Wittig reaction using perfluorinated ylides

Article abstract of DOI:10.1016/S0040-4039(01)01055-3

Wittig reactions could be performed in perfluorosolvents using perfluorinated ylides, allowing both a very easy separation of the alkene from the phosphine oxide and a re-use of the latter by simple reduction of the crude oxide.

Full text of DOI:10.1016/S0040-4039(01)01055-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 5425–5427
Wittig reaction using perfluorinated ylides
Aure´lie Galante, Paul Lhoste and Denis Sinou*
Laboratoire de Synthe`se Asyme´trique, associe´ au CNRS, CPE Lyon, Universite´ Claude Bernard Lyon 1,
43, boulevard du 11 novembre 1918, 69622 Villeurbanne Cedex, France
Received 11 June 2001; revised 15 June 2001; accepted 16 June 2001
Abstract—Wittig reactions could be performed in perfluorosolvents using perfluorinated ylides, allowing both a very easy
separation of the alkene from the phosphine oxide and a re-use of the latter by simple reduction of the crude oxide. © 2001
Elsevier Science Ltd. All rights reserved.
In 1994, Horva`th and Ra`bai introduced the concept of
fluorous biphasic system in catalysis,1 followed in 1998
by Curran’s concept of an ‘ideal purification’.2 In these
concepts, the product(s) of the reaction is(are) sepa-
rated into a different phase from everything else present
in the mixture.3 Since fluorous biphasic catalysis is
becoming increasingly important during recent years,
the use of fluorous organic reagents is also rapidly
developing, since they allow an easy purification or
removal of the fluorous compound from organic ones
by simple liquid–liquid extraction techniques. A num-
ber of fluorous reagents (tin hydrides,4 allyltin
reagents,5 allyl stannanes,6 organoselenium reagent7)
and protecting groups8 have been introduced recently in
organic synthesis.
The Wittig reaction is one of the most used methodol-
ogy for CꢀC bond formation,9 giving good to excellent
stereoselectivities. However, one of the problems is the
separation of the formed alkene from the by-product
Ph3PO, which is usually done by chromatography or by
recrystallization. Recently an easy separation of alkenes
from the phosphine oxide was performed using water-
soluble phosphonium salts10 or ionic salt as the
solvent.11
In this communication, we demonstrate the usefulness
of perfluorinated ylides in this coupling reaction, allow-
ing the reaction to be performed in perfluorinated
solvents, and most importantly an easy separation of
perfluorinated phosphine oxide from the formed alkene.
NEt3
(p-C7F15CH2OC6H4)3P=CH-Z
(p-C7F15CH2OC6H4)3P
+
BrCH2-Z
2 a-b
3 a-b
1
a: Z = CO2Et
b: Z = CN
a: Z = CO2Et
b: Z = CN
+ (p-C7F15CH2OC6H4)3PO
R-CH=CH-Z
5 a-j
(p-C7F15CH2OC6H4)3P=CH-Z + R-CHO
4 a-e
3 a-b
a: R = C6H5
b: R = p-CH3OC6H4
c: R = p-NO2C6H4
d: R = o-CH3C6H4
e: R = C6H12
Scheme 1.
Keywords: perfluorinated ylides; Wittig reaction; perfluorinated solvents; recycling.
* Corresponding author. Tel.: +33 (0)4 72446263; fax: +33 (0)4 72448160; e-mail: sinou@univ-lyon1.fr
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01055-3

5426
A. Galante et al. / Tetrahedron Letters 42 (2001) 5425–5427
Table 1. Wittig reactions of ylides 3 with aldehydes 4
Entry
Aldehyde
Bromide
Time (h)
Conversion of 4 (%)a
Yield olefin 5 (%)b
E/Zc
1
2
3
4
5
6
7
8
9
4a
4b
4c
4d
4e
4a
4b
4c
4d
4e
2a
2a
2a
2a
2a
2b
2b
2b
2b
2b
3
17
4.5
15
13
22
28
19
17
13
79
76
84
88
84
73
70
91
75
77
5a (66)
5b (64)
5c (80)
5d (65)
5e (61)
5f (50)
5g (41)
5h (56)
5i (56)
5j (51)
95/5
96/4
92/8
95/5
97/3
77/23
73/27
68/32
69/31
84/16
10
a Determined by GC and 1H NMR.
b Yield based on the product obtained by extraction after elimination of the aldehyde.
c Determined by GC and 1H NMR.
In conclusion, Wittig reactions of stabilized perfluori-
nated ylides with aldehydes are easily performed in
perfluorosolvents. This method offers an attractive pos-
sibility for an easy separation of the alkene and the
phosphine oxide. Moreover, the phosphine oxide could
be easily reduced and recycled. Work is in progress in
order to improve this reaction and to extend it to other
reactions using perfluorinated triphenylphosphine as
reactant.
Benzaldehyde 4a and phosphorane 3a were selected as
the model to develop this methodology (Scheme 1). The
phosphorane 3a was prepared in situ in a mixture of
perfluorosolvent D-100 and toluene starting from
perfluorophosphine 112 and ethyl bromoacetate. At the
end of the reaction, the obtained alkene was extracted
with diethyl ether and the perfluorocompounds with
perfluorosolvent.13 Evaporation of the organic solvent
gave the alkene 5a as a mixture of the E/Z isomers in
a 95/5 ratio in 66% yield (Table 1, entry 1), without any
trace of phosphine oxide detected by 31P NMR. Other
aldehydes were used in this reaction. p-Methoxy and
p-nitrobenzaldehyde 4b and 4c bearing an electron-
donating and withdrawing group, respectively, reacted
under these conditions to give the corresponding alkenes
5b and 5c in 64 and 80% yield, respectively (Table 1,
entries 2 and 3). It is also the case for a sterically hindered
benzaldehyde such as o-methylbenzaldehyde 4e, which
gave the olefin 5e in 65% yield (Table 1, entry 4).
Acknowledgements
We are grateful to Ausimont s.p.A. Bollate (Italy) for
generously providing perfluorinated solvent Galden D-
100 (mainly perfluorooctane).
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13. Experimental procedure: In a Schlenk tube under argon
were added the perfluorophosphine (300 mg, 0.2 mmol)
in D-100 (2 mL) and ethyl bromoacetate (33.4 mg, 0.2
mmol) in toluene (2 mL). After being stirred for 1 h at
80°C, NEt3 (21.2 mg, 0.21 mmol) was added and the
solution was stirred for 0.5 h at 80°C. The aldehyde (0.19
mmol) was added and the mixture stirred for the desired
time. At the end of the reaction, water (2 mL) and diethyl
ether (2 mL) were added, and the different phases were
separated. The aqueous and organic phases were
extracted with D-100 (2×2 mL) and the aqueous phase
with diethyl ether (2×2 mL). Evaporation of the fluorous
phase gave the perfluorophosphine oxide, although evap-
oration of the organic phase gave the alkene together
with the unreacted aldehyde.
.