Development and Application of a Poly(ethylene glycol)-Supported Triarylphosphine Reagent: Expanding the Sphere of Liquid-Phase Organic Synthesis

Article abstract of DOI:10.1021/jo9903712

Continuing studies into the utility of poly(ethylene glycol) (PEG)-supported triarylphosphines as functional polymer reagents in liquid-phase organic synthesis (LPOS) are being pursued. This report describes the synthesis and NMR characterization of an aryl-alkyl ether-linked PEG-triarylphosphine derivative (2) and its subsequent application in LPOS. The utility of 2 as a mild stoichiometric reagent for ozonide reduction has been demonstrated, and a direct comparison between 2, a Merrifield resin-bound triarylphosphine derivative, and a solution-phase triphenylphosphine reagent revealed that the highest observed yields occur under liquid-phase conditions. Transformation of phosphine 2 into a phosphonium salt (3) then allowed the inherent aqueous solubility of PEG-functionalized moieties to be exploited by enabling a Wittig reaction, between a range of aldehydes and 3, to occur under mildly basic aqueous conditions. This led to the generation of substituted stilbenes in good to excellent yields. Finally, regeneration of 2 was achieved by reduction of the PEG-supported triphenylphosphine oxide byproduct 4 with alane (100% conversion, 75% yield). This combination of reaction, recovery, and regeneration expands the utility of PEG-supported triarylphosphine reagents across the spectra of both organic chemistry and solution-phase combinatorial strategies.

Full text of DOI:10.1021/jo9903712

5
188
J . Org. Chem. 1999, 64, 5188-5192
Develop m en t a n d Ap p lica tion of a P oly(eth ylen e
glycol)-Su p p or ted Tr ia r ylp h osp h in e Rea gen t: Exp a n d in g th e
Sp h er e of Liqu id -P h a se Or ga n ic Syn th esis
,
†
Frank Sieber, Paul Wentworth J r.,* J onathan D. Toker, Anita D. Wentworth,
§
,‡
William A. Metz, Neal N. Reed, and Kim D. J anda*
Department of Chemistry, The Scripps Research Institute and the Skaggs Institute for Chemical Biology,
1
0550 North Torrey Pines Road, La J olla, California 92037
Received March 2, 1999
Continuing studies into the utility of poly(ethylene glycol) (PEG)-supported triarylphosphines as
functional polymer reagents in liquid-phase organic synthesis (LPOS) are being pursued. This report
describes the synthesis and NMR characterization of an aryl-alkyl ether-linked PEG-triarylphos-
phine derivative (2) and its subsequent application in LPOS. The utility of 2 as a mild stoichiometric
reagent for ozonide reduction has been demonstrated, and a direct comparison between 2, a
Merrifield resin-bound triarylphosphine derivative, and a solution-phase triphenylphosphine reagent
revealed that the highest observed yields occur under liquid-phase conditions. Transformation of
phosphine 2 into a phosphonium salt (3) then allowed the inherent aqueous solubility of PEG-
functionalized moieties to be exploited by enabling a Wittig reaction, between a range of aldehydes
and 3, to occur under mildly basic aqueous conditions. This led to the generation of substituted
stilbenes in good to excellent yields. Finally, regeneration of 2 was achieved by reduction of the
PEG-supported triphenylphosphine oxide byproduct 4 with alane (100% conversion, 75% yield).
This combination of reaction, recovery, and regeneration expands the utility of PEG-supported
triarylphosphine reagents across the spectra of both organic chemistry and solution-phase
combinatorial strategies.
In tr od u ction
For many years functionalized polymers have been
ered reactivities, site-site interactions, extended reaction
times, diffusion-limited reactivity, and reagent leaching,
5
have meant that soluble matrixes such as poly(ethylene
employed as stoichiometric reagents and catalysts, and
also for reaction purification. However, their development
and application in organic synthesis is undergoing a
tremendous renaissance at present and is undoubtedly
being fueled by the special requirements of both combi-
natorial and “green” chemistry.1,2 There are a number of
key advantages which link functionalized polymers to
synthetic chemistry, including ease of product isolation,
the ability to use an excess of reagents to drive a reaction
to completion, and the fact that they can, in certain cases,
be recycled for repeated use. In addition, solution-phase
combinatorial chemistry is demanding an ever expanding
6
7
8-10
glycol) (PEG), fluorous supports, linear poly(styrenes),
11
and poly(ethylenes) are receiving increasing attention
both for combinatorial synthesis and as supports for
heterogeneous catalysts.
Our group recently communicated an extension of
PEG-supported chemistry into the field of functionalized
12-14
polymers as reagent supports.
We prepared a novel
triarylphosphine derivative of PEG (1) and showed that,
when compared to a heterogeneous commercially avail-
able counterpart, it possesses favorable reaction kinetics
in both the Staudinger and Mitsunobu etherification
reactions. The present study expands on those prelimi-
nary investigations in the following ways. The synthesis
and NMR characterization of the more stable (ether-
linked) PEG-triarylphosphine derivative 2 is reported.
The application of 2 is then studied in the context of
LPOS for a redox reaction involving ozonide decomposi-
tion. In parallel, a comparison of the soluble polymer-
supported phosphine 2 with a solid-phase triarylphos-
“
tool box” of polymer-supported reagents and catalysts
to sustain the plethora of chemistries being probed for
both library construction and purification.3
,4
At present, the vast majority of available functionalized
polymers are insoluble, being polystyrene based and
possessing either low (Merrifield resin) or high (macro-
porous resins) degrees of cross-linking.1 However, emerg-
ing problems associated with the use of insoluble poly-
meric derivatives under heterogeneous conditions, low-
,2
(
(
(
5) Gravert, D. J .; J anda, K. D. Chem. Rev. 1997, 97, 489-509.
6) Geckeler, K. E. Adv. Polym. Sci. 1995, 121, 31-79.
7) Curran, D. P. Science (Washington, D.C.) 1997, 275, 823-826.
†
Telephone: (619) 784-2476. Fax: (619) 784-2590. E-mail: paulw@
(8) Chen, S.; J anda, K. D. J . Am. Chem. Soc. 1997, 119, 8724-8725.
(9) Chen, S.; J anda, K. D. Tetrahedron Lett. 1998, 39, 3943-3946.
(10) Harrison, C. R.; Hodge, P.; Hunt, B. J .; Khoshdel, E.; Richard-
son, G. J . Org. Chem. 1983, 48, 3721-3728.
(11) Caraway, J . W.; Bergbreiter, D. E. Chem. Ind. 1996, 68, 361-
366.
scripps.edu.
‡
Telephone (619) 784-2515. Fax: (619) 784-2595. E-mail:
kdjanda@scripps.edu.
§
On sabbatical leave from Hoechst-Marrion Roussel, New J ersey.
(
1) Shuttleworth, S. J .; Allin, S. M.; Sharma, P. K. Synthesis 1997,
7, 1217-1239.
2) Sherrington, D. C.; Hodge, P. In Synthesis and Separations Using
Functional Polymers; J ohn Wiley & Sons: New York, 1988.
3) Wentworth, P., J r.; J anda, K. D. Curr. Opin. Biotech. 1998, 9,
09-115.
4) Booth, R. J .; Hodges, J . C. Acc. Chem. Res. 1999, 32, 18-26.
2
(12) Wentworth, P., J r.; Vandersteen, A. M.; J anda, K. D. Chem.
Commun. 1997, 759-760.
(
(13) Wipf, P.; Venkatraman, S. Tetrahedron Lett. 1996, 37, 4659-
(
4663.
1
(14) Harris, J . h.; Liu, Y.; Chai, S.; Andrews, M. D.; Vederas, J . C.
J . Org. Chem. 1998, 63, 2407-2409.
(
1
0.1021/jo9903712 CCC: $18.00 © 1999 American Chemical Society
Published on Web 06/16/1999

Poly(ethylene glycol)-Supported Triarylphosphine Reagent
J . Org. Chem., Vol. 64, No. 14, 1999 5189
phine reagent and a solution-phase reagent is undertaken.
Subsequent transformation of 2 into polymer-supported
phosphonium salt 3 then facilitates the first example of
polymer-supported Wittig reactions in aqua. Finally, with
the concept of economy firmly entrenched in our strategy,
the regeneration of the oxidized phosphine 4 is examined,
such that reagent 2 can be facilely recycled for continued
use.
Sch em e 1
The synthetic strategy involves an initial concise
preparation of the key hydroxyphosphine 5,16 followed by
1
7
its attachment to PEG via the dimesylate 6. p-Bro-
mophenol 7 was protected as the TBDMS ether 8, which
1
8
was then phosphinylated under standard conditions to
give the triarylphosphine 9. The silyl ether was removed
and the resultant hydroxyphosphine 5 was obtained in
8
5% yield for the three steps. Mesylate 6 was obtained
by heating (50 °C) a neat solution of PEG3400 10 in
methanesulfonyl chloride. No base was required under
these conditions, which had the benefit that the purifica-
1
7
tion of 6 was simplified from its original preparation.
Etherification between 6 and 5 was performed in rigor-
ously degassed DMF. Phosphine 2 was then isolated by
addition of the reaction mixture into degassed diethyl
ether, followed by filtration and sequential washing of
the polymeric precipitate with i-Pr alcohol (to remove
salts) followed by diethyl ether to give reagent 2 in 92%
Resu lts a n d Discu ssion
Syn th esis of Liqu id -P h a se P h osp h in e Rea gen t 2.
For a successful functional polymer-supported reagent
strategy, two features have to be optimal: loading and
stability across a broad range of reaction conditions.
When choosing a soluble polymer for liquid-phase syn-
thesis, a compromise has to be reached between loading
capacity and solubility profile. In the original report,
dihydroxy-PEG of molecular weight 3400 (PEG3400, equiva-
lent to a loading of ca. 0.5 mmol g-1) was found to be the
lowest molecular weight PEG that when functionalized
as reagent 1 would reproducibly maintain its physical
3
1
yield, based on the weight of polymer isolated. P NMR
confirmed that the oxidation state of the phosphine
termini of 2 were P(III) (δ -6.4 ppm) with little detectable
P(V) (δ 28 ppm) contamination (<2%) (Figure 1,a and
1
b). H NMR of 2 also confirms the oxidation state of the
phosphine termini, with the chemical shift of the aro-
matic ring protons clearly being dependent on the pres-
ence or absence of the phosphinyl oxygen bond. The
oxidation state of the phosphine termini of 2 was rou-
tinely quantified by 31P NMR after certain periods of
storage. This revealed that even after prolonged exposure
to air (2-3 weeks), little oxidation to the phosphine oxide
(<5%) occurs.
properties: soluble in H
2
O, DMSO, DMF, dichloromethane
(
CH Cl ), toluene, benzene, and warm THF but insoluble
2
2
in diethyl ether, t-Bu ether, and i-Pr alcohol. For this
study, therefore, dihydroxy-PEG3400 was again selected
as the matrix of choice. A concern with the original
reagent (1) was the carbamate ester moiety incorporated
as a linker between the triarylphosphine and the PEG
support. The known base and acid sensitivity of the
urethane linkage, coupled with worries about its lability
in the presence of Lewis acids and metalating reagents,
linked any further exploitation of PEG-supported tri-
arylphosphines to an immediate replacement of this
carbamate ester group. An aryl-alkyl ether moiety was
chosen as the replacement linker, the chemical stability
of which is comparable to that of the poly(ethylene oxide)
backbone; therefore reagent 2 became the functionalized
polymer of choice. Reported herewith is the primary high-
yielding synthesis, isolation, and characterization of pure
The derivatization level of the polymer is also deter-
1
mined by inspection of the H NMR of 2. The chemical
shift of R-methylene protons of PEG and its derivatives
is a function of the moiety attached to the termini
hydroxyl groups. For underivatized PEG3400 the chemical
shift of these R-protons is δ 3.8 ppm, for PEG-mesylate
6
this changes to δ 4.35 ppm (also detectable are the
â-methylene protons δ 3.74 ppm), and for the phosphine-
terminated polymer 2 this changes to δ 4.16 ppm (â-
1
methylene protons δ 3.64 ppm). Inspection of the H NMR
(16) A recent report descibes a one-step route to phosphine 5 in
P(III) bistriphenylphosphine terminated poly(ethylene
moderate yield (63% yield) [Herd, H.; Hessler, A.; Hingst, W.; Tepper,
M.; Stelzer, O. J . Organomet. Chem. 1996, 522, 69-76]. However, in
our hands the obtained yields were even lower (38%). Therefore, we
adopted a three-step approach to 5, with the overall yield being 85%
(Scheme 1).
(17) Zhao, X.-Y.; J anda, K. D. Tetrahedron Lett. 1997, 38, 5437-
5440.
glycol) 2 (Scheme 1).15
(15) A recent report attempts the synthesis of 2 for use as a
macroinitiator in block copolymer synthesis (Choi, Y. K.; Bae, Y. H.;
Kim, S. W. Macromolecules 1995, 28, 8419-8421). However, the
authors observed significant oxidation of the phosphine end groups
during its isolation which they did not isolate in pure form.
(18) Relles, H. M.; Schluenz, R. W. J . Am. Chem. Soc. 1974, 96,
6469-6475.

5
190 J . Org. Chem., Vol. 64, No. 14, 1999
Sieber et al.
F igu r e 1. (A) H and 31P NMR spectra of PEG-supported triarylphosphine 2. (B) H and 31P NMR spectra of PEG-supported
1
1
triarylphosphine 4.
of 2 shows that no mesylate 6 remains. However,
potential side reactions during the workup procedure,
following the etherification reaction, to generate 2 could
invoke alternative routes of hydrolysis of the methane-
sulfonate ester of 6. Washing of the isolated precipitate
from the etherification reaction with i-Pr alcohol contain-
ing traces of water could conceivably lead to contamina-
tion with either polymer bound i-Pr ether or free hydroxyl
chemistry, however, because of the problems of removing
both the excess PPh and reaction byproduct, tri-
phenylphosphine oxide, from the reaction mixture. The
use of polystyrene-supported PPh as a stoichiometric
reagent for this reaction has been reported as an alterna-
3
3
2
1
tive and gives good to excellent yields of aldehydes.
Therefore, an important part of this study was a direct
comparison between this new liquid-phase approach with
2 and a solid-phase approach with commercially available
1
termini. However, the H NMR of 2 reveals no signals to
support such a conclusion; therefore there is high confi-
dence that the polymeric phosphine 2 is quantitatively
substituted with terminal triarylphosphine residues (ca.
PPh
A range of alkenes 11a -e were treated with ozone at
-78 °C in CH Cl until a blue reaction mixture persisted.
At this point the excess ozone was removed by purging
with N . The incipient ozonides were then decomposed
into the product aldehydes (12a -e) by addition of one of
three reagents: PPh , polystyrene-supported PPh , or
(2). The results are tabulated in
3
.
2
2
-
1
0
.5 mmol g ).
The ease of NMR characterization of soluble polymer
2
reagent 2 offers a considerable advantage over its solid-
phase homologue which, to determine the oxidation state
of the phosphine center, must involve either gel- or solid-
phase NMR or single-bead FTIR techniques.19
3
3
PEG-supported PPh
Table 1.
3
Liqu id -P h a se Ozon id e Red u ction . As an entry level
into the utility of 2 in organic chemistry, the mild
chemical decomposition of ozonides was selected. Ozo-
nolysis of alkenes has a broad scope of application in
organic chemistry, and the range of methods for destruc-
tion of the intermediary ozonides is equally broad.
However, the two major methods of choice, Zn/acetic acid
or dimethyl sulfide, have limitations, a result of potential
chemical substituent sensitivity in the former case or
noxious reagents and high-boiling-point byproducts in the
The isolation procedure for the PEG-supported reagent
involved a simple precipitation of the spent reagent into
ether and concentration. This consistently removed >99%
of the polymer byproduct. Passage of the ether concen-
trate through a short silica pad completely removed the
remaining polymer traces, giving the product aldehydes
in analytically pure form. The solid-phase reagent was
separated from the reaction mixture by filtration. The
product was isolated by then washing the resin with
2 2
volumes of CH Cl . The solution-phase reactions were
latter. For these reasons PPh
3
is an excellent alterna-
tive.20 It has received only limited use in solution-phase
(20) Feiser, M.; Feiser, L. F. In Reagents for Organic Synthesis; Mir,
Moscow: USSR, 1978; pp 1238-1239.
(
21) Ferraboshi, P.; Gambero, C.; Azadani, M. N.; Santaniello, E.
(19) Yan, B. Acc. Chem. Res. 1998, 31, 621-630.
Synth. Commun. 1986, 16, 667-672.

Poly(ethylene glycol)-Supported Triarylphosphine Reagent
J . Org. Chem., Vol. 64, No. 14, 1999 5191
efforts in recent years.2
2-24
There are isolated examples
Ta ble 1. Dir ect Com p a r ison of Ozon id e Hyd r olysis
betw een Solu tion -P h a se, Solid -P h a se, a n d Liqu id -P h a se
Tr ip h en ylp h osp h in e
25
of Wittig reactions in water: nitrostyrenes, p-carboxy-
26
27
styrene, and vitamin A acetate have all been synthe-
sized in water via aqueous formaldehyde and their
respective ylides. However, Wittig reactions with less
reactive aldehydes resulted in hydrolysis of the phospho-
nium salts.28 Wittig reactions and Horner-Wadsworth-
Emmons reactions when conducted in the presence of
water generally occur under biphasic conditions with a
phase transfer catalyst, undoubtedly due to the limita-
tions imposed by the solubility and stability of the
phosphonium salts and/or the component aldehydes and
ketones.2
9-33
The Wittig olefination reaction has been much studied
throughout the evolution of cross-linked polymer-sup-
ported reagents, and considerable success has been
achieved.3
4-39
Bernard and Ford noted an inverse
39
correlation between the yield of alkene obtained from
polymer-supported Wittig reagents with aldehydes and
ketones in solution and the degree of divinylbenzene
(DVB) cross-linking in the resin. Progressing from 0.5 to
2
0% DVB cross-linking, i.e., from gel to macroporous
resins, can result in a fall of 20% in the yield of alkenes.
These results suggested that a soluble polymer-supported
phosphonium salt may give excellent yields in the Wittig
reaction.
The physical properties of the PEG backbone are such
that a PEG-supported phosphonium salt would be emi-
nently water soluble and offer the tantalizing prospect
of facilitating the first soluble polymer-supported Wittig
olefination reactions in aqua. Treatment of PEG-sup-
ported phosphine 2 with benzyl bromide followed by
precipitation into diethyl ether yielded the soluble polymer-
supported benzyltriarylphosphonium salt 3 in 81% yield
a
Reaction conditions: the respective triphenylphosphine (2
equiv) was added to the ozonide (1 equiv) of the alkene in CH2Cl2
and left to stir for 2 h. Yields are based on HPLC comparison to
authentic product standards. Commercially available PPh3 (Al-
drich). Commercially available polystyrene-PPh3 resin (Aldrich).
Isolated yield.
b
c
d
(
based on the weight of polymer obtained). This polymeric
purified by silica gel chromatography to remove the
excess PPh and the byproduct PPh O.
3 3
phosphonium salt (3) is completely soluble in water at
pH 7. The reaction of this novel Wittig salt (3) was then
studied with a range of aldehydes (12a and 13a -d ) in
aqueous sodium hydroxide solution (Scheme 2). The
results are tabulated in Table 2.
Generally, it is considered that liquid-phase chemistry
can be wasteful in terms of the volumes of solvents
required to precipitate the polymer support at the end
of the reaction (in relation to solid-phase methods). When
one is working with functionalized resins, however, the
product is present in solution; therefore the resin has to
be washed copiously to obtain the product in optimal
The isolated yields of the alkenes 14a -e by this
method were good to excellent, proving that the rate of
reaction of the ylide with the substrate aldehydes is
indeed much faster than decomposition to 4. Isolation of
the stilbenes (14a -e) was achieved by partitioning the
2 2
yield. In our hands, the volumes of CH Cl required to
completely wash out the aldehyde products from the
Merrifield resin were comparable to that of the diethyl
ether necessary to precipitate the spent PEG reagent.
In all cases studied, the yields of aldehyde were highest
with the soluble polymer-supported reagent 2, and with
the exception of 12d the soluble reagent gave higher
yields than the solid-phase reagent. This result may be
a composite of three factors: increased reducing power
of the soluble polymer-supported phosphine 2 when
compared to both the solid- and solution-phase reagents,
a result of the p-ethoxy ether functionality which links
the reagent to the soluble polymer support, the homoge-
neous nature of the ensuing chemical process when
compared to the hetereogeneous resin reagent, and the
ease of isolation and purification of the products when
compared with solution-phase strategy.
2 2
reaction mixture with CH Cl , followed by removal of the
(
(
24) Lubineau, A.; Aug e´ , J .; Queneau, Y. Synthesis 1994, 741-760.
25) Butcher, M.; Mathews, R. J .; Middleton, S. Aust. J . Chem. 1973,
26, 2067-2069.
(26) Broos, R.; Tavernier, D.; Anteunis, M. J . Chem. Educ. 1978,
5
5, 813.
27) Schleich, K.; Zollikerberg, C. H.; Stoller, H.; Reinach, C. H.
Chem. Abstr. 1977, 88, P7191170e.
(
(
(
(
28) Broos, R.; Antenius, M. Synth. Commun. 1976, 6, 53-57.
29) Markl, G.; Merz, A. Synthesis 1973, 295-297.
30) Piechucki, C. Synthesis 1976, 187-188.
(31) D’Incan, E.; Seyden-Penne, J . Synthesis 1975, 5, 516-517.
(
32) Mikolajczyk, M.; Grzejszczak, S.; Midura, W.; Zatorski, A.
Synthesis 1975, 278-280.
33) Mikolajczyk, M.; Grzejszczak, S.; Midura, W.; Zatorski, A.
Synthesis 1976, 396-398.
34) McKinley, S. V.; Rakshys, J . W. J . Chem. Soc., Chem. Commun.
972, 134-135.
35) Heitz, W.; Michels, R. Angew. Chem., Int. Ed. Engl. 1972, 11,
(
(
1
(
Liqu id -P h a se Wittig Rea ction s in Aqu a . Organic
chemistry in water has been the focus of considerable
298-299.
(
36) Heitz, W.; Michels, R. J ustus Liebigs Ann. Chem. 1973, 227-
2
30.
(
37) Clarke, S. D.; Harrison, C. R.; Hodge, P. Tetrahedron Lett. 1980,
(
22) Li, C.-J .; Chan, T.-H. In Organic Reactions in Aqueous Media;
J ohn Wiley & Sons: New York, 1997.
23) Li, C.-J . Chem. Rev. 1993, 93, 2023-2035.
21, 1375-1378.
(38) Hodge, P.; Waterhouse, J . Polymer 1981, 22, 1153-1154.
(39) Bernard, M.; Ford, W. T. J . Org. Chem. 1983, 48, 326-332.
(

5
192 J . Org. Chem., Vol. 64, No. 14, 1999
Sieber et al.
Sch em e 2
Ta ble 3. Regen er a tion of P EG-Su p p or ted
Tr ia r ylp h osp h in e 2
P(V) to
a
entry
reagent
conditions
CH2Cl2/rt
benzene/reflux 20 h
THF/reflux 20 h
benzene/reflux 20 h
THF/rt 30 min
P(III), %
b
1
2
3
4
5
PMHS, CH2Cl2
20
33
40
56
100
PMHS
PMHS
HSiCl3c
AlH3‚THF
a
Measured by 31P NMR of the reaction mixtures. b Polymeth-
ylhydrosiloxane. c With triethylamine.
polymer interactions between the polymeric reductant
Ta ble 2. Aqu eou s Wittig Rea ction s betw een
P EG-Su p p or ted P h osp h on iu m Sa lt 3 a n d Ald eh yd es (12a
42,43
and the PEG backbone. Trichlorosilane,
while leading
to a significant reduction of the phosphine group (56%),
completely cleaved the terminal phosphine from the
polymer. However, quantitative reduction of 4 was
a n d 13a -d )
a
entry
aldehyde
conditions
yield, % (E/Z ratio)b
4
4
1
2
3
4
5
6
7
8
13a
1 N NaOH, rt
1 N NaOH, 90 °C
1 N NaOH, rt
1 N NaOH, 90 °C
1 N NaOH, rt
1 N NaOH, rt
65 (56:44)
62 (75:25)
80 (46:54)
78 (75:25)
95 (48:52)
38 (49:51)
49 (47:53)
63 (54:46)
3
achieved with freshly prepared alane (AlH ) in THF as
31
determined by P NMR vide supra. The polymer was
isolated in 75% yield following the usual precipitation
into degassed ether. The incomplete polymer recovery is
attributed to problems associated with the byproduct
aluminum salts either complexing to the polymer support
and thus preventing precipitation or polymer-backbone
hydrolysis during the reduction process.
13b
13c
12a
1 N NaOH, 90 °C
1 N NaOH, rt
13d
a
All yields are isolated stilbenes (14a -e). b Determined by H
NMR of the crude mixture.
1
In conclusion, we have generated stable PEG-tri-
arylphosphine derivative 2 as a stoichiometric reagent
for a number of key chemical reactions. The broad nature
of triphenylphosphine as a reagent in organic chemistry
means that the potential scope of 2 is very wide. A direct
comparison of the utility of this reagent (2) with a
Merrifield-bound reagent and triphenylphosphine in
solution has revealed that the observed yields for ozonide
reduction are greatest under the liquid-phase conditions.
In addition, the conferred water solubility of phospho-
nium salt 3 has facilitated high-yielding Wittig reactions
under aqueous condition, a reaction inconceivable with
Merrifield-supported triphenylphosphine. The utility of
this reagent was made complete by its facile regeneration
by quantitative reduction with alane and reisolation in
water by addition of anhydrous magnesium sulfate and
then precipitation of the polymer-supported triphenylphos-
phine oxide byproduct 4 into diethyl ether and concentra-
tion of the etheric solution to dryness.
In a recent report describing Wittig reactions in basic
aqueous media with base soluble phosphonium salts, the
authors noted that the E:Z ratio, under certain condi-
tions, was skewed during the product isolation process
4
0
which involved filtration of the reaction mixture. The
liquid-phase strategy with 3 which involves partitioning
is much more powerful, because it allows full extraction
of both isomeric stilbenes without having to worry about
contamination with the byproduct phosphine oxide which
is removed by a simple precipitation.
7
5% yield.
To explore the scope of this reaction, two components
were varied: base strength and temperature. Increasing
the base strength (from 1 to 2 N NaOH) neither affected
the yield of stilbenes (14a -e) nor the E:Z isomer distri-
bution. However, elevating the temperature (up to 90 °C)
resulted in improved yields of 14d and as to be expected
an increase in the E:Z ratio for all the stilbene products.
Regen er a tion of Sp en t Rea gen t 4. A number of
standard methods were employed to regenerate the
oxidized polymer-supported phosphine 4 (Table 3). Only
poor to moderate reduction of 4 to 2 occurred with
polymethylhydrosiloxane (PMHS)41 using various condi-
tions. The reason is perhaps due to unfavorable polymer-
Insoluble polymer-supported strategies for organic
chemistry and solution-phase combinatorial strategies
are in a rapid phase of expansion at the moment. Soluble
polymer supported strategies are developing in parallel
and offer unique potentials, both in terms of the reactions
available and the solvents in which they can be con-
ducted. This report pushes back the boundary of soluble
polymers as supports for stoichiometric reagents showing
the broad solvent breadth that may be exploited and
highlighting the regeneration of the reagent for recycling.
Ack n ow led gm en t. This work was supported by the
Skaggs Institute for Chemical Biology. J .D.T. acknowl-
edges FCAR-Qu e´ bec. W.A.M. thanks HMR for support
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