A three-component reaction between alkenes, secondary phosphanes, and elemental selenium: A novel, efficient, atom-economic synthesis of diselenophosphinic esters

Article abstract of DOI:10.1016/j.tetlet.2011.10.094

A novel, convenient, atom-economic approach toward the synthesis of diselenophosphinic esters has been developed via the three-component reaction between aryl- or hetarylalkenes secondary phosphanes, and elemental selenium. The reaction proceeds without a

Full text of DOI:10.1016/j.tetlet.2011.10.094

Tetrahedron Letters 52 (2011) 6985–6987
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Tetrahedron Letters
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A three-component reaction between alkenes, secondary phosphanes,
and elemental selenium: a novel, efficient, atom-economic synthesis of
diselenophosphinic esters
⇑
Nina K. Gusarova, Alexander V. Artem’ev, Svetlana F. Malysheva, Ol’ga A. Tarasova, Boris A. Trofimov
A.E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 1 Favorsky Str., 664033 Irkutsk, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel, convenient, atom-economic approach toward the synthesis of diselenophosphinic esters has
been developed via the three-component reaction between aryl- or hetarylalkenes secondary phos-
phanes, and elemental selenium. The reaction proceeds without a catalyst (85 °C, 3 h, 1,4-dioxane) to
afford the target compounds in good to high yields.
Received 6 September 2011
Revised 29 September 2011
Accepted 17 October 2011
Available online 20 October 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Alkenes
Esters
Multicomponent reactions
Phosphanes
Selenium
Currently, the chemistry of diselenophosphinates is progressing
rapidly.1–5 These compounds are used extensively as convenient
single-source precursors of nanocrystalline materials,2 anionic
ligands for metal complexes,6 promising extractants of heavy
metals, and as building blocks for organic synthesis.3
Recently, increasing attention has been paid to the synthesis of
diselenophosphinic esters,3 R12P(Se)SeR2 (R1, R2 = alkyl or aryl),
which are selenium heteroanalogues of dithiophosphinates,
R12P(S)SR2. The latter are a known class of biologically active chal-
cogenophosphorus compounds.7 Taking into account that sele-
nium itself is a biologically important element and represents a
key active factor in numerous drugs,8 it might be expected that
replacement of the two sulfur atoms of the dithiophosphinates
by Se would allow new, promising drugs and pesticides to be
developed. In addition, diselenophosphinic esters are efficient inif-
erters (RAFT-agents) for pseudo-living radical polymerization of
alkenes.3c,d
Recently, a new approach3e for the synthesis of diselenophos-
phinic esters by the alkylation of diverse alkali metal dise-
lenophosphinates with primary organic halides has been
reported (Scheme 2). The starting alkali metal diselenophosphi-
nates were prepared from secondary phosphanes, elemental sele-
nium, and alkali metal hydroxides.4c
The objective of this Letter was to develop a conceptually new,
one-pot, atom-economic approach to the synthesis of diseleno-
phosphinic esters. We herein describe the three-component reac-
tion between secondary phosphanes, elemental selenium, and
alkenes.
The experimental results show that secondary phosphanes 1–3
react with elemental selenium and various aryl- or hetarylalkenes
4–9 under mild conditions (85 °C, 3 h, 1,4-dioxane, molar ratio
1–3:Se:4–9 being 1:2:1.2) to furnish previously unknown racemic
mixtures of chiral deiselenophosphinic esters 10a–i in good to high
yields (Table 1).9
At the same time, only two synthetic methods for the prepara-
tion of diselenophosphinic esters have been described. The most
common3a,c,d is based on a two-step sequence involving the oxida-
tion of monochlorophosphanes by elemental selenium (toluene,
120 °C, 3 h) and treatment of the intermediate selenophosphinic
chlorides with R2SeMgCl, prepared via an insertion reaction of
Grignard reagents with elemental selenium (Scheme 1).
The results (Table 1) demonstrate the generality of this new reac-
tion for the aryl- and hetarylalkene series. Indeed, diverse aryl- and
hetarylalkenes having functional, heterocyclic, and bulky substitu-
ents participate readily in this reaction. In many cases the synthesis
of the diselenophosphinic esters was almost quantitative. The only
exception was product 10d, the moderate yield of which probably
resulted from the presence of the bulky naphthyl group in starting
alkene 7 (Table 1, entry 4). In this case, the major by-product was
bis(selenophosphoryl)selenide, (R2PSe)2Se [R = Ph(CH2)2], which
was formed via a side reaction, as recently described,10 between
secondary phosphane 1 and elemental selenium.
⇑
Corresponding author. Tel.: +7 395242 14 11; fax: +7 395241 93 46.
E-mail address: boris_trofimov@irioch.irk.ru (B.A. Trofimov).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.10.094

6986
N. K. Gusarova et al. / Tetrahedron Letters 52 (2011) 6985–6987
R2SeMgCl, THF
R
Ph
R1
Ph
R1
Se
Cl
Se, toluene
120 oC, 3 h
KOH/H2O/toluene
P
Cl
P
Pred
r.t., 1 h
PH3/H2
80-90 oC
KOH/DMSO/H2O
Ph
R1
Se
R1 = Ph, i-Pr;
R2 = Alkyl, Bn, 4-MeOC6H4
R
P
R = Ph (1), 4-MeOC6H4 (2),
2-furyl (3)
SeR2
PH
up to 75%
R
51-91%
Scheme 1. Conventional synthesis of diselenophosphinic esters.
Scheme 3. Synthesis of the starting secondary phosphanes 1–3 from red phospho-
rus and styrenes or 2-vinylfuran.
R1
EtOH
+
2 Se
+
MOH
P
H
R1
R1
R1
r.t., 5 min
Se
R1 Se
P
Se
P
R1
H
P
R1
SeH
R1
H
R1
Se
Se
R2CH2Hal, EtOH
55 oC, 0.5 h
R1 Se
A
P
P
M
R1 Se CH2R2
R1
R1 Se
P
R1
Se
R2
Me
R2
71-96%
77-95%
P
R1
Se
R1
SeH
R1 = aryl, arylalkyl, hetarylalkyl; M = alkali metal
R2 = H, alkyl, Ph, vinyl, ethynyl
B
Scheme 4. Possible mechanism for the three-component reaction between sec-
ondary phosphanes, elemental selenium, and alkenes.
Scheme 2. Synthesis of diselenophosphinic esters via reaction of organic halides
with alkali metal diselenophosphinates prepared from secondary phosphanes,
elemental selenium, and MOH.
equivalent of elemental selenium to provide diselenophosphinic
acid B. The addition of the latter to the alkene results in dise-
lenophosphinates (Scheme 4).
The preparative advantages of the developed method are the
following: atom-economic, halogen-free and organometallic-free
protocols, simple experimental procedure and relatively mild con-
ditions. In addition, this new approach allows the synthesis of hith-
erto unknown diselenophosphinic esters bearing heterocyclic or
functional substituents. Bearing in mind that the starting second-
ary phosphanes 1–3 employed in this Letter are readily accessi-
ble11 from red phosphorus and vinylarenes or vinylhetarenes
(Scheme 3), this three-component reaction represents a concise
and expedient route to diselenophosphinic esters.
All the compounds synthesized are air-stable oils which are solu-
ble in most organic solvents and insoluble in water. Their structures
were established by 1H, 13C, 31P and 77Se NMR and IR spectroscopy.
The formation of diselenophosphinic esters via the three-com-
ponent reaction can be rationalized as follows: oxidation of the
secondary phosphane by elemental selenium gives a secondary
phosphane selenide A which is further oxidized by a second
Formally, this reaction is assumed to be the first example of the
addition of diselenophosphinic acids R2P(Se)SeH (unknown so far)
to alkenes. Certainly, this type of addition is electrophilic in nature
and proceeds regioselectively in agreement with Markovnikov’s
rule allowing diselenophosphinates with a SeCH(R2)Me structural
unit to be prepared. Until now, only one representative of such
compounds has been described.3d The generation of the intermedi-
ate diselenophosphinic acids is in keeping with the result obtained
for 2-vinylpyridine, which as an organic base gives, instead of the
expected adduct, a salt-like product. According to the electrophilic
character of the addition, the key intermediate of this step should
be a carbocation +[CHR2(Me)], which in the case of aryl- or
hetarylalkenes is stabilized by the adjacent aromatic or heteroaro-
matic moieties, R2. This is additionally supported by the fact that
when R2 = alkyl, and is less able to stabilize the neighboring
Table 1
One-pot atom-economic synthesis of diselenophosphinic esters 10a–i from secondary phosphanes 1–3, elemental selenium, and aryl- or hetarylalkenes 4–9a
R1
R1
Se
Se
R1
R1
85 oC, 3 h
Me
R2
P
P
H
+
2 Se
+
R2
4-9
1,4-dioxane
10a-i
1-3
Entry
Phosphane
R1
Alkene
R2
Ester
Yieldb (%)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
2
3
3
Ph(CH2)2
Ph(CH2)2
Ph(CH2)2
Ph(CH2)2
Ph(CH2)2
Ph(CH2)2
4-MeOC6H4(CH2)2
2-Furyl(CH2)2
2-Furyl(CH2)2
4
5
6
7
8
9
5
8
9
Ph
10a
10b
10c
10d
10e
10f
10g
10h
10i
85
90
86
54c
91
95
89
90
94
4-t-BuC6H4
4-ClC6H4
2-Naphthyl
2-Furyl
1-Pyrrolyl
4-t-BuC6H4
2-Furyl
1-Pyrrolyl
a
b
c
Reaction conditions: secondary phosphane 1–3 (1.0 mmol), alkene 4–9 (1.2 mmol), Se (2.0 mmol), 1,4-dioxane (8 mL), 85 °C, ca. 3 h.
Yield of isolated product after flash chromatography.
Yield of isolated product after column chromatography.

N. K. Gusarova et al. / Tetrahedron Letters 52 (2011) 6985–6987
6987
2669–2677; (b) Kawai, T.; Hasegawa, Y.; Adachi, T. U.S. Patent WO 2007/
102271, 2007; Chem. Abstr. 2007, 147, 368034.; (c) Panneerselvam, A.; Nguyen,
C. Q.; Waters, J.; Malik, M. A.; O’Brien, P.; Raftery, J.; Helliwell, M. Dalton Trans.
2008, 4499–4506; (d) Hasegawa, Y.; Adachi, T.; Tanaka, A.; Afzaal, M.; O’Brien,
P.; Doi, T.; Hinatsu, Y.; Fujita, K.; Tanaka, K.; Kawai, T. J. Am. Chem. Soc. 2008,
130, 5710–5717; (e) Maneeprakorn, W.; Nguyen, C. Q.; Malik, M. A.; O’Brien, P.;
Raftery, J. Dalton Trans. 2009, 2103–2108; (f) Panneerselvam, A.; Nguyen, C. Q.;
Malik, M. A.; O’Brien, P.; Raftery, J. J. Mater. Chem. 2009, 19, 419–427; (g)
Tanaka, C. Q.; Adachi, T.; Hasegawa, Y.; Kawai, T. J. Alloy. Compd. 2009, 488,
538–540; (h) Maneeprakorn, W.; Malik, M. A.; O’Brien, P. J. Mater. Chem. 2010,
20, 2329–2335; (i) Cossairt, B. M.; Owen, J. S. Chem. Mater. 2011, 23, 3114–
3119.
85 oC, 3 h
Se
H
+
Se
+
P
Ph
1,4-dioxane
Se
Me
P
Se
3. (a) Kimura, T.; Murai, T. J. Org. Chem. 2005, 70, 952–959; (b) Kimura, T.; Murai,
T.; Mizuhata, N. Heteroatom. Chem. 2005, 16, 185–191; (c) Moon, J.; Nam, H.;
Kim, S.; Ryu, J.; Han, C.; Lee, C.; Lee, S. Tetrahedron Lett. 2008, 49, 5137–5140;
(d) Song, E.; Jo, Y.; Bae, G.; Oh, I.-K.; Jung, H. M.; Lee, S. Bull. Korean Chem. Soc.
2009, 30, 2129–2131; (e) Artem’ev, A. V.; Chernysheva, N. A.; Gusarova, N. K.;
Malysheva, S. F.; Yas’ko, S. V.; Albanov, A. I.; Trofimov, B. A. Synthesis 2011,
1309–1313.
Ph
10a
Scheme 5. One-pot synthesis of diselenophosphinate 10a from
phosphane selenide, elemental selenium, and styrene.
a secondary
4. For very recent publications on advances on the synthesis of salts of
diselenophosphinic acids, see: (a) Trofimov, B. A.; Artem’ev, A. V.; Malysheva,
S. F.; Gusarova, N. K. J. Organomet. Chem. 2009, 694, 4116–4120; (b) Trofimov, B.
A.; Artem’ev, A. V.; Gusarova, N. K.; Malysheva, S. F.; Fedorov, S. V.; Kazheva, O.
N.; Alexandrov, G. G.; Dyachenko, O. A. Synthesis 2009, 3332–3338; (c)
Artem’ev, A. V.; Malysheva, S. F.; Gusarova, N. K.; Trofimov, B. A. Synthesis
2010, 2463–2467; (d) Artem’ev, A. V.; Malysheva, S. F.; Gusarova, N. K.;
Belogorlova, N. A.; Trofimov, B. A. Synthesis 2010, 1777–1780; (e) Artem’ev, A.
V.; Gusarova, N. K.; Malysheva, S. F.; Trofimov, B. A. Russ. Chem. Bull. 2010, 59,
1671; (f) Artem’ev, A. V.; Gusarova, N. K.; Malysheva, S. F.; Kraikivskii, P. B.;
Belogorlova, N. A.; Trofimov, B. A. Synthesis 2010, 3724–3730; (g) Gusarova, N.
K.; Artem’ev, A. V.; Malysheva, S. F.; Fedorov, S. V.; Kazheva, O. N.; Alexandrov,
G. G.; Dyachenko, O. A.; Trofimov, B. A. Tetrahedron Lett. 2010, 51, 1840–1843.
positive charge, the three-component reaction does not take place
(as was the case with 1-octene).
Besides, the mechanism proposed (Scheme 4) is in agreement
with our finding that bis(2-phenethyl)phosphane selenide reacts
with one equivalent of elemental selenium and one equivalent of
styrene under the same conditions (85 °C, 3 h, 1,4-dioxane) to form
diselenophosphinate 10a in 86% yield12 (Scheme 5).
The synthesis of diselenophosphinic esters reported here is
strictly atom-economic: in most cases, all the starting materials
are consumed to produce the target compounds with no side prod-
ucts being observed.
5. For
a
recent review describing the chemistry and applications of
diselenophosphinates, see Artem’ev, A. V.; Malysheva, S. F.; Gusarova, N. K.;
Trofimov, B. A. Org. Prep. Proc. Int. 2011, 43, 381–449.
6. For the synthesis of heavy metal diselenophosphinate complexes, see: (a)
Müller, A.; Christophliemk, P.; Rao, V. V. K. Chem. Ber. 1971, 104, 1905–1914;
(b) Müller, A.; Rao, V. V. K.; Christophliemk, P. J. Inorg. Nucl. Chem. 1974, 36,
472–475; (c) Nguyen, C. Q.; Adeogun, A.; Afzaal, M.; Malik, M. A.; O’Brien, P.
Chem. Commun. 2006, 2182–2184; (d) Lobana, T. S.; Wang, J.-C.; Liu, C. W.
Coord. Chem. Rev. 2007, 251, 91–110; (e) Artem’ev, A. V.; Malysheva, S. F.;
Gusarova, N. K.; Trofimov, B. A. Russ. J. Gen. Chem. 2011, 81, 1449–1452.
7. (a) Mel’nikov, N. N.; Novozhilov, K. V.; Pylova, T. N. The Pesticide, Chemistry,
Moscow, 1980.; (b) Matolcsy, G.; Nadasy, M.; Andriska, V. Pesticide Chemistry;
Elsevier: Budapest, 1988; (c) Edmundson, R. S. In The Chemistry of
Organophosphorus Compounds; Hartley, F. R., Ed.; Ter- and quinque-valent
phosphorus acids and their derivatives; Wiley: New York, 1996; Vol. 4, pp 397–
494; (d) Haiduc, I. J. Organomet. Chem. 2001, 623, 29–42.
To summarize, a new, efficient, atom-economic, three-compo-
nent reaction between alkenes, secondary phosphanes, and
elemental selenium to give previously unknown diselenophosphi-
nic esters has been discovered and elaborated. The results contrib-
ute to the fundamental chemistry of organic phosphanes, elemental
selenium, and alkenes, as well as to the synthesis of organoseleno-
phosphorus compounds via multi-component reactions. Diseleno-
phosphinic esters represent promising building blocks, potential
precursors of drugs, and active iniferters (RAFT-agents).
8. (a) Selenium in Nutrition: Revised Edition, National Academy Press, Washington,
1983.; (b) Parker, J. N.; Parker, P. M. Selenium: A Medical Dictionary, Bibliography,
and Annotated: Research Guide to Internet References; Icon Group International:
San Diego, 2004; (c) Reilly, C. Selenium in Food and Health; Springer: New York,
2006; (d)Selenium: Its Molecular Biology and Role in Human Health; Hatfield, D.
L., Berry, M. J., Gladyshev, V. N., Eds., 2nd ed.; Springer: New York, 2006.
9. General procedure for the synthesis of diselenophosphinic esters 10a–i: To a
solution of secondary phosphane 1–3 (1.0 mmol) in 1,4-dioxane (8 mL) were
added consecutively alkene 4–9 (1.2 mmol) and powdered grey selenium
(0.158 g, 2.0 mmol) at ambient temperature under argon. The suspension was
stirred until dissolution of the selenium (ca. 3 h) at 85 °C to give a yellowish
transparent solution. The solvent was removed under reduced pressure (1 Torr,
50–60 °C) and the residue purified by flash chromatography (neutral alumina,
hexane) to give diselenophosphinate 10a–c,e–i in 85–95% yield.
Diselenophosphinate 10d was isolated by column chromatography (neutral
alumina, toluene) in 54% yield.
Acknowledgments
This work was supported by the Russian Foundation for Basic
Research (Grant No: 11-03-92003-HHC_a) and the President of
the Russian Federation [programs for the support of leading scien-
tific schools (Grant NSh-3230.2010.3) and young Russian scientists
(Grant MK-629-2010.3)].
Supplementary data
Supplementary data (general remarks, experimental proce-
dures, and characterization data for compounds 10a–i) associated
with this article can be found, in the online version, at
doi:10.1016/j.tetlet.2011.10.094.
10. Artem’ev, A. V.; Gusarova, N. K.; Malysheva, S. F.; Ushakov, I. A.; Trofimov, B. A.
Tetrahedron Lett. 2010, 51, 2141–2143.
11. For reviews on the availability of secondary phosphines, see: (a) Trofimov, B.
A.; Arbuzova, S. N.; Gusarova, N. K. Russ. Chem. Rev. 1999, 68, 215–228; (b)
Trofimov, B. A.; Gusarova, N. K. Mendeleev Commun. 2009, 19, 295–302.
12. Three-component reaction between bis(2-phenethyl)phosphane selenide,
elemental selenium and styrene: To a solution of bis(2-phenethyl)phosphane
selenide (0.321 g, 1.0 mmol) in 1,4-dioxane (8 mL) were added consecutively
styrene (0.115 g, 1.2 mmol) and powdered grey selenium (0.079 g, 1.0 mmol)
at ambient temperature under argon. The suspension was stirred until
dissolution of the selenium (ca. 3 h) at 85 °C to give a yellowish transparent
solution. The solvent was removed under reduced pressure (1 Torr, 50–60 °C)
and the residue purified by flash chromatography (neutral alumina, hexane) to
give diselenophosphinate 10a in 86% yield.
References and notes
1. For recent examples of the synthesis of salts of diselenophosphinic acids, see:
(a) Davies, R. P.; Martinelli, M. G. Inorg. Chem. 2002, 41, 348–352; (b) Davies, R.
P.; Francis, C. V.; Jurd, A. P. S.; Martinelli, M. G.; White, A. J. P.; Williams, D. J.
Inorg. Chem. 2004, 43, 4802–4804; (c) Hua, G.; Zhang, Q.; Li, Y.; Slawin, A. M. Z.;
Woollins, J. D. Tetrahedron 2009, 65, 6074–6082; (d) Davies, R. P.; Martinelli, M.
G.; Patel, L.; White, A. J. P. Inorg. Chem. 2010, 49, 4626–4631.
2. For the application of heavy metal diselenophosphinates as single-source
precursors of remarkable nanomaterials, see: (a) Nguyen, C. Q.; Afzaal, M.;
Malik, M. A.; Helliwell, M.; Raftery, J.; O’Brien, P. J. Organomet. Chem. 2007, 692,