Mild and selective silicon-mediated access to enantioenriched 1,2-mercaptoamines and β-amino arylchalcogenides

Article abstract of DOI:10.1039/c9nj00657e

Metal-free ring opening reactions of activated and unactivated aziridines with different silyl chalcogenides are described. Judicious tuning of the reaction conditions enables the synthesis of chiral enantioenriched N-Ts and N-Boc 1,2-mercaptoamines in good yields from the corresponding aziridines and bis(trimethylsilyl)sulfide. N-Protected and N-H unactivated aziridines are efficiently converted into the corresponding β-arylchalcogeno amines upon treatment with suitable arylchalcogenosilanes. The silicon-mediated ring opening reactions proceed with excellent regioselectivity and stereospecificity, allowing to access a wide array of synthetically and biologically valuable enantioenriched chalcogenoamines.

Full text of DOI:10.1039/c9nj00657e

View Article Online
View Journal
NJC
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: D. Tanini, C.
Borgogni and A. Capperucci, New J. Chem., 2019, DOI: 10.1039/C9NJ00657E.
This is an Accepted Manuscript, which has been through the
Volume 40 Number
1 January 2016 Pages 1–846
Royal Society of Chemistry peer review process and has been
accepted for publication.
NJC
Accepted Manuscripts are published online shortly after
New Journal of Chemistry
www.rsc.org/njc
A journal for new directions in chemistry
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1144-0546
PAPER
Jason B. Benedict et al.
The role of atropisomers on the photo-reactivity and fatigue of
diarylethene-based metal–organic frameworks
rsc.li/njc

Please do not adjust margins
Page 1 of 7
New Journal of Chemistry
1
2
3
4
5
6
7
View Article Online
DOI: 10.1039/C9NJ00657E
ARTICLE
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Mild and Selective Silicon-mediated access to enantioenriched
1,2-mercaptoamines and -amino arylchalcogenides
Received 00th January 20xx,
Accepted 00th January 20xx
Damiano Tanini,* Cosimo Borgogni and Antonella Capperucci*
DOI: 10.1039/x0xx00000x
Metal-free ring opening reactions of activated and unactivated aziridines with different silyl chalcogenides are described.
Judicious tuning of the reaction conditions enables the synthesis of chiral enantioenriched N-Ts and N-Boc 1,2-
mercaptoamines in good yields from the corresponding aziridines and bis(trimethylsilyl)sulfide. N-Protected and N-H
unactivated aziridines are efficiently converted into the corresponding -arylchalcogeno amines upon treatment with
suitable arylchalcogenosilanes. The silicon-mediated ring opening reactions proceed with excellent regioselectivity and
stereospecificity, allowing to access
chalcogenoamines.
a
wide array of synthetically and biologically valuable enantioenriched
However, despite a number of methods have been described
for the synthesis of -aminothiols, the development of a
general and mild route to directly access these compounds,
Introduction
Chalcogenoamines (chalcogens S, Se, Te) are important and
versatile organic compounds. Among the variety of these
molecules, -aminothiols represent arguably the most
important class. They are ubiquitous motifs in naturally
occurring molecules (i.e., penicillamine, cysteine, cysteamine,
glutathione), pharmaceuticals (i.e., enzyme inhibitors,1
radioprotective agents2), and materials. -Aminothiols find
wide application in synthetic organic chemistry, medicinal
chemistry, and catalysis.3 They are commonly used as
intermediates for the synthesis of biologically relevant
molecules, such as peptides,4 thiazolidines,5 thiazolines,6
thiomorpholines,7 and thiazepines.8
Several methods for the synthesis of -aminothiols have been
reported,9 including the multistep conversion of aminoalcohols
and aminoacids into the corresponding thiols, commonly
achieved by nucleophilic substitution10 or by Mitsunobu
reaction.11 Alternatively, -aminothiols can be obtained
through nucleophilic ring opening reactions (NROR) of three-
and five-membered heterocycles, such as aziridines,12
sulfamidates,13 thiazolidinones,14 and thiazolidines15 with a
diverse array of sulfurated nucleophiles. Aminoethanethiols
can also be synthesized by ring opening of thiiranes with
amines.16 To the best of our knowledge, most of these
procedures involve multistep sequences and all share a final
deprotection or reduction step necessary to obtain the free
thiol moiety.
without requiring
a further deprotection of the thiol
functionality, remains challenging and highly desirable.
Besides -aminothiols, also -arylchalcogeno amines
respresent versatile molecules in biology17 and in synthesis
and, for these reasons, have attracted considerable interest. -
aminochalcogenides find wide application as valuable
synthetic intermediates and as chiral ligands in asymmetric
reactions.18 For example, chiral -aminosulfides bearing a free
amino group have been used as ligands in Ir-catalyzed
asymmetric transfer hydrogenation of prochiral ketones19 and
in asymmetric epoxidation reactions of aldehydes.20
Furthermore, chiral -aminosulfides have been employed for
the synthesis of sulfoxide-Shiff base ligands for Cu-catalyzed
asymmetric Henry reactions21 and for the preparation of
hybrid P,S ligands for asymmetric Pd-catalyzed decarboxilative
[4+2] cycloadditions.22
-Arylchalcogeno amines are commonly prepared by ring
opening reactions of aziridines,23 -lactones24, and cyclic
sulfamidates,25 by nucleophilic substitution,26 and by reaction
of olefins with benzeneselenenyl chloride and amines.27
However, although several methods have been reported for
the preparation of N-protected -arylchalcogeno amines, only
a relatively limited number of procedures have been reported
for the synthesis of more useful analogues bearing a free
amino functionality. Furthermore, whilst -aminosulfides have
been deeper studied, the related selenium- and tellurium-
containing derivatives have received less attention. In
addition, only a few examples of NRORs of N-H unactivated
aziridines with chalcogen-containing nucleophiles have been
reported.23a,b,e,f In this context, whilst silylated nucleophiles
have been used in nucleophilic ring opening reactions of N-
protected aziridines,28 to the best of our knowledge their
Dipartimento di Chimica ”Ugo Schiff”, Università di Firenze, Via della Lastruccia 3-
13, 50019 Sesto Fiorentino, Italy. E-mail: antonella.capperucci@unifi.it;
damiano.tanini@unifi.it.
Electronic Supplementary Information (ESI) available: Full experimental details,
products characterization, and NMR spectra. See DOI: 10.1039/x0xx00000x
Please do not adjust margins

Please do not adjust margins
New Journal of Chemistry
Page 2 of 7
ARTICLE
Journal Name
1
2
3
4
5
6
7
8
9
reactivity with the unactivated N-H analogues has never been noticed the formation of ca. 20% of the sulfide,ViaewrisAirnticgle fOrnolimne
reported.
the nucleophilic attack of the thiolDO(Io: 1r0.1t0h3e9/Ct9hNiJo0s0il6a5n7eE
We recently reported alternative approaches to functionalized intermediate) onto a second molecule of aziridine. The effect
sulfur-, selenium-, and tellurium-containing compounds, of reaction time, reaction temperature, and amount of catalyst
proceeding through the silicon-mediated regioselective ring was then evaluated. We found that just reducing the reaction
opening reaction of strained heterocycles.29 We recognized time to 5 min, the 3a:4a ratio increased to 65:35 (Table 1,
that the extension of this reactivity to N-protected or N-H entry 5) maintaining
a high conversion; under these
aziridines and suitable silyl chalcogenides could provide a conditions, the use of a lower amount of TBAF led to a poor
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
novel method to access -aminothiols and -arylchalcogeno conversion (35% of starting aziridine remained unreacted),
amines.
In this communication, we report the effective development of entry 6). On the other hand, we were delighted to find that
new procedure in which N-activated aziridines are performing the reaction at 0°C for 10 min in the presence of 10
conveniently converted into 1,2-mercaptoamines and - mol% of TBAF, the desired 1,2-mercaptoamine 3a was
whilst the 3a:4a ratio was only slightly improved (Table 1,
a
arylchalcogeno
bis(trimethylsilyl)sulfide
amines
upon
reaction
with smoothly formed in excellent yield and, as observed for all
and these NRORs, with complete regioselectivity (Table 1, entry 7).
(phenylchalcogeno)trimethylsilane, respectively. Furthermore,
the study of the first NROR example of N-H aziridines with silyl
chalcogenides led to disclose an alternative direct route to -
arylchalcogenoamines bearing a free amino function.
Table 1: Optimization of the reaction conditions
Ts
Ts
NH
Ts
NH
Catalyst (mol%)
N
R
S
(Me3Si)2S
(1.2 eq.)
2
HS
R
+
S
R
+
R
THF
4a
1a
R = Bn
3a
HN
Temperature, Time
Citric acid
Ts
Results and discussion
We began our investigations by establishing the optimal conditions
required to obtain the N-tosyl 1,2-mercaptoamine 3a from the
corresponding enantioenriched N-Tosyl protected aziridine 1a,
Entry Temp. (°C) Time (min) Catalyst, mol%
(3a:4a)
Conversion (%)a
PhONBu4, 10
PhONBu4, 10
PhONBu4, 20
TBAF, 20
1
2
3
4
5
r.t.
0
10
5
60:40
80:20
90:10
90
65
0
10
>95
>95
>95
easily synthesized from L-phenylalanine through
a reported
r.t.
r.t.
15
5
<2:78b
65:35
70:30
>95:5
procedure,30 and bis(trimethylsislyl)sulfide (HMDST) 2. On the basis
TBAF, 20
of previous results related to the ring opening of epoxides and
6
7
r.t.
0
5
TBAF, 10
TBAF, 10
65
31
thiiranes with thiosilanes, two different catalysts such as PhONBu4
10
>95c
and TBAF28a,b,29 were evaluated in order to functionalize the S-Si
bond and promote the desired transformation. Aziridine 1a was
therefore treated with (Me3Si)2S 2 at room temperature in the
presence of 10 mol% of PhONBu4 (Table 1, entry 1); under these
conditions, the desired -aminothiol 3a was achieved, albeit
together with an almost equimolar amount of the corresponding
disulfide 4a. Taking advantage of our recent findings in the
synthesis of labile selenols,32 we next evaluated the effect of
reaction time, the reaction temperature, and amount of catalyst on
the 3a:4a ratio. When reaction temperature and reaction time were
decreased (0°C for 5 min, Table 1, entry 2), the ratio between 3a
and 4a resulted improved, although a poor conversion was
achieved (ca. 35% of the aziridine 1a remained unreacted).
Nonetheless, using 20 mol% of PhONBu4 and performing the
reaction at 0°C for 10 min, a good thiol vs disulfide selectivity
(90:10) and an excellent conversion were obtained (Table 1, entry
3).
Having explored the PhO─-induced ring opening of aziridines
with HMDST, we turned our attention on the evaluation of the
F─ catalyzed reaction. Aziridine 1a was initially treated with 2
at room temperature in the presence of 20 mol% of TBAF until
complete consumption of the substrate (Table 1, entry 4).
However, although a silicon mediated ring opening reaction
readily occurred, under these conditions the desired -
aminothiol 3a was not isolated, being the corresponding
disulfide 4a the main reaction product. Intriguingly, we also
a Conversion was determined by 1H NMR; b ca. 20% of the corresponding
sulfide was formed; c 92% yield.
Having established optimal conditions for the effective synthesis of
1,2-mercaptoamines, we next explored the scope of this procedure.
Thus, differently N-protected aziridines, conveniently prepared
from the corresponding natural aminoacids (L-Phe, L-Ala, L-Val, L-
Ile, L-Leu), were treated with (Me3Si)2S as reported in the Scheme 1.
Pg
Pg
NH
TBAF (0.3 eq.)
N
HS
(Me3Si)2S
+
R
R
THF
0°C, 10 min
Citric acid
2
3a-e: Pg = Ts
6a-c: Pg = Boc
1a-e: Pg = Ts
5a-c: Pg = Boc
Ts
Ts
Ts
Ts
NH
NH
NH
NH
HS
HS
HS
HS
Ph
HS
3a, 92%a
3b, 87%a
3c, 90%a
Boc
3d, 91%a
Ts
Boc
NH
Boc
NH
NH
NH
HS
HS
6a, 93%a,b
Ph
HS
6b, 87%a,b
3e, 84%a
6c, 76%a,b
a Yield refers to isolated product; b Ring opening reaction carried out at r.t.,
for 1h, in the presence of 1.0 eq. of TBAF.
Scheme 1. Scope of the synthesis of 1,2-mercaptoamines through
the ring opening of aziridines with HMDST
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 3 of 7
New Journal of Chemistry
Please do not adjust margins
Journal Name
ARTICLE
1
2
3
4
5
6
7
Variously substituted enantioenriched N-tosyl aziridines 1a-e reacted with benzyl-, methyl-, and isopropyl-substituted
View Article Online
DOI: 10.1039/C9NJ00657E
were smoothly converted into the corresponding 1,2- unprotected aziridines 10a-c to give the corresponding
mercaptoamines 3a-e in very good yields (Scheme 1). phenylsulfides 11aa-11ac, bearing free NH2 groups (Scheme 3).
Furthermore, the reaction was also amenable to N-Boc Furthermore, the related selenosilane 7b and tellurosilane 7c could
be successfully employed in this reaction, allowing to directly access
protected aziridines; optically pure N-Boc -aminothiols 6a-c
8
9
were easily achieved from 5a-c under slightly modified unprotected -amino- selenides and tellurides 11ba-11bc and 11ca-
reaction conditions. Indeed, N-Boc aziridines proved to be less 11cc, respectively, without requiring further deprotection steps26a,37
reactive with respect to the N-Tosyl analogues23f and, (Scheme 3).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
therefore, the ring opening reaction was carried out at
ambient temperature in the presence of 1.0 eq. of TBAF
NH2
TBAF (0.4 eq.)
HN
PhYSiMe3
PhY
R
+
R
THF, r.t., 6 h
(Scheme 1). All the synthesized 2-alkyl- and 2-benzyl-1,2-
mercaptoamines arose from a clean nucleophilic attack of the
sulfur atom on the less hindered side of the three-membered
ring.33 Remarkably, treatment of 2-phenyl-1-tosylaziridine 1f
with (Me3Si)2S under the optimized reaction conditions led to
the formation of a mixture of regioisomers (75:25 r.r.).34 This
finding is in line with previous results describing the erosion of
regioselectivity observed in the ring opening of 2-aryl-
substituted aziridines and epoxides.28a,35
Having successfully developed a convenient procedure for the
synthesis of 1,2 mercaptoamines, we then evaluated the use of
aromatic silyl chalcogenides to access -phenylchalcogeno amines.
As stated above, chiral -arylchalcogeno amines represent an
interesting class of compounds and the study of an alternative,
general and mild methodology for their synthesis would be
desirable.
Thus, in order to evaluate a novel silicon-mediated route to this
class of compounds, we investigated the reactivity of silyl
chalcogenides 7a-c with aziridines 1a and 5a. As reported in the
Scheme 2, in the presence of a catalytic amount of TBAF, the
phenylthio, phenylseleno, and phenyltelluro moieties were
smoothly transferred onto the aziridine, leading smoothly to the
formation of N-protected -phenylchalcogeno amines 8a-c and 9a-c
in good yields.
7a: Y = S
7b: Y = Se
7c: Y = Te
10a-c
11aa-11ac: Y = S
11ba-11bc: Y = Se
11ca-11cc: Y = Te
NH2
NH2
NH2
PhS
PhS
11aa, 63%
Ph
PhS
11ab, 56%
11ac, 64%
NH2
NH2
NH2
PhSe
PhSe
11ba, 65%
NH2
Ph PhSe
11bb, 55%
11bc, 62%
NH2
NH2
PhTe
PhTe
11ca, 63%
Ph PhTe
11cb, 58%
11cc, 67%
Scheme 3. Reactivity of PhSSiMe3, PhSeSiMe3, and PhTeSiMe3 with
unprotected aziridines.
Furthermore, to demonstrate the possibility to apply this procedure
to differently substituted silyl sulfides, -arylthioamines 13a-c
bearing both electron-rich (pMeC6H4) and electron-deficient
(mBrC6H4 and pBrC6H4) aromatics, were successfully obtained by
reaction of the corresponding thiosilanes 12a-c with the
unprotected aziridine 10b in the presence of a catalytic amount of
TBAF (Scheme 4, part a), thus illustrating the versatility of the
methodology.
In addition, arylseleno- and aryltelluro-amines 16 and 17 could also
be obtained exploiting the reactivity of p-tolylselenosilane 14 and p-
tolyltellurosilane 15 with 10b (Scheme 4, part b).
Pg
Pg
NH
Ph
TBAF (0.4 eq.)
N
PhY
Ph
PhYSiMe3
+
THF
r.t., 5 h
7a: Y = S
7b: Y = Se
7c: Y = Te
1a: Pg = Ts
5a: Pg = Boc
8a-c: Pg = Ts
9a-c: Pg = Boc
NH2
S
TBAF (0.3 eq.)
S
HN
SiMe3
+
a)
R
R
THF
0°C to r.t., 6 h
Ts
Boc
Ts
NH
NH
NH
10b
12a: R = p-Me
12b: R = m-Br
12c: R = p-Br
13a: R = p-Me, 56%
13b: R = m-Br, 58%
13c: R = p-Br, 66%
PhS
Ph
Ph
PhS
Ph
PhSe
Ph
8a, 89%
9a, 76%
8b, 82%
NH2
Boc
Ts
Boc
Y
NH
NH
NH
TBAF (0.3 eq.)
Y
HN
SiMe3
+
PhSe
PhTe
Ph
PhTe
Ph
b)
THF
0°C to r.t., 6 h
9b, 79%
8c, 84%
9c, 73%
10b
14: Y = Se
15: Y = Te
16: Y = Se, 55%
17: Y = Te, 69%
Scheme 4. Synthesis of aminosulfides 13a-c, aminoselenide 16 and
aminotelluride 17 through the reaction of substituted silyl
chalcogenides with 10b.
Scheme 2. Reactivity of PhSSiMe3, PhSeSiMe3, and PhTeSiMe3 with
N-protected aziridines.
Having demonstrated that N-Tosyl and N-Boc aziridines could be
reacted with silyl chalcogenides to afford the corresponding
arylchalcogeno amines, we wished to extend this reactivity to N-H
unactivated aziridines.36 We were pleased to find that PhSSiMe3 7a
The methodology here developed is also important in order to
straightforwardly access small molecules with catalytic
antioxidant activity. Indeed, -phenylseleno- and -
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
New Journal of Chemistry
Page 4 of 7
ARTICLE
Journal Name
1
2
3
4
5
6
7
8
9
broad singlet, bd = broad doublet, ecc.), coupling constant (J) or line
DOI: 10.1039/C9NJ00657E
separation (ls), and assignment. Where reported, NMR assignments
phenyltelluro-amines bearing a free amino function behave as
much more active glutathione peroxidase mimics with respect
to their N-Tosyl protected analogues.37
View Article Online
are made according to spin systems, using, where appropriate, APT
and 2D NMR experiments (COSY, HSQC) to assist the assignment.
Naming of Compounds. Compound names are those generated by
ChemBioDraw 15.0 software (PerkinElmer), following IUPAC
nomenclature.
Conclusions
In conclusion, we have developed a novel, mild, convenient
procedure to access chiral enantioenriched -aminothiols through
the ring opening reaction of N-Ts and N-Boc aziridines with
bis(trimethylsilyl)sulfide. N-Activated aziridines were also
successfully employed in reactions with arylchalcogenosilanes,
enabling the synthesis of N-protected enantioenriched
arylchalcogenoamines. Furthermore, the reaction of N-H
unactivated aziridines with silyl chalcogenides has been for the first
time investigated, leading to unveil a new protocol for the synthesis
of arylchalcogenoamines bearing a free amino function. The
reactions proceed via fluoride or phenoxide ion-induced
functionalization of silyl chalcogenides, providing a stereospecific
and highly regioselective access to variously substituted
aminochalcogenides.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
General Procedure for the synthesis of N-Tosyl -aminothiols 3a-e.
A
solution of N-Tosyl aziridine 1 (0.5 mmol, 1.0 eq.) and
bis(trimethylsilyl)sulfide (HMDST, 2) (0.6 mmol, 1.2 eq.) in dry THF
(2 mL) was cooled under inert atmosphere at 0°C, and treated with
TBAF (0.12 mL of 1M THF solution, 0.12 mmol). The reaction was
stirred for 10 min and then citric acid (50% aq solution) was added.
Afterwards, the mixture was diluted with diethyl ether, washed
with water, and dried over Na2SO4. The solvent was evaporated
under vacuum affording N-Tosyl -aminothiols 3a-e pure enough to
be used without further purification.
General procedure for the synthesis of N-Boc -aminothiols 6a-c.
A
solution of aziridine
5
(0.5 mmol, 1.0 eq.) and
bis(trimethylsilyl)sulfide (HMDST, 2) (0.6 mmol, 1.2 eq.) in dry THF
(3 mL) was treated with TBAF (0.6 mL of 1M THF solution, 1.2
mmol). The reaction was stirred at room temperature for 1 h and
then citric acid (50% aq solution) was added. Afterwards, the
mixture was diluted with diethyl ether, washed with water, and
dried over Na2SO4. The solvent was evaporated under vacuum
affording the desired N-Boc -aminothiols 6a-c pure enough to be
used without further purification.
General procedure for the synthesis of -phenylchalcogenoamines
by NRORs of aziridines with phenylchalcogeno silanes. A solution
of aziridine (1, N-Ts aziridine; 5, N-Boc aziridine or 10, N-H aziridine)
(0.5 mmol, 1.0 eq.) and phenylchalcogeno silane (7a, PhSSiMe3; 7b,
PhSeSiMe3; 7c, PhTeSiMe3) (0.6 mmol, 1.2 eq.) in dry THF (3 mL)
was treated with TBAF (0.24 mL of 1M THF solution, 0.24 mmol).
The reaction was stirred at room temperature for 5-6 h, until
complete consumption of starting material was observed by TLC.
Afterwards, NH4Cl (sat. aq solution) was added, the mixture was
diluted with diethyl ether, washed with water, and dried over
Na2SO4. The solvent was evaporated under vacuum and the crude
material was purified by flash column chromatography to afford -
phenylchalcogenoamines 8, 9 or 11.
Experimental
General
All reactions were carried out in an oven-dried glassware under
inert atmosphere (N2). Solvents were dried using
a solvent
purification system (Pure-Solv™). All commercial materials were
purchased from various commercial sources and used as received,
without further purification. N-Ts,38 N-Boc,39 N-H40 aziridines and
silyl chalcogenides41 were prepared according to literature reported
procedures.
Flash column chromatography purifications were performed with
Silica gel 60 (230-400 mesh). Thin layer chromatography was
performed with TLC plates Silica gel 60 F254, which was visualised
under UV light, or by staining with an ethanolic acid solution of p-
anisaldehyde followed by heating. High resolution mass spectra
(HRMS) were recorded by Electrospray Ionization (ESI). GC-MS was
performed on a Varian CP 3800/Saturn 2200 instrument.
1H and 13C NMR spectra were recorded in CDCl3 using Mercury 400,
Bruker 400 Ultrashield, and Varian Gemini 200 spectrometers
1
operating at 400 MHz and 200 MHz (for H), 100 MHz and 50 MHz
(for 13C). 77Se NMR spectra were recorded using Bruker 400
Ultrashield and Varian Gemini 200 spectrometers, operating at 76 Conflicts of interest
MHz and 38 MHz, respectively. 125Te NMR spectra were recorded in
There are no conflicts to declare.
CDCl3 at 126 MHz with a Bruker Ultrashield 400 Plus instrument.
NMR signals were referenced to nondeuterated residual solvent
signals (CDCl3: 7.26 ppm for 1H, 77.0 ppm for 13C). Diphenyl
diselenide (PhSe)2 was used as an external reference for 77Se NMR
(δ = 461 ppm). (PhTe)2 was used as an external reference for 125Te
(δ = 420 ppm). Chemical shifts () are given in parts per million
(ppm), and coupling constants (J) are given in Hertz (Hz), rounded to
Notes and references
1
(a) J. D. Park and D. H.Kim, J. Med. Chem., 2002, 45, 911; (b)
H. Chen, B. P. Roques and M. C. Fournié-Zaluski, Bioorg.
Med. Chem. Lett., 1999, 9, 1511; (c) L. Martin, F. Cornille, P.
Coric, B. P. Roques and M. C. Fournié-Zaluski, J. Med. Chem.,
1998, 41, 3450.
P. Auzeloux, J. Papon, R. Pasqualini and J. C.Madelmont, J.
Med. Chem., 2001, 44, 1116.
1
the nearest 0.1 Hz. H NMR data are reported as follows: chemical
2
shift, integration, multiplicity (s = singlet, d = doublet, t = triplet, ap
d = apparent doublet, m = multiplet, dd = doublet of doublet, bs =
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 7
New Journal of Chemistry
Please do not adjust margins
Journal Name
ARTICLE
1
2
3
4
5
6
7
8
9
3
A. L. Braga, F. Z. Galetto, O. E. D. Rodrigues, C. C. Silveira
Petra, P. C. J. Kamer, A. L. Spek, H. E. Schoemaker and P. W.
View Article Online
andM. W. Paixão, Chirality, 2008, 20, 839. For a review see:
N. M. van Leeuwen, J. Org. Chem., 200D0,O6I:51,03.1001390/.C9NJ00657E
M. Mellah, A. Voituriez and E. Schultz, Chem. Rev., 2007, 20 (a) M. Namutebi, E. M. McGarrigle and V. K. Aggarwal,
107, 5133
(a) L. Hu, H. Zhu, D. Du-Ming and J. Xu, J. Org. Chem., 2007,
72, 4543; (b) D. Hesek, M. Toth, V. Krchnak, R. Fridman and
S. Mobashery, J. Org. Chem., 2006, 71, 5848; (c) S. Mourtas,
C. Katakalou, A. Nicolettou, C. Tzavara, D. Gatos and K. 21 (a) L. Y. Chen, J. R. Chen, H. G. Cheng, L. Q. Lu and W. J. Xiao,
Barlos, Tetrahedron Lett., 2003, 44, 179.
(a) D. Tanini, G. Barchielli, F. Benelli, A. Degl’Innocenti and A.
Capperucci, Phosphorus Sulfur Silicon Relat. Elem., 2015, 190,
Phosphorus, Sulfur, and Silicon 2010, 185, 1250; (b) V. K.
Aggarwal, E. M. McGarrigle and M. A. Shaw in Science of
Synthesis, Stereoselective Synthesis 2, ed. G. A. Molander,
George Thieme Verlag, 2010, 311.
4
Eur. J. Org. Chem., 2014, 4714; (b) H. G. Cheng, L. Q. Lu, T.
Wang, J. R. Chen and W. J. Xiao, Chem. Commun., 2012, 48,
5596.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
5
1265; (b) C. Gros, C. Boulègue, N. Galeotti, G. Niel and P. 22 Y. Wei, L. Q. Lu, T. R. Li, B. Feng, Q. Wang, W. J. Xiao and H.
Jouin, Tetrahedron, 2002, 58, 2673. Alper, Angew. Chem. Int. Ed., 2016, 55, 2200.
For a review see: A. C. Gaumont, M. Gulea and J. Levillain, 23 (a) J. Lugiņina and M. Turks, Synlett, 2017, 28, 939; (b) P. C.
6
7
Chem. Rev., 2009, 109, 1371 and references cited therein.
(a) O. A. Attanasi, P. Filippone, S. Lilliani, F. Mantellini, S.
Nicolini, J. M. de los Santos, R. Ignacio, D. Aparicio and F.
Palacios, Tetrahedron, 2008, 64, 9264; (b) G. Ziakas, E. A.
Rekka, A. M. Gavalas, P. T. Eleftheriou and P. N. Kourounakis,
Bioorg. Med. Chem., 2006, 14, 5616; (c) M. T. Gallego, E.
Brunet and J. L. Garcia Ruano, J. Org. Chem., 1993, 58, 3905.
Inter alia: (a) J. Drewe, S. Kasibhatla, B. Tseng, E. Shelton, D.
Sperandio, R. M. Yee, J. Litvak, M. Sendzik, J. R. Spencer and
S. X. Cai, Bioorg. Med. Chem. Lett., 2007, 17, 4987; (b) J. I.
Trujillo, H. C. Huang, W. L. Neumann, M. W. Mahoney, S.
Long, W. Huang, D. J. Garland, C. Kusturin, Z. Abbas, M. S.
Silva, E. L. Borges, D. B. Lima, R. G. Jacob, E. J. Lenardão, G.
Perin and M. S. Silva, Arkivoc, 2016, 5, 376; (c) M. Senatore,
A. Lattanzi, S. Santoro, C. Santi and G. Della Sala, Org.
Biomol. Chem., 2011, 9, 6205; (d) B. Movassagh and E. S.
Morovat, J. Sulfur Chem., 2011, 32, 117; (e) S. M. Salman, S.
Narayanaperumal, R. S. Schwab, C. R. Bender, O. E. D.
Rodrigues and L. Dornelles, RSC Adv., 2012, 2, 8478; (f) A. L.
Braga, R. S. Schwab, E. E. Alberto, S. M. Salman, J. Vargas and
J. B. Azeredo, Tetrahedron Lett., 2009, 50, 2309; (g) V.
Ganesh and S. Chandrasekaran, Synthesis, 2009, 3267; (h) O.
Ploux, M. Caruso, G. Chassaing and A. Marquet, J. Org. Chem.
1988, 53, 3154.
8
9
South and D. B. Reitz, Bioorg. Med. Chem. Lett., 2007, 17, 24 A. Schneider, O. E. D. Rodrigues, M. W. Paixão, H. R. Appelt,
4568.
A. L. Braga and L. A. Wessjohann, Tetrahedron Lett., 2006,
47, 1019.
25 C. Venkateswarlu, B. Datta and S. Chandrasekaran, RSC Adv.,
2014, 4, 42952.
For a review see: G. Mercey, V. Reboul, M. Gulea, J. Levillain,
and C. Gaumont, Eur. J. Org. Chem., 2012, 5423.
10 (a) V. V. Sureshbabu, T. M. Vishwanatha and B. Vasantha,
Synlett, 2010, 1037; (b) S. L. Tseng and T. K. Yang, 26 (a) H. R. Rajegowda, P. R. Kumar, A. Hosamani and R. J.
Tetrahedron: Asymmetry, 2005, 16, 773; (c) G. A. Cran, C. L.
Gibson and S. Handa, Tetrahedron: Asymmetry, 1995, 6,
1553.
Butcher, New. J. Chem., 2018, 42, 6264; (b) R. H. Revanna, R.
P. Kumar, A. Hosamani and P. B. Siddagangaiah, J.
Organomet. Chem., 2015, 799-800, 61.
11 V. T. Myllymäki, M. K. Lindvall and A. M. P. Koskinen, 27 27. Boivin, S.; Outurquin, F.; Paulmier, C. Tetrahedron Lett.,
Tetrahedron, 2001, 57, 4629. 2000, 41, 663.
12 Inter alia: (a) J. Y. Wu, Z. B. Luo, L. X. Dai and X. L. Hou, J. Org. 28 (a) D. Tanini, A. Capperucci and A. Degl’Innocenti, Eur. J. Org.
Chem., 2008, 73, 9137; (b) D. Sureshkumar, T. Gunasundari,
V. Ganesh and S. Chandrasekaran, J. Org. Chem., 2007, 72,
2106; (c) L. Hu, H. Zhu, D. M. Du and J. Xu, J. Org. Chem.,
2007, 72, 4543; (d) S. Fanjul, A. N. Hulme and J. W. White,
Org. Lett., 2006, 8, 4219; (e) D. Rosenthal, G. Brandruf, K. H.
Davis, J. Wall and M. E. Wall, J. Org. Chem., 1965, 30, 3689.
13 R. B. Nasir Baig, N. Y. Phani Kumar, J. Mannuthodikayil and S.
Chandrasekaran, Tetrahedron, 2011, 67, 3111.
Chem,. 2015, 357; (b) A. Capperucci and D. Tanini,
Phosphorus Sulfur Silicon Relat. Elem., 2015, 190, 1320; (c) S.
Nakamura, M. Hayashi, Y. Kamada, R. Sasaki, Y. Hiramatsu,
N. Shibata and T. Toru, Tetrahedron Lett., 2010, 51, 3820; (d)
S. Minakata, Y. Okada, Y.Oderaotoshi and M. Komatsu, Org.
Lett., 2005, 7, 3509; (e) J. Wu, X. L. Hou and L. X. Dai, J. Org.
Chem., 2000, 65, 1344.
29 (a) D. Tanini, A. Grechi, S. Dei, E. Teodori and A. Capperucci,
Tetrahedron, 2017, 73, 5646; (b) A. Capperucci, D. Tanini, C.
Borgogni and A. Degl'Innocenti, Heteroatom Chem., 2014,
25, 678; (c) A. Degl’Innocenti, A. Capperucci, A. Cerreti, S.
Pollicino, S. Scapecchi, I. Malesci and G. Castagnoli, Synlett
2005, 3063.
14 M. Yamakuchi, H. Matsunaga, R. Tokuda, T. Ishizuka and M.
Nakajima, T. Kunieda, Tetrahedron Lett., 2005, 46, 4019.
15 H. Yang, X. C. Sheng, E. M. Harrington, K. Ackermann, A. M.
Garcia and M. D. Lewis, J. Org. Chem. 1999, 64, 242.
16 (a) J. Harfouche, D. Hérault, M. L. Tommasino, S. Pellet-
Rostaing and M. Lemaire, Tetrahedron: Asymmetry, 2004, 30 M. B. Bieber and M. C. F. de Araujo, Molecules, 2002, 7, 902.
15, 3413; (b) M. Taddei, A. Papini, M. Fiorenza and A. Ricci, 31 (a) A. Capperucci, C. Tiberi, S. Pollicino and A. Degl’Innocenti,
Tetrahedron Lett., 1983, 24, 2311.
17 Inter alia: (a) A. Angeli, D. Tanini, A. Capperucci and C. T.
Supuran, Bioorg. Chem., 2018, 76, 268; (b) A. Angeli, D.
Tetrahedron Lett., 2009, 50, 2808; (b) M. Michida and T.
Mukaiyama, Chem. Lett., 2008, 37, 26; (c) M. Michida and T.
Mukaiyama, Chem. Asian J., 2008, 3, 1592.
Tanini, A. Capperucci, G. Malevolti, F. Turco, M. Ferraroni, C. 32 (a) D. Tanini, C. Tiberi, C. Gellini, P. R. Salvi, A. Capperucci,
T. Supuran, Bioorg. Chem., 2018, 81, 642; (c) A. Angeli, D.
Tanini, A. Capperucci and C. T. Supuran, ACS Med. Chem.
Lett., 2017, 8, 1213; (d) D. Tanini, V. D'Esopo, D. Chen, G.
Adv, Synth. Catal., 2018, 360, 3367; (b) A. Angeli, D. Tanini,
A. Nocentini, A. Capperucci, M. Ferraroni, P. Gratteri and C.T.
Supuran, Chem. Commun., 2019, 55, 648.
Barchielli and A. Capperucci, Phosphorus, Sulfur Silicon Relat. 33 All the obtained 1,2-mercaptoamines were isolated pure
Elem., 2017, 192, 166.
18 (a) A. Alcaide and A. Llebaria, Tetrahedron Lett., 2012, 53,
enough to be used without requiring further purification
step.
2137; (b) M. V. Voronkov, R. C. Kanamarlapudi and P. 34 Ring opening reaction of 2-phenyl-1-tosylaziridine with
Richardson, Tetrahedron Lett., 2005, 46, 6907; (c) S. berlin, C.
Ericsson and L. Engman, J. Org. Chem., 2003, 68, 8386.
(Me3Si)2S gave a mixture of regioisomers in a 75:25 r.r. (3f:18
ratio).
Ts
i) (Me3Si)2S
19 (a) J. K. Ekegren, P. Roth, K. Källström, T. Tarnai and P. G.
Andersson, Org. Biomol. Chem., 2003, 1, 358; (b) D. G. I.
SH
H
ii) TBAF (0.3 eq.)
N
H
N
+
Ts
SH
N
Ph
Ts
Ph
THF
0°C, 10 min
Citric acid
Ph
1f
3f
18
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Please do not adjust margins
New Journal of Chemistry
Page 6 of 7
ARTICLE
Journal Name
1
2
3
4
5
6
7
8
9
View Article Online
DOI: 10.1039/C9NJ00657E
35 A. Degl’Innocenti, A. Capperucci, A. Cerreti, S. Pollicino, S.
Scapecchi, I. Malesci and G. Castagnoli, Synlett 2005, 3063.
36 Reaction of HMDST with N-H unactivated aziridines 10
showed a poor selectivity, leading to a mixture of products.
37 D. Tanini, A. Grechi, L. Ricci, S. Dei, E. Teodori, A. Capperucci,
New J. Chem., 2018, 42, 6077.
38 M. B. Bieber and M. C. F. de Araujo, Molecules, 2002, 7, 902.
39 H. M. I. Osborn and J. Sweeney, Tetrahedron: Asymmetry
1997, 8, 1693.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
40 M. S. I. Veitía, P. L. Brun, P. Jorda, A. Falguières and C.
Ferroud, Tetrahedron: Asymmetry 2009, 20, 2077.
41 (a) S. Yamago, K. Iida and J. I. Yoshida. Tetrahedron Lett.,
2001, 42, 5061; (b) K. Sasaki, Y. Aso, T. Otsubo and F. Ogura
Tetrahedron Lett., 1985, 26, 453; (c) S. Kozuka, T. Higashino
and T. Kitamura, Bull. Chem. Soc. Jpn., 1981, 54, 1420.
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 7 of 7
New Journal of Chemistry
View Article Online
DOI: 10.1039/C9NJ00657E
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
141x42mm (300 x 300 DPI)