Trifunctional N,N,O-terdentate amido/pyridyl carboxylate ligated Pd(II) complexes for heck and suzuki reactions

Article abstract of DOI:10.1021/jo900361c

(Chemical Equation Presented) Trifunctional N,N,O-terdentate amido/pyridyl carboxylate Pd(II) complexes were highly active and stable phosphinefree catalysts for Heck and room-temperature Suzuki reactions with high turnover numbers up to ca. 10⁴.

Full text of DOI:10.1021/jo900361c

donating functionality that favors both the oxidative addition
and reductive elimination steps in the catalytic cycle.3 However,
phosphine-containing ligands are toxic, air-sensitive, and quite
expensive. Therefore, the development of phosphine-free cata-
lysts for C-C bond-forming reactions would be an important
topic of interest.
Trifunctional N,N,O-Terdentate Amido/Pyridyl
Carboxylate Ligated Pd(II) Complexes for Heck
and Suzuki Reactions
M. Lakshmi Kantam,*,† P. Srinivas,† Jagjit Yadav,†
Pravin R. Likhar,*,† and Suresh Bhargava‡
To date, a number of phosphine-free ligands with different
donor-functionalities such as N-heterocyclic,4 carbocyclic,5 and
anionic carbocyclic6 carbenes, oxazolines,7 Schiff bases,8 py-
ridines,9 amines,10 imidazoles,11 pyrazoles,12 hydrazones,13
selenides,14 ureas,15 and thioureas16 have appeared for C-C
cross-coupling reactions. Most of these ligands are mono- or
bifunctional ligands. They reveal that each donor-functional
group has its own characteristic nature to influence the efficacy
of its palladium complex and also disclose that none of the
functional groups have all of the properties that make the pal-
ladium very stable and catalytically active. Therefore, we
assumed that the design and development of phosphine-free
multifunctional ligands using different donor-functionalities may
provide stable and well-defined active palladium catalysts.
Recently, we have reported N4-tetradentate dicarboxyamidate/
dipyridyl palladium(II) complexes as catalysts for the Heck
Inorganic and Physical Chemistry DiVision, Indian Institute
of Chemical Technology, Hyderabad-500 607, India, and
School of Applied Sciences, RMIT UniVersity,
Melbourne, Australia
mlakshmi@iict.res.in; plikhar@iict.res.in
ReceiVed March 2, 2009
(3) (a) Herrmann, W. A.; Bo¨hm, V. P. W.; Reisinger, C.-P. J. Organomet.
Chem. 1999, 576, 23. (b) Whitcombe, N. J.; Mimi Hii, K. K.; Gibson, S. E.
Tetrahedron 2001, 57, 7449. (c) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed.
2002, 41, 4176. (d) Bedford, R. B. Chem. Commun. 2003, 1787. (e) Beletskaya,
I. P.; Cheprakov, A. V. J. Organomet. Chem. 2004, 689, 4055. (f) Christmann,
U.; Vilar, R. Angew. Chem. Int. Ed. 2005, 44, 366. (g) Dupont, J.; Consorti,
C. S.; Spencer, J. Chem. ReV. 2005, 105, 2527. (h) Martin, R.; Buchwald, S. L.
Acc. Chem. Res. 2008, 41, 1461.
(4) (a) Gstottmayr, C. W. K.; Bo¨hm, V. P. W.; Herdtweck, E.; Grosche, M.;
Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1363. (b) Navarro, O.; Kelly,
R. A., III; Nolan, S. P. J. Am. Chem. Soc. 2003, 125, 16194.
(5) (a) Herrmann, W. A.; Ofele, K.; Schneider, S. K.; Herdtweck, E.;
Hoffmann, S. D. Angew. Chem., Int. Ed. 2006, 45, 3859. (b) Wass, D. F.;
Haddow, M. F.; Hey, T. W.; Guy Orpen, A.; Russell, C. A.; Wingad, R. L.;
Green, M. Chem. Commun. 2007, 2704.
Trifunctional N,N,O-terdentate amido/pyridyl carboxylate
Pd(II) complexes were highly active and stable phosphine-
free catalysts for Heck and room-temperature Suzuki reac-
tions with high turnover numbers up to ca. 104.
(6) Yao, Q.; Zabawa, M.; Woo, J.; Zheng, C. J. Am. Chem. Soc. 2007, 129,
3088.
(7) (a) Tao, B.; Boykin, D. W. Tetrahedron Lett. 2002, 43, 4955. (b) Gossage,
P. A.; Jenkins, H. A.; Yadav, P. N. Tetrahedron Lett. 2004, 45, 7689. (c) Lee,
S. J. Organomet. Chem. 2006, 691, 1347.
(8) (a) Grasa, G. A.; Hillier, A. C.; Nolan, S. P. Org. Lett. 2001, 3, 1077.
(b) Wu, K.-M.; Huang, C.-A.; Peng, K.-F.; Chen, C.-T. Tetrahedron 2005, 61,
9679.
(9) (a) Buchmeiser, M. R.; Wurst, K. J. Am. Chem. Soc. 1999, 121, 11101.
(b) Kawano, T.; Shinomaru, T.; Ueda, I. Org. Lett. 2002, 4, 2545. (c) Najera,
C.; Gil-Moito, J.; Karlstrum, S.; Falvello, L. R. Org. Lett. 2003, 5, 1451.
(10) (a) Tao, B.; Boykin, D. W. J. Org. Chem. 2004, 69, 4330. (b) Li, J.-H.;
Liu, W.-J. Org. Lett. 2004, 6, 2809. (c) Xie, Y.-X.; Li, J.-H.; Yin, D.-L. Chin.
J. Org. Chem. 2006, 26, 1155.
(11) (a) Park, S. B.; Alper, H. Org. Lett. 2003, 5, 3209. (b) Xiao, J. C.;
Twamley, B.; Shreeve, J. M. Org. Lett. 2004, 6, 3845. (c) Haneda, S.; Ueba, C.;
Eda, K.; Hayashi, M. AdV. Synth. Catal. 2007, 349, 833. (d) Kawamura, K.;
Haneda, S.; Gan, Z.; Eda, K.; Hayashi, M. Organometallics 2008, 27, 3748.
(12) (a) Mukherjee, A.; Sarkar, A. Tetrahedron Lett. 2005, 46, 15. (b)
Montoya, V.; Pons, J.; Branchadell, V.; Garcia-Anto´n, J.; Solans, X.; Font-Bard´ıa,
M.; Ros, J. Organometallics 2008, 27, 1084. (c) Li, F.; Hor, T. S. A. AdV. Synth.
Catal. 2008, 350, 2391.
(13) (a) Mino, T.; Shirae, Y.; Sakamoto, M.; Fujita, T. Synlett 2003, 882.
(b) Mino, T.; Shirae, Y.; Sakamoto, M.; Fujita, T. J. Org. Chem. 2005, 70, 2191.
(c) Mino, T.; Shirae, Y.; Sakamoto, M.; Fujita, T. J. Org. Chem. 2006, 71, 6834.
(14) Yao, Q.; Kinney, E. P.; Zheng, C. Org. Lett. 2004, 6, 2997.
(15) Cui, X.; Zhou, Y.; Wang, N.; Liu, L.; Guo, Q.-X. Tetrahedron Lett.
2007, 48, 163.
(16) (a) Dai, M. J.; Liang, B.; Wang, C. H.; You, Z. J.; Xiang, J.; Dong,
G. B.; Chen, J. H.; Yang, Z. AdV. Synth. Catal. 2004, 346, 1669. (b) Yang, D.;
Chen, Y. C.; Zhu, N. Y. Org. Lett. 2004, 6, 1577. (c) Chen, W.; Li, R.; Han, B.;
Li, B. J.; Chen, Y. C.; Wu, Y.; Ding, L. S.; Yang, D. Eur. J. Org. Chem. 2006,
1177.
Palladium-catalyzed C-C bond-formation reactions such as
the Heck and Suzuki cross-couplings have found applications
in the synthesis of natural products and pharmaceuticals and
materials science.1 The great importance of C-C bond-forming
reactions has encouraged the chemical community to search for
highly active and stable palladium catalysts, which should be
versatile and efficient.2 Recently, well-designed phosphine-based
ligands have contributed significantly to improving catalytic
activity as a result of their increasing bulkiness and electron-
† Indian Institute of Chemical Technology.
‡ RMIT University.
(1) (a) Link, J. T.; Overman, L. E. In Metal-Catalyzed Cross-Coupling
Reactions; Diederich, F., Stang, P. J., Eds.; Wiley-VCH: New York, 1998;
Chapter 6. (b) Smith, G. B.; Dezeny, G. C.; Hughes, D. L.; King, A. O.;
Verhoeven, T. R. J. Org. Chem. 1994, 59, 8151. (c) Goa, K. L.; Wagstaff, A. J.
Drugs 1996, 51, 820. (d) Birkenhager, W. H.; de Leeuw, P. W. J. Hypertens.
1999, 17, 873. (e) Cacchi, S.; Fabrizi, G. Chem. ReV. 2005, 105, 2873. (f) Step-
Growth Polymers for High-Performance Materials; Hedrick, J. L., Labadie, J. W.,
Eds.; ACS Symposium Series 624; American Chemical Society: Washington,
DC, 1996; Chapters 1, 2 and 4.
(2) (a) Beletskaya, I. P.; Cheprakov, A. V. Chem. ReV. 2000, 100, 3009. (b)
Bedford, R. B.; Cazin, C. S. J.; Holder, D. Coord. Chem. ReV. 2004, 248, 2283.
(c) Heck, R. F. In ComprensiVe Organic Synthesis; Trost, B. M., Fleming, I.,
Eds.; Pergamon Press: Oxford, 1991; Vol 4. (d) De Meijere, A.; Braese, S. In
Transition Metal Catalyzed Reactions; Davies, S. G., Murahashi, S. I., Eds.;
Blackwell Science: Oxford, U.K., 1999.
4882 J. Org. Chem. 2009, 74, 4882–4885
10.1021/jo900361c CCC: $40.75  2009 American Chemical Society
Published on Web 05/21/2009

SCHEME 1. Design of Multifunctional Pd(II) Complexes
SCHEME 2.
Palladium(II) Complexes
Synthesis of Amido/Pyridyl Carboxylate
reaction of deactivated aryl chlorides.17 This was the first report
on the use of purely N-donor ligands that show significant
catalytic activity with deactivated aryl chlorides in the Heck
reaction. It was observed that the anionic amide (deprotonated
amide) ligands strongly donate electrons to the metal center,
thus stabilizing the various oxidation states of the metals.18 Such
ionic-type amidate bonding in palladium complexes could impart
larger thermodynamic stabilization to active metal species.
As reported by Yao et al. in 2003 and demonstrated by the
theoretical study of Amatore and Jutand, the coordination by
anionic carboxylates could enhance the activity of Pd toward
oxidative addition.19 In addition, Reetz et al. and Liu et al. have
shown that alkylamine and pyridine are good neighboring groups
to enhance the effect of a carboxylate group in Pd catalysis.20
Owing to the impressive activity of the anionic carboxyamide
as an ancillary ligand in the Heck reaction,17 enhancement of
the catalytic activity might be expected by introducing car-
boxyamide into the bifunctional pyridine-2-carboxylic acid
ligand as the pendant functionality (Scheme 1).
TABLE 1. Heck Reaction between Bromoanisole and n-Butyl
Acrylatea
entry
base
solvent
T (°C)
yield (%)
TON
TOFb
1
2
3
4
5
6
7
8
K2CO3
DMF
DMF
DMF
DMF
DMF
DMF
DMA
NMP
DMSO
DMF
DMF
DMF
DMF
DMF
145
145
145
145
145
145
145
145
145
130
145
145
145
145
81
92
3
78
5
13
80
40
9
44
89c
12d
22e
51f
8100
9200
300
7800
500
1300
8000
4000
900
4400
8900
1200
2200
5100
405
460
15
390
25
Na2CO3
NaOAc
K3PO4
DIPEA
MDCHA
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
65
In this paper, we report the successful synthesis of palla-
dium(II) complexes of trifunctional amido/pyridyl carboxylate
ligands and their catalytic activity for the C-C bond-formation
reactions. The investigation of the reactivity of the resulting
trifunctional Pd(II) complexes would provide a new and efficient
catalyst system for Heck and Suzuki reactions under phosphine-
free conditions.
400
200
45
220
445
60
9
10
11
12
13
14
110
255
The ligands 3a and 3b were prepared in good yields using
the method described in our previous work.17 The palladium(II)
complexes (4a and 4b) were prepared, in almost quantitative
yields, by simple addition of N,N,O-terdentate ligands (3a and
3b) to a orange-colored solution of Pd(OAc)2 in tetrahydrofuran
at room temperature (see Scheme 2). Complex 4a is soluble in
polar organic solvents such as CHCl3, CH2Cl2, THF, MeOH,
DMF, and DMSO, whereas complex 4b is soluble only in very
highly polar organic solvents such as DMSO, DMF, and DMA.
Complex 4a and 4b have been fully characterized by spectros-
copy (NMR, MS, FT-IR) and by elemental analysis. The
solution structure of the palladium complexes were studied by
1H and 13C NMR spectroscopy, and these studies show the
presence of amidate bonding to palladium similar to that
observed in our previous work. Remarkably, both palladium(II)
complexes show high thermal stability up to 280 °C as analyzed
a Reaction conditions: bromoanisole (1 mmol), n-butyl acrylate (2
mmol), base (1.2 mmol), solvent (2 mL) for 20 h. b TOF ) turnover
frequency (mol product per mol catalyst h-1). c 4b was used. DIPEA )
N,N-diisopropylethylamine; MDCHA
) N-methyl-dicyclohexylamine.
d With Pd(OAc)2. e With picolinic acid/Pd(OAc)2 (1:1). f With picolinic
acid/Pd(OAc)2 (2:1).
by TGA (see Supporting Information). It was therefore of
interest to examine the activity of the 4a and 4b complexes as
catalysts for Heck and Suzuki coupling reactions.
To begin our study, we examined the Heck reaction between
aryl halides and olefins, and the results are presented in Tables
1 and 2. In order to optimize the efficiency of the catalytic
system, we initially examined the coupling of bromoanisole and
n-butyl acrylate in the presence of 4a under a variety of reaction
conditions, and the progress of the reaction was monitored by
gas chromatography. Among the bases employed, Na2CO3 was
found to be the best in the present protocol (Table 1, entry 2).
Excellent yield of 4-methoxy-trans-cinnamic acid n-butyl ester
was isolated in 92% yield by carrying out the reaction in N,N-
dimethylformamide (DMF) at 145 °C for 20 h. It was found
that in the absence of ligand, Pd(OAc)2 indeed could catalyze
the Heck reaction,21 but the maximum yield was 12% in our
(17) Srinivas, P.; Likhar, P. R.; Maheswaran, H.; Sridhar, B.; Ravikumar,
K.; Kantam, M. L. Chem.sEur. J. 2009, 15, 1578.
(18) (a) Ray, M.; Ghosh, D.; Shirin, Z.; Mukherjee, R. Inorg. Chem. 1997,
36, 3568. (b) Noveron, J. C.; Olmstead, M. M.; Mascharak, P. K. Inorg. Chem.
1998, 37, 1138. (c) Marlin, D. S.; Olmstead, M. M.; Mascharak, P. K. Inorg.
Chem. 1999, 38, 3258. (d) Patra, A. K.; Ray, M.; Mukherjee, R. Inorg. Chem.
2000, 39, 652. (e) B-James, K. Acc. Chem. ReV. 2005, 38, 671. (f) Kang, S. O.;
Hossain, M. A.; B-James, K. Coord. Chem. ReV. 2006, 250, 3038. (g) Kang,
S. O.; Begum, R. A.; Bowman-James, K. Angew. Chem., Int. Ed. 2006, 45, 7882.
(19) (a) Yao, Q.; Kinney, E. P.; Yang, Z. J. Org. Chem. 2003, 68, 7528. (b)
Amatore, C.; Jutand, A. Acc. Chem. Res. 2000, 33, 314.
(20) (a) Reetz, M. T.; Westermann, E.; Lohmer, R.; Lohmer, G. Tetrahedron
Lett. 1998, 39, 8449. (b) Cui, X.; Li, Z.; Tao, C.-Z.; Xu, Y.; Li, J.; Liu, L.; Guo,
Q.-X. Org. Lett. 2006, 8, 2467. (c) Cui, X.; Li, J.; Zhang, Z.-P.; Fu, Y.; Liu, L.;
Guo, Q.-X. J. Org. Chem. 2007, 72, 9342.
(21) (a) de Vries, A. H. M.; Mulders, J. M. C.A.; Mommers, J. H. M.;
Henderickx, H. J. W.; de Vries, J. G. Org. Lett. 2003, 5, 3285. (b) Reetz, M. T.;
de Vries, J. G. Chem. Commun. 2004, 1559. (c) Alimardanov, A.; de
Vondervoort, L. S.; de Vries, A. H. M.; de Vries, J. G. AdV. Synth. Catal. 2004,
346, 1812.
J. Org. Chem. Vol. 74, No. 13, 2009 4883

TABLE 2.
Heck Reaction of Aryl Halides and Olefinsa
TABLE 3.
Acidsa
Suzuki Reaction of Aryl Halides and Arylboronic
entry
R, X
H, Br
H, Br
H, Br
4-MeOC, Br
4-MeOC, Br
4-NO2, Br
4-NO2, Br
4-Me, Br
4-Me, Br
4-Me, Br
4-MeO, Br
4-MeO, Br
4-MeO, Br
H, I
R1
yield (%)
TON
TOF
entry
R, X
R1
time(h) yield (%) TON TOF
1
2
3
4
5
6
7
8
Ph
94
92
93
91
45
92
90
95
93
92
94
92
90
95
96
90
94
95
91
94
90
88
70b
80b
9400
9200
9300
9100
4500
9200
9000
9500
9300
9200
9400
9200
9000
9500
9600
9000
9400
9500
9100
9400
9000
8800
70
470
460
465
455
225
460
450
475
465
460
470
460
450
475
480
450
470
475
455
470
450
440
3.5
CO2Bun
4-Me-C6H4
Ph
1
2
3
4
5
6
7
8
H, Br
H
H
H
H
H
H
H
4-MeO
4-Me
2-Me
5
10
10
10
5
84
76
75
70b
95
94
45
55
76
80
74
81c
78c
85c
96
93
94
82
84
85
84
85
82
61e
8400 1680
4-Me, Br
4-MeO, Br
4-MeO, Br
4-MeOC, Br
4-NO2, Br
2-MeO, Br
H, Br
H, Br
H, Br
H, Br
4-Me, Br
4-MeO, Br
4-MeOC, Br 4-MeO
H, I
4-Me, I
4-MeO, I
H, I
H, I
H, I
H, I
7600
7500
7000
760
750
700
CO2Bun
Ph
9500 1900
9400 1880
CO2Bun
Ph
5
10
10
10
10
10
16
16
16
5
5
5
5
5
4500
5500
7600
8000
7400
8100
7800
8500
450
550
760
800
740
506
488
531
9
CO2Bun
4-Me-C6H4
Ph
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
CO2Bun
4-Me-C6H4
Ph
3-Me
4-MeO
4-MeO
H, I
H, I
4-Me, I
4-Me, I
CO2Bun
4-Me-C6H4
Ph
H
H
H
4-MeO
4-Me
2-Me
3-Me
4-MeO
4-MeO
H
9600 1920
9300 1860
9400 1880
8200 1640
8400 1680
8500 1700
8400 1680
8500 1700
8200 1640
CO2Bun
4-Me-C6H4
Ph
4-Me, I
4-MeO, I
4-MeO, I
4-MeO, I
4-NO2, Cl
4-NO2, Cl
CO2Bun
4-Me-C6H4
Ph
5
5
5
5
4-Me, I
4-MeO, I
4-MeO, Br
4-Me-C6H4
80
4.0
a Reaction conditions: aryl halide (1 mmol), olefin (2 mmol), Na2CO3
10
6100
610
(1.2 mmol), DMF (2 mL) at 145 °C for 20 h. b With 1 mol % 4a at 160
°C.
a Reaction conditions: aryl halide (1 mmol), arylboronic acid (1.5
mmol), LiOH ·H2O (1.2 mmol), and methanol (2 mL). b 4b was used.
c Reaction carried out at 50 °C. e With Pd(OAc)2.
reaction conditions (entry 12) (compared to 9% as reported by
Yao et al.19a with 0.1 mol % Pd(OAc)2). The same reaction
was performed using picolinic acid/Pd(OAc)2 in different Pd:
ligand ratios, and the yields obtained were lower than for the
catalyst 4a (entries 13 and 14). The strength of the Pd-amidate
bond, chelation, or steric shielding of the metal center have
greater effect on the catalytic activity. No marked difference in
the reactivity between 4a and 4b was observed (entries 2 vs
11).
To explore the scope of the reactions catalyzed by 4a,we next
examined the application of 4a to the cross-coupling of aryl
halides with olefins under our optimized conditions (0.01 mol
% 4a, 1.2 equiv of Na2CO3, DMF, 145 °C), and the results are
presented in Table 2. It is clear from the Table 2 that aryl
bromides containing electron-withdrawing and electron-donating
groups are coupled in high yields, with turnover numbers of
about 104 (entries 4-13). Besides aryl bromides, aryl iodides
could also be successfully used under the same reaction
conditions (entries 14-22). Moreover, the catalysts were stable
and active enough to handle electron-deficient aryl chlorides at
160 °C (entries 23 and 24).
We next explored the efficacy of 4a in the Suzuki reactions.
It was found that 4a was active enough to promote the Suzuki
reaction at room temperature in the presence of air. After
extensive screening, the following set of standard reaction
conditions were established with respect to the aryl halide: 0.01
mol % 4a, 1.5 equiv of ArB(OH)2, and 1.2 equiv of LiOH ·H2O
in methanol (see Supporting Information, Table S1). Here also
we observed no marked difference in the reactivity between 4a
and 4b (Table 3, entries 3 vs 4). A variety of aryl halides and
boronic acids were subjected to the optimized conditions
mentioned above, and the results are shown in Table 3. The
room-temperature Suzuki reaction worked well with both
electron-rich and electron-poor aryl bromides, and the turnover
numbers were about 104 (entries 2-6). The sterically hindered
ortho-substituted substrates could also couple efficiently at room
temperature with low catalyst loading (entries 7 and 10). The
reactions corresponding to entries 12-14 were performed at
50 °C in order to give good isolated yields. Aryl iodides could
also be successfully used under the same reaction conditions
(entries 15-23). The resulting products were consistently
obtained in moderate to good isolated yields. It is very clear
from results that both trifunctional palladium complexes 4a and
4b are stable enough and active for the Heck and Suzuki
coupling reactions.
The important advantages associated with these catalysts,
compared to many of the previous phosphine-free catalysts, are
that these catalysts are air- and heat-stable and have long
lifetimes. We have achieved room-temperature Suzuki reactions,
which were accomplished previously either by using compli-
cated phosphine or heterocyclic carbene ligands22 or by using
a relatively high loading of Pd (i.e., >1 mol %).23 Unlike most
previously reported systems for C-C cross-coupling reactions,
additional co-catalysts such as [NBu4]Br or[PPh4]Cl are not
required to achieve high catalytic activity.24 Moreover, we have
(22) (a) Guo, M.; Jiang, F.; He, R. Tetrahedron Lett. 2006, 47, 2033. (b)
Navarro, O.; Marion, N.; Mei, J.; Nolan, S. P. Chem.sEur. J. 2006, 12, 5142.
(23) (a) Deng, Y.; Gong, L.; Mi, A.; Liu, H.; Jiang, Y. Synthesis 2003, 337.
(b) Zhang, G. Synthesis 2005, 537.
(24) (a) Herrmann, W. A.; Brossmer, C.; Ofele, K.; Reisinger, C.-P.;
Priermeier, T.; Beller, M.; Fischer, H. Angew. Chem., Int. Ed. Engl. 1995, 34,
1844. (b) Herrmann, W. A.; Brossmer, C.; Reisinger, C.-P.; Riermeier, T. H.;
Ofele, K.; Beller, M. Chem.sEur. J. 1997, 3, 1357. (c) Reetz, M. T.; Lohmer,
G.; Schwickardi, R. Angew. Chem., Int. Ed. 1998, 37, 481. (d) Bedford, R. B.;
Cazin, C. S. J.; Holder, D. Coord. Chem. ReV. 2004, 248, 2283. (e) Herrmann,
W. A.; Ofele, K.; Schneider, S. K.; Herdtweck, E.; Hoffmann, S. D. Angew.
Chem., Int. Ed. 2006, 45, 3859.
4884 J. Org. Chem. Vol. 74, No. 13, 2009

374.9962. Anal. calcd for C15H12N2O3Pd: C 48.08, H 3.23, N 7.48.
Found: C 47.64, H 3.14, N 7.34.
achieved high turnover numbers with different aryl bromides
in both Heck and Suzuki reactions.
Typical Procedure for the Heck Reaction. The reaction vessel
was charged with bromobenzene (1 mmol), n-butyl acrylate (2
mmol), Na2CO3 (1.2 mmol), and the catalyst (0.01 mol %) in N,N-
dimethylformamide (2 mL). The reaction mixture was heated to
145 °C, and the progress of reaction was monitored by GC. At the
end of the reaction, the reaction mixture was cooled to room
temperature, diluted with EtOAc (20 mL), and washed with 1 N
aq HCl and water. The combined organic phase was dried over
anhydrous Na2SO4. After removal of the solvent, the residue was
subjected to column chromatography on silica gel using ethyl acetate
and hexane mixtures to afford the Heck product in high purity.
In conclusion, we have shown that the trifunctional N,N,O-
terdentate palladium(II) complexes 4a and 4b are excellent
catalysts for Heck and room-temperature Suzuki reactions. It
is also shown that the amidate donor-functional group was a
good supporting functionality to enhance the thermal stability
and at the same time enhance the activity of the Pd catalysts in
C-C cross-coupling reactions. We have also demonstrated the
importance of multifunctional ligands for Pd catalysis.
Experimental Section
1
trans-Cinnamic acid n-butyl ester: H NMR (300 MHz, CDCl3,
Synthesis of Complex 4a. Compounds 3a and 3b were prepared
according to our previously reported work. The N,N,O-tridentate
ligand 3a (266.4 mg, 1.2 mmol) was added to a stirred orange-
colored suspension of palladium acetate (224.49 mg, 1 mmol) in
tetrahydrofuran (20 mL) in one portion. After the solution stirred
for 12 h at room temperature, a pale yellow precipitate was obtained.
The solvent was removed completely under reduced pressure, and
the resulting solid was washed with excess diethylether to obtain
pure 4a in 94% yield. Compound 4b was prepared following the
same experimental procedure using 3b as tridentate ligand. Complex
4a: Mp, decomposed to black metal above 262 °C; 1H NMR (200
MHz, CDCl3, TMS) δ 1.20-1.23 (m, 6H), 2.61-2.71 (m, 1H),
4.32 (d, J ) 3.8 Hz, 1H, CH), 7.45-7.50 (m, 1H), 7.76 (d, J ) 6.8
Hz, 1H), 8.01 (dt, J ) 1.3, 7.7 Hz, 1H), 8.23 (d, J ) 5.5 Hz, 1H);
13C NMR (50 MHz, CDCl3) δ 18.1, 19.7, 31.6, 69.1, 125.1, 126.8,
140.1, 146.4, 156.3, 168.0, 191.9; IR (KBr) ν ) 1737, 1637 cm-1
(CdO), 1600, 1560 cm-1 (CdC), 1240 cm-1 (C-O), 1099 cm-1
(C-N); ESI-MS (M + H)+ ) 327, (M + Na)+ ) 349; HRMS
calcd for C11H12N2O3NaPd (M + Na)+ ) 348.9780, found
348.9798. Anal. Calcd for C11H12N2O3Pd: C 40.45, H 3.70, N 8.58.
Found: C 40.27, H 3.69, N 8.43. Complex 4b: Mp, decomposed to
black metal above 282 °C; 1H NMR (200 MHz, DMSO-d6, TMS)
δ 2.98 (dd, J ) 2.9, 13.2 Hz, 1H), 3.49 (dd, J ) 5.9, 13.16 Hz,
1H), 4.31-4.44 (m, 1H, CH), 7.08-7.29 (m, 6H), 7.68 (t, J ) 7.3,
13.2 Hz, 1H), 7.78 (d, J ) 7.3 Hz, 1H), 8.23 (t, J ) 7.3, 15.4 Hz,
1H); 13C NMR (50 MHz, DMSO-d6) δ 37.0, 63.5, 124.9, 126.2,
127.8, 128.1, 129.6, 137.6, 141.5, 148.0, 155.0, 167.3, 183.5; IR
(KBr) ν ) 1734, 1636 cm-1 (CdO), 1563 cm-1 (CdC), 1239 cm-1
(C-O), 1101 cm-1 (C-N); ESI-MS (M + H)+ ) 375, (M + Na)+
) 397; HRMS calcd for C15H13N2O3 Pd (M + H)+ 374.9960, found
TMS) δ 0.97 (t, J ) 7.6 Hz, 3H), 1.37-1.50 (m, 2H), 1.63-1.72
(m, 2H), 4.18 (t, J ) 6.8 Hz, 2H), 6.39 (d, J ) 15.9 Hz, 1H),
7.33-7.34 (m, 3H), 7.48-7.50 (m, 2H), 7.63 (d, J ) 15.9 Hz,
1H); 13C NMR (75 MHz, CDCl3) δ 13.6, 19.0, 30.7, 63.8, 118.2,
127.8, 128.5, 129.7, 134.4, 144.0, 166.0.
Typical Procedure for the Suzuki Reaction. The reaction vessel
was charged with bromobenzene (1 mmol), phenylboronic acid (1.5
mmol), lithium hydroxide monohydrate (1.2 mmol), and the catalyst
(0.01 mol %) in methanol (2 mL). The reaction mixture was stirred
at the given temperature, and the progress of reaction was monitored
by GC. At the end of the reaction, the methanol was removed under
reduced pressure, and the reaction mixture was diluted with EtOAc
(20 mL) and washed with 1 N aq HCl and water. The combined
organic phase was dried over anhydrous Na2SO4. After removal of
the solvent, the residue was subjected to column chromatography
on silica gel using ethyl acetate and hexane mixtures to afford the
Suzuki product in high purity. Biphenyl: 1H NMR (300 MHz,
CDCl3, TMS) δ 7.28-7.33 (m, 2H), 7.40 (t, J ) 7.6 Hz, 4H), 7.56
(d, J ) 8.3 Hz, 4H); 13C NMR (75 MHz, CDCl3) δ 127.12, 127.20,
128.7, 141.2.
Acknowledgment. P.S. thanks UGC and J.Y. thanks CSIR,
India for their fellowships.
Supporting Information Available: General experimental
procedures, characterization data of complexes and products.
This material is available free of charge via the Internet at
http://pubs.acs.org.
JO900361C
J. Org. Chem. Vol. 74, No. 13, 2009 4885