NiCl2(PCy3)2: A simple and efficient catalyst precursor for the Suzuki cross-coupling of aryl tosylates and arylboronic acids

Article abstract of DOI:10.1021/ol016526l

matrix presented NiCl₂(PCy₃)₂ associated with PCy₃ promotes the selective cross-coupling of aryltosylates with arylboronic acids under relatively mild reaction conditions, and a variety of functional groups are tolerated in both arenes. This is one of the simplest and most efficient experimental procedures for the coupling of arylboronic acids with aryl tosylates reported to date.

Full text of DOI:10.1021/ol016526l

ORGANIC
LETTERS
2
001
Vol. 3, No. 19
049-3051
NiCl (PCy ) : A Simple and Efficient
2
3 2
3
Catalyst Precursor for the Suzuki
Cross-Coupling of Aryl Tosylates and
Arylboronic Acids
Danilo Zim, Vanusa R. Lando, Jairton Dupont, and Adriano L. Monteiro*
Laboratory of Molecular Catalysis, Instituto de Qu ´ı mica, UFRGS,
AV. Bento Gon c¸ alVes 9500, Porto Alegre 91501-970, CP 15003, RS, Brazil
almonte@iq.ufrgs.br
Received August 2, 2001
ABSTRACT
2 3 2 3
NiCl (PCy ) associated with PCy promotes the selective cross-coupling of aryltosylates with arylboronic acids under relatively mild reaction
conditions, and a variety of functional groups are tolerated in both arenes. This is one of the simplest and most efficient experimental procedures
for the coupling of arylboronic acids with aryl tosylates reported to date.
The transition metal catalyzed Suzuki cross-coupling reaction
hydrolyze readily, associated with the higher price of
triflating agents, restricts their application. From a synthetic
point of view, the use of aryl sulfonates (in particular
tosylates) is a very attractive alternative because they are
easily prepared from phenols, are more stable than triflates,
and are cheap and easily available starting materials.
However, there are only few reports on the application of
arene sulfonates in catalytic Suzuki coupling reactions. Yields
up to 81% have been obtained using large quantities (∼10%)
is one of the most efficient methods for the construction of
1
C
aryl-Caryl bonds. Indeed, in recent years various efficient
Pd catalyst precursors have been developed that allow aryl
iodides, bromides, triflates, and chlorides to be effectively
coupled with aryl boronic acids under mild reaction condi-
2
tions. Moreover, Ni-based catalysts have also been success-
3
fully used for the Suzuki reaction of aryl chlorides. Aryl
triflates and sulfonates are regarded as synthetic equivalents
of aryl halides; however, the propensity of triflates to
2
of NiCl (dppf) and Zn (1.7 equiv) for the coupling of aryl
4
mesylates with boronic acids. Higher yields have been
5
(1) Suzuki, A. J. Organomet. Chem. 1999, 576, 147 and references
obtained employing lithium arylborates. However, this
therein.
reaction is limited to mesylates and tosylates containing an
electron-withdrawing group. Herein, we report the use of a
simple and general catalyst system for the nickel-catalyzed
Suzuki cross-coupling reaction of aryl tosylates.
(2) (a) Wolfe, J. P.; Singer, R. A.; Yang, B. H.; Buchwald, S. L. J. Am.
Chem. Soc. 1999, 121, 9550-9561. (b) Old, D. W.; Wolfe, J. P.; Buchwald,
S. L. J. Am. Chem. Soc. 1998, 120, 9722-9723. (c) Littke, A. F.; Da ´ı , C.;
Fu, G. C. J. Am. Chem. Soc. 2000, 122, 4020-4028. (d) Littke, A. F.; Fu,
G. C. Angew. Chem., Int. Ed. Engl. 1998, 37, 3387. (e) Bei, X.; Crevier,
T.; Guran, A. S.; Jandeleit, B.; Powers, T. S.; Turner, H. W.; Uno, T.;
Weinberg, W. H. Tetrahedron Lett. 1999, 40, 3855-3858. (f) Zhang, C.
M.; Huang, J. K.; Trudell, M. L.; Nolan, S. P. J. Org. Chem. 1999, 64,
A series of experiments were performed in order to
determine the feasibility of using aryl tosylates in the Ni-
catalyzed Suzuki reaction. Initially, we examined the cou-
3
804-3805. (g) Zim, D.; Gruber, A. S.; Ebeling, G.; Dupont, J.; Monteiro,
A. L. Org. Lett. 2000, 2, 2881-2884.
3) (a) Saito, S.; Oh-tani, S.; Miayaura, N. J. Org. Chem. 1997, 62, 8024-
030. (b) Indolese, A. F. Tetrahedron Lett. 1997, 38, 3513-3516. (c)
Lipshutz, B. H.; Sclafani, A.; Blomgren, P. A. Tetrahedron 2000, 56, 2139-
144.
(
8
(4) Percec, V.; Bae, J.-Y.; Hill, D. H. J. Org. Chem. 1995, 60, 1060-
1065.
(5) Kobayashi, Y.; Mizojiri, R. Tetrahedron Lett. 1996, 37, 8531-8534.
2
1
0.1021/ol016526l CCC: $20.00 © 2001 American Chemical Society
Published on Web 08/21/2001

pling of 4-tert-butylphenyltosylate with PhB(OH)
Ni(0) viz. [Ni(cod) ] in the presence of phosphine ligands,
or NiCl (L ) PPh and PCy ) under various reaction
conditions. 1,4-Dioxane was found to be the most effective
solvent, and K PO was the base of choice. The addition of
further phosphine ligands is necessary, and PCy gave the
2
using
are efficiently coupled to provide the corresponding biaryl
products in excellent isolated yields (>94%). Although
complete conversion was not observed for the coupling of
the aryl tosylates containing electron-donating groups, the
corresponding biaryl products were isolated in good yields
(79-89%, entries 3-6). Side reactions such as the homo-
coupling of aryl boronic acid and aryl tosylate hydrolysis
were negligible. Ortho methyl-substituted aryl tosylates (entry
7) gave lower yields as compared to meta- and para-
substituted analogues (entries 5 and 6, respectively). Lower
2
2
L
2
3
3
3
4
3
best results. Similar results were obtained using Ni(0) or
Ni(II) catalyst precursors in the presence of an excess of
PCy
3 2 3 2
. Since NiCl (PCy ) is a stable complex and easy to
prepare and manipulate, we used it instead of the unstable
6
and air-sensitive Ni(cod)
2
. To our surprise, we found that
yields were found for the Suzuki reaction of 2-CH
OTs with PhB(OH) (entry 8). Ni-catalyzed reactions are
more sensitive to steric hindrance than those involving Pd-
3 2 6 4
O CC H -
the reaction can be carried out using 1.5-3 mol % of
2
4
NiCl
The coupling of a wide variety of aryl tosylates with
PhB(OH) was examined using NiCl (PCy under opti-
mized reaction conditions (Table 1).
2 3 2
(PCy ) in the absence of reducing agents such as Zn.
2
a,3a
catalysis.
Attempts to perform the cross-coupling of 2,4,6-
gave only modest
2
2
3
)
2
trimethylphenyltosylate with PhB(OH)
2
yields (30%) of biphenyl product. However, the promising
results obtained for para- and meta-substituted aryl tosylates
render this system a new and useful tool in the Suzuki cross-
coupling reaction. For instance, the combination of the
Aryl tosylates containing electron-withdrawing groups
entries 1 and 2) and naphthyl tosylates (entries 9 and 11)
(
7
present reaction and the Pd-catalyzed Suzuki reaction can
be used to produce unsymmetrically substituted terphenyl
compounds in high yields (Scheme 1).
2 3
Table 1. NiCl (PCy )-catalyzed Suzuki Cross-Coupling of Aryl
a
Tosylates and PhB(OH)
2
Scheme 1. Synthesis of an Unsymmetric Terphenyl
Compound
3 n
The catalytically active species are probably Ni(PCy )
formed from the sequence involving aryl boronic acid
transmetalation and reductive elimination (Scheme 2). In-
Scheme 2. Reaction Path for Ni-Catalyzed Suzuki
Cross-Coupling Reaction of Aryltosylates
deed, in all cases 2-3% of the aryl boronic acid homo-
coupled product was observed. The general mechanism of a
transition metal catalyzed cross-coupling reaction between
a
Reaction conditions: 1.0 equiv of aryl tosylate, 1.5 equiv of PhB(OH)2,
.0 equiv of K3PO4, 1.5 mol % NiCl2(PCy3)2 (entries 1, 2, 9, and 10), 3
mol % NiCl2(PCy3)2 (entries 3-8), PCy3/NiCl2(PCy3)2 ) 4, dioxane (5
mL), 130 °C, 14-60 h. Isolated yields (average of two runs).
2
(6) This compound is easily prepared by reaction of PCy3 with NiCl2‚
6H2O. Barnett, K. W. J. Chem. Educ. 1974, 51, 422-423.
(7) Zim, D.; Monteiro, A. L.; Dupont, J. Tetrahedron Lett. 2000, 41,
8199-8202.
3050
Org. Lett., Vol. 3, No. 19, 2001

organo-electrophiles and organometallic reagents involving
sequential oxidative addition, transmetalation, and reductive
elimination can explain the observed results. In the first step,
the electron-rich Ni(0) complex formed is stabilized by PCy
3
,
and it undergoes the oxidative addition to aryl tosylates.
The low reactivity of aryl sulfonates and chlorides can be
correlated with their poor reactivity toward oxidative addition
in the catalytic cycle. A plot of the relative reactivity of
substituted aryl tosylates against the σ constant gave a value
of F ) 2.0 and 1.6 for the coupling with 4-MePhB(OH)
2
and 4-MeOPhB(OH) , respectively, as shown in Figure 1.
2
Figure 2. Effects of substituents on aryl boronic acids: 4-NCC
6 4
H -
OTs (O), PhOTs (2), and 4-MeOC OTs (0).
6 4
H
has been proposed for the reductive elimination of biaryls.10
Since the relative reactivity increases when aryl boronic acids
containing electron-withdrawing groups are used, the trans-
metalation step is more likely to be the rate-determining step.
Further evidence that transmetalation is the rate-determining
step for aryl tosylates is that the reaction of 4-tBuC
with PhB(OH) proceeds more rapidly once the amounts of
boronic acid and K PO are increased. A yield of 35% in
biaryl product was obtained after 1.5 h with 1.5 equiv of
PhB(OH) and 2.0 equiv of K PO , whereas a 50% yield
was observed after the same period of time when 3.0 equiv
of PhB(OH) and 4.0 equiv of K PO were employed.
6 4
H OTs
2
3
4
2
3
4
Figure 1. Effects of substituents on aryl tosylates: 4-MePhB(OH)
b) and 4-MeOPhB(OH) (0).
2
(
2
2
3
4
In conclusion, we have developed the first active and
general system for the Suzuki coupling of aryl tosylates based
on NiCl (PCy ) , which is stable and easy to prepare and
2 3 2
This electronic effect is not surprising, since electron-
withdrawing groups are expected to accelerate the Ar-OTs
oxidative step. However, the F value is too low compared
to those observed for aryl chlorides. These values suggest
that oxidative addition is not the rate-determining step in
the case of aryl tosylates. We have noted that in a competitive
manipulate. From a synthetic point of view, these results open
new possibilities for exploiting the Suzuki reaction, since
aryl tosylates are easily prepared from phenols, are less
susceptible to hydrolysis than aryl triflates, and are cheap
and easily available starting materials. Moreover, in the case
of aryl tosylates the transmetalation reaction is the rate-
determining step. Further mechanistic studies are currently
under investigation.
8
experiment using NiCl
2 3 2
(PCy ) , aryl tosylates react twice as
fast as aryl chlorides.9
The plot of the relative reactivity of substituted aryl
tosylates against the σ constant shows that the relative
reactivity is sensitive to the substituents on the aryl boronic
acids (Figure 2). The correlation yields a value of F ≈ 0.8
independent of the substituents on the aryl tosylate (4-
Acknowledgment. We thank PADCT, CNPq, and
FAPERGS for partial financial support and CNPq for a
scholarship (D.Z. and VL). We also thank Dr. John Spencer
(U.K.) for proofreading the manuscript.
NCC
6 4
H OTs F ) 0.76; PhOTs F ) 0.81; 4-MeOC
6 4
H OTs F
)
0.85). This indicates a subsequent rate-determining step
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.
such as transmetalation or reductive elimination. A concerted
process with the participation of the π-orbitals of aryl groups
(
8) R ) 8.6 for substituent groups with σ > 0.23 (see ref 3a).
(
9) The reaction of 4-tBuC6H4OTs (10 mmol) and 4-MeC6H4Cl (10
OL016526L
mmol) with PhB(OH)2 (1 mmol) gave 15% conversion based on PhB(OH)2
after 1 h (67:33 proportion of 4-tbutylbiphenyl to 4-methylbiphenyl).
(10) Ozawa, F.; Yamamoto, A. J. Chem. Soc. Jpn. 1987, 773-784.
Org. Lett., Vol. 3, No. 19, 2001
3051