Palladium-Catalyzed Suzuki - Miyaura Cross-Couplings of Sulfonyl Chlorides and Boronic Acids

Article abstract of DOI:10.1021/ol036131x

(Equation presented) Arene-, arylmethane, and alk-2-ene-1-sulfonyl chlorides undergo Suzuki - Miyaura cross-coupling with arene-, heteroarene-, and alkeneboronic acids in THF at reflux. The reactivity order is Arl > ArSO₂Cl > ArBr ? ArCl.

Full text of DOI:10.1021/ol036131x

ORGANIC
LETTERS
2
004
Vol. 6, No. 1
5-98
Palladium-Catalyzed Suzuki−Miyaura
Cross-Couplings of Sulfonyl Chlorides
and Boronic Acids
9
Srinivas Reddy Dubbaka and Pierre Vogel*
Institute of Molecular and Biological Chemistry, Swiss Institute of Technology,
BCH CH-1015 Lausanne, Switzerland
pierre.Vogel@epfl.ch
Received October 31, 2003
ABSTRACT
Arene-, arylmethane, and alk-2-ene-1-sulfonyl chlorides undergo Suzuki−Miyaura cross-coupling with arene-, heteroarene-, and alkeneboronic
acids in THF at reflux. The reactivity order is ArI > ArSO Cl > ArBr . ArCl.
2
The palladium-catalyzed Suzuki-Miyaura reaction has
emerged as an extremely powerful method for the cross-
coupling of aryl bromides, iodides, and triflates with boronic
the palladium-catalyzed Stille cross-coupling of sulfonyl
chlorides and organostannanes. We are reporting here that
arene-, phenylmethane-, and 2-methylprop-2-enesulfonyl
chlorides can be condensed with arene-, heteroarene-, and
alkeneboronic acids in the presence of a palladium catalyst
(Scheme 1).
9
1
acids. Coupling between electron-rich or electron-neutral
aryl chlorides and arene boronic acids is also possible by
using palladium complexes with sterically hindered, electron-
rich, or carbene ligands such as those developed by Buch-
2
3
4
wald, Fu, and Herrmann, respectively. Aryl arenesulfonates
5
6
can cross-couple with arylboronic acids. Vinylation, car-
bonylation and homocoupling of arenesulfonyl chlorides
have already been described. Recently, we have disclosed
Scheme 1. Cross-Coupling of Sulfonyl Chlorides with
7
8
Boronic Acids
(1) For reviews, see for example: (a) Miyaura, N.; Suzuki, A. Chem.
ReV. 1995, 95, 2457-2483. (b) Littke, A. F.; Fu, G. C. Angew. Chem., Int.
Ed. 2002, 41, 4176-4211. (c) Hassan, J.; S e´ vignon, M.; Gozzi, C.; Schulz,
E.; Lemaire, M. Chem. ReV. 2002, 102, 1359-1469. (d) Kotha, S.; Lahiri,
K.; Kashinath, D. Tetrahedron 2002, 58, 9633-9695. (e) Agrofoglio, L.
A.; Gillaizeau, I.; Saito, Y. Chem. ReV. 2003, 103, 1875-1916.
In our first search for optimal reaction conditions, we
explored the condensation of p-toluenesulfonyl chloride
(
2) (a) Wolfe, J. P.; Buchwald, S. L. Angew. Chem., Int. Ed. 1999, 38,
413-2416. (b) Wolfe, J. P.; Singer, R. A.; Yang, B. H.; Buchwald, S. L.
J. Am. Chem. Soc. 1999, 121, 9550-9561.
3) (a) For a recent review, see: Littke, A. F.; Fu, G. C. Angew. Chem.,
(5) (a) Percec, V.; Bae, J.-Y.; Hill, D. H. J. Org. Chem. 1995, 60, 1060-
1065. (b) Nguyen, H. N.; Huang, X.; Buchwald, S. L. J. Am. Chem. Soc.
2003, 125, 11818-11819.
2
(
(6) (a) Kasahara, A.; Izumi, T.; Kudou, N.; Azami, H.; Yamamato, S.
Chem. Ind. (London) 1988, 51-52. (b) Miura, M.; Hashimoto, H.; Itoh,
K.; Nomura, M. Tetrahedron Lett. 1989, 30, 975-976. (c) Miura, M.;
Hashimoto, H.; Itoh, K.; Nomura, M. J. Chem. Soc., Perkin. Trans. 1 1990,
8, 2207-2211.
Int. Ed. 2002, 41, 4176-4211. (b) Littke, A. F.; Fu, G. C. Angew. Chem.,
Int. Ed. 1998, 37, 3387-3388.
(4) (a) For recent review, see: Herrmann, W. A. Angew. Chem., Int.
Ed. 2002, 41, 1290-1309. (b) Hillier, A. C.; Grasa, G. A.; Viciu, M. S.;
Lee H. M.; Yang, C.; Nolan S. P. J. Organomet. Chem. 2002, 653, 69-82.
(7) Miura, M.; Itoh, K.; Nomura, M. Chem. Lett. 1989, 77-78.
(8) Miura, M.; Hashimoto, H.; Itoh, K.; Nomura, M. Chem. Lett. 1990,
459-460.
(
1
c) Herrmann, W. A.; Reisiner, C. P.; Spieger, M. J. Organomet. Chem.
998, 557, 93-96. (d) Zhang, C.; Huang, J.; Trudell, M. L.; Nolan S. P. J.
Org. Chem. 1999, 64, 3804-3805.
(9) Dubbaka, S. R.; Vogel, P. J. Am. Chem. Soc. In press.
1
0.1021/ol036131x CCC: $27.50 © 2004 American Chemical Society
Published on Web 12/10/2003

(TsCl) with 3-nitrobenzeneboronic acid in the presence of
various catalysts such as Pd(PPh
3
)
4
, PdCl
2
(PhCN)
2
, Pd
2
(dba)
3
+
+
P(t-Bu)
3
, Pd
2
(dba)
3
+ tri-2-furylphosphine, and Pd (dba)
2
3
2-(di-tert-butylphosphino)biphenyl in boiling DME, DMF,
10
THF, or dioxane. Cross-coupling occurred only in the
presence of a base such as K CO , Cs CO , K PO , or Et N.
The best yield (60%) was obtained using 8 mol % Pd(PPh
and 2.0-3.0 equiv of K CO
2
3
2
3
3
4
3
3 4
)
2
3
.
Then, we searched to optimize the proportion of palladium
employed, screening different sterically hindered, electron-
11
rich, or carbene ligands, as well as bases and solvents
Table 1 and Figure 1) for 1-naphthalenesulfonyl chloride
(
reacting with 4-methylbenzeneboronic acid.
Table 1. Screening of Bases for Suzuki-Miyaura
Cross-Coupling of Sulfonyl Chloride and Boronic Acid
entry
base
Et3N
NaOAc
Cs2CO3
K3PO4
K2CO3
Na2CO3
Li2CO3
yielda
1
2
3
4
5
6
7
10
5
0
19
41
60
28
Figure 1. Screening of ligands for Suzuki-Miyaura cross-coupling
of sulfonyl chloride and boronic acid.
a
Yields of cross-coupling products determined after flash chromatog-
raphy.
observed in some cases as a concurrent reaction.13 The
proportion of the latter was lower in boiling THF than in
boiling dioxane, acetonitrile, 1,2-dimethoxyethane, or p-
xylene. When Pd(PPh ) was used as a catalyst, traces of
3 4
diarylsulfide were frequently observed. For instance, treat-
We found that Na
acid (without destroying the sulfonyl chloride) compared to
other bases such as Et N, Cs CO , NaOAc, K PO , K CO
or Li CO . When using Cs CO as a base, the formation of
2 3
CO is a better activator for the boronic
3
2
3
3
4
2
3
,
2
3
2
3
ment of p-toluenesulfonyl chloride with 4-methoxyben-
the cross-coupling product was not observed, but all the
starting sulfonyl chloride was consumed. When NaOAc was
used as a base, the cross-coupling product was isolated in
low yield (6%). Under these conditions, starting sulfonyl
chloride was consumed in ca. 5 h. This is explained by the
fact that the sulfonyl chloride is converted into the corre-
sponding sulfonate, which retards the reaction.
zeneboronic acid in the presence of Pd(PPh
3 4 2 3
) and K CO
(3 equiv) led to Tol-S-Ar (Ar ) 4-methoxyphenyl) that was
isolated in 8% yield. This byproduct results probably from
the reduction of the sulfonyl chloride into the corresponding
9,14
sulfenyl chloride, which is then coupled with the boronic
acid following the Suzuki-Miyaura catalytic cycle (Figure
A small library of ligands was tested, and it was found
that the carbene derived by HCl R-elimination from 7
generates, with palladium, the best catalyst (Figure 1).
A wide range of electronically and structurally diverse
sulfonyl chlorides and boronic acids can be cross-coupled
efficiently under these conditions.12 Thus, with respect to
the electron-rich, electron-neutral, and electron-poor arene-
sulfonyl chlorides, they react with the boronic acids to
provide the corresponding biaryl products in good yields in
most cases (Table 2). Self-coupling of boronic acids was
(
12) Typical Experimental Procedure for Catalyst B (Table 3). A
round-bottom flask was dried under vacuum, and to the flask were added
the corresponding sulfonyl chloride (1.00 mmol), Pd2dba3 (0.015 mmol),
ligand 7 (0.06 mmol), Na2CO3 (3 mmol), and the boronic acid (2 mmol)
(were weighed in a glovebox) under a nitrogen atmosphere. Then, the flask
was connected to a vacuum line and then filled with argon (three times),
and THF (5 mL) was added under argon. The reaction mixture was stirred
at reflux for 15-35 h. After cooling to room temperature, the mixture was
diluted with ether and washed with water. The aqueous layer was extracted
again with ether (three times). The combined organic phases were dried
(
Na2SO4), filtered, and concentrated under reduced pressure (solvents were
removed under reflux on cooling to -20 °C in the cases of compounds
with low boiling points or low molecular masses). The residue was purified
by FC.
(
13) Ma n˜ as, M. M.; Perez, M.; Pleixats, R. J. Org. Chem. 1996, 61,
(
(
10) See Supporting Information for screening of catalysts and solvents.
11) All ligands were bought from Strem Chemicals, Inc.
2346-2351.
(14) Oae, S.; Togo, H. Bull. Chem. Soc. Jpn. 1983, 56, 3802-3812.
96
Org. Lett., Vol. 6, No. 1, 2004

Table 2. Palladium-Catalyzed Suzuki-Miyaura
Cross-Couplings of Sulfonyl Chlorides and Boronic Acids
yield*
R1
cat. A /cat. Bb
a
entry
R
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
4-methylphenyl phenyl
55
4-methylphenyl 4-methylphenyl
4-methylphenyl 3-nitrophenyl
4-methylphenyl 3-formylphenyl
4-methylphenyl 4-methoxyphenyl
4-methylphenyl fur-2-yl
4-methylphenyl (E)-2-phenylvinyl 35
4-methylphenyl 4-chlorophenyl
4-methylphenyl 1-naphthyl
70
60
55
50
40
92
65
48
78
76
60
64
65
62
55
61
55
58c
tracee
42f
78
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4-chlorophenyl
4-chlorophenyl
1-naphthyl
1-naphthyl
1-naphthyl
1-naphthyl
1-naphthyl
1-naphthyl
3-nitrophenyl
3-nitrophenyl
4-nitrophenyl
benzyl
3-nitrophenyl
4-methylphenyl
3-formylphenyl
3-nitrophenyl
4-methylphenyl
4-methylphenyl
4-methylphenyl
4-methylphenyl
3-nitrophenyl
4-methylphenyl
4-methylphenyl
4-methylphenyl
3-nitrophenyl
3-nitrophenyl
Figure 2. Probable catalytic cycle for Suzuki-Miyaura cross-
coupling of sulfonyl chlorides and boronic acids.
80
72
82
14d
reactions described here) was more efficient than the classical
catalyst A (Table 2).
Under nonbasic conditions, the cross-coupling reaction was
more efficient in the presence of CuCl (3 equiv) than with
CuBr‚Me
2
S. With 3 equiv of CuI, no reaction was observed.10
70
64
30
35
With p-halogenobenzenesulfonyl chlorides 10, 13, and 17,
we have observed that the sulfonyl chloride group is more
reactive than the bromo- and chloroarene moieties (Scheme
benzyl
methallyl
52
50
35
16
2
). However, iodoarenes are more reactive than arenesulfo-
*
Catalyst A: 8-10 mol % Pd(PPh3)4 and 2-3 equiv of K2CO3. Catalyst
a
B: 1.5 mol % Pd2dba3, 6 mol % ligand 7, and 3 equiv of Na2CO3. R-
nyl chlorides.
b
S-R was isolated as a side product. R-R was isolated as a side product.
Recently, Leadbeater and Marco have reported transition-
metal-free Suzuki-type coupling reactions using tetrabutyl-
ammonium bromide (TBAB) as a phase transfer reagent.17
We have applied these conditions to our sulfonyl chlorides,
but without success. When the reaction is performed in
the presence of a palladium catalyst and TBAB, the corre-
sponding cross-coupling product is obtained in a lower yield
than in the absence of TBAB (Table 2, entry 15).
c
e
d
Catalyst A and activated charcoal. Catalyst B with 1.0 equiv of TBAB.
f
Performed with 1.5 mol % Pd(OH)2/C and Na2CO3 as a base. Performed
with 5 mol % Pd(OAc)2, 10 mol % PPh3, and K2CO3 as a base.
1
8
2
). In contrast, when using carbene, sterically hindered, or
electron-rich ligands, the arylpalladium chloride intermediates
can give the corresponding homocoupled product1 (Figure
).
After screening the different ligands (1-9) (Figure 1), we
have found that catalyst B (although not tested for all the
5
2
When TsCl was mixed with 1 equiv of PdCl
2 2
(PhCN) in
19
THF-d , a signal (δ 145.2 ppm) typical of the C-Pd bond
8
c
Scheme 2. Reactivity Order for Suzuki-Miyaura Cross-Coupling Is ArI > ArSO Cl > ArBr . ArCl
2
Org. Lett., Vol. 6, No. 1, 2004
97

appeared in the 13C NMR spectra after 10 min at 45 °C. At
least two mechanisms can be envisaged for this observa-
chlorides, and arene-, heteroarene-, and alkeneboronic acids
is possible. The reaction provides a useful complement to
our recently described work of Stille cross-couplings of
sulfonyl chlorides and organostannanes and should open new
possibilities for medicinal chemistry and material science.
tion: (1) the metal inserts into the SO
rapid subsequent elimination of SO (Figure 2), or (2) the
oxidative addition of the palladium occurs first onto the C-S
bond, with subsequent elimination of SO
2
-Cl bond first with
9
2
2
.
Acknowledgment. We thank the Swiss National Science
Foundation (Grant No. 2000-20100002/1) and the Office
Federal de l‘Education et de la Sciences, (Grant No. COI.
0071, COST D13/010/01). We thank also Mr. Martial Rey
and Franscico Sep u´ lveda for technical help.
We also examined nickel-catalyzed Suzuki-Miyaura
cross-coupling reactions between various sulfonyl chlorides
and areneboronic acids in the presence of a base, but none
of our assays have been met with success.20
In summary, a palladium-catalyzed cross-coupling reaction
between arene-, phenylmethane-, 2-methylprop-2-enesufonyl
Supporting Information Available: Experimental pro-
cedures, characterization of unknown compounds, and refer-
ences to known compounds. This material is available free
of charge via the Internet at http://pubs.acs.org.
(15) Clark, F. R. S.; Norman, R. O. C.; Thomas, C. B. J. Chem. Soc.,
Perkin Trans. 1 1975, 121-125.
(
(
(
16) For more details, see also ref 9.
17) Leadbeater, N. E.; Marco, M. J. Org. Chem. 2003, 68, 5660.
18) Acetonitrile was used as a solvent instead of water, and K2CO3 was
OL036131X
used as a base.
19) Bergbreiter, D. E.; Osburn, P. L.; Wilson, A.; Sink, E. M. J. Am.
Chem. Soc. 2000, 122, 9058-9064.
(
(20) See Supporting Information for reaction details.
98
Org. Lett., Vol. 6, No. 1, 2004