Synthesis of new water-soluble phosphonium salts and their Wittig reactions in water

Article abstract of DOI:10.1039/a909495d

Some new water-soluble alkyltriarylphosphonium salts are reported. Their solubility is due to the presence of either carboxy or hydroxy groups on the phenyl rings attached to phosphorus. Examples of both benzyl-and butylphosphonium salts are presented and investigation into their Wittig reactions with a range of aldehydes using water as the solvent is described. The Royal Society of Chemistry 2000.

Full text of DOI:10.1039/a909495d

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Synthesis of new water-soluble phosphonium salts and their Wittig
reactions in water
Matthew G. Russell and Stuart Warren*
1
University Chemical Laboratories, Lensfield Road, Cambridge, UK CB2 1EW
Received (in Cambridge, UK) 1st December 1999, Accepted 22nd December 1999
Some new water-soluble alkyltriarylphosphonium salts are reported. Their solubility is due to the presence
of either carboxy or hydroxy groups on the phenyl rings attached to phosphorus. Examples of both benzyl-
and butylphosphonium salts are presented and investigation into their Wittig reactions with a range of aldehydes
using water as the solvent is described.
Introduction
reason for pre-mixing the reagents in the reactions above).
Deprotonation of the phosphonium salt to give the ylide is also
likely to be in competition with the alkaline hydrolysis of the
We have previously reported new phosphonium salts designed
to be soluble in aqueous base and their Wittig reactions in water
14
phosphonium salt to give the phosphine oxide.
1
with substituted benzaldehydes. In this paper, we report more
fully on the synthesis and chemistry of these and other new
phosphonium salts and discuss the limitations of carrying out
Wittig reactions in water. Generally, reactions in water have a
lower impact on the environment than reactions carried out in
organic solvents. The Wittig reaction is a good candidate for
aqueous conditions with the additional benefit that any water-
soluble phosphine oxide by-products could be more easily
separated from the olefin products.
Results and discussion
Synthesis of new phosphonium salts
We have designed several phosphonium salts which are soluble
in aqueous base; these are derived from alkyltriphenyl-
phosphonium salts where the phenyl rings bear groups to pro-
mote solubility in water. Our initial targets were phosphonium
bromides 1a and 1b (with one phenyl group bearing a p-COOH
Wittig reactions and Horner–Wadsworth–Emmons reactions
have previously been carried out in the presence of water, most
typically in either biphasic solutions using strong bases (e.g.
2–6
aqueous 50% sodium hydroxide)
or in an organic solvent
with trace amounts of water using solid sodium hydroxide or
7–9
sodium carbonate.
In both these instances, the natural
behaviour of phosphonium salts as phase transfer catalysts is
used to promote the formation of the ylides used in the reac-
tion. In Horner–Wadsworth–Emmons reactions, tetrabutyl-
ammonium iodide is sometimes added as a phase transfer
4–6
catalyst.
There are fewer examples of aqueous Wittig reactions
carried out in the absence of organic solvent; the first example
is the reaction of (nitrobenzyl)triphenylphosphonium bro-
10
mides with formaldehyde to give nitrostyrenes. The synthesis
of p-carboxystyrene from ( p-carboxyphenylmethyl)triphenyl-
11
phosphonium bromide is also known. The authors note that
in these cases, only formaldehyde could be used in the Wittig
reactions; attempts with other aldehydes proved unsuccess-
12
ful. Vitamin A acetate is synthesised industrially in water. In
all cases, pre-mixing of phosphonium salt and aldehyde was
necessary for the reaction to proceed.
What is perhaps surprising is that fairly dilute solutions of
aqueous base (10–20% aqueous sodium hydroxide or sodium
carbonate) were used to form the ylides. The proton removed to
form the ylide in benzyl- or allylphosphonium salts has a pK
a
13
value in the region of 17–18; in these weak aqueous bases,
complete deprotonation will not occur. As long as the ylide is in
equilibrium with the phosphonium salt, however, the Wittig
reaction may proceed.
group); this substituent was known to promote solubility in the
synthesis of p-carboxystyrene and should have a minimal elec-
tronic effect on the phosphonium salt. Other phosphonium
bromides (2–5) contain one or more phenyl groups with a
hydroxy substituent in either a para or meta position relative to
phosphorus. These substituents were chosen as they will be
deprotonated in aqueous base and the resulting charged species
may be soluble in water.
Although these isolated examples of aqueous Wittig reac-
tions are known, we expected some difficulty in developing a
more general method. Specifically, side-reactions may compete
with Wittig reactions using aqueous base. Enolisable aldehydes
easily undergo self-condensation in carbonate or hydroxide
solution at room temperature or below (and this may be the
Phosphonium bromides 1a and 1b were synthesised from
phosphine 6 and benzyl bromide in refluxing toluene or
DOI 10.1039/a909495d
J. Chem. Soc., Perkin Trans. 1, 2000, 505–513
This journal is © The Royal Society of Chemistry 2000
505

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Table 1 Phosphines and methoxy- and hydroxy-substituted phosphonium salts
Methoxy-substituted
phosphonium salt
Hydroxy-substituted
phosphonium salt
Phosphine
Yield (%)
Yield (%)
Yield (%)
8
8
8
(4-OMe; n = 1)
(3-OMe; n = 1)
(4-OMe; n = 2)
86
55
76
9 (4-OMe; n = 1; R = Ph)
97
75
87
81
87
2a (4-OH; n = 1; R = Ph)
2b (4-OH; n = 1; R = Pr)
3a (3-OH; n = 1; R = Ph)
3b (3-OH; n = 1; R = Pr)
4 (4-OH; n = 2; R = Ph)
5 (3-OH; n = 2; R = Ph)
99
61
95
91
95
40
9
(4-OMe; n = 1; R = Pr)
9 (3-OMe; n = 1; R = Ph)
(3-OMe; n = 1; R = Pr)
9 (4-OMe; n = 2; R = Ph)
(3-OMe; n = 2; R = Ph)
9
a
9
81
a
Yield calculated from one-pot reduction–alkylation of phosphine oxide 10.
refluxing bromobutane respectively. Phosphine 6 was obtained
conveniently “protects” the phosphorus against oxidation in
the demethylation step.
15
by a modified literature procedure; we found that the Grig-
nard reagent derived from phosphine 7 when reacted with car-
bon dioxide gave the required phosphine 6 in an improved 62%
yield over the literature method which uses n-butyllithium.
Phosphonium bromide 1a was obtained in 37% yield over the
three steps; phosphonium bromide 1b was obtained in 36%
overall yield (Scheme 1).
A fast and reliable method for distinguishing between phos-
phines, phosphine oxides and phosphonium salts was essential
to be certain of the oxidation state of the phosphorus in these
reactions. Although a mass spectrum can identify the molecular
1
2
ion, we discovered that we were able to use the J and J
CP
CP
13
coupling constants of the C NMR signals of the aryl groups
attached to phosphorus. Phosphines show coupling constants
of 8–12 and 19–21 Hz respectively, phosphine oxides have
coupling constants of 100–110 and 9–12 Hz respectively and
phosphonium salts coupling constants of 84–94 and 9–12 Hz
respectively, allowing a clear assessment of the nature of the
phosphorus compound.
An unexplained oxidation was observed in the reaction of m-
bromoanisole with dichlorophenylphosphine; a mixture of the
required phosphine 8 (3-OMe; n = 2) and the phosphine oxide
1
0 was obtained. The mixture was oxidised with hydrogen per-
oxide to give the phosphine oxide 10 in a quantitative yield.
Phosphonium bromide 9 (3-OMe; n = 2; R = Ph) was syn-
thesised directly from the phosphine oxide by a one-pot
reduction with polymethylhydrosiloxane and titanium()
Scheme 1
17
isopropoxide and subsequent alkylation with benzyl bromide
in 81% yield.
The hydroxy-substituted phosphonium bromides 2–5 were
synthesised from the corresponding m- or p-bromoanisoles. The
Grignard derivatives were quenched with either chlorodiphenyl-
phosphine (for the series with one hydroxyphenyl substituent)
or dichlorophenylphosphine to give (methoxyphenyl)phos-
phines 8 in good yields. Phosphonium bromides 9 were syn-
thesised using similar conditions to those outlined above and
were subsequently demethylated in refluxing hydrobromic acid
to give the hydroxy-substituted phosphonium salts 2–5 (Scheme
In spite of these difficulties, we obtained the methoxy-
substituted phosphonium salts 9 in good yields. The subsequent
demethylation in most cases gave our target phosphonium salts
2
–5 in near quantitative yield. Phosphonium salts 1–5 are all
insoluble in water at pH 7 but dissolve completely (at approxi-
16
Ϫ3
mately 0.1 mol dm ) in 10% aqueous sodium hydroxide.
Stirring in aqueous base at room temperature for up to 24
hours and subsequent addition of aqueous acid caused the
phosphonium salts to reprecipitate. They were recovered
quantitatively by filtration, showing that alkaline hydrolysis of
these phosphonium salts is slow; presumably, the presence of
2
and Table 1). We opted for this route as we had difficulties
Ϫ
Ϫ
the –COO or –O groups inhibits this process. Other phos-
phonium salts are known to hydrolyse in water; more specific-
ally, water-soluble phosphonium salts bearing sulfonate groups
1
8
hydrolyse very quickly.
Wittig reactions with benzylphosphonium salts in aqueous
solution
Our initial conditions broadly followed those of previous
Wittig reactions carried out in water; phosphonium bromide 1a
(
with one p-carboxy group) and benzaldehyde were suspended
in water and 20% aqueous sodium hydroxide was added drop-
wise. The phosphonium salt, as expected, dissolved upon
addition of base. The reaction mixture was left to stir at room
temperature for two hours and then extracted with diethyl
ether to give stilbene 11, but only in a low yield of 13% and as a
mixture of E- and Z-isomers (approximately 1:1) (Scheme 3).
The phosphine oxide remained in the aqueous basic solution but
precipitated on addition of aqueous acid and was subsequently
isolated by filtration. No phosphonium salt was recovered.
Addition of ethanol (up to 40% of the solvent content) to the
aqueous solutions led to an increase of yield, presumably by
Scheme 2
with demethylation of the (methoxyphenyl)phosphines 8,
obtaining a mixture of the (hydroxyphenyl)phosphine and its
phosphine oxide in each case; alkylation of the phosphine
5
06
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Scheme 4
Scheme 3
Phosphonium bromide 1a (with one p-carboxy group)
showed lower reactivity than the hydroxy-substituted phos-
phonium bromides 2a, 3a, 4 and 5. The reactions required
longer reaction times (days rather than hours) and did not give
clean precipitation of olefin products; instead a slurry was
observed. Extraction with dichloromethane gave good to excel-
lent yields of olefins, requiring no further purification. The
yields of stilbenes 11–14 reflect the reactivity of the benzalde-
hyde starting materials. In most examples, acidification and
filtration of the aqueous residue were carried out to recover
(4-carboxyphenyl)diphenylphosphine oxide.
Phosphonium bromides containing hydroxy groups on the
whole gave good results (Table 3); the reaction between alde-
hydes and the phosphonium bromides 2a, 3a, 4 and 5 occurred
within hours, but were usually left overnight. In all cases, a
white precipitate was observed which was isolated by simple
filtration. Again, the phosphine oxide by-products could be
recovered by acidification and subsequent filtration of the
aqueous filtrate.
We wish to be precise about the processes occurring in this
reaction. Phosphonium bromide 3a (for example) does not dis-
solve in water but upon addition of aqueous base goes into
solution. We presume the ylide 16 is formed via the zwitterionic
species 15 (Scheme 5). The ylide can then react with p-nitro-
benzaldehyde (for example) to give the stilbene 14, which pre-
cipitates out of the reaction mixture as it is insoluble in water.
The ionised phosphine oxide 17 remains in solution. After the
stilbene has been removed by filtration, aqueous acid is added
to the reaction mixture and a second precipitate—the phos-
phine oxide 18—evolves. Both products of the reaction are
therefore recovered by filtration. The yield of p-nitrostilbene in
this case is 98%.
With the exception of stilbene 11, the olefins were isolated
as (E)- and (Z)-alkene mixtures; the yields of stilbene 11
appear lower as no attempt was made to recover the Z-isomer.
In one isolated case (the reaction of benzaldehyde with phos-
phonium bromide 3a), however, an extraction of the aqueous
filtrate with diethyl ether recovered an additional 42% yield of
stilbene 11 (E:Z, 72:28), giving a total yield of 70% of
stilbenes.
promoting dissolution of either starting materials or intermedi-
ates. Similar results were observed with phosphonium salt 2a,
although lower concentrations of ethanol were required to give
acceptable yields of stilbene (Table 2).
We had hoped, however, to be able to recover the olefin
products by filtration from the aqueous solution. Stilbene 11
itself is only sparingly soluble in water so we had hoped that it
would precipitate from the aqueous basic solution. We felt we
could encourage this by increasing the concentration of the
reagents. Our initial experiments, requiring extraction with an
organic solvent (typically diethyl ether) to recover the olefin,
used a concentration of reagents of 0.08 M. We repeated our
initial reaction conditions (i.e. no ethanol) using 0.22 M
reagents.
Phosphonium bromide 2a (with one p-hydroxy group) and
benzaldehyde were suspended in 10 cm water. 10% Aqueous
3
sodium hydroxide was added dropwise such that the final con-
centration of base was 5%. The suspension dissolved and the
mixture was stirred overnight at room temperature, although a
white precipitate was observed after only one hour. Simple
filtration and an aqueous wash gave pure (E)-stilbene in a 40%
yield. Addition of dilute hydrochloric acid to the aqueous fil-
trate gave a second precipitate. This too was isolated in an 86%
yield by filtration and was identified as (4-hydroxyphenyl)-
diphenylphosphine oxide.
The yield of stilbene is lower than that of phosphine oxide;
this is probably because only the E-isomer is a solid at room
temperature. (Z)-Stilbene is a liquid at room temperature and
would not therefore be recovered by filtration. A number of
substituted benzaldehydes which would give solid stilbenes were
therefore investigated under the same conditions with phos-
phonium bromides 1a, 2a, 3a, 4 and 5 (Scheme 4 and Table 3).
Table 2 Effect of addition of ethanol
Yield of stilbene 11 from aqueous
Wittig reaction with . . .
Addition of
ethanol (%)
Phosphonium
salt 1a
Phosphonium
salt 2a
The number and position of hydroxy groups present in the
phosphonium salt have a remarkable effect on the efficacy of
the Wittig reaction. The presence of one hydroxy group
certainly has a good effect (benzyltriphenylphosphonium
bromide did not react and indeed did not even dissolve in aque-
ous base) but two hydroxy groups seem to have a detrimental
effect. The position of the hydroxy group on the phenyl ring is
a
0
8
5
8
13
34
45
78
—
88
94
96
1
3
a
Reaction not carried out.
Table 3 Yields of stilbenes
Yield (%) (E:Z) of stilbene
Phosphonium
salt
11
12
13
14
a
a
a
a
1
2
3
4
5
a
a
a
91 (46:54)
40
28
17
43 (45:55)
40 (79:21)
72 (68:32)
58 (50:50)
91 (72:28)
87 (74:26)
100 (50:50)
76 (63:37)
98 (60:40)
b
b
b,c
c
c
c
0
0
6 (91:9)
b
45
24 (100:0)
81 (86:14)
73 (82:18)
a
b
c
Products recovered by extraction with CH Cl . Only (E)-stilbene 11 is recovered by filtration. Phosphonium salt 4 recovered.
2
2
J. Chem. Soc., Perkin Trans. 1, 2000, 505–513
507

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Scheme 5
Table 4 Wittig reactions of 3a with other aldehydes
also significant; a meta-hydroxy group seem to promote the
Wittig reaction more thoroughly than one in the para position.
Phosphonium bromide 4 (with two para-hydroxy groups)
gave low yields of olefins but, in all cases, a precipitate was
observed after 1–2 hours of stirring at room temperature in the
basic aqueous solution. This precipitate was isolated after an
aqueous wash as phosphonium bromide 4. No Wittig reaction
took place and presumably one of the deprotonated intermedi-
ates is insoluble in water and came out of solution. More
importantly, no hydrolysis was detected and no phosphine
oxides were isolated.
Entry
Aldehyde
Products and yields (%)
1
2
3
4
2-Furaldehyde
Alkene – 75
Phosphine oxide – 67
Alkene – 47
Phosphine oxide – 80
Phosphonium salt recovered
Aldehyde recovered
Phosphonium salt recovered
Aldehyde recovered
Phosphine oxide – 79
Phosphine oxide – 42
Phosphine oxide – 54
Phosphonium salt recovered
Phosphonium salt recovered
Phosphonium salt recovered
Pyridine-2-carbaldehyde
3-Hydroxybenzaldehyde
4-Hydroxybenzaldehyde
Ϫ
5
6
7
8
9
Terephthaldehyde
Aq. formaldehyde
Butyraldehyde
Isobutyraldehyde
Chloral
The high electron-donating potential of the oxido (O ) group
may explain why phosphonium salts 3a and 5 (with meta-
hydroxy groups) give higher yields of olefins than 2a and 4
Ϫ
respectively; the substituent coefficients σ for para-O and
Ϫ
19
meta-O are Ϫ0.81 and Ϫ0.47 respectively. A para-oxido
group will therefore have a much greater effect on the phos-
phonium salt making the deprotonation to form the ylide
more difficult and this is reflected in the yields of olefins.
Phosphonium salt 3a is deprotonated to give phosphonium salt
10
Glutaraldehyde
overall reaction with substituted benzaldehydes in water, on the
grounds of ease of synthesis, rate of reaction and simplicity of
work-up.
1
5 and, subsequently, ylide 16 (Scheme 5). Presumably, the equi-
We studied the reaction of our best phosphonium bromide
librium is more towards the ylide than in the para-substituted
analogues derived from phosphonium salt 2a. This effect is
much more evident in the bis-hydroxy salts 4 and 5.
3
a with a wider range of aldehydes (Table 4). The results were
less encouraging. Attention is drawn to the range of aldehydes
listed in the table: entries 1–6 are non-enolisable aldehydes;
entries 7–10 are all enolisable. In addition, entries 3–6, and 9
and 10 are all water-soluble aldehydes. 2-Furaldehyde and
pyridine-2-carbaldehyde (entries 1 and 2) are water-insoluble
and non-enolisable and show similar reactivities to the benz-
aldehydes. Wittig reactions carried out under the same condi-
tions gave olefin products (by filtration or extraction with
dichloromethane) in acceptable yields.
By comparing the reactions of phosphonium salts 2a and 3a
with 4 and 5, it is clear that better yields of olefins are obtained
when only one hydroxy group is present. In basic solution, the
hydroxy groups are likely to be ionised and will therefore inhibit
formation of the phosphorus ylides for two reasons. In addition
to the electron-donating potential of the oxido group reducing
the positive charge on phosphorus, the phosphorus ylides
would be either dianions (for ylides derived from phosphonium
salts 2a and 3a) or even trianions (for ylides derived from
phosphonium salts 4 and 5, each containing two hydroxy
groups); each successive deprotonation will be less favoured.
The ylides derived from phosphonium salts 4 and 5 are there-
fore likely to be present in lower concentrations, slowing down
or even stopping the Wittig reaction.
Water-soluble phosphonium salts provide an improved prac-
tical synthesis of substituted stilbenes by the Wittig reaction.
Although the stilbenes could be recovered by extraction of the
basic aqueous solution with an organic solvent (diethyl ether or
dichloromethane), in most cases a simple filtration gave good
yields, comparable to extraction. Similarly, the phosphine oxide
by-product can be recovered either by filtration from an acidic
aqueous solution or by extraction with an organic solvent. Both
products of the reaction are therefore recovered separately in
good to excellent yields in spectroscopically pure form. The
reactions require no organic solvent, either during the reaction
or in the isolation of the product. Phosphonium bromide 3a
Surprisingly, water-soluble aldehydes did not undergo Wittig
reactions in water. We expected the hydroxybenzaldehydes
(
entries 3 and 4) to dissolve in aqueous base to react to give
hydroxystilbenes (which should remain in the aqueous basic
solution). The aldehydes did indeed dissolve upon addition of
base, but only starting materials were recovered—both alde-
hyde and phosphonium salt—in quantitative yield after
acidification and filtration in both cases. The water-soluble
dialdehydes (entries 5 and 6) also yielded no olefins but phos-
phine oxide was recovered after acidification and filtration. The
enolisable water-soluble aldehydes (entries 9 and 10) also did
not react and the phosphonium bromide 3a was recovered.
Other enolisable aldehydes (entries 7 and 8) also led to recovery
of phosphonium bromide 3a; base-catalysed self-condensations
of aldehyde took place preferentially in these cases.
Attempted aqueous Wittig reactions with butylphosphonium salts
Under the optimal conditions previously determined, phos-
(
with one hydroxy group meta to phosphorus) gives the best
phonium bromide 1b was added to benzaldehyde in 5%
5
08 J. Chem. Soc., Perkin Trans. 1, 2000, 505–513

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aqueous NaOH. The phosphonium bromide 1b dissolved upon
addition of base and the mixture was stirred overnight. No
precipitation was observed and extraction with diethyl ether
and subsequent evaporation gave butyldiphenylphosphine
oxide 17 in a 31% yield. Acidification of the aqueous residue
and subsequent extraction gave phosphine oxide 18 in a 67%
yield (Scheme 6). This was the first evidence of any hydrolysis
were recorded on Bruker WM 200, WM 250 or WM 400
Fourier transform spectrometers, using an internal deuterium
lock. The C NMR spectra were recorded with broad band
13
decoupling and attached proton test (APT). The symbols ϩ
13
and Ϫ after the C NMR chemical shifts indicate odd and even
numbers respectively of attached protons. δ Values are given in
ppm relative to tetramethylsilane. J Values are given in hertz
1
13
(
Hz). In the assignment of the H and C NMR spectra of
phosphorus compounds, the following notation has been used:
Ph refers to a phenyl ring attached to phosphorus or a C᎐C
᎐
bond and numbering starts from the point of attachment, Ar
refers to phenyl rings with more than one substituent and
numbering starts from the point of attachment to phosphorus
or a C᎐C bond, where appropriate.
᎐
Mass spectra were determined by electron impact (EI) or fast
atom bombardment (ϩFAB). All mass spectra were recorded
on a Kratos MS890 double-beam mass spectrometer by tech-
nical staff. Microanalyses were performed by technical staff
using either Carlo Elba 1106 or Perkin Elmer 240 automatic
analysers.
Scheme 6
having occurred with these compounds; hydrolysis with loss of
phenyl anion or p-carboxyphenyl [or possibly p-(COO )phenyl]
Ϫ
anion to give phosphine oxides 17 and 18 occurs in a statistical
ratio with almost quantitative conversion. No Wittig reaction
took place between the ylide and benzaldehyde.
Phosphonium bromides 2b and 3b and benzaldehyde under
the same conditions led only to quantitative recovery of start-
ing material. No hydrolysis of the phosphonium salts occurred
and it may be that the oxido group makes the phosphonium
salts resistant to hydrolysis by deactivation of the phosphorus
towards attack by hydroxide. Increasing concentrations of base
(
4-Bromophenyl)diphenylphosphine 7
15
By the method of Ravindar et al., the phosphine was obtained
(62%) as white plates, mp 74–77 ЊC (from MeOH) (lit., 79–
80 ЊC). No NMR data were recorded previously: δ (250 MHz;
CDCl ) 7.53 (2 H, dd, J 1.2 and J 8.4, ArH-2), 7.43–7.40
1
5
H
3
3
HP
4
(10 H, m, 2 × Ph) and 7.26 (2 H, dd, J 6.9 and J 8.4, ArH-3);
HP
Ϫ
Ϫ
ϩ
δ (63 MHz; CDCl ) 136.8 (PhC-1), 136.7 (ArC-1), 135.3 (d,
C
3
2
ϩ
2
ϩ
3
JCP 20.0, ArC-2), 133.9 (d, J 19.7, PhC-2), 131.8 (d, J
CP
CP
ϩ
ϩ
3
(
up to 50% aqueous NaOH) were used in similar reactions but
6.8, ArC-3), 128.8 (PhC-4), 128.7 (d, J 8.7, PhC-3) and
123.5 (ArC-4).
CP
Ϫ
in all cases only phosphonium salts were recovered. Increasing
the temperature to reflux and increasing the reaction time did
eventually lead to hydrolysis of the phosphonium salt; (hydroxy-
phenyl)phenylphosphine oxides 19 or 20 and starting material
4
-(Diphenylphosphanyl)benzoic acid 6
15
We report an improved synthesis of phosphine 6. Dry mag-
nesium turnings (0.60 g, 25.0 mmol) were stirred in dry THF
3
(
(
20 cm ) under argon. (4-Bromophenyl)diphenylphosphine 7
3
8.35 g, 24.48 mmol) was dissolved in dry THF (20 cm ) and
approximately one half of this was added to the magnesium.
One crystal of iodine was added and the reaction vessel was
heated until the Grignard reaction was initiated. The remaining
phosphine solution was added at such a rate so as to maintain
reflux and the solution was then refluxed until all the mag-
nesium had been consumed, giving a red solution. The solution
(
to a greater or lesser extent) were recovered after refluxing
the reaction mixtures for 1 day. In other related experiments, the
addition of ethanol also promoted hydrolysis.
was allowed to cool and was poured onto crushed CO kept at
2
Ϫ78 ЊC. A gum developed which was subsequently covered with
3
CO pellets. Dry THF (20 cm ) was added and the solution was
2
Conclusion
allowed to stir overnight giving a yellow suspension. Further
We have shown that our new phosphonium salts dissolve in
aqueous base (5–10% aqueous NaOH) and are resistant to
hydrolysis at room temperature. Wittig reactions of benzyl-
containing phosphonium bromides 1a, 2a, 3a, 4 and 5 with
substituted benzaldehydes in aqueous NaOH gave unsym-
metrical stilbenes (predominantly E) in good yields. Phos-
phonium bromide 3a, containing one hydroxy group meta to
phosphorus, gave the best results under these conditions.
CO was added and allowed to dissolve. Saturated aqueous
2
3
Na CO (20 cm ) was added to quench the reaction, followed by
2
3
3
water (20 cm ). 3 M HCl was added to pH 1 and the solution
3
was extracted with diethyl ether (3 × 20 cm ). The combined
3
organic extracts were washed with 3 M HCl (20 cm ), dried
(
MgSO ) and evaporated under reduced pressure to give a
4
yellow residue. This residue was recrystallised from acetic acid
to give the phosphine 6 (2.13 g, 29%) as pale yellow needles. The
remaining solution was evaporated under reduced pressure and
a further recrystallisation gave more phosphine 6 (2.45 g, 33%)
Experimental
Flash chromatography was carried out using Merck Kieselgel
again as pale yellow needles, mp 159–162 ЊC (from AcOH)
15
[
lit., 156–158 ЊC (from MeOH–H O)]. No NMR data were
2
6
0 (230–400 mesh). Thin layer chromatography (TLC) was
carried out on commercially available pre-coated glass plates
Merck silica Kieselgel 60F254). All solvents were distilled before
recorded previously: δ (250 MHz; d -DMSO) 13.04 (1 H, br s,
H
6
3
COOH), 7.9 (2 H, dd, J 0.9 and J 7.9, ArH-2) and 7.5–7.2
HP
(
Ϫ
(
(
12 H, m, ArH-3 and 2 × Ph); δ (62.9 MHz; d -DMSO) 168.2
C 6
Ϫ 1 Ϫ 1
use. Anhydrous solvents were distilled from lithium aluminium
hydride in the case of tetrahydrofuran and diethyl ether, and
from calcium hydride in the case of toluene.
COOH), 140.2 (d, J 12.3, ArC-1), 136.5 (d, J 11.3,
CP
CP
Ϫ
ϩ
2
ϩ
PhC-1), 136.3 (ArC-4), 133.5 (d, J 19.6, PhC-2), 132.7 (d,
JCP 25.5, ArC-2), 129.3 , 129.0 and 128.9 .
CP
2
ϩ
ϩ
ϩ
Melting points were determined on a Reichart hot stage
microscope or a Stuart SMP1 melting point apparatus and are
uncorrected. Infra-red spectra were recorded on a Perkin-Elmer
4
-(Benzyldiphenylphosphonio)benzoic acid bromide 1a
1
13
1
600 series FTIR spectrometer. All H and C NMR spectra
4-(Diphenylphosphanyl)benzoic acid 6 (1.37 g, 4.47 mmol) was
J. Chem. Soc., Perkin Trans. 1, 2000, 505–513
509

View Article Online
3
suspended in dry toluene (10 cm ) under argon. Benzyl bromide
(
analysis showed this to be a mixture of bis(3-methoxyphenyl)-
3
3
0.53 cm , 4.47 mmol) in dry toluene (5 cm ) was added and the
phenylphosphine and its oxide. The oil was dissolved in THF
3
mixture refluxed for 24 h. The white precipitate was collected
and washed with diethyl ether to give the phosphonium salt (2.07
g, 95%) as a powder, mp 308–310 ЊC (white plates from EtOH)
(50 cm ) and hydrogen peroxide (100 vol solution in water) was
added dropwise until no further temperature rise was observed.
The solution was evaporated under reduced pressure to give the
(
Found: C, 65.1; H, 4.6; P, 6.5. C H BrO P requires C, 65.4;
phosphine oxide (38.5 g, 100%) as white needles, mp 68–70 ЊC
2
6
22
2
Ϫ1
Ϫ1
H, 4.65; P, 6.5%); νmax(Nujol)/cm 3500–2000 (COOH), 1710
C᎐O) and 1461 (P–Ph); δ (250 MHz; d -DMSO) 13.7 (1 H,
(from cyclohexane); R (EtOAc) 0.23; νmax(Nujol)/cm 1595
f
(
and 1574 (Ph), 1463 (P–Ph) and 1285 (P=O); δ (400 MHz;
᎐
H
6
H
4
br s, COOH), 8.22 (2 H, dd, J 3.0 and J 8.4, ArH-3), 8.0–7.7
(
CH PhH-4), 7.24 (2 H, br t, J 7.3, CH PhH-3), 7.00 (2 H,
dd, J 1.4 and J 7.3, CH PhH-2) and 5.29 (2 H, d, J
1
(
1
CDCl ) 7.65–7.60 (2 H, m), 7.52–7.47 (1 H, br t, J 7.4, PhH-4),
HP
3
6
12 H, m, ArH-2 and PPh), 7.29 (1 H, dt, J 1.6 and J 7.3,
7.43–7.40 (2 H, m), 7.32–7.23 (4 H, m), 7.13–7.08 (2 H,
ddd, J 0.7, 7.4 and 11.7), 7.04–7.01 (2 H, m) and 3.74 (6 H, s,
HP
2
2
4
2
Ϫ
3
OMe); δ (101 MHz; CDCl ) 159.6 (d, JCP 15.0, ArC-3),
C 3
Ϫ 1 ϩ ϩ
HP
2
HP
Ϫ
Ϫ
5.8, PCH ); δ (101 MHz; d -DMSO) 166.2 (COOH), 136.5
ArC-4), 135.3 (CH PhC-4), 134.6 (d, J 10.3, PPhC-4),
34.2 (CH PhC-2 or CH PhC-3), 134.1 (CH PhC-2 or
133.4 (d, JCP 103.9, ArC-1), 132.1 (PhC-4), 132.1 (d,
2 Ϫ 1 ϩ 3
2
C
ϩ
6
ϩ
4
JCP 10.3, PhC-2), 132.0 (d, J 104.9, PhC-1), 129.7 (d, J
CP CP
ϩ 3 ϩ 2
2
CP
ϩ
ϩ
14.5, ArC-5), 128.6 (d, J 12.3, PhC-3), 124.3 (d, J 10.1,
CP CP
ϩ 4 ϩ 2
2
2
2
ϩ
ϩ
CH PhC-3), 130.9 (d, J 5.3, ArC-2 or ArC-3), 130.2 (d,
J 12.5, PPhC-2 or PPhC-3), 128.9 (PPhC-2 or PPhC-3), 128.5
ArC-6), 118.3 (d, J 2.3, ArC-4), 116.8 (d, J 10.8, ArC-
CP CP
ϩ ϩ
2
ϩ
ϩ
2) and 55.4 (OMe); m/z (EI) 338.1076 (5%, M . M requires
338.10723), 337.1 (12%, M Ϫ H), 188.0 (60), 84.0 (100) and
49.0 (85).
Ϫ
2
Ϫ
(
ArC-2 or ArC-3), 127.7 (d, J 8.6, CH PhC-1), 122.6 (d,
CP
1
2
1
Ϫ
Ϫ
JCP 84.1, PPhC-1), 117.4 (d, J 85.6, ArC-1) and 28.1
CP
1
ϩ
(
d, J 46.3, PCH ); m/z (ϩFAB) 397 (M ), 352 (M Ϫ COOH).
CP 2
Benzyl(4-methoxyphenyl)diphenylphosphonium bromide 9
M is defined here as the phosphonium cation.
(
4-OMe; n ؍ 1; R ؍ Ph)
4
-(Butyldiphenylphosphonio)benzoic acid bromide 1b
4
4
-Methoxyphenyldiphenylphosphine 8 (4-OMe; n = 1) (12.00 g,
3
1.0 mmol) was suspended in dry toluene (150 cm ) under
4
-(Diphenylphosphanyl)benzoic acid 6 (1.886 g, 6.16 mmol)
3
3
argon. Benzyl bromide (4.9 cm , 41.0 mmol) was added and the
mixture refluxed overnight. A white precipitate was collected
and washed with diethyl ether to give the phosphonium salt
was stirred in n-bromobutane (10 cm ) at reflux overnight under
argon. A white precipitate was collected and washed with
diethyl ether to give the phosphonium salt (2.53 g, 92%) as a
white powder, mp 233–238 ЊC (Found: C, 65.7; H, 5.3; P, 6.3.
C H BrO P requires C, 64.6; H, 5.3; P, 6.0%); νmax(Nujol)/
cm 1709 (C᎐O) and 1462 (P–Ph); δ (400 MHz; d -DMSO)
1
ArH-3), 8.0–7.7 (12 H, m, ArH-2 and 2 × Ph), 3.6 (2 H, m,
PCH ), 1.5 (4 H, m, PCH CH CH Me) and 0.9 (3 H, t, J 6.8,
Me); δ (101 MHz; d -DMSO) 166.2 (COOH), 136.3 (ArC-4),
(
18.37 g, 97%) as a powder, mp 221–224 ЊC (white needles from
16
EtOH–EtOAc) (lit., 225–228 ЊC). Only melting point and
23
Ϫ1
24
2
16
analytical data were previously published: δ (500 MHz; d -
H 6
4
H
6
4
DMSO) 7.9 (2 H, br t, J 7.6, PPhH-4), 7.7 (4 H, dt, J 3.5 and
HP
3
3.7 (1 H, br s, COOH), 8.2 (2 H, dd, J 2.9 and J 8.4,
HP
J 7.6, PPhH-3), 7.6 (4 H, dd, J 7.6 and J 12.5, PPhH-2), 7.6
HP
3
(
2 H, dd, J 8.9 and J 12.0, ArH-2), 7.3 (3 H, m, ArH-3 and
HP
2
2
2
2
Ϫ
Ϫ
CH PhH-4), 7.2 (2 H, t, J 7.1, CH PhH-3), 7.0 (2 H, br d, J 7.1,
2 2
2
C
ϩ
6
ϩ
2
ϩ
2
CH PhH-2), 5.1 (2 H, d, J 15.6, PCH ) and 3.9 (3 H, s,
2 HP 2
Ϫ ϩ 2
1
1
1
35.1 (PhC-4), 134.2 (d, J 10.4, ArC-2), 133.7ϩ (d, J
CP
CP
ϩ
3
3
OMe); δ (101 MHz; CDCl ) 164.8 (ArC-4), 136.5 (d, J
C 3 CP
ϩ 4 ϩ 2
0.3, PhC-2), 130.5 (d, JCP 12.6, ArC-3), 130.4 (d, JCP
Ϫ
1
Ϫ
1
11.4, ArC-2), 134.8 (d, J 2.6, PPhC-4), 134.2 (d, J 9.8,
CP CP
ϩ 4 ϩ 3
2.5, PhC-3), 123.4 (d, J 84.1, ArC-1), 118.1 (d, J 85.5,
CP
CP
Ϫ
2
Ϫ
3
PPhC-2), 131.5 (d, J 5.3, CH PhC-3), 130.1 (d, J 12.5,
CP 2 CP
ϩ 5 ϩ 3
PhC-1), 23.8 (d, J 4.3, PCH CH ), 23.2 (d, J 17.4,
CH Me), 19.9 (d, JCP 49.2, PCH ) and 13.3 (Me); m/z
CP
1
2
2
CP
Ϫ
ϩ
PPhC-3), 128.8 (d, J 3.0, CH PhC-4), 128.3 (d, J 3.6,
CP 2 CP
Ϫ 2 Ϫ 1
2
2
ϩ
CH PhC-2), 127.3 (d, J 8.5, CH PhC-1), 118.5 (d, J
2 CP 2 CP
ϩ 3 Ϫ 1
(
ϩFAB) 363.1533 (100%, M . M requires 363.1544). M is
8
6.3, PPhC-1), 116.0 (d, J 13.9, ArC-3), 107.0 (d, J 93.6,
CP CP
ϩ Ϫ 1
defined here as the phosphonium cation.
ArC-1), 55.9 (OMe) and 31.2 (d, J 48.0, PCH ).
CP
2
4
-Methoxyphenyldiphenylphosphine 8 (4-OMe; n ؍ 1)
Butyl(4-methoxyphenyl)diphenylphosphonium bromide 9
(4-OMe; n ؍ 1; R ؍ Pr)
16
By the method of McEwen et al., the phosphine was obtained
16
1
20
(
86%) as needles. The melting point and H NMR data are
4
2
-Methoxyphenyldiphenylphosphine 8 (4-OMe; n = 1) (5.96 g,
0.4 mmol) was stirred in n-bromobutane (30 cm ) at reflux
consistent with previous data.
3
overnight under argon. A white precipitate was collected and
washed with diethyl ether to give the phosphonium salt (6.56 g,
75%) as a powder, mp 142–145 ЊC (Found: C, 64.1; H, 6.0; Br,
3
-Methoxyphenyldiphenylphosphine 8 (3-OMe; n ؍ 1)
In the same way, the phosphine was obtained (55%) as needles.
The melting point and H NMR data are consistent with previ-
ous data.
1
18.3; P, 7.4. C23H26BrOP requires C, 64.3; H, 6.1; Br, 18.6; P,
16
Ϫ1
7.2%); νmax(Nujol)/cm 1587 (Ph) and 1462 and 1442 (P–Ph);
4
δ (400 MHz; CDCl ) 7.70–7.55 (12 H, m), 7.11 (2 H, dd, J
H
3
HP
2
.6 and J 9.0, ArH-3), 3.80 (3 H, s, OMe), 3.47–3.38 (2 H, m,
Bis(4-methoxyphenyl)phenylphosphine 8 (4-OMe; n ؍ 2)
PCH ), 1.59–1.41 (4 H, m, PCH CH CH Me) and 0.78 (3 H,
t, J 6.9, CH Me); δ (101 MHz; CDCl ) 164.8 (ArC-4), 135.7
2
2
2
2
In the same way, the phosphine was obtained (76%) as plates,
Ϫ
ϩ
2
C
3
21
1
mp 87–88 ЊC (from MeOH) (lit., 89–90 ЊC); low-field
H
2
ϩ
ϩ
2
(
d, J 11.5, ArC-2), 134.9 (br s, PhC-4), 133.4 (d, J
CP CP
ϩ 3 Ϫ 1
2
2
NMR data were recorded previously: δ (400 MHz; CDCl )
H
3
10.0, PhC-2), 130.4 (d, JCP 12.5, PhC-3), 118.9 (d, JCP
4
7
.3 (3 H, m), 7.25 (4 H, dd, J 7.5 and J 8.4, ArH-3), 7.25
ϩ 3 Ϫ 1
HP
86.4, PhC-1), 116.4 (d, J 13.7, ArC-3), 107.3 (d, J 93.4,
CP CP
ϩ Ϫ 2 Ϫ
(
2 H, m), 6.88 (4 H, br d, J 8.4, ArH-2) and 3.84 (6 H,
ArC-1), 56.1 (OMe), 24.5 (d, J 4.3, PCH CH ), 23.7 (d,
CP
2
2
Ϫ
Ϫ
1
s, Me); δ (101 MHz; CDCl ) 160.3 (ArC-4), 138.6 (d, J
1
PhC-1), 133.1ϩ (d, J 18.7, PhC-2), 128.4 (m, PhC-3 and
PhC-4), 114.2 (d, J 7.8, ArC-3) and 55.2 (OMe).
3
Ϫ
1
ϩ
C
3
CP
JCP 16.3, CH Me), 22.9 (d, JCP 51.5, PCH ) and 13.7
2 2
ϩ
ϩ
2
Ϫ
1
0.5, ArC-1), 135.3 (d, J 21.0, ArC-2), 134.0 (d, J 4.0,
CP
CP
(CH Me); m/z (ϩFAB) 349.1702 (100%, M . M requires
2
ϩ
2
ϩ
CP
349.1721). M is defined here as the phosphonium cation.
3
ϩ
CP
Benzyl(3-methoxyphenyl)diphenylphosphonium bromide 9
(3-OMe; n ؍ 1; R ؍ Ph)
Bis(3-methoxyphenyl)phenylphosphine oxide 10
In the same way, dry magnesium turnings (6.00 g, 0.25 mol),
3-Methoxyphenyldiphenylphosphine 8 (3-OMe; n = 1) (6.82 g,
3
3
3
-bromoanisole (34.0 cm , 0.27 mol) and dichlorophenyl-
23.3 mmol) was dissolved in dry toluene (100 cm ) under argon.
3
13
3
phosphine (16.7 cm , 0.13 mol) gave a yellow oil. C NMR
Benzyl bromide (2.8 cm , 23.5 mmol) was added and the mix-
5
10 J. Chem. Soc., Perkin Trans. 1, 2000, 505–513

View Article Online
3
ture refluxed overnight. A white precipitate was collected and
(17.3 cm , 58.2 mmol) was added to a stirred solution of
3
washed with diethyl ether to give the phosphonium salt (9.44 g,
polymethylhydrosiloxane (34.7 cm , 582 mmol, 10 eq.) and
bis(3-methoxyphenyl)phenylphosphine oxide 10 (19.68 g, 58.2
mmol) in dry THF (100 cm ) under argon. The yellow solution
was refluxed overnight. The solution was allowed to cool and
1
6
8
2
7%) as a powder, mp 261–265 ЊC (from EtOH) [lit., 264–
3
66 ЊC (from EtOH–Et O)]. Only melting point and analytical
2
16
data were previously published: δ (500 MHz; CDCl ) 7.77–
H
3
4
3
7
.70 (6 H, m, PPhH-2 and PPhH-4), 7.61 (4 H, dt, J 3.5 and
J 8.0, PPhH-3), 7.51 (1 H, dt, J 4.0 and 7.9, ArH-5), 7.25
benzyl bromide (7.0 cm , 58.85 mmol) was added. The solution
HP
4
was refluxed for a further 4 h and, after cooling, was filtered and
washed with diethyl ether to give the phosphonium salt (23.32 g,
81%) as a powder, mp 233–236 ЊC (yellow needles from EtOH–
EtOAc); νmax(Nujol)/cm 1589 and 1571 (Ph) and 1462 (P–Ph);
δ (500 MHz; CDCl ) 7.74–7.70 (3 H, m, PPhH-2 and PPhH-4),
7.60 (2 H, dt, J 3.4 and J 7.6, PPhH-3), 7.48 (2 H, dt, J 4.7
and 8.3, ArH-5), 7.26–7.19 (7 H, m), 7.13–7.11 (4 H, m), 5.44
(2 H, d, J 14.5, PCH ) and 3.83 (6 H, s, OMe); δ (101
HP
(
1 H, t, J 2.3), 7.23–7.17 (3 H, m), 7.12–7.11 (4 H, m), 5.43 (2 H,
2
d, J 14.5, PCH ) and 3.84 (3 H, s, OMe); δ (101 MHz;
CDCl ) 160.4 (d, J 15.6, ArC-3), 135.0 (br s, PPhC-4),
1
1
1
8
HP
2
C
Ϫ
3
ϩ
Ϫ1
3
ϩ
CP
2
ϩ
4
34.4ϩ (d, J 9.8, PPhC-2), 131.5 (d, J 5.5, CH PhC-3),
CP
CP
2
H
3
3
ϩ
3
4
4
31.4 (d, J 15.0, ArC-5), 130.1 (d, J 12.6, PPhC-3),
CP
CP
H
P
H
P
ϩ
ϩ
Ϫ
2
28.8 (br s, CH PhC-2), 128.4 (br s, ArC-4), 127.3 (d, J
2
CP
ϩ
2
ϩ
2
.5, CH PhC-1), 126.4 (d, JCP 9.7, ArC-6), 121.3 (br s,
2
HP
2
C
Ϫ
1
ϩ
2
Ϫ
3
ϩ
4
CH PhC-4), 119.1 (d, J 85.4, ArC-1), 118.8 (d, J 15.9,
ArC-2), 117.9 (d, J 85.6, PPhC-1), 56.4 (s, OMe) and 30.9
MHz; CDCl ) 160.3 (d, J 15.9, ArC-3), 135.0 (d, J
3 CP CP
ϩ 2 ϩ 3
2
CP
CP
Ϫ
1
ϩ
Ϫ
2.5, PPhC-4), 134.3 (d, J 9.9, PPhC-2), 131.5 (d, J 8.5,
CP
CP
CP
1
ϩ
ϩ
3
(
d, J 46.5, PCH ).
ArC-5), 131.4 (s, CH PhC-2), 130.1 (d, J 12.5, PPhC-3),
CP
2
2
CP
4
ϩ
4
ϩ
1
1
1
1
28.8Ϫ (d, J 2.8, CH PhC-3), 128.4 (d, J 3.6, ArC-4),
CP
2
CP
2
ϩ
2
Butyl(3-methoxyphenyl)diphenylphosphonium bromide 9
27.3ϩ (d, J 8.5, CH PhC-1), 126.3 (d, J 9.6, ArC-6),
CP
2
CP
5
Ϫ
1
(
4-OMe; n ؍ 1; R ؍ Pr)
21.2ϩ (d, J 2.4, CH PhC-4), 118.9 (d, J 85.5, ArC-1),
CP
2
CP
2
Ϫ
1
18.9 (d, J 11.3, ArC-2), 117.7 (d, J 85.9, PPhC-1),
CP
CP
3
1
-Methoxyphenyldiphenylphosphine 8 (3-OMe; n = 1) (4.02 g,
3.8 mmol) was stirred in n-bromobutane (50 cm ) at reflux
ϩ
Ϫ
1
3
56.3 (s, OMe) and 30.7 (d, J 46.7, PCH ); m/z (ϩFAB)
CP 2
ϩ
4
12.1598 (20%, M Ϫ H. C H O P requires 412.1670)
27 25 2
ϩ
temperature overnight under argon. The white precipitate was
collected and washed with diethyl ether to give the phosphonium
salt (4.78 g, 81%) as a powder, mp 154–155 ЊC (Found: C, 64.0;
H, 6.0; Br, 18.2; P, 7.3. C H BrOP requires C, 64.3; H, 6.1; Br,
and 322.1 (100%, M Ϫ CH Ph). M is defined here as the
2
phosphonium cation.
23
26
Ϫ1
Benzyl(4-hydroxyphenyl)diphenylphosphonium bromide 2a
1
8.6; P, 7.2%); νmax(Nujol)/cm 1592 and 1574 (Ph) and 1463
(
P–Ph); δ (400 MHz; CDCl ) 7.85–7.7 (6 H, m), 7.7–7.6 (4 H,
H
3
Benzyl(4-methoxyphenyl)diphenylphosphonium bromide
9
m), 7.60–7.55 (1 H, m), 7.3–7.2 (3 H, m), 3.86 (3 H, s, OMe),
3
(
4-OMe; n = 1; R = Ph) (36.60 g, 79 mmol) was stirred in hydro-
3
.72 (2 H, m, PCH ), 1.7–1.5 (4 H, m, PCH CH CH Me) and
2 2 2 2
Ϫ
bromic acid (250 cm of a 48% solution in water) at reflux
overnight under argon. A white precipitate was collected and
washed with diethyl ether. It was then dried over two days under
reduced pressure to give the phosphonium salt (35.21 g, 99%) as
a white powder, mp 317–319 ЊC (from aqueous MeOH) (Found:
C, 66.6; H, 4.9; Br, 17.6; P, 7.0. C H BrOP requires C, 66.8; H,
0
.88 (3 H, t, J 7.0, CH Me); δ (101 MHz; CDCl ) 160.7 (d,
2 C 3
ϩ 4 ϩ 2
3
JCP 15.8, ArC-3), 135.0 (d, J 2.6, PhC-4), 133.7 (d, J
CP
CP
ϩ
3
ϩ
3
9
.9, PhC-2), 131.8 (d, J 14.7, ArC-5), 130.5 (d, J 12.5,
CP CP
ϩ 2 ϩ 4
PhC-3), 125.5 (d, J 9.6, ArC-6), 120.7 (d, J 2.4, ArC-4),
1
1
PCH CH ), 23.7 (d, J 16.4, CH Me), 22.7 (d, J 50.0,
PCH ) and 13.8 (CH Me); m/z (ϩFAB) 349.1704 (100%, M .
CP
CP
Ϫ
1
ϩ
2
19.8Ϫ (d, 1 JCP 85.3, ArC-1), 118.7 (d, JCP 11.6, ArC-2),
25
22
ϩ Ϫ 2
Ϫ1
18.3 (d, J 86.0, PhC-1), 56.4 (OMe), 24.7 (d, J 4.4,
CP
CP
4.9; Br, 17.8; P, 6.9%); νmax(Nujol)/cm 1601 and 1578 (Ph)
and 1461 (P–Ph); δ (500 MHz; d -DMSO) 11.1 (1 H, s, OH),
Ϫ
3
Ϫ
1
2
2
CP
2
CP
H
6
ϩ
ϩ
4
2
2
7.9 (2 H, t, J 7.6, PPhH-4), 7.7 (4 H, dt, J 3.4 and J 7.6,
PPhH-3), 7.6 (4 H, dd, J 7.6 and J 12.4, PPhH-2), 7.45
2 H, dd, J 8.7 and J 11.9, ArH-2), 7.3 (1 H, br t, J 7.3,
CH PhH-4), 7.2 (2 H, t, J 7.3, CH PhH-3), 7.1 (2 H, dd, J
HP
3
M requires 349.1721). M is defined here as the phosphonium
cation.
HP
3
(
HP
4
2
2
HP
Benzyl[bis(4-methoxyphenyl)]phenylphosphonium bromide 9
2
.5 and J 8.7, ArH-3), 7.0 (2 H, d, J 7.3, CH PhH-2) and 5.1
2
2 Ϫ
(
4-OMe; n ؍ 2; R ؍ Ph)
(
(
2 H, d, J 16.0, PCH ); δ (101 MHz; d -DMSO) 163.6
HP 2 C 6
4 ϩ 2 ϩ
23
d, J 2.4, ArC-4), 136.3 (d, J 12.0, ArC-2), 134.9 (d,
CP CP
ϩ 2 ϩ
The phosphonium chloride has previously been reported.
Bis(4-methoxyphenyl)phenylphosphine 8 (4-OMe; n = 2) (3.10
g, 9.6 mmol) was dissolved in dry toluene (150 cm ) under
argon. Benzyl bromide (1.14 cm , 9.6 mmol) was added and the
mixture refluxed overnight. A white precipitate was collected
and washed with diethyl ether to give the phosphonium salt
4
JCP 2.0, PPhC-4), 133.9 (d, J 10.0, PPhC-2), 130.9 (d,
CP
3
4
ϩ
ϩ
3
JCP 5.0, CH PhC-3), 130.0 (d, J 12.0, PPhC-3), 128.7
2
CP
5
Ϫ
2
3
(
d,
J
2.5, CH PhC-4), 128.4 (d, JCP 9.0, CH PhC-1),
CP
2
2
ϩ
3
Ϫ
1
1
28.3 (d,
J
2.5, CH PhC-2), 118.9 (d,
J
86.0,
CP
ϩ
2
CP
3
Ϫ
1
PPhC-1), 117.3 (d, J 14.0, ArC-3), 104.6 (d, J 94.0,
ArC-1) and 28.7 (d, J 48.0, PCH ); m/z (ϩFAB) 369.3
CP
1
CP
Ϫ
(
4.13 g, 87%) as a powder, mp 167–173 ЊC (white prisms from
CP
2
ϩ
(
100%, M ), 154.1 (70%) and 136.1 (55%). M is defined here as
EtOH–EtOAc) (Found: C, 63.7; H, 5.5; P, 6.2. C H BrO P
2
7
26
2
Ϫ1
the phosphonium cation.
requires C, 65.7; H, 5.3; P, 6.3.%); νmax(Nujol)/cm 1594 and
566 (Ph) and 1455 (P-Ph); δ (500 MHz; CDCl ) 7.7 (1 H, m,
1
H
3
Butyl(4-hydroxyphenyl)diphenylphosphonium bromide 2b
PPhH-4), 7.6 (8 H, m), 7.2 (1 H, br t, J 7.3, CH PhH-4), 7.1
2
2
(
8 H, m), 5.1 (2 H, d, J 14.3, PCH ) and 3.8 (6 H, s, OMe);
HP 2
Ϫ 4 ϩ 2
In the same way, butyl(4-methoxyphenyl)diphenylphosphon-
ium bromide 9 (4-OMe; n = 1; R = Pr) (4.14 g, 9.7 mmol) gave
δ (101 MHz; CDCl ) 164.7 (d, J 2.7, ArC-4), 136.4 (d, J
C
3
CP
CP
ϩ
4
ϩ
2
1
1.3, ArC-2), 134.7 (d, J 2.5, PPhC-4), 134.1 (d, J 9.7,
CP CP
ϩ 4 ϩ 3
the phosphonium salt (2.43 g, 61%) as needles, mp 177–180 ЊC
PPhC-2), 131.4 (d, J 5.3, CH PhC-3), 130.0 (d, J 12.4,
PPhC-3), 128.8 (d, J 3.1, CH PhC-4), 128.3 (d, J 3.6,
Ϫ1
CP
2
CP
(
from EtOH–Et O); νmax(Nujol)/cm 1598 and 1576 (Ph) and
2
ϩ
5
ϩ
3
CP
2
CP
Ϫ
1
463 and 1436 (P–Ph); δ (400 MHz; d -DMSO) 10.9 (1 H,
H 6
5
Ϫ
2
CH PhC-2), 127.6 (d, JCP 8.6, CH PhC-1), 119.1 (d,
2
2
br s, OH), 7.87 (2 H, dt, J 2.8 and J 5.9, PhH-4), 7.80–7.72
HP
1
1
ϩ
3
Ϫ
JCP 86.7, PPhC-1), 115.9 (d, J 13.6, ArC-3), 107.7 (d,
JCP 93.9, ArC-1), 55.9 (OMe) and 31.6 (d, J 49.0, PCH );
3
CP
(
8 H, m, PhH-2 and PhH-3), 7.60 (2 H, dd, J 8.8 and J 12.0,
HP
4
ϩ
Ϫ
1
CP
2
ArH-2), 7.13 (2 H, dd, J 2.6 and J 8.8, ArH-3), 3.52–3.44
HP
ϩ
m/z 412.1580 (60%, M Ϫ H. C H O P requires 412.1670)
and 322.1 (100%, M Ϫ CH Ph). M is defined here as the
phosphonium cation.
27
25
2
(
(
1
1
8
2 H, m, PCH ), 1.50–1.45 (4 H, m, PCH CH CH Me) and 0.87
2 2 2 2
Ϫ
ϩ
2
3 H, t, J 6.8, Me); δ (101 MHz; d -DMSO) 163.3 (ArC-4),
C 6
ϩ 2 ϩ ϩ 2
35.9 (d, J 11.6, ArC-2), 134.6 (PhC-4), 133.4 (d, J
CP CP
ϩ 3 Ϫ 1
0.0, PhC-2), 130.2 (d, JCP 12.3, PhC-3), 119.7 (d, JCP
Benzyl[bis(3-methoxyphenyl)]phenylphosphonium bromide 9
ϩ
3
Ϫ
1
6.1, PhC-1), 117.4 (d, J 13.7, ArC-3), 105.6 (d, J 93.9,
CP
CP
(
3-OMe; n ؍ 2; R ؍ Ph)
Ϫ
2
Ϫ
3
ArC-1), 23.9 (d, J 3.6, PCH CH ), 23.2 (d, J 17.1,
CH Me), 20.6 (d, JCP 51.2, PCH ) and 13.4 (Me); m/z
CP
1
2
2
CP
17
Ϫ
ϩ
By the method of Coumbe et al., titanium() isopropoxide
2
2
J. Chem. Soc., Perkin Trans. 1, 2000, 505–513
511

View Article Online
ϩ
(
ϩFAB) 335.1554 (100%, M . M requires 335.1565). M is
Benzyl[bis(3-hydroxyphenyl)]phenylphosphonium bromide 5
defined here as the phosphonium cation.
In the same way, benzyl[bis(3-methoxyphenyl)]phenylphos-
phonium bromide 9 (3-OMe; n = 2; R = Ph) (22.3 g, 45.2 mmol)
Benzyl(3-hydroxyphenyl)diphenylphosphonium bromide 3a
gave the phosphonium salt (8.41 g, 40%) as a powder, mp 268–
Ϫ1
In the same way, benzyl(3-methoxyphenyl)diphenylphosphon-
ium bromide 9 (3-OMe; n = 1; R = Ph) (3.50 g, 7.6 mmol) gave
the phosphonium salt (3.22 g, 95%) as a powder, mp 279–281 ЊC
2
1
1
72 ЊC (precipitated from water); νmax(Nujol)/cm 1596 and
574 (Ph) and 1458 and 1436 (P–Ph); δ (400 MHz; d -DMSO)
0.46 (2 H, br s, OH), 7.89 (1 H, br t, J 7.6, PPhH-4), 7.73 (2 H,
dt, J 3.6 and J 7.6, PPhH-3), 7.66 (2 H, dd, J 7.6 and J
12.3, PPhH-2), 7.54 (2 H, dt, J 4.6 and 8.0, ArH-5), 7.31–
H
6
4
3
(
white prisms from aqueous MeOH) (Found: C, 66.5; H, 4.9;
HP
HP
4
Br, 17.6; P, 6.9. C H BrOP requires C, 66.8; H, 4.9; Br, 17.8; P,
25
22
Ϫ1
HP
6
.9%); νmax(Nujol)/cm 1602 and 1574 (Ph) and 1460 and 1436
7.25 (2 H, m, CH PhH-4 and ArH-4), 7.23 (2 H, t, J 7.3,
2
3
(
7
P–Ph); δ (500 MHz; d -DMSO) 7.86 (2 H, br t, J 7.6, PPhH-4),
H
6
CH PhH-3), 7.10 (2 H, dd, J 8.0 and J 12.2, ArH-6), 7.01
2
HP
4
3
.70 (4 H, dt, J 3.3 and J 7.6, PPhH-3), 7.64 (4 H, dd, J 7.6
HP
3 4
(2 H, br d, J 7.3, CH PhH-2), 6.94 (2 H, br d, J 14.1, ArH-2)
2 HP
2
and J 12.3, PPhH-2), 7.51 (1 H, dt, J 4.7 and 7.7, ArH-5),
HP
HP
and 5.10 (2 H, d, J 15.7, PCH ); δ (101 MHz; d -DMSO)
HP 2 C 6
Ϫ 3 ϩ ϩ
7
.28–7.23 (2 H, m, CH PhH-4 and ArH-4), 7.19 (2 H, t, J 7.4,
2
3
158.3 (d, J 15.9, ArC-3), 135.1 (br s, PPhC-4), 134.0 (d,
CP
ϩ 3 ϩ 4
2
CH PhH-3), 7.07 (1 H, dd, J 7.8 and J 12.1, ArH-6), 6.98
2
HP
JCP 9.7, PPhC-2), 131.5 (d, J 14.9, ArC-5), 130.9 (d, J
CP CP
ϩ 3 ϩ
3
(
2 H, br d, J 7.4, CH PhH-2), 6.92 (1 H, br d, J 14.1, ArH-2)
2 HP
2
5.2, CH PhC-3), 130.1 (d, JCP 12.3, PPhC-3), 128.8 (s,
2
ϩ Ϫ 2
and 5.15 (2 H, d, J 15.65, PCH ); δ (101 MHz; d -DMSO)
HP
2
C
6
CH PhC-2), 128.4 (s, ArC-4), 128.1 (d, J 8.5, CH PhC-1),
2 CP 2
ϩ 2 ϩ ϩ
Ϫ
3
ϩ
ϩ
1
58.4 (d, J 16.0, ArC-3), 140.3 (br s, PPhC-4), 139.2 (d,
CP
124.4 (d, J 9.4, ArC-6), 122.1 (s, CH PhC-4), 120.2 (d,
CP 2
Ϫ 1 Ϫ 1
2
ϩ
3
ϩ
4
2
JCP 9.8, PPhC-2), 136.7 (d, J 15.0, ArC-5), 136.1 (d, J
CP
CP
JCP 10.8, ArC-2), 118.8 (d, J 84.8, ArC-1), 118.1 (d, J
CP CP
Ϫ 1
ϩ
3
ϩ
3
5
2
.4, CH PhC-3), 135.3 (d, J 12.4, PPhC-3), 133.95 (d, J
2 CP
ϩ 4 Ϫ 2
CP
85.4, PPhC-1) and 28.3 (d, J 46.8, PCH ); m/z (ϩFAB)
CP 2
ϩ
.5, CH PhC-2), 133.5 (d, J 3.2, ArC-4), 133.3 (d, J 8.6,
2
CP
CP
385.1345 (100%, M . M requires 385.1357). M is defined here
ϩ
2
ϩ
CH PhC-1), 129.65 (d, JCP 9.5, ArC-6), 127.3 (br s,
CH PhC-4), 125.4 (d, J 10.9, ArC-2), 123.9 (d, J 84.8,
ArC-1), 123.1 (d, J 85.5, PPhC-1) and 28.3 (d, J 46.8,
2
as the phosphonium cation.
ϩ
2
Ϫ
1
2
CP
CP
Ϫ
1
Ϫ
1
CP
CP
Typical Wittig reaction in water
ϩ
PCH ); m/z (ϩFAB) 369.1404 (100%, M . M requires
2
Benzyl(3-hydroxyphenyl)diphenylphosphonium bromide 3a
3
69.1408). M is defined here as the phosphonium cation.
(
0.203 g, 0.45 mmol) and 4-nitrobenzaldehyde (83.1 mg, 0.55
3
3
mmol) were suspended in 1 cm water. NaOH (1 cm of a 10%
solution in water) was added dropwise and the phosphonium
salt dissolved. The solution was left to stir overnight at room
temperature. It was then filtered and washed with base to give
the stilbene 14 (100 mg, 98%) as a mixture of stereoisomers
Butyl(3-hydroxyphenyl)diphenylphosphonium bromide 3b
In the same way, butyl(3-methoxyphenyl)diphenylphosphon-
ium bromide 9 (3-OMe; n = 1; R = Pr) (2.40 g, 5.6 mmol) gave
the phosphonium salt (2.12 g, 91%) as needles, mp 164–167 ЊC
Ϫ1
(
1
from EtOH–Et O); νmax(Nujol)/cm 1597 and 1567 (Ph) and
2
5
(
E:Z, 60:40). The aqueous solution was acidified by 3 M HCl
463 (P–Ph); δ (400 MHz; d -DMSO) 7.89 (2 H, dt, J 1.3
H 6 HP
to pH 1 and then filtered to give 3-hydroxyphenyldiphenyl-
phosphine oxide 18 (117 mg, 87%).
and J 6.8, PhH-4), 7.84–7.74 (8 H, m, PhH-2 and PhH-3), 7.58
4
5
(
1H, dt, J 4.7 and J 8.2, ArH-5), 7.27 (1 H, dd, J 1.0 and
HP HP
3
All alkenes synthesised are known compounds and the E:Z
ratios were all determined by integration of discrete peaks in
J 8.2, ArH-4), 7.22 (1 H, dd, J 8.2 and J 12.4, ArH-6), 7.07
HP
3
(
(
1 H, d, J 14.1, ArH-2), 3.60–3.51 (2 H, m, PCH ), 1.52–1.45
1
HP
2
the H NMR spectra of the crude isolated alkene. The alkenes
4 H, m, PCH CH CH Me) and 0.88 (3 H, t, J 6.9, Me); δ (101
MHz; d -DMSO) 158.4 (d, J 15.7, ArC-3), 134.8 (PhC-4),
33.5ϩ (d, JCP 10.1, PhC-2), 131.7 (d, JCP 14.9, ArC-5),
30.2 (d, J 12.4, PhC-3), 123.9 (d, J 9.6, ArC-6), 121.9
24
2
2
2
C
include 1,2-diphenylethene 11,
1-(4-methoxyphenyl)-2-
Ϫ
3
ϩ
25
25
6
CP
phenylethene 12, 1-(4-chlorophenyl)-2-phenylethylene 13,
-(4-nitrophenyl)-2-phenylethylene 14,
yl)furan and 2-(2-phenylethen-1-yl)pyridine.
ϩ
2
ϩ
3
1
1
(
25
1
2-(2-phenylethen-1-
3
ϩ
2
ϩ
26
27
CP
CP
ϩ
2
Ϫ
1
ArC-4), 119.6 (d,
J
11.1, ArC-2), 119.3 (d, JCP
Ϫ 2
CP
Ϫ
1
8
5.0, ArC-1), 118.6 (d, J 85.5, PhC-1), 23.9 (d, J 4.2,
CP CP
Ϫ 3 Ϫ 1
Attempted Wittig reaction between 4-(butyldiphenylphosphonio)-
benzoic acid bromide 1b and benzaldehyde
PCH CH ), 23.1 (d, J 17.1, CH Me), 20.1 (d, J 49.9,
2
2
CP
2
CP
ϩ
ϩ
PCH ) and 13.3 (Me); m/z (ϩFAB) 335.1540 (100%, M . M
2
4
0
-(Butyldiphenylphosphonio)benzoic acid bromide 1b (0.208 g,
requires 335.1565). M is defined here as the phosphonium
cation.
3
.47 mmol) was suspended in water (1 cm ). Benzaldehyde (50
3
µm , 0.47 mmol) was added and the suspension stirred. NaOH
(1 cm of a 10% solution in water) was added dropwise to the
3
Benzyl[bis(4-hydroxyphenyl)]phenylphosphonium bromide 4
mixture. The phosphonium salt dissolved upon addition of
the aqueous base. The solution was stirred overnight at room
temperature and extracted with diethyl ether (3 × 2 cm ). The
In the same way, benzyl[bis(4-methoxyphenyl)]phenylphos-
phonium bromide 9 (4-OH; n = 2; R = Ph) (2.16 g, 4.4 mmol)
gave the phosphonium salt (1.94 g, 95%) as a powder, mp 336–
3
combined organic extracts were dried (MgSO ) and evaporated
4
3
39 ЊC (white needles from aqueous MeOH) (Found: C, 64.0;
28
under reduced pressure to give the phosphine oxide 17 (37
H, 4.75; P, 6.9. C H BrO P requires C, 64.5; H, 4.8; P, 6.7%);
2
5
22
2
mg, 31%) as yellow crystals. The aqueous fraction was acidified
Ϫ1
νmax(Nujol)/cm 1598 and 1575 (Ph) and 1462 (P–Ph); δ (500
H
to pH 1 with 3 M HCl and extracted with dichloromethane
MHz; d -DMSO) 10.9 (2 H, s, OH), 7.8 (1 H, t, J 7.5, PPhH-4),
6
3
(
3 × 5 cm ). The combined organic extracts were dried (MgSO )
4
4
7
.7 (2 H, dt, J 3.2 and J 7.5, PPhH-3), 7.6 (2 H, dd, J 7.5 and
HP
and evaporated under reduced pressure to give the phosphine
oxide 18 (96 mg, 67%) as a white foam; δ (400 MHz; d -
3
3
JHP 12.4, PPhH-2), 7.4 (4 H, dd, J 8.7 and J 11.9, ArH-2),
HP
H
6
7
7
.3 (1 H, br t, J 7.2, CH PhH-4), 7.2 (2 H, t, J 7.2, CH PhH-3),
2 2
4
DMSO) 7.98–7.72 (9 H, m) 2.45–2.40 (2 H, m, PCH ), 1.39–
2
.05 (4 H, dd, J 2.6 and J 8.7, ArH-3), 6.95 (2 H, d, J 7.2,
HP
2
1
.34 (4 H, m, PCH CH CH Me) and 0.8 (3 H, t, J 6.9, Me).
2 2 2
CH PhH-2) and 4.9 (2 H, d, J 15.5, PCH ); δ (101 MHz;
2
HP
2
ϩ
C
Ϫ
4
2
d -DMSO) 163.3 (d, J 2.5, ArC-4), 136.2 (d, J 11.4,
6
CP
CP
Attempted Wittig reaction between butyl(3-hydroxyphenyl)-
diphenylphosphonium bromide 3b and benzaldehyde
ϩ
ϩ
2
ϩ
ArC-2), 134.7 (s, PPhC-4), 133.8 (d, J 9.8, PPhC-2), 130.9ϩ
CP
4
ϩ
3
(
(
d, J 5.2, CH PhC-3), 130.1 (d, J 12.2, PPhC-3), 128.7
CP 2 CP
Ϫ ϩ
s, CH PhC-4), 128.7 (s, CH PhC-1), 128.2 (s, CH PhC-2),
In the same way, butyl(3-hydroxyphenyl)diphenylphosphonium
2
2
2
Ϫ
1
ϩ
3
3
1
1
19.9Ϫ (d, J 86.3, PPhC-1), 117.2 (d, J 13.7, ArC-3),
bromide 3b (0.174 g, 0.42 mmol) and benzaldehyde (50 µm ,
CP
CP
1
Ϫ
1
3
05.9 (d, J 94.5, ArC-1) and 29.2 (d, J 49.2, PCH ); m/z
0.47 mmol) in water (1 cm ) were reacted, except that NaOH
CP
CP
2
ϩ
3
(
ϩFAB) 464.0577 (3%, M . M requires 464.0541), 385.4 (100%,
(1 cm of a 30% solution in water) was used and the mixture
M Ϫ Br).
was stirred overnight at reflux. The dichloromethane extract
5
12
J. Chem. Soc., Perkin Trans. 1, 2000, 505–513

View Article Online
9 M. Delmas, Y. Le Bigot, A. Gaset and J. P. Garrichon, Synth.
was dried (MgSO ) and evaporated under reduced pressure to
give butyl(3-hydroxyphenyl)phenylphosphine oxide 20 (66 mg,
4
Commun., 1982, 107.
0 M. Butcher, R. J. Mathews and S. Middleton, Aust. J. Chem., 1973,
1
5
8%); δ (400 MHz; d -DMSO) 9.9 (1 H, br s, OH), 7.8–7.7
H 6
2
6, 2067.
(
2 H, m, PhH-3), 7.53–7.47 (3 H, m, PhH-2 and PhH-4), 7.3
1
1 R. Broos, D. Tavernier and M. Anteunis, J. Chem. Educ., 1978, 55,
4
(
1 H, dt, J 3.8 and J 7.8, ArH-5), 7.2 (1 H, d, J 7.8, ArH-4),
HP
813.
3
3
7
.1 (1 H, d, J 2.3, ArH-2), 6.9 (1 H, dd, J 2.3 and J 7.8,
12 K. Schleich, C. H. Zollikerberg, H. Stoller and C. H. Reinach, 1977,
HP
HP
ArH-6), 2.33–2.26 (2 H, m, PCH ), 1.43–1.29 (4 H, m,
GP 2733231 C2 (Chem. Abstr., 1977, 88, P 191170e).
3 X. M. Zhang and F. G. Bordwell, J. Am. Chem. Soc., 1994, 116,
968.
2
1
PCH CH CH Me) and 0.8 (3 H, t, J 7.0, Me); δ (101 MHz;
2
2
2
C
Ϫ
3
Ϫ
1
d6-DMSO) 157.5 (d, J 14.1, ArC-3), 135.0 (d, J 95.5,
ArC-1 or PhC-1), 133.8 (d, J 96.0, ArC-1 or PhC-1), 131.5
PhC-4), 130.4 (d, JCP 9.3, PhC-2), 130.0 (d, JCP 13.5,
ArC-5), 128.7 (d, J 11.1, PhC-3), 120.9 (d, J 9.2, ArC-2
or ArC-6), 118.6 (ArC-4), 117.0 (d, JCP 9.7, ArC-2 or
ArC-6), 28.1 (d, J 71.8, PCH ), (23.25–22.38) (m, PCH -
CH CH Me) and 13.6 (Me).
CP
CP
1
1
4 M. Grayson and P. T. Keough, J. Am. Chem. Soc., 1960, 82, 3919.
5 V. Ravindar, H. Hemling, H. Schumann and J. Blum, Synth.
Commun., 1992, 22, 841.
Ϫ
1
ϩ
CP
ϩ
2
ϩ
3
(
ϩ 3 ϩ 2
CP
CP
16 W. E. McEwen, W.-I. Shiau, Y.-I. Yeh, D. N. Schulz, R. U. Pagilagan,
J. B. Levy, C. Symmes Jr., G. O. Nelson and I. Granoth, J. Am.
Chem. Soc., 1975, 97, 1787.
ϩ
ϩ
2
Ϫ
1
Ϫ
CP
2
2
ϩ
17 T. Coumbe, N. J. Lawrence and F. Muhammad, Tetrahedron Lett.,
2
2
1
994, 35, 625.
1
1
8 C. Larpent and H. Patin, Tetrahedron, 1988, 44, 6107.
9 R. A. Y. Jones, Physical and Mechanistic Organic Chemistry,
Cambridge University Press, Cambridge, 1984.
Acknowledgements
We thank the EPSRC Clean Technology Unit and Zeneca
Specialties for grants (to M. G. R.). We also wish to thank
Dr A. Collins of Zeneca Specialties for his support throughout
the project.
20 S. E. Tunney and J. K. Stille, J. Org. Chem., 1987, 52, 748.
2
2
2
2
1 A. E. Senear, W. Valient and J. Wirth, J. Org. Chem., 1960, 25,
001.
2 C. M. Whitaker, K. L. Kott and R. J. McMahon, J. Org. Chem.,
995, 60, 3499.
3 G. L. Kelden and W. E. McEwen, J. Am. Chem. Soc., 1978, 100,
312.
2
1
7
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8
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513