Polymer-Assisted Solution-Phase (PASP) Suzuki Couplings Employing an Anthracene-Tagged Palladium Catalyst

Article abstract of DOI:10.1021/jo035129g

A general method for polymer-assisted solution-phase (PASP) Suzuki reactions employing a combination of anthracene-tagged palladium catalyst and anthracene-tagged boronic acid with a polymer-supported carbonate base is reported. The anthracene-tagged catalyst allows for the easy removal of the Pd catalyst along with the dissociated phosphine ligand and phosphine oxide byproducts by sequestration through a chemoselective Diels-Alder reaction with a maleimide resin. The polymer-supported carbonate base facilitates the removal of excess boronic acid and the borane-containing byproducts present at the end of the coupling reaction. The Suzuki coupling reaction can be efficiently conducted by using combinations of the anthracene-tagged Pd catalyst, polymer-supported carbonate base, and anthracene-tagged boronic acid to yield the desired product in high purity and yield without the use of chromatography.

Full text of DOI:10.1021/jo035129g

P olym er -Assisted Solu tion -P h a se (P ASP ) Su zu k i Cou p lin gs
Em p loyin g a n An th r a cen e-Ta gged P a lla d iu m Ca ta lyst
Ping Lan,† Daniela Berta,§ J ohn A. Porco, J r,‡ Michael S. South,† and J ohn J . Parlow*,†
Department of Medicinal and Combinatorial Chemistry, Pharmacia Corporation,
800 North Lindbergh Boulevard, St. Louis, Missouri 63167, Department of
Medicinal Chemistry, Pharmacia Corporation, Viale Pasteur, 10,
20014 Nerviano, Italy, and Department of Chemistry and Center for
Chemical Methodology and Library Development, Boston University,
590 Commonwealth Avenue, Boston, Massachusetts 02215
john.j.parlow@pfizer.com
Received J uly 31, 2003
A general method for polymer-assisted solution-phase (PASP) Suzuki reactions employing a
combination of anthracene-tagged palladium catalyst and anthracene-tagged boronic acid with a
polymer-supported carbonate base is reported. The anthracene-tagged catalyst allows for the easy
removal of the Pd catalyst along with the dissociated phosphine ligand and phosphine oxide
byproducts by sequestration through a chemoselective Diels-Alder reaction with a maleimide resin.
The polymer-supported carbonate base facilitates the removal of excess boronic acid and the borane-
containing byproducts present at the end of the coupling reaction. The Suzuki coupling reaction
can be efficiently conducted by using combinations of the anthracene-tagged Pd catalyst, polymer-
supported carbonate base, and anthracene-tagged boronic acid to yield the desired product in high
purity and yield without the use of chromatography.
In tr od u ction
starting materials. Suzuki coupling reactions generally
employ organic solvents such as DMF and THF in the
presence of soluble Pd(II) or Pd(0) catalysts. Commonly
used Pd catalysts are Pd(PPh3)4 and Pd(PPh3)2Cl2. Fre-
quently used bases are inorganic carbonates such as Na2-
CO3, K2CO3, and Cs2CO3. Substituted aryl halides (bro-
mides or iodides) and triflates along with boronic acids
or esters are suitable substrates. The major problems
associated with the broad application of this reaction in
parallel synthesis are the removal of the homogeneous
Pd catalyst, disassociated ligand byproducts, unreacted
starting materials (aryl halide and boronic acid), and the
inorganic base. An additional problem is the formation
of byproducts from two competing side reactions: the
coupling of arylboronic acid with the phenyl group from
the triphenylphosphine-stabilizing ligand and the self-
coupling products generated from the starting aryl
substrates when the desired cross-coupling is very slow.3
One of the chemical transformations that has received
little attention in polymer-assisted solution-phase (PASP)
based approaches is the Suzuki reaction. The Suzuki
reaction, a palladium-catalyzed cross-coupling of orga-
noboranes such as boronic acids, boronates, and trialkyl-
boranes with organic halides and triflates in the presence
of a base, has become a powerful tool in organic synthe-
sis.1 The Suzuki reaction has proved extremely versatile
and has found extensive use in the formation of carbon-
carbon bonds, especially the formation of aryl-aryl
bonds. In particular, the biaryl unit is represented in
many biologically active compounds and novel organic
materials.2
The Suzuki reaction has gained popularity due to the
mild reaction conditions, commercial availability of di-
verse boronic acids/esters, reaction efficiency, and com-
patibility with many functional groups present in the
Over the past decade, several new methodologies have
been developed to address some aspects of these problems
associated with the Pd-catalyzed Suzuki reaction. One
approach that allows for easy removal of the Pd catalyst
employs the use of a supported catalyst that can be
readily removed by filtration. The kind of supports
studied thus far include polystyrene resin,4 amphiphilic
* Corresponding author. Phone: 314-274-3494.
† Department of Medicinal and Combinatorial Chemistry, Pharma-
cia Corporation.
§ Department of Chemistry, Pharmacia Corporation.
‡ Boston University.
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9633-9695. (b) Suzuki, A. J . Organomet. Chem. 1999, 576, 147-168.
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Suzuki, A. Chem. Rev. 1995, 95, 2457-2483.
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44, 4779-4782. (b) Parrish, C. A.; Buchwald, S. L. J . Org. Chem. 2001,
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10.1021/jo035129g CCC: $25.00 © 2003 American Chemical Society
Published on Web 11/18/2003
9678
J . Org. Chem. 2003, 68, 9678-9686

Polymer-Assisted Solution-Phase Suzuki Couplings
SCHEME 1. Syn th esis a n d Sequ estr a tion of An th r a cen e-Ta gged P d Ca ta lyst 2
polymers,5 and glass beads,6 which take advantage of the
reaction’s tolerance for aqueous phase, and application
of ligandless charcoal.7 A strategy that employs a fluorous
biphase system, in which the perfluoro-tagged Pd catalyst
is located in the fluorous phase, has also been reported.8
These methods allow for the removal of the Pd catalyst
but still rely on further purification for removal of the
remaining unwanted species. Solid-phase Suzuki cou-
plings, which involve reacting a resin-bound aryl halide
with a solution-phase boronic acid, are an excellent
approach to solve all the problems in terms of removing
the catalyst, the base, and unreacted boronic acid along
with the byproducts in one filtration step.9 However, this
approach is not always practical for a single step in a
solution-phase synthesis. Recently, there have been
reports of a similar approach involving immobilization
of the boronic acid instead of the aryl halide on the solid
phase.10 However, products after Pd-catalyzed cleavage
may still require purification.
SCHEME 2. Su zu k i Rea ction Eva lu a tin g P d
Ca ta lyst 2
the intense fluorescence of the anthracene permits easy
monitoring of reaction progress. We have demonstrated
the use of anthracene-tagged reagents for the Mitsunobu
reaction permitting the simple removal of excess reagent
and reagent byproducts.11a Another application employs
anthracene-tagged substrates in the Stille coupling al-
lowing for chemistry to be conducted in the solution phase
followed by “phase switching” immobilization onto a solid
support via Diels-Alder cycloaddition to aid compound
purification, and cleavage of the desired purified pro-
ducts.11b Others have demonstrated the use of anthracene-
tagged substrates by immobilizing an anthracene-tagged
carboxylic acid followed by solid-phase Suzuki couplings,
activation, and then cleavage with nucleophiles to afford
ester and amide products.12 Herein, we report the use of
an anthracene-tagged catalyst and substrates in conjunc-
tion with a polymer-bound base for parallel PASP Suzuki
coupling reactions.
As part of our interest to develop new methodology for
PASP synthesis and purification of final products, we
have studied the application of Diels-Alder cycloaddi-
tion-removable tags, specifically anthracene-tagged re-
agents or substrates.11 The anthracenyl moiety has been
shown by us and other researchers to be a useful
chemical “tag” aiding in the purification process.11,12
A
major advantage of the cycloaddition-removable an-
thracene tag is the highly orthogonal and chemoselective
reactivity of the Diels-Alder reaction for the immobiliza-
tion and removal of the tagged molecule, thus allowing
the presence of numerous functional groups. Additionally,
Resu lts a n d Discu ssion
Previously, anthracene-tagged triphenylphosphine 1
was synthesized and applied in PASP Mitsunobu reac-
tions.11a We reasoned that an anthracene-tagged catalyst
prepared by complexation of phosphine 1 with palladium
would allow for the sequestration of both the Pd catalyst
and any dissociated ligand byproducts from the Suzuki
reaction. Thus, the tagged phosphine 1 was reacted with
palladium dichloride to afford the anthracene-tagged Pd
catalyst 2 (Scheme 1).
Catalyst 2 was evaluated and compared to the corre-
sponding untagged catalyst, Pd(PPh3)2Cl2, in a Suzuki
coupling (Scheme 2). Both catalysts gave very similar
yields of the coupled product 7 (81% vs 80%). However,
with the tagged catalyst 2, the amount of side-product 8
from the reaction between the boronic acid 6 and the
phenyl of triarylphosphine ligand was reduced (4% vs
9%), presumably due to the increased crowdedness
around the phosphine.13
(5) (a) Yamada, Y. A.; Takeda, K.; Takahashi, H.; Ikegami, S. Org.
Lett. 2002, 4, 3371-3374. (b) Uozumi, Y.; Nakai, Y. Org. Lett. 2002, 4,
2997-3000. (c) Uozumi, Y.; Danjo, H.; Hayashi, T. J . Org. Chem. 1999,
64, 3384-3388.
(6) Lawson Daku, K. M.; Newton, R. F.; Pearce, S. P.; Vile, J .;
Williams, J . M. J . Tetrahedron Lett. 2003, 44, 5095-5098.
(7) (a) Organ, M. G.; Mayer, S. J . Comb. Chem. 2003, 5, 118-124.
(b) Sakurai, H.; Tsukuda, T.; Hirao, T. J . Org. Chem. 2002, 67, 2721-
2722. (c) LeBlond, C. R.; Andrews, A. T.; Sun, Y.; Sowa, J . R., J r. Org.
Lett. 2001, 3, 1555-1557. (d) Ennis, D. S.; McManus, J .; Wood-
Kaczmar, W.; Richardson, J .; Smith, G. E.; Carstairs, A. Org. Proc.
Res. Dev. 1999, 3, 248-252. (e) Gala, D.; Stamford, A.; J enkins, J .;
Kugelman, M. Org. Proc. Res. Dev. 1997, 1, 163-164. (f) Marck, G.;
Villiger, A.; Buchecker, R. Tetrahedron Lett. 1994, 35, 3277-3280.
(8) Schneider, S.; Bannwarth, W. Helv. Chim. Acta 2001, 84, 735-
742.
(9) For review see: Bra¨se, S.; Kirchhoff, J . H.; Ko¨bberling, J .
Tetrahedron 2003, 59, 885-939 and references therein.
(10) (a) Pourbaix, C.; Carreaux, F.; Carboni, B. Org. Lett. 2001, 3,
803-805. (b) Li, W.; Burgess, K. Tetrahedron Lett. 1999, 40, 6527-
6530.
(11) (a) Lan, P.; Porco, J . A., J r.; South, M. S.; Parlow, J . J . J . Comb.
Chem. 2003, 5, 660-669. (b) Wang, X.; Parlow, J . J .; Porco, J . A., J r.
Org. Lett. 2000, 2, 2999-3001.
(12) Li, X.; Abell, C.; Ladlow, M. J . Org. Chem. 2003, 68, 4189-
4194.
(13) It is known that a bulky phosphine ligand such as MOP can
help retard the phenyl shifting side reaction. See ref 1a.
J . Org. Chem, Vol. 68, No. 25, 2003 9679

Lan et al.
1
90% yield. H and 13C NMR showed high purity of the
product without detectable boronic acid 9E or other
byproducts. Analysis of the filtered reaction mixture by
31P NMR indicated the complete removal of phosphine
ligand, and ICP-AES analysis showed that palladium was
completely removed.17
SCHEME 3. Mu ltip le Roles of P olym er -Su p p or ted
Ca r bon a te Ba se 10
To demonstrate the application of this methodology, a
parallel array of reactions was designed involving a
variety of aryl bromides 13 and aryl boronic acids 9, each
containing electron-withdrawing or electron-donating
substituents (Figure 1). Thus, all combinations of each
of the four substituted aryl bromides 13 with each of the
five substituted aryl boronic acids 9 were subjected to
the established coupling conditions with the tagged
catalyst 2 and polymer-supported carbonate 10 (Scheme
4). After heating overnight, PS-maleimide resin 3 was
added and heating continued at 90 °C for 10 h. Filtration
removed the polymer-sequestered catalyst and dissoci-
ated phosphine or phosphine oxide, the polymer-sup-
ported base, and any species attached to the base.
Subsequent evaporation afforded a product mixture
containing the desired product 14 and varying amounts
of minor products 15-17. The purities of the coupling
products were determined by GC analysis after filtration
and by NMR analysis after concentration and drying. The
yields were determined based on the weights. The results
are shown in Table 1.
A model sequestration study was performed by incu-
bating polymer-bound maleimide 3 with catalyst 2 in
deuterated DMF at 90 °C for 10 h. Catalyst 2 was
completely sequestered, affording polymer-bound pal-
ladium catalyst 414 as indicated by phosphorus NMR
(Scheme 1). Filtration and evaporation left a residue-free
vial.
It is known that there are several side reactions
competing with the major reaction pathway of the Suzuki
coupling. The ratio of the products depends on the
reaction rate of each step in the cycle. Scheme 4 shows
the common products resulting from the Suzuki reac-
tion: the desired product 14 and the major byproducts
15, 16, and 17. For aryl bromides, the oxidative addition
is believed to be rate determining,16 and the results from
Table 1 support this observation. For aryl bromides with
electron-withdrawing substituents (13a and 13b), the
coupling reactions generally gave higher than 92% (GC
purity, Table 1) of the desired product 14. Self-coupling
(15) from the boronic acid 9 was the only significant
byproduct. This reflected a much faster reaction rate of
the major pathway. When the aryl bromide was substi-
tuted with a slightly electron-donating group (13c), the
GC purity ratio of the product was slightly lower with
an average of 89% desired product 14. The major byprod-
ucts 15 and 17 resulted from self-coupling of boronic acid
9 and from debromination of the aryl bromide 13c,
respectively. The debromination was presumably due to
the ortho-substitution of the starting material. Aryl
bromide 13d , with a strong electron-donating substitu-
ent, afforded the desired product 14 with an average GC
purity of 73%. The major byproducts, 15 and 16, resulted
from self-coupling of boronic acid 9 and cross-coupling
between the boronic acid 9 and the phenyl group of the
phosphine ligand, respectively. The substituents on the
aryl boronic acids did not have much influence on the
outcome of the reactions, as the product ratio for each
With a sequesterable Pd catalyst in hand, attention
was focused evaluation of bases. A polymer-supported
carbonate, such as tetraalkylammonium carbonate resin
10,15 should act in the same way as an inorganic
carbonate base to activate the boronic acid 9 for coupling
and to neutralize the boric acid byproduct 12 (Scheme
3). In addition, any unreacted boronic acid should be
sequestered by the polymer-supported base. The mecha-
nistic study from Smith and his colleagues16 suggested
-
that the ArB(OH)3 anion, resulting from the reaction
between Lewis acid boronic acid and carbonate base is
likely the reactive species rather than boronic acid itself.
Therefore, additional water and carbonate base are
necessary to neutralize the coupling byproduct boric acid
to afford the boric anion B(OH)4-. Thus, replacement of
the inorganic base with polymer-supported carbonate 10
can serve multiple roles: as the base to activate the
boronic acid for coupling and as the scavenger to seques-
ter the unreacted boronic acid and boric acid byproduct.
A model Suzuki reaction with use of the anthracene-
tagged palladium catalyst 2 and polymer-supported
carbonate base 10 was examined (Scheme 4). The cou-
pling of 4′-bromoacetophenone 13b with 1.2 equiv of
4-ethoxyphenylboronic acid 9E occurred smoothly in the
presence of 10 mol % of palladium complex 2 and 3.6
equiv of polymer-supported carbonate 10 in a mixed
solvent DMF/H2O (2 mL/0.1 mL) at 80 °C to give biphenyl
product 14bE, which was 97% pure as determined by GC
analysis. Subsequent addition of PS-maleimide 3 and
continued heating at 90 °C for 10 h followed by filtration
and evaporation afforded the desired product 14bE in
(17) An ICP-AES analysis for palladium was conducted on the
product mixture of 14bE after sequestration with PS-maleimide 3. ICP-
AES analysis showed less than 1 ppm of Pd present with an expected
theoretical value without sequestration of 91 000 ppm. A second
analysis on the same sample prior to sequestration had an actual value
of 5 430 ppm. The difference between the theoretical and actual value
was due to lack of solubility of the sample. Thus, >99.98% of palladium
had been removed from the product mixture.
(14) Polymer-supported palladium catalyst 4 may also serve as a
polystyrene-based palladium catalyst such as those cited in ref 4.
(15) The polymer-supported tetraalkylammonium carbonate was
purchased from Aldrich (50-90 mesh, 2.5 mmol/g-3.5 mmol N/g.)
(16) Smith, G. B.; Dezeny, G. C.; Hughes, D. L.; King, A. O.;
Verhoeven, T. R. J . Org. Chem. 1994, 59, 8151-8156.
9680 J . Org. Chem., Vol. 68, No. 25, 2003

Polymer-Assisted Solution-Phase Suzuki Couplings
SCHEME 4. P ASP Su zu k i Cou p lin g
bromide was required. Aminomethylanthracene 18 was
coupled with 4-bromobenzoic acid 19 to afford the tagged
aryl bromide 20 (Scheme 5). Anthracene-tagged aryl
bromide 20 proved to be an excellent partner in the
Suzuki coupling and both the coupled product and
starting anthracene-tagged bromide 20 were quantita-
tively sequestered by the maleimide resin 3.
A second option was to design an anthracene-tagged
boronic acid to react with and sequester excess aryl
bromide. The anthracene-tagged boronic acid 25 was
synthesized employing the elegant protocol developed by
Hall and co-workers (Scheme 6).18 Boronic acid 22 was
loaded onto the N,N-diethanolaminomethyl polystyrene
21 (PS-DEAM) followed by coupling with aminomethyl-
anthracene 18 to afford polymer-bound amide 24. Cleav-
age of the boronic acid from the solid phase afforded the
tagged boronic acid 25 in good yield and high purity.
To prove the anthracene-tagged boronic acid 25 could
react with excess aryl bromide and subsequently be
sequestered, 25 was subjected to a Suzuki coupling with
a fluoro-labeled aryl bromide 26 under typical conditions
(Scheme 7). GC/MS and 19F NMR confirmed the disap-
pearance of the aryl bromide 26 and formation of the
tagged derivative 27. After addition of the maleimide
resin 3, complete sequestration of the coupling product
27 was evident by a 19F NMR of the PS-maleimide resin
28, revealing a signal at -134.54 ppm (Scheme 7), and a
19F NMR of the resulting solution, with no observable
fluorine signal.
F IGURE 1. Aryl bromides 13 and aryl boronic acids 9 for
Suzuki couplings.
specific aryl bromide was essentially the same for boronic
acids having an electron-withdrawing or -donating group.
The formation of self-coupling byproduct from the aryl
bromide 13 and competitive hydrolytic deboronation of
the arylboronic acid 9 was negligible in all cases.
An improved protocol for the Suzuki reaction involving
electron-rich aryl bromides was investigated. Variations
of the stoichiometric amounts of the Suzuki substrates
were considered in an attempt to increase the percent of
desired product relative to the byproducts. At the end of
the reaction, the excess substrate could be removed by
reacting it with the corresponding anthracene-tagged
Suzuki partner followed by sequestration with the ma-
leimide resin.
Initially, 9-bromoanthracene and 9,10-dibromoan-
thracene were evaluated as potential Suzuki aryl bromide
coupling partners for reaction with excess boronic acid.
Each was evaluated in a sequestration study with ma-
leimide resin 3. Despite prolonged reaction times and the
use of excess maleimide resin 3, starting material
remained. Thus, a more reactive anthracene-tagged aryl
Thus, with both anthracene-tagged Suzuki substrates
prepared, optimization of the Suzuki reaction with the
electron- rich aryl bromide 13d was evaluated by varying
the stoichiometric amounts of each substrate. Not sur-
prisingly, using an excess of boronic acid resulted in an
increase in the self-coupling product 15 from the boronic
substrate 9 (Scheme 4). To eliminate formation of the
self-coupled byproduct, an excess of the aryl bromide
rather than an excess of the boronic acid was used. By
using an excess of the aryl bromide, an increased amount
of the oxidative addition intermediate should be available
for transmetalation with the boronic acid, effectively
(18) (a) Gravel, M.; Thompson, K. A.; Zak, M.; Be´rube´, C.; Hall, D.
G. J . Org. Chem. 2002, 67, 3-15. (b) Hall, D. G.; Tailor, J . i; Gravel,
M. Angew. Chem., Int. Ed. 1999, 38, 3064-3067.
J . Org. Chem, Vol. 68, No. 25, 2003 9681

Lan et al.
TABLE 1. P ASP Su zu k i Cou p lin g Resu lts: P er cen ta ge Ra tio of P r od u cts (14:15:16:17)a a n d Yield sb of 14
aryl
boronic
acids
aryl bromides
13c
14cA
13a
14a A
13b
14bA
13d c
14d A
13d d
14d A
9A
95:5:0:0 (89)
14a B
94:6:0:0 (100)
14a C
94:5:1:0 (80)
14a D
95:3:2:0 (69)
14a E
94:6:0:0 (89)
14bB
92:8:0:0 (99)
14bC
94:5:1:0 (82)
14bD
95:3:2:0 (66)
14bE
89:6:0:5 (72)
14cB
86:9:0:5 (86)
14cC
91:7:0:5 (86)
14cD
89:9:0:2 (84)
14cE
70:22:8:0 (83)
14d B
73:19:8:0 (92)
14d C
73:18:9:0 (96)
14d D
75:17:8:0 (88)
14d E
84:9:6:0 (84)
14d B
90:4:6:0 (80)
14d C
87:7:6:0 (78)
14d D
87:7:6:0 (80)
14d E
9B
9C
9D
9E
97:2:1:0 (97)
96:3:1:0 (99)
90:7:0:3 (70)
76:17:7:0 (94)
81:8:11:0 (82)
a
The GC purities are reported as the percentage ratio of the desired coupling product 14, the self-coupling byproduct 15 from the
boronic acid 9, byproduct 16 formed between the boronic acid 9 and phenyl group from the phosphine ligand, and desbromo product 17
b
from debromination of the aryl halide 13. Yield is based on mass recovery. c Products generated form Suzuki protocol in Scheme 4.
d
Products generated from modified Suzuki protocol in Scheme 8.
SCHEME 5. Syn th esis of An th r a cen e-Ta gged Ar yl
Br om id e 20
development of an anthracene-tagged catalyst allows for
the easy removal of the Pd catalyst along with the
dissociated phosphine ligand and phosphine oxide byprod-
ucts by a Diels-Alder cycloaddition with polymer-bound
maleimide followed by removal of the polymer-bound
adducts via filtration. It was demonstrated that the
Diels-Alder reaction of the anthracene-tagged Pd cata-
lyst with PS-maleimide is highly efficient, as no observ-
able phosphorus or palladium was detected in solution
after the sequestration process. Thus, the Suzuki cou-
pling can be efficiently conducted by using both the
tagged catalyst and polymer-supported carbonate to yield
the desired product in high purity and yield without the
use of chromatography. For the sluggish aryl bromide
substrates with strong electron-donating groups, a slightly
modified protocol can be applied by increasing the stoi-
chiometric amount of aryl bromide, which upon comple-
tion of the reaction can be consumed by addition of
anthracene-tagged boronic acid followed by sequestration
with PS-maleimide. Using this modified procedure af-
forded an increase in the desired Suzuki coupled product
and minimized the byproduct formation. The anthracene-
tagged catalyst and substrates are easily prepared in
large quantities and stable under storage at low temper-
ature for several months. The removal of anthracene-
tagged species by PS-maleimide via Diels-Alder reaction
is highly chemoselective and allows for the tolerance of
many functional groups. One can envision applying this
basic methodology to other Pd-catalyzed reactions, al-
lowing for their use in a parallel format.
minimizing the amount of self-coupling product from the
boronic acid substrate.
The improved Suzuki reaction involving electron-rich
aryl bromides is shown in Scheme 8. The reaction was
conducted with 1.8 equiv of aryl bromide 13d relative to
the boronic acid 9. Upon complete consumption of the
boronic substrate 9, a second Suzuki coupling was
initiated by the addition of the tagged boronic acid 25.
This transformed starting aryl bromide 13d into seques-
terable anthracene-tagged species 29. Incubation of the
product mixture with the PS-maleimide 3 resulted in
sequestration of the unreacted tagged boronic acid 25,
anthracene derivative 29, and Pd catalyst 2. Filtration
and evaporation afforded the purified products 14. Com-
parisons of the product ratio with use of this modified
protocol vs the standard protocol are impressive (Table
1). The average desired product ratio increased from 73%
to 86% with the modified protocol, and a significant
decrease in both byproducts 15 and 16 was observed.
In conclusion, we have developed a practical and
efficient protocol for PASP parallel Suzuki couplings by
employing the combination of anthracene-tagged catalyst,
anthracene-tagged boronic acid, and polymer-supported
tetramethylammonium carbonate as base. Polymer-sup-
ported carbonate base, the inorganic base necessary for
the reaction, greatly facilitates the removal of excess
boronic acid and the borane-containing byproducts present
at the end of the coupling via a simple filtration, therefore
eliminating the need for aqueous workup. Similarly, the
Exp er im en ta l Section
1
Gen er a l In for m a tion . H NMR spectra were recorded on
a
300-MHz spectrometer at ambient temperature unless
otherwise stated. 13C NMR spectra were recorded on a 75.4-
MHz spectrometer at ambient temperature. 31P NMR spectra
were recorded on
a 121.1-MHz spectrometer at ambient
temperature. 19F NMR spectra were recorded on a 282.2-MHz
spectrometer at ambient temperature. Chemical shifts are
1
reported in parts per million relative to TMS. Data for H NMR
are reported as follows: chemical shift, integration, multiplic-
ity (s ) singlet, d ) doublet, t ) triplet, q ) quartet, m )
multiplet) and coupling constants. All 13C and 31P NMR spectra
were recorded with complete proton decoupling. GC-MS was
performed on Agilent Technologies 6890N Network GC Sys-
tem. Column: 5% phenyl methyl siloxane; capillary 30.0 m ×
0.25 mm; film thickness 0.25 µm; the flow rate of He, 1.0 mL/
min. GC oven temperature: initial at 100 °C for 1 min,
9682 J . Org. Chem., Vol. 68, No. 25, 2003

Polymer-Assisted Solution-Phase Suzuki Couplings
SCHEME 6. Syn th esis of An th r a cen e-Ta gged Ar yl Bor on ic Acid 25
SCHEME 7. Ap p lica tion of An th r a cen e-Ta gged Bor on ic Acid 25
increase to 300 °C at 20 °C/min, hold for 5 min. The detector
was an Agilent 5973 Network Mass Selective Detector. LC-
MS was performed on a Hewlett-Packard (series 1100), using
5 to 95% of B (4.5 min, 50 °C), then 95% of B (0.5 min, 50 °C),
with water (0.5% TFA) as A and CH3CN as B, and a flow rate
of 1 mL/min. The column was an Eclipse XDB-C18 Rapid
Resolution cartridge 2.1 × 30 mm × 3.5 µm from P. J . Cobert
Associates. Retention times are in minutes. Thin-layer chro-
matography was performed on 0.25 mm silica gel 1B-F plates
(J . D. Baker). The XPERTEK filtration cartridge (15 mL and
70 mL) was obtained from P. J . Cobert Associates. All reagents,
including polymer-bound tetraalkylammonium carbonate (PS-
TAA carbonate) (macroporous, 50-90 mesh, typical loading:
2.5-3.5 mmol N/g), and solvents were purchased from com-
mercial vendors.
The mixed solution was degassed again under N2 with
ultrasonic cleaner, which acted as a stirrer also. The mixed
solution was initially clear, but the formation of solid was
observed shortly after mixing. The mixture was left to stand
still to allow the continuing formation of the solid until the
31P NMR of the upper solution showed no presence of phos-
phine ligand. The mixture was filtered under N2, and the solid
was collected and dried to afford the Pd complex 2 as a light
yellow powder (3.2 g, 80% yield). 31P NMR of the complex
showed one sharp signal at 24.3 ppm in THF.
P r ep a r a tion of An th r a cen e-Ta gged Ar yl Br om id e (20).
To a solution of 4-bromobenzoic acid 19 (2.13 g, 10.6 mmol) in
DCM (120 mL) and DMF (10 mL) was added 1-hydroxyben-
zotriazole (HOBt) (1.4 g, 10.6 mmol), 1-(3-dimethylaminopro-
pyl)-3-ethylcarbodiimide hydrochloride (EDC) (2 g, 10.6 mmol),
and 9-methylaminoanthracene 18 (2 g, 9.6 mmol) in the above
order. The mixture was stirred overnight at room temperature,
followed by addition of polyamine resin (20.2 g, 53 mmol, 2.63
mmol/g), and the resulting slurry was stirred at room tem-
perature for 2 h. The slurry was filtered and rinsed with a
mixture of DCM/DMF 10:1 and the yellow filtrate was
evaporated to dryness. The crude solid was crystallized from
P r ep a r a tion of P d Com p lex P d (P An P h 2)2Cl2 (2). A
suspension of PdCl2 (0.6 g, 3.4 mmol) was mixed with CH3CN
(125 mL) in a flask with stirring under N2. After being stirred
overnight, the afforded orange solution was degassed under
N2 with ultrasonic cleaner for 30 min and then cannulated
into another flask containing a pre-degassed THF solution of
the phosphine ligand 1 (3.4 g, 6.8 mmol, in 85 mL of THF).
J . Org. Chem, Vol. 68, No. 25, 2003 9683

Lan et al.
SCHEME 8. P ASP Su zu k i Cou p lin g Em p loyin g An th r a cen e-Ta gged Bor on ic Acid 25
a mixture of hexane, ethyl acetate, and DCM (500 mL) to yield
pure 20 (2.5 g, 66%) as a yellow solid. 1H NMR (DMSO-d6,
300 MHz) δ 8.97 (1H, br t), 8.59 (1H, s), 8.44 (2H, d, J ) 6.3
Hz), 8.09 (2H, d, J ) 6.0 Hz), 7.76 (2H, d, J ) 6.6 Hz), 7.57
(2H, d, J ) 6.3 Hz), 7.58-7.48 (4H, m), 5.46 (2H, d, J ) 3.9
Hz); 13C NMR (DMSO-d6, 75.4 MHz) δ 165.9, 133.9, 131.8,
131.7, 130.9, 130.3, 130.3, 129.5, 128.1, 126.8, 125.8, 125.5,
125.3, 36.6; HPLC purity (retention time) 98% (3.42 min);
LRMS (ESI) for C22H16BrNO (M + H) 390.
Im m obiliza tion of 4-Ca r boxyp h en ylbor on ic Acid to
P S-DEAM Resin (23). PS-DEAM resin 21 (loading 2.1 mmol/
g, 8.9 g, 18.8 mmol) was weighed into a polypropylene bottle
(120 mL), followed by the addition of 4-carboxyphenylboronic
acid 22 (4.34 g, 26.2 mmol) and dry THF (115 mL). The bottle
was shaken at room temperature for 3 h and then the resin
was transferred to a polypropylene filtration cartridge for
draining and washing with dry THF (3 × 115 mL ). The resin
was dried in vacuo overnight, affording the boronic acid
immobilized resin 23 (11.7 g). The loading of the resin was
calculated to be 1.79 mmol/g based on the weights.
P r ep a r a tion of An th r a cen e-Ta gged Bor on ic Acid (25).
Into a polypropylene bottle (125 mL) was added the PS-DEAM
resin immobilized boronic acid 23 (5.3 g, 9.5 mmol), followed
by HOBT as a solid in one portion (3.9 g, 28.6 mmol). Then
9-aminomethylanthracene 18 (5.92 g, 28.6 mmol) was trans-
ferred in as a NMP solution followed by addition of diisopro-
pylcarbodiimide (DIC) (4.5 mL, 3.6 g, 28.6 mmol). The bottle
was shaken on an orbit shaker overnight, after which the resin
was drained through a polypropylene filtration cartridge and
washed with dry NMP (3 × 60 mL), dry THF (5 × 60 mL) and
dry CH2Cl2 (5 × 60 mL) followed by a final washing with dry
THF (3 × 60 mL) to give pale yellow resin 24. The resin-bound
boronic acid was cleaved by vortexing the resin 24 with 10%
H2O/THF (5 × 60 mL) for 10 min at room temperature. The
filtrate from each cleavage was combined and concentrated to
afford the anthracene-tagged boronic acid 25 asa pale yellow
solid (2.52 g, 67% yield). The product was used without
purification. 1H NMR (acetone-d6, 300 MHz) δ 8.63 (1H, s),
8.56 (2H, d, J ) 9.0 Hz), 8.15 (2H, d, J ) 7.8 Hz), 7.94-7.88
(4H, m), 7.65-7.54 (4H, m), 7.32 (1H, s), 5.69 (2H, d, J ) 5.1
Hz); 13C NMR (acetone-d6, 75.4 MHz) δ 166.7, 136.5, 134.1,
132.0, 131.0, 130.0, 129.2, 127.9, 126.6, 126.5, 125.4, 125.3,
124.9, 36.2; LC-MS tR ) 2.6 min, m/z 191 (fragmentation), 356
(M + 1), 733 (2M + 23); HRMS m/z calcd for C22H19BNO3 (M
+ H) 356.1457, found 356.1469.
supported tetraalkylammonium carbonate 10 (loading 2.86
mmol/g, 0.2 g, 0.6 mmol, 4 equiv), Pd complex 2 (17.5 mg, 0.015
mmol, 0.1 equiv), water (0.1 mL), and DMF (2 mL). The vial
was tightly capped and the mixture was set onto a heating
block, which was preheated and remained at 80 °C, for 16 h
with stirring. During the reaction, the color of the carbonate-
bound resin 10 changed from light brown to deep dark, and
the solution of the reaction became yellow. At the end of the
reaction, GC-MS analysis of the crude solution was taken to
determine the identity and the percentage ratio of each
product. Then, PS-maleimide resin 3 was added to the reaction
mixture (loading 1.56 mmol/g, 0.1 g, 0.16 mmol, 10 equiv to
catalyst 2) and the mixture was heated at 90 °C for 10 h. The
resin was filtered with use of a filtration cartridge and washed
with CH2Cl2 (2 × 5 mL). The collected filtrate was concentrated
in a dry-down box with constant N2 blowing to give the
product. In some cases, a second filtration was needed by
adding CH2Cl2 (2 mL) to the solid and filtering through a
cartridge to remove an insoluble residue (believed to be tiny
particles from resin degradation), which was not soluble in
either CH2Cl2 or water. The filtrate was dried in vacuo to
afford the product 14, which was weighed and fully character-
ized.
4′-Nitr o-1,1′-bip h en yl-4-ca r bon itr ile (14a A). 1H NMR
(CDCl3, 300 MHz) δ 8.38 (2H, d, J ) 9.0 Hz), 7.85-7.75 (6H,
m); 13C NMR (CDCl3, 75.4 MHz) δ 145.6, 143.4, 133.2, 128.4,
128.3, 128.2, 124.6, 124.5, 118.6; GC-MS tR ) 9.98 min, m/z
224; HRMS m/z calcd for C13H8N2O2 (M+) 224.0586, found
224.0603.
Eth yl 4′-Nitr o-1,1′-bip h en yl-4-ca r boxyla te (14a B). 1H
NMR (CDCl3, 300 MHz) δ 8.34 (2H, d, J ) 8.7 Hz), 8.19 (2H,
d, J ) 8.7 Hz), 7.80 (2H, d, J ) 8.7 Hz), 7.72 (2H, d, J ) 8.7
Hz), 4.45 (2H, q, J ) 7.2 Hz), 1.46 (3H, t, J ) 7.2 Hz); 13C
NMR (CDCl3, 75.4 MHz) δ 166.3, 146.6, 143.1, 130.6, 130.4,
128.3, 127.6, 127.4, 124.4, 61.5, 14.6; GC-MS tR ) 10.64 min,
m/z 271; HRMS m/z calcd for C15H13NO4 (M+) 271.0845, found
271.0861.
4-Ch lor o-3-m eth yl-4′-n itr o-1,1′-biph en yl (14aC). 1H NMR
(CDCl3, 300 MHz) δ 8.32 (2H, d, J ) 9.0 Hz), 7.73 (2H, d, J )
8.7 Hz), 7.52-7.42 (3H, m); 13C NMR (CDCl3, 75.4 MHz) δ
146.8, 137.5, 137.2, 135.7, 130.1, 127.9, 126.2, 124.4, 20.5; GC-
MS tR ) 9.72 min, m/z 247; HRMS m/z calcd for C13H10ClNO2
(M+) 247.0400, found 247.0380.
4-Isobu tyl-4′-n itr o-1,1′-biph en yl (14aD). 1H NMR (CDCl3,
300 MHz) δ 8.32 (2H, d, J ) 9.0 Hz), 7.77 (2H, d, J ) 9.0 Hz),
7.59 (2H, d, J ) 8.1 Hz), 7.31 (2H, d, J ) 8.1 Hz), 2.58 (2H, d,
J ) 7.2 Hz), 2.03-1.89 (1H, m), 0.98 (6H, d, J ) 6.9 Hz); 13C
NMR (CDCl3, 75.4 MHz) δ 147.9, 143.2, 136.3, 130.2, 127.8,
Gen er a l P r oced u r e of Su zu k i Cou p lin g of Ar yl Br o-
m id e Su bstr a tes 13a , 13b, a n d 13c w ith Bor on ic Acid s
9. Each vial (8 mL) was charged with aryl bromide 13 (0.15
mmol, 1 equiv), boronic acid 9 (0.18 mmol, 1.2 equiv), polymer-
9684 J . Org. Chem., Vol. 68, No. 25, 2003

Polymer-Assisted Solution-Phase Suzuki Couplings
127.4, 124.4, 45.3, 30.5, 22.6; GC-MS tR ) 9.95 min, m/z 255;
HRMS m/z calcd for C16H17NO2 (M+) 255.1259, found 255.1239.
4-Eth oxy-4′-n itr o-1,1′-bip h en yl (14a E). 1H NMR (CDCl3,
300 MHz) δ 8.29 (2H, d, J ) 9.0 Hz), 7.72 (2H, d, J ) 9.0 Hz),
7.60 (2H, d, J ) 9.0 Hz), 7.04 (2H, d, J ) 9.0 Hz), 4.13 (2H, q,
J ) 6.9 Hz), 1.49 (3H, t, J ) 6.9 Hz); 13C NMR (CDCl3, 75.4
MHz) δ 160.1, 147.5, 146.8, 131.1, 128.8, 127.3, 124.4, 115.4,
63.9, 15.0; GC-MS tR ) 9.89 min, m/z 243; HRMS m/z calcd
for C14H13NO3 (M+) 243.0895, found 243.0871.
MS tR ) 10.96 min, m/z 322; HRMS m/z calcd for C21H20ClO
(M + H) 323.1197, found 323.1215.
4′-Isob u t yl-2-[(2-m et h ylp h en oxy)m et h yl]-1,1′-b ip h e-
1
n yl (14cD). H NMR (CDCl3, 300 MHz) δ 7.74-7.71 (1H, m),
7.48-7.36 (5H, m), 7.30-7.12 (4H, m), 6.91 (1H, t, J ) 7.5
Hz), 6.76 (1H, d, J ) 8.1 Hz), 5.05 (2H, s), 2.59 (2H, d, J ) 7.2
Hz), 2.33 (3H, s), 2.02-1.93 (1H, m), 1.01 (6H, d, J ) 6.6 Hz);
13C NMR (CDCl3, 75.4 MHz) δ 157.1, 141.9, 141.1, 138.2, 134.9,
130.9, 130.3, 129.3, 129.1, 129.0, 128.1, 127.7, 127.4, 127.0,
120.8, 111.8, 68.3, 45.4, 30.5, 22.7, 16.7; GC-MS tR ) 11.14
min, m/z 330; HRMS m/z calcd for C24H27O (M + H) 331.2056,
found 331.2083.
1
4′-Acetyl-1,1′-bip h en yl-4-ca r bon itr ile (14bA). H NMR
(CDCl3, 300 MHz) δ 8.10 (2H, d, J ) 8.4 Hz), 7.78-7.70 (6H,
m), 2.68 (3H, s); 13C NMR (CDCl3, 75.4 MHz) δ 197.8, 144.6,
143.8, 137.2, 133.2, 133.0, 129.4, 128.2, 127.7, 118.9, 27.0; GC-
MS tR ) 9.71 min, m/z 221; HRMS m/z calcd for C15H11NO
(M+) 221.0841, found 221.0820.
Eth yl 4′-Acetyl-1,1′-bip h en yl-4-ca r boxyla te (14bB). 1H
NMR (CDCl3, 300 MHz) δ 8.16 (2H, d, J ) 8.4 Hz), 8.08 (2H,
d, J ) 8.4 Hz), 7.74 (2H, d, J ) 8.0 Hz), 7.71 (2H, d, J ) 8.0
Hz), 4.44 (2H, q, J ) 7.2 Hz), 2.67 (3H, s), 1.45 (3H, t, J ) 7.2
Hz); 13C NMR (CDCl3, 75.4 MHz) δ 197.9, 166.5, 144.8, 144.3,
4′-E t h oxy-2-[(2-m e t h ylp h e n oxy)m e t h yl]-1,1′-b ip h e -
1
n yl (14cE). H NMR (CDCl3, 300 MHz) δ 7.72-7.69 (1H, m),
7.46-7.35 (5H, m), 7.22-7.12 (2H, m), 7.02-6.98 (2H, m), 6.91
(1H, t, J ) 7.5 Hz), 6.77 (1H, d, J ) 8.1 Hz), 5.02 (2H, s), 4.12
(2H, q, J ) 6.9 Hz), 2.33 (3H, s), 1.50 (3H, t, J ) 6.9 Hz); 13C
NMR (CDCl3, 75.4 MHz) δ 158.6, 157.1, 141.6, 134.9, 133.1,
130.9, 130.5, 130.3, 129.1, 128.1, 127.5, 127.3, 127.0, 120.8,
114.5, 111.7; GC-MS tR ) 11.10 min, m/z 318; HRMS m/z calcd
for C22H23O2 (M + H) 319.1693, found 319.1722.
136.7, 130.4, 129.2, 127.7, 127.4, 61.4, 26.9, 14.6; GC-MS tR
)
10.50 min, m/z 268; HRMS m/z calcd for C17H16O3 (M+)
268.1099, found 268.1116.
Gen er a l P r oced u r e of Su zu k i Cou p lin g of 4-Br o-
m oa n isole 13d w ith Bor on ic Acid s 9. Each vial (8 mL) was
charged with 4-bromoanisole 13d (0.27 mmol, 1.8 equiv),
boronic acid 9 (0.15 mmol, 1 equiv), polymer-supported tet-
raalkylammonium carbonate 10 (loading 2.86 mmol/g, 0.2 g,
0.6 mmol, 4 equiv), Pd complex 2 (17.5 mg, 0.015 mmol, 0.1
equiv), water (0.1 mL), and DMF (2 mL). The vial was tightly
capped and the mixture was set onto a heating block, which
was preheated and remained at 80 °C, for 16 h with stirring.
To consume the unreacted starting material 13d , the an-
thracene-tagged boronic acid 25 was added (115 mg, 0.324
mmol) followed by another charge of Pd catalyst 2 (18.7 mg,
0.016 mmol) and polymer-supported carbonate 10 (0.34 g,
0.972 mmol). The reaction was resumed at 80 °C and left
overnight. A GC-MS analysis was taken at this point to assess
the completion of the reaction and the product ratio. Then,
PS-maleimide resin 3 was added to the reaction mixture
(loading 1.56 mmol/g, 1.13 g, 1.76 mmol, 5 equiv to all the
anthracene-tagged species presented in the reaction including
the anthracene-tagged catalyst) and the mixture was heated
at 90 °C for 10 h. The resin was filtered through a filtration
cartridge and washed with CH2Cl2 (2 × 5 mL). The collected
filtrate was concentrated in a dry-down box with constant N2
blowing to give a solid. In some cases, a second filtration was
needed by adding CH2Cl2 (2 mL) to the solid and filtering
through a cartridge to remove an insoluble residue (believed
to be tiny particles from resin degradation), which was not
soluble in either CH2Cl2 or water. The filtrate was dried in
vacuo to afford the product 14, which was weighed and fully
characterized.
1-(4′-Chloro-3′-methyl-1,1′-biphenyl-4-yl)ethanone (14bC).
1H NMR (CDCl3, 300 MHz) δ 8.05 (2H, d, J ) 8.4 Hz), 7.67
(2H, d, J ) 8.4 Hz), 7.52-7.42 (3H, m), 2.67 (3H, s), 2.48 (3H,
s); 13C NMR (CDCl3, 75.4 MHz) δ 197.9, 145.0, 138.6, 136.9,
136.3, 134.9, 130.0, 129.8, 129.2, 127.3, 126.1, 26.9, 20.5; GC-
MS tR ) 9.53 min, m/z 244; HRMS m/z calcd for C15H13ClO
(M+) 244.0655, found 244.0654.
1-(4′-Isobu tyl-1,1′-bip h en yl-4-yl)eth a n on e (14bD). 1H
NMR (CDCl3, 300 MHz) δ 8.06 (2H, d, J ) 8.1 Hz), 7.72 (2H,
d, J ) 8.1 Hz), 7.59 (2H, d, J ) 8.1 Hz), 7.28 (2H, d, J ) 8.1
Hz), 2.67 (3H, s), 2.57 (2H, d, J ) 7.2 Hz), 2.02-1.88 (1H, m),
0.98 (6H, d, J ) 6.3 Hz); 13C NMR (CDCl3, 75.4 MHz) δ 198.0,
146.0, 142.3, 137.4, 135.9, 130.0, 129.2, 127.2, 45.4, 30.5, 26.9,
22.7; GC-MS tR ) 9.78 min, m/z 252; HRMS m/z calcd for
C
18H20O (M+) 252.1514, found 252.1510.
1-(4′-Eth oxy-1,1′-biph en yl-4-yl)eth an on e (14bE). 1H NMR
(CDCl3, 300 MHz) δ 8.04 (2H, d, J ) 8.4 Hz), 7.68 (2H, d, J )
8.4 Hz), 7.60 (2H, d, J ) 8.8 Hz), 7.02 (2H, d, J ) 8.8 Hz),
4.12 (2H, q, J ) 7.2 Hz), 2.66 (3H, s), 1.48 (3H, t, J ) 7.2 Hz);
13C NMR (CDCl3, 75.4 MHz) δ 198.0, 159.6, 145.7, 135.5, 132.3,
129.2, 128.6, 126.8, 115.2, 63.8, 26.9, 15.1; GC-MS tR ) 9.70
min, m/z 240; HRMS m/z calcd for C16H16O2 (M+) 240.1150,
found 240.1133.
2′-[(2-Meth ylp h en oxy)m eth yl]-1,1′-bip h en yl-4-ca r bon i-
tr ile (14cA). 1H NMR (CDCl3, 300 MHz) δ 7.75-7.70 (3H, m),
7.59-7.47 (4H, m), 7.37-7.34 (1H, m), 7.21-7.13 (2H, m),
6.95-6.90 (1H, m), 6.74 (1H, d, J ) 8.1 Hz), 4.94 (2H, s), 2.26
(3H, s); 13C NMR (CDCl3, 75.4 MHz) δ 156.8, 145.7, 140.2,
134.6, 133.2, 132.4, 131.1, 130.2, 130.1, 130.0, 128.9, 128.6,
127.2, 127.0, 121.2, 119.0, 111.6, 68.2, 16.6; GC-MS tR ) 11.26
4′-Meth oxy-1,1′-biph en yl-4-car bon itr ile (14dA). 1H NMR
(CDCl3, 300 MHz) δ 7.84-7.66 (4H, m), 7.58 (2H, d, J ) 8.7
Hz), 7.04 (2H, d, J ) 8.7 Hz), 3.90 (3H, s); 13C NMR (CDCl3,
75.4 MHz) δ 160.5, 145.5, 133.2, 132.8, 128.6, 128.2, 127.4,
119.4, 114.8, 55.7; GC-MS tR ) 8.90 min, m/z 209; HRMS m/z
calcd for C14H11NO (M+) 209.0841, found 209.0834.
min, m/z 299; HRMS m/z calcd for
300.1383, found 300.1388.
C21H18NO (M + H)
E t h yl 2′-[(2-Met h ylp h en oxy)m et h yl]-1,1′-b ip h en yl-4-
1
ca r boxyla te (14cB). H NMR (CDCl3, 300 MHz) δ 8.14 (2H,
Eth yl 4′-Meth oxy-1,1′-bip h en yl-4-ca r boxyla te (14d B).
1H NMR (CDCl3, 300 MHz) δ 8.12 (2H, d, 8.7 Hz), 7.65 (2H, d,
J ) 8.7 Hz), 7.61 (2H, d, J ) 9.0 Hz), 7.03 (2H, d, J ) 9.0 Hz),
4.43 (2H, q, J ) 6.9 Hz), 3.89 (3H, s), 1.45 (3H, t, J ) 6.9 Hz);
13C NMR (CDCl3, 75.4 MHz) δ 166.9, 160.1, 145.4, 132.7, 130.4,
130.3, 128.6, 126.7, 114.6, 61.2, 55.6, 14.6; GC-MS tR ) 9.81
min, m/z 256; HRMS m/z calcd for C16H16O3 (M+) 256.1099,
found 256.1078.
4′-Ch lor o-3′-m et h yl-1,1′-b ip h en yl-4-yl Met h yl E t h er
(14d C). 1H NMR (CDCl3, 300 MHz) δ 7.52 (2H, d, J ) 9.0 Hz),
7.45-7.32 (3H, m), 7.01 (2H, d, J ) 9.0 Hz), 3.89 (3H, s), 2.47
(3H, s); 13C NMR (CDCl3, 75.4 MHz) δ 159.6, 139.6, 136.4,
133.2, 133.0, 129.6, 129.5, 128.3, 125.6, 114.5, 55.6, 20.5; GC-
MS tR ) 8.69 min, m/z 232; HRMS m/z calcd for C14H13ClO
(M+) 232.0655, found 232.0644.
d, J ) 8.1 Hz), 7.76-7.71 (1H, m), 7.54 (2H, d, J ) 8.1 Hz),
7.51-7.37 (3H, m), 7.21-7.11 (2H, m), 6.91 (1H, dd, J ) 6.6,
6.6 Hz), 6.74 (1H, d, J ) 8.1 Hz), 4.98 (2H, s), 4.46 (2H, q, J )
6.9 Hz), 2.30 (3H, s), 1.47 (3H, t, J ) 6.9 Hz); 13C NMR (CDCl3,
75.4 MHz) δ 166.7, 156.9, 145.5, 141.0, 134.7, 131.0, 130.1,
129.8, 129.6, 129.4, 128.3, 127.5, 127.3, 127.0, 121.0, 111.6,
68.2, 61.3, 16.7, 14.6; GC-MS tR ) 11.96 min, m/z 346; HRMS
m/z calcd for C23H23O3 (M + H) 347.1642, found 347.1621.
4′-Ch lor o-3′-m eth yl-2-[(2-m eth ylp h en oxy)m eth yl]-1,1′-
bip h en yl (14cC). 1H NMR (CDCl3, 300 MHz) δ 7.73-7.70
(1H, m), 7.49-7.33 (6H, m), 7.24-7.13 (3H, m), 6.92 (1H, t, J
) 7.5 Hz), 6.77 (1H, d, J ) 8.1 Hz), 4.99 (2H, s), 2.43 (3H, s),
2.33 (3H, s); 13C NMR (CDCl3, 75.4 MHz) δ 157.0, 141.0, 139.4,
136.2, 134.8, 133.9, 132.0, 131.0, 130.2, 129.5, 129.1, 128.3,
128.1, 128.0, 127.3, 127.0, 120.9, 111.7, 68.3, 20.3, 16.7; GC-
J . Org. Chem, Vol. 68, No. 25, 2003 9685

Lan et al.
4′-Isobu tyl-1,1′-bip h en yl-4-yl Meth yl Eth er (14d D). 1H
NMR (CDCl3, 300 MHz) δ 7.57 (2H, d, J ) 9.0 Hz), 7.51 (2H,
d, J ) 8.1 Hz), 7.24 (2H, d, J ) 8.1 Hz), 7.01 (2H, d, J ) 9.0
Hz), 3.88 (3H, s), 2.55 (2H, d, J ) 7.2 Hz), 2.02-1.88 (1H, m),
0.99 (6H, d, J ) 6.6 Hz); 13C NMR (CDCl3, 75.4 MHz) δ 159.2,
140.5, 138.4, 134.0, 129.8, 128.2, 126.7, 114.4, 55.6, 45.3, 30.5,
22.7; GC-MS tR ) 8.93 min, m/z 240; HRMS m/z calcd for
115.0, 114.4, 63.8, 55.6, 15.2; GC-MS tR ) 8.82 min, m/z 228;
HRMS m/z calcd for C15H16O2 (M + H) 228.1150, found
228.1139.
Ack n ow led gm en t. The authors thank J effery W.
Weber for the ICP-AES palladium analysis.
C
17H20O (M+) 240.1514, found 240.1515.
4-E t h oxy-4′-m et h oxy-1,1′-b ip h en yl (14d E ). 1H NMR
Su p p or tin g In for m a tion Ava ila ble: Characterization
and spectral data for all compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
(CDCl3, 300 MHz) δ 7.52 (2H, d, J ) 8.7 Hz), 7.51 (2H, d, J )
9.0 Hz), 7.00 (2H, d, J ) 8.7 Hz), 6.99 (2H, d, J ) 9.0 Hz),
4.11 (2H, q, J ) 6.9 Hz), 3.88 (3H, s), 1.48 (3H, t, J ) 6.9 Hz);
13C NMR (CDCl3, 75.4 MHz) δ 158.9, 158.3, 133.8, 133.6, 128.0,
J O035129G
9686 J . Org. Chem., Vol. 68, No. 25, 2003