Nucleophilic α-addition to β-nitroacrylates: application to the synthesis of α-thioacrylates

Article abstract of DOI:10.1016/j.tet.2006.03.015

The α-addition of alkyl or aryl thionucleophiles to β-nitro-α,β-unsaturated alkenoates in THF in the presence of TEA or DBU gave access to the α-thio-α,β-unsaturated alkenoates. The reaction occurred via formation of β-nitro-α-thioalkanoates and concomitant elimination of nitrous acid from the α-adducts.

Full text of DOI:10.1016/j.tet.2006.03.015

Tetrahedron 62 (2006) 4879–4883
Nucleophilic a-addition to b-nitroacrylates: application
to the synthesis of a-thioacrylates
*
Elzbieta Lewandowska
Department of Chemistry, University of Agriculture, ul Wojska Polskiego 75, 60-625 Poznan, Poland
Received 14 December 2005; revised 10 February 2006; accepted 2 March 2006
Available online 27 March 2006
Abstract—The a-addition of alkyl or aryl thionucleophiles to b-nitro-a,b-unsaturated alkenoates in THF in the presence of TEA or DBU
gave access to the a-thio-a,b-unsaturated alkenoates. The reaction occurred via formation of b-nitro-a-thioalkanoates and concomitant
elimination of nitrous acid from the a-adducts.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
b-addition to the abnormal a-addition when triphenylphos-
phine is used as a catalyst. They have shown that PPh3-
catalyzed addition of amines to 2-alkynoates esters D occurs
at the a-carbon to give 2-amino alkenoates G. The overall
a-addition resulted from b-addition of PPh3 to alkynoates
D, which led to the formation of the vinyl phosphonium in-
termediate E. The latter serves as an a-Michael acceptor
(relative to the carbonyl group) and reacts with the nucleo-
phile to give intermediate F, which furnishes, after elimina-
tion of triphenylphosphine, product G with a net result being
overall a-substitution (Scheme 2).
The Michael reaction is one of the most versatile methods in
organic synthesis for the construction of new carbon–carbon
or carbon–heteroatom bonds.1 The Michael addition be-
tween various nucleophiles and a,b-unsaturated alkenoates
A (Scheme 1) in most cases occurs regioselectively at the
b-position to give products of type B (b-adduct). The regio-
selectivity of the Michael reaction can be inverted by attach-
ing groups with strongly electron-withdrawing properties
at the b carbon, which leads to the formation of the
a-substituted products2–4 of type C (a-adduct).
O
PPh3
COOR'
R
COOR'
Ph3P
R
R
OEt
AcOH/AcONa
A
D
1) Nuc–
2) H+
E
Nuc
R = strong EWG
+ shift
-Ph3P
COOR'
Nuc
COOR'
Nuc
H
Ph3P
R
O
Nuc O
α
R
α
R
β
OEt
R
OEt
β
Nuc
G
F
B
C
Michael addition
(β-addition)
anti-Michael addition
(α-addition)
Scheme 2. The a-addition of nucleophiles to 2-alkynoates in the presence of
PPh3.
Scheme 1. The a- vs b-addition of the nucleophiles to Michael acceptors.
Our recent theoretical studies of the Michael reaction re-
veal that the reaction barriers to a- vs b-addition decrease
as the strength of the electron-withdrawing group on the b
carbon increases. For those with sufficiently strong electron-
withdrawing groups, a-addition becomes favoured.6 For
instance, it was predicted that methyl 3-nitropropenoate
should react with nucleophiles to give an a-substituted
Recently, Trost and Dake5 showed that the regioselectivity
of Michael additions can be redirected from the classical
Keywords: anti-Michael addition; a-Thio-a,b-unsaturated alkenoates;
b-Nitroacrylates; Nitrous acid elimination.
* Tel.: +48 61 8487847; fax: +48 61 8487824; e-mail: elalew@au.poznan.pl
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.03.015

4880
E. Lewandowska / Tetrahedron 62 (2006) 4879–4883
adduct.6a On the basis of the theoretical calculations we
rationalized that 3-nitro-2-alkenoates would serve as a con-
venient substrate leading to the formation of anti-Michael
adducts. After in situ elimination of nitrous acid, such an ad-
duct would be expected to provide access to a-substituted
a,b-unsaturated alkenoates, which can serve as precursors
for further chemical transformations. Herein, we report
application of b-nitroacrylates as a-Michael acceptors in
a new approach for the synthesis of a-thioacrylates through
an in situ elimination of nitrous acid from the a-adducts.
Table 1. Reaction parameters for the a-addition of thiolate nucleophiles to
b-nitroacrylates
Entry
Product
Yield (%)a
Conditionb
1
2
3
4
5
6
3a
3b
3c
3d
4c
4d
78
84
79
78
86
72
c
c
c
c
c
c
a
Isolated yield.
See Scheme 3.
b
Very recently, Ballini and his group7 utilized reactions of
b-nitroacrylic esters with C-nucleophiles for the synthesis
of polyfunctionalized a,b-unsaturated esters prepared via
an a-substitution and elimination process. The a-addition
of organozinc cuprates, dialkylzinc reagents or trimethylalu-
minium to b-nitroacrylate esters has been used in the synthe-
sis of optically active b-amino acids.8 Addition of indoles to
the a-carbon of b-nitroacrylates has also been reported.9
ethylamine (TEA) in tetrahydrofuran (THF) at ambient tem-
perature provided the a-substituted product 3a in 78% yield
(Table 1, entry 1). Analogous treatment of 3-nitrocrotonate
2b(E ) and 3-nitrocinnamate 2c–d(E/Z ) afforded a-adducts
3b–d as a 1:1 mixture of diastereomers (Table 1, entries
2–4). In the case of 3b, the diastereomers were separated
1
by column chromatography. The H NMR spectrum for
The a-thioacrylates have been used as Michael acceptors10
and as dienophiles in Diels–Alder reactions.11 They have
been synthesized by procedures that involve multistep reac-
tions such as: (i) condensation of a-phenylthio acetate carb-
anions with aldehydes and ketones,12 (ii) Pummerer-style
dehydration of sulfoxides,13 (iii) ipso-substitution of the bro-
mine in a-bromo Michael acceptors,14 or (iv) nucleophilic
substitution—Wittig reaction of a-hypervalent iodine func-
tionalized phosphonium ylide.15 The above procedures often
require harsh conditions and frequently give products with
low selectivity.
3b verified that the adduct was derived from an a-addition
since the presence of two sets of signals corresponding to
the hydrogens at C2 (d, J¼10.5 Hz) and C3 (dq, J¼10.5,
7,0 Hz) instead of signals for two hydrogens at C2 was
observed.
Contrary to the reactions with propanethiol, treatment of b-
nitroacrylates with thiophenol produced the stable a-adducts
4c and 4d only in the case of b-nitrocinnamic substrates 2c–
d (Table 1, entries 5 and 6). Treatment of aliphatic 2a and 2b
with thiophenol initially produced the anti-Michael addition
products 4a and 4b (TLC) as well, but these adducts under-
went subsequent in situ elimination of HNO2 to produce
a-thioacrylates 6a and 6b even in the absence of TEA
(Scheme 4).
2. Results and discussion
The starting 3-nitroacrylates 2a–b were prepared in 70–75%
yield by reactions of the corresponding acrylic esters 1a–b
with NaNO2–ceric ammonium nitrate (CAN) followed
O
NO2
O
d or e
R1
OR2
ꢁ
OR2
R1
by dehydration (MsCl/Et3N/CH2Cl2/ꢀ20 C) as reported
SR3
recently (Scheme 3).16 The b-nitrocinnamate derivatives
2c–d were obtained directly from the corresponding cinna-
mates 1c–d with NaNO2–CAN in 57–65% yields. Attempts
to prepare the 4-nitrocinnamate analogue using this method
were unsuccessful. The 3-nitroacrylic esters 2a and 2b were
obtained as single E isomers while 2c and 2d were obtained
as a mixture of E and Z isomers in ratios of 2:1 and 5:1,
respectively.
5 R3 = Pr
6 R3 = Ph
2
Series: a R1 = H, R2 = Et
b R1 = Me, R2 = Me
c R1 = Ph, R2 = Et
d R1 = p-MeOPh, R2 = Et
Scheme 4. Synthesis of a-thioacrylates. Reagents and condition: (d) R3SH/
Et3N/THF rt; (e) R3SH/DBU/THF (60 ꢁC oil bath).
In order to optimalize the formation of a-thio-a,b-unsatu-
rated alkanoates 5 and 6 we tested different reaction condi-
tions, such as various ratios of the substrates to nucleophiles
and base, as well as different solvents and temperature. We
found that for the reaction of aliphatic alkenoates 2a and
2bwith propanethiol, the highest yields of 5aand 5b were ob-
tained with a 1:1.2:1 ratio of 2a or 2b/propanethiol/TEA in
THF at ambient temperature (Table 2, entries 1 and 2). Using
the same reaction conditions the a-phenylthioalkenoates 6a
and 6b were also obtained (Table 2, entries 5 and 6) in high
yield. The a-thiocrotonates 5b and 6b were isolated as Z
isomers. The Z-stereochemistry of 6b was established by
comparison of the chemical shift of b-vinyl proton signal,
which occurs at a lower field (d 7.48) than of the correspond-
ing E isomer (d 6.54) with the literature values.13d,15a
NO2
O
O
NO2
O
a or b
c
OR2
R1
OR2
OR2
R1
R1
SR3
3 R3 = Pr
4 R3 = Ph
1
2
Series: a R1 = H, R2 = Et
b R1 = Me, R2 = Me
c R1 = Ph, R2 = Et
d R1 = p-MeOPh, R2 = Et
Scheme 3. a-Addition of thiolate nucleophiles to b-nitroacrylates. Reagents
and condition: (a) CAN/NaNO2/CH3CN; (b) (i) CAN/NaNO2/CH3CN,
(ii) MsCl/Et3N/CH2Cl2/20 ꢁC; (c) R3SH/Et3N (cat)/THF rt.
Treatment of 3-nitroacrylates 2a(E ) (Scheme 3) with
propanethiol in the presence of a catalytic amount of tri-

E. Lewandowska / Tetrahedron 62 (2006) 4879–4883
Table 2. Reaction parameters for the synthesis of a-thioacrylates
4881
the signals for the respective isomers were assigned based
on the COSY and HETCOR experiments. Mass spectra
(MS) and HRMS were obtained with electron impact (EI,
20 eV) technique. Merck kieselgel 60-F254 sheets were
used for TLC and products were detected with 254 nm light.
Merck kieselgel 60 (230–400 mesh) was used for column
chromatography.
Entry
Product
Yield (%)a
Conditionb
Ratioc of E/Z
1
2
3
4
5
6
7
8
5a
5b
5c
5d
6a
6b
6c
6d
82
88
79
40
78
84
78
44
d
d
e
e
d
d
e
e
—
0:1
1:0
1:0
—
0:1
0:1
0.6:1
4.1.1. Ethyl 3-nitro-2-propylthiopropanoate (3a) (proce-
dure A). Propanethiol (0.15 mL, 126 mg, 1.66 mmol) and
TEA (24 mL, 17 mg, 0.17 mmol) were added to a stirred so-
lution of 2a (60 mg, 0.41 mmol) in THF (2 mL) at ambient
temperature. After 10 min, the resulting mixture was evapo-
rated to dryness under vacuum and the oily residue was
column chromatographed (hexane/5% EtOAc/hexane) to
give 3a (71 mg, 78%) as an oil: IR (CHCl3) 1735 (C]O),
1550 (NO2) cmꢀ1; 1H NMR d 1.01 (t, J¼7.3 Hz, 3H), 1.32
(t, J¼7.1 Hz, 3H), 1.64 (dq, J¼2.1, 7.3 Hz, 2H), 2.68 (dt,
J¼2.1, 7.3 Hz, 2H), 3.94 (dd, J¼10.2, 5.1 Hz, 1H), 4.27
(q, J¼7.1 Hz, 2H), 4.58 (dd, J¼14.8, 5.1 Hz, 1H), 4.90
(dd, J¼14.8, 10.2 Hz, 1H); 13C NMR d 13.2, 13.4, 22.6,
33.8, 42.1, 62.1, 74.4, 169.5; HRMS (EI) m/z calcd for
C8H15NO4S (M+) 221.0722, found 221.0711.
a
Isolated yield.
See Scheme 4.
b
c
Estimated by 1H NMR.
In the reaction of cinnamates 2c–d, the propylthio-3c–d as
well as phenylthio a-adducts 4c–d were stable, so stronger
base (DBU) and longer reaction times and/or higher temper-
atures were necessary for the conversion to a-thioacrylates
5 and 6 (Scheme 4). Thus, treatment of 2c (E/Z, 1.0:0.5)
with propanethiol in the presence of 1.2 equiv DBU
ꢁ
in THF at 60 C for 24 h led to the formation of a-(propane-
thiol)cinnamate 5c as a single E isomer in 79% yield. Anal-
ogous treatment of 2c with thiophenol (4 h) afforded 6c
in 82% yield as a mixture of isomers (E/Z, 0.2:1.0).13d,15a
Prolonged heating led to conversion of the isomers resulting
in formation of the more stable Z isomer, which was isolated
in 78% yield (Table 2, entries 3 and 7). In both the cases the
intermediary a-addition products 3c or 4c were also isolated
in low yields from the reaction mixture (<10%). Interest-
ingly, even treatment of 3-nitro-p-methoxycinnamate 2d
with propanethiol as well as with thiophenol led to the for-
mation of quite stable a-adducts 3d and 4d, which required
heating to convert them to the a-thiocinnamates 5d(E ) or
6d (E/Z; 0.6:1.0) isomers (Table 2, entries 4 and 8).
4.1.2. Methyl 3-nitro-2-propylthiobutanoate (3b). Treat-
ment of 2b (E; 76 mg, 0.52 mmol) with propanethiol
(0.19 mL, 158 mg, 2.08 mmol) by procedure A gave 3b
(93 mg, 84%) as a separable mixture (1:1) of two diastereo-
mers: IR (CHCl3) 1736 (C]O), 1550 (NO2) cmꢀ1. The less
1
polar isomer had: H NMR d 0.97 (t, J¼7.3 Hz, 3H), 1.61
(qd, J¼7.3, 3.5 Hz, 2H), 1.78 (d, J¼7.0 Hz, 3H), 2.64 (td,
J¼7.3, 2.1 Hz, 2H), 3.71 (d, J¼10.5 Hz, 1H), 3.77 (s, 3H),
4.84 (dq, J¼10.5, 7.0 Hz, 1H); 13C NMR d 13.2, 17.8,
22.4, 33.6, 48.5, 52.8, 82.1, 170.2. The more polar isomer
1
had: H NMR d 0.91 (t, J¼7.3 Hz, 3H), 1.51–1.58 (m col-
lapsed with d, J¼6.7 Hz, 5H), 1.78 (d, J¼7.0 Hz, 3H),
2.54–2.61 (m, 2H), 3.65 (d, J¼10.0 Hz, 1H), 3.72 (s, 3H),
4.79 (dq, J¼10.0, 6.7 Hz, 1H); 13C NMR d 13.3, 18.1,
22.6, 34.4, 49.3, 52.8, 83.4, 169.6; HRMS (EI) m/z calcd
for C8H15NO4S (M+) 221.0722, found 221.0710.
It was found that addition of thionucleophiles to b-nitro-
acrylic esters 2a–d in THF with an equivalent amount of
base affords a-thioacrylates 5 or 6 in a one pot process via
anti-Michael addition with the formation of b-nitro-a-thio
intermediates 3 or 4 and subsequent elimination of nitrous
acid. These results indicate that the kind of substituents at
the b-position (alkyl or aryl) in b-nitroacrylates and the
pKa of the thionucleophiles are two important factors con-
tributing to the stabilization of a-addition products 3 and 4.
4.1.3. Ethyl 3-nitro-3-phenyl-2-propylthiopropanoate
(3c). Treatment of 2c (E/Z, 1.0:0.5; 47 mg, 0.19 mmol)
with propanethiol (0.07 mL, 58 mg, 0.76 mmol) by proce-
dure A gave 3c (50 mg, 79%) as a mixture (1:1) of two dia-
stereomers as yellow oil: IR (CHCl3) 1752 (C]O), 1568
(NO2) cmꢀ1. One isomer had: 1H NMR d 0.80 (t,
J¼7.3 Hz, 3H), 0.90 (t, J¼7.1 Hz, 3H), 1.62 (sextet,
J¼7.3, 2.8 Hz, 2H), 2.30–2.38 (m, 2H), 3.90 (q, J¼7.1 Hz,
2H), 4.56 (d, J¼11.5 Hz, 1H), 5.39 (d, J¼11.5 Hz, 1H),
7.18–7.27 (m, 5H, Ar); 13C NMR d 13.2, 13.4, 22.3, 33.9,
48.5, 63.0, 91.3, 128.0, 128.5, 128.8, 136.3, 162.2. Second
3. Conclusion
In summary, we have developed an efficient method for the
synthesis of a-alkyl(or aryl)thio-a,b-unsaturated alkenoates
via a-addition of nucleophiles to b-nitroalkenoates, fol-
lowed by in situ elimination of nitrous acid from the result-
ing a-adducts in basic conditions.
1
isomer had: H NMR d 0.80 (t, J¼7.3 Hz, 3H), 1.29 (t,
J¼7.1 Hz, 3H), 1.62 (sextet, J¼7.3, 2.8 Hz, 2H), 2.30–
2.38 (m, 2H), 4.27 (qd, J¼7.1, 2.7 Hz, 2H), 4.57 (d,
J¼10.7 Hz, 1H), 5.34 (d, J¼10.7 Hz, 1H), 7.18–7.27 (m,
5H, Ar); 13C NMR d 13.2, 13.9, 22.4, 34.4, 49.7, 63.4,
92.0, 128.4, 128.5, 128.9, 136.8, 162.6; HRMS (EI) m/z
calcd for C14H19NO4S (M+) 297.1035, found 297.1032.
4. Experimental
4.1. General
THF was distilled from sodium benzophenone under nitro-
gen. 1H (400 MHz) and 13C (100 MHz) NMR spectra were
determined in CHCl3 on a Bruker Avance-400 instrument.
When the spectra were recorded for the mixture of isomers
4.1.4. Ethyl 3-(4-methoxyphenyl)-3-nitro-2-propylthio-
propanoate (3d). Treatment of 2d (E/Z, 1.0:0.2; 52 mg,
0.21 mmol) with propanethiol (74 mL, 69 mg, 0.83 mmol)

4882
E. Lewandowska / Tetrahedron 62 (2006) 4879–4883
by procedure A gave 3d (53 mg, 78%) as a mixture (1:1) of
two isomers as an oil: IR (CHCl3) 1752 (C]O), 1569
(NO2) cmꢀ1. One isomer had: 1H NMR d 0.91 (t,
J¼7.3 Hz, 3H), 1.05 (t, J¼7.1 Hz, 3H), 1.52–1.55 (m, 2H),
2.36–2.44 (m, 2H), 3.81 (s, 3H), 4.03 (m, 2H), 4.62 (d,
J¼11.4 Hz, 1H), 5.42 (d, J¼11.4 Hz, 1H), 6.86–6.89 (m,
2H, Ar), 7.27–7.30 (m, 2H, Ar); 13C NMR d 13.3, 13.6,
22.4, 33.8, 48.1, 55.2, 63.0, 91.6, 114.2, 127.9, 129.2,
159.6, 162.3. Second isomer had: 1H NMR d 0.91 (t,
J¼7.3 Hz, 3H), 1.36 (t, J¼7.1 Hz, 3H), 1.52–1.55 (m, 2H),
2.36–2.44 (m, 2H), 3.82 (s, 3H), 4.37 (qd, J¼7.1, 2.4 Hz,
2H), 4.64 (d, J¼10.5 Hz, 1H), 5.39 (d, J¼10.3 Hz, 1H),
6.86–6.89 (m, 2H, Ar), 7.27–7.30 (m, 2H, Ar); 13C NMR
d 13.2, 13.9, 22.4, 34.2, 49.1, 55.4, 63.4, 92.2, 114.3,
128.5, 129.7, 159.6, 162.7; HRMS (EI) m/z calcd for
C15H21NO5S (M+) 327.1140, found 327.1138.
EtOAc/hexane) to give 5a (28 mg, 82%) as an oil: IR
(CHCl3) 1712 (C]O), 1614 (C]C) cmꢀ1 1H NMR
;
d 0.97 (t, J¼7.3 Hz, 3H), 1.26 (t, J¼7.1 Hz, 3H), 1.64
(sextet, J¼7.3 Hz, 2H), 2.62 (t, J¼7.3 Hz, 2H), 4.20 (q,
J¼7.1 Hz, 2H), 5.33 (s, 1H), 6.27 (s, 1H); 13C NMR
d 13.6, 14.1, 21.2, 33.5, 61.7, 118.8, 137.9, 164.6; HRMS
(EI) m/z calcd for C8H14O2S (M+) 174.0714, found
174.0710.
4.1.8. Methyl 2-propylthio-2(Z )-butenoate (5b). Treat-
ment of 2b (E; 46 mg, 0.32 mmol) with propanethiol
(34 mL, 29 mg, 0.38 mmol) and TEA (44 mL, 32.3 mg,
0.32 mmol) by procedure B gave 5b (27 mg, 88%) as an
oil: IR (CHCl3) 1710 (C]O), 1610 (C]C) cmꢀ1 1H
;
NMR d 0.89 (t, J¼7.3 Hz, 3H), 1.46 (sextet, J¼7.3 Hz,
2H), 1.95 (d, J¼7.0 Hz, 3H), 2.61 (t, J¼7.3 Hz, 2H), 3.72
(s, 3H), 7.21 (q, J¼7.0 Hz, 1H); 13C NMR d 13.2, 16.6,
23.0, 35.7, 52.7, 128.3, 146.5, 166.2; HRMS (EI) m/z calcd
for C8H14O2S (M+) 174.0714, found 174.0708.
4.1.5. Ethyl 3-nitro-3-phenyl-2-phenylthiopropanoate
(4c). Treatment of 2c (E/Z, 1.0:0.5; 57 mg, 0.26 mmol)
with thiophenol (32 mL, 34 mg, 0.31 mmol) by procedure
A (without addition of TEA) gave 4c (73 mg, 86%) as a mix-
ture (1:1) of two isomers as an oil: IR (CHCl3) 1752 (C]O),
4.1.9. Ethyl 3-phenyl-2-propylthio-2(E )-propenoate (5c).
Treatment of 2c (E/Z, 1.0:0.5; 47 mg, 0.21 mmol) with pro-
panethiol (23 mL, 19 mg, 0.25 mmol) and DBU (31 mL,
32 mg, 0.21 mmol) by procedure B (stirring was continued
1
1566 (NO2) cmꢀ1. One isomer had: H NMR d 0.90 (t,
J¼7.1 Hz, 3H), 3.89–3.96 (m, 2H), 4.84 (d, J¼10.6 Hz,
1H), 5.46 (d, J¼10.6 Hz, 1H), 6.99–7.05 (m, 2H, Ar),
7.15–7.21 (m, 8H, Ar); 13C NMR d 13.4, 52.2, 63.1, 90.5,
127.8, 128.4, 128.6, 128.9, 129.1, 130.6, 134.8, 135.7,
ꢁ
for 24 h at 60 C) gave separable mixture of 5c (42 mg,
79%) and 4c (5 mg, 8%; as a mixture of two isomers).
Compound 5c had: IR (CHCl3) 1693 (C]O), 1602
1
162.1. Second isomer had: H NMR d 1.29 (t, J¼7.1 Hz,
(C]C) cmꢀ1
;
1H NMR d 0.83 (t, J¼7.2 Hz, 3H), 1.32
3H), 4.22–4.27 (m, 2H), 4.87 (d, J¼11.5 Hz, 1H), 5.49 (d,
J¼11.5 Hz, 1H), 6.99–7.05 (m, 2H, Ar), 7.15–7.21 (m,
8H, Ar); 13C NMR d 13.9, 53.7, 63.5, 91.3, 128.4, 128.5,
128.7, 129.0, 129.2, 131.5, 135.1, 135.8, 162.6; HRMS
(EI) m/z calcd for C17H17O4SN (M+) 331.0878, found
331.0889.
(t, J¼7.1 Hz, 3H), 1.46 (sextet, J¼7.2 Hz, 2H), 2.37 (t,
J¼7.2 Hz, 2H), 4.25 (q, J¼7.1 Hz, 2H), 5.93 (s, 1H),
7.33–7.35 (m, 2H, Ar), 7.39–7.41 (m, 3H, Ar); 13C NMR
d 13.2, 14.4, 23.0, 34.7, 60.0, 115.9, 128.0, 128.4, 128.7,
138.8, 160.6, 165.9; HRMS (EI) m/z calcd for C14H18O2S
(M+) 250.1027, found 250.1029.
4.1.6. Ethyl 3-(4-methoxyphenyl)-3-nitro-2-phenylthio-
propanoate (4d). Treatment of 2d (E/Z, 1.0:0.2; 50 mg,
0.2 mmol) with thiophenol (24 mL, 26 mg, 0.22 mmol) by
procedure A gave 4d (52 mg, 72%) as a mixture (1:1) of
two isomers as an oil: IR (CHCl3) 1752 (C]O), 1569
(NO2) cmꢀ1. One isomer had: 1H NMR d 1.04 (t,
J¼7.1 Hz, 3H), 3.78 (s, 3H), 4.03–4.06 (m, 2H), 4.92 (d,
J¼10.5 Hz, 1H), 5.52 (d, J¼10.5 Hz, 1H), 6.77–6.81 (m,
2H, Ar), 7.02–7.07 (m, 2H, Ar), 7.26–7.27 (m, 4H, Ar),
7.29–7.32 (m, 1H, Ar); 13C NMR d 13.5, 51.9, 55.3, 63.1,
90.7, 114.0, 127.5, 128.9, 129.0, 130.8, 132.2, 134.7,
159.6, 162.1. Second isomer had: 1H NMR d 1.38 (t,
J¼7.1 Hz, 3H), 3.80 (s, 3H), 4.26–4.35 (m, 2H), 4.94 (d,
J¼11.4 Hz, 1H), 5.53 (d, J¼11.4 Hz, 1H), 6.77–6.81 (m,
2H, Ar), 7.02–7.07 (m, 2H, Ar), 7.26–7.27 (m, 4H, Ar),
7.29–7.32 (m, 1H, Ar); 13C NMR d 13.9, 53.1, 55.5, 63.5,
91.4, 114.1, 127.7, 129.1, 129.6, 131.6, 132.6, 135.1,
159.6, 162.6; HRMS (EI) m/z calcd for C18H19O5SN (M+)
361.0984, found 361.1004.
4.1.10. Ethyl 3-(4-methoxyphenyl)-2-propylthio-2(E )-
propenoate (5d). Treatment of 2d (E/Z, 1.0:0.2; 70 mg,
0.21 mmol) with propanethiol (30 mL, 25 mg, 0.33 mmol)
and DBU (50 mL, 51 mg, 0.33 mmolꢁ) by procedure B
(stirring was continued for 24 h at 60 C) gave separable
mixture of 5d (31 mg, 40%) and 4d (28 mg, 30%; as a
mixture of two isomers). Compound 5d had: IR (CHCl3)
1693 (C]O), 1607 (C]C) cmꢀ1 1H NMR d 0.85 (t,
;
J¼7.2 Hz, 3H), 1.32 (t, J¼7.1 Hz, 3H), 1.46 (sextet,
J¼7.2 Hz, 2H), 2.41 (t, J¼7.2 Hz, 2H), 3.85 (s, 3H), 4.23
(q, J¼7.1 Hz, 2H), 5.92 (s, 1H), 6.91–6.93 (m, 2H, Ar),
7.29–7.31 (m, 2H, Ar); 13C NMR d 13.3, 14.4, 23.0, 29.7,
34.8, 55.3, 59.9, 113.8, 115.7, 129.4, 131.2, 160.1, 165.9;
HRMS (EI) m/z calcd for C15H20O3S (M+) 280.1133, found
280.1128.
4.1.11. Ethyl 2-phenylthiopropenoate (6a) (procedure C).
Thiophenol (25 mL, 27.3 mg, 0.25 mmol) and TEA (3 mL,
2.5 mg, 0.025 mmol) were added to a stirred solution of 2a
(30 mg, 0.21 mmol) in THF (2 mL) at ambient temperature
and stirring was continued for 2 h. The resulting mixture was
evaporated to dryness under vacuum and the residue was
column chromatographed (hexane/1% EtOAc/hexane) to
give 6a13b (33 mg, 78%) as an oil: IR (CHCl3) 1720
(C]O), 1610 (C]C) cmꢀ1; 1H NMR d 1.24 (t, J¼7.1 Hz,
3H), 4.26 (q, J¼7.1 Hz, 2H), 5.26 (s, 1H), 6.32 (s, 1H),
4.1.7. Ethyl 2-propylthiopropenoate (5a) (procedure B).
Propanethiol (37 mL, 31.4 mg, 0.41 mmol) and TEA
(47 mL, 34.3 mg, 0.34 mmol) were added to a stirred solu-
tion of 2a (50 mg, 0.34 mmol) in THF (2 mL) at ambient
temperature and stirring was continued for 10 h. The result-
ing mixture was evaporated to dryness under vacuum and
the residue was column chromatographed (hexane/1%

E. Lewandowska / Tetrahedron 62 (2006) 4879–4883
4883
7.34–7.42 (m, 3H, Ar), 7.48–7.51 (m, 2H, Ar); 13C NMR
d 14.1, 61.8, 122.6, 128.7, 129.5, 134.1, 139.1, 143.4, 164.7.
References and notes
1. (a) Bergman, E. D.; Gonsburg, D.; Pappo, R. Org. React. 1959,
10, 179–555; (b) Comprehensive Organic Synthesis; Trost,
B. M., Ed.; Pergamon: Oxford, UK, 1991; Vol. 4; (c) Perl-
mutter, P. Conjugate Addition Reactions in Organic Synthe-
sis; Pergamon: Oxford, UK, 1992.
2. (a) Knunyanta, I. L.; Cheburkov, Ya. A. Izv. Akad. Nauk, SSSR
Ser. Khim. 1960, 2162; (b) Solodin, I. V.; Eremeev, A. V.;
Chervin, I. I.; Kostyanovskii, R. G. Khim. Geterotsikl. Soedin.
1985, 1359.
4.1.12. Methyl 2-phenylthio-2(Z )-butenoate (6b). Treat-
ment of 2b (E; 50 mg, 0.34 mmol) with thiophenol or benz-
enethiol (42 mL, 45.5 mg, 0.41 mmol) by procedure C gave
6b13d (61 mg, 84%) as an oil: IR (CHCl3) 1715 (C]O),
1
1607 (C]C) cmꢀ1; H NMR d 2.02 (d, J¼7.0 Hz, 3H),
3.61 (s, 3H), 7.07–7.10 (m, 1H, Ar), 7.12–7.19 (m, 4H,
Ar), 7.48 (q, J¼7.0 Hz, 1H); 13C NMR d 16.7, 52.5, 125.9,
127.3, 127.9, 128.9, 135.7, 149.3, 165.9.
3. Martin, V.; Molines, H.; Wakselman, C. J. Org. Chem. 1992,
57, 5530.
4. Lewandowska, E.; Kinastowski, S.; Wnuk, S. F. Can. J. Chem.
2002, 80, 192.
4.1.13. Ethyl 3-phenyl-2-phenylthio-2(Z )-propenoate
(6c). DBU (33 mL, 33 mg, 0.22 mmol) was added to a stirred
solution of 2c (E/Z, 1.0:0.5; 48 mg, 0.22 mmol) in THF
(2 mL) containing thiophenol (27 mL, 29ꢁmg, 0.26 mmol),
and stirring was continued for 24 h at 60 C. After cooling
to ambient temperature, CH2Cl2 (5 mL) and 5% HCl
(4 mL) were added. The organic layer was separated and
was washed (H2O, brine), dried (MgSO4) and column chro-
matographed (hexane/1% EtOAc/hexane) to give 6c15a
(48 mg, 78%) and 4c (5 mg, 7%; as a mixture of two iso-
mers). Compound 6c had: IR (CHCl3) 1706 (C]O), 1602
5. Trost, B. M.; Dake, G. R. J. Am. Chem. Soc. 1997, 119, 7595.
6. (a) Chatfield, D. C.; Augsten, A.; D’Cunha, C.; Lewandowska,
E.; Wnuk, S. F. Eur. J. Org. Chem. 2004, 313; (b) Lewandow-
ska, E.; Chatfield, D. C. Eur. J. Org. Chem. 2005, 3297.
7. Ballini, R.; Fiorini, D.; Palmeri, A. Tetrahedron Lett. 2005, 46,
1245.
8. (a) Rimkus, A.; Sewald, N. Org. Lett. 2002, 4, 3289; (b)
Rimkus, A.; Sewald, N. Org. Lett. 2003, 5, 79; (c) Eilitz, U.;
Lebmann, F.; Seidelmann, O.; Wendisch, V. Tetrahedron:
Asymmetry 2003, 14, 189.
1
(C]C) cmꢀ1; H NMR d 0.97 (t, J¼7.1 Hz, 3H), 4.03 (q,
J¼7.1 Hz, 2H), 7.07–7.12 (m, 1H, Ar), 7.14–7.23 (m, 4H,
Ar), 7.28–7.35 (m, 3H, Ar), 7.73–7.77 (m, 2H, Ar), 8.00
(s, 1H); 13C NMR d 13.6, 61.8, 125.8, 126.4, 127.8, 128.3,
128.4, 128.7, 128.9, 129.9, 130.8, 134.4, 135.7, 145.1, 166.1.
9. Bartoli, G.; Bosco, M.; Giuli, S.; Guliani, A.; Lucarelli, L.;
Marcantoni, E.; Sambri, L.; Torregiani, E. J. Org. Chem.
2005, 70, 1941.
10. (a) Fang, J.-M. J. Org. Chem. 1982, 47, 3464; (b) Warren, S.
Chem. Ind. (London) 1980, 824.
11. (a) Aggarwal, V. K.; Jones, D. E.; Martin-Castro, A. M. Eur. J.
Org. Chem. 2000, 2939; (b) Aggarwal, V. K.; Anderson, E. S.;
Jones, D. E.; Obierey, K. B.; Giles, R. Chem. Commun. 1998,
1985.
4.1.14. Ethyl 3-(4-methoxyphenyl)-2-phenylthio-2(E/Z )-
propenoate (6d). Treatment of 2d (E/Z, 1.0:0.2; 40 mg,
0.16 mmol) with thiophenol (20 mL, 21 mg, 0.19 mmol)
and DBU (31 mL, 22 mg, 0.22 mmol) as described for 6c
gave 6d (E/Z, 0.6:1.0; 22 mg, 44%): IR (CHCl3) 1706
(C]O), 1601 (C]C) cmꢀ1. Z-Isomer had: 1H NMR
d 1.09 (t, J¼7.1 Hz, 3H), 3.86 (s, 3H), 4.13 (q, J¼7.1 Hz,
2H), 6.92–6.94 (m, 2H, Ar), 7.23–7.31 (m, 5H, Ar), 7.91–
7.93 (m, 2H, Ar), 8.12 (s, 1H); 13C NMR d 13.9, 55.2,
61.7, 113.8, 116.0, 126.0, 128.1, 128.9, 130.2, 133.0,
12. (a) Takaki, K.; Okamura, A.; Ohshiro, Y.; Agawa, T. J. Org.
Chem. 1978, 43, 402; (b) Ymagiwa, S.; Sato, H.; Hoshi, N.;
Kosugi, H.; Uda, H. J. Chem. Soc., Perkin Trans. 1 1979, 570.
13. (a) Hagiwara, H.; Nakayama, K.; Uda, H. Bull. Chem. Soc. Jpn.
1975, 48, 3769; (b) Monteiro, H. J.; Gemal, A. L. Synthesis
1975, 437; (c) Durman, J.; Hunt, P. G.; Warren, S. Tetrahedron
Lett. 1983, 24, 2113; (d) Durman, J.; Grayson, J. I.; Hunt, P. G.;
Warren, S. J. Chem. Soc., Perkin Trans. 1 1986, 1939.
14. Rosnati, V.; Saba, A.; Salimbeni, A. Tetrahedron Lett. 1981, 22,
167.
15. (a) Yu, X.; Huang, X. Synlett 2002, 1895; (b) Zhdankin, V. V.;
Maydanovych, O.; Herschbach, J.; Bruno, J.; Matveeva, E. D.;
Zefirov, N. S. Tetrahedron Lett. 2002, 43, 2359.
16. Jayakanthan, K.; Madhusudanan, K. P.; Vankar, Yashwant D.
Tetrahedron 2004, 60, 397.
1
145.9, 161.1, 166.5. E Isomer had: H NMR d 1.36 (t,
J¼7.1 Hz, 3H), 3.72 (s, 3H), 4.28 (q, J¼7.1 Hz, 2H), 6.09
(s, 1H), 6.64–6.66 (m, 2H, Ar), 7.06–7.11 (m, 2H, Ar),
7.14–7.19 (m, 5H, Ar); 13C NMR d 14.3, 55.4, 60.2, 113.2,
122.0, 127.0, 127.5, 128.4, 130.7, 133.5, 136.0, 158.2,
159.8, 165.9; HRMS (EI) m/z calcd for C18H18O3S (M+)
314.0977, found 314.0988.
Notes: The 4-methoxybenzaldehyde and 4d were also
detected in the reaction mixture.