Palladium-Catalyzed Stille Cross-Couplings of Sulfonyl Chlorides and Organostannanes

Article abstract of DOI:10.1021/ja038328q

Arene and phenylmethanesulfonyl chlorides can be cross-coupled with aryl, heteroaryl, and alkenylstannanes with desulfitation in the presence of 10 mol % CuBr·Me₂S, 1.5 mol % Pd₂dba₃, and 5 mol % tri-2-furylphosphine in tetrahydrofuran or toluene under reflux. This extension of the Stille cross-coupling reaction realizes a new and economical method for the generation of C?C bonds. The palladium-catalyzed carbonylative Stille cross-coupling reactions of arenesulfonyl chlorides and organostannanes in the presence of CO (60 bar) at 110 °C in toluene generate the corresponding ketones. Arenesulfonyl chlorides are more reactive than aryl chlorides and aryl bromides in their Stille cross-coupling with organostannanes but less reactive than aryl iodides. The new methods disclosed for the generation of C?C bonds open new possibilities for medicinal chemistry and material sciences. Copyright

Full text of DOI:10.1021/ja038328q

Published on Web 11/18/2003
Palladium-Catalyzed Stille Cross-Couplings of Sulfonyl Chlorides and
Organostannanes
Srinivas Reddy Dubbaka and Pierre Vogel*
Institute of Molecular and Biological Chemistry, Swiss Institute of Technology,
BCH CH-1015 Lausanne, Switzerland
Received September 4, 2003; E-mail: pierre.vogel@epfl.ch
Table 1. Catalysts Screening
The efficient methods for the construction of carbon-carbon
bonds represent an ongoing, central theme of research of organic
synthesis.1 Transition-metal-catalyzed cross-coupling of organo-
metallic reagents with halides or triflates constitutes today one of
the most powerful methods to generate carbon-carbon bonds. In
the Stille reaction,2,3 organostannanes are used as reaction partners.
They remain attractive because of their availability and air and
moisture stability, as well as their compatibility with a variety of
functional groups. Arene- and alkanesulfonyl chlorides are readily
available compounds but have rarely been used as coupling partners
in transition-metal-catalyzed cross-coupling reactions with orga-
nometallic species to construct carbon-carbon bonds. Arenesulfonyl
chlorides have been engaged in carbon-vinylation,4 carbon-carbo-
nylation,5 and homo-couplings.6 To our knowledge, they have never
been used in Stille cross-coupling reactions. We report here that
arene and phenylmethanesulfonyl chlorides can be cross-coupled
with aryl, heteroaryl, vinyl, and alkenylstannanes with desulfitation
in the presence of palladium and copper catalysts.
entry
Pd catalysts
yield (%)a
1
2
3
4
5
1.5% Pd2dba3/5% TFP
4% Pd2dba3/15% TFP
8% Pd(PPh3)4
8% PdCl2(PhCN)2
8% PdCl2(PPh3)2
90 (92)b
93
41
36
35
a
Yields of cross-coupling products, determined after chromatography.
In toluene.
b
obtained in 85% yield. This solvent effect contrasts with what
Guillaumet and co-workers found. In their case, DME did not favor
homocoupling of organostannanes.11
We also examined the palladium-catalyzed carbonylative Stille
cross-coupling reaction of arenesulfonyl chlorides and organostan-
nanes in the presence of carbon monoxide (60 bar) at 110 °C in
toluene.12 The carbonylative cross-coupled products were obtained
in moderate yields only due to the formation of the carbonylative
homocoupled products of stannanes (Scheme 1).
When we used THF instead of toluene as solvent in the
carbonylative Stille reaction, the Ar-S-CO-Ar1 product was
obtained as traces. The amount of thioester increased with the
amount of TFP added to the reaction mixture. The formation of
the thioethers arises from the reduction of the sulfonyl chloride by
the phosphine into the corresponding sulfenyl chloride,13 which then
undergoes the arylcarbonylation (Scheme 2). This process is
analogous to the known Co2(CO)8-catalyzed carbonylation of
thiols14 and to the thiocarbonylation of acetylenes with thiols and
carbon monoxide catalyzed by palladium15 or platinum complexes.16
When TsCl was mixed with 1 equiv of PdCl2(PhCN)2 in THF-
d8, a signal (δc 145.2 ppm) typical of the C-Pd bond17 appeared
in the 13C NMR spectrum after 10 min at 45 °C. The metal may
We examined first the condensation of 1-naphthalenesulfonyl
chloride with tributyl(4-fluorophenyl)stannane in the presence of
10 mol % of CuBr‚Me2S. Four different palladium catalysts were
assayed, and, as shown in Table 1, the best conditions were found
with 1.5 mol % of Pd2dba3 + 5 mol % tri-2-furylphosphine (TFP).
We then explored the possibility to generalize this new reaction
to other arenesulfonyl chlorides and to phenylmethanesulfonyl
chloride using organostannanes of different types. The results are
summarized in Table 2. With Pd(PPh3)4 as catalyst, the correspond-
ing cross-coupled products were obtained in moderate to poor yields
(Table 2). In this case, two major products were obtained: the one
arising from the self-coupling of the organostannanes (heteroaryl)
and another one, a diarylsulfide, which could be obtained after
reduction of the first formed sulfone.7 However, with 1.5 mol %
Pd2dba3, 5 mol % TFP, and 10 mol % CuBr‚Me2S, a wide range
of electronically and structurally diverse sulfonyl chlorides and
organostannanes can be cross-coupled efficiently with desulfitation.8
Thus, with respect to the electron-rich, electron-neutral, and
electron-poor arenesulfonyl chlorides, they react with organostan-
nanes to provide the corresponding biaryl products in good yields
in most of the cases. Traces of the byproducts arising from self-
coupling of organostannanes were observed in some cases.9
When a larger amount of CuBr‚Me2S (e.g., 1.3 equiv) was used
as cocatalyst, the reaction was faster, but the major product was
the one arising from the self-coupling of organostannane.10 Cross-
coupling without cocatalyst is somewhat slower than when using
10 mol % of CuBr‚Me2S. Poorer yield was obtained when
performing the same reaction under air atmosphere (entry 22, Table
2).
insert into the SO2-Cl bond first with rapid subsequent elimination
of SO2 or first onto the C-S bond with subsequent elimination of
SO2. Both mechanisms convert the arenesulfonyl chloride into an
arylpalladium species, which then undergoes the cross-coupling
reaction with the organostannane, in a similar way as aryl halides
or triflates would undergo the Stille condensations.2 In those
reactions and under our conditions,8 the sulfonyl chloride group is
more reactive (entries 9-11, Table 2) than the corresponding
chloride18 and bromide.19 For example, in the reaction of 4-bro-
mobenzenesulfonyl chloride with tributyl(4-fluorophenyl)stannane,
the cross-coupled product (38%) (entry 11, Table 2) and the bis
cross-coupled product (traces) are obtained together with 4-bro-
mobenzenesulfonic acid (32%) and 4′-fluoro-1,1′-biphenyl-4-sul-
fonic acid (2.5%).20 However, sulfonyl chlorides proved to be less
We have observed that in the reaction of tributyl(thien-2-yl)-
stannane with toluenesulfonyl chloride (entry 24, Table 2) in DME
instead of THF as solvent at 65 °C, the homocoupled product was
9
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J. AM. CHEM. SOC. 2003, 125, 15292-15293
10.1021/ja038328q CCC: $25.00 © 2003 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Palladium-Catalyzed Stille Cross-Couplings of Sulfonyl
Chlorides and Organostannanes
heteroaryl, vinyl, and alkenylstannanes are presented. This opens
new possibilities for medicinal chemistry and material sciences.
Acknowledgment. We thank the Swiss National Science
Foundation (Grant No. 2000-20100002/1) and the office Fe´de´ral
de l’Education et de la Science (OFES) (Grant No. COI. 0071,
COST D13/010/01).
1
entry
R
R
yielda
1b
1-naphthyl
1-naphthyl
1-naphthyl
1-naphthyl
1-naphthyl
1-naphthyl
1-naphthyl
4-fluorophenyl
4-fluorophenyl
4-fluorophenyl
4-methylphenyl
3-methylphenyl
3-methylphenyl
3-nitrophenyl
phenyl
4-methylphenyl
4-fluorophenyl
4-fluorophenyl
4-fluorophenyl
4-fluorophenyl
4-methylphenyl
4-methylphenyl
3-nitrophenyl
3-methylphenyl
3-methylphenyl
4-fluorophenyl
4-fluorophenyl
phenyl
90 (92)c
93
41
81
81
2d
Supporting Information Available: Experimental procedures,
unknown compound characterization and references to known com-
pounds(PDF). This material is available free of charge via the Internet
at http://pubs.acs.org.
3e
4b
5b
6e
39
82
84
7b
8b
phenyl
References
9b
4-chlorophenyl
4-chlorophenyl
4-bromophenyl
4-iodophenyl
4-nitrophenyl
4-nitrophenyl
4-methylphenyl
4-methylphenyl
4-methylphenyl
4-methylphenyl
4-methylphenyl
4-methylphenyl
4-methylphenyl
4-methylphenyl
4-methylphenyl
4-methylphenyl
4-methylphenyl
4-methylphenyl
4-methylphenyl
benzyl
66f
51f
38g
tracesg
89
10b
11b
12b
13b
14b
15b
16b
17b
18e
19b
20e
21b
22e
23b
24i
25b
26b
27b
28b
29c
30c
(1) (a) Heck, R. F. Palladium Reagents in Organic Synthesis; Academic
Press: New York, 1985. (b) Tsuji, J. Palladium Reagents and Catalysts:
InnoVations in Organic Synthesis; Wiley & Sons: New York, 1995. (c)
Mitchell, T. N. In Metal-Catalyzed Cross-Coupling Reactions; Diederich,
F., Stang, P. J., Eds.; Wiley-VCH: Weinheim, 1998, Chapter 4.
(2) For reviews of the Stille reaction, see (a) Stille, J. K. Angew. Chem., Int.
Ed. Engl. 1986, 25, 508-524. (b) Farina, V.; Krishnamurthy, V.; Scott,
W. J.; The Stille Reactions, Organic Reactions; Wiley & Sons: New York,
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E.; Lemaire, M. Chem. ReV. 2002, 102, 1359-1469.
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(b) Kosugi, M.; Sasazawa, K.; Shimizu, Y.; Migita, T. Chem. Lett. 1977,
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Ind. (London) 1988, 51-52. (b) Miura, M.; Hashimoto, H.; Itoh, K.;
Nomura, M. Tetrahedron Lett. 1989, 30, 975-976. (c) Miura, M.;
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(5) Miura, M.; Itoh, K.; Nomura, M. Chem. Lett. 1989, 77-78.
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(7) Oae, S.; Togo, H. Bull. Chem. Soc. Jpn. 1983, 56, 3802-3812.
(8) Typical experimental procedure: In a round-bottom flask dried under
vacuum were placed CuBr‚Me2S (0.10 mmol), the corresponding sulfonyl
chloride (1.00 mmol), Pd2dba3 (0.015 mmol), and tri-2-furylphosphine
(0.05 mmol). Then the solvent (5 mL) and the organostannane (1.3 mmol)
were added under an argon atmosphere. The reaction was stirred at reflux
for 2-4 h, and then 5 mL of aqueous KF (1 M) solution was added and
stirred for 10 min. The solution was filtered through a pad of Celite, rinsed
with ether, and washed with brine (3 times). The aqueous layer was
extracted again twice with ether. The combined organic phases were dried
(MgSO4), filtered, concentrated under reduced pressure (solvents were
removed under reflux on cooling to -20 °C in the cases of low boiling
point or low molecular mass compounds), and purified by flash chroma-
tography.
89
78
80
73
35
70
38
68
phenyl
2-thienyl
2-thienyl
35 (22)h
38
8j
3-[(E)-2-phenylethenyl]
41
25
55
vinyl
3-pyridinyl
4-fluorophenyl
3-methylphenyl
4-methylphenyl
19 (41)c
38
benzyl
benzyl
38
a
Yields of cross-coupling products, determined after flash chromatog-
raphy. In THF. In toluene for 6 h. 4 mol % Pd2dba3, 15 mol % of
TFP in THF. 8 mol % Pd(PPh3)4 in THF. Traces of the homocoupling
of arenesulfonyl chloride were isolated. See text for byproducts. 8 mol
% Pd(PPh3)4 under air atmosphere. 1.5 mol % Pd2dba3, 5 mol % of TFP/
AsPh3 in DME. 85% of the homocoupled product of stannane was isolated,
b
c
d
e
f
g
h
i
j
based on the organostannane.
Scheme 1. Carbonylative Stille Cross-Coupling
(9) Piers, E.; Wong, T. J. Org. Chem. 1993, 58, 3609-3610.
(10) Posner, G. H. An Introduction to Synthesis Using Organocopper Reagents;
Wiley-Interscience: New York, 1980.
(11) Alphonse, F.-A.; Suzenet, F.; Keromnes, A.; Lebret, B.; Guillaumet, G.
Org. Lett. 2003, 5, 803-805.
(12) For reaction in CH3CN, see ref 5.
(13) See Supporting Information for reaction from sulfonyl chloride to sulfenyl
chloride.
(14) (a) Holmquist, H. E.; Carnahan, J. E. J. Org. Chem. 1960, 25, 2240. (b)
Shim, S. C.; Antebi, S.; Alper, H. J. Org. Chem. 1985, 50, 147-149. (c)
Antebi, S.; Alper, H. Tetrahedron Lett. 1985, 26, 2609-2612.
(15) Kunniyasu, H.; Ogawa, A.; Miyazaki, S.-I.; Ryu, I.; Kambe, N.; Sonoda,
N. J. Am. Chem. Soc. 1991, 113, 9796-9803.
Scheme 2. Preparation of Thioesters
(16) Kawakami, J.-I.; Mihara, M.; Kamiya, I.; Takeda, M.; Ogawa, A.; Sonoda,
N. Tetrahedron 2003, 59, 3521-3526.
(17) Berbriter, D. E.; Osburn, P. L.; Wilson, A.; Sink, E. M. J. Am. Chem.
Soc. 2000, 122, 9058-9064.
(18) Aryl chlorides react only when using electron-rich or sterically hindered
ligands. See, for example: (a) Littke, A. F.; Fu, G. C. Angew. Chem., Int.
Ed. 1999, 38, 2411-2413. (b) Wolfe, J. P.; Buchwald, S. L. Angew. Chem.,
Int. Ed. 1999, 38, 2413-2416.
(19) Aryl bromides are reactive under these conditions. See, for example:
Farina, V.; Krishnan, B. J. Am. Chem. Soc. 1991, 113, 9585-9595.
(20) For reaction work up, see Supporting Information.
reactive20 than the corresponding iodides. Thus, reactivity order is
ArI > ArSO2Cl > ArBr . ArCl.
In summary, palladium-catalyzed, copper-mediated couplings of
readily available arene-, phenylmethanesufonyl chlorides, and aryl,
JA038328Q
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J. AM. CHEM. SOC. VOL. 125, NO. 50, 2003 15293