E- and chemoselective thia-Michael addition to benzyl allenoate

Article abstract of DOI:10.1080/10426507.2020.1799365

Different thiols were successfully reacted with benzyl allenoate resulting in E-selective thia-Michael addition product with α,β-unsaturation as confirmed by single crystal x-ray crystallographic analysis. The thia-Michael addition is chemoselective and free amine and alcohol groups were well tolerated. Catalytic triethylamine was required for high conversion. Fair to excellent yields were obtained for a variety of aliphatic, aryl and heteroaryl thiols.

Full text of DOI:10.1080/10426507.2020.1799365

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/gpss20
E- and chemoselective thia-Michael addition to
benzyl allenoate
Rifhat Bibi , Amna Murtaza , Khalid Mohammed Khan , Zia ur Rehman ,
Aamer Saeed , Muhammad Nawaz Tahir & Abbas Hassan
To cite this article: Rifhat Bibi , Amna Murtaza , Khalid Mohammed Khan , Zia ur Rehman , Aamer
Saeed , Muhammad Nawaz Tahir & Abbas Hassan (2020): E- and chemoselective thia-Michael
addition to benzyl allenoate, Phosphorus, Sulfur, and Silicon and the Related Elements, DOI:
10.1080/10426507.2020.1799365
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PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
https://doi.org/10.1080/10426507.2020.1799365
E- and chemoselective thia-Michael addition to benzyl allenoate
a
a
b
a
a
Rifhat Bibi , Amna Murtaza , Khalid Mohammed Khan , Zia ur Rehman , Aamer Saeed , Muhammad Nawaz
c
a
Tahir , and Abbas Hassan
a
b
Department of Chemistry, Quaid-i-Azam University, Islamabad, Pakistan; HEJ Research Institute of Chemistry, International Center for
c
Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan; Department of Physics, Sargodha University, Sargodha, Pakistan
ABSTRACT
ARTICLE HISTORY
Different thiols were successfully reacted with benzyl allenoate resulting in E-selective thia-Michael
addition product with a,b-unsaturation as confirmed by single crystal x-ray crystallographic ana-
lysis. The thia-Michael addition is chemoselective and free amine and alcohol groups were well
tolerated. Catalytic triethylamine was required for high conversion. Fair to excellent yields were
obtained for a variety of aliphatic, aryl and heteroaryl thiols.
Received 31 January 2020
Accepted 18 July 2020
KEYWORDS
Thia-Michael addition;
a-b-unsaturation;
E-selective; b-substituted
thioenoates; chemoselective
GRAPHICAL ABSTRACT
[
6c]
1
. Introduction
has been reported to give 1:1 mixture of E/Z isomers.
Interestingly, the resulted b-substituted thioenoates upon fur-
ther reaction with in situ generated alkyl cuprates, afforded the
thiol-substituted products in stereospecific fashion (Scheme 1,
reaction 2). This methodology has been applied in the total syn-
Michael addition reaction is a widely utilized and historically
[
1]
important reaction in organic synthesis. It is more than a
century old reaction in which addition of soft nucleophiles to
[
2]
electron deficient alkenes occurs. The nucleophiles consist
of stabilized enolates, organocuprates, and oxygen, nitrogen
and sulfur anion or pronucleophiles. The electrophiles include
unsaturation attached to electron withdrawing groups such as
enone, enoate, enal, nitroalkene, alkene nitrile and analogous
alkyne compounds. Sulfur containing compounds are consid-
ered to be soft nucleophiles and the thia-Michael addition
[6a]
thesis of juvenile hormones.
Owing to the importance of the olefin selectivity in thia-
Michael addition, herein, we report a general and mild E-
selective and chemo-selective thia-Michael addition to benzyl
allenoate as surrogate for alkynoate.
[
3]
2. Results and discussion
reactions are well documented. a,b-Unsaturated carbonyl
compounds demonstrated their higher ability as Michael
In a typical reaction, when thiophenol 1a was treated with
benzyl allenoate in THF with 150 mol% of triethylamine, it
resulted in benzyl b-phenylthio-2-butenoate 2a in 60% yield
as single E-isomer selectively. Lowering the amount of trie-
thylamine increased the yield and in the presence of only
[
4]
acceptor when reacted with thiols.
Similar reactivity
have been utilized to a great extent for the annulation and the
[
5]
synthesis of diverse heterocyclic structures.
Mostly the reaction reported for thia-Michael addition to
[
6]
allenoate and alkynoates result the Z-isomer as main product.
For instance, the thia-Michael addition to ethyl 2-methylbuta-
,3-dienoate have been reported to give mixture of products in
the absence of any additive, favoring the conjugated Z-selective
2
0 mol% of triethylamine, 72% of 2a was isolated (Table 1,
entries 1 and 2).
The catalytic amount of triethylamine was found to be
optimal for other examples as well. When 2-aminothiophe-
2
[
7]
Michael addition product. This is, however, not the case nol 1b was treated with benzyl allenoate and 20 mol% of
when PBu was utilized as the catalyst and only the non-conju- triethylamine, (E)-benzyl 3-(2-aminophenylthio)but-2-enoate
3
gated Michael addition product is observed (Scheme 1, reaction 2b was isolated in 68% yield. As the substrate contains an
1
). Recently, a nonselective thia-Michael addition of thiophenol ortho amino group, it was assumed that the reaction will not
to methyl 2-butynoate in the presence of sodium hydroxide require any additional triethylamine. Surprisingly, with only
CONTACT Abbas Hassan
ahassan@qau.edu.pk
Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan.
Supplemental data for this article is available online at https://doi.org/10.1080/10426507.2020.1799365.
ß 2020 Taylor & Francis Group, LLC

2
R. BIBI ET AL.
Scheme 1. Thia-Michael addition reaction and its utility in stereospecific transformation.
Table 1. Triethylamine optimization for thia-Michael addition to benzyl allenoate.
S. No.
RSH
Et
3
N (mol %)
Yield (%) (E:Z)
1
2
3
4
5
6
PhSH
PhSH
150
20
20
10
–
60% (>20:1)
72% (>20:1)
68% (>20:1)
60% (>20:1)
26% (>20:1)
92% (>20:1)
2-NH
2-NH
2-NH
2-NH
2
C
6
C
6
C
6
C
6
4
H SH
4
H SH
4
H SH
4
H SH
2
2
2
150
1
0 mol% of triethylamine, 2b was isolated in 60% yield entry 5), there was low conversion and in addition to the
while, in the absence of triethylamine only 26% of 2b was product 2b, the reaction tube had minor amount of
isolated (Table 1, entries 4 and 5). This suggested that a physically different crystals than the crystals for 2b. It sin-
[
8]
catalytic amount of triethylamine acts as proton shuttle.
However, in the presence of 150 mol% of triethylamine, 2b 3b (Figure 1). All attempts to isolate the compound 3b in
was isolated in much higher 92% yield as single E-isomer. large quantity and its spectroscopic characterization were
In the case of 2b, it was important to confirm the che- unsuccessful.
gle crystal X ray analysis showed unconjugated product
moselectivity for thia vs aza-Michael addition and the
To check the scope of the reaction, a variety of thiols were
configuration of the double bond. Although NMR analysis tested. Apart from 1a and 1b, when 2-amino-4-chlorobenze-
was useful, single crystal X-ray analysis confirmed the nethiol 1c was reacted with benzyl allenoate, thia-Michael
structure of 2b. The product was indeed thia-Michael adduct 2c was formed in 93% yield. Again, no aza-Michael
adduct with E-enone geometry (Figure 1). We were adduct, or Z isomer was detected from reaction mixture.
unable to detect any Z-2b from the NMR analysis of the Further aryl thiols including 2-bromobenzenethiol 1d and 2,6-
crude reaction mixture. Interestingly, when the reaction dichlorothiophenol 1e and 2-naphthalenethiol 1f under the
was carried out in the absence of triethylamine, (Table 1, same reaction conditions resulted in Michael adducts 2d, 2e

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
3
Figure 1. Single-crystal X-ray structures of 2 b and 3 b. The C-S bond and E-geometry of the product is confirmed. For details, see supporting information.
a
b
Scheme 2. Scope of reaction for thia-Michael addition. Isolated yields, Reaction with 150 mol% triethylamine.

4
R. BIBI ET AL.
and 2f in 84%, 82% and 68% yields, respectively. Furthermore, the crystal. From
a sealed ceramic diffraction tube
heteroaryl thiols smoothly undergo thia-Michael addition to (SIEMENS) having graphite-monochromated Mo-Ka radi-
benzyl allenoate. Benzo[d]thiazole-2-thiol 1g resulted in 83% ation, different intensities were determined. Then using
of the thia-Michael adduct 2g. 2-Pyridinethiol resulted in Patterson and DIRDIF method, the structure of the com-
quantitative yield of the desire product 2h. Similarly, pound was solved. The Supplemental Materials contains
1
13
highly functionalized 5-(4-nitrophenyl)-1,3,4-oxadiazole-2- sample H and C NMR spectra for the products 2 (Figures
thiol 1i effectively reacts in thia-Michael fashion under the
S 1 – S 25).
same reaction conditions to give 2i in 75% yield.
Aliphatic thiols were also exposed to thia-Michael add-
ition. 2-Mercaptoethanol afforded thia-Michael adduct 2j in
4
.1. Synthesis of substrate benzyl buta-2,3-dienoate
9
2% yield. In case of 2j thia-Michael adducts formation also
The benzyl buta-2,3-dienoate was synthesize in a slightly
role. Sterically demanding 2-methylpropane-2-thiol leads to modified procedure to the previously reported method.
demonstrated that free hydroxyl does not play a competitive
[
9]
product 2k in 68% yield. A long chain aliphatic thiol dodec- See the Supplemental Materials for the detailed experimen-
ane-1-thiol efficiently resulted in adduct 2l in 82% yield tal procedure.
(Scheme 2). The reaction scope suggested that the reaction
is general toward a variety of aliphatic, aryl, heteroaryl thiols
in the presence of free hydroxyl and amine functionality.
4
.2. General procedure for the addition of different
thiols to allenoate
3
. Conclusion
Oven-dried sealed tube was charged with benzyl buta-2,3-
In summary, we were able to obtain E-selective thia-Michael dienoate (123 lL, 0.75 mmol, 150 mol%), distilled triethyl-
addition of aryl, heteroaryl and aliphatic thiols to benzyl amine (19.2 lL, 0.1 mmol, 20 mol%) and nucleophile 1a-s
allenoate. The reaction is facilitated by catalytic amount of
triethylamine and is chemoselective toward thia-Michael
addition in the presence of free amine and alcohol func-
tional groups. The chemoselectivity and geometrical charac-
terization were confirmed though single crystal X-ray
analysis of 2b. Additional characterization details for the X-
ray structural studies are presented in the Supplemental
Materials (Tables S1 and S2).
(
0.5 mmol, 100 mol%). Freshly distilled THF (1 mL, 0.5 M) was
added and purged with nitrogen. The mixture was placed in
an oil bath at 70 C and was allowed to stir for 24 h. Solvent
was evaporated over dry silica gel and purification by flash col-
umn chromatography gave the desired product 2a-s.
ꢁ
4
.3. Benzyl (E)-3-(phenylthio)but-2-enoate (2a)
The reaction was performed with thiophenol 1a (51 lL,
.5 mmol, 100 mol%) and compound 2a was obtained as
4
. Experimental
Commercially available reagents were used without further brownish oil in 72% yield; H NMR (300 MHz, CDCl
purification unless necessary. Solvents were dried and dis- (ppm) 7.51 ꢂ 7.32 (m, 10H), 5.31 (s, 1H), 5.07 (s, 2H), 2.45
0
1
): d
3
13
tilled before their use. Reactions to be run in non-aqueous (s, 3H); C NMR (75 MHz, CDCl ): d (ppm) 165.3, 160.7,
3
solvents were accomplished under an inert atmosphere of 136.3, 135.5, 129.9, 129.7, 129.4, 128.5, 128.2, 128.0, 110.3,
þ
nitrogen. For Michael addition reaction of thiol, 65.5, 20.2; HRMS (CI) Calcd for C17
1
H
17
O
S [M þ H] :
2
3 ꢀ 100 mm sealed test tubes were used. To dry combined 285.0949; found, 285.0951; IR (neat) 3063, 3031, 2954, 2893,
organic extracts, anhydrous sodium sulfate was used. Thin 1708, 1593, 1473, 1440, 1378, 1327, 1168, 1099, 1016, 747,
ꢂ1
Layer Chromatography (TLC) was used for monitoring the 688, 581, 512 cm
reaction progress. UV visible spots were inspected under
UV light at 254 nm. For visualization of UV inactive spots,
different staining reagents such as potassium permanganate,
4
.4. Benzyl (E)-3-(2-aminophenylthio)but-2-enoate (2b)
phosphomolybdic acid (PMA), anisaldehyde or ninhydrin
solution were used as appropriate. Flash column chromatog-
raphy using silica gel was performed for purification of most
of the products. Mass spectrometric (HRMS) experiments
were carried out on Finnigan MAT-311A (Germany) mass
spectrometer with (CI) ionization techniques. NMR spectra
were obtained using a Bruker 300 NMR MHz spectrometer
The reaction was performed with 2-aminothiophenol 1b
(
62.5 mg, 0.5 mmol, 100 mol%) and compound 2b was
ꢁ
obtained as light brown crystals (mp 123 C) in 92% yield;
1
H NMR (300 MHz, CDCl ): d (ppm) 7.37-7.20 (m, 7H),
3
6
.77-6.71 (m, 2H), 5.29 (q, J ¼ 0.9 Hz, 1H), 5.07 (s, 2H), 4.09
13
(broad s, 2H), 2.45 (d, J ¼ 0.9 Hz, 3H); C NMR (75 MHz,
in deuterated solvents using TMS as internal reference, at CDCl
): d (ppm) 165.0, 158.0, 148.7, 137.1, 136.1, 132.1,
3
1
13
3
00 MHz ( H NMR) and 75 MHz ( C NMR). Chemical 128.4, 128.3, 128.0, 118.8, 115.5, 111.3, 109.5, 65.5, 19.9;
þ
shifts are mentioned in delta (d) units while coupling con- HRMS (CI) Calcd for C17
stants (J) values are in Hertz unit (Hz). The single crystal X- found, 300.1065; IR (neat) 3454, 3360, 3064, 3031, 2947,
H18NO
S [M þ H] : 300.1058;
2
rays analysis was carried out with a Bruker Kapa APEX-II 2919, 2891, 1681, 1597, 1479, 1378, 1322, 1181, 1101, 1020,
ꢂ1
CCD diffractometer having a CCD detector set 40 mm from 927, 848, 743, 698 cm

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
5
4
.5. Benzyl (E)-3-(2-amino-4-chlorophenylthio)but-2-
4.9. Benzyl (E)-3-(5-chlorobenzo[d]thiazol-2-ylthio)but-2-
enoate (2g)
enoate (2c)
The reaction was performed with 2-amino-4-chlorothiophe- The reaction was performed with 5-chlorobenzo[d]thiazole-
nol 1c (100.8 mg, 0.5 mmol, 100 mol%) and compound 2c 2-thiol 1g (100.87 mg, 0.5 mmol, 100 mol%) and compound
1
1
was obtained in 93% yield;
H
NMR (300 MHz, 2g was obtained in 83% yield; H NMR (300 MHz,
CDCl ): d (ppm) 7.33-7.23 (m, 6H), 6.76-6.69 (m, 2H), 5.30 CDCl ): d (ppm) 8.01 (d, J ¼ 1.8 Hz, 1H), 7.72 (d,
3
3
(
q, J ¼ 0.9 Hz, 1H), 5.10 (s, 2H), 4.36 (broad s, 2H), 2.45 (d, J ¼ 8.7 Hz, 1H), 7.38-7.32 (m, 6H), 6.20 (q, J ¼ 1.2 Hz, 1H),
13
13
J ¼ 0.9 Hz, 3H); C NMR (75 MHz, CDCl ): d (ppm) 164.9, 5.15 (s, 2H), 2.56 (d, J ¼ 1.2 Hz, 3H); C NMR (75 MHz,
3
1
1
57.3, 149.5, 138.2, 137.9, 136.1, 128.4, 128.3, 128.1, 118.9, CDCl ): d (ppm) 164.2, 161.4, 154.1, 152.9, 135.6, 135.1,
3
15.1, 109.9, 109.8, 65.6, 19.7; HRMS (CI) Calcd for 132.6, 128.4, 128.2, 128.1, 126.3, 122.9, 121.9, 118.4, 66.0,
þ
þ
C H ClNO S [M þ H] : 334.0639; found, 334.0643; IR 20.4; HRMS (CI) Calcd for C18
H15ClNO
S
2
[M þ H] :
1
7
17
2
2
(
neat) 3466, 3369, 2958, 2927, 2872, 1712, 1681, 1595, 1476, 376.0233; found, 376.0236; IR (neat) 3088, 3064, 3031, 2952,
1
5
419, 1378, 1274, 1186, 1092, 1028, 945, 908, 839, 695, 2925, 1712, 1609, 1542, 1496, 1454, 1423, 1377, 1333, 1261,
ꢂ1
ꢂ1
97, 500 cm
1170, 1097, 987, 906, 865, 799, 732, 695, 578 cm
4
.10. Benzyl (E)-3-(pyridin-2-ylthio)but-2-enoate (2h)
The reaction was performed with 2-pyridinethiol 1h
55.58 mg, 0.5 mmol, 100 mol%) and compound 2h was
4
.6. Benzyl (E)-3-(2-bromophenylthio)but-2-enoate (2d)
The reaction was performed with 2-bromothiophenol 1d
94.5 mg, 0.5 mmol, 100 mol%) and compound 2d was
(
(
1
1
obtained in quantitative yield;
CDCl ): d (ppm) 8.62-8.60 (m, 1H), 7.69-7.63 (m, 1H),
H
NMR (300 MHz,
obtained
in
84%
yield;
H
NMR
(300 MHz,
3
CDCl ): d (ppm) 7.73-7.61 (m, 1H), 7.62-7.59 (m, 1H),
3
7
.47-7.44 (m, 1H), 7.34-7.32 (m, 5H), 7.26-7.20 (m, 1H),
7
.36-7.28 (m, 7H), 5.26 (q, J ¼ 0.9 Hz, 1H), 5.09 (s, 2H), 2.47
13
5.85 (q, J ¼ 1.2 Hz, 1H), 5.11 (s, 2H), 2.49 (q, J ¼ 1.2 Hz,
(
1
1
d, J ¼ 0.9 Hz, 3H); C NMR (75 MHz, CDCl ): d (ppm)
3
13
3
1
H); C NMR (75 MHz, CDCl ): d (ppm) 164.7, 156.3,
53.6, 150.7, 137.3, 136.0, 128.3, 128.1, 128.0, 122.9, 114.9,
3
64.9, 158.0, 137.5, 136.1, 134.0, 131.5, 130.8, 130.4, 128.46,
28.45, 128.2, 128.0, 110.8, 65.6, 19.9; HRMS (CI) Calcd for
þ
þ
65.6, 20.5; HRMS (CI) Calcd for C H NO S [M þ H] :
16
16
2
C H BrO S [M þ H] : 363.0054; found, 363.0057; IR
1
7
16
2
2
86.0902; found, 286.0904; IR (neat) 3430, 3034, 2924, 2856,
(neat) 3062, 3031, 2950, 1707, 1600, 1446, 1376, 1332, 1257,
ꢂ1
1709, 1603, 1572, 1449, 1417, 1377, 1333, 1170, 1096, 1022,
1
168, 1096, 1019, 824, 747, 694, 595 cm
ꢂ1
7
38, 695 cm
4
.7. Benzyl (E)-3-(2,6-dichlorophenylthio)but-2-enoate (2e)
The reaction was performed with 2,6-dichlorothiophenol 1e
89.5 mg, 0.5 mmol, 100 mol%) and compound 2e was
4
.11. Benzyl (E)-3-(5-(4-nitrophenyl)-1,3,4-oxadiazol-2-
ylthio)but-2-enoate (2i)
(
The reaction was performed with 5-(4-nitrophenyl)-1,3,4-
oxadiazole-2-thiol 1i (111.60 mg, 0.5 mmol, 100 mol%) and
compound 2i was obtained in 75% yield; H NMR
1
obtained in 82% yield; H NMR (300 MHz, CDCl ): d (ppm)
3
7
.47-7.28 (m, 8H), 5.19 (q, J ¼ 1.2 Hz, 1H), 5.09 (s, 2H), 2.48
1
13
(d, J ¼ 1.2 Hz, 3H); C NMR (75 MHz, CDCl ): d (ppm)
3
(
7
5
300 MHz, CDCl ): d (ppm) 7.83 (d, J ¼ 8.4 Hz, 2H), 7.35-
3
1
1
64.8, 156.2, 141.7, 136.1, 131.8, 129.0, 128.4, 128.3, 128.12,
28.10, 109.8, 65.7, 19.7; HRMS (CI) Calcd for C H C O S
.26 (m, 5H), 6.72 (d, J ¼ 9 Hz, 2H), 6.09 (q, J ¼ 0.9 Hz, 1H),
13
17
15 l2 2
.14 (s, 2H), 2.48 (d, J ¼ 0.9 Hz, 3H); C NMR (75 MHz,
þ
[
3
1
M þ H] : 353.0170; found, 353.0176; IR (neat) 3558, 3065,
CDCl ): d (ppm) 168.1, 164.1, 157.1, 151.0, 150.3, 135.7,
3
033, 2953, 1709, 1602, 1555, 1424, 1377, 1333, 1169, 1099,
1
28.9, 128.8, 128.5, 128.3, 117.8, 114.6, 112.5, 66.2, 20.0;
ꢂ1
022, 824, 777, 735, 695, 596 cm
þ
HRMS (CI) Calcd for C H N O S [M þ H] : 398.0811;
19
16 3 5
found, 398.0815; IR (neat) 3447, 3406, 3349, 3224, 2927,
1
7
713, 1601, 1480, 1444, 1334, 1291, 1174, 1071, 947, 837,
37, 696, 594 cm
4
.8. Benzyl (E)-3-(naphthalen-2-ylthio)but-2-enoate (2f)
The reaction was performed with 2-naphthalenethiol 1f
80.1mg, 0.5 mmol, 100 mol%) and compound 2f was obtained
ꢂ1
(
4
.12. Benzyl (E)-3-(2-hydroxyethylthio)but-2-enoate (2j)
1
in 68% yield; H NMR (300MHz, CDCl ): d (ppm) 8.04 (s,
3
1
5
H), 7.89-7.82 (m, 3H), 7.57-7.49 (m, 3H), 7.33-7.27 (m, 5H), The reaction was performed with 2-mercaptoethanol 1j
.37 (q, J ¼ 0.9 Hz, 1H), 5.07 (s, 2H), 2.51 (d, J ¼ 0.9 Hz, 3H); (39 mg, 0.5 mmol, 100 mol%) and compound 2j was
1
3
1
C NMR (75MHz, CDCl ): d (ppm) 165.0, 160.6, 136.2, 135.4, obtained as light brown oil in 92% yield; H NMR
3
1
1
33.7, 133.4, 131.4, 129.4, 128.5,4 128.2, 128.0, 127.9, 127.7, (300 MHz, CDCl ): d (ppm) 7.37-7.26 (m, 5H), 5.62 (s, 1H),
3
27.4, 126.7, 126.6, 110.6, 65.4, 20; HRMS (CI) Calcd for 5.13 (s, 2H), 3.81 (t, J ¼ 6.3 Hz, 2H), 2.97 (t, J ¼ 6.3 Hz, 2H),
þ
13
C H O S [Mþ H] : 335.1106; found, 335.1106; IR (neat) 2.41 (s, 3H); C NMR (75 MHz, CDCl ): d (ppm) 164.8,
21
19
2
3
3
1
053, 3029, 2955, 2927, 2858, 1909, 1595, 1494, 1454, 1378, 158.6, 136.1, 128.5, 128.2, 128.1, 108.5, 65.6, 59.7, 34.1, 20.9;
ꢂ1
þ
323, 1268, 1172, 1098, 1013, 866, 824, 750, 694, 583, 500 cm
HRMS (CI) Calcd for C H O S [M þ H] : 253.0898;
13
17 3

6
R. BIBI ET AL.
found, 253.0896; IR (neat) 3367, 1707, 1591, 1373, 1336,
Oxford, 1992. XIX, 373 S., Broschur 28.50£, geb. 58.95£.-ISBN
0-08-0370675 (Broschur), 0-08-0370667 (geb.). Angew. Chem.
ꢂ1
1
172, 1105, 1025, 832, 740, 696 cm
1
993, 105, 1738–1739. DOI: 10.1002/ange.19931051144;(c)
Woodward, S., Decoding the ‘Black Box’ Reactivity That Is
Organocuprate Conjugate Addition Chemistry. Chem. Soc. Rev.
4.13. Benzyl (E)-3-(tert-butylthio)but-2-enoate (2k)
2
000, 29, 393–401. DOI: 10.1039/B002690P;(d) L oꢀ pez, F.;
Minnaard, A. J.; Feringa, B. L., Catalytic Enantioselective
Conjugate Addition with Grignard Reagents. Acc. Chem. Res.
The reaction was performed with tert-butylthiol 1k (45 mg,
0
.5 mmol, 100 mol%) and compound 2k was obtained as
2
007, 40, 179–188. DOI: 10.1021/ar0501976.
1
colorless oil in 68% yield;
H
NMR (300 MHz,
[
2] (a) Huang, G.; Li, X., Applications of Michael Addition
CDCl ): d (ppm) 7.38-7.34 (m, 5H), 5.92 (q, J ¼ 0.9 Hz,
Reaction in Organic Synthesis. Curr. Org. Synth. 2017, 14,
3
13
568–571.(b) Little, R. D.; Masjedizadeh, M. R.; Wallquist, O.;
1
H), 5.14 (s, 2H), 2.40 (d, J ¼ 0.9 Hz, 3H), 1.47 (s, 9H);
C
Mcloughlin, J. I., The Intramolecular Michael Reaction. In
Organic Reactions; Paquette, L. A., Ed.; 2004; pp 315–552;(c)
Michael, A.; Schulthess, O., Ueber Die Addition Von
Natriumacetessig- Und Natriummalons €a ure €a thern Zu Den
Aethern Unges €a ttigter S €a uren. J Prakt. Chem. 1892, 45, 55–63.
DOI: 10.1002/prac.18910450104.
NMR (75 MHz, CDCl ): d (ppm) 165.0, 128.4, 128.3, 128.2,
3
1
28.1, 87.8, 79.4, 65.5, 46.9, 30.4, 22.2; HRMS (CI) Calcd for
þ
C H O S, 265.1262 [M þ H] : found, 265.1265; IR (neat)
1
5
21 2
3
1
067, 3033, 2959, 1969, 1712, 1589, 1497, 1455, 1327, 1242,
ꢂ1
150, 1081, 1024, 1000, 853, 735, 695, 592 cm
[
3] (a) Nair, D. P.; Podg ꢀo rski, M.; Chatani, S.; Gong, T.; Xi, W.;
Fenoli, C. R.; Bowman, C. N., The Thiol-Michael Addition
Click Reaction:
A Powerful and Widely Used Tool in
4
.14. Benzyl (E)-3-(dodecylthio)but-2-enoate (2l)
Materials Chemistry. Chem. Mater. 2014, 26, 724–744.(b) Ho,
T.-L., Hard Soft Acids Bases (Hsab) Principle and Organic
Chemistry. Chem. Rev. 1975, 75, 1–20. DOI: 10.1021/
cr60293a001;(c) Wadhwa, P.; Kharbanda, A.; Sharma, A.,
Thia-Michael Addition: An Emerging Strategy in Organic
Synthesis. Asian J. Org. Chem. 2018, 7, 634–661. DOI: 10.
1002/ajoc.201700609.
The reaction was performed with 1-dodecanthiol 1l
(101.2 mg, 0.5 mmol, 100 mol%) and compound 2l was
1
obtained
in
82%
yield;
H
NMR
(300 MHz,
CDCl ): d (ppm) 7.40-7.25 (m, 5H), 5.55 (d, J ¼ 0.6 Hz,
3
1
1
H), 5.14 (s, 2H), 2.77-2.72 (s, 2H), 2.41 (d, J ¼ 0.6 Hz, 3H),
13
[
4] (a) Tamura, Y.; Tsugoshi, T.; Mohri, S.; Kita, Y., Michael
Addition to 1,3-Bis(Alkoxycarbonyl)Allenes: Synthesis of
Heterocyclic Compounds Having Glutaconate Structure in the
Molecules. J. Org. Chem. 1985, 50, 1542–1544. DOI: 10.1021/
jo00209a039;.(b) Cheng, Y.; Wang, B.; Wang, X.-R.; Zhang, J.-
H.; Fang, D.-C., An Experimental and Theoretical Study on the
Interaction of N-Heterocyclic Carbene-Derived 1,3-Dipoles with
Methoxycarbonylallenes: Highly Regio- and Stereoselective
.69-1.26 (m, 20H), 0.88 (m, 3H); C NMR (75 MHz,
CDCl ): d (ppm) 164.9, 160.1, 136.4, 128.4, 128.1, 128.0,
3
1
2
07.7, 65.4, 31.8, 31.5, 29.6, 29.5, 29.4, 29.3, 29.0, 28.9, 28.8,
7.4, 22.6, 21.0, 14.1; HRMS (CI) Calcd for C H O S
23
37 2
þ
[
1
8
M þ H] : 377.2516; found, 377.2514; IR (neat) 2921, 2852,
710, 1593, 1455, 1377, 1336, 1258, 1170, 1104, 1025, 953,
ꢂ1
32, 734, 695 cm
[
3 þ 2]-Cycloadditions Controlled by the Structures of N-
Heterocycles of 1,3-Dipoles. J. Org. Chem. 2009, 74, 2357–2367.
DOI: 10.1021/jo802687m;(c) Xia, X.-F.; Zhang, G.-W.; Zhu, S.-
L., Visible-Light-Induced Synthesis of Benzothiophenes and
Benzoselenophenes Via the Annulation of Thiophenols or 1,2-
Diphenyldiselane with Alkynes. Tetrahedron 2017, 73,
5
. Supplementary data
See the attached supporting information file with detailed
experimental procedures and spectra for all compounds. The
single crystal X-ray data associated with this article can be
found at CCDC repository numbers, 1560208 and 1560209.
2727–2730. DOI: 10.1016/j.tet.2017.03.053;(d) Hassan, A. A.;
Mohamed, N. K.; El-Shaieb, K. M. A.; Tawfeek, H. N.; Br €a se, S.;
Nieger, M., The Reactivity of Dimethyl Acetylenedicarboxylate
and Heterocyclization of Hydrazinecarbothioamides to 1,3-
Thiazolidin-4-Ones. J. Heterocycl. Chem. 2016, 53, 46–50. DOI:
1
0.1002/jhet.2392;(e) Avonto, C.; Taglialatela-Scafati, O.;
Disclosure statement
Pollastro, F.; Minassi, A.; Di Marzo, V.; De Petrocellis, L.;
Appendino, G., An Nmr Spectroscopic Method to Identify and
Classify Thiol-Trapping Agents: Revival of Michael Acceptors
for Drug Discovery? Angew. Chem. Int. Ed. 2011, 50, 467–471.
DOI: 10.1002/anie.201005959.
No potential conflict of interest was reported by the author(s).
Funding
[
5] (a) Cabiddu, S.; Cadoni, E.; Ciuffarin, E.; Fattuoni, C.; Floris, C.,
Synthesis of 1,3-Benzodioxoles, 1,3-Benzoxathioles and 1,3-
Benzodithioles from Allenic Derivatives. J. Heterocycl. Chem. 1991,
We are grateful to Higher Education Commission (HEC), Pakistan for
the financial support under the NRPU program (Project No. 20-3069/
NRPU.R&D/13) and Start up Research Grant (Project No. PM-IPFP-
HRD-HEC-2011-402). Rifhat Bibi is thankful to HEC for Indigenous
Ph. D. Fellowship.
2
8, 1573–1580.(b) Doad, G. J. S.; Okor, D. I.; Scheinmann, F.; Bates,
P. A.; Hursthouse, M. B., Cyclophilic Reactions of Allene-1,3-
Dicarboxylic Ester. Part 7. Synthesis of Bicyclic and Tricyclic
Heterocyclic Compounds Involving Nitrogen, Sulphur, and
Carbon as Nucleophiles. J. Chem. Soc., Perkin Trans. 1 1988,
2993–3003. DOI: 10.1039/P19880002993;(c) Sugita, T.; Eida, M.;
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