Palladium-catalyzed biaryl-coupling reaction of arylboronic acids in water using hydrophilic phosphine ligands

Article abstract of DOI:10.1016/S0040-4020(02)00576-8

Hydrophilic phosphine ligands possessing a carbohydrate side-chain, such as N-(4-diphenylphosphinophenyl)methyl gluconamide (9), N-[4-(2′-dicyclohexylphosphinobiphenyl)phenylmethyl] gluconamide (10), and N-[4-(2′-di-t-butylphosphinobiphenyl)]phenylmethyl gluconamide (11), were newly synthesized to carry out palladium-catalyzed biaryl coupling of arylboronic acids in a single aqueous medium. The catalyst prepared in situ from Pd(OAc)₂ and 10 exhibited a higher efficiency than that of 9, 11, Ph₂P(m-C₆H₄SO₃Na) (TPPMS) or P(m-C₆H₄SO₃Na)₃ (TPPTS) for representative aryl bromides, chlorides, or triflates. The catalyst prepared in situ from Pd(OAc)₂ (0.001mol%) and 10 (0.002mol%) achieved 96,000 TON in the reaction of p-tolylboronic acid with 4-bromoacetophenone in water.

Full text of DOI:10.1016/S0040-4020(02)00576-8

TETRAHEDRON
Pergamon
Tetrahedron 58 (2002) 5779±5787
Palladium-catalyzed biaryl-coupling reaction of arylboronic acids
in water using hydrophilic phosphine ligands
Masato Nishimura, Masato Ueda and Norio Miyaurap
Division of Molecular Chemistry, Graduate School of Engineering, Hokkaido University, Sapporo 060-8628, Japan
Received 30 April 2002; accepted 3 June 2002
AbstractÐHydrophilic phosphine ligands possessing a carbohydrate side-chain, such as N-(4-diphenylphosphinophenyl)methyl glucona-
mide (9), N-[4-(20-dicyclohexylphosphinobiphenyl)phenylmethyl] gluconamide (10), and N-[4-(20-di-t-butylphosphinobiphenyl)]phenyl-
methyl gluconamide (11), were newly synthesized to carry out palladium-catalyzed biaryl coupling of arylboronic acids in a single
aqueous medium. The catalyst prepared in situ from Pd(OAc)2 and 10 exhibited a higher ef®ciency than that of 9, 11, Ph2P(m-
C6H4SO3Na) (TPPMS) or P(m-C6H4SO3Na)3 (TPPTS) for representative aryl bromides, chlorides, or tri¯ates. The catalyst prepared in
situ from Pd(OAc)2 (0.001 mol%) and 10 (0.002 mol%) achieved 96,000 TON in the reaction of p-tolylboronic acid with 4-bromoaceto-
phenone in water. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
coupling product of phosphine-bound aryls,5 complete
conversion is not always possible under ligandless con-
ditions, especially in slow reactions of electron-rich and
sterically hindered bromo- and chloroarenes. Catalysts
derived from water-soluble ligands such as TPPMS 1 and
TPPTS 2 are alternatives for stabilizing the resting state of
palladium intermediates in water6 (Scheme 1).
Reactions in aqueous media are advantageous for large-
scale industrial processes because of the simplicity of
catalyst-product separation and the economy and safety of
using water as a solvent.1 Such reactions in aqueous media
are also useful for the biaryl coupling of arylboronic acids.2
3
A ®ne metallic palladium generated in situ from Pd(OAc)2
or Pd(OAc)2/Bu4NBr4 provided an excellent catalyst for the
coupling of arylboronic acids with bromoarenes in water.3
Although such catalysts containing no phosphine ligand are
advantageous for eliminating the side-reaction giving a
Glycosides of triphenylphosphine 3 are of the new class of
ligands designed to solve the basic problems of homo-
geneous catalysts, namely, the separation and recycling of
catalysts.7 These ligands achieved higher turnover numbers
than that of TPPTS in both biaryl coupling of arylboronic
acids and Heck coupling in a two-phase, basic aqueous-
organic medium. Quaternary ammonium salts derivatives
of di-t-butylphosphines such as 4 and 5 were designed for
reaction with chloroarenes because of their strong electron-
donating ability to the palladium metal center.8 Phosphine
supported on a graft copolymer of styrene and ethylene
glycol 6 is an ef®cient ligand in a single aqueous medium
that can be recovered and reused with no decrease in
activity.9 Among such catalysts, Pd(OAc)2,3 Pd(OAc)2/
Bu4NBr,4 and (h3-C3H5)PdCl/69 have been utilized in a
single, basic aqueous medium without employing organic
co-solvents miscible to water.
We report here the synthesis of new hydrophilic phosphine
ligands possessing a sugar side-chain (9±11) and their cata-
lyst ef®ciency in the biaryl-coupling reaction of arylboronic
acids in a single aqueous medium (Scheme 2).10
Scheme 1. Ligands for water-soluble catalysts.
Keywords: cross-coupling; palladium; biaryls; aqueous medium; water-soluble hydrophilic phosphine; arylboronic acids.
Corresponding author. Fax: 181-11-706-6561; e-mail: miyaura@org-mc.eng.hokudai.ac.jp
p
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00576-8

5780
M. Nishimura et al. / Tetrahedron 58 (2002) 5779±5787
provided highly active catalysts for chloroarenes even at
room temperature. The high reactivity of these catalysts is
attributable to a strong electron-donating ability to the metal
center and the easy dissociation of the ligand to generate a
coordinatively unsaturated species. It has also been noted
that less bulky phosphines, such as P(Cy)3,11 (dicyclohexyl-
phosphino)arylphosphines,12 N-heterocyclic carbene,13 and
tBu2POH,14 are more practical ligands yielding palladium
catalysts stable at high temperature. From these previous
observations, 2-(dicyclohexylphosphino)biphenyl (10)
and 2-(di-t-butylphosphino)biphenyl (11) developed by
Buchwald12 together with triphenylphosphine (9) were
functionalized with a gluconamide group to convert them
into the corresponding hydrophilic ligands.
The synthesis of the gluconamide derivative of triphenyl-
phosphine (GLCAphos: 9) is shown in Scheme 3. The
two-step procedure from 4-bromobenzonitrile afforded
(4-diphenylphosphinophenyl)methylamine (12) in 60%
yield. 4-Lithiobenzonitrile15 thus generated in situ from
4-bromobenzonitrile and BuLi was unstable at the tempera-
ture higher than 2788C, but the subsequent reaction with
Ph2PCl was suf®ciently fast to trap the intermediate in a
yield of 70%. Treatment of 12 with d-glucono-1,5-lactone
in re¯uxing methanol gave 9 in 96% yield.16 The reaction of
PdCl2(cod) and GLCAphos (9, 2 equiv.) in MeCN at 1008C
precipitated a red-brown solid, which was assigned to be
PdCl2(GLCAphos)2.
Scheme 2. Biaryl coupling in water.
2. Results and discussions
2.1. Synthesis of ligands
Various phosphine ligands are effective in stabilizing palla-
dium(0) species, but the stoichiometry of phosphine to
palladium and the bulkiness or donating ability of phosphine
ligands change the reactivity of catalysts toward oxidative
addition and transmetalation. Although triarylphosphines
are excellent ligands for organic iodides, bromides, and
tri¯ates, their reaction with chlorides is very slow. Bulky
and highly donating ligands overcome this limitation; for
4-Cyanophenylboronic acid synthesized via lithiation±
borylation of 4-bromobenzonitrile was coupled with 1,2-di-
bromobenzene to yield 13 in 50% yield. Phosphorylation of
the C±Br bond (75%) was followed by reduction of the
nitrile group with LiAlH4 to furnish 14 (84%). The reaction
of 14 with d-glucono-1,5-lactone gave 10 in 90% yield
(Scheme 4).
11
example, P(t-Bu)3 and 2-(di-t-butylphosphino)biphenyl12
Scheme 3.
Scheme 4.

M. Nishimura et al. / Tetrahedron 58 (2002) 5779±5787
5781
The synthesis of 17 suffered from the dif®culty of intro-
ducing a bulky di-t-butylphosphino group at the sterically
hindered ortho-carbon. The procedure used for the synthesis
of 10 failed due to instability of the lithium intermediate and
its very slow reaction with t-Bu2PCl. Alternatively, it was
found that the phosphine oxide derivative 16 can be synthe-
sized by cross-coupling reaction of 15. Although the pro-
cedure is very convenient because 1517 is easy to obtain via
ortho-lithiation and iodonation of di-t-butyl(phenyl)phos-
phine oxide, 15 and 16 had strong resistance to HSiCl3/
Et3N or LiAlH4. Reduction of 16 with a 5-fold excess of
HSiCl3 and Et3N in a sealed ampule at 1508C failed. Finally,
the cross-coupling reaction of 13 with di-t-butylphosphine±
borane complex gave 17.18 Although the hydrogenolysis of
a C±Br bond yielding 4-cyanobiphenyl (70%) predomi-
nated over the desired phosphorylation, the reaction directly
provided a desired borane-free phosphine 17 in 25%
yield. The reduction of the nitrile group was followed by
amidation to furnish 11 (Scheme 5).
Scheme 5.
2.2. Reaction conditions
The cross-coupling reaction of p-tolylboronic acid with
4-bromoanisole was carried out in the presence of various
catalysts and bases to optimize the reaction conditions
(Table 1). In the presence of 0.1 mol% of PdCl2/9 in
water, various bases were effective for completing the reac-
tion within 16 h at 808C (entries 1±5). Among them, K3PO4
and Et3N provided yields of over 90%. The yield of
4-methylbiphenyl derived from the coupling of phosphine-
bound phenyl5 was a less than 0.5% when K3PO4 was used.
The formation of a homo-coupling product2a,f of p-tolyl-
boronic acid (bitolyl) varied depending on the base
employed; e.g. NaOH (8%), Et3N (8%), K3PO4 (0.5±3%),
Na2CO3 (2%), and CsF (2%). The use of 4 equiv. of GLCA-
phos 9 to PdCl2 gave the most ef®cient catalyst since the
yields decreased by reducing the stoichiometry of the ligand
(entries 2, 6 and 7).
Table 1. Reaction conditions
Entry Catalyst/ligand (equiv.) Base (equiv.) Convn (%) Yield (%)
1a
PdCl2/GLCAphos (4)
PdCl2/GLCAphos (4)
PdCl2/GLCAphos (4)
PdCl2/GLCAphos (4)
PdCl2/GLCAphos (4)
PdCl2/GLCAphos (3)
PdCl2/GLCAphos (2)
Pd(OAc)2/10 (1)
Na2CO3 (2)
K3PO4 (2)
KOH (2)
CsF (4)
98
98
94
96
98
94
89
46
95
0
78
90
75
73
92
84
71
35
90
0
2a
3a
4a
5a
Et3N (5)
6a
K3PO4 (2)
K3PO4 (2)
K3PO4 (2)
K3PO4 (2)
K3PO4 (2)
K3PO4 (2)
7a
8b
9b
10b
11b
Pd(OAc)2/10 (2)
Pd(OAc)2/10 (4)
Pd(OAc)2/11 (2)
75
62
a
All reactions were carried out at 808C for 16 h in water (3 mL) in the
presence of 4-bromoanisole (1 mmol), p-tolylboronic acid (1.3 mmol), a
palladium catalyst (0.1 mol%), and a base (2±5 equiv.). The catalyst was
prepared in situ from GLCAphos (9, 0±2 equiv.) and PdCl2(GLCAphos)2.
The reactions were carried out at 258C for 16 h in water (3 mL) in
the presence of 4-bromobenzoic acid (1 mmol), p-tolylboronic acid
(1.3 mmol), a palladium catalyst (0.1 mol%), and K3PO4 (2 mmol). The
catalyst was prepared in situ by mixing Pd(OAc)2 and 10 (1±4 equiv.) or
11 (2 equiv.).
The complex synthesized in situ from Pd(OAc)2 and 10
catalyzed the reaction at room temperature (entries 8±10).
The most active catalyst was obtained when 2 equiv. of 10
to Pd(OAc)2 were used (entry 9), while further increase in
the ligand reversely deactivated the catalyst (entry 10). The
t-butyl derivative 11 resulted in a lower yield than that of the
cyclohexyl derivative (entry 11).
b
Table 2. Effect of ligands
Entry
Catalyst/ligand (equiv.)
Yield (%)a
4-MeOC6H4Br at 808C
4-C6H5C6H4Br at 608C
4-HO2CC6H4Br at 258C
4-HO2CC6H4Cl at 808C
1
2
3
4
5
6
7
Pd(OAc)2
Pd(PPh3)4
63
74
70
69
90
90
±
,1
52
,1
38
68
74
96
37
,1
,1
15
43
90
,1
,1
,1
,1
,1
62
Pd(OAc)2/TPPTS (3)
PdCl2/TPPMS (3)
PdCl2/GLCAphos (4)
Pd(OAc)2/10 (2)
Pd(OAc)2/11 (2)
62
24
A mixture of a haloarene (1 mmol), p-tolylboronic acid (1.3 mmol), a palladium catalyst (0.1 mol%), and K3PO4 (2 mmol) in water (3 mL) was stirred for 16 h
at the temperature shown in this table.
GC yields.
a

5782
M. Nishimura et al. / Tetrahedron 58 (2002) 5779±5787
Table 4. Synthesis of biaryls from bromoarenes
2.3. Effect of ligands
Entry
ArBr (1) Rˆ
Yield (%)a
Pd(OAc)2/10c
Four different types of haloarenes were coupled with
p-tolylboronic acid in the presence of Pd(OAc)2,
Pd(PPh3)4, and a catalyst synthesized from TPPMS 1,
TPPTS 2, GLCAphos 9, 10, or 11 (0.1 mol%) to investigate
the ef®ciencies of the new ligands (Table 2).
PdCl2/9b
1
2
3
4
5
6
7
8
4-NO2
4-CN
2-CN
4-COCH3
4-CHO
4-CO2C2H5
4-F
4-Ph
3-CH3O
4-CH3O
4-NH2
4-N(CH3)2
1-Bromonaphthalene
2-OH
4-OH
4-CO2H
3-CO2H±4-OH
2-CHvCHCO2H
4-CHvCHCO2H
2-Bromopyridine
3-Bromopyridine
3-Bromoquinoline
96
94
85
94
99
99
95
99
93
89
90
74
99
44
99
99
77
,40
,40
18
89
99
The emulsion of 4-bromoanisole in water resulted in the
slow conversion into a white suspension of 4-methoxy-40-
methylbiphenyl at 808C (®rst column). All catalysts, inclu-
ding water-soluble and water-insoluble ligands, were effec-
tive for catalyzing such a liquid±liquid, two-phase system at
808C. Among them, 9 and 10, soluble in both organic and
water phases, were found to be the most ef®cient ligands.
Solid substrates, such as 4-bromobiphenyl, suspended in
water at 608C gradually changed to a ®ne suspension of
another precipitate of 4-methyl-p-terphenyl over a period
of 16 h (second column). Palladium black in situ generated
from Pd(OAc)2 and the TPPTS complex were not effective
for such a two-phase, liquid±solid system due to their
low solubility in the solid phase. On the other hand, the
palladium complexes of PPh3, 9, 10, and 11 gave the
coupling product. Among them, a bulky and highly
electron-donating t-butyl derivative 11 exhibited the best
ef®ciency (entry 7). The effect for water-soluble 4-bromo-
benzoic acid was examined at room temperature because the
reactions catalyzed by the complexes of 9 and 10 were very
fast at a high temperature (third column). The mixture initi-
ally yielded a clear solution followed by the precipitation of
a white solid of potassium 4-tolylbenzoate. The order of
9
10
11
12
13
14
15d
16e
17f
18
19
20
21
22
87
90
90
42
All reactions were carried out at 808C for 16 h in water (3 mL) in the
presence of a bromoarene (1 mmol), p-tolylboronic acid (1.3 mmol), a
palladium catalyst (0.1 mol%), and K3PO4 (2 mmol).
a
Isolated yields by chromatography.
PdCl2(GLCAphos)2 (0.1 mol%) and GLCAphos (9, 0.2 mol%).
Pd(OAc)2 (0.1 mol%) and 10 (0.2 mol%).
The reaction completed within 2 h.
The reaction completed within 30 min.
The reaction was carried out at 208C.
b
c
d
e
f
yields was 10.11.9.TPPMS 1qTPPTS 2. Due to the
2
electron-withdrawing property of the SO3
group
(smˆ0.30)19 and strong electron-donating abilities of alkyl-
phosphines, the observed relative ef®ciency is in the order of
the donating abilities of the ligands, except for 11, which
unexpectedly resulted in a lower yield than that of 10. On
the other hand, the coupling reaction of 4-chlorobenzoic
acid was signi®cantly slow even at 808C (fourth column).
Alkylphosphine derivatives (10 and 11) limitedly catalyzed
the reaction of chloroarenes.
loading showed the superiority of 9, presumably due to the
greater air-sensitivity of alkylphosphines 10 than that of
arylphosphines 9 (entries 5 and 6). On the other hand,
both 10 and 9 resulted in 700±900 TON for 4-chloroaceto-
phenone with a 0.1 mol% catalyst loading.
2.4. Scope and limitation
Biaryl coupling of 4-tolylboronic acid with representative
bromoarenes at 808C in the presence of PdCl2/GLCAphos 9
or Pd(OAc)2/10 (0.1 mol%) is summarized in Table 4.
PdCl2/GLCAphos afforded high yields of biaryls for
bromoarenes having an electron-withdrawing or -donating
group (entries 1±13). Dif®culties associated with the base
were not encountered. No Cannizzaro reaction giving an
acid and an alcohol was observed for 4-bromobenzaldehyde
(entry 5). Functional group-sensitive bases such as ester and
nitrile remained completely intact due to the insolubility of
both substrates and products in water (entries 2, 3, and 6).
In contrast to the slow reaction of a heterogeneous of
a liquid±liquid or liquid±solid, two-phase system, the
coupling reactions of bromophenols and bromobenzoic
acids soluble in a basic water were signi®cantly fast (entries
15±17). Although the Hammett constant19 of the p-O2
group (spˆ20.81) is comparable to that of p-NMe2
(spˆ20.83), the reaction of 4-bromophenol was completed
within 2 h (entry 15). 4-Bromobenzoic acid was consumed
completely within 30 min at 808C (entry 16) and 3-carbo-
hydroxy-4-hydroxybromobenzene coupled with the boronic
acid at room temperature (entry 17). However, the ligand 10
The ef®ciencies of two ligands (GLCAphos 9 and 10) were
demonstrated by the turnover number of the catalyst (TON)
(Table 3).20 Both 9 and 10 exhibited an excellent catalyst
activity, exceeding 90,000 TON, with a 0.001 mol% cata-
lyst loading (entries 3 and 4). Further decrease in catalyst
Table 3. Turnover number of catalysts
Entry
Catalyst/ligand (equiv.)
Mol%
Yield (%)a
TON
1
2
3
4
5
6
PdCl2/GLCAphos (4)
Pd(OAc)2/10 (2)
PdCl2/GLCAphos (4)
Pd(OAc)2/10 (2)
PdCl2/GLCAphos (4)
Pd(OAc)2/10 (2)
0.01
0.01
0.001
0.001
0.0001
0.0001
95
95
95
96
,50
,35
9500
9500
95,000
96,000
,500,000
,350,000
All reactions were carried out at 808C for 24 h in water (3 mL) in the
presence of 4-bromoacetophenone (1 mmol), p-tolylboronic acid
(1.3 mmol), a palladium catalyst (0.1 mol%), and K3PO4 (2 mmol).
PdCl2/GLCAphos was prepared in situ by mixing PdCl2(GLCAphos)2
and GLCAphos (9, 2 equiv.), and Pd(OAc)2/10 from Pd(OAc)2 and 10
(2 equiv.).
a
GC yields.

M. Nishimura et al. / Tetrahedron 58 (2002) 5779±5787
5783
Table 5. Synthesis of biaryls from chloroarenes
rich substrates (entries 7±13). Similar to the effect of an
o-OH group (entry 14 in Table 4), the intramolecular
chelation of a carboxylato anion strongly retarded the reac-
tion of 2-chlorobenzoic acid (entry 8). Chloropyridines and
chloroquinolines, including 2-chloro derivatives, gave the
corresponding biaryls in high yields (entries 14±18).
Entry
ArCl (1) Rˆ
Catalyst (mol%)
Yield (%)a
PdCl2/9b Pd(OAc)2/10c
1
2
3
4
5
6
7
2-CN
4-CN
4-CHO
4-COCH3
2-CO2C2H5
4-CO2C2H5
4-OCH3
2-CO2H
4-CO2H
2-CHvCHCO2H
4-CHvCHCO2H
4-CO2H±3-OH
3-CO2H±4-OH
2-Chloropyridine
3-Chloropyridine
4-Chloropyridine
0.1
0.1
0.1
0.1
0.1
0.1
2.0
1.0
1.0
1.0
1.0
3.0
3.0
0.1
1.0
1.0
,1
46
±
71
96
90
93
95
66
98
79
0
73
90
88
84
45
88
96
70
97
Preliminary results for cross-coupling reaction of aryl
tri¯ates in aqueous media are shown in Table 6. The tri-
¯uoromethanesulfoxy group is highly sensitive to the base,
but the reaction was faster than the saponi®cation of this
group. Arylphosphine 9 can be used for electron-de®cient
substrates (entries 1 and 2), but 10 is recommended for more
electron-rich tri¯ates (entry 3).
,1
,1
,10
0
,1
,1
,30
,1
,1
43
8d
9d
10d
11d
12d
13d
14
15
17d
18
±
±
±
3. Experimental
3.1. Reagents
2-Chloroquinoline 0.1
All reactions were carried out at 808C for 16 h in water (3 mL) in the
presence of a chloroarene (1 mmol), p-tolylboronic acid (1.3 mmol), a
palladium catalyst (0.1 mol%), and K3PO4 (2 mmol).
p-Tolylboronic acid was purchased from Lancaster. P(m-
C6H5SO3Na)3 (TPPTS), Ph2P(m-C6H5SO3Na) (TPPMS),
Pd(PPh3)4, and Pd(OAc)2 are available from Aldrich.
Water was boiled and cooled under argon before use.
a
Isolated yields by chromatography.
PdCl2(GLCAphos)2 and GLCAphos (9, 2 equiv.).
Pd(OAc)2 and 10 (2 equiv.).
K3PO4 (3 mmol) was used.
b
c
d
Other phosphine ligands were synthesized by the following
methods.
was more effective than 9 for two coupling reactions of
more electron-rich bromocinnamic acids (entries 18 and
19). Among these water-soluble substrates, the reaction of
2-bromophenol was strongly retarded, presumably due
to the intramolecular chelation of a phenoxy anion to the
palladium metal center (entry 14). The reactions of
2-bromopyridine resulted in 18 and 42% yields, respec-
tively, for the two catalysts (entry 20), while the boronic
acid readily coupled with 3-bromopyridine (entry 21),
3-bromoquinoline (entry 22), and presumably also 4-bromo-
pyridine.
3.1.1. 4-(Diphenylphosphino)benzonitrile. A solution of
4-bromobenzonitrile (1 g, 5.5 mmol) in THF (25 mL) and
hexane (7 mL) was cooled to 21008C. BuLi in hexane
(1.52 M, 3.6 mL, 5.5 mmol) was then added. After being
stirred for 5 min, Ph2PCl (0.99 mL, 5.5 mmol) was added.
The bath temperature was gradually allowed to warm to
room temperature over 3 h. The product was extracted
with ether, washed with 1 M NaOH, and dried over
MgSO4. Chromatography over silica gel gave a pale yellow
1
solid; yield 1.1 g (70%); H NMR (400 MHz, CDCl3) d
7.29±7.38 (m, 12H), 7.56 (d, Jˆ8.3 Hz, 2H); 13C NMR
(100 MHz, CDCl3) d 111.8, 118.7, 128.8 (d, Jˆ7.4 Hz),
129.4, 131.6 (d, Jˆ5.7 Hz), 133.4 (d, Jˆ18.1 Hz), 134.0
(d, Jˆ19.8 Hz), 135.3 (d, Jˆ10.7 Hz), 145.1 (d, Jˆ
17.3 Hz); IR (Nujol) 2200 cm21; exact mass calcd for
C19H14NP 287.0942, found 288.0956 (M11, FAB).
The synthesis of biaryls from chloroarenes is summarized in
Table 5. Chloroarenes are economical substrates that are
desirable for large-scale preparations; however, the reac-
tions are very slow due to their slow oxidative addition to
a palladium(0) complex.11,12,21 Thus, ligand 10, which has a
greater donating ability, exhibited a higher catalyst activity
than that of GLCAphos 9. The coupling reaction of
activated chloroarenes proceeded smoothly at 808C
with 0.1 mol% catalyst loading (entries 1±6), whereas
1±3 mol% of a catalyst was required for more electron-
3.1.2. 4-(Diphenylphosphino)phenylmethylamine (12).
A solution of 4-diphenylphosphinobenzonitrile (4.3 g,
15 mmol) was added to LiAlH4 (0.68 g) in ether (30 mL).
The resulting mixture was then re¯uxed for 1 h. Water
(0.7 mL), 20% NaOH (0.5 mL), and water (2.5 mL) were
added successively at 08C to precipitate orange solid of the
aluminum residue. The organic layer was separated by
®ltration through a celite pad and the solid was repeatedly
washed with ether. Chromatography over silica gel with
benzene/MeOH (8/1) gave a white solid; yield, 2.89 g
Table 6. Synthesis of biaryls from aryl tri¯ates
Entry
ArOTf (1) Rˆ
Yield (%)a
Pd(OAc)2/10c
PdCl2/9b
1
2
3
4-CN
4-CO2CH3
4-OCH3
90
88
46
±
±
93
1
(66%); H NMR (400 MHz, CDCl3) d 1.42 (s, 2H), 1.91
(s, 2H), 7.21±7.26 (m, 14H); 13C NMR (100 MHz, CDCl3)
d 45.9, 127.0 (d, Jˆ7.4 Hz), 128.3 (d, Jˆ7.4 Hz), 128.5,
133.4 (d, Jˆ19.9 Hz), 133.9 (d, Jˆ19.9 Hz), 135.1 (d, Jˆ
9.9 Hz), 137.1 (d, Jˆ10.8 Hz), 143.8; IR (Nujol)
3400 cm21; exact mass calcd for C19H18NP 291.1255,
found 292.1259 (M11, FAB).
All reactions were carried out at 808C for 16 h in water (3 mL) in the
presence of a tri¯ate (1 mmol), p-tolylboronic acid (1.3 mmol), a palladium
catalyst (0.1 mol%), and K3PO4 (2 mmol).
a
Isolated yields by chromatography.
PdCl2(GLCAphos)2 (0.1 mol%) and GLCAphos (9, 0.2 mol%).
Pd(OAc)2 (1 mol%) and 10 (2 mol%).
b
c

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M. Nishimura et al. / Tetrahedron 58 (2002) 5779±5787
3.1.3. N-[(4-Diphenylphosphinophenyl)methyl] d-gluco-
namide (9). 4-Diphenylphosphinobenzylamine (2.89 g,
9.93 mmol) and d-glucono-1,5-lactone (1.78 g, 10 mmol)
were dissolved in MeOH (75 mL) and the mixture was
then re¯uxed for 1.5 h. The white solid precipitated was
collected by ®ltration, washed with cold MeOH, and dried
in vacuo to give a white solid; 4.46 g (96%); 1H
NMR(400 MHz, CD3OD) d 3.30 (dt, Jˆ1.7, 3.2 Hz, 1H),
3.59±3.87 (m, 7H), 3.98 (d, Jˆ9.5 Hz, 1H), 4.06 (m, 1H),
4.14 (dd, Jˆ2.9, 5.6 Hz, 1H), 4.28 (d, Jˆ3.2 Hz, 1H), 4.42
(d, Jˆ15.4 Hz, 1H), 4.48 (d, Jˆ15.4 Hz, 1H), 7.19±7.26 (m,
6H), 7.31±7.35 (m, 8H); 13C NMR (100 MHz, CD3OD) d
43.36, 64.65, 71.83, 72.93, 74.31, 75.49, 128.54, 128.62,
129.57, 129.64, 129.94, 134.52, 134.72, 134.82, 135.02,
136.94, 138.52, 140.79, 175.33; 31P NMR (161.7 MHz,
CD3OD) d 24.05; IR (Nujol) 3300, 1650 cm21; exact
mass calcd for C25H28NO6P 469.1733, found 470.1750
(M11, FAB).
AcOEt (30/1) to give a white solid; yield, 2.2 g (75%); IR
1
(Nujol) 2226 cm21; H NMR (400 MHz, CDCl3) d 0.97±
1.28 (m, 10H), 1.53±1.86 (m, 18H), 7.21±7.24 (m, 1H),
7.39±7.43 (m, 4H), 7.61±7.64 (m, 1H), 7.65 (d, Jˆ
8.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) d 26.30, 27.02,
27.05, 27.09, 27.17, 29.10, 29.18, 30.27, 30.44, 34.44,
34.58, 110.48, 119.12, 127.42, 128.55, 129.72, 129.78,
131.19, 131.45, 131.50, 133.14, 133.18, 133.67, 133.89,
147.70, 147.77, 148.55, 148.83; 31P NMR (161.7 MHz,
CDCl3) d 213.09; MS m/z 154, 179, 209, 292, 376 (M1,
100); exact mass calcd for C25H30NP 375.2116, found
376.2172 (M11, FAB).
3.1.7. 2-Dicyclohexylphosphino-40-methylaminobiphenyl
(14). To a solution of 2-dicyclohexylphosphino-40-cyano-
biphenyl (1 g, 2.6 mmol) in ether (10 mL) was added
LiAlH4 (0.11 g, 3.0 mmol) at 08C and the mixture was
then stirred for 2 h at room temperature. The mixture was
treated with water at 08C and the product was extracted with
ethyl acetate, washed with brine, and dried over MgSO4.
Chromatography over silica gel with MeOH gave a white
3.1.4. PdCl2(GLCAphos)2. A mixture of PdCl2(1,5-
cyclooctadiene) (0.172 g, 0.6 mmol) and
9 (0.62 g,
1
1.3 mmol) in CH3CN (26 mL) was stirred for 1 h at 1008C.
The brown solid precipitated was collected by ®ltration,
washed with ether, and dried in vacuo.
solid; yield, 0.81 g (84%); H NMR (400 MHz, CDCl3): d
1.0±1.27 (m, 10H), 1.55±1.85 (m, 14H), 3.92 (s, 2H), 7.24±
7.38 (m, 7H), 7.58±7.60 (m, 1H); 13C NMR (100 MHz,
CDCl3) d 26.39, 27.14, 26.17, 27.22, 27.28, 29.16, 29.25,
30.30, 29.25, 30.30, 30.47, 34.60, 34.74, 46.31, 126.00,
126.39, 128.16, 130.24, 130.30, 130.74, 130.78, 132.84,
132.87, 133.83, 134.03, 141.47, 150.23, 150.51; 31P NMR
(161.7 MHz, CDCl3) d 213.04; exact mass calcd for
C25H34NP 379.2429, found 380.2503 (M11, FAB).
3.1.5. 2-Bromo-40-cyanobiphenyl (13). To a solution of
4-bromobenzonitrile (6.66 g, 30 mmol) in ether (30 mL)
was added BuLi (1.5 M in hexane, 20 mL) at 2788C.
After being stirred for 1 h, a solution of B(OiPr)3 (6.9 mL,
30 mmol) in ether (15 mL) was then added. The mixture
was stirred for 1 h at 2788C, slowly warmed up to room
temperature, and stand overnight. The resulting mixture was
treated with 3 M HCl (20 mL), extracted with ether, and
washed with brine. Evaporation of solvent followed by
crystallization from hot water gave a white solid (65%).
3.1.8.
N-[4-(2-Dicyclohexylphosphinophenyl)phenyl-
methyl] d-gluconamide (10). 2-Dicyclohexylphosphino-
40-methylaminobiphenyl (14) (0.81 g, 2.1 mmol) and
d-glucono-1,5-lactone (0.38 g, 2.15 mmol) was dissolved
in MeOH (15 mL) and the mixture was then re¯uxed for
3 h. Chromatography over silica gel with ethyl acetate/
A ¯ask charged with Pd(PPh3)4 (6.6 g, 5.8 mmol, 5 mol%),
4-cyanophenylboronic acid (16.9 g, 115 mmol), Na2CO3
(69 g, 651 mmol) was ¯ushed with argon. DME (160 mL),
water (320 mL), and 1,2-diboromobenzene (27.1 g, 115
mmol) were added and the mixture was then re¯uxed for
24 h. The product was extracted with ethyl acetate, washed
with brine, and dried over MgSO4. Chromatography over
silica gel with hexane/AcOEt (40/1) was followed by
crystalization from hexane/CH2Cl2 to give a white solid;
1
MeOH (10/1) gave a white solid; yield, 1.09 g (90%); H
NMR (400 MHz, CD3OD): d 0.96±1.28 (m, 10H), 1.51±
1.87 (m, 12H), 3.61±3.81 (m, 5H), 4.18 (t, Jˆ2.8 Hz, 1H),
4.31 (d, Jˆ3.2 Hz, 1H), 4.50 (s, 2H), 7.18±7.22 (m, 3H),
7.31±7.36 (m, 4H), 7.59±7.62 (m, 1H); 13C NMR
(100 MHz, CD3OD) d 27.53, 28.04, 28.07, 28.15, 30.56,
30.65, 31.81, 31.98, 36.03, 36.17, 43.53, 64.74, 71.90,
72.97, 74.34, 75.56, 127.51, 127.75, 129.59, 131.27,
131.33, 131.88, 131.92, 134.06, 134.09, 134.65, 134.84,
138.03, 143.09, 143.14, 151.49, 151.77, 175.19; 31P NMR
(161.7 MHz, CD3OD) d 213.28; IR (Nujol) 3349,
1648 cm21; MS m/z 392, 475, 558 (M1); exact mass calcd
for C31H44NO6P 557.2906, found 558.2964 (M11, FAB).
yield, 15.7 g, (53%); IR (Nujol) 2229 cm21 1H NMR
;
(400 MHz, CDCl3) d 7.25±7.30 (m, 2H), 7.40 (dd, Jˆ7.9,
8.0 Hz, 1H), 7.52 (d, Jˆ8.0 Hz, 1H), 7.69 (d, Jˆ8.0 Hz,
1H), 7.73 (d, Jˆ8.0 Hz, 2H); MS m/z 151 (42), 177 (42),
178 (35), 257 (98), 259 (100); exact mass calcd for
C13H8NBr 256.9840, found 256.9826 (M, EI).
3.1.9. 2-Di-tert-butylphosphino-40-cyanobiphenyl (17).
t-Bu2PCl (1.9 mL, 10 mmol) in THF (10 mL) was added
BH3 in THF (1 M, 15 mL, 15 mmol) and LiAlH4 (0.57 g,
15 mmol) at 08C. After being stirred for 2 h at room
temperature, the mixture was treated with water at 08C.
The product was extracted with ethyl acetate, dried over
Na2SO4, chromatographed over silica gel, and ®nally crys-
tallized from hexane to give a white solid of t-Bu2PH´BH3;
3.1.6. 2-Dicyclohexylphosphino-40-cyanobiphenyl. A 100
mL ¯ask charged with 2-bromo-40-cyanobiphenyl (2.0 g,
7.8 mmol) in THF (20 mL) was cooled to 21008C. BuLi
in hexane (2.6 M, 3 mL, 7.8 mmol) was added and the
mixture was stirred for 1 h. A solution of dicyclohexyl-
chlorophosphine (1.8 mL, 8.0 mmol) in THF (5 mL) was
then added. After being stirred for 1 h at 21008C, the
bath temperature was allowed to warm to room temperature
over 3 h. The product was extracted with ethyl acetate,
washed with brine, dried over Na2SO4, and ®nally isolated
by chromatography over neutral silica gel with hexane/
1
yield, 1.5 g (94%); H NMR (400 MHz, CDCl3): d 0.51
(broad q, Jˆ95.7, 3H), 1.31 (s, 9H), 1.34 (s, 9H), 4.11
(dq, Jˆ6.4, 351 Hz, 1H); 13C NMR (100 MHz, CDCl3) d
28.87, 28.89; 31P NMR (161.7 MHz, CDCl3) d 48.20 (q,

M. Nishimura et al. / Tetrahedron 58 (2002) 5779±5787
5785
Jˆ50.1 Hz, 1P); 11B NMR (128 MHz, CDCl3) d 243.236
(d, 1B); MS m/z 57 (100), 90 (11), 91 (9), 146 (M12BH3,
52).
(2.0 mmol) was ¯ushed with nitrogen. Water (3 mL) and
4-bromoanisole (1.0 mmol) were then added. After being
stirred for 16 h at 808C, the product was extracted with
benzene. The yield was estimated by GC analysis using
tridecane as the internal standard. The Pd(OAc)2/10 and
Pd(OAc)2/11 catalysts were prepared in situ by adding a
solution of Pd(OAc)2 in CH3CN (0.01 M, 0.1 mL,
0.1 mmol) to 10 (0.1±0.4 mmol) or 11 (0.2 mmol).
A 50 mL ¯ask charged with 2-bromo-40-cyanobiphenyl
(0.78 g, 3.0 mmol), t-Bu2PH´BH3 (0.48 g, 3.0 mmol),
Pd(dba)2 (0.052 g, 3 mol%), PhOK (0.83 g, 6.0 mmol) was
¯ashed with argon. Toluene (9 mL), P(OPh)3 (0.047 mL,
6 mol%) were added and the mixture was then stirred at
1008C for 3 h. The product was extracted with ethyl acetate,
washed with brine, and dried over MgSO4. GC analysis
indicated the formation of 17 in 25% yield. Thinlayer
chromatography (Merck Silica gel 60 PF254) gave a white
3.3. Representative procedure for cross-coupling
reaction of p-tolylboronic acid with haloarenes
solid; 0.013 g (13%); IR (Nujol) 2229 cm21
;
1H NMR
PdCl2(9)2 (1.3 mg, 0.001 mmol, 0.1 mol%), 9 (1.2 mg,
0.002 mmol) and p-tolylboronic acid (0.177 g, 1.3 mmol)
were added to a 20 mL ¯ask containing a magnetic stirring
bar. The ¯ask was ¯ushed with argon and then charged with
H2O (2 mL), K3PO4 (2 M, 1 mL, 2 mmol), and ®nally aryl
halide (1.0 mmol) by using a syringe through the septum
inlet. After being stirred for 16 h at 808C, the product was
extracted with benzene, washed with brine, and dried over
MgSO4. Chromatography over silica gel gave a biaryl.
(400 MHz, CDCl3): d 1.12 (s, 9H), 1.15 (s, 9H), 7.19±
7.22 (m, 1H), 7.36 (d, Jˆ8.1 Hz, 2H), 7.38±7.44 (m, 2H),
7.63 (d, Jˆ8.1 Hz, 2H), 7.92 (d, Jˆ7.1 Hz, 1H); 13C NMR
(100 MHz, CDCl3) d 30.53, 30.68, 32.77, 33.01, 110.24,
119.23, 126.74, 128.74, 130.01, 130.07, 131.06, 131.36,
131.40, 135.51, 148.70, 149.17, 149.49; 31P NMR
(161.7 MHz, CDCl3) d 15.42; exact mass calcd for
C21H26NP 323.1881, found 324.1910 (M11, FAB).
3.1.10. 2-Di-tert-butylphosphino-40-methylaminobiphenyl.
2-Di-tert-butylphosphino-40-cyanobiphenyl (17) (0.07 g,
0.22 mmol) in ether (5 mL) was added LiAlH4 (0.01 g,
0.26 mmol). After being stirred for 2 h at room temperature,
the mixture was treated with water at 08C. Chromatography
over silica gel with ethyl acetate and MeOH gave a white
The compounds in Tables 4 and 5 were synthesized by
above general procedure. Among them, we previously
reported the analytical data of 4-methyl-40-nitrobiphenyl,22
4-cyano-40-methylbiphenyl,22 2-cyano-40-methylbiphenyl,22
4-acetyl-40-methylbiphenyl,23 4-formyl-40-methylbiphenyl,24
4-methyl-40-methoxycarbonylbiphenyl,23 4-methyl-20-meth-
oxycarbonylbiphenyl,23 4-methyl-p-terphenyl,23 4-methyl-
1
solid; yield, 0.06 g (85%); H NMR (400 MHz, CD3OD) d
40-methoxybiphenyl,24
4-methyl-30-methoxybiphenyl,24
4-N,N-dimethylamino-40-
1.09 (s, 9H), 1.12 (s, 9H), 3.82 (s, 2H), 7.17±7.21 (m, 3H),
7.30 (d, Jˆ8.08 Hz, 2H), 7.31±7.39 (m, 2H), 7.91
(d, Jˆ7.08 Hz, 1H); 13C NMR (100 MHz, CD3OD) d
31.13, 31.29, 33.41, 33.66, 46.47, 126.99, 127.34, 129.80,
131.64, 131.70, 131.84, 131.88, 136.19, 136.48, 136.51,
141.46, 143.81, 143.88, 152.26, 152.59; 31P NMR
(161.7 MHz, CD3OD) d 17.66; MS m/z 215, 270, 327
(M1, 100); exact mass calcd for C21H30NP 327.2116,
found 327.2120 (M, EI).
4-amino-40-methylbiphenyl,24
methylbiphenyl,24 2-(4-methylphenyl)pyridine,22 3-(4-methyl-
phenyl)pyridine,22 4-(4-methylphenyl)pyridine,22 and 2-(4-
methylphenyl)quinoline.24
1
3.3.1. 4-Fuluoro-40-methylbiphenyl. H NMR (400 MHz,
CDCl3): d 2.39 (s, 3H), 7.08±7.12 (m, 2H), 7.24 (d, Jˆ
7.9 Hz, 2H), 7.43 (d, Jˆ7.9 Hz, 2H), 7.48±7.53 (m, 2H);
MS m/z 165 (40), 170 (12), 186 (M1, 100); exact mass calcd
for C13H11F 186.0845, found 186.0866 (M, EI).
3.1.11. N-[4-(Di-t-butylphosphinophenyl)phenylmethyl]
d-gluconamide (11). 2-Di-tert-butylphosphino-40-methyl-
aminobiphenyl (0.06 g, 0.18 mmol) and d-glucono-1,5-
lactone (0.034 g, 0.19 mmol) was dissolved in MeOH
(3 mL). After being re¯uxed for 3 h, the solvent was evapo-
rated in vacuo. Chromatography over silica gel with ethyl
acetate and then MeOH gave a white solid; yield, 0.07 g
3.3.2. 1-(4-Methylphenyl)naphthalene. 1H NMR (400
MHz, CDCl3): d 2.45 (s, 3H), 7.30 (d, Jˆ7.8 Hz, 2H),
7.36±7.53 (m, 9H); MS m/z 202 (51), 203 (59), 218 (M1,
100); exact mass calcd for C16H12 218.1096, found 218.1084
(M, EI).
(81%); IR (Nujol) 1510, 1347, 1650 cm21 1H NMR
;
3.3.3. 2-Hydroxy-40-methylbiphenyl. IR (Neat) 3540,
(400 MHz, CD3OD) d 1.10 (s, 9H), 1.13 (s, 9H), 3.61±
3.80 (m, 5H), 4.18 (s, 1H), 4.31 (d, Jˆ2.7 Hz, 1H), 4.51
(s, 2H), 7.16±7.18 (m, 3H), 7.30±7.39 (m, 4H), 7.92 (d,
Jˆ6.8 Hz, 1H); 13C NMR (100 MHz, CD3OD) d 31.06,
31.21, 33.45, 33.69, 43.52, 64.76, 71.94, 72.99, 74.36,
75.56, 127.03, 127.34, 129.86, 131.68, 131.76, 131.80,
136.47, 136.49, 137.78, 144.01, 144.07, 152.15, 152.48;
31P NMR (161.7 MHz, CD3OD) d 17.59; MS m/z 136,
154, 289, 307, 443, 460, 506 (M11); exact mass calcd for
C27H40NO6P 505.2672, found 506.2681 (M11, FAB).
1
1290 cm21; H NMR (400 MHz, CDCl3): d 2.40 (s, 3H),
5.22 (s, 1H), 6.96 (d, Jˆ7.9 Hz, 1H), 6.95±6.99 (m, 2H),
7.21±7.26 (m, 2H), 7.29 (d, Jˆ8.1 Hz, 2H), 7.35 (d, Jˆ
8.1 Hz, 2H); MS m/z 115 (23), 128 (18), 141 (19), 152
(11), 155 (10), 169 (51), 184 (M1, 100); exact mass calcd
for C13H12O 184.0888, found 184.0881 (M, EI).
3.3.4. 4-Hydroxy-40-methylbiphenyl. IR (Nujol) 3400
1
cm21; H NMR (400 MHz, CDCl3): d 2.38 (s, 3H), 4.76
(s, 1H), 6.88 (d, Jˆ8.5 Hz, 2H), 7.22 (d, Jˆ8.2 Hz, 2H),
7.43 (d, Jˆ8.2 Hz, 2H), 7.46 (d, Jˆ8.5 Hz, 2H); MS
m/z 155 (11), 165 (14), 167 (7), 183 (35), 184 (M1, 100);
exact mass calcd for C13H12O 184.0888, found 184.0892
(M, EI).
3.2. Reaction conditions (Table 1)
A 25 mL ¯ask charged with PdCl2(9)2 (1.3 mg, 0.001 mmol,
0.1 mol%), 9 (1.2 mg, 0.002 mmol, 0.2 mol%), and a base

5786
M. Nishimura et al. / Tetrahedron 58 (2002) 5779±5787
3.3.5. 4-Hydroxy-3-methoxycarbonyl-40-methylbiphenyl.
Before isolation, the product was treated with BF3´OEt2
(2 mL) in MeOH (20 mL) at re¯ux over night to convert
the acid into the corresponding ester derivative: IR (Neat)
Netherlands, 1997. (c) Aqueous-Phase Organometallic
Catalysis; Cornils, B., Herrmann, W. A., Eds.; Wiley-VCH:
Weinheim, 1998.
2. For reviews: (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95,
2457. (b) Suzuki, A. In Metal Catalyzed Cross-Coupling
Reactions; Diederich, F., Stang, P. J., Eds.; Wiley: New
York, 1998; Chapter 2. (c) Miyaura, N. Advance in Metal-
Organic Chemistry; Liebeskind, L. S., Ed.; Jai: London,
1998; Vol. 6, pp 187±243. (d) Stanforth, S. P. Tetrahedron
1998, 54, 263. (e) Palladium in Heterocyclic ChemistryÐA
Guide for the Synthetic Chemist; Li, J. J., Gribble, G. W., Eds.;
Pergamon: Amsterdam, 2001. (f) Miyaura, N. In Cross-
Coupling Reactions; Miyaura, N., Ed.; Springer: Berlin,
2002; pp 11±59.
1
3169, 1675 cm21; H NMR (400 MHz, CDCl3): d 2.37 (s,
3H), 3.95 (d, Jˆ0.5 Hz, 3H), 7.03 (d, Jˆ8.8 Hz, 1H), 7.21
(d, Jˆ8.8 Hz, 2H), 7.42, (d, Jˆ8.1 Hz, 2H), 7.66 (dd, Jˆ2.2,
6.4, 2.4 Hz, 1H), 8.03 (d, Jˆ2.4 Hz, 1H), 10.74 (s, 1H); 13C
NMR (100 MHz, CDCl3) d 21.01, 52.29, 112.41, 117.91,
119.50, 126.39, 127.80, 129.48, 132.23 (d, Jˆ19.9 Hz),
134.21, 136.84 (d, Jˆ19.8 Hz), 138.35: MS m/z 139 (12),
153 (20), 182 (16), 210 (100), 242 (M1, 65); exact mass
calcd for C15H14O3 242.0943, found 242.0942 (M, EI).
3.3.6. 3-Hydroxy-4-methoxycarbonyl-40-methylbiphenyl.
The product was treated with BF3´OEt2 (2 mL) in MeOH
(20 mL) at re¯ux over night to convert the acid into the
3. Bumagin, N. A.; Bykov, V. V.; Beletskaya, I. P. Dan SSSR
1990, 315, 1133.
4. (a) Badone, D.; Baroni, M.; Cardamone, R.; Ielmini, A.;
Guzzi, U. J. J. Org. Chem. 1997, 62, 7170. (b) Bussolari,
J. C.; Rehborn, D. C. Org. Lett. 1999, 1, 965. (c) Hesse, S.;
Kirsch, G. Synthesis 2001, 755.
corresponding ester: IR (Nujol) 3191, 1680, 1618 cm21
;
1H NMR (400 MHz, CDCl3): d 2.39 (s, 3H), 3.95 (s, 3H),
7.10 (dd, Jˆ0.98, 7.3 Hz, 1H), 7.20 (s, 1H), 7.24, (d, Jˆ
7.8 Hz, 2H), 7.50 (d, Jˆ8.1 Hz, 2H), 7.85 (d, Jˆ8.3 Hz, 1H),
10.80 (s, 1H); 13C NMR (100 MHz, CDCl3) d 21.15, 52.21,
110.86, 115.36, 117.93, 127.00, 129.58, 130.21, 136.66,
138.42, 148.42, 161.77, 170.49: MS m/z 153 (22), 182
(38), 195 (10), 210 (100), 242 (M1, 57); exact mass calcd
for C15H14O3 242.0943, found 242.0951 (M, EI).
5. (a) Kong, K.-C.; Cheng, C.-H. J. Am. Chem. Soc. 1991, 113,
6313. (b) Goodson, F. E.; Wallow, T. I.; Novak, B. M. J. Am.
Chem. Soc. 1997, 119, 12441. (c) Grushin, V. V. Organo-
metallics 2000, 19, 1888.
6. (a) Casalnuovo, A. L.; Calabrese, J. C. J. Am. Chem. Soc.
1990, 112, 4324. (b) Galland, J.-C.; Savingnac, M.; Genet,
J.-P. Tetrahedron Lett. 1999, 40, 2323. (c) Gelpke, A. E. S.;
Veeman, J. J. N.; Goedheijt, M. S.; Kamer, P. C. J.; Hiemstra,
H. Tetrahedron 1999, 55, 6657. (d) Dupuis, C.; Adiey, K.;
Charruault, L.; Michelet, V.; Savignac, M.; Genet, J.-P.
Tetrahedron Lett. 2001, 42, 6523.
3.3.7. Methyl 4-(4-methylphenyl)cinnamate. The product
was isolated after conversion into the corresponding ester:
IR (Nujol) 1710, 1632, 1463, 1314, 1196, 1175, 984,
1
810 cm21; H NMR (400 MHz, CDCl3): d 2.31 (s, 3H),
3.73 (s, 3H), 6.37 (d, Jˆ16.1 Hz, 1H), 7.16 (d, Jˆ7.6 Hz,
2H), 7.41 (d, Jˆ7.8 Hz, 2H), 7.47±7.52 (m, 4H), 7.64 (d,
Jˆ16.1 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 21.10,
51.64, 117.34, 126.80, 127.22, 128.51, 129.58, 132.96,
137.15, 137.71, 142.94, 144.42, 167.44; MS m/z 149
(100), 185 (8), 205 (7), 221 (19), 252 (M1, 30); exact
mass calcd for C17H16O2 252.1150, found 252.1138 (M, EI).
7. Beller, M.; Krauter, J. G. E.; Zapf, A. Angew. Chem., Int. Ed.
1997, 36, 772.
8. Shaughnessy, K. H.; Booth, R. S. Org. Lett. 2001, 3, 2757.
9. Uozumi, Y.; Danjo, H.; Hayashi, T. J. Org. Chem. 1999, 64,
3384.
10. Preliminary results were reported in Ueda, M.; Nishimura, M.;
Miyaura, N. Synlett 2000, 856.
11. (a) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 1998, 37,
3387. (b) Littke, A. F.; Dai, C.; Fu, G. C. J. Am. Chem. Soc.
2000, 122, 4020.
3.3.8. Methyl 2-(4-methylphenyl)cinnamate. The product
was converted into the corresponding ester before isolation:
IR (Neat) 1713, 1632 cm21; 1H NMR (400 MHz, CDCl3): d
2.40 (s, 3H), 3.74 (s, 3H), 6.39 (d, Jˆ16.1 Hz, 1H), 7.19±
7.25 (m, 4H), 7.33±7.43 (m, 3H), 7.67, (d, Jˆ8.5 Hz, 1H),
7.75 (d, Jˆ16.1 Hz, 1H); 13C NMR (100 MHz, CDCl3) d
21.13, 51.53, 118.51, 126.75, 127.37, 129.00, 129.65,
129.80, 130.48, 132.53, 136.88, 137.28, 142.92, 144.15,
167.29: MS m/z 178, 193, 221, 252 (M1); exact mass
calcd for C17H16O2 252.1150, found 252.1155 (M, EI).
12. (a) Old, D. W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem.
Soc. 1998, 120, 9722. (b) Wolfe, J. P.; Singer, R. A.; Yang,
B. H.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121, 9550.
(c) Yin, J.; Rainka, M. P.; Zhang, X.-X.; Buchwald, S. L.
J. Am. Chem. Soc. 2002, 124, 1162. (d) For a review, see:
Buchwald, S. L.; Fox, J. M. Strem Chemiker 2000, 1, 1.
13. (a) Zhang, C.; Huang, J.; Trudell, M. L.; Nolan, S. P. J. Org.
Chem. 1999, 64, 3804. (b) Zhang, C.; Trudell, M. L.
Tetrahedron Lett. 2000, 41, 595.
1
3.3.9. 3-(4-Methylphenyl)quinoline. H NMR (400 MHz,
14. (a) Li, G. Y. Angew. Chem., Int. Ed. 2001, 40, 1523. (b) Li,
G. Y.; Zheng, G.; Noonan, A. F. J. Org. Chem. 2001, 66, 8677.
15. Parham, W. E.; Jones, L. D. J. Org. Chem. 1976, 41, 1187.
16. (a) Kobayashi, K.; Sumitomo, H.; Ina, Y. Polym. J. 1983, 15,
667. (b) Kobayashi, K.; Sumitomo, K. J. Macromol. Sci.
Chem. A 1988, 25, 655.
CDCl3): d 2.43 (s, 3H), 7.33 (d, Jˆ7.8 Hz, 2H), 7.56 (dd,
Jˆ8.1, 8.1 Hz, 1H), 7.61 (d, Jˆ7.8 Hz, 2H), 7.68±7.72 (m,
1H), 7.86 (d, Jˆ8.1 Hz, 1H), 8.13 (d, Jˆ8.3 Hz, 1H), 8.27
(d, Jˆ2.2 Hz, 1H), 9.17 (d, Jˆ2.2 Hz, 1H); exact mass calcd
for C16H13N 219.1048, found 219.1049 (M, EI).
17. Gray, M.; Snieckus, V. Synlett 1998, 422.
18. Coupling reaction of haloarenes with R2PHYBH3 was
reported. (a) Oshiki, T.; Inamoto, T. J. Am. Chem. Soc.
1992, 114, 3975. (b) Lipshutz, B. H.; Buzard, D. J.; Yun,
C. S. Tetrahedron Lett. 1999, 40, 201. (c) Al-Masum, M.;
Livinghouse, T. Tetrahedron Lett. 1999, 40, 7731. (d) Herd,
O.; Tepper, M.; Stelzer, O. Catal. Today 1998, 42, 413.
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8000±9000 TON for 4-bromoacetophenone in H2O/
EtOH/toluene7 and Pd(OAc)2/5 achieved 97,000±734,000
TON for 4-bromotoluene in H2O/CH3CN.8
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