Aziridines ring opening by silyl chalcogenides: A stereoselective access to polyfunctionalized molecules as precursor of sulfurated and selenated heterocycles

Article abstract of DOI:10.1080/10426507.2014.1002615

Aziridines react efficiently with bis(trimethyl)silyl-sulfide and -selenide to afford a direct access to β-amino thiols and selenols. Synthesis of 2,4-disubstituted 1,3-selenazolidines is obtained through reaction of 1,2-amino selenols with aldehydes.

Full text of DOI:10.1080/10426507.2014.1002615

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Aziridines Ring Opening by Silyl
Chalcogenides: a Stereoselective Access
to Polyfunctionalized Molecules as
Precursor of Sulfurated and Selenated
Heterocycles
Damiano Taninia, Giulia Barchiellia, Francesca Benellia, Alessandro
Degl’Innocentia & Antonella Capperuccia
a Dipartimento di Chimica “Ugo Schiff”, University of Florence, Via
della Lastruccia 3-13, 50019, Sesto Fiorentino, Italy
Accepted author version posted online: 11 Mar 2015.
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To cite this article: Damiano Tanini, Giulia Barchielli, Francesca Benelli, Alessandro Degl’Innocenti &
Antonella Capperucci (2015) Aziridines Ring Opening by Silyl Chalcogenides: a Stereoselective Access
to Polyfunctionalized Molecules as Precursor of Sulfurated and Selenated Heterocycles, Phosphorus,
Sulfur, and Silicon and the Related Elements, 190:8, 1265-1270, DOI: 10.1080/10426507.2014.1002615
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Phosphorus, Sulfur, and Silicon, 190:1265–1270, 2015
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2014.1002615
AZIRIDINES RING OPENING BY SILYL CHALCOGENIDES:
A STEREOSELECTIVE ACCESS TO
POLYFUNCTIONALIZED MOLECULES AS PRECURSOR
OF SULFURATED AND SELENATED HETEROCYCLES
Damiano Tanini, Giulia Barchielli, Francesca Benelli,
Alessandro Degl’Innocenti, and Antonella Capperucci
Dipartimento di Chimica “Ugo Schiff”, University of Florence, Via della
Lastruccia 3-13, 50019, Sesto Fiorentino, Italy
GRAPHICAL ABSTRACT
Abstract Aziridines react efficiently with bis(trimethyl)silyl-sulfide and -selenide to afford a
direct access to β-amino thiols and selenols. Synthesis of 2,4-disubstituted 1,3-selenazolidines
is obtained through reaction of 1,2-amino selenols with aldehydes.
Keywords Aziridines; silyl-sulfide; silyl-selenide; β-amino thiols; β-amino-selenols; selena-
zolidines
INTRODUCTION
β-(Alkyl)aminothiols represent important building blocks for the synthesis of a vari-
ety of biologically active compounds.1 They found wide application as versatile intermedi-
ates to obtain more complex organic structures, and chiral 1,2-aminothiols have been used
as catalysts and ligands in asymmetric synthesis.2
In addition, the last decades have shown an increasing interest in the chemistry of
organoselenium compounds, due to their applications in different fields, as biological and
food chemistry.3 They are also used as useful intermediates in synthetic organic chemistry.4
2-Aminoalcohols represent the starting reagents used in most of the procedures
described to access to 1,2-aminothiols, and generally the methods for their synthesis require
a multistep sequence, such as the Mitsunobu reaction.1,5 Other procedures, based on the
ring opening of five membered N,S-heterocycles are reported.5b Aziridines and thiiranes
Received 10 November 2014; accepted 21 December 2014.
Address correspondence to Damiano Tanini, Dipartimento di Chimica “Ugo Schiff,” University of Florence,
Via della Lastruccia 3-13, 50019 Sesto Fiorentino, Italy. E-mail: damiano.tanini@unifi.it
1265

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D. TANINI ET AL.
have been described as well in the reaction of sulfur or nitrogen heterocycles to synthesize
β-amino thiols. Typically, reaction of differently protected aziridines with S-nucleophiles6
allows the formation of protected thiols, thus the subsequent cleavage of protecting groups
is necessary to afford amino thiols. To the best of our knowledge, only very few examples
of direct conversion of aziridines to β-aminothiols are reported through reaction with
H2S.7 On the other hand, when selenated nucleophiles were reacted with aziridines, the
corresponding β-amino seleno derivatives have been obtained.6a,8
Our long-dated interest in the chemistry of sulfur and silicon compounds led us to
find a convenient access to β-mercaptoalcohols through the treatment of epoxides with
bis(trimethylsilyl)sulfide (HMDST) under TBAF or PhONnBu4 catalysis.9 Preliminary
results on the reactivity of HMDST with N-Tosyl-aziridines led to the formation of 1,2-
mercaptoamines in rather low yields, together with the corresponding disulfides.10 When the
selenated analogue bis(trimethylsilyl)selenide (HMDSS) was reacted with tosyl-aziridines,
this time a direct entry to chiral β-aminodiselenides was achieved.11
RESULTS AND DISCUSSION
We report in this letter our recent results on the reactivity of silyl-chalcogenides
HMDST and HMDSS with N-Ts- and N-Boc-aziridines, obtained from natural amino
acids.
In a first set of experiments, we reinvestigated the ring opening of N-tosyl-aziridines
1 with HMDST 3, in the presence of TBAF as catalyst. We observed that this reaction
led to 1,2-aminothiols together with the corresponding disulfides as major products. When
the reaction was performed under different controlled conditions (0◦C) and citric acid
was added during the work-up, 1,2-aminothiols 4 were obtained, and the formation of
disulfides was minimized (Scheme 1). Under these conditions a direct entry to several β-
mercaptoamines was obtained in good yields. Attack occurs at the less hindered position of
aziridines to provide a regioselective and enantioconservative access to the title compounds.
Scheme 1
Also N-Boc protected aziridines 2 were efficiently reacted, even if longer reaction
time was necessary to obtain the N-Boc-1,2-aminothiols 5.
Once established the efficiency of HMDST/TBAF based procedure, we turned our
attention to the selenated analogue bis(trimethylsilyl)selenide 6 to evaluate its behavior
under these conditions. When (S)-2-isobutyl-1-tosyl-aziridine 1b was treated with HMDSS
in the presence of fluoride ion, the desired β-aminoselenol 7b was formed (Scheme 2).
Nevertheless, nor under these antioxidant conditions it was possible to avoid the formation
of the corresponding diselenide 8b.

AZIRIDINES RING OPENING BY SILYL CHALCOGENIDES
1267
Scheme 2
This result is however quite interesting as far as it demonstrates the possibility of
obtaining these unstable selenated derivatives. So far, several attempts performed to increase
the yield of β-amino selenols were unsuccessful, and the diselenides were always formed
(ratio selenol:diselenide ∼ 1.5:1).
In order to verify if the so obtained β-amino selenol 7b could behave as efficient
bifunctionalized reagent to obtain five-membered heterocycles, preliminary experiments
were performed with aldehydes. Thus, 1,2-amino selenol 7b was reacted with benzaldehyde
.
in the presence of BF3 Et2O, providing a smooth, direct access to N-tosyl-2-phenyl-4-
isobutyl-1,3-selenazolidine 9b (Scheme 3). The amino selenol 7b was used in mixture with
the diselenide, for the difficulties encountered for its purification due to the high tendency to
be oxidized. Nevertheless, the desired heterocyclic product was formed, even if in moderate
yield, thus evidencing a novel access to this class of compounds.
Scheme 3
In conclusion, we have devised a mild procedure to synthesize β-amino thiols and
-selenols through reaction of bis(silyl)sulfide and -selenide with aziridines. Treatment
of β-amino selenol with benzaldehyde provided a 2,4-disubstituted 1,3-selenazolidine.
Investigation on possible generalization of this protocol and optimization for the synthesis
and purification of amino selenols are currently under investigation in our laboratory.
EXPERIMENTAL
Typical Procedure for the Synthesis of N-Ts-β-amino Thiols
A solution of aziridine 1 (1 mmol) and bis(trimethylsilyl)sulfide 3 (1.4 mmol) in
dry THF was cooled to 0◦C under inert atmosphere, and added with TBAF (0.49 mL of
1M THF solution, 0.49 mmol). After stirring for ca. 30 min, the mixture was treated with
aqueous solution of citric acid, extracted with diethyl ether, washed with water, and dried
over Na2SO4. The solvent was removed under vacuum to afford the aminothiols were
obtained pure enough to be used without further purification.

1268
D. TANINI ET AL.
(S)-N-(1-Mercapto-3-methylbutan-2-yl)-4-methylbenzenesulfonamide
(4a)
Following the typical procedure, starting from 50 mg (0.21 mmol) of aziridine 1a,
46 mg of aminothiol were obtained. Yield 81%. 1H NMR (200 MHz, CDCl3): δ (ppm) 0.78
(3H, d, J = 6.6 Hz), 0.80 (3H, d, J = 7.0 Hz), 1.15 (1H, dd, J = 8.0 Hz, 9.4 Hz), 1.79–1.93
(1H, m), 2.42 (3H, s), 2.46 (1H, ddd, J = 5.6, 9.4, and 12.8 Hz, partially overlapped with
CH3 of tosyl group), 2.64 (1H, ddd, J = 4.4, 8.0, and 12.8 Hz), 3.04–3.15 (1H, m), 4.94
(1H, bd, J = 8.8 Hz), 7.29 (2H, ap.d, ls = 8.4 Hz), 7.77 (2H, ap.d, ls = 8.4 Hz). 13C NMR
(50 MHz, CDCl3): δ(ppm) 18.1, 18.9, 21.5, 27.2, 29.5, 60.0, 127.0, 129.6, 137.9, 143.4.
MS m/z (%): 226 [M+-CH2SH, (69)], 155 (58), 91 (100), 65 (22).
Typical Procedure for the Synthesis of N-Ts-β-amino Selenols
A solution of aziridine 1 (1 mmol) and bis(trimethylsilyl)selenide 6 (1.6 mmol) in dry
THF was treated with TBAF (0.64 mL of 1M THF solution, 0.64 mmol) at 0◦C under inert
atmosphere. After stirring for ca. 10 min, the mixture was added with aqueous solution
of citric acid, extracted with diethyl ether, washed with water, and dried over Na2SO4.
The solvent was evaporated under vacuum to afford the β-amino selenols together with a
variable amount of the corresponding diselenides.
(S)-N-(1-Hydroseleno-4-methylpentan-2-yl)-4-methylbenzenesulfonamide
(7b)
Following the typical procedure, starting from 100 mg (0.40 mmol) of aziridine 1b,
the β-amino selenol was obtained as 1.5:1 mixture with the diselenide 8b. Yield: 49%
(determined by NMR). 1H NMR (200 MHz, CDCl3): δ (ppm) -0.88 (1H, ap t, J = 8.0 Hz),
0.71 (3H, d, J = 6.6 Hz), 0.81 (3H, d, J = 6.4 Hz), 1.16-1.30 (2H, m), 1.39-1.53 (1H, m),
2.42 (3H, s), 2.55-2.62 (2H, m), 3.38-3.61 (1H, m), 4.78 (1H, d, J = 8.4 Hz), 7.30 (2H,
ap.d, ls = 8.0 Hz), 7.76 (2H, ap.d, ls = 8.0 Hz). 13C NMR (50 MHz, CDCl3): δ(ppm) 21.7,
22.0, 23.0, 24.9, 21.5, 43.7, 56.4, 127.6, 129.5, 137.7, 142.9. 77Se NMR (38 MHz, CDCl3)
-93.2.
N,N’-((2S,2’S)-Diselanediylbis(4-methylpentane-2,1-diyl))bis(4-methyl-
benzenesulfonamide) (8b)
1H NMR (400 MHz, CDCl3): δ (ppm) 0.62 (6H, d, J = 6.0 Hz), 0.79 (6H, d, J =
6.4 Hz), 1.22-1.34 (2H, m), 1.36-1.46 (4H, m), 2.42 (6H, s), 3.01 (2H, dd, J = 6.4 Hz,
12.8 Hz), 3.21 (2H, dd, J = 4.0 Hz, 12.8 Hz) 3.46-3.56 (2H, m), 4.98 (2H, d, J = 8.0 Hz),
7.30 (4H, ap.d, ls = 8.4 Hz), 7.79 (4H, ap.d, ls = 8.4 Hz). 13C NMR (50 MHz, CDCl3):
δ(ppm) 21.5, 21.7, 22.8, 24.5, 37.2, 43.7, 52.4, 127.2, 129.7, 137.9, 143.4. 77Se NMR
(38 MHz, CDCl3): 282.3. ESI-MS m/z: 667 (M+.).
(4S)-4-Isobutyl-2-phenyl-3-tosyl-1,3-selenazolidine (9b)
A solution of 90 mg of amino selenol 7b (as 1.5:1 mixture with the diselenide 8b)
and benzaldehyde (0.12 mmol, 12 mg) in dry dichloromethane was treated under inert

AZIRIDINES RING OPENING BY SILYL CHALCOGENIDES
1269
atmosphere with boron trifluoride etherate (0.12 mmol, 13 μL) and then cooled to -18◦C.
After stirring for ca. 12h, the mixture was neutralized with 0.1N solution of NaOH, extracted
with diethyl ether, washed with water, and dried over Na2SO4. The solvent was evaporated
under vacuum to afford the crude product, which was purified on silica gel (hexanes/diethyl
ether 3:1) to give 21 mg of the title compound (41%). 1H NMR (400 MHz, CDCl3): δ (ppm)
0.67 (3H, d, J = 6.8 Hz), 0.92 (3H, d, J = 6.8 Hz), 1.10–1.22 (1H, m), 1.48–1.69 (2H,
m), 2.46 (3H, s), 2.63–2.75 (2H, m), 4.52–4.73 (1H, m), 6.65 (1H, s), 7.23–7.40 (5H, m),
7.55–7.57 (2H, m), 7.78–7.80 (2H, m). 13C NMR (50 MHz, CDCl3): δ(ppm) 21.7, 22.3,
24.8, 32.1, 44.3, 61.0, 64.8, 126.8, 127.5, 128.1, 129.8, 135.5, 141.8, 144.1. 77Se NMR
(38 MHz, CDCl3): 327.1. ESI-MS m/z: 422 (M+.).
FUNDING
Financial support from MiUR, National Project PRIN 2010-2011 “Processi ossidativi
e radicalici: aspetti innovativi ed applicazioni allo sviluppo di biopolimeri melanici e
antiossidanti di rilevanza biomedica e tecnologica (PROxi)” is gratefully acknowledged.
REFERENCES
1. Mercey, G.; Bre´geon, D.; Gaumont, A.-C.; Levillain, J.; Gulea, M. Tetrahedron Lett. 2008, 49,
6553-6555 and references cited.
2. (a) Tseng, S.-L.; Yang, T.-K. Tetrahedron: Asymmetry 2005, 16, 773-782 and references cited
(b) Wipf, P.; Jayasuriya, N.; Ribe, S. Chirality 2003, 208-212 (c) Kang, J.; Kim, J. B.; Kim, J.
W.; Lee, D. J. Chem. Soc., Perkin Trans. 2 1997, 189-194.
3. For more recent examples: (a) Bhuyan, B. J.; Mugesh, G. in Organoselenium Chemistry (Ed.: T.
Wirth), Wiley-VCH Verlag & Co, Weinheim, Germany, 2012, chapter 9, p. 361-396 (b) Santosa,
D. B.; Schiara, V. P. P.; Ribeiroa, M. C. P.; Schwaba, R. S.; Meinerza, D. F.; Allebrandta, J.;
Rochaa, J. B. T.; Nogueira, C. W.; Aschnerb, M.; Barbosaa, N. B. V. Mutat. Res.-Genet. Tox.
2009, 676, 21-26 and references cited (c) Kade, I. J.; Paixa˜o, M. W.; Rodrigues, O. E. D.; Ibukun,
E. O.; Braga, A. L.; Zeni, G.; Nogueira, C. W.; Rocha, J. B. T. Toxicol. in Vitro 2009, 23, 14-20
(d) C. W. Nogueira; G. Zeni; G. J. B. T. Rocha, Chem. Rev. 2004, 104, 6255-6285.
4. (a) Organoselenium Chemistry. Synthesis and Reactions (Ed.: T. Wirth) Wiley-VCH Verlag &
Co, Weinheim, Germany, 2012 (b) Młochowski, J.; Kloc, K.; Lisiak, R.; Potaczek, P.; Wo´jtowicz,
H. Arkivoc 2007, (vi), 14-46 (c) Tiecco, M.; Testaferri, L.; Bagnoli, L.; Marini, F.; Santi, C.;
Temperini, A.; Scarponi, C.; Sternativo, S.; Terlizzi, R.; Tomassini, C. Arkivoc 2006, (vii), 186-
206 (d) Krief, A. in Comprehensive Organometallic Chemistry, Vol. 11 (Eds.: E. W. Abel, E. G.
A. Stone, G. Wilkinson), Pergamon, Oxford, 1995, p. 515.
5. (a) Madhu, C.; Hemantha, H. P.; Vishwanatha, T. M.; Sureshbabu, V. V. Synth. Commun. 2013,
43, 228-235 (b) Mercey, G.; Reboul, V.; Gulea, M.; Levillain, J.; Gaumont, A.-C. Eur. J. Org.
Chem. 2012, 5423-5434 and references cited.
6. Inter alia: (a) Ganesh, V.; Chandrasekaran, S. Synthesis, 2009, 3267-3278 (b) D’hooghe, M.;
Rottiers, M.; Kerkaert, I.; De Kimpe, N. Tetrahedron 2005, 61, 8746-8751 (c) Concello´n, J.
M.; Bernad, P. L.; Sua´rez, J. R.; Garc´ıaGranda, S.; D´ıaz, M. R. J. Org. Chem. 2005, 70, 9411-
9416 (d) Sureshkumar, D.; Koutha, S. M.; Chandrasekaran, S. J. Am. Chem. Soc. 2005, 127,
12760-12761 (e) Galonic´, D. P.; van der Donk, W. A.; Gin, D. Y. J. Am. Chem. Soc. 2004, 126,
12712-12713 (f) Anderson, J. C.; Cubbon, R.; Harding, M.; James, D. S. Tetrahedron: Asymmetry
1998, 9, 3461-3490 (g) Bucciarelli, M.; Forni, A.; Moretti, I.; Prati, F.; Torre, G. Tetrahedron:
Asymmetry 1995, 6, 2073-2080.
7. (a) Potekhin, A. A.; Shevchenko, S. M. Chem. Heterocycl. Compd. 1981, 17, 1013-1020 (b) Wohl,
R. A.; Headley, D. F. J. Org. Chem. 1972, 37, 4401-4406.

1270
D. TANINI ET AL.
8. (a) Sureshkumar, D.; Gunasundari, T.; Saravanan, V.; Chandrasekaran, S. Tetrahedron Lett. 2007,
48, 623-626 and refereces cited therein (b) Braga, A. L.; Lu¨dtke, D. S.; Paixa˜o, M. W.; Alberto,
E. E.; Stefani, H. A.; Juliano, L. Eur. J. Org. Chem. 2005, 4260-4264 (c) Braga, A. L.; Paixa˜o,
M. W.; Lu¨dtke, D. S.; Silveira, C. C.; Rodrigues, O. E. D. Org. Lett. 2003, 5, 2635-2638.
9. (a) Capperucci, A.; Tiberi, C.; Pollicino, S.; Degl’Innocenti, A. Tetrahedron Lett. 2009, 50, 2808-
2810 (b) Degl’Innocenti, A.; Capperucci, A.; Cerreti, A.; Pollicino, S.; Scapecchi, S.; Malesci,
I.; Castagnoli, G. Synlett 2005, 3063-3066.
10. Capperucci, A.; Degl’Innocenti, A.; Pollicino, S.; Acciai, M.; Castagnoli, G.; Malesci, I.; Tiberi,
C. Heteroat. Chem. 2007, 18, 516-526.
11. Degl’Innocenti, A.; Capperucci, A.; Castagnoli, G.; Malesci, I.; Tiberi, C.; Innocenti, B. Phos-
phorus, Sulfur Silicon Relat. Elem. 2008, 183, 966-969.