Cross-coupling reactions of aryl chlorides and bromides with phenyltrimthoxysilane catalyzed by palladium-phosphinous acid complexes

Article abstract of DOI:10.1055/s-2003-41018

Three palladium-phosphinous acid complexes, POPd, POPd1, and POPd2, have been employed in cross-coupling reactions of aryl halides and phenyltrimethoxysilane activated by tetrabutylammonium fluoride. A variety of biaryls were prepared from aryl and hetaryl chlorides and bromides in good to high yields under mild reaction conditions. Bromides afford better results than their chloride analogs and acetonitrile was found to be a superior solvent over DMF, ethyl acetate, and isopropyl alcohol. This coupling procedure tolerates nitrile, ketone and ester groups and converts 4,7-dichloroquinoline to 7-chloro-4-phenylquinoline with high regioselectivity.

Full text of DOI:10.1055/s-2003-41018

PAPER
2069
Cross-Coupling Reactions of Aryl Chlorides and Bromides with Phenyl-
trimthoxysilane Catalyzed by Palladium-Phosphinous Acid Complexes
P
alladium-Phosp
h
r
Complex
i
es-Cat
s
alyze
d
Cr
t
oss-C
o
i
upling
aReactions n Wolf,* Rachel Lerebours, Elizabeth H. Tanzini
Department of Chemistry, Georgetown University, Washington, DC 20057, USA
Fax +1(202)6876209; E-mail: cw27@georgetown.edu
Received 9 May 2003
tive for industrial use. The introduction of catalytically ac-
tive and easy to handle palladium-phosphinous acid
complexes to C–C bond formation based on arylsiloxanes
would provide a broadly applicable methodology that al-
Abstract: Three palladium-phosphinous acid complexes, POPd,
POPd1, and POPd2, have been employed in cross-coupling reac-
tions of aryl halides and phenyltrimethoxysilane activated by tet-
rabutylammonium fluoride. A variety of biaryls were prepared from
aryl and hetaryl chlorides and bromides in good to high yields under lows one to use commercially available aryl chlorides and
mild reaction conditions. Bromides afford better results than their
chloride analogs and acetonitrile was found to be a superior solvent
over DMF, ethyl acetate, and isopropyl alcohol. This coupling pro-
{[(t-Bu)2P(OH)(t-Bu)2PO)]PdCl}2 (POPd1) and
cedure tolerates nitrile, ketone and ester groups and converts 4,7-
dichloroquinoline to 7-chloro-4-phenylquinoline with high regiose-
bromides. Herein, we wish to report on the usefulness
of palladium catalysts [(t-Bu)2P(OH)]2PdCl2 (POPd),
[(t-Bu)2P(OH)PdCl2]2 (POPd2) in cross-coupling reac-
tions that utilize hypervalent arylsiloxanes as non-toxic
transmetalation reagents (Figure 1).
lectivity.
Key words: cross-coupling reaction, palladium phosphinous acid
complexes, phenyltrimethoxysilane, aryl halides, biaryls
t-Bu
t-Bu
t-Bu
t-Bu
Cl
P
P
Cl
Cl
P
OH
OH
Pd
Pd
HO
Transition metal-catalyzed Suzuki, Negishi, Hiyama, Ku-
mada, and Stille couplings are among the most important
C–C bond forming reactions and widely used in organic
synthesis. Usually, the best results are observed with aryl
iodides that easily undergo oxidative addition to the cata-
lyst.1 However, aryl iodides are often not commercially
available and need to be prepared from aryl chlorides and
bromides via halide exchange or by electrophilic aromatic
substitution.2 A range of highly active transition metal
complexes that catalyze aryl–aryl or aryl–alkyl coupling
reactions utilizing readily available but less reactive chlo-
rides or bromides have therefore been developed.3 Some
of the above mentioned coupling methodologies require
the use of toxic metalloids such as organostannanes.
DeShong at al. observed that tin compounds might be re-
placed by siloxane derivatives without compromising re-
sults. A variety of classes of compounds including vinyl
and aryl halides or allylic benzoates have been demon-
strated to undergo Pd-catalyzed cross-coupling reactions
with hypervalent siloxanes.4 Li and co-workers employed
highly active palladium-phosphinous acid complexes in
coupling reactions utilizing non-activated aryl halides.5 In
general, palladium-phosphinous acid complexes have
been shown to combine high catalytic activity in various
coupling reactions with simplicity of operation because of
their stability to air and hydrolysis.
Cl
P
t-Bu
t-Bu
HO t-Bu
t-Bu
POPd
t-Bu
t-Bu
OH
t-Bu
t-Bu
t-Bu
P
Cl
P
O
P
P
Cl
P
O
Cl
Cl
t-Bu
Pd
Pd
H
Pd
Pd
H
t-Bu
t-Bu
Cl
O
P
O
Cl
t-Bu
t-Bu
t-Bu
HO
t-Bu
POPd1
POPd2
Figure 1 Structures of POPd, POPd1 and POPd2
We were pleased to find that employing 7 mol% POPd1
in the coupling reaction of 2-bromonaphthalene (1) with
phenyltrimethoxysilane affords 2-phenylnaphthalene (2)
in 81% yield (Scheme 1).
7 mol% POPd1
2 eq. PhSi(OMe)3, 2 eq. TBAF
MeCN, 80 °C
Br
Ph
1
2
81 %
Scheme 1 POPd1-catalyzed cross-coupling of 2-bromonaphthalene
(1) and phenyltrimethoxysilane
Comparison of the coupling reaction of phenyltri-
methoxysilane and 2-methyl-4-chloroquinoline (3) in dif-
ferent solvents at 80 °C revealed that POPd1 affords the
best results when acetonitrile is used as the solvent, i.e. 2-
methyl-4-phenylquinoline (4) was obtained in 89%. Re-
placing acetonitrile by DMF, isopropyl alcohol or ethyl
acetate decreased the yields to 72, 51 and 80%, respec-
The development of an environmentally benign coupling
procedure that avoids toxic reagents and water-miscible,
non-volatile solvents such as DMF would be very attrac-
Synthesis 2003, No. 13, Print: 18 09 2003. Web: 19 08 2003.
Art Id.1437-210X,E;2003,0,13,2069,2073,ftx,en;M02103SS.pdf.
DOI: 10.1055/s-2003-41018
© Georg Thieme Verlag Stuttgart · New York

2070
C. Wolf et al.
PAPER
tively (entries 1, 2, 5, and 6, Table 1). We also found that procedure. The introduction of hetaryls such as quinoline
POPd1 affords significantly better results than POPd and derivatives into coupling reactions using mild reaction
POPd2 (entries 2, 7, and 8, Table 1).6 Using DMF as the conditions is important for the development of new drugs
solvent, POPd1-catalyzed coupling of chloride 3 with because quinolines have been reported to display pro-
phenyltrimethoxysilane provides biaryl 4 in 72%, where- nounced biological activites.8 For instance, chloroquine
as POPd and POPd2 afford only 14 or 20%. An increase has been used as a very potent antimalarial drug. Howev-
in the temperature of the POPd1-catalyzed coupling in er, the increasing drug resistance of malarial parasites
DMF did not improve yields of biaryl 4 (entries 2–4, such as plasmodium falciparum requires a convenient ac-
Table 1). Notably, attempts to utilize vinyl and allylsilox- cess to structural analogs of chloroquine. The high selec-
anes for the POPd1-catalyzed coupling reaction with aryl tivity in the arylation of readily available 5 is remarkable
halide 3 were not successful and addition of Cy2NMe to because it provides an entry to the synthesis of new malar-
facilitate reductive elimination did not increase yields.
ia drugs exhibiting the 7-chloroquinolyl pharmacophore
(entry 3, Table 2).9
Table 1 POPd1-Catalyzed Cross-Coupling Reactions Using Differ-
ent Solvents
In analogy to the catalytic cycle reported for Stille and
similar coupling reactions, it is assumed that oxidative ad-
dition of aryl halides to POPd1 and transmetalation is fol-
Cl
Si(OMe)3
Pd(0)
TBAF
Ph
N
+
N
Me
Me
Table 2 POPd1-Catalyzed Cross-Coupling Reactions Using Phe-
nyltrimethoxysilane
3
4
Entry
Catalyst
POPd1
POPd1
POPd1
POPd1
POPd1
POPd1
POPd
Solvent
Temp (°C)
Yield (%)
Entry
1
Aryl Halide
Product
Yield (%)
81
1
2
3
4
5
6
7
8
MeCN
DMF
80
80
89
72
71
73
51
80
14
20
1
3
2
Br
Ph
DMF
110
140
80
2
3
4
89
75
88
Ph
Cl
N
DMF
4
N
Me
Me
Cl
i-PrOH
EtOAc
DMF
Ph
80
5
6
80
Cl
N
Cl
N
Cl
N
Ph
N
POPd2
DMF
80
7
8
We decided to apply our optimized cross-coupling proce-
dure to a variety of aryl chlorides and bromides. A variety
of aryl halides including pyridyl and quinolyl derivatives
were converted to the corresponding biaryls in good to ex-
cellent yields (Table 2). Introduction of aryl halides carry-
ing nitrile, ketone and ester functions showed that these
functional groups are tolerated under the conditions em-
ployed (entries 5, 6, 9–11, Table 2).7 In general, aryl bro-
mides gave better results than their chloride analogs
(entries, 5–10, Table 2). Replacing 2-chlorobenzonitrile
(8) with its bromo derivative 11 improved the yield of 2-
cyanobiphenyl (10) from 77% to 92% (entries 5 and 6,
Table 2). Employing 3-bromopyridine (14) in the cou-
pling reaction with phenyltrimethoxysilane provided 3-
phenylpyridine (13) in 92% yield, whereas 3-chloropyri-
dine (12) gave biaryl 13 in only 58% (entries 7 and 8,
Table 2). Similarly, 3-phenylacetophenone (16) was ob-
tained from 3-chloroacetophenone (15) and 3-bromoace-
tophenone (17) in 63% and 71% yield, respectively
(entries 9 and 10, Table 2).
5
6
77
92
9
10
Ph
Cl
CN
CN
CN
CN
10
Ph
11
Br
Cl
7
8
9
58
92
63
13
Ph
12
14
N
N
N
N
13
Ph
Br
15
16
Ph
Cl
Br
O
O
10
11
71
80
17
16
Ph
O
O
Notably, coupling with chloroquinolines afforded biaryls
4, 6, and 8 in high yields (entries 2–4, Table 2). We were
pleased to find that 4,7-dichloroquinoline (5) was convert-
ed to 7-chloro-4-phenylquinoline (6) in 75% using our
19
Ph
18
MeO
MeO
Cl
O
O
Synthesis 2003, No. 13, 2069–2073 © Thieme Stuttgart · New York

PAPER
Palladium-Phosphinous Acid Complexes-Catalyzed Cross-Coupling Reactions
2071
Br
Pd(0)Ln
2
1
LnPdBr
PdLn
Si(OMe)3
OMe
SiF(OMe)3
MeO
F
Si OMe
+
Bu4NF
NBu4
Bu4NBr
Scheme 2 Mechanism of the Pd-catalyzed cross-coupling of 2-bromonaphthalene (1) and phenyltrimethoxysilane
THF (1 M, 2.0 mL) was stirred in MeCN (10 mL) at 80 °C for 24 h.
The reaction mixture was allowed to cool to r.t., quenched with
H2O, and extracted with Et2O. The combined organic layers were
washed with brine, dried (MgSO4), and the solvents were removed
under vacuum. The residue was purified by flash chromatography
on silica gel.
lowed by reductive elimination to complete the catalytic
cycle (Scheme 2). We employed 2 equivalents of tetra-
butylammonium fluoride for activation of phenyltri-
methoxysilane. It is believed that fluoride binds to silicon
to form a pentavalent sp3d-hybridized siloxane that under-
goes transmetalation with the palladium complex.10
2-Phenylnaphthalene (2)
In summary, we have demonstrated the high catalytic ac-
tivity of palladium-phosphinous acid complex POPd1 in
cross-coupling reactions utilizing phenyltrimethoxy-
silane. Optimization studies using various solvents and
fluoride sources at different temperatures showed that
POPd1 affords excellent results in acetonitrile at 80 °C
when TBAF is used to activate the arylsiloxanes for trans-
metalation. Employing aryl chlorides and bromides ex-
hibiting nitrile, ketone or ester groups in the coupling
reaction provided the corresponding biaryls in good to
high yields. This methodology requires mild reaction con-
ditions and avoids the use of very polar and non-volatile
solvents such as DMF, which could exhibit a waste dis-
posal problem when used on an industrial scale. The
regioselectivity of this methodology toward 4,7-dichloro-
The crude product was purified by chromatography using hexanes–
CH2Cl2 (10:1) as the mobile phase to give 165 mg (81%) of 2 as col-
orless crystals.
1H NMR (CDCl3): d = 7.37 (m, 1 H), 7.45–7.50 (m, 4 H), 7.71–7.76
(m, 3 H), 7.81–7.91 (m, 3 H), 8.03 (s, 1 H).
13C NMR (300 MHz, CDCl3): d = 126.0, 126.2, 126.4, 126.7, 127.8,
127.9, 128.1, 128.7, 128.9, 129.3, 133.1, 134.1, 138.9, 141.5.
EI-MS (70 eV): m/z (%) = 204 (100, M+), 127 (5, M+ – Ph), 77 (3,
Ph).
2-Methyl-4-phenylquinoline (4)
Purified by chromatograpy using hexanes–Et2O–Et3N (100:100:1)
as the mobile phase; yield: 194 mg (89%); colorless oil.
1H NMR (300 MHz, CDCl3): d = 2.78 (s, 3 H), 7.23 (s, 1 H), 7.43
(ddd, J = 1.4, 7.6, 8.5, 1 H), 7.47–7.51 (m, 5 H), 7.69 (ddd, J = 1.4,
quinoline provides a new entry toward the synthesis of 4- 7.6, 8.4 Hz, 1 H), 7.86 (dd, J = 1.4, 8.4 Hz, 1 H), 8.08 (dd,
J = 1.4, 8.5 Hz, 1 H).
substituted 7-chloroquinolines, which could be useful for
13C NMR (300 MHz, CDCl3): d = 25.4, 122.1, 125.0, 125.5, 125.6,
128.2, 128.49, 128.9, 129.2, 129.47, 138.0, 148.2, 148.3, 158.3.
the development of new antimalarial drugs.
EI-MS (70 eV): m/z (%) = 219 (100, M+), 204 (50, M+ – Me), 142
All chemicals used were of reagent grade and were purchased from
Aldrich. All cross-coupling reactions were carried out under N2.
Flash chromatography was performed on silica gel (Merck Kiesel-
gel 60, particle size 0.032–0.063 mm). NMR spectra were obtained
at 300 MHz (1H NMR) and 75 MHz (13C NMR) on a Varian FT-
NMR spectrometer in CDCl3. Chemical shifts are reported in ppm
relative to TMS. GC-MS was performed on a Fison Instrument
MD800 capillary GC-Mass spectrometer. Elemental analysis data
were collected using a Perkin Elmer 2400 CHN analyzer.
(2, M+ – Ph), 127 (10, M+ – Me, – Ph).
Anal. Calcd for C16H13N: C, 87.64; H, 5.98; N, 6.39. Found: C:
87.52; H, 5.82; N, 6.35.
7-Chloro-4-phenylquinoline (6)
Purification by chromatography on silica gel using hexanes–
CH2Cl2–Et3N (100:50:1) gave 181 mg (75%) as a yellow oil.
1H NMR (CDCl3): d = 7.35 (d, J = 4.3 Hz, 1 H), 7.40–7.55 (m, 6 H),
7.91 (d, J = 9.1 Hz, 1 H), 8.09 (d, J = 1.9 Hz, 1 H), 8.98 (d, J = 4.3
Hz, 1 H).
Cross-Coupling of Aryl halides with Phenyltrimethoxysilane;
General Procedure
A mixture of POPd1 (56 mg, 7 mol%), aryl chloride or bromide (1.0
mmol), phenyltrimethoxysilane (400 mg, 2.0 mmol), and Bu4NF in
13C NMR (300 MHz, CDCl3): d = 121.7, 125.4, 127.5, 127.8, 128.9,
129.6, 135.4, 137.7, 147.0, 148.7, 149.3, 151.2.
Synthesis 2003, No. 13, 2069–2073 © Thieme Stuttgart · New York

2072
C. Wolf et al.
PAPER
EI-MS (70 eV): m/z (%) = 239 (100, M+), 204 (63, M+ – Cl), 162 (9,
EI-MS (70 eV): m/z (%) = 212 (45, M+), 181 (100, M+ – OMe), 153
M+ – Ph), 127 (25, M+ – Cl, – Ph).
(45, M+ – CO2Me), 77 (11, Ph), 76 (30, M+ – Ph, – CO2Me).
Anal. Calcd for C15H10ClN: C, 75.16; H, 4.21; N, 5.84. Found: C:
74.78; H, 4.13; N, 5.57.
Acknowledgments
4-Phenylquinoline (8)
We thank Combiphos Catalysts, Inc., New Jersey (www.combi-
phos.com) for a generous supply of POPd, POPd1 and POPd2.
The crude product was chromatographed using hexanes–EtOAc–
Et3N (100:10:1) as the mobile phase to give 180 mg (88%) as a yel-
low oil.
1H NMR (300 MHz, CDCl3): d= 7.34 (d, J = 4.4 Hz, 1 H), 7.50–
7.52 (m, 6 H), 7.73 (dd, J = 7.0, 8.2 Hz, 1 H), 7.92 (d, J = 7.0 Hz, 1
H), 8.18 (d, J = 8.2 Hz, 1 H), 8.95 (d, J = 4.4 Hz, 1 H).
References
(1) For a recent review: Littke, A. F.; Fu, G. C. Angew. Chem.
Int. Ed. 2002, 41, 4176.
13C NMR (300 MHz, CDCl3): d = 121.5, 126.1, 126.8, 128.6, 128.8,
(2) (a) Meyer, G.; Rollin, Y.; Perichon, J. Tetrahedron Lett.
1986, 27, 3497. (b) Yang, S. H.; Li, C. S.; Cheng, C. H. J.
Org. Chem. 1987, 52, 691. (c) Bozell, J. J.; Vogt, C. E. J.
Am. Chem. Soc. 1988, 110, 2655. (d) Merkushev, E. B.
Synthesis 1988, 923. (e) Barluenga, J.; Gonzalez, J. M.;
Garcia-Martin, M. A.; Campos, P. J.; Asensio, G. J. Org.
Chem. 1993, 58, 2058. (f) Milne, J. E.; Jarowicki, K.;
Kocienski, P. J. Synlett 2002, 607. (g) Schlosser, M.;Cottet,
F. Eur. J. Org. Chem. 2002, 4181. (h) Klapars, A.;
129.5, 129.7, 130.0, 138.2, 148.7, 148.8, 150.0.
EI-MS (70 eV): m/z (%) = 205 (85, M+), 204 (100, M+ – H), 77 (10,
Ph).
2-Cyanobiphenyl (10)
The crude product obtained from cross-coupling using chloride 8
was purified by chromatography using hexanes–EtOAc (8:1) as the
mobile phase to give 139 mg (77%) as a colorless oil.
Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 14844.
(3) (a) Riermeier, T. H.; Zapf, A.; Beller, M. Top. Catal. 1997,
4, 301. (b) Shirakawa, E.; Yamasaki, K.; Hiyama, T.
Synthesis 1998, 1544. (c) Littke, A. F.; Fu, G. C. J. Org.
Chem. 1999, 64, 10. (d) Suzuki, A. J. Organomet. Chem.
1999, 576, 147. (e) Shiota, T.; Yamamori, T. J. Org. Chem.
1999, 64, 453. (f) Littke, A. F.; Fu, G. C. Angew. Chem., Int.
Ed. 1999, 38, 2411. (g) Zhang, C. M.; Huang, J. K.; Trudell,
M. L.; Nolan, M. L. J. Org. Chem. 1999, 64, 3804. (h) Bei,
X.; Turner, H. W.; Weinberg, W. H. Tetrahedron Lett. 1999,
40, 3855. (i) Bei, X.; Turner, H. W.; Weinberg, W. H.;
Guram, A. S. J. Org. Chem. 1999, 64, 6797. (j) Wolfe, J. P.;
Singer, R. A.; Yang, B. H.; Buchwald, S. L. J. Am. Chem.
Soc. 1999, 121, 9550. (k) Huang, J.; Nolan, S. P. J. Am.
Chem. Soc. 1999, 121, 9889. (l) Bohm, V. P. W.; Herrmann,
W. A. Chem.–Eur. J. 2000, 6, 1017. (m)Gruber, A. S.; Zim,
D.; Ebeling, G.; Monteiro, A. I.; Dupont, J. Org. Lett. 2000,
2, 1287. (n) Morales-Morales, D.; Redon, R.; Yung, C.;
Jensen, C. M. Chem. Commun. 2000, 1619. (o) Bohm, V. P.
W.; Weskamp, T.; Gstottmayr, C. W. K.; Herrmann, W. A.
Angew. Chem. Int. Ed. 2000, 39, 1602. (p) Beletskaya, I. P.;
Cheprakov, A. V. Chem. Rev. 2000, 100, 3009. (q) Littke,
A. F.; Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2000, 122, 4020.
(r) Zapf, A.; Ehrentraut, A.; Beller, M. Angew. Chem., Int.
Ed. 2000, 39, 4153. (s) Stambuli, J. P.; Stauffer, S. R.;
Shaughnessy, K. H.; Hartwig, J. F. J. Am. Chem. Soc. 2001,
123, 2677. (t) Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2001,
123, 2719. (u) Littke, A. F.; Fu, G. C. J. Am. Chem. Soc.
2001, 123, 6989. (v) Whitcombe, N. J.; Hii, K. K.; Gibson,
S. E. Tetrahedron 2001, 57, 7449. (w) Yin, J. J.; Rainka, M.
P.; Zhang, X. X.; Buchwald, S. L. J. Am. Chem. Soc. 2002,
124, 1162. (x) Bedford, R. B.; Cazin, C. S. J.; Hazelwood, S.
L. Chem. Commun. 2002, 2608. (y) Bedford, R. B.; Cazin,
C. S. J.; Hazelwood, S. L. Chem. Commun. 2002, 2610.
(4) (a) Brescia, M.-R.; DeShong, P. J. Org. Chem. 1998, 63,
3156. (b) Mowery, M. E.; DeShong, P. J. Org. Chem. 1999,
64, 1684. (c) Mowery, M. E.; DeShong, P. Org. Lett. 1999,
1, 2137. (d) DeShong, P.; Handy, C. J.; Mowery, M. E. Pure
Appl. Chem. 2000, 72, 1655. (e) Correia, R.; DeShong, P. J.
Org. Chem. 2001, 66, 7159. (f) Hoke, M. E.; Brescia, M.-
R.; Bogaczyk, S.; DeShong, P.; King, B. W.; Crimmins, M.
T. J. Org. Chem. 2002, 67, 327.
1H NMR (300 MHz, CDCl3): d = 7.42–7.59 (m, 7 H), 7.65 (ddd,
J = 1.4, 7.7, 7.7 Hz, 1 H), 7.77 (dd, J = 0.8, 7.7 Hz, 1 H).
13C NMR (300 MHz, CDCl3): d = 111.5, 118.9, 127.7, 128.9, 130.3,
133.0, 133.9, 138.3, 145.7.
EI-MS (70 eV): m/z (%) = 179 (100, M+), 153 (25, M+ – CN), 76
(37, M+ – CN, – Ph).
3-Phenylpyridine (13)
The crude product obtained from cross-coupling using bromide 13
was chromatographed using hexanes–CH2Cl2 (5:1) as the mobile
phase to give 143 mg (92%) as yellow crystals.
1H NMR (300 MHz, CDCl3): d = 7.33–7.51 (m, 4 H), 7.56–7.61 (m,
2 H), 7.88 (ddd, J = 0.6, 1.7, 7.8 Hz, 1 H), 8.59 (dd, J = 1.7, 4.7 Hz,
1 H), 8.85 (dd, J = 0.9, 2.5 Hz, 1 H).
13C NMR (300 MHz, CDCl3): d = 123.7, 127.3, 128.3, 129.3, 134.5,
136.8, 138.1, 148.5, 148.6.
EI-MS (70 eV): m/z (%) = 155 (100, M+), 78 (5, M+ – Ph), 77 (10,
M+ – py).
3-Phenylacetophenone (16)
Column purification of the crude product obtained from cross-cou-
pling with bromide 16 using hexanes–CH2Cl2 (5:1) as the mobile
phase afforded 139 mg (71%) as a yellow oil.
1H NMR (CDCl3): d = 2.99, (s, 1 H), 7.38–7.63, (m, 6 H), 7.80 (ddd,
J = 0.8, 3.0, 7.7 Hz, 1 H), 7.93 (ddd, J = 0.6, 2.8, 7.7 Hz, 1 H), 8.18
(dd, J = 0.6, 3.3 Hz, 1 H).
13C NMR (300 MHz, CDCl3): d = 27.1, 127.2, 127.4, 128.0, 129.1,
129.2, 131.9, 137.9, 140.0, 142.0, 194.0.
EI-MS (70 eV): m/z (%) = 196 (90, M+), 181 (100, M+ – Me), 77
(20, Ph).
Methyl 3-Phenylbenzoate (19)
The crude residue obtained from cross-coupling with bromide 16
was chromatographed using hexanes–CH2Cl2 (5:1) as the mobile
phase to give 170 mg (80%) as colorless crystals.
1H NMR (CDCl3): d = 3.95 (s, 3 H), 7.33–7.50 (m, 3 H), 7.61–7.69
(m, 4 H), 8.10 (d, J = 8.1 Hz, 2 H).
13C NMR (300 MHz, CDCl3): d = 52.5, 127.2, 127.5, 128.3, 129.1,
130.3, 140.7, 145.8, 167.1.
(5) (a) Li, G. Y. Angew. Chem., Int. Ed. 2001, 40, 1513. (b) Li,
G. Y.; Zheng, G.; Noonan, A. F. J. Org. Chem. 2001, 66,
8677. (c) Li, G. Y. J. Org. Chem. 2002, 67, 3643.
Synthesis 2003, No. 13, 2069–2073 © Thieme Stuttgart · New York

PAPER
Palladium-Phosphinous Acid Complexes-Catalyzed Cross-Coupling Reactions
2073
(6) We observed significant formation of biquinaldine and
(9) (a) O’Neill, P. M.; Bray, P. G.; Hawley, S. R.; Ward, S. A.;
Park, B. K. Pharmacol. Ther. 1998, 77, 29. (b) Blauer, G.;
Akkawi, M.; Fleischhacker, W.; Hiessboeck, R. Chirality
1998, 10, 556. (c) Egan, T. J.; Hunter, R.; Kaschula, C. H.;
Marques, H. M.; Misplon, A.; Walden, J. J. Med. Chem.
2000, 43, 283.
biphenyl using POPd and POPd2.
(7) Employing aryl halides exhibiting nitro, alcohol, phenol or
carboxylic acid groups in the POPd1-catalyzed coupling
reaction with phenyltrimethoxysilane did not afford the
desired products.
(8) El Sayed, K.; Al-Said, M. S.; El-Feraly, F. S.; Ross, S. A. J.
Nat. Prod. 2000, 63, 995.
(10) Replacement of TBAF by CsF resulted in lower yields.
Synthesis 2003, No. 13, 2069–2073 © Thieme Stuttgart · New York