu4OAc gave the best results, although DABCO (di- electron-donating groups where the reaction should be
azabicyclo[2.2.2]octane) can be also used (Table 2, en- performed at highertemperatures (entries 18 and 19, Ta-
tries 1 and 8). Interestingly, the reaction can be per- ble 3) and the phosphine adduct 3 must be used.
formed at room temperature using 1% of 1 (Table 2, en-
The same protocol can be used with other alkynes
tries 1 and 2) or 3 (Table 2, entry 5), and relative short such 1-heptyne and 2-methyl-3-butyn-2-ol. (Table 4).
reaction times (4 h). The loadings of 1 and 3 can be re- However the reaction fails when acetylenes containing
duced down to 0.00005% (Table 2, entries 7 and 10) giv- electron-withdrawing groups are used (Entry 10, Ta-
ing good yield in the diphenylacetylene, but in these cas- ble 4).
es the temperature should be higher (1208C) and longer
reaction times are required.
It is clear that the alkynylation of iodobenzene can be Catalytically Active Species
performed with the phosphine-free palladacycle 1. The
presence of a bulky electron-rich phosphine has a detri- It is now accepted that in most of the cases, the catalyti-
ꢀ
mental effect on the yield (compare entries 2 and 4 of Ta- cally active species involved in C C coupling reactions,
ble 2) although the presence of an electron-poor phos- in particular for Heck and Suzuki protocols, are based
phine has no significant effect on the reaction yield on Pd(0) and that the reaction proceeds through a
(compare entries 6 and 9 of Table 2). Once the best reac- Pd(0)/Pd(II) catalytic cycle whatever the nature of the
tion conditionswere established the catalytic system was catalyst precursor (ionic, molecular, colloidal, support-
Adv. Synth. Catal. 2006, 348, 133 – 141
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135

Crestina S. Consorti et al.
FULL PAPERS
Table 2. Coupling of phenylacetylene with iodobenzene promoted by palladacycles 1–3.[a]
Entry
Pd
[PhI]/[Pd]
Base
T [0C]
t [h]
Conv. [%][b]
Yield [%][b]
1
2
3
4
5
6
7
8
9
1
1
1
2
3
1
1
1
3
3
1.0ꢁ102
1,0ꢁ102
1.0ꢁ103
1.0ꢁ102
1.0ꢁ102
5.0ꢁ104
5.0ꢁ105
5.0ꢁ104
5.0ꢁ104
5.0ꢁ105
DABCO
30
30
30
30
30
120
120
120
120
120
4
4
4
4
4
24
24
24
24
24
89
100
32
52
100
98
82
60
100
62
88
97 (91)
22
NBu4OAc
NBu4OAc
NBu4OAc
NBu4OAc
NBu4OAc
NBu4OAc
DABCO
43
97 (87)
95 (80)
80
52
97 (90)
62
NBu4OAc
NBu4OAc
10
[a]
Reaction conditions: DMA(3 mL), NBu OAc or DABCO (0.7 mmol), phenylacetylene (0.54 mmol), PhI (0.5 mmol).
Yield and conversion obtained by GC (using methyl benzoate as internal standard). Isolated yield in parenthesis.
4
[b]
Table 3. Coupling of bromoarenes with phenylacetylene promoted by palladacycles 1 and 3.[a]
Entry
Pd
ArBr
[ArBr]/[Pd]
T [ 8C]
Conv. [%][b]
Yield [%][b]
1
2
3
4
5
1
1
1
1
1
1
1
1
1
1
1
3
3
3
3
3
3
3
3
2-BrPy
1.0ꢁ102
1.0ꢁ102
1.0ꢁ103
1.0ꢁ104
1.0ꢁ105
1.0ꢁ103
1.0ꢁ102
1.0ꢁ102
1.0ꢁ104
1.0ꢁ105
1.0ꢁ103
1.0ꢁ102
1.0ꢁ103
1.0ꢁ104
1.0ꢁ105
1.0ꢁ102
1.0ꢁ104
1.0ꢁ102
1.0ꢁ102
80
30
50
120
150
80
30
80
120
150
80
92
95
100
87
35
100
77
99
94
42
47
89
100
89
38
68
100
89
94
74
95
97 (90)
82
40
97
75
95 (87)
91
40
50
89
98 (92)
89
39
65
98
78 (60)
90 (80)
4-NCC6H4Br
4-NCC6H4Br
4-NCC6H4Br
4-NCC6H4Br
4-NCC6H4Br
4-MeCOC6H4Br
4-MeCOC6H4Br
4-MeCOC6H4Br
4-MeCOC6H4Br
4-MeCOC6H4Br
4-CNC6H4Br
4-CNC6H4Br
4-CNC6H4Br
4-CNC6H4Br
4-MeCOC6H4Br
4-MeCOC6H4Br
4-MeOC6H4Br
4-MeC6H4Br
6[d]
7[c]
8
9
10
11[d]
12
13
14
15
16
17
18
19
30
50
120
150
30
120
130
130
[a]
Reaction conditions: 4 h, DMA(3 mL), NBu OAc (0.7 mmol), phenylacetylene (0.54 mmol), ArBr (0.5 mmol).
Yield and conversions obtained by GC (using methyl benzoate as internal standard), Isolated yield in parenthesis.
Reaction time 24 hours.
4
[b]
[c]
[d]
DABCO (0.7 mmol) used as base instead of NBu4OAc.
ed or “heterogeneous”).[32–38] In this respect several ap- probe the species involved in the Heck reaction promot-
proaches, such as poisoning experiments, intrinsic kinet- ed by palladacycles only limited conclusions have ap-
ics, and physical-chemical analysis can be used as probes peared so far, most of them indicating that they are
to determine the nature of the ”true“ catalyst.[39,40] Al- pre-catalysts of ill-defined Pd(0) catalytically active spe-
though some of these approaches have been used to cies. In the case of the alkynylation of aryl halides the sit-
136
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Copper-Free Catalytic System for Arylation of Alkynes
Table 4. Coupling of aryl halides with alkynes promoted by palladacycles 1 and 3 under different reaction conditions.[a]
FULL PAPERS
Entry
Pd
ArX
R
[ArX]/[Pd]
T [ 8C]
Conv. [%][b]
Yield [%][b]
1
2
3
4
5
6
7
8
9
1
1
1
3
1
1
1
3
3
1
PhI
PhI
n-C4H9
n-C4H9
n-C4H9
n-C4H9
C(Me2)OH
C(Me2)OH
C(Me2)OH
C(Me2)OH
C(Me2)OH
CO2Et
1.0ꢁ102
1.0ꢁ103
1.0ꢁ102
1.0ꢁ103
1.0ꢁ102
1.0ꢁ102
1.0ꢁ102
1.0ꢁ102
1.0ꢁ102
1.0ꢁ102
30
120
120
120
80
120
120
80
100
98
100
100
75
93
92
72
100
0
98(90)
97
93(85)
98
70
85
45
68
97(90)
0
4-MeCOC6H4Br
PhI
PhI
PhI
4-MeCOC6H4Br
PhI
PhI
PhI
120
30
10
[a]
Reaction conditions: 4 h, DMA(3 mL), NBu OAc (0.7 mmol), acetylene (0.54 mmol), ArX (0.5 mmol).
Yield and conversions obtained by GC (using methyl benzoate as internal standard), isolated yield in parenthesis.
4
[b]
Table 5. Catalytic activity of palladacycle 1 with polymer-
uation is much more complicated since no systematic
investigation has been performed so far in order to
identify the possible catalytic species involved in this
process.
supported alkyne.[a]
Entry Substrate
Acetylene [ArX]/
[Pd]
T
Yield[b]
[ 8C] [%]
In order to characterize the involvement of homoge-
neous or heterogeneous components in the alkynylation
of aryl halides by 1 we have performed the Hg poisoning
test. This test relies on the formation of an amalgam with
colloidal palladium although poisoning of molecular
Pd(0) cannot be excluded.[41] Moreover, a Hg poisoning
test can confirm a homogeneous catalytic system but not
a heterogeneous one. The Hg(0) poisoning test was per-
formed in the coupling of iodobenzene with phenylace-
tylene promoted by palladacycle 1 at room temperature.
When compared to control reactions, a complete inhib-
ition of the catalytic activity was observed after Hg (300
equivalents) addition, confirming the intervention of
Pd(0) species.
1
1.0ꢁ102 30 100
1.0ꢁ105 130 100
2
3
1.0ꢁ106 130
58
[a]
Reaction conditions: 24 h, DMA(3 mL), resin
(0.35 mmol), NBu4OAc (0.7 mmol), phenylacetylene
(0.5 mmol).
[b]
Yield obtained by 1H NMR (using 1,3,5-trihydroxyben-
zene as internal standard) after resin cleavage with TFA/
CH2Cl2
Second, we have performed the Collman test that is
Inasmuch as the Collman test indicates the involve-
based on the ability of substrates attached to cross- ment of homogeneous palladium species we decided
linked polymers in distinguishing homogeneous or het- to run the test with the homogeneous species selective
erogeneous catalytically active species.[42] In this system inhibitor dibenzo[a, e]cyclooctatetraene (DCT). This
only soluble or highly solvated species are able to diffuse test is based on the ability of this diene to form stable
through the polymeric matrix and as a consequence only and inert homogeneous complexes with platinum met-
homogeneous catalytically active species are expected als.[44] However, the irreversibility of the DCT-Pd com-
to show catalytic activity. The catalytic activity of the re- plex formation depends on the temperature and as a
action of iodoarene attached to cross-linked polystyrene consequence, the testꢁs validity also depends on the re-
(Wang resin) promoted by palladacycle 1 is almost sim- action temperature. The general experimental protocol
ilar to those conducted with free substrates and quanti- includes the prior generation of the catalytically active
tative yields of the coupling products can be obtained af- species and the subsequent contact of the active species
ter resin cleavage.
with DCT for at least two hours prior to the addition of
Huge catalytic activities were obtained ([ArX]/[Pd]¼ substrates. With minor adaptation, the Crabtree test was
1.0ꢁ105) (entries 2 and 3, Table 5) even without low applied to the reactions of iodobenzene and iodoarene
concentrations of free substrate (three phase test).[43] attached to the Wang resin with phenylacetylene per-
These results strongly suggest that homogeneous cata- formed at room temperature (Table 6). After 15 mi-
lytically active species are responsible for the catalytic nutes, aliquots were taken from the reactions for quanti-
activity observed.
fication and DCT (2 equivalents.) was added to one re-
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137

Crestina S. Consorti et al.
Relative activity (%)
FULL PAPERS
Table 6. DCT inhibition tests.[a]
Reaction
[DCT]/[Pd]
0
2
100[b]
100[b]
0
2
100[c]
100[c]
[a]
Reaction conditions: DMA(5 mL), phenylacetylene (1.2 mmol) ArI (1 mmol),
1 (1.0ꢁ10ꢀ3 mmol) and NBu4OAc
(1.4 mmol). Experiment with Wang resin with coupled substrate: DMA(3 mL), resin (0.35 mmol), NBu 4OAc
(0.5 mmol), phenylacetylene (0.5 mmol). DCT (2: 1 DCT:Pd) added after reaction time of 15 minutes. Relative activities
were calculated by the yields obtained at reaction times of 15 minutes and 24 h.
[b]
[c]
Yields obtained by GC (using methyl benzoate as internal standard).
1
Yields obtained by H NMR (using 1,3,5-trihydroxybenzene as internal standard) after resin cleavage with TFA/CH2Cl2.
action vessel. After 24 hours, the reactions were stopped coupling products were observed in control experiment
for conversion quantification and comparison. In both performed without the catalytic precursor.
cases no inhibition of the catalytic activity was observed,
suggesting that no Pd(0) molecular complex is involved
in the process.
Effect of Aromatic Substituent on Reaction Rate
The combined Hg, Collman and Crabtree test results
suggest that soluble non-monometallic Pd(0) species To gain some insight into the electronic influence of the
are the catalytically active species. Of note is that the in- p-substituent of the iodoarene on the reaction rate, com-
volvement of Pd(0) nanoparticles as the catalytically ac- petitive experiments using seven aryl iodides were per-
tive species, or as the source of Pd catalytically active formed under pseudo-zero order conditions with re-
species, similar to those proposed in Heck arylation of spect to the iodoarenes. The reaction rates were deter-
alkenes, cannot be ruled out at this stage of our studies mined in the competitive experiments by measuring
but all attempts to identify Pd nanoparticles by transmis- the relative initial reaction rate of iodobenzene and sub-
sion electron microscopy were unsuccessful. However, stituted iodobenzene conversions (activated from deac-
we propose that the reaction probably proceeds through tivated aryl halides). The resulting Hammett plots are
the oxidative addition of the aryl halide to the Pd(0) cat- presented in Figure 2.
ꢀ
ꢀ
alytic species that generates homogenous Ar Pd X
species. The coordination of the alkyne to the metal cen-
ꢀ
ter followed based-assisted H X elimination gave the
ꢀ
ꢃ
Ar Pd-C CR that by reductive elimination yields the
coupling product and Pd(0), analogous to the recently
proposed mechanism of Cu-free Sonogashira cou-
pling.[21]
We do not have any significant information on the
mechanism of formation of the Pd(0) catalytically active
species starting from the palladacycles employed in this
study. However, it is important to note that in all catalyt-
ic tests performed in this study small amounts of the ho-
mocoupling product of the terminal acetylene[45–49] were
observed (1–4 mol %) even for those tests performed
with low initial concentrations of palladium. Moreover,
no experimental evidence was found to support the
hypothesis of the reductive coupling of the terminal ace-
tylene being responsible for the generation of Pd(0) spe-
cies. The homocoupling product of the terminal acety-
lene was not observed when palladacycle 1 was reacted
with a slight excess of phenylacetylene in the presence of
Figure 2. Hammett correlation for the Heck competitive re-
action between iodo arenes and phenylacetylene at 808C in
DMApromoted by 1 using the s0 constants. ( ) DABCO
&
*
the base NBu4OAc. Neither the Sonogashira nor homo- (1¼1.0; R¼0.98) and ( ) NBu4OAc (1¼0.96; R¼0.98).
138
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ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2006, 348, 133 – 141

Copper-Free Catalytic System for Arylation of Alkynes
FULL PAPERS
The use of s0 constants results in good fits and correla- Preparation of Adduct 2
tions yielding a value close to 1¼1.0 independent of the
ASchlenk flask was charged with palladacycle 1 (0.5 mmol,
168 mg) and CH2Cl2 (5 mL). Di-t-butylphosphine (175 mg,
1.2 mmol) dissolved in CH2Cl2 (1 mL) was added to the solu-
tion. After two hours stirring at room temperature, the
CH2Cl2 was concentrated to 0.5 mL and hexane (10 mL) was
added. The reaction mixture was filtered and after removal
of volatiles complex 2 was obtained as a faint yellow solid;
yield: 193 mg (80%). Elemental analysis: C19H32Cl2NPPd
(482.77) requires: C 47.27, H 6.68, N 2.90; found: C 47.38, H
6.54, N 2.99; 1H NMR (CDCl3): d¼7.33–6.93 (m, 5H, H
base used, indicating that the electronic influence on the
reaction rate is not so pronounced if compared with
Heck or Suzuki coupling reactions where 1 values for io-
doarenes can reach 1.8–2.0[50] that are close to the value
of 2.0 observed for the oxidative addition reaction of io-
doarenes with [Pd(PPh3)4].[51,52] Therefore in case of aryl
iodides the rate-determining step (which is sensitive to
the electronic influence of aryl iodide) is most probably
not the oxidative addition of the aryl halide to Pd(0) spe-
cies for the alkynylation promoted by palladacycle 1.
This may also explain why the presence of an electron-
rich phosphine in adduct 2 has a detrimental effect on
the catalytic performance since it is expected that elec-
tron-rich ligands improve the oxidative addition of
aryl halides. Therefore it is probably that in these cases
the rate-determining step is related with the reductive
4
arom), 3.66 (d, 2H, CH2N, JP, H ¼1.4 Hz), 2.86 [d, 6H,
4
N(Me)2, JP,H ¼2.4 Hz], 2.75 (d, 1H, HP, JP, H ¼359.3 Hz), 1.31
3
(d, 9H, t-Bu, JP, H ¼14.6 Hz); 13C{1H} NMR (CDCl3): d¼
3
2
¼
146.1 (d, JP, C ¼7.3 Hz, C C-Pd), 120.3 (d, JP, C ¼4.4 Hz,
¼
C C-Cl), 147.3, 131.7, 127.9, 127.8, 125.3 (C arom), 73.1 (d,
3JP, C ¼2.6 Hz, CH2N), 49.9 [d, JP, C ¼2.6 Hz, N(Me)2], 34.9 [d,
3
1JP, C ¼20.5 Hz, C(CH3)3], 30.1 [d, 2JP,C ¼4.0 Hz, C(CH3)3].
ꢀ
ꢀ ꢃ
elimination path involving Ar Pd C CR species.
Preparation of Adduct 3
ASchlenk flask was charged with palladacycle 1 (0.5 mmol,
168 mg) and CH2Cl2 (5 mL). Tris-p-trifluoromethane-phenyl-
phosphine (560 mg, 1.2 mmol) dissolved in CH2Cl2 (1 mL)
was added to the solution. After two hours stirring at room
temperature, the CH2Cl2 was concentrated to 0.5 mL and hex-
ane (10 mL) was added. The reaction mixture was filtered
and after removing of volatiles complex 3 was obtained as a
faint yellow solid; yield: 280 mg (70%). Elemental analysis:
C32H25Cl2F9NPPd (802.84) requires: C 47.87, H 3.14, N 1.74;
Conclusion
In conclusion, we have established new catalysts based
on palladacycles for the alkynylation reaction. From
the view point of TON values the arylation of acetylenes
ranks with the best in the literature for palladacycles and
their phosphine adducts. The catalyst precursor 1 prob-
1
found: C 47.88, H 3.04, N 1.53; H NMR (CDCl3): d¼7.69–
ably acts as reservoir of catalytically active Pd(0) species 7.5 (m, 12H, H arom, PPhp-CF3), 6.87þ6.52 (m, 5H, H arom,
4
Ph), 3.88 (d, 2H, CH2N, JP, H ¼1.9 Hz), 2.98 [d, 6H, N(Me)2,
and the alkynylation reaction follows a Pd(0)/Pd(II)
3
4JP, H ¼2.9 Hz]; 13C{1H} NMR (CDCl3): d¼142.9 (d, JP, C
¼
mechanism. The poisoning tests indicated the involve-
ment of soluble Pd(0) species as the catalytically active
species generated from the palladacycle 1.
¼
5.1 Hz, C C), 134.2 (d, JP, C ¼49.1 Hz, C-P), 149.3 134.4,
2
127.9, 126.9, 125.4, 125.1 (C arom), 121.8 (d, JP, C ¼3.7 Hz,
3
2
¼
C C), 132.5 (q, JF,C ¼31.3 Hz CCF3), 123.5 (q, JF,C
¼
¼
3
3
272.8 Hz CF3), 74.8 (d, JP, C ¼2.9 Hz CH2N), 50.4 [d, JP, C
2.9 Hz, N(Me)2].
Experimental Section
Typical Experiment for the Alkynylation Reaction
A10-mL resealable Schlenk flask was evacuated and back-fil-
led with argon and charged with tetrabutylammonium acetate
(0.7 mmol, 224 mg), N,N-dimethylacetamide (3 mL), iodoben-
zene (0.5 mmol, 56 mL, 102 mg), phenylacetylene (0.6 mmol,
66 mL) and methyl benzoate as internal standard (35 mg). Af-
ter the addition of the palladacycle 1 in N,N-dimethylaceta-
mide (1.6 mg, 5ꢁ10ꢀ3 mmol) the reaction mixture was stirred
at 308C for 4 h. GC analysis indicated 98% yield in diphenyl-
acetylene and 2% of homocoupling acetylene product. The sol-
ution was added to a 10 wt % HCl (20 mL) and the product ex-
tracted with hexane (2ꢁ10 mL). The organic phase was dried
over MgSO4 and the solvent evaporated under vacuum, to give
diphenylacetylene; yield: 84 mg (95%);>95% pure by 1H
NMR and GC. 1H NMR (CDCl3): d¼7.23 (m, 10H, CH
arom); GC-MS (EI, 70 eV): m/z (%)¼178 (Mþ, 30), 152
(10), 126 (15), 111 (6), 98 (15), 87 (16).
General Remarks
All reactions involving organometallic compounds were car-
ried out under an argon or nitrogen atmosphere in oven-dried
Schlenk tubes. Solvents were dried with suitable drying agents
and distilled under argon prior to use. The palladacycle 1 was
prepared using the procedure reported previously.[26] All other
chemicals were purchased from commercial sources (Acros or
Aldrich) and used without further purification. NMR spectra
were recorded on a Varian Inova 300 spectrometer. Infrared
spectra were performed on a Bomem B-102 spectrometer.
Gas chromatographic analyses were performed with a Hew-
lett-Packard 5890 Gas Chromatograph with an FID and 30 me-
ter capillary column with a dimethylpolysiloxane stationary
phase. Mass spectra were obtained using a GC/MS Shimadzu
QP-5050 (EI, 70 eV).
Adv. Synth. Catal. 2006, 348, 133 – 141
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
139

Crestina S. Consorti et al.
FULL PAPERS
Attachment of 4-Iodobenzoic Acid to Wang Resin
Typical Experiment for the Hammet Competition
Reaction
Wang resin (2 g, OH loading: 1 mmol gꢀ1, 2 mmol of OH) was
suspended in 9:1 (v/v) CH2Cl2/DMF in a Schlenk flask. The 4-
iodobenzoic acid (6 mmol), dicyclohexylcarbodiimide (1.24 g,
6 mmol) and 4-dimethylaminopiridine (25 mg, 0.2 mmol)
were added to the resin suspension and the reaction mixture
was refluxed for 4 h. The resin was collected on a filter funnel,
washed with 3ꢁDMF, 3ꢁH2O, 3 ꢁDMF, 3ꢁCH2Cl2, 3ꢁ
MeOH and dried under vacuum.
Estimation of resin loading: 300 mg of Wang resin modified
with the4-iodobenzoic acid were suspended in trifluoroacetic
acid:CH2Cl2 1:1 (v/v) and stirred for 2 h. The cleavage solution
was dried under vacuum and the residual amount of free halo-
benzoic acid was employed to obtain the resin loading.
A10-mL resealable Schlenk flask was evacuated and back-fil-
led with argon and charged with tetrabutylammonium acetate
(0.7 mmol, 224 mg), N,N-dimethylacetamide (3 mL), phenyl-
acetylene (0.2 mmol, 22 mL), methyl benzoate, as internal
standard (35 mg), 0.6 mmol of PhI and 0.6 mmol of one of
the substrates: 4-MeOC6H4I, 4-MeC6H4I, 3-MeC6H4I,
4-ClC6H4I, 3-ClC6H4Br or 3-CF3C6H4Br. After the addition
of the palladacycle 1 in N,N-dimethylacetamide (1.6 mg, 5ꢁ
10ꢀ3 mmol) the reaction mixture was stirred at 808C. The reac-
tion was monitored by GC the initial relative rates were used to
plot Hammett correlation.
X-RayCrystallographic Study
Crystals of 2 were first prepared by slow diffusion of hexane
into an acetone solution. Ayellow crystal (polyhedron), di-
mensions 0.27ꢁ0.25ꢁ0.25 mm3, was mounted on a glass fiber
with perfluoropolyether. The measurements were made on a
Bruker SMART-CCD diffractometer with graphite mono-
chromated Mo-Ka radiation, lambda¼0.71073 Š, crystal sys-
Hg(0) Poisoning Test
Two identical Sonogashira experiments consisting of phenyl-
acetylene (0.6 mmol, 66 mL), iodobenzene (0.5 mmol, 56 mL,
102 mg), 3 mL of N,N-dimethylacetamide, tetrabutylammoni-
um acetate (0.7 mmol, 224 mg) and palladacycle 1 in N,N-di-
methylacetamide (1.6 mg, 5ꢁ10ꢀ3 mmol) were stirred at
308C. Aliquots were taken from both reactions and analyzed
by GC. After two hours, Hg (0.3 mmol, 60 mg) was added to
one reaction vessel.
¯
tem triclinic, space group P1, Z¼4, a¼11.2665(1) Š, b¼
11.6317(1) Š, c¼18.0339(1) Š, a¼87.573(1)8, b¼78.682(1)8,
g¼87.020(1)8, V¼2312.98(3) Š3, r¼1.386 g/cm3, T¼230(2)
K, 2Vmax ¼27.648, 50 kV, 40 mA, 1116 0.5 deg omega-scans,
10 s each, covering a whole sphere in reciprocal space, 23933
reflections measured, 10495 unique (R(int)¼0.0312), 7813 ob-
served (I>2s(I)), intensities were corrected for Lorentz and
polarization effects, an empirical absorption correction was ap-
plied using SADABS[53] based on the Laue symmetry of the re-
ciprocal space, m¼1.10 mmꢀ1, Tmin ¼0.75, Tmax ¼0.77, struc-
ture solved by direct methods and refined against F2 with a
full-matrix least-squares algorithm using the SHELXTL-
PLUS (5.10) software package,[54] 447 parameters refined, hy-
drogen atoms were treated using appropriate riding models ex-
cept of atoms H1 at P1, which were refined isotropically, good-
ness of fit 1.02 for observed reflections, final residual values
R1(F)¼0.037, wR(F2)¼0.084 for observed reflections, residu-
al electron density ꢀ0.66 to 0.98 e Šꢀ3. CCDC 279491 con-
tains the supplementary crystallographic data for this struc-
ture. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax: þ
441223336033; e-mail: deposit@ccdc.cam.ac.uk)
Typical Experiment for the Alkynylation Reaction of
Phenylacetylene Attached to the Wang Resin
A10-mL resealable Schlenk flask was evacuated and back-fil-
led with argon and charged with tetrabutylammonium acetate
(0.5 mmol, 160 mg) and the Wangresin containing the attached
4-iodobenzoic acid (500 mg,
I ,
loading: 0.68 mmol gꢀ1
0.35 mmol of I), DMA(3 mL), phenylacetylene (0.5 mmol,
55 mL) and palladacycle 1 (1.2 mg, 3.5ꢁ10ꢀ3 mmol). The reac-
tion mixture was stirred at 308C for 24 h. The Wang resin was
collected in a filter funnel, washed with 3 mL portions of 3ꢁ
DMF, 3ꢁH2O, 3 ꢁDMF, 3ꢁCH2Cl2, 3ꢁMeOH and dried un-
der vacuum.
Determination of yield: The Wang resin was suspended in the
cleavage solution [3 mL, trifluoroacetic acid:CH2Cl2, 1:1 (v/v)]
and stirred for 2 h. The cleavage solution was dried under vac-
uum and 1,3,5-trihydroxybenzene utilized as internal standard
for 1H NMR quantification of the Sonogashira product.
Acknowledgements
Financial support from FAPERGS and CNPq (Brazil) is grate-
fully acknowledged.
DCT Inhibition Test
Two identical Sonogashira experiments consisting of phenyl-
acetylene (0.6 mmol, 66 mL), iodobenzene (0.5 mmol, 56 mL,
102 mg), 3 mL of N,N-dimethylacetamide, tetrabutylammoni-
um acetate (0.7 mmol, 224 mg) and palladacycle 1 in N,N-di-
methylacetamide (1.6 mg, 5ꢁ10ꢀ3 mmol) were stirred at
308C. Aliquots were taken from both reactions and analyzed
by GC. After two hours, DCT (2ꢁ10ꢀ2 mmol, 4 mg) was added
to one reaction vessel. Aliquots were taken from both reactions
and analyzed by GC.
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141