Palladium-phosphinous acid-catalyzed NaOH-promoted cross-coupling reactions of arylsiloxanes with aryl chlorides and bromides in water

Article abstract of DOI:10.1021/ol049851s

(Equation presented) A palladium-phosphinous acid-catalyzed and NaOH-promoted coupling method using arylsiloxanes and aryl halides in water has been developed. The POPd1-catalyzed reaction between aryl chlorides or bromides and arylsiloxanes is compatible with various functional groups and affords biaryls in up to 99% yield. This cross-coupling reaction does not require additives such as surfactants or organic cosolvents and proceeds under air, which greatly facilitates operation and catalyst handling.

Full text of DOI:10.1021/ol049851s

ORGANIC
LETTERS
2004
Vol. 6, No. 7
1147-1150
Palladium−Phosphinous Acid-Catalyzed
NaOH-Promoted Cross-Coupling
Reactions of Arylsiloxanes with Aryl
Chlorides and Bromides in Water
Christian Wolf* and Rachel Lerebours
Department of Chemistry, Georgetown UniVersity, Washington, D.C. 20057
cw27@georgetown.edu
Received January 26, 2004
ABSTRACT
A palladium−phosphinous acid-catalyzed and NaOH-promoted coupling method using arylsiloxanes and aryl halides in water has been developed.
The POPd1-catalyzed reaction between aryl chlorides or bromides and arylsiloxanes is compatible with various functional groups and affords
biaryls in up to 99% yield. This cross-coupling reaction does not require additives such as surfactants or organic cosolvents and proceeds
under air, which greatly facilitates operation and catalyst handling.
Palladium-catalyzed cross-coupling methods utilizing aryl
halides and boronic acids, organostannanes, organosiloxanes,
organozinc compounds, or Grignard reagents have found
widespread popularity in synthetic chemistry.1 One of the
major remaining limitations to most currently available cross-
coupling methods is the need for highly toxic and reactive
organometallic substrates that require inert reaction condi-
tions and anhydrous solvents. The replacement of expensive,
hazardous, and flammable organic solvents by water is highly
desirable for reducing costs and for developing environmen-
tally benign synthetic processes. To date, few examples of
aqueous Suzuki,2 Buchwald-Hartwig,3 Sonogashira,4 Stille,5
and Heck reactions6 have been reported.7 The introduction
of amphiphilic resin-supported palladium catalysts and
microwave-assisted Suzuki couplings using palladium acetate
has provided new means for time-efficient and versatile high-
throughput cross-coupling reactions in aqueous solutions.8
Since Hiyama introduced arylfluorosilanes to the Pd-
catalyzed coupling reaction with aryl iodides,9 others have
employed alkenylalkoxysilanes in fluoride-promoted cou-
pling reactions of alkenyl and aryl halides.10 Lee and co-
workers reported efficient cross-couplings of aryl chlorides
and bromides with phenyl- or vinyltrimethoxysilane mediated
(2) (a) Badone, D.; Baroni, M.; Cardamone, R.; Ielmini, A.; Guzzi, U.
J. Org. Chem. 1997, 62, 7170-7173. (b) Uozomi, Y.; Danjo, H.; Hayashi,
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Lett. 2001, 42, 6523-6526. (h) Ueda, M.; Nishimura, M.; Miyaura, N.
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2002, 67, 5588-5594. (l) Bedford, R. B.; Blake, M. E.; Butts, C. P.; Holder,
D. Chem. Commun. 2003, 466-467. (m) Li, C.-J. Angew. Chem., Int. Ed.
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4211. (b) Miyaura, N., Ed. Cross-Coupling Reactions; Springer: Berlin,
2002.
(3) Wuellner, G.; Jaensch, H.; Kannenberg, S.; Schubert, F.; Boche, G.;
Chem. Commun. 1998, 1509-1510.
10.1021/ol049851s CCC: $27.50 © 2004 American Chemical Society
Published on Web 03/09/2004

by palladium acetate in the presence of an imidazolium
chloride.11 DeShong at al. employed vinyl and aryl halides,
aryl triflates, and allylic benzoates in Pd-catalyzed cross-
coupling reactions with hypervalent siloxanes.12 Notably,
Denmark and others have developed a variety of Lewis base-
promoted stereoselective reactions utilizing hypervalent
silicates as active intermediates.13 Because of the increasing
availability and remarkable reactivity in conjugate additions
to R,â-unsaturated carbonyl compounds or Hiyama-like
coupling reactions,14 organosiloxanes have recently been
employed in aqueous transition metal-catalyzed C-C bond-
forming reactions using 10-40% water in dioxane.15 How-
ever, aqueous Hiyama-type coupling procedures developed
to date require aryl bromides and substantial amounts of
organic cosolvents but do not proceed with less reactive aryl
chlorides.
and 1 equiv of TBAF dissolved in deionized water (Table
1, entry 1). Replacement of 4 by 2-furan-, 2-thiophen-,
Table 1. Screening of Aqueous Hiyama-Type Cross-Coupling
Reaction Conditionsa
Recently, we and others reported the use of highly active
palladium-phosphinous acid complexes in various C-C,
C-N, and C-S bond-forming reactions using a wide range
of aryl halides.16 Because of the remarkable stability of this
class of catalysts to air and water and on the basis of our
previously reported findings that palladium-phosphinous
acid complex [[(t-Bu)2P(OH)(t-Bu)2PO)]PdCl]2 (POPd1)
catalyzes Hiyama-type reactions of aryl halides in the
presence of tetrabutylammonium fluoride in organic solvents
in good to high yields,16e we decided to employ POPd1 in
cross-coupling reactions between aryl chlorides or bromides
and arylsiloxanes using water as the solvent. Initially, we
employed 3-bromopyridine, 1, 3-chloropyridine, 2, and
2-methyl-4-chloroquinoline, 3, and various arylsiloxanes in
optimization studies to elucidate the feasibility of palladium-
phosphinous acid-catalyzed Hiyama-type cross-coupling in
water (Scheme 1).
Scheme 1. POPd1-Catalyzed Cross-Coupling of
3-Bromopyridine, 1, and Phenyltrimethoxysilane, 4a
a General conditions: A mixture of 100 mg of aryl halide, 2.0 equiv of
arylsiloxane, and 7 mol % POPd1 in 5 mL of deionized water was heated
to 135-140 °C for 24 h in a closed vessel. b In the presence of 1 equiv of
TBAF. c In the presence of 0.1 M NaOH. d In the presence of 0.5 M NaOH.
e Performed with 1 equiv of 4. f T ) 100 °C.
4-tolyl-, and 4-anilinotrimethoxysilane, 6-9, gave the cor-
responding cross-coupling products 10-13 in 61-90% yield
(entries 2-5). As expected, aryl chorides give lower yields
than bromides (compare entries 1 and 6). It has been assumed
a Typical cross-coupling procedure. A mixture of 100 mg of 1,
2 equiv of 4, and 7 mol % of POPd1 was stirred in 5 mL of 0.5 M
NaOH at 135 °C for 24 h. All reactions were carried out using a
high-pressure vessel (i.d. 31.7 cm) made of 4.0 mm Pyrex 7740
heavy wall glass and equipped with a 4 mm bore valve and Aegis
backing O-ring.
(7) (a) Genet, P. J.; Savignac, M. J. Organometallic Chem. 1999, 576
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Organomet. Chem. 2002, 653, 58-61.
We were pleased to find that 1 and 4 afford 3-phenylpy-
ridine, 5, in 95% yield in the presence of 7 mol % POPd1
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1148
Org. Lett., Vol. 6, No. 7, 2004

that palladium-phosphinous acids undergo reduction and
deprotonolysis in the presence of a base to form a highly
active anionic Pd(0) complex.16 We rationalized that genera-
tion of such an electron-rich phosphine-containing Pd
complex should proceed in the presence of aqueous sodium
hydroxide. In addition, formation of a pentavalent silicate
should also be feasible under basic aqueous conditions
through nucleophilic attack of a hydroxide ion at the
arylsiloxane (Scheme 2). It is well-known that cross-coupling
To demonstrate the scope of NaOH-promoted POPd1-
catalyzed C-C bond formation we applied our optimized
procedure to a variety of aryl halides and arylsiloxanes (Table
2). Coupling of bromide 1 with siloxanes 4 and 6-9 in 0.5
Table 2. Cross-Coupling of Arylsiloxanes and Aryl Halides in
Watera
Scheme 2. Proposed Catalytic Cycle of the NaOH-Promoted
POPd1-Catalyzed Cross-Coupling Reaction
reactions require subsequent oxidative addition of the aryl
halide to the catalyst, transmetalation, and reductive elimina-
tion to form the biaryl product and to regenerate the
catalytically active species. Because arylsiloxanes are less
reactive than their corresponding stannanes or boronic acids,
they need to be activated to undergo transmetalation with
the palladium complex. This can be accomplished via
formation of a hypervalent sp3d-hybridized siloxane in the
presence of TBAF or hydroxide ions. Thus, sodium hydrox-
ide would fulfill two fundamental functions, i.e., activation
of the catalyst for oxidative addition and activation of the
arylsiloxane for the transmetalation step.
Indeed, we obtained biaryl 5 using 0.1 M NaOH solution
in 90% yield, and further optimization of the NaOH
concentration increased the yield to 99% (Table 1, entries 8
and 9). It is noteworthy that this procedure does not require
any surfactant additives or organic cosolvents and proceeds
under air, which greatly facilitates operation and catalyst
handling. Employing equimolar amounts of 4 in the coupling
reaction with 1 or reducing the reaction temperature to 100
°C reduced the yields of biaryl 5 to 80 and 90%, respectively
(Table 1, entries 10 and 11).
a All reactions were carried out with 100 mg of aryl halide, 2.0 equiv of
arylsiloxane, and 7 mol % POPd1 in 5 mL of 0.5 M NaOH at 135-140 °C
for 24 h using a closed vessel.
M NaOH gave slightly better results than we had obtained
using aqueous TBAF solutions (entries 1-5). We observed
that ortho-substituted aryl halides 15 and 21 undergo coupling
Org. Lett., Vol. 6, No. 7, 2004
1149

in 77-81% yield, and cyano, ketone, amino, and heteroaryl
groups are well tolerated (entries 2, 3, 5-7, 13-15).
As expected, electron-deficient pyridyl and quinolyl
chlorides readily undergo POPd1-catalyzed cross-coupling
in 72-88% yields (Table 2, entries 10-12). Unactivated,
electron-rich aryl chlorides are commonly known to reluc-
tantly undergo oxidative addition to transition metals and
therefore provide low yields in cross-coupling reactions.
Accordingly, we obtained relatively low yields for the
synthesis of 2-phenylthiophene, 28, from 2-chlorothiophene,
22 (entry 15). However, the availability of siloxanes 6, 7,
and 9 provides a successful cross-coupling strategy for the
preparation of biaryls exhibiting an electron-rich aryl ring
(entries 2, 3, and 5).
In summary, a variety of aryl halides and arylsiloxanes
have successfully been employed in NaOH-promoted POPd1-
catalyzed cross-coupling reactions to afford biaryls in good
to high yields. This facile coupling reaction proceeds in 0.5
M aqueous NaOH solution under air and in the absence of
commonly used additives such as CsF and TBAF or other
surfactants. We have thus developed an environmentally
benign cross-coupling method that utilizes an air-stable
palladium-phosphinous acid complex in water while avoid-
ing toxic reagents such as stannanes and the use of hazardous
organic cosolvents. The mechanism of the catalytic process,
including the structure of the resting state of the active
palladium catalyst and the role of NaOH in activating the
palladium-phosphinous acid and in promoting transmeta-
lation of arylsiloxanes, is currently under investigation in
our laboratories.
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Acknowledgment. We thank Combiphos Catalysts, Inc.,
New Jersey (www.combiphos.com) for POPd1.
Supporting Information Available: Experimental pro-
cedures and full characterization of compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
OL049851S
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