Cross-linked poly(4-vinylpyridine/styrene) copolymers as a support for immobilization of ytterbium triflate

Article abstract of DOI:10.1016/j.tet.2005.01.068

Eight cross-linked poly(4-vinylpyridine/styrene) (P/S) resins (as beads) were prepared by radical suspension polymerization. Ytterbium triflate was immobilized in the range of 0.10-0.24 mmol/g by mixing with the P/S resins. The ytterbium triflate-immobilized P/S resins exhibited good activity in two Lewis acid-catalyzed reactions. Low pyridine containing resins were recycled with no loss of activity, while a slight loss of activity was observed with the higher pyridine containing resins.

Full text of DOI:10.1016/j.tet.2005.01.068

Tetrahedron 61 (2005) 3081–3086
Cross-linked poly(4-vinylpyridine/styrene) copolymers
as a support for immobilization of ytterbium triflate
*
Byoung Se Lee, Suresh Mahajan and Kim D. Janda
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute,
10550 North Torrey Pines Road, La Jolla, CA 92037 USA
Received 7 January 2005; accepted 19 January 2005
Abstract—Eight cross-linked poly(4-vinylpyridine/styrene) (P/S) resins (as beads) were prepared by radical suspension polymerization.
Ytterbium triflate was immobilized in the range of 0.10–0.24 mmol/g by mixing with the P/S resins. The ytterbium triflate-immobilized P/S
resins exhibited good activity in two Lewis acid-catalyzed reactions. Low pyridine containing resins were recycled with no loss of activity,
while a slight loss of activity was observed with the higher pyridine containing resins.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
of the polymer for recovery of the catalyst.3c Similarly, the
insoluble lightly cross-linked polystyrene/divinylbenzene
(PS/DVB) copolymer-supported Sc(OTf)3 has a short-
coming in that it requires an intricate six step synthesis.3d
Therefore, the development of solid polymeric support, that
can be readily synthesized, possesses good activity and
stability, and can be recycled efficiently would be of
synthetic utility.
Rare earth metal triflates (RE(OTf)3) including lanthanide
(III) triflates (Ln(OTf)3) have been employed as mild Lewis
acid in many organic transformations including aldol,
Diels–Alder, Michael addition, aziridination, oxidation/
reduction, rearrangement and protection/deprotection reac-
tions.1 The use of these compounds has gained prominence
not only due to their chemical versatility but also because of
their stability in the presence of most polar functional
groups and organic solvents including aqueous media.
Moreover, RE(OTf)3 are catalytically active in the presence
of Lewis bases containing nitrogen, oxygen, phosphorous
and sulfur atoms. These catalysts are used as homogeneous
catalysts in organic solvents in most applications and since
RE(OTf)3 are more soluble in water than in common
organic solvents, they can be recovered by aqueous
extraction and reused.2 Alternatively, immobilization of
these catalysts on solid supports affords improved recycling
and facile use in synthetic schemes, a consummate goal in
catalyst development. Several methods for the immobiliz-
ation of RE(OTf)3 on polymer supports have been
developed,3 including microencapsulation using soluble
polystyrene and lightly cross-linked polystyrene-supported
scandium triflate. These immobilized catalysts were
recycled without any loss of catalytic activity. However,
while the microencapsulated catalysts has very good
activity, a drawback to its use is the required precipitation
Recently, highly cross-linked polystyrene resins with
pendant pyridine functional groups have been reported for
immobilization of dirhodium tetracarboxylates.4,5 The
immobilization was considered to be due to both ligand
coordination and physical encapsulation. Another example
of catalyst immobilization on a pyridine-based polymer is
the commercially available poly(4-vinylpyridine) supported
osmium catalysts.6 These two examples led us to speculate
that cross-linked pyridine/styrene polymers could serve as
potential supports for Ln(OTf)3. Herein, we describe the
synthesis of a series of cross-linked poly(4-vinylpyridine/
styrene) copolymers, immobilization of Yb(OTf)3 on these
polymers, and their catalytic activity and reusability in two
model reactions.
2. Results and discussion
A series of cross-linked poly(4-vinylpyridine/styrene)
copolymers (abbreviated as P/S resins, where superscript
x
Keywords: Lanthanide triflate; Poly(4-vinylpyridine/styrene); Catalyst
immobilization.
* Corresponding author. Tel.: C1 858 784 2515; fax: C1 858 784 2592;
e-mail: kdjanda@scripps.edu
x equates to % pyridine content) with varying ratios of
styrene, 4-vinylpyridine and (cross-linker) 1,4-bis(4-vinyl-
phenoxy)butane7 were synthesized as beads by aqueous
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.01.068

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B. S. Lee et al. / Tetrahedron 61 (2005) 3081–3086
suspension radical polymerization in the presence of
benzoyl peroxide (Scheme 1). Low cross-linked P/S resins
1a–1g were prepared using 1 mol% of the 1,4-bis(4-vinyl-
phenoxy)butane cross-linker. A highly cross-linked poly-
(4-vinylpyridine) (abbreviated as 90P/DVB) resin 1h, was
prepared with 10% divinylbenzene as the cross-linker. All
resins were sieved to a range of 40–400 mesh.
Scheme 2. Immobilization of Yb(OTf)3 into P/S resins.
between 9.2 and 52.0. No change in swelling of the xP/S(Yb)
resins was observed relative to the starting P/S resins.
x
Prior reports using soluble polymer supported Sc(OTf)3
have described that the interaction between Sc(OTf)3 and
the phenyl groups of polystyrene may contribute to catalyst
encapsulation.3c We prepared an insoluble cross-linked
polystyrene resin 2a, and applied the immobilization
technique used to prepare resins 2b–2h. However, no
Yb(OTf)3 was detected in this resin, confirming that phenyl
groups residing within the resin do not play a major role in
the immobilization, and the Yb(OTf)3 immobilization on
x
Scheme 1. The preparation of P/S resins. Actual nitrogen (pyridine) content
(mmol/g) found in experimental section (Table 5).
the P/S resin occurs primarily by the ligand interaction
between the metal and the pyridine moieties of each of the
resins (Fig. 1).
For lightly cross-linked resins, swelling in common organic
solvents is an important factor in the success of solid-phase
reactions.8 The swollen volumes for these resins were
determined by the syringe method9 in several organic
solvents (Table 1). All P/S resins displayed outstanding
swelling in dichloromethane and modest swelling in
methanol and acetonitrile. As expected the swelling of the
high cross-linked PS/DVB resin 1h was low and unaffected
by the choice of solvent.
Immobilization of Yb(OTf)3, a representative Ln(OTf)3
having relatively high acidity due to its small ionic radii,10
onto P/S resins was achieved by shaking a suspension of P/S
resins and Yb(OTf)3 for 24 h in a 1:1 mixture of methanol/
dichloromethane (Scheme 2). This mixture is an optimal
solvent for immobilization since Yb(OTf)3 has good
solubility and the resins also exhibit good swelling. The
loading of Yb(OTf)3 was determined by measuring the
increase in the weight of the resulting resins, and verified by
measuring the residual Yb(OTf)3 in the filtrate. Yttebium
Figure 1. IR spectrum of 50P/S (1d, gray) and 50P/S(Yb) (2d, black).
The key to the successful development of an immobilized
catalyst requires that the twin goals of high activity and
good stability be achieved. In the context of immobilized
metal catalysts, contamination of the product by the
homogeneous catalyst is a significant issue, therefore
catalyst leaching should be kept to a minimum. Two
preliminary tests were performed to determine the extent
Yb(OTf)3 leaching from P/S resins and to determine the
activity of the immobilized catalyst. First, the effect of
solvent on catalyst leaching was determined by suspending
x
triflate was immobilized into 200 mg of P/S resins 1b–1g
and 90P/DVB resin 1h resulting in a loading of 0.10–
0.24 mmol/g of xP/S(Yb) 2b–2g and 90P/DVB(Yb) 2h
(Table 1). Loading of Yb(OTf)3 increased from 10P/S to
70P/S, and then decreased as the pyridine content was raised
in 90P/S and 100P/S. The corresponding N/Yb ratio ranged
Table 1. Swollen volume of P/S resins and loading amounts of Yb(OTf)3
Swollen volume (mL/g)
Loadinga
N/Yb
CH2Cl2
MeOH
MeCN
1a
1b
1c
1d
1e
1f
23.8
19.6
10.5
18.3
10.4
9.5
5.6
4.6
3.2
6.5
6.6
10.2
11.7
—
2.6
2.7
3.2
2.9
4.1
4.1
5.2
—
2a
2b
2c
2d
2e
2f
0
—
9.2
0.10
0.15
0.20
0.24
0.23
0.18
0.23
18.9
23.1
26.9
35.7
52.0
36.5
1g
1h
10.7
—
2g
2h
a mmol/g, Determined by weight increase.

B. S. Lee et al. / Tetrahedron 61 (2005) 3081–3086
3083
x
spectrums before and after the test. The P/S(Yb) and 90P/
DVB(Yb) resins were found to be stable in dichloro-
methane, acetonitrile, and methanol. In DMF, significant
x
Yb(OTf)3 was leached out from low pyridine-content P/
S(Yb) resins 2b and 2c, while no leaching was observed in
high pyridine-containing resins 2d–2h. However, in 10%
pyridine/dichloromethane, almost all the Yb(OTf)3 was
removed from all tested resins, further confirming the
chelation of Yb(OTf)3 by the pyridine moieties of the
polymer.
Scheme 3. b-Amino ketone synthesis.
Table 2. Leaching testa
Entry
Solvent
(%)
Conversionb
Loss of
IR signalc (%)
1
2
3
4
5
CH2Cl2
MeCN
MeOH
MeCN/CH2Cl2 (1:1)
MeOH/CH2Cl2 (1:1)
3
0
8
49
0
47
Second, the activity of the catalyst and leaching of the
catalyst was investigated in the context of a b-amino ketone
synthesis11 (Scheme 3) on 50P/S(Yb) resin 2d (Table 2).
Since the resins contain pyridine moieties, the activity of the
catalyst could be adversely affected by pyridine-catalyst
interactions. However, we determined that the catalytic
activity of Yb(OTf)3 is retained in a homogenous version of
the probe reaction even in the presence of pyridine. In a non-
polar solvent such as methylene chloride, catalytic activity
was low, but no discernable leaching of the catalyst was
observed. In contrast, significant catalytic activity was
obtained in acetonitrile and methanol solvents, but unac-
ceptable levels of catalyst leaching were also observed.
Since good activity is achieved in polar solvents and the
catalyst is more stable in non-polar solvents, a mixed
solvent system was required to optimize activity and
stability. Using methanol/dichloromethane (1:1) or aceto-
nitrile/dichloromethane (1:1), relatively low leaching of the
catalyst was observed and 95% conversion to the desired
b-amino ketone was obtained. An optimal solvent ratio of
acetonitrile and dichloromethane was found to be 3:1,
resulting in 95% conversion in 1 h with no apparent
leaching of the catalyst; by comparison the homogeneous
reaction was complete in 10 min under similar reaction
conditions.
96
100
91
95
a All reactions were carried out on a 0.1 mmol scale.
b Determined by HPLC.
c Calculated by IR integration of used P/S(Yb) resins.
Figure 2. Kinetics for the synthesis of 5 with resins (2b–2h) and Yb(OTf)3
(10 mol%).—(B, Yb(OTf)3), ($, 10P/S(Yb)), (&, 30P/S(Yb)), (:,
50P/S(Yb)), (!, 70P/S(Yb)), (%, 90P/S(Yb)), (*, 100P/S(Yb)), (,,
90P/DVB(Yb)).
the immobilized catalyst in solvent for 30 min, followed by
filtration, washing and drying. An IR technique was used as
a semi-quantitative tool to determine the extent of leaching.†
The degree of leaching was determined by comparing the IR
The entire array of the immobilized catalysts 2b–2h were
tested using the probe b-amino ketone synthesis consisting
Table 3. Recycling results for the synthesis of 5a
Resin
1st
2nd
3rd
4th
5th
6th
7th
Ave.
2b
2c
2d
2e
2f
98
99
95
96
89
86
91
98
98
95
96
85
82
75
98
98
95
95
82
80
84
97
98
95
93
79
76
86
98
98
95
93
83
74
89
98
97
95
88
72
72
89
98
98
95
92
84
81
88
98
98
95
93
82
79
87
2g
2h
a All reactions were carried out on a 1 mmol scale, and conversion yield (%) was determined by HPLC.
of aromatic imine 3 and vinyl silyl ether 4. The kinetics
(Fig. 2) and the conversion (Table 3) reveal that the
reactivity of the Yb(OTf)3-immobilized catalyst is related to
the ratio of N/Yb: higher activity is obtained at lower N/Yb
ratios. Although lanthanides have weak interactions with
heteroatoms, high pyridine concentration surrounding the
metal might limit the accessibility of the metal to the
substrate resulting in lower activity at high N/Yb ratios. This
observation is comparable to the reported decrease in
catalytic activity for a palladium/monophosphine poly-
styrene catalyst as the ligand to metal ratio was increased.12
† In addition to the IR bands of the xP/S resins, xP/S(Yb) and 90P/DVB(Yb)
resins show two broad bands 1252, 1154 cmK1 and one sharp band at
1029 cmK1 in the IR spectrum due to the triflate ligand.3c Since these
Yb(OTf)3-specific IR bands do not overlap with the IR bands of the
resins, the extent of leaching of Yb(OTf)3 could be determined by relative
comparison to polymer specific bands. To validate this IR technique, we
prepared Yb(OTf)3-immobilized 50P/S(Yb) resins with six different
loadings (The loading amount was obtained by weight increase of the
resin and confirmed by the amount of Yb(OTf)3 in filtrates after
immobilization), followed by an IR (1252 cmK1) integration. A linear
correlation between the IR integration and ytterbium loading was
obtained.

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B. S. Lee et al. / Tetrahedron 61 (2005) 3081–3086
Resins 2b, 2c and 2d containing 10–50% pyridine showed
good activity and were recycled six times with no loss of
activity (Table 3). However, resins 2e, 2f and 2g (70, 90 and
100% pyridine, respectively) had lower reactivity and
exhibited a small decrease in activity after the sixth recycle.
The highly cross-linked resin 2h was also recycled six times
with no loss of activity. In particular, for the case of resin
2d, filtrates from the first three recycled reactions were
analyzed for ytterbium by ICP-AES analysis to quantitate
catalyst retention and leaching. A very small amount of
ytterbium (detection limit corresponded to !0.2% of
ytterbium on the catalyst) was observed in the three filtrates.
Further corroboration was obtained by IR spectroscopy;
integration of the IR spectra of resin 2d before and after use
yielded no change. Finally, reaction curves and rates from
six recycled reactions revealed that the activity of the
immobilized catalyst is not altered after recycling. These
observations show that there is no leaching of Yb(OTf)3
during the reaction, as well as no loss of activity.
demonstrated the use of these resins in preparation of a
b-amino ketone and tetrahydroquinoline, the development
of immobilized lanthanide triflate clearly provides a clean
route for preparing many potentially useful compounds.
With the current emphasis on green chemistry, the use of
pyridine-based polymers to immobilize other metal-based
catalysts affords an interesting area for further research.
4. Experimental
4.1. General methods
All chemicals were obtained from commercial suppliers and
were used without further purification unless otherwise
stated. All of the glassware used in the solid-phase reactions
was silanized by treating with Sigmacotew. Flash chroma-
tography was carried out using Merck silica gel 60 (230–400
mesh). Preparative TLC was carried out on Merck 60 F254
plates (0.5 mm) eluting with ethyl acetate/hexanes. FT-IR
spectra were recorded using a Thermo Nicolet AVATA 360
spectrometer equipped with a Golden Gate single reflection
To demonstrate the versatility of the immobilized Yb(OTf)3
resin, we chose to study its application in a second model
reaction; the Diels–Alder reaction of imine 6 and ethyl vinyl
ether for the synthesis of tetrahydroquinolines13 (Scheme 4,
Table 4). Three xP/S(Yb) resins with low N/Yb ratio (2b, 2c,
2d) were used under identical reaction conditions as that for
b-amino ketone synthesis (Table 4). As observed in the
former example, the order of reactivity was 2bO2cO2d.
Furthermore, these resins could be used five times without
any loss of activity or alteration of the trans/cis ratio of
products. These results show that the immobilized catalyst
is not substrate-dependant, as the optimum conditions
developed for the b-amino ketone synthesis were success-
fully employed in the synthesis of tetrahydroquinoline.
1
diamond ATR accessory. H and 13C NMR spectra were
recorded using a Varian INOVA-399 (400 MHz) and
calibrated using residual undeuterated solvent as an internal
reference. High performance liquid chromatography
(HPLC) was performed using a Hitachi system: L-5000
LC controller, 655A variable wavelength UV monitor,
655A-12 liquid chromatograph, and D-2000 chromato-
integrator. HPLC conditions: Vydac 201SP column (5 mm
RP C18) 4.6 mm !250 mm, acetonitrile/water isocratic
65:35 (for compound 5), 50:50 (for compound 7), flow:
1 mL minK1, detection UV (lZ254 nm), injection loop
20 mL. High-resolution mass spectra (HRMS) were
recorded at The Scripps Research Institute using an IonSpec
Ultima high-resolution FTMS instrument (MALDI-FTMS)
and low-resolution mass spectra were obtained using
electrospray ionization (ESI).
4.2. General procedure for synthesis of P/S resins
Scheme 4. Imino Diels–Alder reaction.
50P/S resin (1d). The aqueous phase used for the suspension
polymerization reactions was prepared by dissolving acacia
gum (30 g) and NaCl (10 g) in deionized water (1 L). This
solution was then filtered to remove insoluble impurities,
and degassed for 15 min under vacuum while being
sonicated. A 300 mL flange flask equipped with 3-necked
lid and mechanical stirrer was charged with 250 mL of the
above aqueous solution. To this preheated solution at 50 8C
was added a homogeneous solution of styrene (13.81 mL,
120.6 mmol), freshly-distilled 4-vinylpyridine (13.00 mL,
120.6 mmol), di(4-vinylphenoxy)-butane (710 mg,
2.41 mmol), benzoyl peroxide (292 mg, 1.21 mmol) and
chlorobenzene (8 mL) prepared by gentle warming. The
suspension was stirred at 500 rpm and 50 8C for about
3–5 min with monitoring droplet size. Once the desired
droplet size was formed, the stirring rate was reduced to
250 rpm and the reaction flask was heated to 80 8C for 6 h.
After cooling, the polymer was filtered with 400-meshed
sieve and washed several times with warm water, followed
by a methanol. The resultant beads were washed by
continuous extraction in Soxhlet apparatus with THF
overnight and sequentially washed with 50% MeOH/THF
Table 4. Recycling results for the synthesis of 7a
Resin
1st
2nd
3rd
4th
5th
Ave. ratio
trans/cisb
2b
2c
2d
93
90
69
94
92
82
93
91
79
93
92
83
92
92
82
13/87
13/87
13/87
a All reactions were carried out on a 0.1 mmol scale, and data in table is %
conversion determined by HPLC.
b The ratio was determined by HPLC and major product was proven to have
cis configuration on the basis of correlation between coupling constants of
four aliphatic protons.
3. Conclusion
A series of P/S resins were prepared by suspension
polymerization and used as polymeric supports to immobi-
lize Yb(OTf)3. These resins are inexpensive and can be
readily prepared and the immobilized catalysts can be
recycled without any loss of activity. Although we have

B. S. Lee et al. / Tetrahedron 61 (2005) 3081–3086
3085
and MeOH and dried under vacuum to give 12.76 g of pale
yellow resin. The dried resin was sieved to give 11.54 g of
the 50P/S resin (1d, 49%) in the 40–400 mesh size. Nitrogen
content (mmol/g) of 1d was obtained from elemental
4.3.1. 3-(Naphthalen-1-yl)-1-phenyl-3-phenylamino-pro-
pan-1-one (5). Compound 3 (23 mg, 0.10 mmol) and 4
(29 mg, 0.15 mmol) were added to a vial containing
acetonitrile/dichloromethane (3 mL, 3:1, v/v) and
x
analysis to be 4.48 mmol/g (Table 5); FTIR: nmax (cmK1
)
0.01 mmol of P/S(Yb) resins (2b, 100 mg; 2c, 68 mg; 2d,
50 mg; 2e, 41 mg; 2f, 43 mg; 2g, 56 mg; 2h, 44 mg). After
shaking for 1 h at room temperature, reaction mixture was
filtered with a plastic syringe equipped with a polyethylene
frit. The filtrate was used for HPLC analysis and purified
3024, 2920, 1596, 1557, 1493, 1451, 1414; Anal. Calcd for
C7.70H7.72N0.50O0.02: C, 85.96; H, 7.23; N, 6.51. Found: C,
82.99; H, 7.35; N, 6.28: other P/S resins were prepared in
the same manner.
x
with preparative TLC for further analysis. The filtered P/
0P/S resin (1a). 17.28 g (64%, 40–400 mesh). FTIR: nmax
S(Yb) resins was washed with acetonitrile/dichloromethane
(v/vZ3:1) three times, and dried under reduced pressure.
These recovered xP/S(Yb) resins were reused up to six times
more in the same procedure. After six-time reuse, the filtrate
was used for another leaching test (as mentioned below) as
(cmK1) 3025, 2920, 1601, 1492, 1451;
10P/S resin (1b). 9.05 g (36%, 40–400 mesh). FTIR: nmax
(cmK1) 3025, 2918, 1598, 1493, 1451; Anal. Calcd for
1
well as HPLC analysis: H NMR (CDCl3) d 3.53 (dd, JZ
C8.10H8.12N0.10O0.02: C, 90.76; H, 7.64; N, 1.30. Found: C,
89.85; H, 8.10; N, 1.73:
16.8, 8.4 Hz, 1H), 3.62 (dd, JZ16.6, 4.2 Hz, 1H), 4.80–5.20
(br s, 1H), 5.81 (dd, JZ8.2, 4.2 Hz, 1H), 6.53 (dd, JZ8.6,
1.0 Hz, 2H), 6.63 (tt, JZ8.0, 0.9 Hz, 1H), 7.03 (dd, JZ8.6,
7.4 Hz, 2H), 7.34–7.41 (m, 3H), 7.48–7.58 (m, 3H), 7.69 (d,
JZ7.2 Hz, 1H), 7.73 (d, JZ8.4 Hz, 1H), 7.85–7.90 (m, 3H),
8.19 (d, JZ8.8 Hz, 1H); 13C NMR (CDCl3) d 44.9, 50.8,
114.0, 118.1, 122.3, 123.6, 125.6, 125.8, 126.5, 127.9,
128.2, 128.7, 129.1, 129.3, 130.5, 133.5, 134.1, 136.6,
137.4, 198.2; HRMS (MALDI-FTMS) m/z Z35275.1514
[MCNa]C, calcd for C25H21NONa Z374.1515.
30P/S resin (1c). 16.15 g (67%, 40–400 mesh). FTIR: nmax
(cmK1) 3025, 2919, 1597, 1557, 1493, 1452, 1415; Anal.
Calcd for C7.90H7.92N0.30O0.02: C, 88.36; H, 7.43; N, 3.91.
Found: C, 84.97; H, 7.12; N, 3.75:
70P/S resin (1e). 13.06 g (51%, 40–400 mesh). FTIR: nmax
(cmK1) 3025, 2920, 1596, 1557, 1493, 1452, 1414; Anal.
Calcd for C7.50H7.52N0.70O0.02: C, 83.59; H, 7.03; N, 9.10.
Found: C, 81.13; H, 7.20; N, 7.68:
4.3.2. 4-Ethoxy-2-phenyl-1,2,3,4-tetrahydroquinoline
(7).13 Compound 6 (18 mg, 0.10 mmol) and ethyl vinyl
ether (29 mL, 0.30 mmol) were used as reactants. The
procedure and reaction scale was the same as the synthesis
of 5. 1H NMR (CDCl3) d 1.23 (t, JZ7.0 Hz, 3H), 2.06 (ddd,
JZ12.0, 12.0, 12.0 Hz, 1H), 2.39 (ddd, JZ12.4, 5.7,
2.7 Hz, 1H), 3.50–3.58 (m, 1H), 3.64–3.72 (m, 1H), 3.97
(br s, 1H), 4.51 (dd, JZ11.6, 2.8 Hz, 1H), 4.80 (dd, JZ10.4,
5.6 Hz, 1H), 6.49 (dd, JZ8.0, 0.8 Hz, 1H), 6.72 (td, JZ7.4,
1.1 Hz, 1H), 7.03 (tm, JZ7.2 Hz, 1H), 7.28–7.46 (m, 6H);
MS (ESI) m/z 254 [MCH]C, 208. (see Ref. 13 for 13C
NMR).
90P/S resin (1f). 14.10 g (55%, 40–400 mesh). FTIR: nmax
(cmK1) 3025, 2920, 1596, 1557, 1414; Anal. Calcd for
C7.30H7.32N0.90O0.02: C, 81.20; H, 6.83; N, 11.67. Found: C,
76.95; H, 7.39; N, 10.98:
100P/S resin (1g). 14.40 g (57%, 40–400 mesh). FTIR: nmax
(cmK1) 3025, 2920, 1596, 1557, 1414; Anal. Calcd for
C7.20H7.22N1.00O0.02: C, 80.01; H, 6.73; N, 12.96. Found: C,
74.74; H, 6/97; N, 11.99:
90P/DVB resin (1h). 3.85 g (51%, 40–400 mesh). FTIR:
nmax (cmK1) 3026, 2925, 1597, 1557, 1415; Anal. Calcd for
C8.30H8.50N0.90O0.20: C, 80.85; H, 6.91; N, 10.16. Found: C,
74.82; H, 7.49; N, 10.92:
4.4. Activity and leaching tests
4.4.1. Test I (ligand-exchange with solvent). One millilitre
of dichloromethane was added to 2 mL vial containing
20 mg of 2d. After shaking for 30 min, the resin was
collected in a plastic syringe equipped with a polyethylene
frit and quickly washed with the same solvent twice, and
dried under reduced pressure. A small amount of the resin
was employed to obtain IR spectra. Leaching tests in
methanol, acetonitrile, DMF and 10% pyridine/dichloro-
methane were performed in the same manner as described
above.
4.3. Immobilization procedure
Each 200 mg of eight resins (1a–1h) was placed in 5 mL-
vial containing 50 mg of Yb(OTf)3. 4 mL of methanol/
dichloromethane (1:1) cosolvent was added to the vial.
After being tightly capped, these vials were shaken for 24 h
at room temperature. The resultant resins were collected in a
plastic syringe equipped with a polyethylene frit and washed
with methanol/dichloromethane (1:1) solvent several times,
and dried under reduced pressure to give Yb(OTf)3-
immobilized resins (2a: 200 mg, 2b: 213 mg, 2c: 220 mg,
2d: 229 mg, 2e: 235 mg, 2f: 233 mg, 2g: 225 mg, 2h:
233 mg).
4.4.2. Test II (activity and ligand-exchange with sub-
strates and products). To a suspension of 2d (50 mg,
0.01 mmol) and dichloromethane (2.5 mL) in a reaction vial
was added 3 (23 mg, 0.10 mmol) and 4 (29 mg, 0.15 mmol).
Table 5. Nitrogen (pyridine) content (mmol/g)
1b
1c
1d
1e
1f
1g
1h
Theoretical
Experimental
0.92
1.24
2.79
2.68
4.65
4.48
6.49
5.48
8.30
7.84
9.25
8.56
8.36
7.79

3086
B. S. Lee et al. / Tetrahedron 61 (2005) 3081–3086
2. Kobayashi, S.; Araki, M.; Ishitani, H.; Nahayama, S.; Hachiya,
I. Synlett 1995, 233–234.
After shaking for 1 h, the resin was collected in a plastic
syringe equipped with a polyethylene frit and quickly
washed with the same solvent twice, and dried under reduced
pressure. A small amount of the resin was employed to obtain
IR spectra. Leaching tests in methanol, acetonitrile, methanol/
dichloromethane (1:1) and acetonitrile/dichlromethane (1:1)
were performed in the same manner as described above (%
Conversion was determined by HPLC).
3. (a) Kobayashi, S.; Nagayama, S. J. Org. Chem. 1996, 61,
2256–2257. (b) Kobayashi, S.; Nagayama, S. J. Am. Chem.
Soc. 1996, 118, 8911–8978. (c) Kobayashi, S.; Nagayama, S.
J. Am. Chem. Soc. 1998, 120, 2985–2986. (d) Nagayama, S.;
Kobyashi, S. Angew. Chem. Int. Ed. 2000, 39, 567–569.
4. Davies, H. M. L.; Walji, A. M. Org. Lett. 2003, 5, 479–482.
5. Davies, H. M. L.; Walji, A. M.; Nagashima, T. J. Am. Chem.
Soc. 2004, 126, 4271–4280.
Acknowledgements
6. Gianfranco Cainelli, G.; Contento, M.; Manescalchi, F.; Plessi,
L. Synthesis 1989, 45–47.
We gratefully acknowledge financial support from The
Skaggs Institute for Chemical Biology and The Scripps
Research Institute.
7. Toy, P. H.; Janda, K. D. Tetrahedron Lett. 1999, 40,
6329–6332.
8. Vaino, A. R.; Janda, K. D. J. Comb. Chem. 2000, 2, 579–596.
9. Lee, B. S.; Mahajan, S.; Clapham, B.; Janda, K. D. J. Org.
Chem. 2004, 69, 3319–3329.
10. Cotton, F. A.; Wilkinson, G. Advanced Inorganic Chemistry,
5th ed.; Wiley: New York, 1988; p 973.
Supplementary data
11. Kobayashi, S.; Nagayama, S. J. Org. Chem. 1997, 62,
232–233.
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tet.2005.01.068.
12. (a) Fenger, S.; Le Drian, C. Tetrahedron Lett. 1998, 39,
4287–4290. (b) Inada, K.; Miyaura, N. Tetrahedron 2000,
8661–8664. (c) Andersson, C.-M.; Karabelas, K.; Hallberg, A.;
Andersson, C. J. Org. Chem. 1985, 50, 3891–3895.
13. Kobayashi, S.; Ishitani, H.; Nagayama, S. Synthesis 1995,
1195–1202.
References and notes
1. Kobayashi, S.; Sugiura, M.; Kitagawa, H.; Lam, W. W.-L.
Chem. Rev. 2002, 102, 2227–2302.