Olefination reactions using tetraarylphosphonium (TAP)-supported phosphorus ylides

Article abstract of DOI:10.1055/s-0030-1260065

Tetraarylphosphonium (TAP)-supported phosphorus ylides were prepared and used in copper-catalyzed olefination reactions with diazo compounds to produce conjugated esters, amides, and phosphonates. The TAP-phosphine oxide can easily be separated from the alkene product, recycled, and reused. Georg Thieme Verlag Stuttgart ? New York.

Full text of DOI:10.1055/s-0030-1260065

PAPER
2275
Olefination Reactions Using Tetraarylphosphonium (TAP)-Supported
Phosphorus Ylides
Olefination
Reacti
é
ons
U
sing
T
l
A
P-Su
è
pported Ph
n
osphorus
Y
l
es
Lebel,* Michaël Davi, Marie-Noelle Roy, Walid Zeghida, André B. Charette*
Department of Chemistry and Centre in Green Chemistry and Catalysis (CGCC), Université de Montréal, Pavillon Roger Gaudry,
2900 Boul. Édouard-Montpetit, Montréal, QC, H3T 1J4, Canada
Fax +1(514)3437586helene.lebel@umontreal.ca
Received 11 March 2011; revised 14 April 2011
–
–
ClO4
Ph3P+
ClO4
Ph3P+
O
Abstract: Tetraarylphosphonium (TAP)-supported phosphorus
ylides were prepared and used in copper-catalyzed olefination reac-
tions with diazo compounds to produce conjugated esters, amides,
and phosphonates. The TAP-phosphine oxide can easily be separat-
ed from the alkene product, recycled, and reused.
Ph2
BrCH2CO2Et
(2.0 equiv)
P
PPh2
+
OEt
Br–
MeCN, r.t., 16 h
94%
1
2
Key words: alkenes, diazo compounds, green chemistry, Wittig re-
action, ylides
Equation 1
level of decomposition of the tetraarylphosphonium was
observed with potassium tert-butoxide in acetonitrile.
Conversely, the use of a milder base such as triethylamine
led to the formation of the corresponding TAP-phospho-
rus ylide, which was not isolated, but directly reacted with
aldehydes. The corresponding a,b-unsaturated esters were
isolated in excellent yields as pure materials after a pre-
cipitation and filtration of the TAP-phosphorus residues
(Table 1). As expected with a stabilized ylide, the E-iso-
mer was the major product. However the ratio was slightly
lower in comparison to a typical olefination reaction with
the triphenylphosphine-derived ester ylide. Aromatic al-
dehydes produced alkenes 3 and 4 in an 88:12 E/Z ratio,
while a modest 78:22 ratio was observed with citronellal.
This might be due to a solvent effect (MeCN), as it is
known that increasing solvent polarity has a detrimental
effect on the E/Z ratio.
Olefination reactions of carbonyl compounds are among
the most commonly used strategies to assemble carbon–
carbon double bonds.1 Among these, the Wittig reaction2
remains very popular, because of the reliability of this
method with a wide range of substrates, as well as good
yields and selectivities.3 However, the use of stoichiomet-
ric amounts of triphenylphosphine that generates triphe-
nylphosphine oxide as a by-product is still an important
drawback associated with this famous reaction.4 Although
a number of solutions have been disclosed to overcome
this problem,5 a general method that shows high reactivity
combined with the ability to recycle the reagent has not
yet been reported. Tetraarylphosphonium (TAP)-support-
ed reagents have recently been reported as an innovative
technology to recover and reuse reagents that could poten-
tially be harmful to the environment, while maintaining a
high level of reactivity. In particular, tetraarylphosphoni-
um (TAP)-supported triphenylphosphine 1 has success-
fully been used in the Corey–Fuchs and Mitsunobu
reactions.6 Herein, we wish to report the use of TAP-phos-
phorus ylides in olefination reactions, as easily separable
and recyclable phosphorus reagents.
Table 1 Olefination of Aldehydes Using TAP-Phosphonium Salt 2a
Entry Product
Yield (%)b E/Zc
O
1
3
77d
88:12
OEt
At the outset, we decided to investigate the olefination of
aldehydes with the TAP-phosphorus ylides generated in
situ via the deprotonation of the corresponding TAP-
phosphonium salts. TAP-PPh3 1 was reacted with two
equivalents of ethyl bromoacetate to produce bisphospho-
nium 2 in 94% yield (Equation 1).
2
3
3
3
87e
99
88:12
88:12
O
4
5
4
5
98
98
88:12
78:22
OEt
Such a species was found to be highly insoluble in nonpo-
lar solvents, such as toluene or tetrahydrofuran, solvents
that are typically used in olefination reactions with bases
such as n-butyllithium, lithium hexamethyldisilazide, or
sodium hexamethyldisilazide. Furthermore, a significant
S
O
OEt
a Reaction was performed on a 1 mmol scale using 1.5 equiv of phos-
phonium 2 and 1.5 equiv of Et3N in MeCN (0.2 M) at 60 °C.
b Isolated and combined yields of E- and Z-isomers.
c Determined by 1H NMR spectroscopy of the crude mixture.
d Et3N (1.2 equiv), 2 (1.2 equiv).
SYNTHESIS 2011, No. 14, pp 2275–2280
x
x.
x
x
.
2
0
1
1
Advanced online publication: 10.06.2011
DOI: 10.1055/s-0030-1260065; Art ID: M27311SS
© Georg Thieme Verlag Stuttgart · New York
e Et3N (1.2 equiv), 2 (1.2 equiv), reflux, sealed tube.

2276
H. Lebel et al.
PAPER
We hypothesized that the corresponding TAP-supported The olefination of hydrocinnamaldehyde in the presence
phosphorus ylide might have a better solubility in nonpo- of ethyl diazoacetate (EDA), TAP-PPh3 1 and 5–10 mol%
lar solvents, thus no longer requiring the use of acetoni- of copper(I) iodide was thus investigated in various non-
trile. Thus, the corresponding TAP-stabilized ylide was polar solvents (Table 3). The desired a,b-unsaturated es-
isolated as follows: after formation of TAP-phosphonium ter 7 was produced in an excellent E/Z ratio ( 95:5) albeit
2, the reaction mixture was diluted with dichloromethane in moderate yields with tetrahydrofuran, 1,4-dioxane, and
and washed with a 10% aqueous sodium hydroxide solu- toluene (Table 3, entries 1–5) as solvents. Conversely, the
tion to produce the desired TAP-ylide 6 as a stable, slight- yield was improved using 1,2-dichloroethane (DCE) at
ly yellow solid in 82% yield (Equation 2).
80 °C, while maintaining a high level of diastereoselectiv-
ity (entry 7). Decreasing the catalyst loading led to lower
yields, whereas the use of 10 mol% copper(I) iodide gave
slightly better results (entries 7–9), although this had no
impact on the isolated yield (entries 10, 11). The amount
of ethyl diazoacetate can be decreased to 1.2 equivalents
if added dropwise (entries 7 vs. 10). Using such a proce-
dure, it was found that excess ethyl diazoacetate was del-
eterious to the olefination reactions as the yield was lower
when using 2 equivalents versus 1.2 equivalents (entries
11–13). The use of an excess of TAP-PPh3 1 was not ben-
eficial to the reaction either (entries 14, 15).
–
–
ClO4
ClO4
O
1) BrCH2CO2Et
(2.0 equiv)
MeCN, r.t.
Ph2
P
Ph3P+
Ph3P+
PPh2
OEt
2) NaOH (aq, 10%)
CH2Cl2
1
6
82%
Equation 2
The reaction of aldehydes with TAP-ylide 6 in tetrahydro-
furan produced the corresponding a,b-unsaturated esters
in high yields and E/Z ratios (Table 2). A simple precipi-
tation and filtration of the TAP-phosphorus residues af-
forded pure alkene products.
Table 3 Copper-Catalyzed Olefination of Hydrocinnamaldehyde
with Ethyl Diazoacetate and TAP-PPh3 1 Producing Alkene 7a
Entry CuI
EDA Conditions
Yield E/Zd
(mol%) (equiv)
(%)b,c
Table 2 Olefination of Aldehydes Using TAP-Ylide 6a
1
2
5
2
THF (0.22 M), 60 °C
48 95:5
Entry Product
Yield (%)b E/Zc
5
2
1,4-dioxane (0.22 M), 60 °C 35 95:5
1,4-dioxane (0.16 M), 80 °C 43 95:5
O
O
1
2
3
3
4
7
91
95
89
95:5
3
5
1.5
2
OEt
OEt
4
5
toluene (0.22 M), 60 °C
toluene (0.16 M), 80 °C
DCE (0.22 M), 60 °C
DCE (0.16 M), 80 °C
DCE (0.16 M), 80 °C
DCE (0.16 M), 80 °C
DCE (0.16 M), 80 °C
52 95:5
46 95:5
62 95:5
69 95:5
58 95:5
77 95:5
73 95:5
5
5
1.5
2
89:11
89:11
6
5
S
7
5
1.5
1.5
1.5
1.2e
O
8
2.5
OEt
9
10
a Reaction was performed on a 1 mmol scale using 1.5 equiv of TAP-
ylide 6 in THF at r.t.
10
5
(68)
b Isolated and combined yields of E- and Z-isomers.
c Determined by 1H NMR of the crude mixture.
11
10
1.2e
DCE (0.16 M), 80 °C
80 95:5
(66)
The additional step to prepare reagent 6, combined with 12
10
10
10
10
1.5e
2.0e
1.2e
1.2e
DCE (0.16 M), 80 °C
DCE (0.16 M), 80 °C
DCE (0.16 M), 80 °C
DCE (0.16 M), 80 °C
74 95:5
71 95:5
75 95:5
71 95:5
the fact that the E/Z ratios were still lower than those ob-
served in the normal Wittig reaction, prompted us to study
13
14f
15g
alternative methods to produce the phosphorus ylide. Re-
cently, a number of methods based on the transition-
metal-catalyzed decomposition of diazo compounds in
the presence of phosphorus reagents to produce alkenes
from aldehydes have been disclosed.7 In particular, cop-
per salts appear to be general, cost-effective and efficient
catalysts for such a reaction.8 As copper-catalyzed olefi-
nation reactions with diazo compounds proceeded under
mild nonbasic reaction conditions, these were particularly
appropriate for sensitive carbonyl substrates that decom-
posed under typical Wittig reaction conditions.8a,c
a Performed on a 0.25 mmol scale.
b Combined yields of E- and Z-isomers determined by 1H NMR spec-
troscopy with bibenzyl as standard.
c Isolated yields in parentheses.
d Determined by 1H NMR of the crude mixture.
e EDA was added over 2 hours.
f Using 1.5 equiv of TAP-PPh3 1.
g Using 2.0 equiv of TAP-PPh3 1.
Synthesis 2011, No. 14, 2275–2280 © Thieme Stuttgart · New York

PAPER
Olefination Reactions Using TAP-Supported Phosphorus Ylides
2277
Finally, alkene 7 was isolated in 68% yield in an E/Z ratio
of 95:5 in the presence of 1.2 equivalents of ethyl diazo-
acetate and TAP-PPh3 1 in 1,2-dichloroethane at 80 °C us-
ing 5 mol% copper(I) iodide (Table 4, entry 7). It is
assumed that ylide 6 is produced under these reaction con-
ditions according to precedent mechanistic investigations
for copper-catalyzed olefination with diazo compounds
(Scheme 1).8a The purification procedure was simplified
to a precipitation of the phosphorus residue using diethyl
ether. Whereas the crude 1H NMR sprectrum of the reac-
tion with triphenylphosphine showed aromatic impurities
(spectrum A), all tetraarylphosphonium residues could be
precipitated with diethyl ether from the reaction mixture
and collected by filtration (spectrum B)9 (Figure 1).
TAP-PPh3=CHCO2Et
6
[CuI]
R
O
EtO2CCHN2
CO2Et
R
TAP-PPh3
TAP-PPh3=O
1
HSiCl3
recycling
1
Figure 1 Crude H NMR spectrum of alkene 7 prepared from hy-
drocinnamaldehyde, after precipitation with Et2O. Reaction conditi-
ons: Method A: EDA (1.2 equiv), Ph3P (1.2 equiv), CuI (5 mol%) in
THF (0.25 M) at 60 °C; Method B: EDA (1.2 equiv), TAP-PPh3 (1.2
equiv), CuI (5 mol%) in DCE (0.15 M) at 80 °C.
Scheme 1 Green cycle using TAP-PPh3 1
Moreover, TAP-PPh3 1 can be easily recycled from TAP-
Ph3P=O by reduction using trichlorosilane6a and reused
in subsequent reactions with the same efficiency
(Scheme 1). Overall we have developed an efficient green
cycle for olefination reaction that allowed for the easy re-
covery and recycle of the phosphine derivative, while
maintaining a good reactivity.
Finally, trifluoromethylketone 16 was also reacted under
these reaction conditions leading to the formation of con-
jugated ester 17 and amide 18 in good yields and selectiv-
ities (Equation 3).
The optimal reaction conditions were tested with various
aldehydes using diazo carbonyl and phosphonate reagents
with TAP-PPh3 1 (Table 4). Good yields and high selec-
tivities were obtained with aromatic aldehydes containing
either electron-withdrawing or -donating groups (Table 4,
entries 1–5). The desired alkenes were produced not only
with ethyl diazoacetate, but also with dimethyl diazoacet-
amide and Seyferth–Gilbert reagent (entries 1 and 4 com-
pared to 5 and 2). Heterocycles such as pyridine are also
compatible under these reaction conditions, and the corre-
sponding conjugated ester was recovered with 55% yield
in an E/Z ratio of 93:7 (entry 6). Aliphatic aldehydes also
produced the desired alkenes in good yields and high
selectivities with ethyl diazoacetate (entries 7 and 9).
Conversely, moderate yields and slightly lower diastereo-
selectivities were observed with dimethyl (diazometh-
yl)phosphonate as the reagent (entries 8 and 10). There is
a good functional group tolerance for Boc-protected
amines (entries 4, 5) and acetal-derived substrates (entry
10).
–
ClO4
Ph3P+
PPh2
CF3
CF3
O
1 (1.2 equiv)
RC(O)CHN2 (1.2 equiv)
CuI (5 mol%)
DCE (0.15 M), 80 °C
Ph
O
Ph
R
16
R = OEt, 17, 71%, E/Z = 11:89
R = NMe2, 18, 62%, E/Z = 3:97
Equation 3
In conclusion, we have shown that TAP-PPh3 1 can be
used to prepare phosphorus ylides that can be isolated or
in situ generated from diazo reagents. Subsequent olefina-
tion reactions were performed with various carbonyl com-
pounds to produce the desired alkenes. Finally, the
separation and the recovery of TAP-PPh3 1 are straight-
forward, allowing an efficient recycling of the phosphorus
reagent.
Synthesis 2011, No. 14, 2275–2280 © Thieme Stuttgart · New York

2278
H. Lebel et al.
PAPER
PPh3 1 was prepared according to literature.6a CAUTION: Al-
though no explosions occurred in any of our experiments, diazo
compounds are toxic and potentially explosive. They should be
stored in refrigerator and handled with caution in a fume hood. Eth-
yl diazoacetate is commercially available, but was prepared from
ethyl glycinate hydrochloride according to the literature.11 N,N-
Table 4 Copper-Catalyzed Olefination of Aldehydes with TAP-
PPh3 1a
Entry Product
Yield (%)b E/Zc
O
Dimethyl
diazoacetamide12
and
dimethyl
(diazometh-
1
2
3
8
78
60
96:4
95:5
OEt
yl)phosphonate13 were prepared according to published procedures.
Analytical TLC was performed using 0.25 mm silica gel 60-F
plates. Visualization of the developed chromatogram was per-
formed by UV absorbance, aqueous cerium molybdate, ethanolic
phosphomolybdic acid, I2, or aq KMnO4. Flash chromatography
was performed using silica gel 60 (230–400 mesh) with the indicat-
ed solvent system according to standard technique.14 Melting points
are uncorrected. IR spectra are reported in cm–1 and recorded neat
O
P
OMe
OMe
O
1
with a Golden Gate Diamond ATR. Chemical shifts for H NMR
3
4
9
83
69
93:7
98:2
OEt
spectra were recorded in parts per million (ppm) on the d scale rel-
ative to an internal standard of residual solvent (chloroform, d =
7.27). Data are reported as follows: chemical shift, multiplicity (us-
ing standard abbreviations), coupling constant in Hz, integration,
and assignment. Chemical shifts for 13C NMR spectra were record-
ed in parts per million from TMS using the central peak of CDCl3
(77.23 ppm) as the internal standard. All spectra were obtained with
complete proton decoupling. When ambiguous, proton and carbon
assignments were established using COSY, HMQC or HSQC, and
DEPT experiments. High-resolution mass spectra were recorded by
the Centre régional de spectroscopie de masse de l’Université de
Montréal. Accurate mass measurements were performed on a LC-
MSD-TOF instrument from Agilent Technologies in positive elec-
trospray. Either protonated molecular ions [M + H]+ or sodium ad-
ducts [M + Na]+ were used for empirical formula confirmation.
Combustion analyses were performed by the Laboratoire d’analyse
élémentaire de l’Université de Montréal.
O2N
O
10
OEt
BocHN
O
5
6
7
11
12
7
70
55
68
97:3
93:7
95:5
NMe2
BocHN
N
O
OEt
O
(2-Ethoxy-2-oxoethyl)(diphenyl)[3-triphenyl(phosphonio)phe-
nyl]phosphonium Bromide Perchlorate (2)
OEt
To a solution of TAP-PPh3 16a (10.0 g, 16.0 mmol, 1.00 equiv) in
MeCN (40 mL, 0.4 M) was added ethyl bromoacetate (3.42 mL,
32.0 mmol, 2.00 equiv). The solution was stirred at r.t. and a precip-
itate formed as the reaction proceeded. After stirring for 16 h, Et2O
(200 mL) was added to precipitate the bisphosphonium salt 2 and
the mixture was vigorously stirred for an additional 20 min. The sol-
id was collected by filtration and further washed with Et2O (50 mL)
to afford the bisphosphonium salt 2 as a white solid; yield: 11.95 g
(94%); mp 190 °C (dec.), 205 °C (melt).
O
P
OMe
OMe
8
9
13
14
53
90:10
92:8
O
57d
OEt
O
P
OMe
OMe
IR (neat): 3422, 2169, 1721, 1585, 1438, 1311, 1188, 1085, 954,
687, 622 cm–1.
1H NMR (400 MHz, CD2Cl2): d = 8.29–8.24 (m, 1 H), 8.02–7.96
(m, 2 H), 7.92–7.77 (m, 16 H), 7.73–7.63 (m, 10 H), 5.43 (d,
J = 14.1 Hz, 2 H), 4.01 (q, J = 7.1 Hz, 2 H), 1.07 (t, J = 7.1 Hz, 3 H).
O
MeO
10
15
57
92:8
O
O
13C NMR (100 MHz, CD2Cl2): d = 165.0 (d, J = 3.2 Hz, 1 C), 141.6
(t, J = 12.6 Hz, 1 C), 141.2 (dd, J = 2.8, 10.5 Hz, 1 C), 140.5 (dd,
J = 2.9, 9.9 Hz, 1 C) 136.1 (d, J = 3.0 Hz, 3 C), 136.0 (d, J = 3.1 Hz,
2 C), 135.5 (d, J = 10.7 Hz, 6 C), 134.5 (d, J = 10.7 Hz, 4 C), 131.8
(t, J = 12.3 Hz, 1 C), 131.0 (d, J = 13.0 Hz, 6 C), 130.9 (d, J = 13.0
Hz, 4 C), 122.0 (dd, J = 13.4, 90.3 Hz, 1 C), 121.5 (dd, J = 13.5,
90.2 Hz, 1 C), 117.0 (d, J = 89.3 Hz, 2 C), 117.0 (d, J = 89.8 Hz, 3
C), 63.6 (1 C), 32.9 (d, J = 13.0 Hz, 1 C), 14.0 (1 C).
a Reaction was performed on a 1 mmol scale using 1.2 equiv of TAP-
PPh3 1, 1.2 equiv of diazo reagent, 5 mol% of CuI in DCE at 80 °C.
b Isolated and combined yields of E- and Z-isomers.
c Determined by GC-MS of the crude mixture.
d Using 10 mol% CuI.
31P NMR (162 MHz, CD2Cl2): d = 23.8 (d, J = 3.6 Hz, 1 P), 21.6 (d,
J = 3.4 Hz, 1 P).
HRMS (API-ES+): m/z calcd for C40H36O2P2 [M]2+: 305.1089;
Unless otherwise noted, all the nonaqueous reactions were per-
formed under an oxygen-free atmosphere of argon with rigid exclu-
sion of moisture from reagents and glassware using standard
techniques for manipulating air-sensitive compounds.10 All glass-
ware were stored in the oven and/or was flame dried prior to use un-
der an inert atmosphere of gas. The solvents were dried using
standard methods prior to use. The commercially available alde-
hydes were purified using standard methods prior to use. (TAP)-
found: 305.1100.
HRMS (ESI–): m/z calcd for ClO4 [M]–: 98.9490; found: 98.9490.
m/z calcd for Br [M]–: 78.9188; found: 78.9187.
Synthesis 2011, No. 14, 2275–2280 © Thieme Stuttgart · New York

PAPER
Olefination Reactions Using TAP-Supported Phosphorus Ylides
2279
Wittig Olefination with TAP-Supported Phosphonium Salt 2;
General Procedure
J = 13.0 Hz, 6 C), 129.2 (d, J = 12.3 Hz, 4 C), 124.6 (d, J = 93.2 Hz,
2 C), 118.2 (dd, J = 89.4, 12.7 Hz, 1 C), 116.5 (d, J = 89.6 Hz, 3 C),
58.0 (s, 1 C), 28.3 (d, J = 130.4 Hz, 1 C), 14.7 (s, 1 C).
31P NMR (162 MHz, CD2Cl2, 25 °C): d = 24.32, 19.44.
HRMS (ESI+): m/z calcd for C40H35O2P2 [M]+: 609.2106; found:
To a suspension of TAP-phosphonium salt 2 (1.19 g, 1.50 mmol,
1.50 equiv) in MeCN (5 mL, 0.2 M), under argon was added Et3N
(210 mL, 1.50 mmol, 1.50 equiv) at r.t. After 15 min, the aldehyde
(1.00 mmol, 1.00 equiv) was added, the mixture stirred for 16 h, and
diluted with CH2Cl2 (40 mL). The CH2Cl2 layer was washed with
aq 10% (w/w) HCl (5 mL), H2O (5 mL), brine (5 mL), dried
(MgSO4), and concentrated under reduced pressure to a minimum
volume (1–2 mL). Et2O (10 mL) was slowly added to the residue to
induce the complete precipitation of the TAP-supported phosphine
oxide and the mixture was vigorously stirred for an additional 20
min. The mixture was filtered on Celite, further washed with Et2O
(20 mL) and the filtrate was concentrated under reduce pressure to
afford pure mixture of E- and Z-olefin isomers.15
609.2128.
HRMS (ESI–): m/z calcd for ClO4 [M]–: 98.9490; found: 98.9493.
Wittig Olefination with TAP-Supported Ylide 6; General Pro-
cedure
To a suspension of the TAP-ylide 6 (1.06 g, 1.50 mmol, 1.50 equiv)
in THF (20 mL, 0.05 M) was added the aldehyde (1.00 mmol, 1.00
equiv) at r.t. under argon and the solution was stirred for 16 h. After
removing the solvent under vacuum, the resulting solid was solubi-
lized in CH2Cl2 (2 mL) and added dropwise to Et2O (20 mL) to in-
duce the complete precipitation of the TAP-supported phosphine
oxide. The mixture was vigorously stirred for an additional 20 min.
The mixture was then filtered and further washed with Et2O (2 × 5
mL). The filtrate was concentrated under vacuum to a volume of 5
mL and the solution was filtered again on a small pad of silica gel.
After removing the solvent under vacuum a pure mixture of E- and
Z-olefin isomers was obtained.15
Ethyl (E)-Cinnamate (3)
Yield: 99%; colorless oil (88:12 dr).
All physical and spectroscopic data were identical to those previ-
ously reported.8d
Ethyl (E)-3-(Thiophen-2-yl)acrylate (4)
Yield: 98%; yellow oil (88:12 dr).
All physical and spectroscopic data were identical to those previ-
ously reported.8d
Ethyl (E)-Cinnamate (3)
Yield: 91%; colorless oil (93:7 dr).
All physical and spectroscopic data were identical to those previ-
ously reported.8d
Ethyl (E)-5,9-Dimethyldeca-2,8-dienoate (5)
Yield: 98%; colorless oil (78:22 dr).
All physical and spectroscopic data were identical to those previ-
ously reported.8d
Ethyl (E)-3-(Thiophen-2-yl)acrylate (4)
Yield: 95%; yellow oil (89:11 dr).
All physical and spectroscopic data were identical to those previ-
ously reported.8d
(2-Ethoxy-2-oxoethyl)(diphenyl)[3-triphenyl(phosphonio)phe-
nyl]phosphorane Perchlorate (6)
To a solution of TAP-PPh3 16a (5.00 g, 8.00 mmol, 1.00 equiv) in
MeCN (20 mL, 0.40 M) was added ethyl bromoacetate (1.70 mL,
16.0 mmol, 2.00 equiv). The solution was stirred at r.t. and a white
precipitate formed as the reaction proceeded. After stirring for 16 h,
Et2O (100 mL) was added to the solution, and the mixture was
stirred vigorously for an additional 20 min. The solid was collected
by filtration and washed with Et2O (2 × 20 mL). The solid was then
dissolved in CH2Cl2 (100 mL) and the CH2Cl2 layer was transferred
to a separatory funnel. Aq 10% NaOH (100 mL) was added and the
separatory funnel was shaken vigorously. The yellow organic layer
was dried (MgSO4) and concentrated under vacuum to a volume of
20 mL. This solution was added dropwise to Et2O (300 mL) and
vigorously stirred for 20 min. The slightly yellow solid was collect-
ed by filtration and washed with Et2O (50 mL) to give the TAP-
ylide 6; yield: 4.66 g (82%); mp 101–105 °C (dec.), 182–186 °C
(melt).
Ethyl (E)-5-Phenylpent-2-enoate (7)
Yield: 89%; colorless oil (89:11 dr).
All physical and spectroscopic data were identical to those previ-
ously reported.8d
Copper-Catalyzed Olefination with TAP-PPh3 1; General Pro-
cedure
To a solution of CuI (10 mg, 0.050 mmol) and phosphonium salt 1
(748 mg, 1.20 mmol) in DCE (6.5 mL), under an argon atmosphere,
was added the aldehyde (1.00 mmol). The mixture was stirred for 5
min and then heated to 80 °C. The diazo compound (1.20 mmol)
was added dropwise over a period of 2 h. The solution was stirred
until the reaction was complete (GC or TLC analysis). The resulting
mixture was cooled to r.t. and the solution was poured dropwise into
Et2O (65 mL) under strong stirring (rpm >1000). The suspension
was removed by filtration and the solution was concentrated under
reduced pressure. The residue was purified by flash chromatogra-
phy on silica gel (eluent: EtOAc–hexanes, 1:19 or 1:9, depending
on the product) (Table 4).
IR (neat): 2971, 1606, 1437, 1326, 1081, 996, 893, 725, 686, 621
cm–1.
1H NMR (500 MHz, CD2Cl2, 25 °C): d = 8.13–7.47 (m, 29 H), 3.88
(br s, 2 H), 2.87 (br s, 1 H), 1.14 (br s, 3 H)
1H NMR (500 MHz, CD2Cl2, –30 °C): d (two isomers in a
ratio of 1:0.14 were visible): 8.14–7.46 (m, 33 H, major + minor),
3.88 (q, J = 6.9 Hz, 2 H, major), 3.56 (br s, 2 H, minor), 2.90 (d,
J = 23.9 Hz, 1 H, major), 2.53 (br d, J = 23.2 Hz, 1 H, minor), 1.15
(t, J = 7.1 Hz, 3 H, major), 0.42 (br s, 3 H, minor).
Ethyl (E)-Cinnamate (3)
Yield: 78%; colorless oil (96:4 dr).
All physical and spectroscopic data were identical to those previ-
ously reported.8d
13C NMR (126 MHz, CD2Cl2, –30 °C): d (major isomer) = 171.2 (d,
J = 14.3 Hz, 1 C), 139.2 (t, J = 11.5 Hz, 1 C), 139.1 (d, J = 11.0 Hz,
1 C), 137.1 (d, J = 10.3 Hz, 1 C), 135.8 (d, J = 3.1 Hz, 1 C), 135.7
(s, 3 C), 134.5 (d, J = 10.6 Hz, 6 C), 132.9 (s, 2 C), 132.6 (d,
J = 10.1 Hz, 4 C), 131.6 (dd, J = 88.6, 12.2 Hz, 1 C), 130.4 (d,
Dimethyl (E)-Styrylphosphonate (8)
Yield: 60%; yellow oil (95:5 dr).
All physical and spectroscopic data were identical to those previ-
ously reported.8d
Synthesis 2011, No. 14, 2275–2280 © Thieme Stuttgart · New York

2280
H. Lebel et al.
PAPER
Ethyl (E)-3-(4-Nitrophenyl)acrylate (9)
Yield: 83%; yellow solid (93:7 dr); mp 135 °C (Lit.16 mp 138–
139 °C).
Liebigs Ann. Chem. 1997, 1283. (b) Murphy, P. J.; Lee, S.
E. J. Chem. Soc., Perkin Trans. 1 1999, 3049. (c) Rein, T.;
Pedersen, T. M. Synthesis 2002, 579. (d) Ramazani, A.;
Kazemizadeh, A. R.; Ahmadi, E.; Noshiranzadeh, N.;
Souldozi, A. Curr. Org. Chem. 2008, 12, 59.
All physical and spectroscopic data were identical to those previ-
ously reported.8d
(4) Constable, D. J. C.; Dunn, P. J.; Hayler, J. D.; Humphrey, G.
R.; Leazer, J. L.; Linderman, R. J.; Lorenz, K.; Manley, J.;
Pearlman, B. A.; Wells, A.; Zaks, A.; Zhang, T. Y. Green
Chem. 2007, 9, 411.
tert-Butyl 4-[(E)-2-(Ethoxycarbonyl)vinyl]phenylcarbamate
(10)
Yield: 69%; yellow solid (98:2 dr); mp 95 °C (Lit.17 mp 92–94 °C).
(5) (a) Clarke, S. D.; Harrison, C. R.; Hodge, P. Tetrahedron
Lett. 1980, 21, 1375. (b) Bernard, M.; Ford, W. T. J. Org.
Chem. 1983, 48, 326. (c) Bernard, M.; Ford, W. T.; Nelson,
E. C. J. Org. Chem. 1983, 48, 3164. (d) Sieber, F.;
Wentworth, P.; Toker, J. D.; Wentworth, A. D.; Metz, W. A.;
Reed, N. N.; Janda, K. D. J. Org. Chem. 1999, 64, 5188.
(e) Westman, J. Org. Lett. 2001, 3, 3745. (f) Fairlamb, I. J.
S. ChemSusChem 2009, 2, 1021. (g) Marsden, S. P. Nat.
Chem. 2009, 1, 685. (h) O’Brien, C. J.; Tellez, J. L.; Nixon,
Z. S.; Kang, L. J.; Carter, A. L.; Kunkel, S. R.; Przeworski,
K. C.; Chass, G. A. Angew. Chem. Int. Ed. 2009, 48, 6836.
(i) Leung, P. S. W.; Teng, Y.; Toy, P. H. Org. Lett. 2010, 12,
4996.
(6) (a) Poupon, J. C.; Boezio, A. A.; Charette, A. B. Angew.
Chem. Int. Ed. 2006, 45, 1415. (b) Zoute, L.; Lacombe, C.;
Quirion, J. C.; Charette, A. B.; Jubault, P. Tetrahedron Lett.
2006, 47, 7931.
(7) (a) Kuhn, F. E.; Santos, A. M. Mini-Rev. Org. Chem. 2004,
1, 55. (b) Lebel, H.; Paquet, V. J. Am. Chem. Soc. 2004, 126,
320. (c) Sun, W.; Kuhn, F. E. Appl. Catal., A 2005, 285,
163. (d) Sun, W.; Yu, B. S.; Kuhn, F. E. Tetrahedron Lett.
2006, 47, 1993. (e) Pedro, F. M.; Santos, A. M.; Baratta, W.;
Kuhn, F. E. Organometallics 2007, 26, 302. (f) Lebel, H.;
Ladjel, C. Organometallics 2008, 27, 2676.
(8) (a) Lebel, H.; Davi, M.; Diez-Gonzalez, S.; Nolan, S. P.
J. Org. Chem. 2007, 72, 144. (b) Lebel, H.; Ladjel, C.;
Brethous, L. J. Am. Chem. Soc. 2007, 129, 13321.
(c) Lebel, H.; Parmentier, M. Org. Lett. 2007, 9, 3563.
(d) Lebel, H.; Davi, M. Adv. Synth. Catal. 2008, 350, 2352.
(e) Lebel, H.; Davi, M.; Stoklosa, G. T. J. Org. Chem. 2008,
73, 6828. (f) Davi, M.; Lebel, H. Org. Lett. 2009, 11, 41.
(9) Although the crude NMR spectra showed >90% product
purity, flash chromatography was performed to remove
diethyl fumarate and maleate formed from ethyl
diazoacetate.
All physical and spectroscopic data were identical to those previ-
ously reported.8d
tert-Butyl 4-[(E)-2-(Dimethylcarbamoyl)vinyl]phenylcarbam-
ate (11)
Yield: 70%; light yellow oil (97:3 dr).
All physical and spectroscopic data were identical to those previ-
ously reported.8d
Ethyl (E)-3-(Pyridin-2-yl)acrylate (12)
Yield: 55%; yellow oil (93:7 dr).
All physical and spectroscopic data were identical to those previ-
ously reported.8d
Ethyl (E)-5-Phenylpent-2-enoate (7)
Yield: 68%; colorless oil (95:5 dr).
All physical and spectroscopic data were identical to those previ-
ously reported.8d
Dimethyl (E)-4-Phenylbut-1-enylphosphonate (13)
Yield: 53%; yellow oil (90:10 dr).
All physical and spectroscopic data were identical to those previ-
ously reported.8d
Ethyl (E)-Oct-2-enoate (14)
Yield: 57%; colorless oil (92:10 dr) using 10 mol% of CuI.
All physical and spectroscopic data were identical to those previ-
ously reported.18
Dimethyl (E)-2-[(3aR,4R,6R,6aR)-Tetrahydro-4-methoxy-2,2-
dimethylfuro[3,4-d][1,3]dioxol-6-yl]vinylphosphonate (15)
Yield: 57%; yellow oil (92:8 dr).
(10) Shriver, D. F.; Drezdzon, M. A. The Manipulation of Air-
Sensitive Compounds; Wiley: New York, 1986.
(11) Searle, N. E. Org. Synth. Coll. Vol. IV; Wiley: New York,
1963, 424.
All physical and spectroscopic data were identical to those previ-
ously reported.8d
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
(12) Bartlett, P. A.; Carruthers, N. I.; Winter, B. M.; Long, K. P.
J. Org. Chem. 1982, 47, 1284.
(13) Ohira, S. Synth. Commun. 1989, 19, 561.
(14) Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43,
2923.
Acknowledgment
(15) When unreacted aldehyde was present, the filtrate was
stirred with aq 10% NaHSO3 (3 mL) at r.t. for 1 h. The two
layers were separated and the organic layer was washed with
H2O (3 mL), dried (MgSO4), and concentrated under
reduced pressure to afford a pure mixture of E- and Z-olefin
isomers.
This research was supported by the Fonds Québécois de la
Recherche sur la Nature et les Technologies (FQRNT), the Centre
in Green Chemistry and Catalysis (CGCC), the Canada Foundation
for Innovation, and the Université de Montréal.
(16) Artuso, E.; Barbero, M.; Degani, I.; Dughera, S.; Fochi, R.
Tetrahedron 2006, 62, 3146.
(17) Rai, R.; Katzenellenbogen, J. A. J. Med. Chem. 1992, 35,
4150.
(18) Felluga, F.; Pitacco, G.; Valentin, E.; Venneri, C. D.
Tetrahedron: Asymmetry 2008, 19, 945.
References
(1) Takeda, T. Modern Carbonyl Olefination; Wiley-VCH:
Weinheim, 2004.
(2) (a) Wittig, G.; Geissler, G. Liebigs Ann. Chem. 1953, 580,
44. (b) Wittig, G.; Schöllkopf, U. Chem. Ber. 1954, 87,
1318.
(3) (a) Nicolaou, K. C.; Harter, M. W.; Gunzner, J. L.; Nadin, A.
Synthesis 2011, No. 14, 2275–2280 © Thieme Stuttgart · New York