Microwave-assisted synthesis of the (E)-α-methylalkenoate framework from multifunctionalized allylic phosphonium salts

Article abstract of DOI:10.1002/hc.21001

A convenient and general microwave-assisted method for the synthesis of stereochemically defined α-methylalkenoic acids and esters from allylic phosphonium salts in a basic aqueous medium is described. A selective preparation of acids or esters was dependent on the base (NaOH or NaHCO ₃) employed in the reaction and could be achieved with good to excellent yields under mild conditions in the absence of hydrides and reducing agents.

Full text of DOI:10.1002/hc.21001

Heteroatom Chemistry
Volume 23, Number 2, 2012
Microwave-Assisted Synthesis of the
(E)-α-Methylalkenoate Framework from
Multifunctionalized Allylic Phosphonium Salts
Lidiane Meier, Misael Ferreira, and Marcus M. Sa´
Departamento de Qu´ımica, Universidade Federal de Santa Catarina, Floriano´polis,
SC 88040-900, Brazil
Received 4 August 2012; revised 12 November 2012
The α-alkylpropenoate backbone generated in
ABSTRACT: A convenient and general microwave-
the MBH reaction is an important structural unit
assisted method for the synthesis of stereochemically
present in insect pheromones and also in many other
defined α-methylalkenoic acids and esters from allylic
biologically active molecules [5]. Consequently,
phosphonium salts in a basic aqueous medium is de-
there are several reports describing the stereoselec-
scribed. A selective preparation of acids or esters was
tive synthesis of α-methylalkenoic acids by chem-
dependent on the base (NaOH or NaHCO3) employed
ical reduction of the corresponding allylic alco-
in the reaction and could be achieved with good to ex-
hols S [6], acetates A [7], and bromides B [8].
cellent yields under mild conditions in the absence of
While many of these methods furnish the expected
ꢀ
C
hydrides and reducing agents. 2012 Wiley Periodicals,
α-methylalkenoates in good yields, there are gener-
ally one or more drawbacks involved such as the use
of metal hydrides or reagents that are not readily ac-
Inc. Heteroatom Chem 23:179–186, 2012; View this article
online at wileyonlinelibrary.com. DOI 10.1002/hc.21001
cessible, the need for anhydrous conditions, or the
formation of side products.
It is known that semistabilized ylides originat-
ing from base-induced deprotonation of allylic and
benzylic phosphonium salts may undergo reduction
in the presence of water to give the corresponding
hydrocarbon and phosphine oxide through a mech-
anism where a phosphonium hydroxide H is invoked
[9] (Scheme 2).
Herein, we report the development of a sim-
ple and efficient methodology for the synthesis of
α-methylalkenoic acids and esters with high di-
astereoselectivity from a sequential base-mediated
redox reaction of type-P phosphonium salts in an
aqueous medium under microwave irradiation, as
described below.
INTRODUCTION
Phosphonium salts have great versatility in chemical
reactions and are used as advanced building blocks
for the synthesis of a wide variety of novel com-
pounds [1]. In particular, phosphonium salts P bear-
ing an allylic appendage, which are often prepared
in situ by reacting triaryl (or trialkyl) phosphines
with allyl acetates A or bromides B, are useful in-
termediates in annulation reactions (with the in-
termediacy of phosphorus ylides) [2] and have
also been occasionally used in Wittig olefination
[3] (Scheme 1). The multifunctional allylic moiety
found in P is readily available from the Morita–
Baylis–Hillman (MBH) reaction [4], which gives al-
lylic alcohols S as precursors of acetates A and bro-
mides B.
RESULTS AND DISCUSSION
Initially, the phosphonium salts 1a–1m were pre-
pared in nearly quantitative yields by mixing an
Correspondence to: Marcus M. Sa´; e-mail: msa@qmc.ufsc.br.
2012 Wiley Periodicals, Inc.
c
ꢀ
179

180 Meier, Ferreira, and Sa´
AcO
O
R
O
R1
R
R1
PR'3
PR'3
W
Z
O
W
OH
O
A
Z
O
R1
R
R1
PR'3X
R
O
R
R1
ArCHO, base
P
S
R
R1
R = H, Alk, Ar; R' = Alk, Ph; R1 = Ar, OAlk; X = Cl, Br, OAc
B
Ar
Br
SCHEME 1
TABLE 2 Preparation of α-Methylalkenoates 3 from Phos-
phonium Salts 1
R = Vinyl, Aryl; R' = Alkyl, Aryl
X = Cl, Br, OAc
RCH2X
PR'3
RCH3
- R'3P=O
O
O
O
base
–HX
RCH PR'3
RCH=PR'3
NaHCO3, H2O
H2O
R
OCH3
R
OCH3
R
OCH3
RCH2PR'3X
RCH2PR'3OH
20 min, MW
100–105°C
1
4
3
H
PPh3Br
Entry
R
Yield (%)a
3:4(%)b
SCHEME 2
1
2
3
4
5
6
7
8
C6H5 (a)
69
80
76
63
72
78
71
74
62
74
76
90:10
100:0
100:0
90:10
95:5
90:10
80:20
85:15
35:65
90:10
100:0
TABLE 1 Preparation of Phosphonium Salts 1 from Allylic
Bromides 2
4-CH3OC6H4 (b)
3,4-(OCH2O)C6H3 (c)
4-CH3C6H4 (d)
4-ClC6H4 (e)
2-ClC6H4 (f)
2,4-Cl2C6H3 (g)
4-BrC6H4 (h)
4-NO2C6H4 (i)
2-C10H7 (l)
(E)-C6H5CH CH (m)
O
O
Ph3P
R
OCH3
R
OCH3
PPh3Br
CH3CN
25°C
1
2
Br
Yield
Time (h)a (%)b (ppm)c
δ
31P
9
10
11
Entry
R
1
2
3
4
5
6
7
8
C6H5 (a)
4-CH3OC6H4 (b)
3,4-(OCH2O)C6H3 (c)
4-CH3C6H4 (d)
4-ClC6H4 (e)
2-ClC6H4 (f)
2,4-Cl2C6H3 (g)
4-BrC6H4 (h)
4-NO2C6H4 (i)
3-NO2C6H4 (j)
2-NO2C6H4 (k)
2-C10H7 (l)
28 [0.5]
30
30 [0.5]
30
99
98
98
95
98
97
98
96
99
95
96
96
97
22.5
22.5
22.1
22.6
22.2
21.7
21.4
22.3
22.1
21.9
20.9
22.4
21.1
aIsolated yields of 3:4, after column chromatography on silica gel (9:1
hexane/EtOAc).
bRatio 3:4 (%) was determined by 1H NMR integration (400 MHz,
CDCl3).
24
24
24
24
binations of base (NaHCO3, Et3N, DABCO, HMTA)
and solvent (water alone or in mixtures with
DMSO or CH3CN) for the selective reduction to α-
methylalkenoates 3. The best results were achieved
with the use of inexpensive sodium bicarbonate
(5 equiv) in water (Table 2).
In all cases studied, the transformation was slow
(20–40 h) at room temperature, but at 100◦C the re-
action time was reduced to 20 min, either by heating
with an oil bath or using microwave irradiation. The
presence of strongly electron-donating R groups fa-
vored the exclusive formation of the desired product
3 (Table 2, entries 2, 3, and 11), whereas the substi-
tution with electron-withdrawing groups on the aro-
matic ring caused the generation of the rearranged
isomer 4 in nonnegligible amounts (Table 2, entries
7–9).
9
24 [0.5]
24
10
11
12
13
24
30
30
(E)-C6H5CH CH (m)
aNumbers in brackets refer to reactions carried out by heating in an oil
bath (kept at a temperature of 100–105◦C) or in a microwave reactor
(Tmax = 105◦C, maximum potency = 50 W, maximum pressure =
50 PSI, t = 1 min ramp, 30 min hold, stirring mode “on”).
bIsolated yields.
c 31P NMR spectra were recorded at 81 MHz (CDCl3, 85% H3PO4 as
external standard).
equimolar mixture of allylic bromide 2 (readily avail-
able [8a,10] from the bromination of MBH adducts
[4] with LiBr in an acidic medium) and Ph3P in
CH3CN at room temperature for the appropriate pe-
riod (Table 1). The reaction time can be dramatically
reduced to 30 min by heating the solution under re-
flux or, alternatively, in a microwave reactor to give
comparable results (Table 1, entries 1, 3, and 9).
Subsequently, a representative number of phos-
phonium salts 1 were submitted to different com-
As expected, in the absence of a base no appre-
ciable reaction was observed, with the starting phos-
phonium 1 being recuperated almost entirely. How-
ever, replacing NaHCO3 as the base with NaOH or
LiOH also led to the redox reaction of phosphonium
Heteroatom Chemistry DOI 10.1002/hc

Microwave-Assisted Synthesis of (E)-α-Methylalkenoate Framework from Multifunctionalized Allylic Phosphonium Salts 181
TABLE 3 Preparation of α-Methylalkenoic Acids 5 from
Phosphonium Salts 1
salts 1. Accordingly, substrate 2, Ph3P, and the base
(NaHCO3 or NaOH) in H2O CH3CN were heated
under microwave irradiation at 100◦C (Table 4). No-
tably, all steps involved in this operation (nucle-
ophilic displacement of bromine with Ph3P, reduc-
tion of phosphonium salt 1, and, depending on the
base employed, ester hydrolysis) occurred smoothly
to give the expected mixture of unsaturated esters
3:4 or carboxylic acids 5:6 with regioselectivity com-
parable to the stepwise process from salt 1 (see Ta-
bles 2 and 3). However, in a few cases, the use of
NaHCO3 led to a partial hydrolysis of the ester group
with concurrent formation of acid 5 (Table 4, entry
6) or its isomer 6 (Table 4, entry 2).
In conclusion, this methodology describes a
convenient and general microwave-assisted synthe-
sis of α-methylalkenoate derivatives in an aque-
ous medium from allylic bromides 2 or phospho-
nium salts 1. Depending on the base employed in
this redox process, the α-methylalkenoates 3 or α-
methylalkenoic acids 5 can be easily accessed. Im-
portant advantages of this transformation include
fast reactions, mild conditions, application of in-
expensive and readily available reagents, opera-
tional simplicity, high yields, and moderate-to-high
selectivity.
O
O
O
NaOH or LiOH
R
OCH3
R
OH
R
OH
H2O, 30 min
MW, 100 °C
1
6
5
PPh3Br
Yield a(%)
Yield a(%)
Entry
R
NaOH (5:6)b
LiOH (5:6)b
1
2
C6H5 (a)
4-CH3OC6H4 (b)
71 (80:20)
82 (95:5)
79 (90:10)
77 (95:5)
3
4
5
6
7
8
9
10
11
3,4-(OCH2O)C6H3 (c) 81 (80:20)
80 (85:15)
88 (90:10)
91 (90:10)
88 (85:15)
4-CH3C6H4 (d)
4-ClC6H4 (e)
2-ClC6H4 (f)
2,4-Cl2C6H3 (g)
4-BrC6H4 (h)
4-NO2C6H4 (i)
2-C10H7 (l)
90 (90:10)
85 (80:20)
85 (80:20)
75 (75:25)
92 (85:15)
86 (80:20)
c
c
76 (90:10)
(E)-C6H5CH CH (m) 84 (>99:1)d
79 (>99:1)d
aIsolated yields.
bRatio 5:6 (%) was determined by 1H NMR integration (400 MHz,
CDCl3).
cComplex mixture of products.
dReaction was carried out for 50 min.
salts 1, but in these cases the concurrent hydrolysis
of the ester group took place to furnish the corre-
sponding α-methylalkenoic acids 5 (Table 3). No dif-
ference between NaOH and LiOH was evident from
the data in Table 3, and both bases were effective in
terms of mediating the reaction. In most cases, the
isolated yields for the α-methylalkenoic acids 5 were
higher than those observed for the corresponding
α-methylalkenoates 3 (compare Tables 2 and 3). In
addition, acid 5 was more easily separated from the
side product (Ph3PO) than ester 3 because the former
was soluble in the aqueous basic medium (as a free
carboxylate), whereas the latter (as well as Ph3PO)
was not, requiring purification by chromatography.
However, the regioselectivity in favor of the more
substituted alkenoic acid 5 was compromised due to
the formation of the rearranged isomer 6 in all but
one case (Table 3, entry 11).
This trend was particularly accentuated for
the products carrying electron-withdrawing groups
(Table 3, entries 5–8), although the selectivity for
the electron-rich piperonyl derivative was also low
(Table 3, entry 3). Modification of the reaction condi-
tions, including time, temperature, amount of base,
and addition of cosolvents, did not lead to any sig-
nificant improvement in the regioselectivity.
EXPERIMENTAL
General
Allylic bromides 2 were prepared according to lit-
erature procedures [10a,b]. Bromides 2a–g,i–m are
1
known compounds, and their infrared (IR) and H
NMR spectra were in accordance with the reported
data [10a,b]. CH3CN was freshly distilled from CaH2.
All chemicals were of reagent grade and were used as
received. Column chromatography was performed
using silica gel (70–230 mesh) and hexane/ethyl ac-
etate as the eluent. TLC analysis was performed
in silica gel plates, using a UV lamp for visualiza-
1
tion. H NMR spectra were recorded at 400 MHz,
and coupling constants (J) are measured in hertz
(Hz). 13C NMR spectra were recorded at 100 MHz.
Chemical shifts were recorded in parts per million
(ppm, δ) relative to TMS at 0.00 ppm or solvent
(CDCl3 at 7.26 ppm or DMSO-d6 at 2.50 ppm for
1H NMR, and CDCl3 at 77.2 ppm or DMSO-d6 at
39.5 ppm for 13C NMR) as the internal standard. 31
P
NMR spectra were recorded at 81 MHz, and chem-
ical shifts were recorded in parts per million (ppm, δ)
relative to 85% H3PO4 at 0.00 ppm. IR spectra were
recorded with the use of KBr (range 4000–400 cm−1).
Elemental analysis was conducted in a CHNS ana-
lyzer instrument. Melting points were determined
by using a hot plate apparatus and are uncorrected.
Finally, we investigated the direct transforma-
tion of allylic bromides 2 into the corresponding
α-methylalkenoic esters 3 and acids 5 through the
one-pot reaction, without isolation of phosphonium
Heteroatom Chemistry DOI 10.1002/hc

182 Meier, Ferreira, and Sa´
TABLE 4 One-Pot Preparation of α-Methylalkenoic Esters 3 and Acids 5 from Allylic Bromides 2
O
O
O
PPh3, base
+
R
OR'
R
OR'
R
OCH3
H2O-CH3CN
MW, 100 oC
2
3
5
R' = CH3
R' = H
4
6
Br
Entry
R
Base
Time (min)
3:4(%)aR ꢁ = CH3
5:6(%)aRꢁ =H
1
2
3
4
5
6
7
8
C6H5 (a)
4-CH3OC6H4 (b)
3,4-(OCH2O)C6H3 (c)
2-ClC6H4 (f)
2,4-Cl2C6H3 (g)
(E)-C6H5CH CH (m)
C6H5 (a)
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaOH
LiOH
NaOH
NaOH
NaOH
30
30
30
60
30
30
40
40
60
60
60
40
80:20
100:0b
100:0
80:20
80:20
100:0c
95:5
C6H5 (a)
90:10
90:10
95:5
85:15
80:20
9
3,4-(OCH2O)C6H3 (c)
4-CH3C6H4 (d)
2-ClC6H4 (f)
10
11
12
2,4-Cl2C6H3 (g)
NaOH
aThe relative product distribution (%) was determined by 1H NMR integration (400 MHz, CDCl3).
bThe crude reaction product contained ca. 15% of the rearranged acid 6b.
cThe crude reaction product contained ca. 15% of the acid 5m.
1
1700, 1625, 1586, 1436, 1268, 1111 cm−1; H NMR
Microwave-assisted reactions were performed in
10-mL sealed tubes in a monomode microwave CEM
Explorer reactor instrument with IR temperature
monitoring and a noninvasive pressure transducer.
(CDCl3): δ 3.39 (s, 3H), 5.01 (d, J = 14.8 Hz, 2H),
7.27–7.33 (m, 5H), 7.58–7.62 (m, 12H), 7.72–7.77 (m,
3H), 7.94 (d, J = 5.1 Hz, 1H); 13C NMR (CDCl3):
δ 24.8 (d, J = 50.6 Hz, CH2), 52.6 (CH3), 117.5 (d,
J = 85.0 Hz, 3 × CP), 121.1 (d, J = 9.6 Hz, C), 128.5
(2 × CH), 129.3 (2 × CH), 129.7 (s, CH), 130.2 (d, J =
12.5 Hz, 6 × CPH), 133.4 (d, J = 3.7 Hz, C), 133.8 (d,
J = 10.3 Hz, 6 × CPH), 135.1 (3 × CPH), 146.4 (d,
J = 10.3 Hz, CH), 166.4 (C); 31P NMR (CDCl3, 85%
H3PO4 as the external standard): δ 22.5; Anal. Calcd
for C29H26BrO2P (%): C, 67.32; H, 5.07. Found: C,
66.93; H, 5.10.
Methyl (Z)-2-(bromomethyl)-3-(4-bromophenyl)-
2-propenoate (2h). Yield 83%, white solid; mp:
58.5–60.0◦C; IR (KBr) νmax 3431, 3054, 2995, 2948,
1712, 1615, 1582, 1490, 1431, 1283, 1202, 1155, 1072
1
cm−1; H NMR (CDCl3): δ 3.87 (s, 3H), 4.33 (s, 2H),
7.43 (d, J = 8.6 Hz, 2H), 7.58 (d, J = 8.6 Hz, 2H), 7.73
(s, 1H); 13C NMR (100 MHz, CDCl3): δ 26.6 (CH2),
52.9 (OCH3), 124.4 (C), 129.5 (C), 131.4 (2 × CH),
132.4 (2 × CH), 133.3 (C), 141.9 (CH), 166.6 (C);
Anal. Calcd for C11H10Br2O2 (%): C, 39.56; H, 3.02.
Found: C, 39.72; H, 3.41.
[(Z)-2-Methoxycarbonyl-3-(4-methoxyphenyl)-
2-propenyl]triphenylphosphonium Bromide (1b).
White solid; mp: 178.0–180.0◦C; IR (KBr): νmax 3462,
3396, 3058, 2948, 2908, 1699, 1629, 1601, 1512,
General Procedure for the Preparation of
Phosphonium Salts 1
1439, 1261, 1112 cm−1; H NMR (CDCl3): δ 3.38 (s,
1
3H), 3.82 (s, 3H), 5.12 (d, J = 14.8 Hz, 2H), 6.86 (d,
J = 8.6 Hz, 2H), 7.39 (d, J = 8.6 Hz, 2H), 7.57–7.62
(m, 6H), 7.65–7.76 (m, 9H), 7.88 (d, J = 4.9 Hz, 1H);
13C NMR (CDCl3): δ 24.9 (d, J = 49.4 Hz, CH2), 52.4
(CH3), 55.6 (CH3), 114.8 (2 × CH), 118.0 (d, J = 85.0
Hz, 3 × CP), 118.3 (d, J = 10.3 Hz, C), 125.6 (d, J =
2.9 Hz, C), 130.1 (d, J = 12.4 Hz, 6 × CPH), 130.9 (2
× CH), 134.0 (d, J = 9.5 Hz, 6 × CPH), 135.0 (3 ×
CPH), 146.2 (d, J = 10.2 Hz, CH), 160.9 (C), 166.9
(C); 31P NMR (CDCl3, 85% H3PO4 as the external
standard): δ 22.5; Anal. Calcd for C30H28BrO3P (%):
C, 65.82; H, 5.16. Found: C, 65.70; H, 5.30.
Allylic bromide 2 (1.0 mmol) and Ph3P (1.0 mmol)
were added to CH3CN (3.0 mL), and the solution
was stirred at 25◦C for the time given in Table 1.
Concentration under reduced pressure gave salt 1
in 95%–99% yields and high purity. Recrystalliza-
tion with CH3CN gave 1 as a crystalline solid with
analytical purity.
[(Z)-2-Methoxycarbonyl-3-phenyl-2-propenyl]tri-
phenylphosphonium Bromide (1a). White solid; mp:
156.5–158.0◦C; IR (KBr): νmax 3445, 3042, 2992, 2949,
Heteroatom Chemistry DOI 10.1002/hc

Microwave-Assisted Synthesis of (E)-α-Methylalkenoate Framework from Multifunctionalized Allylic Phosphonium Salts 183
[(Z)-2-Methoxycarbonyl-3-(3,4-methylenedioxyph
[(Z)-3-(2-Chlorophenyl)-2-methoxycarbonyl-2-
propenyl]triphenylphosphonium Bromide (1f).
enyl)-2-propenyl]triphenylphosphonium
Bromide
(1c). White solid; mp: 192.0–194.0◦C; IR (KBr):
νmax 3443, 3404, 3057, 2899, 1700, 1610, 1491, 1436,
White solid; mp: 127.0–128.5◦C; IR (KBr): νmax 3418,
3375, 3004, 2950, 2889, 1716, 1634, 1587, 1437, 1265,
1111 cm−1; 1H NMR (CDCl3): δ 3.32 (s, 3H), 5.00 (d,
J = 15.2 Hz, 2H), 7.07 (d, J = 7.8 Hz, 1H), 7.25 (t,
J = 7.8 Hz, 1H), 7.47–7.60 (m, 13H), 7.67–7.71 (m,
3H), 7.88 (d, J = 7.4 Hz, 1H), 7.98 (d, J = 5.5 Hz,
1H); 13C NMR (CDCl3): δ 24.1 (d, J = 50.0 Hz, CH2),
52.9 (CH3), 117.7 (d, J = 85.7 Hz, 3 × CP), 122.8
(d, J = 9.6 Hz, C), 128.9 (CH), 130.0 (CH), 130.4
(d, J = 12.4 Hz, 6× CPH), 131.0 (CH), 131.3 (CH),
132.6 (C), 133.4 (C), 134.1 (d, J = 10.2 Hz, 6 × CPH),
135.2 (3 × CPH), 144.2 (d, J = 9.6 Hz, CH), 166.0 (C);
31P NMR (CDCl3, 85% H3PO4 as external standard):
δ 21.7; Anal. Calcd for C29H25BrClO2P (%): C, 63.12;
H, 4.57. Found: C, 62.90; H, 4.70.
1
1234, 1113 cm−1; H NMR (CDCl3): δ 3.38 (s, 3H),
5.07 (d, J = 14.8 Hz, 2H), 5.97 (s, 2H), 6.62 (s, 1H),
6.80 (d, J = 8.0 Hz, 1H), 7.03 (d, J = 8.0 Hz, 1H),
7.60–7.71 (m, 12H), 7.75–7.79 (m, 3H), 7.82 (d, J =
4.7 Hz, 1H); 13C NMR (CDCl3): δ 25.3 (d, J = 50.3
Hz, CH2), 52.8 (CH3), 101.9 (CH2), 108.6 (CH), 109.5
(CH), 118.1 (d, J = 84.6 Hz, 3 × CP), 119.5 (d, J =
10.0 Hz, C), 124.3 (CH), 127.4 (C), 130.4 (d, J =
12.2 Hz, 6 × CPH), 134.2 (d, J = 9.2 Hz, 6 × CPH),
135.3 (3 × CPH), 146.3 (d, J = 9.9 Hz, CH), 148.5
(C), 149.3 (C), 166.9 (C); 31P NMR (CDCl3, 85%
H3PO4 as external standard): δ 22.1; Anal. Calcd for
C30H26BrO4P (%): C, 64.18; H, 4.67. Found: C, 64.37;
H, 5.05.
[(Z)-3-(2,4-Dichlorophenyl)-2-methoxycarbonyl-
2-propenyl]triphenylphosphonium Bromide (1g).
White solid; mp: 178.0–180.0◦C; IR (KBr): νmax 3415,
3059, 3006, 2949, 1715, 1641, 1586, 1438, 1289,
[(Z)-2-Methoxycarbonyl-3-(4-methylphenyl) -2-
propenyl]triphenylphosphonium
Bromide
(1d).
White solid, mp 180.0–181.0◦C; IR (KBr): νmax 3450,
3396, 3056, 3006, 2951, 2897, 1710, 1631, 1586,
1
1255, 1109 cm−1; H NMR (CDCl3): δ 3.36 (s, 3H),
1
1436, 1263, 1110 cm−1; H NMR (CDCl3): δ 2.34 (s,
5.28 (d, J = 15.6 Hz, 2H), 7.01 (d, J = 2.0 Hz, 1H),
7.52–7.57 (m, 6H), 7.62–7.73 (m, 10H), 7.97 (d, J =
5.6 Hz, 1H), 8.25 (d, 8.2 Hz, 1H); 13C NMR (CDCl3):
δ 24.1 (d, J = 49.5 Hz, CH2), 52.9 (CH3), 117.6 (d,
J = 84.6 Hz, 3 × CP), 123.3 (d, J = 10.0 Hz, C), 129.3
(CH), 129.4 (CH), 130.3 (d, J = 13.0 Hz, 6 × CPH),
131.0 (C), 132.8 (CH), 133.8 (C), 134.0 (d, J = 10.0
Hz, 6 × CPH), 135.0 (3 × CPH), 136.1 (C), 142.9 (d,
J = 10.0 Hz, CH), 165.7 (C); 31P NMR (CDCl3, 85%
H3PO4 as external standard): δ 21.4; Anal. Calcd for
C29H24Cl2BrO2P (%): C, 59.41; H, 4.14. Found: C,
59.10, H, 4.43.
3H), 3.39 (s, 3H), 5.10 (d, J = 14.8 Hz, 2H), 7.13 (d,
J = 8.0 Hz, 2H), 7.23 (d, J = 8.0, 2H), 7.57–7.70 (m,
12H), 7.72–7.77 (m, 3H), 7.92 (d, J = 4.9 Hz, 1H);
13C NMR (CDCl3): δ 21.1 (CH3), 24.5 (d, J = 49.3 Hz,
CH2), 52.3 (CH3), 117.5 (d, J = 84.9 Hz, 3× CP), 119.8
(d, J = 9.1 Hz, C), 128.4 (2 × CH), 129.7 (2 × CH),
129.9 (d, J = 11.4 Hz, 6 × CPH), 133.6 (6 × CPH),
134.0 (C), 134.8 (3 × CPH), 139.9 (C), 146.2 (d,
J = 8.3 Hz, CH), 166.3 (C); 31P NMR (CDCl3, 85%
H3PO4 as external standard): δ 22.6; Anal. Calcd for
C30H28BrO2P (%): C, 67.80; H, 5.31. Found: C, 67.90;
H, 5.50.
[(Z)-3-(4-Chlorophenyl)-2-methoxycarbonyl-2-
[(Z)-3-(4-Bromophenyl)-2-methoxycarbonyl-2-
propenyl]triphenylphosphonium
Bromide
(1e).
propenyl]triphenylphosphonium
Bromide
(1h).
White solid; mp: 169.5–171.5◦C; IR (KBr): νmax 3435,
White solid; mp: 118.0–120.0◦C; IR (KBr): νmax 3489,
3408, 3048, 3003, 2948, 1701, 1623, 1588, 1436,
3428, 3054, 3006, 2952, 1713, 1634, 1584, 1437,
1
1
1293, 1110 cm−1; H NMR (CDCl3): δ 3.38 (s, 3H),
1264, 1111 cm−1; H NMR (CDCl3): δ 3.36 (s, 3H),
5.22 (d, J = 15.2 Hz, 2H), 7.31 (d, J = 8.2 Hz,
2H), 7.43 (d, J = 8.2 Hz, 2H), 7.55–7.60 (m, 6H),
7.64–7.75 (m, 9H), 7.90 (d, J = 4.8 Hz, 1H); 13C NMR
(CDCl3): δ 24.3 (d, J = 49.8 Hz, CH2), 52.6 (CH3),
117.5 (d, J = 85.0 Hz, 3 × CP), 121.4 (d, J = 9.6 Hz,
C), 129.4 (2 × CH), 130.0 (d, J = 12.5 Hz, 6 × CPH),
130.1 (2 × CH), 131.8 (C), 133.8 (d, J = 9.6 Hz,
6 × CPH), 134.9 (3 × CPH), 135.5 (C), 144.9 (d,
J = 8.8 Hz, CH), 166.1 (C); 31P NMR (CDCl3, 85%
H3PO4 as external standard): δ 22.2; Anal. Calcd for
C29H25BrClO2P (%): C, 63.12; H, 4.57. Found: C,
63.10; H, 4.60.
5.09 (d, J = 15.0 Hz, 2H), 7.31 (d, J = 8.6 Hz,
2H), 7.43 (d, J = 8.6 Hz, 2H), 7.54–7.64 (m, 12H),
7.70–7.75 (m, 3H), 7.86 (d, J = 5.5 Hz, 1H); 13C
NMR (CDCl3): δ 24.6 (d, J = 48.8 Hz, CH2), 52.9
(CH3), 118.0 (d, J = 84.5 Hz, 3 × CP), 121.8 (d, J =
10.0 Hz, C), 124.2 (C), 130.3 (d, J = 12.2 Hz, 6 ×
CPH), 130.6 (2 × CH), 132.5 (C), 132.7 (2 × CH),
134.2 (d, J = 10.0 Hz, 6 × CPH), 135.2 (3 × CPH),
145.4 (d, J = 10.7 Hz, CH), 166.5 (C); 31P NMR
(CDCl3, 85% H3PO4 as external standard): δ 22.3;
Anal. Calcd for C29H25Br2O2P (%): C, 58.41; H, 4.23.
Found: C, 58.10; H, 4.40.
Heteroatom Chemistry DOI 10.1002/hc

184 Meier, Ferreira, and Sa´
[(Z)-2-Methoxycarbonyl-3-(4-nitrophenyl)-2-pro-
penyl]triphenylphosphonium Bromide (1i). Yellow
solid; mp: 128.0–130.0◦C; IR (KBr): νmax 3421, 3042,
3003, 2987, 1707, 1593, 1518, 1437, 1347, 1316, 1110
[(Z)-2-Methoxycarbonyl-3-(2-naphthyl)-2-prope-
nyl]triphenylphosphonium Bromide (1l). White
solid; mp: 159.5–160.5◦C; IR (KBr): νmax 3454,
3394, 3051, 3000, 2948, 1705, 1626, 1586, 1434,
1
1
cm−1; H NMR (CDCl3): δ 3.41 (s, 3H), 5.34 (d, J =
1341, 1270, 1110 cm−1; H NMR (CDCl3): δ 3.40 (s,
15.4 Hz, 2H), 7.54–7.59 (m, 6H), 7.66–7.74 (m, 9H),
7.77 (d, J = 8.6 Hz, 2H), 7.98 (d, J = 5.1 Hz, 1H), 8.16
(d, J = 8.6 Hz, 2H); 13C NMR (CDCl3): δ 24.8 (d, J =
50.3 Hz, CH2), 53.1 (CH3), 117.7 (d, J = 84.5 Hz, 3 ×
CP), 124.1 (d, J = 10.0 Hz, C), 124.5 (2 × CH), 130.3
(2 × CH), 130.4 (d, J = 13.0 Hz, 6 × CPH), 134.2
(d, J = 10.0 Hz, 6 × CPH), 135.3 (3 × CPH), 140.0
(C), 143.9 (d, J = 10.7 Hz, CH), 148.0 (C), 166.0 (C);
31P NMR (CDCl3, 85% H3PO4 as external standard):
δ 22.1; Anal. Calcd for C29H25BrNO4P (%): C, 61.93;
H, 4.48; N, 2.49. Found: C, 61.70; H, 4.40; N, 2.50.
3H), 5.21 (d, J = 15.0 Hz, 2H), 7.35–7.38 (m, 2H),
7.43–7.66 (m, 16H), 7.75–7.79 (m, 2H), 7.94–7.96
(m, 1H), 8.01 (s, 1H), 8.09 (d, J = 5.5 Hz, 1H); 13C
NMR (CDCl3): δ 24.5 (d, J = 49.5 Hz, CH2), 52.6
(CH3), 117.7 (d, J = 85.5 Hz, 3 × CP), 121.0 (d, J =
10.0 Hz, C), 125.5 (CH), 126.8 (CH), 127.5 (2 x CH),
128.6 (CH), 128.9 (CH), 129.1 (CH), 130.0 (d, J =
13.0 Hz, 6 × CPH), 130.8 (C), 133.1 (C), 133.3 (C),
133.9 (d, J = 9.2 Hz, 6 × CPH), 134.9 (3 × CPH),
146.5 (d, J = 10.0 Hz, CH), 166.5 (C); 31P NMR
(CDCl3, 85% H3PO4 as external standard): δ 22.4;
Anal. Calcd for C33H28BrO2P (%): C, 69.85; H, 4.97.
Found: C, 69.60; H, 5.10.
[(Z)-2-Methoxycarbonyl-3-(3-nitrophenyl)-2-pro-
penyl]triphenylphosphonium Bromide (1j). Yellow
solid; mp: 126.5–127.5◦C; IR (KBr): νmax 3459, 3387,
3048, 2992, 1712, 1615, 1586, 1526, 1437, 1355, 1314,
1113 cm−1; 1H NMR (CDCl3): δ 3.36 (s, 3H), 5.07 (d,
J = 15.4 Hz, 2H), 7.50–7.70 (m, 16H), 7.73 (appt,
J = 8.0 Hz, 1H), 7.92 (d, J = 5.3 Hz, 1H), 8.03 (dd,
J = 8.2 and 2.0 Hz, 1H), 8.34 (d, J = 7.6 Hz, 1H);
13C NMR (CDCl3): δ 24.6 (d, J = 49.0 Hz, CH2), 53.1
(CH3), 117.6 (d, J = 85.5 Hz, 3 × CP), 122.9 (CH),
123.9 (d, J = 10.0 Hz, C), 124.0 (CH), 130.4 (d, J =
13.0 Hz, 6 × CPH), 131.7 (CH), 134.1 (d, J = 9.2 Hz,
6 × CPH), 135.1 (C), 135.3 (3 × CPH), 135.9 (CH),
143.8 (d, J = 9.0 Hz, CH), 148.2 (C), 166.0 (C); 31P
NMR (CDCl3, 85% H3PO4 as external standard): δ
21.9; Anal. Calcd for C29H25BrNO4P (%): C, 61.93; H,
4.48; N, 2.49. Found: C, 61.80; H, 4.60; N, 2.50.
[(2Z,4E)-2-Methoxycarbonyl-5-phenyl-2,4-pen-
tadienyl]triphenylphosphonium
Bromide
(1m).
White solid; mp >198.0◦C (dec); IR (KBr): νmax 3447,
3402, 3047, 3005, 2980, 2878, 1711, 1618, 1602,
1
1591, 1439, 1256, 1110, 970 cm−1; H NMR (CDCl3,
DMSO-d6 as internal standard): δ 3.34 (s, 3H), 4.81
(d, J = 15.2 Hz, 2H), 6.75 (d, J = 15.2 Hz, 1H), 6.89
(dd, J= 15.2 and 11.5 Hz, 1H), 7.24–7.31 (m, 5H),
7.48 (dd, J = 11.5 and 5.5 Hz, 1H), 7.57–7.61 (m,
6H), 7.67–7.72 (m, 9H); 13C NMR (CDCl3, DMSO-d6
as internal standard): δ 24.3 (d, J = 50.5 Hz, CH2),
52.4 (CH3), 117.0 (d, J= 11.7 Hz, C), 117.4 (d, J =
85.0 Hz, 3 × CP), 122.9 (d, J = 5.1 Hz, CH), 128.0
(2 × CH), 128.7 (2 × CH), 129.9 (CH), 130.2 (d, J =
12.5 Hz, 6 × CPH), 134.2 (d, J = 9.5 Hz, 6 × CPH),
135.3 (C), 135.4 (3 × CPH), 144.0 (d, J = 4.4 Hz,
CH), 145.8 (d, J = 9.5 Hz, CH), 166.6 (C); 31P NMR
(CDCl3, 85% H3PO4 as external standard): δ 21.1;
Anal. Calcd for C31H28BrO2P (%): C, 68.52; H, 5.19.
Found: C, 68.30; H, 5.30.
[(Z)-2-Methoxycarbonyl-3-(2-nitrophenyl)-2-pro-
penyl]triphenylphosphonium Bromide (1k). Yellow
solid; mp: 144.0–146.0◦C; IR (KBr): νmax 3445, 3053,
3007, 2989, 2950, 1715, 1638, 1586, 1522, 1435, 1345,
General Procedure for the Microwave-Assisted
Synthesis of α-Methylalkenoates 3
1
1270, 1111 cm−1; H NMR (CDCl3): δ 3.36 (s, 3H),
5.30 (d, J = 15.6 Hz, 2H), 7.48–7.75 (m, 16H), 7.87
(dd, J = 8.0 and 1.0 Hz, 1H), 8.19 (dt, J = 8.0 and
1.0 Hz, 1H), 8.26 (d, J = 5.7 Hz, 1H), 8.28 (d, J =
8.0 Hz, 1H); 13C NMR (CDCl3, DMSO-d6 as internal
standard): δ 23.3 (d, J = 50.6 Hz, CH2), 52.8 (CH3),
116.9 (d, J = 85.0 Hz, 3 × CP), 120.5 (d, J = 10.2 Hz,
C), 125.6 (CH), 130.1 (C), 130.2 (d, J = 12.5 Hz, 6 ×
CPH), 130.6 (CH), 131.4 (CH), 133.8 (d, J = 9.5 Hz,
6 × CPH), 135.3 (3 × CPH), 136.1 (CH), 144.4 (d, J =
10.3 Hz, CH), 145.8 (C), 165.5 (C); 31P NMR (CDCl3,
85% H3PO4 as external standard): δ 20.9; Anal. Calcd
for C29H25BrNO4P (%): C, 61.93; H, 4.48; N, 2.49.
Found: C, 61.70; H, 4.60; N, 2.50.
Phosphonium salt 1 (1.0 mmol), NaHCO3 (5.0 m
mol), and water (5.0 mL) were placed in a 10-mL
glass tube. The vessel was sealed with a septum,
placed into the microwave cavity of the monomode
reactor (CEM-Explorer, with IR temperature and
noninvasive pressure transducer) and irradiated by a
single pulse (Tmax = 100–105◦C, maximum potency =
50 W, maximum pressure = 50 PSI, t = 1 min ramp,
20 min hold, stirring mode “on”) under the condi-
tions given in Table 2. After the mixture had cooled
to room temperature, the reaction vessel was opened
and the contents were treated with 1 M HCl until
Heteroatom Chemistry DOI 10.1002/hc

Microwave-Assisted Synthesis of (E)-α-Methylalkenoate Framework from Multifunctionalized Allylic Phosphonium Salts 185
pH ∼7.0. The aqueous mixture was extracted with
CH2Cl2 and the organic extracts were washed with
water, dried over Na2SO4, filtered, and concentrated
under reduced pressure. The crude product was pu-
rified by column chromatography on silica gel (9:1
hexane/EtOAc) to give ester 3 and, in some cases, 3
and 4 as a mixture of isomers that we were unable to
separate by conventional silica gel chromatography;
their spectroscopic characterizations were in agree-
ment with the published data [6e,7a,b,8a].
are available from the corresponding author (e-mail:
msa@qmc.ufsc.br) on request.
ACKNOWLEDGMENTS
The authors wish to thank the Central de Ana´lises
(Departamento de Qu´ımica, Universidade Fed-
eral de Santa Catarina, Floriano´polis, Brazil) for
spectroscopic analysis. LM and MF are grate-
ful to Conselho Nacional de Desenvolvimento
Cient´ıfico e Tecnolo´gico (CNPq) and Coordenac¸a˜o
de Aperfeic¸oamento de Pessoal de N´ıvel Superior
(CAPES) (Brazil) for fellowships. MMS is grateful
to CNPq for the research fellowship. Financial sup-
port from Instituto Nacional de Cieˆncia e Tecnolo-
gia de Cata´lise/CNPq (INCT-Catalysis), Fundac¸a˜o de
Amparo a` Pesquisa e lnovac¸a˜o do Estado de Santa
Catarina (FAPESC), and CNPq (Universal project
471274/2009-7) is also gratefully acknowledged.
General Procedure for the Microwave-Assisted
Synthesis of α-Methylalkenoic Acid 5
Phosphonium salt 1 (1.0 mmol), NaOH (or LiOH)
(5.0 mmol), and water (5.0 mL) were placed in a
10-mL glass tube. The vessel was sealed with a
septum, placed into the microwave cavity of the
monomode reactor (CEM-Explorer, with IR temper-
ature and noninvasive pressure transducer) and irra-
diated by a single pulse (Tmax = 100◦C, maximum po-
tency = 50 W, maximum pressure = 50 PSI, t = 1 min
ramp, 30 min hold, stirring mode “on”) under the
conditions given in Table 3. After the mixture had
cooled to room temperature, the reaction vessel was
opened, the neutral contents were extracted with
CH2Cl2, and the organic extract was discharged. The
aqueous layer was acidified with 6 M HCl until pH
1.0 and the acid formed was extracted with CH2Cl2,
dried over Na2SO4, filtered, and concentrated to give
the isomeric products 5 and 6 as a mixture of isomers
that we were unable to separate by conventional sil-
ica gel chromatography; their spectroscopic char-
acterizations were in agreement with the published
data [6e,7c,11].
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