One-pot synthesis of 1,2,4-oxadiazoles from chalcogen amino acid derivatives under microwave irradiation

Article abstract of DOI:10.1016/j.tet.2021.132222

A series of sulfur- and selenium-bearing, amino acid-derived 1,2,4-oxadiazoles were obtained by a simple procedure. The method consists of EDC-promoted coupling of chalcogen amino acid derivatives with arylamidoximes in acetone, followed by solvent removal and microwave irradiation in water medium. Influence of amidoxime substituents, of the chalcogen atom and of the amino acid side chain is discussed. The results showed this to be a fast, easy and effective method to obtain these compounds, with good functional-group tolerance, potentially favouring future applications in organic synthesis.

Full text of DOI:10.1016/j.tet.2021.132222

Tetrahedron 91 (2021) 132222
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
One-pot synthesis of 1,2,4-oxadiazoles from chalcogen amino acid
derivatives under microwave irradiation
a
a
a
a
b
~
ꢀ
ꢀ
Lucas Wolf , Joao C.P. Mayer , Natalia Quoos , Andre C. Sauer , Ricardo S. Schwab ,
Oscar E.D. Rodrigues a, Luciano Dornelles a
a Departamento de Química, LabSelen-NanoBio, CCNE, Universidade Federal de Santa Maria, Santa Maria, RS, 97105-900, Brazil
,
*
b
~
~
Departamento de Química, Universidade Federal de Sao Carlos, 13565-905, Sao Carlos, SP, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of sulfur- and selenium-bearing, amino acid-derived 1,2,4-oxadiazoles were obtained by a simple
procedure. The method consists of EDC-promoted coupling of chalcogen amino acid derivatives with
arylamidoximes in acetone, followed by solvent removal and microwave irradiation in water medium.
Influence of amidoxime substituents, of the chalcogen atom and of the amino acid side chain is dis-
cussed. The results showed this to be a fast, easy and effective method to obtain these compounds, with
good functional-group tolerance, potentially favouring future applications in organic synthesis.
© 2021 Elsevier Ltd. All rights reserved.
Received 9 March 2021
Received in revised form
1 May 2021
Accepted 7 May 2021
Available online 23 May 2021
Keywords:
1,2,4-oxadiazoles
Organochalcogen
Amino acids
Microwave
Water
1. Introduction
molecules containing selenium and sulfur in modern organic syn-
thesis [7a,11] and asymmetric catalysis [11d,12]. Organoselenium
Heterocycles form, by far, the largest of the classical divisions of
organic chemistry, having been used successfully in different fields,
such as pharmaceutics, agriculture and industry. Most pharma-
ceutical products that mimic natural products with biological ac-
tivity are heterocycles. 1,2,4-oxadiazoles are an important class of
heterocyclic compounds [1] with a broad biological spectrum of
activities, including cytotoxic [2], larvicidal [3], antibiotic [4], anti-
viral [5], antioxidant [6] and anti-inflammatory [6] activities, and
some have also been investigated for their liquid crystal [7] and
fluorescent properties [8].
Accordingly, many methods have appeared in the literature for
the synthesis of 3,5-disubstituted 1,2,4-oxadiazoles [9]. The most
efficient and widely used protocol involves the coupling of an
amidoxime with an activated carboxyl group [10], leading to the
formation of O-acyl amidoximes, which then undergo dehydrative
cyclization.
compounds perform multiple therapeutic functions [11d,13] of
great importance, for example, as antimicrobial [11e,14], anti-
inflammatory [15], anticancer [16], antioxidant [15a,17], antithy-
roid [18], antinociceptive [19], antidepressant [20] and anticon-
vulsant [21] agents, as well as in a variety of situations where free
radicals are involved [22]. The design of new organoselenium
compounds and other developments have attracted considerable
attention, particularly due to the importance of seleno-amino acid
derivatives [23], which have emerged as an exceptional class of
structures in recent years, because of their potential biological ac-
tivity, for example, to protect against neurodegenerative diseases
such as Parkinson's and Alzheimer's diseases [17a,24]. Significant
attention has also been focused on sulfur-containing groups as
model compounds of active sites of both natural enzymes [25] and
catalytic metal surfaces [26].
Much effort has been devoted to the synthesis of 1,2,4-
oxadiazoles under environmentally friendly procedures. Among
them, we can highlight the replacement of hazardous solvents by
more sustainable ones in order to minimize the environmental
impacts caused by the use of toxic and volatile solvents [27]. To help
chemists in the selection of more sustainable practices, many
pharmaceutical companies have elaborated solvent selection
On the other hand, the attention gained by organochalcogen
compounds has been driven by the potential applications of small
* Corresponding author.
E-mail address: ldornel@gmail.com (L. Dornelles).
https://doi.org/10.1016/j.tet.2021.132222
0040-4020/© 2021 Elsevier Ltd. All rights reserved.

L. Wolf, J.C.P. Mayer, N. Quoos et al.
Tetrahedron 91 (2021) 132222
guides [28]. In recent years, numerous reports on the synthesis of
heterocyclic compounds under microwave irradiation conditions
have appeared in the literature [29]. The introduction of new
energy-saving sources, such as microwave irradiation which has
dramatically shortened reaction times and access to reaction con-
ditions that are not attainable under conventional thermal heating
have been also used for the synthesis of 1,2,4-oxadiazoles
[29c,d,30].
lithium hydroxide 1.0 M, affording the chalcogen a-acetamido acid
derivatives 5a-f in good yields [33c].
The amidoximes were prepared using classic procedures from
the corresponding nitriles through a reaction with hydroxylamine
in refluxing ethanol [34].
Due to the efficiency of microwave-promoted synthesis of 1,2,4-
oxadiazoles [30], this method was chosen to synthesize the target
molecules. To identify the best reaction conditions for the synthesis
Based on our insights about the synthesis of amino acid de-
rivatives containing sulfur and selenium atoms and their applica-
tions in biological and asymmetric transformations [12,31] and
considering the increasing importance of synthesizing small li-
braries of compounds with programmed variations of substituents
[10c], we present here an easy and short synthetic route for the
preparation of a new class of 3,5-disubstituted 1,2,4-oxadiazoles,
together with the potential remarkable properties of the chalcogen
amino acid derivatives. The synthesis of these compounds pro-
ceeded smoothly in the eco-friendly solvents acetone and water, in
the absence of an inert atmosphere [32].
of 3,5-disubstituted 1,2,4-oxadiazoles from chalcogen a-acetamido
acid derivatives, a set of experiments was carried out employing
(S)-2-(2-(phenylthio)acetamido)propanoic acid 5a, benzamidox-
ime 6a and N,N0-dicyclohexyl-carbodiimide (DCC) as a model sys-
tem (Table 1). In the first experiment the (S)-2-(2-(phenylthio)
acetamido)propanoic acid 5a was allowed to react with DCC in 1,4-
dioxane under room temperature for 20 min, to allow the activation
of the carboxylic acid moiety. The active intermediate was not
isolated and it immediately reacted in the next step with benza-
midoxime 6a, forming the coupled intermediate, and delivering the
3,5-disubstituted 1,2,4-oxadiazole derivative 7aa after being heated
to 100 ꢀC for 15 min under microwave irradiation, in 80% yield after
purification. Despite the good initial result, this method invariably
produces N,N0-dicyclohexylurea (DCU) as a byproduct, which is
very difficult to remove from the crude product, even by means of
filtering or column chromatography. Thus, another coupling re-
agent, N-(3-(dimethylamino)propyl)-N0-ethylcarbodi-imide hy-
drochloride (EDC) was also tested, as its water-soluble
corresponding urea is easily removed during extraction. In an
attempt to improve the yield, a series of different solvents was
evaluated, including protic polar (H2O), aprotic polar (1,4-dioxane,
CH3CN, THF, DMF, EtOAc and Acetone) and non-polar (Toluene)
solvents (Table 1, entries 1e12) for both DCC and EDC-promoted
reactions.
In tetrahydrofuran (entries 3 and 4) and in acetonitrile (entries 7
and 8), product 7aa was obtained in satisfactory yields (72e87%)
when employing either DCC or EDC coupling reagents. A more
significant discrepancy was observed with solvents 1,4-dioxane
(entries 1 and 2) and toluene (entries 5 and 6), presumably due
to low solubility of EDC in these solvents, in which cases DCC was
more effective.
Many efforts have been made to substitute hazardous solvents
with greener ones [35], which provide better environmental, health
and safety profiles. Prat and co-workers have compiled a solvent
selection guide [28c,d], which classifies solvents as “recom-
mended”, “problematic”, “hazardous”, and “highly hazardous”.
Based on this guide and in order to make our methodology more
sustainable for the synthesis of 3,5-disubstituted 1,2,4-oxadiazoles,
water was chosen as a green solvent for the two steps. Unfortu-
nately, under these conditions, the product was not obtained
employing DCC (entry 11), and only slightly more than traces were
observed for the EDC-coupled product (entry 12).
2. Results and discussion
According to our objectives and as the starting point for the
synthesis of 3,5-disubstituted 1,2,4-oxadiazoles we devised an
efficient method for preparation of chiral chalcogen amino acid
derivatives 5a-f in a short and high-yielding sequence. To accom-
plish this task we used some methodologies previously reported in
the literature [11c,33]. The synthesis of the chalcogen amino acid
derivatives 5a-f is illustrated in Scheme 1. Amino esters 2a-c were
synthesized using the commercially available
L
-amino acids,
alanine 1a, leucine 1b and phenylalanine 1c as starting materials
[33a]. In the next step, the amino esters were then treated with
chloroacetyl chloride at 0 ꢀC in the presence of potassium car-
bonate, followed by a purification step, to afford the compounds
3a-c in good yields [33a]. We then inserted the organochalcogen
moiety into the chloro amides through the nucleophilic attack of
chalcogen anions generated by the reaction of diphenyl diselenide
with NaBH4 in a mixture of THF [33b] and ethanol or thiophenol
with Et3N in MeCN [11c]. The target compounds were obtained in
moderate to good yields; compound 4a was obtained in 92% yield.
Changing the amino acid residue did not produce a pronounced
effect on the yield of the products. However, when selenium was
employed as a nucleophile, the yields were slightly lower in com-
parison to the sulfur analogues. In the final step, the hydrolysis of
methyl ester was achieved by reaction with aqueous solution of
Aiming to achieve good yields for the product 7aa employing a
relatively “green” protocol, we attempted to modify the procedure
by conducting each of the two steps of the reaction in a different
solvent. For this experiment, acetone and water were selected as
solvents. The first step involved the reaction of (S)-2-(2-(phenyl-
thio)acetamido)propanoic acid with DCC or EDC in acetone for
20 min to obtain the reactive intermediate. After this, benzami-
doxime 6a was added and the mixture was homogenized. Acetone
was then removed under vacuum, and water (1.0 mL) was added to
the mixture. The tube was sealed and heated under microwave
irradiation (100 W) at 100 ꢀC for 15 min (Table 1, entries 13 and 14),
furnishing the product in 85 and 83% yields for DCC and EDC-
coupling, respectively. Thus, acetone/water was chosen to carry
out the following experiments.
Scheme 1. Synthetic strategies to prepare chiral chalcogen amino acid derivatives 5a-
f. Reagents and conditions: (i) MeOH, SOCl2, r.t., 12 h; (ii) chloroacetyl chloride, H2O/
ethyl acetate (1:3), K2CO3, r.t., 12 h (iii) PhSeSePh, NaBH4, THF:EtOH (3:1), r.t., 12 h,
under argon atmosphere, or PhSH, triethylamine, MeCN, reflux, 12 h, under argon
atmosphere. (iv) 1.0 M LiOH aqueous solution, THF, r.t., 1 h.
Focusing on the influence of the microwave heating conditions,
2

L. Wolf, J.C.P. Mayer, N. Quoos et al.
Tetrahedron 91 (2021) 132222
Table 1
Synthesis of L-Chalcogen amino acid-derived 1,2,4-oxadiazoles.
Entry
Coupling reagent
Solvent A/B
Temp/time (ꢀC/min)
Yield (%)c
1
2
3
4
5
6
7
8
DCC
EDC
DCC
EDC
DCC
EDC
DCC
EDC
DCC
EDC
DCC
EDC
DCC
EDC
DCC
EDC
DCC
EDC
DCC
EDC
1,4-Dioxanea
1,4-Dioxanea
THFa
100/15
100/15
100/15
100/15
100/15
100/15
100/15
100/15
100/15
100/15
100/15
100/15
100/15
100/15
120/15
120/15
100/10
100/10
100/20
100/20
80
48
72
81
70
55
75
87
50
74
e
THFa
Toluenea
Tolueneaa
MeCNa
MeCNa
9
Acetonea
10
11
12
13
14
15
16
17
18
19
20
Acetonea
H2Oa
H2Oa
2
Acetone/H2Ob
Acetone/H2Ob
Acetone/H2Ob
Acetone/H2Ob
Acetone/H2Ob
Acetone/H2Ob
Acetone/H2Ob
Acetone/H2Ob
85
83
71
72
86
90
80
86
Conditions.
a
i) Chalcogen amino acid derivative 5a (1.0 mmol), EDC or DCC (1.2 equiv.), solvent (1.0 mL), r.t., 20 min; then, benzamidoxime 6a; followed by microwave heating (100 W,
100 ꢀC, 10 min).
b
i) Chalcogen amino acid derivative 5a (1.0 mmol), EDC or DCC (1.2 equiv.), acetone (1.0 mL), r.t., 20 min; then, benzamidoxime 6a. ii) Solvent was then removed under
vacuum; water (1.0 mL) was added, followed by microwave heating (100 W, 100 ꢀC, 10 min).
c
Isolated yields.
we carried out the reaction at different temperatures (100e120 ꢀC)
and times (10e20 min). When temperature was increased to
120 ꢀC, the product yield decreased to 71e72% (entries 15 and 16).
We also standardized the time conditions, as time influenced
product yields, with 10 min being the most appropriate, since the
yields of 7aa increased to 86 and 90% (entries 17 and 18, respec-
tively). Increasing the reaction time to 20 slightly decreased the
yields (entries 19 and 20) when compared to the 10 min reactions.
Notably, N-(3-(dimethylamino)propyl)-N0-ethylcarbodiimide hy-
drochloride (EDC) was selected for its overall better performance
among the screened coupling reagents, furnishing the desired
product in better yields (Table 1), and resulting in an easier puri-
fication step (see Scheme S1 in the Supporting Information for the
proposed reactions mechanisms).
better yields when compared to those bearing electron-
withdrawing groups like chloro and nitro. The nature of the side
chain played a significant role in terms of conversion to the desired
heterocycle, since the results varied according to the parent amino
acid.
In most cases, except for entries 6, 7 and 13, selenium-bearing
examples were obtained in lower yields than their sulfur-bearing
analogues. Characteristically, diphenyl diselenide was detected as
an impurity in all the crude selenium-bearing oxadiazoles 7da-fe,
indicating that decomposition is a major challenge when reacting
these organoselenium compounds. These chalcogen-related yield
differences were thus attributed to the greater sensitivity of orga-
noselenium as compared to organosulfur derivatives.
After optimization of the reaction conditions, the reaction was
extended to a broader range of chiral chalcogen amino acid de-
rivatives 5a-f shown in Scheme 1 and to a set of C-aryl-substituted
amidoximes 6a-e. All reactions were carried out in acetone in the
first step, beginning with EDC-promoted activation of the carbox-
ylic acid for 20 min at room temperature, followed by addition of
the amidoximes 6a-e. Acetone was then removed under vacuum
and water was added. The mixture was heated under microwave
conditions (100 W, 100 ꢀC) for 10 min, and monitored by TLC. The
results are shown in Table 2.
As summarized in Table 2, a series of 3,5-disubstituted 1,2,4-
oxadiazoles was obtained in moderate to good yields. The reac-
tion was performed using sulfur- and selenium-bearing chalcogen
amino acid derivatives with lipophilic (alanine, phenylalanine and
leucine) side chains. The electronic effect of the substituents on the
arylamidoximes was also studied. Arylamidoximes bearing the
electron-donating groups methyl and methoxy usually afforded
3. Conclusions
We have developed an efficient, eco-friendly and broadly
applicable general method for the preparation of new 3,5-
disubstituted 1,2,4-oxadiazoles derivatives containing chalcogen
atoms. These compounds were prepared in moderate to good yields
in a one-pot protocol using environmentally benign solvents and an
easily removable coupling reagent. Moreover, the cyclization was
carried out under microwave irradiation, with water as solvent,
allowing the synthesis of the target compounds in a short reaction
time, followed by an easy workup. Even though a limited number of
substituents have been presented, the method can be extended to
other substrates, since amino acids are inexpensive and easily
available starting materials. The compounds prepared here showed
interesting structures for future biological screenings, which will be
conducted at our institution.
3

L. Wolf, J.C.P. Mayer, N. Quoos et al.
Tetrahedron 91 (2021) 132222
Table 2
Synthesis of 3,5-disubstituted 1,2,4-oxadiazoles 7aa-fe by microwave irradiation.a
Entry
1
Product
Yield (%)b
90
Entry
16
Product
Yield (%)b
5a þ 6a
5a þ 6b
5a þ 6c
5a þ 6d
5a þ 6e
7aa
7 ab
7ac
7ad
7ae
5d þ 6a
5d þ 6b
5d þ 6c
5d þ 6d
5d þ 6e
7da
7 db
7dc
7dd
7de
79
81
59
56
45
2
3
4
5
86
72
64
67
17
18
19
20
6
5b þ 6a
5b þ 6b
5b þ 6c
5b þ 6d
5b þ 6e
5c þ 6a
7ba
7bb
7bc
7bd
7be
7ca
52
57
77
79
57
76
21
22
23
24
25
26
5e þ 6a
5e þ 6b
5e þ 6c
5e þ 6d
5e þ 6e
5f þ 6a
7ea
7eb
7ec
7ed
7ee
7fa
70
73
47
45
41
50
7
8
9
10
11
12
5c þ 6b
7 cb
67
27
5f þ 6b
7 fb
32
4

L. Wolf, J.C.P. Mayer, N. Quoos et al.
Tetrahedron 91 (2021) 132222
Table 2 (continued)
Entry
13
Product
Yield (%)b
35
Entry
28
Product
Yield (%)b
5c þ 6c
5c þ 6d
5c þ 6e
7cc
7cd
7ce
5f þ 6c
5f þ 6d
5f þ 6e
7fc
7fd
7fe
47
38
22
14
15
51
45
29
30
a
Conditions: i) Chalcogen amino acid derivatives 5a-f (1.0 mmol), EDC (1.2 equiv.), acetone (1.0 mL), r.t., 20 min. Then, arylamidoxime 6a-e. ii) Solvent was removed under
vacuum; then, water (1.0 mL) was added, followed by microwave heating (100 W, 100 ꢀC, 10 min).
b
Isolated yields.
4. Experimental section
obtained was used in the next reaction without purification.
4.1.2. General procedure for the synthesis of 3aec [33a]
4.1. General information
Crude -amino ester hydrogen chloride salt (2a-c) (100.0 mmol)
L
Proton nuclear magnetic resonance spectra (1H NMR) were
obtained at 400 MHz in a Brucker Avance III HD NMR spectrometer.
Chemical shifts are reported in ppm, referenced to the solvent peak
of tetramethylsilane (TMS) as the external reference. Data are re-
was dissolved in water (50.0 mL). K2CO3 (41.46 g; 300 mmol) was
added, followed by ethyl acetate (30.0 mL) and the mixture was
cooled in an ice-water bath. The 2-chloroacetyl chloride
(150.0 mmol) in ethyl acetate (50.0 mL) was added dropwise. The
mixture was stirred at room temperature overnight. The solvent
was then removed on a rotary evaporator to near dryness. Then,
saturated NH4Cl and ethyl acetate (3 ꢁ 20.0 mL) were added. The
layers were separated and the organic phase was washed with
brine, dried (MgSO4), filtered and concentrated under reduced
pressure. The crude products were purified by column chroma-
tography on silica gel, using hexane/ethyl acetate (8:2) as the
eluent, furnishing the pure compounds 3a-c.
ported as follows: chemical shift (d) expressed in ppm, multiplicity
(br ¼ broad, s ¼ singlet, d ¼ doublet, dd ¼ double doublet,
t ¼ triplet, q ¼ quartet, m ¼ multiplet), and coupling constant (J) in
Hertz and integrated intensity. Carbon-13 nuclear magnetic reso-
nance (13C NMR) spectra were obtained either at 100 MHz in an
AVANCE III HD NMR spectrometer. Spectra were recorded in CDCl3
or DMSO‑d6 solutions. Chemical shifts are reported in ppm, refer-
enced to the solvent peak of CDCl3 or DMSO‑d6. Samples were
diluted in 1:1 (v/v) acetonitrile:water mixture, containing 0.1%
formic acid. Analyses were performed by infusion mode in an
ACQUITYTM UPLC system from Waters Corp. (Milford, MA, USA)
equipped with sampler manager and quadrupole time of flight (Q-
TOF) MS detector. The Xevo G2 Q-TOF mass spectrometer was
equipped with an electrospray ionization source (ESI). Detections
were performed in positive ion mode and high resolution. Opti-
mized MS conditions were: capillary voltage 2.50 kV, cone voltage
15 V, extractor cone 3.30 V, desolvation gas 300 L/h, cone gas 10 L/h,
desolvation temperature 300 ꢀC, and source temperature 150 ꢀC.
Acquisition mass range was monitored from 50 to 1000 Da. System
control and data acquisition were performed using MassLynx V 4.1
software. Column chromatography was performed using Merck
Silica Gel (230e400 mesh). Thin layer chromatography (TLC) was
performed using Merck Silica Gel GF254 (0.25 mm thickness). For
visualization, TLC plates were placed under ultraviolet light
(254 nm) and then soaked in acidic vanillin, followed by heating.
The product yields included in all Tables refer to isolated yields.
4.1.2.1. (S)-Methyl-2-(2-chloroacetamido)propanoate
(3a).
Yield: 15.27 g, 85%; gum; Rf ¼ 0.45 (Hexane/EtOAc, 8:2). 1H NMR
(400 MHz, CDCl3):
d
¼ 7.14 (s, 1H), 4.52 (q, J ¼ 8.0 Hz, 1H), 3.99 (s,
2H), 3.69 (s, 3H), 1.38 (d, J ¼ 4.0 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d
¼ 172.7, 165.7, 52.4, 48.4, 42.3, 17.9.
4.1.2.2. (S)-Methyl-2-(2-chloroacetamido)-4-methyl-pentanoate
(3b). Yield: 15.52 g, 70%; gum; Rf ¼ 0.40 (Hexane/EtOAc, 8:2). 1H
NMR (400 MHz, CDCl3):
d
¼ 7.11 (d, J ¼ 7.5 Hz, 1H), 4.66e4.61 (m,
1H), 4.08 (s, 2H), 3.75 (s, 3H), 1.72e1.60 (m, 3H), 0.96 (d, J ¼ 6.2 Hz,
6H); 13C NMR (100 MHz, CDCl3):
41.1, 24.7, 22.6, 21.8.
d
¼ 172.7, 165.9, 52.3, 51.0, 42.3,
4.1.2.3. (S)-Methyl-2-(2-chloroacetamido)-3-phenyl-propanoate
(3c). Yield: 17.39 g, 68%; White solid, mp: 73.3e74.5 ꢀC; Rf ¼ 0.40
(Hexane/EtOAc, 8:2). 1H NMR (400 MHz, CDCl3):
d
¼ 7.33e7.26 (m,
3H), 7.13 (d, J ¼ 8.0 Hz, 2H), 7.00 (s, 1H), 4.90e4.85 (m, 1H), 4.00 (s,
2H), 3.73 (s, 3H), 3.21e3.10 (m, 2H); 13C NMR (100 MHz, CDCl3):
d
¼ 171.3, 165.6, 135.5, 129.3, 128.7, 127.3, 53.5, 52.4, 42.4, 37.9.
4.1.1. General procedure for the synthesis of 2aec [33a]
To a suspension of -amino acid (1a-c) (100 mmol) in MeOH
L
(100.0 mL), cooled in an ice-water bath, thionyl chloride (11.89g;
7.25 mL; 100 mmol) was added dropwise while stirring. After this
period, the solvent was evaporated under vacuum and the residue
was dissolved in methanol and precipitated with diethyl ether. The
salt was collected by filtration and washed with diethyl ether to
4.1.3. General procedure for the synthesis of 4aec [11c]
In a twin-necked round-bottom flask under argon atmosphere,
at room temperature, Et3N (25.0 mmol) was added to a solution of
thiophenol (22.0 mmol in 30.0 mL of MeCN). After a solution of
compound 3a-c (20.0 mmol) dissolved in MeCN (20.0 mL) was
added slowly to this solution. The reaction mixture was stirred
give the a-amino esters hydrochlorides 2a-c solids. The white solid
5

L. Wolf, J.C.P. Mayer, N. Quoos et al.
Tetrahedron 91 (2021) 132222
under reflux for 12 h. Following this period, the reaction content
was extracted with dichloromethane (3 ꢁ 30.0 mL) and washed
with saturated aqueous NH4Cl (50.0 mL). The combined organic
layers were dried over anhydrous MgSO4 and filtered. Then, the
solvent was removed under reduced pressure. The crude product
was purified by flash chromatography on silica gel, being eluted
with a mixture of hexane/ethyl acetate.
4.84e4.80 (m, 1H), 3.68 (s, 3H), 3.52 (s, 2H), 3.07e3.04 (m, 2H); 13
NMR (100 MHz, CDCl3):
129.2, 128.7, 127.8, 127.3, 53.8, 52.4, 38.0, 30.3.
C
d
¼ 171.7, 168.5, 135.8, 132.5, 129.5, 129.3,
4.1.5. General procedures for the synthesis of chalcogen a-
acetamido acid derivatives (5a-f) [33c]
30.0 mL (30.0 mmol) of a 1.0 M solution of LiOH(aq) was added to
solution of chalcogen -acetamido ester derivatives (4a-f)
a
a
4.1.3.1. (S)-Methyl-2-[2-phenylthio)acetamido]propanoate
(4a).
(10.0 mmol) in THF (30.0 mL). This mixture was stirred at room
temperature for 1 h (monitored by TLC). After removal of THF under
reduced pressure, the basic aqueous residue was acidified by
addition of aqueous 1.0 M HCl and then extracted with ethyl acetate
(3 ꢁ 20.0 mL). The layers were separated and the organic phase was
washed with brine, dried (MgSO4), filtered and concentrated under
reduced pressure. The crude products were purified by column
chromatography on silica gel, using hexane/ethyl acetate/methanol
as the eluent, affording the pure compounds 5a-f.
Yield: 4.66 g, 92%; White solid, mp: 61.6e63.9 ꢀC; Rf ¼ 0.35 (Hex-
ane/EtOAc, 8:2). 1H NMR (400 MHz, CDCl3):
d
¼ 7.36e7.27 (m, 5H),
7.23e7.21 (m, 1H), 4.58e4.54 (m, 1H), 3.70 (s, 3H), 3.63 (s, 2H), 1.33
(d, J ¼ 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d
¼ 172.9, 167.6,
134.6, 129.3, 129.0, 127.0, 52.5, 48.4, 37.8, 18.2.
4.1.3.2. (S)-Methyl-4-methyl-2-[2-(phenylthio)acetamido]penta-
noate (4b). Yield: 4.90 g, 83%; gum; Rf ¼ 0.35 (Hexane/EtOAc, 8:2).
1H NMR (400 MHz, CDCl3):
d
¼ 7.33e7.26 (m, 4H), 7.21e7.17 (m,1H),
7.09e7.07 (m, 1H), 4.58e4.57 (m, 1H), 3.69 (d, J ¼ 17.2 Hz, 1H); 3.66
(s, 3H), 3.61 (d, J ¼ 17.2 Hz, 1H), 1.62e1.55 (m, 1H), 1.48e1.29 (m,
4.1.5.1. (S)-2-[2-(phenylthio)acetamido]propanoic
acid
(5a).
Yield: 1.67 g, 70%; White solid, mp: 99.0e100.8 ꢀC; Rf ¼ 0.33
22
2H), 0.82 (d, J ¼ 6.0 Hz, 6H); 13C NMR (100 MHz, CDCl3):
d
¼ 172.9,
(Hexane/EtOH, 7:3); [
a
]
¼ 4.40 (c ¼ 0.001; EtOAc). 1H NMR
D
167.7, 134.6, 129.3, 128.6, 126.8, 52.3, 51.1, 41.4, 37.5, 24.7, 22.8, 21.8.
(400 MHz, DMSO‑d6):
d
¼ 8.34 (d, J ¼ 7.0 Hz, 1H), 7.37 (d, J ¼ 8.1 Hz,
2H), 7.31e7.27 (m, 2H), 7.20e7.16 (m, 1H), 4.25 (q, J ¼ 8.0 Hz, 1H),
4.1.3.3. (S)-Methyl-3-phenyl-2-[2-(phenylthio)acetamido]prop-
3.69 (s, 2H), 1.27 (d, J ¼ 8.0 Hz, 3H); 13C NMR (100 MHz, DMSO‑d6):
anoate (4c). Yield: 5.07 g, 77%; White solid. Rf ¼ 0.32 (Hexane/
d
¼ 173.8, 167.6, 136.1, 128.9, 128.1, 125.9, 47.9, 36.3, 17.3. HRMS (TOF
EtOAc, 8:2). 1H NMR (400 MHz, CDCl3):
d
¼ 7.29e7.19 (m, 9H),
MS ESþ) m/z calculated for C11H13NO3S [M þ H]þ: 240.0694; found:
6.98e6.96 (m, 2H), 4.87e4.82 (m, 1H), 3.67 (s, 3H), 3.61 (s, 2H),
240.0673.
3.07e3.04 (m, 2H); 13C NMR (100 MHz, CDCl3)
d
¼ 171.6, 167.8,
135.7, 134.7, 129.4, 129.3, 128.7, 128.6, 127.2, 126.9, 53.5, 52.4, 38.0,
37.7.
4.1.5.2. (S)-4-Methyl-2-[2-(phenylthio)acetamido]pentanoic
acid
(5b). Yield: 2.33 g, 83%; White solid, mp: 125.0e127.6 ꢀC; Rf ¼ 0.32
22
(Hexane/EtOH, 7:3); [
a]
¼ þ3.20 (c ¼ 0.001; EtOAc). 1H NMR
D
4.1.4. General procedure for the synthesis of 4def [33b]
(400 MHz, DMSO‑d6):
d
¼ 8.30 (d, J ¼ 8.0 Hz, 1H), 7.35 (d, J ¼ 7.8 Hz,
Under an argon atmosphere, NaBH4 (0.945 g, 25.0 mmol) was
added to a solution of diphenyl diselenide (11.0 mmol) in THF
(15.0 mL) at room temperature. Ethanol was added dropwise
(3.3 mL) and the mixture was stirred for 10 min. After this time, a
solution of compound (3a-c) (20.0 mmol) in THF (15.0 mL) was
added and the resulting mixture was stirred at room temperature
overnight. Then, saturated NH4Cl and ethyl acetate (3 ꢁ 5.0 mL)
were added. The layers were separated and the organic phase was
washed with brine, dried (MgSO4), filtered and concentrated under
reduced pressure. The crude products were purified by column
chromatography on silica gel, using hexane/ethyl acetate as the
eluent, furnishing the pure compounds 4d-f.
2H), 7.29e7,26 (m, 2H), 7.19e7.16 (m, 1H), 4.25e4.20 (m, 1H), 3.73
(d, J ¼ 14.6 Hz, 1H), 3.65 (d, J ¼ 14.6 Hz, 1H, 1.54e1.49 (m, 3H), 0.85
(d, J ¼ 6.1 Hz, 3H), 0.78 (d, J ¼ 6.1 Hz, 3H); 13C NMR (100 MHz,
DMSO‑d6):
d
¼ 173.9,167.9,136.1,128.9,128.0,125.9, 50.7, 36.2, 24.2,
22.9, 21.3., 21.2. HRMS (TOF MS ESþ) m/z calculated for C14H19NO3S
[M þ H]þ: 282.1164; found: 282.1164.
4.1.5.3. (S)-3-Phenyl-2-[2-(phenylthio)acetamido]propanoic
acid
(5c). Yield: 2.42 g, 77%; White solid, mp: 159.0e161.7 ꢀC; Rf ¼ 0.32
22
(Hexane/EtOH, 7:3); [
(400 MHz, DMSO‑d6):
a]
¼ þ44.80 (c ¼ 0.001; EtOAc). 1H NMR
D
d
¼ 8.40 (d, J ¼ 7.9 Hz, 1H), 7.33e7.18 (m,
10H), 4.49e4.44 (m, 1H), 3.66 (s, 2H), 3.06 (dd, J [1] ¼ 13.8 Hz, J
[2] ¼ 4.6 Hz, 1H), 2.90 (dd, J [1] ¼ 13.7 Hz, J [2] ¼ 9.0 Hz, 1H); 13C
4.1.4.1. (S)-Methyl-2-[2-(phenylselenyl)acetamido]propanoate (4d).
Yield: 4.38 g, 73%; White solid, Rf ¼ 0.35 (Hexane/EtOAc, 8:2); 1H
NMR (100 MHz, DMSO‑d6):
d
¼ 172.6,167.9,137.3,136.1,129.1,128.9,
128.2, 127.8, 126.5, 125.7, 53.7, 36.8, 36.1. HRMS (TOF MS ESþ) m/z
NMR (400 MHz, CDCl3):
d
¼ 7.54e7.52 (m, 2H), 7.25e7.24 (m, 3H),
calculated for C17H17NO3S [M þ H]þ: 316.1007; found: 316.0985.
7.09 (d, J ¼ 6.8 Hz, 1H), 4.47e4.41 (m, 1H), 3.68 (s, 3H), 3.55 (s, 2H),
1.30 (d, J ¼ 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d
¼ 172.6, 168.3,
4.1.5.4. (S)-2-[2-(phenylselenyl)acetamido]propanoic
acid
(5d).
132.4, 128.9, 128.8, 127.3, 52.0, 48.0, 29.7, 17.6.
Yield: 1.71 g, 60%; White solid, mp: 96.0e99.0 ꢀC; Rf ¼ 0.20 (Hex-
22
ane/EtOH, 6:4); [
DMSO‑d6):
a]
¼ ꢂ0.60 (c ¼ 0.001; EtOAc. 1H NMR (400 MHz,
D
4.1.4.2. (S)-Methyl-4-methyl-2-[2-(phenylselenyl)acetamido]penta-
d
¼ 8.35 (d, J ¼ 7.2 Hz, 1H), 7.53 (d, J ¼ 7.2 Hz, 2H),
noate (4e). Yield: 4.31 g, 63%; White solid, Rf ¼ 0.32 (Hexane/EtOAc,
7.31e7.23 (m, 3H), 4.23e4.16 (m, 1H), 3.63 (d, J ¼ 12.6 Hz, 1H), 3.58
8:2); 1H NMR (400 MHz, CDCl3):
d
¼ 7.53e7.50 (m, 2H), 7.28e7.24
(d, J ¼ 12.6 Hz, 1H), 1.23 (d, J ¼ 7.2 Hz, 3H); 13C NMR (100 MHz,
(m, 3H), 6.77 (d, J ¼ 7.9 Hz, 1H), 4.59e4.54 (m, 1H), 3.68 (s, 3H), 3.59
(d, J ¼ 14.6 Hz, 1H), 3.55 (d, J ¼ 14.6 Hz, 1H), 1.62e1.54 (m, 1H),
1.51e1.42 (m, 2H), 0.85 (d, J ¼ 6.4 Hz, 6H); 13C NMR (100 MHz,
DMSO‑d6):
d
¼ 173.8, 168.6, 131.4, 130.3, 129.1, 126.8, 47.8, 28.8, 17.2.
HRMS (TOF MS ESþ) m/z calculated for C11H13NO3Se [M þ H]þ:
288.0139; found: 288.0126.
CDCl3):
30.1, 24.7, 22.8, 21.9.
d
¼ 173.1, 168.5, 132.4, 129.4, 129.3, 127.7, 52.2, 51.2, 41.5,
4.1.5.5. (S)-4-Methyl-2-[2-(phenylselenyl)acetamido] pentanoic acid
(5e). Yield: 1.74 g, 53%; White solid, mp: 139.0e144.0 ꢀC; Rf ¼ 0.20
22
4.1.4.3. (S)-Methyl-3-phenyl-2-[2(phenylselenyl)acetamido]prop-
(Hexane/EtOH, 7:3); [
a
]
¼ ꢂ2.20 (c ¼ 0.001; EtOAc. 1H NMR
D
anoate (4f). Yield: 5.27 g, 70%; White solid, Rf ¼ 0.32 (Hexane/
(400 MHz, DMSO‑d6):
d
¼ 8.15 (d, J ¼ 7.2 Hz, 1H), 7.5547.51 (m, 2H),
EtOAc, 8:2); 1H NMR (400 MHz, CDCl3):
7.26e7.22 (m, 6H), 7.03e7.01 (m, 2H), 6.82 (d, J ¼ 7.2 Hz, 1H),
d
¼ 7.44e7.41 (m, 2H),
7.30e7.22 (m, 3H), 4.25e4.19 (m, 1H), 3.65 (d, J ¼ 12.6 Hz, 1H), 3.57
(d, J ¼ 12.6 Hz, 1H), 1.63e1.53 (m, 1H), 1.51e1.47 (m, 2H), 0.87 (d,
6

L. Wolf, J.C.P. Mayer, N. Quoos et al.
Tetrahedron 91 (2021) 132222
J ¼ 6.4 Hz, 3H), 0.82 (d, J ¼ 6.4 Hz, 3H); 13C NMR (100 MHz,
129.4, 129.2, 128.9, 127.3, 126.9, 123.5, 43.0, 37.7, 21.4, 19.4. HRMS
(TOF MS ESþ) m/z calculated for C19H19N3O2S [M þ H]þ: 354.1276;
found: 354.1271.
DMSO‑d6):
d
¼ 173.5, 168.7, 131.3, 130.1, 128.9, 126.6, 50.4, 28.8, 24.1,
22.6, 21.3, 21.2. HRMS (TOF MS ESþ) m/z calculated for C14H19NO3Se
[M þ H]þ: 330.0608; found: 330.0601.
4.1.7.3. (S)-N-{1-[3-(4-methoxyphenyl)-1,2,4-oxadiazol-5-yl]ethyl}-
4.1.5.6. (S)-3-Phenyl-2-[2-(phenylselenyl)acetamido] propanoic acid
2-(phenylthio)acetamide (7ac). Yield: 265.8 mg, 72%; White solid,
23
(5f). Yield: 2.64 g, 73%; White solid, mp: 155.0e159.0 ꢀC; Rf ¼ 0.24
mp: 77.0e78.5 ꢀC; Rf ¼ 0.29 (Hexane/EtOAc, 8:2); [
a
]
¼ ꢂ72.70
D
22
(Hexane/EtOH, 7:3); [
a
]
¼ þ55.00 (c ¼ 0.001; EtOAc). 1H NMR
(c ¼ 0.01; MeOH). 1H NMR (400 MHz, CDCl3):
¼ 7.94 (d, J ¼ 8.9 Hz,
d
D
(400 MHz, DMSO‑d6):
d
¼ 8.36 (d, J ¼ 8.0 Hz,1H), 7.49e7.47 (m, 2H),
2H), 7.54 (d, J ¼ 7.9 Hz, 1H), 7.36 (d, J ¼ 7.9 Hz, 2H), 7.27e7.23 (m,
2H), 7.19e7.15 (m, 1H), 6.95 (d, J ¼ 8.9 Hz, 2H), 5.43e5.35 (m, 1H),
3.83 (s, 3H), 3.67 (s, 2H), 1.54 (d, J ¼ 7.1 Hz, 3H); 13C NMR (100 MHz,
7.26e7.19 (m, 8H), 4.50e4.45 (m, 1H), 3.60 (s, 2H), 3.06 (dd,
J1 ¼ 14.0 Hz, J2 ¼ 5.2 Hz, 1H), 2.91 (dd, J1 ¼14.0 Hz, J2 ¼ 5.2 Hz, 1H);
13C NMR (100 MHz, DMSO‑d6):
d
¼ 172.5, 168.8, 137.3, 131.2, 130.4,
CDCl3):
d
¼ 178.6, 167.8, 167.7, 161.9, 134.2, 129.1, 128.9, 128.9 (2C),
129.0, 129.0, 128.1, 126.6, 126.3, 53.6, 36.8, 28.8. HRMS (TOF MS
ESþ) m/z calculated for C17H17NO3Se [M þ H]þ: 364.0452; found:
364.0443.
126.8, 118.7, 114.1, 55.2, 42.9, 37.6, 19.2. HRMS (TOF MS ESþ) m/z
calculated for C19H19N3O3S [M þ H]þ: 370.1225; found: 370.1202.
4.1.7.4. (S)-N-{1-[3-(4-nitrophenyl)-1,2,4-oxadiazol-5-yl]ethyl}-2-
4.1.6. General procedures for the synthesis of arylamidoximes (6a-
e) [33]
(phenylthio)acetamide (7ad). Yield: 245.8 mg, 64%; White solid,
23
mp: 92.0e93.5 ꢀC; Rf ¼ 0.28 (Hexane/EtOAc, 8:2); [
a
]
¼ ꢂ42.50
D
NH2OH$HCl (66.0 mmol) was slowly added to a stirred solution
of the corresponding nitrile (30.0 mmol) and Et3N (69.0 mmol) in
ethanol (50.0 mL) at room temperature. The mixture was heated at
75 ꢀC until complete disappearance of the starting material (as
monitored by TLC). Then, the solvent was removed on a rotary
evaporator to near dryness. Saturated NH4Cl and ethyl acetate
(3 ꢁ 30.0 mL) were then added. The combined organic layers were
dried over MgSO4 and evaporated on a rotary evaporator. The res-
idue was purified by flash chromatography on silica gel using
hexane/ethyl acetate (7:3) as the eluent.
(c ¼ 0.01; MeOH). 1H NMR (400 MHz, CDCl3):
¼ 8.31 (d, J ¼ 8.8 Hz,
d
2H), 8.19 (d, J ¼ 8.8 Hz, 2H), 7.43 (d, J ¼ 7.8 Hz,1H), 7.36 (d, J ¼ 7.9 Hz,
2H), 7.31e7.28 (m, 2H), 7.24e7.20 (m, 3H), 5.49e5.41 (m, 1H), 3.71
(s, 2H), 1.61 (d, J ¼ 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3):
¼ 180.1,
d
167.7, 166.8, 149.6, 134.2, 132.3, 129.3, 128.7, 128.5, 127.0, 124.0, 43.1,
37.5, 19.3. HRMS (TOF MS ESþ) m/z calculated for C18H16N4O4S
[(M þ H)þ]: 385.0971; found: 385.0969.
4.1.7.5. (S)-N-{1-[3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl]ethyl}-2-
(phenylthio)acetamide (7ae). Yield: 250.0 mg, 67%; White solid,
23
mp: 86.0e87.0 ꢀC; Rf ¼ 0.38 (Hexane/EtOAc, 8:2); [
a
]
¼ ꢂ46.32
D
4.1.7. General procedures for the synthesis of 1,2,4-oxadiazoles
(7aa-fe) [29d]
(c ¼ 0.01; MeOH). 1H NMR (400 MHz, CDCl3):
¼ 7.94 (d, J ¼ 8.5 Hz,
d
2H), 7.47e7.42 (m, 3H), 7.35 (d, J ¼ 7.7 Hz, 2H), 7.29e7.26 (m, 2H),
7.22e7.18 (m, 1H), 5.45e5.38 (m, 1H), 3.69 (s, 2H), 1.57 (d, J ¼ 7.1 Hz,
In a sealed tube in a microwave reactor, 1.0 mmol of chalcogen
a
-acetamido acid derivatives (5a-f) was added to EDC.HCl
3H); 13C NMR (100 MHz, CDCl3):
d
¼ 179.3, 167.6, 167.4, 137.5, 134.2,
(1.1 mmol, 0.199 g) and the two were dissolved in acetone (1.0 mL).
The mixture was magnetically stirred for approximately 20 min to
form the reactive intermediate. After this time, 1.1 mmol of aryla-
midoxime (6a-e) was added and the mixture was homogenized.
The acetone was removed in a rotary evaporator without heating
and H2O (1.0 mL) was added to the mixture. The tube was sealed
and placed into a microwave irradiation CEM Discover® at 100 W
power, temperature of 100 ꢀC for 10 min. Then, saturated NH4Cl and
ethyl acetate (3 ꢁ 5.0 mL) were added. The combined organic layers
were dried over MgSO4 and evaporated on a rotary evaporator. The
crude products were purified by column chromatography on silica
gel, using hexane/ethyl acetate as the eluent, furnishing the pure
products 7aa-fe.
129.3, 129.1, 128.8, 128.7, 127.0, 124.9, 43.0, 37.6, 19.4. HRMS (TOF
MS ESþ) m/z calculated for C18H16ClN3O2S [M þ Na]þ: 396.0549;
found: 396.0559.
4.1.7.6. (S)-N-[3-methyl-1-(3-phenyl-1,2,4-oxadiazol-5-yl)butyl]-2-
(phenylthio)acetamide (7ba). Yield: 225.2 mg, 52%; White solid,
23
mp: 75.6e77.5 ꢀC; Rf ¼ 0.51 (Hexane/EtOAc, 8:2); [
a]
¼ ꢂ29.76
D
(c ¼ 0.01; MeOH). 1H NMR (400 MHz, CDCl3):
¼ 8.01 (d, J ¼ 8.2 Hz,
d
2H), 7.51e7.43 (m, 3H), 7.36e7.32 (m, 3H), 7.28e7.24 (m, 2H),
7.19e7.15 (m, 1H), 5.46e5.40 (m, 1H), 3.75 (d, J ¼ 16.9 Hz, 1H), 3.66
(d, J ¼ 16.9 Hz, 1H), 1.82e1.69 (m, 2H), 1.49e1.39 (m, 1H), 0.88 (d,
J ¼ 6.6 Hz, 6H); 13C NMR (100 MHz, CDCl3):
d
¼ 178.9, 168.1, 167.7,
134.0, 131.2, 129.2, 128.7, 128.3, 127.4, 126.8, 126.3, 45.2, 42.5, 37.2,
24.4, 22.6, 21.5. HRMS (TOF MS ESþ) m/z calculated for
4.1.7.1. (S)-N-[1-(3-phenyl-1,2,4-oxadiazol-5-yl)ethyl]-2-(phenyl-
thio)-acetamide (7aa). Yield: 305.2 mg, 90%; White solid, mp:
C
21H23N3O2S [M þ H]þ: 382.1589; found: 382.1603.
23
81.0e82.0 ꢀC; Rf ¼ 0.32 (Hexane/EtOAc, 8:2); [
a]
¼ ꢂ97.94
4.1.7.7. (S)-N-{3-methyl-1-[3-(p-tolyl)-1,2,4-oxadiazol-5-yl]butyl}-
2-(phenylthio)acetamide (7bb). Yield: 198.2 mg, 57%; White solid,
D
(c ¼ 0.01; MeOH). 1H NMR (400 MHz, CDCl3):
d
¼ 8.00 (d, J ¼ 8.0 Hz,
23
2H), 7.56 (d, J ¼ 7.9 Hz, 1H), 7.49e7.40 (m, 3H), 7.35 (d, J ¼ 8.1 Hz,
mp: 63.8e67.3 ꢀC; Rf ¼ 0.53 (Hexane/EtOAc, 8:2); [
a
]
D
¼ ꢂ55.85
2H), 7.26e7.22 (m, 2H), 7.18e7.14 (m, 1H), 5.44e5.36 (m, 1H), 3.66
(c ¼ 0.01; MeOH). 1H NMR (400 MHz, CDCl3):
¼ 7.90 (d, J ¼ 8.2 Hz,
d
(s, 2H), 1.54 (d, J ¼ 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d
¼ 179.1,
2H), 7.34 (d, J ¼ 7.2 Hz, 2H), 7.30 (d, J ¼ 8.8 Hz, 1H), 7.28e7.24 (m,
4H), 7.19e7.16 (m, 1H), 5.45e5.39 (m, 1H), 3.74 (d, J ¼ 16.9 Hz, 1H),
3.65 (d, J ¼ 16.9 Hz, 1H), 2.40 (s, 3H), 1.81e1.68 (m, 2H), 1.50e1.40
(m, 1H), 0.88 (d, J ¼ 6.6 Hz, 6H); 13C NMR (100 MHz, CDCl3):
168.2, 167.8, 134.3, 131.3, 129.2, 129.0, 128.8, 127.4, 127.0, 126.4, 43.0,
37.7, 19.3. HRMS (TOF MS ESþ) m/z calculated for C18H17N3O2S [M þ
H]þ: 340.1120; found: 340.1124.
d
¼ 178.8, 168.2, 167.6, 141.6, 134.2, 129.5, 129.3, 128.6, 127.4, 126.9,
4.1.7.2. (S)-2-(phenylthio)-N-{1-[3-(p-tolyl)-1,2,4-oxadiazol-5-yl]
ethyl}-acetamide (7 ab). Yield: 303.7 mg, 86%; White solid, mp:
123.7, 45.4, 42.7, 37.4, 24.5, 22.6, 21.7, 21.5. HRMS (TOF MS ESþ) m/z
calculated for C22H25N3O2S [M þ Na]þ: 418.1565; found: 418.1559.
23
84.0e87.5 ꢀC; Rf ¼ 0.35 (Hexane/EtOAc, 8:2); [
a]
¼ ꢂ90.52
D
(c ¼ 0.01; MeOH). 1H NMR (400 MHz, CDCl3):
d
¼ 7.90 (d, J ¼ 8.1 Hz,
4.1.7.8. (S)-N-{1-[3-(4-methoxyphenyl)-1,2,4-oxadiazol-5-yl]-3-
2H), 7.50 (d, J ¼ 7.6 Hz,1H, 7.36 (d, J ¼ 7.8 Hz, 2H), 7.28e7.16 (m, 5H),
5.44e5.37 (m, 1H), 3.67 (s, 2H), 2.39 (s, 3H), 1.55 (d, J ¼ 7.1 Hz, 3H);
methylbutyl}-2-(phenylthio)acetamide(7bc). Yield: 316.6 mg, 77%;
White solid, mp: 63.8e68.3 ꢀC; Rf ¼ 0.44 (Hexane/EtOAc, 8:2);
23
13C NMR (100 MHz, CDCl3):
d
¼ 178.8, 168.1, 167.6, 141.5, 134.2,
[
a
]
¼ ꢂ29.88 (c ¼ 0.01; MeOH). 1H NMR (400 MHz, CDCl3):
D
7

L. Wolf, J.C.P. Mayer, N. Quoos et al.
Tetrahedron 91 (2021) 132222
d
¼ 7.95 (d, J ¼ 8.9 Hz, 2H), 7.35e7.32 (m, 3H), 7.27e7.24 (m, 2H),
129.2, 129.1 (2C), 128.7, 128.6, 128.5, 127.3, 126.9, 118.9, 114.2, 55.3,
48.1, 39.3, 37.5. HRMS (TOF MS ESþ) m/z calculated for C25H23N3O3S
[M þ H]þ: 446.1538; found: 446.1526.
7.19e7.15 (m,1H), 6.96 (d, J ¼ 8.9 Hz, 2H), 5.44e5.38 (m,1H), 3.85 (s,
3H), 3.74 (d, J ¼ 16.8 Hz, 1H), 3.66 (d, J ¼ 16.8 Hz, 1H), 1.81e1.68 (m,
2H), 1.51e1.40 (m, 1H), 0.88 (d, J ¼ 6.6 Hz, 6H); 13C NMR (100 MHz,
CDCl3):
d
¼ 178.6, 167.9, 167.6, 162.0, 134.1, 129.2, 129.0, 128.5, 126.8,
4.1.7.14. (S)-N-{1-[3-(4-nitrophenyl)-1,2,4-oxadiazol-5-yl]-2-
118.9, 114.2, 55.3, 45.3, 42.6, 37.3, 24.5, 22.5, 21.6. HRMS (TOF MS
ESþ) m/z calculated for C22H25N3O3S [M þ Na]þ: 434.1514; found:
434.1521.
phenylethyl}-2-(phenylthio)acetamide (7cd). Yield: 142.6 mg, 51%;
White solid, mp: 133.5e137.0 ꢀC; Rf ¼ 0.39 (Hexane/EtOAc, 8:2);
23
[
d
a
]
D
¼ ꢂ18.98 (c ¼ 0.01; EtOAc). 1H NMR (400 MHz, CDCl3):
¼ 8.30 (d, J ¼ 8.9 Hz, 2H), 8.17 (d, J ¼ 8.9 Hz, 2H), 7.44 (d, J ¼ 8.1 Hz,
4.1.7.9. (S)-N-{3-methyl-1-[3-(4-nitrophenyl)-1,2,4-oxadiazol-5-yl]
1H), 7.27e7.18 (m, 8H), 7.01e6.99 (m, 2H), 5.69e5.64 (m, 1H), 3.65
butyl}-2-(phenylthio)acetamide(7bd). Yield: 336.6 mg, 79%; White
(s, 2H), 3.29e3.26 (m, 2H); 13C NMR (100 MHz, CDCl3):
d
¼ 178.9,
solid, mp: 85.8e86.3 ꢀC; Rf
¼
0.48 (Hexane/EtOAc, 8:2);
167.9, 166.7, 149.5, 134.4, 134.2, 132.2, 129.3, 129.0, 128.8, 128.5,
128.4, 127.5, 126.9, 124.0, 48.1, 39.2, 37.3. HRMS (TOF MS ESþ) m/z
calculated for C24H20N4O4S [M þ Na]þ: 483.1103; found: 483.1086.
23
[
a
]
¼ ꢂ27.10 (c ¼ 0.01; EtOAc). 1H NMR (400 MHz, CDCl3):
D
d
¼ 8.29 (d, J ¼ 8.9 Hz, 2H), 8.18 (d, J ¼ 9.0 Hz, 2H), 7.33 (d, J ¼ 7.9 Hz,
2H), 7.29e7.22 (m, 3H), 7.20e7.17 (m, 1H), 5.46e5.40 (m, 1H), 3.74
(d, J ¼ 16.8 Hz, 1H), 3.67 (d, J ¼ 16.8 Hz, 1H), 1.85e1.72 (m, 2H),
1.56e1.45 (m, 1H), 0.91 (d, J ¼ 6.6 Hz, 3H), 0.90 (d, J ¼ 6.6 Hz, 3H);
4.1.7.15. (S)-N-{1-[3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl]-2-
phenylethyl}-2-(phenylthio)acetamide (7ce). Yield: 202.1 mg, 45%;
13C NMR (100 MHz, CDCl3):
d
¼ 180.1, 167.8, 166.8, 149.7, 134.3,
White solid, mp: 116.5e120.0 ꢀC; Rf ¼ 0.51 (Hexane/EtOAc, 8:2);
23
132.5, 129.3, 128.5 (2C), 126.9, 124.0, 45.6, 42.6, 37.4, 24.7, 22.5, 21.7.
HRMS (TOF MS ESþ) m/z calculated for C21H22N4O4S [M þ Na]þ:
449.1259; found: 449.1266.
[
a
]
D
¼ ꢂ7.46 (c ¼ 0.01; EtOAc). 1H NMR (400 MHz, CDCl3):
¼ 7.92
d
(d, J ¼ 8.7 Hz, 2H), 7.50 (d, J ¼ 8.3 Hz, 1H), 7.43 (d, J ¼ 8.6 Hz, 2H),
7.27e7.17 (m, 8H), 6.98e6.96 (m, 2H), 5.67e5.62 (m, 1H), 3.64 (s,
2H), 3.26e3.23 (m, 2H); 13C NMR (100 MHz, CDCl3):
d
¼ 178.1, 167.8,
4.1.7.10. (S)-N-{1-[3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl]-3-
167.3, 137.4, 134.4, 134.1 (2C), 129.2, 129.1, 129.0, 128.7, 128.3, 127.4,
methylbutyl}-2-(phenylthio)acetamide (7be). Yield: 236.6 mg, 57%;
126.8, 124.7, 48.0, 39.2, 37.3. HRMS (TOF MS ESþ) m/z calculated for
White solid, mp: 81.0e82.0 ꢀC; Rf ¼ 0.47 (Hexane/EtOAc, 8:2);
C
24H20ClN3O2S [M þ H]þ: 450.1043; found: 450.1028.
23
[
d
a
]
¼ ꢂ28.46 (c ¼ 0.01; EtOAc). 1H NMR (400 MHz, CDCl3):
D
¼ 7.94 (d, J ¼ 8.7 Hz, 2H), 7.43 (d, J ¼ 8.7 Hz, 2H), 7.34e7.31 (m,
4.1.7.16. (S)-N-[1-(3-phenyl-1,2,4-oxadiazol-5-yl)ethyl]-2-(phenyl-
selenyl)acetamide(7da). Yield: 305.8 mg, 79%; White solid, mp:
3H), 7.28e7.24 (m, 2H), 7.20e7.16 (m, 1H), 5.44e5.38 (m, 1H), 3.75
(d, J ¼ 16.9 Hz, 1H), 3.67 (d, J ¼ 16.9 Hz, 1H), 1.81e1.69 (m, 2H),
1.50e1.40 (m, 1H), 0.88 (d, J ¼ 6.6 Hz, 6H); 13C NMR (100 MHz,
23
76.5e80.0 ꢀC; Rf ¼ 0.22 (Hexane/EtOAc, 8:2); [
a
]
D
¼ ꢂ22.52
(c ¼ 0.01; EtOAc). 1H NMR (400 MHz, CDCl3):
¼ 8.03 (d, J ¼ 8.2 Hz,
d
CDCl3):
d
¼ 179.2, 167.8, 167.4, 137.4, 134.1, 129.3, 129.1, 128.8, 128.4,
2H), 7.56e7.54 (m, 2H), 7.50e7.44 (m, 3H), 7.26e7.24 (m, 3H), 7.10
(d, J ¼ 8.0 Hz, 1H), 5.43e5.36 (m, 1H), 3.59 (s, 2H), 1.54 (d, J ¼ 7.1 Hz,
126.9,125.0, 45.4, 42.5, 37.2, 24.5, 22.5, 21.6. HRMS (TOF MS ESþ) m/
z calculated for C21H22ClN3O2S [M þ H]þ: 416.1200; found:
416.1220.
3H); 13C NMR (100 MHz, CDCl3):
d
¼ 179.1, 168.4, 168.2, 132.8, 131.3,
129.4, 128.8, 128.6, 127.9, 127.4, 126.4, 43.1, 30.0, 19.5. HRMS (TOF
MS ESþ) m/z calculated for C18H17N3O2Se [M þ H]þ: 410.0384;
found: 410.0370.
4.1.7.11. (S)-N-[2-phenyl-1-(3-phenyl-1,2,4-oxadiazol-5-yl)ethyl]-2-
(phenylthio)acetamide (7ca). Yield: 315.5 mg, 76%; White solid, mp:
23
67.0e70.5 ꢀC;Rf ¼ 0.43 (Hexane/EtOAc, 8:2); [
a
]
¼ ꢂ16.84
4.1.7.17. (S)-2-(phenylselenyl)-N-{1-[3-(p-tolyl)-1,2,4-oxadiazol-5-
yl]ethyl}acetamide (7 db). Yield: 324.9 mg, 81%; White solid, mp:
D
(c ¼ 0.01; EtOAc). 1H NMR (400 MHz, CDCl3):
d
¼ 8.00 (d, J ¼ 6.8 Hz,
23
2H), 7.51e7.42 (m, 4H), 7.25e7.18 (m, 8H), 6.99e6.97 (m, 2H),
94.5e98.0 ꢀC; Rf ¼ 0.25 (Hexane/EtOAc, 8:2); [
a
]
¼ ꢂ19.72
D
5.68e5.62 (m, 1H), 3.63 (s, 2H), 3.26e3.24 (m, 2H); 13C NMR
(c ¼ 0.01; EtOAc). 1H NMR (400 MHz, CDCl3):
¼ 7.92 (d, J ¼ 8.1 Hz,
d
(100 MHz, CDCl3):
d
¼ 177.9, 168.2, 167.7, 134.6, 134.2, 131.3, 129.3,
2H), 7.57e7.54 (m, 2H), 7.28e7.23 (m, 5H), 7.04 (d, J ¼ 8.1 Hz, 1H)],
5.42e5.35 (m, 1H), 3.60 (s, 2H), 2.41 (s, 3H), 1.54 (d, J ¼ 7.1 Hz, 3H);
129.1, 128.8, 128.7, 128.6, 127.5, 127.4, 126.9, 126.4, 48.1, 39.4, 37.5.
HRMS (TOF MS ESþ) m/z calculated for C24H21N3O2S [M þ Na]þ:
438.1252; found: 438.1246.
13C NMR (100 MHz, CDCl3):
d
¼ 179.1, 168.4 (2C), 141.8, 133.1, 129.7,
129.6, 128.8, 128.1, 127.6, 123.7, 43.3, 30.3, 19.8. HRMS (TOF MS ESþ)
m/z calculated for C19H19N3O2Se [M þ H]þ: 402.0721; found:
402.0715.
4.1.7.12. (S)-N-{2-phenyl-1-[3-(p-tolyl)-1,2,4-oxadiazol-5-yl]ethyl}-
2-(phenylthio)acetamide (7 cb). Yield: 287.5 mg, 67%; White solid,
23
mp: 80.5e82.5 ꢀC; Rf ¼ 0.46 (Hexane/EtOAc, 8:2); [
a
]
D
¼ ꢂ5.28
4.1.7.18. (S)-N-{1-[3-(4-methoxyphenyl)-1,2,4-oxadiazol-5-yl]ethyl}-
2-(phenylselenyl)acetamide (7dc). Yield: 246.1 mg, 59%; White
(c ¼ 0.01; EtOAc). 1H NMR (400 MHz, CDCl3):
d
¼ 7.89 (d, J ¼ 8.2 Hz,
2H), 7.46 (d, J ¼ 8.4 Hz, 1H), 7.24e7.16 (m, 10H), 6.99e9.97 (m, 2H),
solid, mp: 83.6e84.8 ꢀC; Rf
¼
0.21 (Hexane/EtOAc, 8:2);
23
5.67e5.61 (m, 1H), 3.63 (s, 2H), 3.26e3.23 (m, 2H), 2.40 (s, 3H); 13
NMR (100 MHz, CDCl3):
C
[
a
]
D
¼ ꢂ22.84 (c ¼ 0.01; EtOAc). 1H NMR (400 MHz, CDCl3):
d
¼ 177.6, 168.1, 167.7, 141.6, 134.6, 134.2,
d
¼ 7.98 (d, J ¼ 9.0 Hz, 2H), 7.57e7.55 (m, 2H), 7.27e7.25 (m, 3H),
129.4, 129.2, 129.1, 128.6 (2C), 127.4, 127.3, 126.8, 123.5, 48.0, 39.3,
37.5, 21.5. HRMS (TOF MS ESþ) m/z calculated for C25H23N3O2S
[M þ Na]þ: 452.1409; found: 452.1409.
7.0l (s, 1H), 6.98 (d, J ¼ 9.0 Hz, 2H), 5.42e5.34 (m, 1H), 3.87 (s, 3H),
3.60 (s, 2H), 1.54 (d, J ¼ 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d
¼ 178.8, 168.3, 167.9, 162.0, 132.9, 129.4, 129.1, 128.6, 118.9, 114.2,
55.3, 43.2, 30.1, 19.6. HRMS (TOF MS ESþ) m/z calculated for
4.1.7.13. (S)-N-{1-[3-(4-methoxyphenyl)-1,2,4-oxadiazol-5-yl]-2-
C
19H19N3O3Se [M þ H]þ: 418.0670; found: 418.0662.
phenylethyl}-2-(phenylthio)acetamide(7 cc). Yield: 155.8 mg, 35%;
White solid, mp: 70.0e75.0 ꢀC; Rf ¼ 0.37 (Hexane/EtOAc, 8:2);
4.1.7.19. (S)-N-{1-[3-(4-nitrophenyl)-1,2,4-oxadiazol-5-yl]ethyl}-2-
23
[
a
]
¼ ꢂ0.42 (c ¼ 0.01; EtOAc). 1H NMR (400 MHz, CDCl3):
d
¼ 7.94
(phenylselenyl)acetamide (7dd). Yield: 25.9 mg, 56%; Yellow solid,
D
23
(d, J ¼ 9.0 Hz, 2H), 7.42 (d, J ¼ 8.3 Hz, 1H), 7.26e7.21 (m, 4H),
mp: 94.0e98.8 ꢀC; Rf ¼ 0.19 (Hexane/EtOAc, 8:2); [
a
]
D
¼ ꢂ10.78
7.19e7.17 (m, 4H), 7.00e6.97 (m, 2H), 6.95 (d, J ¼ 9.0 Hz, 2H),
(c ¼ 0.01; EtOAc). 1H NMR (400 MHz, CDCl3):
¼ 8.33 (d, J ¼ 8.9 Hz,
d
5.65e5.60 (m, 1H), 3.84 (s, 3H), 3.62 (s, 2H), 3.25e3.23 (m, 2H); 13
C
2H), 8.22 (d, J ¼ 8.9 Hz, 2H), 7.56e7.54 (m, 2H), 7.28e7.26 (m, 3H),
6.96 (d, J ¼ 6.9 Hz, 1H), 5.46e5.39 (m, 1H), 3.62 (s, 2H), 1.58 (d,
NMR (100 MHz, CDCl3):
d
¼ 177.6, 167.9, 167.7, 162.0, 134.7, 134.3,
8

L. Wolf, J.C.P. Mayer, N. Quoos et al.
Tetrahedron 91 (2021) 132222
J ¼ 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d
¼ 180.1, 168.4, 166.8,
H]þ: 475.0885; found: 475.0867.
149.6, 132.6, 132.3, 129.5, 128.5, 128.0, 126.6, 124.1, 43.3, 30.0, 19.5.
HRMS (TOF MS ESþ) m/z calculated for C18H16N4O4Se [M þ H]þ:
433.0415; found: 433.0429.
4.1.7.25. (S)-N-{1-[3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl]-3-
methylbutyl}-2-(phenylselenyl)acetamide(7ee). Yield: 189.8 mg,
41%; White solid, mp: 78.3e82.4 ꢀC; Rf ¼ 0.56 (Hexane/EtOAc, 8:2);
23
4.1.7.20. (S)-N-{1-[3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl]ethyl}-2-
[
d
a
]
D
¼ ꢂ15.90 (c ¼ 0.01; EtOAc). 1H NMR (400 MHz, CDCl3):
(phenylselenyl)acetamide (7de). Yield: 189.4 mg, 45%; Yellow solid,
¼ 7.97 (d, J ¼ 8.6 Hz, 2H), 7.52e7.50 (m, 2H), 7.44 (d, J ¼ 8.7 Hz,
23
mp: 110.0e114.0 ꢀC; Rf ¼ 0.21 (Hexane/EtOAc, 8:2); [
a
]
¼ ꢂ1.02
2H), 7.25e7.23 (m, 3H), 6.96 (d, J ¼ 8.6, 1H), 5.42e5.36 (m, 1H), 3.64
(d, J ¼ 14.8 Hz, 1H), 3.59 (d, J ¼ 14.8 Hz, 1H), 1.80e1.67 (m, 2H),
1.55e1.45 (m, 1H), 0.91 (d, J ¼ 6.6 Hz, 3H), 0.90 (d, J ¼ 6.6 Hz, 3H);
D
(c ¼ 0.01; EtOAc). 1H NMR (400 MHz, CDCl3):
¼ 7.97 (d, J ¼ 8.5 Hz,
d
2H), 7.56e7.53 (m, 2H), 7.45 (d, J ¼ 8.5 Hz, 2H), 7.27e7.24 (m, 3H),
7.00 (d, J ¼ 7.2 Hz, 1H), 5.46e5.39 (m, 1H), 3.60 (s, 2H), 1.55 (d,
13C NMR (100 MHz, CDCl3):
d
¼ 179.3, 168.4, 167.4, 137.4, 132.3,
J ¼ 6.0 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d
¼ 179.4, 168.3, 167.5,
129.4, 129.1, 128.8, 128.7, 127.8, 125.0, 45.5, 42.7, 29.8, 24.6, 22.5,
21.7. HRMS (TOF MS ESþ) m/z calculated for C21H22ClN3O2Se [M þ
H]þ: 464.0644; found: 464.0652.
137.5, 132.8, 129.5, 129.2, 128.8, 128.6, 128.0, 124.9, 43.2, 30.1, 19.6.
HRMS (TOF MS ESþ) m/z calculated for C18H16ClN3O2Se [M þ H]þ:
422.0175; found: 422.0164.
4.1.7.26. (S)-N-[2-phenyl-1-(3-phenyl-1,2,4-oxadiazol-5-yl)ethyl]-2-
4.1.7.21. (S)-N-[3-methyl-1-(3-phenyl-1,2,4-oxadiazol-5-yl)butyl]-2-
(phenylselenyl)acetamide (7ea). Yield: 300.3 mg, 70%; White solid,
(phenylselenyl)acetamide (7fa). Yield: 231.5 mg, 50%; Yellow solid,
23
mp: 115.0e118.0 ꢀC; Rf ¼ 0.52 (HexaneeEtOAc, 8:2); [
a
]
¼ ꢂ0.08
D
23
mp: 75.6e77.5 ꢀC; Rf ¼ 0.48 (Hexane/EtOAc, 8:2); [
a
]
¼ ꢂ26.88
(c ¼ 0.01; EtOAc). 1H NMR (400 MHz, CDCl3):
¼ 7.97 (d, J ¼ 8.8 Hz,
d
D
(c ¼ 0.01; EtOAc). 1H NMR (400 MHz, CDCl3):
d
¼ 8.03 (d, J ¼ 8.2 Hz,
2H), 7.47e7.43 (m, 4H), 7.26e7.23 (m, 6H), 7.09e7.04 (m, 4H),
2H), 7.52e7.42 (m, 5H), 7.24e7.20 (m, 3H), 7.07 (d, J ¼ 8.6, 1H),
5.43e5.37 (m, 1H), 3.63 (d, J ¼ 14.6 Hz, 1H), 3.58 (d, J ¼ 14.6 Hz, 1H),
1.80e1.67 (m, 2H), 1.56e1.45 (m, 1H), 0.90 (d, J ¼ 6.6 Hz, 3H), 0.89
5.66e5.63 (m, 1H), 3.58 (s, 2H), 3.29e3.26 (m, 2H); 13C NMR
(100 MHz, CDCl3):
d
¼ 178.3, 168.5, 167.4, 137.5, 134.7, 132.5, 129.4,
129.2, 129.1, 128.8 (2C), 127.8, 127.4, 124.9, 48.3, 39.4, 30.0. HRMS
(TOF MS ESþ) m/z calculated for C24H21N3O2Se [M þ H]þ: 464.0877;
found: 464.0854.
(d, J ¼ 6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d
¼ 179.2, 168.7,
168.3, 132.5, 131.3, 129.5, 128.9, 128.8, 127.9, 127.5, 126.6, 45.6, 42.8,
30.0, 24.6, 22.6, 21.9. HRMS (TOF MS ESþ) m/z calculated for
C
21H23N3O2Se [M þ Na]þ: 452.0853; found: 452.0842.
4.1.7.27. (S)-N-{2-phenyl-1-[3-(p-tolyl)-1,2,4-oxadiazol-5-yl]ethyl}-
2-(phenylselenyl)acetamide (7 fb). Yield: 152.6 mg, 32%; Yellow
4.1.7.22. (S)-N-{3-methyl-1-[3-(p-tolyl)-1,2,4-oxadiazol-5-yl]butyl}-
2-(phenylselenyl)acetamide (7eb). Yield: 323.5 mg, 73%; White
solid, mp: 95.5e100.0 ꢀC; Rf
¼
0.52 (Hexane/EtOAc, 8:2);
23
[
a
]
D
¼ ꢂ12.12 (c ¼ 0.01; EtOAc). 1H NMR (400 MHz, CDCl3):
¼ 7.90
d
solid, mp: 59.6e60.2 ꢀC; Rf
¼
0.51 (Hexane/EtOAc, 8:2);
(d, J ¼ 8.1 Hz, 2H), 7.45e7.42 (m, 2H), 7.25 (d, J ¼ 7.9 Hz, 2H),
23
[
a
]
¼ ꢂ22.86 (c ¼ 0.01; EtOAc). 1H NMR (400 MHz, CDCl3):
7.22e7.18 (m, 6H)], 7.10 (d, J ¼ 8.1 Hz, 1H), 7.02e7.01 (m, 2H),
D
d
¼ 7.92 (d, J ¼ 8.2 Hz, 2H), 7.53e7.50 (m, 2H), 7.27e7.22 (m, 5H),
5.64e5.58 (m, 1H), 3.53 (s, 2H), 3.25e3.22 (m, 2H), 2.39 (s, 3H); 13
C
7.00 (d, J ¼ 8.6 Hz, 1H), 5.43e5.37 (m, 1H), 3.63 (d, J ¼ 14.6 Hz, 1H),
3.58 (d, J ¼ 14.7 Hz, 1H), 2.40 (s, 3H), 1.80e1.66 (m, 2H), 1.55e1.45
(m, 1H), 0.90 (d, J ¼ 6.7 Hz, 3H), 0.89 (d, J ¼ 6.6 Hz, 3H); 13C NMR
NMR (100 MHz, CDCl3):
d
¼ 177.7, 168.5, 168.1, 141.6, 134.7, 132.5,
129.5, 129.4, 129.2, 128.7, 128.6, 127.8, 127.4, 127.3, 123.6, 48.3, 39.3,
30.0, 21.5. HRMS (TOF MS ESþ) m/z calculated for C25H23N3O2Se
[M þ H]þ: 478.1034; found: 478.1024.
(100 MHz, CDCl3):
d
¼ 178.9, 168.4, 168.2, 141.5, 132.4, 129.5, 129.4,
128.7, 127.7, 127.4, 123.6, 45.5, 42.7, 29.9, 24.5, 22.5, 21.7, 21.5. HRMS
(TOF MS ESþ) m/z calculated for C22H25N3O2Se [M þ H]þ: 444.1190;
found: 444.1187.
4.1.7.28. (S)-N-{1-[3-(4-methoxyphenyl)-1,2,4-oxadiazol-5-yl]-2-
phenylethyl]-2-(phenylselenyl)acetamide(7fc). Yield: 109.7 mg, 47%;
Yellow solid, mp: 76.5e80.0 ꢀC; Rf ¼ 0.39 (Hexane/EtOAc, 8:2);
23
4.1.7.23. (S)-N-{1-[3-(4-methoxyphenyl)-1,2,4-oxadiazol-5-yl]-3-
methylbutyl}-2-(phenylselenyl)acetamide (7ec). Yield: 215.8 mg,
[
d
a
]
D
¼ ꢂ10.34 (c ¼ 0.01; EtOAc). 1H NMR (400 MHz, CDCl3):
¼ 7.95 (d, J ¼ 8.7 Hz, 2H), 7.44e7.42 (m, 2H), 7.21e7.19 (m, 6H), 7.11
47%; White solid, mp: 51.4e52.3; Rf ¼ 0.49 (Hexane/EtOAc, 8:2);
(d, J ¼ 7.9 Hz, 1H), 7.03e7.01 (m, 2H), 6.95 (d, J ¼ 8.4 Hz, 2H),
5.63e5.58 (m, 1H), 3.83 (s, 3H), 3.53 (s, 2H), 3.25e3.22 (m, 2H); 13
NMR (100 MHz, CDCl3):
23
[
d
a
]
¼ ꢂ21.02 (c ¼ 0.01; EtOAc). 1H NMR (400 MHz, CDCl3):
C
D
¼ 7.97 (d, J ¼ 9.0 Hz, 2H), 7.53e7.51 (m, 2H), 7.25e7.23 (m, 3H),
d
¼ 177.6, 168.5, 167.8, 162.0, 141.6, 134.8,
6.97 (d, J ¼ 9.0 Hz, 2H), 6.96 (d, J ¼ 8.6 Hz, 1H), 5.42e5.36 (m, 1H),
3.86 (s, 3H), 3.64 (d, J ¼ 14.8 Hz, 1H), 3.58 (d, J ¼ 14.7, 1H), 1.80e1.66
(m, 2H), 1.55e1.44 (m, 1H), 0.90 (d, J ¼ 6.7 Hz, 3H), 0.89 (d,
132.5, 129.3, 129.1, 128.6, 127.7, 127.3, 123.5, 118.8, 114.2, 55.3, 48.3,
39.3, 30.0. HRMS (TOF MS ESþ) m/z calculated for C25H23N3O3Se
[M þ H]þ: 494.0983; found: 494.0996.
J ¼ 6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d
¼ 178.8, 168.4, 168.0,
162.0, 132.5, 129.5, 129.1, 128.7, 127.9, 119.0, 114.3, 55.4, 45.6, 42.9,
4.1.7.29. (S)-N-{1-[3-(4-nitrophenyl)-1,2,4-oxadiazol-5-yl]-2-
30.0, 24.6, 22.6, 21.8. HRMS (TOF MS ESþ) m/z calculated for
phenylethyl}-2-(phenylselenyl)acetamide (7fd). Yield: 193.1 mg,
C
22H25N3O3Se [M þ H]þ: 460.1139; found: 460.1150.
38%; Yellow solid, mp: 122.5e125.0 ꢀC; Rf ¼ 0.43 (Hexane/EtOAc,
23
8:2); [
d
a]
¼ ꢂ0.26 (c ¼ 0.01; EtOAc). 1H NMR (400 MHz, CDCl3):
D
4.1.7.24. (S)-N-{3-methyl-1-[3-(4-nitrophenyl)-1,2,4-oxadiazol-5-yl]
¼ 8.33 (d, J ¼ 9.0 Hz, 2H), 8.20 (d, J ¼ 9.0 Hz, 2H), 7.43e7.41 (m,
butyl}-2-(phenylselenyl)acetamide (7ed). Yield: 193.1 mg, 45%;
2H), 7.25e7.23 (m, 6H), 7.07 (d, J ¼ 8.1 Hz, 1H), 7.04e7.02 (m, 2H),
White solid, mp: 88.2e92.1 ꢀC; Rf ¼ 0.48 (Hexane/EtOAc, 8:2);
5.67e5.61 (m, 1H), 3.58 (s, 2H), 3.28e3.26 (m, 2H); 13C NMR
23
[
d
a
]
¼ ꢂ16.60 (c ¼ 0.01; EtOAc). 1H NMR (400 MHz, CDCl3):
(100 MHz, CDCl3):
d
¼ 179.0, 168.5, 166.7, 149.5, 134.4, 132.3, 129.5,
D
¼ 8.32 (d, J ¼ 9.0 Hz, 2H), 8.21 (d, J ¼ 9.1 Hz, 2H), 7.53e7.50 (m,
129.1, 128.9, 128.5, 127.8, 127.8, 127.6, 124.1, 123.8, 48.4, 39.3, 29.9.
HRMS (TOF MS ESþ) m/z calculated for C24H20N4O4Se [M þ H]þ:
509.0728; found: 509.0730.
2H), 7.27e7.25 (m, 3H), 6.96 (d, J ¼ 8.4 Hz, 1H), 5.44e5.38 (m, 1H),
3.66 (d, J ¼ 14.8 Hz, 1H), 3.61 (d, J ¼ 14.8 Hz, 1H), 1.83e1.70 (m, 2H),
1.57e1.46 (m, 1H), 0.93 (d, J ¼ 6.5 Hz, 3H), 0.91 (d, J ¼ 6.4 Hz, 3H);
13C NMR (100 MHz, CDCl3):
d
¼ 180.1, 168.5, 166.7, 149.5, 132.4,
4.1.7.30. (S)-N-{1-[3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl]-2-phe-
nylethyl}-2-(phenylselenyl)acetamide(7fe). Yield: 129.2 mg, 22%;
Yellow solid, mp: 79.5e83.0 ꢀC; Rf ¼ 0.43 (Hexane/EtOAc, 8:2);
132.2, 129.5, 128.7, 128.4, 127.8, 124.0, 45.6, 42.5, 29.7, 24.6, 22.6,
21.7. HRMS (TOF MS ESþ) m/z calculated for C21H22N4O4Se [M þ
9

L. Wolf, J.C.P. Mayer, N. Quoos et al.
Tetrahedron 91 (2021) 132222
23
(e) T. Sharonova, V. Pankrat'eva, P. Savko, S. Baykov, A. Shetnev, Tetrahedron
Lett. 59 (2018) 2824e2827.
[11] (a) A.Q. Acton (Ed.), Sulfur Compounds: Advances in Research and Application,
Scholarly Editions, Atlanta, GA, 2012;
[
d
a
]
¼ ꢂ0.596 (c ¼ 0.01; EtOAc). 1H NMR (400 MHz, CDCl3):
D
¼ 8.01 (d, J ¼ 8.3 Hz, 2H), 7.48e7.42 (m, 4H), 7.22e7.18 (m, 7H),
7.03e7.00 (m, 2H), 5.65e5.60 (m, 1H), 3.54 (s, 2H), 3.26e3.23 (m,
2H); 13C NMR (100 MHz, CDCl3):
d
¼ 177.9, 168.6, 168.1, 134.6, 132.4,
(b) S. Santoro, J.B. Azeredo, V. Nascimento, L. Sancineto, A.L. Braga, C. Santi,
RSC Adv. 4 (2014) 31521e31535;
131.3, 129.3, 129.1, 128.7 (2C), 128.6, 127.7, 127.4, 127.3, 126.2, 48.2,
39.2, 29.9. HRMS (TOF MS ESþ) m/z calculated for C24H20ClN3O2Se
[M þ H]þ: 498.0488; found: 498.0485.
(c) A.C. Sauer, J.G. Leal, S.T. Stefanello, M.T.B. Leite, M.B. Souza, F.A.A. Soares,
O.E.D. Rodrigues, L. Dornelles, Tetrahedron Lett. 58 (2017) 87e91;
~
(d) E.J. Lenardao, C. Santi, L. Sancineto, New Frontiers in Organoselenium
Compounds, Springer, Switzerland, 2018;
(e) I. Di Leo, F. Messina, V. Nascimento, F.G. Nacca, D. Pietrella, E.J. Lenardao,
~
Declaration of competing interest
G. Perin, L. Sancineto, Mini-Reviews Org. Chem. 16 (2019) 589e601.
[12] (a) T. With, Tetrahedron 55 (1999) 1e28;
(b) E.M. McGarrigle, E.L. Myers, O. Illa, M.A. Shaw, S.L. Riches, V.K. Aggarwal,
Chem. Rev. 107 (2007) 5841e5883;
(c) C. Santi, S. Santoro, B. Battistelli, Curr. Org. Chem. 14 (2010) 2442e2462;
(d) L. Dornelles, O.E.D. Rodrigues, E.F. Heck, C.R. Bender, M.B. Cansian,
R.S. Schwab, W.A. Severo Filho, Arkivoc 7 (2015) 131e134;
The authors declare that they have no known competing
financial interests or personal relationships that could have
appeared to influence the work reported in this paper.
(e) A. Breder, S. Ortgies, Tetrahedron Lett. 56 (2015) 2843e2852.
[13] (a) C.W. Nogueira, G. Zeni, J.B.T. Rocha, Chem. Rev. 104 (2004) 6255e6285;
(b) A.R. Patra, S.S. Roy, A. Basu, A. Bhuniya, A. Bhattacharjee, S. Hajra, , U. H. Sk,
R. Baral, S. Bhattacharya, Sci. Rep. 8 (2018) 2194.
Acknowledgments
The authors gratefully acknowledge CNPq (LD/Produtividade
em Pesquisa-Pq 2015e307312/2015-1), CAPES-FinanceCode 001
(CAPES-PROEX), and FAPERGS (Ed. PqG 01/2013 - 2009e2551/13-5)
for financial support and fellowships.
[14] (a) I.E. El-Shamy, A.M. Abdel-Mohsen, A.A. Alsheikh, M.M.G. Fouda, S.S. Al-
Deyab, M.A. El-Hashah, Tetrahedron Lett. 56 (2015) 1183e1188;
(b) M.S. Gularte, J.M. Anghinoni, L. Abenante, G.T. Voss, R.L. de Oliveira,
~
R.A. Vaucher, C. Luchese, E.A. Wilhelm, E.J. Lenardao, A.R. Fajardo, Carbohydr.
Polym. 219 (2019) 240e250.
[15] (a) B.K. Sarma, G. Mugesh, Chem. Eur. J. 14 (2008) 10603e10614;
(b) S.A. Akhoon, T. Naqvi, S. Nisar, M.A. Rizvi, Asian J. Chem. 27 (2015)
2745e2752.
Appendix A. Supplementary data
[16] (a) R. Brigelius-Flohe, Chem. Biodivers. 5 (2008) 389e395;
(b) J. He, D. Li, K. Xiong, Y. Ge, H. Jin, G. Zhang, M. Hong, Y. Tian, J. Yin, H. Zeng,
Bioorg. Med. Chem. 20 (2012) 3816e3827.
[17] (a) Z. Luo, L. Liang, J. Sheng, Y. Pang, J. Li, L. Huang, X. Li, Bioorg. Med. Chem. 22
(2014) 1355e1361;
(b) R. Borges, F.C.D. Andrade, R.S. Schwab, F.S.S. Sousa, M.N. de Souza,
L. Savegnago, P.H. Schneider, Tetrahedron Lett. 57 (2016) 3501e3504.
[18] G. Roy, G. Mugesh, Chem. Biodivers. 5 (2008) 414e439.
[19] G. Sartori, J.S.S. Neto, A.P. Pesarico, D.F. Back, C.W. Nogueira, G. Zeni, Org.
Biomol. Chem. 11 (2013) 1199e1208.
[20] B.M. Gai, A.L. Stein, J.A. Roehrs, F.N. Bilheri, C.W. Nogueira, G. Zeni, Org. Bio-
mol. Chem. 10 (2012) 798e807.
[21] E.A. Wilhelm, C.R. Jesse, C.F. Bortoletto, C.W. Nogueira, L. Savegnago, Brain Res.
Bull. 79 (2009) 281e287.
[22] (a) G. Mugesh, H. Singh, Chem. Soc. Rev. 29 (2000) 347e357;
(b) A.S. Prestes, S.T. Stefanello, S.M. Salman, A.M. Pazini, R.S. Schwab,
A.L. Braga, N.B.V. Barbosa, J.B.T. Rocha, Mol. Cell. Biochem. 365 (2012) 85e92;
(c) C. Santi, C. Tidei, C. Scalera, M. Piroddi, F. Galli, Curr. Chem. Biol. 7 (2013)
25e36.
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tet.2021.132222.
References
[1] R.O. Bora, B. Dar, V. Pradhan, M. Farooqui, Mini Rev. Med. Chem. 14 (2014)
355e369.
[2] C.V. Maftei, E. Fodor, P.G. Jones, M.H. Franz, G. Kelter, H. Fiebig, I. Neda, Beil-
stein J. Org. Chem. 9 (2013) 2202e2215.
[3] Q. Liu, R. Zhu, S. Gao, S.-H. Ma, H.-J. Tang, J.-J. Yang, Y.-M. Diao, H.-L. Wang, H.-
J. Zhu, Pest Manag. Sci. 73 (2017) 917e924.
[4] (a) C.G. Fortuna, C. Bonaccorso, A. Bulbarelli, G. Caltabiano, L. Rizzi, L. Goracci,
G. Musumarra, A. Pace, A.P. Piccionello, A. Guarcello, P. Pierro, C.E.A. Cocuzza,
R. Musumeci, Eur. J. Med. Chem. 65 (2013) 533e545;
(b) D. Ding, M.A. Boudreau, E. Leemans, E. Spink, T. Yamaguchi, S.A. Testero,
P.I. O'Daniel, E. Lastochkin, M. Chang, S. Mobashery, Bioorg. Med. Chem. Lett.
25 (2015) 4854e4857.
[23] (a) L.A. Wessjohann, A. Schneider, Chem. Biodivers. 5 (2008) 375e388;
(b) S. Narayanaperumal, K. Gul, C.Y. Kawasoko, D. Singh, L. Dornelles,
O.E.D. Rodrigues, A.L. Braga, J. Braz. Chem. Soc. 21 (2010) 2079e2087;
(c) T. Yonezawa, M. Yamaguchi, M. Ninomiya, M. Koketsu, Tetrahedron 73
(2017) 6085e6091.
[24] (a) S. Xiong, W.R. Markesbery, C. Shao, M.A. Lovell, Antioxidants Redox Signal.
9 (2007) 457e467;
(b) E.E. Battin, J.L. Brumaghim, Cell. Biochem. Biophys. 55 (2009) 1e23.
[25] C. Jacob, G.I. Giles, N.M. Giles, H. Sies, Angew. Chem. Int. Ed. 42 (2003)
4742e4758.
[5] N.I. Zhurilo, M.V. Chudinov, A.V. Matveev, A.V. Matveev, O.S. Smirnova,
I.D. Konstantinova, A.I. Miroshnikov, A.N. Prutkov, L.E. Grebenkina,
N.V. Pulkova, V.I. Shvets, Bioorg. Med. Chem. Lett. 28 (2018) 11e14.
[6] S. Yatam, S.S. Jadav, R. Gundla, K.P. Gundla, G.M. Reddy, M.J. Ahsan,
J. Chimakurthy, ChemistrySelect 3 (2018) 10305e10310.
[7] (a) J. Guo, R. Hua, J. Cao, Tetrahedron Lett. 55 (2014) 15571560;
(b) F. Vita, K. Sparnacci, G. Panzarasa, I.F. Placentino, S. Marino, N. Scaramuzza,
G. Portale, E. Di Cola, C. Ferrero, S.I. Torgova, G. Galli, M. Laus,
O. Francescangeli, ACS Macro Lett. 3 (2014) 91e95.
[8] (a) C. Carvalho, I. Brinn, W. Baumann, H. Reis, Z. Nagy, J. Chem. Soc., Faraday
Trans. 93 (1997) 3325e3329;
(b) W. Liu, G. Wu, X. Gu, X. Yuan, J. Li, H. Wang, J. Fluoresc. 25 (2015) 557e561.
[9] (a) S. Borg, K. Luthman, F. Nyberg, L. Terenius, U. Hacksell, Eur. J. Med. Chem.
28 (1993) 801e810;
[26] (a) R.J. Angelici, Acc. Chem. Res. 21 (1988) 387e394;
(b) T. Xu, Q. Zhang, D. Jiang, Q. Liang, C. Lu, J. Cen, X. Li, RSC Adv. 4 (2014)
33347e33354.
[27] (a) A.R. Katritzky, A.A. Shestopalov, K. Suzuki, Arkivoc 2005 (2005) 36e55;
(b) B. Kaboudin, L. Malekzadeh, Tetrahedron Lett. 52 (2011) 6424e6426.
[28] (a) Y. Wang, R.L. Miller, D.R. Sauer, S.W. Djuric, Org. Lett. 7 (2005) 925e928;
(b) J.R. Young, R.J. DeVita, Tetrahedron Lett. 39 (1998) 3931e3934;
(c) R.M. Srivastava, A.A. Lima, O.S. Vianna, M.J.C. Silva, T.J. A Catanho, J.O.F. de
Morais, Bioorg. Med. Chem. 11 (2003) 1821e1827;
(d) A. Pace, P. Pierro, Org. Biomol. Chem. 7 (2009) 4337e4348;
(e) N. Nowrouzi, D. Khalili, M. Irajzadeh, J. Iran. Chem. Soc. 12 (2015)
801e806;
(f) P.D. Parker, J.G. Pierce, Synthesis 48 (2016) 1902e1909;
(g) J.C.P. Mayer, A.C. Sauer, B.A. Iglesias, T.V. Acunha, D.F. Back,
O.E.D. Rodrigues, L. Dornelles, J. Organomet. Chem. 841 (2017) 1e11;
(h) A.A. Golushko, O.V. Khoroshilova, A.V. Vasilyev, J. Org. Chem. 84 (2019)
7495e7500;
ꢀ
ꢀ
(b) R.K. Henderson, C. Jimenez-Gonzalez, D.J.C. Constable, S.R. Alston,
G.G.A. Inglis, G. Fisher, J. Sherwood, S.P. Binks, A.D. Curzons, Green. Chem. 13
(2011) 854e862;
(c) D. Prat, O. Pardigon, H.-W. Flemming, S. Letestu, V. Ducandas, P. Isnard,
E. Guntrum, T. Senac, S. Ruisseau, P. Cruciani, P. Hosek, Org. Process Res. Dev.
17 (2013) 1517e1525;
(d) D. Prat, J. Hayler, A. Wells, Green. Chem. 16 (2014) 4546e4551.
€ €
[29] (a) A. Das¸ tan, A. Kulkarni, B. Torok, Green Chem. 14 (2012) 17e37;
(b) A. Majumder, R. Gupta, A. Jain, Green Chem. Lett. Rev. 6 (2013) 151e182;
ꢀ
(c) V.N.M. de Oliveira, F.G. dos Santos, V.P.G. Ferreira, H.M. Araújo, C. do O
(i) X. Wang, J.-P. Fu, J.-X. Xie, Q.-H. Teng, H.-T. Tang, Y.-M. Pan, Org. Biomol.
Chem. 18 (2020) 4936e4940.
Pessoa, R. Nicolete, R.N. de Oliveira, Synth. Commun. 48 (2018) 2522e2532;
(d) A.C. Sauer, L. Wolf, N. Quoos, M.B. Rodrigues, A.L. Braga, O.E.D. Rodrigues,
L. Dornelles, J. Chem. 12 (2019) 1e9.
ꢀ
[10] (a) A. Hamze, J.-F. Hernandez, P. Fulcrand, J. Martinez, J. Org. Chem. 68 (2003)
7316e7321;
[30] (a) M.D. Evans, J. Ring, A. Shoen, A. Bell, P. Edwards, D. Berthelot,
R. Nicewonger, C.M. Baldino, Tetrahedron Lett. 44 (2003) 9337e9341;
(b) V. Santagada, F. Frecentese, E. Perissutti, D. Cirillo, S. Terracciano,
G. Caliendo, Bioorg. Med. Chem. Lett. 14 (2004) 4491e4493;
(b) M.D. Evans, J. Ring, A. Schoen, A. Bell, P. Edwards, D. Berthelot,
R. Nicewonger, C.M. Baldino, Tetrahedron Lett. 44 (2003) 9337e9341;
(c) A.L. Braga, D.S. Lüdtke, E.E. Alberto, L. Dornelles, W.A.S. Filho,
V.A. Corbellini, D.M. Rosa, R.S. Schwab, Synthesis 10 (2004) 1589e1594;
(d) S.C. Karad, V.B. Purohit, R.P. Thummar, B.K. Vaghasiya, R.D. Kamani,
P. Thakor, V.R. Thakkar, S.S. Thakkar, A. Ray, D.K. Raval, Eur. J. Med. Chem. 126
(2017) 894e909;
(c) A. Porcheddu, R. Cadoni, L. de Luca, Org. Biomol. Chem.
9 (2011)
7539e7546;
(d) N. Baral, S. Mohapatra, B.P. Raiguru, N.P. Mishra, P. Panda, S. Nayak,
10

L. Wolf, J.C.P. Mayer, N. Quoos et al.
Tetrahedron 91 (2021) 132222
S.K. Pandey, P.S. Kumar, C.R. Sahoo, J. Heterocycl. Chem. 56 (2019) 552e565.
[31] (a) J. Vargas, S. Narayanaperumal, K. Gul, B.B. Ravanello, L. Dornelles,
L.C. Soares, C.F.S. Alves, T. Schneider, R.A. Vaucher, R.C.V. Santos,
O.E.D. Rodrigues, Tetrahedron 68 (2012) 10444e10448;
(c) C. Reichardt, T. Welton, Solvents and Solvent Effects in Organic Chemistry,
fourth ed., Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany, 2011.
[33] (a) E. Doni, S. Zhou, J.A. Murphy, Molecules 20 (2015) 1755e1774;
(b) E.E. Alberto, L.C. Soares, J.H. Sudati, A.C.A. Borges, J.B.T. Rocha, A.L. Braga,
Eur. J. Org. Chem. 2009 (2009) 4211e4214;
(b) C.A. Bayse, J.L. Brumaghim, Biochalcogen chemistry: the biological chem-
istry of sulfur, selenium, and tellurium, in: ACS Symposium Series, American
Chemical Society, Washington, DC, 2013;
(c) A.D. Photiadou, C.I. Stathakis, J.K. Gallos, J. Heterocycl. Chem. 45 (2008)
1251e1253.
(c) S. Shaaban, A. Negm, A.M. Ashmawy, D.M. Ahmed, L.A. Wessjohann, Eur. J.
Med. Chem. 122 (2016) 55e71.
[32] (a) V. Polshettiwar, R.S. Varma, Chem. Soc. Rev. 37 (2008) 1546e1557;
(b) C.O. Kappe, D. Dallinger, S.S. Murphree, Practical Microwave Synthesis for
Organic Chemists, first ed., Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim,
Germany, 2009;
[34] (a) R.M. Srivastava, I.M. Brinn, J.O. Machuca-Herrera, H.B. Faria, G.B. Carpenter,
D. Andrade, C.G. Venkatesh, L.P.F. de Morais, J. Mol. Struct. 406 (1997)
159e167;
(b) T. Gerfaud, H.-L. Wei, L. Neuville, J. Zhu, Org. Lett. 13 (2011) 6172e6175.
[35] C. Capello, U. Fischer, K. Hungerbühler, Green Chem. 9 (2007) 927e934.
11