Synthesis of nonsymmetric divinylarenes by a heck/wittig reaction combination

Article abstract of DOI:10.1080/00397910903395235

A protocol for a one-pot Heck reaction/Wittig olefination to divinylarenes has been developed. Copyright Taylor & Francis Group, LLC.

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Synthesis of Nonsymmetric Divinylarenes
by a Heck/Wittig Reaction Combination
Christian Burmester a , Shuntaro Mataka a & Thies Thiemann a b
a Institute of Materials Chemistry and Engineering, Kyushu
University, Kasuga-shi, Japan
b Interdisciplinary Graduate School of Engineering Sciences, Kyushu
University, Kasuga-shi, Japan
Published online: 04 Oct 2010.
To cite this article: Christian Burmester , Shuntaro Mataka & Thies Thiemann (2010) Synthesis of
Nonsymmetric Divinylarenes by a Heck/Wittig Reaction Combination, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 40:21, 3196-3208,
DOI: 10.1080/00397910903395235
To link to this article: http://dx.doi.org/10.1080/00397910903395235
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Synthetic Communications1, 40: 3196–3208, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903395235
SYNTHESIS OF NONSYMMETRIC DIVINYLARENES
BY A HECK/WITTIG REACTION COMBINATION
Christian Burmester,1 Shuntaro Mataka,1
and Thies Thiemann1,2
1Institute of Materials Chemistry and Engineering, Kyushu University,
Kasuga-shi, Japan
2Interdisciplinary Graduate School of Engineering Sciences, Kyushu
University, Kasuga-shi, Japan
A protocol for a one-pot Heck reaction/Wittig olefination to divinylarenes has been
developed.
Keywords: Chalcones; Heck reaction; one-pot synthesis; Wittig olefination
INTRODUCTION
The utilization of fast screening techniques for the synthesis and evaluation of
new pharmaceutical compounds has led to an increasing demand for reliable and
easy synthetic protocols. One-pot procedures are highly desirable because they
minimize time-consuming workup and purification steps and furthermore often
provide greater yields because they have less purification losses. Because of possible
side reactions induced by an increasing number of reagents, the development of new
one-pot reaction protocols remains a challenge, however.
Over the years, we have been studying the reactivity of stabilized phosphorus-
ylides in palladium-catalyzed reactions.[1] This has led to protocols for one-pot
Suzuki–Wittig and Sonogashira–Wittig reactions. Recently, we became interested
in developing an efficient synthetic procedure for a combination of Heck and Wittig
reactions, which would lead to a broader entry to substituted chalcones and nonsym-
metric divinyl-substituted aromatic compounds. Substituted chalcones have been
shown to possess a number of interesting biological properties such as antileishma-
nial,[2,3] anti-inflammatory,[4] and antifungal[5] activities. More recently, attention
has been directed toward their antimalarial activity.[3] Until now, good access to
vinyl-substituted chalcones has been scarce, even though they are useful intermedi-
ates for further modifications. Nonsymmetric divinyl-substituted aromatic com-
pounds have found use in optical applications, and some of these chalcones have
been evaluated as to their nonlinear optical properties.[6]
Received May 23, 2009.
Address correspondence to Thies Thiemann, Kyushu University, 6-1, Kasuga-koh-en, Kasuga-shi
816-8580, Japan. E-mail: thies@cm.kyushu-u.ac.jp
3196

HECK/WITTIG REACTION COMBINATION
3197
RESULTS AND DISCUSSION
The Heck reaction[7] has become a powerful and indispensible tool in organic
chemistry, both in academia and in industry.[8] Nevertheless, the selection of appro-
priate reaction conditions for specific reactants may present difficulties and often
requires a laborious optimization because small changes in the employed reagents
can have a large influence on the outcome of the Heck reaction.[9]
The choice of the catalyst is often crucial for the performance of the Heck reac-
tion. To develop a robust system for a one-pot protocol, we chose 1,2-bis(diphenylpho-
sphino)ethane (dppe) as ligand because bidentate ligands form stable Pd(0) complexes,
so that an excess phosphine is not needed. Furthermore, it was believed that stable
complexes should lead to higher turnover numbers (TONs) in this reaction and that
the catalysts would likely tolerate the presence of other additives in the reaction such
as the phosphoranes needed for the Wittig olefination that otherwise could also have
served as ligands for the catalyst, thereby altering the effectiveness of the catalyst. An
early report by R. F. Heck[10] that reported that bidentate ligands can also be poor
choices as ligands for the catalyst in Heck reactions was explained by the formation
of stable PdL2 complexes when the active species are generated in situ from Pd(OAc)2
and the ligand. Normally, this can be circumvented by the utilization of PdCl2(L) com-
plexes as sources for the catalytically active species, and reactions employing bidentate
ligands have quite good TONs. For purposes of simplicity, initially we chose to employ
PdCl2(dppe); however, we observed (Table 1, entry 2) that Pd(OAc)2 and dppe can
be used with equal success. Another important factor in palladium catalysis is the
influence of the base. We tried several bases, among which K2CO3 proved to be a good
choice. With diazabicycloundecene (DBU) as base, no Heck reaction could be
observed, although no precipitation of Pd black occurred even after 2 days at
100 ꢀC. On the other hand, with K2CO3 as base, palladium precipitates at the end of
the reaction. Generally, carbonates are also more environmentally friendly than
commonly used amines. To investigate the effectiveness of the reaction conditions,
the reaction of 4-bromobenzaldehyde (1a) and tert-butyl acrylate (2a) in a 1:1.1 mixture
Table 1. Heck=Wittig reaction with 4-bromobenzaldehyde (1a), employing P ylides or phosphonium salts
Entry
R0
R
Product
Yield (%)
1
2
Ph-CO- (4a)
CO2tBu (2a)
CO2Me (2b)
Ph (2c)
6a
6b
6c
6d
6e
6f
62
75
45
65
70
70
78a
75b
64
52
50
41
65
3
4
CONMe2 (2d)
CO2tBu (2a)
CO2tBu (2a)
CO2Me (2b)
CO2tBu (2a)
CO2Me (2b)
CO2tBu (2a)
CO2Me (2b)
CO2tBu (2a)
CO2tBu (2a)
5
4-Br-Ph-CO- (4b)
Ac (4c)
Ph (5a)
6
7
6g
6h
6i
8
9
H (5b)
Ac (5c)
10
11
12
13
6f
6j
1,4-Ph (5d)
CO2Me (4d)
6k
6l
a25% (Z)-isomer, 53% (E)-isomer.
b41% (Z)-isomer, 34% (E)-isomer.

3198
C. BURMESTER, S. MATAKA, AND T. THIEMANN
Scheme 1. Optimizing the reaction conditions: Heck reaction with 4-bromobenzaldehyde (1a).
under Heck conditions (3 mol% PdCl2(dppe), 3 eq. K2CO3, DMF, 100 ꢀC, 12 h) was
examined and 4-[2-(tert-butoxycarbonyl)ethenyl]-benzaldehyde (3) was isolated in
1
93% yield (Scheme 1). By H NMR spectroscopy, no other reaction products could
be detected in the reaction mixture.
Next, one-pot Heck-=Wittig reactions with 4-bromobenzaldehyde (1a) were
carried out under the same reaction conditions (Scheme 2; Tables 1 and 2). The com-
bination with the Wittig reaction could be conducted in one pot either in a one-step
procedure or by sequentially carrying out first the Heck reaction and then the Wittig
reaction and adding the Wittig reagent to the reaction mixture of the Heck reaction.
The yield of the desired product was found to be slightly less when the two reactions
were conducted simultaneously. Thus, stilbene 6h was obtained in 70% yield in one
step and in 75% yield in two steps in one pot (Table 1). The yields reported in Table 1
refer to the two-step, one-pot procedure. It must be stressed that none of the reac-
tants is used in excess, but aldehyde, olefin component, and phosphorane are used
in a ratio of nearly 1:1:1. A similar result was obtained with 2-bromobenzaldehyde
(1b), albeit with slightly lower yields (Scheme 2, Table 3).
As P components for the Wittig reaction, P ylides (4) as well as phosphonium
salts (5) can be used, thus eliminating the need for the isolation of the free ylides 4.
However, the yield obtained for products derived from stabilized ylides 4 is higher
than the yield, when generating the ylides from the corresponding phosphonium salts
5 in situ. Also, it is possible to carry out one-pot Wittig–Heck reactions with phos-
phonium salts 5 that lead to nonstabilized and semistabilized ylides 4a, 4b, and 4d.
Scheme 2. Heck=Wittig one-pot reaction with 4-bromobenzaldehyde (1a).

HECK/WITTIG REACTION COMBINATION
3199
Table 2. Heck=Wittig reaction with 2-bromobenzaldehyde (1b) employing P ylides
Entry
R0
R
Product
Yield (%)
1
2
CN (4d)
COCH3 (4c)
CO2tBu (2a)
CO2tBu (2a)
7a
7b
58
63
All the products are E-configured in respect to the olefinic moiety affected by the
Suzuki cross coupling and E-configured in respect to the olefinic moiety created by
the Wittig reaction when stabilized phosphoranes are used. Reactions with alkoxycar-
bonylmethylidenetriphenylphosphoranes can give up to 9% Z product. The Z pro-
ducts are separated readily from the E isomers, and the yields in the tables are for
the E isomers only, unless stated otherwise. The reaction of cyanomethylidenetriphe-
nylphosphorane (4d) with 1b gives 7a as a mixture of E and Z products (Table 2). E-7a
1
and Z-7a can be differentiated well by H and 13C NMR, where the values of the
coupling constants 3JCH¼CHCN are very similar to values reported[11] for similar phe-
nylacrylonitriles (Jtrans 16.7 Hz versus Jcis 11.9 Hz) The semistabilized phosphorane
phenylmethylidenetriphenylphosphorane, prepared from the corresponding phos-
phonium salt 5a, yields Wittig products as mixtures of E and Z isomers. Again, the
3
values of the coupling constants JCH¼CHPh found are very similar to values
reported[12] for substituted E and Z stilbenes (Jtrans 16.4 Hz versus Jcis 12.5 Hz).
Bromoheteroarene carbaldehydes 8 can be used as substrates instead of
bromoaryl carbaldehydes 1, which is important for an access to pharmaceutically
interesting intermediates (Scheme 4, Table 3). The expected products 9 could be
obtained when reacting 2-bromo-5-furylcarbaldehyde (8a) and 2-bromo-5-thiophene-
carbaldehyde (8b), albeit in slightly lower yields than with 1a. Here, the Wittig
reagents used were exclusively phosphoranes. Generally, there are some limitations
as to the haloheteroaryl carbaldehydes that can be used as substrates under the
reaction conditions. Thus, the desired products could not be obtained with
5-bromo-3-indolecarbaldehyde 10 (Fig. 1) because the N-unprotected carbaldehyde
(10a) reacts with acrylates to give the corresponding Michael addition products, N-
alkoxycarbonylethyl-5-bromo-3-indolecarbaldehydes. Also, N-acetyl and N-BOC
protected 5-bromo-3-indolecarbaldehydes, 10b and 10c, did not give the desired pro-
ducts as the N-protective groups were cleaved under the highly basic conditions used.
The tert-butyl cinnamates 6f, 6l, and 7b were converted to the respective
cinnamic acids (11) by action of trifluoroacetic acid in CH2Cl2 (Scheme 5). The
cinnamic acids and a larger number of the synthesized divinylarenes were sent for
Table 3. Heck=Wittig reaction with 2-bromohetarylcarbaldehydes 8
Entry
X
P ylide
Alkene
Product Yield (%)
1
2
3
4
5
2,5-Thien-diyl (8a) Ph-CO- (4a)
Ac (4c)
CO2tBu (2a)
CO2Me (2b)
CO2Me (2b)
Ph (2c)
9a
9b
9c
9d
9e
55
56
55
60
45
2,5-Fur-diyl (8b)
Ph-CO-(4a)
CONMe2 (2d)

3200
C. BURMESTER, S. MATAKA, AND T. THIEMANN
Scheme 3. Heck=Wittig one-pot reaction with 2-bromobenzaldehyde (1b).
Scheme 4. Heck=Wittig one-pot reaction with 5-bromohetarylcarbaldehydes.
Figure 1. 5-Bromoindole-3-carbaldehydes.
Scheme 5. Preparation of vinylcinnamic acids.

HECK/WITTIG REACTION COMBINATION
3201
microbial testing to the Tuberculosis Antimicrobial Acquisition and Coordinating
Facility (TAACF) of the Southern Research Institute, Birmingham, Alabama,
USA.[13] The forthcoming results will be disseminated elsewhere.
SUMMARY
We have developed a new one-pot protocol for a combined Wittig–Heck reac-
tion that enables the simple synthesis of a broad range of products derived from bro-
moarylaldehydes with ylides preformed or generated in situ and acrylates or styrenes.
The products are formed in good yields, with none of the reactants used in excess.
EXPERIMENTAL
General
Melting points were measured on a Yanaco microscopic hotstage and are
uncorrected. Infrared (IR) spectra were measured with a Jasco IR-900 machine.
1H and 13C NMR spectra were recorded with a Jeol EX-270 spectrometer. The
chemical shifts are relative to tetramethylsilance (TMS; solvent CDCl3, unless other-
wise noted). Assignments of the signals were aided by distortionless enhancement by
polarization transfer (DEP) measurements; (þ) denotes primary and tertiary, (–)
denotes secondary, and (o) denotes quaternary carbon atoms. Mass spectra were
measured with a JMS-01-SG-2 spectrometer (EI, 70 eV, unless noted otherwise).
Column chromatography was carried out on Wakogel 300.
4-Bromobenzoylmethylidenetriphenylphosphorane (4b), benzoylmethylidene-
triphenylphosphorane (4a),[7,14] and acetylmethylidenetriphenylphosphorane (4c)[14]
were prepared according to literature procedures. Other compounds were purchased
from commercial sources and used as received.
General Wittig–Heck Procedure
A solution of the bromoaldehyde (1.0 mmol), alkene (1.1 eq.), K2CO3 (3.0 eq.),
and PdCl2(dppe) (3 mol%) was heated in degassed N,N-dimethylformamide (1 mL)
at 100 ꢀC for 12 h. To the reaction mixture, phosphonium salt (1 eq.) or P ylide
(1 eq.) was added. After additional heating for 6 h, the reaction mixture was diluted
with ethyl acetate (30 mL) and extracted twice with water (2 ꢁ 30 mL). The aqueous
phase was extracted with ethyl acetate (10 mL), and the combined organic phase was
dried and evaporated under reduced pressure. The crude product was purified either
by crystallization or column chromatography on silica.
4-[2-(tert-Butoxycarbonyl)ethenyl]benzaldehyde (3)
Yield 93%, yellow solid, mp 100–101 ꢀC (from MeOH) (lit.[15,16] 108–109 ꢀC);
n
max(KBr)=cmꢂ1 2971, 2934, 2816, 2719, 1704, 1637, 1604, 1324, 1213, 1149, 995,
847, 822, 516, and 498; dH(270 MHz; CDCl3; Me4Si) 1.54 (s, 9H), 6.49 (d, 1H, J
16.0), 7.61 (d, 1H, J 16.0), 7.66 (d, 2 H, J 8.4), 7.89 (d, 2 H, J 8.2 Hz), and 10.02

3202
C. BURMESTER, S. MATAKA, AND T. THIEMANN
(s, 1 H); m=z (EI) 232.1101 (Mþ C14H16O3 requires 232.1099), 232 (6%), 176 (64), 159
(37), 104 (23), 79 (14), and 61 (100).
tert-Butyl (E,E)-4-[2-Benzoylethenyl]cinnamate (6a)
Yield 62%, yellow needles, mp 176 ꢀC (from MeOH) (found: C, 78.74; H, 6.57;
C22H22O3 requires C, 79.02; H, 6.63%); nmax(KBr)=cmꢂ1 2978, 2931, 1702, 1660,
1632, 1595, 1366, 1320, 1220, 1152, 1017, 983, 826, 695, 541, 505; dH(270 MHz;
CDCl3; Me4Si) 1.55 (s, 9 H), 6.43 (d, 1 H, J 16.0), 7.46–7.70 (m, 9 H), 7.80 (d, 1
H, J 16.0), and 8.00–8.06 (m, 2 H); m=z (EI) 334 (9%), 277 (100), 261 (10), 233
(19), 201 (16), 152 (7), and 77 (15).
Methyl (E,E)-4-[2-Benzoylethenyl]cinnamate (6b)
Yield 75%, yellow needles, mp 142 ꢀC (from MeOH) (found: C, 77.76; H, 5.50;
C19H16O3 requires C, 78.06; H, 5.52%); nmax(KBr)=cmꢂ1 2948, 1717, 1657, 1633,
1607, 1439, 1313, 1281, 1171, 980, 829, 779, 692, and 512; dH(270 MHz; CDCl3;
Me4Si) 3.82 (s, 3 H), 6.49 (d, 1 H, J 16.0) and 7.46–8.06 (m, 11 H); dC(67.8 MHz;
CDCl3; Me4Si) 51.7 (þ), 119.1 (þ), 123.1 (þ), 128.6 (þ), 128.7 (þ), 128.8 (þ),
129.0 (þ), 133.0 (þ), 136.5 (o), 136.8 (o), 138.2 (o), 143.6 (þ), 143.8 (þ), 167.3
(o), and 190.4 (o); m=z (EI) 292 (41%), 277 (100), 261 (12), 233 (8), 203 (7), 155
(7), and 77 (17).
(E,E)-4-[2-Benzoylethenyl]styryl Benzene (6c)
Yield 45%, yellow solid, mp 176 ꢀC (from MeOH); nmax (KBr)=cmꢂ1 3022,
1658, 1631, 1607, 1445, 1336, 1222, 971, 823, 775, 721, 690, 617, and 533;
dH(270 MHz; CDCl3; Me4Si) 7.12 (d, 1 H, J 16.4), 7.22 (d, 1 H, J 16.4), 7.27–7.70
(m, 13 H), 7.83 (d, 1 H, J 15.7), and 8.00–8.10 (m, 2 H); dC(67.8 MHz; CDCl3;
Me4Si) 121.7 (þ), 126.8 (þ), 127.1 (þ), 127.9 (þ), 128.2 (þ), 128.6 (þ), 128.7 (þ),
128.9 (þ), 129.0 (þ), 130.4 (þ), 132.8 (þ), 134.2 (o), 137.0 (o), 138.4 (o), 139.8
(o), 144.5 (þ), 190.7 (o); m=z (EI) 310.1355 (Mþ C23H18O requires 310.1358), 310
(100%), 233 (8), 207 (9), 105 (14), and 77 (19).
N,N-Dimethyl-(E,E)-4-[2-benzoylethenyl]cinnamyl amide (6d)
Yield 65%, yellow solid, mp 203–204 ꢀC (from ethyl acetate) (found: C, 78.54;
H, 6.33; N, 4.67; C20H19NO2 requires C, 78.66; H, 6.27; N, 4.59%); nmax(KBr)=cmꢂ1
2924, 1650, 1603, 1418, 1391, 1335, 1220, 1138, 1018, 982, 825, 779, 702, 525, and
502; dH(270 MHz; CDCl3; Me4Si) 3.09 (s, 3H), 3.20 (s, 3H), 6.96 (d, 1 H, J 15.5),
7.5–7.70 (m, 9 H), 7.80 (d, 1 H, J 15.5), and 7.95–8.07 (m, 2H); dC(67.8 MHz; CDCl3;
Me4Si) 35.9 (þ), 37.3 (þ), 118.7 (þ), 122.7 (þ), 128.4 (þ), 128.6 (þ), 128.7 (þ), 128.9
(þ), 133.0 (þ), 136.0 (o), 137.5 (o), 138.2 (o), 141.3 (þ), 143.9 (þ), 166.5 (o), 190.5
(o); m=z (EI) 305.1419 (Mþ C20H19NO2 requires 305.1416), 305 (10%), 277 (3), 261
(12), 105 (9), and 61 (100).

HECK/WITTIG REACTION COMBINATION
3203
tert-Butyl-(E,E)-4-[2-(4-brombenzoyl)ethenyl]cinnamate (6e)
Yield 70%, yellowish needles, mp 166–167 ꢀC (from MeOH) (found: C, 63.72;
H, 5.22; C22H21BrO3 requires C, 63.93; H, 5.12%); nmax(KBr)=cmꢂ1 2975, 2929,
1698, 1657, 1635, 1607, 1598, 1584, 1417, 1364, 1331, 1222, 1156, 981, 842, 818,
537, 521, 469, and 452; dH(270 MHz; CDCl3; Me4Si) 1.55 (s, 9 H), 6.43 (d, 1 H, J
16.0), 7.44–7.70 (m, 8 H), 7.80 (d, 1 H, J 15.7), and 7.90 (d, 2 H, J 8.5); dC(67.8 MHz;
DCl3; Me4Si) 28.1 (þ), 80.8 (o), 121.7 (þ), 122.2 (þ), 128.2 (o), 128.6 (þ), 129.0 (þ),
130.1 (þ), 132.1 (þ), 136.2 (o), 136.9 (o), 137.1 (o), 142.4 (þ), 144.4 (þ), 166.2 (o),
and 189.3 (o); m=z (FAB) 413.0752 (Mþ C22H22O3Br requires 413.0752), 413 (20%),
357 (10), and 341 (2).
tert-Butyl-(E,E)-4-[2-acetylethenyl]cinnamate (6f)
Yield 70%, yellow solid, mp 104 ꢀC (from MeOH) (found: C, 74.74; H, 7.40;
C17H20O3 requires C, 74.97; H, 7.40%); nmax(KBr)=cmꢂ1 2981, 2932, 1705, 1668,
1636, 1367, 1328, 1258, 1211, 1154, 989, 970, 870, 847, 825, 810, 555, and 503;
dH(270 MHz; CDCl3; Me4Si) 1.54 (s, 9 H), 2.39 (s, 3 H), 6.41 (d, 1 H, J 16.0),
6.74 (d, 1 H, J 16.3), 7.50 (d, 1 H, J 16.3), 7.54 (s, 4 H), and 7.57 (d, 1 H, J 16.0);
dC(67.8 MHz; CDCl3; Me4Si) 27.5 (þ), 28.0 (þ), 80.7 (o), 121.5 (þ), 127.8 (þ),
128.5 (þ), 128.7 (þ), 135.9 (o), 136.7 (o), 142.29 (þ), 142.33 (þ), 166.1 (o), and
198.2 (o); m=z (EI) 272.1413 (Mþ C17H20O3 requires 272.1412), 272 (46%), 216
(67), 201 (85), 199 (55), 171 (100), 128 (28), and 102 (9).
Methyl-(E,E)-4-styrylcinnamate (6g)
Yield 53%, colorless solid, mp 183–184 ꢀC (from MeOH) (lit.[7,17] 184–186 ꢀC);
n
max(KBr)=cmꢂ1 3025, 2946, 1718, 1634, 1439, 1328, 1311, 1199, 1172, 984, 972, 964,
820, 692, and 539; dH(270 MHz; CDCl3; Me4Si) 3.82 (s, 3 H), 6.45 (d, 1 H, J 16.0),
7.10 (d, 1 H, J 16.4), 7.18 (d, 1 H, J 16.4), 7.28–7.60 (m, 9 H), 7.69 (d, 1 H, J 16.0);
m=z (EI) 264.1145 (Mþ C18H16O2 requires 264.1150), 264 (100%), 233 (15), 203 (21),
178 (15), and 77 (4).
tert-Butyl-(E,E)-4-styrylcinnamate (6h)
Yield 34%, colorless plates, mp 185–186 ꢀC (from MeOH) (found: C, 82.04; H,
7.19; C21H22O2 requires C, 82.32; H, 7.24%); nmax(KBr)=cmꢂ1 2975, 2926, 1708, 1633,
1328, 1169, 990, 970, 822, 688, and 537; dH(270 MHz; CDCl3; Me4Si) 1.54 (s, 9 H),
6.38 (d, 1 H, J 15.9), 7.09 (d, 1 H, J 16.3), 7.17 (d, 1 H, J 16.4), 7.25–7.55 (m, 9 H),
and 7.58 (d, 1 H, J 15.9); dC(67.8 MHz; CDCl3; Me4Si) 28.1 (þ), 80.5, 119.9 (þ),
126.7 (þ), 127.0 (þ), 127.9 (þ), 128.1 (þ), 128.5 (þ), 128.8 (þ), 130.0 (þ), 134.0
(o), 137.1 (o), 139.2 (o), 143.1 (þ), 166.6 (o); m=z (EI) 306.1619 (Mþ C21H22O2
requires 306.1620), 306 (48%), 250 (100), 233 (12), 203 (21), 178 (21), and 77 (3).
Methyl-(E)-4-ethenylcinnamate (6i)
Yield 64%, colorless solid, mp 73–74 ꢀC (lit.[8,18] 73–74 ꢀC); nmax(KBr)=cmꢂ1
2945, 2847, 1719, 1637, 1439, 1328, 1280, 1207, 1172, 984, 930, 837, 705, and 483;

3204
C. BURMESTER, S. MATAKA, AND T. THIEMANN
dH(270 MHz; CDCl3; Me4Si) 3.79 (s, 3 H), 5.30 (d, 1 H, J 10.9), 5.79 (d, 1 H, J 17.6),
6.41 (d, 1 H, J 16.0), 6.70 (dd, 1 H, J 10.9 and 17.6), 7.39 (d, 2 H, J 8.4), 7.46 (d, 2 H,
J 8.4), 7.66 (d, 1 H, J 16.0); dC(67.8 MHz; CDCl3; Me4Si) 51.5 (þ), 115.2 (þ), 117.4
(þ), 126.6 (þ), 128.3 (þ), 133.8 (o), 136.1 (þ), 139.5 (o), 144.3 (þ), and 167.5 (o); m=z
(EI) 188.0835 (Mþ C12H12O2 requires 188.0837), 188 (100%), 157 (96), and 128 (75).
Methyl (E,E)-4-[2-Acetylethenyl]cinnamate (6j)
Yield 50%, yellow solid, mp 150–151 ꢀC; nmax(KBr)=cmꢂ1 2948, 1712, 1661,
1633, 1433, 1328, 1258, 1205, 1172, 1000, 975, 814, 554, and 503; dH(270 MHz;
CDCl3; Me4Si) 2.40 (s, 3 H), 3.82 (s, 3H), 6.49 (d, 1 H, J 16.0), 6.75 (d, 1 H, J
16.3), 7.50 (d, 1 H, J 16.3), 7.56 (s, 4 H), and 7.69 (d, 1 H, J 16.0); dC(67.8 MHz;
CDCl3; Me4Si) 27.6 (þ), 51.8 (þ), 119.1 (o), 128.0 (o), 128.7 (þ), 128.8 (þ), 136.3
(o), 136.5 (o), 142.2 (þ), 143.7 (þ), 167.3 (o), and 198.3 (o); m=z (EI) 230.0940 (Mþ
C14H14O3 requires 230.0943), 230 (21%), 215 (100), 199 (17), 183 (22), 171 (10), 155
(18), 127 (23), and 102 (10).
1,4-Di(4-[2-(E)-(tert-butoxycarbonyl)ethenyl]styryl)benzene (6k)
Yield 41%, yellow plates, mp > 350 ꢀC (from MeOH) (found: C, 80.32; H, 7.11;
C36H38O4 requires C, 80.87; H, 7.16%); nmax(KBr)=cmꢂ1 2978, 2929, 1704, 1629, 1329,
1209, 1151, 968, 836, and 549; dH(270 MHz; CDCl3; Me4Si) 1.55 (s, 18 H), 6.38 (d, 2 H,
J 15.9), 7.11 (d, 2 H, J 16.3), 7.18 (d, 2 H, J 16.3), 7.50–7.54 (m, 12 H), and 7.58 (d, 2 H,
J 15.9); dC(67.8 MHz; CDCl3; Me4Si) 28.1 (þ), 80.5 (o), 120.0 (þ), 127.0 (þ), 127.2 (þ),
128.1 (þ), 128.5 (þ), 129.5 (þ), 134.1 (o), 136.9 (o), 139.1 (o), 143.1 (þ), and 166.6 (o);
m=z (FAB) 534.2771 (Mþ C36H38O4 requires 534.2770), 534 (1%).
tert-Butyl-4-(2-(E)-methoxycarbonylethenyl)-(E)-cinnamate (6l)
Yield 65%, colorless plates; mp 128 ꢀC (from ether=hexane) (found: C, 70.65;
H, 6.87; C17H20O4 requires C, 70.81; H, 6.99%); nmax(KBr)=cmꢂ1 1706, 1634,
1327, 1311, 1207, 1173, 1149; dH(270 MHz, CDCl3) 1.54 (s, 9H, But), 3.82 (s, 3H,
3
3
COOCH3), 6.40 (d, 1H, J 15.9), 6.46 (d, 1H, J 16.5), 7.52 (bs, 4H), 7.57 (d, 1H,
3J 16.5), 7.67 (d, 1H, 3J 15.9); dC(67.8 MHz, CDCl3) 51.8, 80.8, 118.7, 121.4,
128.4, 128.5, 135.8, 136.5, 142.3, 143.8, 166.0, 167.2; m=z (FAB, 3-nitrobenzyl alco-
hol) 288.1363 (Mþ C17H20O4 requires 288.1362), 289 (MHþ, 43), 288 (Mþ, 21).
tert-Butyl 2-(2-Cyanoethenyl)cinnamate (7a)
Yield 58%, as a mixture of E=Z (3=2); colorless oil; nmax(neat)=cmꢂ1 3060, 2978,
2930, 2216, 1709, 1635, 1478, 1368, 1323, 1257, 1152, 974, 762; dH(Z-) (270MHz,
3
3
CDCl3) 1.54 (s, 9H, But), 5.63 (d, 1H, J 11.9), 6.26 (d, 1H, J 15.7), 7.42–7.92 (m,
6H); dH(E-) (270MHz, CDCl3) 1.56 (s, 9H, But), 5.83 (d, 1H, J 16.5), 6.26 (d, 1H,
3
3J 15.7), 7.42–7.92 (m, 6H); dC(Z-) (67.8 MHz, CDCl3) 28.15, 81.03, 99.14, 116.56,
124.18, 127.56, 128.61, 129.96, 130.60, 133.02, 134.15, 139.72, 147.19, 165.69; dC(E-)
(67.8 MHz, CDCl3) 28.15, 81.18, 99.48, 117.71, 124.80, 126.74, 127.94, 129.90,
132.87, 130.96, 134.40, 139.38, 147.64, 165.45; m=z (FAB, 3-nitrobenzyl alcohol)
255.1262 (Mþ C16H17NO2 requires 255.1259), 256 (MHþ, 25), 255 (Mþ, 31), 199 (48).

HECK/WITTIG REACTION COMBINATION
3205
tert-Butyl 2-(2-(E)-Acetylethenyl)-(E)-cinnamate (7b)
Yield 63%, colorless oil; nmax(neat)=cmꢂ1 3060, 2976, 2930, 1705, 1675, 1634,
1611, 1476, 1391, 1367, 1322, 1256, 1217, 975, 870, 761; dH(270 MHz, CDCl3) 1.55
(s, 9H, But), 2.41 (s, 3H, CH3), 6.29 (d, 1H, 3J 15.7), 6.61 (d, 1H, 3J 16.2), 7.40 (m, 2H),
3
3
7.57 (m, 2H), 7.88 (d, 1H, J 16.2), 7.94 (d, 1H, J 15.7); dC(67.8 MHz, CDCl3) 27.85
(CH3), 28.47 [3C, C(CH3)3], 81.21, 124.18, 127.86, 127.94, 130.16, 130.47, 130.71,
134.43, 134.93, 140.32, 140.40, 166.01, 198.45; m=z (EI, 70 eV) 272.1414 (Mþ C17H20O3
requires 272.1412), 272 (Mþ, 0.6), 216 (15), 198 (14), 173 (33), 157 (45), 128 (100).
Methyl-3-[5-(3-oxo-3-phenyl-(E)-propenyl)-thien-2-yl]-(E)-acrylate (9a)
Yield 55%, yellow solid, mp 115–117 ꢀC (found: C, 68.44; H, 4.73; C17H14O3S
requires C, 68.53; H, 4.73%); nmax(KBr)=cmꢂ1 3083, 2946, 2847, 1698, 1647, 1617,
1585, 1573, 1439, 1338, 1317, 1277, 1174, 1040, 1013, 964, 813, 778, 697, 653, and
507; dH(270 MHz; CDCl3; Me4Si) 3.81 (s, 3 H), 6.29 (d, 1 H, J 15.7), 7.22 (d, 1 H,
J 3.8), 7.28 (d, 1 H, J 3.8), 7.35 (d, 1 H, J 15.4), 7.46–7.65 (m, 3 H), 7.74 (d, 1 H, J
15.7), 7.87 (d, 1 H, J 15.3), and 8.00–8.10 (m, 2 H); dC(67.8 MHz; CDCl3; Me4Si)
51.8 (þ), 118.5 (þ), 122.3 (þ), 128.5 (þ), 128.8 (þ), 131.9 (þ), 132.8 (þ), 133.1 (þ),
136.3 (þ), 136.6 (þ), 138.0 (o), 142.1 (o), 142.8 (o), 167.0 (o), and 189.6 (o); m=z
(EI) 298.0669 (Mþ C17H14O3S requires 298.0664), 298 (25%), 77 (9), and 58 (100).
tert-Butyl 3-[5-(3-Oxo-(E)-but-1-enyl)-thien-2-yl]-(E)-acrylate (9b)
Yield 56%, orange oil; nmax(KBr)=cmꢂ1 2976, 2930, 1703, 1668, 1622, 1593,
1367, 1311, 1285, 1254, 1148, 967, 854, 804, 552, and 504; dH(270 MHz; CDCl3;
Me4Si) 1.53 (s, 9 H), 2.35 (s, 3H), 6.21 (d, 1 H, J 15.7), 6.53 (d, 1 H, J 15.9), 7.16
(d, 1 H, J 3.8), 7.21 (d, 1 H, J 3.8), 7.55 (d, 1 H, J 15.9), 7.61 (d, 1 H, J 15.7);
dC(67.8 MHz; CDCl3; Me4Si) 28.0 (þ), 80.9 (o), 121.2 (þ), 126.9 (þ), 131.3 (þ),
132.3 (þ), 135.0 (þ), 135.3 (þ), 141.7 (o), 142.7 (o), 165.8 (o), 197.6 (o); m=z (EI)
278.0979 (Mþ C15H18O3S requires 278.0977), 278 (20), 222 (62), 207 (100), 205
(21), 177 (11), and 134 (8).
Methyl-3-[5-(3-oxo-3-phenyl-(E)-propenyl)-fur-2-yl]-(E)-acrylate (9c). Yield
55%, yellow solid, mp 144–145 ꢀC (found: C, 71.71; H, 5.07; C17H14O4 ꢃ 0.1 H2O
requires C, 71.87; H, 5.04%); nmax(KBr)=cmꢂ1 3102, 2944, 2844, 1712, 1654, 1634,
1598, 1575, 1437, 1384, 1301, 1227, 1208, 1168, 1019, 970, 806, 779, 704, 636, and
501; dH(270 MHz; CDCl3; Me4Si) 3.82 (s, 3 H), 6.52 (d, 1 H, J 15.7), 6.70 (d, 1 H,
J 3.6), 6.76 (d, 1 H, J 3.6), 7.44 (d, 1 H, J 15.8), 7.48–7.65 (m, 5 H), and 8.00–8.10
(m, 2 H); dC(67.8 MHz; CDCl3; Me4Si) 51.8 (þ), 117.2 (þ), 117.8 (þ), 118.2 (þ),
121.1 (þ), 128.5 (þ), 128.8 (þ), 129.7 (þ), 130.4 (þ), 133.1 (þ), 138.0 (o), 152.7 (o),
153.4 (o), 167.2 (o), and 189.6 (o); m=z (EI) 282.0890 (Mþ C17H14O4 requires
282.0892), 282 (100%), 267 (7), 251 (15), 223 (29), 197 (28), 105 (47), and 77 (27).
(E,E)-5-[2-Benzoylethenyl]-2-styryl Furan (9d)
Yield 60%, orange solid, mp 108 ꢀC (from hexane=cyclohexane) (found: C,
83.59; H, 5.46; C21H16O2 ꢃ 0.1H2O requires C, 83.47; H, 5.40%); nmax(KBr)=cmꢂ1

3206
C. BURMESTER, S. MATAKA, AND T. THIEMANN
2924, 1650, 1583, 1568, 1222, 1031, 1016, 971, 956, 801, 778, 747, 689, 639, 499, and
474; dH(270 MHz; CDCl3; Me4Si) 6.46 (d, 1 H, J 3.5), 6.72 (d, 1 H, J 3.5), 6.89 (d, 1
H, J 16.3), 7.28–7.62 (m, 11 H), and 8.00–8.10 (m, 2 H); dC(67.8 MHz; CDCl3;
Me4Si) 111.8 (þ), 115.7 (þ), 118.8 (þ), 119.1 (þ), 126.7 (þ), 128.3 (þ), 128.4 (þ),
128.6 (þ), 128.8 (þ), 130.1 (þ), 130.2 (þ), 132.7 (þ), 136.5 (o), 138.4 (o), 151.3
(o), 155.9 (o), and 189.9 (o); m=z (EI) 300.1148 (Mþ C21H16O2 requires 300.1150),
300 (100%), 272 (7), 223 (4), 197 (9), and 105 (75).
N,N-Dimethyl-3-[5-(3-oxo-3-phenyl-(E)-propenyl)-fur-
2-yl]-(E)-acrylamide (9e)
Yield 45%, orange solid, mp 165 ꢀC (from MeOH) (found: C, 72.98; H, 5.83; N,
4.78; C18H17NO3 requires C, 73.20; H, 5.80; N, 4.74%); nmax(KBr)=cmꢂ1 3110, 2921,
1645, 1603, 1574, 1541, 1502, 1408, 1391, 1240, 1133, 1016, 987, 816, 784, 706, 696,
638, 617, 546; dH(270 MHz; CDCl3; Me4Si) 3.09 (s, 3 H), 3.22 (s, 3 H), 6.65 (d, 1 H, J
3.5), 6.77 (d, 1 H, J 3.5), 6.97 (d, 1 H, J 15.2), 7.40–7.65 (m, 6 H), and 7.99–8.06 (m, 2
H); dC(67.8 MHz; CDCl3; Me4Si) 35.9 (þ), 37.4 (þ), 116.2 (þ), 117.4 (þ), 118.3 (þ),
120.7 (þ), 128.4 (þ), 128.5 (þ), 128.7 (þ), 130.2 (þ), 132.9 (þ), 138.2 (o), 152.7 (o),
153.9 (o), 166.2 (o), and 190.1 (o); m=z (EI) 295.1209 (Mþ C18H17NO3 requires
295.1208), 295 (81%), 277 (11), 251 (100), 223 (38), 105 (76), and 77 (35).
General Procedure for the Synthesis of Cinnamic Acids
Trifluoroacetic acid (2.5 eq.)[19] was added to a solution of tert-butyl cinnamate
(1.0 mmol) in CH2Cl2 (15 mL) at 0 ꢀC. Thereafter, the reaction mixture was stirred at
rt for 1 h. The mixture was recooled to 0 ꢀC, further trifluoroacetic acid (1.25 eq.) was
added, and the resulting solution was stirred for another 30 min. Thereafter, the mix-
ture was concentrated to dryness, and the residue was taken up in a solvent mixture
of hexane=ether (1:1 v=v), where the acid precipitated. For further purification, the
acid was subjected to short-column chromatography on silica gel (CHCl3=ether
1:1) if necessary.
4-(2-(E)-Methoxycarbonylethenyl)-(E)-cinnamic Acid (11a)
Yield 89%, colorless solid, mp 250 ꢀC (from ether) (found: C, 66.80; H, 5.14;
C13H12O4 ꢃ 0.1 H2O requires C, 66.72; H, 5.25%); nmax (KBr)=cmꢂ1 3419 (bs, OH),
2946, 1715, 1668, 1626, 1424, 1323, 1286, 1219, 1197, 1171, 1113, 1002, 978, 827,
3
689, 546, 510; dH(270 MHz, DMSO-d6) 3.72 (s, 3H, COOCH3), 6.59 (d, 1H, J
16.2), 6.70 (d, 1H, J 15.9), 7.58 (d, 1H, J 16.2), 7.66 (d, 1H, J 15.9), 7.72 (d, 2H,
3
3
3
3
3J 8.6), 7.76 (d, 2H, J 8.6), 12.51 (bs, OH); dC(67.8 MHz, DMSO-d6) 51.6, 118.8,
120.4, 128.7, 128.9, 135.6, 136.1, 143.0, 143.7, 166.6, 167.5; m=z (EI, 70 eV) 232.0737
(Mþ C13H12O4 requires 232.0736), 232 (Mþ, 100), 201 (81), 183 (30), and 127 (47).
4-(2-(E)-Acetylethenyl)-(E)-cinnamic Acid (11b)
Yield 93%; colorless solid; mp 240 ꢀC (from ether); nmax(KBr)=cmꢂ1 3416
(bs, OH), 3030, 1682, 1625, 1424, 1256, 1226, 977, 820; dH(270 MHz, CDCl3) 2.40

HECK/WITTIG REACTION COMBINATION
3207
(s, 3H, CH3), 6.50 (d, 1H, 3J 15.9), 6.76 (d, 1H, 3J 16.2), 7.51 (d, 1H, 3J 15.9), 7.59 (s,
4H), 7.77 (d, 1H, 3J 16.2); m=z (EI, 70 eV) 216.0782 (Mþ C13H12O3 requires 216.0786),
216 (Mþ, 1.2), 215 (2.6), 155 (28), 128 (100).
2-(2-(E)-Methoxycarbonylethenyl)-(E)-cinnamic Acid (11c)
Yield 85%; colorless solid, mp 140 ꢀC (from ether=hexane) (found: C, 66.73; H,
5.21; C13H12O4 ꢃ 0.1H2O requires C, 66.72; H, 5.25%); nmax(KBr)=cmꢂ1 3478 (bs,
OH), 1710, 1690, 1629, 1478, 1420, 1315, 1278, 1214, 1199, 1173, 976, 863, 769;
3
3
dH(270 MHz, CDCl3) 3.84 (s, 3H, COOCH3), 6.36 (d, 1H, J 15.9), 6.39 (d, 1H, J
3
3
15.9), 7.43 (m, 2H), 7.58 (m, 2H), 8.05 (d, 1H, J 15.9), 8.16 (d, 1H, J 15.9);
dC(67.8 MHz, CDCl3) 51.91, 121.82, 127.76 (2C), 130.12, 130.49, 133.76, 134.51,
141.33, 141.37, 143.58, 165.95, 166.79; m=z (EI, 70 eV) 232.0739 (Mþ C13H12O4
requires 232.0736), 232 (Mþ, 7), 186 (45), 155 (69), and 128 (100).
2-(2-(E)-Acetylethenyl)-(E)-cinnamic Acid (11d)
Yield 83%; colorless solid; mp 152 ꢀC (from ether=hexane) (found: C, 71.16; H,
5.56; C13H12O3 ꢃ 0.2 H2O requires C, 71.03; H, 5.69); nmax(KBr)=cmꢂ1 3418 (bs, OH),
1682, 1624, 1476, 1419, 1325, 1292, 1260, 1216, 975, 764; dH(270 MHz, CDCl3) 2.43
(s, 3H, CH3), 6.39 (d, 1H, 3J 15.9), 6.64 (d, 1H, 3J 15.9), 7.44 (m, 2H), 7.60 (m, 2H),
3
3
7.88 (d, 1H, J 15.9), 8.15 (d, 1H, J 15.9); dC(67.8 MHz, CDCl3) 27.85, 120.80,
127.80, 127.87, 130.28, 130.55, 130.69, 130.95, 134.53, 139.72, 143.54, 170.96,
198.00; m=z (EI, 70 eV) 216.0782 (Mþ C13H12O3 requires 216.0786), 216 (Mþ, 2.2),
215 (2.8), 155 (30), 128 (100).
REFERENCES
1. (a) Thiemann, T.; Umeno, K.; Ohira, D.; Inohae, E.; Sawada, T.; Mataka, S. Suzuki–
Kumada coupling with bromoaroylmethylidenephosphoranes. New J. Chem. 1999, 23,
1067–1070; (b) Thiemann, T.; Umeno, K.; Wang, J.; Arima, K.; Watanabe, M.; Tabuchi,
Y.; Tanaka, Y.; Gorohmaru, H.; Mataka, S. Elongated phosphoranes by CꢂC coupling
of haloaroylmethylidenephosphoranes: Synthesis and applications. J. Chem. Soc., Perkin
Trans. 1 2002, 2090–2110; (c) Thiemann, T.; Watanabe, M.; Tanaka, Y.; Mataka, S.
One-pot Suzuki coupling–Wittig olefination reactions. J. Chem. Res. 2004, 723–727; (d)
Watanabe, M.; Mataka, S.; Thiemann, T. One-pot Sonogashira coupling=Wittig olefina-
tion procedures. J. Chem. Res. 2005, 636–639.
2. Nielsen, S. F.; Christensen, S. B.; Cruciani, G.; Kharazmi, A.; Liljefors, T. Antileishma-
nial chalcones: Statistical design, synthesis, and three-dimensional quantitative structure–
activity relationship analysis. J. Med. Chem. 1998, 41, 4819–4832.
3. Liu, M.; Wilairat, P.; Croft, S. L.; Lay-Choo Tan, A.; Go, M.-L. Structure–activity
relationships of antileishmanial and antimalarial chalcones. Bioorg. Med. Chem. 2003,
11, 2729–2738.
4. Herencia, F.; Ferrandiz, M. L.; Ubeda, A.; Dominguez, J. N.; Charris, J. E.; Lobo, G. M.;
Alcaraz, M. Synthesis and anti-inflammatory activity of chalcone derivatives. Bioorg.
Med. Chem. Lett. 1998, 8, 1169–1174.
5. Lopez, S. N.; Castelli, M. V.; Zacchino, S. A.; Dominguez, J. N.; Lobo, J.;
Charris-Charris, J.; Cortes, J. C. G.; Ribas, J. C.; Devia, C.; Rodriguez, A. M.; Enriz,

3208
C. BURMESTER, S. MATAKA, AND T. THIEMANN
R. D. In vitro antifungal evaluation and structure–activity relationships of a new series of
chalcone derivatives and synthetic analogues, with inhibitory properties against polymers
of the fungal cell wall. Bioorg. Med. Chem. Lett. 2001, 9, 1999–2013.
6. Zhao, B.; Lu, W.-Q.; Zhou, Z.-H.; Wu, Y. The important role of the bromo group in
improving the properties of organic nonlinear optical materials. J. Mat. Chem. 2000,
1513–1517.
7. (a) Mizoroki, T.; Mori, K.; Ozaki, A. Arylation of olefin with aryl iodide catalyzed by
palladium. Bull. Chem. Soc. Jpn. 1971, 44, 581–581; (b) Heck, R. F.; Nolley Jr., J. P.
Palladium-catalyzed vinylic hydrogen substitution reactions with aryl, benzyl, and styryl
halides. J. Org. Chem. 1972, 37, 2320–2322.
8. De Vries, J. G. The Heck reaction in the production of fine chemicals. Can. J. Chem. 2001,
79, 1086.
9. Beletskaya, I. P.; Cheprakov, A. V. The Heck reaction as a sharpening stone of palladium
catalysis. Chem. Rev. 2000, 100, 3009–3066.
10. Heck, R. F. Palladium-catalyzed vinylation of organic halides. Org. React. 1982, 27,
345–390.
11. Chakraborty, A.; Kar, D. S.; Guchhait, N. Photophysical properties of trans-3-(4-
monomethylamino-phenyl)acrylonitrile: Evidence of intramolecular charge-transfer
process. Chem. Phys. 2006, 324, 733–741.
12. Sun, X.; Zhu, J.; Zhong, C.; Izumi, K.; Zhang, C. A concise and convenient synthesis of
stilbenes via benzils and arylmethyldiphenylphosphine oxides. Chin. J. Chem. 2007, 25,
1866–1870.
13. For the use of cinnamic acid and derivatives against Mycobacterium tuberculosis, see:
Rastogi, N.; Seng Goh, K.; Horgen, L.; Barrow, W. W. Synergistic activities of antituber-
culosis drugs with cerulenin and trans-cinnamic acid against Mycobacterium tuberculosis.
FEMS Immunol. Med. Microbiol. 1998, 21, 149–157, and refs. cited therein.
14. Ramirez, F.; Dershowitz, S. Phosphinemethylenes II: Triphenylphosphineacylmethylenes.
J. Org. Chem. 1957, 22, 41–45.
15. Parrish, J. P.; Jung, Y. C.; Shin, S. I.; Jung, K. W. Mild and efficient aryl-alkenyl coupling
via Pd(II) catalysis in the presence of oxygen or Cu(II) oxidants. J. Org. Chem. 2002, 67,
7127–7130.
16. Niiya, K.; Thompson, R. D.; Silvia, S. K.; Olsson, R. A. 2-(N0-Aralkylidenehydrazino)
adenosines: Potent and selective coronary vasodilators. J. Med. Chem. 1992, 35, 4562–4566.
17. Plevyak, J. E.; Dickerson, J. E.; Heck, R. F. Selective palladium-catalyzed vinylic substitu-
tions with bromoiodo aromatics. J. Org. Chem. 1979, 44, 4078–4080.
18. Annunziata, R.; Benaglia, M.; Cinquini, M.; Cozzi, F.; Puglisi, A. Sequential stereoselec-
tive catalysis: Two single-flask reactions of a substrate in the presence of a bifunctional
chiral ligand and different transition metals. Eur. J. Org. Chem. 2003, 1428–1432.
19. Greene, T. W.; Wuts, P. M. Protective Groups in Organic Chemistry, 2nd ed.; John Wiley &
Sons: New York, 1991; 245.