explored, this type of ligands has been shown lately to have
interesting applications in the Heck reaction. Very recent
Pd and 30% mol of 1. Reaction at 130 °C for 10 h provided
the desired product in an almost quantitative yield. It is worth
noting that 1 would create a five-membered ring with Pd
when they form a bidentate complex. We wondered whether
by changing the ring size we could attain a more efficient
catalyst. Thus, we studied the use of 2 in the Heck reaction
between bromobenzene and styrene and compared its
performance with 1 and 4-(N,N-dimethylamino)butanoic acid
(3). In our study, the ratio between Pd and the ligand was
set to 1:1, contrary to 1:20 in Reetz’s study. After a few
solvent systems were examined, we concluded that NMP was
the best solvent (see Table 1). Instead of 1 mol mol, it was
6
7
examples include thioureas, imines and oximes, bispy-
ridines,8 phenanthrolines, hydrazones, tetramethylgua-
9
10
11
12
13
nidines, hydroxyquinolines, oxazolines, thiosemicarba-
zones,14 tetrazoles, bisimidazoles,16 and amino acids.
15
17
These phosphine-free ligands are potentially advantageous
for being chemically stable and economically inexpensive.
As a result, further synthetic as well as mechanistic studies
on these ligands are highly warranted.
1
9
We recently started a systematic study on how to use
more economically competitive metals (e.g., Fe, Ni, and Cu)
and/or ligands (in particular, phosphine-free ligands) to
accomplish the classical Pd-catalyzed reactions.18 We aim
at not only finding novel catalysts but also, more importantly,
a mechanstic understanding of the catalytic processes. In
continuing such efforts, our attention was drawn to an
intriguing finding by Reetz et al. that Pd(II) salts in the
presence of N,N-dimethylglycine ligand (1) constitute “the
simplest and one of the most reactive and selective catalyst
systems for the Heck reaction”.17 Herein, we report our
finding that N,N-dimethyl-â-alanine (2) is an even more
efficient ligand for the Heck reaction (Figure 1). Furthermore,
a
Table 1. Heck Reaction between Bromobenzene and Styrene
Pd
T
(°C)
time
(h)
yieldb
(%)
entry (mol %) ligand
base
solvent
1
2
3
4
5
6
7
8
9
1
1
1
1
0.1
0.01
0.1
0.1
0.1
2
2
2
2
2
2
K2CO3 130
K2CO3 130
K2CO3 130
K2CO3 130
K2CO3 130
K2CO3 130
K2CO3 130
K2CO3 130
K2CO3 130
10
10
10
10
10
20
10
10
10
DMF
DMA
DMSO
NMP
NMP
NMP
NMP
NMP
NMP
86
83
38
99
99
96
42
81
70
1
3
a
Reaction conditions: bromobenzene (0.5 mmol), styrene (0.75 mmol),
base (1 mmol), solvent (1 mL), under Ar. b GC yields.
Figure 1. N,O-Bidentate ligands used for the Heck reaction.
found that 0.1 mol % of Pd/2 was active enough for giving
a quantitative yield in 10 h. A further decrease of Pd/2 to
0.01 mol % could lead to a significant TON as high as about
we report the first theoretical study on how the N,O-bidentate
ligands operate in the Pd catalysis.
To begin our study, we noted that the optimal reaction
condition reported by Reetz et al. consisted of 1.5% mol of
4
10 . However, the relatively long reaction time would not
2
be considered desirable for pragmatic applications. Com-
pared to Pd/2, the yield in the absence of any ligand was
much lower (42%) presumably due to the rapid formation
of Pd black, a visible phenomenon we confirmed in our
experiment. Furthermore, the yields for Pd/1 (81%) and Pd/3
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(70%) were also determined to be lower than that of Pd/2
(99%) under the same reaction conditions. Thus, we con-
(7) (a) Grasa, G. A.; Singh, R.; Stevens, E. D.; Nolan, S. P. J. Organomet.
Chem. 2003, 687, 269. (b) Arellano, C. G.; Corma, A.; Iglesias, M.; Sanchez,
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cluded temporarily that 2 was superior to 1 and 3 in the
catalysis.
(15) Gupta, A. K.; Song, C. H.; Oh, C. H. Tetrahedron Lett. 2004, 45,
4113.
(
8) (a) Buchmeiser, M. R.; Wurst, K. J. Am. Chem. Soc. 1999, 121,
1
1101. (b) Buchmeiser, M. R.; Schareina, T.; Kempe, R.; Wurst, K. J.
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(
7
0, 2191.
11) Li, S. H.; Xie, H. B.; Zhang, S. B.; Lin, Y. J.; Xu, J. N.; Cao, J. G.
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(19) Compound 1 was purchased. Compound 2 was prepared by
methylation of â-alanine. Compound 3 was prepared by hydrolysis and
subsequent methylation of N-methyl-2-pyrrolidone. They were all used as
their hydrochloride salts.
(
(
(
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(
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Org. Lett., Vol. 8, No. 12, 2006