Chloropalladated propargyl amine: A highly efficient phosphine-free catalyst precursor for the Heck reaction

Article abstract of DOI:10.1021/ol027337l

Figure presented The palladacycle {Pd[k¹-C, k ¹-N-C=(C₆H₅)C(Cl)CH₂NMe ₂](μ-Cl)}₂ 1 derived from the chloropalladation of 3-(dimethylamino)-1-phenyl-1-propyne promotes the arylation of olefins under relatively mild reaction conditions. The coupling of iodoarenes and activated bromoarenes with n-butylacrylate and styrene occurs at room temperature. Turnover numbers of up to 85 000 have been achieved with deactivated bromoarenes and up to 1000 for activated chloroarenes at higher temperatures (80-150°C).

Full text of DOI:10.1021/ol027337l

ORGANIC
LETTERS
2003
Vol. 5, No. 7
983-986
Chloropalladated Propargyl Amine: A
Highly Efficient Phosphine-Free Catalyst
Precursor for the Heck Reaction
Crestina S. Consorti, Mara L. Zanini, Sheila Leal, Gunter Ebeling, and
Ja1ırton Dupont*
Laboratory of Molecular Catalysis, IQ UFRGS, AV. Bento Gonc¸alVes,
9500 Porto Alegre, 91501-970 RS, Brazil
dupont@iq.ufrgs.br
Received November 22, 2002
ABSTRACT
The palladacycle {Pd[k1-C, k1-N-Cd(C H )C(Cl)CH NMe2](µ-Cl)}2 1 derived from the chloropalladation of 3-(dimethylamino)-1-phenyl-1-propyne
6
5
2
promotes the arylation of olefins under relatively mild reaction conditions. The coupling of iodoarenes and activated bromoarenes with
n-butylacrylate and styrene occurs at room temperature. Turnover numbers of up to 85 000 have been achieved with deactivated bromoarenes
and up to 1000 for activated chloroarenes at higher temperatures (80−150 °C).
Palladacycles are among the most simple and efficient
catalyst precursors to promote the arylation of olefins with
aryl halides (Heck reaction).1 Since the first report on the
use of a cyclopalladated compound derived from the ortho-
palladation of tris(o-tolyl)phosphine,2 a plethora of dimeric
palladacycles with PC, NC, and SC coordination modes and
PCP, NCN, and SCS pincer-type complexes (Figure 1) have
atures above 80 °C even for highly activated iodoarenes. It
has been recently proposed that, at least for NC palladacycles,
the reaction proceeds through the classical phosphine-free
Pd(0)/Pd(II) catalytic cycle.4
The catalytic activity differences observed with these
different palladacycle precursors have been rationalized in
terms of catalyst preactivation. In these cases, the pallada-
(1) For recent reviews, see: (a) Dupont, J.; Pfeffer, M.; Spencer, J. Eur.
J. Inorg. Chem. 2001, 1917-1927. (b) Albrecht, M.; van Koten, G. Angew.
Chem., Int. Ed. 2001, 40, 3750-3781. (c) Beletskaya, I. P.; Cheprakov, A.
V. Chem. ReV. 2000, 100, 3009-3066.
(2) Herrmann, W. A.; Brossmer, C.; Ofele, K.; Reisinger, C. P.;
Priermeier, T.; Beller, M.; Fischer, H. Angew. Chem., Int. Ed. Engl. 1995,
34, 1844-1848.
(3) See for example: (a) Ohff, M.; Ohff, A.; Milstein, D. Chem. Commun.
1999, 357-358. (b) Zim, D.; Gruber, A. S.; Ebeling, G.; Dupont, J.;
Monteiro, A. L. Org. Lett. 2000, 2, 2881-2884. (c) Bergbreiter, D. E.;
Osburn, P. L.; Wilson, A.; Sink, E. M. J. Am. Chem. Soc. 2000, 122, 9058-
9064. (d) Munoz, M. P.; Martin-Matute, B.; Fernandez-Rivas, C.; Cardenas,
D. J.; Echavarren, A. M. AdV. Synth. Catal. 2001, 343, 338-342. (e) Alonso,
D. A.; Najera, C.; Pacheco, M. C. AdV. Synth. Catal. 2002, 344, 172-183.
(f) Morales-Morales, D.; Redon, R.; Yung, C.; Jensen, C. M. Chem.
Commun. 2000, 1619-1620. (g) Albisson, D. A.; Bedford, R. B.; Scully,
P. N. Tetrahedron Lett. 1998, 39, 9793-9796.
Figure 1. Example of palladacycles used as catalyst precursors.
been reported to effectively promote the Heck reaction of
various bromo- and iodoarenes.3 However, all palladacycles
reported to date only promote the Heck reaction at temper-
(4) Beletskaya, I. P.; Kashin, A. N.; Karlstedt, N. B.; Mitin, A. V.;
Cheprakov, A. V.; Kazankov, G. M. J. Organomet. Chem. 2001, 622, 89-
96.
10.1021/ol027337l CCC: $25.00 © 2003 American Chemical Society
Published on Web 03/11/2003

cycle serves as a “reservoir” of Pd catalytic species under
the given reaction conditions.4,5 The key step in these cases
is the slow release of a low-ligated active Pd(0) species.
Therefore, the most efficient palladacycles will be those
where the release of active Pd is neither too fast (typical of
poorly thermally stable palladacycles that preferentially result
in the formation of inactive metallic palladium) nor too slow
(typical of thermally robust palladacycles, which would
require higher temperatures to start the reaction in order to
maintain a reasonable rate).
We have recently reported that various types of pallada-
cycles can be easily obtained by the chloropalladation of
heterosubstituted alkynes.6 Moreover, we have found that
depending upon the reaction conditions, the alkyne can be
regenerated together with soluble Pd(II) and Pd(0) species
(Scheme 1).7 Therefore, these chloropalladated alkynes are
and in the presence of N(nBu)4Br (entry 1, Table 1) are not
exceptional since the coupling of iodobenzene with n-
butylacrylate under the reaction conditions can be promoted
by almost any palladium catalyst precursor.8 However, this
coupling can be performed at room temperature (entries 8
and 10, Table 1), and this is an exceptional result since
examples of Pd catalyst precursors that catalyze the Heck
coupling at room temperature are very rare.9 Moreover, this
coupling reaction can be performed in the absence of
N(nBu)4Br10 using K3PO4 as the base with minimal reduction
in the TON (entry 9, Table 1).
The reaction of bromoarenes substituted with electron-
withdrawing groups can also be performed under mild
reaction conditions (entries 17 and 27), although better
conversions were achieved at higher temperatures (50-80
°C, Table 1, entries 15, 16, and 26). In the case of
nonactivated and deactivated bromoarenes, temperatures
above 120 °C are necessary to achieve good reaction yields
(entries 19 and 23). This is also evident for chloroarenes
where only those substituted with electron-withdrawing
groups give reasonable yields in coupling products (entries
28-30). Nonactivated and deactivated chloroarenes failed
to react with n-butylacrylate and styrene under the conditions
presented in Table 1.11
Scheme 1. Retrochloropalladation Reaction
To gain insight into the mechanism of the reaction, a
competitive experiment with seven aryl bromides was
performed under pseudo-first-order conditions with respect
to n-butylacrylate (Scheme 2).
potentially good candidates for the generation of catalytically
active species of Pd(0) for the Heck reaction.
We report herein that indeed the palladacycle {Pd[k1-C,k1-
N-Cd(C6H5)C(Cl)CH2NMe2](µ-Cl)}2 1 derived from the
chloropalladation of 3-(dimethylamino)-1-phenyl-1-propyne
is among the most effective catalyst precursors for the
coupling of haloarenes with alkenes.
Scheme 2
The catalyst precursor is easily obtained, in almost
quantitative yield, by simple addition of 3-(dimethylamino)-
1-phenyl-1-propyne6 to a methanolic solution of Li2PdCl4
at room temperature (see also Supporting Information). This
yellow compound is air and water stable in both solid and
solution (CH2Cl2, acetone, DMSO, etc.) at room temperature.
Palladacycle 1 starts to decompose at 172-175 °C in the
solid state and in solution (DMSO) at around 80 °C
A solution containing 1.0 × 10-5 mmol of catalyst
precursor 1, 0.14 mmol of each of the aryl bromides, 10
mmol of n-butylacrylate, 0.2 mmol of N(nBu)4Br, and 1.4
mmol of NaOAc was heated at 150 °C with stirring in 5
mL of DMA. The concentrations of the various coupling
products were determined by GC using methyl benzoate as
an internal standard.12 The resulting Hammett plot is
exhibited in Figure 2.
1
(monitored by variable-temperature H NMR).
The catalytic performance of 1 in the coupling of halo-
arenes with n-butylacrylate and styrene under different
reactions conditions is summarized in Table 1.
The initial experimental protocol was based on our
previous results that indicated, for the Heck coupling
promoted by sulfur-containing palladacycles, that DMA is
the best solvent and NaOAc is the base of choice. The
turnover numbers (TON) of 1 000 000 achieved at 150 °C
The use of σp constants results in a good fit, and correlation
yields a value of r ) 2.7. This electronic effect is not
(8) Gruber, A. S.; Pozebon, D.; Monteiro, A. L.; Dupont, J. Tetrahedron
Lett. 2001, 42, 7345-7348.
(9) (a) Littke, A. F.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 6989-
7000. (b) Deshmukh, R. R.; Rajagopal, R.; Srinivasan, K. V. Chem.
Commun. 2001, 1544-1545.
(10) For a review about the use of molten salts in catalysis, see: Dupont,
J.; deSouza, R. F.; Suarez, P. A. Z. Chem. ReV. 2002, 102, 3667-3692.
(11) For a recent review of Pd-catalyzed coupling reactions of chloro-
arenes, see: Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41, 4176-
4211.
(12) Experiment was validated by determining the relative initial reaction
rate of experiments performed separately (activated from deactivated
bromoarenes).
(5) Biffis, A.; Zecca, M.; Basato, M. Eur. J. Inorg. Chem. 2001, 1131-
1133.
(6) (a) Dupont, J.; Basso, N. R.; Meneghetti, M. R. Polyhedron 1996,
15, 2299-2302. (b) Dupont, J.; Basso, N. R.; Meneghetti, M. R.; Konrath,
R. A.; Burrow, R.; Horner, M. Organometallics 1997, 16, 2386-2391. (c)
Ebeling, G.; Meneghetti, M. R.; Rominger, F.; Dupont, J. Organometallics
2002, 21, 3221-3227.
(7) Zanini, M. L.; Ebeling, G.; Livotto, P. R.; Marken. F.; Meneghetti,
M. R.; Dupont, J. Polyhedron 2003, accepted for publication.
984
Org. Lett., Vol. 5, No. 7, 2003

Table 1. Heck Reaction between Alkenes and Aryl Halides Catalyzed by Palladacycle 1a
entry
ArX
alkene
[ArX]/[Pd]
T (°C)
t (h)b
yield (%)c
TONd
1
2
3
4
5
6
7
8
PhI
PhI
4-MeOC6H4I
4-MeOC6H4I
PhI
PhI
PhI
PhI
PhI
4-MeOC6H4I
4-MeOC6H4I
4-MeOC6H4I
4-CF3C6H4Br
4-CNC6H4Br
4-CNC6H4Br
4-CNC6H4Br
4-CNC6H4Br
4-CNC6H4Br
4-MeC6H4Br
4-MeC6H4Br
4-MeCOC6H4Br
4-MeCOC6H4Br
4-MeOC6H4Br
4-MeOC6H4Br
4-NO2C6H4Br
4-NO2C6H4Br
4-NO2C6H4Br
4-CNC6H4Cl
4-MeCOC6H4Cl
4-NO2C6H4Cl
4-MeC6H4Cl
n-butylacrylate
styrene
n-butylacrylate
styrene
1 000 000
1 000 000
1 000 000
1 000 000
10 000
1000
150
150
150
150
80
50
30
30
30
30
30
80
150
120
80
50
30
150
150
150
150
150
150
150
150
50
24
48
24
48
24
24
120
24
48
72
160
24
24
24
24
24
48
24
24
24
24
24
24
24
24
24
48
24
24
24
24
100 (92)
68
90
57
100
100 (95)
50
100
76
93
40
95 (90)
100
100
100
100
50
100 (93)
80
85
1 000 000
680 000
900 000
570 000
10 000
1000
n-butylacrylate
n-butylacrylate
n-butylacrylate
n-butylacrylate
n-butylacrylate
n-butylacrylate
n-butylacrylate
n-butylacrylate
n-butylacrylate
n-butylacrylate
n-butylacrylate
n-butylacrylate
n-butylacrylate
n-butylacrylate
n-butylacrylate
n-butylacrylate
n-butylacrylate
n-butylacrylate
n-butylacrylate
styrene
1000
100
100
100
500
100
76
93
9e
10
11
12
13
14
15
16
17
18
19
20e
21
22
23
24
25
26
27
28
29
30
31
1000
400
10 000
100 000
10 000
1000
9 500
100 000
10 000
1000
100
100
100
50
100 000
100 000
100 000
100 000
1 000 000
10 000
10 000
100 000
100
100 000
80 000
85 000
100 000
800 000
7200
6500
100 000
100
100 (97)
80
72
65
n-butylacrylate
n-butylacrylate
n-butylacrylate
n-butylacrylate
n-butylacrylate
n-butylacrylate
n-butylacrylate
100 (99)
100 (99)
80
60
33
100
1000
1000
1000
30
80
600
330
1000
150
150
150
150
100 (91)
traces
100
a Reaction conditions: DMA (5 mL), NaOAc (1.4 mmol), alkene (1.2 mmol) ArX (1 mmol), and N(nBu)4Br (0.2 mmol). b This is the time after which
the reaction was analyzed. The reaction might have been over at an earlier stage. c GC yield in trans-n-butylcinnamates and trans-stilbenes (using methyl
benzoate as an internal standard); isolated yields are shown in parentheses. d TON (mol of product/mol of Pd). e K3PO4 as the base and in the absence of
NnBu4Br.
surprising, since electron-withdrawing substituents are ex-
pected to accelerate the Ar-Br oxidative addition step. The
r value is between those observed for oxidative addition of
aryl chlorides to electron-rich Pd(0) complexes (r ) 5.2)13
and those obtained for the Heck reaction of aryl iodides
involving Pd pincer complexes (r ) 1.34).14 Moreover,
similar r values have been estimated for the coupling of aryl
bromides with methyl acrylate catalyzed by sulfur-containing
palladacycles.15 This result strongly suggests that the rate-
determining step is oxidative addition of the aryl bromide
to Pd(0) species.16
This reaction probably involves the formation of soluble
palladium particles17 as the catalytically active species since
(13) Portnoy, M.; Milstein, D. Organometallics 1993, 12, 1665-1673.
(14) Weissman, H.; Milstein, D. Chem. Commun. 1999, 1901-1902.
(15) Gruber, A. S.; Zim, D.; Ebeling, G.; Monteiro, A. L.; Dupont, J.
Org. Lett. 2000, 2, 1287-1290.
(16) For recent studies on the Heck reaction mechanism, see: (a)
Amatore, C.; Carre´, E.; Jutand, A.; Medjour, Y. Organometallics 2002,
21, 4540-4545. (b) Amatore, C.; Jutand, A. Acc. Chem. Res. 2000, 33,
314-321.
(17) See for example: Choudary, B. M.; Madhi, S.; Chowdari, N. S.;
Kantam, M. L.; Sreedhar, B. J. Am. Chem. Soc. 2002, 124, 14127-14136.
Reetz, M. T.; Westermann, E. Angew. Chem., Int. Ed. 2000, 39, 165-168.
Note that PdCl2 does not promote the Heck coupling at room temperature
(see ref 9).
Figure 2. Hammett correlation of the competitive reaction of
p-substituted aryl bromides with n-butylacrylate at 150 °C in DMA
promoted by palladacycle 1 using σp constants.
Org. Lett., Vol. 5, No. 7, 2003
985

Scheme 3
through the investigation of the catalytic performance of the
analogous pincer palladacycle 2 (Scheme 3). This compound,
in opposition to 1, is much more reluctant to undergo
retrochloropalladation under the conditions investigated (up
to 120 °C in DMSO). As expected, the pincer palladacycle
2 gave only 7% yield in the coupling of iodo benzene with
n-butylacrylate at 30 °C after 24 h (PhI/Pd ) 100).
In summary, the phosphine-free chloropalladated propar-
gylamine 1 is one of the most simple and efficient catalyst
precursors for the arylation of alkenes. The system exhibits
unprecedented catalytic activity for the Heck reaction at room
temperature. The palladacycle probably acts as a reservoir
of soluble catalytically active Pd(0) species. Further inves-
tigations on the scope of this class of palladacycles and on
the mechanism of the catalytic coupling are currently under
investigation in our laboratory.
Figure 3. Conversion vs time plot for PhI and n-butylacrylate
(reaction conditions: DMA (5 mL), NaOAc (1.4 mmol), alkene
(1.2 mmol), PhI (1 mmol), 1 (10-3mmol), and N(nBu)4Br (0.2 mmol
at 80 °C)). (9) Control experiment; (O) Hg(0) (300:1 Hg/Pd)
poisoning experiment.
a Hg test18 was positive (Figure 3). Attempts to isolate and
characterize by transmission electron microscopy (TEM) the
species isolated during the catalytic processes have so far
met with little success.19 The formation of Pd(0) species
probably follows the same pathway proposed earlier by
Beletskaya.4
Acknowledgment. We thank FAPERGS and CNPq
(Brazil) for partial financial support and scholarships to
C.S.C. and S.L..
Further indirect evidence that palladacycle 1 serves as a
reservoir of catalytically active palladium was obtained
Supporting Information Available: Detailed experi-
mental procedure and characterization of the products. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(18) Hg(0) poisoning was performed according to: Weddle, K. S.; Aiken,
J. D.; Finke, R. G. J. Am. Chem. Soc. 1998, 120, 5653-5666.
(19) After the submission of this manuscript, Gladysz reported the
identification of Pd nanoparticles in Heck coupling promoted by pallada-
cycles: Rocaboy, C.; Gladysz, J. A. New J. Chem. 2003, 27, 39-49.
OL027337L
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Org. Lett., Vol. 5, No. 7, 2003