Traceless solid phase synthesis with polystyrene-bound tellurium and in comparison with polystyrene-bound selenium

Article abstract of DOI:10.1055/s-2004-831202

A novel traceless linking strategy by use of polystyrene-bound tellurium is described. The application of the tellurium linker is demonstrated by the solid phase synthesis of a small library of single alkyl aryl ethers containing two points of diversity.

Full text of DOI:10.1055/s-2004-831202

PAPER
2323
Traceless Solid Phase Synthesis with Polystyrene-Bound Tellurium and in
Comparison with Polystyrene-Bound Selenium
T
raceless Solid
h
Phase Synth
o
esis
w
ith
P
ol
m
ystyrene-Bound
T
e
a
llurium s Ruhland,* Jakob Torang, Henrik Pedersen, Jens Christian Madsen, Kia Svane Bang
Medicinal Chemistry Research, H. Lundbeck A/S, 9 Ottiliavej, 2500 Valby, Denmark
Fax +4536438237; E-mail: tr@lundbeck.com
Received 17 May 2004; revised 1 June 2004
possibilities of polystyrene-bound selenium in the SPOS
of e.g. carbohydrates (2-deoxy glycosides),4i glycopep-
tides (vancomycin derivatives)4h,j and heterocycles (indo-
lines, benzopyrans, furanones and others).4c,g,5f,j
Abstract: A novel traceless linking strategy by use of polystyrene-
bound tellurium is described. The application of the tellurium linker
is demonstrated by the solid phase synthesis of a small library of
single alkyl aryl ethers containing two points of diversity. Polysty-
rene-bound tellurium and polystyrene-bound selenium are com- Obviously, compounds attached to polystyrene-bound se-
pared by their cleavage performance under radical conditions
lenium are allowed to bear a broad range of functional
(homolysis) at different temperatures. In addition, polystyrene-
groups and are also allowed to undergo diverse chemical
bound substrates were analysed by the use of high-resolution magic
transformations prior to cleavage.
angle spinning (HR–MAS) NMR spectroscopy.
However, cleavages from polystyrene-bound selenium
under radical conditions have so far been performed at el-
evated temperature (90–100 °C, toluene). The high tem-
Key words: combinatorial chemistry, solid phase synthesis, trace-
less linker, polystyrene-bound chalcogenes, HR–MAS NMR spec-
troscopy
perature is
a drawback for temperature-sensitive
compounds and it complicates parallel synthesis in auto-
mation routines since reaction vessels (generally made of
polypropylene) are not resistant to toluene at this temper-
ature. Since literature reports suggested that homolysis of
phenyl alkyl tellurides could take place at lower tempera-
ture in comparison to phenyl alkyl selenides,7 we have ex-
tended our linker-strategy towards the chalcogen atom,
tellurium. Only a few tellurium-containing polymers have
found applications in organic synthesis. For instance,
polystyrene-bound diaryl telluroxides8 are reported as
mild and selective oxidation agents and very recently sol-
uble poly(ethylene glycol)-bound tellurides9 have been
used as catalysts for Wittig-type olefination reactions. In
solution-phase organic synthesis, tellurium plays general-
ly only a minor and exotic role.
Introduction
Solid phase organic synthesis (SPOS) of combinatorial li-
braries of non-peptidic compounds with low molecular
weight and suitable physicochemical properties has be-
come an established tool in pharmaceutical companies for
the discovery of biologically active compounds.1 Trace-
less SPOS2 is of high importance in particular for the de-
sign of biologically active target molecules since the
cleaved target compounds have no memory of their
former attachment point and therefore are bearing exclu-
sively those functionalities that have been chosen for their
biological activity.
Examples of traceless linkers which enables the cleavage
of products under aliphatic C(sp3)-H bond formation are
rare compared with traceless linkers, from which products
are released under aromatic C(sp2)-H bond formation.2
We and others have recently reported that the chalcogen
atoms, sulfur and selenium, are suitable and robust linking
elements for the traceless synthesis of aliphatic com-
pounds.3–6 Traceless cleavage from polystyrene-bound se-
lenium takes place smoothly under radical conditions at
elevated temperature (using tributyltin hydride and cata-
lytic amounts of AIBN) by C(sp3)-H bond formation.
In the present paper, the element tellurium is given an im-
portant role as linking element for traceless SPOS. To the
best of our knowledge we herein describe for the first time
the preparation of polystyrene-bound tellurium as a suit-
able solid support for SPOS. In the following, we compare
the cleavage performance of polystyrene-bound tellurium
with polystyrene-bound selenium in the synthesis of a li-
brary of single aryl alkyl ethers using the Mitsunobu reac-
tion. In addition, each step of the synthesis can be
monitored by high-resolution magic angle spinning
(HR–MAS) 1H NMR spectroscopy.
The first library synthesised on polystyrene-bound seleni-
um was a library consisting of six alkyl aryl ethers with
two points of diversity.3 Within the last few years, publi- Results and discussion
cations from K. C. Nicolaou et al.4 and others5 have initi-
ated impressive demonstrations of application The preparation of polystyrene-bound tellurium was
achieved in analogy to the synthesis protocol for the prep-
aration of polystyrene-bound selenium (Scheme 1).3
Commercially available polystyrene (100–200 mesh,
cross-linked with 1% divinylbenzene) was brominated
SYNTHESIS 2004, No. 14, pp 2323–2328
Advanced online publication: 25.08.2004
DOI: 10.1055/s-2004-831202; Art ID: Z09304SS
© Georg Thieme Verlag Stuttgart · New York
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x.
x
x
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T. Ruhland et al.
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under thallium acetate catalysis to obtain bromopolysty-
rene 1 (loading: 3.67 mmol/g). Bromine-lithium exchange
(with excess n-BuLi) in hexane–toluene (1:1) generated
lithiated polystyrene 2 which was treated with tellurium
powder (approximately 350 mesh) under reflux to gener-
ate polystyrene-bound tellurium 3. Excess tellurium was
liberated from resin 3 by reduction with NaBH4 in MeOH.
Scheme 2
recovered due to re-oxidation of the polystyrene-bound
sodium telluro(triethyl)borate complex 4.
The solid-phase synthesis of a [2 × 3] sized alkyl aryl ether
library is outlined in Scheme 3. In order to compare the
cleavage results of polystyrene-bound tellurium with
polystyrene-bound selenium, identical building blocks
and reaction conditions were chosen. The first point of di-
versity was introduced by alkylation of resin 4 (after acti-
vation of polystyrene-bound tellurium 3) with 2-[2-(2-
chloroethoxy)ethoxy]ethanol and 6-bromohexanol, re-
spectively, yielding the polystyrene-bound alcohols 6 and
7. The second point of diversity was introduced by ether
formation with phenols under Mitsunobu reaction condi-
tions. Coupling of each of the polystyrene-bound alcohols
6 and 7 with 4-phenyl-, 2-fluoro-, and 3-methoxy phenol
furnished the six polystyrene-bound alkyl aryl ethers 8a–
c and 9a–c. Cleavage by homolysis of the resins 8a–c and
9a–c furnished the aryl alkyl ethers 10a–c and 11a–c, re-
spectively.
Scheme 1
The removal of elemental tellurium is much more tena-
cious compared with selenium and required many more
intensive reduction cycles. After exposure to air and dry-
ing in vacuo, resin 3 was obtained as a stable, deep purple
coloured resin. Like polystyrene-bound selenium, resin 3
displayed non-visible swelling properties in any solvent.
The poor swelling properties are caused by high cross-
linking of the resin due to rapid Te-Te bond formation un-
der air exposure. However, reduction of the Te-Te bonds
with NaBH4 in EtOH generates within 1–2 hours an al-
most colourless and highly swollen resin 4. In analogy to
the investigations by Miyashita et al.10 and our previous
investigation of polystyrene-bound selenium,3 we pro-
pose that the reduction results in the formation of the poly-
styrene-bound sodium telluro(triethyl)borate complex 4.
Further support for the formation of the polystyrene-
bound telluride complex 4 is the excellent swelling prop-
erties of this resin in EtOH. Even though elemental tellu-
rium is insoluble in THF, the desired reaction with
lithiated polystyrene 2 proceeded smoothly. In analogy to
our previous investigations of polystyrene-bound seleni-
um,3 we propose that the reaction between elemental tel-
lurium and excess n-BuLi leads to soluble lithium
polytellurides11 which, in a Trojan horse manner, are able
to migrate into the reactive, lithiated sites of resin 2.
In order to compare the cleavage performance of polysty-
rene tellurium and selenium at different temperatures,
identical cleavage conditions for both resins were used
(4.2 equiv of tributyltin hydride and 0.1 equiv of AIBN in
toluene). Cleavages were performed at 90 °C and 60 °C
(for all members 10a–c and 11a–c of the library, Table 1)
and exemplarily at 50 °C and 40 °C (for compound 10a).
The results (yields and purities after column chromatogra-
phy) are shown in Table 1.
As mentioned earlier, we expected that cleavage for poly-
styrene-bound tellurium would be more efficient com-
pared with polystyrene-bound selenium. To our surprise,
this was not the case. By use of polystyrene-bound seleni-
um (loading: 2.34 mmol/g) yields for the cleaved products
10a–c and 11a–c were similarly high at both 90 °C and 60
°C (and not significantly different from those earlier re-
ported).3 However, the yields obtained by use of polysty-
rene-bound tellurium were approximately 20–30% lower
at 60 °C in comparison to cleavage at 90 °C. In addition,
yields after cleavage from polystyrene-bound tellurium
are in general significantly lower in comparison with
polystyrene-bound selenium at all temperatures [approxi-
mately 10–20% and 25–30% lower yields at 90 °C and 60
°C, respectively; (exception: 11b entry 9, Table 1)]. In ad-
dition, cleavage of the alkyl aryl ether 10a from polysty-
rene-bound selenium and tellurium was performed at 50
°C and 40 °C, respectively. With polystyrene-bound sele-
nium a yield of 78% (GC–MS purity: 93%) for 10a was
obtained, which is slightly lower in comparison to cleav-
age performed at 60 °C (entry 1, Table 1). With polysty-
In order to determine the loading of polystyrene-bound
tellurium resin 3, the polystyrene-bound sodium tel-
luro(triethyl)borate complex 4 was converted by alkyla-
tion with 2,4-dichlorobenzyl chloride to the almost
colourless resin 5 (Scheme 2). Elemental analysis of resin
5 for the element tellurium revealed a loading of 2.36
mmol/g for resin 3. No bromine was found by elemental
analysis indicating that the bromine-lithium exchange on
resin 1 must have gone to completion. The alkylation of
resin 4 with chloro-N,N-dimethylacetamide, which has
been used previously to determine the loading of polysty-
rene-bound selenium, failed and the starting resin 3 was
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PAPER
Traceless Solid Phase Synthesis with Polystyrene-Bound Tellurium
2325
Scheme 4
Figure 1 HR–MAS 1H NMR spectra of 8a (a) and 12 (b). In each ca-
se, 16 scans were acquired. In (a) a CPMG sequence consisting of 50
echoes resulting in a total echo time of 150 ms was applied for back-
bone suppression. In (b) a single pulse of flip angle 30° was em-
ployed. The spin rate was 4 kHz in both cases.
Scheme 3
rene-bound tellurium a yield of 58% (GC–MS purity:
93%) for 10a was obtained, which is similar in compari-
son to cleavage performed at 60 °C (entry 2, Table 1).
However, yields are dropping dramatically when cleavage
is performed below 50 °C. Only traces of the product 10a
were isolated after cleavage at 40 °C for both, polysty-
rene-bound selenium (yield: 9%, GC–MS purity: 14%),
and polystyrene bound tellurium (yield: 11%, GC–MS pu-
rity: 9%).
Assignments of the proton chemical shifts of 8a in
Figure 1a are based on the gradient COSY spectra
(Figure 2a). Although the signals from protons of the me-
thylene group adjacent to the Te-atom (labelled a in
Figure 1) are invisible in the Carr–Purcell–Meiboom–Gill
(CPMG) spectrum (due to the poor T2 relaxation proper-
ties), they are clearly visible in the COSY spectrum
(Figure 2a). Figure 1b shows the 1H HR–MAS spectra of
polystyrene-bound tributylstannyl telluride 12. Thus we
clearly demonstrate that the cleavage reaction went to
completion. The assignments of 1H-signals are (in analo-
gy to polystyrene-bound tributylstannyl selenide) based
on multiplicity and line shape without the need of the
COSY spectrum. As expected, the NMR spectra of 8a and
12 show a strong resemblance to those of the correspond-
ing Se-analogues.3 Only the methylene groups, adjacent
to the linking heteroatom, display significant chemical
shift differences. In the case of 8a, the chemical shift of
the methylene protons a (Figure 1a) is 3.0 ppm while it is
3.1 ppm in the Se-analogue. For 12, the chemical shift for
protons l (Figure 1b) is 1.0 ppm while it is 1.1 ppm in the
Se-analogue.
It is not obvious to us why the reactivity of polystyrene-
bound tellurium towards homolysis is lower in compari-
son to polystyrene-bound selenium. A possible explana-
tion could be that traces of elemental tellurium (still
remaining within the resin) are interfering with the radical
chain process in the cleavage step at lower temperature
(<90 °C).
Recently, we have demonstrated that HR–MAS NMR
spectroscopy is a very powerful tool in analysing sub-
strates attached to polystyrene-bound selenium.3 In analo-
gy we are able to monitor the synthesis and cleavage (at
90 °C) of substrates attached to polystyrene-bound tellu-
rium, as exemplified by resins 8a and 12 (Scheme 4).
1
Figure 1 shows the H HR–MAS spectra of polystyrene-
bound tellanyl ether 8a and, after its cleavage, of the re-
sulting polystyrene-bound tributylstannyl telluride 12.
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2326
T. Ruhland et al.
PAPER
Table 1 Cleavage Performance of Polystyrene-Bound Selenium vs. Polystyrene-Bound Tellurium
Entry
Product
Cleavage from
90 °Ca,b
60 °Ca,b
X =
Se
Te
Se
Te
Se
Te
Se
Te
Se
Te
Se
Te
Yield (%)
96
Purity (%)
Yield (%)
Purity (%)
98
1
2
10a
10b
10c
11a
11b
11c
96
100
96
99
95
99
80
99
96
98
95
96
95
55
91
60
87
56
86
57
57
48
86
62
73
100
97
3
97
4
83
100
96
5
94
6
74
99
7
86
96
8
86
100
82
9
51
10
11
12
73
97
99
98
84
95
a Yields are reported for the individual and isolated compound after purification by solid phase extraction (silica gel) and are based on the initial
loading of resins 8a–c and 9a–c.
b Purities are measured by GC–MS.
described procedure is very tenacious compared with
polystyrene-bound selenium. Cleavages were performed
Conclusions
We have described the preparation of polystyrene-bound under radical conditions using tributyltin hydride and
tellurium and its first application in traceless SPOS. Addi- AIBN in toluene. Polystyrene-bound tellurium and seleni-
tionally we demonstrated that substrates attached to this um were compared by their cleavage performance at dif-
linker could be analysed by HR–MAS NMR spectrosco- ferent temperatures. Cleavages at 90 °C and 60 °C from
py. The preparation of polystyrene-bound tellurium by the polystyrene-bound selenium furnished comparable and
Figure 2 Magnitude gradient COSY spectrum of 8a (a) and 12 (b). The relaxation delay was 1.5 s. In both cases, 512 × 64 point matrices
with 4 scans per increment were acquired. In the w1-dimension, linear prediction to 256 complex points was applied. The data were sine-bell
weighted in both dimensions and zero-filled to a final size of 2048 × 512 complex points.
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Traceless Solid Phase Synthesis with Polystyrene-Bound Tellurium
2327
ed NaBH4 (5.0 g, 132.0 mmol) (CAUTION: generation of heat, hy-
drogen, and toxic sodium tellurides). Immediately after the gas
evolution ended, further NaBH4 (5.0 g, 132.0 mmol) was added and
just before the second gas evolution ended, the resin was filtered un-
der Ar and washed with MeOH (3 × 50 mL). The tenacious proce-
dure was repeated approximately 50 times until the main part of
unreacted tellurium was removed. The combined resin fractions
were suspended in MeOH (300 mL) and treated with NaBH4 as de-
scribed above for each single portion. This procedure was also re-
peated approximately 50 times. Finally, the resin and NaBH4 (5 g,
132.0 mmol) were refluxed in EtOH–MeOH (20:1, 300 mL) for 2–
3 h under Ar. The resin was filtered hot and washed with MeOH (3
× 250 mL) and THF (3 × 250 mL). This procedure was repeated 3
times. Finally, the resin was washed with water (3 × 500 mL),
MeOH (3 × 250 mL) and THF (3 × 250 mL). Note: Washing with
CH2Cl2 should be omitted at any time during the entire procedure
because the solvent could couple to the resin. After drying in vacuo
at r.t., an intensively dark red coloured resin (11.7 g) was obtained.
The loading of the resin 3 was calculated to be 2.36 mmol/g as de-
termined by elemental analysis for tellurium after alkylation with
2,4-dichloro benzylchloride as described below.
high yields. In comparison, yields obtained from polysty-
rene-bound tellurium are generally lower and are also
dropping significantly when temperature is changed from
90 °C to 60 °C. Yields for cleavages below 50 °C are
dropping dramatically for both, polystyrene-bound seleni-
um and tellurium, and only traces of the cleaved products
were found at 40 °C. In our hands and under the reported
conditions, polystyrene-bound selenium has shown to be
superior to polystyrene-bound tellurium for its use in
SPOS.
All reactions were carried out under positive pressure of N2. Unless
otherwise noted, starting materials were obtained from commercial
suppliers and used without further purification. THF and toluene
were distilled under N2 from sodium/benzophenone immediately
prior to use. For solid-phase extraction, Scharlau 60 (230–400
mesh) silica gel (sorbil) was used. TLC was performed on Merck 60
F
254 0.25 mm silica gel plates. Unless otherwise stated, the Rf values
were determined with the solvent used for column chromatography.
1H NMR and H-decoupled 13C NMR spectra were recorded at
1
Alkylation of Resin-Bound Tellurium: 2,4-Dichloro Benzyl Tel-
lanyl Polystyrene 5; Typical Procedure
500.13 MHz and 125.67 MHz, respectively, on a Bruker Avance
DRX 500 instrument. HR–MAS NMR spectra of polymer-bound
1
substances were recorded with a 4 mm H/13C double resonance
Polymer-bound tellurium (50 mg) was suspended in EtOH–MeOH
(10:1, 0.5 mL) and treated with NaBH4 (50 mg, 1.3 mmol) at r.t. Af-
ter approximately 1 h, gas and heat generation occurred and the res-
in became swollen and almost colourless. The mixture was stirred
for approximately 5 h until the gas evolution stopped. The resin was
washed with EtOH (1 × 20 mL) under argon and treated with 2,4-
dichloro benzyl chloride (352 mg) in EtOH (0.5 mL). After stirring
for 12 h at r.t., the resin was washed with EtOH (1 × 25 mL), water
(2 × 25 mL), EtOH (1 × 25 mL), water (2 × 25 mL), acetone (1 × 25
mL), and CH2Cl2 (3 × 25 mL) and dried in vacuo at r.t.
HR–MAS probe head optimised for proton observation and
equipped with single axis pulsed field gradient coil. Unless other-
wise noted, compounds were measured in CD2Cl2 (99.8%). Chem-
1
ical shifts for H NMR are reported in ppm with TMS as internal
reference. Chemical shifts for 13C NMR and 1H HR–MAS NMR are
reported in ppm relative to chemical shifts of deuterated solvents.
Coupling constants (J values) are in Hertz. For GC–MS, samples
were dissolved in CH2Cl2 (c = approximately 1 mg/mL). GC was
performed on a Varian Star 3400 CX instrument using an injector
temperature of 200 °C, detector temperature of 325 °C, gas flow of
4.9 mL/min at 65 °C, a split flow of 150 mL/min, and a Restek Rtx-
5 column with a length of 15 m, inner diameter of 0.32 mm, and a
cross-bonded phase of 0.50 mm. A temperature gradient of 15 °C/
min from 65 °C to 275 °C was used. Retention times (Rt values) are
in min. Elemental analyses were performed at the University of Vi-
enna, Department of Physical chemistry (Vienna, Austria), with a
Perkin-Elmer 2.400 CHN elemental analyser. Polystyrene for the
preparation of bromopolystyrene according to the procedure de-
scribed by Ferrall and Fréchet12 was purchased from Rapp Poly-
mere GmbH (Tübingen, Germany) (H 1000, 100–200 mesh,
crosslinked with 1% divinylbenzene).
Anal. Found: C, 55.40; H, 4.28; N, < 0.05; Br, < 0.2; Cl, 13.65; Te,
21.86.
According to the elemental analysis for tellurium, a loading of 1.71
mmol/g was calculated for resin 5, which corresponds to a loading
of 2.36 mmol/g for the initial loading of polystyrene-bound telluri-
um, assuming that the alkylation went to completion. The resins 6
and 7 were prepared according to the procedure described above by
alkylation with 2-[2-(2-chloroethoxy)ethoxy]ethanol and 6-bromo-
hexanol, respectively.
Alkyl Aryl Ether Synthesis by Mitsunobu Reaction: 2-{2-[2-(3-
Methoxyphenoxy)ethoxy]ethoxy}ethyltellanyl Polystyrene 8c;
Typical Procedure
Preparation of Resin-Bound Tellurium; General Procedure
Bromopolystyrene 1 (10.0 g, 36.7 mmol) was pre-swollen in dry
toluene (80 mL) for 15 min, and BuLi (50 mL, 80 mmol, 1.6 M in
hexane) was added. The mixture was stirred for 2 h at r.t., and the
resin was allowed to settle. The solvents were carefully removed by
decantation followed by addition of anhyd toluene (80 mL) and
BuLi (70 mL, 112.0 mmol, 1.6 M in hexane). The suspension was
heated at 60 °C for 3 h. After cooling to r.t., the solvent was re-
moved by decantation without further washing. The mixture was
cooled to 0 °C and additional BuLi (2 mL, 3.2 mmol, 1.6 M in hex-
ane) and anhyd THF (120 mL) were added. Immediately after-
wards, tellurium powder (11.0 g, 86.0 mmol) was carefully added
in small portions (0.5–1.0 g) under intensive stirring (CAUTION:
generation of heat). The black suspension was heated at 50 °C for
16 h and the mixture was cooled to r.t. before filtration. The black
residue was washed with THF (3 × 100 mL), MeOH (1 × 100 mL),
2 N aq HCl–THF (1:2, 1 × 100 mL), and water (3 × 250 mL). For
safety reasons only small portions (approximately 2.5 g) of the res-
idue were suspended in MeOH (100 mL) in a 2 L Erlenmeyer flask
and treated carefully in small portions with excess of fine granulat-
Polystyrene-bound alkyl alcohol 6 (650 mg, 1.16 mmol) was pre-
swollen for 5 min in a solution of triphenylphosphine (1.57 g, 6.0
mmol) and 3-methoxyphenol (745 mg, 6.0 mmol) in 4-methylmor-
pholine (8 mL). Neat diisopropyl azodicarboxylate (1.22 g, 6.0
mmol) was added in small portions over a period of 20 min at r.t.
After the suspension was stirred for 12 h at r.t., the resin was filtered
and subsequently washed with THF (3 × 10 mL), DMSO (2 × 10
mL), THF (2 × 10 mL), water (2 × 10 mL), MeOH (2 × 10 mL), and
CH2Cl2 (3 × 10 mL) and dried in vacuo at r.t. for 12 h. An almost
colourless resin 8c (730 mg) was obtained which was calculated to
have a loading of 1.51 mmol/g, assuming the Mitsunobu reaction
went to completion. The resins 8a, 8b, 9a, 9b and 9c were prepared
according to the procedure described above.
Cleavage by Homolysis: 1-[2-(2-Ethoxyethoxy)ethoxy]-3-meth-
oxybenzene 10c; Typical Procedure
Resin 8c (0.60 g, 0.91 mmol) was pre-swollen for 5 min in a freshly
prepared solution of tributyltin hydride (1.11 g, 3.82 mmol) and
AIBN (10 mg, 61 mmol) in anhyd toluene (6 mL). The mixture was
heated in a sealed tube to 90 °C for 12 h. After cooling to r.t., the
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T. Ruhland et al.
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Affleck, R. L.; Lillig, J. E. J. Am. Chem. Soc. 2000, 122,
resin was filtered and washed with THF (2 × 2 mL), acetone (2 × 2
mL), and CH2Cl2 (2 × 2 mL). The filtrates were combined, and the
solvents removed in vacuo. The residue was purified by solid-phase
extraction. Non-polar tin impurities were removed by washing the
column with pure hexane. Subsequently, elution with heptane–
EtOAc (15:1) gave 161 mg (74%; GC–MS purity: 99%) of 10c. The
same experiment, carried out at 60 °C instead of 90 °C, furnished
122 mg (56%, GC–MS purity: 99%). The aryl alkyl ethers 10a, 10b,
11a, 11b and 11c were prepared (at 60 °C and 90 °C) and purified
by solid phase extraction, according to the procedure above. Yields
and GC–MS purities are given in Table 1. 1H NMR and 13C NMR
data were identical to those given in the literature.3
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Acknowledgment
The helpful secretarial assistance of Ms. Annick Somerville is high-
ly appreciated.
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