An easy synthesis of robust polymer-supported chiral 1,1′-bi-(2-naphthol)s (BINOLs): application to the catalysis of the oxidation of prochiral thioethers to chiral sulfoxides

Article abstract of DOI:10.1016/j.tetasy.2006.08.011

Polystyrene beads bearing chiral 1,1′-bi-(2-naphthol) (BINOL) moieties are readily prepared by Suzuki couplings between chiral 6-bromo-1,1′-bi-(2-naphthol)s and crosslinked polystyrene beads containing phenylboronic acid residues. With this method, no protecting groups for the phenolic residues are required; any boronic acid groups that do not take part in the Suzuki coupling are removed from the support by in situ hydrolysis, and the BINOL moieties are bound to the support via strong C-C bonds. To test the performance of the new polymer-supported (PS) BINOLs, they were reacted with titanium tetraisopropoxide to give catalysts for the oxidation of aryl methyl thioethers using t-butyl hydroperoxide in tetrahydrofuran at 0 °C. The expected sulfoxides were obtained in up to 91% ee. The results obtained with the present catalysts are comparable to those obtained with PS catalysts prepared using more elaborate syntheses, and that have the catalyst moieties bound to the support by potentially labile linking groups.

Full text of DOI:10.1016/j.tetasy.2006.08.011

Tetrahedron: Asymmetry 17 (2006) 2401–2407
An easy synthesis of robust polymer-supported chiral
1,10-bi-(2-naphthol)s (BINOLs): application to the catalysis
of the oxidation of prochiral thioethers to chiral sulfoxides
Xiao-Ya Yuan,a Hai-Yan Li,a Philip Hodge,b,* Michael Kilner,b
Christophe Y. Tastardb and Zheng-Pu Zhanga,*
aKey Laboratory for Functional Polymeric Materials, Ministry of Education, Nankai University and Institute of Polymer Chemistry,
Nankai University, Tianjin 300071, PR China
bChemistry Department, University of Manchester, Oxford Road, Manchester M13 9PL, UK
Received 11 August 2006; accepted 16 August 2006
Available online 20 September 2006
Abstract—Polystyrene beads bearing chiral 1,10-bi-(2-naphthol) (BINOL) moieties are readily prepared by Suzuki couplings between
chiral 6-bromo-1,10-bi-(2-naphthol)s and crosslinked polystyrene beads containing phenylboronic acid residues. With this method, no
protecting groups for the phenolic residues are required; any boronic acid groups that do not take part in the Suzuki coupling are
removed from the support by in situ hydrolysis, and the BINOL moieties are bound to the support via strong C–C bonds. To test
the performance of the new polymer-supported (PS) BINOLs, they were reacted with titanium tetraisopropoxide to give catalysts for
the oxidation of aryl methyl thioethers using t-butyl hydroperoxide in tetrahydrofuran at 0 ꢀC. The expected sulfoxides were obtained
in up to 91% ee. The results obtained with the present catalysts are comparable to those obtained with PS catalysts prepared using more
elaborate syntheses, and that have the catalyst moieties bound to the support by potentially labile linking groups.
ꢁ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
ical modification of preformed polymer beads that already
have appropriate physical properties. Robustness includes
both physical stability and chemical stability. The former
can be a problem when PS catalysts are used in stirred
batch reactions, because the beads tend to degrade,
although they survive much better in flow reactors and
these are currently a topic of growing interest.14–16 The
chemical stability includes not only that of the actual cata-
lytic site but also that of the link binding the catalyst moi-
ety to the support. Clearly linkages such as acid-sensitive
acetals, for example, are not ideal. With regards to the sta-
bilities of the catalytic sites, in general, relatively little is
known because PS catalysts have rarely been reused to
their limits and any degradation processes identified.17
Organic reactions where one reactant is bound to a cross-
linked, and therefore insoluble, polymer support have been
of great interest ever since Merrifield introduced the tech-
nique of ‘solid phase’ peptide synthesis in 1963.1 The main
advantage of using an insoluble polymer is that at the end
of a reaction, the polymer-supported (PS) species can be
separated easily from the soluble species, usually by filtra-
tion. Innumerable PS reactions have been studied since,2–5
especially in the context of combinatorial chemistry and
high throughput synthesis.6
PS catalysts are of particular interest because they can of-
ten be reused.7–13 However, in order to obtain the full ben-
efits from such catalysts, they should be (a) relatively easy
to prepare and (b) sufficiently robust to withstand repeated
use. Usually, the preparation is best achieved by the chem-
1,10-Bi-(2-naphthol) (BINOL) is one of the simplest
C2-symmetric ligands and its enantiomers have been used
extensively in the asymmetric catalysis.18,19 Several PS
BINOLs have already been described. They are either (i)
linear polymers prepared by condensation polymerization
between halogen-, boronic acid-, acetylenic- or aldehyde-
substituted BINOLs, and appropriate comonomers,20–24
(ii) linear polymers prepared by free radical polymerization
*
Corresponding authors. Tel.: +44 161 275 4707/+44 1524 791 728; fax:
+44 1524 793 252 (P.H.); tel.: +86 22 23502051; fax: +86 22 23503510
(Z.Z.); e-mail addresses: Philip.Hodge@man.ac.uk; zhangzp@nankai.
edu.cn
0957-4166/$ - see front matter ꢁ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.08.011

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X.-Y. Yuan et al. / Tetrahedron: Asymmetry 17 (2006) 2401–2407
Br
OH
OH
+
OH
OH
B(OH)2
1
(R)-enantiomer 2
(S)-enantiomer 3
(R)-enantiomer 4
(S)-enantiomer 5
Scheme 1. Reaction used to prepare PS chiral BINOLs.
of BINOL-containing vinyl monomers,25–27 or (iii) cross-
linked, and therefore insoluble, polymer beads prepared
by attaching BINOL derivatives containing carboxylic
acid,28 hydroxyl,29,30 or aldehyde groups31,32 to preformed
polymer beads. These latter syntheses give final products in
which the BINOL moieties are linked to the support via
amide,28 ether,29,31,32 or acetal groups.31,32 One problem
with some of these linking groups is that they are sensitive
to common reaction conditions and this limits their use.
Another problem with this approach (iii) is that any unre-
acted residues on the beads that remain from the linking
reaction might interfere in subsequent applications.
Beads containing boronic acid residues 1 were prepared by
treating 1% or 2% crosslinked gel-type polystyrene beads
(100–200 mesh) with n-butyl-lithium and then trimethyl
borate.36 Direct lithiation of the beads was used because
bromination followed by a bromide-lithium exchange
might leave some bromo residues on the beads that could
react with boronic acid residues 1 to give crosslinks in the
subsequent Suzuki couplings. In general, increasing the
crosslinking of gel-type polymers, even slightly, decreases
swelling and hence restricts access to the reactive sites.37
PS chiral BINOLs 4 and 5 were prepared by the Suzuki
coupling of bromo compounds 2 and 3 with PS boronic
acid 1 (Scheme 1).38 A relatively long reaction time was
used to allow boronic acid residues 1 that did not take part
in the Suzuki coupling to hydrolyze.38 The elemental anal-
ysis of the products indicated that <0.1 mmol/g of residues
1 remained. The loadings of residues 4 and 5 were esti-
mated from the gains in the weights of the beads accompa-
nying the Suzuki couplings, and/or by esterifying the OH
groups with thiophen-2-carbonyl chloride followed by an
elemental analysis for sulfur. The results are summarized
in Table 1. It is evident that where loadings were estimated
by both methods, the results were similar. As expected,37
the Suzuki coupling was more efficient with the 1% cross-
linked beads than with the 2% crosslinked beads.
Herein, we report a facile synthesis of crosslinked polymer
beads bearing chiral BINOL moieties that are attached to
the support via very stable linkages (Scheme 1). The effi-
cacy of these new PS BINOLs has been tested by using
them to prepare catalysts for the oxidation of prochiral
thioethers to chiral sulfoxides (Scheme 2). These reactions
are complex and PS versions have not been studied in
detail.30 This oxidation was selected because chiral
sulfoxides have emerged as versatile building blocks and
chiral auxiliaries in the synthesis of biologically important
compounds.33
2. Results and discussion
2.1. Catalyst preparation
The attractive features of this general approach are (i) that
the chiral BINOL moiety is linked to the support via an ex-
tremely stable aryl–aryl linkage; (ii) the attachment method
is a one-pot procedure, (iii) since the Suzuki coupling is tol-
erant of many functional groups, the phenolic groups of
the BINOL moiety do not need protection; (iv) dry reac-
tion conditions are not necessary, and (v) boronic acid
residues 1 that do not take part in the coupling are simply
removed from the support by hydrolysis. A similar
approach has recently been used successfully to synthesize
PS (S)-a,a-diphenylprolinol39 and PS (S)-a,a-diphenyl-N-
methylprolinol.40
In the present work, chiral BINOL moieties were introduced
into crosslinked polystyrene beads using the reaction sum-
marized in Scheme 1. First, racemic BINOL was resolved
using N-benzylcinchonidinium chloride.34 Each enantiomer
was then converted into the corresponding 6-bromo-
BINOL following the procedure used by Cai et al. to
prepare racemic 6-bromo-BINOL (Scheme 3).35 Thus treat-
ment of (R)-BINOL 10 with pivaloyl chloride and pyridine
gave monopivalate 11 (74% yield). The latter was then selec-
tively brominated at the 6-position of the phenolic naphtha-
lene moiety by treatment with bromine in a 50:50 v/v
mixture of acetonitrile and toluene at 0 ꢀC to give com-
pound 12 (90% yield). The hydrolysis of 12 with sodium
hydroxide gave the required (R)-6-bromo-BINOL 2 (90%).
By an analogous series of reactions, (S)-BINOL 13 was
converted, via compounds 14 and 15, into (S)-6-bromo-
BINOL 3.
2.2. Catalyzed oxidations
To assess the performance of the new PS BINOLs, PS cat-
alysts were prepared by treatment with titanium tetraiso-
propoxide. The catalysts were then used for the oxidation
of aryl thioethers by tert-butyl hydroperoxide.

X.-Y. Yuan et al. / Tetrahedron: Asymmetry 17 (2006) 2401–2407
2403
first, as sulfoxides are usually obtained in good yields. It
is well known that with soluble BINOL-derived catalysts,
the minor sulfoxide enantiomer oxidizes faster than the
major enantiomer.41,42 As a consequence, the % ee of
the remaining sulfoxide increases as more sulfone is
formed.
S
CH3
X
6a : X = H
6b: X = CH3
6c : X = Br
Herein, the oxidation catalysts were prepared in situ by
treating the PS BINOLs with titanium tetraisopropoxide
in the chosen reaction solvent at its reflux temperature, fol-
lowed by the addition of a small amount of water at ambi-
ent temperature. Oxidations were then carried out by
treating the aryl methyl thioether in the same reaction sol-
vent with aqueous tert-butyl hydroperoxide (TBHP) in the
presence of the catalyst.
Initially, the oxidations of methyl phenyl thioether 6a were
carried out using PS Catalyst I. Uemura et al., in their stud-
ies using soluble BINOLs (see above), achieved the best
% ees with carbon tetrachloride as the reaction solvent:
aromatic solvents and ether solvents gave somewhat lower
% ees.41 In the present work, however, when either carbon
tetrachloride or diethyl ether was used as the reaction sol-
vent, the oxidation was extremely slow at 23 ꢀC, probably
due to the poor swelling of the polymer beads.37 Using tet-
rahydrofuran (THF) or toluene as the reaction solvent
gave much better results. The oxidations were monitored
by TLC and stopped when sulfone was first detected. To
improve the selectivity, the oxidations were carried out at
0 ꢀC: reaction times were generally 36 h. The composition
of the final product and the % ee of the sulfoxides were
then determined by HPLC over a chiral stationary phase.
The results are summarized in Table 2, entries 1–5.
O
O
S
S
CH3
CH3
+
X
X
(R)-enantiomer
(S)-enantiomer
7a: X = H
8a : X = H
8b: X = CH3
8c: X = Br
7b: X = CH3
7c: X = Br
Several conclusions can be drawn from these results.
(i) The use of THF or toluene as the solvent resulted in
similar chemical yields and, in each case, sulfoxides
7a/8a were obtained with a 60% excess of the (R)-
enantiomer 7a.
(ii) Certain mixtures of THF and toluene gave better ste-
reochemical results than either solvent alone. Thus,
the use of these solvents in the ratios 1:1, 2:3 and
3:2 gave ees of 82%, 89% and 84%, respectively: com-
pare entries 1 and 2 with 3–5. These results almost
certainly reflect differences in the swelling of the poly-
mer beads.37
O
O
S
CH3
X
9a: X = H
9b: X = CH3
9c: X = Br
(iii) Uemura et al. noted that in the preparation of the cat-
alyst by reaction of BINOL with titanium tetraiso-
propoxide, the moles of water added affected the
% ee, and that there was an optimum amount.41 This
was also found to be the case with the present PS
reactions. Thus, a repeat of the reaction summarized
in entry 3 but with 4.0 mol % of water per mole of
thioether gave an ee of 57%, while one with
8.0 mol % gave an ee of 72%.
Scheme 2. Oxidation of aryl methyl thioethers. Note that S–O bonds are
shown as single to allow the stereochemistry to be shown clearly.
The oxidation of aryl methyl thioethers to give chiral sulf-
oxides using tert-butyl hydroperoxide in the presence of
the catalyst prepared in situ from soluble (R)-BINOL
and a titanium alkoxide has been studied in detail by
Uemura et al.41,42 The oxidation products generally
contained unreacted thioether and sulfone, as well as the
desired sulfoxides (Scheme 2).41,42 Thus a typical oxida-
tion of thioanisole 6a gave the starting material, sulfoxides
7a/8a and sulfone 9a in a molar ratio of 24:66:10.41 Hence,
some of the sulfoxide mixture was oxidized further to sul-
fone 9a. Clearly this second oxidation is slower than the
PS Catalyst II was then used to oxidize thioanisole 6a in
THF at 0 ꢀC, with the aim of this reaction to maximize
the yield of the sulfoxides (entry 6). The reaction was mon-
itored by 1H NMR spectroscopy: starting material 6a, sulf-
oxides 7a/8a and sulfone 9a give well-resolved singlets due

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X.-Y. Yuan et al. / Tetrahedron: Asymmetry 17 (2006) 2401–2407
OH
OH
OH
OCOC(CH3)3
11:(R)-isomer
14:(S)-isomer
10:(R)-BINOL
13:(S)-BINOL
Br
OH
2:6-bromo-(R)-BINOL
3:6-bromo-(S)-BINOL
OCOC(CH3)3
12:(R)-isomer
15:(S)-isomer
Scheme 3. Preparation of 6-bromo-BINOLs 2 and 3 from BINOLs 9 and 13. As in the procedure of Cai et al.,35 intermediates 12 and 15 were not isolated.
Table 1. Preparation of PS BINOLs and designations of the derived PS catalysts
Entry Crosslinking (%) of BINOL
Loading of residues 4 or 5 (mmol/g)a
Degree of
Coupling PS Catalyst
starting beads
enantiomer
substitutionc yield (%) preparedd
By weight gain Via thiophen ester analysisb Average
1
2
3
2e
1f
1f
R
R
S
0.66
1.16
1.45
—
0.93
1.37
0.66
1.05
1.41
0.11
0.13
0.17
46
41
53
I
II
III
a By elemental analysis the final beads contained <0.1 mmol/g of residues 1.
b BINOL residues were esterified using thiophen-2-carbonyl chloride, followed by elemental analysis for sulfur.
c Calculated from average loading of residues 4 or 5.
d Designation of final catalyst prepared by treating the PS-BINOL with titanium tetraisopropoxide.
e Boronic acid had a loading of 1.66 mmol/g of residues 1: corresponds to a degree of substitution of 0.24.
f Boronic acid had a loading of 2.73 mmol/g of residues 1: corresponds to a degree of substitution of 0.32.
Table 2. Oxidation of thioethers 6a–6c Using PS Catalysts I–IIIa
Entry
PS Catalyst
Thioether
Reaction conditions
Composition of
product (%)b
Major enantiomer
% eeb
Solvent
Time (h)
S
SO
SO2
Trace
Trace
Trace
Trace
Trace
9
11
29
29
10
1
2
3
4
5
6
7
8
9
I
I
I
I
6a
6a
6a
6a
6a
6a
6a
6b
6b
6c
THF
Toluene
THF/toluene (1:1 v/v)
THF/toluene (2:3 v/v)
36
36
36
36
36
48
24
48
48
48
46
45
45c
40
41
30
0
20
18
57
54
55
55
60
59
61
89
51
53
33
R
R
R
R
R
R
R
R
S
60
60
82
89
84
82
9
91
89
73
I
THF/toluene (3:2 v/v)
II
II
II
III
III
THF
THF
THF
THF
THF
10
S
a See Section 4 for typical reaction procedures.
b Determined by HPLC.
c Using the same reaction conditions but with 111 lL of water added, the chemical yield was 53% and the ee was 57%. With 222 lL of water, the chemical
yield was 60% and the ee was 72%.

X.-Y. Yuan et al. / Tetrahedron: Asymmetry 17 (2006) 2401–2407
2405
to the S-methyl groups. After a reaction time of 48 h, the
reaction gave the corresponding sulfoxides 7a and 8a in a
combined yield of 61% with an ee of 82% in favour of
the (R)-enantiomer. The increased % ee compared with
the reaction summarized in entry 1 was considered to be
due, mainly, to the minor sulfoxide enantiomer 8a being
oxidized more rapidly than the major sulfoxide enantiomer
7a to the sulfone 9a. To test this, the racemic sulfoxide of
thioanisole was treated with the PS Catalyst II under the
usual reaction conditions but for only 24 h. The product
was analyzed using HPLC in the usual way (entry 7). As
expected the sulfoxide present in the final reaction mixture
contained an excess of (R)-enantiomer 7a. Thus, (S)-enan-
tiomer 8a was oxidized to sulfone 9a faster and the PS reac-
tion behaved analogously to the non-supported reactions
discussed above.41,42
acid groups that do not take part in the Suzuki coupling
are simply removed by in situ hydrolysis.
To assess the performance of the present PS BINOLs, they
were reacted in situ with titanium tetraisopropoxide to give
catalysts for the oxidation of aryl methyl thioethers
with aqueous tert-butyl hydroperoxide in THF at 0 ꢀC.
The sulfoxides were obtained in chemical yields of
33–61% and ees of 60–91%. These values compare well with
those obtained by Uemura et al. who, using soluble
BINOL in carbon tetrachloride as the reaction solvent at
0 ꢀC,40 obtained chemical yields of 39–67% and ees of
80–93%, while those using a PS BINOL employing an ace-
tal linker gave chemical yields of 60–67% and ees of
78–88%.30 The catalysts containing (R)-BINOL moieties
predominantly gave the (R)-sulfoxides, while that
with (S)-BINOL residues predominantly gave the (S)-
sulfoxides.
Several other oxidations similar to that summarized in
entry 6 were carried out using Catalysts II and III. The re-
sults are summarized in entries 8–10. It is evident (compare
entries 8 and 9 with entry 6) that 4-methylthioanisole 6b is
more reactive than thioanisole 6a (less starting material
remaining), while 4-bromothioanisole 6c is less reactive.
This explains, at least in part, the higher % ees in the
former case and the lower % ee in the latter. As expected,
Catalyst III affords the (S)-sulfoxides in excess whilst
Catalyst II affords the (R)-sulfoxides.
4. Experimental
4.1. General
Experimental details are as described previously.39 HPLC
was carried out using a Chiralcel OD column; UV detec-
tion at k 254 nm; eluant hexane/i-PrOH (9 vol:1 vol), at a
flow rate of 1.0 mL/min.
The reuse of the catalysts was also investigated briefly.
Comparing the performance of the reused and original cat-
alyst is complicated by the fact the % ees of the sulfoxides
depend on how much of each sulfoxide is oxidized to
sulfone. Initially Catalyst I recovered from the reaction
summarized in entry 4 was, without being retreated with
titanium tetraisopropoxide, reused twice under similar
reaction conditions. The chemical yields of the sulfoxides
and sulfone were almost unchanged but the % ees fell from
89% to 79%. This was considered to be most certainly due
to the loss of titanium but not loss or racemization of the
BINOL moieties. Consistent with this, when Catalyst II
was recovered from the reaction summarized in entry 6,
it was retreated with titanium tetraisopropoxide and reused
under the previous conditions to give an ee of 81%. The
catalyst was again recovered and the procedure repeated
twice more. Yields of the sulfoxides and sulfone were sim-
ilar to before: the ees were 79% and 84%. A more detailed
study of the recycling of the catalysts will be made in future
using the catalysts for long periods under the more repro-
ducible reaction conditions of a flow system.
4.2. Preparation of 6-bromo-BINOLs
Racemic BINOL was obtained from Aldrich and resolved
using N-benzylcinchonidium chloride.34 This gave (R)-
21
BINOL 10, mp 207–210 ꢀC, ½aꢀD ¼ þ29:5 (c 1, THF)
21
{lit.,34 206–207 ꢀC; ½aꢀD ¼ þ28:6 (c 1, THF)} and (S)-BI-
21
NOL 13, mp 204–206 ꢀC, ½aꢀD ¼ ꢁ29:0 (c 1, THF) {lit.,34
21
205–206 ꢀC; ½aꢀD ¼ ꢁ28:5 (c 1, THF)}. By HPLC both
enantiomers were 100% of the desired enantiomer.
Each BINOL enantiomer was converted into the corre-
sponding 6-bromo-BINOL using the reaction sequence
shown in Scheme 3. The experimental details are as given
by Cai et al. for the synthesis of racemic products.35 As
in the procedure of Cai et al.,35 intermediates 12 and 15
were not isolated.
(R)-BINOL monopivalate 11 (74% yield) had a mp of
23
63–65 ꢀC and ½aꢀD ¼ þ58:0 (c 1.0, THF). (S)-BINOL
monopivalate 14 (50%) had a mp of 63–65 ꢀC and
20
½aꢀD ¼ ꢁ57:1 (c 1.0, THF). Lit.43 reports for (S)-enantio-
39
mer ½aꢀD ¼ ꢁ56:8 (c 0.51, THF).
3. Conclusions
(R)-6-Bromo-BINOL 2 (90%) had a mp of 82–84 ꢀC and
20
Polystyrene beads bearing chiral 1,10-(bi-2-naphthol) (BI-
NOL) moieties 4 or 5 can be prepared readily by a one-
pot attachment procedure using Suzuki couplings between
the appropriate chiral 6-bromo-1,10-bi-(2-naphthol) 2 or 3
and polystyrene beads containing phenylboronic acid resi-
dues 1. With this method of synthesis, the BINOL moieties
are linked to the support via strong C–C bonds. No pro-
tecting groups are needed during the attachment reaction,
the reaction conditions need not be dry, and any boronic
½aꢀD ¼ ꢁ7:5 (c 1.0, THF). It was >99% pure on chiral
HPLC analysis. (S)-6-Bromo-BINOL 3 (70%) had a mp
21
of 83–85 ꢀC and ½aꢀD ¼ þ7:6 (c 1.0, THF). Lit.43 reports
25
for (S)-enantiomer ½aꢀD ¼ þ6:3 (c 0.49, THF).
4.3. Synthesis of PS boronic acids
The following is typical of the syntheses used for preparing
the catalysts described in Table 1.

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X.-Y. Yuan et al. / Tetrahedron: Asymmetry 17 (2006) 2401–2407
4.3.1. Beads used for the experiments summarized in entries
2 and 3. Using the procedures described by Farrall and
Frechet,36 polystyrene beads (11.2 g, 1% crosslinked) were
first lithiated by treating a suspension in dry cyclohexane
(80 mL) and tetramethylethylenediamine (16 mL) with n-
butyl-lithium (54 mL; 2.5 M in hexane) for 5 h at 50 ꢀC,
then the lithiated product was treated immediately with tri-
methyl borate (15.2 mL) in dry THF (120 mL) at 20 ꢀC for
68 h. This gave pale orange beads (11.0 g). These had mmax
1360 cmꢁ1 (B–O). Found C, 80.45; H, 7.25; B, 2.95. The
latter corresponds to a loading of 2.73 mmol of boronic
acid groups per gram of beads.
4.5. Oxidation reactions
The following procedures are typical for the reactions
summarized in Table 2.
4.5.1. Entry 5. A mixture of Catalyst I (0.50 g, 0.33 mmol),
THF (4 mL), toluene (6 mL) and titanium tetraisopropox-
ide (47.87 lL, 0.16 mmol) was heated at reflux under an
argon atmosphere for 1 h. After cooling to 20 ꢀC, water
(16.7 lL, 0.93 mmol, as a 5% solution in THF) was added
and the mixture stirred for 2 h at 20 ꢀC. The mixture was
then cooled to 0 ꢀC and thioanisole (183 lL, 1.55 mmol)
added. Aqueous tert-butyl hydroperoxide (70%, 430 lL,
3.1 mmol) was added dropwise. The reaction was monitored
by TLC and stopped at the appearance of the spot due to
sulfone. The reaction time was 36 h. The excess of peroxide
was quenched by saturated aqueous potassium iodide and
the product was extracted with ethyl acetate and washed
with saturated aqueous sodium thiosulfate. The organic
solution was dried and evaporated to dryness to give the
crude product. The amounts of starting material, sulfoxides
and sulfone and the ee value were determined by HPLC
analysis. The major enantiomer had a retention time of
11.0 min, the minor enantiomer had a retention time of
13.1 min. Column chromatography of the crude product
4.4. Synthesis of PS BINOLs
The following synthesis is typical of the reactions summa-
rized in Table 1.38
4.4.1. Entry 2. PS boronic acid 1 (2.95 g, 8.1 mmol), (R)-6-
bromo-BINOL 2 (3.10 g, 8.5 mmol) and THF (20 mL)
at 20 ꢀC were introduced in a round-bottomed flask
(250 mL). Tetrakis(triphenylphosphine)palladium[0] (0.343 g,
0.30 mmol) dissolved in THF (4 mL) was added via a sep-
tum. The flask was screened from light with an aluminium
foil. The mixture was stirred for 15 min, then THF
(100 mL) and aqueous potassium carbonate (16 mL, 1 M,
16 mmol) were injected. The mixture was stirred and heated
at 70 ꢀC for 72 h. A second portion of tetrakis(triphenyl
phosphine)palladium[0] (0.11 g, 0.10 mmol) was added
and the reaction left at 72 ꢀC for a further 24 h. Bromobenz-
ene (0.5 mL) was then added and the mixture stirred a fur-
ther 24 h at 72 ꢀC. The beads were filtered off and washed
successively with THF, THF–water (1 vol:1 vol), HCl
(0.5 M), THF–HCl (1 vol:4 vols), THF–ethyl acetate
(4 vols:6 vols), THF–acetone (4 vols:6 vols), THF–metha-
nol (4 vols:6 vols), THF–ether (4 vols:6 vols), methanol
and ether. The beads were dried (3.88 g, 56%). The loading
calculated by the weight gain was 1.16 mmol of (R)-BINOL
over silica gel (ethyl acetate/hexane: 2 vols to 3 vols) gave
20
a mixture of sulfoxides 7a/8a with ½aꢀD25¼ þ133:7 (c 1.0,
acetone) {lit.44 for pure (R)-isomer ½aꢀD ¼ þ149 (c 1.0,
1
95% ethanol)}; H NMR (300 MHz, CDCl3): d 2.85 (s,
3H), 7.53–7.57 (m, 3H), 7.65–7.68 ppm (m, 2H).
4.5.2. Entry 6. The reaction was carried out using the
above procedure except that the reaction was monitored
1
by H NMR spectroscopy. Thioether 6a shows a singlet
at d 2.60 ppm, sulfoxides 7a/8a show a singlet at d
2.85 ppm, and sulfone 9a shows a singlet at d 3.10 ppm.
The reaction was stopped when the percentage of sulfoxide
was near maximal. The reaction time was 48 h. The prod-
uct was analyzed using HPLC. The mixture of sulfoxides
per gram of beads. The beads had mmax 3519 and 1619 cmꢁ1
.
Found: C, 88.00; H, 6.36; B, less than 0.1%.
isolated by column chromatography was obtained as an
oil with ½aꢀD ¼ þ121 (c 1.0, 95% ethanol).
25
4.4.2. Estimation of the loading of polymer-supported
BINOL using thiophen-2-carbonyl chloride (Table 1, entry
2). PS (R)-BINOL 4 (0.203 g, 0.55 mmol maximum) was
placed in a 50 mL three-neck-round-bottomed flask fitted
with a condenser and a gas inlet adaptor. The mixture
was left for 1 h under nitrogen prior to the addition of thio-
phene-2-carbonyl chloride (0.20 mL, 1.87 mmol) and dry
pyridine (4 mL). The reaction mixture was stirred for
20 h under nitrogen at 80 ꢀC. The beads were then filtered
off and washed with a solution of HCl–H2O–THF
(2 vols:20 vols:10 vols), with water (2 · 25 mL), THF
(2 · 25 mL) and finally ether (2 · 25 mL). The product
was dried under vacuum overnight to yield orange-yellow
beads (0.233 g). They had mmax 1726 cmꢁ1. Found: C,
79.91; H, 5.44; S, 5.17. The latter corresponds to a loading
of BINOL ester of 0.81 mmol/g. Allowing for the weight
change, the loading of BINOL moieties on the original
polymer was 0.93 mmol/g.
4.5.3. Entries 8 and 10. The reactions were carried
out using the general procedures given above. After
HPLC analysis, samples of sulfoxide were isolated using
column chromatography. The mixture of sulfoxides 7b/8b
25
was obtained as a solid at a mp of 70–73 ꢀC, ½aꢀD
¼
þ128 (c 1.0, 95% ethanol) {lit.45 mp 73–74.5 ꢀC,
25
½aꢀD ¼ þ141 (c 1.0, 95% ethanol)}. The mixture of sulfox-
ides 7c/8c was obtained as a solid at a mp of 85–87 ꢀC,
25
½aꢀD ¼ þ76 (c 0.5, chloroform) {lit.46 for (S)-enantio-
25
mer ½aꢀD ¼ ꢁ105 (c 0.44, chloroform)}.
Acknowledgements
We thank the EU Erasmus Scheme for an M.Sc. Student-
ship (C.Y.T.) and Ann E. Bracegirdle and Mohammad
Nisar for preliminary experiments.

X.-Y. Yuan et al. / Tetrahedron: Asymmetry 17 (2006) 2401–2407
2407
24. Fan, Q.-H.; Liu, G.-H.; Deng, G.-J.; Chen, X. M.; Chan, A.
S. C. Tetrahedron. Lett. 2001, 42, 9047.
References
25. Sekiguti, T.; Lizuka, Y.; Takizawa, S.; Jayaprakash, D.; Arai,
T.; Sasai, H. Org. Lett. 2003, 5, 2647.
26. Jayaprakash, D.; Sasai, H. Tetrahedron: Asymmetry 2001, 12,
2589.
27. Yamada, Y. M. A.; Ichinohe, M.; Takahashi, H.; Ikegami, S.
Tetrahedron Lett. 2002, 43, 3431.
28. Fan, Q.-H.; Wang, R.; Chan, A. S. C. Bioorg. Med. Chem.
Lett. 2002, 12, 1867, and references cited therein.
29. Kobayashi, S.; Kusakable, K. I.; Ishitani, H. Org. Lett. 2000,
2, 1225.
30. Lipshutz, B. H.; Shin, Y. J. Tetrahedron Lett. 2000, 41, 9515.
31. Nogami, H.; Matsunaga, S.; Kanai, M.; Shibasaki, M.
Tetrahedron Lett. 2001, 42, 279.
32. Mastsunaga, S.; Oshima, T.; Shibasaki, M. Tetrahedron Lett.
2000, 41, 8473.
33. Fernandez, I.; Khiar, N. Chem. Rev. 2003, 103, 3651.
34. Cai, D.; Hughes, D. L.; Verhoeven, T. R.; Reider, P. J. Org.
Synth. 1999, 76, 1.
1. Merrifield, R. B. J. Am. Chem. Soc. 1963, 85, 2149.
2. Ley, S. V.; Baxendale, I. R.; Bream, R. N.; Jackson, P. S.;
Leach, A. G.; Longbottom, D. A.; Nesi, M.; Scott, J. S.;
Storer, R. I.; Taylor, S. J. J. Chem. Soc., Perkin Trans. 1
2000, 3815.
3. Polymer-Supported Reactions in Organic Synthesis; Hodge,
P., Sherrington, D. C., Eds.; Wiley: Chichester, 1980.
4. Syntheses and Separations Using Functional Polymers; Sher-
rington, D. C., Hodge, P., Eds.; Wiley: Chichester, 1988.
5. Polymeric Materials in Organic Synthesis and Catalysis;
Buchmeiser, M. R., Ed.; Wiley Interscience: Weinheim, 2003.
6. Nicolaou, K. C.; Hanko, R.; Hartwig, W. In Handbook of
Combinatorial Chemistry; Wiley-VCH: Wienheim, 2002; Vols.
1 and 2.
7. De Miguel, Y. R. J. Chem. Soc., Perkin Trans. 1 2000, 4213.
8. De Vos, D. E.; Vankelecom, I. F. J.; Jacobs, P. A. Chiral
Catalyst Immobilization and Recycling; Wiley-VCH: Wein-
heim, 2000.
35. Cai, D.; Larsen, R. D.; Reider, P. J. Tetrahedron Lett. 2002,
43, 4055.
36. Farrall, M. J.; Frechet, J. M. J. J. Org. Chem. 1976, 41, 3877.
37. Hodge, P. Chem. Soc. Rev. 1997, 26, 417.
38. Kell, R. J.; Hodge, P.; Nisar, M.; Williams, R. T. J. Chem.
Soc., Perkin Trans. 1 2001, 3403.
39. Kell, R. J.; Hodge, P.; Snedden, P.; Watson, D. Org. Biomol.
Chem. 2003, 1, 3238.
40. Kell, R. J.; Hodge, P.; Nisar, M.; Watson, D. Biorg. Med.
Chem. Lett. 2002, 12, 1803.
9. Song, C. E.; Lee, S. Chem. Rev. 2002, 102, 3495.
10. Fan, Q.; Li, Y.-M.; Chan, A. S. C. Chem. Rev. 2002, 102,
3385.
11. De Vos, D. E.; Dams, M.; Sels, B. F.; Jacobs, P. A. Chem.
Rev. 2002, 102, 3615.
12. Leadbeater, N. E.; Marco, M. Chem. Rev. 2002, 102, 3217.
13. Bergbreiter, D. E. Chem. Rev. 2002, 102, 3345.
14. Hodge, P. Curr. Opin. Chem. Biol. 2003, 1, 2419.
15. Hodge, P. Ind. Eng. Chem. Res. 2005, 44, 8542.
16. Jas, G.; Kirschning, A. Chem. Eur. J. 2003, 9, 5708.
17. Hodge, P.; Sung, D.; Stratford, P. W. J. Chem. Soc., Perkin
Trans. 1 1999, 2335.
41. Komatsu, N.; Hashizumi, M.; Sugita, T.; Uemura, S. J. Org.
Chem. 1993, 58, 4529.
42. Komatsu, N.; Hashizumi, M.; Sugita, T.; Uemura, S. J. Org.
Chem. 1993, 58, 7624.
18. Chen, Y.; Yektas, S.; Yudin, A. K. Chem. Rev. 2003, 103,
3155.
43. Hocke, H.; Uozumi, Y. Tetrahedron 2003, 59, 619.
44. Jacobus, J.; Mislow, K. J. Am. Chem. Soc. 1967, 89, 5228.
45. Mislow, K.; Green, M. M.; Laur, P.; Mellilo, J. T.; Simmons,
T.; Ternay, A. L. J. Am. Chem. Soc. 1965, 87, 1958.
46. Kokubo, C.; Katsuki, T. Tetrahedron Lett. 1996, 52, 13895.
19. Aspinall, H. C. Chem. Rev. 2002, 102, 1807.
20. Pu, L. Chem. Rev. 1998, 98, 2405.
21. Carreno, M. C. Chem. Rev. 1995, 95, 1717.
22. Pu, L. Tetrahedron: Asymmetry 1998, 9, 1457.
23. Pu, L.; Yu, H. Chem. Rev. 2001, 101, 757.