One-pot, fluoride-promoted wittig reaction

Article abstract of DOI:10.1080/00397910802654633

A one-pot, fluoride-promoted Wittig reaction was developed. The reactions of ethyl -bromoacetate with aliphatic, aromatic, and heteroaromatic aldehydes in the presence of tri-n-butylphosphine and tetrabutylammonium fluoride produced ,-unsaturated esters in good to excellent yields and E-stereoselectivity. Under the same conditions, reactions of ethyl -bromopropionate, -bromo acetonitrile, and -bromoacetophenone with aliphatic and aromatic aldehydes in the presence of tri-n-butylphosphine and tetrabutylammonium fluoride produced the expected ,-unsaturated derivatives in good E-stereoselectivity. The protocol was extended to semistabilized ylides and applied to the synthesis of some combretastatin analogs.

Full text of DOI:10.1080/00397910802654633

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One-Pot, Fluoride-Promoted
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Tiziano Fumagalli a , Guido Sello a & Fulvia Orsini a
a Department of Organic and Industrial Chemistry,
University of Milan, Milan, Italy
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Synthetic Communications1, 39: 2178–2195, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802654633
One-Pot, Fluoride-Promoted Wittig Reaction
Tiziano Fumagalli, Guido Sello, and Fulvia Orsini
Department of Organic and Industrial Chemistry, University of Milan,
Milan, Italy
Abstract: A one-pot, fluoride-promoted Wittig reaction was developed. The
reactions of ethyl a-bromoacetate with aliphatic, aromatic, and heteroaromatic
aldehydes in the presence of tri-n-butylphosphine and tetrabutylammonium
fluoride produced a,b-unsaturated esters in good to excellent yields and
E-stereoselectivity. Under the same conditions, reactions of ethyl a-bromopropio-
nate, a-bromo acetonitrile, and a-bromoacetophenone with aliphatic and
aromatic aldehydes in the presence of tri-n-butylphosphine and tetrabutylammo-
nium fluoride produced the expected a,b-unsaturated derivatives in good
E-stereoselectivity. The protocol was extended to semistabilized ylides and
applied to the synthesis of some combretastatin analogs.
Keywords: Tetra-n-butylammonium fluoride, a,b-unsaturated compounds,
Wittig reaction
INTRODUCTION
The Wittig reaction is one of the most important methods for the carbon–
carbon double bond synthesis starting from carbonyl compounds.[1] It is
traditionally carried out in a homogeneous medium using a base [BuLi,
PhLi, NaNH2, sodium bis(trimethylsilyl)amide (NaHMDS), or lithium bis
(trimethylsilyl)amide (LiHMDS)] to generate a stabilized or a semistabilized
phosphonium ylide, in anhydrous aprotic solvents [tetrahydrafuran (THF),
dimethylformamide (DMF), C6H6, CHCl3]. Heterogeneous Wittig
Received October 17, 2007.
Address correspondence to Fulvia Orsini, Dipartimento di Chimica Organica
`
ed Industriale, Universita degli Studi di Milano, via Venezian 21, 20133 Milan,
Italy. E-mail: Fulvia.Orsini@unimi.it
2178

One-Pot, Fluoride-Promoted Wittig Reaction
2179
Scheme 1. X ¼ Br, CI; R ¼ -COOEt, -COPh, -CN, 3,4,5-trimethoxyphenyl-;
R0 ¼ Ph-,PhCH2CH2-, 4-MeO-Ph-, 4-Br-Ph-, 4-NO2-Ph-, 3-4-dimethoxyphenyl-
,2-(2-formyl)-phenyl-,2-furanyl-, 2-thiophenyl-2, 2-(5-hydroxymethyl)-furanyl-,
(2,2-dimethyldioxolanyl)-; and R00 ¼ H,Me.
reactions, in liquid–liquid[2] or solid–liquid phase,[3] are less common. Since
the discovery of the Wittig reaction in the 1950s, several variations of the
experimental conditions have been reported to improve the efficiency of this
fundamental reaction. Higher temperatures[4] or pressures,[5] additives,[6]
microwaves,[7] sonication,[8] ionic solvents,[9] and water[10] have been consid-
ered to improve yields, experimental conditions, and environmental impact.
In this article, we report a one-pot Wittig reaction performed using
the fluoride anion as the base[11](Scheme 1).
RESULTS AND DISCUSSION
Our attention was focused first on stabilized ylides to obtain a,b-unsatu-
rated compounds (esters, ketones, nitriles), useful precursors of hydroxy
and amino acids (or ketones) and their derivatives.
Two series of experiments were carried out. In the first series, a vari-
ety of electrophiles (aldehydes and ketones) was reacted with the same
halogen derivative, ethyl a-bromoacetate, in the presence of n-Bu3P[12]
(Table 1); in the second series, the investigation was extended to a variety
of haloderivatives, precursors of either stabilized or semistabilized ylides
(Tables 2 and 3). For one model system (ethyl a-bromo acetate and
benzaldehyde), the reaction was also carried out by replacing n-Bu3P with
the less nucleophilic but more convenient (crystalline, air-stable, and
odorless) Ph3P, with no significant influence on product formation and
stereochemistry (Table 1, footnote f ).
The data are summarized in Tables 1–3 and illustrate some general
features of this new protocol. In Table 1, the results previously obtai-
ned[10a] in water and SDS (sodium dodecyl sulfate)–water solution have
been reported for comparison.
In each case, with only the exception of aldehyde 2m (Table 1, entry
12), the main, if not only, product was the E-isomer. Diastereoisomeric
ratios and yields depended on both the electrophile and the halogen deri-
vative and were generally good to very good for aldehydes (alkyl, aryl,
heteroaryl). Phthalyldialdehyde (2f) yielded the E,E product exclusively:
no E,Z or Z,Z isomers were observed.

2180

2181

2182
T. Fumagalli, G. Sello, and F. Orsini
Table 2. Wittig reaction of aromatic and aliphatic aldehydes with a-bromo
derivatives in the presence of tri-n-butyl phosphine
Bromo
derivative
Reaction Product, isolated E=Z ratio
timea
Entry
1
Electrophile
yield (%)
(%)b
16 h
3ba, 42
95:5
2
16 h
3bb, 49
89:11
3
4
2.5 h
2.5 h
3ca, 88
3cb, 78
>99:1
>99:1
5
0.5 h
3de, 68c
>99:1c
aConditions: 1=n-Bu3P=2=n-Bu4NF ¼ 1:1:1.1:1.2; THF at room temperature.
1
bE=Z determined by H NMR.
cThe reported yield concerns the E isomer only. By 1H NMR, the crude mixture
contains 95% yield of E=Z (72:28) isomers: the E isomer only was purified.
Table 3. Wittig reaction of aromatic aldehydes with 3,4,5-trimethoxybenzyl
chlorides in the presence of tri-butyl phosphine: synthesis of functionalized
stilbenes
Chloro
derivative
Reaction Product, isolated E=Z ratio
(%)b
Entry
1
Electrophile
timea
yield (%)
16 h
3ed, 81
71:29
2
3
16 h
16 h
3ec, 50
3el, 36
68:32
65:35
aConditions:1=n-Bu3P=2=n-Bu4NF ¼ 1:1.1:1.1:1.
bBoth E and Z isomers were isolated and characterized.

One-Pot, Fluoride-Promoted Wittig Reaction
2183
In contrast, longer reaction times, poor yields, and very poor diaster-
eoselection were observed when ketones were used as electrophiles
(Table 1, entries 9 and 10), although no by-products were observed and
the unreacted ketones were easily recovered.
Longer reaction times were also observed when a branched a-bromo
ester was used (Table 2, entries 1 and 2) to create a trisubstituted double
bond: in this case, the reaction with aldehydes proceeded in reasonable
yields and high stereoselection to give a-methyl-a,b-unsaturated esters,
useful intermediates in the synthesis of insect pheromones and other
natural products.[13]
To enlarge the scope of the method, an a-bromoketone and an a-
bromonitrile were tested: the former gave the E-isomer in excellent stereo-
selectivity and good yields (Table 2, entries 3 and 4), whereas the latter gave
a mixture of E=Z isomers of the a,b-unsaturated nitrile (Table 2, entry 5).
Some other points are worth mentioning: no aldol self-condensation
occurred with carbonyl substrates containing a-hydrogen atoms (Table
1, entries 2 and 12; Table 2, entries 2 and 4) and no racemization, even par-
tial, were observed in the presence of an a-stereogenic carbon (Table 1,
entry 12). Furthermore, a free hydroxyl function is tolerated: for example
the compound 3ak, an important building block in the preparation of a
polymer employed in photography and microlithography[14] was obtained
from 2k in 81% yield and with good stereoselectivity (Table 1, entry 11). A
slightly better yield (87%) was obtained by protecting the hydroxylic
function as its tert-butyldimethylsilyl derivative (TBDMS) derivative.
The investigation was then extended to semistabilized ylides from
benzyl chlorides and applied to the synthesis of multifunctionalized stil-
benes[15a] with the final aim of optimizing a new and convenient synthetic
approach to biologically active molecules, analogs to combretastatins
and resveratrol (Table 3).[15b–f] A trimethoxybenzyl phosphonium halide
was required for this; it is a highly deactivated substrate toward deproto-
nation as compared to an ethoxycarbonylmethyl-phosphonium halide.
Nevertheless, the reaction of trimethoxybenzyl chloride (1e)
proceeded equally well (81% yield) with respect to a-bromoacetate 1a
when 4-bromobenzaldehyde (2d) was used, although with a longer
reaction time (16 h) and little stereoselectivity. Even the less electrophilic
aldehydes 2c and 2l reacted to give compounds 3ec (50%) and 3el (36%),
albeit in lower yields.
CONCLUSIONS
a,b-Unsaturated compounds (such as esters, nitriles, ketones) are gener-
ally prepared by Wittig, HWE,[16] Heck,[17] Stille,[18] Peterson,[19] and

2184
T. Fumagalli, G. Sello, and F. Orsini
Reformatsky=b-elimination reactions.[20] These compounds can be also
prepared via Cope rearrangement,[21] olefin methatesis,[22] or from
acetylenic derivatives.[23] Despite their general usefulness, all these meth-
odologies have some limitations such as lack of stereochemistry control
(in particular, when the trisubstituted double bond is concerned), expen-
sive reagents, requirement of anhydrous solvents and=or inert atmo-
sphere, high temperature, multistep processes, or metal activation.
In this article, we have presented a convenient access to a,b-unsatu-
rated esters and a,b-unsaturated ketones, in good yields and with good=
total E stereoselectivity via a one-pot Wittig reaction promoted by tetra-
butyl ammonium fluoride. In contrast to other methods reported in the
literature, readily enolizable aldehydes can be used: fluoride is
sufficiently basic to deprotonate the phosphonium salt but it does not cat-
alyze side reactions such as aldol condensation. For the same reason, other
functionalities such as hydroxyl groups are compatible with the transforma-
tion. In addition, this transformation takes place even in an open atmo-
sphere, with no requirement of anhydrous solvents, through a one-pot
sequential process where consecutive reactions (three or four depending
on the substrate) are performed without workup and=or intermediate iso-
lation [phosphonium salt formation, phosphonium salt deprotonation,
Wittig condensation, deprotection of a silyl group when present].
In addition, this method can be also utilized to stereoselectively prepare
trisubstituted b-alkyl-a,b-unsaturated esters, although in lower yields.
EXPERIMENTAL
General
1H NMR spectra were measured on spectrometers at 400 MHz, and 13C
NMR were measured on spectrometers at 50 and 100 MHz. Thin-layer
chromatography (TLC) was carried out on plates with 250 mm of silica
gel. THF, hexane, and AcOEt were commercial products, as were
n-Bu3P, Ph3P, tetra-n-butylammonium fluoride (TBAF) solution (1M
in THF), halo derivatives 1a–e, aldehydes, and ketones 2a–m.
General Procedure for One-Pot, Fluoride-Promoted Wittig Reaction
Ethyl (E)-3-phenyl-prop-2-Enoate (3aa)
Ethyl a-bromo acetate (0.50 mmol, 87.0 mg) was weighed in a test tube
(equipped with magnetic bar). The solvent (technical grade THF,

One-Pot, Fluoride-Promoted Wittig Reaction
2185
0.5 mL) was added, and the test tube was cooled in an ice bath at 0ꢀC. n-
Bu3P (0.50 mmol, 127 mL) was then added dropwise. When the addition
was completed, the ice bath was removed. After 5 min, benzaldehyde was
added (0.55 mmol, 56 mL), followed by the n-Bu4NF solution (1 M in
THF, 0.6 mL). The reaction was monitored by TLC (silica gel;
AcOEt=petroleum ether 1=99). After 2.5 h, the solvent was removed
under reduced pressure, and the crude material was purified by column
chromatography (SiO2, AcOEt=hexane 1=99) to remove salts, phosphine
oxide, and unreacted benzaldehyde, yielding 3aa (80.9 mg, 92%).
Colorless oil (lit.[24]: mp ¼ 12ꢀC). 1H NMR (CDCl3, 400 MHz) d 7.70
(d, J ¼ 16.0 Hz, 1H), 7.53 (m, 2H), 7.39 (m, 3H), 6.44 (d, J ¼ 16.0 Hz, 1H),
(q, J ¼ 7.1 Hz, 2H), 1.34 (t, J ¼ 7.1 Hz, 3H). 13C NMR (CDCl3, 50 MHz)
d 167.2, 44.8, 134.6, 130.4, 130.4, 129.1, 128.2, 60.7, 14.5. HRMS calcd.
for C11H12O2 (Mþ): 176.083730; found: 176.083300.
Data
Ethyl (E)-5-Phenyl-pent-2-enoate (3ab)[25]
1
Colorless oil. H NMR (CDCl3, 400 MHz) d 7.33 (m, 2H), 7.23 (m, 3H),
7.04 (dt, J ¼ 9.1 Hz, J ¼ 15.8 Hz, 1H), 5.89 (d, J ¼ 15.8 Hz, 1H), (q,
J ¼ 7.1 Hz, 2H), 2.81 (m, 2H), 2.56 (m, 2H), 1.32 (t, J ¼ 7.1 Hz, 3H).
13C NMR (CDCl3, 100 MHz) d 166.4, 147.9, 140.7, 128.4, 128.3, 126.1,
121.8, 60.1, 34.3, 33.8, 14.2. HRMS calcd. for C13H16O2 (Mþ):
204.115030; found: 204.115810.
Ethyl (E)-3-(4-Methoxyphenyl)-prop-2-enoate (3ac)[24c,26]
Colorless crystals; mp ¼ 48–50ꢀC (CH2Cl2, petroleum ether) (lit.[24c]
:
mp ¼ 48–50ꢀC). 1H NMR (CDCl3, 400 MHz) d 7.73 (d, J ¼ 15.9 Hz,
1H), 7.50 (d, J ¼ 8.76 Hz, 2H), 6.93 (d, J ¼ 8.76 Hz, 2H), 6.33 (d,
J ¼ 15.9 Hz, 1H), 4.28 (q, J ¼ 7.1 Hz, 2H), 3.86 (s, 3H), 1.36 (t, J ¼ 7.1 Hz,
3H). 13C NMR (CDCl3, 100 MHz) d 167.3, 161.3, 144.2, 129.6, 127.2,
115.7, 114.3, 60.3, 55.3, 14.3. HRMS calcd. for C12H42O3 (Mþ):
206.094294; found: 206.094310.
(E)-3-(4-Bromophenyl)-prop-2-enoate (3ad)[24d,27]
1
Colorless oil. H NMR (CDCl3, 400 MHz) d 7.62 (d, J ¼ 16.0 Hz, 1H),
7.52 (d, J ¼ 8.4 Hz, 2H), 7.39 (d, J ¼ 8.4 Hz, 2H), 6.43 (d, J ¼ 16.0 Hz,
1H), 4.28 (q, J ¼ 7.1 Hz, 2H), 1.35 (t, J ¼ 7.1 Hz, 3H). 13C NMR (CDCl3,

2186
T. Fumagalli, G. Sello, and F. Orsini
100 MHz) d 166.6, 143.1, 133.4, 132.1, 129.3, 124.4, 119.0, 60.5, 14.2.
HRMS calcd. for C11BrH11O2 (Mþ): 253.994241; found: 253.994610.
Ethyl (E)-3-(4-Nitrophenyl)-prop-2-enoate (3ae)[24a,d,3b,1]
Colorless crystals; mp ¼ 139–140ꢀC (CH2Cl2, petroleum ether) (lit[24d]
:
1
140–141ꢀC). H NMR (CDCl3, 400 MHz) d 8.26 (d, J ¼ 8.8 Hz, 2H),
7.72 (d, J ¼ 16.4 Hz, 1H), 7.68 (d, J ¼ 8.8 Hz, 2H), 6.57 (d, J ¼ 16.4 Hz,
1H), 4.30 (q, J ¼ 7.1 Hz, 2H), 1.36 (t, J ¼ 7.1 Hz, 3H). 13C NMR (CDCl3,
100 MHz) d 165.9, 148.4, 141.5, 140.5, 128.5, 124.1, 122.5, 60.9, 14.2.
HRMS calcd. for C11H11NO4(Mþ): 221.068808; found: 221.068510.
Diethyl 3,30-(1,2-Phenylene)-bisacrylate (3af)[28]
Colorless crystals; mp ¼ 77–78ꢀC (CH2Cl2, petroleum ether) (lit.[28]
:
mp ¼ 75–76ꢀC). 1H NMR (CDCl3, 400 MHz) d 8.06 (d, J ¼ 15.8 Hz,
2H), 7.59 (m, 2H), 7.41 (m, 2H), 6.37 (d, J ¼ 15.8 Hz, 2H), 4.32 (q,
J ¼ 7.1 Hz, 4H), 1.37 (t, J ¼ 7.1 Hz, 6H). 13C NMR (CDCl3, 100 MHz)
d 166.3, 141.2, 134.3, 129.9, 127.6, 121.9, 60.6, 14.2. HRMS calcd. for
C16H18O4 (Mþ): 274.120509; found: 274.120670.
Ethyl (E)-3-Furan-2-yl-prop-2-enoate (3ag)[29,26b]
Colorless oil. 1H NMR (CDCl3, 400 MHz) d 7.49 (m, 1H), 7.44 (d,
J ¼ 15.8 Hz, 1H), 6.62 (m, 1H), 6.48 (m, 1H), 6.33 (d, J ¼ Hz, 1H), 4.26
(q, J ¼ 7.1 Hz, 2H), 1.34 (t, J ¼ 7.1 Hz, 3H). 13C NMR (CDCl3,
100 MHz) d 166.3, 151.5, 144.6, 130.9, 115.9, 114.5, 112.2, 60.4, 14.3.
HRMS calcd. for C9H10O3 (Mþ): 166.062994; found: 166.063540.
Ethyl (E)-3-Thiophen-2-yl-prop-2-enoate (3ah)[30]
1
Colorless oil. H NMR (CDCl3, 400 MHz) d 7.81 (d, J ¼ 15.7 Hz, 1H),
7.39 (m, 1H), 7.27 (m, 1H), 7.07 (m, 1H), 6.26 (d, J ¼ 15.7 Hz, 1H),
4.27 (q, J ¼ 7.1 Hz, 2H), 1.35 (t, J ¼ 7.1 Hz, 3H). 13C NMR (CDCl3,
100 MHz) d 166.8, 139.6, 137.0, 130.7, 128.3, 128.0, 117.1, 60.5, 14.3.
HRMS calcd. for C9H10O2S (Mþ): 182.040151; found: 182.039690.
Ethyl (E)-3-(5-Hydroxymethylfuran-2-yl)-prop-2-enoate (3ak-E)[31]
1
Colorless oil. H NMR (CDCl3, 400 MHz) d 7.39 (d, J ¼ 15.7 Hz, 1H),
6.56 (d, J ¼ 3.3 Hz, 1H), 6.39 (d, J ¼ 3.3 Hz, 1H), 6.31 (d, J ¼ 15.7 Hz,

One-Pot, Fluoride-Promoted Wittig Reaction
2187
1H), 4.65 (s, 2H), 4.25 (q, J ¼ 7.1 Hz, 2H), 2.30 (bs, 1H), 1.33 (t,
J ¼ 7.1 Hz, 3H). 13C NMR (CDCl3, 100 MHz) d 167.0, 156.4, 150.6,
130.7, 115.7, 115.4, 110.0, 60.3, 57.4 14.1. HRMS calcd. for C10H12O4
(Mþ): 196.073559; found: 196.073590.
Ethyl (z)-3-(5-Hydroxymethylfuran-2-yl)-prop-2-enoate (3ak-Z)[31]
Colorless oil. 1H NMR (CDCl3, 400 MHz) d 7.64 (d, J ¼ 3.4 Hz, 1H), 7.77
(d, J ¼ 12.8 Hz, 1H), 6.43 (d, J ¼ 3.4 Hz, 1H), 5.76 (d, J ¼ 12.8 Hz, 1H),
4.65 (s, 2H), 4.25 (q, J ¼ 7.1 Hz, 2H), 2.30 (bs, 1H), 1.35 (t, J ¼ 7.1 Hz,
3H). 13C NMR (CDCl3, 100 MHz) d 165.9, 155.3, 150.5, 130.1, 117.8,
115.9, 110.4, 60.0, 57.5 14.1. HRMS calcd. for C10H12O4 (Mþ):
196.073559; found: 196.074280.
Ethyl (Z)-3-((S)-2,2-Dimethyl-[1,3]dioxolan-4-yl)-prop-2-enoate
(3am-Z)[32]
Colorless oil. [a]25 ¼ þ129.35 (c ¼ 0.02, chloroform) (lit.[32d]
:
D
[a]17 ¼ þ124.3; c ¼ 0.534, chloroform). H NMR (CDCl3, 400 MHz) d
1
D
6.36 (dd, J ¼ 6.8 Hz, J ¼ 11.6 Hz, 1H), 5.85 (d, J ¼ 11.6 Hz, 1H), 5.50
(m, 1H), 4.38 (m, 1H), 4.18 (q, J ¼ 7.1 Hz, 2H), 3.63 (m, 1H), 1.45 (s,
3H), 1.39 (s, 3H), 1.29 (t, J ¼ 7.1 Hz, 3H). 13C NMR (CDCl3,
100 MHz) d 165.6, 120.7, 109.6, 73.5, 69.3, 60.4, 26.5, 25.3, 14.1. HRMS
calcd. for C10H16O4 (Mþ): 200.104859; found: 200.105109.
Ethyl (E)-2-Methyl-3-phenyl-prop-2-enoate (3ba)[33]
1
Colorless oil. H NMR (CDCl3, 400 MHz) d 7.72 (s, 1H), 7.42 (m, 4H),
7.34 (m, 1H), 4.30 (q, J ¼ 7.1 Hz, 2H), 2.15 (s, 3H), 1.37 (t, J ¼ 7.1 Hz,
3H). 13C NMR (CDCl3, 100 MHz) d 168.6, 138.5, 135.9, 129.5, 128.6,
128.3, 128.1, 60.8, 14.2, 13.9. HRMS calcd. for C12H14O2 (Mþ):
190.099380; found: 190.099520.
Ethyl (E)-2-Methyl-5-phenyl-pent-2-enoate (3bb)[34]
1
Colorless oil. H NMR (CDCl3, 400 MHz) d 7.32 (m, 2H), 7.24 (m, 3H),
6.84 (t, J ¼ 14.6 Hz, 1H), 4.21 (q, J ¼ 7.1 Hz, 2H), 2.78 (m, 2H), 2.53 (m,
2H), 1.82 (s, 3H), 1.37 (t, J ¼ 7.1 Hz, 3H). 13C NMR (CDCl3, 100 MHz) d
168.1, 141.1, 140.8, 128.4, 128.3, 128.2, 126.0, 60.3, 34.6, 30.5, 14.2, 12.2.
HRMS calcd. for C14H18O2 (Mþ): 218.130680; found: 218.130910.

2188
T. Fumagalli, G. Sello, and F. Orsini
(E)-1,3-Diphenyl-propenone (3ca)[35]
Colorless crystals; mp ¼ 56–57ꢀC (petroleum ether) (lit.[35d]: mp ¼ 57–
1
58ꢀC). H NMR (CDCl3, 400 MHz) d 8.06 (d, J ¼ 7.3 Hz, 2H), 7.85 (d,
J ¼ 15.7 Hz, 1H), 7.55 (m, 9H). 13C NMR (CDCl3, 100 MHz) d 190.3,
144.7, 138.1, 134.7, 132.6, 130.4, 128.8, 128.5, 128.4, 128.3, 121.1. HRMS
calcd. for C15H12O (Mþ): 208.088815; found: 208.088680.
(E)-1,5-Diphenyl-pent-2-en-1-one (3cb)[36]
Colorless oil. 1H NMR (CDCl3, 400 MHz) d 7.94 (d, J ¼ 7.9 Hz, 2H), 7.39
(m, 8H), 7.14 (m, 1H), 6.92 (d, J ¼ 15.4 Hz, 1H), 2.90 (m, 2H), 2.69 (m,
2H). 13C NMR (CDCl3, 100 MHz) d 190.8, 148.4, 140.7, 137.7, 132.5,
128.6, 128.5, 128.4, 128.3, 126.4, 126.1, 34.5, 34.4. HRMS calcd. for
C17H16O (Mþ): 236.120115; found: 236.120940.
(E)-3-(4-Nitrophenyl)-acrylonitrile (3de-E)[37]
Colorless crystals; mp ¼ 200–201ꢀC (CH2Cl2, petroleum ether) (lit.[37b]
:
1
mp ¼ 200–201ꢀC). H NMR (CDCl3, 400 MHz) d 8.30 (d, J ¼ 8.7 Hz,
2H), 7.66 (d, J ¼ 8.7 Hz, 2H), 7.49 (d, J ¼ 16.6 Hz, 1H), 6.08 (d,
J ¼ 16.6 Hz, 1H); 13C NMR (CDCl3, 100 MHz) d 149.0, 147.7, 139.1,
128.1, 124.3, 116.9, 101.0. HRMS calcd. for C9H6N2O2 (Mþ):
174.042928; found: 174.042950.
(E)-2-(40-Bromophenyl)-1-(3,4,5-trimethoxyphenyl)ethene (3ed-E)[38]
Colorless crystals; mp ¼ 157–158ꢀC (CH2Cl2, petroleum ether). 1H NMR
(CDCl3, 400 MHz) d 7.50 (d, J ¼ 8.6 Hz, 2H), 7.39 (d, J ¼ 8.6 Hz, 2H),
7.05 (d, J ¼ 16.2 Hz, 1H), 6.95 (d, J ¼ 16.2 Hz, 1H), 6.75 (s, 2H), 3.94
(s, 6H), 3.90 (s, 3H). 13C NMR (CDCl3, 100 MHz) d 153.4, 138.2,
136.1, 132.6, 131.7, 129.3, 127.9, 126.8, 121.2, 103.7, 60.9, 56.1. HRMS
calcd. for C17H17BrO3 (Mþ): 348.036106; found: 348,034760.
(Z)-2-(40-Bromophenyl)-1-(3,4,5-trimethoxyphenyl)ethene (3ed-Z)[38]
Colorless oil. 1H NMR (CDCl3, 400 MHz) d 7.39 (d, J ¼ 8.4 Hz, 2H), 7.18
(d, J ¼ 8.4 Hz, 2H), 6.56 (d, J ¼ 12.1 Hz, 1H), 6.53 (d, J ¼ 12.1 Hz, 1H),
6.46 (s, 2H), 3.86 (s, 3H), 3.70 (s, 6H). 13C NMR (CDCl3, 100 MHz) d
152.9, 137.4, 136.2, 132.0, 131.3, 130.8, 130.6, 128.5, 120.9, 106.0, 60.8,

One-Pot, Fluoride-Promoted Wittig Reaction
2189
55.8. HRMS calcd. for C17H17BrO3 (Mþ): 348.036106; found:
348.036290.
(E)-2-(40-Methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)ethene
(3ec-E)[38b,c]
Colorless crystal; mp ¼ 156–157ꢀC (CH2Cl2, petroleum ether) (lit.[38c]
:
mp ¼ 152–155ꢀC).1H NMR (CDCl3, 400 MHz) d 7.47 (m, 2H), 6.94 (m,
4H), 6.74 (s, 2H), 3.95 (s, 6H), 3.90 (s, 3H), 3.86 (s, 3H). 13C NMR
(CDCl3, 100 MHz) d 159.3, 153.3, 137.7, 133.4, 130.0, 127.7, 127.5,
126.5, 114.1, 103.4, 60.9, 56.1, 55.2. HRMS calcd. for C18H20rO4 (Mþ):
300.136159; found. 300.136200.
38b,c
]
(Z)-2-(40-Methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)ethene (3ec-Z)[
Colorless oil. 1H NMR (CDCl3, 400 MHz) d 7.26 (d, J ¼ 8.7 Hz, 2H), 6.81
(d, J ¼ 8.7 Hz, 2H), 6.52 (m, 3H), 6.45 (d, J ¼ 12.1 Hz, 1H), 3.87 (s, 3H),
3.81 (s, 3H), 3.71 (s, 6H). 13C NMR (CDCl3, 100 MHz) d 157.7, 152.9,
132.8, 130.2, 129.6, 129.4, 128.6, 113.5, 106.0, 108.7, 60.8, 55.8, 55.2.
HRMS calcd. for C18H20rO4 (Mþ): 300.136159; found: 300,135800.
(E)-2-(30,40-Dimethoxyphenyl)-1-(3,4,5-trimethoxyphenyl)ethene
(3el-E)[39]
Colorless crystals; mp ¼ 141–142ꢀC (CH2Cl2, petroleum ether) (lit.[39a]
:
mp ¼ 139–140ꢀC).1H NMR (CDCl3, 400 MHz) d 7.07 (m, 2H), 6.91 (m,
3H), 6.74 (s, 2H), 3.95 (s, 3H), 3.92 (s, 6H), 3.90 (s, 3H), 3.88 (s, 3H).
13C NMR (CDCl3, 100 MHz) d 153.3, 149.0, 148.8, 137.7, 133.2, 130.2,
127.8, 126.6, 119.6, 111.2, 108.7, 103.3, 60.8, 56.0, 55.8, 55.7. HRMS
calcd. for C19H22O5 (Mþ): 330.146724; found; 330.146360
(Z)-2-(30,40-Dimethoxyphenyl)-1-(3,4,5-trimethoxyphenyl)ethene
(3el-Z)[39]
1
Colorless oil. H NMR (CDCl3, 400 MHz) d 6.85 (m, 3H), 6.55 (s, 2H),
6.53 (d, J ¼ 12.1 Hz, 1H), 6.48 (d, J ¼ 12.1 Hz, 1H), 3.88 (s, 3H), 3.85 (s,
3H), 3.73 (s, 6H), 3.70 (s, 3H). 13C NMR (CDCl3, 100 MHz) d 152.9,
148.4, 148.2, 137.1, 133.0, 129.8, 129.7, 128.8, 121.9, 111.8, 110.8,
105.9, 60.8, 55.9, 55.8, 55.6. HRMS calcd. for C19H22O5 (Mþ):
330.146724; found: 330.146580.

2190
T. Fumagalli, G. Sello, and F. Orsini
ACKNOWLEDGMENTS
ꢀ
Universita degli Studi di Milano and MIUR (Ministero dell’ Istruzione,
dell’ Universita e della Ricerca) are acknowledged for financial support.
ꢀ
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