Two variations of solvent-reduced wittig olefination reactions - Comparison of solventless wittig reactions to wittig reactions under ultrasonication with minimal work-up

Article abstract of DOI:10.1515/znb-2005-0816

Stabilized and semi-stabilized phosphoranes can be subjected to solventless Wittig reactions with carbaldehydes. Simple heating of a mixture of added components at 100°C in an electric oven gives the corresponding olefins in good yield. Alternatively, the Wittig reactions can be carried out in a biphasic medium under ultrasonication. In this case, the Wittig products can be isolated by simple evaporation of the organic phase without additional work-up.

Full text of DOI:10.1515/znb-2005-0816

Two Variations of Solvent-Reduced Wittig Olefination Reactions –
Comparison of Solventless Wittig Reactions to Wittig Reactions
under Ultrasonication with Minimal Work-up [1]
Masataka Watanabea, Goreti Ribeiro Moraisb,c, Shuntaro Matakab, Keiko Idetab, and
Thies Thiemannb
a Interdisciplinary Graduate School of Engineering Sciences and
b Institute of Materials Chemistry and Engineering, Kyushu University, Fukuoka 816-8580, Japan
c Centro de Estudos Farmaceuticos, Faculdade de Farmacia, Universidade Coimbra,
P-3000-295 Coimbra, Portugal
Reprint requests to T. Thiemann. E-mail: thies@cm.kyushu-u.ac.jp
Z. Naturforsch. 60b, 909 – 915 (2005); received May 13, 2005
Stabilized and semi-stabilized phosphoranes can be subjected to solventless Wittig reactions with
carbaldehydes. Simple heating of a mixture of added components at 100 ◦C in an electric oven gives
the corresponding olefins in good yield. Alternatively, the Wittig reactions can be carried out in a
biphasic medium under ultrasonication. In this case, the Wittig products can be isolated by simple
evaporation of the organic phase without additional work-up.
Key words: Wittig Olefination, Ultrasound, Solventless Reaction
A number of criteria have to be considered when discussed, which are characterized by reduced use of
setting reaction conditions for a chemical transforma- solvents and simplicity of operation, no special equip-
tion. While in former times such criteria as product ment being needed.
yield, simplicity of operation, cost of starting materials
and reagents were considered, recently, further evalu-
ation points such as the toxicity of the reagents and
solvents used, energy requirements and waste produc-
tion have been added to the list, even when perform-
ing reactions at laboratory scale. A further important
factor that is not to be underestimated is the amount
of time needed for the synthetic step or sequence. For
many chemical transformations, a multitude of dif-
ferent reaction conditions have been published, from
which it is important to choose carefully for the indi-
vidual transformation in question. One such transfor-
mation, which offers a choice of reaction conditions, is
the Wittig olefination of carbaldehydes with stabilized
and semi-stabilized ylides. In former times the reaction
was carried out in organic solvents such as DME [2a],
chloroform [2b], benzene [2c,d] or toluene [2e], often
under reflux conditions and in the presence of addi-
tives such as acids [2c,d, 3] or salts [4]. More recently,
waste-saving alternatives have been explored such as
performing the reactions in solventless systems [1, 5]
utilizing special techniques such as microwave irradia-
tion [5b,c,d,f] and ball-mill mixing [5e]. In the follow-
ing, two procedures for the Wittig olefination will be
We observed that many aromatic and heteroaro-
matic carbaldehydes undergo exothermic olefination
reactions with stabilized Wittig reagents, when one re-
action partner is added to the other, resulting in sol-
ventless Wittig olefination reactions without the neces-
sity of microwave irradiation (Table 1). Liquid aryl-
and hetarylcarbaldehydes, such as 1c and 1e, form uni-
form melts with the phosphoranes. Aldehydes with low
melting points, such as 1i, mix equally well with the
phosphoranes as the◦heat released can generate tem-
peratures of 60 – 70 C. In cases, where the aldehydes
have a higher melting point, the mixture of aldehyde
◦
and phosphorane is heated at 100 C for 10 min – 2 h.
to produce the olefinic products in good yield. Alkoxy-
carbonylmethylidenetriphenylphosphoranes 2a,b and
aroylmethylidenetriphenylphosphoranes 2c – e can be
used in these reactions. With these stabilized phos-
phoranes, the olefins formed are predominantely E-
configurated. As in solution, also under solventless
conditions the reactivity of alkoxymethylidenephos-
phoranes is higher than that of aroylmethylidenephos-
phoranes which is reflected in the shorter reaction
times needed. Nevertheless, the alkoxymethylidene-
triphenylphosphoranes 2a,b react selectively with the
c
0932–0776 / 05 / 0800–0909 $ 06.00 ꢀ 2005 Verlag der Zeitschrift fu¨r Naturforschung, Tu¨bingen · http://znaturforsch.com
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910
M. Watanabe et al. · Two Variations of Solvent-Reduced Wittig Olefination Reactions
Table 1. Solventless Wittig ole-
fination with stabilized phos-
phoranes.
carbaldehyde moiety of ketoarylcarbaldehydes such as especially the allylmethylidenetriphenylphosphorane,
in 1h and 1i. Under more forcing conditions such as derived from 4a, give the olefins in poorer yields with-
under microwave irradiation the keto functionality also out significant E/Z-selectivity.
undergoes reaction.
Double-Wittig olefinations are possible under sol-
ventless conditions as is witnessed by the transfor-
mation of 2,3-diformylthiophene (2n) with Wittig
Benzylidenetriphenylphosphorane also reacts selec-
tively with carbaldehydes rather than with ketones
in pure mixtures. This can be seen in the reaction
of benzylidenetriphenylphosphorane with an equimo-
lar amount of phenylglyoxal monohydrate (1i), where
only the carbaldehyde function reacts to give a sep-
arable mixture of E-6c and Z-6c (E/Z = 44/56)
(Scheme 1). Instead of benzylidenetriphenylphospho-
rane itself, the corresponding phosphonium bromide
salt 4b is used as starting material with addition of
◦
reagents 2c, 2f, and 2g at 100 C (Scheme 2). No
side products are observed from◦a potential triene cy-
clization of the products at 100 C. In fact, in contrast
to other known dialkyl hexatriene-1,6-dicarboxylate
derivatives, which undergo triene cyclization [6], 7a
has been found to be stable up to 155 ◦C (48 h, solution
in diphenyl ether).
In certain cases, Wittig olefinations do not progress
solid potassium tert-butanolate. Analogously, allylt- in solution, but proceed in solventless systems. In one
riphenylphosphonium bromide 4a can be used in sol- such example, the Wittig olefination of 16-formyl-
ventless systems. These semi-stabilized phosphoranes, estra-1,3,5(10)-trien-17-one [7] does not work out in
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M. Watanabe et al. · Two Variations of Solvent-Reduced Wittig Olefination Reactions
911
Scheme 2. Double Wittig reaction under solventless condi-
tions.
to the 17-keto group. In a pure mixture with ethoxy-
carbonylmethylidenetriphenylphosphorane (2a), how-
ever,◦ the compound undergoes Wittig olefination at
100 C (oven, 30 min) in acceptable yield, where the
initial product undergoes a 1,3-proton shift to pro-
vide 9a as a single isomer (Scheme 3). The double
bond configuration of 9a was established by DPFGSE-
NOE-experiment (Double Pulsed Field Gradient Spin
Echo NOE [8], irradiated at ν = 1924.7 Hz [protons at
C-20; 2.1% observed for H16α, H16β]. The analogous
reaction with cyanomethylidenetriphenylphosphorane
(2h) also proceeds, the analogous product 10 being
formed in a little lower yield under the same condi-
tions. Acetylmethylidenetriphenylphosphorane (2g) is
not reactive enough to undergo a reaction in the pure
Scheme 1. Solventless Wittig reaction with semi-stabilized
phosphoranes prepared in situ.
◦
solution. Partly this is due to the poor solubility of
the starting material. The reactivity of the 16-formyl
group is much reduced because of hydrogen bonding
mixture of starting materials at 100 C.
The main drawback of all these reactions, however,
lies in the work-up as it still necessitates the use of
Scheme 3. Derivatisation of es-
trane derivatives by solventless
Wittig reaction.
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912
M. Watanabe et al. · Two Variations of Solvent-Reduced Wittig Olefination Reactions
Scheme 4. Wittig reaction of stabilized phosphoranes under
ultrasonication.
interfacial layer. It is in this layer that the Wittig olefi-
nation takes place.
Benzyltriphenylphosphoniumbromide (4b) also un-
dergoes Wittig olefination under sonication in aqueous
medium, e.g. with 5-methylthien-2-ylcarbaldehyde, to
give (5-methylthien-2-yl)styrene (54%, E/Z = 1:1).
Here, however, the advantage of an easy separation
of the product by evaporation of the overlying hexane
phase is not in evidence, as the reaction does not go to
completion and product and starting aldehyde have to
be separated over a short column.
In conclusion, we have shown that aryl- and hetaryl-
carbaldehydes undergo rapid Wittig olefination under
solventless conditions with a number of stabilized and
semi-stabilized phosphoranes. A chromatographicsep-
aration of the products is mandatory. Carbaldehydes
can also be reacted in aqueous solution or in a mixture
of non-polar organic solvents and water. In this case,
the organic layer can be siphoned off and the prod-
uct can be obtained by evaporation of the solvent, in
a purity sufficient for subsequent transformations. Sol-
ventless Wittig olefination can be combined with an
extraction of the solid/liquid product under ultrasoni-
cation. Here, however, the yields can be lower due to
remaining product adsorbed to the solids formed.
Table 2. Wittig olefination in a biphasic medium under ultra-
sonication.
solvents as eluents for short column chromatographic
separations, mainly to separate triphenylphosphaneox-
ide and small amounts of triphenylphosphane. On the
other hand, olefins are also produced, albeit in slightly
lower yields, when the carbaldehydes and phospho-
ranes are reacted at room temperature in an aqueous
solvent or a mixture of hexane/ether (95/5 v/v) and
water under ultrasound [9 – 11]. Reaction times are
longer. The work-up, however, is minimal. In the case
of solely using water as reaction medium, hexane can
be added to the mixture near the completion of the re-
action, where the product is extracted into the organic
phase under ultrasound. Frequently, the product is suf-
ficiently pure to be used in a subsequent reaction step
without further purification. In other cases simple fil-
tration over a pad with a thin layer of silica gel provides
the pure product.
Experimental Section
General remarks
Melting points were measured on a Yanaco microscopic
hotstage and are uncorrected. Infrared spectra were mea-
sured with JASCO IR-700 and Nippon Denshi JIR-AQ2OM
instruments. 1H and 13C NMR spectra were recorded with
a JEOL EX-270 spectrometer (1H at 270 MHz, 13C at
67.8 MHz) and a JEOL Lambda 400 FT-NMR spectrom-
eter (1H at 395.7 MHz, 13C at 99.45 MHz). The chemical
shifts are relative to TMS (solvent CDCl3, unless otherwise
noted). The DPFGSE-NOE experiment was carried out with
a Lambda 600 spectrometer. Mass spectra were measured
with a JMS-01-SG-2 spectrometer. Column chromatography
was carried out on Wakogel 300. For the heating experi-
In these experiments, the starting materials can be
either the phosphorane or the phosphonium salt, which
under the conditions is transformed to the phospho-
rane by the aqueous base. When an ultrasonic bath
is used for the reaction, a semi-solid forms at the in-
terphase of the aqueous and the organic phase (hex-
ane/ether = 95/5). At the beginning the solid consists
mostly of phosphorane, at the end of the reaction of
residual phosphorane and triphenylphosphane oxide.
During the sonication there is cavitation in the lower,
aqueous phase which impinges on the bottom of the ments, an electric oven, EYELA NDO-450N, preheated at
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M. Watanabe et al. · Two Variations of Solvent-Reduced Wittig Olefination Reactions
913
◦
100 C, was used. For the ultrasonication, a 35 KHz Elma m/z (%) = 220 (M+, 15), 177 (100), 163 (46), 134 (26). –
Transsonic T-460 bath was used. The sonication experiments HRMS (found) 220.0558; calcd. for C12H12O2S: 220.0558.
were carried out at 35 ◦C.
2,3-(E,E)-Bis(benzoylethenyl)thiophene (7c), yellow
◦
needles, m. p. 167 C. – IR (KBr): ν = 3070, 1655, 1576,
1335, 1314, 1274, 1248, 1215, 1019, 970, 776, 700,
573 cm−1. – 1H NMR (270 MHz, CDCl3): δ = 7.38 – 7.63
(m, 10H), 7.99 – 8.08 (m, 5H), 8.23 (d, 1H, 3J = 15.1 Hz). –
13C NMR (67.8 MHz, CDCl3): δ = 122.82, 124.21, 126.76,
127.94, 128.47 (4C), 128.69 (4C), 132.99 (2C), 133.56,
134.54, 137.83, 137.94, 139.81, 141.54, 189.27, 190.20. –
MS (EI, 70 eV): m/z (%) = 344 (M+, 6), 239 (100), 105
(55). – HRMS (found) 344.0874; calcd. for C22H16O2S:
344.0871. – C22H16O2S (344.09): calcd. C 76.72, H 4.68;
found C 76.54, H 4.72.
The phosphoranes 2a [12a], 2b [12a], 2c [12b], 2d [13],
2e [13], 2f [12a], 2g [12b], 2h [12c] and the phosphonium
salts 4a [12d], 4b [12e], 4c – e [12a] were prepared according
to literature procedures. Estrane derivatives 8a/b were syn-
thesized analogous to a procedure by Tapolcsanyi et al. [7].
Typical procedures [14]
Wittig olefination under solventless conditions – Ethyl 2-
[4-(trimethylsilylethynyl)-1,2-dihydronaphthalen-3-yl] acry-
late (3t). – Aldehyde 1f (1.27 g, 5.0 mmol) was reacted with
phosphorane 2a (2.61 g, 7.5 mmol) for 10 min at 100◦C. The
melt was transferred to silica gel and chromatography (hex-
ane/ether 5:1) gave 3t (1.5 g, 93%) as yellow needles; m. p.
80 – 81 ◦C. – IR (neat): ν = 3068, 2958, 2892, 2136, 12708,
Ethyl 3-(4’-bromo-1’,2’-dihydronaphthalen-3’-yl)-acry-
◦
late (3s), colorless needles; m. p. 89 C. – IR (KBr): ν =
1700, 1614, 1475, 1453, 1364, 1299, 1269, 1234, 1173,
1037, 971, 943, 854, 762 cm−1. – 1H NMR (270 MHz,
CDCl3): δ = 1.34 (t, 3H, 3J = 7.3 Hz), 2.58 (dd, 2H,
3J = 8.6 Hz, 3J = 5.9 Hz), 2.88 (dd, 2H, 3J = 8.6 Hz,
3J = 5.9 Hz), 4.26 (q, 2H, 3J = 7.3 Hz), 6.12 (d, 1H,
3J = 15.7 Hz), 7.13 – 7.31 (m, 3H), 7.77 (m, 1H), 8.11 (d,
1H, 3J = 15.7 Hz). – 13C NMR (67.8 MHz, CDCl3): δ =
14.35, 25.91, 27.49, 60.58, 120.46, 126.98, 128.61, 129.27,
133.19, 133.98, 137.14, 144.02, 167.03. – MS (EI, 70 eV):
m/z (%) = 308 ([81Br]M+, 9), 306 ([79Br]M+, 9), 227
(71), 199 (100), 181 (21). – HRMS (found) 306.0259; calcd.
for C15H15O279Br: 306.0255. C15H15O2Br (307.18): calcd.
C 58.65, H 4.92; found C 58.66, H 4.92.
1613, 1302, 1169, 1042, 984 cm−1. – H NMR (270 MHz,
1
CDCl3): δ = 0.32 (s, 9H, SiMe3), 1.34 (t, 3H, 3J = 6.9 Hz),
2.54 (t, 2H, 3J = 7.6 Hz), 2.84 (t, 2H, 3J = 7.6 Hz), 4.25
(q, 2H, 3J = 6.9 Hz), 6.10 (d, 1H, 3J = 15.8 Hz), 7.12 –
3
3
7.27 (m, 3H), 7.71 (d, 1H, J = 5.3 Hz), 8.25 (d, 1H, J =
15.8 Hz). – 13C NMR (99.45 MHz, CDCl3): δ = 0.04, 14.37,
23.45, 27.05, 60.48, 100.27, 105.86, 119.42, 125.94, 126.84,
126.92, 127.23, 128.80, 132.72, 140.10, 143.33, 167.22. –
MS (EI, 70 eV): m/z (%) = 324 (M+, 100), 295 (21), 161
(59), 149 (38), 134 (100). – HRMS (found) 324.1549; calcd.
for C20H24O2Si: 324.1546. – C20H24O2Si (324.48): calcd.
C 74.09, H 7.46; found C 74.03, H 7.45.
Wittig olefination under ultrasonication – Methyl 2-
(thien-2-yl)acrylate (3m-Me). A suspension of thiophene-
2-carbaldehyde (1e) (348 mg, 3.1 mmol) and methoxy-
carbonylmethyltriphenylphosphonium bromide (4c) (1.93 g,
4.6 mmol) in a mixture of a 2 M aq. Na2CO3 solution (10 ml)
and hexane/ether (5 ml, 95/5 v/v) was sonoirradiated for
3 × 30 min, where the temperature of the mixture was kept
Selected data for further compounds obtained by solvent-
less Wittig olefination:
Dimethyl thienyl-2,3-(E,E)-diacrylate (7a), colorless
◦
needles, m. p. 128 C. – IR (KBr): ν = 1721, 1622, 1281,
1173, 1034, 963, 851, 751, 707 cm−1. – 1H NMR (270 MHz,
CDCl3): δ = 3.82 (s, 6H, 2 COOCH3), 6.29 (d, 1H, 3J =
15.9 Hz), 6.34 (d, 1H, 3J = 15.9 Hz), 7.87 (d, 1H, 3J =
15.9 Hz), 8.02 (d, 1H, 3J = 15.9 Hz). – 13C NMR (67.8 MHz,
CDCl3): δ = 51.88, 118.71, 119.96, 126.37, 127.83, 133.78,
134.71, 138.22, 139.80, 166.70, 167.19. – MS (EI, 70 eV):
m/z (%) = 252 (M+, 45), 193 (64), 161 (59), 149 (38), 134
(100). – HRMS (found) 252.0453; calcd. for C12H12O4S:
252.0456. – C12H12O4S (252.29): calcd. C 57.13, H 4.79;
found C 57.10, H 4.81.
◦
at 35 C. Therafter, the upper organic layer was separated,
and the remaining mixture was extracted under ultrasonica-
tion with hexane/ether (95/5 v/v, 2×30 ml). The combined
organic phase was evaporated in vacuo to give 3m-Me (0.4 g,
77%) with triphenylphosphine oxide as an impurity (5%).
Further purification by filtration over a pad of silica gel can
be carried out to give analytically pure 3m-Me.
16-(2’-(E)-Ethoxycarbonylethylidene-3-methoxyestra-
2,3-(E,E)-Bis(acetylethenyl)thiophene (7b), yellow nee- 1,3,5(10)-trien-17-one (9a). – 16-Formyl-3-methoxyestrone
dles, m. p. 144 ◦C. – IR (KBr): ν = 3082, 1645, 1604, (8a) (312 mg, 1.0 mmol) was mixed with ethyl (triph-
1361, 1257, 954, 768 cm−1. – 1H NMR (270 MHz, CDCl3): enylphosphoranylidene)acetate (2a) (523 mg, 1.5 mmol).
◦
δ = 2.58 (s, 3H, COCH3), 2.65 (s, 3H, COCH3), 6.33 The mixture was heated in an electric oven at 100 C for
(d, 2H, 3J = 15.4 Hz), 7.29 (d, 1H, 3J = 5.7 Hz), 7.37 30 min. The reaction mixture was then subjected directly
(d, 1H, 3J = 5.7 Hz), 7.79 (d, 1H, 3J = 15.4 Hz), 7.93 to column chromatography on silica gel (toluene : ethyl
(d, 1H, 3J = 15.4 Hz). – 13C NMR (67.8 MHz, CDCl3): acetate = 5 / 1) ◦to give 9a (250 mg, 65%) as a colorless solid;
δ = 28.06, 28.42, 126.56, 127.22, 128.15, 128.71, 131.60, m. p. 93 – 103 C. – IR(KBr): ν = 3438, 2936, 1731, 1653,
132.67, 139.00, 140.57, 197.14, 198.04. – MS (EI, 70 eV): 1611, 1576, 1497, 1451, 1394, 1375, 1305, 1280, 1259,
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M. Watanabe et al. · Two Variations of Solvent-Reduced Wittig Olefination Reactions
1182, 1101, 1084, 1052, 1036, 869, 843, 818, 783 cm−1. – separation by column chromatography on silica gel (hex-
1H NMR (270 MHz, CDCl3): δ = 0.92 (s, 3H, CH3), 1.28 ane : ether : CH2Cl2 = 4 / 1 / 1) to give 9b (437 mg, 98%)
◦
(t, 3H,3J = 7.4 Hz, CH3), 1.44 – 2.92 (m, 13H), 3.21 (d, 2H, as a colorless prisms. m. p. 118 C. – IR (KBr): ν = 3032,
3J = 7.5 Hz), 3.78 (s, 3H, OCH3), 4.18 (q, 2H, 3J = 7.4 Hz, 3931, 2857, 1735, 1654, 1605, 1574, 1498, 1454, 1436,
OCH2), 6.65 (d, 1H, 4J = 2.7 Hz, C-1), 6.73 – 6.77 (m, 2H, 1377, 1340, 1304, 1280, 1256, 1230, 1199, 1173, 1119,
C-2 and olefinic proton), 7.21 (d, 1H, 3J = 8.7 Hz, C-1). 1100, 1084, 1050, 1017, 985, 949, 905, 888, 844, 819, 788,
– MS (70 eV): m/z (%) = 383 (MH+, 27%), 382 (M+, 733, 696, 646, 575 cm−1. – 1H NMR (270 MHz, CDCl3)
100%). – HRMS (found): 382.2144; calcd. for C24H30O4: δ = 0.92 (s, 3H, CH3, C-18), 1.43 – 2.43 (m, 10H), 2.62 –
382.2146. – C24H30O4+0.05H2O (383.39): calcd. C 75.19, 2.69 (m, 1H), 2.88 – 2.91 (m, 2H), 3.22 (d, 2H, 3J = 6.4 Hz),
H 7.91; found C 74.92, H 7.86.
3.72 (s, 3H, OCH3), 5.04 (s, 2H, OCH2Ph), 6.70 – 6.76 (m,
2H, C-1 and olefin), 6.79 (d, 1H, 3J = 8.6 Hz, C-2), 7.20 (d,
1H, 3J = 8.6 Hz), 7.26 – 7.44 (m, 5H). – C29H32O4 (444.56):
calcd. C 78.35, H 7.26; found C 78.10, H 7.27.
16-(2’-(E)-Methoxycarbonylethylidene-3-benzyloxyes-
tra-1,3,5(10)-trien-17-one (9b). – 8b (388 mg, 1.0 mmol)
and 2f (401 mg, 1.2 mmol) were reacted to give after
[1] Part 1: T. Thiemann, M. Watanabe, Y. Tanaka,
S. Mataka, New J. Chem. 28, 578 (2004).
lion, M. Soufiaoui, J. L. Luche, J. Prakt. Chem. 339,
176 (1997); b) H. El Faikh, F. Pautet, H. Fillion, J. L.
Luche, Tetrahedron Lett. 33, 4909 (1992); c) H. Fil-
lion, B. Refouvelet, M. H. Pera, V. Dufaud, J. L. Luche,
Synth. Commun. 19, 3343 (1989); see also ref. [10].
[10] a) A. Fuentes, J. M. Marinas, J. V. Sinisterra, Tetra-
hedron Lett. 28, 2951 (1987); b) J. V. Sinisterra,
A. Fuentes, J. M. Marinas, J. Org. Chem. 52, 3875
(1987).
[11] For reports on the effect of ultrasound on Wittig re-
actions in toluene and other organic solvents, see:
a) C. Yang, D. T. C. Yang, R. G. Harvey, Synlett
799 (1992); b) S. Ring, G. Teichmueller, G. We-
ber, S. Schwarz, B. Erhart, B. Undeutsch, H. Raethe,
P. Moellmann, C. Pfeiffer, H.-J. Palme, Eur. Pat. Appl.
EP 643070, 1995; Chem. Abstr. 123, 33509 (1995).
[12] a) O. Isler, H. Gutmann, M. Montavon, R. Ruegg,
G. Ryser, P. Zeller, Helv. Chim. Acta 40, 1242 (1957);
b) F. Ramirez, S. Dershowitz, J. Org. Chem. 22, 41
(1957); c) S. Trippett, D. M. Walker, J. Chem. Soc. C
3874 (1959); d) G. Wittig, U. Schoellkopf, Chem. Ber.
Rec. 87, 1318 (1954); e) Autorenkollektiv, Organikum,
p. 203, VEB Deutscher Verlag der Wissenschaften,
Berlin (1988).
[13] a) T. Thiemann, K. Umeno, D. Ohira, E. Inohae,
T. Sawada, S. Mataka, New J. Chem. 23, 1067 (1999);
b) T. Thiemann, K. Umeno, J. Wang, K. Arima,
M. Watanabe, Y. Tabuchi, Y. Tanaka, H. Gorohmaru,
S. Mataka, J. Chem. Soc., Perkin Trans. 1, 2090 (2002).
[14] All compounds gave satisfactory 1H NMR, 13C NMR,
IR, MS and HRMS data. The following compounds
have been reported before: 3b: S. Frattini, M. Quai,
E. Cereda, Tetrahedron Lett. 42, 6827 (2001); 3c:
P. Berthelot, C. Vaccher, N. Flouquet, M. Debaert,
M. Luyckx, C. Brunet, J. Med. Chem. 34, 2557
(1991); 3e: J. P. Yadav, K. Anuradha, B. V. S. Reddy,
B. Eeschwaraiah, Tetrahedron Lett. 44, 8959 (2003);
3f: G. Dannhardt, W. Kiefer, G. Kramer, S. Maehrlein,
V. Nowe, B. Fiebich, Eur. J. Med. Chem. 35, 499
[2] For typical examples, see: a) E. J. Corey, D. A. Clark,
G. Goto, A. Marfat, C. Mioskowski, B. Samuelsson,
S. Hammerstro¨m, J. Am. Chem. Soc. 102, 1436 (1980)
(for DME); b) S. Flisza`r, R. F. Hudson, G. Salvadori,
Helv. Chim. Acta 47, 159 (1964) (for chloroform);
c) D. Spitzner, H. Swoboda, Tetrahedron Lett. 27, 1281
(1986) (for benzene); d) T. Thiemann, D. Ohira, Y. Q.
Li, T. Sawada, S. Mataka, K. Rauch, A. de Meijere, J.
Chem. Soc., Perkin Trans. 1 2968 (2000) (for benzene);
e) J.-P. Surivet, J.-N. Volle, J. M. Vate´le, Tetrahedron:
Asymmetry 7, 3305 (1996) (for toluene).
[3] a) C. Ru¨chardt, P. Panse, S. Eichler, Chem. Ber. 100,
1144 (1967); b) D. P. Mariott, S. R. Bantick, Tetrahe-
dron Lett. 22, 3657 (1981).
[4] H. Moison, F. Texier-Boullet, A. Foucaud, Tetrahedron
43, 537 (1987).
[5] a) F. Toda, H. Akai, J. Org. Chem. 55, 3446 (1990);
b) W. Liu, Q. Xu, Y. Ma, Y. Liang, N. Dong, D. Guan, J.
Organomet. Chem. 625, 128 (2001); c) C. Xu, G. Chen,
X. Huang, Org. Prep. Proceed. Int. 27, 559 (1995);
d) A. Spinella, T. Fortunati, A. Sorienti, Synlett 93
(1997); e) V. P. Balema, J. M. Wiench, M. Pruski,
V. K. Pecharsky, J. Am. Chem. Soc. 124, 6244 (2002);
f) H. Valizadeh, A. Shockravi, M. M. Heravi, H. A.
Ghadmin, J. Chem. Res. 718 (2003).
[6] a) K. Voigt, P. von Zezschwitz, K. Rosauer, A. Lan-
sky, A. de Meijere, Eur. J. Org. Chem. 1521 (1998);
b) P. von Zezschwitz, F. Petry, A. de Meijere, Chem.
Eur. J. 7, 4035 (2001).
[7] P. Tapolcsanyi, J. Woelfling, G. Falkay, A. Marki,
R. Minorics, G. Schneider, Steroids 67, 371 (2002).
[8] a) K. Scott, J. Stonehouse, J. Keeler, T.-L. Hwang,
A. J. Shaka, J. Am. Chem. Soc. 117, 4199 (1995);
b) S. Berger, S. Braun, 200 and more NMR experi-
ments, p. 492, Wiley-VCH, Weinheim (2004).
[9] For reports on Wittig Horner reactions under ultra-
sound, see: a) H. El Faikh, F. Pautet, D. Peters, H. Fil-
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M. Watanabe et al. · Two Variations of Solvent-Reduced Wittig Olefination Reactions
915
(2000); 3i: M. Moreno-Manas, M. Perez, R. Pleix-
ats, Tetrahedron Lett. 37, 7449 (1996); 3j: M. Knoll-
muller, M. Ferencic, P. Gartner, U. Girreser, M. Klinge,
L. Gaishin, K. Mereiter, C. R. Noe, Monatsh. Chem.
130, 769 (1999); 3k: A. E. Lipkin, N. I. Putokhin, S. I.
Borisov, Khim. Geterotsk. Soedin. 476 (1966); for
3m-Me, 3m-Et, 3n, 3o, and 3p: see ref. 1; 3m-Bzl
and 3v: A. Katritzky, P. Zhang, A. Soares, M. Wang,
ARKIVOC 54 (2001); 3r: Y. Z. Jin, N. Yasuda,
J. Inanaga, Green Chem. 4, 498 (2002); 3u: T. Thie-
mann, C. Thiemann, S. Sasaki, V. Vill, S. Mataka,
M. Tashiro, J. Chem. Res. (S) 248 (1997); 5a: Q. Wang,
M. El Khoury, M. Schlosser, Chemistry 6, 420 (2000);
6b: B. B. Corson, Org. Synth. 16, 28 (1936).
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