Oxidative cross-coupling between secondary phosphine selenides and thiols or dithiols: A facile regio-selective synthesis of thioselenophosphinic S-esters and S-diesters

Article abstract of DOI:10.1016/j.tetlet.2013.04.117

Reactions between secondary phosphine selenides and a wide range of aliphatic, aromatic and heteroaromatic thiols or dithiols proceed in the Et ₃N/CCl₄ oxidative system under mild conditions (rt 1-3 h) to give thioselenophosphinic S-esters or S-diesters in 80-92% isolated yields.

Full text of DOI:10.1016/j.tetlet.2013.04.117

Tetrahedron Letters 54 (2013) 3543–3545
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Oxidative cross-coupling between secondary phosphine selenides and thiols
or dithiols: a facile regio-selective synthesis of thioselenophosphinic
S-esters and S-diesters
Nina K. Gusarova a, Pavel A. Volkov a, Nina I. Ivanova a, Yurii V. Gatilov b, Boris A. Trofimov a,
⇑
a A.E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 1 Favorsky Str., 664033 Irkutsk, Russian Federation
b N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentjev Ave. 9, 630090 Novosibirsk, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
Reactions between secondary phosphine selenides and a wide range of aliphatic, aromatic and heteroar-
omatic thiols or dithiols proceed in the Et3N/CCl4 oxidative system under mild conditions (rt 1–3 h) to
give thioselenophosphinic S-esters or S-diesters in 80–92% isolated yields.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 14 March 2013
Revised 15 April 2013
Accepted 26 April 2013
Available online 3 May 2013
Keywords:
Secondary phosphine selenides
Thiols
Dithiols
Thioselenophosphinic S-esters
Thioselenophosphinic S-diesters
Chalcogenophosphinic thioesters have attracted considerable
attention due to their applications as ligands for the design of me-
tal-complexes,1 drug intermediates,1a–c,2 flame retardants,3 RAFT-
agents for controlled styrene polymerization4 and building blocks
in organic and elementoorganic synthesis.5
Se
R
RMgX
R
Se
R'SLi
PhPCl2
+ Se
P
P
Ph Cl
61-91%
Ph SR'
79-99%
R = i-Pr, t-Bu; R' = n-Bu, Ph
Thioselenophosphinic S-esters are of particular interest as
promising selenium sources for the fabrication of selenium-con-
taining nanoparticles. However, the syntheses of these S-esters
are very limited6 and have difficulties associated with the typical
initial reagents such as phosphorus chlorides and organometallic
compounds, which exhibit their own problems, including mois-
ture- and air-sensitivity and issues in handling.
Scheme
phenyldichlorophosphane.
1. Synthesis
of
thioselenophosphinic
S-esters
from
R1
R1
R1
R1
R1
R1
Se
S
Se
S
R2-Hal
+
P
+
M
P
P
Se R2
For example, Murai et al. published6d a method for the prepara-
tion of chiral thioselenophosphinic S-esters which utilized phen-
yldichlorophosphane, elemental selenium, Grignard reagents and
alkali metal thiolates (Scheme 1).
R2
S
78-99%
traces
R
1 = Alk, Ar, ArAlk, HetArAlk;
R2 = Alk, Bn, Allyl, Propargyl;
M+ +NBu4, Na+, K+, Cs+;
Hal = Cl, Br, I
=
Esters of thioselenophosphinic acids have also been synthesized
by alkylation of their ammonium6d,7 or alkali metal8 salts. How-
ever, the main products of these reactions were thioselenophos-
phinic Se-esters (Scheme 2).
Scheme 2. Regio-selective reaction of thioselenophosphinates with organic halides.
The goal of this work was to elaborate a novel, general and sim-
ple approach to the regio-selective synthesis of thioselenophosphi-
nic S-esters and S-diesters.
⇑
Corresponding author. Tel.: +7 395242 14 11; fax: +7 395241 93 46.
E-mail address: boris_trofimov@irioch.irk.ru (B.A. Trofimov).
Scheme 3. Synthesis of secondary phosphine selenides.
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.04.117

3544
N. K. Gusarova et al. / Tetrahedron Letters 54 (2013) 3543–3545
Table 1
Synthesis of thioselenophosphinic S-esters 10a–ia
R1
R1
R1
R1
Se
H
Se
Et3N/CCl4, r.t.
R2SH
3-9
+
P
P
SR2
10a-i
- [Et3NH]Cl
- CHCl3
1, 2
Entry
R12P(Se)H (1 mmol)
R1
R2SH (1 mmol)
R2
Time (h)
S-ester
Yieldb (%)
1
2
1
1
Ph(CH2)2
Ph(CH2)2
3
4
Et
n-hept
2
2
10a
10b
91
90
Me
Et
Me
Ph
Ph
3
1
Ph(CH2)2
Ph(CH2)2
5
2
10c
80
4
5
1
2
6
6
1
1
10d
10e
92
85
PhCH(Me)CH2
6
7
1
1
Ph(CH2)2
7
8
3
2
10f
90
88
N
N
Ph(CH2)2
10g
O
N
N
8
9
1
2
Ph(CH2)2
9
9
1.5
2
10h
10i
90
87
S
PhCH(Me)CH2
S
a
All experiments were carried out under an argon atmosphere at rt for 1–3 h; Et3N (1 mmol) and CCl4 (4 mL) were used.
Isolated yield.
b
Se
S
Se
S
Se
H
R
R
R
R
R
Et3N/CCl4, r.t., 1-1.5 h
2
P
P
+
P
HS
O
SH
R
- [Et3NH]Cl
- CHCl3
O
1,2
11
12a: R = Ph(CH2)2, 90%
12b: R = PhCH(Me)CH2, 88%
Scheme 4. Synthesis of thioselenophosphinic S-diesters 12a,b.
(i)
(ii)
CCl4
- e-
(20–22 °C, 1–3 h) to afford thioselenophosphinic S-esters 10a–i in
80–92% isolated yields (Table 1).
R1 Se
P
Et3N
R1
R1
R1
R1
Se
Se +
P
CCl4
P
B
R1
H
_ Et3HN
The generality and preparative efficiency of the developed
method was demonstrated by the synthesis of S-diesters 12a and
b in 88–90% yield from phosphine selenides 1,2 and dithiol 11 in
a 2:1 molar ratio under the same conditions11 (Scheme 4).
It should be noted that triethylammonium chloride and CHCl3
are also formed in the studied reactions (Table 1; Scheme 4). The
experimental results obtained are in good agreement with the
reaction mechanism (Scheme 5), which we proposed earlier for
the cross-coupling of secondary phosphine chalcogenides with pri-
mary and secondary amines,12 alcohols and phenols.13 The depro-
tonation of secondary phosphine selenides 1,2 by triethylamine
produces P,Se-ambident selenophosphinite-anion A (step i). The
latter participates in a one-electron transfer with CCl4 (oxidizer)
to give secondary phosphine selenide free radical B and anion rad-
ical C (step ii). The interaction of species B and C affords phosphi-
A
C
1, 2
R1 Se
P
(iii)
+
+
B
C
CCl3
+
R1
Cl
D
(iv)
+
Et3N
CHCl3
CCl3
Et3HN
(v)
R1
Se
P
Et3N
HSR2
+
D
+
[Et3NH]Cl
SR2
R1
Scheme 5. A possible mechanism for the formation of thioselenophosphinic S-
esters 10a–i.
noselenoic chloride
D
and the ÀCCl3 carbanion (step iii).
To achieve this goal we have studied, for the first time, the oxi-
dative transition metal free cross-coupling between secondary
phosphine selenides and various thiols or dithiols in a Et3N/CCl4
system.
Protonation of the latter by a triethylammonium cation leads to
regeneration of triethylamine and formation of chloroform (step
iv). The reaction between chloride D and the thiol in the presence
of triethylamine results in the final product, a thioselenophosphi-
nic S-ester, and triethylammonium chloride (step v).
The structures of thioselenophosphinic S-esters 10a–i and S-
diesters 12a,b were established using multinuclear 1H, 13C, 31P
and 77Se NMR spectroscopy, as well as X-ray diffraction analysis
(for compound 10h) (Fig. 1).14
The starting secondary phosphine selenides were easily pre-
pared via a halogen-free method from red phosphorus, styrenes
and elemental selenium (Scheme 3).9
The experiments showed10 that bis(2-phenylalkyl)phosphine
selenides 1 and 2 react with aliphatic 3–5, aromatic 6 and hetero-
aromatic 7–9 thiols in the Et3N/CCl4 system under mild conditions

N. K. Gusarova et al. / Tetrahedron Letters 54 (2013) 3543–3545
3545
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Figure 1. ORTEP diagram of the molecular structure of 10h. Selected bond lengths
[Å] and angles [deg]: P = Se 2.0963(16), P–S 2.127(2), P–C 1.804(5) and 1.815(5) A;
Se–P–S 108.60(7), Se–P–C 113.8(2) and 116.1(2), S–P–C 105.2(2) and 106.4(2), C–P–
C 106.0(2).
7. Kimura, T.; Murai, T. Chem. Commun. 2005, 32, 4077.
8. Artem’ev, A. V.; Gusarova, N. K.; Bagryanskaya, I. Y.; Verkhoturova, S. I.;
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9. (a) Sukhov, B. G.; Gusarova, N. K.; Ivanova, N. I.; Bogdanova, M. V.; Kazheva, O.
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In summary, the oxidative transition metal free cross-coupling
between secondary phosphine selenides and thiols or dithiols in
the Et3N/CCl4 system at room temperature for 1–3 h affords regiose-
lectively thioselenophosphinic S-esters and S-diesters in high
yields. The compounds synthesized are novel representatives of rare
derivatives of thioselenophosphinic acids, which can be used as sin-
gle-source precursors of nanomaterials, RAFT-agents for pseudo-liv-
ing radical polymerization and as potential drug candidates.
10. General procedure for the synthesis of thioselenophosphinic S-esters 10a–i. A
mixture of secondary phosphine selenide
1 or 2 (1.0 mmol) and Et3N
(1.0 mmol) in CCl4 (4 mL) was stirred at 20–22 °C for 10 min. Thiols 3–9
(1.0 mmol) were added, and the reaction mixture was stirred at 20–22 °C for
1–3 h. The solvent was removed under reduced pressure, and 1,4-dioxane
(3 mL) was added. The precipitated white solid (triethylammonium chloride)
was removed by filtration, and the 1,4-dioxane was evaporated. Hexane (2 mL)
was added to the residue obtained, and the resulting mixture was allowed to
stand for 12 h at 0–1 °C. The solution was removed from the precipitate by
decantation, the solvent was evaporated and the residue was dried under
vacuum to give thioesters 10a–c, e, i. In the cases of thioesters 10d,f–h the
residue (after 1,4-dioxane was evaporated under vacuum) was washed with
hexane (3 Â 1 mL) and dried under vacuum to afford 10d, f–h.
Acknowledgments
This work was supported by leading scientific schools of the
President of the Russian Federation (Grant NSh-1550.2012.3) and
the Russian Fund for Basic Research (Grant No. 12-03-31631).
11. General procedure for the synthesis of thioselenophosphinic S-diesters 12a and b. A
mixture of secondary phosphine selenide
1 or 2 (1.0 mmol) and Et3N
(1.0 mmol) in CCl4 (4 mL) was stirred at 20–22 °C for 10 min. The dithiol 11
(0.5 mmol) was added, and the mixture was stirred at 20–22 °C for 1–1.5 h. The
solvent was removed under reduced pressure and 1,4-dioxane (3 mL) was
added. The precipitated white solid (triethylammonium chloride) was
removed by filtration, and the 1,4-dioxane was evaporated. The residue was
reprecipitated from CHCl3 (1 mL) into hexane (10 mL) to give 12a and b.
12. Gusarova, N. K.; Volkov, P. A.; Ivanova, N. I.; Larina, L. I.; Trofimov, B. A.
Tetrahedron Lett. 2011, 52, 2367.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2013.04.
117.
13. Gusarova, N. K.; Volkov, P. A.; Ivanova, N. I.; Larina, L. I.; Trofimov, B. A.
Synthesis 2011, 3723.
14. X-ray crystallographic data for compound 10h. C23H22NPS2Se, Mr = 486.493, R-
References and notes
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