Tetrahedron Letters
Bisamides as ligands in Suzuki coupling reactions catalyzed
by palladium
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Daniel P. da Costa, Sabrina M. Nobre
Escola de Química e Alimentos, Universidade Federal do Rio Grande, Av. Itália, km 08, Campus Carreiros, 96203-900 Rio Grande-RS, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
This protocol uses palladium chloride and bisamides as ligands for Suzuki cross-coupling reactions, in
mild (25° for 2 h) aerobic conditions. This study was efficient for arylboronic acids and/or aryl bromides
with activating or deactivating substituents in the ring with high yields (81–95%).
Ó 2013 Elsevier Ltd. All rights reserved.
Received 2 May 2013
Revised 18 June 2013
Accepted 22 June 2013
Available online 1 July 2013
Keywords:
Symmetrical bisamide
Suzuki cross-coupling reaction
Palladium
Aerobic conditions
Introduction
Results and discussion
Cross-coupling reactions are one of the most efficient methods
for the construction of molecules Caryl–Caryl bonds with widespread
Different types of ligands have been used over the past few
years; however, there are few examples using bisamide com-
pounds as ligands. In this Letter, we aimed at reporting that a sim-
ple system, such as palladium chloride and bisamide as ligands, is
able to perform the Suzuki cross-coupling of arylbromides in mild
conditions and with low loadings of catalyst.
1
–4
use in organic synthesis.
There was substantial growth in terms
of publications and patents with the Suzuki–Miyaura cross-
coupling, Heck, Sonogashira, and Negishi coupling reactions in
5
the last decade. Due to these important reactions, Richard Heck,
Ei-ichi Negishi, and Akira Suzuki were awarded the Nobel Prize
in Chemistry in 2010. Furthermore, these reactions have been
Firstly, we synthesized two different bisamides, compounds
1a31 and 1b, both derived from etylenediamine (Scheme 1).
These bisamides, which provided yields above 70%, were not ap-
plied to cross-coupling. After being synthesized and characterized,
these bisamides were used as ligands in Suzuki reactions. Firstly, a
set of experiments was carried out with 4-bromotoluene and phen-
ylboronic acid in order to establish the best conditions for cross-cou-
6,7
extensively used in the synthesis of pharmaceuticals,
liquid
8
crystal compounds, natural products, industrial intermediates,
9
,10,3
and molecular materials.
Phosphine ligands and derivatives
have been most commonly employed in reactions,1
1–13
though
most of these phosphines are sensitive to air and moisture, besides
being expensive and toxic. Needless to say, it places significant lim-
its on their synthetic applications.14 Therefore, new ligands have
been studied for the Suzuki reaction such as N-heterocyclic
pling. Bases (K
dioxane, acetonitrile, MeOH, and toluene). For both auxiliary ligands
1a and 1b, the best base was K CO and the best solvent was MeOH.
For both auxiliary ligands, catalytic precursor Pd(OAc) and
PdCl (Table 1) were tested. Although two catalyst precursors pro-
3 4 2 3
PO , K CO ) were evaluated in the solvent (THF,
2
3
1
5,16
17
18,19
20
carbenes,
mes,
imine
diamino,
iminophosphine,
aryloxi-
2
2
1–23
24–26
ligandless 27–30 and few examples with
guanidenes,
2
1
0
bisamides. In this Letter, we have reported a simple system—
composed by palladium chloride and bisamide as ligands—
which is able to perform the Suzuki cross-coupling reaction with
both arylboronic acids and/or aryl bromides with activating or
deactivating substituents in the ring, in aerobic and mild
conditions.
vided the expected coupling product, palladium chloride showed
better results in reactions.
Low conversion were obtained in the absence of bisamide
ligand (Table 1, entries 3 and 6). Both ligands were found to be
efficient. However, PdCl was more efficient, principally for ligand
2
2
1b. It may have occurred because, in PdCl , the metal is more avail-
able to undergo oxidative addition.
Temperatures ranging from 25 to 130 °C were screened in this
system (Table 2). Table 2 also compares the efficiency of both
catalytic bisamide ligands and ethylenediamine, precursor of the
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